Abstracts and case study poster sessions will be conducted during the 2014 College of American Pathologists Annual Meeting, which is scheduled for September 7 to 10, 2014. The meeting will take place at the Hyatt Regency Hotel, Chicago, Ill. The poster sessions will occur in the CAP '14 Exhibit Hall. Specific dates and times for each poster session are listed below. Also shown before each poster session are the subject areas that will be presented during each session.
Gastrointestinal and Liver Pathology; Breast Pathology; Pulmonary and Mediastinal Pathology – A Case of Intraductal Tubulopapillary Neoplasm: A Rare Intraductal Neoplasm of the Pancreas With Foci of Invasion: (Poster No. 1)
Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a rare tumor, accounting for less than 1% of pancreatic exocrine neoplasms. We report a case of a 74-year-old man with a mass in the pancreatic head. Imaging studies showed significant pancreatic ductal dilation with a nondilated common bile duct. Clinical suspicion was for an endocrine or acinar cell neoplasm. A pancreaticoduodenectomy was performed. Pathologic examination demonstrated a 6-cm, intraductal mass that protruded into the ampulla, not involving the intestinal mucosa. The mass showed tubulopapillae lined by dysplastic cells with eosinophilic cytoplasm without intracytoplasmic mucin and with rare foci of stromal carcinoma, consistent with ITPN with invasive carcinoma (Figure 1). Immunohistochemistry was focally positive for MUC1 and negative for MUC2, MUC5AC, synaptophysin, and trypsin. The ITPNs are grossly visible, intraductal tubule-forming epithelial neoplasms with high-grade dysplasia and ductal differentiation without overt mucin production. They are immunoreactive for MUC1 and MUC6 and negative for MUC2, MUC5AC, endocrine, and acinar markers. The main differential diagnosis for ITPN is intraductal papillary mucinous neoplasm and pancreatic ductal adenocarcinoma. Intraductal tubulopapillary neoplasms are relatively indolent neoplasms, with significantly better prognosis than pancreatic ductal adenocarcinomas. The prognosis of noninvasive ITPNs is as favorable as noninvasive intraductal papillary mucinous neoplasms. Further investigation is needed to assess the comparative prognosis of invasive ITPN. This case demonstrates that ITPN can be reliably distinguished from other pancreatic neoplasms, but additional studies regarding prognosis in the setting of invasion are needed.
Widespread Breast Metastasis Discovered on Routine Colonoscopy: (Poster No. 2)
Distant metastasis is the most common form of recurrence and the main cause of death in patients with breast cancer. The most common site for breast cancer metastasis is bone followed by visceral organs. It has also been shown that breast cancer metastasis to visceral organs has a shorter disease-free survival. This is a case of a 51-year-old woman with a history of infiltrating lobular carcinoma treated with a left modified radical mastectomy and axillary dissection. The tumor was a multifocal, 3.5 cm, infiltrating lobular carcinoma, grade III tumor that was estrogen and progesterone receptor positive but HER2/neu negative by fluorescent in situ hybridization. One of 19 lymph nodes was positive for tumor, and she was classified as pT2N1aMx, stage IIIA. She started chemotherapy, and her breast cancer follow-up was thereafter negative. However, routine screening colonoscopy done 4.5 years after completion of treatment showed a 3-mm cecal polyp. Microscopically, sections of the polyp demonstrated colonic mucosa with infiltrating, poorly differentiated, single cells in the lamina propria (Figure 2, a and b). The tumor cells stained positive for CK7 (Figure, c) and GCDFP-15 (focally) (Figure, d). The morphologic and immuno-histochemical pattern was consistent with metastatic lobular carcinoma. The patient has since had a positron emission tomography scan, which showed increased uptake in the porta hepatis lymph node and in the vertebral bodies. A computed tomography scan showed prominent lymphadenopathy in chest, abdomen, and pelvis. The patient has since been started on capecitabine. This case illustrates how asymptomatic, disseminated breast carcinoma can be discerned incidentally on routine colonoscopy.
Expression of S100P, IMP3, and CK19 in Hepatocellular Carcinoma: (Poster No. 3)
Context: S100P, IMP3, and CK19 have been found in other studies to be independent predictors of early tumor recurrence in hepatocellular carcinomas (HCCs) with poor prognoses. However, no study has analyzed the expression of the 3 markers together. In this study, the panel of 3 markers was examined and correlated with HCC stage, grade, and clinical outcome.
Design: Seventy cases of HCC from 2003 to 2012 were identified and retrieved from our archives. The specimens included cases with varying stages and grades: 22 stage I, 35 stage II, 13 stage III and IV cases; 14 were well-differentiated, 35 moderately differentiated, and 21 poorly differentiated tumors. All cases were stained with a monoclonal antibody for S100P, IMP3, and CK19 proteins, and the results were evaluated independently by 3 observers. A positive result was defined as a cytoplasmic (IMP3 and CK19) or nuclear (S100P) stain in more than 10% of the tumor cells.
Results: Significantly greater coexpression of these markers was found in stage III and IV tumors: 5/13 cases (38%) showed double or triple stain positivity versus 23% (5 of 22) in stage I and 26% (9 of 35) in stage II tumors (see Table).
Conclusions: The panel of S100P, IMP3, and CK19 expression is positively correlated with the histologic grade and clinical stage. However, the low number of positive results suggests that expression of the studied biomarkers does not correlate with overall survival, and further investigation may be necessary for this conclusion.
IgG4-Related Pseudotumor of the Colon Mimicking Colon Cancer in a Patient With a History of Inflammatory Bowel Disease: (Poster No. 4)
Immunoglobulin G4–related disease is a tumefactive, fibroinflammatory process that has been described in numerous organ systems. The diagnosis IgG4-related disease relies on the presence of characteristic histologic findings, including a dense, lymphoplasmacytic infiltrate with elevated numbers of IgG4 immunopositive plasma cells, sclerotic fibrosis, focally, with a storiform pattern and obliterative thrombophlebitis. Here, we report a case of IgG4-related pseudotumor of the colon mimicking colon carcinoma clinically. A 64-year-old man with a history of inflammatory bowel disease (IBD) underwent a surveillance colonoscopy, which showed a 3-cm sessile mass arising in the ascending colon. This mass was biopsied and showed ulceration and active colitis; however, no dysplasia or malignancy was seen. Because of the size of the mass and concern for cancer, the patient underwent a segmental colectomy. Microscopic examination of the mass showed a dense plasma-cell infiltrate with associated lymphocytes and eosinophils and extensive sclerotic fibrosis in the lamina propria and submucosa. No obliterative thrombophlebitis was seen. Immunostain for IgG4 showed numerous IgG4-positive plasma cells (>50/high power field) with an IgG4:IgG ratio greater than 40%, consistent with IgG4-related pseudotumor. No dysplastic changes or malignancy were seen. Serum IgG4 levels were not obtained. To our knowledge, an IgG4-related pseudotumor of the colon mimicking malignancy in a patient with history of IBD has never been described. Some studies have shown an increased incidence of IBD in patients with autoimmune pancreatitis (a prototypic IgG4-related disease). Further studies are needed to elucidate the possible relationship between IgG4-related disease and IBD (Figure 3).
A Case of Hepatocellular Carcinoma That Mimicked Cholangiocarcinoma on Preoperative Imaging Studies: (Poster No. 5)
Imaging studies are being widely used in diagnosis of various liver lesions. However, in some cases, they may be misleading for a vital diagnosis. We present an interesting case that was considered hilar cholangiocarcinoma (CC) on preoperative imaging studies but diagnosed as hepatocellular carcinoma (HCC) histopathologically. A 78-year-old man presented with a history of abdominal discomfort and constipation; his history was negative for any liver diseases. Endoscopic retrograde cholangiopancreatography revealed a filling defect in the left hepatic duct that was highly suspicious for hilar CC (Figure 4). During surgery, frozen-section examination of a lesion revealed HCC. Patient underwent left hepatectomy plus caudate resection. The final histopathologic diagnosis was a moderately differentiated HCC (Figure, B), grade 2 of 4, involving segments 2, 3, and 4, with caudate lobe and bile duct microvascular invasion. There was no cirrhotic or chronic liver disease changes in the background. It is essential to differentiate HCC from CC because the former has a higher recurrence rate, poor survival, and may require chemotherapy. Filling defect in the biliary tree in our patient may be related to blood clots, sludge, or intrabiliary tumoral growth; HCC is strongly associated with chronic viral hepatitis B and C and liver cirrhosis. Very few HCCs have been observed in patients with normal liver (like our patient), and they may have better prognosis compared with patients with chronic liver disease in background. On follow-up, the patient is doing well with normal α-fetoprotein level and no recurrence.
A Limited Immunohistochemical Panel for Subtyping Hepatocellular Adenomas in Routine Clinical Practice: (Poster No. 7)
Context: There are 4 subtypes of hepatocellular adenomas (HCAs). Hepatocyte nuclear factor 1α-mutated (H-HCA) and those without known molecular abnormalities (unclassifiable HCA [UHCA]) have no known therapeutic import. β-catenin-mutated HCA (β-HCA) is resected because of its markedly elevated risk of hepatocellular carcinoma. Inflammatory HCA (IHCA) is associated with a systemic inflammatory syndrome that may be cured with resection. Definitive subtyping requires molecular studies, but immunohistochemistry is helpful in routine practice. This study evaluated whether HCAs could be divided into clinically relevant subgroups using only limited immunohistochemistry.
Design: Representative blocks from 41 HCA resections were immunostained against a panel including serum amyloid A (Dako, Carpinteria, Calif), glutamine synthetase (Biocare, Concord, Calif), and β-catenin (Cell Marque, Rocklin, Calif). Amyloid was scored as none/ patchy or diffuse. Glutamine synthetase was scored as none/perivenular, maplike, diffuse, or uninterpretable. β-catenin was membranous or nuclear. Working diagnoses of β-HCA, IHCA, other HCA, focal nodular hyperplasia, and nondiagnostic were assigned using the diagrammed diagnostic algorithm.
Results: Sixteen IHCAs, 7 β-HCAs, and 18 other HCAs were diagnosed. No cases showed maplike glutamine synthetase staining denoting focal nodular hyperplasia or uninterpretable staining, as in some indeterminate lesions.
Conclusions: This panel successfully subtyped all cases as IHCA, β-HCA, or other HCA. None showed focal, nodular, hyperplasia-like, or uninterpretable patterns. Although H-HCAs and UHCAs cannot be determined by this panel, subtyping them has no direct therapeutic impact. This study shows that HCAs can be subtyped in a clinically meaningful way with minimal immunostaining. Further study could determine whether this panel performs similarly on biopsies (Figure 5).
EZH2 Is a Useful Marker to Confirm Diagnosis of Colorectal Adenocarcinoma in Suboptimal Biopsy Specimens: (Poster No. 8)
Context: The diagnosis of colorectal adenocarcinoma in biopsy specimens can be difficult if the specimens are suboptimal because of cauterizing artifacts, small sizes, and/or extensive necrosis. Overexpression of enhancer of zeste homolog 2 (EZH2) has been shown in colorectal cancer. We investigated whether EZH2 could be used as a tumor marker to aid in diagnosis of colonic adenocarcinoma in suboptimal biopsy specimens.
Design: EZH2 expression was studied by immunohistochemistry in 4 different conditions: normal colon, tubular adenoma, intramucosal adenocarcinoma, and invasive adenocarcinoma. The expression levels were qualitatively graded, and the overall percentage of positivity in glandular/tumor cells for each condition was calculated. Next, EZH2 expression was retrospectively investigated in cases where suboptimal conditions of the specimens rendered cancer diagnosis indeterminate on initial biopsy and confirmed on repeat biopsy.
Results: The data showed, in contrast to normal colonic mucosa and tubular adenoma where EZH2 expression was negative to weakly positive in 5% to 10% of normal epithelial/tumor cells, intramucosal and invasive colonic adenocarcinomas demonstrated strong EZH2 signal in cancer cells with significantly higher overall percentage of positivity. These findings indicated EZH2 was a highly sensitive diagnostic tumor marker for colonic adenocarcinoma. Furthermore, carcinoma cells that were initially ambiguous or unidentifiable on the hematoxylineosin sections of minute and/or extensively necrotic biopsy tissues could be clearly highlighted by EZH2 immunostain (Figure 6), suggesting EZH2 may aid in adenocarcinoma diagnosis in such specimens.
Conclusions: EZH2 is a highly sensitive tumor marker for colonic adenocarcinoma. It is helpful in the diagnosis of colonic adenocarcinoma in suboptimal biopsy specimens frequently encountered in daily pathology practice.
Identification of a Useful Immunostaining Panel in the Distinction Between Esophageal and Pancreatic Adenocarcinomas: (Poster No. 12)
Context: When working on tumors of uncertain origin, CK7+ adenocarcinomas (ADCs) are frequently encountered. Among those CK7+ ADCs, the distinction between esophageal and pancreatic ADCs is challenging because of the lack of tissue-specific biomarkers. In this study, we investigated the expression of more than 70 commonly used biomarkers in both esophageal and pancreatic ADCs. These immuno-markers included (1) various cytokeratins, (2) transcription factors/nuclear staining markers (ER, p53, p63, p40, CDX2, SATB2, PAX8, TTF1, DPC4, SOX2, SOX10, HNF1B, GATA3, ERG, SALL4, OCT4, CDK4), (3) mucin genes (MUC1, MUC2, MUC4, MUC5AC, MUC6), and (4) tumor-associated proteins (β-catenin, cadherin-17, HBME1, mammaglobin, galectin-3, glypican 3, napsin A, TTF1, maspin, S100, S100P, P504S, melanoma markers, and more).
Design: Immunohistochemical evaluation of the aforementioned immunomarkers in 48 esophageal and 49 pancreatic ADCs on tissue microarray sections was performed and was recorded as positive if more than 5% of tumor cells stained.
Results: The immunostaining results from the selected immuno-markers and the comparison of their expression in esophageal and pancreatic ADCs are summarized in the Table. Expression of HepPar1, SALL4, and FLI1 was seen in 12.5%, 2%, and 6.4% of esophageal ADCs, respectively. Expression of ER, TTF1, arginase-1, PAX8, RCC, S100, uroplakin II, inhibin-α, OCT4, GATA3, glypican 3, and ERG was not observed in either esophageal or pancreatic ADCs.
Conclusions: Tissue-specific immunomarkers were not identified for either esophageal ADCs or pancreatic ADCs. However, the panel of immunomarkers in the Table is potentially useful in the distinction of these 2 entities.
Darling Disease Masquerading As Malignancy/Disseminated Tuberculosis: (Poster No. 13)
Disseminated histoplasmosis (Darling disease) is often unrecognized in immunocompetent patients, leading to delays and inaccurate diagnosis. We present a case of a 74-year-old woman with previous exposure to Mycobacterium tuberculosis (TB) presenting with failure to thrive, cognitive decline, and ataxia. She developed a productive cough, dyspnea, nausea, and abdominal pain. Upon hospitalization, she became febrile, and an abdominal computed tomography (CT) scan showed pneumoperitoneum. An urgent exploratory laparotomy was performed, and she was found to have a jejunal perforation (45 cm from the duodenojejunal flexure) with multiple nodules throughout the small bowel, concerning for malignancy. The patient developed T-cell lymphopenia with normal immunoglobulins without evidence of TB. Histologically, the resected bowel showed acute necrotizing enteritis, perforation, and a dense histiocytic infiltrate with scattered, poorly formed granulomas and innumerable yeast forms within the histiocytes, consistent with histoplasma (Figure 7). Subsequently, her urine histoplasma antigen was found to be elevated (12.07 ng/mL), and bronchial washings revealed Histoplasma capsulatum, correlating with a chest CT finding of innumerable, miliary centrilobular nodules. Gastrointestinal histoplasmosis can manifest with protean symptoms. Diarrhea, dysphagia, abdominal pain, fever, weight loss, and less frequently, obstruction or perforation can mimic TB, inflammatory bowel disease, or carcinoma. As illustrated by this case, gastrointestinal involvement may be the presenting and dominant manifestation of disseminated histoplasmosis. Moreover, histopathologic identification of fungal organisms may be the initial clue to the diagnosis of this often-fatal disease.
Crownlike Structures in Peripancreatic Adipose Tissue in Patients With Pancreatic Ductal Adenocarcinoma: (Poster No. 16)
Context: Studies in mice and human mammary glands have shown that crownlike structures (CLSs) formed by macrophage infiltration surrounding a necrotic adipocyte correlate with the activation of NFκB, elevated aromatase levels, and elevated body mass index, and they have an important role in the development of breast cancer. Our study is the first to analyze CLS in peripancreatic adipose tissue in patients with pancreatic cancer.
Design: Our study population consisted of 84 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent pancreaticoduodenectomy at MD Anderson Cancer Center (Houston, Texas). The representative areas of peripancreatic adipose tissue were selected by reviewing the hematoxylin-eosin–stained slides. The CLS foci were counted on 5 different representative sections from each case and were stained with CD68 immunohistochemistry (Figure 8). The average number of CLS foci per slide in each case was correlated using χ2 analysis with clinicopathologic parameters, such as tumor stage, lymph node metastasis, recurrence, survival, fibrosis, inflammation, and pancreatic intraepithelial neoplasia, and with radiologic parameters, including body mass index, total body fat, and visceral and subcutaneous adipose tissue.
Results: The CLSs were present in 44 of 84 cases (52.4%), which correlated with total body fat and visceral adipose tissue content (P =.03 and P = .02, respectively). However, there were no correlations of CLS with any other parameter studied.
Conclusions: Although the presence of CLS correlated with total body fat and visceral fat in cases of pancreatic ductal adenocarcinoma and unclear associations exist in the literature between obesity and pancreatic cancer, no correlation of the presence of CLS can be shown with the disease parameters.
An Unusual Pattern of CK7/20 Concordance Staining in a Case of Gastric Adenocarcinoma: (Poster No. 17)
A 77-year-old woman underwent an exploratory laparotomy (for reasons unknown to the pathologist) for peritoneal carcinomatosis. Biopsy of the pelvic sidewall is shown (Figure 9, A). Immunohistochemistry showed the malignant cells to be strongly and diffusely positive for cytokeratin 20 (CK20; Figure, B), negative for cytokeratin 7 (CK7, Figure, C). Although that immunoprofile suggests a colon cancer primary, we were later informed that the patient underwent an endoscopically guided biopsy of a gastric mass at another institution that revealed a poorly differentiated, signet-ring–type adenocarcinoma of the stomach. Given the additional clinical history and histomorphology of the tumor, a gastric primary was favored. Gastric adenocarcinomas can present as either an intestinal type or a diffuse type (signet-ring cells), both with similar immunohistochemical staining patterns. However, unlike other malignancies, such as breast and colon cancer, CK7 and CK20 coordinate staining patterns are often heterogeneous for gastric adenocarcinomas of either subtype. CK7+/ CK20− and CK7+/CK20+ are the predominant patterns, followed by CK7−/CK20− (suggesting undifferentiation) and CK7−/CK20+ (the least common pattern). Although the lack of uniform coordinate CK7/CK20 staining may reflect differences in intermediate filament expression in gastric adenocarcinomas, it may also be due to the lack of definite cutoff percentages at which staining is classified as positive or negative. This case demonstrates a pitfall of relying on the utility of CK7 and CK20 staining to characterize gastric adenocarcinoma and its metastases. Clinical and histopathologic correlation is required to make an accurate diagnosis, including adequate discussion with the clinician if warranted.
A Case of Cronkhite-Canada Syndrome Without Polyposis and a Review of the Literature: (Poster No. 22)
Cronkhite-Canada syndrome (CCS) is a rare, noninherited disease associated with high morbidity and characterized by diffuse hamartomatous polyposis, diarrhea, weight loss, and ectodermal manifestations. We report an unusual case of CCS presented without polyposis. A 74-year-old, white man presented with altered sense of taste, abdominal pain, bloating, diarrhea, and marked weight loss (45 lbs [20.9 kg]) for 6 months. His past medical history was significant for hypothyroidism. Physical examination demonstrated onychodystrophy of finger and toe nails, cutaneous hyperpigmentation of palms, and alopecia. The esophagogastroduodenoscopy revealed severely thickened gastric folds and markedly edematous duodenal mucosa. Colonoscopy showed markedly edematous colonic mucosa with diverticulosis. Multiple biopsies were obtained from the stomach, duodenum, jejunum, terminal ileum, and colon. All of the biopsies showed marked, diffuse lamina propria edema. Prominent mucosal and villous atrophy was particularly evident in the small bowel and duodenum. Focal acute enteritis and colitis were also seen. Immunohistochemical stains revealed an increase of immunoglobulin G4 (IgG4)-positive plasma cells in all biopsies (up to 20 per high-power field; Figure 10). Given the positivity of IgG4 and the good response to immunosuppressant therapy reported in the literature, the etiology of CCS is probably autoimmune related. Even without polyposis, the classic clinical presentations with the finding of diffuse gastrointestinal mucosal edema should raise the index of suspicion for the diagnosis of CCS.
A 7-Month-Old Infant With Inflammatory Fibroid Polyp of the Small Intestine: (Poster No. 23)
Since the first description of the entity in 1949 by Vanek, inflammatory fibroid polyps were only exceptionally reported in children. To our knowledge, no prior case diagnosed before the first year of age has been reported to date. We present a case of inflammatory fibroid polyp occurring in a 7-month-old, female infant who presented with acute abdomen and concern for intestinal obstruction. Emergency exploratory laparotomy revealed a mass at the distal jejunum/proximal ileum junction that was thought to represent a perforated Meckel diverticulum. The resected 3.7-cm segment of small bowel showed a 3.0-cm-long thickening of the wall with focal perforation. Histologic examination showed a proliferation of bland spindle cells infiltrating the full thickness of the bowel wall, focally extending to the mucosa and causing ulceration (Figure 11, A). Cellularity was variable, with focal perivascular onion skinning (Figure, B). No necrosis and only occasional mitoses were seen. Focal lymphoid aggregates and interspersed eosinophils, mast cells, lymphocytes, and plasma cells were present (Figure, C). Immunohistochemistry showed strong reactivity of tumor cells with CD34 (Figure, D) and vimentin and low Ki-67 proliferation index (<5%). There was no expression of smooth muscle antigen, ALK-1, desmin, myogenin, CD117, S100, CD99, BCL2, pankeratin, WT1, calretinin, D2-40, CD1a, myeloperoxidase, TdT, mast cell tryptase, CD45, CD30, CD15, CD31, CD21, CD23, or inhibin. No PDGFRA mutation was identified. This case stresses the importance of considering inflammatory fibroid polyp in the differential diagnosis of gastrointestinal tract spindle cell tumors, even in cases occurring in childhood or infancy.
Rectal Adenocarcinoma With Prominent Rhabdoid Features: A Case Report and Review of the Literature: (Poster No. 26)
Colonic adenocarcinoma with rhabdoid features is extremely rare, and only 10 cases have been previously reported in the literature. An 85-year-old man presented with an ulcerated rectal mass. A biopsy revealed a neoplasm with epithelioid features. The patient underwent pelvic exenteration, and a 6.3 × 2.1 × 1.0-cm, ulcerated, necrotic mass, located in the anterior rectum was identified. Microscopically, a bi-phenotypic tumor composed of a glandular component (Figure 12, A1) of moderately differentiated adenocarcinoma (CK20+, CDX2+, CK7−, and preserved nuclear stain for INI [Figure, B1]), and a rhabdoid component (Figure, A2) of loosely cohesive, large epithelioid cells (CKMNF+, vimentin+, EMA+, CK+ and AE1/AE3+, and CK7−. CDX2− and loss of nuclear staining for INI [Figure, B2]) with vesicular nuclei, prominent nucleoli, and significant amount of eosinophilic cytoplasm was identified. A histologic diagnosis of adenocarcinoma with rhabdoid features was made. No loss of expression of mismatch repair protein by immunohistochemistry or BRAF V600E gene mutation was identified. To date (11 months after surgery), our patient is alive and doing well without evidence of recurrent disease. Colon cancers with rhabdoid features are extremely rare and are not yet included in the most recent World Health Organization classification of large-bowel tumors. Such tumors have a very poor prognosis, proving fatal in 75% to 100% of patients within 6 months after having been diagnosed. Rhabdoid tumors should be considered in the differential diagnosis of malignant tumors involving the gastrointestinal tract.
Spindle-Type Predominant GIST With a Minor Epithelioid Component Exhibiting PDGFRα Mutation: A Case Report and Review of the Literature: (Poster No. 27)
Gastrointestinal stromal tumors (GISTs) occur throughout the GI tract, mesentery, and omentum, but mostly arise from the stomach (60%) and small intestine (25%). Histologically, they are subtyped as spindle cell, epithelioid, or mixed types. Most GISTs tend to be positive for c-Kit (>95%), DOG1 (>95%), and CD34 (70%) by immunohistochemistry. Spindle-cell–type GISTs tend to be KIT mutated, whereas epithelioid-type GISTs are often PDGFRα mutated. Both components of a mixed-type GIST show the same receptor kinase-type mutation, relevant for therapy prediction to imatinib. We report a case of a 73-year-old woman who presented with abdominal discomfort and early satiety. Endoscopic ultrasound revealed a 1.4-cm submucosal gastric mass. Fine-needle aspiration was suggestive of GIST. A partial gastrectomy was performed. Pathologic examination revealed a 1.4-cm, well-circumscribed, submucosal mass. Histologically, it was a low-grade GIST, predominantly spindle with a minor epithelioid component. Immunohistochemistry revealed the epithelioid component was positive for PDGFRα and negative for c-Kit and CD 34, whereas the spindle component was positive for c-Kit, CD34, and weakly positive for PDGFRα. Both components were negative for DOG1. Mutational analysis revealed a D842V PDGFRα mutation. Identification of a GIST's oncogenic mutation is crucial to identify patients who may be less responsive or resistant to imatinib therapy, that is, exon 9-KIT mutation, wild-type KIT, and D842V-PDGFRα mutation. Even though this GIST was predominantly spindle-type with a minor epithelioid component, it harbored a PDGFRα mutation. A combination of histomorphology and PDGFRα immunostaining is a reliable predictor of PDGFRα genotype in GIST, even in tumors with small epithelioid components (Figure 13).
Follicular Pancreatitis: Yet Another Mimic of Pancreatic Cancer?: (Poster No. 29)
Follicular pancreatitis is a recently described, histologically distinctive, lymphoplasmacytic pancreatitis, characterized by florid ductulo-centric lymphoid follicles, collagenous fibrosis, absent granulocytic epithelial lesions, and normal count of immunoglobulin G4 (IgG4)-positive plasma cells in pancreatic tissue, along with normal levels of IgG4 in serum. Both clinically and on gross examination, follicular pancreatitis has mimicked carcinoma of the head in reported cases. We report a 60-year-old, African-American man who underwent distal pancreatectomy. On gross examination, there was a 3 × 2 × 2.6-cm, firm, discrete mass in the pancreatic tail, which, on frozen section and routine hematoxylineosin, revealed chronic pancreatitis with multiple ductulocentric and lobulocentric lymphoid follicles, very focal storiform fibrosis, obliterative phlebitis, and occasional granulocytic epithelial lesions. Germinal center lymphocytes were negative for BCL2, and IgG4 plasma cells were not increased in the inflammatory infiltrate. Serum IgG4 was also within reference range. Although we cannot completely exclude an unusual variant of type 1 or type 2 autoimmune pancreatitis, the histopathologic features in our case favor follicular pancreatitis, the first such reported case arising in the tail of the pancreas. Awareness of this rare and benign mimic of pancreatic cancer is important for surgeons, radiologists, and surgical pathologists alike because it could be treated conservatively and not with surgery (Figure 14).
Unique Case of An Extrahepatic Biliary Tree, Grade 2, Well-Differentiated Neuroendocrine Tumor: (Poster No. 30)
A 29-year-old man presented with signs and symptoms of obstructive jaundice. Endoscopic cholangiopancreatography demonstrated a common bile duct stricture as well as a mass that appeared to compress the duct. The mass was resected and histologic examination revealed a well-differentiated neuroendocrine tumor with round nuclei with granular chromatin, abundant eosionophilic granular cytoplasm, and a portion of the cells had intracytoplasmic inclusions. Immunohistochemical examination revealed positive staining with synaptophysin and chromogranin. The inclusion stained strongly positive for Cam 5.2. Additionally the tumor had some higher-grade features, including focal punctuate necrosis, a Ki-67 index of 3%, and perineural invasion. Well-differentiated neuroendocrine tumors of the extrahepatic biliary tree are very rare, with only 150 cases reported. It is unclear how many of these prior cases may have had higher-grade features, and there are no well-accepted guidelines on how to stage these tumors. To our knowledge, this is the first reported case of a grade 2 extrabiliary neuroendocrine tumor in a patient with multiple endocrine neoplasia type 1 (Figure 15).
The above authors are employees of the US Federal Government and the US Army and Air Force. The opinion(s) or assertion(s) contained herein are the private views of the authors and do not reflect the official policy or position of Brooke Army Medical Center, the US Army Medical Department, the US Army Office of the Surgeon General, the Department of the Army, Department of Defense, or the US government.
Diagnosis of Hepatocellular Adenomas on Biopsy: A Clinicoradiopathologic Experience in a Single US-Based Institution: (Poster No. 31)
Context: Hepatocellular adenomas (HCAs) have recently been subclassified according to molecular analyses yielding diagnostic categories that can be assessed by immunostaining of tissue samples: inflammatory HCA (iHCA), confirmed by C-reactive protein (CRP) expression; HNF-1α-inactivated HCA (hHCA), confirmed by loss of liver fatty acid–binding protein (LFABP); and β-catenin mutated HCA (β-HCA) confirmed by nuclear β-catenin and increased glutamine synthetase (GS) expression. Definitive diagnosis on biopsies is becoming imperative because these subtypes have prognostic and management implications. We reviewed the epidemiologic and radiologic characteristics of biopsy-proven HCAs and analyzed the histopathologic features encountered.
Design: We retrieved 16 in-house cases and 15 consult cases (all from New York state) diagnosed as HCA on biopsy from 2009 to 2013 from our institution's database. Prebiopsy computed tomography/ magnetic resonance imaging with contrast studies using Eovist and extracellular contrast media (ECCM) were obtained for the in-house cases. The radiologic, epidemiologic, and pathologic characteristics including immunohistochemistry were studied.
Results: Results are shown in the Table.
Conclusions: Our institution shows a marked predominance of iHCA (≈75% of classifiable HCAs), which may reflect this subtype's association with metabolic syndrome and, therefore, be related to epidemic obesity in the United States. Radiologic features were not consistent for any particular subtype, suggesting that biopsy of radiologically identified lesions is necessary for the performance of diagnostic immunohistochemical tests. Small biopsy samples showing diffuse CRP coupled with diffuse GS staining, but without altered β-catenin expression, could not definitively resolve the possibility of β-catenin activating mutations; that would require resection for confident assessment.
Progression of Signet-Ring Cell Carcinoma In Situ of the Esophagus to Adenocarcinoma With Signet-Ring Cell Features in a Background of Barrett Metaplasia: (Poster No. 36)
Signet-ring cell (SRC) carcinoma in situ in the gastrointestinal tract is a rare and poorly defined entity with little pathologic documentation reporting progression to SRC carcinoma. Invasive esophageal adenocarcinoma with SRC features is associated with a diffuse growth pattern, advanced stage at presentation, and worsened prognosis. We present a case documenting the progression from adenocarcinoma in situ with SRC features in a background of Barrett metaplasia to invasive esophageal adenocarcinoma with SRC features in an obese 63-year-old, white man. The patient presented with an esophageal nodule diagnosed endoscopically as T1N0. Endoscopic mucosal resection was performed, revealing adenocarcinoma in situ with SRC features arising in metaplastic intestinal epithelium. Immunostain for type IV collagen was positive around the cancerous glands (Figure 16), supporting a diagnosis of carcinoma in situ with SRC features. A biopsy of a recurrent nodule during surveillance revealed adenocarcinoma in situ with SRC features, extending under the surface of the squamous epithelium. Because of this finding, the patient underwent another endoscopic resection with pathology revealing invasive, well-differentiated adenocarcinoma with SRC features. Rather than a diffuse growth pattern, the invasive adenocarcinoma with SRC features appeared well differentiated and maintained glandular architecture, although the cancerous glands lacked surrounding type IV collagen by immuno-staining. It is unclear whether this may represent signet ring carcinoma in situ in transition to invasive signet-ring cell carcinoma. This case represents a rare finding of signet-ring cell carcinoma in situ of the esophagus that progressed to invasive adenocarcinoma.
An Unusual Case of Exclusive, Early Liver Metastasis From Adenoid Cystic Carcinoma of the Parotid Gland: (Poster No. 38)
Liver is an unusual metastatic site for adenoid cystic carcinoma (ACC) of the salivary gland. Most liver metastases originate from nonparotid ACCs. We report a rare case of isolated, early liver metastasis of ACC from the parotid gland. A 61-year-old woman presented with a right parotid mass for 6 months. A fine-needle aspiration biopsy was reported as a malignant salivary gland neoplasm. Right total parotidectomy with right neck dissection was performed. Macroscopy revealed a 3.2 × 1.9 × 1.4-cm, ill-defined, gray-white mass abutting the surface of the parotid gland. On microscopy, the tumor was composed of basaloid cells arranged in solid, trabecular, and focal cribriform patterns (Figure 17, A). There were brisk mitotic activities but no necrosis. A diagnosis of high-grade adenoid cystic carcinoma (pT3N0Mx) was rendered. The patient was subsequently treated with external beam radiotherapy. Eleven months later, follow-up positron emission tomography/computed tomography scan revealed a 3.5 × 3.5-cm, hypodense nodule in the left hepatic lobe. There were no lesions elsewhere in the body. A resection of the left lower lobe was performed. Microscopy confirmed a metastatic ACC. However, the tumor cells were more well differentiated (Figure, B). Comparison of the morphology of primary tumor and immunoreactivity for CD117 (Figure, C) and DOG1 (Figure, D) helped in establishing the diagnosis. Exclusive early hepatic metastasis of ACC from the parotid gland is very unusual. Liver metastases are usually associated with local recurrence or metastases to other organs. The present case highlights the unpredictable biologic behavior of ACC.
