Abstract

Abstract and case study poster sessions will be conducted during the College of American Pathologists Annual Meeting (CAP '09), which is scheduled for October 11 to October 14, 2009. The meeting will take place at the Gaylord National Resort, National Harbor, Maryland. The poster sessions will occur in the Connection Café and Exhibits Hall. Specific dates and times for each poster session are listed below. Also shown below each poster session listing are the subject areas that will be presented during that session.

POSTER SESSION 100: SUNDAY, OCTOBER 11, 2009, 9:00 am–11:30 am

Gastrointestinal and Liver Pathology

Blue Nevus of the Colorectal Mucosa (Poster No. 1)

Zvika J. Schreiber, MD (zschreiber@notes.cc.sunysb.edu); Timothy R. Pal, MD; Sonya Hwang, MD. Department of Pathology, Stony Brook University Medical Center, Stony Brook, New York.

The blue nevus is a benign melanocytic proliferation that generally occurs on the skin. Infrequently, blue nevi are found on mucosal surfaces. The most common location for mucosal blue nevi is the oral mucosa, with reported cases in the sinonasal mucosa, genital tract, and other locations. To our knowledge, blue nevi of the anorectal mucosa have not been reported. We report the case of an asymptomatic 60-year-old woman who presented for a high-risk screening colonoscopy after being diagnosed with 2 tubular adenomas during the previous year. The study revealed a pigmented lesion in the colorectal region, adjacent to the anal transition zone. Histologic sections revealed otherwise unremarkable colonic and transitional mucosa with pigmented cells in the lamina propria. The pigmented cells consisted predominantly of long dendritic melanocytes with scant cytoplasm and abundant fine melanin granules. The nuclei were round to ovoid with a uniform chromatin pattern and inconspicuous nucleoli. No cytologic atypia or mitotic figures were identified. Scattered melanophages were also present. All of the previously mentioned features are consistent with the diagnosis of blue nevus (Figure 1). As with any pigmented lesion, the possibility of melanoma should be considered. Although mucosal melanomas are rare, 24% arise in the anorectal region. These patients commonly present with pain, rectal bleeding, and a polypoid mass. There are also rare reports of malignant transformation of cutaneous blue nevi. Pigmented lesions, including blue nevi, of the anorectal region are rare and sampling is indicated to rule out malignancy.

Evaluation of Mast Cells and Their Association to Eosinophils in the Gastrointestinal Tract of the Pediatric Population (Poster No. 2)

Yasi Saffari, MD1 (yasi7th@yahoo.com); Kristen Thomas, MD1; Kerry Zabriskie, NP2; Joseph Levy, MD2; M. Alba Greco, MD.1 Departments of 1Pediatric Pathology and 2Pediatrics, New York University, New York.

Context: Intestinal mast cells have been known to be related to food allergy and immediate hypersensitivity and are implicated as a th2-mediated regulator in eosinophilic gastritis. In this study, numbers of mast cells and eosinophils were investigated in biopsies from the upper gastrointestinal tract of children (n = 30; mean age, 14 years) with histopathologically confirmed eosinophilic enteropathy (n = 7), inflammatory bowel disease (n = 10), nonspecific chronic inflammation (n = 6), and no pathologic changes (n = 7).

Design: Paraffin sections of formalin-fixed samples from stomach and duodenum were stained using toluidine blue to highlight the mast cells. Quantitative evaluation of mast cells and eosinophils was performed counting their number per 10 high-power fields.

Results: Within the histopathologically defined groups, clear correlation between mast cell and eosinophil numbers was detected in patients with eosinophilic enteropathy (stomach, P = .02; duodenum, P = .03) and inflammatory bowel disease (stomach, P = .004; duodenum, P = .02). Overall, the mean number of mast cells was higher in stomach than in duodenum in all groups aside from their pathologic diagnosis (11.6 ± 1.3 stomach vs 8.1 ± 1.9 duodenum, mean ± standard error of the mean, P = .004).

Conclusions: Our results demonstrate the participation of mucosal mast cells in stomach and duodenum in disease process with more eosinophils and in inflammatory bowel disease. In these cases, increased numbers of mucosal mast cells along with eosinophils may indicate a role of mast cells as a regulatory mediator of visceral hypersensitivity due to either dietary antigens or inflammatory stimulator. Further studies will help in understanding the role and distribution of mast cells particularly in the gastrointestinal tract of children.

A Case of Systemic Mastocytosis and Anal Squamous Carcinoma (Poster No. 3)

Michele K. McElroy, MD1 (mkmcelroy@ucsd.edu); Lance L. Stein, MD2; Bard Cosman, MD3; Samuel B. Ho, MD4; Jessica Wang-Rodriguez, MD.5  Departments of 1Pathology, 2Gastroenterology, and 3Surgery, University of California, San Diego; Departments of 4Gastroenterology and 5Pathology, VA San Diego Healthcare System, San Diego, California.

Systemic mastocytosis is an uncommon disease of mast cells, which leads to clonal mast cell proliferation involving several different sites including the bone marrow, skin, liver, spleen, and gastrointestinal tract. Treatment for this disease includes glucocorticoids, interferon α, and cytoreductive therapy. Generally systemic mastocytosis is associated with other hematologic malignancies, but association with solid organ malignancies is rare. We describe a case of a human immunodeficiency virus– negative male with systemic mastocytosis and acquired factor VIII inhibitor who was treated with various cycles of immunosuppression and chemotherapy. After several years relatively symptom-free, he developed clinical symptoms of nausea, diarrhea, and weight loss. Colonoscopy revealed multiple sessile polyps throughout but most prominently in the proximal colon that were infiltrated by mast cells as well as a diminutive p16-positive anal squamous cell carcinoma. The development of human papilloma virus–related malignancy in this patient occurred despite a relatively short duration of immunosuppression, raising the possibility that increased surveillance for anorectal dysplasia may be warranted in patients receiving immunosuppression in the setting of systemic mastocytosis.

Acinar Cell Carcinoma With a Prominent Intraductal Growth Pattern (Poster No. 4)

Adam D. Toll, MD (adam.toll@jeffersonhospital.org); Agnieszka K. Witkiewicz, MD. Department of Pathology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.

Acinar cell carcinoma of the pancreas is rare, accounting for less than 1% of pancreatic cancer. Patients are typically between the fifth and seventh decade of life and show a 2:1 male predominance. Symptoms tend to be nonspecific, and approximately 50% of patients have metastasis at time of presentation. There have been recent case reports of acinar cell carcinoma showing both intraductal and/or papillary patterns of growth that could potentially be mistaken for intraductal neoplasia. The cases reported to date have presented as solitary nodules. We describe the first case of acinar cell carcinoma with intraductal and tubuloglandular growth diffusely involving the pancreas. The patient is a 31-year-old woman who had suffered from multiple attacks of pancreatitis beginning in March 2007 requiring several hospitalizations. Imaging studies showed chronic obstructive pancreatitis and diffuse duct dilatation. The patient underwent distal pancreatectomy and splenectomy. Microscopic examination revealed acinar cell carcinoma with an intraductal growth pattern diffusely involving the pancreas (Figure 2) and extending to the proximal margin. Histologic findings in the completion pancreatectomy specimen revealed multiple foci of tumor with similar histologic findings to those seen in the distal pancreatectomy. Despite chemotherapy, the patient developed liver metastasis 6 months following her second surgery. We present a case of acinar cell carcinoma with a rare, diagnostically challenging histologic appearance. It is important to correlate clinical, histologic, and immunohistochemical findings to differentiate this lesion from a more benign intraductal neoplasm, notably intraductal papillary mucinous neoplasm.

Acute Fulminant Hepatic Necrosis in First 12 Hours of Amiodarone Administration (Poster No. 5)

Vladislav Zakharov, MD (vladislav-zakharov@ouhsc.edu); Lewis A. Hassell, MD. Department of Pathology, University of Oklahoma, Health Sciences Center, Oklahoma City.

Amiodarone is a commonly used antiarrhythmic with well-known common side effects with prolonged therapy. We present a case of fulminant hepatic necrosis proven by liver biopsy following intravenous administration of amiodarone within the first 12 hours of infusion. A 60-year-old man with a history of congestive heart failure, chronic renal insufficiency, and positive serology for hepatitis C antibody was admitted to the hospital with complaints of gradually increasing shortness of breath and dyspnea on exertion. The results of initial liver function tests showed values within the reference range. An electrocardiogram on admission revealed atrial flutter with a variable rate and the patient was administered intravenous amiodarone. Within the first 12 hours of infusion repeat liver function testing showed extremely high hepatic parameters: aspartate aminotransferase 3491 U/L, alanine aminotransferase 2029 U/L, and bilirubin 3.77 mg/dL. Infusion of amiodarone was stopped. The patient developed symptoms of acute abdomen and an exploratory laparotomy was performed with a concern of ischemic bowel. However, other than an acutely edematous liver, there was no evidence of acute pathology, and wedge liver biopsy was taken. Microscopic examination of the liver sample revealed acute hepatic necrosis with minimal steatosis and mild chronic inflammation. The findings were consistent with acute fulminant hepatic necrosis secondary to intravenous amiodarone administration. Electron microscopy showed hepatocytes with phospholipid inclusions with occasional foci suggestive of amiodarone-type inclusions, with areas of cholestasis and steatosis. Although acute amiodarone hepatic toxicity is rare, pathologists should be aware of this possibility and associated histologic findings.

Assessment for Residual Intestinal Metaplasia and Dysplasia in Postablative Barrett Esophagus Using Deeper Jumbo Biopsies (Poster No. 6)

Ajay J. Patel, MD (ajpatel1@gmail.com); Dawn Bradly, MD; Maria McIntire, MD; Deborah Giusto, MD; Shriram Jakate, MD. Department of Pathology, Rush University Medical Center, Chicago, Illinois.

Context: Recent therapeutic trends for Barrett esophagus (BE) with high-grade dysplasia (HGD) are evolving toward local ablative therapies. Such therapy resolves both the dysplastic area and metaplastic bed. However, this poses new challenges in follow-up as residual and recurrent metaplastic or dysplastic foci become endoscopically invisible, buried under regenerated neosquamous lining. This study documents our surveillance of postablative BE with deeper jumbo biopsies, ensuring recovery of buried glands.

Design: Review of our records from 2004 to 2008 identified 8 patients with BE who underwent ablation and follow-up surveillance with jumbo biopsies. The following characteristics were reviewed: indication, follow-up duration, presence of residual or recurrent metaplasia, dysplasia, and/ or carcinoma.

Results: All 8 patients (6 men, 2 women; 62–83 years; mean age, 69 years) had ablation for metaplasia and HGD with margins free of dysplasia. Their follow-up ranged from 1 month to 5.4 years with a median of 1 year. Protocol surveillance jumbo biopsies included mucosa and superficial submucosa. At follow-up, 3 of 8 (37.5%) had no metaplasia or dysplasia, 3 of 8 had residual metaplasia without dysplasia, and 2 of 8 (25%) had metaplasia and focal HGD beneath neosquamous mucosa.

Conclusions: Ablative therapy for BE with HGD produces prolonged dysplasia-free states in 75% of cases and metaplasia-free states in 37% of cases. When residual or recurrent metaplasia or dysplasia occurs, it is likely to be buried under a regenerated squamous lining. Although the endoscopic distinctiveness of the BE segment is lost through neoepithelialized squamous mucosa, protocol surveillance using jumbo forceps is essential in ensuring assessment of submerged glands.

Morphoproteomics Defines the Cell Cycle Biology of Fibrolamellar Hepatocellular Carcinoma (Poster No. 7)

Sadhna Dhingra, MD1 (Sadhna.Dhingra@uth.tmc.edu); Wei Li, MD1; Dongfeng Tan, MD2; Robert E. Brown, MD.11Department of Pathology and Laboratory Medicine, University of Texas Health Sciences Center-Medical School, Houston; and 2Department of Pathology, MD Anderson Cancer Center, Houston, Texas.

Context: Fibrolamellar hepatocellular carcinoma (FLHCC) has a better prognosis than conventional hepatocellular carcinoma. Nevertheless, it has a propensity to recur and has limited responsiveness to chemotherapy, and its biology has not been defined. This study sought to provide insight into the biology of FLHCC and, specifically, its cell cycle biology as it relates to its relatively indolent nature and chemoresponsiveness.

Design: Morphometric and protein analytes indicating cell cycle progression and inhibition were assessed in 7 cases of FLHCC. These included Ki-67 (G1, S, G2, and M phases), S-phase kinase-associated protein (Skp) 2, and mitotic index. Inhibitors of G1 to S phase included p27Kip1 and p16INK4a. The percentage of Ki-67–positive nuclei was determined by an automated cellular imaging system. Immunoreactivity of other markers was assessed for subcellular localization by bright-field microscopy.

Results: The mean percentage of Ki-67 nuclear positivity in neoplastic hepatocytes ranged from 1.0% to 29.7% in the 7 cases. Nuclear Skp2 immunoexpression was negative and the mitotic index was very low (0–1 per 10 high-power fields). Correspondingly, all showed p16INK4a nuclear positivity. The adjacent nonneoplastic hepatocytes were negative for p16INK4a expression. Immunoreactivity for p27Kip1 was negative in 6 of 7 cases.

Conclusions: Morphoproteomic analysis reveals cell cycle arrest in the G0/G1 phase in FLHCC, associated with overexpression of the cell cycle inhibitor p16INK4a in the nuclei of tumoral cells vis-à-vis the nonneoplastic hepatocytes. In conjunction with our previous demonstration of a constitutively activated NF-κB pathway in FLHCC, cell cycle arrest helps explain the biology of its indolent nature and also its relative chemoresistance.

A Rare Finding in a Patient With Crohn Disease (Poster No. 8)

Sanda Alexandrescu, MD (sanda@erdani.com); Robert E. Brown, MD.  Department of Pathology, University of Texas–Houston.

Crohn disease can occur anywhere in the gastrointestinal tract, with ileum and colon being the most affected parts. Rarely, it can occur in other places like the upper digestive tract, peritoneum, or tonsils. We report a case of involvement of the palatine tonsils, manifested as chronic tonsillitis. A 23-year-old African American woman with a history of Crohn disease that was managed with immunosuppressive therapy presented with an episode of tonsillitis. A year prior she had experienced a sore throat and a peritonsillar abscess, which was treated with incision, drainage, and antibiotics. Considering the recurrent nature of the tonsillitis, it was decided to proceed with a tonsillectomy. Microscopic examination of the tonsils revealed noncaseating epithelioid granulomas, along with reactive follicular hyperplasia, but no active inflammation. Acid-fast, Gomori methenamine silver, and Gram stains were performed to exclude tuberculous infection, fungi, and bacteria, respectively, and were read as negative. Considering the patient's history, the findings were consistent with involvement of tonsils by Crohn disease. This is a rare manifestation of Crohn disease. Repeated episodes of tonsillitis in such a clinical setting should always raise the suspicion for granulomatous tonsillitis to proceed with the best management for the patient.

Second Primary Colon Cancers Associated With First Primary Colon Cancers: A Population-Based Study (Poster No. 9)

Noa Sagy, MPH1 (Noasagy@gmail.com); Donald E. Henson, MD2; Heather Young, PhD1; Steven Patierno, PhD.31Department of Epidemiology, George Washington University School of Public Health and Health Services, Washington, DC; and 2Department of Pathology and 3The Molecular and Cellular Oncology Program, George Washington University Cancer Institute, Washington, DC.

Context: Patients diagnosed with a primary colorectal cancer are at increased risk of developing a second primary colorectal cancer. We studied second primary colon cancers in a population.

Design: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) registry for 1973 to 2005. Data included the first and second primary invasive colorectal carcinoma. According to SEER, a tumor is considered a second primary if diagnosed more than 2 months after the first primary. The SEER Multiple Primary-Standardized Incidence Ratio tool was used to calculate the incidence of second primary cancers (observed/expected [O/E]).

Results: Of 574 726 cases with a first primary cancer in the colorectum, 7137 developed a second primary in the colorectum (O/E, 1.45). Mean age at first primary was 67.9 years and for the second primary was 73.5 years. When stratified by race, African Americans had higher incidence of second primary tumors than whites (O/E, 1.83 vs 1.43), as well as a higher age-adjusted rate of first primary tumors. First and second primaries occurred at an earlier age in African Americans than in whites. All anatomical divisions of the colon showed a decrease in O/E with age. When analyzed by surface area, the mucosal surface of the colorectum was equally susceptible to second primary cancers in all anatomic divisions.

Conclusions: Persons with a first primary colorectal cancer are more susceptible to second primary cancers, specifically in the colon. First and second primary cancers in the colorectum show racial variations. No anatomic division of the colon appears to be more susceptible than any other to a second primary.

Cystic Lesions of the Pancreas: A Review of Cases in a 4-Year Period (Poster No. 10)

Carlos E. Parra-Herran, MD (cparraherran@med.miami.edu); Monica T. Garcia, MD; Loren P. Herrera, MD; Pablo A. Bejarano, MD. Department of Pathology, University of Miami-Jackson Memorial Hospital, Miami, Florida.

Context: Cystic lesions of the pancreas represent a significant proportion of pancreatic tumors. The characterization and classification of these has evolved in recent years and will continue changing according to the increasing number of biopsies and resections performed.

Design: Pancreatectomy specimens collected during a 4-year period that had diagnosis of pancreatic cyst(s) were reviewed. The demographic and pathologic features were recorded.

Results: Of 361 pancreatic lesions, 97 cysts corresponding to 95 patients were studied. Overall, 61% occurred in women and the mean age was 60 years. Among the 97 cysts, 8% were nonneoplastic (pseudocysts, enterogenous, congenital, oncocytic, and squamous cysts) and 92% were neoplastic (58% benign, 10% borderline, 24% malignant) (Table). Intraductal papillary mucinous neoplasm (IPMN) was the most common diagnosis (48%). Benign and borderline neoplasms were mostly seen in the head (42% and 70%, respectively), whereas nonneoplastic and malignant cysts were more common in the tail (37% and 42%, respectively). Excluding patients with solid and cystic pseudopapillary tumor (SCPT) who were significantly younger (23 years; range, 16–38 years; P = .001), patients with borderline and malignant neoplasms were older (mean, 65.6 and 65.1 years, respectively) than patients with nonneoplastic cysts and benign neoplasms (mean, 61.6 and 61.1 years, respectively). Malignant cysts were significantly larger than benign and borderline lesions (mean, 4.7 cm; P = .05).

Conclusions: In our series, most cystic lesions were neoplastic, mostly benign mucinous and malignant tumors. Location is not useful in differentiating malignant from nonneoplastic cysts. Malignancy in cystic neoplasms was associated with older age (when excluding SCPT) and larger size.

 
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Discriminating Between Benign and Malignant Gastrointestinal Stromal Tumors Using CD10 Immunohistochemistry (Poster No. 11)

Sharif Ali, MD (sali2@hfhs.org); Hwajeong Lee, MD; Adrian Ormsby, MD. Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, Michigan.

Context: Prediction of gastrointestinal stromal tumor (GIST) behavior has been studied for many years. The problem is that proposed tumor risk indices do not correlate closely with the malignant potential. Researchers are developing targeted anti-CD10 monoclonal antibody therapy, which may impact the future management of CD10 immunoreactive tumors. Our study aims to assess the utility of CD10 immunostaining in GIST and whether it can be a useful adjuvant to define malignant tumor.

Design: Seventeen cases occurring since 2000 with at least 3 years of clinical follow-up were retrieved. Tumor locations included stomach (10 cases), small intestine (3), and colon (4). Two microarray blocks were created using a 3-mm needle, 2 cores from each case and the 5 metastatic sites.

Results: Cases were divided into benign (10 cases; no metastasis, local invasion, high-risk morphology, or recurrence) and malignant (7 cases; 6 exhibited distant metastases, 1 was locally invading the fallopian tube [Table]). Histologically only the malignant cases exhibited variable cytologic atypia, high mitotic rate (>6–10 per high-power fields), areas of necrosis, and large tumor size. All benign tumors showed no reactivity with CD10 (0 of 6). In contrast, 3 of 6 (50%) malignant metastatic cases were strongly CD10-positive (3+). One case (1 of 6) showed weak (1+) staining in the corresponding metastatic liver tissue. The locally invasive case was negative.

Conclusions: CD10 immunoreactivity may be helpful in identifying cases of GIST with metastatic potential (50% of cases are positive). Also CD10-positive cases may be of clinical interest with the new therapy.

 
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Angiosarcoma of the Sigmoid Colon Complicated by Disseminated Intravascular Coagulation: A Case Report and Literature Review (Poster No. 12)

Christopher N. Thompson, MD (cthompson@swmail.sw.org); Debby Rampisela, MD; Ludvik R. Donner, MD, PhD. Department of Pathology, Scott and White Hospital, Temple, Texas.

We report a case of angiosarcoma of the sigmoid colon in an elderly man. Multiple metastases to the liver were identified during sigmoid colon resection. The tumor cells were strongly and diffusely positive for endothelial markers CD31, CD34, Fli-1, and von Willebrand factor. The patient later developed disseminated intravascular coagulation and expired 4 months after surgery. A review of the literature was performed. Eighteen cases of colonic angiosarcoma, including our case, are known. A slight majority (55%) of the patients were female. The patient ages ranged from 16 to 77 years with a mean age of 55 years. Most patients presented with rectal bleeding. Nine cases involved the sigmoid colon, 4 cases the cecum, 3 cases the rectum, 1 case the descending colon, and 1 case involved the cecum, transverse colon, and rectum. Six of 7 patients with colonic angiosarcoma less than 5 cm were alive at last follow-up (13– 48 months postoperatively), whereas only 2 of 8 patients with tumor size greater than 5 cm were alive at last follow-up. Five of 6 patients younger than 50 years were alive at last follow-up, whereas 8 of 12 patients older than 50 years had rapid progression of their disease leading to death. The longest survival without evidence of recurrence was 3 years and occurred in a 16-year-old girl.

Positive Immunoreactivity of Thyroid Transcription Factor 1 in Colorectal Carcinoma: A Tissue Microarray Study of 104 Cases (Poster No. 13)

Bo Xu, MD, PhD1 (bxu@buffalo.edu); Tyuyen Thong, MD1; Dongfeng Tan, MD2; Thaer Khoury, MD.31Department of Pathology, State University of New York at Buffalo; 2Department of Pathology, MD Anderson Cancer Center, Houston, Texas; and 3Department of Pathology, Roswell Park Cancer Institute and State University of New York at Buffalo.

Context: Thyroid transcription factor 1 (TTF-1) is a member of homeodomain transcription family expressed in epithelial cells of thyroid and lung. Although TTF-1 nuclear expression is generally considered a specific marker for lung and thyroid neoplasms, nuclear immunoreactivity was reported in other types of tumor. Few studies examined TTF-1 expression in colorectal carcinoma (CRC) with inconsistent results. The purpose of this study is to investigate TTF-1 expression in CRC.

Design: During metastatic adenocarcinoma workup for patients who have history of CRC, we identified 4 of 14 cases that had TTF-1 expression using a more specific antibody clone (clone 8G7G3/1). Therefore, we sought to retrospectively investigate the expression of TTF-1 in 90 CRC cases constructed in tissue microarray (TMA) blocks as well as whole tissue sections of the 4 primary tumors corresponding to the 4 positive metastases.

Results: In TMA studies, although all 90 cases had negative nuclear expression of TTF-1, cytoplasmic expression was seen in 1 case (1%). Four of 14 cases of metastatic CRC displayed positive nuclear staining of TTF-1. Three of the 4 corresponding primary carcinomas were also positive for TTF-1 in the whole tissue sections.

Conclusions: Our results suggest that during immunohistochemical workup, especially when the differential diagnosis includes lung and CRC, TTF-1 results should be interpreted with caution as a small subset of CRC expresses this marker. Positive TTF-1 nuclear expression in a metastatic carcinoma cannot rule out colorectal primary. Clinicopathologic correlation combined with a panel of immunohistochemical markers is essential to render correct diagnosis.

Correlation of Histologic and Endoscopic Scores for Evaluation of Crohn Disease Recurrence After Ileal Resection and Infliximab Therapy (Poster No. 14)

Miguel F. Palma Diaz, MD1; Miguel Regueiro, MD2; Wolfgang Schraut, MD2; Leonard Baidoo, MD2; Marilyn Pesci, MD2; Janet Harrison, MD2; Kevin E. Kip, PhD, FAHA3; Scott E. Plevy, MD4; Antonia R. Sepulveda, MD PhD1 (asepu@mail.med.upenn.edu). 1Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia; 2Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; 3College of Nursing Research Center, University of South Florida, Tampa; and 4Department of Medicine, University of North Carolina, Chapel Hill.

Context: Evaluation of Crohn disease recurrence after ileal resection requires assessment of endoscopy with biopsy. Studies evaluating the correlation between histologic and endoscopic grading for follow-up of disease activity and response to infliximab are lacking.

Design: Twenty-four adult Crohn disease patients who underwent ileocolonic resection were assigned to receive either intravenous infliximab 5 mg/kg or placebo for 1 year in a randomized 2-armed double-blind placebo-controlled trial. Follow-up endoscopy with neoterminal ileal biopsy at 1 year was performed in all patients. Endoscopic grading ranged from 0 to 4. Biopsy samples stained with hematoxylin-eosin were scored with a modified grading system for epithelial damage, crypt architectural changes, mononuclear or neutrophils in the lamina propria or epithelium, erosion or ulcer, and granulomas and pyloric metaplasia.

Results: The overall Pearson correlation coefficient between histologic activity score and endoscopy grade was 0.73 (P < .001). Among individual histologic criteria, endoscopy grades correlated with neutrophils (R2 = 0.74, P < .001), presence of erosion or ulcer (R2 = 0.60, P = .004), epithelial damage (R2 = 0.76, P < .001), and crypt architecture changes (R2 = 0.61, P = .003). Agreement between endoscopy grades and histologic scores was significant for the presence of neutrophils, erosion or ulcer, and crypt architectural changes with κ values of 0.82, 0.58, and 0.75, respectively.

Conclusions: Application of a well-defined histologic scoring system for evaluation of Crohn disease activity in the neoterminal ileum of patients randomized to receive placebo or infliximab therapy correlated well with endoscopic activity grades. The single most significant histopathologic change correlating with endoscopic evaluation of Crohn disease activity was the presence or absence of neutrophils in biopsy specimens.

Primary Rectal Kaposi Sarcoma: Presentation of a Case in a 23-Year-Old Human Immunodeficiency Virus–Positive Male (Poster No. 15)

Renuka Kulkarni, MBBS (rkulkarni@mcg.edu); Ningli Cheng, MD; Scott Drury, MD; Michelle Reid-Nicholson, MBBS. Department of Pathology, Medical College of Georgia, Augusta.

A 23-year-old homosexual male with HIV and full-blown acquired immunodeficiency syndrome presented with rectal bleeding and constipation. He was diagnosed with HIV at 14, used illicit drugs, was noncompliant with antiretrovirals, and had steadily decreasing CD4 counts with quadrupling viral titers in the previous months. Rectal examination revealed a mass involving 80% of the rectal circumference. Rectal biopsy revealed CD31- and CD34-positive spindled cells, slitlike vascular channels, extravasated red blood cells, and hyaline globules, consistent with Kaposi sarcoma (KS). Because of the absence of concomitant skin lesions the tumor was classified as primary rectal KS. Abdominal and chest computerized tomography (CT) scan revealed a circumferential submucosal 15 × 12 × 12-cm rectal mass with extensive muscularis propria invasion. CT also showed a single 5-mm lung nodule and several subcentimeter liver nodules. The patient opted for local radiation. One month later he presented to the emergency room with acute dyspnea and chest pain. CT revealed multiple “too numerous to count” bilateral lung and liver lesions that had not been seen on the earlier CT scan. Chemotherapy was then initiated and the patient remains alive 2 months postdiagnosis. This case is notable because of the unusual primary location of KS in the rectum, the patient's extremely young age, and his extensive local and metastatic disease. The tumor's rapid progression was likely the result of the patient's long-standing, untreated HIV, high viral load, and the tumor's propulsion by human herpes virus type 8.

Medullary Carcinoma Also Occurs in the Ampulla of Vater: Report of a Case and Its Association With Microsatellite Instability (Poster No. 16)

Haitham Nasser, MD1 (haitham.nasser@stjohn.org); Paul Kowalski, MD1; N. Volkan Adsay, MD.21Department of Pathology, St John Hospital and Medical Center, Detroit, Michigan; and 2Department of Pathology, Emory University Hospital, Atlanta, Georgia.

Medullary carcinoma of the gastrointestinal tract is a distinct tumor type that has been shown to have strong association with microsatellite instability and, in some cases, with hereditary nonpolyposis colorectal carcinoma. We report a 22-year-old woman with family history of colon cancer who presented with a tumor arising in the ampullary region causing obstructive jaundice. Grossly, it appeared solid, homogenous, and tan fleshy. Histologically, it revealed a poorly differentiated carcinoma without any precursor lesions in the ampulla, duodenum, or pancreas. The tumor showed characteristic “medullary” morphology, displaying syncytial growth pattern, pushing-border–like infiltration, and prominent lymphoplasmacytic infiltrates. Tumor cells were positive only for pankeratin (AE1/AE3). Among microsatellite instability markers analyzed immunohistochemically, mlh1 and msh6 were retained, but there was a loss of msh2. Studies have shown that medullary carcinomas are different not only morphologically but also biologically and prognostically from the conventional adenocarcinomas of the respective sites. In fact, the experience in lower gastrointestinal tract has shown that microsatellite instability–related cancers including medullary carcinomas should receive a different chemotherapy protocol than ordinary carcinomas. The case presented here is, to our knowledge, the first pure medullary carcinoma to be reported in the ampulla. The young age of the patient and family history, combined with the morphology and loss of msh2, suggests that this tumor is most likely genetically driven. As more cases accumulate, it will be possible to determine whether the ampullary examples of this entity also have the same prognostic and therapeutic implications of their kindreds in the lower gastrointestinal tract.

Pseudopolyposis of the Stomach Presenting in a Bariatric Patient With Atrophic Gastritis (Poster No. 17)

James F. Shikle, MD1 (JFSHIKLE@yahoo.com); Bradley C. Bandera, MD.2 Departments of 1Pathology and 2Surgery, Eisenhower Army Medical Center, Fort Gordon, Georgia.

A 60-year-old woman with morbid obesity underwent a laparoscopic sleeve gastrectomy with removal of the gastric remnant and the specimen was submitted for pathologic examination. Gross examination revealed numerous (greater than 50) polypoid lesions measuring from 0.3 cm to 2.6 cm (Figure 3). Microscopic analysis of the nonpolypoid mucosa showed histologic features of atrophic gastritis with intestinal metaplasia. Histologically the polypoid lesions consisted of preserved oxyntic mucosa without evidence of atrophy consistent with pseudopolyps. No dysplasia was present in either the pseudopolyps or the background atrophic gastric mucosa. Pseudopolyposis is a rarely observed finding in patients with atrophic gastritis. The gross differential diagnosis is broad and includes fundic gland polyposis, hyperplastic polyps, and lymphoma among others. This unusual case of pseudopolyposis with lesions measuring up to 2.6 cm in the setting of morbid obesity in a surgical specimen highlights the need to sample the background gastric mucosa in these cases to demonstrate the underlying atrophic gastritis, which explains the etiology of the pseudopolyps.

Morphologic Assessment of Intestinal Metaplasia at the Gastroesophageal Junction and Association with Helicobacter pylori Status as Detected by Multiplex Polymerase Chain Reaction (Poster No. 18)

Benjamin L. Witt, MD1 (b-witt@northwestern.edu); Tat K. Tsang, MD2; Marc Scheer, MD3; Xiangwen Meng, MS4; William G. Watkin, MD.1 Departments of 1Pathology, 2Gastroenterology, and 3Medicine, Evanston Hospital, NorthShore University HealthSystem, Evanston, Illinois; and 4Department of Pathology, NorthShore University HealthSystem, Research Institute, Evanston, Illinois.

Context: Gastroesophageal reflux disease–associated Barrett esophagus (BE) and Helicobacter pylori–associated carditis with intestinal metaplasia (CIM) differ in their risk of malignancy and implications for patient management but are difficult to distinguish in biopsies of the gastroesophageal junction (GEJ). We used a polymerase chain reaction (PCR) assay for H pylori in a series of GEJ biopsies to establish the prevalence of H pylori in groups diagnosed as BE and CIM on the basis of established histologic criteria.

Design: Ninety patients with reflux-induced esophageal disease who underwent upper endoscopy and had GEJ biopsies were the study subjects. Biopsies with intestinal metaplasia (IM) were divided into BE and CIM using established histologic criteria. Helicobacter pylori status was determined by multiplex PCR performed on concomitant esophageal biopsies.

Results: Twenty-seven (30%) patients demonstrated IM at the GEJ. Of these, 13 of 27 (48%) were classified as BE (4 or more BE histologic features) and 14 of 27 (52%) as CIM (fewer than 4 BE histologic features). The incidence of H pylori infection determined by PCR is shown in the Table. The infection rate at the distal esophagus did not significantly differ among those with IM versus those without, or in relation to the number of BE features among those demonstrating IM.

Conclusions: As determined by PCR, there is a high prevalence of esophageal H pylori infection in patients with reflux-induced esophageal disease, irrespective of their histologic categorization. The role of PCR for H pylori in stratifying the risk of development of neoplasia in gastroesophageal reflux disease requires further study.

 
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The Role of JAK3/STAT3 Pathway in Colorectal Carcinogenesis and Colorectal Carcinoma Progression in Egyptian Patients: An Immunohistochemical Study (Poster No. 19)

Mohamed M. Shareef, MD, PhD1 (mm_shareef2000@hotmail.com); Maha M. Shamloula, MD, PhD1; Asem A. Elfert, MD, PhD2; Mohamed I. El-sawaf, MD, PhD3; Hanan H. Soliman, MD, PhD.2 Departments of 1Pathology, 2Tropical Medicine, and 3Surgery, Faculty of Medicine, Tanta University, Tanta, Egypt.

Context: The JAK3/STAT3 pathway is involved in the genesis of several cancers and proposed as a molecular target in such malignancies as colorectal carcinoma (CRC) in Western patients. The unique clinicopathologic and molecular characteristics of CRC in Egyptian patients has stimulated us to investigate the JAK3/STAT3 pathway in CRC and its precursors in Egyptian patients.

Design: Tissue sections from 10 samples of normal colonic mucosa, 10 colonic adenomas, 15 cases with ulcerative colitis, and 45 cases with primary CRC were evaluated immunohistochemically for JAK3 and STAT3 expression and their phosphorylated forms (p-JAK3 and p-STAT3).

Results: Frequency of p-JAK3 expression was positively correlated with degree of dysplasia in adenomas (P = .01). The frequency of p-STAT3 expression increased significantly with the degree of dysplasia in cases with ulcerative colitis (P = .003). The frequency of expression of all the JAK3/STAT3 pathway proteins was significantly higher in CRC than in precancerous lesions (P = .01, .03, .04, and .002 for JAK3, p-JAK3, STAT3, and p-STAT3, respectively). In CRC cases, p-STAT3 expression showed significant correlation with grading (P = .002) and nodal status (P = .04). The expression of JAK3, p-JAK3, and STAT3 in CRC showed positive correlation with the pathologic stage (P = .046, 003, and .046, respectively) (Table).

Conclusions: Increased expression of the components of JAK3/STAT3 pathway with increasing grades of dysplasia and malignant transformation points to their potential role in colorectal carcinogenesis. The significant correlation of the JAK3/STAT3 pathway components with anaplasia and invasion suggests a definitive role in progression of CRC, making this pathway a promising target for therapy in Egyptian patients.

 
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Histopathologic Characterization of 350 Consecutive Pancreatic Resections: The University of Miami/Jackson Memorial Hospital Experience (Poster No. 20)

Loren P. Herrera, MD1 (lherrera@med.miami.edu); Monica T. Garcia, MD2; Pablo A. Bejarano, MD.21Department of Pathology, Jackson Memorial Hospital, Miami, Florida; and 2Department of Pathology, University of Miami, Miami, Florida.

Context: Pancreatectomies are performed for many benign and malignant conditions. The histopathologic findings of pancreatic resections performed in a high-volume center are described.

Design: Slides from 350 pancreatectomy specimens (361 lesions) collected during a 4-year period were reviewed. Clinicopathologic findings were analyzed.

Results: Neoplastic conditions comprised most cases (91%) (Table). Pancreatic adenocarcinomas represented 66%, whereas ampullary were 29%. Moderate differentiation was seen in 56% of cases and poor differentiation in 33%. Stage pT3 was more prevalent (63%), followed by pT2 (23%). Lymphovascular invasion (LVI) was found in 68%, perineural invasion (PNI) in 60%, and lymph node metastasis in 52% of adenocarcinomas. The number of benign and malignant neuroendocrine tumors (NETs) was identical (20). Among the malignant NETs, 40% were low grade, 55% intermediate, and 5% high grade. Necrosis, LVI, PNI, and node metastasis were seen in 15%, 55%, 22%, and 80% of malignant NETs, respectively. Among intraductal papillary mucinous neoplasms, 35% were adenomas, 15% were borderline, and 50% harbored in situ or invasive carcinoma or were associated with ductal adenocarcinoma. Cystadenomas represented 64% of the mucinous cystic neoplasms, whereas 21% were borderline tumors, 14% noninvasive carcinomas, and 1% cystadenocarcinomas. Metastasis from kidney (40%), lung (20%), colon (20%), choriocarcinoma (10%), and melanoma (10%) were observed.

Conclusions: This is one of the largest single institution series of pancreatic resections. Carcinomas of the pancreatic head and ampulla of Vater were the most common neoplasms. These lesions often present at advanced stage, with aggressive histologic features as demonstrated by a high incidence of LVI, PNI, and regional node metastasis.

 
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A Unique Simultaneous Presence of Adenocarcinoma, Carcinoid Tumor, and Gastrointestinal Stromal Tumor in the Stomach (Poster No. 21)

Shouying Du, MD, PhD (sdu@ucsd.edu); Farnaz Hasteh, MD; Noel Weidner, MD; Ahmed Shabaik, MD. Department of Pathology, University of California, San Diego Medical Center, San Diego.

We report a unique synchronous presence of an adenocarcinoma, carcinoid tumor, and gastrointestinal stromal tumor in a near-total gastrectomy specimen from a 75-year-old woman with a long-standing history of pernicious anemia (Figure 4). A pedunculated polypoid mass (6.2 × 4.1 × 3.0 cm) was identified in the middle third of the gastric body with the stalk base attaching to the lesser curvature. Microscopic examination of the polyp revealed a moderately differentiated adenocarcinoma invading the lamina propria of the stalk. In the polyp stalk, a carcinoid tumor of 0.6 cm in greatest dimension was noted consisting of monotonous cells with granular cytoplasm and centrally located nuclei, which are strongly and diffusely positive for both chromogranin and synaptophysin, confirming their neuroendocrine origin. Approximately 11.2 cm away, in the subserosa of the greater curvature, one 0.8 × 0.8-cm firm nodule with a tan cut surface was incidentally identified consisting of spindle cells with high nuclear to cytoplasmic ratio, displaying a fascicular or storiform growth pattern, and with a diffuse and strong positive immunoreaction for CD117. It was negative for smooth muscle actin and desmin, consistent with gastrointestinal stromal tumor. The adenocarcinoma and carcinoid components in our case were entirely separated into adjacent but distinct areas, with no transition or intermixing between these 2 different tumors, indicating a collision pattern. To the best of our knowledge, this is the first case of such a triple entity occurring simultaneously in the stomach.

α-Methylacyl Coenzyme A Racemase Expression in Barrett Esophagus, Low- and High-Grade Dysplasia, and Carcinoma (Poster No. 22)

Anupama Gupta, MD; Woojin Yu, MD (wy2121@columbia.edu); Fabrizio Remotti, MD; Helen Remotti, MD. Department of Pathology, Columbia University, New York, New York.

Context: Surveillance biopsies in patients with Barrett esophagus (BE) are done for morphologic detection of preneoplastic/neoplastic lesions to determine future therapy. It is often a challenge to histologically distinguish reactive changes from preneoplastic/neoplastic changes in this location. Some authors have proposed the use of α-methylacyl coenzyme A racemase (AMACR) in such situations. This study was performed to evaluate utility of AMACR expression in detecting low-grade dysplasia (LGD), high-grade dysplasia (HGD), and carcinoma (CA) in patients with BE.

Design: Twenty-three esophageal resection and 5 endoscopic mucosal resection (EMR) specimens with histologically confirmed dysplasia and/ or CA in BE were obtained from the archival files of the Department of Pathology, Columbia University. Immunohistochemical staining for AMACR (Dako, rabbit anti-human P504S, Clone 13H4) was performed on all cases. The percentage of lesional cells staining with AMACR was noted and the intensity of staining was graded from 1+ (faint) to 4+ (strong). Less than 1% of lesional cells staining was considered negative. BE, LGD, HGD, and CA were evaluated and graded separately on each case.

Results: AMACR positivity was seen in 0% (0 of 19) of BE, 0% (0 of 6) of LGD, 20% (3 of 15) of HGD, and 32% (7 of 22) of CA. When positive, the percentage of immunoreactive lesional cells ranged from 1% to 40% in HGD and 5% to 80% in CA (Table).

Conclusions: AMACR staining when positive is helpful; however, negative staining does not rule out HGD or CA. Low sensitivity and variability in extent of staining limits the diagnostic utility of AMACR immunostaining for detection of preneoplastic/neoplastic lesions in BE, especially in small surveillance biopsies.

 
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Serrated Lesions of the Appendix: Morphologic and Immunohistochemical Appraisal (Poster No. 23)

Jonathan Rock, MD (Jonathan.Rock@osumc.edu); Andrew M. Bellizzi, MD; William L. Marsh, MD; Wendy L. Frankel, MD. Department of Pathology, The Ohio State University Medical Center, Columbus.

Context: There is increasing interest in serrated colorectal polyps. Less is known regarding morphologically similar appendiceal lesions. We performed a morphologic and immunohistochemical assessment, appropriating diagnostic terminology and immunohistochemical markers shown useful in differentiating serrated polyps of the colon.

Design: Fifty-three noninvasive epithelial appendiceal lesions were classified hyperplastic polyp (HP), sessile serrated adenoma (SSA), mucinous cystadenoma (MCA), MCA with serrated features (MCAS), or conventional adenoma (CAD). Cytokeratin (CK) 20, Ki-67, MUC6, and β-catenin staining was performed. CK20 was normal (Nl, surface staining), expanded (Ex, beyond surface), expanded/irregular (Ex/I, expanded with random expression in deep crypts), diffuse, or no pattern. Ki-67 was Nl (base), Ex (beyond base), Ex/I (expanded with asymmetry), or no pattern. MUC6 was positive or negative. β-Catenin was Nl (membranous) or abnormal (nuclear/decreased membranous).

Results: Diagnoses of HP (6), SSA (12), indeterminate (3), MCA (14), MCAS (16), and CAD (2) were rendered. All HPs showed Ex CK20 expression and Ex (3/6) or Nl (3/6) Ki-67 expression; MUC6 was positive in 1. Most SSAs and MCASs showed Ex or Ex/I CK20 expression, and Ex, Ex/I, or Nl Ki-67 expression. MUC6 was positive in all SSAs and 8 of 16 MCASs. Flat architecture of MCAs made CK20 and Ki-67 difficult to interpret; MUC6 was negative. CAD expressed CK20 and Ki-67 Ex/I and MUC6 negative; abnormal β-catenin was noted in one.

Conclusions: Serrated appendiceal lesions can be categorized using terminology from the colon. MUC6 is most associated with SSA morphology. Similar patterns of MUC6, CK20, and Ki-67 reactivity in SSA and MCAS suggest a link between these lesions.

A Rare Case of Gastric Leiomyosarcoma in a Young Hispanic Man (Poster No. 24)

Nisrin Motiwala, MD1 (nmotiwala@mcg.edu); Jeffrey Lee, MD3; Nidia Messias, MD1; Suash Sharma, MD1; Asha Nayak-Kapoor, MD.2 Departments of 1Pathology and 2Hematology, Medical College of Georgia, Augusta; and 3Department of Pathology, Charlie Norwood Veterans Affair Medical Center, Medical College of Georgia, Augusta.

Leiomyosarcomas of the stomach are vanishingly rare neoplasms. In fact according to the World Health Organization, classification of tumors as true gastric leiomyomas and leiomyosarcomas are so infrequent that there are no significant data on demographic, clinical, or gross features. In the few cases found in literature, patients presented at older age (median age, 60 years). Most of the tumors historically designated as leiomyosarcomas are now classified as gastrointestinal stromal tumor (GIST), hence the older literature on gastric leiomyosarcomas largely pertain to malignant GISTs. This is a case of a 26-year-old Hispanic man who initially presented with gastrointestinal bleeding. Gross examination revealed a circumscribed, exophytic proximal gastric mass measuring 7.0 cm in maximum dimension, located within the submucosa, and arising from the muscularis mucosa. Microscopic findings were that of a highly cellular pleomorphic tumor with eosinophilic cytoplasm and abundant mitoses (>20 per 10 high-power fields) with atypical mitotic figures. Immunohistochemistry was diffusely positive for desmin and smooth muscle actin and negative for CD117 and CD34. Molecular studies were negative for C-KIT and PDGFR-α mutations, thus confirming the diagnosis of leiomyosarcoma and not GIST, which is one of the most important differential diagnoses. GIST accounts for 2.2% of malignant gastric tumors in the SEER data. It is extremely important to differentiate leiomyosarcoma from GIST, as they require radically different courses of treatment. Most GISTs (80%) are responsive to the tyrosine kinase inhibitor imatinib, whereas leiomyosarcomas are treated with chemotherapy.

Clostridium difficile Colitis Presenting as Collagenous Colitis on Biopsy: Case Report and Review of Literature (Poster No. 25)

Saryn V. Stramecki Doucette, MD1 (sdoucette@rwmc.org); Alan Epstein, MD.2 Departments of 1Pathology and 2Gastroenterology, Roger Williams Medical Center, Providence, Rhode Island.

Rare reports describe the development of collagenous colitis after prolonged Clostridium difficile infection. We describe C difficile colitis presenting as collagenous colitis on initial biopsies. A 49-year-old man with a history of bipolar disorder and polysubstance abuse in remission presented with a 1-month history of acute-onset watery diarrhea. His medications included celecoxib, methadone, and quetiapine fumarate. Colonoscopy was suggestive of ulcerative colitis and showed pancolitis, scattered ulcerations, and a normal terminal ileum and rectum. Multiple biopsies throughout the colon and rectum showed increased subepithelial collagen deposition (trichrome verified), increased lamina propria chronic inflammation, and minimal neutrophilic infiltrates without crypt architectural abnormalities (Figure 5). Biopsy of the terminal ileum showed normal villous architecture and increased intraepithelial lymphocytes. Results of stool cultures, C difficile assay, and celiac serologies were negative. Treatment with metronidazole and 5-aminosalicylic acid mildly improved the diarrhea. However, because of continuing diarrhea 4 weeks later, colonoscopy was repeated and showed pancolitis with rectal involvement and ulcerations. Subsequent biopsies showed less collagen deposition and more active inflammation. A repeated C difficile toxin assay was positive and vancomycin was given with prompt resolution of diarrhea. Our case is an unusual histologic presentation of C difficile colitis. We wish to emphasize that a histologic diagnosis of collagenous colitis with endoscopically evident colitis should prompt rigorous workup for a cause. Expansion of the subepithelial collagen layer may be a protective/reactive response to enterotoxins produced by C difficile. Although the exact etiology of idiopathic collagenous colitis is unknown, luminal antigens/toxins are believed to be triggers.

Granulomatous Inflammation Presenting as an Ileocecal Mass With Involvement of the Bladder and Abdominal Wall (Poster No. 26)

Yuanming Zhang, MD1; Roberto Bergamaschi, MD, PhD2; Philip Kane, MD1; Meenakshi Singh, MD1 (meenakshi.singh@stonybrook.edu). 1Department of Pathology and 2Division of Colorectal Surgery, State University of New York at Stony Brook University Medical Center, Stony Brook.

A 34-year-old man presented with signs and symptoms of subacute intestinal obstruction. Radiology revealed a mass involving the ileocecum, bladder, and abdominal wall. There were no prior biopsies. The ileocecal resection specimen consisted of distorted adherent bowel with a 5.5 cm firm, tan-yellow mass that extended transmurally. Frozen and permanent sections revealed transmural granulomatous inflammation and marked fibrinopurulent infiltrate extending to margins. The bladder “mass” and pelvic/abdominal wall “mass” also showed granulomatous inflammation. No neoplasm or features of Crohn disease were identified. Special stains did not show acid-fast bacilli. The granulomatous inflammation had abundant foreign body–type giant cells, some of which contained polarizable foreign material, including vegetable matter. This is consistent with a phlegmon, secondary to long-standing bowel perforation. This case emphasizes that the history may not be particularly helpful in arriving at an accurate diagnosis and the etiology may not be evident at frozen section analysis. Cultures should be submitted to rule out an infectious agent. Crohn disease and tuberculosis are certainly more common causes of granulomatous inflammation of the bowel and tuberculosis may produce a mass effect. Gross and histologic examination with adequate sampling, negative cultures, and special stains for organisms can help exclude this diagnosis. A careful look at the giant cells and a polarized light examination can help identify the foreign body nature of the granulomatous inflammation. Food material in the wall of the bowel serves as “foreign matter.” An exuberant response to it can lead to a mass effect and may mimic a neoplasm.

Adenomyoma of the Jejunum: Report of an Unusual Case (Poster No. 27)

Xin Qing, MD, PhD (drqingx@yahoo.com); Samuel French, MD.  Department of Pathology, Harbor-UCLA Medical Center, Torrance, California.

Adenomyoma of the small intestine is an extremely rare benign nonneoplastic lesion. The rarity of this entity may be attributed to underreporting or nonrecognition by both surgeons and pathologists. Although it has been theorized that this lesion may represent incomplete heterotopic pancreas, its pathogenesis is not clearly understood. We describe an unusual case of adenomyoma in the jejunum with new pathologic and immunohistochemical features. The patient was a 61-year-old woman with cancer of the sigmoid colon and multiple liver cysts who underwent exploratory laparotomy and sigmoidectomy for cancer. At surgery, a polypoid lesion was incidentally found in the lower jejunum, which was resected. On histologic examination, the lesion was located in the submucosa and composed of an admixture of different types of glandular structures and surrounding smooth muscle. The large glands were lined by columnar/cuboidal epithelium with occasional goblet cells. The surrounding small glands were morphologically similar to, but immunohistochemically different from, Brunner glands. There were foci of connection between the epithelial component of the lesion and the overlying small intestine mucosal epithelium. No pancreatic tissue was identified. The immunohistochemical features are summarized in the Table. In conclusion, these novel findings suggest that adenomyoma of the small intestine is a form of intestinal epithelial hamartoma with altered differentiation, instead of incomplete heterotopic pancreas. Increased vigilance in watching for this entity and a better pathologic knowledge of it may result in an increase in its diagnosis and spare the patient unnecessary surgery.

 
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Mesenteric Fibromatosis Mimicking a Gastrointestinal Stromal Tumor: Case Report and Review of Literature (Poster No. 28)

Kilak Kesha, MD (kilak.kesha@danhosp.org); Ramapriya Vidhun, MD.  Department of Pathology, Danbury Hospital, Danbury, Connecticut.

The differentiation of mesenteric fibromatosis (MF) from a gastrointestinal stromal tumor (GIST) involves careful analysis of specific pathologic features. We report a case of MF initially diagnosed as a GIST. A 33-year-old man presented to the emergency department with a history of nausea and vomiting. Computerized tomography (CT) scan showed a partial small bowel obstruction. On resection, a diagnosis of GIST was made. Two years later the patient was diagnosed by CT scan with a mass in the mesentery. The patient underwent a second resection for a well-circumscribed, tan white, firm nodule measuring 2.5 cm in greatest dimension. Histologic sections showed fascicles of monotonous spindle and stellate cells. These cells had abundant eosinophilic cytoplasm and bland basophilic nuclear features. The cells were strongly positive for c-Kit and were negative for CD34, actin, desmin, and S100. These morphologic and immunohistochemical features are consistent with a MF. On retrospective review of the slides from the prior resection 2 years prior, it was noted that the morphologic and immunohistochemical features are similar and consistent with a fibromatosis. Historically, even though there is an overlap in their immunohistochemical profiles, these entities can be distinguished primarily by their light microscopic and ultrastructural features. Recent studies have shown that β-catenin can be used to distinguish between these entities (90% positive staining in fibromatoses; 0% in GIST) (Table). We recommend that multiple diagnostic features including CD34 and β-catenin expression be used in conjunction with c-Kit to accurately differentiate GIST from MF.

 
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Russell Body Gastritis: A Unique Association With Gastric MALToma and Gastric Ulcer (Poster No. 29)

Sreelakshmi Ravula, MD (sree_lrus@yahoo.com); Jacek Polski, MD.  Department of Pathology, University of South Alabama Medical Center, Mobile.

Russell body gastritis is a recently recognized lesion of the gastric mucosa associated with inflammatory conditions like Helicobacter pylori, human immunodeficiency virus, and fungal infections. We report a case of Russell body gastritis in an elderly patient. A 90-year-old male patient was admitted to our emergency department with bleeding gastric ulcer. Partial gastrectomy was performed. There was thickening of the stomach wall and a transmural gastric ulcer with granular border and slight palisading of the rugae at the edge. Microscopic analysis revealed gastric ulcer, extranodal marginal zone lymphoma (MALToma) with perigastric lymph node involvement, and chronic active and Russell body gastritis (Figure 6). No H pylori microorganisms were identified on Wright stain. Fungal yeast forms colonizing some glandular crypts were identified. Flow cytometry confirmed B-cell lymphoma, consistent with marginal zone lymphoma. The Russell bodies stained mostly for κ light chains. Our case represents a unique combination of gastric ulcer, gastric MALToma, and Russell body gastritis in the same patient not associated with H pylori infection. Only about less than 10 cases of Russell body gastritis were reported in the literature so far, none with associated MALToma. To our knowledge, this is the first case of Russell body gastritis associated with gastric MALToma and gastric ulcer.