Primary Cystic Leiomyosarcoma of Duodenojejunal Junction: (Poster No. 41)
Primary leiomyosarcoma of the gastrointestinal tract is considered rare in the post–gastrointestinal stromal tumor (GIST) era. We report a case of a 54-year-old man presenting with a 1.7-cm, submucosal, partially cystic mass (Figure 18, A) causing intestinal obstruction of the duodenojejunal junction at the ligament of Treitz. Microscopically, the wall of the cyst was lined by interlacing fascicles of epithelioid to spindle cells having eosinophilic cytoplasm, cigar-shaped nuclei with moderate atypia (Figure, B), and a mitotic rate up to 5 high-power fields (Figure, C). Its submucosal location, histologic features, and muscular differentiation and given its immunoreactivity with both smooth muscle actin and desmin (Figure, D) and negative staining for GIST markers (CD117, DOG1, and CD34), neural marker S100, and vascular marker CD34, confirmed the diagnosis of a leiomyosarcoma. This tumor was somewhat peculiar given its anatomic location, size, and partially cystic nature. It is important to differentiate leiomyosarcoma in this setting from the more-common GIST because specific chemotherapy options are available for the latter. Despite the usual aggressive behavior and overall poor prognosis expected for an intestinal leiomyosarcoma, an excellent prognosis is expected for this patient given a relatively early detection (possibly attributable to its special anatomic location) and complete surgical resection without clinically detectable metastatic disease.
Hyalinizing Cholecystitis With Features of IgG4-Related Disease: Coincidence or an Unrecognized Association?: (Poster No. 42)
Hyalinizing cholecystitis (HC), a recently described subtype of chronic cholecystitis, is characterized by dense, paucicellular to acellular, hyalinizing mural sclerosis. The lesion is rare, occurring in approximately 1.6% of cholecystectomy specimens. Immunoglobulin G4 (IgG4)-associated cholecystitis, a lesion in the spectrum of IgG4-related disease (IgG4-RD), is also a newly described variant of cholecystitis characterized by mainly extramural, lymphoplasmacytic inflammation; lymphoid follicles; storiform fibrosis; phlebitis; and increased tissue IgG4+ plasma cells. Herein, we describe a case of a 76-year-old, asymptomatic, white man with a porcelain gallbladder discovered on ultrasound. The cholecystectomy specimen revealed characteristic features of hyalinizing cholecystitis with the additional aforementioned histopathologic features of IgG4-associated cholecystitis, including elevated IgG4 plasma cells (up to 30–50 per high-power field). Our patient also had a significantly elevated serum IgG4 level. To our knowledge, this association of HC with IgG4-RD has not yet been described in literature. Although it is difficult to draw any strong conclusions, our case suggests that some cases of HC may be the result of IgG4-RD. Moreover, because gallbladders are common specimens in surgical pathology laboratory, recognizing mural fibrosis of any extent accompanied by robust lymphoplasmacytic inflammation may serve as an important sentinel finding for patients at risk of developing systemic IgG4-RD (Figure 19).
Erdheim-Chester Disease Discovered as an Incidental Finding in Explanted Liver of a Patient With Hepatitis C Cirrhosis: (Poster No. 43)
We report a case of Erdheim-Chester disease discovered incidentally in a 65-year-old man with end-stage liver disease secondary to hepatitis C cirrhosis requiring liver transplant. Our patient was first diagnosed with hepatitis C in 1993 and with cirrhosis in 2002. He was doing well until 2010 when he presented with ascites requiring frequent paracentesis. Histologic examination of the explanted liver confirmed chronic hepatitis with bridging necrosis and advanced fibrosis bordering on cirrhosis. In addition, there were prominent foamy histiocytes on the capsular surface and in some portal areas associated with fibrosis. By immunohistochemical staining, those foamy histiocytes were strongly positive for CD68 and factor XIIIa but negative for CD1a and S100 (Figure 20). Mutations were discovered in the PDGFRA, PTEN, and HNF1A genes. We noted that this patient also had symptoms of paraproteinemia with pancytopenia, and a bone marrow biopsy in 2012 demonstrated sheets of similar histiocytes that are rarely positive for factor XIIIa. Of interest, this patient's magnetic resonance imaging and positron emission tomography scans showed increased heterogenous uptake in bilateral humeral and femoral diaphyses, which could be the skeletal manifestation of the same disease process. A diagnosis of Erdheim-Chester disease was thus rendered, with at least liver and bone marrow involvement. Erdheim-Chester disease is a very rare form of xanthogranulomatous, non-Langerhans cell systemic histiocytosis of unknown etiology that typically affects 50- to 70-year-old adults. Manifestations in skeletal and extraskeletal organs have been reported. This case highlights the importance of histologic examination with correlation of imaging and clinical presentations to identify this rare unique disease.
Cytokeratin (CK) Changes Induced by p120-catenin (p120ctn) Loss and Epidermal Growth Factor Receptor Overexpression in Esophageal Squamous Cell Carcinoma: (Poster No. 44)
Context: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy and its molecular pathogenesis is not well known because of the lack of models to study it. No comprehensive study has been done on keratin changes in ESCC. Epidermal growth factor receptor (EGFR) is commonly overexpressed and p120ctn down-regulated in ESCC. This study aims to investigate keratin changes induced by p120ctn down-regulation and EGFR overexpression in a 3-dimensional organotypic tissue culture system (OTC) and human ESCC.
Design: The OTC control samples and those with both p120ctn down-regulation and EGFR overexpression (PE) were obtained. Keratins were studied by immunohistochemistry (IHC) in 5 control and PE OTC samples, 10 human normal esophageal, and 24 ESCC specimens. Morphology (hematoxylin-eosin) was analyzed using ImageJ, and proliferation was quantified by Ki-67 immunohistochemistry (IHC).
Results: EGFR was overexpressed in 83% of ESCC samples, and p120ctn was down-regulated in 67%. The intersection of those genes (p120ctn down-regulation and EGFR overexpression) occurs in 63% of ESCCs. The IHC studies of keratin expression in human specimens showed that ESCCs retain K1 and K5, gain K8, and lose K4, K10, and K15. In our OTC system, PE samples showed significantly increased cellularity, nuclear size, and proliferation (all P < .05). Interestingly, they contained apparently transformed epithelium resulting in cellular invasion into the matrix (Figure 21). The IHC studies demonstrated similar keratin patterns between normal human esophagus and OTC controls and also between human ESCC and OTC PE samples.
Conclusions: The ESCCs retain K1 and K5, gain K8, and lose K4, K10, and K15. Our genetically modified OTC PE epithelium resembles human ESCC with similar morphologic changes and keratin patterns.
Colonic Malakoplakia Presenting as Lymphoma: (Poster No. 45)
Malakoplakia is a rare, chronic, inflammatory condition characterized by the presence of aggregates of histiocytes known as von Hansemann histiocytes that contain intracytoplasmic targetoid bodies known as Michaelis-Gutmann bodies (MGB). Although originally and most commonly described in the genitourinary tract, in the past several years, malakoplakia has been described in several organs with increasing frequency, including colon, stomach, appendix, and prostate. The etiology of malakoplakia is poorly understood, but a deficient cellular immunity and phagocytic activity associated with infection or immunosuppression has been thought to be the underlying mechanism. Ultrastructurally, MGB have been shown to consist of partially digested and degenerated bacteria. We received 3 unusual specimens submitted as polyps on different occasions. All 3 specimens were predominantly lymphocytic tissue and thought to be suspicious for lymphoma. On careful examination, we identified von Hansemann histiocytes and MGB within the lymphoid aggregates (Figure 22). Special stains like von Kossa, iron, and Fite highlighted abundant MGB to confirm our impression of malakoplakia. We would like to present these cases to emphasize that malakoplakia can be easily missed by pathologists if they are unaware of its presentation as polyps or raised lesions within the gastrointestinal tract because of its subtle presentation. These patients need to be diagnosed and thoroughly worked up to rule out any underlying infections or causes of immunodeficiency and to be treated by appropriate antibiotics to prevent the progression of the disease.
Review of Radiologic and Histopathologic Features of Hepatic Echinococcal Cysts: Retrospective Study of 10 Years in an Urban Tertiary-Care Center: (Poster No. 47)
Context: Echinococcal cyst (EC) or hydatid cyst is a parasitic infection caused by larval stage of the tapeworm Echinococcus granulosus. The infection is acquired by ingestion of parasitic eggs. This is a rare disease in developed countries. Although the diagnosis is made from a combination of clinical and radiologic presentations, the histopathology is not always representative because of chronic changes, such as fibrosis and calcification.
Design: From January 2004 to February 2014, all cases of EC were retrieved from our database. We reviewed the epidemiology, clinical presentation, and radiologic and histologic features. The slides were reviewed, and features were noted in an attempt to correlate helpful features that aid in the diagnosis.
Results: Eight cases of hepatic EC were identified. The age range was 41 to 77 years. Male to female ratio was 1:1. Six of 8 patients were Middle Eastern. Clinical features included abdominal pain (7/8), nausea and low appetite (3/8), and sepsis because of ruptured EC (2/8). The cyst size ranged from 3.4 to 13 cm. Histologic features noted were scolices and hooklet (4/8), laminated membranous structure with focal calcification (6/8), fibrotic and calcified cyst wall (2/8), and necrosis (3/8). All cases showed nonspecific inflammatory changes in adjacent hepatic tissue. Figure 23 shows the cyst wall with scolices.
Conclusions: Although a rare diagnosis, EC should be considered in the differential diagnosis of hepatic cysts if suspected clinically and radiologically, especially in the Middle Eastern population.
Intraductal Tubulopapillary Neoplasm of Pancreas: A Rare Case Report With Initial Misdiagnosis on Fine-Needle Aspiration: (Poster No. 51)
Intraductal tubulopapillary neoplasm of the pancreas (ITPN) represents less than 1% of exocrine pancreatic neoplasms, and the criteria for its diagnosis has only recently been established. Only a few studies have reported the cytologic findings for this neoplasm on fine-needle aspiration (FNA). We present a case that was initially misdiagnosed on ultrasound-guided, FNA as an intraductal papillary mucinous neoplasm and diagnosed on resection as ITPN. Here, we review the cytologic features of this neoplasm and highlight the diagnostic pitfalls during cytologic examination on endoscopic ultrasound FNA. The cytoarchitectural features identified in our case included a hypercellular aspirate with many branching, staghorn, tubular, and focally papillary clusters in a background of discohesive cells (Figure 24, a). High-power magnification showed uniform cells demonstrating mild to moderate cytologic atypia, absence of intracellular mucin, and rare intranuclear pseudoinclusions. Based on the presence of scant extracellular mucin (Figure, b) and papillary clusters, a diagnosis of intraductal papillary mucinous neoplasm was rendered; however, on histologic exam, an ITPN was diagnosed (Figure, c and d). In retrospective review, the main cytologic features helpful for a correct diagnosis of ITPN are (in addition to already established criteria and the radiologic findings): (1) absence of intracytoplasmic mucin in the constituent cells, and (2) correct interpretation of the scant extracellular mucin as an expression of gastrointestinal contaminant and not as a constituent part of this neoplasm.
Extramedullary Hematopoiesis as a Cause of Abnormal Liver Function Test in Posttransplant Liver: (Poster No. 52)
Advances in surgical techniques and postoperative care have significantly improved patient outcomes after liver transplantation. Although posttransplant complications are markedly reduced, it remains an important factor in morbidity and mortality. Any dramatic or persistent increase in liver function tests (LFTs) after transplant mandates a series of diagnostic tests to evaluate the possibility of complications, such as rejection, ischemic injury, and infections. We report a case of a 68-year-old man who underwent liver transplant for alcoholic cirrhosis and had persistent elevation of liver enzymes starting 4 months posttransplant. Acute cellular rejection with progressive fibrosis was attributed as the cause of enzyme elevation at that time, and the patient was managed appropriately. At 8 months, however, his liver enzymes again started rising, and biopsy of the liver showed no evidence of acute cellular rejection but the presence of extramedullary hematopoiesis (EMH) (see Table). The histologic features of liver EMH include focal sinusoidal congestion, increased cellularity in sinusoidal spaces, and the finding of immature precursor cells and large atypical megakaryocytes (Figure 25, A and B). The liver enzymes trended down with supportive therapy. Such EMH in an allograft is a rare occurrence. Its pathophysiology remains unclear and could be attributed to expansion of quiescent liver-based hematopoietic progenitor cells in response to liver injury or because of hematopoietic microchimerism of donor origin. It is important to consider this entity as a cause of elevated liver enzymes after transplant in the absence of cellular rejection or other etiologies. The treatment is only supportive, and the liver functions stabilized spontaneously without intervention in this case.
Peculiar Filamentous Intranuclear Inclusion in Rectal Leiomyoma: (Poster No. 53)
Intranuclear inclusion is an enigmatic cytologic phenomenon, which appears as an optically clear nucleus on hematoxylin-eosin–stained sections. It can either be a true inclusion, or a pseudoinclusion. True inclusions result from intranuclear accumulation of viral particles, cytoplasmic materials, biotin, or nuclear lamins. Pseudoinclusions, on the other hand, represent invagination of cytoplasm into the nucleus. Here, we present a case of rectal leiomyoma with unusual intranuclear inclusions. A 56-year-old man with no significant past medical history presented to the gastroenterology clinic for cancer screening. A colonoscopy was performed, which revealed a 3-mm sessile rectal polyp that was biopsied. Microscopic examination revealed a submucosal leiomyoma, confirmed by immunoreactivity for caldesmon. A striking finding was the presence of optically clear nuclei in many of the tumor cells. Deparaffinized tissue was submitted for electron microscopic evaluation following standard procedure. Ultrastructural examination revealed electron-dense, intranuclear inclusions within the tumor cells, with peripheral displacement of the nuclear chromatin (Figure 26). These inclusions were composed of 8 to 10-nm-diameter fibrillar filamentous structures, which morphologically resembled intermediate filaments. The inclusions were devoid of any cytoplasmic organelle, indicative of pseudoinclusion. To our knowledge, this case represents the first report of the demonstration of true intranuclear inclusion in a leiomyoma, with ultrastructural resemblance to intermediate filaments. It highlights the utility of electron microscopy in differentiating true intranuclear inclusions from nuclear pseudoinclusions.
Expression of p62 and Ubiquitin in Liver Neoplastic and Nonneoplastic Disease: Correlation Between Visual and Automated Image Analytic Quantitation, Prognosis, and Outcome: (Poster No. 54)
Context: p62 and ubiquitin are associated with hepatocellular injury. We examined their expression in liver disease using immunohistochemistry, compared visual versus image analytic quantitation methods of immunostains, and examined correlation with outcome in hepato-cellular carcinoma.
Design: Tissue microarrays from neoplastic and nonneoplastic liver were immunostained for p62 and ubiquitin (Dako, Carpinteria, Calif). Two pathologists scored intensity as 0 (negative), 1, 2, or 3 (strong). The Q score (intensity × percentage of tumor cells staining) was calculated. Computer-assisted image analysis using the Aperio system (Aperio, Vista, Calif) quantified the amount of immunostain. Q scores and Aperio scores were ranked as low or high using their means as the cutoff. Multivariate regression analysis compared both methodologies. Clinical variables were compared across both score ranks using a t test for nominal variables and a Fisher exact test for categoric variables. Kaplan-Meier survival curves generated for both methods were compared using a log-rank test for significance.
Results: For p62 and ubiquitin (n = 119 cases), high Q scores were associated with high Aperio scores for all comparisons by linear regression and Fisher exact test, except for nuclear p62. No statistically significant association was found between overall survival and Q scores (see Table). There was a trend toward worsened survival with higher p62 Aperio scores (P = .20).
Conclusions: Prognostic parameters and overall survival did not show significant correlation with p62 and ubiquitin expression in liver neoplastic tissue; however, automated image analytic quantitation of both immunostains correlated well with cytoplasmic visual quantitation, suggesting that the former can be a useful ancillary tool.
Intraductal Oncocytic Papillary Neoplasm of Pancreas: Report of a Case Associated With Multifocal, Clear Cell Renal Cell Carcinoma and Oncocytoma: (Poster No. 55)
Intraductal oncocytic papillary neoplasm (IOPN), a rare subtype of intraductal papillary mucinous neoplasm, was first described in a small case series in 1996. This tumor is typically composed of papillary projections with cuboidal cells and oncocytic cytoplasm. The IOPNs generally have an indolent clinical course but can be associated with invasive foci and a more-aggressive prognosis. We present a case of a 77-year-old woman with a history of colon cancer, multifocal clear cell renal cell carcinoma of the right kidney, and oncocytoma of the left kidney. Upon surveillance for renal tumors, computed topography of the abdomen demonstrated abnormal soft tissue causing dilation of the pancreatic duct and ampulla. The patient underwent a Whipple procedure. Grossly, the tumor was tan-white and friable, encompassing 2.5 cm of the pancreatic duct (Figure 27, left, arrow at ampulla). It extended into the duodenal papilla with no definitive invasion. The entire pancreas and ampulla were submitted. Histologically, the tumor was a high-grade oncocytic carcinoma, with a predominantly solid growth pattern, minor papillary components, and markedly pleomorphic cells with medullary-like features (Figure, right, inset hematoxylin-eosin, original magnification × 20). Because of the history of colon and renal cell carcinomas, immunostaining performed proved the pancreatic tumor was an independent primary. This case illustrates a rare presentation of the high-grade histologic spectrum of IOPN. To our knowledge, the association of this rare entity with clear cell and oncocytic renal tumors has not been described. Whether they represent a spectrum of a syndromic process requires further investigation.
Concurrent Occurrence of Microcystic Serous Cystadenoma and Intraductal Papillary Mucinous Neoplasm of Pancreas and Islet Cell Amyloidosis: (Poster No. 57)
Microcystic serous cystadenomas (MSC) generally are solitary lesions. However, there have been reports associating serous cystadenomas with other pancreatic tumors. We report a case of a 75-year-old woman with history of type II diabetes who was found to have a cystic lesion in the tail of the pancreas. This asymptomatic patient was followed for 4 years with imaging studies. The last computed tomography scan showed increased size and morphologic changes of the mass. The Ca19-9 and CEA tumor markers were 71.7 U/mL and 2 ng/mL, respectively. Because of the high risk for malignancy, the patient underwent distal pancreatectomy with splenectomy. Grossly, the pancreas showed a 2.7 × 1.7 × 1.5-cm, white-tan, multicystic mass. Microscopically, there were multiple microcysts lined by a single layer of cuboidal cells with round, centrally located nuclei and clear cytoplasm with no atypia. Adjacent to this was a 1-cm cyst lined by columnar mucinous cells with elongated nuclei and foveolar appearance (Figure 28). An MSC and a branch-type intraductal papillary mucinous neoplasm (IPMN) with low-grade dysplasia, gastric-subtype, were diagnosed. Additionally, diffuse islet cell hyperplasia with amyloid deposition was identified. The amyloid showed apple-green birefringence on Congo red stain and was negative for amyloid A, κ, λ, and transthyretin, consistent with islet amyloid polypeptide. This case displays an unusual coexistence of MSC with branch-type gastric IPMN in the background pancreatic islet cell amyloidosis. The latter can be found in patients with type II diabetes. To our knowledge, there are only 2 previously reported cases of combined MCS and IPMN in the literature.
Neuromuscular and Vascular Hamartoma: (Poster No. 59)
Neuromuscular and vascular hamartoma (NMVH) is very rare with only 20 cases reported in the English literature since its initial characterization by Fernando and McGovern in 1982. Whether this lesion is truly hamartomatous or represents a burnt-out phase of varying chronic pathologies is debatable. Examples of NMVH have been reported in the setting of diaphragm disease, Crohn disease, radiation, and ischemia. Herein, we present the case of a 73-year-old woman with partial small-bowel obstruction and a past surgical history notable for cholecystectomy and abdominal hysterectomy. A computed tomography scan revealed an ill-defined mass with the same density as muscle extending to the mesentery, generating the differential of lymphoma versus metastatic disease. Upon laparotomy, a 2.5-cm, constrictive, mural, and mesenteric mass was notable. The more-proximal bowel was dilated, and there were dense, serosal adhesions. Grossly, the transmural lesion had a tan-yellow cobweblike cut surface. Histologically, lesional tissue contained fascicles of smooth muscle, irregularly placed nerve bundles and thick-walled, elastotic vessels haphazardly arranged within hypocellular fibrous bands and entrapped fat, consistent with NMVH. Yet, in contrast to findings commonly reported, the mucosa was not significantly altered. No stigmata of Crohn disease were observed, and the patient's history was negative for chronic nonsteroidal antiinflammatory use, radiation, and hyperlipidemia. This case of NMVH is presented as a reminder of benign mass-forming lesions causing small-bowel obstruction and raises the potential chronic effect of abdominal serositis and adhesions as a plausible risk factor for the development of NMVH (Figure 29).
A Comparison of the World Health Organization (WHO) 2004 and 2010 Classification Systems in Pancreatic Neuroendocrine Tumors (PNETs): (Poster No. 61)
Context: PNETs are rare tumors with multiple classification systems. We compared the WHO 2004 and 2010 classification systems in predicting mortality, metastasis, and associations with mortality.
Design: Pathologic parameters were reviewed, including nuclear grade, tumor size, mitotic count, perineural/lymphovascular invasion, Ki-67 positivity, and the presence of metastasis. These parameters were used to classify all tumors in both the WHO 2004 and WHO 2010 classification systems. The relationship between the WHO 2004 and WHO 2010 grading was investigated using an exact χ2 test. The WHO grade categorization was next explored by vital status to determine whether there was a difference in survival and metastasis by grading system.
Results: The WHO grades were significantly associated with one another (P < .001). As shown in the Table, both grading systems were strongly associated with predicting mortality; all cases of mortality were in the higher grades. The 2010 grades do slightly better than the 2004 grades do in predicting metastasis because metastases occur only in high grades (G2 and G3). Mitotic index was significantly different, with a median of 0 in live patients versus 15 in deceased (P < .001). This was similarly borne out in the survival analysis using Cox proportional model, where, for every one unit increase in mitotic index, there was about a one-third increase in the hazard of death (P =.001). There was no significant difference in survival by tumor size, comorbidities, or margins.
Conclusions: The WHO 2010 grading system is strongly associated with predicting mortality and performs better in predicting liver metastasis than the 2004 grading system does.
Gastric Foveolar Adenocarcinoma Arising in a Patient With Muir-Torre Variant Lynch Syndrome: (Poster No. 62)
Lynch syndrome predisposes individuals to developing cancer, with colorectal and endometrium cancer carrying the highest risk. Gastric cancer risk is not as well defined, making surveillance guidelines less straightforward. The Netherland's Hereditary Cancer Registry documents gastric cancer risk as being 3.4 times higher in patients with Lynch syndrome, specifically those with MLH1 or MSH2 mutations, compared with their general population. Foveolar-type dysplasia is a morphologic subset of gastric dysplasia different from intestinal-type dysplasia in that its background mucosa generally lacks atrophy and intestinal metaplasia. Foveolar-type dysplasia has a documented association with FAP, and gastric foveolar carcinoma has a documented association with microsatellite instability; however, these microsatellite instability-associated foveolar gastric carcinomas showed hMLH1 promoter hypermethylation rather than familial microsatellite instability. We present a 61-year-old man with Muir-Torre variant Lynch syndrome who underwent endoscopic mucosal resection for a persistent gastric fundic lesion. Previous history included metachronous colon cancers (at age 45 and 59 years) and multiple sebaceous adenomas. MSH2 sequencing was positive for germline mutation c.811del4. Histologic examination of the fundic mass revealed a well-differentiated, intramucosal adenocarcinoma arising in a 1.3-cm, foveolar-type adenoma. The background gastric mucosa was normal without atrophy or intestinal metaplasia (Figure 30, a). There was loss of MSH2/MS6 protein expression by immunohistochemical staining with retained expression of MLH1/PMS2 in the adenoma and adenocarcinoma (Figure, b). A geographically separate, foveolar-type adenoma with high-grade dysplasia was also removed at the time of the endoscopic mucosal resection. To our knowledge, this is the first documented case of gastric foveolar adenocarcinoma arising in a patient with Lynch syndrome.
Primary B-Cell Lymphoma of the Extrahepatic Bile Duct Mimicking Periductal Infiltrating Cholangiocarcinoma: (Poster No. 64)
Primary extranodal non-Hodgkin lymphoma arising from the extra hepatic biliary tract is a rare phenomenon, with fewer than 20 cases reported in the literature. Most of the cases are diffuse large B-cell lymphomas, which account for 30% to 40% of all cases of lymphomas. Up to 40% of diffuse large B-cell lymphomas will initially present at extranodal sites, most commonly the gastrointestinal tract, and rarely, the biliary tree. Lymphomas account for approximately 1% of cases of biliary obstruction related to malignancy, and in most of those cases, the obstruction is extrinsic, related to enlarged lymph nodes in the area. We report the unusual case of a 46-year-old, previously healthy man who presented with acute postprandial right upper-quadrant pain unaccompanied by jaundice. Radiologic and gross images were strongly suggestive of a periductal infiltrating cholangiocarcinoma, but microscopic examination revealed a primary, diffuse large B-cell lymphoma arising in the extrahepatic bile ducts and extending in a periductal fashion into the intrahepatic bile ducts, thereby expanding the portal triads and inducing a histiocytic reaction. Although rare, primary extranodal B-cell lymphomas should be considered in the differential diagnosis of Klatskin tumors because that could dramatically change the course of management (Figure 31).
Intraductal Papillary Neoplasm of the Bile Ducts: Case Report of an Uncommon Tumor Variant and Review of the Literature: (Poster No. 65)
Intraductal papillary neoplasm of the bile duct (IPNB) is an uncommon variant of bile duct carcinoma, recently recognized by the World Health Organization as precursor to invasive carcinoma. Its clinicopathologic features are still poorly defined, and its identification can represent a diagnostic challenge. We report a case of a 38-year-old woman with a history of choledocholithiasis who presented in December 2012 because of alcoholic stools and jaundice. Blood workup was consistent with obstructive jaundice. A magnetic resonance cholangiopancreatography showed a common bile duct mass and 3 liver masses. The patient received preoperative chemotherapy, underwent a partial hepatectomy, and is currently receiving adjuvant chemotherapy. The liver showed a 1.5 × 1.5 × 1.0-cm, tan, friable, papillary mass at the right hepatic duct and common bile duct junction and 6 pale-tan, homogenous masses, ranging from 1.0 to 6.0 cm. Microscopically, a dilated bile duct showed an intraductal papillary mass adjacent to infiltrative adenocarcinoma. The papillary fronds had fine vascular cores and were lined by epithelial cells with different degrees of dysplasia and foveolar-like mucinous cytoplasm (Figure 32). By immunohistochemistry, the epithelium was positive for MUC5 and negative for MUC1, MUC2, and CDX2, which is consistent with gastric foveolar subtype of IPNB. We describe the histomorphology and immunohistochemistry of an IPNB with invasive adenocarcinoma in a young, female patient who is still alive after 15 months. Accurate distinction of this tumor from cholangiocarcinoma is necessary to recognize patients with better prognosis and to further investigate the natural history of this precursor of bile duct carcinoma.
Intracholecystic Papillary-Tubular Neoplasm Arising in Adenomyoma of the Gallbladder: (Poster No. 71)
A 72-year-old man with a recent history of abdominal pain underwent a cholecystectomy for a clinical diagnosis of cholecystitis with cholelithiasis. The resected gallbladder had 3 choleliths and a 2.5-cm mural mass in the fundus. The fundic mural mass had features of an adenomyoma with glandular elements intermixed with proliferating bands of smooth muscle. The glandular elements included an intraluminal proliferation with papillary architecture having focal, mild to moderate dysplasia. The remainder of the gallbladder had features of chronic and subacute cholecystitis. The margins of resection and the single pericystic lymph node were not involved by tumor. The overall findings were interpreted as an intracholecystic papillary-tubular neoplasm (ICPN) with mild to moderate dysplasia, arising in an adenomyoma. There is not a consensus on classification of preinvasive neoplasms and papillary tumors in the gallbladder. A recent proposal classifies these lesions under a uniform category of intracholecystic papillary-tubular neoplasms (ICPN) of the gallbladder. To our knowledge, ICPN of the gallbladder arising in an adenomyoma has not been previously described. Approximately half of ICPNs of the gallbladder are found incidentally, stressing the importance of increased awareness of this entity. Given the high incidence of associated, invasive malignancy in ICPN, it is important to completely examine the lesion, even if found in the background of a common benign lesion, such as adenomyoma. Even histologically bland ICPN can progress to invasive carcinoma, further emphasizing the need for accurate diagnosis to ensure appropriate clinical management (Figure 33).
Extrapancreatic, Solid, Pseudopapillary Tumor in the Subhepatic Region: A Diagnostic Dilemma: (Poster No. 73)
Solid pseudopapillary tumor of pancreas (SPT) is an uncommon and enigmatic pancreatic neoplasm that occurs mainly in young women. Rare cases of extrapancreatic SPT have been reported. We present a case of SPT that posed a diagnostic challenge by presenting at an unusual location. A 32-year-old woman presented with dull, upper-abdominal pain for 3 months. Computed tomography scan revealed a well-defined heterogeneous mass in the subhepatic region between the head of the pancreas and the second portion of the duodenum. Radiologic features were suggestive of a gastrointestinal stromal tumor. The tumor was subsequently excised under general anesthesia. At operation, the tumor appeared to be adherent to the inferior surface of the head of the pancreas, but it could be easily separated from the pancreas. Macroscopically, the tumor was a well-circumscribed, hemorrhagic mass, measuring 10.0 × 8.0 × 3.0 cm. On microscopy, the tumor exhibited a predominant, solid growth pattern with focal pseudopapillary formation (Figure 34, A and B). The tumor cells were polygonal with abundant eosinophilic to clear cytoplasm and round to oval nuclei with fine nuclear chromatin. There was no ectopic pancreas histologically. Immunohistochemistry showed strong expression of CD10, vimentin, CD56 (Figure, C) and α1-antitrypsin, whereas synaptophysin was focally positive. β-catenin immunostain showed strong nuclear expression (Figure, D). A final diagnosis of SPT was rendered. The SPTs occur as primary tumors outside the pancreas exceedingly rarely; only 12 cases have been reported in the English literature. Awareness of the existence of this tumor in extrapancreatic sites is essential to avoid misdiagnosis.
A Case of Schwannian Pseudohypertrophy of Muscularis Propria in Rectum: (Poster No. 74)
Fibrosis as a response to change of milieu is not uncommon in the gastrointestinal tract, but fibrotic thickening limited to muscularis propria accompanied by an increase in Schwann cells has not been reported. We report a case of a 69-year-old woman who presented with irreducible segmental rectal prolapse and underwent resection. Grossly, the rectum demonstrated focal erosion and ulcer in the mucosa. There was hypertrophy-like thickening of the muscularis propria to 2 or 3 times the normal thickness in areas uninvolved by erosion or ulcer (Figure 35, A, arrow). Histologically, the thickened areas demonstrated fibrotic thickening (Figure, B, arrow, trichrome) that was limited only to the muscularis propria. The fibrosis (Figure, C, trichrome) nicely followed the distribution of the inner muscle layer and tapered off at the periphery without accompanying fibrosis in the surrounding tissue. Some bland spindle cells, reminiscent of Schwann cells, were present, and those cells were immunoreactive for S100 (Figure, D). Electron microscopy was performed and features of Schwann cells were demonstrated in those cells. No increase in neurons or axons was demonstrated by immunohistochemistry for PGP9.5 or neurofilament proteins. We named this unique change schwannian pseudohypertrophy because this is not genuine hyperplasia or hypertrophy because of its lack of increase in cellularity or enlarged cell bodies. It is indeed a pseudohypertrophy because of fibrosis. This term also reflects the increase in Schwann cells. This type of change may be mistaken as a tumor of peripheral nerve origin in small biopsies and thus deserves recognition.
Ossifying Colonic Adenocarcinoma: Case Report With Brief Review of Literature: (Poster No. 77)
Within the gastrointestinal tract, osseous metaplasia is an extremely rare phenomenon. It represents dystrophic ossification and may occur in benign or neoplastic conditions. The cause of osseus metaplasia is controversial. Some authors think the best explanation for ossification in epithelial tumors is that it follows metaplasia of undifferentiated stromal tumors into osteoblasts. The first 2 cases of heterotopic ossification in a colorectal carcinoma were reported by Hasegawa in 1923. Very few cases of carcinoma with osseous metaplasia have been reported since. Of the cases of colon tumors, mucinous adenocarcinomas have been more frequently associated with rare cases of osseous metaplasia. We report a case of adenocarcinoma with osseous metaplasia of the cecum and ascending colon in a 55-year-old man. The patient was found to have a partially obstructing mass of the cecum. Grossly, the hemicolectomy specimen (20 × 10 × 7 cm) revealed a fungating tumor mass in the cecum and ascending colon (6 × 5 × 5 cm). Cut surface showed tumor with hard bony areas and extension into the subserosal tissue. Histologically (Figure 36), the tumor was a well to moderately differentiated, invasive adenocarcinoma with prominent osseous metaplasia, which infiltrated the subserosa. One lymph node of 16 was positive for metastatic adenocarcinoma. Osseous metaplasia is generally a radiologic and histologic curiosity with an unknown significance. It is important to be aware of this phenomenon as being distinct from carcinosarcoma, which has a poorer prognosis.
Gastric Zygomycosis in a Previously Healthy 56-Year-Old Man: (Poster No. 81)
Zygomycosis refers to infections caused by bread mold fungi of the Zygomycota phylum. Infections generally occur in immunocompromised individuals. The following case is of a previously healthy 56-year-old man admitted to the hospital following a motor vehicle accident. During his hospitalization, there was a significant drop in hemoglobin, which led to an upper gastrointestinal endoscopy. The endoscopy revealed numerous, large, 30-mm, craterlike gastric ulcers with an adherent clot. Biopsies of the ulcer margins revealed broad pauciseptate, ribbonlike, slightly refractile fungal forms, which were highlighted with periodic acid–Schiff stain. A Gomori methenamine silver stain was negative. These forms were suggestive of zygomycetes. A subsequent gastrectomy was performed that revealed similar findings. The patient experienced severe trauma, which may have contributed to the progression of his condition; however, this is an unusual presentation because the patient was previously healthy and did not illustrate any conditions that might compromise his immunity. The severity and rarity of this condition makes this a unique and intriguing case (Figure 37).
Immunohistochemical Evaluation of c-Myc Expression in Carcinomas From Various Organs: (Poster No. 86)
Context: c-Myc is a transcription factor and oncoprotein. As well established, the t(8;14) translocation is critical for the development of Burkitt lymphoma. In addition, c-Myc overexpression has been reported in other malignancies. In this study, we investigated c-Myc expression in a large series of carcinomas.
Design: Immunohistochemical evaluation of the expression of c-Myc (EP121 or Y69, Epitomics Inc, Burlingame, Calif) in 912 carcinomas on tissue microarray sections and 18 medullary carcinomas of the large intestine on routine tissue sections was performed. The staining intensity and distribution were recorded.
Results: Some of the results are summarized in the Table. One hundred percent of medullary carcinomas were positive for c-Myc. Papillary thyroid carcinomas, renal cell carcinomas, endometrial carcinomas, hepatocellular carcinomas, and pancreatic neuroendocrine tumors were negative for c-Myc.
Conclusions: These data suggest that (1) c-Myc can be useful in confirming a diagnosis of colorectal carcinoma because c-Myc overexpression is present in nearly 100% of colorectal carcinomas, including medullary carcinomas; and (2) c-Myc can be used in differentiating lung squamous cell carcinoma from lung adenocarcinoma. Additionally, a carcinoma with c-Myc overexpression may potentially respond to c-Myc–targeted cancer therapy.
Application of the 2010 World Health Organization Classification Can Classify Previously Uncategorized Hepatobiliary Tumors as Combined Hepatocellular-Cholangiocarcinoma Subtypes: (Poster No. 87)
Context: The 2010 World Health Organization (WHO) liver tumor classification divides combined hepatocellular-cholangiocarcinoma (HCC-CC) into classic type and subtypes with stem cell features (SCFs). The HCC-CCs with SCFs include (1) typical subtype, showing clustered hepatocytes encircled by progenitor-like cells; (2) intermediate-cell subtype, composed of nested cells in desmoplastic stroma with both hepatocellular and cholangiocellular differentiation; and (3) cholangiolocellular subtype with small cells forming anastomosing tubules. This study examines whether the WHO definitions standardize classification of hepatobiliary neoplasms.
Design: One hundred hepatobiliary neoplasms, including hepato-cellular carcinomas, cholangiocarcinomas, and primary hepatic tumors with mixed features, resected between January 2008 and September 2013 were retrieved from departmental files. Slides from 69 cases were available for review, and 3 more cases of primary hepatic tumors with mixed features were additionally included, totaling 72 cases for review. All hematoxylin-eosin–stained tumor sections were examined for combined HCC-CC morphology. Ten cases with combined features were found, including 7 originally reported using only descriptive terminology, and immunostained to further assess for SCFs (see Table). Ten and 9 pure hepatocellular and cholangiocarcinomas, respectively, were stained as controls.
Results: Tumors showing combined morphology included 2 combined HCC-CCs, classic type; 2 combined HCC-CCs with SCFs, cholangiolocellular subtype; and 6 combined HCC-CCs with SCFs, intermediate subtype. Immunostaining was confirmatory in the pure hepatocellular and cholangiocarcinomas and helped confirm the presence or absence of SCFs in combined HCC-CC (Table).
Conclusions: Tumors with mixed features, including those reported descriptively, could be categorized by WHO criteria. Immunohistochemistry supported morphologic impressions. Overall, the WHO subtypes help to classify hepatobiliary tumors, eliminating variable descriptive terminology in reporting.
Olmesartan-Associated Celiac Diseaselike Enteropathy in a Patient With Severe Diarrhea: (Poster No. 89)
A 62-year-old woman with a history of hypertension presented with severe diarrhea. Endoscopic examination of the gastrointestinal tract revealed erythema of the sigmoid colon and rectum, and granularity in the second part of duodenum. Biopsies from left colon, rectum, and sigmoid colon were histologically unremarkable. Duodenal biopsies showed multifocal surface ulceration, villous blunting, and intraepithelial lymphocytosis (Figure 38, A). These changes were suspicious for celiac disease in a background of erosive injury. Serologic testing was suggested to exclude celiac disease, which turned out negative. The patient continued to have severe diarrhea and developed dehydration that required hospitalization. Review of the patient's medication revealed use of olmesartan for hypertension during previous 2 years, which was stopped as a probable cause of her symptoms. She recovered from diarrhea within 3 days of discontinuation. Repeat duodenal biopsy after 1 month showed histologic recovery (Figure, B). Olmesartan is an angiotensin II receptor antagonist that is used to manage hypertension. Olmesartan-associated celiac diseaselike enteropathy has been rarely described in the past, and the underlying mechanism is unknown. However, the long delay between onset of therapy and the development of diarrhea suggests a role for cell-mediated immunity. Inhibition of transforming growth factor β has been also suggested as a possible mechanism. In summary, we present a unique case of olmesartan-associated celiac diseaselike enteropathy in a patient with severe diarrhea. Pathologists and clinicians should consider this entity in the differential diagnosis when dealing with a case of seronegative celiac diseaselike enteropathy.
Clinicopathologic Features of Fibroadenoma With Atypia and Carcinoma In Situ: A Single Institution Experience: (Poster No. 94)
Context: Fibroadenoma (FA) is a common, benign, biphasic tumor arising from the terminal-duct lobular unit and demonstrating epithelial and stromal elements. Usual ductal hyperplasia commonly arises within FAs. Atypical proliferations, carcinoma in situ (CIS), and invasive carcinoma arising within FAs is rare. This study's purpose was to assess the clinical findings and follow-up pathology in patients with FA associated with atypia or carcinoma.
Design: The FAs diagnosed from 2007 to 2013 were reviewed and categorized as follows: group 1, FAs with usual ductal hyperplasia; group 2, FAs with atypical proliferations including atypical ductal hyperplasia, atypical lobular hyperplasia, and flat epithelial atypia; and group 3, FAs with ductal CIS or lobular CIS. Patients with a history of carcinoma were excluded. Patient history was reviewed.
Results: The clinical findings, as seen in the Table, were not significantly different between the 3 groups. However, the BIRADS score was notably higher in group 3. Within the 30 FA cases in group 1, one developed invasive carcinoma 12 months later. Group 2 had 5 FA cases, 3 of which included atypical ductal hyperplasia, whereas 2 included atypical lobular hyperplasia. Of the 7 FA cases in group 3, there were 3 with ductal CIS, 3 had lobular CIS, and 1 case had both.
Conclusions: Atypical proliferations and CIS are rarely detected within FAs. A higher BIRADS score might be a good screening indicator for cases in which there is concurrent atypia or carcinoma arising within a FA on follow-up pathology. This will warrant further follow-up with excision to confirm the diagnosis and exclude malignancy.
Correlation Between Magnetic Resonance Imaging (MRI) Findings and Gross and Microscopic Pathology in Breast Surgical Specimens After Neoadjuvant Therapy: A Review of 30 Cases: (Poster No. 97)
Context: Breast MRIs are often performed to evaluate the extent of disease before neoadjuvant therapy, after treatment, and before surgery to assess tumor response.
Design: We reviewed 30 breast specimens from patients who received neoadjuvant chemotherapy. Twenty-three patients underwent total mastectomy, and 7 patients had lumpectomies performed after the completion of therapy. Breast magnetic resonance imaging (MRI) was performed at baseline and preceding surgery. We compared the response to therapy based on MRI assessment with the findings on gross and microscopic examination of the surgical specimens. A copy of the MRI report was available at the time of grossing for correlation in all cases. Samples were taken from all areas of concern identified on MRI to correlate with histologic diagnosis.
Results: In 22 cases (73.3%), the MRI detected the presence of residual tumor with an accuracy of ±5 mm (14 cases) or the presence of a complete response confirmed by microscopic examination (8 cases). In 4 cases, the size of the residual carcinoma was overestimated on MRI by more than 1.5 cm (Table). In 4 cases, the size of the carcinoma was underestimated by MRI (Table).
Conclusions: An MRI is an accurate method of evaluating response to neoadjuvant chemotherapy in 73.3% of cases. In this study, overestimation of residual tumor by MRI was seen in 13.3% of cases (strongly associated with florid fibrotic reaction) and underestimation in 13.3% of cases. Underestimation by MRI in select cases may reflect the inherent limitations of identifying viable carcinoma in treated tissues on a microscopic level.
Breast Carcinoma in Nonagenarians: An Institutional Experience: (Poster No. 100)
Context: A number of breast carcinoma cases in the elderly are seen at our institution.
Design: Data of the Hartford Hospital Tumor Registry files from 2000 to 2012 of patients 90 years and older presenting with breast carcinoma were analyzed; histology, stage, and treatment modalities in this patient population were assessed.
Results: Sixty-one patients were retrieved from the registry files, with ages ranging from 90 to 103 years (mean, 94.2 years). Histology showed 6 in situ and 55 invasive (67.3% ductal [n = 37]; 9.1% lobular [n = 5]; and 23.6% mixed [n = 13]) carcinomas. Most tumors were positive for ER and PR, and 9 were positive for HER2-neu. See Table for stage and mode of treatment.
Conclusions: (1) There are a significant number of breast carcinoma cases in nonagenarians and above. (2) Most are invasive with some at advanced stage. (3) Many patients can tolerate surgical treatment, but fewer were given radiation, and none had chemotherapy; hormonal therapy was offered to node-positive patients. (4) Continued surveillance should be made among this patient population to catch breast carcinomas at an early, resectable stage. (5) Analysis of complications from treatment and survival data was compiled to determine success of therapy.
Sentinel Lymph Node Evaluation: A Prospective Comparison of Gross and Microscopic Intraoperative Examination: (Poster No. 103)
Context: The sensitivity of detecting metastatic breast cancer in sentinel lymph nodes (SLN) using intraoperative cytologic examination (ICE) ranges from 36.5% to 95%; ICE may lead to increased detection of clinically insignificant micrometastases and isolated tumor cell clusters (ITC). Intraoperative gross and macroscopic examination (IGE) of SLNs may be an alternative strategy for preferentially detecting macro-metastases (MM) now that completion axillary dissection (ALND) is being questioned for micrometastases and ITCs.
Design: We prospectively gathered IGE and ICE data during intraoperative SLN evaluation from 2005 to 2007. Each pathologist performed IGE of each SLN followed by microscopic examination using ICE. All SLNs were sectioned at 2-mm intervals, processed for permanent histologic examination (PHE), and examined using hematoxylin-eosin stains.
Results: A total of 565 SLNs from 175 consecutive, clinically node-negative patients were reviewed. Overall, detection sensitivity for IGE was 29% (9/31) and for ICE was 71% (22/31). The MM sensitivity for IGE and ICE were 44% and 89%, respectively. All 22 patients positive by ICE had immediate ALND. However, only 1 of 11 patients with false-negative SLN on ICE elected subsequent completion ALND (Table).
Conclusions: ICE has higher sensitivity than IGE for detection of any SLN metastases and or MM. Patients may not elect ALND even when MM is detected by PHE. Thus, IGE appears to be an option for patients reluctant to undergo immediate ALND for SLN micrometastases or ITCs. Although all patients with positive intraoperative SLNs underwent completion ALND (100%), only 1/11 (9%) underwent subsequent completion ALND when a positive SLN was identified on PHE.
Benign Phyllodes Tumor Recurring as a Malignant Phyllodes Tumor and Metaplastic Carcinoma: A Case Report With Molecular Analysis and Immunohistochemistry: (Poster No. 105)
Metaplastic breast carcinoma (MBC) arising within a phyllodes tumor (PT) has been recognized only in rare case reports. Both MBC and malignant PT possess complex genomes; however, the molecular biology of these neoplasms and the relationship between the 2 remain unclear. Furthermore, differentiating the malignant stromal component of PT from MBC can be diagnostically challenging because they both may show malignant spindle cells and heterologous elements. We report a unique case of a 59-year-old woman diagnosed with a benign PT (Figure 39, A), which recurred twice in the same location during a 7 year period, first as a malignant PT (Figure, B), and then, a malignant PT with coexisting MBC (Figure, C). The second recurrence contained malignant spindle cells that expressed cytokeratins (CK) AE1/3 (Figure, D), MDF-116, CK5/6, and p63, and thus was diagnosed as a MBC. Using the Ion Torrent PGM (Life Technologies, Carlsbad, Calif) and the AmpliSeq v2 Cancer Hotspot Panel (Life Technologies), which targets hotspot regions of 50 oncogenes and tumor suppressor genes, we sequenced areas of interest from the patient's prior PTs (benign and malignant) and the MBC. The benign PT and the first recurrent malignant PT shared the same mutation in FBXW7, a tumor suppressor gene found in ~6% of human cancers. The most recent malignant PT recurrence and coexisting MBC lacked any identifiable mutations with this panel. This unusual case illustrates a progression of benign PT to malignant PT and development of coexisting MBC, identifies a molecular alteration, and highlights the utility of immunohistochemistry to distinguish between malignant PT and MBC.
Utility of Immunohistochemical Markers in Irradiated Breast Tissue: An Analysis of the Role of Myoepithelial Markers, P53, and Ki-67: (Poster No. 106)
Context: The diagnosis of recurrent/de novo carcinoma in a background of radiation atypia (RA) is difficult, especially on small biopsies. The utility and characteristics of immunostains for myoepithelial cells have not been previously studied in irradiated breast. We also explored the utility of the proliferative marker Ki-67 and the tumor suppressor protein p53 in discriminating RA from carcinoma.
Design: We identified 29 irradiated breast resection specimens with RA, +/− carcinoma in situ (CIS), and invasive carcinoma. Blocks were stained with antibodies to the myoepithelial proteins p63, smooth muscle myosin heavy chain, calponin, Ki-67, and p53. Nonirradiated breast tissue was also stained with Ki-67 and p53 (CIS, normal, contralateral).
Results: In irradiated breast, myoepithelial markers demonstrated abundant myoepithelial cells in all RA and nearly all CIS, with focal stain attenuation seen with smooth muscle myosin and calponin in CIS. As expected, myoepithelial cell staining was absent in invasive carcinoma. p63 staining revealed unique nuclear morphology in RA including multinucleation and nucleomegaly. p53 staining was increased in irradiated nonneoplastic breast when compared with controls (t = 2.66, P = .01); however, irradiated CIS had lower p53 staining when compared with control CIS (t = 3.19, P = .005) (Table).
Conclusions: Immunohistochemical staining for myoepithelial markers is a useful diagnostic adjunct in irradiated breast, with caveats similar to nonirradiated breast. Ki-67 is elevated in some cases of CIS as compared with RA, similar to nonirradiated breast. Surprisingly, CIS in irradiated breast had attenuated p53 staining as compared with nonirradiated CIS, which may indicate different activity of this tumor suppressor pathway postradiation.
Unilateral Malignant Adenomyoepithelioma of the Breast With Contralateral Extensive Ductal Carcinoma In Situ: (Poster No. 107)
Adenomyoepithelioma of the breast is a rare tumor characterized by biphasic epithelial and myoepithelial differentiation encompassing a spectrum of histologic patterns. Although most tumors are benign, malignant degeneration of the epithelial and/or myoepithelial component occurs rarely. Heterogeneity of the tumor makes diagnosis challenging, especially on evaluation of needle-biopsy specimens. Recognition of the biphasic cytophenotype and the characteristic architecture, in conjunction with immunohistochemistry, is essential for accurate diagnosis. We report a case of a 55-year-old woman with bilateral large breast masses (right, 4 cm; left, 7 cm). The morphologic and immunophenotypic features of the right mass were those of infiltrating epithelial carcinoma derived from an adenomyoepithelioma, which is associated with extensive proliferative fibrocystic changes (Figure 40, A, benign adenomyoepithelioma; Figure, B, CAM 5.2+ epithelioid component; Figure, C, SMA+ spindle component). The infiltrating tumor was diffusely permeative with multifocal perineurial infiltration, was mitotically inactive, lacked necrosis, and generally showed minor to moderate pleomorphism and/or atypia (Figure, D, malignant component). The contralateral breast mass consisted of multifocal, comedo-type ductal carcinoma in situ associated with extensive proliferative fibrocystic changes. No metastasis was identified on bilateral biopsy of sentinel lymph nodes. Although their metastatic potential and patterns are not well studied, adenomyoepithelioma-derived malignant neoplasms appear to favor hematogenous rather than lymphatic spread, and those with high mitotic activity and/or infiltrating margins have a potential for local recurrence and/or metastasis.
Granular Cell Tumors of the Breast: A Clinicopathologic and Immunohistochemical Study: (Poster No. 110)
Context: Granular cell tumor (GCT) of the breast is a rare neoplasm affecting mostly premenopausal African-American women. Despite the benign nature of this tumor, it may mimic invasive breast carcinoma clinically and radiologically, making the diagnosis challenging.
Design: Twelve cases of GCT were identified (December 1992 to June 2013). Clinicopathologic data were reviewed, and immunohisto-chemistry for estrogen receptor (ER), progesterone receptor (PR), S100, and mammaglobin was performed on paraffin-embedded tissue.
Results: See Table. Six of the 12 women (50%) were white, 5 were African American (42%), and one was Hispanic (8%). Age at excision ranged from 20 to 78 years (median, 54.5 years). Right and left breasts were equally affected. Tumors ranged in size from 0.2 cm to 3.0 cm (average, 1.0 cm). Three patients had history of breast carcinoma, all occurring in the same breast as the GCT; one was synchronous and the other 2 metachronous. One patient developed recurrent GCT 4 years after the original tumor was excised. All cases of GCT were positive for S100 and negative for mammaglobin. One case showed focal positivity for ER and PR, whereas the others were negative.
Conclusions: GCTs can occur as synchronous or metachronous tumors with breast carcinoma; therefore, clinically and radiologically, they may mimic invasive carcinoma. Despite racial heterogeneity of our patient population, we encountered a greater number of GCT cases in white women. These tumors have potential for local recurrence if incompletely excised. Mammaglobin, ER, and PR negativity, and S100 positivity are consistent with Schwann cell origin of GCT of breast.
Expression of SMURF2, a Ubiquitin Ligase, Is Decreased in Triple-Negative Breast Ductal Carcinoma: (Poster No. 118)
Context: SMURF2 is an ubiquitin ligase involved in diverse biologic events, such as cell division, cell polarity, cell migration, and receptor signaling. Evidence suggests that SMURF2 is a tumor suppressor and has important roles in cancer development. This project examines immunohistochemical expression of SMURF2 in breast-infiltrating ductal carcinomas and analyzes correlations between SMURF2 expression and ER, PR, and HER2/neu status.
Design: Tissue from 51 cases of triple-negative infiltrating ductal carcinoma and 51 cases of receptor-positive infiltrating ductal carcinoma were analyzed. SMURF2 expression was detected by immunohistochemistry using polyclonal anti-SMURF2 antibody (Santa Cruz Biotechnology, Dallas, Tex). SMURF2 staining was scored as 1+, 2+, or 3+ according to the percentage of tumor cells staining and intensity of staining. The results were analyzed by a 2 sample proportion z test.
Results: The triple-negative cases had statistically significant decreased expression of SMURF2 compared with receptor-positive cases. When comparing unequivocal high SMURF2 expression (2+/3+), 80.4% of receptor-positive cases were unequivocally positive, whereas only 56.9% of the triple-negative cases displayed unequivocally positive staining (P < .05). In contrast, decreased SMURF2 expression (1+) was observed in 19.6% of receptor-positive cases compared with 43.1% of triple-negative cases (P < .05) (Figure 41).
Conclusions: SMURF2 expression is significantly decreased in triple-negative breast carcinomas when compared with receptor-positive cases. Our data support the accumulating evidence that decreased expression of SMURF2 in tumor cells is associated with invasive breast cancers. We also report a new finding that expression is decreased more often in triple-negative breast carcinomas.
Hypersecretory Hyperplasia of the Breast in a Nonpregnant Woman Showing a Histomorphologic Spectrum of Benign, Atypical, and Malignant Changes: Report of a Case and Review of the Literature: (Poster No. 120)
Hypersecretory hyperplastic lesions of the breast can present as benign hypersecretory hyperplasia (HH), a combination of benign and atypical epithelium (HHA), or a combination of atypical and frankly malignant epithelium (HHM); HH is not included in the World Health Organization classification of breast lesions. Careful clinical follow-up is recommended for lesions that display atypical features in HH, HHA, or in a histologically combined lesion (HHM). If these lesions are found in a breast needle core biopsy specimen, an excisional biopsy is recommended. In this setting, ductal carcinoma in situ, usually micropapillary or cystic hypersecretory types, and rarely invasive carcinoma can arise. Affected patients are typically younger than those with more-common types of breast carcinoma. We present a case of a 42-year-old, nonpregnant woman who underwent excision of 3 irregularly thickened areas in 3 different quadrants of the left breast, some with microcalcifications, identified during a routine mammogram. Histologic examination showed cystically dilated ducts of various sizes with colloidlike material, and ducts lined by flat, orderly, bland columnar epithelial cells. Although most of the tissue displayed features of HH with focal microcalcifications (Figure 42, A and B), scattered areas showed transition to HHA (Figure, C), and other areas even showed transition to frank HHM (Figure, D). The identified carcinoma was ductal carcinoma in situ grade 2 without necrosis. This case supports prior reports suggesting that HH breast lesions encompass a spectrum of pathologic lesions, including HH, atypical HHA, and HHM. We did not identify invasive components, which are rarely reported.
Decreased Claudin 7 Expression Is Associated With Mammary Paget Disease: (Poster No. 124)
Context: Mammary Paget disease is a rare form of breast cancer characterized by the invasion of epidermis by breast cancer cells, and its pathogenesis remains unclear. Dysregulation of claudins, tight junction membrane proteins, has been described in multiple malignancies, including breast cancer. We hypothesized that alteration in claudin expression may be involved in the development of Paget disease. We investigated expression of claudins 1, 3, 4, 7, and 8 in Paget cells in comparison with underlying ductal carcinoma in situ (DCIS) in this study.
Design: We identified 22 cases with both Paget disease and underlying DCIS from the Rhode Island Hospital. Paraffin-embedded tissue microarrays were analyzed for immunohistochemistry expression of claudins 1, 3, 4, 7, 8, HER2, and ER. Claudin immunoreactivity was assessed semiquantitatively and analyzed by χ2 test.
Results: All claudins demonstrated a membranous staining pattern in the nonneoplastic breast tissue, Paget cells, and underlying DCIS. The positivity of claudins ranged from 13.3% to 77% in Paget cells and the DCIS component (see Table). Both Paget cells and underlying DCIS were more frequently positive for claudin 3 and 4, as opposed to claudins 1, 7, and 8. Expression of claudin 7 was significantly decreased in Paget cells as opposed to DCIS (13.3% versus 40%; P = .02). Most DCIS (79%) and Paget cells (86%) were positive for HER2. All except one case were negative for ER expression.
Conclusions: The significantly decreased claudin 7 expression in Paget cells may be associated with the transition from DCIS to Paget disease to facilitate spread of the tumor cells to the epidermis.
Multiplexed Ion-Beam Imaging of 10 Markers in Human Breast Tumors Using Metal-Tagged Antibodies With Potential for Hectaplexing: (Poster No. 130)
Context: Existing immunohistochemical (IHC) methods rely on antibodies tagged with fluorophores or chromogenic enzyme reporters. Because of the potential for spectral and spatial overlap, it can be difficult to use more than a few probes simultaneously. Consequently, multiplexed IHC is not routinely employed in clinical settings. We have developed a novel method that images mass-tagged antibodies using secondary ion mass spectrometry (MS) with potentially better-than-light-microscope resolution.
Design: Multiplexed ion beam imaging (MIBI) employs primary antibodies coupled to isotopically enriched, stable lanthanides. Tissue sections are stained simultaneously with all primary antibodies before imaging analysis using a NanoSIMS 50-L mass spectrometer. Multiplexed staining for ER, PR, HER2, E-cadherin, Ki-67, keratin, vimentin, actin, and double-stranded DNA was performed on human fresh-frozen, paraffin-embedded breast tumors and compared with conventional immunoperoxidase staining. Moving to time-of-flight mass spectrometry detection will allow between 40 and 100 antibodies to be imaged simultaneously.
Results: Comparison of HER2-, ER-, and PR-positivity demonstrates appropriate expression with respect to immunophenotypes established by conventional IHC staining performed in a clinical laboratory. Side-by-side comparison of MIBI and quantitative imaging analysis of ER IHC in 9 breast tumors demonstrated robust agreement between the 2 methods in mean nuclear staining intensity and H score (r = 0.99, P < .001; and r = 0.99, P < .001, respectively).
Conclusions: A MIBI analysis will generate highly multiplexed tissue-imaging results with sensitivity and resolution comparable to conventional IHC methodologies (Figure 43). This approach could provide new insights by integrating tissue microarchitecture with multiparameter cellular expression patterns for basic research, drug discovery, and clinical diagnostics.
Synchronous Occurrence of Primary Breast Adenoid Cystic Carcinoma and Invasive High-Grade Urothelial Carcinoma in a 75-Year-Old Man: Case Report and Review of the Literature: (Poster No. 131)
Adenoid cystic carcinoma (AdCC) of the breast is a rare malignancy accounting for 0.1% of all breast carcinomas. In contrast to the aggressive nature of AdCC at other sites, AdCC of the breast has a favorable prognosis, low rate of lymph node involvement, and uncommon distant metastases. It is generally cured by simple mastectomy. Chemotherapy, radiation, and hormonal treatment are infrequently used. We report a rare case of primary breast AdCC in a 75-year-old man who presented with a subareolar, well-defined, 2.2-cm mass. Breast core biopsy showed invasive AdCC (Figure 44, A) with triple-negative phenotype (negative for ER, PR, and HER2/neu). The cells were positive for p63 (Figure, D), c-Kit (Figure, E), SMMHC, and E-cadherin. Ki-67 labeling index was 28% and Her2:CEP17 by fluorescence in situ hybridization (FISH) was not amplified (Figure, F). Our patient underwent total mastectomy (Figure, B, C). The AJCC pathologic staging was pT2 pN0 pM0. After 2 months of AdCC diagnosis, he was diagnosed with invasive high-grade papillary urothelial carcinoma of urinary bladder with lamina propria invasion. Transurethral resection of the bladder tumor showed 2 urothelial carcinomas. The first was 3 cm located at the bladder base and the second was 6 cm located at the posterior wall. He subsequently received local Bacillus Calmette-Guerin treatment and methotrexate/5-fluoro-uracil adjuvant chemotherapy. Patient is doing well without evidence of local recurrence or distant metastasis of either AdCC or urothelial carcinoma. The pathogenesis of synchronous occurrence of primary breast AdCC and bladder carcinoma is not clear and needs further investigation. We reviewed the literature about male primary breast AdCC (see Table).
KIT (CD117) Is Overexpressed in a Subset of Lung Adenocarcinomas: A Morphologic and Genetic Analysis: (Poster No. 133)
Context: Lung carcinoma–related mortality is still the leading cause of cancer deaths worldwide; therefore, identifying potential pharmacologic targets is of great importance. KIT (CD117) is a receptor tyrosine kinase, and its mutations have been linked to some cancers; however, its role in lung cancer is controversial. Here, we aimed to correlate KIT-expressing carcinomas with their morphologic features and molecular alterations and identify potential predictors of the tumor KIT expression status.
Design: One hundred fifty-two surgically resected non–small cell lung carcinomas for which tissue was available for ancillary studies were analyzed. KIT (CD117) immunohistochemistry was performed and graded according to intensity (0–3+). Histomorphologic features were documented, including predominant growth pattern. KIT polymerase chain reaction sequencing was performed.
Results: A total of 42 KIT positive adenocarcinomas (ADC) (27.5%) were identified, 15 with weak (35.7%), 19 with moderate (45.2%), and 8 with strong (19.1%) staining patterns. KIT-positive ADC showed more acinar (48.9% versus 37%) and papillary (25.6% versus 14%) growth patterns. Invasive mucinous ADC showed less KIT expression than conventional ADC (7% versus 13%). All solid ADCs (6.4%), squamous cell carcinomas (3.2%), and adenosquamous carcinomas (2.6%) were KIT negative. No mutations on KIT exons 9, 11, or 13 were identified. A representative KIT-positive ADC is shown (Figure 45).
Conclusions: KIT-expressing cases failed to show mutations in exons 9, 11, or 13, likely representing wild-type KIT overexpression. KIT-overexpressing ADCs display more papillary and acinar growth patterns, with all solid ADCs failing to overexpress KIT. Therapeutic strategies directed at KIT should be focused on posttranscriptional events.
Eosinophilic Granulomatosis With Polyangiitis Concurrent With Primary Lung Adenocarcinoma: A Case Study and Review of the Literature: (Poster No. 136)
Eosinophilic granulomatosis with polyangiitis (EGPA/Churg-Strauss syndrome) is an uncommon systemic vasculitis first described by Drs Jacob Churg and Lotte Strauss in 1951. EGPA is currently defined by the American College of Rheumatology by having 4 or more of the following: (1) asthma; (2) eosinophilia (>10%); (3) neuropathy; (4) migratory or transient radiographic pulmonary findings of small centrilobular nodules, peripheral ground-glass opacities, consolidation, bronchial dilatation, wall thickening, and interlobular septal thickening; (5) paranasal sinus abnormality; and (6) a biopsy demonstrating necrotizing vasculitis, extravascular granuloma, and eosinophils. EGPA is currently classified as an antineutrophil cytoplasmic antibody-associated small-vessel vasculitis, along with microscopic polyangiitis and granulomatosis with polyangiitis. Recent studies suggest an increased cancer risk with microscopic polyangiitis and granulomatosis with polyangiitis; however, an increased cancer risk with EGPA has not been established, with 2 case reports of solid organ malignancies documented. We present a case of a 52-year-old woman with a history of asthma, chronic sinusitis/rhinitis, and peripheral eosinophilia who underwent a right upper lung lobectomy lymphadenectomy. This revealed a 2-cm, nonmucinous invasive adenocarcinoma, acinar predominant, with concurrent abundant extravascular granulomas and eosinophils with eosinophilic and granulomatous small vessel vasculitis. Three thoracic lymph nodes demonstrated abundant extravascular nonnecrotizing granulomas and eosinophils. This allowed for the diagnosis of concurrent lung adenocarcinoma and previously undiagnosed EGPA. EGPA is a clinically challenging diagnosis to make and is underrecognized with disease onset lagging diagnosis by 12 years. This case highlights the third case of EGPA associated with solid organ malignancy and the first with lung adenocarcinoma (Figure 46).
Correlation of Immunohistochemical Stain for Pepsin on Transbronchial Biopsy With Pepsin Levels in Bronchoalveolar Lavage Fluid in Lung Transplant Patients: (Poster No. 141)
Context: Gastroesophageal reflux disease (GERD) is a potential risk factor for allograft survival in patients with lung transplants. The GERD symptoms along with detectable pepsin in bronchoalveolar lavage (BAL) reflexes patients to laparoscopic antireflux surgery. Immunohistochemical (IHC) detection of pepsin in laryngeal mucosa has been reported to be a sensitive and specific test for diagnosing laryngopharyngeal reflux (LPR). Our goal was to test the correlation between detectable BAL pepsin and pepsin IHC stain to further the possibility of using pepsin IHC stain in transbronchial biopsies from transplant patients as a marker for GERD.
Design: One hundred fifty-seven transbronchial biopsies obtained from 74 patients in 2009–2010 were selected. Paraffin sections were stained for pepsin using appropriate positive controls (stomach) and negative controls (lung from nontransplant patients). Slides were evaluated by 2 pathologists with consensus achieved on discrepant cases. Intracellular and extracellular positivity was recorded and compared with BAL pepsin levels (n = 65). Fischer exact test was used for statistical analysis; P value <.05 was considered statistically significant.
Results: Our results show that pepsin IHC staining did not correlate with BAL pepsin levels (see Table). Calculated P value for intracellular and extracellular positivity was .67 and .42, respectively, which was not statistically significant.
Conclusions: The immunostain for pepsin was poorly reproducible in transbronchial biopsies with high interobserver and intraobserver variability. More so, there was no correlation between BAL pepsin levels and IHC staining pattern in transbronchial biopsies from transplant patients. We conclude that IHC stain for pepsin has no role in the diagnosis of GERD in transplant patients.
Synchronous Small Cell Carcinoma and Typical Carcinoid Tumor in the Same Lung Lobe: (Poster No. 142)
Based on World Health Organization classification, primary pulmonary neuroendocrine carcinoma has 4 subtypes: typical carcinoids, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma. Synchronous lung neuroendocrine tumor in the same lobe has not been found in the literature, to our knowledge. Here, we present the case of a 71-year-old woman with a history of chronic obstructive pulmonary disease, hypertension, and congestive heart failure who came to the hospital for productive cough. She had smoked one pack of cigarettes per day for the past 58 years. Positron emission tomography-computed tomography identified a peripherally located 2.3 × 1.1-cm nodule in the left lower lobe of lung, which contacted the peripheral pleural surface. A left video-assisted thoracoscopic wedge resection was performed. The 24-g, 10 × 5.7 × 3-cm lung wedge showed a gray nodular area (1.8 cm) in the pleura, which connected to a 2.3 × 1.9 × 1.2-cm, irregular, firm, pink-white lesion in the parenchyma. Microscopically, the lesion contained one larger mass (2.3 cm) and 3 well-circumscribed nodules (2–4 mm). The larger mass contained a sheet of small cells with minimal cytoplasm, salt-and-pepper chromatin, and without prominent nucleoli. Smudging cells, nuclear molding, and necrosis were present, and mitotic figure was high (Ki-67 > 95%). Nests of bland, polygonal cells with finely granular chromatin were seen in the nodules without necrosis or frequent mitosis (Ki-67 was 5%). Synaptophysin immunostain was positive for the tumor cells both in the larger mass and smaller nodules (Figure 47).