Signet Ring Cell Change in Pseudomembranous Colitis: An Underrecognized Gastrointestinal Phenomenon? (Poster No. 30)

Paula A. Navarro, MD (pnavarro@tuftsmedicalcenter.org); Tee U. Lang, MD; Jennifer J. O'Brien, MD, PhD; Joseph Alroy, DVM; Maria L. Garcia-Moliner, MD. Department of Pathology, Tufts Medical Center, Boston, Massachusetts.

Context: Signet ring cells are characteristic of high-grade adenocarcinoma, particularly of the gastrointestinal tract. Signet ring cell change (SCC) has also been reported in benign gastrointestinal processes, such as pseudomembranous colitis (PMC), tubular adenomas, and inflammatory bowel disease. The purpose of our study is to determine the incidence of SCC in cases of PMC because this phenomenon can represent a diagnostic challenge to pathologists, especially in small biopsies.

Design: Archival hematoxylin-eosin–stained slides from 21 resected colonic specimens with the diagnosis of PMC accessioned at Tufts Medical Center between 1994 and 2008 were reviewed for the presence of SCC and their pattern of distribution in the colon.

Results: Of these 21 cases, 18 (86%) demonstrated SCC within the crypts and within overlying exudate. Interestingly, one case showed signet ring–like cells in the lamina propria. The remaining 3 cases show the classic histologic changes of PMC but no SCC.

Conclusions: Our study highlights that SCC is a common finding in colon specimens with PMC. These changes may be focal and, hence, go unrecognized. When more extensive or, as in one of our cases, when the crypts are disrupted with spillage of signet ring–like cells into the lamina propria, there may be diagnostic confusion with adenocarcinoma. The mechanism for the production of this change is unclear but may represent a degenerative change. Pathologists must become aware that SCC is a phenomenon present in a variety of nonneoplastic gastrointestinal processes. Overdiagnosis of this pathologic change as signet ring cell adenocarcinoma may have serious consequences.

Polarity Rather Than Count of Eosinophils Better Discriminates Between Eosinophilic and Reflux Esophagitis (Poster No. 31)

Dawn Bradly, MD (dawn_bradly@rush.edu); Ajay Patel, MD; Maria McIntire, MD; Deborah Giusto, MD; Shriram Jakate, MD. Department of Pathology, Rush University Medical Center, Chicago, Illinois.

Context: Eosinophilic esophagitis (EE) and gastroesophageal reflux disease (GERD) often have overlapping histologic features, particularly eosinophilia. Previous attempts to differentiate based on the quantity of intraepithelial eosinophils have shown conflicting results. We sought to demonstrate eosinophilic polarity as a better discriminator between EE and GERD.

Design: From March 2007 to July 2008, 50 patients (31 male, 19 female; age range, 1–80 years) diagnosed clinically, endoscopically, and histologically with EE and GERD were selected. Twenty patients had pure EE, 20 patients had pure GERD, 5 patients had primary EE with histologically overlapping GERD (EE-GERD), and 5 patients had primary GERD with histologically overlapping EE (GERD-EE). Hematoxylin-eosin preparations were evaluated. The epithelial polarity of distribution of eosinophils was noted nearest the surface (“top heavy”) or nearest the basal layer (“bottom heavy”). Additionally, the presence of discrete luminal eosinophilic colonies (DLECs) was assessed.

Results: There were 2 to 35 eosinophils per high-power field for all cases. Fifteen of 20 (75%) EE cases showed DLEC and top heavy eosinophilia. Eighteen of 20 (90%) GERD cases demonstrated bottom heavy eosinophils, and none showed DLEC. EE-GERD showed 2 of 5 (40%) top heavy cases, 3 of 5 (60%) cases were bottom heavy, and none showed DLEC. All GERD-EE cases demonstrated bottom heavy eosinophils.

Conclusions: DLEC is most encountered in EE. DLEC is missing in GERD, EE-GERD, and GERD-EE. Bottom heavy eosinophilia appears strongly supportive of GERD or GERD-EE. This polarity pattern recognition is a more practical, easily reproducible, and adaptable method of differentiation between these 2 closely related but separately treated entities.

Collagenous Sprue: Case Study and Review of Literature (Poster No. 32)

Xiangrong Zhao, MD, PhD (xzhao@bhs1.org); Rebecca Johnson, MD.  Department of Pathology and Laboratory Medicine, Berkshire Medical Center, Pittsfield, Massachusetts.

Collagenous sprue is a rare, severe malabsorptive disorder. There are only 49 cases reported to date in the English medical literature worldwide, including cases reported under different terms in early records, for example it was first described as idiopathic malabsorption in 1947. We report a case of collagenous sprue in a 69-year-old Caucasian woman who presented with severe watery diarrhea. She was seronegative for classic celiac disease. History, physical examination, and laboratory tests excluded other etiologies for diarrhea. Endoscopy revealed diffuse tiny white mucosal papillae, especially prominent in the distal jejunum. Biopsies showed severe small intestinal villous blunting with crypt atrophy, in contrast to the crypt hyperplasia seen in classic celiac disease. Characteristic for collagenous sprue, there were diffuse subepithelial collagen deposits (thicker than 12 μm) entrapping small capillaries and lamina propria cellular elements, as shown in hematoxylin-eosin (Figure 7) and trichrome (inset A) stains of biopsies from duodenum, jejunum, and ileum. There were aberrant intraepithelial and lamina propria CD3-positive (inset B), CD8-negative (inset C) T lymphocytes. Due to the rarity of collagenous sprue, its exact relationship with classic celiac disease and other refractory spruelike intestinal disorders remains controversial. Our report represents the 50th collagenous sprue case described to date, with relevant literature reviewed and the histologic phenotype characterized with special and immunochemical stains.

A Rare Case of Lipomatous Polyposis of the Colon (Poster No. 33)

Niloofar Nasseri-Nik, MD (niloofar_nik@yahoo.com); Dana L. Altenburger, MD; Raymond B. Franklin, MD, PhD. Department of Pathology, Orlando Health, Orlando, Florida.

Adipose tissue can be present in the colonic submucosa as nonspecific diffuse lipomatous infiltrate related to obesity, as multiple solitary lipomas, and as lipomatous polyposis. Although the first 2 are common, lipomatous polyposis is a rare condition first described in 1959 with only 3 well-documented cases reported in the English literature. We report a case of a 64-year-old male patient with no familial history of cancer who on endoscopy in 1998 was found to have hundreds of polyps throughout his colon, several of which were biopsied and found to be hyperplastic and adenomatous. The patient was then followed for 10 years during which he was diagnosed with large B-cell lymphoma and prostate cancer. The patient opted to have a subtotal colectomy in 2008 given his previous diagnosis of colonic adenomas. One hundred and twenty centimeters of his colon was removed and found to be diffusely involved by innumerable polyps ranging from 0.2 to 0.5 cm (Figure 8). A total of 50 polyps were microscopically examined, all of which were submucosal lipomas. No additional adenomatous polyps were identified. Our case is unique given the previous diagnoses of hyperplastic and adenomatous polyps.

Intestinal Necrosis Following Oral Administration of Sodium Polystyrene Sulfonate (Kayexalate) in Sorbitol: A Report of 5 Cases (Poster No. 34)

Bryan L. Janssen, MD (BLJanssen@tmhs.org); Hema Khurana, MD; Ashok Balsaver, MD. Department of Pathology, The Methodist Hospital, Houston, Texas.

Sodium polystyrene sulfonate (Kayexalate) in sorbitol, a cation exchange resin used to treat hyperkalemia in uremic patients, has been well implicated in cases of intestinal necrosis. The incidence of this complication, however, is not known and the literature for many years has represented this as something of a rare entity. We report here a series of 5 patients at our institution in whom, during a 1-year period, Kayexalate crystals were observed on either endoscopic biopsy (n = 1) or surgical resection specimens (n = 4) demonstrating intestinal necrosis. All of the patients had documented oral administration of Kayexalate on admission to the hospital and clinical history of renal insufficiency with 3 of the 5 patients receiving hemodialysis. Currently, the available literature reports only sporadic cases and the largest case study (n = 15) spans a 10-year period. We propose that Kayexalate-induced intestinal damage continues to be an underrecognized and underreported entity. The purpose of this study is to further highlight the clinical and pathologic features of Kayexalate-associated intestinal necrosis.

The Use of IgG4 to Distinguish Autoimmune Hepatitis From Hepatic Cholangiopathic Diseases (Poster No. 35)

Sherry M. Thompson, MD1 (smthompson78@hotmail.com); Pablo A. Bejarano, MD1; Monica T. Garcia, MD1; Chakradhar Reddy, MD.2 Departments of 1Pathology and 2Gastroenterology, University of Miami Hospital/Jackson Memorial Hospital, Miami, Florida.

Context: Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), and the so-called overlap syndrome (OS) share clinical and histologic characteristics, making them difficult to distinguish from each other. Immunoglobulin (Ig) G4–positive plasma cells detected by immunohistochemistry have been identified in patients with extrahepatic autoimmune disorders. However, the role of IgG4 in distinguishing various liver diseases has not been fully investigated.

Design: Eighty-one patients with needle biopsies showing features consistent with PBC, PSC, AIH, OS, or ductopenia were selected and stained for IgG4. Quantitation of IgG4-positive plasma cells and portal tracts (PTs), done blinded to the clinical diagnosis, and the ratio of IgG4:PTs, was obtained for each biopsy. Findings were then correlated to the patient's final clinical diagnosis.

Results: Portal triads with IgG4-positive plasma cells showed strong cytoplasmic staining. Of the 81 patients, 64 had the following clinical diagnoses: 24 AIH, 14 PBC, 10 OS, 3 PSC, 1 ductopenia of adulthood, 1 Alagille syndrome, and 11 non-AIH, noncholangiopathic (NANC) diagnoses. The mean ratio of IgG4-positive plasma cells to PTs was 1.80 for AIH, 0.22 for PBC, 0.19 for OS, 0.54 for PSC, and 0.39 for NANC. The P value of IgG4 separating AIH from PBC was .02, and was .02, .03, and .06 for OS, NANC, and PSC, respectively.

Conclusions: IgG4-positive cells are more predominant in AIH compared with other hepatic diseases with cholangiopathic features. Staining plasma cells with IgG4 may elucidate disease processes among various hepatic entities. Although the numbers of PSC cases were few, PSC may also be driven by an association with IgG4.

Histoplasma capsulatum Granulomatous Hepatitis: Clinicopathologic Analysis of 6 Cases (Poster No. 36)

Kirtee Raparia, MD (kirteeraparia@gmail.com); Mary R. Schwartz, MD; Alberto G. Ayala, MD; Steven S. Shen, MD; Jae Y. Ro, MD. Department of Pathology, The Methodist Hospital, Houston, Texas.

Context: The increased rate of Histoplasma capsulatum infection is an emerging issue among immunocompromised individuals. The differential diagnosis of granulomatous inflammation in the liver is important for the accurate identification of the etiology and appropriate treatment.

Design: We report 6 cases of H capsulatum granulomatous hepatitis seen at our institution from 1999 to 2008, three of them in 2008. Gomori methenamine silver (GMS) and acid-fast bacilli stains were performed in all cases.

Results: There were 4 women and 2 men ranging from 42 to 73 years. All patients had underlying diseases: 2 patients had rheumatoid arthritis, 1 had systemic lupus erythematosus, 1 patient was infected with human immunodeficiency virus, and 2 patients had received neoadjuvant chemotherapy for colon/rectal carcinoma. Two patients with rheumatoid arthritis were on Remicade medication. A urine histoplasma antigen test was performed in 3 of the 6 cases and all showed moderate elevation (4.73–5.58 ng/mL). A liver biopsy showed multiple noncaseating granulomata mainly in the lobular parenchyma in 4 of 6 cases. Hyalinized and calcified granulomata were present in the remaining 2 cases. The organisms were generally few in number and were both intracellular and extracellular. The organisms were highlighted by the GMS stain but were generally not well visualized with periodic acid–Schiff with diastase stain.

Conclusions: Infection by H capsulatum should be considered in the differential diagnosis of granulomatous hepatitis in immunocompromised patients. Urine Histoplasma antigen assay, liver tissue culture, and identification of the fungal organisms by GMS stain can be critical in identifying this infection.

IMP3, S100P, and XIAP Are Valuable Biomarkers in the Distinction Between Chronic Pancreatitis and Pancreatic Ductal Adenocarcinoma (Poster No. 37)

Ognjen Kosarac, MD1 (okosarac@tmhs.org); Qihui Zhai, MD2; Hidehiro Takei, MD2; Dina R. Mody, MD2; Mary R. Schwartz, MD2; Philip T. Cagle, MD.21Department of Pathology, The Methodist Hospital, Houston, Texas; and 2Department of Pathology, The Methodist Hospital and Weill Cornell Medical College, Houston, Texas.

Context: The differential of pancreatic ductal adenocarcinoma (PDA) versus chronic pancreatitis is a challenge in daily practice with significant therapeutic implications. The aim of our study was to evaluate a panel of biomarkers in this setting.

Design: Following a search of our database for PDA from 2003 to 2008, 14 pancreatic resections of PDA were selected with paired chronic pancreatitis from 10 men and 4 women with mean age of 66.2 years (range, 48–82 years). Immunostains for IMP3, S100P, and XIAP were performed on formalin-fixed, paraffin-embedded sections. Staining intensity (0, no staining; 1+, weak; 2+, moderate; 3+, strong) and proportion of positive cells (<10%, negative; 1+, 10%–25%; 2+, 25%–75%; 3+, >75%) were assessed. Positive stains were defined as >10% cells with at least 1+ intensity.

Results: The sensitivity of S100P, IMP3, and XIAP immunoreactivity for a diagnosis of PDA was 100.0%, 85.7%, and 100.0%, respectively. All 3 immunostains were negative in all tested nonneoplastic pancreatic tissue (Table). Eleven of 14 (78%) PDAs had positive staining for all 3 biomarkers. Additionally, S100P (85%) and IMP3 (75%) showed more consistent moderate to strong staining than XIAP in most cases.

 
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Conclusions: These novel biomarkers have high sensitivity and specificity in the diagnosis of PDA, especially when used as a panel. We recommend using at least 2 of these biomarkers in difficult cases of well-differentiated PDA versus chronic pancreatitis. Studies of additional cases are needed to confirm the sensitivity and specificity of these antibodies for this differential diagnosis.

Spectrum of Hepatic Dysgenesis and Associated Disorders in Explanted Polycystic Liver Disease (Poster No. 38)

Marlene Gallegos, MD (marlene_gallegos@rush.edu); Shriram M. Jakate, MD. Department of Pathology, Rush University Medical Center, Chicago, Illinois.

Context: Polycystic liver disease (PCLD) belongs to a family of hepatic ductal plate malformations, with variable presence of other components of biliary dysgenesis and cysts in other organs. PCLD may be associated with intracranial aneurysms and inguinal hernias, and its complications include infected liver cysts and cholangiocarcinoma. Our study addresses the spectrum of dysgenesis and associated conditions in 4 PCLD patients.

Design: We searched our databases for PCLD and found 3 cases in 1200 OLTs between the years 1996 to 2008 (<0.3%) and 1 autopsy case. The patients’ clinical data, imaging studies, and pathology findings were reviewed. A search was performed for cysts in other organs, associated clinical features, spectrum of biliary dysgenesis, and complications of PCLD.

Results: All 4 patients were women (34–61 years; mean, 48.5 years) and had hepatic PCLD and renal cysts. One third of the patients with OLT had concomitant renal transplant, while 1 of 4 had inguinal hernia. All 4 patients had enlarged livers (average, 2800 g) with diffuse cysts and admixed von Meyenberg complexes (VMCs). Three cases had infected cysts and the autopsy case had cholangiocarcinoma with VMCs, partial congenital hepatic fibrosis, extensive biliary dysplasia, and widespread metastasis.

Conclusions: PCLD is quite rare and is seen predominantly in middle-aged women. There is a strong concomitance of renal cysts, but cysts in other organs and other associated conditions are uncommon. PCLD is always admixed with VMCs and sometimes with congenital hepatic fibrosis. Explanted native livers frequently show infected cysts and when cholangiocarcinoma occurs, it tends to be multifocal with extensive biliary dysplasia and poor prognosis.

Colorectal Mucinous Adenocarcinoma: A Clinicopathologic Study of 74 Cases (Poster No. 39)

Xiaoxian Li, MD PhD (xli@tmhs.org); Jae Y. Ro, MD PhD; Mary R. Schwartz, MD; Steven S. Shen, MD, PhD. Department of Pathology, The Methodist Hospital, Houston, Texas.

Context: Mucinous adenocarcinoma is defined as adenocarcinoma with significant extracellular mucin. Some studies have suggested that colorectal mucinous adenocarcinoma has unique clinical presentations and is associated with more advanced stage and worse prognosis. However, these results have not been corroborated by others. In this study, we present our experience with 74 colorectal mucinous adenocarcinomas.

Design: Slides and reports of 521 invasive colorectal adenocarcinomas were reviewed. Only cases of conventional and mucinous adenocarcinomas (≥50% extracellular mucin) were included. Carcinomas associated with inflammatory bowel disease or familial polyposis syndromes were excluded. Multiple clinicopathologic factors were studied to compare mucinous adenocarcinoma with conventional adenocarcinoma.

Results: Seventy-four of the 521 cases were identified as mucinous adenocarcinoma. The average tumor size of mucinous adenocarcinoma was slightly larger than that of conventional adenocarcinoma (4.9 vs 3.8 cm, P < .001). Mucinous adenocarcinoma tended to present at more locally advanced stage (81.1% vs 61.5%, P = .001) and was more likely to be associated with adenomatous change than conventional adenocarcinoma (45.9% vs 22.8%, P < .001). In addition, mucinous adenocarcinoma was more likely to be located in the right colon (48.6% vs 31.8%, P < .001). No significant difference was found in age, total number of lymph nodes recovered, incidence of positive lymph nodes, or grade distribution between mucinous and conventional adenocarcinoma.

Conclusions: Compared with conventional adenocarcinoma, mucinous adenocarcinoma tends to be in the right colon, present with larger tumor size and more advanced stage, and is more commonly associated with adenomatous changes. Our results suggest that mucinous adenocarcinoma has distinctive clinicopathologic features and may warrant special attention.

Duodenal Inflammatory Pseudotumor: An Additional Extrapancreatic Manifestation of Autoimmune Pancreatitis (Poster No. 40)

Jane I. Bernstein, BA (janeila@mail.med.upenn.edu); Rachel H. Gormley, BS; Emma E. Furth, MD. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia.

Autoimmune pancreatitis may present as a localized sclerosing process; however, it is now recognized that this inflammatory process is part of a wider, systemic IgG4-associated sclerosing disorder. We report the first case of a duodenal inflammatory pseudotumor with concomitant autoimmune pancreatitis, in which the duodenal polyp exhibits a similar lymphoplasmacytic sclerosing process with infiltration of IgG4-positive plasma cells as seen in the pancreas. A 71-year-old man presented to his clinician with a 30-lb weight loss during the preceding 6 months. A computed tomography scan of the abdomen revealed a 5.7-cm mass in the head of the pancreas. Because of the clinical suspicion of pancreatic carcinoma, the patient underwent a pancreaticoduodenectomy. Intraoperative gross examination revealed a diffusely firm, white pancreas and multiple white nodules studding the liver. Histologic evaluation of the pancreas revealed a dense lymphoplasmacytic infiltrate centered on the ducts and vessels. Biopsy of the hepatic nodules showed a similar process with a sclerosing cholangitic pattern. Examination of the resection specimen revealed a previously unsuspected duodenal polyp located approximately 5 cm distal to the ampulla (Figure 9). Microscopic examination of this lesion revealed a histologic pattern similar to that seen in both the liver and pancreas. Immunohistochemically, IgG4-positive plasma cells were identified infiltrating the duodenal lesion. This case adds to the broadening collection of extrapancreatic lesions associated with autoimmune pancreatitis. It also raises this entity as a potential consideration in the differential diagnosis of a small bowel polyp.

The Demographics and Clinical Course of Carcinoid Tumors and Small Cell Carcinomas of the Gallbladder and Extrahepatic Bile Ducts (Poster No. 41)

Jorge Albores-Saavedra, MD1 (alboresjorge@yahoo.com); Arnold M. Schwartz, MD, PhD2; Kristen Batich, BA3; Nadera Ahmadzai, MBBS, MPH4; Donald E. Henson, MD.31Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico; 2Department of Pathology, George Washington University Medical Center, Washington, DC; 3Department of Cancer Prevention and Control, George Washington University Cancer Institute, Washington, DC; and 4Department of Epidemiology and Biostatistics, The George Washington University School of Public Health and Health Services, Washington, DC.

Context: Neuroendocrine tumors of the gallbladder (GB) and extrahepatic bile ducts (EHBD) include carcinoid tumors (CTs) and small cell carcinomas (SCCs). They are uncommon and little is known about their demographics and clinical course.

Design: Using data from National Cancer Institute's SEER Program (1973–2005), demographics and 10-year survival rates of patients with CTs and SCCs of the GB and EHBD were analyzed. Logarithmic transformation plots of age-adjusted incidence were analyzed.

Results: Among GB cancers, 119 cases (0.85%) were CTs and 54 (0.39%) were SCCs. Within EHBD, 31 cases (0.34%) were CTs and 17 (0.19%) were SCCs. The female to male ratios of CTs in the GB and EHBD were 2.7 and 1.6, respectively. The ratios for SCC in the GB and EHBD were 2.2 and 1.1, respectively. In the GB the mean age of diagnosis for CT and SCC were 64.5 and 67.5 years, respectively. In the EHBD the mean ages for CT and SCC were 58.2 and 68.4 years, respectively. The 10-year relative survival rate of CTs of the GB and EHBD were respectively 36% and 79%. For SCC, there were no survivors in either site at 10 years. Transformation plots identified CT and SCC as separate carcinogenic pathways.

Conclusions: CT and SCC of the extrahepatic biliary tree are more common in women, more frequent in the GB, and show differences in biologic behavior. Therefore, these tumors should be separately classified and not designated with the single generic term “neuroendocrine carcinoma” without further specification. CTs and SCCs, though possibly similar in histogenetic origin, have distinct carcinogenic pathways.

Persistent Gastrocutaneous Fistulas: A Histopathologic Analysis of Antral and Oxyntic Mucosa Containing Fistulas in the Pediatric Population (Poster No. 42)

Michael A. Gilger, MD1 (gilger@bcm.edu); Todd M. Leleux, MD1; Edwina J. Popek, DO.1,21Department of Pathology, Baylor College of Medicine, Houston, Texas; and 2Department of Pathology, Texas Children's Hospital, Houston, Texas.

Context: Percutaneous endoscopic gastrostomy (PEG) is the preferred method of tube feeding gastrostomy in pediatric patients. PEG placement typically occurs above the incisura angularis, along the greater curvature, corresponding to the region of oxyntic gland mucosa. It has been reported that up to 24% of cases develop a persistent gastrocutaneous fistula (GF) following PEG removal. Previous research links the duration of tube placement, fibrosis of tract, and obesity as significant factors involved in GF formation. Published data are lacking regarding the type of gastric mucosa found in this population.

Design: Archived hematoxylin-eosin–stained slides limited to GF cases following PEG placement from the past 5 years at a single large pediatric institution were retrieved for review. Two pathologists, blinded to the mucosa type, reviewed the slides. Mucosa type was placed into one of 3 categories: oxyntic mucosa only, antral mucosa only, or both types.

Results: A total of 161 cases were reviewed. Eighty-two cases (51%) showed only antral mucosa, 35 cases (22%) showed only oxyntic mucosa, and 43 cases (27%) showed features of both. Statistical analysis between groups revealed the P value for the source of variation between these groups to be P < .001.

Conclusions: A statistically significant difference was detected when comparing GF mucosa types among pediatric patients at our institution. Although the oxyntic mucosa region of the stomach is the typical target for PEG tube insertion, GF with antral gland mucosa was the predominant finding in our study. This finding raises questions regarding the pathophysiology of antral mucosa in GF formation.

A Case of Esophageal Lymphangioma Clinically Suspicious for a Gastrointestinal Stromal Tumor (Poster No. 43)

C. A. Arnold, MD1 (carnold77@gmail.com); S. W. Carmack, MD1; A. A. Siddiqui, MD2; D. R. Nussenzveig, MD, PhD.31Department of Pathology, University of Texas Southwestern Medical Center, Dallas; and Departments of 2Internal Medicine-Division of Digestive and Liver Diseases and 3Pathology, Veterans Affairs Hospital, Dallas, Texas.

We present the case of a 62-year-old Hispanic man with a long-standing history of dysphasia who was found to have a 1.0-cm esophageal ulcer and a large hiatal hernia on endoscopic examination. Six months later a routine follow-up endoscopic exam revealed resolution of the previous ulcerative esophagitis; however, a new 1.5-cm submucosal mass on the posterior wall of the distal esophagus was identified, which was suspicious for a gastrointestinal stromal tumor. Endoscopic ultrasound evaluation showed the mass to have a heterogenous, cystic, multiseptated, well-circumscribed appearance. Fine-needle aspiration was inconclusive and suggested the possibility of a mucosal lymphoid aggregate. Owing to the clinical suspicion of a malignancy, the nodule was removed by banding with endoscopic mucosal resection. The tumor histologically consisted of variably sized cystic spaces filled with lymph and lined by flat endothelial cells with occasional intramural reactive lymphoid follicles. Further, the endothelial cells were positive for D2-40 staining, a marker specific for lymphatic endothelial cells. Taken together, the diagnosis of lymphangioma was rendered. Lymphangiomas most commonly occur in the head and neck and are exceedingly rare lesions of the esophagus with only 14 cases reported. We report the previous case to draw attention to this rare lesion whose clinical appearance can mimic that of a malignant process and to describe its endoscopic appearance.

Mucosal Hyperplasia of the Appendix: A Retrospective Review of 33 Cases (Poster No. 44)

Robert Willim, BS (robert.willim@hsc.stonybrook.edu); Sui Y. Zee, MD.  Department of Pathology, Stony Brook University Hospital, Stony Brook, New York.

Context: The term “mucosal hyperplasia” (MH) of the appendix has been used to describe nondysplastic serrated hyperplastic lesions of the mucosa. Recent attempts were made to reclassify some of these lesions as sessile serrated adenoma (SSA). This entity is similar to its colonic counterpart. An association between MH and colorectal carcinoma has been reported. We evaluated cases with a diagnosis of MH to determine its incidence in our patient population, to see if this association exists in our cohort, and to better classify the epithelial proliferations.

Design: We identified 33 appendices diagnosed with MH. Each appendiceal epithelial proliferation (AEP) was categorized as reactive hyperplasia (RH), hyperplastic polyp (HP), SSA, serrated adenoma (SA), or mixed lesion (ML).

Results: Of the 33 cases, 16 were reclassified SSA, 10 as HP, 4 as ML, 2 as RH, and 1 as SA. Four patients (3 HP and 1 SSA) had colorectal carcinoma (12%). Fifteen patients (8 SSA, 3 HP, 3 ML, and 1 RH) had gynecologic neoplasms (46%). Eleven patients (5 SSA, 3 HP, 1 RH, 1 ML, and 1 SA) presented with acute appendicitis (33%). Three patients (2 SSA and 1 HP) had other pathologies (9%) (Table).

Conclusions: Many of the AEPs were reclassified as SSAs. In our study, a lower percentage of patients had AEP with concurrent or past history of colon carcinoma. In addition, we identified an unexpectedly large number of patients with AEP and concurrent gynecologic neoplasia. Further studies are needed to determine the significance of this finding.

 
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Appendiceal Mucinous Neoplasms: The Mayo Clinic Experience (Poster No. 45)

David A. Barrett, MD (barrett.david@mayo.edu); Tsung-Teh Wu, MD, PhD; Thomas Smyrk, MD. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Context: There has been a debate in the literature as to the terminology applied to appendiceal neoplasms. This is especially true when peritoneal mucin is discovered. Various terms have been used to describe these neoplasms including low-grade appendiceal mucinous neoplasm (LAMN), mucinous neoplasm of low malignant potential, disseminated peritoneal adenomucinosis, peritoneal mucinous carcinomatosis, and mucinous adenocarcinoma. In this study we looked at 52 patients with mucinous appendiceal neoplasms (not including typical mucinous cystadenomas) to determine the correlation between histologic features and clinical outcomes.

Design: The slides were then reviewed by 2 pathologists and divided into 5 groups: group 1, low-grade morphology with mucin/epithelium confined to periappendiceal tissue; group 2, high-grade morphology with mucin/epithelium confined to periappendiceal tissue; group 3, low-grade morphology with intraabdominal mucin (no epithelium); group 4, low-grade morphology with intraabdominal mucin and mucinous epithelium; and group 5, high-grade morphology with intraabdominal mucin and mucinous epithelium. These patients had a follow-up period ranging from 6 to 151 months (mean, 43.2 months).

Results: The outcomes by group are shown in the Table.

Conclusions: When there is mucin plus epithelium in the abdominal cavity, there is significant potential for recurrence and an ultimately fatal course. Intraabdominal mucin without epithelium appears to have an intermediate prognosis. Although the numbers in this study are small, mucin and low-grade epithelium confined to the periappendiceal area had a uniformly benign outcome.

 
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Choledochal Cyst With Associated Signet Ring Cell Carcinoma of the Ampulla (Poster No. 46)

Timothy R. Pal, MD1 (tpal@notes.cc.sunysb.edu); Kevin Watkins, MD2; Sui Y. Zee, MD.1 Departments of 1Pathology and 2Surgery, Stony Brook University Medical Center, Stony Brook, New York.

A choledochal cyst is a dilatation of the biliary system with a well-established increased risk of carcinoma. Although many of the neoplasms arise within the cyst wall, some have been described in the gallbladder, the pancreas, and nondilated portions of the biliary system. We report the first case of a type I choledochal cyst with a concurrent ampullary signet ring cell carcinoma. A 48-year-old woman presented with right upper quadrant abdominal pain, elevated liver enzymes, and jaundice. Computed tomography and magnetic resonance imaging revealed a type 1 choledochal cyst. The patient underwent excision of the choledochal cyst. The gallbladder was received with an attached cystic duct and an 8-cm choledochal cyst. Following the excision of the cyst, palpation of the duodenum revealed a 1.5-cm mass in the ampulla of Vater. The ampullary mass was excised and on frozen section showed signet ring cell carcinoma. A subsequent pancreaticoduodenectomy was performed. Histologic examination of the cyst showed mucosal ulceration, marked acute and chronic inflammation, and fibrosis. The ampulla was infiltrated by signet ring cell carcinoma involving the duodenal wall (Figure 10). Lymphovascular invasion was present, but the lymph nodes were uninvolved. To our knowledge, this is the first case of ampullary signet ring cell carcinoma seen in conjunction with a type I choledochal cyst.

Signet Ring Cell Change of the Gallbladder: Case Report and Review of the Literature (Poster No. 47)

Amanda C. Mullins, MD1 (amullin3@utmem.edu); Thomas R. Callihan, MD.21Department of Pathology, University of Tennessee-Memphis; and 2Department of Pathology, Trumbull Laboratories, LLC, Germantown, Tennessee.

The presence of signet ring cells in gastrointestinal specimens typically indicates malignancy. Rarely, however, they can be found in benign specimens as a degenerative feature. We present the case of a 65-year-old woman who presented with symptoms of cholecystitis. A cholecystectomy was performed and the gallbladder submitted to pathology. Gross examination showed numerous gallstones. Microscopic examination of hematoxylin-eosin slides revealed acute, subacute, and chronic cholecystitis. Scattered throughout from the cystic duct margin to the fundus were multiple aggregates of signet ring cells on the mucosal surface and within gland lumens. Mitotic activity was not noted and nuclei were bland. The signet ring cells were positive for mucin, for cytokeratin (CK) 7, for E-cadherin, and variably for CK20. They were predominantly negative for carcinoembryonic antigen and for Ki-67. These features are consistent with benign signet ring cell change. Awareness of this rare degenerative finding can prevent mistaken diagnoses of signet ring cell carcinoma.

Is the Diagnosis of Flat Low-Grade Dysplasia on Surveillance Biopsy for Inflammatory Bowel Disease an Indication for Colectomy?: The Hartford Hospital Experience (Poster No. 48)

Christopher J. Nero, MD (cjnero@gmail.com); Saverio Ligato, MD. Department of Pathology & Laboratory Medicine, Hartford Hospital, Hartford, Connecticut.

Context: In patients with chronic inflammatory bowel disease (IBD) the presence of flat high-grade dysplasia (fHGD) is a major risk factor for the development of adenocarcinoma and is an indication for colectomy. However, there is controversy regarding the appropriate management of patients with flat low-grade dysplasia (fLGD). The goal of our study is to assess whether the discovery of fLGD during surveillance colonoscopy for IBD may represent an indication for colectomy.

Design: We reviewed 175 colectomies performed for IBD at Hartford Hospital (1998–2009). All patients had at least one surveillance colonoscopy within a year prior to colectomy. All diagnoses of dysplasia were independently reviewed by the authors.

Results: Dysplasia was identified in 8 (6 fLGD and 2 fHGD) of 138 (5.8%) colectomies performed for IBD without a prior diagnosis of dysplasia. fHGD was identified in 2 of 7 (29%) colectomies with a prior diagnosis (within 4.5 months after surveillance biopsy) of fLGD. Invasive carcinoma was found in 6 of 13 (46%) colectomies with a prior diagnosis of fHGD.

Conclusions: In our IBD population, the failure rate of surveillance colonoscopy and biopsy to identify dysplasia was 5.8%. We confirmed that fHGD is associated with a high rate (46%) of adenocarcinoma. The finding of fLGD is associated with a significant risk (29%) of concurrent advanced dysplasia and in our opinion justifies serious consideration for a colectomy in these patients.

Preexisting Villous Adenoma in Colorectal Adenocarcinoma Predicts the Status of KRAS Mutation in Targeted Therapy (Poster No. 49)

Hui Chen, MD, PhD (hui.chen@hitchcock.org); Joel A. Lefferts, PhD; Gregory J. Tsongalis, PhD; Arief A. Suriawinata, MD. Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.

Context: Cetuximab is an epidermal growth factor receptor inhibitor effective in treating advanced colorectal adenocarcinoma (CA); however, patients with downstream mutations, such as KRAS mutants at codon 12 or 13, respond poorly to cetuximab. Although KRAS mutations had been previously reported to associate with isolated villous adenoma (16%– 40%), the correlation of KRAS mutation with a histologic subset of CA is still lacking.

Design: Recent surgical resection specimens of CA (n = 27) were collected. The histopathologic features of these CAs were thoroughly reviewed, including tumor types, differentiation, and the presence of persistent preexisting adenomatous polyp. DNA was extracted from formalin-fixed paraffin-embedded sections. These DNA samples were amplified by polymerase chain reaction, using a pair of primers flanking the first coding exon of the KRAS, sequenced using the CEQ 8000 platform (Beckman Coulter), and analyzed for mutations in codons 12 and 13.

Results:KRAS mutation was found in 4 cases (15%) and was undetectable in the remaining 23 cases (85%). The mutations (G12D, G12V, G12C, and G13D) were consistent with previously identified mutations that predict poor response to cetuximab treatment. Interestingly, all 4 cases with KRAS mutation had gross and histologic features of CA with a persistent preexisting adenomatous polyp with villous architecture (4 of 4; 100%). None of the cases without KRAS mutation showed this feature. Furthermore, other histologic features are not associated with KRAS mutation.

Conclusions:KRAS mutations have a strong association with CA with persistent preexisting villous adenoma. Patients with a large villous adenoma that progresses to invasive adenocarcinoma may not respond to cetuximab.

An Unusual Coexistence and Impending Collision of a Malignant Gastrointestinal Stromal Tumor and Ovarian Cystadenocarcinomas (Poster No. 50)

Roy E. Lee, MD (rlee@tuftsmedicalcenter.org); Rolf Pfannl, MD. Department of Pathology, Tufts Medical Center, Boston, Massachusetts.

Malignant gastrointestinal stromal tumors (GISTs) are infrequent neoplasms that are usually solitary and are rarely associated with other malignant neoplasms. We present a case of coexisting malignant GIST of the colon and bilateral ovarian cystadenocarcinomas. A 59-year-old woman was admitted for deep venous thrombosis, pulmonary embolism, upper gastrointestinal bleed, renal failure, and a large abdominal mass. Exploratory laparotomy revealed a large intraperitoneal mass wrapping around a segment of colon and bilateral ovarian masses. The ovarian tumors were cystadenocarcinomas with serous and endometrioid differentiation. There were multiple invasive metastatic tumor nodules in the pericolic fat that were composed of pure adenocarcinoma. The colon and peritoneum had multiple, necrotic, friable tumor nodules with transmural tumor extension into colonic mucosa. These tumors were composed of spindle cells with varying degree of nuclear pleomorphism, large areas of necrosis, and more than 50 mitoses per 50 high-power fields. Additionally, some of these spindle cell tumors were admixed with areas of metastatic ovarian cystadenocarcinoma. The spindle cell tumors stained positive for c-Kit, smooth muscle actin (SMA), desmin, and myoglobin and were negative for cytokeratin (CK) 20, CD34, S100, estrogen receptor, and progesterone receptor. These findings were consistent with the diagnosis of malignant GIST. Both the ovarian cystadenocarcinomas and the glands admixed with the GIST were positive for pancytokeratin, CK7, CAM 5.2, and progesterone receptor, and negative for desmin, c-Kit, SMA, and CK20. Neither carcinosarcoma nor sarcomatous differentiation was identified in the ovarian tumors. This case represents an unusual coexistence and impending collision of a malignant colonic GIST and ovarian cystadenocarcinomas.

Retroperitoneal Margin Involvement in Whipple Procedure Correlates with Tumor Characteristics (Poster No. 51)

Hayma Al-Ghawi, MD1; Oluyomi Asojo, MD1 (asojooa@ucmail.uc.edu); Ninad Patil, MD1; Laura James, MS2; Syed Ahmad, MD3 Departments of 1Pathology and Laboratory Medicine, 2Surgery, and 3Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, Ohio.

Context: Pancreatic cancer is a malignant tumor with extremely poor prognosis. The status of the retroperitoneal resection margin (RPM) in Whipple procedure is an independent prognostic factor in predicting survival. We attempt to evaluate if certain tumor characteristics are associated with positive RPM.

Design: Seventy cases of Whipple procedure performed to treat pancreatic ductal adenocarcinoma were retrospectively studied to assess the relation between the status of RPM and certain tumor characteristics. These include site, size, histologic grade, lymph nodes metastasis, vascular and perineural microscopic involvement, and extrahepatic extension.

Results: The pancreatic head was the primary site of tumor in 93% of cases. The RPM was microscopically involved by tumor in 14 cases and the superior mesenteric artery was grossly and microscopically involved in only one case. Positive RPM was significantly associated with tumor size (t = −2.27, P = .02). The mean size was 3.67 cm in the positive RPM group and 2.84 cm in the negative group. Microscopic vascular involvement correlated with positive RPM (χ2 = 5.03, P = .02) with 71.4% in the positive RPM group versus 33.9% in the negative group. Histologic grade, perineural involvement, lymph nodes metastasis, and extrapancreatic extension did not correlate with positive RPM (P values .19, .47, .66, and .20, respectively).

Conclusions: The retroperitoneal margin in Whipple procedure tends to be involved by tumor in cases of larger tumor size and intratumoral vascular involvement.

Enteritis Cystica Profunda Mimicking Invasive Adenocarcinoma in an Adolescent Patient with Peutz-Jeghers Syndrome (Poster No. 52)

Susan L. Haley, MD1 (slhaley@utmb.edu); Mary R. Schwartz, MD2; Garth P. Davis, MD3; Qihui “Jim” Zhai, MD.41Department of Pathology, The University of Texas Medical Branch, Galveston; 2Department of Pathology, The Methodist Hospital/Baylor College of Medicine, Houston, Texas; 3Department of Surgery, The Methodist Hospital, Houston, Texas; and 4Department of Pathology, The Methodist Hospital/Weill Cornell Medical College, Houston, Texas.

Enteritis cystica profunda is a rare benign intestinal lesion associated with Peutz-Jeghers syndrome and other conditions, including Crohn disease. It mimics adenocarcinoma radiographically, grossly, and histologically and, thus, may pose a difficult diagnostic challenge. We describe the case of a 16-year-old boy with Peutz-Jeghers syndrome who presented with intussusception. At exploratory laparotomy, there was a hemorrhagic mass emerging from a previous staple line, and a segment of small bowel was resected. Extending through the intestinal wall and onto the serosal surface was a Peutz-Jeghers polyp whose stalk displayed features suggestive of infiltrative adenocarcinoma, including dilated glands, mucin pools, and transmural misplaced epithelium. However, the lack of significant cytologic atypia and desmoplasia, as well as the lamina propria associated with the misplaced epithelium, supported a benign lesion. Immunohistochemical staining for biomarkers that are frequently overexpressed in malignancy, specifically p53, MIB-1, IMP3, and XIAP, was similar to that of adjacent normal mucosal tissue. Patients with Peutz-Jeghers syndrome develop hamartomatous polyps throughout the gastrointestinal tract, though few develop epithelial misplacement. Additionally, “pseudoinvasion” has been infrequently described in children, in adolescents, or in the small intestine. Because of the increased incidence of malignancy in individuals with Peutz-Jeghers syndrome, atypical findings such as enteritis cystica profunda may be misinterpreted and overcalled as adenocarcinoma. Differentiation between the two is paramount for appropriate patient management, especially in younger patients, who are particularly vulnerable to long-term complications of unnecessary intervention. Careful assessment of all histologic details and selected immunohistochemical studies is necessary for an accurate diagnosis.

The Overexpression of RNA-Binding Protein IMP3 in Human Gastric Adenocarcinoma (Poster No. 53)

Wei Feng, MD1 (fengpossible@gmail.com); Camtu D. Truong, MD1; Qihui Zhai, MD2; Dongfeng Tan, MD.11Department of Pathology, MD Anderson Cancer Center, Houston, Texas; and 2Department of Pathology, The Methodist Hospital, Houston, Texas.

Context: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein highly expressed in fetal tissue and malignant tumors such as endometrial carcinomas, renal cell carcinomas, and melanoma but only rarely within adult benign tissues. In this study, we evaluated the expression of IMP3 in gastric adenocarcinoma (GAC).

Design: Samples from 207 cases of GAC and 25 cases of nonneoplastic gastric mucosa (NNGM) within formalin-fixed paraffin-embedded tissue microarray blocks were examined. Cases with preoperative treatment were excluded. Tissue microarrays were stained with mouse monoclonal anti-IMP3 antibody (1:80; Dako). The percent (0%–100%) and intensity (1–3+) of positive cytoplasmic and/or membranous IMP3 staining cells were determined. IMP3 expression was also correlated with American Joint Committee on Cancer (AJCC) stage grouping and Lauren classification.

Results: A portion of GAC cases (70 of 207; 34%) showed positive cytoplasmic and/or membranous IMP3 staining (1+ in 42 [20%]; 2 to 3+ in 28 [14%]). On the other hand, only 1 of 25 (4%) NNGM controls showed focal IMP3 staining. Two samples of intestinal metaplasia were negative for IMP3. AJCC stage grouping 3 and 4 cases showed statistically significant higher IMP3 expression compared with AJCC stage grouping 1 and 2 cases (P < .05). Intestinal type GAC showed statistically significant higher IMP3 expression compared with diffuse type GAC (P = .007).

Conclusions: IMP3 is overexpressed in a subset of GAC and is usually not overexpressed in NNGM. Higher level of IMP3 overexpression is seen in intestinal type GAC than in diffuse type GAC. Furthermore, higher level of IMP3 expression is associated with higher tumor stage.

Downregulation of Bax-Interacting Factor 1 in Pancreatic Ductal Adenocarcinoma (Poster No. 54)

Domenico Coppola, MD1 (domenico.coppola@moffitt.org); Leslie M. Turner, MD1; James Helm, MD2; Mo Malafa, MD2; Hong-Gang Wang, PhD.31Department of Anatomic Pathology, 2Gastrointestinal Program, and 3Drug Discovery Program, Moffitt Cancer Center, Tampa, Florida.

Context: Bax-interacting factor 1 (Bif-1) protein is a member of the endophilin B family that plays a critical role in apoptosis, autophagy, and mitochondrial morphology. Loss of Bif-1 suppresses programmed cell death and promotes tumorigenesis. To date the role of Bif-1 in pancreatic carcinogenesis has not been studied.

Design: To determine Bif-1 expression in human pancreatic ductal adenocarcinoma (PDA), we performed immunohistochemistry (IHC) using pancreatic cancer tissue microarrays containing 82 PDAs and 82 samples of nonneoplastic pancreatic ductal epithelium (NMP). Both PDA and NMP from the same patient were stained in 75 cases. In an additional 7 patients only PDA samples were stained. In an additional 7 patients only NMP samples were stained. Formalin-fixed, paraffin-embedded core sections on the tissue array were immunostained using the avidin-biotin-peroxidase method and the anti–Bif-1 murine monoclonal antibody (dilution 1:2500; Imgenex, San Diego, California). The Bif-1 stain was scored by 2 independent observers.

Results: High Bif-1 expression (IHC score 6–9) was identified in 55% (45 of 82) of PDAs but 77% (63 of 82) of NMPs. This difference was statistically significant (P = .003; RR 0.58). Low Bif-1 staining (IHC score 0–4) was present in 45% (37 of 82) of PDAs but in only 23% (19 of 82) of NMPs. This difference was also statistically significant.

Conclusions: We report the downregulation of Bif-1 during the transition from NMP to PDA in a subset of PDAs. This is a novel finding in agreement with the tumor suppressor function of Bif-1.

Activation of Mammalian Target of Rapamycin (mTOR) in Gastrointestinal Stromal Tumors (Poster No. 55)

James W. Horvath, MD1 (james.horvath@osumc.edu); Wendy L. Frankel, MD1; Andrew M. Bellizzi, MD1; Mark Bloomston, MD2; Obiajulu H. Iwenofu, MD.1 Departments of 1Pathology and 2Surgery, The Ohio State University Medical Center, Columbus.

Context: Recent data suggest that alteration of PI3K/Akt could be a crucial survival pathway in gastrointestinal stromal tumors (GISTs). Mammalian target of rapamycin (mTOR) is a serine/threonine kinase of the PI3/Akt signaling pathway known to play an important role in tumor growth as well as a therapeutic target in cancer therapy. Phosphoribosomal S6 protein (p-S6rp) is a downstream molecule and a surrogate marker of mTOR activation. We examined the reactivity of 61 GISTs for p-S6rp expression.

Design: Tissue microarrays were built from 61 cases of GIST. Cases included high-risk (n = 18), intermediate-risk (n = 22), and low-risk (n = 21) tumors. Outcome data on the response to imatinib, stratified into complete response, partial response, stable disease, and progressive disease, were available in 15 of 61 patients. Sections were stained with the antibody to p-S6rp (cell signaling) and cytoplasmic staining was scored 0 to 3+.

Results: There is a high frequency of p-S6rp expression indicating activation of the mTOR pathway in GIST. Overall, 41 of 61 cases were positive (67%) and 20 were negative (33%). Twenty-four were 1+ (39%), 11 were 2+ (18%), and 6 were 3+ (10%). Approximately a third of the cases showed intermediate to high expression. Response to imatinib did not correlate with expression of p-S6rp.

Conclusions: Our data show a high frequency of activation of mTOR (a third with intermediate to high-level expression), suggesting a possible role for mTOR inhibitor therapy in addition to conventional treatment. Testing a large cohort in a prospective fashion is needed to confirm clinical utility.

Primary Small Bowel Mucosal Melanoma in a Patient With a Previous History of Lentigo Maligna (Poster No. 56)

Laura L. Nelsen, MD (laura.nelsen@usd.edu); Ali D. Jassim, MD, PhD.  Department of Pathology, Sanford School of Medicine of the University of South Dakota, Sioux Falls.

Although metastatic melanoma can commonly spread to the small bowel, it rarely is the primary presentation and usually involves the serosa; mucosal melanoma is a rare condition. A completely excised lentigo maligna also rarely progresses to metastatic melanoma. Five years after complete excision of a lentigo maligna on his left temple, a 65-year-old man presented to our hospital for gastrointestinal bleeding. The patient had an exploratory laparoscopy with small bowel resection; along with a 20-cm segment of small bowel, an obstructive 4-cm mass was removed. The heavily pigmented tumor grossly appeared to mostly involve the mucosal surface with cut sections showing minimal extension into the muscularis propria of the small bowel. Microscopically, the tumor consisted of diffuse sheets of highly malignant cells with large nuclei, prominent nucleoli, and abundant cytoplasm with occasional pigmentation (Figure 11). Immunohistochemically, these cells were positive for S100, HMB-45, and MART-1 and negative for CD117. Molecular studies (fluorescence in situ hybridization using ESRW1 probe) did not demonstrate t(12,22) commonly seen in clear cell sarcoma. Further cutaneous survey and evaluation failed to assess a primary site for the current melanoma. It is exceedingly rare to see metastatic disease with this magnitude from a lentigo maligna. It is also exceedingly rare to see a primary malignant melanoma of the small bowel. In light of the absent source of a distant primary melanoma, we believe this tumor represents a primary small bowel mucosal melanoma. The relationship between the patient's previous lentigo maligna and this lesion is undetermined.

Sclerosing Mesenteritis: Intraoperative Evaluation of a Clinically Nonspecific Mesenteric Lesion (Poster No. 57)

Daniel S. Atherton, MD (daniel.atherton@bhsala.com). Department of Pathology, Baptist Health System, Birmingham, Alabama.

Sclerosing mesenteritis is a rare disease characterized by an expansile tumorlike process that can affect both the small and large bowel mesenteries. Because it is not a common diagnosis, along with the fact that its presentation can be identical to more common abdominal disorders, sclerosing mesenteritis is often only first suspected and diagnosed intraoperatively. A 48-year-old woman presented to our institution with progressive symptoms of upper abdominal pain along with sporadic episodes of nausea and occasional vomiting. Imaging showed a complex left upper quadrant lesion with both solid and cystic components. Exploratory laparotomy revealed a mesenteric mass with extensive adhesions affecting the small bowel. A portion of small bowel with the associated mesenteric mass was received for frozen section. Microscopically, the mass demonstrated elements of chronic inflammation, fat necrosis, and significant areas of characteristic fibrosis, indicating a diagnosis of sclerosing mesenteritis. The nomenclature attached to this process has been less rigid in the past, with terms such as “mesenteric lipodystrophy,” “mesenteric panniculitis,” and “retractile” or “sclerosing mesenteritis” commonly used in conjunction with the relative proportions of the 3 most common histopathologic findings: fat necrosis, chronic inflammation, and collagen deposition. It has been suggested that the term sclerosing mesenteritis is adequate when there is some degree of characteristic fibrosis. This case underscores the importance of recognizing sclerosing mesenteritis, especially in the absence of clinical suspicion, in the differential of nonspecific mesenteric lesions and supports the contention that sclerosing mesenteritis can be confidently diagnosed intraoperatively.

Improved Identification of Dysplastic Lesions in Barrett Esophagus (Poster No. 58)

Tanya Varma, MD1 (tvarma@lsuhsc.edu); Mary L. Nordberg, PhD.2 1Department of Pathology, Louisiana Health Sciences Center, Shreveport; and 2Department of Pathology, Feist-Weiller Cancer Center, Shreveport, Louisiana.

Context: Detection of certain biomarkers is useful in identifying cases of Barrett esophagus with dysplasia (high and low grade). The detection of low-grade dysplasia remains the grey zone as many dysplastic lesions are missed using light microscopy alone.

Design: Eleven cases of Barrett esophagus with no dysplasia and low-grade dysplasia on light microscopy were studied. Immunohistochemistry (IHC) for Ki-67 (Ventana Medical Systems, Inc, Tuscon, Arizona), p53 (Ventana), and α-methylacyl coenzyme A racemase (AMACR) (Abcam, Cambridge, Massachusetts) was performed. The cases that showed increased expression by IHC were analyzed by fluorescence in situ hybridization (FISH) for loss of heterozygosity (LOH) at 17p13.1 (p53 gene) and abnormal copy numbers of chromosome 17 using centomeric enumeration probe (CEP17).

Results: The IHC results for Ki-67, p53, AMACR, and FISH are shown in the Table.

 
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Conclusions: The p53 stain by IHC was normal in all but 3 cases; therefore, its expression is usually unaltered in low-grade dysplasia. FISH analysis showed trisomy of chromosome 17 but no LOH at 17p13.1(p53). Ki-67 is a proliferation marker; hence its expression would be increased in regeneration or repair. The efficacy of this marker is not reliable in the 5 biopsies with increased expression but with significant inflammation. AMACR proved to be a sensitive marker to detect dysplasia. The cases with increased staining with AMACR also showed trisomy of chromosome. Studies to include more cases of high-grade dysplasia are ongoing.

Assessment and Follow-Up of Explanted Livers in α1-Antitrypsin Deficiency (Homozygous ZZ Genotype) (Poster No. 59)

Dawn Bradly, MD (dawn_bradly@rush.edu); Ajay Patel, MD; Maria McIntire, MD; Deborah Giusto, MD; Shriram Jakate, MD. Department of Pathology, Rush University Medical Center, Chicago, Illinois.