Pleuroparenchymal Fibroelastosis: A Report of the First 2 Cases Diagnosed at Autopsy: (Poster No. 144)
Pleuroparenchymal fibroelastosis is a rare condition characterized by the proliferation of interstitial elastic fibers, predominantly subpleural and more commonly seen in upper lobes. The etiology is unknown, and no specific diagnostic criteria have been reported. Because the condition was initially characterized in 2004, only 25 cases have been described in the literature. Here, we report the first 2 cases in which diagnosis has been made at the time of autopsy. One patient, a 58-year-old woman, carried a diagnosis of familial idiopathic pulmonary fibrosis made on imaging for 5 years before her final admission. The second case was an 87-year-old woman with multiple comorbidities residing at a long-term care facility who experienced a prolonged and progressive downhill course with no specific, acute event suspected at the time of her demise. In both cases, microscopy revealed a diffuse interstitial pneumonia characterized by a diffuse proliferation of predominantly elastic fibers (Figure 48). The more extensive nature of the parenchymal fibroelastosis in these cases, as compared with previously reported cases, is likely attributable to the longer duration of the disease. Additionally, the condition in these patients was discovered on autopsy when the entirety of both lungs could be histologically examined, rather than being limited to imaging and biopsy. Our findings suggest that pleuroparenchymal fibroelastosis may be a more diffuse condition than previously reported and that it must be considered in the differential diagnosis of fibrous interstitial pneumonia at the time of autopsy and in examination of explanted lungs.
Pulmonary Smooth Muscle Tumors of Uncertain Malignant Potential: Possible Malignant Transformation From a Benign Metastasizing Leiomyoma?: (Poster No. 146)
Pulmonary smooth muscle tumors are not an uncommon finding in females with concomitant uterine leiomyomas. These have been previously described as benign, metastasizing leiomyomas in the literature. We present a case of a 58-year-old, HIV-positive woman who presented with multiple pulmonary nodules in the upper lobe of the right lung. Review of previous pathology revealed she had undergone total hysterectomy for a uterine leiomyoma 3 years prior. Histologically, the uterine tumor showed minimal atypia with rare mitosis (1/10 high-power field [HPF]) and no necrosis. There were 2 well-circumscribed nodules from the upper lobe of the right lung (1.3 and 0.5 cm) showing a tan-white, bulging, and whorled cut surface. These were composed of plump spindle cells admixed with scattered cleft-like spaces lined by cuboidal epithelium. The spindle cells exhibited mild to moderate atypia with increased mitosis (9/10 HPF) (Figure 49). Immunohistochemistry showed the spindle cells were positive for smooth muscle antigen and ER with 30% Ki-67 positivity. HHV8, Epstein-Barr virus, and PR were negative. Controversy still exists as to whether these entities represent true metastatic lesions or are multicentric leiomyomatous tumors. There has been some recent evidence showing clonality in cases where both the pulmonary and uterine tumors are benign-appearing. In this particular case, the histology of the pulmonary and uterine tumors gives rise to the possibility of a metastasizing uterine leiomyoma with subsequent malignant transformation.
Sebaceous Gland Carcinoma Presenting as an Airway Obstruction: (Poster No. 151)
Metastatic sebaceous gland carcinomas are extremely rare, and when they do occur, the primary site is typically the eyelid adnexae or skin. We report a case of a 57-year-old woman with a recent diagnosis of lung cancer with metastases to the mediastinum and brain. No known skin lesions were identified during her oncologic evaluation. She presented with an acute airway obstruction and 100% occlusion of the right mainstem bronchus. Sections of the obstructing tumor, removed by bronchoscopy, showed a carcinoma characterized by lobulated cells with foamy cytoplasm, marked nuclear pleomorphism, and abundant coagulative necrosis. Other areas of the tumor showed mucin-producing glands. The mitotic count was 21/10 high-power fields with atypical figures. The differential diagnosis initially included a squamous cell carcinoma with sebaceous differentiation, a salivary gland type tumor, or a metastatic sebaceous gland carcinoma. Adipophilin (×40) showed strong, dotlike staining of lipid globules and a focal vesicular pattern (Figure 50, arrows) in a subset of foamy cells with membranous staining for CAM 5.2 and CK7. The tumor cells were nonreactive for TTF1, PAX8, CD56, CK20, p40, and p63. Although the patient's presentation was advanced, the diagnosis of sebaceous gland carcinoma was important because of its association with Muir-Torre syndrome. In such a case, the metastases present in this patient most likely represented an aggressive sebaceous gland carcinoma. Currently, the tumor is being tested for microsatellite instability. The initial clinical presentation also raises the possibility of a primary lung sebaceous gland carcinoma, an entity with only one such case known in the literature.
Pulmonary Adenoleiomyomatous Hamartoma: A Case Report of a Rare Presentation: (Poster No. 153)
We report a rare variant of a pulmonary hamartoma with unusual adenoleiomyomatous features. This is a case of a 56-year-old woman with a solitary pulmonary nodule that increased in size for 3 years. She also reported unintentional weight loss (15 lb [6.8 kg]) and significant progressive dysphagia within the same period. A computed tomography scan of the lungs showed an 8-mm mass at the periphery of the right lower lobe with features suspicious for a primary lung cancer. Because of concerns of a malignancy, a wedge resection was performed. Gross examination of the lesion revealed a small, lobulated, and ovoid mass with a homogenous, firm, white cut surface. Microscopically, the tumor was composed of nodular proliferation of interlacing bundles of smooth muscle and slitlike spaces lined by glandular epithelium. The cuboidal to columnar epithelium was cytologically bland with eosinophilic cytoplasm and basally located oval nuclei. The smooth muscle component also appeared benign with no cytologic atypia or increased mitosis. No cartilage or adipose tissue was seen (Figure 51, A). A panel of immunostains was performed. The epithelial cells were positive for TTF1 (Figure, B), confirming the pulmonary origin, and the smooth muscle component was positive for calponin (Figure, C), smooth muscle myosin (Figure, D) and desmin. p63 and S100 stains were negative. The patient showed no evidence of disease recurrence at 3 months follow-up. This case illustrates an unusual clinical and radiologic presentation of a rare, adenoleiomyomatous variant of a pulmonary hamartoma.
Reevaluation of Expression of Immunomarkers in Lung Adenocarcinomas: (Poster No. 155)
Context: When working on tumors of uncertain origin, lung adenocarcinomas (ADCs) are often a differential consideration. TTF1 and napsin A are relatively specific lung adenocarcinoma immuno-markers, expressed in approximately 75% of cases. Other organ-specific immunomarkers may infrequently be expressed in lung ADCs. To investigate the frequency of aberrant expression of other tissue-specific immunomarkers in lung ADCs, we evaluated the expression of more than 80 commonly used immunomarkers in lung ADCs, including (1) epithelial markers, (2) transcription factors/nuclear staining markers, (3) mucin genes, and (4) tumor-associated proteins, such as HBME1, calretinin, mammaglobin, GCDFP-15, uroplakin II, RCC, PSA, galectin-3, arginase 1, HepPar1, glypican 3, inhibin-α, pVHL, TFF1, maspin, S100, S100P, IMP3, β-catenin, P504S, and melanoma markers.
Design: Immunohistochemical evaluation of the aforementioned immunomarkers in 84 lung ADCs on tissue microarray sections was performed, which were graded as positive when more than 5% of the tumor cells stained.
Results: Expression of TTF1 and napsin A was seen in 81% and 75% of the cases, respectively. The aberrant expression of selected immunomarkers in lung ADCs is summarized in the Table. The expression of ER, GATA3, GCDFP-15, CDX2, SATB2, SALL4, OCT4, uroplakin II, PAX8, RCC, ERG, PSA, D2-40, glypican 3, and melanoma markers (S100, MART-1, HMB-45, MiTF, and SOX10) was not observed.
Conclusions: Caution should be taken to avoid potential pitfalls because some tissue-specific immunomarkers can be significantly or rarely expressed in lung ADCs. It is preferable to use a small panel of immunomarkers when working on a tumor of uncertain origin, especially if a lung primary is considered.
Concurrent Mediastinal Lymph Node Metastases From Carcinoma of the Lung and the Breast: (Poster No. 156)
Metastatic disease to mediastinal lymph node from extrathoracic neoplasms is an infrequent event. The most common extrathoracic primary cancers are genitourinary, head and neck, breast, and malignant melanoma. Concurrent metastasis from both lung and breast carcinoma have not been reported in the literature. A 59-year-old, white woman with past medical history of breast cancer in 1999 and adenocarcinoma of the right lung in 2011 underwent a positron emission tomography/computed tomography of the chest, which demonstrated an increased trace uptake activity of the pretracheal and paratracheal lymph nodes, concerning for lymph node metastasis. Biopsies of these 2 lymph nodes were performed. Microscopic examination of high right paratracheal lymph nodes revealed infiltration of malignant cells that were large and strongly and diffusely positive for CK7, TTF1, napsin, and E-cadherin; partially and weakly positive for ER; and negative for mammaglobin, CK20, PR, and GCDFP-15. The findings support the diagnosis of metastatic adenocarcinoma from a lung primary. Microscopic examination of the pretracheal lymph nodes showed nests of smaller tumor cells with small and relatively round nuclei. The tumor cells were strongly and diffusely positive for ER, CK7, and E-cadherin, and negative for TTF1, napsin, mammaglobin, CK20, PR, and GCDFP-15. The findings support the diagnosis of metastatic adenocarcinoma from a breast primary. The present report demonstrated the first case of concurrent mediastinal metastases from both intrathoracic and extrathoracic carcinomas, and careful evaluations of the histology of every lymph node with a panel of immunohistochemistry studies along with clinical history will lead to the correct diagnosis (Figure 52).
Simple Tumor Enucleation, Without Hilar Vasculature Clamping, for Small Renal Cancers—Is it Feasible?: (Poster No. 2)
Context: Small renal cancers are increasingly detected in aging patients with reduced nephron mass and vascular comorbidities, which put them at risk for loss of renal function requiring dialysis. A simple tumor enucleation without clamping of hilar vasculature may be applicable to small renal tumors, thus affording maximal nephron sparing as well as avoidance of ischemia because of clamping. However, despite generally excellent oncologic outcomes, concerns have been raised regarding the oncologic safety of such procedures.
Design: A total of 31 small renal tumors were removed by a simple enucleation between March 2012 and June 2013. We evaluated the gross and microscopic morphology of tumor pseudocapsule and correlated those with tumor size, nuclear grade, and tumor subtype.
Results: All tumors were grossly intact with smooth, focally semitransparent pseudocapsules, except for one specimen that became fragmented during evaluation via laparoscopic port. Microscopically, the pseudocapsules were composed of fibrous tissue and adjacent compressed renal parenchyma, frequently with sclerosed glomeruli and tubules. In 7 tumors, despite grossly intact appearance, microscopically, there were focal pseudocapsule penetration and positive margins. The presence of pseudocapsule penetration is significantly associated with tumor Fuhrman grade (Figure 53).
Conclusions: This study indicated that most small renal masses demonstrate a continuous, nonfenestrated, fibrous pseudocapsule. Pseudocapsule penetration represents an additional prognostic factor in patients with early stage renal cell carcinoma. Careful evaluation of the status of the pseudocapsule is important in patients treated with nephron-sparing procedures, in particular, enucleation.
Urethral Enteric-Type Adenocarcinoma Mimicking Primary Clear Cell Adenocarcinoma: A Case Report With Evidence of Stepwise Pathogenesis: (Poster No. 7)
Primary urethral adenocarcinoma is a rare entity, and little is known about its pathogenesis. Although many of these tumors are identified in association with intestinal metaplasia, the role of intestinal metaplasia in the pathogenesis has been debated. We report a case of a 71-year-old woman with a history of long-standing urethral diverticulum, complicated by urethral-vaginal fistula, who presented with hematuria. Cystoscopic biopsy of the trigone confirmed an unusual malignancy, originally favored to be clear cell (so-called mesonephric ) adenocarcinoma. Subsequently, radical cystectomy and urethrectomy revealed a pT3b pNX pM0 adenocarcinoma of the proximal bladder and urethra. The dominant mass was composed of large cells with abundant clear cytoplasm arranged in mixed solid, tubular, and cribriform architecture (Figure 54, A). Scattered eosinophilic luminal secretions were present (Figure, B). Interestingly, sampling of the associated urethral diverticulum revealed extensive intestinal metaplasia with a discrete transition to high-grade dysplasia (Figure, C). The enteric-type high-grade dysplasia and the dominant clear cell tumor shared similar immuno-phenotype (CDX2+ and p53+, Figure, D; PAX8−). Further, an identical p53 point mutation was identified by next-generation sequencing using the Ion Torrent AmpliSeq Cancer HotSpot Panel (version 2, Life Technologies, Carlsbad, Calif) strongly supporting a direct pathogenetic relationship. Herein, we report distinctive findings of an enteric-type adenocarcinoma mimicking clear cell adenocarcinoma of the urethra. Further, our data provide concrete evidence of urethral adenocarcinoma arising directly from intestinal metaplasia via a dysplasia-to-invasive carcinoma sequence. At 6-month follow-up, the patient was found to have multiple pulmonary metastases but no evidence of pelvic recurrence. The findings and differential diagnosis are reviewed.
An Unusual Composite Tumor: Chromophobe Renal Cell Carcinoma Associated With Foci of Collecting Duct-Type Carcinoma: (Poster No. 11)
We report the case of a 69-year-old woman who originally presented with an incidental renal mass, at the time diagnosed as oncocytoma by cytology and needle core biopsy. In less than 2 years, the mass doubled in size, raising concern for malignancy. Surgical management was pursued. The nephrectomy specimen contained a 6.0-cm, relatively circumscribed, tan-brown cystic and solid mass confined to the kidney. Upon microscopic evaluation, there were 2 morphologically distinct neoplastic populations. The tumor was predominantly composed of monotonous, eosinophilic cells with distinct cytoplasmic borders and raisinoid nuclei with a perinuclear halo, in keeping with chromophobe renal cell carcinoma. In the midaspect of the tumor, high-grade tubulopapillary foci with hobnailed pleomorphic nuclei and extracellular mucin were present, which resembled collecting duct carcinoma. Both components stained with CK7 and E-cadherin, while expectedly, only the collecting duct carcinoma stained with vimentin (Figure 55). As anticipated, Hale-Colloidal iron showed a differential pattern of staining in chromophobe renal cell carcinoma and collecting duct carcinoma. A few case reports of collision tumors involving chromo-phobe carcinoma are described in the English literature; the current case describes yet another extremely unusual variant. Awareness of these entities is of paramount importance in the determination of prognosis, management, and diagnosis of patients with chromophobe renal cell carcinoma. Detailed attention to the evolving clinical course and radiologic features as well as the adequacy of tumor sampling is critical as highlighted by the current case.
A Rare Case of Urachal Carcinoma Presenting as Umbilical Hernia: (Poster No. 14)
The urachus is an embryologic remnant that connects the umbilicus to the bladder. It regresses into the median umbilical ligament before birth. Urachal carcinoma is a rare, highly malignant tumor that requires clinical suspicion, imaging, and pathologic examination for appropriate diagnosis. It is slightly more common in males than females. It usually present with hematuria, symptoms of bladder irritation, abdominal pain, or as an abdominal mass. We present a case of a 50-year-old woman who was noted to have an umbilical hernia during breast reconstruction. The pathologic examination of the hernia sac revealed nests of pleomorphic, malignant cells with a high nuclear to cytoplasmic ratio, and hyperchromatic nuclei with prominent nucleoli. The tumor cells were positive for CK7, CDX2, CK19, and CEA and were negative for mucin, uroplakin, p63, CK20, CA 125, CA 19-9, TTF1, ER, mammaglobin, CD56, and GCDFP-15. Based on the staining profile, a specific primary tumor could not be identified. Before clinical workup, the diagnosis was poorly differentiated metastatic carcinoma, and the differential diagnosis included upper gastrointestinal, pancreatic, cholangiocarcinoma, or colorectal carcinoma, among others, with recommendation for clinical correlation. Computed tomography and positron emission tomography scans revealed a heterogenous density at the umbilicus, which showed intense hypermetabolic activity and soft tissue thickening. Based on the radiologic, pathologic, and clinical findings, a diagnosis of urachal carcinoma, with no evidence of metastasis or spread beyond the umbilical area, was concluded. The patient currently awaits partial cystectomy, umbilectomy with urachal remnant excision (Figure 56).
MMP-26 May Detect Prostate Cancer Risk Regardless of Needle Biopsy Pathology: (Poster No. 15)
Context: Several molecular diagnostic approaches have been proposed to detect coexisting, unsampled prostate cancer in histologically negative biopsy cores, or urine. Most have relied on DNA promoter methylation, particularly that of GSTP1. Matrix metalloprotease 26 (MMP-26) was reported as overexpressed in prostate cancer tissues, with peak expression in high-grade prostatic intraepithelial neoplasia. We compared these 2 alterations in prostate biopsy specimens.
Design: Curls of paraffin-embedded prostate biopsy tissue were cut into microfuge tubes. Complementary DNA was prepared using SuperScript First-Strand Synthesis (Invitrogen, Grand Island, NY), and specific forward and reverse MMP-26 primers were used in 35 thermal cycles of quantitative reverse transcription-polymerase chain reaction (RT-PCR); ΔCT (difference in threshold cycle) normalized to 18S RNA was scored:+++, 10−6 or more;++, 10−7 or more; and +, 10−8 or more. Fluorogenic, methylation-specific PCR of the bisulfite-converted GSTP1 promoter was performed on the same specimens, and the methylation index was determined by normalizing computed tomography to β-actin.
Results: The Table shows the 12-part biopsy cases 1 and 2 with differing amounts and grades of cancer: 20% to 99% cancer in 5 cores, and 5% cancer in 1 core respectively. In case 3 with 14 cores of benign prostatic tissue, MMP-26 was positive in 3, suggesting increased risk. In another 6-core case of all-benign prostatic tissue, the left midcore biopsy had the highest MMP-26 expression; at the 3-year follow-up biopsy, the left midsample was diagnosed with Gleason 3 +3 =6 cancer in 5% of the core.
Conclusions: In this pilot study, MMP-26 overexpression occurred more frequently than GSTP1 promoter methylation in prostate biopsies. Validation in a larger population with repeat biopsies is required.
Polyomavirus-Associated, Poorly Differentiated Clear Cell Adenocarcinoma of the Urinary Bladder in a Kidney Transplant Patient: (Poster No. 18)
Clear cell adenocarcinoma of the urinary tract is a rare neoplasm predominantly affecting the urethra and is more common in women. We report a case of 32-year-old man with a history of bilateral lung transplant for cystic fibrosis and kidney transplant for immunoglobulin A (IgA) nephropathy. Six years after the kidney transplant, he presented with dysuria, and cystoscopic examination showed a 4.5-cm mass in the bladder. Urinary bladder barbotage and biopsy was obtained. A concomitant plasma BK virus DNA polymerase chain reaction (PCR) showed 84 525 copies/mL. The histologic sections of the tumor showed poorly differentiated adenocarcinoma with tubulocystic, clear cell, and sarcomatoid differentiation, which was also observed in the bladder barbotage and the subsequent partial cystectomy specimen (Figure 57, A). Immunohistochemical stains are outlined as below: positive: SV40 (polyomavirus; Figure, B and inset), PAX8 (Figure, C), cytokeratin 5/6, and CD10 (Figure, D); negative: AMACR, PAX2, and CK7. Recent reports on clear cell adenocarcinoma of the urinary bladder raise the possibility of a renal tubular/mesonephric origin for some of these tumors. Rare reports of coexistence of polyomavirus-associated urothelial carcinoma of the urinary bladder with BK viruria have been published. Our case showed diffuse positivity for SV40 (polyomavirus) immunohistochemical stain in the tumor cells, whereas adjacent normal cells were negative. Additionally, BK virus DNA PCR was not detected after the tumor excision. To our knowledge, this is the first case of clear cell adenocarcinoma associated with polyomavirus. This case adds to evidence for the possibility of BK virus in the pathogenesis of bladder cancer, especially in immunosuppressed patients.
Not All Renal Masses Are Wilms Tumor in Patients With Prior Wilms Tumor History: Meet IgG4-Related Kidney Disease: (Poster No. 19)
Wilms tumor is the most common renal tumor of childhood. Wilms tumor has the potential for both local and distant spread; approximately 5% to 10% of children present with bilateral or multicentric tumors. The most frequent sites of late recurrence are abdomen, lungs, and contralateral kidney. This is a case of an 11-year-old boy with left total nephrectomy for Wilms tumor 6 years previously, who presented with a new mass in his right kidney. Because of a high clinical suspicion of Wilms tumor recurrence, a partial nephrectomy was pursued. The specimen contained a 3-cm, circumscribed but unencapsulated, gray-tan, myxoid, somewhat lobulated mass that was histologically characterized by a florid tubulointerstitial nephritis predominated by plasma cells. Most lymphocytes were composed of T cells as shown by a CD3 immunostain. There was no evidence of Wilms tumor or infectious agents. An immunoglobulin G4 (IgG4) immunostain showed multiple foci of strong plasma cell immunoreactivity, greater than 30 IgG4+ plasma cells/high-power field in the most concentrated area (Figure 58). The IgG4-related kidney disease is a recently recognized autoimmune disorder, often manifest as inflammatory masses, which responds very well to steroid treatment. Although its clinical diagnostic criteria are in progress, plasma cell–rich tubulointerstitial nephritis with more than 10 IgG4+ plasma cells/high-power field in the most concentrated field is believed to meet the pathologic diagnosis, as seen in our cases. Because IgG4-related kidney disease is rare in the pediatric population, our case underscores the need to keep this rare disorder in the differential for late recurrence after Wilms tumor history.
Angiomyolipoma With Regional Lymph Node Involvement in a Patient With Hemochromatosis: A Case Report and Literature Review: (Poster No. 20)
Angiomyolipoma (AML) is a mesenchymal tumor belonging to a family of lesions characterized by proliferation of perivascular epithelioid cells, accounting for 1% of renal tumors. Conventional AMLs (nonepithelioid type) are known to be benign, whereas epithelioid variants are known to be clinically more aggressive. Usually, AML occurs sporadically; however, when seen in familial syndromes, most commonly tuberous sclerosis, it tends to be bilateral and multifocal. A 54-year-old man with a history of hemochromatosis and no clinical evidence of tuberous sclerosis presented with a solitary left renal mass, extending into the perirenal fat. Subsequent radical nephrectomy with periaortic lymph node dissection revealed a 4.6-cm, lobulated, hemorrhagic mass involving kidney and perinephric adipose tissue. Histopathologically, a classic triphasic histology, composed of mature fat, spindle and epithelioid smooth muscle cells, and abnormal, thick-walled blood vessels, was seen (Figure 59, A). Five periaortic lymph nodes ranging from 0.3 cm to 0.7 cm were also involved (Figure, B and C). Immunostains for HMB-45 (Figure, D), Melan-A, SMA, and vimentin were positive in both the kidney and lymph nodes, confirming the AML diagnosis. PAX8, S100, CD10, desmin, and EMA were negative. Lymph node involvement should not be considered metastasis but rather multifocal growth pattern of the tumor. Although AML can rarely show vascular invasion and regional lymph node involvement, the true incidence of lymph node involvement is not known. Moreover, the affected genes in tuberous sclerosis are TSC1 and TSC2, whereas the HFE gene is mutated in hemochromatosis. An extensive literature review did not reveal any reported association between hemochromatosis and AML.
Immunohistochemical Distinction Between Metastatic Renal Cell Carcinoma to the Adrenal and Primary Adrenal Lesions: (Poster No. 23)
Context: The morphology of clear cell renal cell carcinoma, when low grade, overlaps with normal adrenal and primary adrenal adenoma, when high grade, with carcinoma. We applied a panel of 10 antibodies to 62 cases to determine the optimal antibody panel to discriminate these entities.
Design: Resection specimens with established diagnoses from the past 18 years were available from Medical College of Wisconsin (28 cases) and Charles University Hospital (34 cases): 34 men and 28 women. As controls, 42 cases contained normal adrenal tissue. Areas of tumor or normal adrenal tissue were punched from paraffin blocks and assembled into tissue microarrays; duplicate spots represented each entity. Immunostains included CAM 5.2 (1:50, Becton Dickinson, Franklin Lakes, NJ), equilibrative nucleoside transporter 1, ENT1 (1:100, Sigma-Aldrich, St Louis, Mo), PAX8 (1:150, Proteintech, Chicago, Ill), and steroid receptor coactivator, SRC1 (1:100, Cell Signaling, Danvers, Mass); RCC marker (1:50) and others (undiluted) were from Dako (Carpinteria, Calif). Reactivity was scored from 0 to 3+.
Results: Area-under-curve analysis (SAS Institute, Cary, North Carolina) ranked the significant markers for each entity (see Table). Logistic regression analysis disclosed that PAX8 nuclear reactivity plus absence of PAX8 cytoplasmic reactivity, discriminated renal cell carcinoma, as did CAIX (all P < .001). For normal adrenal and primary adrenal adenoma and carcinoma, there were 2 to 3 significant markers. No markers significantly discriminated oncocytic adrenal carcinoma; however, synaptophysin was near significant.
Conclusions: Two markers proved discriminatory for renal cell carcinoma; 6 markers were most effective for adrenal lesions. The rare entity of oncocytic adrenal carcinoma has no ideal marker but can usually be distinguished by its oncocytic histology. Prospective evaluation with a larger sample size is pending.
An Immunohistochemical and Targeted Molecular Analysis of Sarcomatoid and Rhabdoid Renal Cell Carcinoma: (Poster No. 24)
Context: Sarcomatoid renal cell carcinoma (sRCC) and renal cell carcinoma with rhabdoid morphology (rRCC) are rare subsets of renal carcinoma associated with very aggressive behavior and a dismal prognosis. These tumors remain relatively undercharacterized. The aim of our study was to use multiple immunohistochemistry antibodies as well as a targeted molecular analysis to compare the expression of proteins in the conventional carcinoma component verses the sarcomatoid/rhabdoid component of these tumors.
Design: Included in this retrospective study were 25 cases of sRCC. Representative areas of sarcoma and carcinoma were selected from each case and compiled into a tissue microarray. Immunohistochemical stains were performed at ARUP Laboratories (Salt Lake City, Utah) with commercially available antibodies for Pim1, Pim2, Pim3, phosphorylated mTOR, phosphorylated S6rib, PTEN, IMP3, β-catenin, E-cadherin, p53, INI-1, and EMA. Cases were graded (0–4) based on the percentage of cells positive for each antibody (0, <5%; 1, 5%–25%; 2, 26%–50%; 3, 51%–75%; 4, >75%). Scores of 2 or greater were considered positive. Molecular testing was performed on paraffin-embedded tissues from 6 samples using a Sequenom (San Diego, Calif) panel of 277 known mutations.
Results: The percentage of tumors with positive staining in conventional carcinoma areas compared with sarcomatoid/rhabdoid areas is provided in the Table. No targetable mutations were detected by the Sequenom panel.
Conclusion: Sarcomatoid and rhabdoid components appear to show increased Pim kinase, IMP3, and p53 expression when compared with the conventional renal cell carcinoma component. Expression of the aforementioned markers may contribute to disease progression and serve as a potential site for targeted therapy.
Primary Renal Angiosarcoma in a 44-Year-Old Man: (Poster No. 25)
Angiosarcomas are one of the rarest forms of soft tissue neoplasms. They account for less than 1% of all sarcomas and have a predilection for skin and superficial soft tissue. We report a case of a 44-year-old man who presented with left flank pain of 2-week duration and 15-pound (6.8 kg) weight loss and fatigue for 2 months. A computed tomography scan of the abdomen and pelvis showed an enlarged diffusely heterogenous mass involving the left kidney, which was considered compatible with renal cell carcinoma. A radical nephrectomy of the left kidney revealed an irregular hemorrhagic mass that extended through the renal capsule into perinephric fat. Microscopic examination revealed a high-grade spindle cell malignant neoplasm, which focally revealed a typical pattern of a high-grade angiosarcoma. Immunohistochemical stains confirmed the vascular nature of the tumor because the malignant cells were strongly positive for CD31 and CD34, whereas they were focally positive for factor XIIIa. The tumor cells were negative for pankeratin and RCC, whereas they were positive for CD10. The morphology of the tumor and immunohistochemical stains strongly support the diagnosis of a high-grade angiosarcoma. The patient was also found to have bone and lung metastasis. Angiosarcomas of the kidney are very rare, and less than a dozen cases only have been documented. The rarity and aggressiveness of this case makes it not only intriguing but also worthy of documentation to aid in diagnosing future cases of renal angiosarcomas (Figure 60).
Tubulocystic Renal Cell Carcinoma With Necrosis: An Unusual Feature in a Rare Tumor: (Poster No. 28)
Tubulocystic renal cell carcinoma is a rare subtype of renal cell carcinoma, in which necrosis has yet to be described. We describe a case in our institution of this tumor with this unusual histologic feature. A 65-year-old man presented with loss of appetite and loss of weight. On physical examination, a palpable mass was noted in the right hypochondrium, which on computed tomography scan of abdomen and pelvis, was revealed to be a complex cystic mass measuring 23.0 × 14.5 ×14.2 cm, involving the entire right kidney. A radical nephrectomy was performed. Gross examination showed an encapsulated, multicystic tumor containing hemorrhagic fluid. On microscopy, the tumor had a tubulocystic appearance (Figure 61). The lining epithelium featured cuboidal, flat, and hobnail cells with eosinophilic cytoplasm and enlarged nuclei with prominent nucleoli. Focally (<5%), the tumor exhibited areas with papillary architecture. No foamy histiocytes or psammomatous calcifications were seen. Areas of necrosis were noted. No infiltrative growth pattern with stromal desmoplasia or sarcomatoid areas was seen. No lymphovascular emboli were present. Electron microscopy was performed on the tumor, and the tumor cells were shown to possess sparse, short microvilli as well as abundant mitochondria. Definite cytoplasmic interdigitation was not observed. The final diagnosis was that of a tubulocystic renal cell carcinoma. The patient developed metastasis within a year of diagnosis. We describe here a case report of such an entity with tumor necrosis, an unusual feature which may portend a more aggressive clinical course although that requires further study.
A Rare Case of Granulomatous Glomerular and Tubulointerstitial Nephritis: (Poster No. 32)
Renal sarcoidosis commonly presents with acute kidney injury but rarely glomerular disease, end-stage renal disease, and obstructive uropathy. To our knowledge, we are presenting the first case of glomerular involvement and effacement from extensive sarcoid granulomas. A 44-year-old man presented who with increased frequency in urination at night was found to have acute kidney injury, hypercalcemia, proteinuria, and hyperproteinemia without monoclonal spike. Computed tomography scan revealed diffuse, bilateral reticulo-nodular pulmonary opacities. An ultrasound-guided 3 renal cores biopsy of the left native kidney revealed near-total effacement of the renal tubules and glomeruli in 2 cores by numerous small, noncaseating granulomas (Figure 62, A and B). They were naked granulomas with multinucleated giant cells and extensive fibrosis with patchy, chronic inflammation (Figure, C). The third core contained 12 glomeruli, of which, 2 are globally sclerotic, 1 ischemic, 3 with mild mesangioproliferative changes, and 6 unremarkable glomeruli. Moderate to marked arteriolar and arterial sclerosis were present. Electron microscopy revealed no obvious abnormalities in the glomeruli not involved by granuloma (Figure, D). No bacteria, acid-fast bacilli or fungus were identified on special stains. Immunofluorescence studies were negative for immunoglobulin (Ig) G, IgA, IgM, C3, and C1q deposits. The classic findings on renal sarcoid biopsy are noncaseating granulomatous interstitial nephritis, giant cells, and normal glomeruli. Our case was unusual because, in addition to the tubulointerstitial damage, there was glomerular involvement and effacement by the sarcoid granuloma intensifying the renal function impairment with proteinuria.
Clear Cell Papillary Renal Cell Carcinoma Masquerading as a Renal Cyst: A Case Report of a Recently Recognized Unique Entity: (Poster No. 37)
Clear cell renal cell papillary carcinoma (CPRCC) is a recently described entity with an immunohistochemical and genetic profile distinct from that of the conventional renal cell carcinoma and papillary carcinoma. It was originally thought to be associated with end-stage and acquired renal cystic disease, but the patients with CPRCC in the large recent series did not have end-stage renal disease. Characteristic histologic features of these tumors are clear cells with nuclei above the basement membrane that imparts an appearance similar to subnuclear vacuoles of early secretory pattern endometrium. Our case is a 55 years-old patient with a history of hypertension-induced renal failure, who underwent workup for renal transplant and was found to have a 2.5-cm complex cystic lesion in the upper pole of the right kidney by ultrasound. The biopsy of the lesion showed predominantly cystic growth pattern. The neoplastic lining cells had low nuclear grade (Fuhrman grade 1 of 4). The lining neoplastic cells were positive for cytokeratin 7, CAIX, and focally for CD 10 and were negative for AMACR, supporting the diagnosis of CPRCC. Grossly, the resection specimen showed a 2.5-cm multilocular cystic tumor. Histologically, papillary and tubular growth pattern with characteristic clear cells and cystic areas were identified. There is no evidence of disease at 6 months follow-up. CPRCC should be considered in the differential diagnosis of cystic lesions and the described immunophenotype helps making the distinction (Figure 63).
Primary Leiomyosarcoma of Prostate: An Autopsy Case of a Rare Neoplasm With an Unusual Presentation: (Poster No. 40)
Primary leiomyosarcoma of the prostate is an extremely rare and aggressive neoplasm accounting for less than 0.1% of primary prostate malignancies. Many patients present with metastasis at the diagnosis. Here, we present an autopsy case of a 68-year-old man who was admitted for sepsis and mental status change with a past medical history of diabetes, hypertension, and hyperlipidemia. The patient had intermittent hematuria and urinary tract infection in the previous 2 years with progressive bowel obstruction. He died soon after from septic shock. Autopsy revealed a 10 ×10-cm solid mass with multifocal necrosis completely replacing the prostate and compressing the bladder at the proximal urethra and compressing but not infiltrating the wall of the rectum. Microscopically, the mass was composed predominantly of spindle cells in an interlacing fascicles pattern, intermixed with some large cells with bizarre nuclei (Figure 64). Immunostains showed positive staining for vimentin, smooth muscle actin and desmin, negative for prostate specific antigen, prostate-specific acid phospha-tase, pankeratin, CD117, Ki-67 shows 25% positivity. No metastasis was found. Leiomyosarcoma of the prostate is a mesenchymal tumor originating from smooth muscles of the prostate. Typically, it is large and has metastasis upon diagnosis. The most common sites of metastasis are lung, liver, and bone. The differential diagnoses for a spindle cell tumor in the prostate also include cellular leiomyoma, gastrointestinal stroma tumor of rectum, stromal sarcoma or stromal tumors of uncertain malignant potential, sarcomatoid carcinoma, inflammatory myofibroblastic tumor, solitary fibrous tumor, and rhabdomyosarcoma, among others.