Context: Accumulation of defective α1-antitrypsin (A1AT) in the liver may lead to hepatocellular injury and cirrhosis. Diastase-resistant periodic acid–Schiff (d-PAS)–positive A1AT globules are currently the only significant pathologic finding. We aim to evaluate pathologic findings in explanted livers, coexistent pulmonary disease, and posttransplantation follow-up.

Design: From January 1993 to May 2008, patients with ZZ genotype (PiZZ) who underwent orthotopic liver transplantation were selected at our institution among 1200 transplants. The explants were reviewed for gross and histologic findings, concomitant liver disease, pulmonary disease, and follow-up hepatic graft biopsies.

Results: A total of 3 patients were identified (0.2% of total transplants). All patients were men (age range, 56–58 years). All showed mixed macronodular and micronodular cirrhosis and abundant d-PAS–positive large hepatocytic cytoplasmic globules. One case showed incidental moderately increased iron. Another case showed severe macrovesicular steatosis consistent with incidental coexistent NASH. None had a dysplastic nodule or carcinoma. There was no symptomatic pulmonary dysfunction, but 2 cases exhibited mild emphysematous changes on computed tomography scan and chest x-ray. One case required retransplantation due to bile cast syndrome within 1 year. Follow-up biopsies of the grafts for up to 5 years showed no reaccumulation of d-PAS–positive globules.

Conclusions: A1AT deficiency is an extremely rare indication for hepatic transplantation. Other than d-PAS–positive globules and incidental findings such as NASH and increased iron, there are no distinctive pathologic findings. No A1AT globule reaccumulation is seen in the graft. There is no coexistent pulmonary dysfunction, and only mild pulmonary emphysema is detected radiologically.

Diagnostic Utility of von Hippel-Lindau Gene Product (pVHL) and S100P in Adenocarcinoma and Dysplasia of the Gallbladder (Poster No. 60)

Fan Lin, MD, PhD1 (flin1@geisinger.edu); Haiyan Liu, MD1; Jianhui Shi, MD, PhD1; Yiran Xu, BS1; Jun Zhang, MD2; Hanlin L. Wang, MD, PhD.3 1Department of Laboratory Medicine, Geisinger Health System, Danville, Pennsylvania; 2Department of Pathology, Mayo Clinic, Rochester, Minnesota; and 3Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California.

Context: Our recent study demonstrated the nearly perfect inverse correlation of upregulation of S100P and downregulation of von Hippel-Lindau gene product (pVHL) in pancreatic intraepithelial neoplasias and ductal adenocarcinoma of the pancreas (Lin et al. AJSP. 2008;32:78–91). This study investigates the utility of these 2 markers in the diagnosis of adenocarcinoma and dysplasia of the gallbladder.

Design: Immunohistochemical stains for S100P and pVHL were performed on 65 gallbladder specimens, including adenocarcinoma (n = 25, 8 cases also containing glandular dysplasia), reactive glandular atypia (n = 20), and normal gallbladder (n = 20). The staining intensity was graded as weak or strong. The distribution was recorded as negative, 1+, 2+, 3+, and 4+.

Results: The results demonstrated a nuclear and cytoplasmic staining pattern of S100P in 19 of 25 (76%) adenocarcinoma cases and 8 of 8 (100%) cases with glandular dysplasia. In contrast, none of the 40 reactive/normal gallbladder cases was positive for S100P. Glandular epithelia in all normal and reactive cases were diffusely (3+ and 4+) positive for pVHL with membranous/cytoplasmic staining. In contrast, all cases of adenocarcinoma and dysplasia were negative for pVHL, whereas the adjacent normal ductal/glandular epithelia were positive for pVHL.

Conclusions: Our data suggest that (1) the findings of upregulation of S100P and downregulation of pVHL in adenocarcinoma and dysplasia are similar to that of pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma, indicating a possible role of these 2 proteins in tumorigenesis and (2) the expression patterns of pVHL and S100P can be used as a pair of diagnostic markers to confirm the diagnosis of adenocarcinoma and dysplasia of the gallbladder.

Unusual Presentations of Cecal Carcinomas (Poster No. 61)

Katherine J. Downey, MD (katherine.downey@bmc.org); Marier Hernandez, MD; Bethany J. Tierno, MD; Sandra Cerda, MD. Department of Mallory Institute of Pathology, Boston Medical Center, Boston, Massachusetts.

With the exception of the rectum and sigmoid, the cecum is the most common site of carcinoma of the large intestine and carries a poorer prognosis than other colon cancers (overall 5-year survival rate, 57%) because of long-standing obscure symptoms including intermittent diffuse abdominal pain (70%), intestinal obstruction (60%), and palpable mass (10%). We report 2 cases of cecal carcinomas with unusual clinical presentations. The first case involves a 68-year-old man with a past medical history of diverticulosis, hypertension, and hyperlipidemia who presented to the emergency room complaining of a 1-week history of intermittent symptoms including severe epigastric abdominal pain exacerbated by movement, decreased appetite, and change in bowel movements. He denied fever or prior abdominal surgeries. Laboratory results showed leukocytosis (15 000/μL, reference range 4000–11 000/μL). Computed tomography imaging showed appendicitis without perforation. Emergent appendectomy was scheduled and a frozen section of the appendix during surgery showed adenocarcinoma at the appendiceal orifice. Final pathology showed low-grade adenocarcinoma with positive nodal metastases (AJCC Stage IIIA [pT2, pN1, pMx]) and acute appendicitis. Our second case involved an 88-year-old woman with past medical history of hypertension and diabetes mellitus who presented to the emergency room complaining of severe abdominal pain. Computed tomography imaging showed perforated bowel. An emergent hemicolectomy was scheduled. Pathology showed low-grade adenocarcinoma (AJCC Stage II [pT2, pN0, pMx]). Cecal carcinomas can have unusual clinical presentations thereby causing a significant delay in diagnosis. These delays are due to a lack of suspicion, and thus cecal carcinomas should always be in the differential.

Possible Histopathologic Changes in Contaminated Heparin (Poster No. 62)

Cesar V. Reyes, MD (creyes@morrishospital.org). Department of Pathology, Morris Hospital, Morris, Illinois.

Contaminated heparin with oversulfated chondroitin sulfate has recently been suggested as the cause of severe anaphylactoid reactions after intravenous heparin. It has also been postulated that the supposed contaminant directly activates the kinin-kallikrein pathway in human plasma, which leads to the generation of bradykinin, along with C3a and C5a, also potent anaphylatoxins. Activation of these pathways is linked and dependent on fluid-phase activation of factor XII. The resulting histopathologic changes, however, have not been documented. This case involves a 27-year-old woman who underwent laparoscopy-assisted vaginal hysterectomy 2 days prior to presenting with acute abdomen due to pelvic hemorrhage. On laparoscopy, large blood clots were found in the lower abdomen and pelvis. Clot removal and lysis were supplemented with heparin washing of the lower abdominal and pelvic cavities and was tolerated well. Ten days later, there was recurrence of acute abdomen, associated with small intestinal obstruction. Laparoscopic reevaluation of the pelvis and lower abdomen revealed a peritoneal/pelvic severe exudative inflammation that was highlighted by nondescript deposits, collared by a thick and dense eosinophilic cell reaction, and occasional granulomata (Figure 12), resulting in intestinal loop fibrinofibrous adhesions and small intestinal obstruction. Removal of the inflammatory debris and lysis of intestinal loop adhesions were also well tolerated. Six-month and 1-year follow-up showed no recurrence of the problem. This nonfatal case is probably the first demonstration of the histopathologic changes associated with contaminated heparin used in pelvic and peritoneal washing to lyze extensive, adherent postoperative blood clots.

Sessile Serrated Adenoma of the Colon: A Case Report and Review of the Literature (Poster No. 63)

Danisha L. Allen, MD1 (danisha@gwu.edu); Anupamjit K. Mehrotra, MD2; Wen Chen, MD3; Suman S. Chauhan, MD.31Department of Pathology, The George Washington University Medical Center, Washington, DC; 2Department of Hepatic and Gastrointestinal Pathology, Armed Forces Institute of Pathology, Washington, DC; and 3Department of Pathology and Laboratory Medicine Services, Veterans Affairs Medical Center, Washington, DC.

Sessile serrated adenomas, a recently described entity of colonic polyps, display features similar to hyperplastic polyps such as serrated architectural growth and lack of cytologic dysplasia. These lesions commonly arise in the proximal colon and appendix. Grossly, they appear flat or slightly raised in relation to the adjacent mucosa (Figure 13, A). Microscopic features include basal dilation and flask-shaped crypts, often oriented parallel to the muscularis mucosae conferring an inverted T- or L-shaped appearance to the crypts. Cells lining the crypts are cytologically bland and serration is often present at the surface and bases of the crypts (Figure 13, B through D). Patients are generally treated and followed the same as those with traditional adenomatous polyps. We present a case of a 54-year-old male smoker who underwent a colonoscopy for hematochezia, notable for an 8-mm sessile polyp in the cecum and a 15-mm polyp in the proximal colon. Macroscopically the polypoid masses were pale tan to dark brown, lobulated, and finely granular. Microscopic examination of both polyps demonstrated the aforementioned characteristic features, consistent with sessile serrated adenomas. Reports have shown that serrated polyps progress to adenocarcinoma via methylation of CpG islands of the promoter regions of suppressor and mutator genes. The adenocarcinomas demonstrate a defect in DNA mismatch repair, with subsequent microsatellite unstable (majority) and microsatellite stable forms. The true incidence of sessile serrated adenoma is unknown, and risk of malignancy is comparable to that of traditional adenomatous polyps. Therefore, this entity is important to consider in the evaluation and diagnosis of colonic polyps.

Constitutive Activation of ERK Pathway Is Associated With Tumoral Angiogenesis and Fibroplasia in Fibrolamellar Hepatocellular Carcinoma (Poster No. 64)

Sadhna Dhingra, MD1 (Sadhna.Dhingra@uth.tmc.edu); Wei Li, MD1; Dongfeng Tan, MD2; Robert E. Brown, MD.11Department of Pathology and Laboratory Medicine, University of Texas Health Sciences Center-Medical School, Houston; and 2Department of Pathology, MD Anderson Cancer Center, Houston, Texas.

Context: Angiogenesis is the propelling force for tumor growth and metastasis of hepatocellular carcinoma (HCC). Antiangiogenic agents like bevacizumab and sorafenib, targeting vascular endothelial growth factor (VEGF)–A and the VEGF receptor (VEGFR), respectively, have become a standard of care for conventional HCC. Because VEGF-A and VEGFR activate the extracellular signal-regulated kinase (ERK) 1/2 pathway, we analyzed the relative expressions of VEGF-A and activated (phosphorylated) ERK 1/2 in this study of fibrolamellar hepatocellular carcinoma (FLHCC).

Design: Morphoproteomic analysis was performed in 7 cases of FLHCC using immunostaining for the detection of VEGF-A and a phosphospecific probe at the putative sites of activation, threonine 202 tyrosine 204 on ERK 1/2. Subcellular immunolocalization of the chromogenic signal was determined and signal intensity was graded on a scale of 0 to 3+ by bright-field microscopy.

Results: All 7 of 7 cases showed strong (3+) pERK 1/2 nuclear expression in endothelial cells of intratumoral vessels and fibroblasts. This overexpression was most prominent at the interface of the neoplastic hepatocytes and fibrosis. VEGF-A expression was observed in the cytoplasm of neoplastic hepatocytes in all 7 cases. The signal intensity was variable (1–3+). Focal cytoplasmic positivity for VEGF was also seen in fibroblasts.

Conclusions: ERK pathway is constitutively activated and contributes to angiogenesis and fibroplasia in FLHCC. Targeting this pathway by therapeutic agents may be beneficial in FLHCC. The molecular mechanism(s) of ERK pathway in FLHCC progression merits further investigation.

Expression of Claudin-3 and Claudin-4 Proteins in Gastric Adenocarcinoma (Poster No. 65)

Reenu Malhotra, MD; Amanda L. Peterson, MD (amanda.l.peterson@uth.tmc.edu); Wei Li, MD. Department of Pathology, University of Texas Health Science Center-Houston.

Context: Claudins comprise a family of integral membrane proteins, which play a major role in tight junction formation and function. Aberrations in expression of claudins have been described in various malignancies and have been suggested as possible biomarkers and targets for cancer therapy. The aim of this study was to determine the expression pattern of claudin-3 and claudin-4 in gastric adenocarcinoma and correlate expression with clinicopathologic variables.

Design: Paraffin-embedded tissue from 21 cases of gastric adenocarcinoma (11 intestinal, 10 diffuse/mixed subtypes) were analyzed for expression of claudin-3 and claudin-4 protein by immunohistochemistry. Additionally, expression of these proteins in 20 gastric biopsies with chronic active gastritis and intestinal metaplasia were evaluated for comparison. The protein expression was categorized into 3 grades: 1+ (weak), 2+ (moderate), or 3+ (strong) based on staining intensity.

Results: Moderate to strong staining of claudin-3 and claudin-4 was detected in 90.1% and 72.7%, respectively, of the intestinal type and 90% and 80%, respectively, of the diffuse subtypes of adenocarcinoma. In comparison, weak to moderate staining of claudin-3 was observed in chronic active gastritis and intestinal metaplasia (P = .007). Significant statistical difference in claudin-4 protein expression was observed between carcinoma and chronic active gastritis and intestinal metaplasia (P < .001).

Conclusions: Claudin-3 and claudin-4 are strongly expressed in intestinal and diffuse subtypes of gastric adenocarcinoma. The upregulation of claudin expression suggests their possible role in gastric carcinogenesis, their potential utility as diagnostic biomarkers, and possible targets for innovative therapy.

A Pancreatic Mass in a 56-Year-Old Woman (Poster No. 66)

Fernando Antelo, MD1 (antelo@ucla.edu); Bruce E. Stabile, MD2; Samuel W. French, MD.1 Departments of 1Pathology and 2Surgery, Harbor-UCLA Medical Center, Torrance, California.

We report a rare case of pancreatic cystic tumor with features of both serous microcystic adenoma and mucinous cystic adenoma. Our patient is a 56-year-old woman evaluated for epigastric pain, with identification of a 9-cm mass in the pancreas on computed tomography (arrow, Figure 14, A). A distal pancreatectomy with splenectomy was performed. On gross examination, the pancreatic tumor was composed largely of innumerable small, thin-walled cysts, ranging in size from less than 0.1 to 0.5 cm (Figure 14, B). Light microscopy revealed that these cysts were lined by a single layer of clear cuboidal epithelial cells (Figure 14, C); staining with periodic acid–Schiff for glycogen and anti-inhibin antibodies was consistent with serous microcystic adenoma. The tumor also contained a focus of cystic spaces lined by a single layer of tall columnar cells with apical vacuoles (Figure 14, D); staining of the epithelium with Alcian blue/periodic acid–Schiff for mucin and of the stroma with anti–smooth muscle actin antibody was diagnostic of mucinous cystadenoma. Three cases have been previously described in Japan (Abe et al. Pancreas. 2005; 31:98–100). To our knowledge, this is the first case of mixed serous and mucinous cystic tumor of the pancreas in the United States.

Primary Rectal Gangliocytic Paraganglioma: Case Report and Review of the Literature (Poster No. 67)

Richard Taylor, MD1; Sarah Eakin, MD1 (seakin@wfubmc.edu); Gregory Waters, MD2; Michael Beaty, MD1; Zachary Lewis, MD.3 Departments of 1Pathology and 2General Surgery, Wake Forest University Baptist Medical Center, Winston Salem, North Carolina; and 3Department of Pathology, Innovative Pathology Services, Knoxville, Tennessee.

Gangliocytic paraganglioma (GP) is a rare tumor that occurs nearly exclusively in the periampullary region of the duodenum with only rare cases reported to involve the jejunum, pylorus, esophagus, pancreas, appendix, and lung. Generally, this tumor has a benign clinical course, although rarely it may recur or metastasize to regional lymph nodes. We report an unusual case of primary GP presenting as a rectal mass found on routine colonoscopy. A 60-year-old woman was referred to surgery after rectal polyp biopsy identified a spindle cell neoplasm, favor neurofibroma versus ganglioneuroma. The resection contained a poorly circumscribed polypoid tan-grey submucosal mass. Histologically the tumor had a triphasic appearance characteristic of GP, composed mostly of neural-type spindled neurofibroma-like tissue with scattered ganglioneuroma cells and paraganglioma nests. By immunohistochemistry, the neurofibroma/ganglioneuroma-like components were both positive for S100, neuron-specific enolase, and synaptophysin. The paraganglioma component was positive for neuron-specific enolase and synaptophysin, while S100 highlighted the sustentacular cells surrounding the paraganglioma component (Figure 15). Due to the typical duodenal location of this lesion, it is generally believed that GPs arise from endodermal/neuroectodermal complexes and represent a pancreatic-type hamartoma. However, reports of GP metastases to locations away from the duodenum, including lungs, mediastinum, esophagus, nasopharynx, and ovary are consistent with the idea that these tumors represent true neoplasms. To our knowledge, this is the first report of a case of primary rectal GP and supports the hypothesis that these lesions arise from neuroendocrine tumors/paragangliomas with ganglionic/neuroectodermal differentiation.

Intraductal Papillary Mucinous Neoplasm of the Pancreas: Histopathologic Characterization of 46 Consecutive Cases (Poster No. 68)

Monica T. Garcia, MD1 (mgarcia22@med.miami.edu); Loren P. Herrera, MD2; Pablo A. Bejarano, MD.11Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida; and 2Department of Pathology, Jackson Memorial Hospital, Miami, Florida.

Context: Intraductal papillary mucinous neoplasms (IPMNs) of pancreas are intraductal mucin-producing cystic tumors showing variable degree of atypia ranging from adenoma to invasive carcinoma. We investigated the incidence and histopathologic characteristics of IPMNs in a single tertiary center.

Design: We reviewed 350 consecutive pancreatectomies performed during a 4-year period. The IPMNs were assessed for size, location, malignant features, perineural invasion (PNI) or lymphovascular invasion (LVI), and TNM when applicable.

Results: Of 243 pancreatic neoplasms, 18.3% were IPMNs. The mean age of patients was 66.9 years and tumor size was 3.3 cm. Sixty-seven percent of IPMNs were located in the head, 15% in the body, 15% in the tail, and 2% in heterotopic pancreas. Forty-eight percent were adenomas, 15% were borderline, 4.3% showed in situ carcinoma, and 32.6% showed invasive carcinoma. Five cases of IPMN-adenoma were associated with ductal carcinoma. Three cases showed IPMN with serous cystadenoma, endocrine microadenoma, and ampullary adenocarcinoma. Most ductal carcinomas with associated IPMN-adenoma were pT3 (83%) or N1 (80%), whereas 53% of the invasive-IPMN were pT3 and 27% were N1. LVI was observed in 33% of the invasive-IPMN and 67% of ductal carcinomas with associated IPMN-adenoma. PNI was observed in 53% of invasive-IPMN and 100% of ductal carcinomas with associated IPMN-adenoma (Table).

Conclusions: In this series, IPMNs represent 18% of all pancreatic tumors. IPMNs without the presence of invasive carcinoma were more common. Patients with invasive-IPMN showed lower TNM stage and less LVI and PNI compared with patients whose pancreas contained both conventional ductal carcinoma and IPMN-adenoma (P < .001).

 
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First Report of a Massive Hepatocellular Carcinoma of the Liver in a Pediatric Patient, as a Sequela of Therapy for a High-Grade Glioma (Poster No. 69)

Sreelakshmi Ravula, MD1 (sree_lrus@yahoo.com); Jeffrey Sosnowski, MD, PhD1; Elizabeth Manci, MD.21Department of Pathology, University of South Alabama Medical Center, Mobile; and 2Department of Pediatric Pathology, University of South Alabama Children's and Women's Hospital, Mobile.

Hepatocellular carcinoma (HCC) of the liver is one of the common malignant tumors in children. We present an unusual case of HCC of the liver in a pediatric patient with high-grade glioma. This is the first reported case of a patient with glioma developing a 12-cm HCC as a sequela of tumor therapy. An 11-year-old white girl with 2- to 3-days' history of headaches and vomiting was referred to our institution. Brain magnetic resonance imaging study revealed a 3.0-cm right parietal mass and a 0.7-cm satellite lesion in the right globus pallidus. She underwent craniotomy and the tumor was diagnosed as high-grade glioma. Her postoperative course was significant for seizures that were controlled with Keppra. She was treated with radiotherapy. After completion of radiotherapy, her maintenance chemotherapy included temozolomide and lomustine. Within 1 month of initiation of chemotherapy she developed nausea, vomiting, epigastric pain, dehydration, and loss of weight. She had multiple hospital admissions during the course of 6 weeks. Her laboratory workup revealed elevated liver enzymes. Abdominal computed tomography scan showed a hypodense mass within the left lobe of the liver measuring 12.0 × 7.5 cm. Her liver lesion was resected with a final diagnosis of HCC. We believe this is the first reported case of HCC in a pediatric patient with high-grade glioma. Second, this is the largest reported mass in a case of HCC postchemotherapy in a pediatric patient.

Direct Immunofluorescence in Esophageal Lichen Planus (Poster No. 70)

Xiuli Liu, MD, PhD (liux3@ccf.org); James McMahon, PhD; Keith K. Lai, MD. Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio.

Esophageal lichen planus (ELP) is a rare but underrecognized inflammatory disorder of the esophagus. Direct immunofluorescence (DIF) plays a critical role in diagnosing cutaneous and oral lichen planus, but its use in ELP has not been reported in published ELP cases. A 76-year-old woman presented with a 5-year history of progressive dysphagia and odynophagia nonresponsive to proton pump inhibitor therapy. Esophagogastroduodenoscopy revealed a proximal esophageal stricture with inflammation, desquamation, and ulceration in the remainder of the esophagus. Biopsy demonstrated bandlike, lymphocytic interface inflammation involving the basal epithelium and superficial lamina propria. Other findings included spongiotic change in the epithelium, many apoptotic keratinocytes, small clefts at the epithelial-lamina propria junction, and rare, scattered collections of intraepithelial eosinophils (<10 per high-power field). Viral cytopathic effect was not identified. Organisms were not seen. DIF studies found shaggy fibrinogen deposition at the epithelial-lamina propria junction (Figure 16) and globular deposition of immunoglobulin (Ig) A, IgM, IgG, and C3. The morphologic and DIF findings established a diagnosis of ELP and a thorough skin and oral cavity examination was recommended. On follow-up 10 weeks after presentation, the patient reported significant improvement of symptoms with flunisolide. Physical examination performed by a dermatologist revealed lesions on the back, occiput, and hard palate consistent with cutaneous and oral lichen planus. Correct diagnosis of ELP is difficult but carries therapeutic and prognostic implications. The DIF findings in this case demonstrate the characteristic pattern seen in cutaneous and oral lichen planus, indicating that DIF may aid differentiation of ELP from other esophagitides.

Donor-Derived Small Cell Neuroendocrine Carcinoma of Pulmonary Origin in a Liver Transplant Recipient (Poster No. 71)

Adeel Ahmad, MD1 (aahmad@tuftsmedicalcenter.org); Faisal A. Khokar, MD1; Janet Cowan, PhD1; Jeffrey Cooper, MD2; Monica Pilichowska, MD, PhD.1 Departments of 1Pathology and 2Transplant Surgery, Tufts Medical Center, Boston, Massachusetts.

Donor-derived malignancies in transplant recipients are rare and found in 0.02% to 0.2% of allograft recipients. We report a case of donor-derived small cell neuroendocrine carcinoma in a liver transplant recipient. To the best of our knowledge such a case has not been previously reported. A 44-year-old man with end-stage liver disease secondary to hepatitis C and hepatocellular carcinoma received a cadaveric liver transplant from a 58-year-old female donor. The donor was an active smoker (2 packs per day) for several years with chronic obstructive pulmonary disease but without history of cancer. Donor screening included chest radiograph, which had normal results. Recipient's clinical course was unremarkable until 8 months posttransplant when he presented with abdominal pain and multiple liver nodules. Computed tomography–guided fine-needle aspiration and core biopsy of the liver revealed sheets and clusters of small cells with high N/C ratio, round nuclei, fine chromatin, and indistinct nucleoli. Tumor cells were positive for pankeratin, cytokeratin 7, thyroid transcription factor 1, and chromogranin and negative for CD45, CDX-2, Hep Par 1, α-fetoprotein, serotonin, somatostatin, vasoactive intestinal peptide, calcitonin, bombesin, and gastrin. The diagnosis of small cell neuroendocrine carcinoma consistent with pulmonary derivation was made. Subsequent workup revealed no primary tumor in the recipient. Fluorescent in situ hybridization analysis of tumor cells revealed a 46,XX chromosome complement consistent with donor origin (Figure 17). The risk of transplant-related tumor xenograft is very low. However, donor-derived small cell carcinoma can occur. A donor's smoking history could be of interest, and expanded smoking screening of donors might be warranted.

Cutaneous Manifestations in a Patient With Juvenile Polyposis Syndrome: A Case Report and Review of the Literature (Poster No. 72)

Luigi K. Rao, MD (LuigiRao@alumni.nd.edu); Joel T. Moncur, MD, PhD. Department of Pathology and Laboratory Services, Walter Reed Army Medical Center, Washington, DC.

Juvenile polyposis syndrome (JPS), associated with SMAD4 and BMPR1A gene mutations, is defined clinically by at least 6 juvenile colon polyps, multiple gastrointestinal tract juvenile polyps, or any number of juvenile polyps along with a family history of juvenile polyps. Many familial polyposes, including Cowden, Gardner, and Muir-Torre syndromes, have been recognized to have distinct cutaneous manifestations. We present a patient with skin lesions believed to represent cutaneous manifestations of JPS, a phenomenon never previously reported based on our review of the literature. The patient presented at 6 months with rectal bleeding and a lesion protruding from the anus. Subsequent colonoscopy revealed innumerable polyps carpeting the colon with multiple biopsies showing juvenile polyps, and a diagnosis of JPS was rendered. No mutations in SMAD4 or BMPR1A were detected during genetic workup. Continued surveillance discovered multiple gastric and small bowel juvenile polyps. Furthermore, several perianal verrucous polypoid lesions were biopsied on 4 separate occasions beginning at age 2. These polyps ranged in size from 0.5 to 1.5 cm. They exhibited a papillomatous architecture and were lined by an epidermis with varying degrees of acute inflammation with overlying hyperkeratosis and parakeratosis. The dermis displayed gaping vessels with prominent lymphocyte and plasma cell–rich chronic inflammation. Parakeratotic spires, keratohyalin granules, or viral cytopathic effect were not identified. In situ hybridization for human papillomavirus was negative. We believe the architecture of these inflamed verruciform fibroepithelial polyps, their recurrent nature, and their proximity to the gastrointestinal tract support the notion that these lesions represent cutaneous manifestations of JPS.

POSTER SESSION 200: SUNDAY, OCTOBER 11, 2009, 1:00 pm–3:30 pm

Clinical Chemistry; Clinical Immunology; Breast Pathology; Gynecologic and Placental Pathology; Pulmonary and Mediastinal Pathology

Serum Protein-Bound Thyroxine Induced Biases in Antibody-Based Single-Phase Assays for Free Thyroxine (Poster No. 1)

Yvette C. Tanhehco, MD, PhD1 (yvette.tanhehco@uphs.upenn.edu); Octavia M. Palmer, PhD2; Linda S. Derrico, MT2; Jorge L. Sepulveda, MD, PhD1; Harry C. Blair, MD.21Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia; and 2Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.

Context: Thyroid function is assessed by measuring free thyroxine (T4) when thyroid-stimulating hormone (TSH) is inconclusive. Interference in single-phase antibody-based assays for free T4 is a major problem. Accurate measurement of free T4 is important when thyroid-binding globulins might vary (eg, during pregnancy). We evaluated the ability of several assays in excluding signal from protein-bound T4.

Design: We examined TSH and free T4 in a mostly female population (50% were pregnant) at Magee-Women's Hospital. Protein-bound T4 bias was assessed by dialyzing samples and assaying retentate with increasing amounts of dialysate being added. TSH was measured for all samples.

Results: Assays of free T4 using the Vitros ECi platform (Ortho-Clinical Diagnostics, Rochester, New York) were essentially independent from serum protein concentration (R2 = 0.009). T4 measurements using Unicel DxI (Beckman Coulter, Fullerton, California), Advia Centaur (Siemens Healthcare Diagnostics, Deerfield, Illinois), and MP radioimmunoassay (MP Biomedical, Irvine, California) were related to serum protein concentration, and dilution curves differed significantly from those with ECi (P < .01; 2-tailed analysis of variance). Degree of interference from protein-bound T4 was similar in these assays, with least squares fits of DxI, Centaur, and MP RIA T4 assays relative to ECi assays having slopes ∼0.4 to 0.5. Negative correlation of free T4 to TSH was weak for all assays tested.

Conclusions: Some single-phase, direct, free T4 immunoassays have important interference from protein-bound T4. The ECi assay was largely unaffected by serum protein. In a mostly female and 50% pregnant population, correlation of TSH to free T4 was poor for all tested assays.

A New Study of Intraosseous Blood for Laboratory Analysis (Poster No. 2)

Larry J. Miller, MD1; Thomas E. Philbeck, PhD1 (thomas.philbeck@vidacare.com); Diana F. Montez, RN, BSN1; Cathy J. Spadaccini, MD.21Department of Science & Clinical, Vidacare Corporation, San Antonio, Texas; and 2Department of Pathology, Ameripath South Texas, San Antonio.

Context: Improved devices that enable providers to deliver critically needed drugs as quickly as central lines have ignited a resurgence in the intraosseous (IO) route to vascular access, leading to other uses of the IO space, including drawing IO blood for laboratory analysis. Despite previously favorable studies, some laboratory staff have concerns about the reliability of IO-derived blood for use in laboratory tests. This study validates earlier studies and addresses concerns raised by laboratory staff regarding the use of IO-derived blood.

Design: We obtained institutional review board approval. Ten adult volunteers consented to participate, and blood samples were obtained from peripheral veins in the forearm. Within 5 minutes, an IO catheter was placed in the proximal humerus, and 2 sets of IO blood samples were obtained from each participant, one set following 2 mL of marrow/blood waste and one set following 6 mL of waste. At a reference laboratory, all sample sets were analyzed for complete blood count and chemistry profile. Means were compared for each blood value of the drawn samples (intravenous, IO-1, and IO-2), with intravenous blood values serving as controls for IO blood values.

Results: IO and intravenous values were clinically similar, except in the case of white blood count and carbon dioxide (Table).

Conclusions: We found that IO space is a reliable source of blood for laboratory analysis when conducting tests commonly performed in emergency medicine, such as complete blood count and chemistry profile. Results, however, may be moderately reliable for carbon dioxide and unreliable for white blood count.

 
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Variation of Analytic Method for High-Density Lipoprotein Cholesterol Determination Is Clinically Significant (Poster No. 3)

Stanley J. Podlasek, MD (spodlas2@jhmi.edu). Department of Pathology, Johns Hopkins University, Baltimore, Maryland.

Context: High-density lipoprotein cholesterol (HDL-C) is lower in hospitalized patients; this has been attributed to stress or dietary changes related to hospitalization. Because outpatients are tested in commercial laboratories while inpatients are tested in hospital laboratories, we hypothesized that different analytic methods might explain the difference in HDL-C values.

Design: We sent 50 random patient samples from physicians' offices to a commercial laboratory where they were simultaneously assayed on the AU2700 chemistry analyzer (Olympus, Melville, New York) and the LX20 chemistry analyzer (Beckman-Coulter, Fullerton, California) on the day of collection. The EP Evaluator (David G. Rhoads Associates, Kennett Square, Pennsylvania) was used to calculate means and bias and to perform regression analysis.

Results: The Olympus method (mean HDL-C, 59.2 mg/dL) had a positive bias of 13.4 mg/dL compared with the Beckman method (mean HDL-C, 45.8 mg/dL). Olympus-based HDL-C equals 1.271 × (Beckman-based HDL-C) + 1 mg/dL.

Conclusions: Patients who go from a laboratory that uses the Olympus analyzer to one that uses the Beckman analyzer experience a significant method-dependent decrease in the level of HDL-C, which may change treatment. Manufacturers and laboratories should note the standardization program for HDL-C sponsored by the Centers for Disease Control and Prevention in which the reference range is specified by the National Cholesterol Education Program and not by a population study. Comparing the frequency of race- and sex-matched individuals with low HDL-C values from a particular laboratory with those published for like segments of the US population by the Centers for Disease Control and Prevention would be of value.

Assessment of Fetal Lung Maturity: Concordance Between TDx-FLM II Values and Lecithin to Sphingomyelin Ratios (Poster No. 4)

Andrea Wiens, DO (awiens@chsmail.org); Thomas Kocoshis, MD. Department of Pathology, Ball Memorial Hospital, Muncie, Indiana.

Context: Respiratory distress syndrome represents a significant disease entity in newborns. Assessment of fetal lung maturity (FLM) is essential when clinicians are determining whether to delay delivery. Several measurements exist to elucidate FLM, including the traditional gold standard ratio of lecithin to sphingomyelin (L/S) and the newer TDx-FLM II assay (Abbott Laboratories, Abbott Park, Illinois). We evaluated concordance between the TDx-FLM II test kit and the traditional L/S ratio assay (Helena Laboratories, Beaumont, Texas) in predicting FLM.

Design: Clinical laboratory values were obtained from 163 consecutive pregnant female patients whose amniotic fluid was collected from 2005 to 2008 for primary determination of FLM. Concordance values were calculated (n = 140) based on maturity cutoff values of 55 mg/g for TDx-FLM II results and 2.0 for L/S ratios. Comparison was made with the same data using a best apparent TDx-FLM II maturity cutoff value of 45 mg/g, as recommended by recent studies.

Results: Overall concordance between the TDx-FLM II and the L/S ratio was approximately 56% using 55 mg/g as the cutoff value for TDx-FLM II results. Concordance rose to nearly 80% when the cutoff value was lowered to 45 mg/g.

Conclusions: Recent studies have shown the TDx-FLM II to be 100% sensitive and 90% specific with a cutoff value of 45 mg/g. We found an overall concordance rate of 78% with this best apparent TDx-FLM II cutoff. We propose implementing a protocol in which the TDx-FLM II test be followed by a reflex L/S ratio for confirmation only when the TDx-FLM II result is interpreted as immature.

Performance of the Direct Hemoglobin A1c Assay on Ortho-Clinical Diagnostics' VITROS 5600 Integrated System (Poster No. 5)

Dean Carlow, MD, PhD1,2 (carlow@WWW.chop.edu); Nancy Kolea, MT.11Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Pennsylvania; and 2University of Pennsylvania School of Medicine, Philadelphia.

Context: Glycohemoglobin measurement as HbA1c is recommended by the American Diabetes Association and provides the most important marker of time-averaged glycemic status.

Design: In this method comparison study of hemoglobin A1c, we used the VITROS 5600 Integrated System (Ortho-Clinical Diagnostics, Rochester, New York) with a National Glycohemoglobin Standardization Program calibrated high-performance liquid chromatography method. Whole blood samples were automatically hemolyzed on the system, and the percentage of A1c was calculated from the measurements of hemoglobin and hemoglobin A1c.

Results: The method has a reportable range for hemoglobin, HbA1c, and percentage of A1c of 6.0 to 22.0 g/dL, 0.2 to 2.5 g/dL, and 4% to 14%, respectively, and has demonstrated linearity throughout the entire assay range. Within-run precision (n = 10) was evaluated using 2 levels of quality control materials (mean, 6.4; 11.9%) and yielded coefficients of variation of 1.6% and 1.8%. Between-day precision was evaluated with different quality control material (mean, 5.4; 9.2%) during a 20-day period using one reagent lot and yielded coefficients of variation of 1.4% and 3.4%, respectively. The accuracy of 53 patient samples ranging in concentration from 4.7% to 14.0% of A1c was tested by correlation of results from the Bio-Rad Variant II ion exchange high-performance liquid chromatography assay (Bio-Rad Laboratories, Hercules, California) and the VITROS assay. Deming regression analysis of the VITROS System versus high-performance liquid chromatography demonstrated a slope of 1.01 (95% confidence interval; range, 0.9485–1.071) with an intercept of −0.254 (95% confidence interval; range, −0.7245 to 0.2169).

Conclusions: The hemoglobin A1c assay on the VITROS System demonstrates rapid, precise, and accurate results for monitoring the percentage of HbA1c levels in patient samples.

Primary Sternal Cryptococcoma With Dissemination in a Human Immunodeficiency Virus–Negative Patient With Selective Idiopathic CD4-Positive T-Cell Lymphocytopenia (Poster No. 6)

Richard H. Siderits, MD1 (richard.siderits@gmail.com); Hong Bing Deng, MD, PhD1; Anup Hazra, MD1; Anamika Patel, MD3; Sujal Singh, RA1; Janusz Godyn, MD1; Osman Ouattara, CT(ASCP).2 Departments of 1Experimental Pathology and 2Cytopathology, Robert Wood Johnson University Hospital, Hamilton, New Jersey; and 3Department of Infectious Disease, Infectious Disease Affiliates of Hamilton, New Jersey.

This case study highlights the importance of considering idiopathic CD4-positive lymphocytopenia in nonimmunosuppressed, human immunodeficiency virus–negative patients who present with atypical fungal infections. Medical history was noncontributory for causes of immunosuppression. Findings included a cavitary sternal lesion. Chest x-ray was unremarkable, and human immunodeficiency virus remained negative. Biopsy of sternum showed granulation tissue with teardrop-shaped, budding yeasts. Culture confirmed Cryptococcus neoformans. Flow cytometry demonstrated selective CD4-positive lymphocytopenia with CD8-positive lymphocytes in the normal range. The patient was diagnosed with idiopathic primary sternal cryptococcoma within a background of CD4-positive lymphocytopenia. Treatment included amphotericin B lipid complex followed by oral fluconazole. Follow-up at 6 months showed persistent CD4-positive lymphocytopenia. The sternal lesion was also persistent. A second cryptococcal hip lesion was identified by computed tomography and was biopsied; results suggested chronic disseminated cryptococcosis with CD4-positive lymphocytopenia. The patient's T4 (helper) count has remained less than 60 cells per microliter for 6 months. Newer treatments may include interleukin 2 to restore T4 levels; prophylaxis for opportunistic infections remains the central treatment. The differential diagnosis may be complicated by false-negative serology in 60% of patients with local cryptococcal infection and by 80% cross-reactivity among blastomycosis, histoplasma, and cryptococcal antigens. CD4-positive lymphocytopenia in human immunodeficiency virus–negative patients with no other explanation for immunosuppression has been associated with opportunistic fungal infections. We believe this is the first reported case of primary sternal cryptococcoma in a patient with idiopathic CD4-positive lymphocytopenia. Idiopathic CD4-positive lymphocytopenia is likely underdiagnosed and should be considered in otherwise healthy patients with atypical fungal infections.

New Multiple Monoclonal Gammopathies Following Autologous Hematopoietic Stem Cell Transplantation in a Patient With Multiple Myeloma: Case Report and Review of Literature (Poster No 7)

Suqing Xie, MD, PhD1 (suqing_xie@yahoo.com); Masoud Ahmadmehrabi, MD1; Sreedhar Katragadda, MD2; Humayun Islam, MD, PhD1; Maria E. Aguero-Rosenfeld, MD.1 Departments of 1Pathology and 2Hematology & Oncology, Westchester Medical Center, Valhalla, New York.

Among treatment options for multiple myeloma, autologous hematopoietic stem cell transplantation (HSCT) is associated with an increased rate of complete remission and an increased rate of survival compared with conventional chemotherapy. HSCT is now considered a choice for patients who are newly diagnosed with multiple myeloma and who are younger than 65 years. We present a case of multiple myeloma in which the patient developed multiple monoclonal immunoglobulins following autologous HSCT. A 41-year-old man presented with anemia. Serum protein electrophoresis and immunofixation found a monoclonal immunoglobulin (Ig) G λ band. Morphology and flow cytometry of bone marrow confirmed the diagnosis of multiple myeloma (IgG λ monoclonal plasma cells expressing CD38, CD138, CD117, and negative for CD19). Two months after auto-HSCT, immunofixation showed 2 new monoclonal IgG κ bands, in addition to the original malignant IgG lambda band, and a significant decrease in total immunoglobulin. The most recent immunofixation (nearly 6 months after transplantation) showed the same pattern, with a slightly decreased intensity in the 2 extra bands; no lymphadenopathy was noted. Cytogenetics examinations showed no abnormality in bone marrow before or after transplantation. Paraproteinemia may appear in recipients of allogeneic bone marrow or other solid organ transplantation. The origin of immunoglobulin abnormality in these cases might be related to the development of graft-vs-host disease, Epstein-Barr virus and/or cytomegalovirus infection in donor or recipient, malignant lymphoproliferation (lymphoma) secondary to high-dose chemotherapy, or hyperproliferation of some immunosensitized B-cell clones among transfused cells during bone marrow reconstitution. The latter might be the mechanism in this transplant patient.

A Systemic Lupus Erythematosus Case With a Wide Spectrum of Autoantibodies and t(1;6)(q25;q23) Translocation (Poster No. 8)

Lei Zhang, MD, PhD1 (leizhang@hawaii.edu); Timothy Donlon, PhD, FACMG2; Stacey Honda, MD, PhD.31Department of Pathology, Hawaii Residency Program, Honolulu; 2Department of The Queen's Genetics Laboratories, Queen's Medical Center, Honolulu, Hawaii; and 3Department of Pathology, Kaiser Permanente Foundation Hospital, Honolulu, Hawaii.

Systemic lupus erythematosus is well known for being difficult to diagnose; diagnosis requires extensive clinical laboratory studies for evidence of autoimmune markers and organ damage. Genetic etiology of this disease also remains elusive. We report a case of a 49-year-old woman who presented with fatigue, shortness of breath for 1 month, and years of menorrhagia. After thorough workup, systemic lupus erythematosus was diagnosed. We detected a wide spectrum of autoantibodies, including antinuclear antibody, anti–double-strand DNA antibody, anti-Smith antibody, antineutrophil cytoplasmic antibody (pANCA and cANCA), antithyroid peroxidase antibody, anti–smooth muscle antibody, and serum warm antibody. These findings parallel the patient's condition, including damage to multiple organs, and highlight her body's loss of tolerance toward its own antigens. Blood cells are negative for JAK2 mutations. Cytogenetic analysis on bone marrow and phytohemagglutinin-stimulated blood cells both revealed a 46 XX, t(1;6)(q25;q23) translocation, which has never been seen in any kind of leukemia. Gene translocation is rarely described in systemic lupus erythematosus. Our case is the second report of systemic lupus erythematosus associated with a chromosome translocation.

A Comparison of HLA Crossmatching Methodologies (Poster No. 9)

Paul J. McGowan, MD (mcgowanpj@health.missouri.edu). Department of Pathology and Anatomical Sciences, University of Missouri–Columbia.

Context: The crossmatch is a vital test performed by the transplant or HLA laboratory. Basic/modified microcytotoxicity, anti-human globulin, and flow-based bead/microparticle assay/enzyme immunoassay crossmatching methods are the major techniques used.

Design: Using data collected from the College of American Pathologists' Proficiency Testing Surveys, we evaluated the relative sensitivities of these 3 major crossmatching methods, changes in sensitivities for each method during a 5-year period, and positive and negative predictive values for each method.

Results: We reviewed 11 College of American Pathologists' Proficiency Testing surveys (MX1 and MX2 surveys for 2003 and 2008) and analyzed 7959 major histocompatibility complex I crossmatches and 2203 major histocompatibility complex II crossmatches. The flow/enzyme method was the most sensitive method in the MX1 and MX2 surveys in both 2003 and 2008 (Table) and showed improved sensitivity during the 5-year period (MX1, P < .001; MX2, P < .001). The other methods showed no improvement or decreased sensitivity during the same period. The flow/ enzyme method had higher positive predictive values (87%–94%) than the other methods.

Conclusions: These results strongly suggest that laboratories and their transplant programs that rely on microcytotoxicity (direct, modified, or anti-human globulin–augmented) crossmatches may be missing a significant number of clinically significant HLA antibodies. Those laboratories and programs should consider more sensitive methods of antibody detection and crossmatching, such as flow-based bead/microparticle assay/ enzyme immunoassay crossmatch methods.

 
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Association Between Low Concentrations of Monoclonal and Oligoclonal Gammopathies and Chronic Illness (Poster No. 10)

Gaofeng Fan, MD, PhD1 (gfan@numc.edu); Min Guo, MD1; Michael Ang-Rabanes, MD2; Jen Lin, MD.11Department of Pathology, Nassau University Medical Center, East Meadow, New York; and 2School of Medicine, American University of Caribbean, St Maarten, Netherlands Antilles.

Context: We evaluated the significance of low levels of monoclonal and oligoclonal gammopathies in serum.

Design: We reviewed 393 patients of which 18 were typed by immunofixation as having a low concentration of monoclonal or oligoclonal bands in serum.

Results: Seven patients (C2, 42-year-old woman with IgG κ; C4, 76-year-old man with IgA λ; C6, 51-year-old woman with IgG λ; C7, 58-year-old man with IgM κ; C10, 80-year-old man with IgA λ; C11, 54-year-old woman with IgG λ; C17, 62-year-old woman with IgG κ) had hypertension, and 4 of these had associated diabetes mellitus (C4, C6, C10, C11). Six patients (C2; C3, 81-year-old woman with IgG κ; C4; C10; C16, 66-year-old man with IgA κ; and C18, 57-year-old man with IgM κ) had chronic kidney disease. Five patients (C1, 66-year-old woman with IgG κ; C3; C6; C9, 43-year-old man with IgM κ; and C15, 81-year-old woman with IgA κ) had sepsis. Seven patients had malignant tumors, including 3 with colon cancer (C4; C5, 60-year-old man with IgG κ; and C12, 60-year-old man with IgG κ), 1 (C13, 60-year-old woman with IgG κ and IgG λ) with chronic lymphocytic leukemia, 1 (C14, 55-year-old man with IgG κ) with tonsillar carcinoma, and 2 (C15 and C17) with myeloma.

Conclusions: It is plausible that chronic processes with long-standing reaction may have induced immunoglobulin modifications. Further studies should be implemented to correlate the relationship between specific concentrations of monoclonal immunoglobulins and chronic illnesses.

Contralateral Breast Cancers: A Population-Based Study (Poster No. 11)

Kristen A. Batich, BA1; Donald E. Henson, MD2 (patdeh@gwumc.edu); Arnold M. Schwartz, MD, PhD3; Stephen Patierno, PhD.21Office of Cancer Prevention and 2Cancer Institute, George Washington University, Washington, DC; and 3Department of Pathology, George Washington University Medical Center, Washington, DC.

Context: Breast cancers are typically unilateral; however, a small number of patients show metachronous contralateral second primary tumors. We investigated the pathologic parameters of first primary and second primary contralateral breast cancers.

Design: Using the Surveillance, Epidemiology, and End Results program (1973–2005), we analyzed data with multiple primary standardized incidence ratios. In situ and invasive cancers were selected. First primary and second primary contralateral cancers were analyzed by race, age, stage, size, and histology.

Results: There were 783 023 women with breast cancer identified with 16 157 (2.1%) having a second primary in the contralateral breast. 43.7% of blacks and 34.8% of whites had a second primary within 2 years. The average size of the second primary was 1.58 cm. Of all combinations of first and second primaries, blacks were concordant for lobular carcinoma and ductal carcinoma in 21% and 54.6% of cases, respectively; whites were concordant for lobular carcinoma and ductal carcinoma in 20.6% and 59.1% of cases, respectively. The mean ages of the first and second primaries in whites were 58.1 and 64.9 years, respectively. The respective mean ages for blacks were 51.9 and 56.9 years. Women with higher stage first primary cancers were more likely to have contralateral second primary tumors.

Conclusions: Often patients with a first primary develop a second contralateral cancer within 2 years. Based on doubling times, many second contralateral primaries were present at the time of the first. For all stages in blacks and whites, more than half the combinations of first and second primary histologic types were discordant.

Lobular Carcinoma In Situ With Pleomorphism and Lobular Carcinoma In Situ With Necrosis (Poster No. 12)

Megan E. Sullivan, MD1 (msulli7777@yahoo.com); Seema A. Khan, MD2; Barbara Susnik, MD, PhD.1 Departments of 1Surgical Pathology and 2Surgery, Northwestern University, Chicago, Illinois.

Context: Classic lobular carcinoma in situ (LCIS) is a risk marker for breast carcinoma (BC). Its variants, LCIS with necrosis (LCIS-N) and pleomorphic LCIS (LCIS-P), may exhibit more aggressive behavior. We examined clinical and immunohistochemical features of LCIS-N and LCIS-P diagnosed in needle core biopsy (CB).

Design: Core biopsies from January 2003 to August 2008 were reviewed, and 30 cases (LCIS-P, n = 19; LCIS-N, n = 11) met criteria. LCIS-P required pleomorphism and nuclear size greater than 3.5 times a lymphocyte in more than 10% of cells. LCIS-N required classic lobular cytology with necrosis. All were E-cadherin negative. Immunohistochemical panel included estrogen receptor (ER), HER2/neu, p53, and Ki-67. Clinical information was obtained.

Results: LCIS variants represented 0.34% (30 of 8712) of all CBs. Average age was 55 years (range, 41–78 years). Seven (23%) patients had a family history, and 8 (31% of LCIS-P and 18% of LCIS-N) had a personal history of BC. Six LCIS-P and 1 LCIS-N were associated with a mass; the remainder were associated with calcifications. Forty percent (12 of 30) of variant LCIS had associated invasive lobular carcinoma (ILC) in either CB or SE, with 58% (7 of 12) staged as T1mic. Twenty-five percent of LCIS variants detected in CB were upstaged in SE: 14% (2 of 14) of LCIS-P and 40% (4 of 10) of LCIS-N.

Conclusions: LCIS variants are often associated with ILC, suggesting they act as direct precursors to BC. LCIS-P can exhibit an unfavorable biomarker profile (high Ki-67, ER negative, p53 positive, and HER2/neu positive), a feature not present in LCIS-N. As 25% of LCIS variants diagnosed in CB are upstaged in SE, complete excision of these lesions is mandatory.

 
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D2-40 Increases Detection of Lymphatic Invasion in Breast Carcinoma (Poster No. 13)

Kyle L. Eskue, MD (kleskue@utmb.edu); Mahmoud Eltorky, MD, PhD; Basim Mohammed, MD. Department of Pathology, University of Texas Medical Branch, Galveston.

Context: Detection of lymphatic invasion is an important component of complete histopathologic evaluation of primary breast carcinoma for accurate determination of prognosis and management. In addition to the potential for missing lymphatic invasion, another problem occurs when artifactual tissue retraction around tumor (false lumen) is confused with true lymphatic invasion. We hypothesized that using D2-40 antibody, a sensitive marker for lymphatic endothelium, can increase the sensitivity of detecting true lymphatic invasion in breast carcinoma, thus helping to identify patients at higher risk for metastatic disease.

Design: Sixteen cases of lymph node–positive invasive breast carcinoma (14 ductal and 2 lobular) from 2003 to 2007 were retrospectively collected from our institutional archives. In the original pathology reports, all cases were negative for lymphovascular invasion within hematoxylin-eosin–stained tissue sections. Original slides from the cases were reviewed to confirm the study's inclusion criteria were met, and tissue blocks were selected for D2-40 immunostaining. The original hematoxylin-eosin– stained and D2-40–stained slides were reviewed independently by 2 pathologists. Only cases with unequivocal tumor emboli within positively stained, endothelial-lined, lymphatic vessels were counted as positive.

Results: Four of 16 (25%) cases showed definitive lymphatic invasion within tissue sections that were previously unidentified by hematoxylin-eosin–stained slides alone.

Conclusions: Using D2-40 immunostain on selective tumor sections may increases the diagnostic sensitivity of lymphatic invasion detection in cases of primary breast carcinoma. This study demonstrates the usefulness of D2-40 immunostain as a tool to confirm or reject suspected foci of lymphatic invasion that are questionable in hematoxylin-eosin–stained slides.

Optimal Cutoff Values of Ki-67 as a Proliferative Marker in Breast Cancer (Poster No. 14)

Oluyomi Asojo, MD (asojooa@ucmail.uc.edu); Fred Lucas, MD; Jiang Wang, MD. Department of Pathology and Laboratory Medicine, University of Cincinnati, Ohio.

Context: Proliferative activity of tumor cells is usually associated with biologic behavior in breast cancer. Ki-67 is the most commonly used proliferative marker; however, no consensus on optimal cutoff values has been defined. Current Ki-67 cutoff values vary in the literature, and this may affect prognosis and management. We attempt to evaluate the correlation among Ki-67 positivity and tumor grade, estrogen receptor, progesterone receptor, and HER2/neu status and to establish rational cutoff values for Ki-67.

Design: We retrospectively reviewed 75 cases of breast carcinoma, including Ki-67, estrogen receptor, progesterone receptor, and HER2/neu data. Immunohistochemical stains were performed following the vendor's protocols. The Ki-67 positivity cutoff groups were <10%, 10% to 20%, >20%, and <10%, 10% to 29%, and >30%.

Results: Fifty-three percent of tumors in the low proliferative Ki-67 group of <10% were grade 1 tumors. Fifty-two percent of tumors with Ki-67 values of 10% to 20% were grade 2 tumors, and 55% of cases with values >20% were grade 3 tumors. At a cutoff value of >30%, 27% of grade 2 and 28% of grade 1 tumors were excluded from the high proliferative group. All grade 3 tumors were in this high proliferative group.

Conclusions: Our study suggests that Ki-67 cutoff values of <10%, 10% to 29%, and >30% are more closely associated with histologic grade and, therefore, may be more representative of low, intermediate, and high proliferative activity. Ki-67 positivity is not associated with estrogen receptor, progesterone receptor, or HER2/neu status. Further studies with a larger number of cases and correlation of Ki-67 positivity with prognosis are required.

The Role of Fibrinolytic Proteins in Angiogenesis and Tumor Progression (Poster No. 15)

Joseph A. Whitten, MD1 (jwhitten@drexelmed.edu); Andrew Keibel, BS2; Mahesh C. Sharma, PhD.2 Departments of 1Pathology and 2Surgery, Drexel University College of Medicine, Philadelphia, Pennsylvania.

Context: Angiogenesis, an essential component of tumor progression, has been studied by various methods. One method is to look for the proteases and protease inhibitors produced in the growth and elongation of existing vessels; another is to look for endothelial cell markers. We used both methodologies to prove that angiogenesis was occurring and to identify the specific sites of angiogenesis in and around mammary carcinoma.

Design: Clinical history, histopathology, and immunohistochemistry results were reviewed for 11 women (range, 41–87 years) with breast cancer who were diagnosed and treated at Hahnemann University Hospital (Philadelphia, Pennsylvania).

Results: Tissue plasminogen activator and annexin II staining were present in both tumor and proximal surrounding tissue, confirming the presence of protease and fibrinolytic/antifibrinolytic protein receptor–regulated steps that are specific to angiogenesis. Additionally, CD105 (endoglin) antibody selectively stained the endothelial cells of angiogenic blood vessels within and adjacent to tumors (Figure 18). Tissue uninvolved by tumor did not show positive staining, thereby serving as an internal control.

Conclusions: Invasive mammary carcinoma and adjacent desmoplastic tissue showed an increased concentration of fibrinolytic proteins and an upregulation of the binding site for proteases and antiproteases. This area of increased fibrinolysis coincides with the area containing blood vessels that stained for CD105, a marker of endothelial cells undergoing angiogenesis. These findings make a strong argument for the existence of the fibrinolytic/antifibrinolytic mechanism of tumor-induced angiogenesis. Of interest, the finding of CD105-positive blood vessels in desmoplastic stroma suggests that the tumor is priming the blood vessels beyond its periphery for local expansion.

Dr. Sharma received a Department of Defense grant (No. W912596357-N608) in support of this research.

A Rare Case of Bilateral Multinodular Pseudoangiomatous Stromal Hyperplasia in a Patient With Gigantomastia (Poster No. 16)

Douglas A. Larsen, MD (dalarsen@swmail.sw.org); William L. Neumann, MD; Lisa M. Lopez, MD. Department of Pathology, Scott & White Hospital and Texas A&M Health Science Center, Temple.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign breast lesion composed of dense collagenous stroma with complex, anastomosing, empty, slitlike pseudovascular spaces that are either acellular or lined by spindled stromal cells. Its appearance mimics a vascular lesion, including angiosarcoma. PASH is usually seen as incidental microscopic foci in normal breast tissue or in association with various benign and malignant breast lesions. Occasionally, it can present as a distinct lesion, either in a diffuse pattern or as a unilateral discrete nodule (nodular PASH). Grossly, the nodule is indistinguishable from fibroadenoma, ranging from 1 to 17 cm. Reports of nodular PASH are rarely present in the literature, and even fewer cases of bilateral nodular PASH are described. We report a case of bilateral multinodular PASH in a 42-year-old woman who has a long history of gigantomastia with progressive enlargement and who has elected to undergo bilateral reduction mammoplasty.

CD1A Expression in Poorly Differentiated Estrogen Receptor– and Progesterone Receptor–Negative Invasive Ductal Carcinoma of the Female Breast (Poster No. 17)

Marlene Gallegos, MD (marlene_gallegos@rush.edu); Paolo Gattuso, MD; Kalliopi P. Siziopikou, MD, PhD; Vijaya B. Reddy, MD. Department of Pathology, Rush University Medical Center, Chicago, Illinois.

Context: Recent studies suggest that primary invasive female breast carcinomas with positive estrogen receptor (ER) and progesterone receptor (PR) have greater dendritic cell infiltration; these patients may also have a better prognosis.

Design: Our study population consisted of patients diagnosed with ER- and PR-negative poorly differentiated invasive ductal carcinoma at Rush University Medical Center between 1975 and 1988. Two distinct groups of patients were compared: group 1 consisted of 16 women who were alive and free of disease for an average of 14 years. Group 2 consisted of 20 women who died of disease within 3 years of diagnosis. The 2 groups were matched for clinical stage and ER/PR receptor status. The following breast cancer marker profile was obtained for all patients: ER (Dako), PR (Dako), and CD1A (Dako).

Results: The average age of group 1 patients was 52.4 years (range, 31– 74 years). The average age of group 2 patients was 52.6 years (range, 34– 80 years). Evaluation of CD1A did not show a difference between the groups: (group 1, 1 of 16; 8%) versus (group 2, 2 of 20; 10%). CD1A expression was observed in dendritic and tumor cells.

Conclusions: Similar expression of CD1A-positive cells was seen in patients with short- and long-term survival. Strong correlation was found between no expression and/or low expression of CD1A-positive cells and ER- and PR-negative tumors. Tumor cells also expressed CD1A, suggesting a possible costimulatory effect by this molecule on the functional immune response. In patients with ER- and PR-negative invasive breast carcinoma, lack of expression or low expression of CD1A does not appear to predict survival.

Tissue-Specific Expression of Estrogen Receptor-β Wild Type and Isoforms (Poster No. 18)

Young Choi, MD (young.choi@yale.edu). Department of Pathology, Yale University School of Medicine, Bridgeport, Connecticut.

Context: Estrogen receptor-β (ER-B) has been mostly studied in breast and some prostate cancers and has been shown to be associated with prognosis. We tested ER-B wild type (wt) and its isoforms in different tissues to further elucidate tissue- and cell-specific expression of ER-B.

Design: Tissue microarray slides of 130 normal and 260 malignant tissues from 13 different organs were tested for ER-Bwt (Biogenex, San Ramon, California), 2 clones of ER-B1 (Dako, Carpinteria, California and AbD Serotec, Raleigh, North Carolina), ER-B2 (AbD Serotec), ER-BCT (Upstate, Lake Placid, New York), ER-B NT (Millipore, Billerica, Massachusetts), and ER-A (Dako) using immunohistochemistry procedures. Nuclear staining less than 5% was considered negative.

Results: ER-Bwt and isoforms were detected in nuclei and/or cytoplasm. In normal tissues, ER-Bwt was expressed in 93% (12 of 13) of the organs in the range of 60% to 90% in breast, stomach, kidney, thyroid, endometrium, bladder, pancreas, prostate, brain, and ovary and less than 10% in lung and colon. Hepatocytes showed only cytoplasmic reaction. ER-B1 and ER-B2 isoforms were expressed heterogenously in only 46% (5 of 13) of the organs. In neoplastic tissues, expression of ER-Bwt, ER-B1, and ER-B2 was decreased in colon, kidney, endometrium, brain, and pancreas and increased in stomach, lung, and ovary. ER-B and ER-A were coexpressed in 30% of normal and malignant endometrium, brain, and ovary tissues.

Conclusions: ER-B is expressed in many normal tissues but variably in neoplastic tissues. ER-B may play a stimulatory or suppressive role in tumorigenesis. Testing ER-B in different tissues may provide further insights on ER-B in tumorigenesis.

Lupus Mastitis: An Unusual and Underrecognized Entity (Poster No. 19)

Chris Kinonen, MD (christopher_kinonen@rush.edu); Paolo Gattuso, MD; Vijaya Reddy, MD. Department of Pathology, Rush University Medical Center, Chicago, Illinois.

Lupus panniculitis is an infrequent manifestation of systemic lupus erythematosus, occurring in approximately 2% to 3% of patients. Up to 70% of patients with lupus panniculitis have discoid lesions. Lupus mastitis (LM) is a rare manifestation of lupus panniculitis involving the breast, and it clinically and radiologically mimics carcinoma. Approximately 20 cases of LM have been reported in the literature. We add 2 additional cases with clinical and radiologic findings suspicious for malignancy. The first patient is a 58-year-old African American woman who was diagnosed with systemic lupus erythematosus in 1995. In July 2005, a firm, palpable mass was discovered in the right upper breast. Mammography showed a 2.6-cm, hazy, ill-defined, soft tissue density that was suspicious for malignancy. An excisional biopsy showed a nodular, angiocentric, and angioinvasive lymphoid infiltrate involving fat lobules with associated hyaline fat necrosis and was diagnostic of lupus panniculitis. The patient was started on Plaquenil and showed improvement in her symptoms; however, in November 2006, a new firm, palpable mass was discovered in her left breast. An excisional biopsy again showed LM. The second patient is a 52-year-old African American woman with a diagnosis of discoid lupus. Mammography and ultrasound in November 2008 revealed 2 suspicious left breast masses with associated microcalcifications and an enlarged axillary lymph node. The masses were excised and showed changes diagnostic of LM. LM has characteristic histologic findings but clinically mimics malignancy and, therefore, necessitates tissue biopsy. LM should be considered in the differential diagnosis of breast masses in patients with lupus.

Low-Grade Adenosquamous Carcinoma of the Male Breast (Poster No. 20)

Xiaohong I. Wang, MD1 (zwang@lsuhsc.edu); Charn Nopajaroonsri, MD.21Department of Pathology, Louisiana State University, Shreveport; and 2Department of Pathology, Overton Brooks VA Medical Center, Shreveport, Louisiana.

Low-grade adenosquamous carcinoma of breast is an uncommon neoplasm in women and is exceedingly rare in men. In the literature, we found only one reported case of low-grade adenosquamous carcinoma in a man. This tumor is known for local recurrence after incomplete excision but also has low metastatic potential. Histologically, the tumor is composed of syringoma-like glandular structures with variable amounts of squamous differentiation in a background of bland spindle cell stroma. Due to its characteristically bland histopathology, this tumor is often confused with infiltrating syringoma of the nipple and tubular carcinoma of breast. We report a case of a 73-year-old man who presented with a 2-cm subareolar left breast hard nodule with increased size and tenderness. Biopsy of the mass revealed the tumor, which was made up of multiple irregular ducts, many of which were curved, commalike, and irregularly dilated (Figure 19). They were lined by 2 rows of epithelium and squamous cells. The epithelial cells showed bland nuclear morphology. Ductal structures and squamous cell nests were seen infiltrating the muscle bundles of nipple and underlying breast and fibroadipose tissue. Following radical mastectomy, the axillary lymph nodes were negative for metastatic carcinoma. The tumor was positive for HER2/neu and negative for p53. This study reports a rare example of low-grade adenosquamous carcinoma arising in a male breast. The histopathology of the present tumor is similar to that seen in low-grade adenosquamous carcinoma occurring in the female breast.

The Expression of Leptin, Polo-like Kinase-1, and HMG-CoA Reductase in Human Carcinomas and Sarcomas (Poster No. 21)

Ashish Barman, MD1 (abarman@mcvh-vcu.edu); Tina Ipe, BA2; Katherine Kimmelshue, MD1; Michael Idowu, MD.11Department of Pathology and 2School of Medicine, Virginia Commonwealth University, Richmond.

Context: Leptin (Lep/Ob), polo-like kinase-1 (PLK1), and HMG-CoA reductase inhibitors (statins; HMGCR inhibitors) have been reported as possible risk factors for cancer incidence, cancer aggressiveness, and cancer-lowering effects, respectively, according to studies using cell lines and epidemiologic studies. There is limited information regarding the expression of these proteins in clinical specimens. This study evaluates the differential expression of these proteins in clinical specimens using immunohistochemistry.

Design: Immunohistochemical stains were performed on 41 randomly selected cases of invasive breast carcinoma with adjacent benign breast and 10 cases of sarcoma using paraffin-embedded tissue with antibodies to Ob, PLK1, and HMGCR (Santa Cruz Biotechnology, Inc, California). Two pathologists evaluated the stains for intensity and cell staining percentage. Cases exhibiting moderate to intense staining with at least 10% positivity were interpreted as positive. χ2 statistical analysis was used.

Results: There was no significant difference between benign breast versus breast carcinoma with Ob (10% vs 24%; P = .08), HMGCR (54% vs 63%; P = .37), and PLK1 (7% vs 12%; P = .46). There was no differential expression between breast carcinoma and sarcoma with Ob (24% vs 40%; P = .32) and HMGCR (63% vs 80%; P = .32); there was differential expression with PLK1 (12% vs 50%; P = .007) (Fisher exact test).

Conclusions: The lack of differential expression of Ob, PLK1, and HMGCR in benign breast and carcinoma suggests that these proteins may not be clinically useful for diagnostic purposes. The apparent differential expression of PLK1 between carcinoma and sarcoma may benefit from further studies.

Intraoperative Frozen Section on Sentinel Lymph Nodes Is Not Indicated in Patients With Ductal Carcinoma In Situ of the Breast or in Those Undergoing Prophylactic Mastectomy (Poster No. 22)

Jaya Mahajan, MD (jmahajan@nshs.edu); Sheng Chen, MD, PhD. Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, New York.

Context: The appropriateness and cost-effectiveness of routine intraoperative sentinel lymph node (SLN) assessment remains to be defined. We aim to determine whether routine intraoperative frozen section (FS) examination of SLNs is worthwhile in all patients undergoing surgery for breast cancer.

Design: We conducted a retrospective study, reviewing 184 consecutive cases of SLN biopsy performed by a single experienced breast surgeon in 2007 with attention to variations by histologic subtype and tumor size. This number included 91 invasive ductal carcinomas, 22 invasive carcinomas with mixed lobular-ductal features, 19 invasive lobular carcinomas, 18 ductal carcinomas in situ, and 34 prophylactic mastectomies. All patients underwent SLN biopsy with intraoperative FS evaluation. The nodes negative on FS were further subjected to an enhanced histopathologic evaluation protocol with 3 levels of routine hematoxylin-eosin–stained sections and 3 levels of immunocytochemical-stained sections using pancytokeratin antibody (AE1/AE3).

Results: The overall sensitivity of intraoperative FS of SLNs was 66%. The intraoperative FS of SLNs was negative for all cases of ductal carcinoma in situ and prophylactic mastectomies. Of 46 cases with invasive breast cancer smaller than 1.0 cm, only 2 (4.3%) cases were found to be positive on intraoperative FS.

Conclusions: Intraoperative FS of SLNs is not worthwhile for patients with ductal carcinoma in situ or for those undergoing prophylactic mastectomy. Whether intraoperative FS of SLNs should be performed on patients with early (smaller than 1.0 cm) invasive tumors will be discussed. An effort to expand the study by increasing the number of cases is currently underway.

Laboratory Compliance With the American Society of Clinical Oncology and College of American Pathologists' Guidelines for HER2 Testing: A College of American Pathologists Survey of 757 Laboratories (Poster No. 23)

Raouf E. Nakhleh, MD1 (Nakhleh.Raouf@mayo.edu); Erin E. Grimm, MD2; Rhona Souers, MS3; Patrick L. Fitzgibbons, MD.41Department of Pathology, Mayo Clinic Florida, Jacksonville; 2Department of Pathology, University of Washington, Seattle; 3Department of Statistics, College of American Pathologists, Northfield, Illinois; and 4Department of Pathology, St Jude Medical Center, Fullerton, California.

Context: To ensure quality HER2 testing in breast cancer, the ASCO/ CAP introduced guidelines with the intent of compliance by 2008. We conducted this survey to assess the effect of these guidelines on pathology laboratories and their ability to address key components.

Design: In late 2008, the survey was distributed with the HER2 immunohistochemistry (IHC) proficiency testing program. It included questions regarding institutional and pathology practice characteristics, assay validation using fluorescence in situ hybridization (FISH) or another IHC laboratory test, and pathologist HER2 scoring competency assessment.

Results: We received 757 of 907 surveys. The median laboratory accessioned 15 000 cases and annually performed 190 HER2 tests. Quantitative computer image analysis was used by 33% of laboratories. In-house FISH was performed in 23% of laboratories. Sixty percent of laboratories addressed the 6- to 48-hour tissue fixation requirement by embedding tissue on the weekend. HER2 testing was performed on the initial biopsy in 40% of laboratories; on the resection specimen in 6%; and either in 56%. Forty-seven percent of laboratories validated with FISH only, 10% with another IHC test only, 13% with both; 12% had not validated; 15% chose “not applicable,” Ninety percent concordance rate with FISH results was achieved in 88% IHC-negative and 81% IHC-positive cases. Ninety percent concordance rate with another IHC test was achieved in 80% negative and 75% positive cases. Ninety-one percent of laboratories had a pathologist competency assessment program.

Conclusions:  This survey demonstrates the extent and characteristics of HER2 testing. Although some ASCO/CAP guidelines have been implemented, gaps remain in validation of HER2 IHC testing.

Intraoperative Axillary Sentinel Lymph Node Evaluation: False-Negative Rate in Neoadjuvant Versus Nonneoadjuvant Cases (Poster No. 24)

Michael O. Idowu, MD, MPH (midowu@mcvh-vcu.edu); Celeste N. Powers, MD, PhD. Department of Pathology, Virginia Commonwealth University Health System/Medical College of Virginia Hospitals, Richmond.

Context: The false-negative (FN) intraoperative interpretation for sentinel lymph nodes may increase the health care cost due to delayed completion axillary dissection. This study evaluates the rates of FN, true positive, true negative, and false positive in patients with and without prior neoadjuvant treatment and compares the differences in the rates for cases evaluated using tumor imprint cytology (TIC) versus TIC and/or frozen section.

Design: We reviewed 174 consecutive cases with intraoperative evaluation of axillary sentinel lymph nodes using both TIC and/or frozen section. The rates of FN, true positive, true negative, and false positive were determined by correlation with permanent hematoxylin-eosin sections. Completion axillary dissection, if performed, was also reviewed.

Results: Thirty-one (17.8%) had neoadjuvant treatment, while 82.2% did not have neoadjuvant treatment (Table). One hundred thirty-three (76.4%) cases were evaluated by TIC only, while 23.6% were evaluated by TIC and/or frozen section (4 cases were evaluated by FS only). There was no false-positive intraoperative diagnosis. Of the 22 total FN, 40.9% had metastasis on permanent hematoxylin-eosin sections larger than 2 mm, while 59.1% had isolated tumor cells (13.6%) and micrometastasis (45.5%). For cases with completion axillary dissection, only 7.1% of the FN intraoperative diagnosis had additional positive lymph nodes, compared with 64% in patients with a true-positive intraoperative diagnosis.

Conclusions: The relatively higher rate of FN in patients with prior neoadjuvant treatment may be due to treatment-induced fibrosis. There appears to be a low chance of additional positive lymph nodes on completion axillary dissection with a FN intraoperative diagnosis.

 
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Discordance Between the Immunohistochemical (Estrogen Receptor, Progesterone Receptor and HER2/neu) Characteristics in Primary Breast Cancer Versus Axillary Lymph Node Metastases: Should Lymph Node Metastases Be Retested? (Poster No. 25)

Salman B. Ayub, MD1 (salman.ayub@danhosp.org); Steven Sieber, MD1; Juan Merayo-Rodriguez, MD1; Kilak Kesha, MD1; Junaid Baqai, MD1; John Pezzimenti, MD.2 Departments of 1Pathology and 2Medicine (Oncology), Danbury Hospital, Danbury, Connecticut.

Context: Patients with stage III breast carcinoma and similar hormone receptor and HER2 gene product status by immunohistochemistry may respond differently to similar therapeutic regimens. The therapy is generally based on the immunohistochemical features of the primary breast tumor, and the metastatic axillary lymph nodes are never tested. We hypothesize that discordance in the immunohistochemical features between the primary tumor and the axillary lymph node metastases might explain different clinical responses to hormonal treatment and/or chemotherapy. In previously published studies, the discordance varied from 0% to 14% for HER2 and from 15% to 37% for estrogen receptor and progesterone receptor.

Design: Danbury Hospital's electronic medical records from the last 2 years were searched to find patients with surgical excisions of primary breast carcinoma and axillary lymph node metastases by axillary lymph node dissection and/or sampling. Only patients who had not received any adjuvant treatment before surgery were included. The paraffin blocks of axillary lymph node macrometastases were retrieved, cut, and stained for estrogen receptor, progesterone receptor, and HER2/neu by immunohistochemistry, and the results were compared with those for the previously stained primary breast carcinomas.

Results: Twenty-nine patients with the previously described tissues were available for study. Discordance percentages were calculated, and a 95% Fisher exact confidence interval was created for each discordance proportion (Table).

 
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Conclusions: Discordance was found for all 3 immunohistochemical markers; the highest was for estrogen receptor (13.8%). Prospective studies with larger sample sizes are needed to establish statistical significance and the possible need to test both the primary and metastatic tumor prior to making treatment decisions.

Protean Manifestations of Amyloidosis of the Breast in Core and Mammotome Biopsy Specimens (Poster No. 26)

Liron Pantanowitz, MD (Liron.pantanowitz@bhs.org); Giovanna M. Crisi, MD, PhD; Christopher N. Otis, MD; Robert A. Goulart, MD. Department of Pathology, Baystate Medical Center/Tufts University School of Medicine, Springfield, Massachusetts.

Context: Core and mammotome breast biopsy (C/M Bx) are presently the primary techniques for initial sampling of most mass lesions and suspicious calcifications. Prior studies of breast amyloidosis (BA) involved primarily excisional specimens. We report our experience with the manifestations of BA within C/M Bx.

Design: An 11-year retrospective search of our pathology archives was conducted for cases with BA identified in C/M Bx. Cases were evaluated with hematoxylin-eosin, Congo red stain, and electron microscopy (1 case). We analyzed clinical findings and subsequent follow-up.

Results: We identified 4 patients with BA in C/M Bx, representing 0.05% of 8170 patients with C/M Bx reviewed during this 11-year period. All patients were women with a mean age of 60 years (range, 49–73 years). BA was unilateral in 2 patients and bilateral in 2 patients. Amyloid distribution was as follows: stromal, perivascular, and/or periductal/perilobular. In 2 patients, BA was associated with infiltrating and/or in situ ductal carcinoma; one case had subsequent documentation of systemic amyloidosis (primary AL κ). One patient had a benign amyloid tumor and serum IgG λ electrophoretic band. The remaining patient had BA associated with a giant cell histiocytic reaction and microcalcifications.

Conclusions: BA may present as a mass lesion, nidus for suspicious calcifications, or in association with infiltrating and/or in situ carcinoma. Its presence within C/M Bx is rare (less than 0.1% of all cases). In limited core material, BA may be misinterpreted as fibrosis or elastosis. Recognition in C/M Bx is critical due to the potential for systemic involvement and/or sinister autoimmune or lymphoproliferative disorders.

MRE11, RAD50, and NBS1 Gene Expression in Breast Cancer Progression (Poster No. 27)

Katherine N. Kimmelshue, MD1 (kkimmelshue@mcvh-vcu.edu); Elizabeth R. Fraley, BSc2; Luciana B. Gentile, PhD2; Nitai D. Mukhopadhyay, PhD3; Michael O. Idowu, MD1; Aylin Rizki, PhD.2 Departments of 1Pathology, 2Radiation Oncology, and 3Biostatistics, Virginia Commonwealth University, Richmond.

Context: MRE11, RAD50, and NBS1 comprise the MRN protein complex involved in DNA double-strand break repair and are reportedly downregulated in invasive breast carcinoma. We compare MRN levels in benign breast tissue, carcinoma in situ, and invasive carcinoma.

Design: Western blot analysis was performed on HMT-3522 cell lines (benign S1, preinvasive S3-C, invasive T4-2 cells) grown in 2- and 3-dimensional cultures. Forty-seven randomly selected cases of invasive breast carcinoma with adjacent in situ tumor and benign epithelium were immunohistochemically stained with antibodies to MRE11, RAD50, and NBS1 (BD Biosciences, San Jose, California). Two pathologists independently scored nuclear staining, using a 0 to 3 scale (negative to strongly positive). Cohort analysis was performed to compare staining between tissue types using a linear model with the tissue type and pathologist as explanatory variables. Variance component due to tissue type was tested using F-distribution (SAS Software, Cary, North Caroline). A P value of .01 or less was considered significant.

Results: Western blot analysis showed MRN protein levels decreasing progressively between S1, S3-C, and T4-2 cells (Figure 20). There were significant differences in expression between benign and in situ, in situ and invasive, and benign and invasive tissues for all 3 proteins (P < .01), except for NBS1 when comparing in situ with invasive (P = .07) at 1% significance level and adjusted for interobserver variability.

Conclusions: These findings suggest the MRN complex is progressively downregulated from benign epithelium to in situ and invasive breast carcinoma, indicating that lack of DNA repair is probably involved in the progression of breast cancer.

Reevaluation of Diagnostic Value of p120 Catenin in Differentiating Lobular Carcinoma From Low-Grade Ductal Carcinoma of the Breast (Poster No. 28)

Haiyan Liu, MD (hliu1@geisinger.edu); JianHui Shi, MD, PhD; Yiran Xu, BS; Jeff Prichard, MD; Fan Lin, MD, PhD. Department of Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania.

Context: The confirmation of lobular carcinoma is usually based on negative E-cadherin staining. A recent study reports that p120 catenin is a sensitive and specific positive marker for lobular carcinoma, with strong and diffuse cytoplasmic staining. To our knowledge, there are few follow-up published studies.

Design: Forty-four cases of invasive lobular carcinoma (ILC) and 26 cases of low-grade invasive ductal carcinoma (IDC) were included in this study. Eighteen of 44 ILC cases also contained lobular carcinoma in situ. All ILC cases were negative for E-cadherin, and all IDC cases were positive for E-cadherin. Most cases (n = 65) also contained normal breast tissue. Immunohistochemical staining was performed with monoclonal antibody to p120 catenin (clone 98; 1:200 dilution; BD Biosciences, San Jose, California). The staining intensity was graded as weak, moderate, or strong. The distribution was recorded as negative, 1+, 2+, 3+, and 4+.

Results: All ILC cases were positive for p120 catenin, with strong and diffuse cytoplasmic staining (greater than 3+) in 34 of 44 (77%) cases and moderate to weak staining in 10 (23%) cases. All IDC cases were positive for p120 catenin, with strong and diffuse membranous staining (greater than 3+) in 22 of 26 cases. Four IDC cases showed focal (1+ or 2+) and weak membranous staining.

Conclusions: Our data show that p120 catenin is useful in differentiating ILC from IDC. However, caution should be taken: Twenty-three percent of ILCs showed moderate to weak cytoplasmic and membranous staining, and a small portion of IDCs showed only focal and weak membranous staining.

Neonates and Fetuses With Intrauterine Growth Restriction: Placental Correlates: A Review of 22 Cases (Poster No. 29)

Vinay Prasad, MD (vinay.prasad@nationwidechildrens.org); Latha Urs, MD; Emily Chenever, MS; Anna Hughes, MS; Peter Baker, MD; Bonita Fung, MD; Kathleen Nicol, MD; Sue Hammond, MD. Department of Pathology, Nationwide Children's Hospital, Columbus, Ohio.

Context: Intrauterine growth restriction is often encountered and implies fetal growth is limited by one or several pathologies. Intrauterine growth restriction may be due to infection, aneuploidy, genetic disorders, or uteroplacental vascular insufficiency. We reviewed placental and autopsy pathology of 22 cases.

Design: Twelve of 22 neonatal intensive care unit babies were small for gestational age. Gestational age ranged from 14 to 38 3/7 weeks. We examined placentas for these features: (1) ischemia: increased intervillous and perivillous fibrin, increased syncytiotrophoblast knotting, infarcts, massive perivillous fibrin deposition (MFD), hypercapillarization, and increased nucleated erythrocytes; (2) inflammation: maternal inflammatory response (MIR), fetal inflammatory response (FIR), villitis, and intervillositis; (3) umbilical cord (UC) abnormalities: hypercoiling, hypocoiling, stricture, and insertion anomaly; (4) others: intraplacental hematoma, villous stromal mineralization (VSM), villous maldevelopment, and chorangiosis.

Results: Ischemia was noted in all cases. Results were as follows: MIR (13 of 22) with grade 2 or worse chorioamnionitis (7 of 13), FIR (4 of 22), villitis (3 of 22), hypercoiled UC (4 of 22), hypocoiling (1 of 22), UC hemangioma (1 of 22), velamentous UC insertion (1 of 22), UC stricture (1 of 22), lack of physiologic conversion of vessels (1 of 22), distal villous hypoplasia (2 of 22), MFD (2 of 22), VSM (5 of 22), and abruption (2 of 22). Results for autopsied cases were as follows: diffuse cerebral gliosis (4 of 10), germinal matrix hemorrhage (1 of 10), and complex congenital cardiac defects (3 of 10). Nine cases had cytogenetic analyses: normal 46,XY karyotype (5 of 9); 69,XXX (2 of 9); 45,X Turner (1 of 9); and del 1p36; dup 4q35.2 (1 of 9).

Conclusions: Placentas in intrauterine growth restriction showed significant pathology. Ischemia and inflammation (90%) and UC abnormalities (36%) were noted. Placental examination in all neonatal intensive care unit babies is vital.

Detection of Chromosomal Anomalies in Uterine Endometrial Carcinoma Using Fluorescence In Situ Hybridization (UteroFISH) (Poster No. 30)

Junqi Qian, MD; Deena Weber, MS; Richard C. Cochran, MD; Deloar Hossain, MD; David G. Bostwick, MD, MBA (mmcdonald@bostwicklaboratories.com). Bostwick Laboratories, Glen Allen, Virginia.

Context: Endometrial cancer is the most common pelvic gynecologic malignancy. The diagnosis of well-differentiated endometrial adenocarcinoma, atypical hyperplasia, and marked hyperplasia is often challenging. We investigated the utility of chromosomal anomalies for the detection of endometrial carcinoma using multitarget fluorescence in situ hybridization (FISH).

Design: Samples were collected by endometrial brush and processed by liquid-based thin-layer cytologic preparation protocol. We collected samples from consecutive cases to include 50 benign, 50 hyperplasia without atypia, 50 atypical hyperplasia, and 50 endometrial cancers. Each was hybridized using fluorescence labeled DNA probes to chromosomes 1, 8, and 10 (UteroFISH). FISH signals were enumerated in 100 cells per case, and the chromosomal anomalies were correlated with pathologic findings, including histologic diagnoses on endometrial tissue samples.

Results: Numeric chromosomal anomalies were found in 0% (0 of 50) of benign, 20% (10 of 50) of hyperplasia, 76% (38 of 50) of atypical hyperplasia, and 86% (43 of 50) of carcinoma specimens. The mean percentage of cells with chromosomal changes was 54% in cancer specimens, which was significantly higher than in nonatypical hyperplasia (13%, P < .001) and atypical hyperplasia (34%, P < .001). The most frequent chromosomal anomaly was gain of chromosome 1. FISH anomalies had an overall sensitivity of 81% and specificity of 90% for the detection of atypical hyperplasia and/or endometrial carcinoma. There was no association with grade of endometrial carcinoma.

Conclusions: Multitarget UteroFISH appeared to be useful for the differential diagnosis of reactive hyperplasia, atypical hyperplasia, and endometrial adenocarcinoma, showing a high level of sensitivity and specificity. Endometrial hyperplasia with chromosomal anomalies may require close follow-up.

Malignant Mixed Müllerian Tumor of the Cervix: Case Report and Review of Literature (Poster No. 31)

Ioan C. Cucoranu, MD1 (icucoranu@usouthal.edu); Michael A. Finan, MD2; Carole W. Boudreaux, MD.1 Departments of 1Pathology and 2Obstetrics and Gynecology, University of South Alabama, Mobile.

Malignant mixed mullerian tumors (MMMTs) of the female reproductive system represent an uncommon, aggressive, and complex set of tumors with histologic features of both carcinomas and sarcomas. Cervical MMMTs are particularly rare, presenting mostly after menopause. We report a rare case of a MMMT of the cervix in a 38-year-old Hispanic woman who had a history of abnormal uterine bleeding for 1 month. Her mother had uterine cancer at age 48. She underwent an exploratory laparotomy with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Grossly, there was a circumferential mass measuring 3.3 cm in greatest dimension located within the endocervix and partially replacing its wall. The tumor extended into the lower uterine segment and infiltrated the endometrium and myometrium. The serosa and parametrial soft tissues were uninvolved by tumor. Three of 10 pelvic and paraaortic lymph nodes were involved by metastatic disease. Histologically, the carcinomatous component was composed of high-grade endometrioid adenocarcinoma, focal clear cell carcinoma, and areas of keratinizing squamous cell carcinoma. A high-grade homologous sarcomatous component was sharply demarcated from the carcinomatous elements. No heterologous sarcomatous component and no lymphatic or vascular invasion were identified. Radiologic imaging included a chest computed tomography scan, which showed multiple pulmonary nodules suspicious for metastatic disease and involving both lungs. Given the complexity and extreme rarity of these tumors and the absence of a large volume of clinical data regarding cervical MMMTs, it is important that all cases be documented as thoroughly as possible to ensure appropriate disease treatment and prognosis.

Twin Reversed Arterial Perfusion Sequence: A Review of 9 Cases With an Emphasis on the Cord Insertion (Poster No. 32)

Rhea J. Birusingh, MD1 (birrhe@sgu.edu); Liset Pelaez, MD1; Victor Gonzalez-Quintero, MD2; Maria M. Rodriguez, MD.1 Departments of 1Pathology and 2Obstetrics and Gynecology, University of Miami, Miami, Florida.

Context: The etiology of twin reversed arterial perfusion sequence has not been clearly defined, even though it remains one the most severe consequences of monozygotic twinning. All theories include one main point: intraplacental vascular communication supporting growth of acardiac fetus.

Design: We retrospectively reviewed the acardiac acephalus twin gestations during a 19-year period (1990–2008). Nine cases were identified, and the placentas and obstetrical histories were reviewed.

Results: Seven of 9 were monoamniotic-monochorionic and 2 of 9 were diamniotic-monochorionic twin placentas. Vascular communications were identified in 7 cases. The other 2 cases were macerated and inappropriate for vascular communication assessment. Five of 9 demonstrated velamentous umbilical cord insertions; 3 cords were marginally and 1 was eccentrically inserted. Five cords supplying the acardiac fetus had a single umbilical artery; 2 cords had 3 vessels, and 2 cords were severely macerated, meaning the number of vessels could not be accurately assessed.

Conclusions: Velamentous cord insertions occur in approximately 1% of placentas and more frequently in multiple gestations. The most serious consequence of velamentous insertions is rupture of unprotected vessels resulting in fetal morbidity and mortality. Twin transfusion syndrome is also associated with velamentous cord insertion. We believe a special type of velamentous cord insertion at the dividing membrane may lead to unidirectional shifting of blood flow from the pump twin to the acardiac cotwin. Characterization of umbilical cord insertion is important in understanding this entity, as there is a need to better assess factors that influence the hemodynamics of vascular communication in the placentas and fetal maldevelopment.

Cutaneous Heterotropia of Cervix: Use of Molecular Tissue Identity Genotyping to Support Diagnosis (Poster No. 33)

Gaurav Sharma, MD1 (gsharma2@hfhs.org); Jennifer I. Lindley, BS2; Milena Cankovic, PhD1; Dhananjay Chitale, MD1; Min W. Lee, MD1; Chad H. Stone, MD.11Department of Pathology & Laboratory Medicine, Henry Ford Hospital, Detroit, Michigan; and 2Department of Graduate Studies, Lake Erie College of Osteopathic Medicine, Erie, Pennsylvania.

Cutaneous derivatives in cervix is a rare type of cervical heterotropia (CH). Diagnostic certainty depends on definitively excluding preanalytical contamination. We used a molecular tissue identity genotyping method to exclude preanalytical contamination. A 56-year-old postmenopausal woman with negative Papanicolaou tests was referred to the gynecology clinic for evaluation of a small polyplike lesion on the cervix. We biopsied this lesion, which was at the 9-o'clock position. It contained 2 distinct tissue fragments. The first fragment was unremarkable ectocervix. The second fragment showed squamous epithelium with multiple underlying hair follicle–like structures and surrounding inflammatory infiltrate suggestive of CH. To rule out preanalytical contamination, we analyzed both fragments for tissue identity using a pinpoint method for DNA extraction (Zymo Research, Orange, California) and polymerase chain reaction (PCR) amplification of microsatellite markers using ABI AMPF/STR Identifiler kit (ABI, Foster City, California). PCR products were analyzed by capillary electrophoresis, and allelic assignment was done using Gene Mapper software (ABI). The frequency of randomly matching 2 individuals in the North American population using this method is less than 1 in 82 billion. Complete match of 16 tissue identity alleles was present, confirming identical genotype of both tissue fragments and excluding preanalytical contamination. The colposcopic examination and histologic findings coupled with this information support the diagnosis of this rare entity. Exclusion of preanalytical contamination by molecular tissue identity genotyping, along with clinical and histologic findings, increases the diagnostic certainty of cutaneous CH. Our findings support this entity being of acquired metaplastic inflammatory origin instead of an aberrant embryonic or fetal implantation disorder.

Squamous Cell Carcinoma Diagnosed by Colonic Biopsy: Case Report of Malignant Transformation of a Mature Cystic Teratoma (Poster No. 34)

Claudia P. Rojas, MD1 (crojas@med.miami.edu); Monica T. Garcia, MD2; Parvin Ganjei-Azar, MD.21Department of Pathology, Jackson Memorial Hospital, Miami, Florida; 2Department of Pathology, University of Miami, Miami, Florida.

Primary squamous cell carcinoma (SCC) of the colon is an exceedingly rare malignancy, occurring in 0.25 to 1 per 1000 colorectal carcinomas. Colorectal SCC most commonly represents metastasis or tumor extension, which is likely from cervical or vaginal carcinomas in female patients. We describe the case of a 72-year-old woman who presented with increased abdominal girth and a 50-lb weight loss. CA 19.9 and carcinoembryonic antigen tumor markers were elevated. A colonoscopy revealed a necrotic mass that was 25 cm from the anal verge. A colonic biopsy showed detached fragments of keratinizing SCC. A subsequent computed tomography scan of the abdomen and pelvis showed a 16-cm right adnexal mass that was inseparable from the colon. The patient underwent a hysterectomy with bilateral salpingooophorectomy and partial colectomy. The right ovary showed a 10.5-cm cystic teratoma with hair, sebaceous material, and an 11-cm solid mass that extended to the adjacent colonic wall (Figure 21). Histologically, arising from the mature cystic teratoma was a keratinizing SCC that extended into the colonic submucosa. Immunohistochemistry was positive for p63 and negative for p16. Malignant transformation occurs in less than 2% of ovarian cystic teratomas and is most commonly SCC. In locally advanced tumors, transmural extension into the adjacent colon occurs. This case illustrates a rare example of malignant transformation of cystic teratoma that was first diagnosed by colonic biopsy.

CD10 Immunoreactivity in Metaplastic and Neoplastic Squamous Lesions of the Endometrium and Cervix and Its Potential Diagnostic Applications (Poster No. 35)

Nicole M. DeMers Riddle, MD1 (ndemers@health.usf.edu); Jeremy W. Bowers, MD1; Ardeshir Hakam, MD2; Xiaowei Xu, MD3; Theresa Pasha, MD3; Paul J. Zhang, MD3; Geza Acs, MD.21Department of Pathology and Cell Biology, University of South Florida, Tampa, Florida; 2Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, Florida; and 3Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia.

Context: The utility of CD10 immunohistochemistry in the differential diagnosis of endometrial stromal lesions and mesonephric glands is established. However, there are limited data available regarding CD10 expression in metaplastic and neoplastic squamous epithelial lesions of the female genital tract.

Design: We examined the expression of CD10 in a series of 278 cervical lesions (99 invasive squamous cell carcinoma, 14 invasive adenocarcinoma, 118 squamous dysplasia, 12 adenocarcinoma in situ, and 35 squamous metaplasia) and 151 endometrial lesions (104 endometrial carcinoma, 42 complex hyperplasia, and 5 atypical polypoid adenomyoma). CD10 immunoreactivity was analyzed on a 4-tier scale and was correlated with clinicopathologic features, the presence and type of squamous differentiation, and patient outcome.

Results: Benign tissues showed no CD10 immunoreactivity. CD10 reactivity was seen in 48 of 118 (41%) squamous dysplasias and in 34 of 99 (34%) invasive squamous cell carcinomas of the cervix; it was also associated with improved recurrence-free survival (P = .03). In contrast, invasive and in situ cervical adenocarcinomas showed no CD10 expression. No CD10 reactivity was observed in glandular components of endometrial lesions, including adenocarcinomas with keratinizing squamous differentiation. However, strong, diffuse CD10 staining was seen in nonkeratinizing squamous metaplasia present in these lesions.

Conclusions: In contrast to squamous metaplasia, CD10 immunoreactivity is present in dysplastic and neoplastic cervical squamous lesions and may be a useful marker in predicting patient outcome. Strong CD10 immunoreactivity in nonkeratinizing squamous metaplasia in endometrial lesions may be a useful marker in their differentiation from solid glandular growth of adenocarcinomas and may aid in tumor grading in difficult cases.

Adenoid Basal Carcinoma of the Cervix: Two Cases of a Rare Pathologic Entity With Distinctive Ages of Presentation (Poster No. 36)

Neil E. Fuehrer, MD (fuehrer@uthscsa.edu); Irina Lytvak, MD; Philip T. Valente, MD. Department of Pathology, University of Texas Health Science Center, San Antonio.

Adenoid basal carcinoma is a very rare neoplasm of the cervix, classically presenting in postmenopausal women (median age 65) in association with high-grade squamous dysplasia of the cervix. The relative rarity of this lesion has kept it an enigma in regard to its precise biologic evolution, but the lesion has been associated with high-risk human papillomavirus type 16 DNA. The first case of adenoid basal carcinoma encountered at our institution (2004) was an asymptomatic lesion in a 25-year-old woman that was diagnosed on cervical conization subsequent to a previous biopsy demonstrating high-grade squamous dysplasia (CIN III). Smooth irregular nests of bland glandular and mildly atypical squamous cells surrounded by basal epithelium were noted. A p16 stain was focally positive in the tumor. A Ki-67 stain subsequently demonstrated a low proliferation index. The second case of adenoid basal carcinoma (2008) was diagnosed in a 63-year-old woman on cervical conization for severe squamous dysplasia (CIN III). A p16 stain demonstrated strong diffuse positivity within the overlying high-grade epithelial dysplasia and within the deeper well-differentiated adenoid basal carcinoma component. Ki-67 showed a low proliferation index with markedly decreased staining compared with the overlying dysplastic epithelium. Adenoid basal carcinoma is a rare neoplasm of the cervix that usually occurs in association with overlying squamous dysplasia. Although adenoid basal carcinoma appears to be associated with high-risk human papillomavirus, this neoplasm has a low proliferation index and excellent prognosis and may present as an incidental finding in women of any age.

An Increase in Uterine Natural Killer Cells in First Trimester Miscarriages With Karyotypic Abnormalities: A Flow Cytometry/Cytogenetic Correlation (Poster No. 37)

Muhammad A. Syed, MD1 (muhammadasim.syed@danhosp.org); Rhea Birusingh, MD2; German Escudero, PA1; Rina K. Siddiqui, MD1; Leonel Edwards, MD.11Department of Pathology, Danbury Hospital, Danbury, Connecticut; and 2Department of Pathology, University of Miami, Miami, Florida.

Context: It has been reported that uterine natural killer cells (uNKCs) may play a role in first trimester miscarriages. The function of these cells in human pregnancy is not completely known; however, they are thought to support placental growth through angiogenesis and immune modulation at the maternal-fetal interface. The most common etiology of miscarriage is karyotypic abnormalities. Therefore, in an effort to understand the relationship of these cells to miscarriage, we determined the percent of uNKCs and compared that with the presence or absence of karyotypic abnormality.

Design: Twenty products of conception specimens from women who miscarried in their first trimester (6–12 weeks) were submitted for cytogenetic analyses and were prospectively studied for CD56+ uNKCs via flow cytometry.

Results: Fifteen patients had an abnormal karyotype; findings included both numerical and structural abnormalities. In 5 specimens, the karyotype was normal. The mean uNKC percent for cases with karyotypic abnormality was 8.76% (range, 0.18%–38.67%), and the mean uNKC percent for cases with no karyotypic abnormality was 0.84% (range, 0%–1.83%; P value = .02).

Conclusions: The percent of uNKCs found in samples with karyotypic abnormality is significantly statistically higher than in samples with normal karyotypes. To our knowledge, this is the first study that correlates the 2 parameters. This finding may be of benefit, possibly indicating a surrogate marker for early detection of karyotypic abnormalities. Additionally, continued study of uNKCs in human products of conception by flow cytometry may help to elucidate the role these cells play in miscarriage.

Primary Peritoneal Carcinosarcoma in Conjunction With Tubal Intraepithelial Dysplasia (Poster No. 38)

Byron H. Moore, MD1 (bhmoore2@tmhs.org); Alan Kaplan, MD2; Jim Zhai, MD.1 Departments of 1Pathology and 2Gynecological Oncology, The Methodist Hospital, Houston, Texas.

A 62-year-old woman (gravida 2, para 2) presented with abdominal pain. The abdominal imaging showed bilateral adnexal masses without a definite connection to the uterus. An exploratory laparotomy was performed to establish a diagnosis. The tumor extensively involved the uterine serosa and parametrial tissue as well as 2 foci on the sigmoid colon serosa. Histologically, the tumor was composed of high-grade, pleomorphic, solid nests of epithelial cells with intervening hyaline cartilage. No involvement of the endometrium was seen. The left fallopian tube had diffuse serous tubal intraepithelial carcinoma, while the right fallopian tube had focal serous tubal intraepithelial carcinoma. Immunohistochemical stains Pax-2 and WT-1 were positive in the epithelial portion of the carcinosarcoma. The left fallopian tube showed overexpression of both p53 and MIB-1. The right fallopian tube showed focal overexpression of p53. Primary carcinosarcoma of the peritoneum (malignancy mixed müllerian tumor) is a rare, aggressive entity. Presumably, the tumor arises from cells of the “secondary müllerian system,” which is the peritoneal mesothelium and adjacent mesenchyme of the pelvis and lower abdomen. Although previously considered to be a collision tumor, carcinosarcomas are now thought to be metaplastic carcinoma with monoclonal epithelial and mesenchymal components. To our knowledge this is the first case of carcinosarcoma with concurrent serous tubal intraepithelial carcinoma, a precursor to pelvic serous carcinoma. Although coincidental concurrence is possible, this case represents a possible link between carcinosarcoma and serous carcinoma, or at least a possible common precursor lesion.

Comparison of Polymerase Chain Reaction and In Situ Hybridization Methods for Detection of Cervical Human Papillomavirus Infection: Cases That May Not Be Identified by Polymerase Chain Reaction But That May Be Detected by In Situ Hybridization (Poster No. 39)

Junquing Shen, MD1; Theodoros Kelesidis, MD2 (tkelesid@gmail.com); Leo Aish, MD, PhD, FCAP1; Irene S. Aish, PhD.1 Departments of 1Pathology and 2Medicine, Caritas St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts.

Context: Detection of epithelial cell abnormalities by cervicovaginal cytology screening necessitates human papillomavirus (HPV) testing. Although polymerase chain reaction (PCR) is a very sensitive method for detecting HPV, it still results in some cases being undiagnosed.

Design: Results from 108 cervicovaginal liquid-based cytology samples analyzed for the presence of HPV DNA by PCR were compared with the results of in situ hybridization (ISH) on 108 cervical biopsies obtained from the same patients using commercial HPV probes and primers.

Results: Positive ISH signals for high-risk, low-risk, and both high- and low-risk HPV types were observed in 70 of 108 (64.8%), 9 of 108 (8.3%), and 5 of 108 (4.6%) cases, respectively, whereas negative signals were found in 24 of 108 (22.2%) cases. By PCR, 52 of 108 (48.2%), 7 of 108 (6.5%), and 5 of 108 (4.6%) cases were positive for the respective HPV risk types. Eight (7.4%) patients were positive for unknown HPV risk types, and in 36 (33.3%) patients, PCR was negative. The degree of concordance between PCR and ISH was 69.4% (75 of 108) for all samples (Table). Interestingly, 16 of 108 (14.8%) cases were negative for HPV by PCR but positive by ISH in cervical biopsies.

Conclusions: A higher number of positive results were detected by ISH in tissue biopsies (84 of 108; 77.8%) than by PCR in liquid-based cytologic specimens (73 of 108; 67.6%). In our series, ISH was an adequate method for detecting HPV in high-grade lesions with similar efficacy to PCR. Patients with abnormal cervicovaginal cytology and undetectable HPV on testing with PCR could be tested by ISH on biopsy specimens.

 
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PAX8: An Immunohistochemical Marker for Endometriosis (Poster No. 40)

Andrew Turk, MD (att2101@columbia.edu); Diane Hamele-Bena, MD; Guo-Xia Tong, MD. Department of Pathology, Columbia University, New York, New York.

Context: Endometriosis is defined as the presence of endometrial tissue outside of the uterine cavity. Although most often confined to the peritoneal cavity, endometriosis may occur in unusual sites, including skin, lung, and brain. Histologic diagnosis of endometriosis is sometimes difficult, especially when the lesion occurs in atypical sites. Variability in the appearance of glands due to cyclic hormonal changes may also confound diagnosis. Characterization of molecular markers of endometriosis enables pathologists to circumvent these diagnostic challenges. In this study, we investigate the transcription factor PAX8 as an immunohistochemical marker of endometriosis.

Design: Twenty-two cases of endometriosis and 1 sample each of endocervical tissue, endometrium, and fallopian tube were retrieved from archived material. PAX8, estrogen receptor, and progesterone receptor immunohistochemical staining was performed using the avidin-biotin peroxidase method after antigen retrieval. Distinct and strong nuclear staining was required for PAX8 positivity.

Results: The 22 endometriosis cases were from women ranging in age from 19 to 70 years. The sites included abdominal wall, appendix, hernia sac, ureter, pelvic wall, and colon. Strong PAX8 nuclear staining was detected in all 22 (100%) cases, as well as in benign endocervical and endometrial glands, fallopian tube epithelium, and lymphocytes. No PAX8 staining was identified in adjacent colonic or appendiceal tissue or in the urothelium.

Conclusions: We observed PAX8 expression in all 22 cases of endometriosis and in benign endocervical, endometrial, and fallopian tube epithelium. These findings suggest that PAX8 is a marker for the mullerian system and that PAX8 immunohistochemistry may be a sensitive method for diagnosing endometriosis.

Invasive Paget Disease of the Vulva With Concurrent Basal Cell Carcinoma (Poster No. 41)

Emily C. Maambo, MD (emaambo@umm.edu); Olga B. Ioffe, MD. Department of Anatomic Pathology, University of Maryland Medical Center, Baltimore.

We report a case of an 81-year-old woman who had a granular, red-tan vulvar lesion that she had noticed for more than a year. The vulvectomy specimen showed invasive vulvar Paget disease with concurrent basal cell carcinoma (BCC). This is the first reported case of BCC associated with invasive vulvar Paget disease and the second reported case of concurrent vulvar Paget disease and BCC. The epidermis of the specimen showed nests of cells with abundant clear cytoplasm, large pleomorphic nuclei with vesicular chromatin, and conspicuous nucleoli. These malignant cells were also seen infiltrating the dermis in direct continuity with the intraepidermal component. The overlying and adjacent epidermis showed extensive pseudoepitheliomatous hyperplasia and several foci of BCC arising immediately adjacent to Paget disease. The intraepidermal nested malignant cells showed immunoreactivity for cytokeratin (CK) 7 and were negative for CK20, S100 protein, Melan-A, and HMB-45. The infiltrating component showed the same immunoprofile. The diagnosis of invasive Paget disease was based on cytologic similarities and intimate association of the intraepidermal and invasive components as well as their shared immunoprofile. The overlying squamous epithelium and pseudoepitheliomatous hyperplasia were positive for high-molecular-weight cytokeratin and negative for CK7. The BCC was weakly positive for CK7. Because the BCC in this case arose in an ulcerated reactive epidermis with pseudoepitheliomatous hyperplasia, it is possible that Paget disease was the predisposing factor for the development of BCC. However, we cannot rule out the possibility that the 2 lesions developed independently.

Severe Dysplasia and Adenocarcinoma In Situ Within an Endocervical Polyp (Poster No. 42)

Paula A. Navarro, MD1 (pnavarro@tuftsmedicalcenter.org); Jennifer J. O'Brien, MD, PhD1; Edward Evantash, MD2; M. L. Garcia-Moliner, MD, PhD.1 Departments of 1Pathology and 2Obstetrics and Gynecology, Tufts Medical Center, Boston, Massachusetts.

Endocervical polyps, the most common benign neoplasia of the uterine cervix, are frequently seen in multigravid women during the fourth to sixth decades of life. The polyps can present with vaginal discharge or bleeding. In situ and invasive carcinoma arising in endocervical polyps is extremely rare. The incidence of squamous dysplasia in polyps is estimated between 0.5% and 2%. The association between adenocarcinoma in situ and squamous dysplasia of the cervix is well known; however, the coexistence of squamous dysplasia and adenocarcinoma in situ within an endocervical polyp has not been previously described. We present a case of an endocervical polyp with severe dysplasia and associated adenocarcinoma in situ. We searched Tufts Medical Center's archival files from 1998 to 2008 (1004 cases) for the diagnosis of dysplasia and adenocarcinoma in situ arising in cervical polyps. We found 9 (0.89%) cases with squamous dysplasia, including CIN 1 (0.39%), CIN 2 (0.09%), and CIN 3 (0.39%). No other cases of severe dysplasia with adenocarcinoma in situ were found. A 58-year-old woman presented with episodic postmenopausal spotting. Pelvic examination revealed atrophic changes in the external genitalia and vagina and a 1.5-cm reddish polyp at the cervical os. Histologic findings showed an endocervical polyp with focal severe squamous dysplasia (CIN 3) (Figure 22, A) and focal adenocarcinoma in situ (Figure 22, B). Carcinoma arising in endocervical polyps is very uncommon and carries an excellent prognosis if limited to the polyp. A subsequent hysterectomy revealed no residual tumor or dysplasia.