Müllerian-Like Stroma in the Seminal Vesicle: Case Report and Literature Review: (Poster No. 42)
Müllerian remnants in male patients are most commonly testicular/ paratesticular lesions with typical müllerian epithelium and are usually of minimal clinical significance. Several neoplasms are known to contain müllerian-like stroma, such as mixed epithelial and stromal tumors of the kidney and mucinous cystic tumors of the pancreas, which occur predominantly, but not exclusively, in women. We present an incidental finding of a focus of müllerian-like stroma in the seminal vesicle. The patient was a 62-year-old man who underwent a radical prostatectomy for prostatic adenocarcinoma, Gleason score 7 (3 + 4), which was confined to the prostate. He was not receiving hormonal treatment before surgery. A small focus (3 mm) of müllerian-like stroma was found in the left seminal vesicle. Histologically, the area showed spindly cells embedded in collagen bundles, reminiscent of müllerian stroma. Immunohistochemical studies (Figure 65) showed strong, diffuse positivity for ER (3+), PR (3+), and CD10 (3+) and strong, focal positivity for SMA (3+) and desmin (3+). An extensive literature search revealed 2 cases of müllerian tumors in the seminal vesicle, both diagnosed as adenosarcoma-like tumors. However, no references of müllerian-like stroma in either the prostate or the seminal vesicle were previously reported. To our knowledge, this would be the first case of a müllerian-like stroma described in the seminal vesicle. Whether this represents a true embryologic rest or a localized stromal reaction to hormones is unknown. Pathologists should be aware that such an entity can occur in the seminal vesicle and potentially give rise to rare neoplasms.
Isolated Renal Metastasis From Neuroendocrine Tumor: How Rare is Rare?: (Poster No. 44)
Neuroendocrine tumors are epithelial neoplasms arising from neuroendocrine cells, most commonly in the gastrointestinal tract and the bronchopulmonary system. Primary neuroendocrine tumors of kidney are hypothesized to arise as a result of stem cell differentiation, metaplastic change, or migration of bronchial or intestinal epithelium to the kidney. The kidney is a rare site for primary neuroendocrine tumors (<1% of renal epithelial tumors) and is even rarer as a metastatic site. We report an extremely rare case of metastatic renal neuroendocrine tumor from a rectal primary without prior or concurrent liver metastasis. The patient was a 57-year-old woman with a history of rectal neuroendocrine tumor after abdominoperineal resection. Surveillance imaging studies 4 years later revealed a solid mass in the lower pole of left kidney. A computed tomography–guided biopsy revealed a neuroendocrine tumor, and a total nephrectomy was subsequently performed. The left kidney demonstrated a 4.0-cm, encapsulated, white mass with foci of hemorrhage. Histologic examination revealed cords and nests of moderately pleomorphic cells with eosinophilic granular cytoplasm, stippled nuclear chromatin, and a few mitoses. The tumor cells were positive for chromogranin, synaptophysin, and CD56 and had a Ki-67 of 18%. The morphologic and immunohistochemical features were consistent with that of the primary rectal mass, except for a new CD56 positivity and a higher proliferative index by Ki-67, indicating a more-aggressive behavior. Diagnosis of neuroendocrine tumor of the kidney, especially in a limited core biopsy sample can be challenging because of its rarity and unusual morphology (Figure 66).
Not All Gleason Grade 4 Prostate Cancer Is Alike: Differential CD44 Variant Expression Between Cribriform Pattern and Fused Small Acini: (Poster No. 45)
Context: Recent articles have demonstrated that the presence and amount of cribriform (or large acinar) pattern as a component of prostate cancer confers a distinct disadvantage in outcome, making both PSA failure and metastasis after prostatectomy more likely. CD44 is a cell-stroma and cell-cell adhesion and signaling protein, and the standard isoform is decreased in prostate cancer, whereas variant isoforms are overexpressed because of aberrant mRNA splicing, including exons coding for CD44v7-10.
Design: We performed immunostaining for CD44 variant 7/8 (clone VFF-17, SeroTec, Raleigh, NC) at a 1:50 dilution with citrate retrieval, on 15 prostatectomy tissues. Other biomarkers with established relevance to high-grade prostate cancer, namely RBM3 (Abnova, Jhongli, Taiwan) and LIMK2 (Epitomics, Burlingame, Calif), both regulators of CD44; E-cadherin (Dako, Glostrup, Denmark), SPARC (Abnova), NSAID-activated gene 1 (Upstate Biotechnology, Billerica, Mass), and telomerase (hTERT, Novus, Littleton, Colorado) were stained for in the same tissues.
Results: Diminished CD44v7 reactivity in cribriform acini as compared with water-fused small acini from the same case was noted in 13 of 15 cases (87%). The figure shows loss of cytoplasmic CD44v7/8 in the cribriform structure, particularly central cells, compared with fused small acini from the same slide (Figure 67). With other proteins, reactivity did not vary by Gleason 4 cancer pattern.
Conclusions: The finding of differentially expressed CD44 variants or other cell adhesion molecules may correlate with prostate cancer morphology. Further studies may suggest that the degree of cell dyshesion, as manifested by CD44 or other adhesion markers, correlates with tumor growth morphology.
High- and Low-Risk Urothelial Carcinomas: Are the IHC Expressions of P53, p21/p27, and p16 Pathways or FGFR3, HRAS, and Retinoblastoma Proteins Valuable Markers for the 2 Different Pathways?: (Poster No. 63)
Context: Urothelial carcinomas result via low-risk FGFR3 pathway or via high-risk pathways like p53 and p21 or via p16INK4a pathway. We conducted an IHC protein-level study of these oncogenes/suppressor proteins in relation to the morphologic behavior of tumor cells.
Design: Formalin-fixed, paraffin-embedded archival noninvasive and invasive urothelial tumors semiquantitatively were analyzed by IHC. Antibodies were p21WAF1Ab-5 HZ52 1:100; p27Kip1 SX53G8 1:150; p53 Ab8 DO-7 + BP53-12 1:250 (Medac, Germany); p16INK4a (mtm Heidelberg, Germany).
Results: For p53 tumor-suppressor protein, we found no/low expression in normal urothelium and in pTaG1/G2; high expression in invasive carcinoma (and adjoining papillary noninvasive carcinoma). For p16INK4a, normal urothelial cells were completely negative; in pTaG1a few, mostly basal tumor cells were reactive in cytoplasm and nucleus. Invasive carcinomas (pT1/2; G3) show intense reaction in nearly all tumor cells. p21 and p27 were tightly controlled by p53; in normal urothelium and pTaG1 there was high intranuclear expression; there was loss of staining in high-grade and invasive carcinomas. For FGFR3, no distinction between invasive and noninvasive tumor cells was possible (IHC). For HRAS and BRAF (nonmutated), there was high expression in noninvasive papillary carcinoma cells and low expression in invasive tumor cells.
Conclusion: Only p53, p16INK4a, and p21 can be used as markers for high-risk pathway in urothelium. Proteins characterizing the low-risk pathway are HRAS and BRAF nonmutated. The differences in the expression of these proteins may give hints for the pathway and with this for biological behavior of the tumor cells. Figure 68 shows p27 in normal urothelial cells.
Castleman Disease Presenting as a Renal Mass: A Case Report and Literature Review: (Poster No. 64)
A 45-year-old woman presented with a chief complaint of low back pain. Review of symptoms was positive for nausea, urinary urgency, and bladder incontinence. The differential diagnosis included musculoskeletal pain and urinary tract infection; however, despite therapy the symptoms persisted. Abdominal computed tomography, ordered for kidney stone protocol, revealed a 3-cm mass in the upper pole of the left kidney suspicious for renal cell carcinoma. The patient underwent a left nephrectomy. Gross inspection revealed a 3.5-cm firm, dark yellow lobate mass within the renal parenchyma, separate from the renal hilum. Microscopic inspection showed the mass to contain lymphoid tissue with numerous involuted follicles with occasional small, hyaline germinal centers. Mildly hyperplastic mantle zones with subtle onion skinning surrounded the germinal centers (Figure 69). Interfollicular areas showed prominent vascular proliferation with hyalinization. Subsequent outside consultation confirmed a diagnosis of Castleman disease, hyaline vascular type, involving the kidney. Castleman disease (angiofollicular hyperplasia) is an uncommon lymphoproliferative disorder with variant forms and unknown etiology. The hyaline-vascular type occurs in approximately 90% of cases, presenting as localized or multicentric. Occurrence is typically within lymph nodes of the mediastinum or abdomen. However, here we present one of just a few reported cases of Castleman disease presenting as a solitary mass in the kidney, without evidence of additional adenopathy. This presentation is exceptionally rare, and while it is typically benign and cured with surgical excision, knowledge of this occurrence is important so that it will be included in the differential diagnosis of solitary renal mass lesions.
Should Electron Microscopy and Direct Immunofluorescence Be Routinely Considered in Post–Kidney-Transplant Biopsies: A Retrospective Review and Prospective Follow-up in 211 Post-Kidney Transplant Biopsies With Electron Microscopy and Direct Immunofluorescence: (Poster No. 65)
Context: Post-kidney transplant biopsies (ktx) are performed to rule out acute cellular rejection, which can be diagnosed by light microscopy alone. However, a few diagnoses can be reached only after electron microscopy (EM) and/or direct immunofluorescence (DIF).
Design: We reviewed all ktx biopsies from January 2010 to December 2012. There were a total of 460 ktx biopsies, out of which 211 had EM and DIF. The glass slides, EM images, and electronic medical record were reviewed for the indications for transplant and for follow-up (14– 50 months).
Results: Forty-two of the 211 biopsies had significant findings for which EM and DIF were essential. The diagnosis and follow-up are as indicated in the Table.
Conclusions: There were significant diagnoses that could be reached only with the help of EM and/or DIF in 42 out of 211 cases. Recurrence of pretransplant pathologic processes was noted in 17 of 42 cases that can only be diagnosed with the help of EM and DIF. The ancillary modalities appear to be justified in ktx.
An Adult Case of Paratesticular Spindle Cell Rhabdomyosarcoma: (Poster No. 68)
Paratesticular rhabdomyosarcoma (RMS) is uncommon, corresponding to 7% of all RMS cases in adults. Spindle cell RMS is a very rare histologic variant of embryonal RMS characterized by a predominant spindle cell population with or without foci of rhabdomyoblastic differentiation (Figure 70, A–D). Spindle cell RMS has an overall good prognosis in children; however, because of paucity of cases, randomized prospective data in adults are lacking. We report a case of paratesticular RMS in a 24-year-old man presenting with a painless right scrotal mass. Clinical and pathologic features of this tumor should prompt an appropriate immunohistochemical workup in order to distinguish this entity from other spindle cell neoplasms because of prognostic and therapeutic implications.
The Cysts in Autosomal-Recessive Polycystic Kidney Disease Come From Distal Nephron Tubules: (Poster No. 71)
Typical cysts in autosomal recessive polycystic kidney disease (AR-PKD) are characterized by a cylinder pattern of long, narrow cysts. Although conventionally the cysts in AR-PKD are believed to come from distal nephron tubules (possible collecting ducts), one study demonstrated that early cysts in AR-PKD were derived from proximal tubules. We report a case of a 31-week-old female infant born with enlarged bilateral kidneys and liver surviving for 3 days with intubation. Autopsy revealed bilateral enlarged kidneys that distended the abdomen. Microscopically the kidneys revealed the typical cylindric pattern of renal tubular cysts extending from renal surface to cortical-medullary junction at arcuate artery level (Figure 71). The cylindric cysts appeared to be present in medullary rays, compressing the labyrinth zone with glomeruli and their associated tubules. In addition, elongated cysts were also present in the medulla. All of the cylindric cysts stained positively for cytokeratin 7 (distal tubular marker) but negatively for kidney injury molecule 1 (KIM-1, proximal tubular marker). KIM-1 showed positive staining in dilated, injured proximal tubules around glomeruli. This cytokeratin-7–positive and KIM-1–negative profile in the AR-PKD is similar to the adult type of PKD that we demonstrated in the past. Our study confirms that the typical cylindric cysts in AR-PKD are most likely derived from distal nephron tubules (possibly collecting ducts due to a ureteric bud defect) in the medullary rays of cortex separating labyrinth zone with glomeruli. The dilated proximal tubules in AR-PKD are a transient, reactive change secondary to the distal cystic transformation.
Histologic Changes in the Prostate and Bladder Following Radiation Therapy for Prostate Cancer: (Poster No. 72)
Context: Approximately 2.5 million men in the United States have been diagnosed with prostate cancer, many of whom were treated with radiation therapy (RT). While histologic changes such as fibrosis, acinar atrophy, epithelial atypia, and vasculopathy have been described in nonneoplastic prostate and bladder parenchyma following RT, few studies have examined these features in post-RT prostate and bladder resections.
Design: Patients with a history of RT for prostate cancer who subsequently underwent cystoprostatectomy, prostatectomy, or cystectomy between January 2005 and July 19, 2013, were retrieved from the pathology archives. All hematoxylin and eosin stain slides were reviewed. Histologic changes in nonneoplastic tissue were graded as absent, focal, or extensive.
Results: We identified 65 cases. Clinical characteristics are listed in the Table. Prostatic stromal fibrosis was extensive in 98.3% of cases. The benign prostatic glands displayed marked epithelial atypia in 83.9% of cases. The extent of acinar atrophy, glandular atypia, and vasculopathy in the prostate was not dependent on RT modality (P ≥ .26, P ≥ .37, P ≥ .25, respectively). In the bladder, the most common histologic changes were stromal fibrosis and stromal atypia. The extent of stromal atypia was significantly greater after combined RT than after brachytherapy alone (P = .02).
Conclusions: While RT is an effective mode of treatment for prostatic adenocarcinoma, some patients may eventually require prostate or bladder resection post-RT. The examination of salvage resections presented here highlights the spectrum of therapy-related changes, which are especially striking in the prostate. An awareness of these changes, particularly prostatic glandular atypia, may be helpful in avoiding overinterpretation.
First Detailed Study of Survival of Patients With Renal Cell Carcinoma in India: (Poster No. 73)
Context: Renal cell carcinoma (RCC) accounts for 2% to 3% of all adult malignancies and approximately 90% of all renal malignancies. The rates of kidney cancers are high in developed countries and low in eastern countries and Africa. Our objective was to conduct a survival study among Indian patients who had nephrectomy for RCC, as there was a paucity of Indian studies in medical literature.
Design: We conducted a follow-up study of 66 RCC patients who had nephrectomy between January 2003 and December 2008. These patients had pathologic diagnosis after nephrectomy. The follow-up were done up to December 2013. The survival statistics were compiled according to Kaplan-Meier survival curves.
Results: The overall survival of patients at 5 years was 74%. The patients with tumor size below or equal to 7 cm and the patients with tumor size above 7 cm showed significant statistical difference at 5-year survival (P < .001; Figure 72). The patients with low nuclear grade (1 and 2) and the patients with high nuclear grade (3 and 4) showed significant statistical difference at 5-year survival (P < .001). The patients with clinical stage below T3 and the patients with clinical stage above and equal to T3 showed significant statistical difference at 5-year survival (P = .003).
Conclusions: This study also has demonstrated the importance of factors like tumor size, nuclear grade, and stage in the assessment of prognosis of RCC patients. More studies in India with more patients are needed to demonstrate the importance of these prognostic factors.
Glomerular Sparing Pattern in Primary Kidney Tumors: Clinical, Morphologic, and Immunohistochemical Study: (Poster No. 76)
Context: Glomerular sparing (GS) is defined as a unique growth pattern where tumor cells replace the majority of renal tubes and overrun intact glomeruli. However, no study has been reported. Here, we studied the clinical-pathologic and immunohistochemical features of primary kidney tumor with glomerular sparing pattern.
Design: The archives of Westchester Medical Center's anatomic pathology department were searched for nephrectomy specimens from 2009 to 2013. All reports were reviewed, cases with tumor were selected, clinicopathologic information was collected, and cases were reevaluated with focus on glomerular sparing pattern. Immunohistochemical stains of Pax-8, p63, and INI-1 were performed.
Results: A total of 204 nephrectomy cases included 163 cases of renal cell carcinoma (RCC); 37 cases of urothelial carcinoma (UC), and 4 cases of others (Wilms tumor, primary diffuse large B-cell lymphoma, angiolipoma, rhabdoid tumor). Finally, we identified 7 cases: 2 cases of clear cell renal cell carcinoma (CCRCC), 2 cases of urothelial carcinoma (Figure 73, A), 1 case of collecting duct carcinoma (CDC, Figure, B), 1 case of diffuse large B-cell lymphoma (Figure, C) and 1 case of rhabdoid tumor (Figure, D). CCRCC and CDC were Pax8+ and P63−; UC were Pax8− and P63+; lymphoma was Pax8+; and rhabdoid tumor was INI1−.
Conclusions: Primary kidney tumors with glomerular sparing pattern are rare and incidence in our study is <4% (7/204). They are associated with RCC, UC, collecting duct carcinoma, lymphoma, and rhabdoid tumor. However, they are found with high-grade, large-size tumors and are typically located at the junction of the tumor and the surrounding renal parenchyma. Careful morphologic evaluation and immunohistochemical stains would be helpful for diagnosis.
G-CSF Therapy Can Induce Bone Marrow Release of Leukemic Blasts in Acute Promyelocytic Leukemia Unmasking an Underlying Subclinical Disease With Catastrophic Consequences: Report of 2 Cases: (Poster No. 80)
Granulocyte colony stimulating factor (G-CSF) promotes conversion of granulocyte colony-forming units into polymorphonuclear leukocytes. Previous studies have shown that G-CSF can also potentiate differentiation induction by all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL). G-CSF's effect on patients with APL who did not receive ATRA has not been previously described. We report 2 patients with neutropenia who were treated with G-CSF. Neither patient had a diagnosis of APL prior to G-CSF therapy. The 2 patients developed rapidly deteriorating clinical course and leukocytosis with circulating immature cells within 2 days of G-CSF administration and died shortly after. APL was suspected based on peripheral blood smear examination and confirmed by FISH testing for PML-RARA. Review of FISH slides by 2 hematopathologists in 1 patient showed that PML-RARA translocation was restricted to blasts and absent in neutrophils. The findings suggest that G-CSF administration in patients with undiagnosed APL can induce bone marrow release of leukemic blasts, triggering a rapidly progressive clinical demise. Additionally, based on FISH studies in 1 patient, G-CSF does not seem to induce differentiation of APL leukemic blasts in the absence of ATRA administration (Figure 74).
Primary Double Hit Diffuse Large B-Cell Lymphoma of the Urinary Bladder: (Poster No. 81)
Primary malignant lymphoma of the urinary bladder is rare. To our knowledge less than 100 cases have been reported. Among these, MALT lymphoma and diffuse large B-cell lymphoma are most common. In some instances the former transforms to the latter. Presented herein is a urinary bladder double-hit diffuse large B-cell lymphoma (DLBCL) of germinal center cell origin. A “double-hit” genetic abnormality in acute lymphoblastic leukemia was described by Mufti et al in 1983. Thereafter this terminology has been used to describe DLBCL with dual BCL-2 and MYC translocation. To ascertain the origin of DLBCL as germinal center or interfollicular, the Hans' Algorithm additionally incorporates immunohistochemistry with CD10, BCL-6 and MUM1. A 57-year-old woman presented with painless hematuria. Computed tomography and positron emission tomography scans revealed a diffusely thickened urinary bladder wall with tumor extension into the perivesical soft tissues, pelvis and abdominal wall. Microscopically, tumor cells are pleomorphic and immunoreactive for LCA, CD20, CD79a, CD10, and MUM1. BCL-6 was negative and Ki67 revealed a high proliferative index. FISH for BCL-2 and MYC genes were abnormal. The tumor was classified as a double-hit DLBCL according to WHO and LSU guidelines. Chemotherapy was commenced with R-CHOP, followed by DA-R-EPOCH. Restaging positron emission tomography showed an excellent and near complete remission with only minimal residual disease (Figure 75).
Myeloid Antigen Expression Is Similar in Pediatric and Adult Acute Lymphoblastic Leukemia Patients: (Poster No. 83)
Context: Acute lymphoblastic leukemia (ALL) is a rapidly fatal malignant neoplasm derived from lymphoid progenitor cells. Myeloid antigens are occasionally expressed in ALLs. One hypothesis is that differences in myeloid antigen expression may partly account for differences in prognosis between pediatric and adult ALL.
Design: The clinical and hematopathologic materials in ALL patients of the past 2 decades were retrospectively reviewed from a single institution. Patients were classified as pediatric group (<18 years at the diagnosis) or adult group (≥18 years at diagnosis). Differences between myeloid antigen expression in adult and pediatric populations were analyzed by using the χ2 test. Survival analyses were performed for the pediatric and adult groups by the Kaplan-Meier method.
Results: A total of 177 ALL patients were included in the present study. There were 36 cases of T-ALLs, and 141 cases of B-ALLs (13 pediatric T-ALLs; 23 adult T-ALLs; 67 pediatric B-ALLs, and 74 adult B-ALLs). As has been widely shown, the pediatric ALL patients had significantly better prognosis than adult ALL patients. Although a slightly higher proportion of adult ALL cases showed myeloid antigen expression, this difference was not significant. In addition, there was no association of myeloid antigen expression with overall survival either in the pediatric or in the adult ALL patients (Figure 76).
Conclusion: There is no significant difference in myeloid antigen expression between pediatric and adult ALLs. The findings indicate that the relatively poor prognosis of adult ALLs is not associated with myeloid antigen expression.
Crystal Storing Histiocytosis Associated With Plasma Cell Neoplasms: Two Cases: (Poster No. 84)
Crystal-storing histiocytosis (CSH) is characterized by intracytoplasmic accumulation of crystallized immunoglobulins in histiocytes and is typically associated with disorders that express monoclonal immunoglobulins. We describe 2 cases of CSH associated with a plasma cell neoplasm (PCN). Case 1: A 43-year-old woman with stage IV chronic kidney disease due to renal tubular acidosis undergoing evaluation for kidney transplant was found to have a 0.2 g/dL serum IgD κ monoclonal protein. Bone marrow core biopsy showed numerous aggregated histiocytes with intracytoplasmic eosinophilic inclusions (Figure 77, A), prominent on the aspirate smears and present in histiocytes and plasma cells (Figure, B). Immunohistochemical stains identified 5%–8% κ monotypic plasma cells. No lytic lesions were seen on imaging. The patient was diagnosed with monoclonal gammopathy of uncertain significance (MGUS). Case 2: A 70-year-old man with a 1-year history of IgG κ MGUS with innumerable hypermetabolic osseous lytic lesions on imaging. Computed tomography guided biopsy of sacral lesion showed a proliferation of histiocytes with numerous intracytoplasmic rhomboid to needle-shaped crystals (Figure, C) and interspersed aggregates of κ restricted plasma cells by ISH (Figure, D). Subsequent iliac crest biopsy showed 10% κ-restricted plasma cells and numerous crystal-laden histiocytes. The patient was diagnosed with plasma cell myeloma. We have illustrated 2 cases of CSH associated with PCN, both with a prominent histiocytic component. In Case 1, the patient's renal failure, with decreased clearance of monoclonal proteins, may have contributed to the presentation. Case 1 also illustrates CSH associated with IgD heavy chain, which has been rarely described.
Primary Myelofibrosis in a 3-Year-Old: A Rare Manifestation of a Predominantly Adult Entity: (Poster No. 86)
Primary myelofibrosis is characterized by a clonal proliferation of hematopoietic stem cells, associated replacement of bone marrow by fibrosis, and resultant extramedullary hematopoiesis. It is a relatively uncommon condition that is predominantly diagnosed in older adults. Exceedingly rare childhood cases have been documented. We report the case of a previously healthy 3-year-old girl who presented with fever, rash, and fatigue. Massive splenomegaly and pancytopenia were noted on initial evaluation. Extensive testing excluded immunologic, metabolic, and infectious processes. The peripheral blood had moderate anisopoikilocytosis with occasional dacrocytes and spherocytes. The bone marrow biopsy was hypocellular with hematopoietic elements comprising <1% of total marrow space. Sinusoids were markedly dilated in a whorled, fibrotic stroma. A reticulin stain confirmed myelofibrosis grade 3 (Figure 78). Cytogenetic studies revealed a normal karyotype. This case posed a diagnostic challenge given the rarity of primary myelofibrosis in this age group. Physical exam, hematologic analysis, and bone marrow features were instrumental in establishing this diagnosis. The patient received myeloablative therapy with a 10/10 HLA-matched, unrelated donor hematopoietic stem cell transplant, after which she developed acute graft-vs-host disease and numerous other complications. Although a bone marrow biopsy at 6 months showed no evidence of myelofibrosis, the patient continued to have a clinical decline and expired approximately a year after diagnosis.
Concordance of Interpathologist and Intrapathologist Diagnosis of Classical Hodgkin Lymphoma With the MultiOmyx HL Profile: (Poster No. 88)
Context: The diagnosis of Hodgkin lymphoma is often difficult. We have developed a fluorescent hyperplexed methodology for paraffin-embedded sections that enables assessment of multiple antigens on a single section, with similar staining characteristics as standard immunohistochemical stains, and evaluation of specific cells (Multi-Omyx).
Design: Historical immunohistochemistry diagnoses were compared to MultiOmyx diagnoses, studying blinded cases consisting of 23 classical Hodgkin lymphomas, 29 other diagnoses, and 3 cases without an original diagnosis. One section from each specimen was probed with CD30, CD15, CD45, Pax5, CD20, CD79a, OCT2, Bob1, and CD3 antibodies. Three independent pathologists viewed each biomarker as a grayscale image, an overlay of multiple biomarkers, or as a pseudodia-minobenzidine (DAB) image.
Results: Of the 52 diagnosed cases 45 (87%) showed complete concordance among all pathologists with the historical diagnosis. Analysis of one discordant case raised doubt to the validity of the historical diagnosis. Review of the other discordant cases showed them to be diagnostically challenging and open to multiple interpretations. Average pairwise agreement among the pathologists was 93% (κ = 0.85). High intrapathologist agreement was also found.
Conclusions: A concordance study of multiple pathologists showed excellent agreement for diagnosis of Hodgkin lymphoma (Table). MultiOmyx is performed on a single section and provides images similar to standard immunohistochemistry stains, and therefore is useful in cases with rare Hodgkin cells or small samples. This novel methodology is practical for routine diagnosis, and will be further validated as an aid to the improved diagnosis of Hodgkin lymphoma.
Sequential Occurrence of Primary Mediastinal B-Cell Lymphoma and Nodular Sclerosis Classical Hodgkin Lymphoma: Clonal Relationship and Implications for Management: (Poster No. 90)
Primary mediastinal diffuse large B-cell lymphoma (PMBCL) and classical Hodgkin lymphoma, nodular sclerosis subtype (cHL-NS), have overlapping clinicopathologic and genetic features. Rarely, synchronous or metachronous PMBCL and cHL-NS occur. These are not technically “mediastinal gray zone lymphomas” as defined by the 2008 WHO classification, but likely represent a related process. Our 22-year-old patient presented with night sweats, cough, and weight loss. Imaging revealed a 16-cm mediastinal mass. Biopsy showed a monotonous population of large lymphoid cells that were strongly positive for CD20 and CD79a, with weak focal CD30 staining and compartmentalizing fibrosis (Figure 79, left). The patient was diagnosed with diffuse large B-cell lymphoma, and treated with rituximab, cyclophosphamide, vincristine, and prednisone (R-CHOP). The mediastinal mass initially decreased in size, but follow-up imaging showed progressive disease; this was treated with proton beam therapy. The patient subsequently developed cervical lymphadenopathy, concerning for a secondary malignancy. Biopsy showed a nodular infiltrate of small lymphocytes, eosinophils, and large atypical cells with polylobated nuclei and prominent nucleoli. These cells expressed CD15 and CD30, and were negative for CD20, consistent with cHL-NS (Figure, right). Molecular studies for immunoglobulin heavy-chain rearrangement demonstrated a clonal peak at 323 bp in the IGH framework 1 reaction in both biopsy specimens, suggesting a clonal relationship between the 2 processes. Though the individual biopsies yielded 2 different diagnoses, the overall findings were consistent with recurrence of the patient's original lymphoma rather than a second primary, making the patient eligible for autologous stem cell transplant.
Primary Cervical Lymphoma Complicated With Bilateral Obstructive Uropathy: (Poster No. 91)
Primary lymphomas of the female genital tract are uncommon and pose a diagnostic challenge if their existence is not suspected, especially in young and immunocompetent patients. A 22-year-old previously healthy woman presented to our institution with complaints of crampy abdominal pain and heavy menstrual periods for 2 months. She was found to have acute renal failure (creatinine 5.2 mg/dL). Computed tomography scan revealed markedly thickened cervix with bilateral obstructive hydronephrosis. Renal radionuclide scan showed absent left renal function. Serum creatinine normalized subsequent to percutaneous nephrostomy tube placement. Magnetic resonance imaging showed a 6.1 × 4.1-cm cervical malignancy extending to the pelvic sidewall continuous with the left side of the sigmoid colon with bulky internal iliac adenopathy. Cervical cone biopsy revealed diffuse infiltration of the cervix with large neoplastic lymphocytes positive for CD20 (Figure 80, A–C) and PAX5 with an activated B-cell immunophenotype (CD10 negative; MUM1 positive) and a normal myc, bcl2, and bcl6 gene status by fluorescent in situ hybridization. The proliferation index was 70%–80% (Figure, D). EBER (Epstein-Barr encoded early RNA) in situ hybridization was negative. Based on the imaging and bone marrow biopsy findings, stage IIE primary diffuse large B-cell lymphoma was diagnosed. The patient has since undergone 3 cycles of R-CHOP (rituximab, cyclophosphamide, hydroxydaunomycin, Oncovin, prednisone) chemotherapy with her most recent imaging scan showing significant response based on reduced size of the cervical mass. In conclusion, we report a case of primary diffuse large B-cell lymphoma of cervix complicated with bilateral obstructive uropathy responding to R-CHOP chemotherapy.
Parvovirus B19 Infection in a Chronic Myelogenous Leukemia Patient on Imatinib Therapy and Failed Allogeneic Bone Marrow Transplant: (Poster No. 98)
Allogeneic bone marrow transplantation recipients are predisposed to common and opportunistic viral infections acquired from donors or community and from reactivation of latent viruses. Imatinib therapy also predisposes to viral infections due to defects in cell-mediated immunity. We present an unusual case of a 53-year-old man with chronic myelogenous leukemia (CML) diagnosed 18 years prior, allogeneic bone marrow transplant from HLA-matched sister 17 years back, on imatinib for 4 years who presented with WBC 20 × 103/μL, hemoglobin 11.3 g/dL, and platelets 467 × 103/μL and whose hemoglobin levels decreased to 8.4 g/dL within a month. Failed bone marrow transplant and accelerated phase of CML was diagnosed on bone marrow biopsy (Figure 81) that had 10%–15% CD34+ blasts, severe myelofibrosis, and t(9;22) male karyotype with multiple cytogenetic abnormalities (normal female karyotype 8 years back). Severe erythroid hypoplasia, rare pronormoblasts with smudged chromatin (Figure), and parvovirus B19+ (PVB19) erythroid precursors by immunohistochemistry were present (Figure). Peripheral blood PVB19 PCR was positive. PVB19 is ubiquitous with 60%–90% seropositivity in adults. PVB19 is highly erythrotropic, causing cessation of erythropoiesis and transient aplastic crisis in hemolytic anemia patients and persistent infection and chronic anemia in immunosuppressed patients. High myeloid to erythroid ratio and decreased erythroid precursors are expected in CML and hemoglobin levels can fall in aggressive phase. High index of suspicion for PVB19 infection is required in such cases. Immunosuppressed patients may not produce PVB19 neutralizing IgG/IgM, complicating serologic test interpretations. Peripheral blood viral assay PCR should be performed and bone marrow biopsy for confirmation can be diagnostic.
Differentiating Between Malignant Erythroid Proliferations and Recovering Marrows Utilizing CD105: (Poster No. 101)
Two patients, one having undergone treatment for acute T-lymphoblastic leukemia, the other with a history of polycythemia vera, had bone marrow specimens submitted for analysis by multidimensional flow cytometry. Both showed an elevated level of immature nucleated erythroid progenitors (12%, and 30% respectively, normal <2% of nucleated cells). Upon further evaluation of the maturational patterns the case with a history of acute leukemia showed normal erythropoiesis, albeit at an elevated rate (Figure 82, B). Meanwhile, the case with a history of polycythemia vera showed dyserythropoiesis, including clonal growth consistent with acute erythroid leukemia (Figure, C). The primary differentiating relationship involved CD105, an antigen present on immature erythroid progenitors. Unlike normal specimens (Figure, A) or the first case when compared to an antigen present on mature nucleated erythroid progenitors (CD235a, CD71, or CD36) the patient does not show the normal pattern of maturation. Cytogenetic analysis of the second specimen revealed a complex result with abnormalities of chromosomes 2, 5, 7, 9, 12, 13, 15, 16, 17 (including loss of the TP53 gene), 19, 21, and 22, validating the flow cytometric findings. Thus we were able to differentiate between a bone marrow recovering from treatment, with increased but normal erythroblasts, from a case with malignant dyserythropoiesis. These 2 cases demonstrate that CD105 is a valuable tool for the assessment of nucleated erythroid progenitors, and when utilized can allow for the correct identification of dyserythropoiesis in cases in which it would not otherwise be possible.
Drs Zehentner, Wells, and Loken are shareholders in HematoLogics, Inc.
Hairy Cell Leukemia Variant Coexistent With Plasma Cell Myeloma: (Poster No. 104)
The hairy cell leukemia variant entity is a rare disease, accounting for approximately 0.4% of chronic lymphoid malignancies and 10% of all conventional hairy cell leukemia cases. We report the case of a 61-year-old man who presented with anxiety and depression after years without medical care. He was found to have extensive lymphadenopathy, splenomegaly, and an IgG λ monoclonal protein by serum electrophoresis. Examination of the peripheral blood smear showed anemia and absolute lymphocytosis with morphologic features of hairy cell leukemia: small mature lymphocytes with cytoplasmic projections and prolymphocyte-like nuclei. The cells marked as positive for CD19, CD20, CD11c, HLA-DR, and IgG/A and negative for CD103 and CD25 by flow cytometry. A bone marrow biopsy revealed hypercellular marrow, trilinear hematopoiesis, and abnormal interstitial/sinusoidal lymphoid infiltrate representing 10%–15% of marrow cells. These cells were CD20 positive by immunohistochemistry. Also present, representing 20%–30% of marrow cells, was a population of plasma cells positive for CD138 and λ light chain by mRNA in situ hybridization. Flow cytometric analysis of the bone marrow aspirate revealed a mature lymphocyte population marking similar to what was seen in the peripheral blood sample, diagnostic of the hairy cell variant of splenic B-cell lymphoma. The plasma cell population could not be further characterized because of insufficient number of viable cells. The patient responded poorly to chemotherapy, and stem cell transplant is currently being considered. To our knowledge, we report the first case of hairy cell variant of splenic B-cell lymphoma with coexisting plasma cell myeloma (Figure 83).
CD8+ Cytotoxic Peripheral T-Cell Lymphoma, Not Otherwise Specified, in a Young Child: Case Report and Literature Review: (Poster No. 108)
Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), is a mature T-cell lymphoma that very rarely occurs in children. The immunophenotype in nodal cases is usually CD 4+/CD8−. We report a highly unusual and diagnostically challenging case of PTCL, NOS exhibiting a cytotoxic phenotype in an 8-year-old boy with massive lymphadenopathy without constitutional symptoms. Initial biopsy of the axillary lymph node demonstrated morphologic features resembling necrotizing lymphadenitis with paracortical expansion by polymorphous T cells associated with prominent karyorrhexis (Figure 84, A–C). Persistence and progression of the lymphadenopathy led to a repeat biopsy of the right cervical lymph node. The atypical T cells demonstrated partial down-regulation of the CD7 pan–T-cell antigen by flow cytometry and immunohistochemistry. The vast majority of the T cells in the paracortex were CD8+/TIA-1+ cytotoxic T cells (Figure, D). T-cell receptor (TCR) gene rearrangement was positive for clonal T cells in both biopsies. A diagnosis of PTCL, NOS was made and confirmed by an outside expert on the repeat biopsy because of the clinical progression of the lymphadenopathy, the expansive proliferation of atypical T cells, and the consistently clonally rearranged T cells. The unusual presentation of PTCL, NOS in this 8-year-old child illustrates the broad differential diagnoses of persistent massive lymphadenopathy in pediatric patients. Furthermore, polymorphous nodal T-cell proliferation exhibiting a CD8+ cytotoxic immunophenotype and associated necrotizing changes should not exclude a diagnosis of PTCL, NOS. Published cases of childhood PTCL, NOS in the literature will be reviewed.
Unusual Association of Inflammatory Pseudotumor of the Spleen and Idiopathic Thrombocytopenic Purpura: (Poster No. 112)
Inflammatory pseudotumor of the spleen (IPTS) is a rare benign lesion of uncertain etiology. Only 5 cases have been reported in association with idiopathic thrombocytopenic purpura so far. Herein, we describe the case of a 65-year-old woman with a history of idiopathic thrombocytopenic purpura that was found to have an IPTS mimicking splenic hamartoma on preoperative imaging studies. Following splenectomy, the spleen measured 11.0 × 8.5 × 5.0 cm and weighed 149 g. Grossly, a 6.2 × 5.8 × 4.5-cm well-circumscribed tan-yellow firm nodular mass was identified adjacent to the splenic capsule (Figure 85). Microscopic examination revealed the presence of a mixture of fibroblast-like spindle cells, small lymphocytes, plasma cells, histiocytes, nonnecrotizing granulomata, and a central area of necrosis with occasional neutrophils (Figure). Immunostaining for CD20 and CD3 revealed scattered B and T lymphocytes. CISH for κ/λ revealed polyclonal plasma cells. The spindle cells were positive for desmin, muscle-specific actin, CD68, CD31, and S100, and negative for CD34, CD1a, CD21, CD23, and ALK. Ki-67 was positive in approximately 30% of the cells. A reticulin stain showed a disorganized vascular pattern. EBER was positive in many tumor cells (Figure) but completely negative in the normal splenic parenchyma. To our knowledge, the identification of Epstein-Barr virus in IPTS with idiopathic thrombo-cytopenia purpura has not been previously described. The exact relationship between IPTS and idiopathic thrombocytopenic purpura and the role of Epstein-Barr virus in its development are yet to be investigated.
Multicentric HHV-8–Positive Castleman Disease and Kaposi Sarcoma as the Presenting Sign of Undiagnosed HIV Infection: (Poster No. 113)
Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder associated with human herpesvirus 8 (HHV-8) and human immunodeficiency virus (HIV). In comparison to the benign, localized lymphoid hyperplasia first described by Castleman in 1956, HHV-8–associated MCD is characterized by multiorgan involvement and severe constitutional symptoms. In addition, HIV-positive patients with MCD frequently develop Kaposi sarcoma (KS) during the course of their disease. We report a case of concurrent MCD and KS as the presenting sign of HIV in a previously undiagnosed patient. Our patient, a 59-year-old man, presented with fever, weight loss, cervical lymphadenopathy, anemia, and thrombocytopenia. Imaging studies showed abdominal, pelvic, and mediastinal lymphadenopathy and splenomegaly, causing clinical concern for lymphoma. Lymph node biopsy showed features suggestive of the plasma cell variant of Castleman disease, and a focal, subtle atypical vascular proliferation concerning for Kaposi sarcoma (Figure 86). Based on these findings, testing for HIV and HHV-8 was recommended. Dual infection by HIV and HHV-8 was confirmed, with viral loads of 108 000 and 603 000 copies/mL, respectively. Immuno-histochemical staining for HHV8 was positive in the atypical vascular proliferations (Figure) and in scattered lymphoid cells. A diagnosis of HIV infection presenting with multicentric Castleman disease and Kaposi sarcoma was made. This case stresses the importance of considering MCD in the differential diagnosis for patients with B symptoms and lymphadenopathy. Careful assessment for subtle evidence of Kaposi sarcoma in lymph nodes showing features of MCD should also be performed, even in patients without a known history of HIV.
Hypercalcemia in a Case of Classical Hodgkin Lymphoma With Abundant Histiocytes: (Poster No. 114)
Hypercalcemia is rare in Hodgkin lymphoma, with only a few cases reported in the medical literature. Herein, we report the case of a 78-year-old woman who presented with nonspecific gastrointestinal symptoms, dehydration, and weakness and was found to have a renal calculus and diffuse lymphadenopathy on imaging studies. Laboratory testing revealed hypercalcemia (12.0 mg/dL; reference range [RR], 8.5–10.5 mg/dL), normal phosphorus (2.9 mg/dL; RR, 2.5–4.9 mg/dL), normal parathyroid hormone (15 pg/mL; RR, 14–72 pg/mL), normal parathyroid hormone-related protein (<3 pmol/L; RR, 0.0–4 pmol/L), elevated vitamin D (122 ng/mL; RR, 30–80 ng/mL) and acute renal failure (BUN 33 mg/dL; RR, 6–24 mg/dL; creatinine 1.4 mg/dL; RR 0.6–1.3 mg/dL). Microscopic examination of an axillary lymph node biopsy revealed effacement of the lymph node architecture by a diffuse infiltrate rich in histiocytes (Figure 87) with confluent nonnecrotizing granulomata, small lymphocytes, plasma cells, neutrophils, fibroblasts, and scattered Hodgkin cells (including Reed-Sternberg cells and other Hodgkin cell variants; Figure). By immunohistochemistry, the Hodgkin cells were positive for PAX-5 (weak), CD15, and CD30 and negative for CD20 and CD45. The morphologic and immunohistochemical findings supported the diagnosis of mixed cellularity classical Hodgkin lymphoma. Several mechanisms of hypercalcemia of malignancy have been described. In this case, we hypothesize that the pathogenesis of hypercalcemia may have involved the conversion of 25-hydroxyvitamin D to 1,25-hydroxyvitamin D by the 1-α-hydroxylase expressed in the histiocytes, in a fashion similar to that described in sarcoidosis. Therefore, the association of classical Hodgkin lymphoma with abundant histiocytes and hypercalcemia may warrant future investigation.
Stromal Rich Variant of Hyaline-Vascular Castleman Disease: A Case Report of an Unusual Tumor With Review of the Literature: (Poster No. 118)
Castleman disease is an uncommon form of lymph node hyperplasia. It commonly involves the mediastinum but can also involve extra-thoracic sites, including the neck, axilla, pelvis, and retroperitoneum. The stroma-rich variant of Castleman disease of the hyaline-vascular type (CDHV) is a rare entity that shows overgrowth of a variety of stromal cells in the expanded interfollicular area. We report here a case of a 20-year-old woman who presented with nausea, vomiting, and a syncopal event. An ultrasound revealed a 5.6-cm right retroperitoneal mass. An excisional biopsy showed a lobulated lymph node architecture effaced by sheets of spindled and ovoid cells forming fascicles in a storiform pattern. At the periphery and interspersed between the spindle cells were residual lymphoid follicles with regressive changes and multi–germinal center pattern. Sclerotic vessels with hyaline walls radially penetrate the germinal centers, reminiscent of the features of hyaline-vascular Castleman disease. The interfollicular spindle cells were positive for smooth muscle actin, and they were negative for CD21, CD34, CD117, CD163, ALK-1, HHV-8, and S-100 proteins. This case was diagnosed as a stromal-rich variant of Castleman disease. This is a rare entity that shows overgrowth of stromal cells in the widened interfollicular area. Clinically, it usually presents as an asymptomatic, solitary nodule that predominantly develops in the retroperitoneum. This stromal-rich lesion is typically hyperplastic and clinically benign, and it must be distinguished from neoplastic stromal proliferation such as follicular dendritic cell tumor or vascular neoplasm associated with Castleman disease because of its potential for recurrence and metastasis (Figure 88).
A Case of Pediatric Interfollicular Hodgkin Lymphoma: (Poster No. 119)
In addition to representing a rare variant of Hodgkin lymphoma, interfollicular Hodgkin lymphoma displays subtle histologic findings, which may closely resemble follicular hyperplasia. Herein, we describe an illustrative case demonstrating interfollicular Hodgkin lymphoma as well as benign follicular hyperplasia in a 6-year-old girl. The patient presented to the university otolaryngology department complaining of painless swelling of the right posterior cervical chain. Previously, local practitioners had placed the patient on antibiotics without improvement. A complete blood count was unremarkable. Imaging revealed bilateral multilevel cervical lymph-adenopathy. A right level 5 cervical lymph node was removed, which demonstrated preserved nodal architecture with expansion of the interfollicular zones by epithelioid histiocytes and eosinophils. Within these zones, Reed-Sternberg cells were seen (Figure 89) as highlighted by CD15 and CD30 immunostains. While dimly positive in the Reed-Sternberg cells, PAX-5 was strongly positive in the follicular and interfollicular B-cells. This case was diagnosed as interfollicular Hodgkin lymphoma, and the patient was started on chemotherapy. After 4 cycles of chemotherapy, positron emission tomography scan and computed tomography showed persistent lymphadenopathy and hypermetabolic activity. A right cervical lymph node excision again displayed preserved architecture with expansion of the interfollicular zones. However, no Reed-Sternberg cells or variants were seen, as confirmed by the absence of CD15, CD30, and PAX-5 expression. The reactive follicular and interfollicular hyperplasia demonstrated in the second lymph node excision without involvement by Hodgkin lymphoma depicts the challenges involved in the diagnosis and surveillance of this rare morphologic variant.
Two Occurrences of Acute Lymphoblastic Leukemia With Concurrent Diffuse Bone Marrow Reticulin Fibrosis in Adults: (Poster No. 128)
Acute lymphoblastic leukemia (ALL) with concurrent diffuse bone marrow reticulin fibrosis is rare. Most of the studies with this association are done in children. Studies in adults are limited because of very low occurrence, small sample size, and technical difficulties due to dry tap. Hence it remains difficult to determine the prognostic significance of this association in adults. We report 2 additional occurrences to support further studies on the prognostic significance of this combination. Case 1: A 32-year-old man was admitted for jaundice. Workup showed thrombocytopenia (18 × 103/μL), splenomegaly, and EBV infection–associated hepatitis. Bone marrow biopsy was a dry tap with markedly hypercellular marrow (90%) with B-cell ALL (36.5% blasts) and marked diffuse reticulin fibrosis (see Figure 90 and inset). Blast population expressed TdT, Pax-5, CD79a, CD20, and CD10. Genetics were negative for Bcr-Abl. Case 2: A 46-year-old man presented with intermittent fever and weakness for 2 weeks. Workup showed leukocytosis (38.51 ×103/μL) with absolute lymphocytes (33.92 × 103/μL) and severe thrombocytopenia (7 × 103/μL). Peripheral blood showed 75% blasts. Subsequent bone marrow biopsy showed markedly hypercellular marrow (80%) with B-cell ALL (90% blasts) and moderate to marked diffuse reticulin fibrosis. Blast population expressed CD19, cCD79a, CD34, HLA-DR, CD10, TdT, and partial dim CD71. Genetics were positive for Bcr-Abl. Both cases were treated with standard ALL chemotherapy (hyper-CVAD) and subsequent bone marrow biopsies showed suppression of marrow reticulin fibrosis with remission of ALL (Figure).
Angiomyomatous Hamartomas of Multiple Lymph Nodes, Clinically Concerning for Malignancy: Clinicopathologic Correlation and Review of the Literature: (Poster No. 131)
Angiomyomatous hamartoma of the lymph node is characterized by a benign vascular and smooth muscle proliferation with unknown etiology. Angiomyomatous hamartoma was first described by Chan et al in 1992 and to date there are only 31 reported cases. We describe a 63-year-old man who presented with fever and left leg edema. Blood work revealed pancytopenia, and a positron emission tomography scan was performed that showed 2 hypermetabolic lymph nodes, one in the left inguinal region and the second in the left deltoid region, both concerning for malignancy. The patient ultimately expired because of sepsis, and an autopsy was performed. Grossly, both lymph nodes measured 3.0 × 2.0 × 1.0 cm and had a gray-tan cut surface. Histologically, the parenchyma was mostly replaced by fibrous tissue with an extensive vascular proliferation, spindle cell bundles, and multiple small foci of adipocytes (Figure 91, A). Immunohistochemical analysis showed strong desmin and smooth muscle actin positivity in the spindle cells, confirming they were smooth muscle fibers (Figure, B, C); also, CD34 highlighted the extensive vascular proliferation (Figure, D) and HMB-45 was negative, ruling out angiomyolipoma. Although angiomyomatous hamartoma of a lymph node is a rare entity, it is important to be recognized by both clinicians and pathologist as benign lesions that may mimic malignancy. To the best of our knowledge this is the first case of angiomyomatous hamartoma affecting more than 1 lymph node and the first case to involve a lymph node in an upper extremity.
Diffuse Large B-Cell Lymphoma With Complex Karyotype and t(13; 14) Involving FOXO1 Gene: A Case Report on a Novel Translocation: (Poster No. 134)
Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin lymphoma accounting for 30 000 cases per year in the United States. Different translocations have been reported in DLBCL, with t(14;18) being the most common. We report a new chromosomal translocation t(13;14) in a 13-year-old girl diagnosed with diffuse large B-cell lymphoma. The patient presented with an isolated upper thigh mass for 3 months. Excisional biopsy showed a large lymph node with a diffuse proliferation of large atypical cells. The tumor cells were positive for CD20, bcl-6, and bcl-2, and negative for CD3, CD5, TdT, and CD30. The Ki-67 proliferation index was 80%–90%. Flow cytometry showed a population of large cells expressing CD10, CD19, CD20, CD22, and CD38, without coexpression of surface immunoglobulin, CD34, and CD15. Cytogenetics showed a near-tetraploid karyotype with 1 X chromosome attached with material of unknown chromosomal origin at the q28 band region, losses of chromosome 1, 4 and 6, and t(13;14)(q13;q32), the latter confirmed by fluorescent initu hybridization (FISH). Furthermore, FISH has confirmed the disruption of IGHG1 and FOXO1 (Figure 92); but no RB1 disruption was found. FOXO1 is a transcription factor that may act as a tumor suppressor. Misregulation/ mutations of FOXO1 have been implicated in multiple cancers, including rhabdomyosarcoma, breast and colon cancers, multiple myeloma, B-CLL, CML, Hodgkin lymphoma, and a few cases of DLBCL; however, disruption of FOXO1 due to t(13;14) has not been reported in DLBCL. To our knowledge, this is the first report of t(13;14) involving FOXO1 in DLBCL.
Myeloid Antigen Expression in Lymphoid Blasts Does Not Impact Prognosis in Acute Lymphoblastic Leukemia: (Poster No. 135)
Context: In acute lymphoblastic leukemia (ALL), the proliferating lymphoblastic cells occasionally express myeloid antigens. The prognostic significance of myeloid antigen expression remains controversial.
Design: To better understand the role of myeloid antigens in the prognosis of ALL, we reviewed flow cytometry results and clinical data in ALL patients from 1995 to 2012. B-lineage and T-lineage ALL cases were included. ALLs were classified into 2 groups: with or without aberrant myeloid antigen expression, in which myeloid expression was defined for one or more of the myeloid markers (CD13, CD33, and CD117). Survival rates were compared in these 2 groups by Kaplan-Meier analysis.
Results: Aberrant myeloid antigens were expressed in 40 of 207 ALL patients (19.3%). The most frequent myeloid antigen in the lymphoid blasts was CD33 (13.5%), followed by CD13 (10.1%) and CD117 (1.9%). Based on the availability of outcome data, a total of 177 ALL patients were included in the survival analysis (F: 47.5%, M: 52.5%, age 0 to 82 years). B-ALL patients (n = 141) with and without myeloid antigen expression had no significant difference in overall survival. Similarly in the T-ALL patients (n = 36), there was no significant difference in overall survival between these 2 groups. Moreover, there was no association of relapse or disease persistence of ALL with myeloid antigen expression (Figure 93).
Conclusions: Expression of myeloid markers does not represent adverse prognosis in ALL patients. This finding suggests that myeloid-surface antigen expression can be excluded from the strategic considerations in ALL treatment planning.
A Rare Case of CD15-Expressing Nodular Lymphocyte Predominant Hodgkin Lymphoma: (Poster No. 136)
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) can be diagnosed by its characteristic morphologic and immunophenotypic features; however, variation in these features can make diagnosis of NLPHL difficult. We report a case of NLPHL with classical morphologic features and rare aberrant expression of CD15. The patient was a 42-year-old man presenting with progressive weakness, muscle wasting, and weight loss. Computed tomography revealed mesenteric and right axillary lymphadenopathy. An excision of the axillary lymph node revealed nodular effacement by predominantly small lymphocytes (that are predominantly B lymphocytes) with clustering of large pleomorphic, multi-lobulated lymphoma cells. These lymphoma cells were positive for CD45, CD20, PAX5, BCL6, OCT2, BOB.1, and CD15 (focal), but negative for CD30 and EMA (Figure 94). Epstein-Barr virus (EBER) in situ hybridization was negative. The lack of CD30 and EBER-encoded RNA coupled with the strong expression of B-cell markers excludes the diagnosis of classical Hodgkin lymphoma. CD15 expressing NLPHL has not been previously described by the World Health Organization; however, few cases have been reported in the literature. We emphasize the importance of recognizing this subset of CD15+ NLPHL because it could present as a diagnostic challenge, mimicking classic Hodgkin lymphoma.
Hodgkin and Reed-Sternberg and Hodgkin- and Reed-Sternberg–Like Cells in Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Reactive Lymphadenitis, and 2 Cases of Hodgkin Lymphoma, Small/Syncytial Cell Variant: (Poster No. 141)
Context: Hodgkin lymphoma is characterized by scattered Hodgkin and Reed-Sternberg (HRS) cells in a background of mixed inflammatory cells. HRS cells are large mononucleated or multinucleated cells that typically express CD15, CD30, PAX5, and MUM1. The presence of HRS cells is not limited to Hodgkin lymphoma. Cells with similar morphology to HRS cells, called HRS-like cells, can be seen in CLL and lymphadenitis. On the other hand, Hodgkin lymphoma may present with HRS variants.
Design: We compared the morphology and IHC phenotype of HRS cells in Hodgkin lymphoma and HRS-like cells in CLL and lymphadenitis (Table).
Results: Similar to HRS cells, HRS-like cells were positive for CD15, CD30, MUM1, and PAX5 and were negative for CD20 and CD45. HRS-like cells express additional markers representing the disorders where they reside, such as CD5, CD23 in CLL. HRS-like cells can be positive for markers that HRS cells don't express, such as BOB.1 and OCT-2. We also examined 2 cases of relapsed Hodgkin lymphoma with atypical HRS cells, which were medium-sized immunoblast-like (Figure 95); positive for CD30, MUM-1, CD15 (partial), and PAX5; negative for CD20, CD45, CD68, CD3, ALK-1, BOB.1, OCT-2, and with variable EBER expression. Thus, we propose there might be a small/syncytial cell variant of Hodgkin lymphoma that has not been reported before.
Conclusions: The presence of HRS cells is not specific for Hodgkin lymphoma. HRS-like cells can be identified in other lymphoma and lymphadenitis. In addition, classical Hodgkin lymphoma may have a variant featuring small/syncytial cells.
Primary Small Intestinal Hodgkin Lymphoma: (Poster No. 143)
Primary gastrointestinal lymphomas are very rare and account for 1%–4% of all gastrointestinal tumors. The gastrointestinal tract, with an incidence of 0.5%, is rarely the primary site for Hodgkin lymphoma. Because of the rarity of Hodgkin lymphoma in this location, strict criteria for the diagnosis are used. We report a case of a 62-year-old man who presented with intermittent abdominal pain, nausea, and vomiting for 8 months' duration. A computed tomography scan showed a 4.8-cm single jejunal mass and multiple pulmonary lesions, which were radiologically suspicious for metastatic disease. A small-bowel resection was performed and revealed a 5.0 × 4.0 × 1.5-cm tan-white, firm, obstructive mass within the jejunum. Microscopically, the bowel mucosa was ulcerated and showed a transmural infiltration by a mixed population of cells including lymphocytes, plasma cells, histiocytes, neutrophils, eosinophils, and malignant tumor cells suggestive of Reed-Sternberg cells. Immunohistochemistry showed that the malignant cells were positive for CD15 and CD30 and negative for CD3, CD20, and CD45, confirming that cells were in fact Reed-Sternberg cells. Based on histomorphology and immunohistochemistry, the diagnosis of Hodgkin lymphoma was established; however, the diagnosis of primary Hodgkin lymphoma is inferred because a single mass within the jejunum with multiple masses within the lungs was present on computed tomography scan at initial presentation. Although rare, Hodgkin lymphoma of the gastrointestinal tract has a good response to therapy and favorable prognosis in many cases (Figure 96).
A Case of Primary Cardiac Epstein-Barr Virus–Positive Diffuse Large B-Cell Lymphoma Arising Within a Left Atrial Myxoma in an Immunocompetent Patient: (Poster No. 145)
Primary cardiac tumors are rare, with more than 90% being benign. Cardiac myxomas represent 84% of all cardiac tumors. While secondary involvement by disseminated lymphoma is fairly common, primary cardiac lymphoma accounts for roughly 2% of all primary cardiac neoplasms and <1% of extranodal lymphomas. We report the case of a 50-year-old man with chest pain. Echocardiography revealed an atrial mass. The specimen was a pedunculated, 7 × 3-cm, brown, gelatinous mass (Figure 97, A). Microscopically, it showed the typical appearance of a cardiac myxoma and displayed positivity for calretinin, CD34, and S-100. However, the periphery of the lesion was composed of large. highly atypical lymphoid cells with abundant mitosis (Figure, B) that were positive for CD20 (Figure, C), CD30, BCL-2, and MUM-1 while negative for CD10, BCL-6, and ALK and demonstrated a high level of Ki-67 expression. The diagnosis of Epstein-Barr virus–positive diffuse large B-cell lymphoma arising within an atrial myxoma was made. Staging studies revealed no evidence of lymphoma elsewhere, indicating this to be a true primary cardiac lymphoma. Recently, it has been proposed that primary cardiac Epstein-Barr virus–positive diffuse large B-cell lymphoma of the immunocompetent patient is a distinct type of primary cardiac lymphoma arising in association with an underlying local pathologic process that generates an altered immune microenvironment conducive to lymphoma development. As evident in recent case reports, primary cardiac Epstein-Barr virus–positive diffuse large B-cell lymphoma appears to have an indolent clinical course; therefore, its recognition may be significant for therapeutic decisions and prognosis.
Therapy-Related T/Myeloid Mixed-Phenotype Acute Leukemia Following R-CHOP Chemotherapy for Primary Cutaneous Diffuse Large B-Cell Lymphoma: (Poster No. 146)
Mixed-phenotype acute leukemia is a rare entity that accounts for 2%–5% of all acute leukemias. Therapy-related mixed-phenotype acute leukemia is an exceedingly rare hematologic neoplasm that accounts for less than 1% of acute leukemias. These leukemias are associated with alkylating agents and topoisomerase II inhibitors and have a poor prognosis. We describe a case of therapy-related mixed-phenotype acute leukemia following chemotherapy for primary cutaneous diffuse large B-cell lymphoma. The patient is a 63-year-old woman who presented with several large cutaneous nodules consistent with primary cutaneous lymphoma. Staging revealed no bone marrow involvement or extracutaneous involvement at the time of diagnosis. The patient was treated with systemic chemotherapy. She was in remission for 4 years when she presented with dyspnea, night sweats, weakness, and diffuse lymphadenopathy. Her presentation was initially concerning for recurrent lymphoma; however, flow cytometry of the peripheral blood revealed 10% CD34+ blasts suspicious for acute leukemia. A bone marrow biopsy and aspirate were performed, with flow cytometry showing 20% CD34+ blasts showing coexpression of CD117, bright CD7, cytoplasmic CD3, and myeloperoxidase (Figure 98, D). The bone marrow biopsy was hypercellular at 80%–90% and showed sheets of blasts (Figure, A). There was no evidence of her cutaneous B-cell lymphoma. Immunostaining of the bone marrow showed the tumor cells positive for CD34, CD117, CD3 (Figure, C), CD7, myeloperoxidase (Figure, B) and TdT and negative for CD5, CD20, and CD79a. Cytogenetics showed an abnormal 46,XX,t(8,12)(q22,p13) karyotype and normal AML/MDS FISH panels. Mutational analyses for NPM1 and FLT3 were negative.
Natural Killer–Cell Enteropathy: An Indolent Mimic of T-Cell Lymphoma: (Poster No. 147)
A recently described benign entity, natural killer (NK)–cell enteropathy is significant for the risk of misdiagnosis as extranodal NK/T-cell lymphoma, peripheral T-cell lymphoma, or enteropathy-associated T-cell lymphoma (type II) with subsequent overtreatment. We report a case of NK-cell enteropathy initially misdiagnosed as a peripheral T-cell lymphoma. A 55-year-old woman presented for routine screening colonoscopy, and was found to have a 7-mm, sessile rectal polyp. Biopsy showed a fairly well-circumscribed, submucosal population of large, atypical lymphoid cells with irregular nuclear contours, occasional prominent nucleoli, and a moderate amount of clear cytoplasm, admixed with small lymphocytes and eosinophils (Figure 99). Immunohistochemical staining showed the atypical cells to be positive for CD2, cCD3, CD7, CD56, and CD45, with focal faint staining for CD8, and negative for CD4, CD5, CD20, CD30, CD68, CD1a, and S100. In situ hybridization for Epstein-Barr virus was also negative. A diagnosis of peripheral T-cell lymphoma was suspected, and the patient was referred to our hospital for treatment and bone marrow transplant evaluation. Staging workup, including a positron emission tomography scan and bone marrow biopsy, showed no evidence of disease. The overall clinical features, morphology, and immunophenotype were found to be compatible with NK-cell enteropathy. A colonoscopy 5 months later showed a single tubular adenoma; random biopsies revealed no atypical lymphoid infiltrates. NK-cell enteropathy is a rare and recently described, apparently benign NK-cell lesion that may be found in asymptomatic patients on routine colonoscopy. Awareness of this lesion is essential to prevent misdiagnosis and unnecessary, potentially harmful therapies.
Mediastinal Lymph Nodes With Mesothelial Inclusions Mimicking Metastatic Carcinoma: (Poster No. 151)
A 27-year-old previously healthy woman presented with a 2-month history of dyspnea at rest, peripheral edema, and chest palpitations. Upon hospital admission she developed superior vena cava thrombosis, recurrent bilateral chylothorax, and pericardial effusions, undergoing thoracic duct ligation and bilateral pleurodesis with no significant improvement. Radiologic workup revealed only enlarged level VII mediastinal lymph nodes, which were subsequently biopsied with a frozen section diagnosis of atypical cells of undetermined significance and permanent sections showing a nest of atypical nonhematolymphoid cells with a sinusoidal pattern of infiltration (Figure 100, A) and immunohistochemical phenotype characteristic of mesothelial cells: cytokeratin AE1/AE3 (Figure, B), cytokeratin 7, cytokeratin 5–6, calretinin (Figure, C), D2-40 (Figure, D), and mesothelin positive and CDX-2, CD20, CD34, CD31, and CD68 negative. A final diagnosis of benign mesothelial inclusions to lymph node was rendered. Patients with these types of processes have been reported in the literature as having a poor prognosis, especially ones with associated chylothorax and severe pleural or pericardial effusions. The majority of these patients have a coexistent malignancy, usually hematolymphoid, or an infectious process in the mediastinum. Although our patient has continued to develop recurrent pleural and pericardial effusions, no underlying malignancy or severe infection has been identified. Surgical pathologists should be aware of the presence of benign mesothelial cells within lymph nodes as an uncommon and underrecognized phenomenon, specifically at the time of frozen section, to avoid a misdiagnosis of metastatic carcinoma or mesothelioma.
A Unique Case of a Myelodysplastic/Myeloproliferative Neoplasm With Distinct Histiocytic and Dendritic Outgrowths: (Poster No. 152)
Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) are rare histiocytic disorders. There are a limited number of case reports of patients with ECD in association with LCH. We report a case of a 61-year-old woman who presented with a truncal rash of several months duration. A skin biopsy showed a dermal infiltrate of histiocytic cells positive for CD68, S100, and CD1a, supporting the diagnosis of LCH (Figure 101, A). Several months later, she was hospitalized for hypernatremia due to diabetes insipidus, anemia, thrombocytopenia, and leukocytosis. A bone marrow biopsy showed a myeloid hyperplasia without definite dysplasia and large, atypical histiocytes showing erythrophagocytosis and neutrophil emperipolesis (Figure, B). These histiocytes were positive for CD68 and negative for S100 and CD1a. The peripheral blood showed neutrophilia with hypogranular and hypersegmented forms and an absolute monocytosis with immaturity, but no increase in blasts. An abdominal computed tomography showed soft tissue infiltration surrounding the aorta and kidneys. The patient's history of diabetes insipidus, the radiographic findings of the aorta and kidneys, and morphologic findings of the bone marrow led to a diagnosis of ECD with evidence of an underlying myelodysplastic/ myeloproliferative neoplasm. A subsequent duodenal biopsy revealed an infiltration of the submucosa by atypical histiocytes positive for CD68 and S100 but negative for CD1a (Figure, C). The patient expired within 1 month after diagnosis of ECD. We presented here a unique case of a patient with multisystem involvement by 3 different histiocytic proliferations with distinct morphologies and immunophenotypes and evidence of an underlying myeloproliferative/myelodysplastic neoplasm.
Performance of Published Algorithms in the Classification of Specimen Types for Coagulation Testing: (Poster No. 153)
Context: Plasma is often separated from cells and transferred into transport tubes for coagulation testing. In this process, certainty about the specimen type is lost. A reference laboratory may generate spurious results unless it can identify inappropriate specimens. Published algorithms use calcium, sodium, and potassium (algorithm 1) or sodium and potassium (algorithm 2) to classify specimens as citrate plasma or other type.
Design: Calcium, sodium, and potassium were measured on 129 sodium citrate specimens and 43 EDTA specimens after completion of coagulation or hematology testing in Intermountain Central Laboratory. Tests results were obtained from a data warehouse for 4903 lithium heparin specimens and 10 096 serum specimens submitted for chemistry testing. Specimen types were classified by algorithms 1 and 2, and classifications were compared against actual specimen types.
Results: Both algorithms correctly classified all EDTA specimens as noncitrated plasma. Algorithm 1 correctly classified 100.0% of citrate specimens, 42.4% of lithium heparin specimens, and 97.9% of serum specimens. Algorithm 2 correctly classified 99.8% of lithium heparin specimens and 100.0% of serum specimens, but only 3.1% of citrate specimens. Figure 102 shows the proportion of each specimen type classified as citrate plasma by each algorithm.
Conclusions: Neither algorithm simultaneously classifies all specimen types correctly. Algorithm 1 lacks specificity, classifying a majority of lithium heparin specimens as citrate plasma. Algorithm 2 lacks sensitivity, placing most citrate specimens into the lithium heparin/ serum category. Alternative algorithms must be developed to use chemistry values in the identification of inappropriate specimens for coagulation testing.
Autopsy and Forensic Pathology; Bone and Soft Tissue Pathology; Gynecologic and Placental Pathology; Head, Neck, and Oral Pathology; Cardiovascular Pathology A Case of Unsuspected Hereditary Hemochromatosis and the Important Role of Autopsy: (Poster No. 1)
Autopsy serves an important role in diagnosis and as a teaching tool for clinicians. The deceased was a 34-year-old man with history of heavy alcoholism (750 mL vodka per day) for the past 2 years. He presented to the emergency room because of fatigue, fever, and abdominal protrusion and pain. On physical examination generalized jaundice, bilateral pleural effusion, and ascites were identified. Serology was negative for HIV and hepatitis B and C. Radiology showed small liver and splenomegaly. The patient was admitted with diagnosis of alcohol-induced liver failure. Shortly after admission, he developed hepatic encephalopathy and quickly became unresponsive and coded. Autopsy confirmed clinical findings including shrunken irregular firm liver besides chronic pancreatitis. Microscopy showed micronodular cirrhosis with extensive iron overload (Figure 103, A and B). Moreover, Prussian blue iron staining revealed generalized iron deposition within heart, thyroid, skin, pancreas, testicle and pituitary (Figure, C and D). After further discussion with the family to exclude any secondary sources for the hemochromatosis, a quantitative liver iron study was done on paraffin-embedded liver tissue. This study demonstrated significant elevation of hepatic iron index at 9.8 μmol/g/y (normal <1.9 μmol/g/y). Given the absence of any secondary reason for hemochromatosis and hepatic iron index of >1.9 μmol/g/y, the diagnosis of hereditary hemochromatosis was confirmed, which was not the leading clinical diagnosis for his cirrhosis, and genetic counseling was done for the family. This case exemplifies the important role of autopsy in diagnosis, clinician education, and prognosis of surviving family members.