Immunohistochemical Study of Squamous Morules and Stromal Changes in Endometrial Hyperplasia (Poster No. 43)

Patrick A. Adegboyega, MD (padegb@lsuhsc.edu). Department of Pathology, Louisiana State University Health Sciences Center–Shreveport.

Context: Morules are nonkeratinizing squamous metaplasia that frequently occur in association with endometrial hyperplasia; their histogenesis and role in the development of endometrial hyperplasia are unknown.

Design: Hematoxylin-eosin–stained glass slides of 247 consecutive cases of endometrial hyperplasia were reviewed for the presence of squamous morules. Cases with squamous morules were stained with CD10 (marker of endometrial stromal cells) and α-smooth muscle actin (αSMA) immunostains. Immunoreactivity was assessed based on the topographic location of the proteins and intensity of immunoreactivity.

Results: Squamous morules were detected in immunostained sections of 19 cases, and they stained strongly positive for CD10 and negative for αSMA in 18 of 19 cases. This finding was associated with complete loss of CD10 expression in the stroma immediately adjacent to the CD10-expressing squamous morules. There was also an overall decrease in CD10 expression in the stromal cells of endometrial hyperplasia, regardless of whether it was simple or complex hyperplasia. The decrease in CD10 expression ranged from reduction in the intensity of the immunoreactivity to negative immunohistochemical reaction in some areas. In endometrial hyperplasia, patchy to diffuse expression of αSMA was noted in the stromal cells, especially in the periglandular areas.

Conclusions: The expression of CD10 by the squamous morules suggests squamous metaplasia in endometrial hyperplasia to be of stromal origin. The downregulation of CD10 in the stroma of endometrial hyperplasia and the concurrent acquisition of αSMA expression by the stromal cells supports the hypothesis that changes in the endometrial stroma may play a very significant role in the pathogenesis of endometrial hyperplasia.

Placental Chorioangioma Associated With Diffuse Fetal Vascular Malformations (Poster No. 44)

Weijie Li, MD (weijie.li@downstate.edu); Virginia Anderson, MD. Department of Pathology, SUNY Downstate, Brooklyn, New York.

Chorioangioma is the most frequently occurring nontrophoblastic tumor of the placenta. Vascular anomalies of the placenta associated with fetal vascular malformations are rarely described. We report on a fetopsy case in which a chorioangioma of the placenta was associated with vascular malformations of the adrenals, bladder, heart, liver, lungs, spleen, and soft tissue of a 21-week-old fetus. We studied the expression of CD34, CD31, vimentin, factor VIII, and cytokeratin in these lesions. The same expression patterns were seen in the lesions of both the placenta and the fetus. The vascular anomalies in the fetus may be related to the chorioangioma of the placenta.

Thyroid Transcription Factor–Positive Primary Endocervical Adenocarcinoma (Poster No. 45)

Sihem Khelifa, MD; Daniela Mihova, MD (damihova@yahoo.com); Marietta Kintiroglou, MD. Department of Pathology, St Barnabas Medical Center, Livingston, New Jersey.

Context: Thyroid transcription factor 1 (TTF-1) is considered a reliable marker in distinguishing primary and metastatic adenocarcinomas of the lung from metastatic tumors of other origin. A challenging case of TTF-1–positive primary endocervical adenocarcinoma metastatic to the mediastinum in a 63-year-old patient interested us, leading us to conduct a study exploring the expression of TTF-1 in primary endocervical adenocarcinoma cases diagnosed at our institution.

Design: Twenty cases of primary endocervical adenocarcinoma with no previously known history of any cancer were retrieved from our archived data and matched against 20 negative control cases of benign endocervical biopsies/excisions. Cases were matched using age and date of exploration as criteria. TTF-1 staining was performed on the 40 cases. TTF-1 positivity was defined by a nuclear pattern (scored from 0 to 3+).

Results: Of 20 cases of primary endocervical adenocarcinoma, 1 (5%) case was TTF-1 strongly positive (nuclear score 3+). Of 20 cases of negative controls, 0 (0%) cases were TTF-1 positive. The TTF-1–positive case was a primary noninvasive endocervical adenocarcinoma in a 37-year-old patient with no history of malignancy.

Conclusions: In our study, 1 of 20 (5%) of the selected primary endocervical adenocarcinomas were TTF-1 positive, whereas none of the benign cervical tissues were positive. The mechanism behind TTF-1 positivity in tumors of other origin than lung or thyroid is not well understood. While waiting for larger studies exploring TTF-1 in different kinds of tumors, we should be overly cautious when dealing with a TTF-1–positive metastasis, especially in the absence of clinical pulmonary and thyroid history.

Morphoproteomic Evidence of a Constitutively Activated and Overexpressed Signal Transducer and Activator of Transcription-3 Pathway With Interleukin 8 Coexpression in Cervical Cancer and High-Grade Dysplasia (Poster No. 46)

Ana Lucia Cota, MD (ana.l.cota@uth.tmc.edu); Robert E. Brown, MD; Sadhna Dhingra, MD; Wei Feng, MD; Xiuzhen Duan, MD. Department of Pathology, University of Texas Medical Center at Houston.

Context: Interleukin 6 (IL-6) is known to be associated with cervical cancer, promoting tumor growth via activation of the signal transducer and activator of transcription 3 (STAT3) pathway. Recent literature also describes increased levels of IL-6 transfection by human papillomavirus type 16, E6 and E7 genes. Both IL-6 and IL-8 levels are increased in cervicovaginal secretions of patients with cervical cancer. IL-8 is a target gene of STAT3. In this study, we apply morphoproteomics to investigate the STAT3 pathway in cervical cancer and dysplasia.

Design: A tissue microarray comprised of benign cervical tissue, high-grade dysplasia, and invasive squamous cell carcinoma was assembled. Immunohistochemical probes using monoclonal antibodies to STAT3 phosphorylated (p-STAT3) on tyrosine 705 and to IL-8 were applied. Results were graded according to intensity of staining (0–3+ scale) and percentage of cells stained (0%–100%).

Results: Our data showed no immunoreactivity for IL-8 and only rare nuclear expression of p-STAT3 in basal cells of the benign squamous epithelium. Ninety-five percent of cancer and dysplasia cases showed strong positivity (2+–3+) for nuclear p-STAT3. Additionally, all cases of carcinoma and dysplasia were strongly positive for IL-8. There was no difference in the intensity or quantity of staining between high-grade dysplasia and invasive squamous carcinoma for these protein analytes.

Conclusions: Morphoproteomic analysis showed constitutive activation and overexpression of the STAT3 pathway in invasive squamous cell carcinoma and high-grade dysplasia versus nonneoplastic cervical mucosa by virtue of p-STAT3 (Tyr 705) nuclear expression and correlative expression of IL-8.

Adenoid Cystic Carcinoma of the Bartholin Gland: Case Report and Review of Literature (Poster No. 47)

Courtney W. Ingram, MD1 (courtney.ingram@bhsala.com); Alfred R. Rector, MD1; D. S. Day, MD1; Clinton T. Holladay, MD.21Department of Pathology, Baptist Health Systems, Birmingham, Alabama; and 2Department of Radiation Oncology, Trinity Medical Center, Birmingham, Alabama.

Primary adenoid cystic carcinoma of the Bartholin gland is a very rare neoplasm, which is characterized by slow growth, perineural invasion, and a high propensity for recurrence. We report a case of a 65-year-old woman who presented with complaints of vaginal pressure and an enlarging cystlike structure in her vagina. A partial deep vulvectomy was performed. Pathologic examination revealed an ovoid portion of pink-tan soft tissue that measured 2.5 × 2.5 × 1.6 cm. Microscopic examination revealed numerous sheets and nests of small, uniform, polygonal to round neoplastic cells, displaying a predominantly cribriform pattern with variably sized spaces. Focally, some of these spaces contained amorphous eosinophilic material. Also present were single cords of malignant cells that infiltrated the stroma. There were rare foci of perineural invasion, as well as foci suspicious for lymphvascular invasion by the neoplasm. The tumor was extensively present at the peripheral surgical margins of the specimen. Currently, due to the small number of cases and lack of well-defined prognostic parameters, there is no consensus regarding the optimal treatment for primary adenoid cystic carcinoma of the Bartholin gland. A review of cases in the literature from 1985 to the present revealed that margin status does not appear to play a significant role in outcome. Additionally, the use of adjuvant radiation therapy may be beneficial when coupled with local excision, partial vulvectomy, or hemivulvectomy, regardless of margin status.

Validation of a Novel Fluorescence In Situ Hybridization Assay and Comparison to p16, Topoisomerase II, and MDM2 Protein Status in Cervical Squamous Intraepithelial Neoplasia (Poster No. 48)

Deniz Peker, MD1 (dpeker@msmc.com); Enma Saiz, MD2; John Alexis, MD1; Robert Poppiti, MD1; Lydia Howard, MD1; Hadi Yaziji, MD.21Department of Pathology, Mount Sinai Medical Center, Miami Beach, Florida; and 2Department of Pathology, Vitro Molecular Laboratories, Miami, Florida.

Context: Human papillomavirus is important for the development of cervical carcinoma. Parallel diagnostic immunohistochemical assays were developed, including p16 test and ProExC (topoisomerase II and MDM2) kits, to differentiate dysplastic lesions and their mimickers. Comparative genomic hybridization has identified genetic and chromosomal alterations as early events in the progression of cervical dysplasia to carcinoma. Several genes and chromosome-targeted probes have been developed. We assessed a novel fluorescence in situ hybridization (FISH) probe set and other gene/chromosome probes for their diagnostic utility.

Design: Forty-three cervical tissue samples were tested against p16 antibody (clone JC8), ProExC testing kit, and 7 FISH probes against p16, chromosome 3 centromere, TERC gene, chromosome 7 centromere, chromosome 8 centromere, MYC gene, and chromosome 17 centromere. Diagnoses ranged from reactive to high-grade lesions.

Results: p16 showed excellent positive predictive value (95%) and negative predictive value (98%) for high-grade cervical intraepithelial lesions. ProExC had 100% positive predictive value and 100% negative predictive value. Only grade 2 and 3 lesions (65%) showed CEP8 triploidy, MYC triploidy, TERC triploidy, and CEP3 triploidy. The p16 gene status did not correlate with the protein status.

Conclusions: Abnormal p16 protein in high-grade lesions showed no relationship to p16 gene status. The most common genetic/chromosomal anomaly in cervical dysplasia was trisomy, confirming earlier studies. Among all evaluated DNA sequences, TERC, CEP8, and MYC showed the most common abnormalities in high-grade dysplasia. Most grade 1 lesions showed normal genetic findings. Our study also showed that the combination of ProExC and p16 provides more sensitive and specific results.

Primary Heterologous Carcinosarcoma or Malignant Mixed Mesodermal Tumor of the Vulva: A Clinicopathologic Case Study (Poster No. 49)

Guanhua Lai, MD, PhD (glai@mcvh-vcu.edu); William J. Frable, MD.  Department of Pathology, Virginia Commonwealth University Health System, Richmond.

Carcinosarcoma of the vulva is a very rare neoplasm. Only 2 vulvar carcinosarcomas in which the carcinomatous component was squamous carcinoma have been reported. The sarcomatous component in one case was osteosarcoma, and in the other case, it was leiomyosarcoma. We present the first case of a primary vulvar adenocarcinomatous carcinosarcoma with homologous leiomyosarcomatous and heterologous osteosarcomatous differentiation. A 51-year-old African American woman presented with a labial mass. She underwent right radical vulvectomy, received whole pelvic radiation therapy, and has been without evidence of disease for 6 months. The multilocular cystic tumor, measuring 7.5 × 6.5 × 3.1 cm, contained papillary excrescences and necrosis, and invaded underlying soft tissue. Microscopically, the adenocarcinomatous component was positive for cytokeratin AE1/AE3 and epithelial membrane antigen; the sarcomatous component contained osteosarcoma and pleomorphic poorly differentiated cells that expressed CD10 and smooth muscle actin. Some of the poorly differentiated sarcomatous cells were also positive for cytokeratin AE1/AE3, which may support the hypothesis that the carcinomatous and sarcomatous components of carcinosarcoma are clonally related; however, further investigation of this tumor is needed. Carcinosarcomas in the female genital tract are usually highly aggressive malignancies with poor clinical prognosis. Therefore, in our case, even though no lymph nodes were available for evaluation and the surgical margins were free of tumor, the patient still underwent whole pelvic radiation therapy postoperatively. Additionally, due to the different histopathologic characteristics, continuous patient follow-up is warranted to monitor clinical outcome for anything unusual and for clinical management.

Endometrial Adenocarcinoma: Intratumor Variability in Estrogen Receptor and Progesterone Receptor Immunostain Results (Poster No. 50)

Sonya Hwang, MD1 (sohwang@notes.cc.sunysb.edu); Harry Hwang, MD3; Allen Gown, MD3; Michael Pearl, MD2; Carmen Tornos, MD.1 Departments of 1Pathology and 2Obstetrics/Gynecology and Gynecology Oncology, Stony Brook University Medical Center, Stony Brook, New York; and 3Department of Pathology, Phenopath Laboratory, Seattle, Washington.

Context: Estrogen receptor (ER) status and progesterone receptor (PR) status are used as prognostic and treatment indicators for endometrial adenocarcinomas. Many studies have reported variable results regarding correlation among prognosis, clinical stage, and histologic grade. Intratumoral differences in receptor status have not been well characterized; this was the purpose of our study.

Design: Twenty-five cases of endometrioid adenocarcinoma with noninvasive and invasive areas were used, with a range of International Federation of Gynecology and Obstetrics grades (10 grade 1, 12 grade 2, and 3 grade 3) and depths of invasion (17 cases ≤50% invasion, 8 cases >50% invasion). Immunostains for ER and PR were performed using an optimized biotin-free, polymer-based immunoperoxidase methodology. The stains were scored as positive (≥10% staining) or negative (<10% staining). In a subset of cases, percentage of tumor and staining intensity (weak, moderate, strong) were evaluated (Table).

Results: In 21 (84%) cases, ER and PR were positive in both noninvasive and invasive areas. In these cases, morphology was similar in the noninvasive and invasive areas. Four cases showed quantitative and qualitative staining differences in areas of different morphologies; these were analyzed in more detail (Table).

Conclusions: We found no intratumoral differences in ER and PR status in invasive versus noninvasive areas when morphology was the same. However, we did see intratumoral differences in ER and PR immunostains, depending on tumor differentiation. Because ER and PR status may indicate prognosis and treatment, we feel immunostains should be done on the least differentiated areas of tumors to provide the most accurate analysis.

 
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Expression of Thyroid Transcription Factor 1 and Loss of Expression of Estrogen Receptors in Endometrial Adenocarcinoma (Poster No. 51)

Haiyan Liu, MD (hliu1@geisinger.edu); J. Shi, MD, PhD; Yiran Xu, BS; Kai Zhang, MD; H. Kaspa, MD; Fan Lin, MD, PhD. Department of Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania.

Context: Thyroid transcription factor 1 (TTF-1) is a relatively sensitive and specific marker for carcinomas of lung and thyroid. In recent studies, TTF-1 expression was observed in tumors other than lung and thyroid, such as small cell carcinoma of the bladder and endometrial and endocervical adenocarcinomas. We investigate the expression of TTF-1 and estrogen receptor in endometrioid adenocarcinomas.

Design: We immunohistochemically evaluated the expression of TTF-1 on conventional tissue sections in 80 cases of endometrioid adenocarcinoma, including 25 cases of grade I, 35 cases of grade II, and 20 cases of grade III tumors. Two TTF-1 monoclonal antibodies were used (1:25, 8G7G3/1, Cell Marque Corporation, Rocklin, California and 1:50, sc-56606, Santa Cruz Biotechology, Santa Cruz, California). We recorded staining intensity (weak or strong) and distribution (negative, 1+, 2+, 3+, and 4+).

Results: Strong and diffuse (4+) nuclear staining for TTF-1 was demonstrated in 2 of 80 (2.5%) cases, with identical patterns for both antibodies. Both cases were grade II endometrioid adenocarcinomas, with a positive cytokeratin 7 and negative estrogen receptor profile. In 1 of the 2 cases, a lung metastasis developed 4 years after a hysterectomy.

Conclusions: Our data confirm previous findings with 2 different antibodies against TTF-1; however, the positive percentage is significantly lower than in a previous study (2.5% vs 19%). Caution should be taken when working on an unknown primary because a small portion of endometrioid adenocarcinomas may carry an immunophenotype of cytokeratin 7 positive, TTF-1 positive, and estrogen receptor negative, which is similar to the immunophenotype of a primary adenocarcinoma of lung.

Primary Small Cell Carcinoma of the Endometrium: Case of a Rare and Aggressive Tumor (Poster No. 52)

Irina Lytvak, MD (Lytvak@uthscsa.edu); Neil Fuehrer, MD; Philip Valente, MD. Department of Pathology, University of Texas San Antonio Health Science Center, San Antonio.

Primary small cell carcinomas of the female genital tract constitute less than 2% of all gynecologic malignancies. Small cell carcinomas of the endometrium are very rare. Most patients present with vaginal bleeding. Macroscopically, the lesions are large, occupying most of the uterus and often showing evidence of an intraabdominal spread. Microscopy shows nests and sheets of small cells with scant cytoplasm, evenly dispersed chromatin, and inconspicuous nucleoli. Immunohistochemical stains demonstrate positivity for one or more neuroendocrine markers. Electron microscopy can be used to demonstrate neurosecretory granules. The patient is a 60-year-old postmenopausal woman who presented with vaginal spotting. Endometrial biopsy was diagnostic of a small cell carcinoma. Gross examination showed an enlarged uterus (770 g) that was almost entirely occupied by a soft, red to brown, ill-defined mass. Microscopy demonstrated an infiltrative lesion composed of small blue cells with scant cytoplasm and a high nuclear to cytoplasmic ratio. Vascular invasion was frequent. Immunohistochemical stains for synaptophysin and chromogranin were positive. Microscopic examination of right fallopian tube and ovary, appendix, portions of large bowel, and mesentery also showed extensive involvement by the tumor and associated necrosis. The patient was surgically staged IV (International Federation of Gynecology and Obstetrics system). Small cell carcinomas of the endometrium are very rare and aggressive neoplasms. They are notorious for rapid systemic spread and poor prognosis. Early and aggressive therapy may improve survival in these patients.

Histologic Type, Stage of Disease, and Tumor Grade Are Unrelated Racial Disparity Among Blacks and Whites for Endometrial Cancer (Poster No. 53)

Kerry L. Campbell, MPH1 (kerrycam49@aol.com); Donald E. Henson, MD2; Steven R. Patierno, PhD.21School of Public Health and Health Services, George Washington University, Arlington, Virginia; and 2The George Washington Cancer Institute, George Washington University, Washington, DC.

Context: It is well known that endometrial cancer varies by race; however, the reason for this disparity remains unclear. Adjusting for clinical pathologic factors may clarify endometrial cancer racial disparities.

Design: Endometrial cancer data were obtained from Surveillance, Epidemiology and End Results registry data (1990–2005). Invasive cancers in blacks and whites were stratified by histologic type and adjusted for stage and grade. Descriptive techniques included age-adjusted temporal trends, age-specific incidence rates, incidence rate ratios, Kaplan-Meier plots, and hazard rates for endometrial cancer-specific deaths. Statistical significance was assessed (α = .05).

Results: There were 81 620 endometrial cancer cases, including 93.0% white individuals and 7.0% black individuals. Age-adjusted incidence rates were higher for whites (incidence rate ratio white to black, 1.38; 95% confidence interval: 1.34, 1.42) and have decreased during the past 15 years, whereas incidence rates for blacks have increased. Despite decreasing rates in mortality, mortality rates for blacks remain significantly higher than for whites (P < .001). Compared with whites, blacks have significantly higher incidence rates of more aggressive histologic types, such as serous carcinoma, clear cell carcinoma, and carcinosarcoma, and higher rates of late-stage and high-grade cancers. Kaplan-Meier plots and hazard rates showed survival was worse for blacks than whites, even after stratifying for histologic type and adjusting for stage and grade.

Conclusions: Endometrial cancer survival rates were worse for blacks than whites, and racial survival disparities persisted even after adjustment for clinical pathologic factors. Histologic type, stage, and tumor grade are not the only determinants that contribute to the disparity seen in endometrial cancer among blacks and whites.

Clinical and Histopathologic Features Differentiating Benign and Malignant Solitary Fibrous Tumors of the Thorax (Poster No. 54)

Hema Khurana, MD1 (hkhurana@tmhs.org); Timothy Allen, MD2; Philip Cagle, MD.11Department of Pathology, The Methodist Hospital, Houston, Texas; and 2Department of Pathology, University of Texas, Tyler.

Context: Solitary fibrous tumor of the thorax (SFT) is a rare tumor that may be either benign or malignant. SFTs have a variety of histologic patterns, including patternless pattern and hemangiopericytoma-like and cellular patterns. We investigated the clinicopathologic features differentiating benign SFT from malignant SFT in a series of SFTs excised during a 14-year period at 2 hospitals.

Design: We searched surgical pathology databases (1994–2008) of 2 hospitals, identifying 24 patients with SFT. The surgical pathology reports were reviewed, and the following demographic and histologic features were analyzed: age, gender, location, size, histologic patterns, mitosis, necrosis, nuclear pleomorphism, and immunohistochemistry.

Results: The group consisted of 17 (71%) patients with benign SFT and 7 (29%) patients with malignant SFT. The average age of patients with benign SFT was 48.5 years (range, 20–77 years), whereas the average age of patents with malignant SFT was 69 years (range, 62–76 years). Female to male ratio was 11:6 for benign SFT and 2:5 for malignant SFT. Average tumor size was 4.5 cm for benign SFT and 11.8 cm for malignant SFT. Histologic patterns in benign SFT were 71% patternless pattern, 23% hemangiopericytoma-like pattern, and 6% cellular pattern. Histologic patterns in malignant SFT were 0% patternless pattern, 72% hemangiopericytoma-like pattern, and 28% cellular pattern.

Conclusions: In our series, malignant SFT occurred in patients older than 60 years, tended to have a large tumor size, and had a predominantly hemangiopericytoma-like pattern. Benign SFT occurred in a wide age range (20–76 years), with a slightly female predominance and a predominantly patternless pattern.

Solitary Fibrous Tumor of Pleura: A Rare Macrocystic Form (Poster No. 55)

Ali Hakan Cermik, MD1 (hakancermik@hotmail.com); Ersin Demirer, MD.2 Departments of 1Pathology and 2Respiratory Disease, Etimesgut Military Hospital, Ankara, Turkey.

A 75-year-old woman presented with shortness of breath for 2 months. Respiratory system findings were suggestive of a mass lesion in the left hemithorax. Thorax computed tomography scan showed a soft tissue mass with several macrocysts in the left pleural cavity that was compressing the left lower lobe. Posterolateral thoracotomy was done for exploration. The tumor was attached to the visceral pleura of lung by a pedicle. Grossly, the surface was smooth and had a shiny, tan-red multilobular appearance. Sectioning revealed a large lobulated tumor (20 × 15 × 15 cm) with tan-pink, soft parenchyma with a multimacrocystic appearance. The biggest cyst measured 5 cm in diameter. Histologically, the tumor consisted of bland looking spindle cells alternating with numerous bundles of small collagen fibers, resulting in an interlaced appearance characteristic of solitary fibrous tumor of pleura. Immunohistochemical stain showed some of the spindle cells were positive for CD34. The clinical presentation of solitary fibrous tumor of pleura varies according to size and intrathoracic localization. The treatment of choice is surgical removal, which is curative in 90% of cases. Cystic degeneration may be seen in addition to the classic presentation of a pleural-based solid mass. Macrocystic degeneration of solitary fibrous tumor of pleura is a rare variant that should be considered in the differential diagnosis of intrathoracic tumors.

Primary Adenoid Cystic Carcinoma of the Bronchus: A Case Report and Review of the Literature (Poster No. 56)

Maximo K. Llaudes, MD (llaudes@gmail.com); Steven Sieber, MD; Michael Walker, MD; Hani El-Fanek, MD. Department of Pathology, Danbury Hospital, Danbury, Connecticut.

Primary salivary gland–like lung cancers are rare neoplasms, constituting less than 0.5% of all respiratory malignancies in the United States. In particular, adenoid cystic carcinoma has been described in the trachea and more rarely in the mainstem bronchus. This carcinoma usually presents clinically as an endobronchial mass lesion, causing obstructive symptoms and pneumonia. We present a rare case of an 82-year-old man who was previously diagnosed with bladder and renal pelvis urothelial carcinomas and an obstructive 1.2-cm endobronchial mass in the left main bronchus. Biopsy and subsequent subtotal resection of the mass showed adenoid cystic carcinoma. The patient was admitted, and a left mainstem bronchial mass was found during metastatic workup for bladder carcinoma. Computed tomography showed a noncalcified 1.2-cm nodule within the left main bronchus and arising from the superior wall of the bronchus. The lesion almost completely occluded the bronchus; atelectasis did not occur. The tumor was biopsied and subsequently resected. The morphology and immunohistochemistry studies showed an adenoid cystic carcinoma (Figure 23). In conclusion, adenoid cystic carcinoma of the bronchus is a rare clinical entity that may present with nonspecific symptoms or incidentally. These tumors generally behave in an indolent fashion, and early detection with surgical removal is indicated. Proper diagnostic evaluation and therapy can increase the long-term survival of patients with bronchial salivary gland–like tumors.

Diagnostic Utility of D2-40 in Pleural Neoplasms (Poster No. 57)

Yingchuan Hu, MD, PhD1 (ying_hu@urmc.rochester.edu); Qi Yang, BSc1; Loralee A. McMahon, BSc1; Hanlin L. Wang, MD, PhD2; Haodong Xu, MD, PhD.11Department of Pathology and Laboratory Medicine, University of Rochester, New York; and 2Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.

Context: Accurate diagnosis of malignant mesothelioma (MM) is crucial. Identification of a biomarker to assist in differential diagnosis between MM and other neoplasms is desirable. D2-40 is a new monoclonal antibody recognizing podoplanin, and it is selective for lymphatic endothelia. Several studies have confirmed the reliability of D2-40 in the diagnosis of pleural MM, but the evaluation of this antibody in other pleural neoplasms is limited. This study aims to determine the diagnostic value of D2-40 in the segregation of MM from other pleural neoplasms.

Design: D2-40 immunohistochemical staining was performed on 36 pleural MMs, 15 solitary fibrous tumors (SFTs), 13 pleomorphic carcinomas, and 3 synovial sarcomas. A tumor was considered positive if more than 10% of tumor cells stained with D2-40 antibody. The staining intensity was graded as weak, moderate, or strong. A P value less than .05 was considered statistically significant.

Results: Twenty-five of 36 (69%) MMs (21 epithelioid and 4 biphasic) and 2 of 15 (13%) SFTs were positive for D2-40. No D2-40 positivity was detected in pleomorphic carcinomas (n = 13) or synovial sarcomas (n = 3). The difference of D2-40 positivity between MMs and SFTs was significant (P < .001).

Conclusions: D2-40 was highly positive in MM, but it was also positive in a small percentage of SFTs. These findings indicate that D2-40 is a useful marker for MM, but caution should be taken in diagnosing small biopsy specimens of D2-40–positive pleural spindle cell neoplasms, especially in rendering the differential diagnosis between SFT and MM.

An Unusual Presentation of Pulmonary Talcosis in a 55-Year-Old Woman (Poster No. 58)

Aarti Goswami, MD (goswami.aarti@danhosp.org); Muhammad Asim Syed, MD; Steven Sieber, MD; Hani El-Fanek, MD. Department of Pathology, Danbury Hospital, Danbury, Connecticut.

Repetitive inhalational exposure to talc can lead to chronic pulmonary disease. This condition has been reported in millers, miners, and drug abusers but has rarely been associated with exposure to cosmetic talc-containing products. A 55-year-old woman presented with a 3- to 4-month history of progressive dyspnea and cough. She had a history of alcohol and cocaine abuse, which was discontinued approximately 10 years ago. There was no known exposure to occupational dusts, pets, or travel. Chest computed tomography scan revealed evidence of interstitial lung disease. Based on this presentation, differential diagnosis included bronchiolitis obliterans-organizing pneumonia, sarcoidosis, and hypersensitivity pneumonitis. A transbronchial biopsy of the right middle and lower lobes was performed. On microscopic examination, biopsy revealed fragments of lung parenchyma with alveolar septal expansion by nonnecrotizing, foreign body–type granulomas. There were scattered multinucleated giant cells, many of which contained polarizable, birefringent, platelike and needle-shaped talc particles. The granulomas and talc particles were not identified in association with blood vessels, ruling out exposure related to intravenous drug abuse. Questioning of the patient revealed no known exposure to talc-containing products, and she admitted only to using a cornstarch-based powder, which she routinely applied to her body after showering. Given her remote history of cocaine abuse, the possibility of talc exposure via inhalation of crushed talc-containing pills was considered. We report a rare case of inhalational pulmonary talcosis with an unclear source of exposure in a 55-year-old woman. This chronic pulmonary disease can progress to interstitial fibrosis, emphysema, and chronic respiratory failure (Figure 24).

Extranodal Natural Killer Cells/T-Cell Lymphoma: A Case of Pulmonary Presentation With Unique Alveolar-Tropic Infiltration Resembling Organoid Pattern Seen in Carcinoid or Other Neuroendocrine Tumors (Poster No. 59)

Kelly L. West, MD, PhD (kelly.west@duke.edu); Charles B. Hutchinson, MD; Endi Wang, MD, PhD. Department of Pathology, Duke University Medical Center, Durham, North Carolina.

A 31-year-old woman presented with cough, shortness of breath, and abdominal pain. Imaging studies revealed a right middle lobe peribronchial lung mass and duodenal wall thickening. Lung biopsy revealed a monotonous population of small- to medium-sized round cells in an intraalveolar distribution showing an organoid pattern at low magnification (Figure 25, original magnification ×100; inset, original magnification ×600). Flow cytometric analysis and immunohistochemical staining demonstrated expression of CD45, CD7, cytoplasmic CD3, CD2, TIA1, granzyme B, CD56, and CD57. There was no expression of surface CD3, CD5, CD4, CD8, CD10, TdT, and CD34. Additionally, there was no expression of B-cell and myeloid-specific antigens. A T-cell receptor gene rearrangement study detected no clonally rearranged product. These findings support a diagnosis of extranodal natural killer/T-cell lymphoma. Duodenal wall biopsy demonstrated involvement by a similar monotonous lymphoid population. After high-dose chemotherapy, the patient underwent matched unrelated donor stem cell transplant and has continued in clinical remission. Extranodal natural killer/T-cell lymphoma is a rare, clinically aggressive neoplasm with frequent involvement of upper aerodigestive tract. Other extranodal sites, such as gastrointestinal tract and skin, can also be preferentially involved; however, primary pulmonary presentation is extremely rare. Although natural killer/T-cell lymphoma usually shows angiocentric/angiodestructive morphology, the alveolar-tropic lung infiltration in our case is unique and has never been reported in English literature to the best of our knowledge. Because of this unusual presentation, potential misdiagnoses include carcinoid tumor in particular, small cell carcinoma, and other tumors of neuroendocrine origin. A panel of immunohistochemical studies, including CD45, is recommended for initial identification.

Squamous Cell Carcinoma of the Lung Secreting Human Chorionic Gonadotropin and β-Human Chorionic Gonadotropin in a Young Female Smoker (Poster No. 60)

Marier Hernandez, MD (marier.hernandez@bmc.org); Katherine Downey, MD; Sandra Cerda, MD. Department of Pathology and Laboratory Medicine, Boston Medical Center, Boston, Massachusetts.

A 43-year-old woman presented with dysfunctional uterine bleeding for approximately 1 year. She had a human chorionic gonadotropin level of 14 000 mIU/mL (normal upper limit, 0.7 mIU/mL) and a β-human chorionic gonadotropin level of 20 132 mIU/mL (normal upper limit, 0.5 mIU/mL). Pelvic examination and ultrasonography showed no abnormal findings and no signs of pregnancy. At that time, the patient developed pain in the left upper quadrant, which was aggravated by deep breathing. She also reported weakness, intermittent night sweats, and an unintentional 12-lb weight loss during the past year. She denied shortness of breath or cough. A computed tomography scan of the thorax showed a 7-cm right lower lobe lung mass and a 1.2-cm left apex nodule contiguous with pleura. A positron emission tomographic scan showed potential metastatic lesions throughout the right and left lobes of the liver, spleen, and left kidney and a left frontal brain lesion. A fine-needle aspirate of a liver mass and bronchoscopy with a Wang needle biopsy of the right lower mass were performed. The pathology showed metastatic squamous cell carcinoma with immunohistochemical staining as follows: positive for human chorionic gonadotropin, AE1/AE3, cytokeratin 7, and p63 and negative for cytokeratin 20, thyroid transcription factor 1, and carcinoembryonic antigen. The patient died 4 months after diagnosis. Although pulmonary squamous cell carcinoma secreting human chorionic gonadotropin is rare (only 2 cases have been reported in the literature), it should be considered in any case in which a woman has elevated human chorionic gonadotropin and no evidence of pregnancy.

Expression of Excision Repair Cross-Complementation Group 1 in Tissue Microarray of 222 Non–Small Cell Lung Cancers: Correlation With Patient Survival (Poster No. 61)

Munir Shahjahan, MD1 (mshahjahan@tmhs.org); Philip T. Cagle, MD1; Timothy C. Allen, MD2; Anna Sienko, MD1; Abida Haque, MD1; Roberto Barrios, MD1; Subhendu Chakraborty, MS1; Bahram R. Oliai, MD3; Rodney T. Miller, MD3; Cary J. Buresh, MD3; Helmut H. Popper, MD4; Qihui (Jim) Zhai, MD.11Department of Pathology and Laboratory Medicine, The Methodist Hospital, Houston, Texas; 2Department of Pathology and Laboratory Medicine, University of Texas at Tyler; 3Department of Pathology, Propath, Dallas, Texas; and 4Department of Pathology, Medical University of Graz, Austria.

Context: Patients with non–small cell lung cancers (NSCLCs) have a poor prognosis, with half of patients with stage I and II cancers dying of their disease despite tumor resection. Excision repair cross-complementation group 1 (ERCC1) is 1 of 16 genes that encode the proteins of the nucleotide excision repair complex. We examined the correlation between ERCC1 expression and long-term survival of patients with resected NSCLC prior to current adjuvant therapy protocols to determine its potential status as an independent prognostic biomarker for survival.

Design: We included 222 cases with pathologically confirmed NSCLC (stages I–II) from the 1970s to early 1990s. Immunohistochemistry was used to measure the expression of ERCC1 in tissue microarray sections with 3 punches from each case. Immunopositivity in tumor cells was graded on a scale from 0 to 3 and was averaged for the 3 punches from each tumor. ERCC1 expression was compared with 5-year survival using Kaplan-Meier analyses, including by cell type and tumor stage.

Results: Negative/weak ERCC1 expression was observed in 157 of 222 (71%) of NSCLC (47% of adenocarcinomas, 20% of squamous cell carcinomas, 18% of large cell carcinomas). In patients with stage I and II disease, absent or weak ERCC1 expression was associated with a strong trend toward shorter survival (P = .06).

Conclusions:ERCC1 expression is absent or weak in more than two thirds of NSCLC patients. Negative or weak expression is associated with a strong trend toward decrease in 5-year survival. ERCC1 expression may serve as a biomarker of prognosis for patients with NSCLC.

Giant Cell Tumor Primary in the Lung (Poster No. 62)

Jo Elle G. Peterson, MD1 (jgpeterson@tmhs.org); Roberto Barrios, MD1; Timothy C. Allen, MD, JD2; Jerry W. Gauthier, MD3; Alberto G. Ayala, MD1; Philip T. Cagle, MD.11Department of Pathology, The Methodist Hospital, Houston, Texas; 2Department of Pathology, The University of Texas Health Science Center at Tyler; and 3Department of Pathology, Spring Branch Medical Center, Houston, Texas.

Giant cell tumors (GCTs) are primarily regarded as tumors of the bone. Despite their potential to metastasize to the lung and other organs, GCTs are commonly benign. Although cases of GCT have been reported in the pancreas, thyroid, skin, lung, and soft tissue, few GCT primary in organs other than bone are included in the literature. We report a case of primary GCT of the lung in a patient without bone involvement. A 75-year-old man presented with a history of heavy smoking, chronic obstructive pulmonary disease, hypertension, hyperlipidemia, glaucoma, and cerebrovascular disease. He had a chronic unproductive cough and was found to have a solitary 1.7-cm right lower lobe lung mass. A transbronchial biopsy of the mass showed a tumor composed of sheets of round to oval cells with a delicate connective tissue stroma. Admixed with the tumor cells were multinucleated giant cells without atypia. An occasional mitotic figure was identified. Cytokeratins were negative in tumor cells. The patient underwent resection of the right lower lobe and has been without evidence of disease for the past 1.5 years. Microscopically, this tumor resembled a GCT of the bone. This is the 11th case reported in the literature to date of a primary GCT of the lung. Pathologists should be aware that GCT may occur as a primary neoplasm in the lung.

CD34 and α-Smooth Muscle Actin Distinguish Idiopathic Cryptogenic Organizing Pneumonia From Secondary Bronchiolitis Obliterans With Organizing Pneumonia (Poster No. 63)

Karen N. Wu, MD1 (karennwu@gmail.com); Tajender S. Vasu, MD2; John L. Farber, MD.1 Departments of 1Pathology and 2Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania.

Context: Secondary bronchiolitis obliterans with organizing pneumonia (BOOP) is a reaction to injury, forming granulation tissue within airspaces. Idiopathic cryptogenic organizing pneumonia (COP) and secondary BOOP are histologically similar. COP has been reported to show increased collagen in the granulation plugs and fewer myofibroblasts and capillaries. Using CD34 for capillaries and α-smooth muscle actin for myofibroblasts, we assessed these stains to differentiate COP from secondary BOOP.

Design: We retrieved and reviewed 21 biopsies diagnosed as secondary BOOP to verify they met criteria for secondary BOOP. Next, they were stained for CD34 and α-smooth muscle actin. Based on the intensity of staining, they were classified as either COP or secondary BOOP. Clinical data were reviewed for evidence of a specific condition to confirm a diagnosis of secondary BOOP. In the absence of such data, the case was clinically classified as COP.

Results: From the α-smooth muscle actin and CD34 staining, 6 of 21 cases were diagnosed as COP. The clinical records revealed a cause in 1 of 6 cases. Thus, 5 of 6 cases were correctly classified as COP. We diagnosed 15 of 21 cases as secondary BOOP. A cause was determined in 9 cases (7 chemoradiation, 1 local effects of cancer, 1 illicit drugs). No cause was found in 6 cases.

Conclusions: Fourteen of 21 cases were correctly classified histologically as COP or secondary BOOP. One case was inappropriately classified; the remaining 6 were classified as secondary BOOP without an apparent clinical etiology. The data suggest that CD34 and α-smooth muscle actin are useful in distinguishing COP from secondary BOOP.

Sclerosing Mediastinitis Presenting as Superior Vena Cava Syndrome in a Patient With History of Coccidioides Pneumonia (Poster No. 64)

Hannah H. Wong, MD1 (hhwong@llu.edu); Heather L. Rojas, MD.2 1Department of Pathology and Laboratory Medicine, Loma Linda University Medical Center, Loma Linda, California; and 2Department of Pathology, Jerry L. Pettis Memorial Veterans Administration Medical Center, Loma Linda, California.

Sclerosing mediastinitis is an extremely rare fibrotic reaction involving the mediastinum and is associated with fungal and mycobacterial infections. In the United States, sclerosing mediastinitis is most commonly associated with Histoplasma capsulatum and often presents as superior vena cava syndrome. A 27-year-old man presented with a 3-week history of dry cough and night sweats. Chest x-ray revealed consolidation of the right upper lobe with lymphadenopathy in the right hilum and mediastinum. Needle biopsy revealed a granulomatous reaction with fibrosis, chronic inflammation, and increased eosinophils. Periodic acid–Schiff, Gomori methenamine silver, and acid-fast bacillus stains were negative for fungal and bacterial forms. However, Coccidioides immitis titers were positive, and the patient was started on fluconazole. Three years later, he presented with complaints of shortness of breath and head pressure. He reported his face turning purple whenever he ran or played basketball. These episodes were associated with dizziness and visual changes. Physical examination revealed prominent veins and swelling in the right anterior chest and shoulder. Radiologic studies revealed a 4-cm mass encasing the superior vena cava with 90% stenosis; all findings were consistent with superior vena cava syndrome. A needle-core biopsy of the mediastinal mass revealed fibrotic scar tissue with chronic inflammation (Figure 26), and periodic acid–Schiff stain showed absence of fungal elements; these findings are most consistent with the diagnosis of fibrosing mediastinitis. The patient was effectively treated with stent placement. We present this rare case of Coccidioides associated with sclerosing mediastinitis and the classic presentation of superior vena cava syndrome.

Invasive Ductal Carcinoma of the Breast With Metastasis to Primary Adenocarcinoma of the Lung (Poster No. 65)

Elizabeth N. Pavlisko, MD (elizabeth.pavlisko@duke.edu); John Papalas, MD; Victor Roggli, MD; Angelica Selim, MD. Department of Pathology, Duke University Medical Center, Durham, North Carolina.

Breast cancer most commonly metastasizes to the brain, liver, lungs, and bone. Solitary pulmonary nodules in women with breast cancer are most likely primary lung cancer. We present a 58-year-old woman diagnosed with invasive ductal carcinoma of the right breast (Nottingham grade 3 of 3) and associated ductal comedocarcinoma in situ. The tumor was positive for hormone receptors. After the patient underwent right modified radical mastectomy, imaging studies showed a 1-cm right upper lobe nodule. Given the patient's extensive smoking history, we were concerned that this represented a primary lung cancer; accordingly, the patient underwent right thoracotomy with right upper lobectomy. The lung was remarkable for a 1.9-cm moderately differentiated primary lung adenocarcinoma, papillary variant. Approximately 1 year after her diagnosis of breast cancer and concurrent lung cancer, we performed a punch biopsy on a chest wall nodule. Within the dermis, there were both clusters and single malignant epithelial cells. The immunoprofile favored a breast primary. Based on the finding of metastatic breast cancer in the skin, the lung lesion was reexamined and showed a small focus of solid tumor in the papillary adenocarcinoma of the lung. This focus was BRST2 positive and thyroid transcription factor 1 negative. The lung primary had the opposite staining pattern. The presence of 2 tumors is not uncommon; however, increased awareness regarding the metastasis of one tumor to another is needed because this information can potentially impact tumor stage at an earlier time. In addition, further molecular study is needed to understand homing of one tumor to another.

Atypical Proteinosis: A Pathologic Disorder Mimicking Pulmonary Alveolar Proteinosis (Poster No. 66)

Michiya Nishino, MD, PhD1 (mnishino1@partners.org); Benjamin D. Medoff, MD2; Walter J. O'Donnell, MD2; Eugene J. Mark, MD1; Richard L. Kradin, MD.1 Department of 1Pathology and 2Pulmonary and Clinical Care Unit, Massachusetts General Hospital, Boston.

Context: Pulmonary alveolar proteinosis (PAP) is a rare condition in which macrophages fail to clear surfactant from the lungs, resulting in the alveolar accumulation of lipoproteinaceous debris. The histopathology of PAP is typified by the diffuse filling of alveoli with granular, periodic acid-Schiff–positive acellular material. However, the significance of cases of proteinosis that vary from the classic morphology of PAP is uncertain.

Design: Clinical histories, radiographic findings, and pathologic features of pulmonary wedge biopsies from patients diagnosed with PAP at the Massachusetts General Hospital between 2006 and 2008 were reviewed.

Results: Three patients with respiratory distress showed histopathologic changes in the lungs that were most consistent with mild PAP; there was no other discernible pathology. The pathologic features of these cases were distinct from “usual” PAP and on ultrastructural examination showed abundant degenerating histiocytes, weak periodic acid–Schiff staining of the intraalveolar lipoproteinaceous material, and few well-formed lamellated bodies. On computed tomography, only one of the cases showed the “crazy-paving” pattern typical of PAP, and bronchoalveolar lavage did not yield the opalescent fluid emblematic of PAP. Of importance, in one case, whole-lung lavage appeared to exacerbate the patient's respiratory distress. All 3 patients showed at least a partial response to high-dose steroid therapy.

Conclusions: The diagnostic distinction between PAP and “atypical proteinosis” may be clinically significant. Despite the diffuse accumulation of lipoproteinaceous material in alveoli in the latter, the presence of abundant degenerating histiocytes and atypical histochemical, ultrastructural, and radiographic features suggests a steroid-responsive form of atypical proteinosis that may not be amenable to whole-lung lavage.

Diffuse Thymic Fibrosis Mimicking Neoplasia: Report of 4 Cases (Poster No. 67)

Konstantin Shilo, MD1 (shilok@afip.osd.mil); Haresh Mani, MD1; Irem H. Ozbudek, MD3; William D. Travis, MD4; Jeffrey R. Galvin, MD2; Teri J. Franks, MD.1 Departments of 1Pulmonary and Mediastinal Pathology and 2Radiologic Pathology, Armed Forces Institute of Pathology, Washington, DC; 3Department of Pathology, University of Akdeniz School of Medicine, Antalya, Turkey; and 4Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.

Context: Extensive thymic fibrosis in the absence of a primary thymic lesion (neoplasm or cyst) is unusual. We describe 4 cases of diffuse thymic fibrosis presenting as mass lesions.

Design: We identified 4 cases of diffuse thymic fibrosis referred to our consultation service between 2001 and 2004. Clinical features, gross reports, and histologic slides were reviewed. Immunohistochemical studies were performed using commercial antibodies to pancytokeratin, CD3, CD1a, and IgG4 (Dako, Carpinteria, California).

Results: The 4 cases included 2 men and 2 women ranging in age from 28 to 62 years (mean, 48 years). Both women had myasthenia gravis; 1 man presented with fever and dyspnea; the mass was discovered incidentally in 1 man. The masses measured 5.5 to 16.5 cm (mean, 9.75 cm) in greatest dimension. The lesions were confined to the thymus/anterior mediastinum by imaging or as determined from intraoperative notes. They were well demarcated and lobulated. There were 3 to 15 (mean, 11) hematoxylin-eosin–stained sections available for review on each case. Microscopically, the fibrosis was diffuse and dense and resembled the fibrosis of fibrosing mediastinitis. No granulomas were identified. There were small residual islands of involuted thymic tissue with paucity of lymphocytes in all cases. One case showed increased IgG4-positive plasma cells.

Conclusions: To the best of our knowledge, the observed diffuse thymic fibrosis is unique and not previously documented in the literature. Although the etiology of the fibrosis is undetermined, the history of myasthenia gravis and the histology resembling fibrosing mediastinitis raise the possibility of autoimmune or infectious causes. Alternatively, the lesions may be idiopathic in nature.

Clinicopathologic Correlation of Pulmonary Dirofilariasis (Poster No. 68)

Oleksandr N. Kryvenko, MD (okryven1@hfhs.org); Linoj P. Samuel, PhD; Chad H. Stone, MD. Department of Pathology, Henry Ford Hospital, Detroit, Michigan.

Human pulmonary dirofilariasis (HPD) is a rare vector-born parasitic infection that is a clinical simulator of malignant lung neoplasm. Dogs and cats are the usual natural hosts of Dirofilaria immitis. Transmission to humans occurs through mosquito bites. Humans are a dead-end host because larvae cannot develop into adult form. HPD develops when the larva dies in circulation, embolizes to the lung, lodges in a small pulmonary artery branch, and releases antigens. These antigens lead to endarteritis with subsequent thrombosis and pulmonary infarction of a size larger than expected. A 59-year-old man presented with complaints of cough, sputum production, and wheezing. He was found to have a peripheral 1.2-cm mass in the upper lobe of the left lung and left hilar lymphadenopathy. The patient had a long history of smoking and alcohol abuse. Wedge resection of the mass revealed necrotizing granuloma on frozen section, and permanent sections demonstrated a discrete necrobiotic granulomatous nodule with a centrally placed thrombosed artery containing a parasitic worm characteristic of D immitis (Figure 27). The preoperative diagnosis of HPD is difficult because of a lack of characteristic clinical symptoms, laboratory results, and roentgenographic findings. The probability of definitely diagnosing HPD on either biopsy or fine-needle aspiration biopsy is low. Extensive sampling of necrobiotic granulomas, with attention specifically directed toward detection and examination of a central supplying artery, is recommended.

POSTER SESSION 300: MONDAY, OCTOBER 12, 2009, 9:00 am–11:30 am

Hematopathology; Kidney and Genitourinary Pathology

Composite Classic Hodgkin Lymphoma and Langerhans Cell Histiocytosis Arising in the Mediastinum of a Pediatric Patient (Poster No. 1)

Katherine J. Robbins, MD1; Thomas W. McLean, MD2; David D. Grier, MD1 (dgrier@wfubmc.edu). Departments of 1Pathology and 2Pediatrics, Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Langerhans cell histiocytosis (LCH) is a neoplastic process defined by a proliferation of Langerhans cells. Rarely, LCH is found to occur asynchronously and synchronously with classic Hodgkin lymphoma (CHL) and other neoplasms. Synchronous occurrences of LCH and CHL have been reported in different anatomic locations (eg, CHL in a lymph node and LCH in the bone) and as composite tumors (eg, CHL and LCH occurring in the same lymph node). Most cases of composite CHL and LCH involve adults and are found in peripheral lymph nodes. We describe a case of a previously healthy 15-year-old adolescent boy who presented to the emergency department with a 2- to 3-week history of progressive superior vena cava syndrome symptoms. A computed tomography scan demonstrated a 22 × 14 × 8-cm heterogenous mediastinal mass with associated mediastinal and right cervical lymphadenopathy. Core biopsies of the mediastinal mass revealed a composite CHL and LCH. By immunohistochemistry, the CHL component was positive for CD30, CD15, and Pax-5 and negative for CD1a, CD20, and S100 protein. The LCH component was positive for CD1a and S100 protein and negative for CD30, CD15, CD20, and Pax-5. While composite CHL and LCH has been described in the literature, this is the youngest patient reported so far to have a composite LCH and CHL and the first case reported to arise in the mediastinum.

Signet Ring Follicular Lymphoma Presenting as a Soft Tissue Mass (Poster No. 2)

Aine Yung, MD (yunga@cshs.org); Brian Kwok, MD; Randa Alsabeh, MD. Department of Hematopathology, Cedars-Sinai Medical Center, Los Angeles, California.

Signet ring follicular lymphoma is a rare morphologic variant of follicular lymphoma. It has been reported in lymph nodes, bone marrow, and various extranodal sites. We report a case of a 54-year-old woman who presented with a popliteal mass. Magnetic resonance imaging performed on the patient's knee showed an oval mass in the posterior subcutaneous tissue that measured 2.8 cm in greatest dimension with no other evidence of disease. Microscopically, the lymphoma showed signet ring follicular lymphoma grade 3/3 with areas of diffuse large B-cell lymphoma (Figure 28). By immunohistochemistry, the tumor was positive for CD20, CD10, Bcl-2, and Bcl-6 and negative for CD5, CD23, CD43, Bcl-1, IgG, IgA, IgM, IgD, κ, and λ. Fluorescence in situ hybridization (FISH) demonstrated a translocation with the BCL-2 gene on chromosome 18q21 and IgH gene on chromosome 14q32. Gene rearrangement by polymerase chain reaction showed that the tumor was positive for clonal Ig heavy chain and Ig light chain rearrangements. To our knowledge, this is the first reported case of a signet ring follicular lymphoma with a documented presence of t(14;18) by FISH and with a presentation of a soft tissue mass clinically mimicking a sarcoma. This case serves to illustrate that follicular lymphoma may morphologically mimic a soft tissue neoplasm and the diagnosis should be considered when other studies do not support a sarcoma or carcinoma.

Primary Cardiac Lymphoma Should Be Included in the Differential Diagnosis of a Right Atrial Mass (Poster No. 3)

Yasin Ahmed, MD1 (YASIN.AHMED@STJOHN.ORG); Daniel Snower, MD1; Dima Abdul Jabbar, MD2; M. Zulfiqar, MD1; Andy Boguszewski, MD3; Edouard Daher, MD3; Ayad Al-Katib, MD.4 Departments of 1Pathology, 2Internal Medicine, and 3Cardiology, St John Hospital and Medical Center, Detroit, Michigan; 4Department of Hematology and Oncology, St John Hospital and Medical Center/Van Elslander Cancer Center, Detroit, Michigan.

A 63-year-old woman with no significant past medical history presented to the emergency room in October 2008 complaining of dyspnea on exertion and chest pain of 3 weeks' duration. Echocardiogram showed a large right atrial mass that extended and prolapsed into the right ventricle. The mass was attached to the interatrial septum with right ventricular inflow obstruction. Preoperative cardiac catheterization showed mild coronary artery disease and a 60% left ventricular ejection fraction. Presumptive diagnosis of large blood clot versus atrial myxoma was made and the patient underwent open chest exploration. Needle core biopsies of the mass were obtained and a frozen section was requested that showed atypical lymphoid infiltrate suggestive of lymphoma. The mass was not resected. Permanent section evaluation displayed diffuse infiltrates of large atypical lymphocytes with moderate mitotic activity. Fresh tissue sent for cell surface analysis by flow cytometry revealed the presence of monoclonal B-cell population with κ light chain restriction. Immunohistochemical studies showed B-cell markers CD20 and CD79a to be positive in the large atypical cells. Proliferative fraction, as measured by Ki-67 staining, was very high and estimated at 90%. These findings were indicative of diffuse large B-cell lymphoma. The right atrium and right ventricle are the 2 most frequently involved sites in primary cardiac lymphomas. This case highlights the importance of adding primary cardiac lymphoma to the preoperative workup as well as the role of intraoperative frozen section examination that may help spare the patient unnecessary as well as risky resection or debulking procedures.