Rare Occurrence of Martinez-Frias/Mitchell-Riley Syndrome With Neonatal Hemochromatosis: A Second Reported Case: (Poster No. 2)
Martinez-Frias Syndrome (MFS) is a rare, fatal, autosomal recessive disorder characterized by pancreatic hypoplasia, intestinal atresia, and gallbladder aplasia/hypoplasia, with or without tracheoesophageal fistula. A variant of this syndrome, Mitchell-Riley syndrome, has features of MFS with neonatal diabetes but without tracheoesophageal fistula. We report a 10-day-old female infant born at 39 weeks gestation with multiple congenital anomalies fulfilling the diagnostic criteria of MFS with neonatal hemochromatosis. To our knowledge, this association has been reported only once. Following vaginal delivery the infant was noted to be growth restricted and was transferred to the NICU for variable hypo-hyperglycemia control. Two days later she underwent repair of duodenal atresia and intestinal malrotation. She expired 10 days later from hypoxic-ischemic encephalopathy. At postmortem examination she demonstrated pallor, jaundice, small face and narrow chin, short nose with anteverted nares, down-slanting palpebral fissures, pancreatic hypoplasia with dispersed islet cells (Figure 104, A), marked hepatic hemosiderosis (Figure, B), intestinal atresia, gallbladder aplasia, Meckel diverticulum, microcolon, and intestinal malrotation. Tracheoesophageal fistula was not identified. Whole genome microarray DNA analysis on peripheral blood detected a region of homozygosity at chromosomal band 6q15 to 6q22.33, containing the RFX6 gene, which has been associated with MFS. This gene has been found to affect the embryogenesis of anterior endodermal organs, pancreatic islets, and insulin production, with mutations causing small-bowel defects and neonatal diabetes, as seen in this case. Whether this gene is associated with neonatal hemochromatosis requires further study.
Case Report of a Rare Fatal Pulmonary Alveolar Proteinosis With Review of Literature: (Poster No. 4)
Pulmonary alveolar proteinosis was first described by pathologists Rosen, Castleman, and Liebow in the New England Journal of Medicine in 1958 as an accumulation of lipoproteineous material in the alveolar spaces with lack of fibrosis. This material was identified as surfactant by Larson and Gordinier in 1965. In recent years, approximately 240 case reports and a 410-case miniseries have been published in English literature. The disease is mainly considered an autoimmune process where inhibition of granulocyte-macrophage colony-stimulating factor (GM-CSF) by blocking autoantibodies results in the lack of surfactant clearance from the alveolar spaces. Pulmonary proteinosis can be secondary to diverse underlying disorders such as infections, hematologic malignancies, immunodeficiencies, or mutations in surfactant protein genes that lead to rare congenital disease presentations. Treatment mainly consists of repeated whole lung lavage or new GM-CSF therapies. Fatalities due to the pulmonary alveolar proteineous are even rarer. At the Wayne County Medical Examiner's Office, we report a case of a 46-year-old woman who died of pulmonary alveolar proteinosis. Conversations with family members disclosed that she suffered from chronic respiratory issues since 2006 and had undergone multiple lung lavages, some of which resulted in respiratory difficulties. Salient findings at autopsy included heavy lungs with firm bilateral consolidation. Microscopic examination showed granular material filling the alveoli (Figure 105, A). Periodic acid–Schiff (PAS) stain showed increased staining in the larger aggregates (Figure, B). Special stains for microorganisms were negative.
Hunting for Immediate Cause of Death in a 75-Year-Old Man With Multiple Diseases: (Poster No. 5)
It can be challenging to discern the immediate cause of death (COD) when a decedent has multiple coexisting severe diseases. Carefully checking the medical history and performing a full autopsy can avoid mistakenly overestimating contributing factors and missing the true COD. We report the autopsy of a 75-year-old man who died after 2 weeks of progressing confusion, difficulty walking, and delirium. Magnetic resonance imaging showed ischemic changes in the midbrain, basal ganglia, and periventricular and subcortical regions. He had just been discharged from a previous hospitalization for persistent hypertension. Prior history was notable for severe coronary artery disease, diabetes, hypertension, lung cancer status post pneumonectomy, and prostate cancer status post radiation therapy. The clinical findings strongly suggested cerebrovascular ischemia as the COD, but metastatic tumor could not be excluded. Initial autopsy findings confirmed severe coronary artery disease, with incidental findings of papillary thyroid carcinoma and papillary renal cell carcinoma, but no evidence of residual lung cancer or prostate cancer. Careful examination of the brain revealed several dusky areas in the left periventricular white matter and brainstem, as well as softening of the periaqueductal gray matter (Figure 106, A). Sections from those areas revealed large CD20+ atypical lymphocytes (Figure, B). Diagnosis of primary diffuse large B-cell CNS lymphoma was made and is considered to be the immediate COD. This case proved the necessity and importance of autopsy in decedents with multiple severe diseases because 3 malignant tumors, including the immediate COD, would have been missed without autopsy.
Unique Adult Autopsy Case of Spontaneous Retroperitoneal Hemorrhage in a Patient With Hepatitis C Viral Infection: (Poster No. 8)
We report a 68-year-old African American man with a past medical history significant for emphysema, hypertension, type II diabetes mellitus, and hepatitis C infection. The patient complained of worsening shortness of breath, chest pain, productive cough, and lower extremity edema. His symptoms began a few weeks prior to presentation and did not improve with the use of a nebulizer and prednisone. Admission examination revealed hypertension, tachycardia, tachypnea, diminished breath sounds, bilateral rhonchi, and bilateral pitting edema of the lower extremities. Laboratory examination revealed leukocytosis and mild hyperkalemia. After admission he complained of right leg pain and examination revealed abdominal ecchymosis followed by hypovolemic shock. Despite aggressive cardiopulmonary resuscitation, he expired. Autopsy findings directly related to his death included hepatic cirrhosis and a large right retroperitoneal hemorrhage measuring 21 ×9 ×9 cm with extension into the proximal right lower extremity and adjacent pericolonic adipose tissue. Hemorrhage was also identified within the right lower lobe of the lung with direct extension to the diaphragm. No bleeding site was identified despite thorough examination. This sudden, large hemorrhage explains the acute onset of hypovolemic shock prior to his death. Spontaneous retroperitoneal hemorrhage has been reported in association with anticoagulant therapy, cirrhosis, and trauma. Diagnosis of retroperitoneal hemorrhage is often difficult because of vague symptoms at presentation, especially in patients without a history of anticoagulant therapy or trauma. Cirrhosis has been implicated in some reports of spontaneous retroperitoneal hemorrhage. Delay in diagnosis can lead to significant morbidity and mortality (Figure 107).
Hepatic and Gastric Pathology Discovered at Autopsy in Neurofibromatosis Type 2: (Poster No. 11)
Neurofibromatosis type 2 is a rare dominantly inherited cancer syndrome associated with multiple tumors of the nervous system, most commonly meningiomas and bilateral vestibular schwannomas, and uncommonly neurofibromas. We report a case of visceral involvement by neurofibromatosis type 2–related neoplasms identified at autopsy. The 20-year-old woman had presented with a 1-year history of unsteady gait and progressive hearing loss, and was found to have bilateral vestibular nerve root lesions and a large meningioma in the foramen magnum compressing the spinal cord. She died suddenly from intracranial hemorrhage approximately 1 week after staged resection of the foramen magnum meningioma. Autopsy identified additional meningiomas of the intracranial dura and spinal cord and schwannomas of multiple cranial and spinal nerve roots, including bilateral vestibular schwannomas. There were multiple cutaneous plexiform schwannomas. An unexpected finding was extensive irregular hepatic fibrosis with an unusual macroscopic appearance, which could not be classified as to etiology, with extensive bile ductule proliferation and portal fibrosis. This was associated with a pattern reminiscent of evolving sinusoidal obstruction. Antemortem liver function tests were not notably abnormal. Several well-circumscribed macronodules containing intrahepatic neurofibromas were identified, focally exhibiting a microscopic intra-sinusoidal growth pattern. A single submucosal plexiform schwannoma was present in the gastric fundus. To our knowledge, this hepatic and gastric pathology in neurofibromatosis type 2 has not been described in the literature (Figure 108).
Diaphragmatic Paralysis in a Patient With Antisynthetase Syndrome: A Case Study at Autopsy and Literature Review: (Poster No. 16)
Antisynthetase syndrome is a rare autoimmune disorder associated with autoantibodies to tRNA synthetase. It includes a constellation of clinical features including interstitial lung disease, inflammatory myopathy, inflammatory polyarthritis, Raynaud's phenomenon, fever, and “mechanic's hands.” Because of a low prevalence, a complete pathophysiologic disease process has yet to be characterized. We report a case of a 72-year-old woman with antisynthetase syndrome and positive anti-JO1 serum antibodies, with onset of progressive muscle weakness for 1 year. She presented, unresponsive, to the emergency department and was admitted for hypercapnic respiratory failure. During her hospital course, she developed severe diaphragmatic paralysis requiring intubation, and, despite aggressive management, died 3 days postadmission. At autopsy, there was severe, multifocal pulmonary fibrosis with chronic inflammation, edema, and pleural effusions. Histologic examination of the diaphragm, psoas, and gastrocnemius muscles showed mild to moderate chronic inflammatory infiltrates with severe endomesial and perimesial fibrosis, degenerating/ regenerating muscle fibers, and marked muscle atrophy, most pronounced in the diaphragm (Figure 109, A). Proximal muscle taken from the pectoralis, however, showed no myopathic changes. These findings suggest an antisynthetase-related myopathic paralysis rather than interstitial lung disease as the primary underlying cause of death. Postmortem immunohistochemical analysis, molecular studies, and literature review were performed.
Sudden Death With Myocardial Bridging in the Setting of Severe Atherosclerotic and Hypertensive Cardiac Disease: (Poster No. 18)
Myocardial bridging, a developmental anatomic variation, proximally affects a single epicardial coronary artery branch that has normally derived from its aortic origin. Bridging is defined by a thick anomalous band of subepicardial myocardium overlying the arterial segment, referred as the “tunneled artery,” usually the mid left anterior descending branch. According to Alegria et al, the tunneled segment may be compressed with each systole, and myocardial bridging has been clinically associated with angina, arrhythmia, depressed left ventricular function, myocardial stunning, early death after cardiac transplantation, and sudden death. We report sudden cardiac death in a 45-year-old man with past medical history of mild hypertension controlled by medication. At autopsy, findings were confined to the enlarged heart (771 g). In addition to concentric left ventricular hypertrophy (2 cm in thickness), microscopic patchy remote subendocardial fibrosis of the left ventricle papillary muscles and posterior wall was observed. No acute ischemic myocardial changes were identified. The aorta was of normal caliber with minimal atherosclerotic changes. Sectioning through the anterior descending artery documented a 0.6-cm segment running intramurally (beneath a 0.4-cm myocardial bridge; Figure 110, A and B). Marked atherosclerotic narrowing (greater than 80%; Figure, C) was present proximal to the stenosed intramural artery segment. The cause of death was attributed to complications of severe atherosclerotic and hypertensive cardiovascular disease, with myocardial bridging as a major contributing factor. Awareness of this anatomic variation is critical in the autopsy of sudden cardiac death cases.
Fatal Hemorrhagic Pneumonia Caused by Stenotrophomonas maltophilia in a Patient With Acute Myeloid Leukemia: An Autopsy Case Report: (Poster No. 19)
Stenotrophomonas maltophilia (SM) is a nonfermenting gram-negative bacillus with emerging importance as a dangerous hospital-acquired opportunistic pathogen, causing pneumonia, sepsis, urinary tract or skin infection, and meningitis. Hemorrhagic pneumonia is one of the most severe SM infections. Although SM is very rare compared to other hemorrhagic pneumonia-causing pathogens such as invasive fungi, SM infection is usually lethal and shows resistance to multiple antibiotics. We report on a 46-year-old man with acute myeloid leukemia who developed chemotherapy-associated pancytopenia, hemorrhagic pneumonia, and acute respiratory failure as the immediate cause of death. Postmortem examination revealed both lungs to be wet, heavy, and hemorrhagic (2140 g left; 2280 g right). Microscopically there were diffuse intra-alveolar hemorrhage and fibrin exudate deposition, with parenchymal necrosis, consistent with hemorrhagic pneumonia (Figure 111, A and B). Many bacilli were seen in both the interstitium and alveolar parenchyma; there was no acute inflammation in this immunosuppressed patient (Figure, B). There was no evidence of cytomegalovirus, herpes simplex virus, or fungal infection. Bone marrow aplasia was observed, explaining the lack of inflammation in the lungs. Postmortem culture of bilateral lung tissue obtained at autopsy revealed SM with multidrug resistance. The patient died shortly after the onset of pneumonia. In summary, we presented an autopsy case with SM-caused hemorrhagic pneumonia, which is usually a fulminant and lethal complication associated with bone marrow failure secondary to hematologic malignancies.
Cardiac Metastasis of Cutaneous Squamous Cell Carcinoma in a Patient With Graft-Versus-Host Disease: (Poster No. 20)
The 63-year-old man had a significant past medical history of follicular lymphoma (1996) treated with chemotherapy. He subsequently relapsed and was treated with allogenic bone marrow transplant (1997) resulting in chronic graft-vs-host disease (GVHD) of skin and lungs (1998). He was treated with immunosuppression therapy until spring 2010 and later with low dose Imatinib. He was diagnosed with cutaneous squamous cell carcinoma (SCC) of his left leg (June 10, 2011) with metastasis to left inguinal lymph nodes, prompting a left leg below knee amputation. The patient was admitted on December 17, 2012 for worsening shortness of breath, chest pain, low-grade fever, and altered mental status. The patient's condition deteriorated and he died on January 10, 2013. His autopsy showed gross and microscopic evidence of metastatic SCC involving pericardium, right ventricle (Figure 112, A and B), and left ventricle. Microscopic examination of interventricular septum showed another focus of metastatic SCC (Figure, C and D). Other gross and microscopic metastases were found in lymph nodes, chest wall, lungs and pleura, diaphragm, liver, kidneys, and adrenal glands. Metastatic tumors in the heart from SCC are rare but have been reported in immunocompetent and post–renal transplant patients. Most cases involve the pericardium, but rarely the myocardium or endocardium is involved. To the best of our knowledge, this is the first report of metastatic cutaneous SCC to the heart of a GVHD patient treated with immunosuppressive therapy.
Fatal Hepatic Vascular Malformation in a Third-Trimester Female Fetus: (Poster No. 22)
A stillborn female fetus, 25 weeks, 3 days gestation, was delivered to a healthy 26-year-old gravida 2 mother with regular prenatal care and a normal sonogram at 21 weeks gestation. At 25 weeks gestation, she felt decreased fetal movement, and ultrasound followed by fetal magnetic resonance imaging (Figure 113, A) revealed an 8.3-cm abdominal mass of uncertain origin with a differential including nephroblastoma, hepatoblastoma, and, because of the rapid change in size, a vascular lesion. The following day, she felt no fetal movement, and ultrasound diagnosed intrauterine fetal demise. Induction of labor and delivery followed the next day. Gross examination at autopsy revealed an 8-cm hemorrhagic, necrotic hepatic lesion (Figure, B), and no other congenital malformations. Histology with trichrome staining (Figure, C) showed the lesion consisted of haphazard, dilated vascular spaces with areas of hemorrhagic infarction. Immunohistochemistry was positive for CD 31/34, confirming vascular origin, and negative for GLUT1 (Figure, D), classifying it as a vascular malformation rather than a hemangioma. Congenital hepatic vascular malformations are rare, nonneoplastic entities with only a few hundred described. Unlike hemangiomas, they do not regress spontaneously, respond to corticosteroids, or express GLUT1. Most present at birth and are resected without recurrence. This exceptional case suggests that an early third-trimester presentation, because of a faster proliferation, may herald a greater risk of infarction and intrauterine fetal demise. Better recognition of the behavior of hepatic vascular malformations in the third trimester would enhance prenatal counseling for these mothers.
Postmortem Findings in a Rare Autopsy Case of Thanatophoric Dysplasia: (Poster No. 24)
We report a newborn delivered at 39 weeks of pregnancy to a 23-year-old G3P1011 woman. Prenatal ultrasound performed in the second trimester revealed multiple congenital defects consistent with the lethal condition thanatophoric dysplasia (TD). The mother decided to continue the pregnancy and a female newborn was delivered at 39 weeks of pregnancy with Apgar scores of 4 at 1 minute and 7 at 5 minutes. Because of the grave prognosis the mother decided to discontinue invasive respiratory support and the newborn expired 9 hours after delivery. Autopsy examination revealed significant abnormalities including platyspondyly, micromelia with arm length 6.5 cm and lower extremity length 9 cm, macrocephaly with prominent forehead, depressed nasal bridge, enlarged abdomen, small thorax with short ribs (Figure 114), hypoplastic lungs weighing 25 g (average, 34.8–64.2 g) and hypoplastic heart weighing 13 g (average, 14.6–24.2 g). Additionally, extensive bilateral pulmonary hemorrhage was identified. The autopsy findings were consistent with respiratory failure due to lung hypoplasia as a result of TD type I. TD is an autosomal dominant disorder characterized by severe skeletal dysplasia. The condition arises because of sporadic mutations within the FGFR3 gene, which is responsible for regulation and development of bone and brain tissues. This condition occurs in 1 in 20 000 to 50 000 newborns. Affected individuals are usually stillborn or die shortly after birth from respiratory failure.
Lung Adenocarcinoma Metastasis to Tunica Adventitia of Ascending Aorta: An Autopsy Case Report: (Poster No. 27)
We report an interesting case of a 53-year-old woman presenting with vague abdominal discomfort and no known history of cancer. On admission, her lab results included marked increased D-dimer, mildly elevated INR, and normal hematocrit and platelets. Chest x-ray revealed normal lung and heart findings with no pericardial or pleural effusions. Her condition soon deteriorated with rapidly increased INR and PTT and decreased hematocrit and platelet count. She expired 14 hours after her admission. The autopsy examination revealed 400 mL of blood in the pericardium, bilateral straw-colored pleural effusions (right 700 mL, left 550 mL), and 1000-mL straw-colored ascites. Thorough examination of the heart and cardiac vasculature revealed a 2.0-cm hemorrhagic area at the anterior surface of ascending aorta. We found one 2.0-cm subpleural firm nodule in the upper lobe of the left lung. Other gross abnormalities included enlarged subaortic and para-aortic lymph nodes. Microscopic examination revealed the nodule as a lung adenocarcinoma, mixed type, which stained positive for TTF1 and CK7 and negative for CK20 and WT1. The hemorrhagic area at the ascending aorta was discovered to be a metastatic adenocarcinoma focus with marked hemorrhage in the tunica adventitia. Extensive tumor thrombi were also noted in microvasculature of the lung, pericardium, ascending aorta, and thymus. We conclude that the cause of death was cardiac tamponade, resulting from active bleeding from metastatic carcinoma foci at the tunica adventitia of the ascending aorta. The bleeding may have been precipitated by malignancy-related disseminated intravascular coagulation (Figure 115).
Current Cytology Examination Is Suboptimal for Microorganism Detection in Lung Transplant Patients: (Poster No. 29)
Context: Infection is one major complication of lung transplantation (tx). Special stains (GMS and PAS) and CMV immunohistochemical stain have been routinely performed to detect infectious pathogens in transbronchial biopsy (bx), bronchoalveolar lavage (BAL), and/or bronchial washing specimens; however, the efficacy of these microorganism detection methods is still controversial.
Design: To evaluate these pathogen detection methods, we retrospectively reviewed the lung tx patients who underwent autopsies from a single tx center in the past 2 decades (during 1992–2013). The microorganism detection methods were compared with regard to premortem transbronchial biopsy, BAL/bronchial washing cytology specimens, and tissue/BAL culture/PCR.
Results: A total of 82 autopsies were included in the present study. Forty-six patients died of infection/sepsis (bacteria/virus/fungus), of which 32 deaths (10 females, 22 males; age, 51.7 ± 2.26 years) were caused by virus/fungus. CMV was the main viral pathogen. Transbronchial biopsies were performed in 30 patients, with CMV detected in 10 patients (10 of 30). Of these 10 patients with CMV infection, cytologic examination was performed only in 5 patients, and none of them had (+) CMV diagnosis. Fungal organisms were detected in 5 patients in transbronchial biopsy, but none of them were detected by cytology. On the other hand, the sensitivity of CMV/fungus detection in tissue/BAL cultures or PCR was much higher than BAL/bronchial washing cytology examination (Figure 116).
Conclusions: Transbronchial biopsy and culture/PCR are more sensitive than BAL/bronchial washing cytologic examination to detect microorganisms. Cytologic examinations for microorganisms need to be further improved in lung tx patients.
A Novel Constellation of Congenital Cardiac Anomalies in the Setting of Monosomy X and 8p23.1 Duplication With Initial Presentation in Utero: (Poster No. 30)
Though monosomy X and 8p23.1 duplications have been well reported in conjunction with certain cardiac defects, we describe a case of a premature female newborn with a combination of monosomy X mosaicism and an 8p23.1 duplication on chromosomal microarray, with novel cardiac features previously unobserved in either entity. The mother is a gravida 6 para 5 with no family history of congenital heart defects. On sonogram, at approximately 19 weeks gestation, heart defects were detected and confirmed by prenatal fetal echocardiogram revealing a nonfunctional pulmonary valve with massive pulmonary artery dilation (Figure 117, A). An emergent Cesarean section was performed at 28 weeks gestation because of hydrops fetalis. Despite medical management, pulmonary hypertension persisted, the pulmonary artery continued to dilate (Figure, B), and the infant died at 45 weeks calculated gestational age. The heart anomalies confirmed at autopsy included severe pulmonary valve dysplasia and pulmonary arterial dilation (Figure, C and D), a bicuspid aortic valve, and dysplastic atrioventricular valves with shortened chordae tendineae and upwardly displaced papillary muscles. We are currently seeking chromosomal analysis to determine familial versus de novo 8p23.1 duplication, which has a phenotypic spectrum ranging from subclinical to more pronounced cardiac defects. In this novel case, we present a fatal constellation of cardiopulmonary manifestations uncommon to either 8p23.1 duplication or monosomy X mosaicism. In a literature review, the dysplastic pulmonary valve cusps and subsequent dilated pulmonary artery in utero are novel to these syndromes.
Senile Systemic Amyloidosis in an Elderly Patient Presenting With Gastrointestinal Bleeding: (Poster No. 31)
Amyloid is an abnormal protein made of continuous nonbranching fibrils in β-pleated conformation, which can accumulate in various tissues and organs insidiously. Senile systemic amyloidosis (SSA) is a common age-related amyloidosis that characterized by accumulation of transthyretin (TTR) predominantly in the heart. We report a case of an 83-year-old woman with history of hypertension, congestive heart failure, and restrictive lung disease, on coumadin therapy for pulmonary embolism, admitted with gastrointestinal bleeding. Despite stabilization of hemoglobin level, she developed progressive hypotension and died. Autopsy revealed significant cardiomegaly (750 g). The sigmoid colon had a hemorrhagic segment with several diverticula. The heart microscopically showed extensive, diffuse, homogenous depositions compressing the myocardial fibers. They are strongly positive with Congo red staining and give apple-green birefringence under polarized light. The lung sections microscopically showed massive diffuse and nodular alveolarseptal thickening by waxy, acellular amyloid deposits. Section of the hemorrhagic colon revealed diverticulosis and amyloid depositions in the vessels walls. The diagnosis of SSA is problematic secondary to lack of specific clinical symptoms or biomarkers. SSA is an acquired late-onset disease affecting patients in their 70s and 80s. However, 4% of the black population in the United States is a carrier of mutant allele of TTR, leading to deposition of mutant TTR mainly in the heart. In our case, congestive heart failure, restrictive lung disease, and gastrointestinal bleeding were the manifestations of an unsuspected SSA. Our case indicates that SSA should be in the differential diagnoses when evaluating cardiopulmonary symptoms in elderly patients (Figure 118).
Metastatic Merkel Cell Carcinoma to the Brain With Diffuse Involvement of Ventricular System: An Autopsy Report: (Poster No. 33)
Merkel cell carcinoma is a rare aggressive primary neuroendocrine carcinoma of the skin. Merkel cell carcinoma is known for its local recurrences. Metastasis to brain is rare and the intraventricular growth pattern has not been reported to our knowledge. The decedent was a 98-year-old woman who presented with acute delirium and confusion. She passed away 2 days after admission because of cardiopulmonary arrest. She had a history of Merkel cell carcinoma 4 years ago on the right index figure that was resected. Laboratory testing revealed severe hyponatremia (118 mmol/L), inappropriate elevation of urinary sodium (194 mmol/L), hypocalcemia (7.2 mg/dL), and hypokalemia (3.2 mmol/ L). The cerebrospinal fluid cytology was positive for malignant cells and brain. Magnetic resonance imaging showed diffuse intraventricular nodularity with focal outcroppings into adjacent white matter. At autopsy, gross findings included diffuse tan-white coating on the inner surface of ventricular cavities with focal extension into the surrounding white matter (Figure 119). Multiple metastatic foci were identified on the spleen capsule. Microscopic evaluation showed ill-defined nodules that were composed of monotonous small round cells with vesicular nucleus and dusty granular chromatin (Figure, inset). Frequent mitosis and extensive necrosis were also observed. Immunohistochemical stains revealed tumor cells positive for EMA, pan-CK, CD56, CK20, and NSE and negative for GFAP, CD45, HMB45, and CD99. The case is interesting because of these unique findings: intraventricular growth pattern mimicking primary neurologic disease, and electrolyte imbalance as a part of paraneoplastic syndrome.
A Rare Case of Wolman Disease Presenting as Hydrops Fetalis: (Poster No. 37)
Wolman disease is a rare autosomal recessive inborn error of metabolism resulting in the deposition of fat in multiple organs. This occurs because of total lack of the enzyme lysosomal acid lipase. There is massive accumulation of cholesterol esters and triglycerides in the spleen, liver, bone marrow, small intestine, adrenal glands, and lymph nodes. Mutations in chromosome 10q23 are usually seen. Wolman disease is estimated to occur in 1 in 350 000 newborns. We report a rare case of Wolman disease in a full-term male neonate presenting as hydrops fetalis. The parents of the baby were genetically related. The abdomen was distended, liver was enlarged and firm, and cut surface was pale yellow and greasy. Spleen was enlarged, firm, and reddish yellow. Thymus was not identified; adrenal was symmetrically enlarged and gritty. Histologic examination of the liver showed vacuolations in Kupffer cells and hepatocytes. There was periductular and periportal fibrosis. Oil red O stain was positive in the vacuolated cells. Adrenals showed areas of calcification and vacuolation. Spleen shows features of extramedullary hematopoiesis. One of the testes showed adrenal rest with vacuolation. In view of the clinical presentation, histopathology, and special stain, a diagnosis of Wolman disease was rendered. The differential diagnosis is cholesterol ester storage disease, which presents much later, is clinically milder, has a benign course, and only involves GIT and liver. Prenatal diagnosis is possible by assaying enzyme levels in cultured chorionic villi and amniocytes. Wolman may present as hydrops fetalis and a perinatal diagnosis is possible (Figure 120).
A Rare Case of Metastatic Oropharyngeal Squamous Cell Carcinoma With Cardiac Involvement: An Autopsy Report: (Poster No. 38)
Distant metastasis of head and neck cancer is not commonly seen, and therefore, the finding of cardiac metastasis in such cases is exceedingly rare. Of neoplasms with cardiac metastases seen at autopsy, oropharyngeal cancer ranks near the end of the list with a frequency of only 1%. We present a case of a 60-year-old man with oropharyngeal squamous cell carcinoma treated with chemoradiation, with metastases to the left lung and kidney. He presented with severe dyspnea and was found to have a low-voltage EKG, which spurred further evaluation with an echocardiogram, discovering a large mass involving the right ventricle. The patient succumbed to his disease within 2 days of this finding and an autopsy was performed. The metastatic disease was more extensive than previously thought, with masses identified in bilateral lungs, kidneys, and adrenals, as well as the heart. Of particular interest was the cardiac metastasis, which consisted of a white-tan mass with foci of hemorrhage and necrosis, mainly occupying the right ventricle wall and chamber (Figure 121, A), which was consistent with metastatic squamous cell carcinoma on histologic sections (Figure, B). P16 immunostain was performed and was negative, which corresponded with the original biopsy. Review of the literature only shows 4 cases of head and neck cancer with cardiac metastases that were discovered premortem, highlighting the rarity of this case. Additionally, this case displays the prognostic importance of assessing P16 status in head and neck cancers, as HPV-negative patients often display a worse disease course than their HPV-positive counterparts.
Proximal-Type Epithelioid Sarcoma With Angiomatoid Features Presenting as a Prevertebral Mass: (Poster No. 42)
Proximal-type epithelioid sarcoma is a rare and aggressive neoplasm that usually affects the axial skeleton of older individuals and primarily occurs in the pelvis, perineum, pubic region, and vulva. Rare variants of this entity have been reported. We describe an unusual case of proximal-type epithelioid sarcoma presenting as a prevertebral thoracic mass in a 44-year-old man. Image-guided fine-needle aspiration (FNA) of the mass demonstrated clusters of neoplastic cells with moderately abundant cytoplasm imparting a rhabdoid appearance, round to oval nuclei, and vesicular chromatin, as well as spindled cells (Figure 122, A). The corresponding tumor resection specimen demonstrated central necrosis surrounded by sheets of rhabdoid and spindled cells with pleomorphic nuclei and conspicuous mitoses. Some cells contained intracytoplasmic hyalinized globules. Prominent vascular spaces were noticeable (Figure, B). Immunohistochemically, the mass was positive for EMA, pancytokeratin (Figure, C), and CD34. Tumor cells werenegative for myogenin, CK7, CK20, S100, WT1, and β-catenin. INI BAF47 nuclear positivity was lost within tumor cells (Figure, D). These findings are compatible with a proximal-type epithelioid sarcoma with angiomatoid features. The presence of ectatic vascular spaces in this rare variant could be misinterpreted as angiosarcoma. Shown in the Figure are a high-power image of epithelioid and spindle tumor cells (Pap stain) (A); a high-power image highlighting angiomatoid spaces (H&E stain) (B); tumor cells are pancytokeratin positive (C); and loss of INI BAF47 nuclear positivity in tumor cells (D).
Thoracic Vertebrae Osteoblastoma With a Secondary Aneurysmal Bone Cyst Causing Neurologic Symptoms in an 11-Year-Old Girl: (Poster No. 44)
Osteoblastoma is a rare benign bone tumor comprising less than 1% of bone tumors, with sporadic secondary aneurysmal bone cyst formation. We present an interesting case of an 11-year-old girl with no significant past medical history who presented with lower extremity weakness and increasing gait instability. Imaging studies revealed an epidural mass extending from the T7–8 intervertebral disc to the T9–10 intervertebral disc, causing moderate to severe spinal cord stenosis. Given the location of the mass, the radiologic differential diagnosis consisted of a schwannoma, neuroblastoma, epidural meningioma, or cavernous hemangioma. Preliminary diagnosis was most consistent with aneurysmal bone cyst. Resection of the mass was performed and the histologic sections demonstrated woven bony trabeculae with osteoblastic rimming, rich stromal vascularity, osteoblastic proliferation, and scattered osteoclast-like multinucleated giant cells consistent with osteoblastoma (Figure 123, A). Some areas displayed blood-filled spaces separated by septa composed of loosely arranged spindle cells interposed with osteoclast-like giant cells and blue bone formation consistent with a secondary aneurysmal bone cyst component (Figure, B). This is a very interesting case of osteoblastoma with secondary aneurysmal bone cyst of the thoracic vertebrae causing neurologic symptoms, radiologically resembling a neurologic process. This case highlights that correct histologic diagnosis can be challenging in this compact lesion, as biopsy is only a limited sampling of the lesion, and may display only one of the components.
Melanocytic Neuroectodermal Tumor of Infancy: A Case Report and Review of the Literature: (Poster No. 46)
This rare tumor of neural crest origin typically presents during the first year of life and most commonly arises in the maxilla, with few case reports of involvement outside of the head and neck region. We report a case of a 4-month-old, full-term, healthy female infant sent for an evaluation of a rapidly growing right upper extremity mass. Ultrasound demonstrated a 3.2-cm complex mass with scalloped edematous edges. An excisional biopsy of the mass revealed a biphasic tumor composed of larger epithelioid cells containing variable amounts of melanin highlighted by Fontana-Masson stain admixed with smaller neuroblast-like cells. The larger epithelioid cells were positive for cytokeratin, CD99, and HMB45 immunostains, whereas the smaller cells were positive for synaptophysin and chromogranin. Additional immunostains (CD45, desmin, MyoD1, WT1, and S100) were all negative in both cell types, excluding other differential diagnoses. Although the majority of these tumors follow a benign course, high rates of local recurrence have been reported and metastases are known to occur. Complete surgical excision with close follow-up is generally recommended. In our case, the lesion was re-excised with negative margins and the patient has no evidence of recurrent disease 6 years following the diagnosis (Figure 124).
Histologic Features of Prognostic Significance in High-Grade Osteosarcoma With Particular Reference to the Development and Validation of a Grading System to Assess Response to Neoadjuvant Chemotherapy: (Poster No. 47)
Context: In osteosarcoma treated with neoadjuvant chemotherapy, the percentage of residual viable tumor is considered to reflect treatment response, correlating with survival in most, but not all, studies. We sought to identify other histomorphologic features of prognostic significance in pretreatment biopsy and primary resection specimens to improve upon existing methods of assessing chemotherapeutic effect.
Design: Slides of biopsy and resection specimens from 165 cases of high-grade osteosarcoma were reviewed. Univariate and multivariate analyses were performed to identify significant clinicopathologic and histologic features associated with overall survival. We proposed a “chemotherapy response score,” defined as the sum of tumor viability (1 [lt;10%] or 2 [≥10%]) and mitotic rate (0 , 1 [lt;10], or 2 [≥10] mitoses/10 high-power fields). External validation of this scoring system was performed on an independent set of 42 osteosarcomas.