Prognostic Significance of Molecular Translocation t(9;11) Involving AF-9/MLL Gene in Infant Acute Lymphoblastic Leukemia (Poster No. 4)

Ashish Bains, MD1 (ashish-bains@ouhsc.edu); Sara Lewis, MD2; William F. Kern, MD.1 Departments of 1Pathology and 2Pediatrics, Oklahoma University Health Sciences Center, Oklahoma City.

The annual incidence of acute lymphoblastic leukemia (ALL) in infants is approximately 19 per million. These leukemias are unique and differ greatly from those of ALL in older children. Many of these are associated with translocation t(4;11)(q21;q23), AF-4/MLL. We present an uncommon case of infant ALL involving translocation t(9;11)(p22;q23), AF-9/MLL, and its associated clinical presentation, immunophenotype, and prognostic significance. The patient is a 9-month-old male infant with an initial white blood cell count of 494 000/μL with 90% blasts on his peripheral smear (Figure 29) expressing a precursor B-cell ALL phenotype (CD19+, CD38+, HLA-DR, CD34, CD10, sIg). The results of a spinal tap performed at admission were positive for central nervous system involvement with leukemic cells. Literature search identified differences in event-free survival (EFS) of infant ALL, in the CCG 107 and 1883 trials, among the more common t(4;11) translocation as compared to other MLL fusion partners including t(9;11). However, a more recent CCG 1953 trial showed no such differences in prognosis between individual MLL translocations. The 5-year EFS in MLL-rearranged cases is reported as 33.6% compared to 60.3% in MLL-nonrearranged cases. Poor prognostic markers are MLL/ 11q23 translocation, CD10 status, and less than 6 months of age. MLL translocation and lack of CD10 expression correspond very closely, and thus it is difficult to assess their independent prognostic significance. Hematopoietic stem cell transplantation (HSCT) at first remission, with less toxic conditioning regimen, has been shown to improve EFS in MLL-rearranged cases, suggesting a possible therapeutic advantage of early HSCT.

Bone Marrow Infiltration of Non-Hodgkin Lymphoma (Poster No. 5)

Xuchen Zhang, MD, PhD (xuchen.zhang@downstate.edu); Jie Ouyang, MD, PhD; Constantine Axiotis, MD. Department of Pathology, SUNY Downstate Medical Center, Brooklyn, New York.

Context: The pattern of bone marrow (BM) involvement and combination of immunophenotyping are important in BM biopsy specimens to establish diagnosis of lymphoma or to determine the extent of disease dissemination for staging purposes.

Design: We retrospectively reviewed 231 BM biopsy specimens obtained from January 2006 to December 2008 in Kings County Hospital Center and investigated the histologic patterns of non-Hodgkin lymphoma (NHL) according to World Health Organization 2008 classification. BM involvement patterns are divided into categories of paratrabecular, diffuse, nodular, interstitial, sinusoidal, and mixed. Immunohistochemistry (IHC) and flow cytometry data were also analyzed.

Results: Of the 231 BM biopsy specimens, 23 cases (10%) with NHL involvement were identified; 11 cases were T-cell lymphomas and 12 cases were B-cell lymphomas. In T-cell lymphomas, the majority (lymphoblastic leukemia/lymphoma, adult T-cell leukemia/lymphoma, peripheral T-cell lymphoma, NOS, and NK/T cell lymphoma, nasal type) showed diffuse or interstitial pattern of infiltration; anaplastic large cell and hepatosplenic lymphomas were characterized by sinusoidal infiltration. In B-cell lymphomas, the majority (plasmablastic lymphoma, lymphoblastic leukemia/ lymphoma, hairy cell leukemia, and marginal zone cell lymphoma) showed interstitial infiltration, sometimes admixed with sinusoidal infiltration; small lymphocytic lymphoma/chronic lymphocytic leukemia presented as nodular or diffuse patterns; and Burkitt lymphoma demonstrated diffuse pattern. Immunophenotyping by IHC or flow cytometry can assist classification and recognize some infiltration patterns, such as interstitial and sinusoidal infiltrations.

Conclusions: Recognition of infiltration pattern is important in the diagnosis and staging of patients with NHL. The combination of histology, IHC, and/or flow cytometry aid the diagnosis and subtyping of NHL BM infiltration.

Subdural Hematoma and Associated Accelerated Phase of BCR/ABL1-Positive Chronic Myelogenous Leukemia Occurring in the Setting of Long-Standing JAK-2V617F–Positive Polycythemia Vera (Poster No. 6)

Ying Zhang, MD1 (yzhang1@lifespan.org); Sheila Pascual, MD2; Cannon Milani, MD2; Diana O. Treaba, MD.11Department of Pathology and 2Division of Hematology/Oncology, Rhode Island Hospital, Providence.

A 74-year-old male patient with a long-standing history of polycythemia vera, pulmonary hypertension, congestive heart failure, and left ventricular thrombus presented with marked shortness of breath and left-sided weakness at the emergency room. A head computerized tomography examination revealed an acute and chronic right subdural hematoma. The complete blood count showed white blood cell count 51.1 × 103/μL; absolute neutrophil count 36.3 × 103/μL; signs of monocytosis 2.6 × 103/ μL, eosinophilia 1.5 × 103/μL, and slight basophilia 0.5 × 103/μL; mean corpuscular volume 69.7 μm3; hemoglobin 6.5 g/dL; and platelets 10 × 103/μL. A leukoerythroblastic picture was noted on the peripheral blood smear, with circulating dysplastic neutrophils. The hypercellular bone marrow had increased trilineage hematopoiesis, dysmegakaryopoiesis, dyserythropoiesis, increased reticulin deposition, and absent iron stores. By immunohistochemistry, there were 5%–6% CD34+ and approximately 20% CD117+ nucleated bone marrow cells. While a 46,XY karyotype was noted, molecular studies detected the BCR/ABL1 translocation in both the peripheral blood and the bone marrow aspirate. The bone marrow was positive for the JAK-2V617F mutation. The findings were in keeping with an accelerated phase of chronic myelogenous leukemia, BCR/ABL1 positive, which evolved in a background of long-standing polycythemia vera. The unusual occurrence of chronic myelogenous leukemia in the setting of polycythemia vera has been rarely reported in the medical literature and should be of consideration in the differential diagnosis of so-called myeloid metaplasias in patients with long-standing polycythemia vera. Whether these findings represent disease evolution or just a random association remains to be discovered.

A Rare Case of Moyamoya Disease with Sickle Cell Trait (Poster No. 7)

Renuka Agrawal, MD1 (renuagra@yahoo.com); Carolyn Wong, BS, BA2; Dana Kruetzfeldt, BS2; Caroline Berube, MD3; Gary Steinberg, MD, PhD4; Tracy George, MD.51Department of Pathology and Laboratory Medicine, Loma Linda University Medical Center, Loma Linda, California; 2Department of RBC Special Studies Laboratory, Stanford Clinical Laboratories, Palo Alto, California; Departments of 3Medicine/Hematology, 4Neurosurgery, and 5Pathology and Laboratory Medicine, Stanford University Hospital & Clinics, Stanford, California.

Moyamoya disease is a rare, idiopathic cerebrovascular disorder primarily affecting children. It features bilateral narrowing/occlusion of the distal internal carotid arteries and presence of a fine network of collateral channels at the base of the brain (moyamoya means “puff of smoke” in Japanese and describes the angiographic appearance). It can be fatal because of intracerebral hemorrhage. We report a rare case of an adult with moyamoya disease and sickle cell trait (HbAS). A 44-year-old East Indian man presented with left-sided weakness. A magnetic resonance angiogram revealed moyamoya disease (Figure 30). Preneurosurgery workup found normal white blood cells (9.6 × 109/μL); red blood cells (RBC) (4.70 × 1012 /μL); hemoglobin (13.5 g/dL); hematocrit (38.8%); mean corpuscular volume (82.6 fL); mean corpuscular hemoglobin (28.6 pg/ cell); mean corpuscular hemoglobin concentration (34.7 g/dL); platelet count (259 × 109/μL); high red cell distribution width (15.6%); normal iron (79 μg/dL); transferrin (381 μg/dL); transferrin saturation (21%); and high ferritin (394 ng/mL). The differential count and RBC morphology were normal. Solubility test result for sickling was positive and hemoglobin electrophoresis by high-performance liquid chromatography showed 40% HbS, <1% HbF (remaining being HbA and HbA2), confirming a diagnosis of sickle cell trait. He had no family history of sickle cell disorder and is doing well postoperatively. Although HbSS, HbSC, HbS-thalassemia, HbSO (Arab), HbFairfax, and β-thalassemia have all been reported in children with moyamoya disease, the association is distinctly rare in adults and in “hematologically benign” conditions like sickle cell trait (HBAS). The possible pathogenesis of cerebrovascular disorder in such a case remains unclear.

Simultaneous Chronic Lymphocytic Leukemia and Chronic Myeloid Leukemia: Identification of Two Distinct Clones by Fluorescence In Situ Hybridization (Poster No. 8)

Brian Kwok, MD1 (briankwok@yahoo.com); Aine Yung, MD1; Keith Lai, MD2; Jerry Hussong, MD.11Department of Hematopathology, Cedars-Sinai Medical Center, Los Angeles, California; 2Department of Pathology, Cleveland Clinic, Cleveland, Ohio.

Chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) are the most common chronic lymphoid and myeloid leukemias, respectively. However, their simultaneous occurrence is rare. We present a case of simultaneous CLL and CML in which fluorescence in situ hybridization (FISH) was used to determine whether the 2 leukemias derive from 1 common clone or 2 distinct clones. A 76-year-old man without significant history presented with leukocytosis. Physical examination was unremarkable. Peripheral blood examination revealed a hemoglobin of 17.0 g/dL, white cell count of 37.5 × 109/L (70% neutrophils, 1% eosinophils, 1% basophils, 2% monocytes, and 26% lymphocytes), and platelet count of 288 × 109/L. Bone marrow examination revealed a markedly hypercellular marrow with myeloid predominance and scattered nonparatrabecular lymphoid aggregates. Flow cytometric characterization of the peripheral blood and bone marrow showed a monoclonal B-cell population expressing CD5, CD11c (dim), CD19, CD20 (dim), CD23, and κ-light chain restriction, consistent with CLL. Karyotyping done on the bone marrow revealed 46,XY,t(9;22)(q34;q11). FISH done on the bone marrow confirmed the presence of a BCR/ABL rearrangement and additionally showed 13q14 deletion (the most common cytogenetic abnormality in CLL). To ascertain the presence of 1 common or 2 distinct clones, the bone marrow was hybridized with 3 separate probes in a single cocktail: BCR, ABL, and 13q14 (D13S319). The FISH results identified one clone (66%) with only a BCR/ABL rearrangement, and the other (27%) with only 13q14 deletion, indicating the presence of 2 distinct clones in this rare case of simultaneous CLL and CML

Utility of Bone Marrow Examination in Systemic Lupus Erythematosus (Poster No. 9)

Manjula Murari, MD (mmurari@sgpgi.ac.in). Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Context: Autoimmune-mediated cell destruction has been considered the most frequent cause of cytopenias in systemic lupus erythematosus (SLE). Both central and peripheral mechanisms may contribute to peripheral cytopenia in most cases of SLE. Since bone marrow examination is not routinely performed for patients with SLE, reported data on the subject are scarce.

Design: The frequency and features of bone marrow abnormalities were studied in 18 patients with systemic lupus erythematosus. Bone marrow aspiration and biopsy were performed to assess the hematopoietic activity and to rule out infectious and infiltrative disorders. Peripheral blood findings showed pancytopenia in most (10/18) of the cases.

Results: Quantitative hematopoietic abnormalities were common including hypocellular marrow in 8 patients and hyperplasia of erythroid or myeloid lineage in each of 4 patients. Stromal changes included cellular depletion, edema, and infiltration by lymphocytes, plasma cells, and macrophages in 10 cases. Focal increase in reticulin fibers was seen in 3 cases. One case showed presence of lymphoid aggregates and epithelioid cell granuloma without demonstrable microorganisms. In one case extensive bone marrow necrosis was present; test results for the patient were found to be negative for anti-phospholipid antibody. In this brief series no case showed hemophagocytic syndrome or overt myelodysplastic changes.

Conclusions: All these features provide persuasive evidence that the bone marrow is a common target organ affected in SLE. Hematopoietic alterations and bone marrow stromal changes may both contribute to peripheral cytopenia in most cases of SLE.

An Unusual Human Herpesvirus-8–Negative Primary Effusion Lymphoma-like Lymphoma With Biphenotypic Features: A Case Report and Review (Poster No. 10)

Liza Escuadro, MD (lescuadro@gmail.com); Ronald M. Angeles, MD; Frederick G. Behm, MD. Department of Pathology, University of Illinois at Chicago.

Primary effusion lymphoma (PEL), as defined by the World Health Organization, is a B-cell neoplasm universally associated with human herpesvirus–8 (HHV-8) and most often occurs in the setting of immunodeficiency. We present a case of a primary effusion lymphoma (PEL)–like large cell lymphoma of undetermined lineage in the ascitic fluid of a 74-year-old man with human immunodeficiency virus (HIV)–negative status, hepatitis C virus (HCV) cirrhosis, and no lymphadenopathy or lymphomatous masses by physical examination or computed tomography scan. From 1997 to 2004 there have been 5 reported cases of HIV-negative patients with chronic HCV infection who had primary lymphomatous effusions involving the abdominal cavity and who were HHV-8 and Epstein-Barr virus (EBV) negative. Like the 5 previously reported cases, our case is also negative for HHV-8 and EBV. Unlike the 5 previously reported cases, which had B-cell phenotypes, our case shows evidence of T-cell differentiation with cytoplasmic CD3 and surface CD7 expression by flow cytrometry and clonal T-cell receptor (TCR) γ rearrangement. The neoplastic cells also have t(8;14)(q24;q32) by karyotyping and cMYC-IgH fusion by fluorescence in situ hybridization. While this translocation is typically associated with Burkitt lymphoma, our case is not morphologically or immunophenotypically consistent with this disease. The Table shows the few reported cases of T-cell PEL-like lymphoma. The case reported herein is different and appears to be an unusual biphenotypic lymphoma, that is, a CD7+, CD3+ T-cell lymphoma with a cMYC-IGH gene rearrangement.

 
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Is CD45 a Reliable Marker to Rule Out Aggressive Non-Hodgkin Lymphomas? (Poster No. 11)

Joanna J. Xie, MD (joanna.xie@cshs.org); Randa Alsabeh, MD. Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California.

Context: Aggressive lymphomas can mimic other neoplastic processes and are considered in the evaluation of undifferentiated malignancies. Except for anaplastic large cell lymphoma (ALCL), CD45 is thought to be consistently expressed in most non-Hodgkin lymphomas (NHLs), and therefore a negative immunostain result is thought to exclude this diagnosis. The aim of this study is to evaluate expression of CD45 in a large number of aggressive lymphomas.

Design: One hundred forty-six cases of aggressive lymphomas were stained with CD45 antibody (1:100; Dako) by using the Dako Autostainer. Cases included 124 diffuse large B-cell lymphomas (DLBCLs), 6 lymphoblastic lymphomas (LBLs), 5 anaplastic T-cell lymphomas (T-ALCLs), and 11 anaplastic B-cell lymphomas (B-ALCLs). The intensity of CD45 staining for each case was evaluated by 2 pathologists. Grades of 0 (negative), 1 (weak), 2 (moderate), and 3 (strong) corresponded to <5%, 5%–25%, 26%–50%, and >50% positivity, respectively.

Results: See the Table.

 
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Conclusions: The largest percentage of cases with negative to weak staining occurred in lymphoblastic lymphoma (33%) followed by T-ALCL (20%) and DLBCL (15%). These findings are especially important in small-needle core biopsies of undifferentiated tumors, as NHL may be falsely excluded when only a minority of cells show CD45 expression and are missed with sampling. Although CD45 can be used as a screening marker for NHL in most cases, a negative CD45 stain result should not be considered as sole evidence for a nonhematopoietic tumor. Additional B- and T-cell lineage specific markers should be routinely performed in undifferentiated tumors when the CD45 immunostain result is negative.

Cutaneous Marginal Zone B-Cell Lymphoma Six Years After Initial Presentation with IgM Monoclonal Gammopathy (Poster No. 12)

Jason Schallheim, MD1 (jmschal@gwu.edu); Alison Huppmann, MD1; Minling Liu, MD, PhD.21Department of Pathology, George Washington Hospital, Washington, District of Columbia; 2Department of Pathology, Washington, DC VA Medical Center, Washington, District of Columbia.

Marginal zone B-cell lymphoma may be associated with monoclonal gammopathy. However, cases with significant IgM paraprotein years before the emergence of marginal zone B-cell lymphoma are rarely reported in the literature. A 65-year-old man presented with a 2-year history notable for IgM-λ monoclonal protein (2.3 g). He had no evidence of lymphadenopathy and a bone marrow biopsy result was negative. A diagnosis of Waldenström macroglobulinemia was clinically rendered. The patient received 1 course of rituximab and the paraprotein amount decreased to 0.5 g. Several months later, the patient experienced lower extremity palpable purpura and an increase of paraprotein to 2.6 g. A biopsy revealed leukocytoclastic vasculitis. Rituximab therapy was repeated, resulting in a decrease of paraprotein that remained stable at 0.5 g. Four years later, he presented with multiple subcutaneous nodules measuring up to 3 cm located on the lower back and upper chest. These nodules were hypermetabolic on positron emission tomography scan. Biopsy of a lower back nodule showed subcutaneous tissue with a diffuse lymphoid infiltrate of heterogenous small to medium lymphocytes including centrocytes, monocytoid cells, plasma cells, and rare centroblasts (Figure 31). Immunohistochemistry staining showed a predominance of CD20+, λ light chain– restricted B cells. They were negative for CD5, cyclin D1, CD10, CD23, and CD43. The morphologic and immunophenotypic features were consistent with extranodal marginal zone B-cell lymphoma with plasmacytic differentiation. This case illustrates an unusual marginal zone B-cell lymphoma presenting with multifocal subcutaneous nodules and diagnosed years after IgM paraproteinemia.

Diagnosis of Hodgkin Lymphoma in a Young Child Contributing to a Diagnosis of Ataxia Telangiectasia (Poster No. 13)

Jennifer M. Hummel, MD, MPH (jenhumme@med.umich.edu); Diane A. Hall, MD, PhD; Megan S. Lim, MD, PhD. Department of Pathology, University of Michigan Health System, Ann Arbor.

Ataxia telangiectasia is associated with neurologic impairment, immunodeficiency, and chromosomal instability. Ten percent of patients develop malignancies at an early age, predominantly leukemias and non-Hodgkin T-cell lymphomas. We report the clinical, pathologic, and molecular features of a child who presented with stage IV Hodgkin lymphoma, which led to the diagnosis of ataxia telangiectasia. A 6-year-old boy with developmental delay and “clumsiness” presented with abdominal pain, fever, and fatigue. A computed tomography scan detected enlarged mediastinal, periaortic, and supraclavicular lymph nodes. The peripheral blood smear showed neutropenia and anemia. The lymph node biopsy revealed scattered large lacunar Reed-Sternberg cells in a background of sclerosis with small lymphocytes and eosinophils. The bone marrow revealed nonnecrotizing granulomas, eosinophilia, and large atypical lymphocytes with prominent nucleoli (Figure 32). These atypical lymphocytes and lacunar Reed-Sternberg cells expressed CD30, PAX5 weakly, and CD15 in a subset, leading to the diagnosis of Hodgkin lymphoma. Subsequent neurologic examination revealed oculomotor apraxia, hand dysmetria, and gait disturbance. Serum α-fetoprotein was elevated, IgG2 was reduced, and cytogenetic evaluation of the blood demonstrated 10% of cells with chromosomal breakage, including 7;7 and 14;14 translocations consistent with ataxia telangiectasia. In situ hybridization for Epstein-Barr virus ribonucleic acid (EBER-1) was performed on the lymph node biopsy and demonstrated numerous positive cells. Although chemotherapy resulted in remission, the patient experienced a relapse 26 months later and has had persistent disease. This case documents a rare presentation of early-onset Hodgkin lymphoma with bone marrow involvement contributing to a diagnosis of ataxia telangiectasia.

Dural Extranodal Marginal Zone Lymphoma Mimicking a Meningioma (Poster No. 14)

Luis Brandi, MD1 (luis.brandi@ttuhsc.edu); Safaa Labib, MD1; Hari Bodhireddy, BS.21Department of Pathology and 2Texas Tech University School of Medicine, Texas Tech Health Sciences Center, Lubbock.

Extranodal marginal zone lymphomas primary to the central nervous system are extremely rare, are typically dural based, and are known to mimic meningiomas. They typically present with single or multiple extra-axial masses that enhance diffusely with additional contrast material and can be easily confused with a meningioma. MALT lymphoma composes 7%–8% of all B-cell lymphomas and up to 50% of primary gastric lymphomas. A 52-year-old woman presented with a complaint of a severe headache that was not responsive to medication. Magnetic resonance imaging demonstrated a 1.1 × 4.7 × 2.3-cm extra-axial enhancing mass through the interhemispheric falx, near the vertex just right of the midline in the right parafalcine region, radiologically reported as a presumed meningioma in the right parafalcine aspect. Frozen section biopsy results were positive for a lymphocytic infiltrate in a fibrous background, possibly dural. Microscopic examination of hematoxylin-eosin–stained sections revealed dural tissue with focal psammomatous calcification and a nodular infiltrate composed of a mixture of monocytoid lymphocytes and plasma cells. Immunohistochemical staining shows strong reactivity of CD20 and bcl-2 by the infiltrating cells. CD3 and CD5 highlighted reactive T lymphocytes in the background. A reported κ light chain restriction was detected in the plasma cell population; there was no expression of epithelial membrane antigen. A diagnosis of extranodal marginal zone lymphoma was made. This case demonstrates that one must be wary because the classic radiologic findings of meningioma can be seen with extranodal marginal zone lymphoma arising in the dura.

Nonsecretory, Nonproducing Plasma Cell Myeloma Presenting with Clinical Features of Hairy Cell Leukemia (Poster No. 15)

Crystal L. Rose, MD, MS (crose@chsmail.org); Janet Roepke, MD, PhD.  Department of Pathology, Ball Memorial Hospital, Muncie, Indiana.

Plasma cell myeloma is not an uncommon diagnosis and 97% of cases demonstrate the presence of an M-spike on immunofixation electrophoresis. Of the 3% of cases that fail to do so, 85% demonstrate clonal light chains in the cytoplasm of the neoplastic cells by immunohistochemistry and are therefore termed nonsecretory. Of the nonsecretory cases, 15% do not have cytoplasmic immunoglobulin synthesis and are termed nonproducing. Consequently, nonsecretory, nonproducing plasma cell myeloma composes less than 0.5% of cases. The presence of this entity as a mimic of hairy cell leukemia has yet to be reported. In our case, a 69-year-old man presented with diarrhea, anorexia, and weight loss. Peripheral blood showed numerous lymphoid cells with oval nuclei and pale blue cytoplasm with circumferential projections best characterized as classic hairy cells. Peripheral blood flow cytometry showed an immunophenotype of dim CD45, dim CD33, CD4, CD38, and CD56 positive cells. This was inconsistent with a diagnosis of hairy cell leukemia. Immunofixation electrophoresis showed hypogammaglobulinemia and no M-spike. The bone marrow showed an abnormal population of cells, 92% of which were positive for CD4, CD38, dim CD33, and dim CD56. Cytogenetic analysis demonstrated multiple abnormalities including t(11;14). κ/λ light chains by in situ hybridization showed a clonal κ population of cells. In conclusion, nonsecretory, nonproducing plasma cell myeloma is rare and can mimic hairy cell leukemia; therefore it constitutes a unique entity that warrants increased awareness.

Systemic Mastocytosis Presenting With Chronic Monocytosis and Osteoblastic Lesions in a Patient With History of Breast Cancer (Poster No. 16)

Karimireddy J. Reddy, MD (karimireddy.reddy@ucdmc.ucdavis.edu); Prashanti Reddy, MD; Edward C. Larkin, MD. Department of Pathology, UC Davis Medical Center, Sacramento, California.

We present an interesting case of an 80-year-old woman with a remote history of breast cancer who presented to an outside hospital with weakness, weight loss, fatigue, loss of appetite, dyspepsia, and loss of muscle tone. Imaging showed sclerotic lesions in the abdomen, pelvis, and thorax that were suggestive of metastases. An extensive workup yielded negative results for bone marrow biopsy, JAK-2 mutation, and BCR/ABL (fluorescence in situ hybridization) and normal cytogenetics. The patient was seen at our institution 2 months later. Peripheral blood showed leukocytosis (13.4 K/μL) and absolute monocytosis (2.4 K/μL). A differential diagnosis of myeloproliferative/myelodysplastic disorders was initially considered. A bone marrow biopsy showed alternating areas of hypercellular marrow with hypocellular spindled cells intermixed with increased reticulin fibrosis amidst markedly thickened bony trabeculae. The fibrosis and osteosclerotic bone, in light of the patient's history of breast cancer, warranted the consideration of a myeloproliferative disorder and/or radiation-induced fibrosis with osteosclerosis. However, the typical morphology of paratrabecular infiltrates of spindled cells resulted in an unexpected diagnosis of systemic mastocytosis (Figure 33). This was confirmed by tryptase immunostaining and elevated serum tryptase levels (505 μg/ L). Systemic mastocytosis is a rare disease and diagnosis requires a high degree of suspicion. Our case is unusual in its presentation with chronic monocytosis, vague constitutional symptoms, and absence of clear clinical symptoms of mast cell degranulation in the context of remote breast cancer. This case also emphasizes the importance of a meticulous bone marrow examination before resorting to more extensive diagnostic testing.

A Retrospective Review of Pathologic Diagnosis of Bone Marrow Biopsy in Hospitalized Patients (Poster No. 17)

Ming Xie, MD (mngxie@yahoo.com); Emily E. Volk, MD. Department of Pathology, William Beaumont Hospital, Troy, Michigan.

Context: Bone marrow biopsy is indicated in the evaluation of a broad variety of diseases including both hematologic lesions and nonhematologic lesions with bone marrow involvement. Many hospitalized patients with abnormal complete blood cell count (CBC) findings undergo bone marrow evaluation. This study evaluates the necessity of the bone marrow biopsy in hospitalized patients by reviewing the bone marrow biopsy reports and related clinical information.

Design: During 2007 a total of 138 bone marrow samples were collected from 133 hospitalized patients. The pathologic reports were retrospectively reviewed. Patient's information, including age, sex, clinical diagnosis for hospitalization, and the clinical indication for bone marrow biopsy were recorded.

Results: The patients consisted of 65 males and 68 females (mean age, 64 years). Hematologic diseases were detected in 64 patients (48.1%). Three patients (2.3%) showed nonhematologic diseases. Another 66 patients (49.6%) showed nonspecific histologic findings without specific pathologic diagnosis. Among these patients, 61 were hospitalized because of nonhematologic diseases, mainly respiratory failure, cardiovascular diseases, and diabetes; 5 because of lymphoma/plasma cell neoplasm without bone marrow involvement. The most frequent abnormal CBC findings are anemia, pancytopenia, bicytopenia, and thrombocytopenia.

Conclusions: In this retrospective study, nearly half (49.6%) of the bone marrow biopsy samples collected from the hospitalized patients showed nonspecific histologic findings without specific pathologic diagnosis. Although the nonspecific or negative bone marrow findings can be important information for patient care during hospitalization, in some patients, the bone marrow biopsy may be performed at an outpatient clinic after discharge for the evaluation of abnormal CBC parameters.

Aberrant Expression of T-Cell Antigens in Diffuse Large B-Cell Lymphoma of the Testis (Poster No. 18)

Jay L. Patel, MA (jay.patel@hsc.utah.edu); Albert K. Ho, MD, PhD; David W. Bahler, MD, PhD. Department of Pathology, University of Utah School of Medicine, Salt Lake City.

The aberrant expression of T-cell antigens in B-cell non-Hodgkin lymphoma occurs rarely. We report the case of a 78-year-old man with a history of diffuse large B-cell lymphoma (DLBCL) in the left testicle that was diagnosed in 1995. He was treated with unilateral orchiectomy plus multiagent chemotherapy and radiation therapy and achieved complete remission. Recently, however, he presented with a contralateral testicular mass. Hematoxylin-eosin–stained sections showed displacement of residual testicular tissue by sheets of large atypical lymphoid cells, consistent with recurrence of DLBCL. On further immunophenotypic characterization by 5-color flow cytometry, a monoclonal B-cell population was identified that expressed dim λ light chains, CD19, CD20, and the T-cell antigens CD5 and CD7 without CD3, CD10, CD22, CD30, CD45, FMC-7, or any additional T-cell markers. Immunohistochemical staining for the proliferation marker MIB-1 was performed and showed positivity in approximately 50% of the neoplastic cells. The patient went on to receive multiple cycles of chemotherapy and has once again achieved complete radiologic remission. The occurrence of T-cell markers in DLBCL is unusual and appears to be primarily of diagnostic relevance. No unusual or aggressive clinical behavior was observed in this case. B-cell non-Hodgkin lymphoma may express 1 or more T-cell antigens. One or more pan–B-cell antigens, such as CD22 in this case, may be absent. Awareness of these possibilities is necessary to avoid diagnostic errors.

Nasopharyngeal Hodgkin Lymphoma With Necrosis and Fungal Proliferation: A Challenging Diagnosis (Poster No. 19)

Melissa M. Rodgers-Ohlau, MD1 (melissa.rodgers-ohlau@ucdmc.ucdavis.edu); Michelle McNamara, MD1; Thomasina Bailey, MD1; Peter Banks, MD2; David Harrison, MD3; Denis Dwyre, MD.11Department of Pathology, University of California Davis Medical Center, Sacramento; 2Department of Pathology, Carolinas Medical Center, Charlotte, North Carolina; 3Department of Hematology and Oncology, University of California Davis, Sacramento.

Classic Hodgkin lymphoma (CHL) is a lymphoid neoplasm with at least some B-cell differentiation, typically arising in lymph nodes. Extranodal presentation is unusual; when it occurs, spleen or bone marrow is commonly affected. We report the case of a 41-year-old woman with primary nasal CHL. She presented with a progressive ulcerative nasal septal lesion. Hematoxylin-eosin–stained slides of nasal biopsies revealed extensive surface necrosis with fungal hyphae. Beneath the necrosis was acute and chronic inflammation with lymphocytic proliferation. Large cells with polylobated nuclei and macronucleoli were also noted. Immunohistochemical staining revealed that the large cells were variably positive for CD20, CD79a, Ki67, and Bcl-2 and negative for CD3, CD5, CD10, and Bcl-6. B-cell lymphoma was first considered. Additional staining showed that the cells were CD30+ and CD45. They were also positive for EBER. A diagnosis of CHL, stage IIe, was made. Because of the necrosis and fungal hyphae, it was initially unclear whether this was reactive or neoplastic, confounding the correct diagnosis. However, as necrosis often accompanies CHL, CHL should be included in the differential diagnosis when necrosis is noted. Extranodal involvement in CHL is rare (approximately 1% of all cases); rarer still is primary nasal septal CHL, mentioned in only a few cases, with no unifying features among these reports. Our case presents 2 key points: (1) it is important to consider CHL in the differential diagnosis whenever marked necrosis is noted and (2) primary CHL in the nasal septum, while rare, does occur and should be included in the differential diagnosis of nasal lesions.

Histiocytic Necrotizing Splenitis: Kikuchi-Fujimoto–like Splenic Findings in Patients With Chronic Autoimmune Disorders (Poster No. 20)

Thomas A. Summers, Jr, MD1 (thomas.a.summers@verizon.net); Aaron Auerbach, MD2; Nadine S. Aguilera, MD.21Department of Pathology, Walter Reed Army Medical Center, Washington, District of Columbia; 2Department of Hematopathology, Armed Forces Institute of Pathology, Washington, District of Columbia.

Autoimmune diseases are associated with enlarged lymph nodes and splenomegaly in many cases. The histologic findings in these lymph nodes have been described as follicular hyperplasia, with similar findings in the splenic white pulp being described less commonly. Histiocytic necrotizing lymphadenopathy has also been reported in autoimmune diseases, but a similar counterpart in the spleen has not been documented. We report 2 cases of histiocytic necrotizing splenitis (Kikuchi-Fujimoto–like) findings in spleens from patients with chronic autoimmune disorders. The patients' medical histories were significant for systemic lupus erythematosus. Splenectomy was performed secondary to thrombocytopenia in one case and to rule out a lymphoproliferative disorder in the other. Both exhibited features characteristic of histiocytic necrosis without acute inflammation similar to Kikuchi-Fujimoto disease described in lymph node specimens. Splenic involvement was extensive and diffuse and centered predominantly in the red pulp or nonwhite pulp areas. Fibrinoid necrosis was present in all cases (Figure 34). The most striking features of the cases were the marked extracellular and intracellular karyorrhectic nuclear debris (apoptotic debris) that was present without an associated neutrophilic or eosinophilic response. Surrounding these necrotic areas were benign histiocytes, immunoblasts, and plasmacytoid mononuclear cells. Plasma cells (a normal splenic constituent) were present in all cases and hematoxylin bodies were not identified. Staining results for infectious organisms were negative in all cases. Splenomegaly in autoimmune disease is rarely studied and is assumed to be hyperplastic in most cases, but we present rare cases of histiocytic necrotizing splenitis, which calls into question that assumption.

Primary Amyloidosis of the Glans Penis: A Painful κ-Positive Lesion (Poster No. 21)

Joo Y. Song, MD1 (joosong@gwu.edu); Suman Chauhan, MD.21Department of Pathology, The George Washington University, Washington, District of Columbia; 2Department of Pathology, Veterans Affairs Hospital, Washington, District of Columbia.

Primary amyloidosis is uncommon and extremely rare when localized to the glans penis. We report a case of a 53-year-old uncircumcised man with a history of diabetes and hypertension presenting with a broad-based flat lesion of the glans penis. The patient had complaints of penile pain for 1 month. The penile biopsy under microscopic examination revealed a pink homogenous subepithelium stroma with thickened blood vessel walls. Congo red-stained section showed apple-green birefringement with polarizing light microscopy in the areas of eosinophilic homogenous stroma (Figure 35). A diagnosis of amyloidosis was rendered. Immunoperoxidase staining was performed on the specimen and found to be positive only for κ light chains. Further workup for systemic amyloidosis was performed (chest x-ray, serum protein electrophoresis, urine protein electrophoresis, immunofixation); the results were normal. Clinical and pathologic correlation rendered a diagnosis of primary amyloidosis localized to the glans penis. Rare cases of localized amyloidosis of the penis present as a painless lesion composed of λ light chains, which have a particular “amyloidogenicity.” Here we illustrate the first case reported in the literature that was painful and positive for κ light chains.

Bilateral Synchronous Testicular Involvement in Multiple Myeloma (Poster No. 22)

Jinous Saremian, MD (jinous-saremian@ouhsc.edu); Alex John, MD; Douglas W. Warden, MD; Stanley A. Lightfoot, MD. Department of Pathology, Oklahoma University Health Science Center, Oklahoma City.

Testicular plasmacytomas are rare tumors and make up 2% of plasma cell neoplasms. In the current report we present the case of a 49-year-old man with bilateral synchronous testicular plasmacytoma. The patient had a 2-year history of multiple myeloma with bone metastasis and presented with bilateral testicular enlargement. He underwent bilateral orchiectomy, which revealed a well-defined, 3-cm, pink mass in the right testis and 2 masses, 1.5 and 1.2 cm, in the left testis (Figure 36). Histologically, the tumor showed an infiltration of plasma cells with round-shaped nuclei, some with prominent nucleoli, clumped chromatin, basophilic cytoplasm, and Golgi apparatus. Immunohistochemical studies showed strong cytoplasmic staining for IgG anti-κ antisera, weak staining for LCA, and negativity for IgG anti-λ antisera, supporting the diagnosis of plasmacytoma. Since the first reported case in 1939, approximately 60 cases of testicular plamacytoma have been reported so far. Most cases reported thus far have been unilateral, or bilateral but with asynchronous testicular involvement. To our knowledge, only 4 cases of synchronous bilateral testicular involvement with plasmacytoma have been reported in the literature.

A Nodal Marginal Zone Lymphoma With Bright CD10 Expression Mimicking Follicular Lymphoma (Poster No. 23)

Dava S. West, MD (dava.west@duke.edu); Endi Wang, MD, PhD. Department of Pathology, Duke University Medical Center, Durham, North Carolina.

Nodal marginal zone lymphoma (NMZL) is a small B-cell neoplasm that lacks a unique immunophenotype. It is thus, in part, a diagnosis of exclusion that must be differentiated from other small B-cell lymphomas, including follicular lymphoma (FL). Previous studies have demonstrated a high specificity for CD10 expression in FL in comparison to other small B-cell neoplasms. Here, we report a CD10+ NMZL in a 62-year-old man who presented with weight loss, night sweats, and anemia. Imaging revealed widespread lymphadenopathy without splenomegaly. Histologic sections of inguinal lymph node showed a nodular lymphoid proliferation with an interfollicular infiltrate of small/medium-sized lymphocytes with a “monocytoid” appearance. Flow cytometry detected a monoclonal B-cell population with bright CD10 expression. Immunohistochemical staining confirmed CD20 and CD10 positivity in both follicle center and interfollicular lymphocytes, with brighter CD10 staining in neoplastic interfollicular areas (Figure 37). Bcl-2 immunohistochemical staining highlighted a marginal zone growth pattern. Interphase fluorescence in situ hybridization for t(14;18)(IGH/BCL2), a genetic hallmark for FL, was performed on paraffin-embedded tissue. No fusion signal was observed. Rare cases of MZL with weak CD10 expression have been described in the literature. However, to our knowledge, this is the first case of a strongly CD10+ NMZL in which FL was definitively excluded by molecular studies. The case underscores the importance of recognizing architectural and cytomorphologic features of NMZL even when CD10 expression suggests FL. Immunohistochemical analysis for B-cell markers and Bcl-2 can be used to highlight NMZL morphologic pattern. Molecular studies can then be used for definitive diagnosis.

CD58 Expression Remains Elevated in Recurrent and Residual Precursor B-Cell Acute Lymphoblastic Leukemia and Decreases in Remission as Nonmalignant B cells Mature in the Bone Marrow (Poster No. 24)

Arthur G. Jones, MD (jonesag@pathology.ufl.edu); Samer Z. Al-Quran, MD. Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville.

Context: Previous studies have demonstrated that CD58 is overexpressed on leukemic blasts in precursor B-cell acute lymphoblastic leukemia (B-ALL) when compared to benign B-cell precursors. However, CD58 expression in B-ALL after treatment has not been evaluated. This study sought to measure the levels of CD58 expression in B-ALL at initial diagnosis, to compare these results to levels found in subsequent posttreatment bone marrows, and to examine CD58 expression in active disease compared to expression in remission.

Design: Diagnostic and follow-up bone marrows from 8 patients with B-ALL with either recurrent or residual disease were included. For comparison, 37 cases of previously diagnosed B-ALL with no evidence of disease were selected. Multiparametric flow cytometric analysis was performed by using panels of informative markers. CD58 mean fluorescent intensity was measured on the neoplastic blasts and maturing B-cell precursors.

Results: Diagnostic bone marrows and subsequent bone marrows with recurrent or residual disease had statistically similar levels of CD58 expression on leukemic blasts (P = .69). Mean fluorescent intensity of CD58 on leukemic blasts for patients with active leukemia was significantly higher than the corresponding intensity for maturing nonmalignant B-cell precursors for cases lacking evidence of leukemia (P < .001).

Conclusions: Our results indicate that CD58 is significantly and consistently overexpressed in B-ALL patients with active disease when compared to its expression in B-ALL patients lacking evidence of ongoing leukemia. The expression of CD58 on leukemic lymphoblasts appears to be a useful biomarker for detecting minimum residual or recurrent disease because it remains elevated in positive cases and is decreased in absence of active leukemia.

CD3+ Primary Mediastinal Large B-Cell Lymphoma in a 42-Year-Old Woman (Poster No. 25)

Maggie Stoecker, MD; Endi Wang, MD, PhD (endi.wang@duke.edu).  Department of Pathology, Duke University Medical Center, Durham, North Carolina.

Primary mediastinal large B-cell lymphoma (PMBCL), a subtype of diffuse large B-cell lymphoma (DLBCL), arises in the anterior mediastinum, presumably from thymic B cells. Whereas aberrant expression of antigens of other lineages is frequently observed in lymphomas, DLBCL with aberrant expression of CD3, a T-cell specific antigen, is rare. We report the case of a 42-year-old woman with chest pain radiating to the left arm that developed during a 2-month period. Radiographs showed a 9.9-cm, anterior mediastinal mass, which was fluoroscopically biopsied. Hematoxylin-eosin–stained sections demonstrated a diffuse proliferation of mixed small and large lymphocytes in a background of fibrosis. The large cells formed cohesive clusters with few intermingled small lymphocytes. Immunohistochemical stains demonstrated homogeneous positive staining in large cells for CD45, CD20, CD79a, Pax-5, bcl-2, bcl-6, and MUM-1. Many large cells had weak-moderate membranous staining with CD3 and CD43. Other T-cell–associated antigens, CD5, CD2, CD7, CD4, and CD8, were negative in large cells. CD30 was positive in a subset of large cells (15%–20%), but CD15 was essentially negative. Polymerase chain reaction–based immunoglobulin (Ig) gene and T-cell receptor (TCR) gene rearrangement studies were performed on paraffin-fixed tissue that revealed a clonally rearranged Ig κ light chain gene without clonal rearrangement of TCR. While rare cases of conventional DLBCL with aberrant CD3 have been recently described, aberrant expression of CD3 in PMBCL has never been reported, to the best of our knowledge. We emphasize application of immunohistochemical antibody panels and the value of molecular tests for definitive diagnosis of uncommon lymphomas with ambiguous phenotype.

Recurrent Classic Hodgkin Lymphoma–Type Posttransplant Lymphoproliferative Disorder (Poster No. 26)

Hannah H. Wong, MD (hhwong@llu.edu); Jun Wang, MD. Department of Pathology and Laboratory Medicine, Loma Linda University Medical Center, Loma Linda, California.

The least common subtype of posttransplant lymphoproliferative disorder (PTLD) is classic Hodgkin lymphoma type (cHL), an entity most often described in renal transplant patients. We present a case of a 17-year-old cardiac transplant recipient with cervical lymphadenopathy, 11 years after transplant. Lymph node biopsy revealed complete effacement of nodal architecture by large, atypical Hodgkin/Reed-Sternberg (HRS) cells against a background of small lymphocytes. The HRS cells expressed Epstein-Barr virus on in situ hybridization and CD30, CD15, PAX-5 weakly, but not CD20 or CD45. The diagnosis of cHL-PTLD was made. Complete remission was achieved following immunosuppression withdrawal. Six years later, the patient died following unrelated multiorgan failure. Autopsy revealed cHL-PTLD in the mediastinal lymph nodes and liver, identical morphologically and immunohistochemically to the lymph node biopsy 4 years earlier. The main differential diagnosis for cHL-PTLD is Hodgkin-like PTLD. Until recently, both were considered the same entity because of their similar morphology. They can be distinguished as follows: HRS cells in cHL-PTLD express CD30, CD15, and Epstein-Barr virus but not CD45 and/or CD20, while HRS-like cells in Hodgkin-like PTLD express CD45, CD20, and/or CD30 but not CD15. Hodgkin-like PTLD also shows expression of Epstein-Barr virus in both HRS-like cells and bystander small lymphocytes and demonstrate Ig gene rearrangement. It is important to distinguish between these 2 entities because cHL-PTLD responds to chemotherapies targeted for Hodgkin lymphoma, while Hodgkin-like PTLD responds to non-Hodgkin lymphoma therapies. To the best of our knowledge, recurrent cHL-PTLD is extremely rare in pediatric cardiac transplant patients. An accurate diagnosis is vital for optimal management.

A Case of Primary Omental Peripheral T-Cell Lymphoma Presenting With Marked Hypereosinophilia, Omental Caking, a Tubo-Ovarian Mass, Ascites, and Elevated CA125: An Illustration of Anchoring Bias in Clinical Decision-Making (Poster No. 27)

Harleen K. Sidhu, MBBCh1 (hsidhu@lifespan.org); Serazul A. Khan, MD2; Jagmohan S. Sidhu, MD.31Department of Pathology and Laboratory Medicine, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Providence, Rhode Island; 2Department of Hematology-Oncology, United Health Services Hospitals, Johnson City, New York; 3Department of Pathology and Laboratory Medicine, Wilson Memorial Regional Medical Center, Johnson City, New York.

A 53-year-old Asian woman with peripheral blood eosinophilia (126 300/μL) presented with left upper-quadrant pain and lethargy. Stool examination for parasites was negative. Bone marrow with molecular and cytogenetic analysis along with flow cytometry was negative for chronic eosinophilic leukemia, chronic myelogenous leukemia, acute leukemia, malignant lymphoma, and other malignancies. Computerized tomography did not show lymphadenopathy but showed a large omental cake, a small amount of ascites, and a small left tubo-ovarian mass. Serum levels of CA125 were elevated (368 U/mL). A clinical diagnosis of metastatic ovarian carcinoma was made. Hysterectomy with bilateral salpingo-oophrectomy, omentectomy, and bilateral iliac lymphadenectomy were done without a preoperative or intraoperative biopsy. Malignant lymphoma was suspected from the postsurgery frozen section done to select tissue for chemotherapeutic sensitivity testing. Flow cytometric analysis of omental tissue showed only CD7+/CD11c+ cells. Hematoxylin-eosin sections showed medium to large lymphoid cells with brisk mitotic activity, angiocentricity, intense eosinophil infiltrate (Figure 38), and focal necrosis in the removed tissue, mass-forming only in omentum. The neoplastic infiltrate was seen only in the serosa and subserosa of bilateral adnexa and uterus. Iliac lymph nodes were negative for lymphoma. Paraffin immunohistochemistry was positive for CD3, CD7, CD43, granzyme, TIA-1, perforin, TCRαβ, and Ki-67 (about 80%). Results for CD56, CD57, EBV-LMP1, and EBER were negative. Polymerase chain reaction for T-cell receptor gene rearrangement yielded positive results. Primary omental peripheral T-cell lymphoma, not otherwise specified, was diagnosed because of a large mass in omentum and lack of any other mass. This represents a good example of anchoring bias in clinical decision-making.

Unusual Immunohistochemical Markers for Megakaryocytes: A Comparison of the Novel Markers LMP1 and CD79a to the More Traditional Markers CD61 and Factor VIII (Poster No. 28)

Justin M. Wells, MD1 (jmwlxa@yahoo.com); Aaron Auerbach, MD2; Aguilera Nadine, MD.21Department of Pathology, Walter Reed Army Medical Center, Washington, District of Columbia; 2Department of Hematopathology, Armed Forces Institute of Pathology, Washington, District of Columbia.

Context: Megakaryocytes (MEGs) can be difficult to recognize in cases of extramedullary hematopoiesis (EMH) or when MEGs are dysmorphic. LMP1 expression in MEGs has not been previously reported. CD79a expression has been previously recognized, but has not been extensively studied. We compared these markers to better-known MEG markers.

Design: Forty cases were examined: 29 bone marrow (5 myeloproliferative disease [MPD]), 3 myeloproliferative disease/myelodysplastic syndrome (MPD/MDS), 21 various diagnoses, and 11 EMH (8 spleen, 3 lymph node). Tests with CD61, LMP1, Factor VIII, and CD79a were performed on paraffin-embedded sections (Table). In situ detection of EBV-encoded RNA was performed in 5 cases that were immunoreactive for LMP1 to exclude Epstein-Barr virus infection. Each stained slide was graded for the percentage of MEGs stained, intensity, and background. Each parameter was given a numerical score from 0–3. The average scores are reported.

Results: LMP1 staining was observed in 39 of 40 cases and the overall staining profile for the 3 characteristics was 2.38/2.05/0.80. CD79a staining was observed in 37of 38 cases (2.84/2.58/0.89); Factor VIII staining in 39 of 39 cases (3.0/2.92/2.08); and CD61 staining in 39 of 40 cases (2.90/2.50/1.75). The presence of EBV-encoded RNA was negative in all cases.

Conclusions: LMP1 staining was not as intense but was consistently positive with a cleaner background. CD79a performed comparably, except in extramedullary tissues because of background. LMP1 and CD79 were expressed in dysmorphic MEGs of MPD and MDS. The mechanism for expression of CD79a and LMP1 is unknown. Use of CD79a and LMP1 increases the repertoire of immunohistochemical stains available for megakaryocytes; in addition, recognition of their expression is helpful in excluding hematopoietic disease and misidentification.

 
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Streck Cell Preservative Reagent Stabilizes Bone Marrow Cells and Their Antigen Expression Profiles for Extended Analysis by Flow Cytometry (Poster No. 29)

Richard J. Baltaro, MD, PhD1 (baltaro@creighton.edu); James A. Grunkemeyer, PhD2; Dominic E. Warrino, PhD2; Wayne L. Ryan, PhD.21Department of Pathology, Creighton University Medical Center, Omaha, Nebraska; 2Department of Research and Development, Streck, Inc, Omaha, Nebraska.

Context: Streck Cell Preservative (SCP, formerly Cyto-Chex Reagent) is a cell and tissue preservative used to stabilize samples for analysis by flow cytometry. Current flow cytometry protocols require analysis of bone marrow samples within 24 hours of collection.

Design: The goal of this study was to determine whether bone marrow is preserved beyond 24 hours by using SCP, thus avoiding the rejection of samples delayed during shipping and eliminating the need for weekend staffing.

Results: We report that SCP can preserve bone marrow samples for flow cytometric analysis for 72 hours. Bone marrow samples drawn from patients were mixed 1:1 with SCP and evaluated by flow cytometry at 6 hours and 72 hours after isolation. We reported on the stabilization of bone marrow samples from 13 patients. Now we report on a total of 23 patient samples that were stabilized by diluting into SCP and tested for CD marker expression by using standard leukemia and lymphoma panels. The SCP-diluted bone marrow sample results were compared to bone marrow samples collected in K2EDTA tubes. We have tested samples with a presumptive clinical diagnosis of myelodysplastic syndrome, chronic lymphocytic leukemia, or acute myeloid leukemia. Results indicate that regardless of the leukemia and lymphoma panel type, the samples diluted in SCP and tested at 6 hours and 72 hours yielded results phenotypically comparable to samples collected in K2EDTA tubes and tested at 6 hours.

Conclusions: We conclude that bone marrow samples diluted in Streck Cell Preservative are stable for immunophenotyping analysis for up to 72 hours.

Flow Cytometry in Predicting Morphologic Patterns of Lymphoma (Poster No. 30)

Neil E. Fuehrer, MD (fuehrer@uthscsa.edu); Jeffrey L. Christal, MD; Aamir Ehsan, MD. Department of Pathology, University of Texas Health Science Center, San Antonio.

Context: Flow cytometry (FC) is generally considered a reliable supplement to tissue diagnosis of lymphomas. However, its use as a stand-alone diagnostic tool for predicting morphologic patterns has been cautiously considered.

Design: FC cases performed in our institution (2003–2008) were reviewed by 4- and 6-color methods. Lymph nodes (LN) or solid tissue biopsies with corresponding definitive tissue diagnosis were selected. Cases were reviewed by FC in blinded fashion to the final diagnosis and findings were then correlated by using tissue diagnosis as the gold standard.

Results: Three hundred and twelve cases were included. Reactive cases (147/147) and small B-cell lymphomas (61/68) approached 100% diagnostic accuracy. Diffuse large B-cell lymphomas and T-cell lymphomas (TCLs) demonstrated an accuracy of 83% (29/35) and 60% (6/10), respectively. All 4 TCLs missed by FC were anaplastic large cell lymphomas. One hundred percent (3/3) of Burkitt lymphomas were predicted by FC. Ninety-four percent (16/17) of nonhematolymphoid (non-H) lesions were ruled out. Thirty cases were nondiagnostic for Hodgkin lymphoma (HL); however, 75% (3/4) of cases of nodular lymphocyte predominant (NLP-HL) were suspected by FC. The diagnostic accuracy of all cases (excluding HL) was 93% (263/282).

Conclusions: FC pattern can reliably predict reactive or non-H lesions and can be used to morphologically subtype B-cell non-Hodgkin lymphomas. Although the use of FC has limitations in HLs, the pattern can predict certain subtypes such as NLP-HL. The application of multiparametric FC may be of greater value in predicting morphologic lesions than previously thought.

Blastic Plasmacytoid Dendritic Cell Neoplasm: Report of 2 Cases with Review of Literature (Poster No. 31)

Anupma Nayak, MD1 (anayak@nshs.edu); Xinmin Zhang, MD1; Sheng Chen, MD3; Jonathan E. Kolitz, MD2; Judith Brody, MD.1 Departments of 1Pathology and 2Medicine, North Shore University Hospital, Manhasset, New York; 3Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, New York.

Blastic plasmacytoid dendritic cell neoplasm is a rare and aggressive hematodermic tumor with distinct clinical, pathologic, and immunophenotypic features. Patients usually present with a cutaneous lesion followed by dissemination to involvement of bone marrow, blood, and lymph nodes and the central nervous system. Clinical course is aggressive with median survival of 14 months. The history of this entity dates back to 1994 when Adachi et al reported the first case. Since then, approximately 150 cases have been reported in literature by using a gamut of names such as blastic NK cell lymphoma, CD4+ CD56+ hematodermic neoplasm, and aggressive agranular NK cell leukemia. For many years, it was believed to be derived from NK cells because of its unique B, T, and myeloid lineage–negative CD4+/CD56+/CD43+/HLA-DR+ immunophenotype. Recent recognition of expression of antigens CD123, blood dendritic cell antigen (BDCA-2), and myxovirus A by tumor cells provided strong evidence that the precursor of the plasmacytoid dendritic cell may be the cell of origin for this rare neoplasm. Incorporation of these data lead to the renaming of this entity as blastic plasmacytoid dendritic cell neoplasm in the revised WHO (2008) classification for hematopoietic and lymphoid neoplasms. We present here 2 cases of blastic plasmacytoid dendritic cell neoplasm recently diagnosed at our institution (Table), along with a review of the literature highlighting its unique clinical, histopathologic, and immunophenotypic features. Awareness and recognition of this rare entity by pathologists is vital for early diagnosis and aggressive treatment of this lethal neoplasm.

 
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Primary Pulmonary Adult T-Cell Lymphoma Presenting With Recurrent Spontaneous Pneumothorax (Poster No. 32)

Wilfredo Blasini, MD1 (wblasini@med.miami.edu); Mauricio Montezuma, MD2; Nydia Martinez, MD2; Jose Ramirez, MD3; Gerald E. Byrne Jr, MD.1 Departments of 1Pathology and 2Medicine, Jackson Memorial Hospital & University of Miami Miller School of Medicine, Miami, Florida; 3Department of Pulmonary Medicine, Cleveland Clinic, Weston, Florida.

Primary pulmonary lymphoma is a very rare condition in adults, accounting for less than 0.5% of all primary lung malignancies. Most of these lymphomas are B-cell type and the incidence of other non–B-cell type of pulmonary lymphomas is unknown. Human T-cell lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2), and human immunodeficiency virus–1 (HIV-1) have been associated with pulmonary lymphomas. Herein, we present a case of a 36-year-old man who presented with recurrent spontaneous pneumothorax with bullae formation and a history of HTLV-1 seropositivity. A diagnosis of lymphocytic interstitial pneumonitis (LIP) was considered initially. However, pathologic examination of a pleural biopsy and a bilateral bullectomy specimen showed a cytologically atypical small T-cell lymphocytic population immunoreactive to CD3 and CD5 antibodies (Figure 39). Gene rearrangement studies performed on the paraffin-embedded tissue demonstrated rearrangement of the T-cell receptor. These findings, in addition to the HTLV-1 seropositivity, pointed to a diagnosis of a primary pulmonary adult T-cell lymphoma. Infection with HTLV-1 has been associated with other pulmonary conditions such as lymphocytic interstitial pneumonitis (LIP) and diffuse panbronchiolitis (DBP). In our case it is unclear whether LIP or DBP existed as a premalignant condition that predisposed to the development of the lymphoma or if the macroscopic pulmonary changes were secondary to the presence of pulmonary lymphoma.

An Unusual Case of Near-Tetraploid Early B-Precursor Acute Lymphoblastic Leukemia With Multiple Chromosomal Abnormalities (Poster No. 33)

Masha C. Nzabi, MD1 (nzabim@umkc.edu); Kevin F. Ginn, MD2; David Zwick, MD.31Department of Pathology, University of Missouri-Kansas City; Departments of 2Hematology Oncology and 3Pathology, Children's Mercy Hospitals and Clinics, Kansas City, Missouri.

In childhood acute lymphoblastic leukemia, gene rearrangement, blast cell DNA content, and ploidy have important prognostic implications. Approximately 1% are near-tetraploid clonal populations. Of these, the median number of chromosomes is 55 with >65 chromosomes being of rare occurrence. ETV6/RUNX1 [TEL/AML1] gene rearrangement is a known favorable prognostic factor. We describe the case of a 15-year-old adolescent female who presented with a 1-month history of fatigue, shortness of breath, and headache. Her initial white blood cell count was 4800/mm3, with 25% blast count and hemoglobin level of 4.7g/dL. The blast cells were markedly enlarged with unusual nuclear configuration. Bone marrow examination revealed increased cellularity with almost complete replacement of the normal marrow elements by the blast cells. These blast cells expressed CD19, TdT, and aberrant coexpression of CD13. DNA ploidy revealed a near-tetraploid population with a DNA index of 1.87. Chromosomal analysis (Figure 40) revealed multiple chromosomal abnormalities and confirmed the near-tetraploid karyotype (87 chromosomes) with loss of chromosomes X, 7, 8, and 14; gain of chromosome 22; and structural rearrangement of 1p, 5q, 12p, 15q, 20p, and 22q. Fluorescence in situ hybridization (Figure) analysis showed ETV6/RUNX1 [TEL/AML1] gene rearrangement. The patient began chemotherapy and the day 8 bone marrow contained 15%–20% blasts, but by day 15 there was no residual disease. She subsequently had good clinical outcome despite multiple chemotherapeutic complications. We will review literature on whether the presence of near-tetraploid population, and subsequently several copies of ETV6/RUNX1 [TEL/AML1] gene, would have had an influence on a patient's clinical outcome.

Concomitant Chronic Lymphocytic Leukemia and Acute Lymphoblastic Leukemia at Initial Presentation: Report of 2 Cases (Poster No. 34)

Shilpa Jain, MD (drsjsinghal@gmail.com); Suqing Xie, MD, PhD; Humayun K. Islam, MD, PhD. Department of Pathology, Westchester Medical Center/New York Medical College, Valhalla, New York.

Chronic lymphocytic leukemia (CLL) has been reported as concurrently presenting with other hematopoietic and nonhematopoietic malignancies, including acute myeloid leukemia, multiple myeloma, systemic mastocytosis, large granular lymphocytic leukemia, and renal cell carcinoma. However, it has never been reported with acute lymphoblastic leukemia (ALL). We describe 2 unique cases of CLL concurrently presenting with ALL and discuss their clinical, immunophenotypic, cytogenetic, and biologic features. Case 1 was that of a 63-year-old man who presented with pancytopenia, while case 2 was that of a 74-year-old man with bicytopenia. Complete hematologic workup was done in both cases, including flow cytometry of peripheral blood (PB) and bone marrow (BM). Both cases had relative lymphocytosis and increased blast counts in PB. BMs were hypercellular in both and essentially packed with blasts. Immunophenotypic analysis by flow cytometry and/or immunohistochemistry revealed that the blasts were precursor B cells expressing CD19, CD22, CD10, and TdT. In addition, flow cytometry on PB showed a second population of mature CD5+ B cells expressing CD19, CD20, CD22, and CD23. The latter also focally involved the BM in the second case. Cytogenetics showed normal karyotype in both cases. True incidence of concurrent CLL and ALL might be underestimated and may be increasingly detected with simultaneous immunophenotypic analysis of PB and BM. Synchronous CLL and ALL represents either a clonal evolution of the initial asymptomatic CLL clone or simultaneous presence of 2 separate clones, a distinction which remains to be confirmed in future studies.

Intratumor Myeloid Sarcoma Occurring Within Glioblastoma Multiforme (Poster No. 35)

Thomasina L. Bailey, MD (thomasina.bailey@ucdmc.ucdavis.edu); Claudia Greco, MD; Denis M. Dwyre, MD. Department of Pathology, University of California at Davis, Sacramento.

A tumor occurring within other malignancies is a rare occurrence. We report a case of myeloid sarcoma (MS) occurring within a primary CNS glioblastoma multiforme (GBM). In this case, the patient's history included acute myelogenous leukemia (AML-M1) with normal cytogenetics. She was treated with cytarabine and an anthracycline, and remission was ultimately achieved after a second reinduction. Three years later, she had a relapse of AML, which was successfully treated with induction chemotherapy. Later, she had neutropenic and infectious complications that required prolonged hospitalization, and she therefore did not receive consolidation chemotherapy. During the prolonged hospitalization, there were changes in her mental status. Subsequent magnetic resonance imaging showed a right temporal lobe lesion. Biopsy of the brain lesion showed GBM with prominent perivascular intratumoral nodules. The GBM stained positively for glial fibrillary acidic protein, while the nodule staining results were negative. Additional staining revealed that the nodules were positive for myeloperoxidase and chloroacetate esterase, consistent with intra-tumor MS. This is the first report of intratumoral MS. Determination of the MS component is critical, as the presence of intracranial relapse has important implications in the decision to offer further treatment. MS most often affects bone, nodes, and skin. Intraparenchymal brain AML relapse is unusual. This report demonstrates not only that the brain microenvironment can be hospitable for leukemic blasts but also that GBM tumor and vascularity are also areas where tumor cells can proliferate, possibly because of the interrupted blood brain barrier.

Unusual Presentation of a Hepatosplenic T-Cell Lymphoma (Poster No. 36)

Jayantha Herath, MD1 (jcherath@yahoo.ca); Arshad Ahsanuddin, MD1; Carmen Morales, MD1; M. Rubinger, MD.2 Departments of 1Pathology and 2Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.

A 42-year-old man presented with 4 months of weight loss, night sweats, pruritic skin rash, and arthralgia for which he was taking large amounts of acetaminophen. Initial clinical examination identified an extensive contiguous skin rash, fever, and hepatosplenomegaly. No peripheral adenopathy was detected. Laboratory data showed the following: white blood cell count, 1.7 × 103/mm3; hemoglobin, 12.7 g/dL; platelets, 17 × 103/mm3; lactate dehydrogenase, 1349 U/L (reference range, 63–200 U/L); alanine transaminase, 1158 U/L (reference range, 0–30 U/L); aspartate transaminase, 1270 U/L (reference range, 10–32 U/L); alkaline phosphastase, 262 U/L (reference range, 30–120 U/L); and normal levels of creatinine. Computed tomographic scans showed no lymphadenopathy but confirmed the splenomegaly. Results of viral hepatitis and human immunodeficiency virus screen were negative; skin biopsy was nondiagnostic. A bone marrow aspirate showed a predominant population of intermediate to large-sized cells with blastic morphology. The bone marrow biopsy showed infiltration by lymphoid cells located in the sinusoidal and interstitial spaces. Flow cytometry showed the infiltrate was predominantly T cells, with virtually all expressing TCR γ-δ and most with loss of CD5. By immunohistochemstry, the abnormal cells were positive for CD45, CD3, CD8, CD56, and Ki-67 (50%) and negative for CD5, CD20, ALK-1, CD30, and CD15. A diagnosis of hepatosplenic γ-δ T-cell lymphoma with blastic morphology was rendered. The confounding factor of toxic hepatitis due to chronic acetaminophen abuse, which could have been responsible for hepatomegaly, might obscure the diagnosis.

Idiopathic Neutropenia in a Cocaine User: A Case Report and Review of the Literature (Poster No. 37)

Tahmeena Ahmed, MD (tahmed@notes.cc.sunysb.edu). Department of Pathology, Stonybrook University Medical Center, Stonybrook, New York.

Idiopathic neutropenia is a rare benign disorder of granulopoiesis characterized by an unexplained reduction in the absolute neutrophil count below the lower limit of the reference range for a prolonged period. Laboratory testing for anti-neutrophil antibodies is technically challenging and not widely available. Neutropenia associated with levamisole contamination of cocaine is becoming a public health hazard. A young male with a history of cocaine use and neutropenia presented with fever, skin lesions, and lymphadenopathy in 2007. The bone marrow was evaluated and showed arrested granulopoiesis at the myelocyte stage and dysplastic megakaryocytes (Figure 41). Anti-neutrophil antibody testing was positive. The patient has been followed up for 2 years and has demonstrated continued cocaine use. The bone marrow morphology is suggestive of chronic idiopathic neutropenia, but the case illustrates the need for adequate history and communication between pathologist and hematologist. This case presents a diagnostic challenge and emphasizes the need for clinicopathologic correlation.

Diagnostic Pitfalls of Chronic Myelogenous Leukemia (Poster No. 38)

Kun Ru, MD, PhD1 (kru@wpahs.org); John Pawloski, MD, PhD2; Patrick Storto, PhD3; Donald Halinka, MBA, BS.3 Departments of 1Pathology and 2Hematology/Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania; 3Department of Medical Genetics, The West Pennsylvania Hospital, Pittsburgh.

As a prototype of myeloproliferative neoplasms, chronic myelogenous leukemia (CML) is constantly associated with the BCR-ABL1 translocation, and often presents with typical morphologic findings. We report 2 cases with unusual morphologic features that were not recognized as CML before the cytogenetic results were available. The first case is that of a 64-year-old woman with history of hypertension and hypercholesterolemia. She presented with an increased blast count in her peripheral blood. The bone marrow biopsy demonstrated a hypercellular marrow with increased nunbers of myeloblasts (10%–15%), myeloid and erythroid hyperplasia, multilineage dysplasia, and reticulin fibrosis. The presence of blasts was confirmed by flow cytometry and immunohistochemistry. These findings were interpreted as refractory anemia with excess blasts. However, the cytogenetic results revealed the BCR-ABL1 translocation in 95% of cells, in addition to other abnormalities: t(6;18) and trisomy 19. The second case is that of a 52-year-old man presenting with thrombocytosis (502 000 /μL). He had a history of adenocarcinoma of lung (T2N0MX) and was treated with surgery and Tarceva 1 year ago. The bone marrow biopsy showed a hypercellular marrow with myeloid hyperplasia and micromegakaryocytes. No obvious eosinophilia or basophilia was noted. This case was described as “reactive changes” before cytogenetic results revealed that the BCR-ABL1 translocation in all cells was the sole abnormality. A diagnosis of CML was finally made in both cases. The patients were treated with Gleevec and were hematologically asymptomatic. Although the definitive diagnosis relies on the cytogenetic or fluorescence in situ hybridization results, CML must be considered in the differential diagnosis when hypercellularity or myeloid hyperplasia is present, even with atypical morphology.

Posttransplant Lymphoproliferative Disorder Presenting as a Plasmocytoma of the Stomach (Poster No. 39)

Emmy Hebert, MD (emmy.hebert@ttuhsc.edu); Jaishree Jagirdar, MD; Irina Lytvak, MD. Department of Pathology, University of Texas Health Sciences Center at San Antonio.

Posttransplant lymphoproliferative disorder (PTLD) is a rare complication of solid-organ and bone marrow transplant. We present an extremely uncommon case of solitary plasmacytoma-like PTLD in a renal transplant patient. The patient is a 51-year-old woman who received a renal transplant in 1996. In 2008, she presented with weakness and midepigastric abdominal pain. Workup revealed a mass along the greater curvature of the stomach. A biopsy was diagnosed as carcinoid tumor because of synaptophysin and CD56 positivity. Subsequently, the patient developed upper-gastrointestinal bleeding and underwent subtotal gastrectomy. Gross examination showed a 6-cm, exophytic mass extending through the entire thickness of the stomach. Microscopic examination showed an infiltrative lesion composed of atypical plasmacytoid cells. One perigastric lymph node was involved. Immunohistochemistry showed strong positivity for CD45, MUM-1, and CD138 (Figure 42), supporting the initial impression of a plasma cell neoplasm. The tumor also showed a predominance of λ-light chain production. Tumor cells were strongly positive for EBV-RNA by fluorescence in situ hybridization. PTLD encompasses a broad range of lymphoid proliferations that develop in transplant recipients. The World Health Organization divides PTLD into early, polymorphic, and monomorphic PTLDs. Early and polymorphic lesions are relatively benign. Monomorphic PTLDs represent a variety of lymphomas and are morphologically similar to corresponding entities occurring in an immunocompetent host. Most cases are EBV-induced. Plasmacytoma-like PTLDs are very rare, with only a few reported cases.

Sex Cord/Gonadal Stromal Tumor, Incompletely Differentiated, Low Malignant Potential (Poster No. 40)

Vighnesh Walavalkar, MD (vwalaval@uci.edu); Fritz Lin, MD; Jane Ellaine Tongson-Ignacio, MD. Department of Pathology and Laboratory Medicine, University of California at Irvine, Orange.

Sex cord–stromal tumors of the testis are rare, comprising approximately 5% of all testicular tumors. Based on World Health Organization classification, these are classified into 4 forms: pure, incompletely differentiated, mixed forms, and malignant. The incompletely differentiated sex cord/gonadal stromal tumors are extremely rare neoplasms composed predominantly of undifferentiated spindle cells admixed with foci of abortive tubules arrested in different stages of maturation. A 25-year-old white man presented with a painless, slow-growing mass in his right testicle. Ultrasongraphy showed a hypoechoic, heterogeneous solid mass with internal flow that measured 3.6 × 3.3 × 2.6 cm and was consistent with seminoma. Computed tomography of chest, abdomen, and pelvis were unremarkable. Laboratory study (α-fetoprotein, LDH, HCG-β subunit) results were all within normal levels. Patient underwent right radical orchiectomy. Grossly, the testis showed a well-circumscribed, homogeneous yellow mass measuring 3.5 cm in greatest diameter. Histologically, the tumor was confined to the testis and composed of spindle cells in fascicular growth pattern with focal epithelioid areas that appeared to form abortive tubular structures (Figure 43). Immunohistochemistry showed coexpression of S100 and smooth muscle markers and negativity for cytokeratins and desmin. The tumor expressed the gonadal stromal tumor markers calretinin and inhibin. While most testicular stromal tumors have a benign clinical course, the findings of increased cellularity, pleomorphism, and mitotic activity of 3/HPF focally in the current case favor a stromal tumor of low malignant potential. To our knowledge, this is the first case of sex cord/gonadal stromal tumor classified as incompletely differentiated with low malignant potential.

Is Digital Planimetry Preferable to Visual Estimate in Routine Evaluation of Prostate Carcinoma? (Poster No. 41)

Maheshwari Ramineni, MD (mramine1@hfhs.org); Daniel Schultz, MD; Zhaoli Lane, MD. Department of Pathology, Henry Ford Hospital, Detroit, Michigan.

Context: Tumor volume (TV) is an important determinant of clinical outcome after radical prostatectomy. Recently, various studies have discussed the digitized methods for estimating TV. We sought to measure TV by digital planimetry (DP) and compare the values with visual estimate (VE).

Design: TV was determined from whole-mount hematoxylin-eosin slides by using VE as well as DP from 70 consecutive patients with prostate carcinoma, Gleason score 8–10. MacroPATH Imaging System was used for digital planimetry. Additionally, correlation of TV by both methods with various parameters such as Gleason grade, margin positivity, extraprostatic extension, seminal vesicle invasion, and angiolymphatic invasion were assessed by Pearson correlation.

Results: TV by DP is statistically significantly correlated to that by VE (r2 = 0.64, P < .001). Mean TV by VE differs significantly between extraprostatic extension negative (16.7) and extraprostatic extension positive (37.3) cases (P = .02) and in angiolymphatic invasion negative (33.2) versus angiolymphatic invasion positive (45) cases (P = .05) (Figure 44). Gleason grade, margin positivity, and seminal vesicle invasion does not show statistically significant association with TV by both methods.

Conclusions: Our findings differ from the previous studies in that we found that both methods (digital planimetry and visual estimate) had positive correlation in estimating tumor volume. Visual estimate can serve as a reliable, inexpensive prognostic indicator in predicting extraprostatic extension and angiolymphatic invasion. Digital planimetry, which is potentially expensive, time consuming, and labor-intensive, may not yield much additional benefit.

Mass-Forming IgG4-Related Tubulointerstitial Nephritis: A Clinical and Radiologic Mimicker of Malignancy (Poster No. 42)

Maheshwari Ramineni, MD1 (MRAMINE1@hfhs.org); Dhananjay Chitale, MD1; Vikram Deshpande, MD2; Nilesh S. Gupta, MD.11Department of Pathology, Henry Ford Hospital, Detroit, Michigan; 2Department of Pathology, Massachusetts General Hospital, Boston.

IgG4-related autoimmune pancreatitis is a well recognized mass-forming lesion of the pancreas. Tubulointerstitial nephritis has been recently described as one of the extrapancreatic manifestations in these patients. A 29-year-old man with past history of type 1 diabetes mellitus, Grave disease, sclerosing cholangitis, and ulcerative colitis presented to our hospital for management of bilateral enhancing hypodense renal masses found on computed tomography (CT) scan workup. CT-guided needle biopsy from 1 of these masses showed tubulointerstitial nephritis with eosinophils and lymphoplasmacytic infiltrate. Flow cytometry results were negative for B-cell lymphoproliferative disorder. T- and B-cell gene rearrangement study results were also negative. Since the clinical and radiologic suspicion for malignancy was high, a partial nephrectomy was performed. Histologic findings of the mass-forming tissue consisted of tubulointerstitial nephritis with extensive interstitial fibrosis and tubular atrophy with focally thickened tubular basement membranes. The infiltrate consisted of numerous eosinophils, lymphocytes, plasma cells, and few histiocytes. Adjacent nonlesional renal parenchyma appeared unremarkable and had a sharp demarcation from the inflamed and fibrotic tissue. Immunohistochemistry for lymphoproliferative disorders and histiocytic malignancies was negative. The plasma cells were polyclonal in nature and strongly expressed IgG4 antibody. Serum IgG4 levels were also high (864 mg/dL). IgG4-related tubulointerstitial nephritis can present as a mass-forming lesion and is a clinical and radiologic mimicker of malignancy. It should be included in the differential diagnosis as one of the pseudotumors in kidney biopsies and resection specimens (Figure 45).

Low-Grade Adenocarcinoma Arising in Nephrogenic Metaplasia at Urinary Bladder Neck of an Adolescent Female (Poster No. 43)

Yi Zhou, MD, PhD (yzhou_06511@yahoo.com); Myron Melamed, MD.  Department of Pathology, New York Medical College, Valhalla.

Nephrogenic metaplasia is a rare benign condition of urothelium that displays tubulo-cystic, papillary-polypoid, or rarely, diffuse growth patterns. Its most important differential diagnosis is clear cell adenocarcinoma, a high-grade carcinoma considered to be its malignant counterpart. Here we report an unusual adenocarcinoma with growth patterns resembling both conditions. The patient had a history of recurrent urinary tract infection and lower back pain for 3 months. Preoperative workup identified a 3.2-cm solid mass at the urinary bladder neck. The cystectomy specimen contained a poorly defined firm tumor involving the anterior wall of bladder neck and the adjoining proximal urethra. Microscopically, the tumor diffusely infiltrated from lamina propria to the perivesical fat. It had a tubulo-cystic pattern lined by a single layer of low cuboidal or hobnail cells with dense eosinophilic luminal secretion in some tubules. Intermingled were areas of solid growth made up of cells arranged in cords or nests, many with intracytoplasmic lumen (Figure 46). Areas of nephrogenic metaplasia were noted in the overlaying urothelium and histologic transition to the invasive carcinoma was identified. Mitoses were rare, and areas of necrosis absent. Ki-67 staining varied, up to 15% in focal areas; p53 staining was weak and diffuse. Results with CK7, EMA, vimentin, CA-125, luminal CD10, and nuclear PAX2 were positive. The malignant tumor differs from nephrogenic metaplasia and clear cell adenocarcinoma in that it is deeply invasive, has low mitotic rate, and lacks areas of necrosis. We believe that the tumor represents an unusual low-grade adenocarcinoma arising in nephrogenic metaplasia.

Demonstration of Lower Expression of BRMS1 in Primary Prostatic Adenocarcinoma Than in Normal Prostatic Glandular Tissue (Poster No. 44)

Erin J. Morris, MD1 (emorris@tuftsmedicalcenter.org); Pushkar A. Phadke, MD, PhD1; Harty Ashby-Richardson, DO1; Annette Shepard-Barry, HT(ASCP)1; Stephen P. Naber, MD, PhD1; Danny R. Welch, PhD.21Department of Pathology, Tufts Medical Center, Boston, Massachusetts; 2Department of Pathology, University of Alabama at Birmingham.

Context: Breast cancer metastasis suppressor 1 (BRMS1) has been implicated as an important gene in preventing multiple steps of the metastatic cascade from occurring in various tumor xenograft models, notably in breast, melanoma, and ovarian models. Evaluation of the expression of BRMS1 in prostatic adenocarcinoma has not been performed. Our purpose was to determine expression of BRMS1 in the evolution of prostatic adenocarcinoma from normal gland to metastatic adenocarcinoma.

Design: A tissue microarray (Biomax, Rockville, Maryland) containing formalin-fixed, paraffin-embedded prostatic tissue was stained with a monoclonal antibody (Clone 3a1.21). Fifteen cores of normal prostatic tissue, 66 cores of prostatic adenocarcinoma, and 4 cores of high-grade prostatic intraepithelial neoplasia (PIN) were evaluated for BRMS1 protein expression. Some cores with absent cellularity were excluded from the study. The intensity of nuclear BRMS1 staining was graded on a scale of 0–3.

Results: BRMS1 was strongly expressed in all cases of normal prostate tissue, with an average staining intensity of 2.73±0.1. Staining was diffuse, intense, and nuclear. There was no statistical difference observed between staining intensity of PIN lesions (2.75±0.25) and normal prostatic tissue. The prostatic adenocarcinoma group demonstrated a significant decrease in staining intensity (2.04±0.1) compared to that in normal and PIN lesions (P = .003).

Conclusions: The staining results are consistent with a decrease in expression of BRMS1 in prostatic adenocarcinoma as compared to that in normal prostate tissue and high-grade PIN lesions, which suggests a role for BRMS1 in prostate tumor progression. Further study of the role of BRMS1 in the regulation of tumor progression is necessary.

Papillary Nephrogenic Adenoma Mimics a Papillary Urothelial Carcinoma in Urinary Bladder: Case Report and Literature Review (Poster No. 45)

William P. Tarrant, MD (wptarrant@gmail.com); Michael Coburn, MD; Luan Truong, MD; Alberto Ayala, MD; Philip Cagle, MD; Jim Zhai, MD.  Department of Pathology, The Methodist Hospital, Houston, Texas.

Nephrogenic adenoma (NA) is a very rare lesion of the urinary tract that occurs predominantly in the bladder. A relatively recent study has shown that this lesion represents an implantation of renal tubular epithelium into a disturbed urothelial mucosa. Thus, predisposing factors include renal transplants, urinary catheterizations, urinary tract infection, trauma, nephrolithiasis, and radiation. We describe a case of NA with papillary configuration presenting in a 19-year-old man with multiple congenital abnormalities, bladder reconstruction, and a history of repeated self-catheterization. On core biopsy, our case demonstrated a predominant papillary configuration lined by reactive urothelium with central fibrovascular cores, mixed inflammatory background, and few microscopic tubular proliferations lined by a single layer of cuboidal and hobnail epithelium. In a major case series, 65% of nephrogenic adenomas demonstrated either a polypoid or papillary configuration. However, there was histologic similarity between this lesion and papillary urothelial carcinoma due to the reactive atypia, fibrovascular cores, and papillary growth pattern. A scant tubular component in combination with limited diagnostic material also posed a diagnostic challenge. PAX-2 nuclear positivity of the tubular epithelium with negative PAX-2 staining of the urothlieum helped support our diagnosis of NA. The differential diagnosis includes the rare clear cell adenocarcinoma and urothelial papillary carcinoma. Our case describes the presentation, morphology, and immunohistochemical staining used to confirm the diagnosis of NA. The management of papillary NA and papillary urothelial carcinoma is dramatically different, and the need to make a clear distinction between these 2 entities is critical.

Plasmacytoid Urothelial Carcinoma: Two Case Reports Demonstrating CD138 and VS38c Positivity (Poster No. 46)

Elizabeth Plocharczyk, MD (elizabeth.plocharczyk@osumc.edu); Gang He, MD, PhD. Department of Pathology, Ohio State University Medical Center, Columbus.

Plasmacytoid urothelial carcinoma is a rare, recently described entity, with fewer than 60 cases reported in the literature. Histologically, tumor cells of this variant appear plasmacytoid with eccentric nuclei, abundant eosinophilic cytoplasm, and a discohesive or Indian-filing pattern, reminiscent of lobular carcinoma of the breast. Immunohistochemistry demonstrates positivity for cytokeratins, confirming the cells' epithelial origin. Positivity for the plasma cell marker CD138 is variable and staining characteristics for another plasma cell marker, VS38c, have not been reported. Herein, 2 cases of plasmacytoid urothelial carcinoma positive for CD138 and VS38c are reported. Case 1 involved a 67-year-old white man who presented to his urologist for worsening dysuria. A computed tomography scan demonstrated a bladder mass. Biopsy revealed poorly differentiated urothelial carcinoma. Final pathology of the cystoprostatectomy specimen demonstrated a poorly differentiated urothelial carcinoma with areas of plasmacytoid differentiation infiltrating the muscularis propria. Case 2 was that of a 71-year-old white woman who developed dysuria and polyuria, and cystoscopy demonstrated a bladder mass. Biopsy of the mass revealed sheets of discohesive malignant cells with abundant, eosinophilic cytoplasm and eccentrically placed large nuclei infiltrating the muscularis. Immunohistochemical staining in both cases was positive for AE1/3, Cam5.2, CK7, CD10, CD138, and VS38c and negative for CK20, CD79a, and CD45, confirming the diagnosis of plasmacytoid urothelial carcinoma. Figure 47 shows a hematoxylin-eosin photomicrograph at ×40 magnification (a), as well as immunohistochemical staining for AE1/3 (b), CD138 (c), and VS38c (d).

Renal Oncocytic Neoplasms: Molecular and Immunohistochemical Analysis With an Emphasis on the Birt-Hogg-Dubé Gene and Mammalian Target of Rapamycin-Related Proteins (Poster No. 47)

Stephen M. Rohan, MD (rohans@mskcc.org); Maria E. Dudas, MD; Samson W. Fine, MD; Anuradha Gopalan, MD; Victor E. Reuter, MD; Satish K. Tickoo, MD. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York.

Context: Patients with Birt-Hogg-Dubé (BHD) syndrome develop renal tumors, wherein renal oncocytic neoplasms (RONs) are overrepresented. Alterations of the BHD gene on chromosome 17 (ch17) have been documented in sporadic renal tumors. The protein product of the BHD gene interacts with the mammalian target of rapamycin (mTOR) pathway. We evaluated the mutational status of the BHD gene, ch17 copy number by fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC) expression of mTOR pathway activation markers (p-S6, p-4EBP1) in sporadic RONs.

Design: Fifty-four RONs (9 oncocytomas [ROs], 26 chromophobe carcinomas [CHRs], and 19 renal cell carcinomas, unclassified, oncocytic type [URCCs]) were examined. The unclassified category included oncocytic tumors with features that precluded their inclusion among RO or CHR. IHC for CK7, CD117, TFE3, p-S6, and p-4EBP1 was performed. Staining was graded as absent/weak (0 or 1+, 0%–25% cells positive) or strong (2+ or 3+, 26%–100%). The BHD gene was sequenced and mutational analysis was performed. FISH was done using a ch17 centromeric probe.

Results:

 
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Most tumors expressed CD117. CK7 was expressed in most CHRs, but in none of the ROs or URCCs. No mutations of the BHD gene were detected. Most (15/25, 60%) CHRs showed loss of ch17. Ch17 loss was seen in 1 URCC. No ROs showed ch17 loss. There was no correlation between ch17 copy number and mTOR marker expression.

Conclusions: Our data suggest that URCCs are more closely related to ROs than CHRs. Mutations of the BHD gene and mTOR marker expression appear to be infrequent in sporadic RON.

p63 Is Not Expressed in Most Micropapillary Urothelial Carcinomas (Poster No. 48)

Liset Pelaez, MD1 (lpelaez@med.miami.edu); Carmen Gomez-Fernandez, MD2; Merce Jorda, MD, PhD.21Department of Pathology, Jackson Memorial Hospital, Miami, Florida; 2Department of Pathology, Jackson Memorial Hospital/University of Miami/Sylvester Comprehensive Cancer Center, Miami, Florida.

Context: Carcinomas with micropapillary features have been described in urinary bladder, ovary, breast, lung, and salivary gland. They are characterized by small papillary clusters of cells located within a lacuna and associated with high pathologic stage with early vascular invasion, metastasis, and high mortality. Micropapillary urothelial carcinoma (MPUC) represents approximately 1% of all bladder urothelial cancers. Because of its aggressive behavior, metastasis may be the initial presentation. p63, a member of the p53 family, is expressed in the nucleus of squamous and urothelial cells and in their carcinomas. However, loss of expression of p63 occurs in a subset of high-grade urothelial carcinomas. The objective was to identify the expression of p63 immunohistochemistry in MPUC and its potential role in distinguishing MPUC from other carcinomas with micropapillary morphology.

Design: Six cases of MPUC were identified in a period of 10 years (1998–2008). Four cases corresponded to transurethral resection of bladder tumor, 1 case to a radical cystectomy, and 1 case to a nephrectomy/ureterectomy. Immunohistochemical analysis for p63 (1:50; M7247, Dako) was performed in all cases by using the LSAB method.

Results: p63 positivity was defined as strong nuclear staining. All cases but one were negative for p63.

Conclusions: p63 is not expressed in most MPUCs. Lack of expression of p63 in MPUC can be associated with a possible glandular differentiation or to a loss of expression of p63 due to the tumor's higher grade. p63 immunostain is not useful in distinguishing MPUC from other micropapillary carcinomas of nonurothelial origin when metastasis is the initial presentation.

Use of Image Analysis for Interpretation of PIN-4 Immunohistochemical Staining in Prostate Needle Biopsies (Poster No. 49)

Robert Monroe, MD, PhD1 (rmonroe@bioimagene.com); Ronald L. Allen, PhD2; Bikash Sabata, PhD.3 Departments of 1Clinical and Regulatory Affairs, 2Image Analysis, and 3Engineering, BioImagene, Cupertino, California.

Context: Immunohistochemistry markers routinely used in the interpretation of prostate biopsies include P504S, p63, and high-molecular-weight cytokeratins. The combination of these in the PIN-4 cocktail can be useful in the distinction between adenocarcinoma, high-grade prostatic intraepithelial neoplasia, and benign glands, particularly in cases with limited tissue. However, interpretation of multiple markers staining different subcellular compartments of different cell types can be challenging. An image analysis algorithm was therefore developed to assist in the interpretation of PIN-4–stained tissue.

Design: Fifty prostate needle biopsy cases, each consisting of corresponding hematoxylin-eosin– and PIN4-stained slides, were selected. Slides were scanned at ×20 magnification on the BioImagene iScan Scanner. Manual interpretation was performed on a computer monitor that permitted the viewing of whole slide images at magnifications from ×1 to ×40. After a 2-week wash-out period, the same cases were reviewed by using image analysis for selected regions of interest in the PIN-4 studies. For both manual and automated scoring, cases were categorized as adenocarcinoma or benign (includes PIN).

Results: A high degree of concordance (>95%) was observed between manual and automated interpretation of benign and malignant biopsies. The algorithm correctly distinguished benign from malignant glands based on PIN-4 staining in almost all cases. PIN was more frequently diagnosed by image analysis than by manual review.

Conclusions: Image analysis can accurately distinguish between benign and malignant prostate glands in PIN4-stained tissue, without assistance from the pathologist. To our knowledge, this is the first example of image analysis of multicolor immunohistochemistry for interpretation of prostate biopsies.

Obstructive Uropathy Secondary to Familial Mediterranean Fever-Related Amyloidosis (Poster No. 50)

Erin Morris, MD (emorris@tuftsmedicalcenter.org); Pushkar A. Phadke, MD, PhD; Monika E. Pilichowska, MD, PhD. Department of Pathology, Tufts Medical Center, Boston, Massachusetts.

Familial mediterranean fever (FMF) is a rare hereditary autosomal disorder characterized by recurrent paroxysmal febrile episodes and serosal inflammation. Secondary amyloidosis, most commonly involving the kidney, is a well-known long-term complication and significant source of morbidity and mortality in FMF. We report a case of a 76-year-old male renal transplant recipient who underwent renal biopsy for increased creatinine 3 years posttransplant. The biopsy revealed tubular epithelial cell injury suggestive of calcineurin inhibitor toxicity and vascular mural eosinophilic deposits positive for amyloid by Congo red staining and apple green birefringence under polarized light. There was no evidence of cellular or antibody-mediated rejection. Direct immunofluorescence did not reveal light chain restriction. Immunohistochemical studies for AA amyloid revealed deposition in blood vessel walls and interstitium. These findings were diagnostic of renal allograft involvement by AA amyloidosis. Detailed history revealed that the end-stage renal disease was due to obstructive uropathy secondary to prostatic hypertrophy. Retrospective immunohistochemical examination of the prostate resection specimen revealed prominent interstitial deposits of AA amyloid. Additionally, the patient and his brother had suffered from episodes of chronic episodic diarrhea. Based on the history and clinical findings, a diagnosis of FMF was made. The patient's presentation in this case is unusual because renal failure was caused by obstructive uropathy secondary to amyloid-related prostatic hypertrophy, as opposed to primary renal involvement, which is the usual case in FMF. Furthermore, this case highlights that AA amyloidosis can recur in a kidney allograft, thereby complicating the clinical course.

Adult Testicular Granulosa Cell Tumor: A Case Report and Review of the Literature (Poster No. 51)

Joshua A. Hanson, MD (Joshua.Hanson@vtmednet.org); Abiy Ambaye, MD. Department of Pathology and Laboratory Medicine, University of Vermont Fletcher Allen Health Care, Burlington.

Adult testicular granulosa cell tumors are rare sex cord–stromal tumors of which only 28 have been reported. As compared to their ovarian counterparts, these tumors follow a more aggressive course and the proportion of malignant cases is higher. To date, there are no features that definitively predict malignancy. We present the 29th case of an adult testicular granulosa cell tumor and review the literature in an attempt to identify features that may predict its malignant potential. Our patient is a 21-year-

 
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old man who was referred to his urologist for a painless left testicular mass. Orchiectomy revealed a 1.0-cm, well-circumscribed mass abutting the tunica albuginea. Histologic sections showed a solid to focally trabecular pattern of medium-sized cells with grooved ovoid nuclei and scant cytoplasm. The cells displayed mild pleomorphism and showed distinct nuclear molding. The mitotic count was 15/10 high-power fields. There was no hemorrhage, necrosis, or lymphovascular invasion. Immunohistochemistry was strongly positive for inhibin, and focally positive for calretinin. At 16 months follow-up, the patient was free of disease. A review of all 29 reported adult testicular granulosa cell tumors shows that size (>5 cm) is the only significant predictor of malignancy (Mann-Whitney, P = .02) (Table). Although the mitotic rate in our patient is high, he has a favorable prognosis because of the small size of his tumor.

Bladder Urothelial Carcinoma Metastatic to the Testicle (Poster No. 52)

Matthew D. Geller, DO1 (mgeller327@yahoo.com); Nicole M. Durie, MD1; Robert D'Esposito, MD2; Andrea Flieder, MD.1 Departments of 1Pathology and 2Urology, Winthrop University Hospital, Mineola, New York.

Most testicular neoplasms are primary in nature; however, an estimated 3.6% are metastatic from distant sites. Numerous cases of neoplasms metastatic to the testicle have been reported. Of these, the most common organs of origin are prostate, lung, kidney, stomach, skin (melanoma), and colon. There have been few reports of bladder urothelial carcinoma metastasizing to the testis. We add to the small repertoire of published reports of this rare occurrence. Our patient is an 87-year-old man with a history of infiltrating, poorly differentiated bladder urothelial carcinoma who presented with a hard right testicle. His testicular tumor was found to be histomorphologically identical to his prior bladder tumor. In addition, his primary and metastatic tumors both showed squamous differentiation, a finding that, to our knowledge, has not been reported.

Collision Angiomyolipoma and Renal Cell Carcinoma in an Elderly Woman: A Case Report and Review of the Literature (Poster No. 53)

Anna T. Vischio, MD, MPH1 (annavischio@gmail.com); Jeet Sandhu, MD2; Hani El-Fanek, MD.1 Departments of 1Pathology and Laboratory Medicine and 2Radiology, Danbury Hospital, Danbury, Connecticut.

The coexistence of a renal cell carcinoma and an angiomyolipoma is quite rare, with only 31 cases cited in the literature. Renal angiomyolipoma is a relatively benign retroperitoneal tumor. Histologically, it is a choristoma composed of an intimate admixture of fat, smooth muscle, and vessels. Despite the lack of cellular anaplasia, angiomyolipomas represent a significant aberration in normal development that cause hematuria, flank pain, renal failure, or even spontaneous hemorrhage and shock, if symptomatic. Angiomyolipomas are highly associated with the hereditary disease tuberous sclerosis; therefore, all patients with renal angiomyolipomas should be evaluated. We present the case of an 80-year-old woman who initially presented with painless hematuria in 2005. An abdominal computed tomography (CT) showed a 2.8-cm left renal mass containing fatty elements and soft tissue suggestive of an angiomyolipoma. In 2008 the patient re-presented with recurrent painless hematuria. A heterogeneously enhancing 4.4 × 4.4 × 3.6-cm mass in the upper pole of the left kidney was seen on CT. An ultrasound-guided core needle biopsy was performed. Histologic examination of the core needle biopsy of the renal mass demonstrated a collision tumor of a well-differentiated renal cell carcinoma, clear cell type, and an associated angiomyolipoma (Figure 48). The angiomyolipoma was composed mainly of smooth muscle fibers without the adipose tissue component. Immunoperoxidase stains demonstrated strong positivity for desmin, actin, and melan-A, and weak positivity for HMB-45. The patient is scheduled for a radical nephrectomy. These tumors are rare and usually have a good prognosis if detected and excised early.

Infiltrating Urothelial Carcinoma May Be of the Clear Cell Variant (Poster No. 54)

Stewart Nash, MD1 (Stewart.Nash@ttuhsc.edu); Allan Haynes, MD2; Mitchell Wachtel, MD1; Dale Dunn, MD.1 Departments of 1Pathology and 2Urology, Texas Tech University Health Sciences Center, Lubbock.

A 62-year-old white man presented with hematuria. A computed tomography scan revealed a thickened urinary bladder with a 7.46 × 5-cm, lobulated, intraluminal mass with obstruction of both ureters and bilateral hydronephrosis, without any other tumor. The patient underwent cystoscopic resection. Received were 11.8 g of tissue chips. A solid tumor comprised nests and sometimes centrally necrotic sheets of cells with clear cytoplasm, sharp cell borders, and large, variably sized round, ovoid, and irregularly shaped nuclei with rare mitoses and occasional apoptotic bodies. Cancer was present in every chip, often invading muscle. Focal conventional urothelial carcinoma in situ was present. Lacking were vascular invasion and normal prostatic epithelium. The tumor was immunohistochemically positive for CK7 and CK20, and negative for prostate-specific antigen and vimentin. The cystoprostatectomy specimen showed the same tumor, with rare foci of non–clear cell change, which invaded perivesicle fat. One lymph node was partly replaced by non–clear cell urothelial carcinoma. The prostate tissue was benign. The patient remains alive, 1 ½ years after cysto-prostatectomy. From this case, one might hypothesize that a predominantly clear cell variant of urothelial carcinoma can arise from urothelial carcinoma in situ. Because the lymph node metastasis was of non–clear cell type, it can be further hypothesized that urothelial tumor cells with clear cytoplasm are less aggressive than are those that lack clear cytoplasm (Figure 49).

Plasma Copper in Leukopenic Dialysis Patients (Poster No. 55)

Claude Burdick, MD (claude.burdick@fmc-na.com); Nabat K. Wadhwania, MS. Spectra Laboratories, Milpitas, California.

Context: Deficiency of copper is unusual, but occasionally occurs in infants or adults fed a copper deficient enteral formula. In these subjects, the blood displays leukopenia with myelodysplastic changes. Recently, there have been reports of sporadic copper deficiency manifested by neutrologic symptoms. Clinical laboratories serving hemodialysis patients receive occasional specimens showing leukopenia resembling that described in copper deficiency. We thought it possible that copper might be lost in the hemodialysis process and tested these specimens for copper deficiency. Previous studies had shown that peritoneal dialysis does not remove copper from the blood. There are no hemodialysis studies.

Design: Plasma copper was measured by inductively coupled plasma emission spectroscopy. Three studies were done. Copper was measured from 27 volunteers, from 29 dialysis patients with normal white blood cell counts, and from 39 dialysis patients who had white blood cell counts of 2000/μL or lower.

Results: Copper levels in normal subjects ranged from 67–247 μg/dL, with a mean of 105 μg/dL and a standard deviation of 38 μg/dL. Copper levels in dialysis patients with normal white counts ranged from 67–152 μg/dL with standard deviation of 23 μg/dL. Copper levels in leukopenic dialysis patients ranged from 44–139 μg/dL, with a mean of 86 μg/dL and standard deviation of 23 μg/dL.

Conclusions: Patients described in the literature with a dysplastic leukopenia due to hypocupremia have copper values in the range of 0–9 μg/ dL. No leukopenic patient approached these levels, so that hypocupremia is not an explanation for their dysplastic leukopenia. Hemodialysis does not remove copper from blood.

Primary Renal Carcinoid: A Case Report and Review of the Literature (Poster No. 56)

Heather Baldwin, MD (hbaldwin@mailshroud.com); Amer Mahmoud, MD; Amanda Mullins, MD; Nadeem Zafar, MD. Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis.

Primary renal carcinoid is a rare tumor, mostly reported as isolated cases in the literature. We report the case of a 52-year-old man who presented with abdominal pain and an abdominal mass at clinical examination. At computed tomography, a solid enhancing mass was seen in the right renal pelvis, which prompted right nephrectomy. At gross pathologic examination, the renal hilum contained a well-circumscribed, 5.0 × 3.5 × 3.0-cm, yellow-tan tumor that compressed the neighboring renal parenchyma into a pseudocapsule. At microscopy (Figure 50), the tumor contained monotonous small cells with “salt-and-pepper” chromatin, arranged in anastomosing trabeculae, cords, and some solid sheets. Extensive lymphovascular involvement was present. The working differential diagnoses included carcinoid tumor, small cell neuroendocrine carcinoma, primitive neuroectodermal tumor, paraganglioma, Wilms tumor, and neuroblastoma. Cellular monomorphism with typical architectural arrangements, immunoreactivity with neuron-specific enolase, chromogranin, synaptophysin, and CD56, as well as no other site evidence for carcinoid tumor, clinched the diagnosis of primary renal carcinoid in this case. Tumor cells also did not immunoreact with EMA, TTF-1, WT-1, CD99 and P504S. Carcinoid tumors are distinct entities within the 2004 World Health Organization classification scheme of renal tumors, with similar features to carcinoid tumors found elsewhere. Awareness for primary renal carcinoid is likely to lead to an accurate diagnosis.

Combined Neoplasm of the Urinary Bladder: Case Report With Review of Literature (Poster No. 57)

Vlada A. Alexeeva, MD (vladkogan@msn.com); Sambit K. Mohanty, MD; Matthew D. Geller, DO; George K. Turi, MD. Department of Pathology, Winthrop University Hospital, Mineola, New York.

Small cell carcinoma of the urinary bladder is a rare tumor known to have a dismal prognosis. This neoplasm often coexists with high-grade invasive transitional cell carcinoma and, in up to 40% of cases, with transitional cell carcinoma in situ. Currently, only a few cases of large cell neuroendocrine tumor of the urinary bladder have been reported in the literature. In our case report, we describe the coexistence of small cell carcinoma of the urinary bladder with large cell neuroendocrine tumor, as well as an invasive transitional cell carcinoma with an in situ component in a 79-year-old male patient. We also show the tumor's immunohistochemical profile. Simultaneous presence of the multiple lines of differentiation in 1 neoplasm raises significant questions about the molecular events of this neoplastic process.

Pathologic Correlation of Radiologically Detected Prostate Cancer Lesions by a Novel Technique (Poster No. 58)

Haresh Mani, MD1; Baris Turkbey, MD1; Marcellino Bernardo, MS3; Vijay Shah, PhD3; Tom Pohida, PhD2; Peter Pinto, MD1; Peter Choyke, MD1; Maria J. Merino, MD1 (mjmerino@mail.nih.gov). 1National Cancer Institute and 2Center for Information Technology, National Institutes of Health, Bethesda, Maryland; 3SAIC-Frederick, National Institutes of Health, National Cancer Institute-Frederick, Maryland.

Context: Whole mount sections of prostates allow pathologic-radiologic correlations and tumor volume determination, factors that are important in patient management. However, whole mount sectioning often results in gland distortion and an inability to achieve these aims.

Design: To alleviate the problems of specimen distortion and for precise sectioning of prostatectomy specimens, we used a novel technique. Eight consecutive patients with biopsy-proven prostate cancer were accrued. Based on preoperative magnetic resonance imaging (MRI), a 3-D prostate model was generated to create a customized mold for each patient. Prostatectomy specimens were differentially inked and sectioned in their respective molds at 6 mm intervals (to facilitate comparison with the 3 mm–interval MRIs). Tumor foci were mapped on whole mount hematoxylin-eosin–stained sections and correlated with MRI findings.

Results: Sectioning in the mold yielded uniform slices, without distortion, and excellent quality histologic results. There were 2 to 5 (mean 2.8) foci of tumor per specimen with tumor volumes up to 11.9 cc. One case showed focal extraprostatic extension. Preoperative imaging had overall detection sensitivity of 69% and specificity of 61%; the sensitivity improved to 90% when central gland tumors and tumors less than 0.125 cc were excluded from analysis. Imaging detected both gland-rich and infiltrating foci of tumors but overestimated extraprostatic extension.

Conclusions: This novel technique of sectioning prevents specimen distortion and allows precise measurement and mapping of prostate cancer. The high correlation of preoperative imaging with histopathology suggests that this technique will aid in directed tissue procurement for research to better understand pathobiology of prostate cancer.

Lymphovascular Invasion in Micropapillary Urothelial Carcinoma (Poster No. 59)

Elizabeth B. McQuitty, MD (emcquitty@tmhs.org); Luan D. Truong, MD; Steven S. Shen, MD, PhD; Jae Y. Ro, MD, PhD; Alberto G. Ayala, MD; Philip T. Cagle, MD; Qihui “Jim” Zhai, MD. Department of Pathology, The Methodist Hospital, Houston, Texas.

Context: Micropapillary urothelial carcinoma (MPUC) is characterized by clusters of tumor cells floating in lacunar spaces that are conventionally understood to represent retraction artifact. This morphology is associated with high frequency of lymph node metastasis and low survival; reasons for this aggressiveness remain unclear. We hypothesize that some lacunae are lymphovascular channels and that invasion of lymphovascular channels may explain MPUC's aggressive behavior.

Design: Twenty-five cases of MPUC were studied retrospectively. Clinical information was gathered by chart review. Consecutive tissue sections were immunostained with D2-40 and CD34 for comparison with routine hematoxylin-eosin–stained sections.

Results: Of 25 patients, 22 were men with a median age of 70 (range, 56–85 years). All cases were associated with high-grade urothelial carcinoma (transitional cell carcinoma grade 3/3). Stage grouping was available in 9 cases; 7 of these (78%) presented with stage III disease and greater. Tissue was available for immunostaining in 22 cases. Lacunar spaces were almost uniformly negative for D2-40 and CD34. However, lymphovascular invasion was present in 21/22 cases (95%), a rate significantly higher than for conventional urothelial carcinoma (28% in previous work at our institution).

Conclusions: Our results confirm that most lacunar spaces are not lymphovascular channels. However, nearly all MPUC tumors (95% in this series) show evidence of lymphovascular invasion. The high incidence of lymphovascular channels in MPUC tumors partially explains MPUC's tendency to present with higher rates of lymph node metastasis than conventional urothelial carcinoma. Our data support the use of MPUC as a morphologic marker for aggressive disease.

Epithelioid Angiomyolipoma of the Kidney With a Unique t(6;11)(q13;p15) Chromosome Translocation (Poster No. 60)

Oksana Yaskiv, MD1 (oksanayask@aol.com); Arvin Rishi, MBBS1; Qiang Hua Chen, MD.21Department of Pathology, North Shore Long Island Jewish Health System-Albert Einstein College of Medicine at Long Island Jewish Medical Center, New Hyde Park, New York; 2Department of Pathology, North Shore University Medical Center, Manhasset, New York.

Epithelioid angiomyolipoma is a potentially malignant, rare variant of renal angiomyolipoma, characterized by proliferation of predominantly or exclusively of epithelioid cells. It often presents as a part of a tuberous sclerosis complex. Peculiar pattern of immunoreactivity includes expression of melanocytic differentiation markers such as human melanoma black–45, Mart1/Melanin-A, and microphthalmia transcription factor and variable expression of smooth muscle markers. Expression of epithelial markers is always negative. Histologic characteristic of epithelioid angiomyolipoma with cells having enlarged nuclei and prominent nucleoli may lead to misdiagnosis of high-grade carcinoma especially renal cell carcinoma. Perivascular cellular arrangement, focal features of otherwise classic angiomyolipoma, and characteristic immunoprofile are clues to the correct diagnosis. Cytogenetic abnormalities include allelic loss of chromosomal arm 16p in classic, epithelioid, and sarcomatoid areas and TP53 mutation mostly detected in epithelioid areas. We report the case of a 76-year-old man with history of left renal mass who subsequently developed local recurrence and distant metastasis to the liver. Histologically, all of the lesions appeared similar and characterized by proliferation of large, bizarre, epithelioid cells with abundant clear to deep eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli. Multinucleated giant cells, coagulative tumor necrosis, mitosis, and atypical mitotic figures are easily discernable. Immunohistochemical staining revealed positivity of neoplastic cells for human melanoma black–45 and melan A and negative staining for S100, pancytokeratin, vimentin, and CD10. Genotypic analysis, with standard GTG banding technique, revealed a unique, previously unreported t(6;11)(q13;p15) chromosome translocation. In conclusion, we present this case because of its rarity and detection of a new, unique chromosome translocation.

Interobserver Agreement for Extracapsular Extension of Prostatic Adenocarcinoma (Poster No. 61)

Michael Baker, MD1 (Michael.L.Baker@hitchcock.org); Larry Dumont, PhD1; Thomas Trainer, MD2; Masatoshi Kida, MD2; Alan Schned, MD1; Vijayalakshmi Padmanabhan, MD.11Department of Pathology, Dartmouth Medical School/Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; 2Department of Pathology, University of Vermont College Of Medicine/Fletcher Allen Health Care, Burlington.

Context: Extraprostatic extension (EPE) of adenocarcinoma beyond the prostatic capsule is a common occurrence and an important factor determining tumor stage but may be difficult to interpret even by experienced urologic pathologists. We measured expert interobserver agreement (multirater κ) from responses to 6 questions that pathologists face when evaluating EPE.

Design: Routinely processed, hematoxylin-eosin–stained slides (n = 46) from 16 prostatectomy cases initially reported as showing EPE were included and retrieved from 1 hospital's archives. Each case provided at least 1 block with EPE and at least 1 either equivocal or negative block. Four urologic pathologists independently reviewed the slides and, for each slide, they recorded their responses, limited to “yes,” “no,” or “equivocal,” to the following questions: (1) is tumor present in fat; (2) is tumor with EPE present; (3) is the tumor stage pT3; (4) is the capsule identified; (5) is extraprostatic fat present; and (6) are deeper levels necessary.

Results: See Table.

Conclusions: Our results demonstrate moderate agreement between expert urologic pathologists on the presence of prostatic adenocarcinoma with EPE and the assignment of tumor stage pT3. As expected, there was only slight agreement when characterizing the capsule and periprostatic soft tissue, with diversity between pathologists regarding the necessity of deeper levels to complete the diagnostic workup. These findings reflect the subjectivity inherent in evaluating adenocarcinoma with EPE and suggest a need for consensus definitions and guidelines to improve agreement, the clinical significance of which has yet to be prospectively determined.

 
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Morphometric and Ultrastructure Study of Peritubular Capillaries in Renal Biopsies of Childhood Idiopathic Nephrotic Syndrome (Poster No. 62)

Kamaljeet Singh, MD1 (ksingh@lifespan.org); Ruma Ray, MD, FRCPath2; Arvind Bagga, MD2; Amit K. Dinda, MD, PhD.21Department of Pathology, Brown University, Providence, Rhode Island; 2Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.

Context: Peritubular capillary (PTC) loss is present in tubulointerstitial damage in adult glomerulonephritis. PTC rarefaction correlates with decreased renal function in kidney transplants. PTC status is not known in childhood idiopathic nephrotic syndrome (CINS).

Design: We performed (1) quantification of PTCs in kidney biopsies of CINS; (2) correlation of PTC number with tubular atrophy, interstitial fibrosis, and renal function; and (3) transmission electron microscopic study of PTCs. Kidney needle biopsies of 30 cases and 7 controls (autopsy) were studied with immunohistochemistry for CD34 (IgG1, κ mouse monoclonal, Dako), Masson trichrome, and transmission electron microscopy. PTC number and interstitial fibrosis were calculated by Image-Pro Plus (Media Cybernetics, USA) image analysis software. Glomerular filtration rate was calculated by Schwartz formula.

Results: Mean PTC number/mm2 was as follows: control (n = 7), 604±16 (Figure 51); minimal change disease (n = 13), 540± 55 (P = .02); focal segmental glomerulosclerosis (n = 10), 461± 54 (P = .001); and mesangioproliferative glomerulonephritis (n = 7), 564±55 (P = .06). For interstitial fibrosis, the results were as follows: control, 5.24±0.93; minimal change disease, 7.25± 2.3 (P =. 04); focal segmental glomerulosclerosis, 16.63±6.0 (P = .005); mesangioproliferative glomerulonephritis, 7.73±3.7, (P = .08). There was a significant positive correlation between PTC number and glomerular filtration rate (P = .04, r2 = 0.15). Transmission electron microscopy showed widening, splitting, and multilayering of endothelial basal lamina in 3/10 cases of focal segmental glomerulosclerosis.

Conclusions: PTC loss is present in CINS. PTC loss is significant in minimal change disease and focal segmental glomerulosclerosis. PTC loss correlates positively with interstitial fibrosis and negatively with renal function. Basal lamina splitting and multilayering consistent with PTC damage was present in focal segmental glomerulosclerosis.

Seminoma With Rete Testis Hyperplasia Mimicking Mixed Germ Cell Tumor: An Entity Every Pathologist Should Be Aware of (Poster No. 63)

Alma R. Reyes, MD (alma.reyes@beaumont.edu); Maryam A. Farinola, MD. Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, Michigan.

Lesions of the intratesticular excretory ducts are rare and include adenocarcinoma, adenoma, adenofibroma, cystic dysplasia, and nodular proliferation of connective tissue involving the rete testis. A more frequently encountered scenario is that of infiltration of the rete testis by adjacent infiltrating testicular tumors, particularly seminoma. We present a case of seminoma with extension into the rete testis in which secondary hyperplasia and secretory change of the rete testis were identified. Microscopic examination revealed a proliferation of arborizing glandular structures with bland nuclear features infiltrating between the seminomatous lesion. The glandular structures were filled with eosinophilic colloidlike material, simulating a yolk sac tumor. We performed tests with a panel of immunohistochemical stains to help differentiate rete testis hyperplasia from yolk sac tumor and from stroma ovarii. Immunohistochemical results revealed vimentin and cytokeratin positivity with lack of staining for α-fetoprotein, TTF-1, and thyroglobulin, supporting the diagnosis of rete testis hyperplasia. Rete testis hyperplasia is a rarely seen lesion and is usually detected as an incidental microscopic finding. It is hypothesized to be a pseudoneoplastic reaction to secondary invasion of the rete testis by tumor. The histologic features of this lesion mimic the well-recognized features of yolk sac tumors. Because of the difference in treatment protocols between seminomatous and nonseminomatous germ cell tumors, it is important to avoid misdiagnosis of this lesion as a mixed germ cell tumor with seminomatous and yolk sac components from a pure seminoma.

Utility of Immunohistochemical Markers to Confirm the Presence of Vas Deferens in Vasectomy Specimens (Poster No. 64)

Kotaro Sasaki, MD (sasakik2@upmc.edu); Sheldon I. Bastacky, MD; Debra L. Zynger, MD; Anil V. Parwani, MD, PhD. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Context: Vasectomy-related cases are one of the most frequent types of malpractice claims filed against urologists. As such, many urologists routinely send vas deferentia (VD) for histologic confirmation. However, in certain cases histology is indeterminate for the presence of VD because of innate properties of the specimen or processing errors. CD10 has recently been described as a marker that can distinguish wolffian duct derivatives from müllerian remnants but has yet to be tested in vasectomy specimens.

Design: We determined whether CD10, as well as nonspecific epithelial marker pankeratin (PK), could corroborate the presence of VD. One hundred three consecutive vasectomy specimens were subjected to immunohistochemical analysis for CD10, PK, and CD31. Luminal and basal layer cells were semiquantitatively analyzed.

Results: In all cases with optimal epithelial histology (92/103), CD10 demonstrated intense apical membranous expression in all VD and weak basal cytoplasmic staining in 98% of cases. PK demonstrated cytoplasmic and membranous expression in both apical and basal layers in 99% of VD. CD31 did not show apical or basal reactivity in any VD. In cases with suboptimal epithelial histology (11/103), the detection of epithelia was 100% for CD10 and PK. Similar CD10 and PK expression was observed in the glandular epithelium of prostate, vas deferens, seminal vesicle, and ejaculatory ducts of radical prostatectomy samples.

Conclusions: CD10 and PK are useful markers to highlight the epithelium of VD and these markers can be used to confirm the presence of VD in vasectomy specimens in which the epithelial histology is suboptimal.

Bilateral Synchronous Testicular Tumors in a 31-Year-Old Man (Poster No. 65)

Masha C. Nzabi, MD1 (nzabim@umkc.edu); Mark M. Gitau, MD2; Daniel C. Dim, MD.1 Departments of 1Pathology and 2Hematology-Oncology, University of Missouri–Kansas City.

Simultaneous bilateral germ cell tumors of the testis are a relatively rare finding, having an incidence of approximately 1%–2%. In most cases the histology is classic seminoma. Seminomas are largely found in an older group of men (mean, 40 years), whereas nonseminomatous germ cell tumors are found in a younger group (mean, 25 years). We present a case of seminoma and embryonal carcinoma occurring simultaneously in the bilateral testes of a 31-year-old man. The patient complained of right testicular enlargement and left testicular pain. The serum α-fetoprotein level was 34.3 ng/mL (reference range, 0–8 ng/mL), serum β-human chorionic gonadotropin level was 2780 mIU/mL (reference range, 0–6 mIU/mL), and serum lactate dehydrogenase level was 512 IU/L (reference range, 98–192 IU/L). Ultrasonography showed echogenic masses in both testes. The patient had bilateral congenital undescended testes, of which one later descended and the other was surgically corrected. The patient subsequently underwent bilateral orchidectomy. Gross examination of the right testis revealed a 3.5 × 2.5 × 2.4-cm, poorly demarcated yellow mass with areas of hemorrhage and necrosis on cut surface. Microscopic and immunohistochemical staining pattern was consistent with embryonal carcinoma (Figure 52, left). The left testis revealed a 1.5 × 1.0 × 1.0-cm, well-demarcated white mass with a 0.5 × 0.5 × 0.5-cm cystic area on cut surface. The microscopic and immunohistochemical staining pattern was consistent with classical seminoma (Figure, right). Our case represents the third reported in the English literature of bilateral synchronous testicular tumors of seminoma and embryonal carcinoma histology.

Isolated Testicular Relapse of Acute Myeloid Leukemia 7 Years After Initial Diagnosis (Poster No. 66)

David D. Grier, MD1 (dgrier@wfubmc.edu); Andrew Eskew, MD3; Thomas White, MD4; Thomas W. McLean, MD.2 Departments of 1Pathology and 2Pediatrics, Wake Forest University School of Medicine, Winston-Salem, North Carolina; 3Department of Urology, High Point Regional Hospital (Piedmont Urological Associates), High Point, North Carolina; 4Department of Pathology, High Point Regional Hospital (North State Pathology), High Point, North Carolina.

Isolated testicular relapse in acute myeloid leukemia (AML) is a rare event in children. We report a case of an 18-year-old man who had an isolated testicular relapse 86 months after the initial diagnosis and 81 months after finishing chemotherapy. He was originally diagnosed with AML with minimal differentiation at age 11. He was treated with cytarabine-based chemotherapy and did well until age 18 when he presented with a left testicular mass. He had no other signs or symptoms and the results of his hematologic workup were unremarkable. An inguinal orchiectomy was performed and he was diagnosed with a myeloid sarcoma. There was no evidence of bone marrow involvement by morphology, immunohistochemistry, flow cytometry, or cytogenetics. The cerebrospinal fluid and a positron emission tomography–computed tomography scan were also negative for disease. The original AML and the myeloid sarcoma were immunophenotypically (CD34, CD117+, CD33+ , myeloperoxidase negative, terminal deoxynucleotidyl transferase negative) and cytogenetically (trisomy 8) identical except for loss of CD15 expression in the myeloid sarcoma. To our knowledge, this is the longest reported interval between remission and an isolated testicular relapse in AML. This case also demonstrates the use of immunophenotyping and cytogenetic studies to differentiate AML relapse from a secondary AML or a de novo myeloid sarcoma. The optimal management of patients with late extramedullary recurrence of AML is unknown.

The Nonneoplastic Kidney in Tumor Resections: Tumor-Related Alterations and Their Clinical Significances (Poster No. 67)

Ying Pei, MD, PhD (ypei@lsuhsc.edu); Brandon Swartz, MD; Stephen M. Bonsib, MD. Department of Pathology, Louisiana State University Health Science Center, Shreveport.

Context: The nonneoplastic changes of kidney are often not reported in tumor nephrectomies. There are 2 published studies on nonneoplastic changes in nephrectomies that focused on glomerular and arterial lesions. Significant diabetic glomerulopathy and arterial sclerosis were common and predicted renal failure. This study investigated peritumoral alterations and their clinical significances in nephrectomies for renal cell carcinoma (RCC).

Design: Nephrectomy specimens from 75 patients with RCC, 60 cases of clear cell RCC, and 15 cases of papillary RCC were reviewed. Tumor-related alterations in the peritumoral cortex were identified and correlated with clinical information.

Results: Sixty-nine of 75 tumors formed a 0.5–5 mm pseudocapsule. Six papillary RCCs lacked a pseudocapsule. Within the pseudocapsule were atrophic tubules, sclerotic glomeruli, and compressed arteries with marked fibrointimal thickening. These changes appeared unrelated to tumor size or stage and occurred in clear cell and papillary RCC. The pseudocapsule was inflamed and associated with lymphangiogenesis in a prior study. In 14/22 cases with follow-up, the creatinine level was elevated (mean, 0.34). Two cases showed postnephrectomy creatinine level >3 mg/ dL. The change in creatinine level after nephrectomy did not correlate with peritumoral changes of the kidney.

Conclusions: Tumor-related alterations in renal cell carcinoma include a peritumoral pseudocapsule representing nephron atrophy and fibrosis, likely a consequence of tubular and vascular obstruction. Peritumoral inflammation is invariably present and associated with lymphangiogenesis. These tumor-related alterations did not correlate with size or staging of the tumor and do not predict deterioration of renal function after nephrectomy.

Atypical Glomus Tumor of Uncertain Malignant Potential in the Urinary Bladder: Case Report and Literature Review (Poster No. 68)

Lindsay L. Waters, MD1 (llwaters@tmhs.org); Qihui “Jim” Zhai, MD1; Scott Buie, MD2; John A. Pumphrey, MD3; Sang Wu, MD.31Department of Pathology, The Methodist Hospital, Houston, Texas; 2Department of Pathology, ProPath Associates, Dallas, Texas; 3Department of Urology, Associates of Urology, Fort Worth, Texas.

We present a case of atypical glomus tumor of uncertain malignant potential arising in the urinary bladder of an 84-year-old woman with recurrent low-grade noninvasive papillary urothelial carcinoma of the bladder, which was previously resected in June 2006. Glomus tumors are mesenchymal neoplasms characterized by small size, benign nature, and location often in the dermis or subcutis of extremities. Histologic features include uniformly round cells with pale eosinophilic cytoplasm and central round to oval nuclei. Immunostaining demonstrates muscle-specific actin and desmin positivity and usually CD34 negativity. Specifically, atypical glomus tumors of uncertain malignant potential are defined by lack of criteria for malignant glomus tumor and the following: high mitotic count (>5/50 HPF) and superficial location or large size only or deep location only. Microscopically, this case has an abnormal proliferation of ovoid cells in the lamina propria, uniform ovoid nuclei with indistinct eosinophilic cytoplasm, sheet-like growth pattern with a prominent capillary network, mild nuclear atypia, and high mitotic rate (2/HPF). This case showed smooth muscle actin and smooth muscle myosin positivity and CD34 negativity. A PubMed search revealed 1 reported case of a malignant glomus tumor and no cases of atypical glomus tumors in the urinary bladder. A recent follow-up, 6 months after the initial diagnosis, did not show recurrences of this lesion. This unique case of atypical glomus tumor of uncertain malignant potential represents a challenging, rare neoplasm occurring in an unusual location. Distinction of this entity from the adjacent noninvasive papillary urothelial carcinoma is important.

A Case of a Collision of Renal Cell Carcinoma and Transitional Cell Carcinoma (Poster No. 69)

Monica I. Ruiz, MD (miruiz@bcm.edu); Linh M. Dang, MD; Chris J. Finch, MD. Department of Pathology, Baylor College of Medicine, Houston, Texas.

Renal cell carcinoma accounts for up to 90%–95% of all neoplasms of the kidney, while transitional cell carcinoma is the most common tumor of the renal pelvis, accounting for more than 90% of renal pelvis tumors. A collision of renal cell carcinoma and transitional cell carcinoma in the kidney is very rare. There have been only 26 cases reported in the English literature. We report an unusual case of a collision of transitional cell carcinoma and renal cell carcinoma in the kidney. The patient was a 57-year-old woman who initially presented with flank pain. Upon imaging studies, a left upper pole renal mass and a left necrotic hilar mass with a staghorn calculus was found. Subsequently, the patient underwent a total left nephrectomy and splenectomy. Grossly, the mass in the upper pole of the kidney was golden-yellow with areas of hemorrhage. The renal pelvis lesion appeared tan-brown with a friable surface. The upper pole mass and the hilar mass appeared to merge together into a single tumor measuring 8 cm in greatest dimension. Microscopically, the upper pole mass showed a high-grade unclassified renal cell carcinoma and the adjacent pelvic mass showed a grade 2 papillary transitional cell carcinoma. Cases of renal cell carcinoma and transitional cell carcinoma found in the same kidney are extremely rare. This case illustrates the importance of a thorough gross examination and generous sampling of surgical specimens to ensure the correct diagnoses and treatment of combined renal malignancies.

The Unproportional Number of Reports on Coexisting Adenocarcinoma and Carcinoid Tumor in the Urinary Bladder (Poster No. 70)

Jiong Zhang, MD, PhD (pathdoc.zhang@gmail.com); Vivekanand Datta, MD, PhD. Department of Pathology, The University of Tennessee Health Science Center at Memphis.

We encountered a rare case of 2 neoplastic processes coexisting in the urinary bladder. These neoplastic processes consist of adenocarcinoma and carcinoid tumors. The mucinous adenocarcinoma is positive for cytokeratin-20 and carcinoembryonic antigen and negative for cytokeratin-7, neuron-specific enolase, prostate-specific antigen, synaptophysin, CDX-2, and chromogranin A. The carcinoid lesion is positive for cytokeratin-7, carcinoembryonic antigen, neuron-specific enolase, synaptophysin, and chromogranin and negative for cytokeratin-20, prostate-specific antigen, and CDX-2. This is the fifth reported case of carcinoid tumors coexisting with another carcinoma in the urinary bladder. Among urinary bladder carcinomas, urothelial carcinomas are more than 10 times more frequent than adenocarcinomas. Therefore, we would normally expect that if another malignancy co-occurs with carcinoid tumor in the urinary bladder, it would most often be urothelial carcinoma by chance alone. Interestingly, only 1 of 5 of these reported mixed tumor cases involved urothelial carcinoma. Four of them involved adenocarcinomas, as in our case. This prompts us to suspect that the co-occurrence of these 2 different tumors in the bladder may have 1 underlying pathogenesis pathway, such as a novel tumor syndrome.

Mucinous Cystadenocarcinoma of the Testis (Poster No. 71)

Alina C. Iuga, MD (aiuga@chpnet.org); Jason Mull, MD; William Miller, MD. Department of Pathology, St.Luke's Roosevelt Hospital Center, New York, New York.

Ovarian-type surface epithelial carcinomas of the testis are a rare primary testicular malignancy, and most of the previously reported cases are of the serous variety. We present a case of unilateral invasive intratesticular cystadenocarcinoma with mucinous differentiation. Extensive literature review revealed only 3 similar reported cases. The patient is a 71-year-old man with a history of melanoma who presented with a left testicular hydrocele secondary to a mass. Imaging studies and colonoscopy revealed no other suspicious lesion. Gross examination of the orchiectomy specimen revealed a 3.5-cm, white, soft, glistening, well-delineated mass with a 0.1-cm yellow undulating border, completely replacing the testicular parenchyma. Microscopically, the mass was a well-differentiated cystic neoplasm with elongated fine pseudopapillary structures lined by columnar epithelium with alternating goblet and ciliated cells. Mitotic activity was rare. Foci of neoplastic epithelial lining overlying fibrous stroma in the testicular mediastinum were identified as a possible in situ component. The tumor invaded into but not through the fibrous capsule. The cyst wall showed extensive inflammatory and xanthogranulomatous reaction, dystrophic calcification, and mucin extravasation. No involvement of the tunica albuginea, rete, or appendix testis was identified. No teratomatous elements were identified. Immunohistochemical studies showed positivity for cytokeratin 20 and carcinoembryonic antigen, negativity for cytokeratin 7 and vimentin, and focal positivity for estrogen receptor. We discuss the histopathologic findings of this unusual testicular neoplasm with a particular immunophenotypic profile and review the existing literature on the subject.

Discrepancy in Cancer Localization Between Prostate Biopsy and Radical Prostatectomy Specimens in Patients With Unilateral Positive Biopsy Cores: Implications for Focal Ablative Therapy (Poster No. 72)

Michael Sinnott, MD (sinnotm@ccf.org); Sara M. Falzarano, MD; Ming Zhou, MD, PhD; Cristina Magi-Galluzzi, MD, PhD. Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio.

Context: Ablative treatment has gained acceptance as treatment strategy for patients with prostate cancer (PCA) who are not candidates for prostatectomy (RP). The success of unilateral ablative strategy depends on the reliable prediction of unilateral PCA by biopsy.

Design: A total of 1326 men had PCA on 12-needle biopsy (12Bx). In 435 (32.8%), PCA was detected only in 1 side. RP was available for 183 patients. All specimens were reviewed by a pathologist who mapped the tumor outline, determined the number of PCA, their volume (TV), zone of origin, Gleason score (GS), and tumor stage.

Results: Mean age, preoperative prostate-specific antigen (PSA) level, and prostate weight were 59 years, 6.1 ng/mL, and 53 g, respectively. In 50 men, 12Bx findings correlated with RP findings (unilateral PCA). In the remaining 133 patients (72.7%), 1–5 PCA foci/RP were detected in the contralateral side. In 110/133 patients, 173 significant PCAs (>5 mm2 and GS ≥ 6) were missed. The contralateral PCAs were GS6 (72%), GS7 (26%), and GS7 with pattern 5 (2%); their TV ranged from 6 to 274 mm2. Stage was T3 (n = 3), T2+ (n = 2), and T2 (n = 168). PCA location was distributed as follows: apex (14.4%), mid (46.2%), base (4%), apical-mid (26%), apical-base (5.2%), and mid-base (4%). Thirty percent of PCAs involved transitional/anterior and 70% involved peripheral zone.

Conclusions: Most men with unilateral positive biopsy have pathologically proven bilateral PCA and focal treatment is unlikely to be curative. Additional biopsies of the mid/apical-mid prostate could be suggested before considering focal ablative therapy.

POSTER SESSION 400: MONDAY, OCTOBER 12, 2009, 1:00 pm–3:30 pm

Autopsy and Forensic Pathology; Bone and Soft Tissue Pathology; Transfusion Medicine and Coagulation; Administrative and Regulatory Affairs

Bile Acid Pneumonitis in a Neonate Born to a Mother With Intrahepatic Cholestasis of Pregnancy: An Emerging Entity to Consider in the Differential Diagnosis of Neonatal Respiratory Distress (Poster No. 1)

Anupma Nayak, MD1 (anayak@nshs.edu); David Dennison, MD2; Morris Edelman, MD.11Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, New York; 2Department of Neonatology, Schneider Children's Hospital, New Hyde Park, New York.

Bile acid pneumonitis is a recently described entity affecting neonates born to mothers who have developed intrahepatic cholestasis of pregnancy. This disease was first described by Zecca et al in 2004. They suggested that maternally derived bile acids enter the fetal lungs by aspiration or circulatory uptake, resulting in inhibition of surfactant activity and consequent respiratory distress syndrome. Very few cases of neonatal bile acid pneumonitis have been reported since then. We present a case of bile acid pneumonitis in a neonate born at 38 weeks' gestation by induced vaginal delivery to a 35-year-old woman who was group B streptococci–positive and was diagnosed with intrahepatic cholestasis of pregnancy (generalized pruritus and increased serum bile acid levels of 22 μmol/L). After birth, Apgar scores were 9 and 9 at 1 and 5 minutes, respectively. Soon after delivery, the baby developed respiratory distress with significant oxygen desaturations. Despite adequate respiratory support, intravenous fluids, and antibiotics, the baby died after 24 hours. At autopsy, the most significant pathologic findings were diffuse alveolar damage with extensive alveolar hyaline pseudomembranes and acute hemorrhage into multiple organs. There was no evidence of lung infection/pneumonia, aspiration, sepsis (blood cultures were negative), or surfactant deficiency (unremarkable pneumocyte lamellar bodies on electron microscopy). Considering the maternal history of intrahepatic cholestasis of pregnancy and having excluded other plausible causes of respiratory distress, we rendered a postmortem diagnosis of neonatal bile acid pneumonitis. Our case highlights the importance of being aware of this emerging entity as a potential cause of respiratory distress.

A Fatal Case of Diffuse Pulmonary Lymphangiomatosis in a Postpartum Patient (Poster No. 2)

Kristinza R. Woodard, MD (kwoodard@u.washington.edu); Dennis Reichenbach, MD; Rodney Schmidt, MD, PhD. Department of Pathology, University of Washington, Seattle.

Diffuse pulmonary lymphangiomatosis is a rare, debilitating disease that is characterized by abnormal lymphatic vessel proliferation and most often presents in the first 2 decades of life. We present an autopsy case of a 32-year-old woman who was incidentally diagnosed with lymphangiomatosis after a motor vehicle accident 4 years before autopsy. On initial diagnosis, the disease involved the right upper lung lobe, mediastinum, and pleural surfaces with refractory bilateral chylous effusions. Subsequent treatments included lung wedge resection, pleurocentesis, bilateral pleurectomies, and pleurodesis. Her baseline symptoms included cough and decreased exercise tolerance. Three weeks before her demise, she gave birth to a 29-week-old male newborn delivered by cesarean delivery secondary to exacerbation of maternal disease symptoms, including chylothoraces, respiratory compromise, and failure to thrive. After delivery, she developed respiratory failure and a persistent pericardial effusion requiring intubation and pericardial sac drainage. She died soon after. At autopsy, the right lung had a 10-cm infiltrative proliferation of lymphatic vessels that extended onto the visceral pleura and adjacent mediastinal soft tissue. The left lung had a similar 13-cm lesion. Histologic findings demonstrated ectatic lymphatic spaces (CD34+, smooth muscle actin–positive, pancytokeratin-positive and HMB-45–negative) with associated fibrovascular tissue. The lack of HMB-45 staining distinguished the lesion from lymphangioleiomyomatosis, a rare entity more commonly associated with women of reproductive age. This is an unusual initial presentation of diffuse pulmonary lymphangiomatosis that was fatal 4 years after diagnosis because of disease progression and increased respiratory complications related to pregnancy.

A Case of Idiopathic Sclerosing Polyserositis With Multiorgan Failure (Poster No. 3)

Oleksandr Kryvenko, MD (oleksandr.kryvenko@yahoo.com); Tarek Hammour, MD; Frederick Meier, MD; Dhananjay Chitale, MD. Department of Pathology, Henry Ford Hospital, Detroit, Michigan.

Sclerosing encapsulating peritonitis, also known as “abdominal cocoon,” is a rare entity. We describe a case of generalized idiopathic sclerosing polyserositis affecting not only peritoneum but also pericardium and pleura. Besides anecdotal reports of prolonged β-blocker therapy– associated idiopathic sclerosing polyserositis, we did not find any cases in the literature. A 66-year-old man was followed up for 9 years for presumptive alcohol-induced liver cirrhosis with low serum albumin, recurrent ascites, pleural effusions requiring paracentesis and thoracentesis. He received transjugular intrahepatic portosystemic shunt procedure for increasing ascites. Past serologic workup was negative for autoimmune diseases and infectious hepatitis. The patient was scheduled for liver transplantation. He presented with unstable condition, lethargy, confusion, drowsiness, and orthopnea and was transferred to intensive care unit where he died after complicated course. Autopsy showed that all organs of the abdominal and thoracic cavity were encased in a thick, hyalinized fibrous tissue. Histologic findings revealed bland paucicellular subserosal fibrocollagenous tissue with focal chronic inflammation (Figure 53). Liver showed chronic passive congestion without evidence of cirrhosis. A stable radiologic abnormality in the upper lobe of left lung was a 0.8-cm, well-differentiated pulmonary adenocarcinoma with no evidence of metastases. Massive upper gastrointestinal bleeding was the terminal event. Cases of sclerosing encapsulating peritonitis have either silent clinical course or acute presentation with intestinal obstruction. In our case, the process was insidious, restrictive-causing multiorgan failure due to the constrictive effect of fibrosis. We term this case idiopathic sclerosing polyserositis in view of the above findings and absence of recognized clinical causes of sclerosing encapsulating peritonitis.

Intrauterine Fetal Demise Caused by Thymic Hyperplasia and Cardiovascular Compromise (Poster No. 4)

Jaimini Vora, MD1; Dominick LoBraico, DO2; Yong Kang, MD, PhD1 (ykang@sbhcs.com). Departments of 1Pathology and 2Obstetric and Gynecology, Monmouth Medical Center, Long Branch, New Jersey.

The thymus is normally large at birth and continues to grow until puberty. Whether enlarged thymus can cause pediatric morbidity and mortality (so-called thymic asthma and thymic death) has been subject to controversy since thymic death was first described 400 years ago. We report a case of intrauterine fetal demise caused by a severely enlarged thymus. The pregnancy was induced when the male fetus was at 30-week gestational age. The 36-year-old mother was gravida 1, para 0, with a history of hypothyroidism. Her thyroxine medication was reduced at admission because of clinical hyperthyroid symptoms. Serum autoantibody studies showed high titers of thyroglobulin antibody (25 250 U/mL) and thyroid peroxidase antibody (2204 U/mL). At fetal autopsy, the thymus was found to be markedly enlarged, weighing 19 g (reference range, 2.8– 4.1 g). It showed thymic hyperplasia on histology; it occupied most of the chest cavity, encompassing the anterior heart. There was also evidence of cardiovascular compromise, including severely congested hepatosplenomegaly and severe congestion in the umbilical cord vein. This is the first reported case of intrauterine fetal demise due to thymic hyperplasia in which the mother was diagnosed with hypothyroidism. Thymic hyperplasia is relatively common in patients with hyperthyroidism and Graves disease, and thyroid autoantibody can cause thymic hyperplasia. Thyrotropin receptors have been identified in human thymus. However, thymic hyperplasia is rare in patients with hypothyroidism. There is one report of thymic enlargement during thyroxine treatment for primary hypothyroidism. The etiology of the severe thymic hyperplasia in this case merits further investigation.

Transfusion-Related Iron Overload in Diamond-Blackfan Anemia: An Autopsy Case Report (Poster No. 5)

Mario Rascon, MD (mrascon@nshs.edu); Morris Edelman, MD. Department of Pathology, North Shore Long Island Jewish Health System, New Hyde Park, New York.

Diamond-Blackfan anemia (DBA) is a rare heterogeneous genetic disorder characterized by red cell aplasia. The degree of anemia, presence of other congenital anomalies, and response to therapy varies significantly among affected individuals. While as many as 80% of patients with DBA respond to corticosteroid therapy, a small group of patients require lifelong blood transfusion therapy and ultimately develop an iron overload syndrome. We report the case of a 27-year-old man with transfusion-dependant DBA who had an atrial septum primum defect corrected during infancy. The patient developed cirrhosis and polyendocrinopathy and eventually died of a cardiac arrhythmia. Autopsy examination confirmed the presence of iron-induced polyendocrinopathy, hepatic cirrhosis, and a dilated cardiomyopathy (see Figure 54), all of which were consequences of his lifelong dependence on blood transfusions. The study of DBA is important because of the dramatic clinical impact the disease has on affected patients and their families. The autopsy findings in this patient illustrate how critical iron chelation therapy is in managing patients with transfusion-dependent DBA. The clinical and genetic heterogenicity of DBA prompted the Schneider Children's Hospital (New Hyde Park, New York) to establish the Diamond-Blackfan Anemia Registry of North America in 1993 in an attempt to create a reliable demographic, clinical, and laboratory database of affected patients.

Fulminant γ/δ T-Cell Lymphoma Presenting as Acute Appendicitis: A Postmortem Study (Poster No. 6)

Katharine E. Van Patten, MD1 (katharine.vanpatten@yale.edu); Deborah L. Ornstein, MD2; Eduardo Zambrano, MD, MS.11Department of Pathology, Yale University School of Medicine, New Haven, Connecticut; 2Department of Hematology/Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.

We report a case of aggressive T-cell lymphoma that diffusely infiltrated all major organs, causing multiorgan failure and death in a previously healthy 4-year-old boy. The patient presented with acute onset of abdominal pain and vomiting. A computed tomography scan suggested acute appendicitis with perforation. The patient underwent emergent appendectomy. Postoperatively, he developed abdominal distension, respiratory distress, and hypotension. He was intubated; however, sufficient oxygenation could not be maintained, and he died on postoperative day 4. At autopsy, there were discrete hyperemic areas along the small-bowel serosa that corresponded to raised mucosal plaques. Extensive lymphadenopathies were most prominently noted in the mesentery. Microscopic evaluation showed diffuse infiltration of virtually all organs by monomorphous atypical lymphocytes. Flow cytometry analysis was performed on tissue after a postmortem interval of 25 hours. We identified an abnormal T-cell population with the following immunophenotype: CD3+, CD4, CD8, TcR δ–positive, and TcR α–negative. Molecular testing of the appendix showed a monoclonal T-cell receptor–γ gene rearrangement. Microarray comparative genomic hybridization was performed. It showed 3 segmental deletions in chromosomes 6q and 9p, including a homozygous 9p21 deletion, which has been associated with an aggressive natural history and poor prognosis in pediatric lymphoproliferative diseases. γ/δ T-cell lymphomas are typically aggressive; however, this type of fulminant presentation is unprecedented. Moreover, the molecular alterations we observed have not been previously described in this disease and likely contributed to the rapidly fatal course. This study underscores the importance of using all available techniques for postmortem evaluation of challenging cases.

Peripartum Aortic Dissection Presented as Sudden Death (Poster No. 7)

Baiyang Xu, MD (baiyang.xu@alleghenycounty.us); Karl E. Williams, MD, MPH; Todd Luckasevic, DO; Abdulrezak M. Shakir, MD. Department of Pathology, Allegheny County Medical Examiner's Office, Pittsburgh, Pennsylvania.

We present a case of peripartum aortic dissection, a rare but documented entity in the literature. The deceased was a 37-year-old white woman (G2P2) with no history of miscarriage or abortion. Shortly after delivery of a healthy, male infant at 32 5/7–week gestational age, she complained of chest and back pain. She had no history of hypertension, connective tissue disease, or congenital heart disease. She was kept under observation in the recovery room. Two and a half hours after her uncomplicated vaginal delivery, she was found unresponsive in bed in asystole. Autopsy findings revealed an extensive descending aortic dissection with left hemothorax, 1400 mL; left subpleural hematoma, 100 mL; and hemoperitonium, 100 mL. Microscopic examination revealed acute aortic dissection with no evidence of inflammation. Fragmentation of the elastic fibers was noted at the site of the rupture with minimal or no medial degeneration. The absence of connective tissue disease, Marfan syndrome and Ehlers-Danlos syndrome indicates that the rupture may have occurred in the peripartum period with no apparent predisposing factors. The cardiovascular system undergoes important adaptation during pregnancy to accommodate fetal and maternal requirements. These changes may weaken the aorta, with the possible surge in blood pressure during the delivery probably acting as an initiator for the dissection. Complaints of chest and back pain during the peripartum period warrant consideration of an aortic dissection.

Novel Mutations in Glycogen Branching Enzyme in Glycogen Storage Disorder Type IV or Andersen Disease (Poster No. 8)

Angshumoy Roy, MD, PhD1 (aroy@bcm.edu); Ayman El-Hattab, MBBS2; M. John Hicks, MD, PhD, DDS1,3; Debra L. Kearney, MD1,3; Deeksha S. Bali, PhD4; Milton J. Finegold, MD.1,3 Departments of 1Pathology and 2Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas; 3Department of Pathology, Texas Children's Hospital, Houston; 4Division of Medical Genetics and Pediatrics, Duke University, Durham, North Carolina.

Glycogen storage disease type IV (type IV GSD), or Andersen disease, is a genetic disease with variable expressivity. This rare autosomal recessive disorder (0.3% of glycogenoses) is caused by a deficiency of the glycogen branching enzyme (GBE1) and presents in childhood as a classic hepatic form or later in life as neuromuscular disease. We report a novel GBE1 mutation in a type IV GSD case of a 4-month-old male infant with hepatomegaly. Liver biopsy demonstrated cirrhosis with hepatocytes and Kupffer cells containing distinctive cytoplasmic, periodic acid-Schiff–positive, Lafora bodylike inclusions and amylopectin-like ultrastructure. The patient died shortly after liver transplantation. Autopsy revealed diffuse myocardial and reticuloendothelial system involvement, including infiltration of lymph nodes, spleen, and lungs by foamy macrophages containing cytoplasmic inclusions of similar tinctorial quality to the hepatocytes and suggesting partially degraded amylopectin-like material. GBE activity in cardiac muscle was undetectable. Analysis of the GBE1 gene revealed compound heterozygosity for c.1279G>A, resulting in a novel G427R missense mutation of an evolutionarily conserved glycine residue, and a previously reported frameshift mutation c.1239delT, leading to premature truncation and likely a null allele. Previously reported mutations in GBE1 displayed marked allelic heterogeneity, including more than 15 alleles associated with different clinical presentations and variable enzyme activities. Diffuse reticuloendothelial system involvement in type IV GSD occurs infrequently. It is unclear whether diffuse reticuloendothelial system involvement represents a worse prognosis with severe enzymatic deficiency resulting from null mutations. This is the first report correlating molecular defects in GBE1 with this presentation.

Particularly Well-Demarcated Field Effect of Known Developmental Genes: A Case of Otocephaly-Agnathia Complex (Poster No. 9)

Rashmi Kanagal Shamanna, MD (rshaman1@hfhs.org); Frederick Meier, MD. Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, Michigan.

Otocephaly-agnathia complex is a rare, lethal malformation, including hypognathia or agnathia, synotia, microstomia, and hypoglossia. Estimated prevalence is 1/70 000, with 80 published cases. A 17-year-old G1P0 adolescent girl presented at 32 weeks' gestation with ruptured membranes and chorioamnionitis. Results from a 21-week obstetrical ultrasonography were normal. She gave birth to a premature male infant with low birth weight (1260 g). Because of multiple head and neck anomalies, he died within an hour. Postmortem imaging and autopsy focused on the pattern and extent of anomalies. Autopsy revealed absent mandibular arch, hemipalate, hypoplastic facial bones, low-set ears, microstomia, and microglossia. Imaging showed malformed hyoid bone, wide sella turcica, and multiple vertebral and rib abnormalities. Dissection demonstrated unusual rostral insertion of neck musculature and inferiorly displaced eustachian tubes. Anterior pituitary was present; nasopharynx and salivary glands were absent. Cardiac atrial septal defect was present. Neuropathologic examination showed arrhinencephaly, lissencephaly and Arnold-Chiari type 1 malformation. Associated anomalies, including synotia, external nose malformation, and situs inversus, were absent. Other findings included hypoplastic lungs, visceral hemorrhages, and dilated heart with normal cytogenetic study (Figure 55: clockwise: absent mandible, upon fetogram and gross examination; arrhinencephaly; vertebral-rib anomalies). This rare case demonstrates a nearly complete presentation of otocephaly-agnathia complex associated with atrial septal defect. Developmentally, maxillary process derived from first pharyngeal arch. Failure of sonic hedgehog (chromosome 7q36) signaling system and pair-related (non-HOX) homeobox Prx-1/Prx-2 expression were implicated. Continued eye development drew a rostral limit to the affected field. However, prosencephalic and vertebral-rib anomalies suggested a more caudal Lim1 transcription factor involvement. Other findings were secondary to hypoxia.

Intravascular Large B-Cell Lymphoma (Poster No. 10)

Maureen Cioffi-Lavina, DO (mcioffilavina@med.miami.edu); Claudia P. Rojas, MD; Wilfredo Blasini, MD; Clarence Withcomb, MD; Gerald Byrne Jr, MD; Clara Milikowski, MD. Department of Pathology, Jackson Memorial Hospital, Miami, Florida.

According to the World Health Organization classification, intravascular large B-cell lymphoma is a rare subtype of extranodal diffuse large B-cell lymphoma and represents less than 1% of all lymphomas. It is characterized by an extensive proliferation of neoplastic lymphocytes within the lumina of blood vessels. The disease can involve multiple organs, including skin, central nervous system, kidneys, adrenals, bone marrow, and others. Therefore, a variety of clinical presentations have been described. Our case is that of an 83-year-old woman with a long history of coronary artery disease, hypertension, aortic and abdominal aneurysm repair, and coronary artery bypass surgery. She presented with impairment of mental status, fever, and recurrent multiple livedoid and reticulated erythematous patches located on the lower extremities, abdomen, and chest. She also had splenomegaly without lymphadenopathy, thrombocytopenia, high lactate dehydrogenase levels, and a left adrenal mass. After admission, the patient's status progressively worsened for 6 days. She died of respiratory failure. Postmortem microscopic analysis revealed intravascular large B-cell lymphoma involving skin, brain, and the left adrenal gland. Intravascular large B-cell lymphoma is a rare, aggressive disease that is very difficult to diagnose because of multiorgan involvement. Most cases reported in the literature were diagnosed after postmortem examination. Therefore, when a patient has splenomegaly without lymphadenopathy, thrombocytopenia, increased high lactate dehydrogenase levels, and skin lesions, the clinician should include intravascular large B-cell lymphoma as one of the top differential diagnoses.

Epithelioid Angiosarcoma of the Adrenal Gland: A Rare Tumor With an Unusual Clinical Presentation (Poster No. 11)

Tiffani Milless, MD (tiffani.milless@yale.edu); Natalia Buza, MD; Matthew Palmer, MD. Department of Pathology, Yale University, New Haven, Connecticut.

Epithelioid angiosarcomas (EASs) of the adrenal gland are extremely rare neoplasms. The diagnosis is difficult due to lack of conclusive radiographic and endocrinologic findings, unusual location, and histologic features. The differential may include pheochromocytoma, primary adrenal epithelial neoplasms, and metastatic disease. Because of the small number of reported cases, we know little about clinical course and prognosis. Our case of adrenal EAS had an unusual clinical presentation and was diagnosed at autopsy. The patient was a 65-year-old woman with a history of melanoma. During evaluation of lower back pain, we discovered a 5-cm, nonfunctioning adrenal mass. The patient underwent laparoscopic adrenalectomy; however, she died postoperatively before diagnosis of the surgical specimen. Microscopic examination of the hemorrhagic retroperitoneal tissue revealed residual adrenal gland with nests and cords of pleomorphic epithelioid cells demonstrating prominent nucleoli and high mitotic activity throughout the cortex and medulla and interspersed with anastomotic vascular spaces. Metastatic foci with identical morphology were also identified in multiple retroperitoneal lymph nodes and in bone marrow. Tumor emboli were noted in the lungs. Immunohistochemical analysis was negative for Melan-A, HMB-45 and S100 and positive for vimentin, CD31, CD34 and factor VIII. We report a case of adrenal EAS that was diagnosed at autopsy. Immunohistochemical analysis helped to rule out metastatic melanoma and to diagnose EAS. The presence of extensive metastatic foci indicates an extremely aggressive course. This report contributes to a better understanding of the natural history of this rare entity.

Agnathia-Otocephaly With Alobar Holoprosencephaly and Visceral Anomalies: A Case Report and Immunohistochemical Study (Poster No. 12)

Robert L. Schmadeka, MD (rlschmadeka@yahoo.com); Lance Needham, MD; Jie Zhang, MD. Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis.

Agnathia-otocephaly with alobar holoprosencephaly and visceral anomalies is a very rare and lethal congenital disorder. Since 1717, less than 50 cases have been reported in the literature. Most cases are sporadic and of normal karyotype. Etiology is unknown and might be related to a mutation of sonic hedgehog, ZIC2, SIX3, and paired-related homeobox genes. The current case is that of a male infant who was born at 35 weeks' gestation to a 16-year-old G2P2 mother. The infant died shortly after birth. We performed autopsy and cytogenetic examinations and immunostaining for chromogranin and inhibin on adrenal glands. Macroscopically, facial dysmorphism showed trigonocephalic microcephaly, cyclopia with anophthalmia, tiny central skin tags, absence of nose and nostrils, microstomia and microglossia, agnathia and hypoplasia of the maxilla, and centrally displaced low-set ears. Alobar form, pancakelike holoprosencephaly showed pachygiria with an 80-mL fluid-filled dorsal sac and undivided thalami and corpora striata. We found no olfactory tracts and bulbs, optic nerves, chiasm and optic tracts, pituitary gland and pineal gland, or corpus callosum. Medulla showed olive hypertrophy and pyramid hypotrophy. Both lungs were hypoplastic with massive hemorrhage. Spleen was bilobed and accessory. Microscopically, adrenal glands demonstrated cortical hypoplasia and medullar hypertrophy and were positive for inhibin and chromogranin. The thyroid gland was hypoplastic, and the testes were small and undescended. Cytogenetics indicated normal male karyotype 46, XY. This rarely reported phenotype suggests that temporal and spatial damage of the anterior embryonic disc occurs during early embryonic development (Carnegie stage 10, embryonic days 22 or 23).

Hyphal Coccidioidomycosis of the Brain in a Patient With Central Nervous System Lymphoma (Poster No. 13)

John B. Carpenter, MD (jbc2@WWW.arizona.edu); Jennifer L. Thorn, MD; Tara A. Saunders, BS; Richard E. Sobonya, MD. Department of Pathology, University of Arizona, Tucson.

Coccidioidomycosis is an opportunistic infection caused by the dimorphic fungi Coccidioides immitis and Coccidioides posadasii. At body temperature, the organism almost always assumes a characteristic spherical morphology. The hyphal morphology has been observed in human tissue, but almost exclusively in the lung. A review of the literature revealed 3 previously reported cases of parenchymal brain disease. We describe the first known case occurring with concurrent lesions of diffuse large B-cell lymphoma of the brain. The patient was a 22-year-old Hispanic woman who presented with dyspnea, weight loss, and fatigue. A workup revealed diffuse large B-cell lymphoma involving the bone marrow, mediastinum, and brain. She was treated with chemotherapy, radiation, and ultimately matched-unrelated stem cell transplantation. She developed multiple infectious complications and died 1 month later. Postmortem examination showed lymphoma of multiple organs, including the left frontal lobe of the brain. Disseminated coccidioidomycosis was observed in the lungs, lymph nodes, kidneys, and brain. Microscopic examination of the left frontal lobe adjacent to the tumor showed spherules admixed with characteristic hyphae and barrel-shaped alternating arthroconidia. Several small arteries bore occlusive thrombi with mural invasion by the coccidioidal mold. Hyphal coccidioidomycosis is exceedingly rare in tissues other than the lung. Only 3 cases of parenchymal brain infection have been previously reported. They include 2 men (ages 26 and 43) with human immunodeficiency virus and one 46-year-old woman with a history of kidney transplantation due to diabetic nephropathy. This is the first known case associated with central nervous system lymphoma and bone marrow transplantation.

Characterization of Triamcinolone in Formalin-Fixed and Paraffin-Embedded Tissue Specimens by Using Infrared Micro-Spectroscopy (Poster No. 14)

Gary L. Cohen, MD, PhD1 (Gary.Cohen@afip.osd.mil); Victor F. Kalasinsky, PhD1; Isabell A. Sesterhenn, MD2; Walter R. Rush, MD3; Maria M. Tomaszewski, MD3; Robert W. Brinsko, MD2; Florabel G. Mullick, MD1; Michael R. Lewin-Smith, MB, BS.1 Departments of 1Environmental and Infectious Disease Sciences, 2Genitourinary Pathology, and 3Dermatopathology, Armed Forces Institute of Pathology, Washington, District of Columbia.

Corticosteroid injection sites have to be differentiated microscopically from other conditions, including rheumatoid nodules, gouty tophi, myxomas, and injection sites of other materials. Infrared microspectroscopy is a noninvasive technique that allows for the molecular characterization of unidentified materials in histopathology specimens. We evaluated 2 specimens for the presence of steroids. In case 1, we received formalin-fixed wet tissue from a postvasectomy spermatic cord stump that contained a pale nodule that was sampled for infrared microspectroscopy. In case 2, we received a formalin-fixed, paraffin-embedded shave biopsy of skin. Consecutive unstained sections were placed on an aluminized glass slide, a carbon disc, and a glass slide. The latter was hematoxylin-eosin– stained, and the areas of interest were located for analysis of the unstained sections, which were deparaffininzed and examined by infrared microspectroscopy and by scanning electron microscopy with energy dispersive x-ray analysis. In both cases, infrared spectra characteristics of triamcinolone acetonide were obtained. A clinical history of multiple prior triamcinolone injections was provided for case 1 but not for case 2. In case 2, scanning electron microscopy with energy dispersive x-ray analysis identified carbon, oxygen, and fluorine in an area of interest. Fluorine is a constituent of triamcinolone. Triamcinolone may be identified by infrared microspectroscopy in both formalin-fixed wet tissue and in formalin-fixed, paraffin-embedded tissue. Fluorine may be identified by scanning electron microscopy with energy dispersive x-ray analysis. This analysis can help in the differential diagnosis of steroid injection sites and can have broader applications in forensics and medico-legal investigations.

Generational Differences in Coronary Artery Atherosclerosis in Women: An Autopsy-Based Study (Poster No. 15)

Andrew J. Wilhorn, MA (wilhorn.andrew@mayo.edu); Dylan V. Miller, MD. Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, Minnesota.

Context: Heart disease remains the leading cause of death for women in the United States, with coronary disease being the most common form. Many studies characterize coronary artery atherosclerosis by autopsy and by in vivo methods, but very few studies in the recent literature focus on women.

Design: This was a retrospective review of autopsy reports from 2003– 2008. We abstracted patient age, sex, height, weight, and cause of death and heart weight and degree of coronary atherosclerosis in the left anterior descending coronary artery, left circumflex coronary artery, and right coronary artery. All autopsies included histologic examination of coronary arteries with grading of stenosis (1 = <25%, 2 = 26%–50%, 3 = 51%– 75%, 4 = >75%). These data were compared to similar data compiled at our institution and published in 1950.

Results:  We included 726 women ranging in age from 30–99. Cases with at least 1 grade 3 lesion in at least 1 coronary artery included 49% of women aged 30–39, 61% aged 40–49, 55% aged 50–59, and 71% aged 60–69. Of these groups, 12%, 15%, 18%, and 18%, respectively, had grade 3 lesions in all 3 arteries. Patients older than 70 years had comparatively lower grade lesions occurring in fewer arteries; this trend was not statistically significant. In 1950, less than 30% of women under age 70 had 1 grade 3 disease in any vessel.

Conclusions:  Potentially significant (>50%) coronary stenosis was found at autopsy in a surprisingly high number of premenopausal women dying from any cause. This represents a major shift from data published 60 years ago.

Abdominal Lymphomatosis (Poster No. 16)

Kotaro Sasaki, MD (sasakik2@upmc.edu); Fiona E. Craig, MD; Lawrence C. Nichols, MD. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Confronted with a gross pathologic finding of massive tumor infiltration of the omentum as shown in the figure below (Figure 56) and a radiologic diagnosis of abdominal carcinomatosis, most pathologists would be very confident that this is an epithelial or mesothelial malignancy; this, however, was a disseminated peritoneal B-cell lymphoma in a 51-year-old woman who presented with severe abdominal pain. Computerized tomography showed extensive peritoneal infiltration of tumor, bilateral adnexal masses, and right pleural effusion, results which prompted the radiologic diagnosis of peritoneal carcinomatosis with possible ovarian primary tumor. The patient died of massive pulmonary thromboembolism before biopsy could be performed. Microscopic examination revealed sheets of intermediate-sized blastlike cells with scant cytoplasm and round nuclei with a fine chromatin pattern. Immunoreactivity was demonstrated for B-cell markers, CD10, CD22, and CD79a, with little to no expression of T-cell or epithelial markers, leading to the diagnosis of B-cell lymphoid neoplasm with high-grade features. This case serves to raise awareness of the entity, abdominal lymphomatosis, which is radiologically difficult to differentiate from peritoneal carcinomatosis.

Postmortem Demonstration of the Source of Pulmonary Thromboembolism: The Importance of the Autopsy (Poster No. 17)

Gina Elhammady, MD (gelhamma@msmc.com); Andrew T. Schubeck, MD; Morton J. Robinson, MD. Department of Pathology, Mount Sinai Medical Center, Miami Beach, Florida.

Pulmonary thromboembolism is a major cause of death. Most emboli have been shown to originate in the veins of the legs. However, recent data have shown an increasing number of thromboemboli arising from the pelvic veins, namely from the periprostatic and periuterine plexuses. Other sites of clot origin, such as the atrial appendage of the right heart or the vessel wall at the tip of a venous catheter, may be identified on the basis of clinical presentation. However, for a group of patients, the site of clot origin remains a clinical enigma. In these cases, an autopsy is critical. We present the case of 2 patients for whom autopsy demonstrated periprostatic venous thrombi as the source of pulmonary emboli. The pathways for emboli migration from periprostatic veins may be through drainage into the inferior vena cava or via Batson plexus into the superior vena cava (Figure 57). This report highlights a rarely considered source of pulmonary thromboemboli that is usually identified by postmortem examination. In such cases, the autopsy also helps determine the possible pathways of clot migration (Figure 57). The periprostatic plexus primarily drains into the internal iliac veins via the vesical veins to reach the inferior vena cava and eventually the pulmonary circulation. Alternatively, this plexus communicates with the Batson vertebral plexus, which reaches pulmonary circulation through either the azygous system or the superior vena cava.

A Case Report on Sirenomelia: Theories of Pathogenesis (Poster No. 18)

Steven Held, MD (held@uthscsa.edu); Josefine Heim-Hall, MD. Department of Pathology