Results: By univariate analysis, histologic features associated with poor prognosis included chondroblastic subtype and presence of spontaneous tumor necrosis assessed in pretreatment biopsies and the presence of lymphovascular invasion, ≥10% residual viable tumor, and ≥10 mitoses/10 high-power fields in posttreatment resections. Only tumor viability and mitotic rate on resection retained significance in the multivariate model adjusted for tumor size, tumor location, and metastatic status. The chemotherapy response score outperformed percentage residual viable tumor in predicting prognosis in both training and validation cohorts (Figure 125).
Conclusions: The amount of residual viable tumor and its proliferative activity posttherapy are independent measures of chemo-therapeutic efficacy and strongly associated with survival outcome. Based on this finding, we developed and validated a grading system for routine clinical use.
Sarcomatous Brain Metastases: A Single Institution, 28 Years of Experience: (Poster No. 48)
Context: Brain metastasis from sarcomas is rare and limited information is available. We examined pathologically confirmed sarcomas brain metastases diagnosed over a period of 28 years.
Design: This is a single-institution retrospective study of 112 cases of brain sarcoma metastasis. Clinical records were reviewed for demographic, clinical, pathologic, and survival data (Table).
Results: Undifferentiated sarcoma was the most common source (28%) followed by alveolar soft part sarcoma. Most common primary location was the extremities (50.0%). The majority were adults (89%) with a mean age of 35.7 years. Headache was the most common presenting symptom. Most showed an evidence of prior metastatic disease to other sites (73%). Median time to brain metastasis was 2.1 years (range: 0.03–16.70 years).Most of the metastatic foci were parenchymal (92%), nonhemorrhagic (70%), and single (78%). Half the tumor deposits were in the frontal lobes. Thirty-one percent of brain metastases recurred, all within 5.8 years. Of the patients, 76% succumbed to the disease, with a mean survival time of 1.37 years. No difference in survival was noted between hemorrhagic versus nonhemorrhagic (P = .22), single versus multiple (P = .72), or primary soft tissue versus bone sarcomas (P = .97). No effect on survival when surgical resection was combined with radiotherapy and/or chemotherapy (P =.19).
Conclusions: Brain metastasis is a late event in sarcoma clinical progression. In our study, undifferentiated sarcomas were the most common source of brain metastasis followed by alveolar soft part sarcoma. The majority of cases showed evidence of prior metastatic disease. Surgical resection is employed to manage symptoms, but prognosis remains dismal.
Emerging Immunohistochemical Markers for Malignant Peripheral Nerve Sheath Tumor: (Poster No. 50)
Context: Malignant peripheral nerve sheath tumor (MPNST) is an uncommon aggressive sarcoma that usually arises in association with nerve tissue. Morphologically, MPNST demonstrates variable histologic patterns rendering distinction from other sarcomas, particularly undifferentiated or unclassified pleomorphic sarcomas (UPS), challenging. Currently, the diagnosis is based on clinical evidence of neurofibromatosis type 1 disease or clinical evidence of neural origin along with the finding of usually high-grade sarcoma that often shows patchy S100 protein expression. We attempted to identify a panel of immunohistochemical markers that can aid in the diagnosis of MPNSTs and allow it to be robustly distinguished from the UPS category.
Design: Previously constructed tissue microarrays (TMAs) for MPNST and UPS were stained for S100 protein, PGP9.5, CD56, and podoplanin. Staining for additional markers including NF1 is currently in progress. The TMAs included 109 MPNST and 233 UPS tumor tissues. Statistical analysis was conducted using SPSS 21 software.
Results: Both PGP9.5 and S100 protein showed a higher percentage of expression in MPNST compared to UPS (P = .03, P < .001, respectively). CD56 was more highly expressed in MPNST compared to UPS but failed to demonstrate statistical significance (P = .19). Podoplanin, however, showed a significantly higher expression in UPS compared to MPNST (P = .005; Figure 126).
Conclusions: The diagnosis of MPNST routinely includes a panel of immunohistochemical markers that are characteristic of this tumor and help exclude histologic mimics including UPS. We suggest that along with S100 protein, other markers such as PGP9.5 and podoplanin could also be considered.
Terminal Deoxynucleotidyl Transferase Immunostaining of Sarcomeres in Rhabdomyosarcoma: (Poster No. 51)
Although skeletal muscle differentiation with sarcomeres is fundamental in the diagnosis of rhabdomyosarcoma, this feature is not always present. The diagnosis is made following multiple immunostaining including desmin and myogenin. We encountered a case of alveolar rhabdomyosarcoma that was evaluated with multiple immunostains prior to diagnosis including terminal deoxynucleotidyl transferase (TdT) to rule out lymphoblastic lymphomas/acute leukemia, which demonstrated positive immunoreactivity for TdT. We retrospectively analyzed a second case of poorly differentiated rhabdomyosarcoma for immunostaining with TdT. Anti-TdT rabbit polyclonal antibody was used in both cases and they were stained using Ventana ultra automated immunostainer. With hematoxylin and eosin stain, while the alveolar rhabdomyosarcoma revealed very rare and faint impression of sarcomeres (Figure 127, A), the latter were not identifiable in poorly differentiated rhabdomyosarcoma. Both rhabdomyosarcoma subtypes showed positive immunostaining of distinct sarcomere bands with TdT (Figure, B). Mild diffuse cytoplasmic staining of tumor cells was also noticed with few streaks of developing sarcomere bands. Normal skeletal muscle sarcomeres at the periphery of tumor in one case also showed positive staining for TdT. As TdT cross reacts with sarcomeres of rhabdomyosarcoma and normal muscle, diagnostic pitfalls during flow cytometry should be avoided. Because the reactivity of TdT is cytoplasmic in rhabdomyosarcoma compared to nuclear in leukemia, this could be of diagnostic value. TdT is a DNA polymerase located in the cell nucleus that catalyzes the polymerization of deoxynucleotides; why this stains sarcomeres in the cytoplasm is unknown at this time.
Decubital Ischemic Fasciitis/Atypical Decubitus Fibroplasia: A Pseudosarcomatous Lesion Commonly Presenting as Sarcoma: (Poster No. 52)
Ischemic fasciitis is a type of reparative/regenerative process, occurring primarily in physically debilitated or immobilized elderly patients. It consists of a fascia-based fibroblastic and myofibroblastic proliferation and is part of the pseudosarcomatous lesions group, which also includes nodular fasciitis, proliferative fasciitis, and proliferative myositis. The pathogenesis consists of intermittent ischemia leading to necrosis and breakdown, followed by a regenerative, reparative process. The lesion can be overdiagnosed as sarcoma clinically, cytologically, and even histologically. While histomorphologically similar to nodular fasciitis, it can be misdiagnosed as epithelioid sarcoma, myxofibrosarcoma, or myxoid liposarcoma. An 85-year-old woman presented with a 5-cm, ill-defined, painless, firm mass involving the right arm deep subcutis, muscle, and fascia, without skin ulceration. The mass was noted 3 weeks earlier, when the patient became bedridden after a complicated hip replacement. An atypical spindle cell lesion was diagnosed on core biopsy. The lesion displayed lobular configuration, fibrinoid necrosis, and prominent myxoid stroma, rimmed by ingrown, ectatic, thin-walled vascular channels (Figure 128, upper images, low power). Atypical, enlarged, degenerated fibroblasts and myofibroblasts with abundant basophilic cytoplasm, and large hyperchromatic smudged nuclei with prominent nucleoli were present (Figure, lower images, high power). Surgical excision of the lesion was performed because sarcoma could not be excluded. No recurrence or other symptoms were observed after 6-month follow-up. Clinical and histologic features of atypical decubital fibroplasia suggest a unique type of pressure sore with degenerative and regenerative features that are distinct from decubitus ulcer. Our case underscores the importance of recognizing this entity in order to avoid misdiagnosis and overtreatment.
Epithelioid Hemangioma of the Penis: (Poster No. 53)
Penile epithelioid hemangioma is a rare vascular tumor that is characterized by tumefactive proliferation of epithelioid endothelial cells and inflammatory infiltrate with lymphocytes and eosinophils. We present a case of penile epithelioid hemangioma. A 41-year-old man presented with a painful nodule on the penis. Physical examination revealed a 0.8-cm erythematous lesion on the dorsal base of the shaft of the penis. Histopathology showed a well-circumscribed vascular proliferation (Figure 129, A and B; low- and high-power view of the lesion). The vascular spaces were lined by plump epithelioid endothelial cells with enlarged nuclei and distinct nucleoli. Background inflammatory cells included lymphocytes and eosinophils. Differential diagnosis included epithelioid hemangioma and epithelioid hemangioendothelioma. The endothelial cells do not have the characteristic hyaline connective tissue matrix, definite hyaline globules, or severe nuclear atypia suggestive of epithelioid hemangioendothelioma. Immunohistochemical stains demonstrated that tumor cells showed strong expression of CD34 and minimal expression of CD31 (Figure, C and D; IHC staining showed strong positive for CD34 and negative for CD31). Ki-67 expression confirmed low proliferation rate. The final diagnosis was epithelioid hemangioma, completely excised. The patient was followed up with no signs of recurrence 6 months after excision. Histologically, penile epithelial hemangioma shows characteristic features of epithelioid appearance of endothelial cells with inflammatory infiltration of lymphocytes and eosinophils. The epithelioid endothelial cells have no nuclear atypia and low proliferation rate. Penile epithelioid hemangioma is a benign lesion. Complete local excision with periodic follow-up is the optimal management.
Primary Epithelioid Angiosarcoma of Bone With Robust Cell Cycle Progression and High Expression of SPARC: Therapeutic Implications: (Poster No. 57)
Epithelioid angiosarcoma is a very rare variant of angiosarcoma and it rarely involves bone as a primary site. SPARC (osteonectin) is a secreted protein that is acidic and cysteine-rich and binds albumin. Expression of SPARC in tumors has been correlated with sensitivity to albumin-bound paclitaxel, particularly in the context of robust cell cycle progression into the mitotic phase. We report a 62-year-old man who presented with lower extremity pain and was found to have lytic bone lesions involving the lower end of femur and upper end of tibia and fibula. The differential diagnoses after computed tomography–guided core biopsy included metastatic carcinoma, epithelioid sarcoma, and malignant epithelioid vascular lesion. Open biopsy showed epithelioid angiosarcoma involving lamellar bone with focal areas of epithelioid hemangioendothelioma. The mitotic figures were 19 per 10 high-power fields in the most mitotically active area. The tumor cells were positive for pancytokeratin, CAM 5.2, vimentin, CD31, CD34, and factor VIII. Ki-67 was positive in 50% of tumor cells. The resection specimen confirmed the diagnosis, with 3 of 3 positive lymph nodes. Multiple pulmonary nodules have been detected 3 months after identification of lytic bone lesions. Expression of SPARC has been reported in some soft tissue sarcoma cases, but has not been studied in epithelioid angiosarcoma of bone. When the resection specimen was examined immunohistochemically, there was strong and diffuse staining for SPARC (Figure 130). This finding could suggest new therapeutic options for further consideration.
Myoepithelioma of Bone: (Poster No. 58)
Myoepitheliomas are unusual tumors resembling salivary gland mixed tumors and showing myoepithelial differentiation. Initially described in salivary glands and later in soft tissue, myoepitheliomas arising in bone have been rarely reported. Herein we present 2 cases of myoepithelioma arising primarily in bone. Hematoxylin and eosin slides, ThinPrep prepared fine-needle aspiration slides, and a battery of immunostains were reviewed. The patients were both males, 70 and 58 years old, with tumors arising in the left proximal humerus and left iliac bones, respectively. The tumors were 11.2 and 12.0 cm in greatest dimension. One tumor showed solid sheets and cords of cells with clear cytoplasm. The fine-needle aspiration of the tumor exhibited cells with clear cytoplasm, enlarged hyperchromatic nuclei, and increased nuclear to cytoplasmic ratio. The other tumor showed similar architecture but with more eosinophilic cytoplasm and focal keratin pearls (Figure 131). Both tumors had a chondromyxoid background and did not show any significant nuclear atypia or increased mitosis. Immunostains showed both tumors to be positive for S100 and cytokeratin AE1/AE3. Other myoepithelial markers such as SMA, calponin and GFAP were negative. Fluorescent in situ hybridization (FISH) on both tumors exhibited an intact EWSR1 gene. The histologic descriptions and immunohistochemical staining pattern of these 2 tumors confirms the diagnosis of a myoepithelioma arising in bone. It is important to include this rare category of tumors in the differential diagnosis of epithelioid-appearing tumors in bone, and not to confuse them with metastasis.
Primary Synovial Sarcoma of the Pleura: A Case Report and Literature Review: (Poster No. 59)
Synovial sarcoma is a rare soft tissue malignancy. However, it has remained as a diagnostic challenge, because of its diverse biological behavior and variable anatomic sites. We present the case of a 16-year-old girl who had right-sided chest pain for 5 years and was managed conservatively as costochondritis. Recently, the nature of her chest pain changed abruptly, resulting in difficulty in breathing. A computed tomography scan of the chest showed a pleura-based soft mass (Figure 132, A). Positron emission tomography imaging showed hypermetabolic activity. A computed tomography–guided biopsy of this lesion was nondiagnostic. The patient subsequently underwent thoracotomy with excision of the mass. Gross evaluation showed a tan-red and hemorrhagic soft mass. Histologic evaluation demonstrated a spindle cell neoplasm in a hemorrhagic background (Figure, B and C). The lesion consisted of alternating hypercellular and hypocellular myxoid areas. The spindle cells were arranged as interlacing fascicles in the hypercellular areas, with overall 5 mitoses/10 high-power fields. The extensive hemorrhage appears to obscure areas of necrosis. Immunohistochemically, tumor cells showed diffuse positivity for TLE-1 (Figure, D), vimentin, BCL-1, CD56, and smooth muscle actin; focal positivity for epithelial membrane antigen, AE1/AE3, CAM5.2, CK7, CD99, and calretinin; and negativity for CD34, S100, ALK-1, p53, and HMB45. Ki67 was moderately increased. The morphology and immunohistochemistry profiles are consistent with monophasic type synovial sarcoma. Translocation between chromosome X and 18 using fluorescence in situ hybridization confirmed the diagnosis.
Transformation of Schwannoma Into Malignant Rhabdoid Tumor in a Patient With Germline SMARCB1/INI-1 Mutation: (Poster No. 60)
Patients with germline SMARCB1/INI-1 mutation are predisposed to either malignant rhabdoid tumors in childhood or schwannomatosis as adults. We previously reported the occurrence of both schwannomatosis in adults and malignant rhabdoid tumors in children within a single family with a germline duplication of exon 6 of SMARCB1/INI1. Herein, we report the transformation of a neuroblastoma-like schwannoma into a high-grade sarcoma with rhabdoid features in a 29-year-old man in this family. The patient developed a rapidly growing mass involving the right sciatic, tibial, and peroneal nerves. Grossly, the tumor was 20.0 cm, tan-pink, soft, and gelatinous with scattered calcifications. Microscopically, it was a high-grade sarcoma, arising from a neuroblastoma-like schwannoma, and showed sheets of small round blue cells with primitive nuclei, prominent nucleoli, and scant amphophilic cytoplasm. Rare neoplastic cells displayed rhabdoid morphology. Immunohistochemistry showed complete loss of INI-1 in the sarcoma, whereas the precursor schwannoma showed patchy loss of INI-1. S100 stain showed strong nuclear reactivity in the schwannoma. The sarcoma cells were focally positive for EMA and negative for S100, desmin, FLI-1, CD99, CD45, CD34, CD31, AE1/AE3, and CAM 5.2. Subsequently, the patient developed multiple vertebral and paravertebral metastases with more prominent rhabdoid features (Figure 133) and diffuse loss of INI-1. The sarcoma showed no specific line of differentiation but demonstrated rhabdoid morphology, suggesting that adults with familial schwannomatosis are at risk for malignant rhabdoid tumors, similar to related children in these families. We suggest close surveillance in adults with germline SMARCB1/INI-1 mutation.
Myxoinflammatory Fibroblastic Sarcoma—A Rare Tumor With Unusual Histomorphology: Report of a Case and Review of the Literature: (Poster No. 61)
Myxoinflammatory fibroblastic sarcoma (MIFS) is a recently recognized low-grade sarcoma, generally located in extremities. Clinically, MIFS is significantly difficult to distinguish from benign lesions. Histologically, it mimics inflammatory reactive changes. Pathologists should be aware of this entity to avoid diagnostic errors as benign conditions. We present this case of a 39-year-old woman who had a long-standing painless right forearm mass. Recently she developed pain and decreased mobility of the right hand. Imaging studies suggested a benign cystic lesion. Surgical biopsy showed a low-grade spindle cell myxoid lesion. Grossly, the excision specimen was an ill-defined 6-cm mass, infiltrating the subcutaneous tissue and focally involving the tendons close to the wrist joint. Microscopically, the mass demonstrated alternating hyaline, fibrous, and myxoid areas in variable proportions (Figure 134, A). There were different types of tumor cells, including large spindle cells (Figure, B), large polygonal and bizarre ganglion-like cells with large inclusion-like nucleoli (Figure, C), and large bubbly multivacuolated lipoblast-like cells (Figure, D). The tumor cells were positive for vimentin and focally positive for CD34, while negative for epithelial and lymphoid markers. After differentiated from potential soft-tissue mimics, such as nodular and proliferative fasciitis and inflammatory myofibroblastic tumor, it was diagnosed as MIFS. The excision margins were negative, except for one small tumor focus near the margin. Six months later, the patient experienced recurrence at the excision site. After re-excision, imaging follow-up every 6 months for 2 years revealed no evidence of recurrence or metastasis. MIFS should be identified early and resected with wide margins.
Lessons Learned: Unusual Initial Clinical Presentations of EWSR1-Rearranged Tumors: (Poster No. 63)
EWSR1-rearranged tumors encompass the Ewing family of tumors, including Ewing sarcoma/primitive neuroectodermal tumor, Askin tumor, and desmoplastic small round cell tumor. While the majority of these tumors present in the early decades of life, involving the musculoskeletal system and peritoneal surfaces, anomalous cases do occur. We present 2 cases of atypical EWSR1 tumors that serve as reminders to keep these entities in the differential at all times. Case 1: A 40-year-old man presented with lower back pain and muscle weakness. Imaging demonstrated a circumscribed mass in the femoral nerve clinically thought to be an MPNST. Biopsy revealed a small round cell tumor within the nerve positive for CD99 and CD56. Ewing sarcoma was suspected and confirmed through RT-PCR demonstrating the EWS-Fli1 gene rearrangement. This case is unusual given the primary location of the tumor. Case 2: An 87-year-old woman presented with flank pain. A destructive and lytic 10-cm mass involving the 10th rib was found and thought to represent metastasis or myeloma. Histology demonstrated a small blue cell tumor positive for CD99. EWSR1 rearrangement was identified and a diagnosis of Ewing sarcoma was rendered. This case is unique because of the age of the patient and axial skeletal system distribution. Regardless of age or clinical presentation, pathologists should always keep EWSR1-rearranged tumors in the differential when evaluating small round cell neoplasms. In cases where EWSR1 are considered, FISH and RT-PCR provide an invaluable set of tools for diagnosis (Figure 135).
Solid Variant of Angiomatoid Fibrous Histiocytoma: Is It More Common Than We Think?: (Poster No. 66)
Angiomatoid fibrous histiocytoma (AFH) is a slow-growing, distinctive tumor of uncertain histogenesis, usually arising in the extremities or neck of children and adolescents, characterized by histiocytoid cells with pseudoangiomatoid spaces, fibrous pseudocapsule, and lymphocytic cuff. The solid variant is rare and often underrecognized or misdiagnosed because of the absence of characteristic pseudoangiomatoid spaces. We report 2 cases of the solid variant in 2 boys, 8 and 15 years old, who presented with slow-growing, dermal-based masses on the chest wall and thigh, respectively. Grossly the lesions were nodular, with tan-yellow fleshy cut surfaces. Microscopically, the characteristic findings of an AFH were noted, although pseudoangiomatoid spaces were absent. One of the tumors showed focal cytologic atypia and germinal centers, mimicking a lymph node (Figure 136, A and B). Wide excisions revealed no residual tumor and both patients are free of recurrences or metastases 6 months postdiagnosis. The differential diagnosis was broad and included lymph node metastasis of epithelial or soft tissue origin, Kaposi sarcoma, and spindle cell lesions, such as nodular or proliferative fasciitis. The solid variant of AFH may be an underrecognized and challenging diagnosis that may occur with greater frequency than reported and should be considered in the differential diagnosis of a well-defined, dermal-based, histiocytoid proliferation without blood-filled pseudocystic spaces. These cases illustrate the importance of recognizing the classic and uncommon features of AFH and the spectrum of features seen in the solid variant to prevent a misdiagnosis or an erroneous diagnosis of lymph node metastasis.
Combined Erdheim-Chester Disease and Langerhans Cell Histiocytosis With BRAF V600E Mutation: (Poster No. 67)
A 76-year-old woman with osteoarthritis was found to have bilateral symmetric mixed lytic-sclerotic intramedullary infiltrates of the tibial metaphyses on x-ray. Core biopsy was initially interpreted as nonspecific chronic inflammation. Subsequent left total knee arthroplasty demonstrated a subchondral sparing proximal tibial medullary infiltrate of finely vacuolated CD68+, CD21−, CD1a−, S100− histiocytes, lacking granulomatous organization or emperipolesis characteristic of ECD. T lymphocytes and Touton giant cells were intermixed. Five percent of the infiltrate showed aggregates of histiocytic cells morphologically and immunophenotypically characteristic of Langerhans cells (S100+, CD1a+, and CD21−, CD68−) with associated T lymphocytes and eosinophils (Figure 137). The Langerhans cell aggregates were associated with areas of bone resorption. BRAF V600E mutation was demonstrated by real-time PCR in DNA extracted from the nondecalcified core biopsy that, upon review, contains an Erdheim-Chester disease (ECD) infiltrate but no Langerhans cells. ECD is a rare systemic histiocytosis. Data are largely derived from case reports. Since the 1980s a relationship between ECD and Langerhans cell histiocytosis (LCH) has been emerging, with reports of concurrent or sequential ECD and LCH, and few reports, like ours, of combined ECD-LCH. In 1992 Reid demonstrated that both CD1a-positive dendritic cells and CD1a-negative macrophages can be derived from the same single cell culture of CD34-positive progenitor cells from adult human bone marrow. It has recently been shown that LCH and ECD show a similar high prevalence of BRAF V600E mutation, 57% and 54% respectively. With increased understanding we may find that combined ECD-LCH is the norm rather than the exception.
Benign Osteoblastic Tumor of the Third Distal Phalanx in the Left Foot of an 11-Year-Old Girl: (Poster No. 69)
Osteoid osteoma and osteoblastoma are benign bone-forming tumors with similar morphology but different growth potentials. Osteoid osteoma may be present in a patient for several years; however, the lesion seldom exceeds 1 cm in greatest diameter. The term osteoblastoma is usually applied if a lesion of similar morphology is greater than 2 cm in diameter. We present a case of benign osteoblastic tumor occurring in the distal third phalanx of the left foot in an 11-year old girl. Imaging studies showed soft tissue proliferation with minimal sclerosis and global enlargement of the third distal phalanx with absent physis. Osteoblastoma versus glomus tumor was suspected clinically based on the imaging results. Histologic examination of the amputation specimen showed a fairly well-circumscribed tumor pushing into the medullary cavity; it was composed of woven bone spicules or trabeculae lined by a single layer of osteoblasts. The tumor showed rich vascularity with osteoblasts and scant osteoclast-like giant cells (Figure 138, A and B). The lesion measured 0.4 cm in greatest dimension. By size definition, our case favored an osteoid osteoma; however, by involvement of the medullary cavity and the size ratio of the tumor to small phalanx bone (1:3), the lesion more closely resembled an osteoblastoma. There is a need for discussion about other factors especially in the small bones regarding not only size criteria for distinguishing osteoid osteoma from osteoblastoma. A review of the literature found 3 articles reporting osteoblastoma in the phalanges (A in the toe, B in the fingers).
HMB-45–Negative Solitary Mesenteric Lymphangioleiomyoma: (Poster No. 72)
Lymphangioleiomyomas are typically associated with lymphangioleiomyomatosis, a multisystem disease, affecting predominantly women in the reproductive period. We present a case of a 44-year-old woman with pain in the left upper quadrant of the abdomen. The computed tomography scan of the abdomen and pelvis showed a large left abdominal and pelvic mass encasing mesenteric vessels and causing displacement of the bowel loops to the right. Grossly, the specimen consisted of a segment of bowel with a 20-cm tan-brown and cystic mass arising from the mesentery and containing milky fluid. The histologic findings were typical of lymphangioleiomyoma and included a ramifying network of lymphatic spaces lined by a single layer of endothelium surrounded by fascicles and bundles of abnormal smooth muscle–like cells (LAM cells), occasional lymphoid follicles, and congested vascular spaces. However, HMB-45 staining, which is typically positive in the tumor cells, was negative. Most commonly, this disease process involves the lungs, which were not involved in our patient. Extrapulmonary lymphangioleiomyomas are rare and mainly occur in the pelvis, mediastinum, and retroperitoneum. The mesentery as an involved site of extrapulmonary lymphangioleiomyomas is an extremely rare location. Only 4 cases of mesenteric lymphangioleiomyomas have been described in the literature (Table); of these 2 also had pulmonary involvement. Our case is unique in that it is not only the largest solitary mesenteric lymphangioleiomyoma, but it is also the first report of an HMB-45-negative lymphangioleiomyoma involving the mesentery.
Pleomorphic Sarcoma of the Ovary With Fast Growing Metastases Into Right Ventricle and Lungs: (Poster No. 73)
We report a 69-year-old woman who presented with a large left pelvic mass occupying the pelvis. Preoperative studies including chest x-ray and electrocardiography did not reveal any evidence of metastatic disease. An extensive resection was performed including exploratory laparotomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic and aortic lymph node dissection. No evidence of metastatic disease or lymphadenopathy was identified during the surgery. Pathologic evaluation of the mass revealed a pleomorphic sarcoma arising from a mature cystic teratoma. Six weeks later, the patient complained of progressively worsening shortness of breath on exertion. Radiologic imaging revealed multiple solid and ground-glass nodules scattered throughout the lungs bilaterally. Transthoracic echocardiography was performed, revealing a large mass occupying the right ventricle of the heart. Three days later she experienced respiratory distress, pulseless electrical activity, and death. Significant autopsy findings included a large infiltrative tumor within the heart measuring 7.5 × 5.5 × 4.5 cm occupying the entire right ventricular cavity, extending into the right atrium with obstruction of the tricuspid valve. Histopathologic examination confirmed metastatic undifferentiated pleomorphic sarcoma involving the heart and lungs. It is likely that the tricuspid valve obstruction and invasion of the interventricular septum caused conduction defects and rhythm disturbances, leading to a fatal cardiac arrhythmia. In this case, we report that metastatic sarcoma can develop without any obvious symptoms and present at advanced stage in a very short period of time (Figure 139).
High-Grade Osteosarcoma of the Mandible in a Patient With History of Irradiated Tonsillar Carcinoma: A Serious Rare Radiation-Induced Complication: (Poster No. 74)
Postirradiation osteosarcoma (PIO) is a rare but serious long-term complication of high-dose irradiation for cancer therapy (latency period up to 53 years, mean of 10–20 years) with estimated risk of 0.03%–0.8%. The prognosis is dependent on site and resectability, with the least favorable prognosis in craniofascial sites. Most have poor prognosis because of their aggressive nature, recurrence, and rapid tumor spread. We report a case of PIO of the mandible in a 63-year-old man who had a history of squamous cell carcinoma of the right tonsil, treated with radiation therapy in 2002. He presented in 2013 with right mandibular tenderness, right V3 hypoesthesia, and trismus. Computer tomodensitometry showed a lytic lesion in the right mandibular ramus and an ill-defined soft tissue mass along the floor of the mouth. The patient underwent right hemimandibulectomy, mandibular reconstruction bar, fibula myoosseous adiposofascial free flap, neck dissection, and full-thickness skin graft. Grossly the tumor (5.5 × 2.6 × 2.3 cm) had hard bony, grey chondroid, and soft tissue areas with necrosis (Figure 140, A and B). Histologically the tumor revealed variable histologic patterns of conventional high-grade osteosarcoma, including chondroblastic, osteoblastic (Figure, C), epithelioid, and malignant fibrous histiocytoma-like patterns with brisk abnormal mitoses >50 mitoses/high-power field (Figure, D), necrosis, and lymph-vascular and perineural invasion. He currently received chemotherapy (cisplatin and adriamycin). Although rare, the possibility of PIO should be considered in the field of radiation therapy and mandates long-term follow-up for early diagnosis and treatment, as PIO tends to be more aggressive compared to the primary osteosarcoma.
Radiation-Induced High-Grade Myxofibrosarcoma (Myxoid MFH) of Chest Wall in a Patient With History of Breast Carcinoma: An Aggressive Tumor With Important Treatment Implications: (Poster No. 75)
Radiation-induced sarcomas (RIS) are rare complications of radiotherapy in the irradiated field after several years of latency (range, 2.5–57.8 years). Sarcoma in itself is a rare malignancy and RIS accounts for 0.5% to 5.5% of all sarcomas. The prognosis of RIS is poor and treatment is challenging because RIS are usually high-grade aggressive sarcomas diagnosed at advanced stage. Undifferentiated pleomorphic sarcoma, also known as malignant fibrous histiocytoma (MFH), is one of the main histologic types of RIS and may display pleomorphicstoriform, giant cell, inflammatory, or myxoid patterns. We report a case of radiation-induced high-grade myxofibrosarcoma (also known as myxoid MFH) in the chest wall in a 77-year-old woman. The patient was diagnosed with stage IIIA (T3N1bM0) left breast carcinoma (1985) treated with lumpectomy followed by radiotherapy. She had a recurrence in the axillary tail (2000), treated with radical mastectomy and postoperative radiotherapy. In 2008 she presented with a large chest wall tumor with destruction of fifth left rib. She underwent excision of the chest wall tumor with reconstruction and latissimus dorsi flap. Grossly, the excised tumor (7.0 ×2.7 × 2.2 cm) was rubbery white-tan, with focal necrosis and hemorrhage (Figure 141). Histologically, the tumor showed markedly pleomorphic undifferentiated sarcoma with a myxoid background and brisk abnormal mitoses (Figure, B and C). The tumor cells were negative for desmin, pancytokeratin (AE/AE3), Melan A, HMB-45, and S100, with focal scattered SMA positivity. RIS, although rare, is an increased potentially fatal risk and is radiation-dose dependent, mandating careful, long-term follow-up for early detection and treatment.
Endometrial Stromal Sarcoma Arising in Foci of Endometriosis in the Sigmoid Colon and Right Ovary: (Poster No. 81)
In this case report we describe a very rare presentation in a 64-year-old woman of a low-grade endometrial stromal sarcoma arising in foci of endometriosis of the ovary and sigmoid colon. In 2011, the patient was examined at an outside hospital and a submucosal tumor was identified in the sigmoid colon during a routine colonoscopy. The patient underwent exploratory laparoscopy to remove the mass and the excised tumor was composed of rounded to slightly spindled cells, vesicular nuclei, and indistinct cytoplasmic borders. Immunohistochemical analysis showed that the tumor was positive for CD10, vimentin, WT-1, estrogen receptor, and progesterone receptor; focally positive for pankeratin and desmin; and weakly positive for synaptophysin. The tumor was negative for CD117/c-kit, S100, CDX2, mammoglobulin, GCDFP15, and TTF-1. Ki67 analysis showed that the proliferation fraction was 10%–20%. The morphologic and immunohistochemical findings were consistent with a low-grade endometrial stromal sarcoma. In February 2012, the patient underwent total hysterectomy and bilateral salpingo-oophorectomy in our hospital. A second tumor was identified involving the right ovary without capsular involvement, and was positive for CD10 but negative for caldesmon and CD117/c-kit. The tumor morphology was similar to the endometrial stromal sarcoma diagnosed in the mass excised from the colon. There was no evidence of endometrial stromal sarcoma involving the uterus. Overall, our findings are most consistent with 2 separate foci of endometrial stromal sarcoma involving the right ovary and sigmoid colon that most likely arose from foci of endometriosis (Figure 142).
Coexistent Abdominal Fibromatosis (Desmoid Tumor) and Endometriosis: An Exceedingly Rare Case Report and Review of Literature: (Poster No. 82)
Endometriosis is a relatively common gynecologic disorder that occurs in up to 15% of menstruating women. Although endometriosis occurs most frequently in the pelvis, endometrial implants have been reported in many unusual sites including surgical scars of abdominal wall. Herein, we report an unusual case of abdominal fibromatosis (desmoid tumor) admixed with florid endometriosis in a 35-year-old woman with a history of morbid obesity and gastric bypass surgery who presented with right-sided abdominal pain. Computed tomography scan demonstrated a right rectus sheath mass. Intraoperative pathology assessment was performed, and a diagnosis of endometriosis was rendered. Histologic examination of the permanent sections showed florid endometriosis with cicatricial fibrosis admixed with bundles of spindle cells infiltrating skeletal muscle fibers (Figure 143). Based on the microscopic findings, the differential diagnosis was scar endometriosis versus coexistent endometriosis and abdominal wall fibromatosis. The diagnosis of fibromatosis was confirmed by diffuse nuclear positivity of the spindle cells for β-catenin by IHC staining. Deep fibromatoses are clonal myofibroblastic proliferations that are prone to aggressive local recurrences. Virtually all deep fibromatoses have somatic β-catenin or adenomatous polyposis coli (APC) gene mutations leading to intranuclear accumulation of β-catenin. To the best of our knowledge, this is the first reported case of coexistent fibromatosis and endometriosis. Considering the impact of the correct diagnosis on patient management and the potential for a missed diagnosis of fibromatosis in a background of florid endometriosis with cicatricial fibrosis, one should be aware of this possibility and the utility of β-catenin IHC staining in difficult cases.
Placental Alkaline Phosphatase in Benign and Malignant Endometrium: Detection and Diagnostic Potential: (Poster No. 85)
Context: Placental alkaline phosphatase (PLAP) is a membrane-bound glycosylated dimeric enzyme. It is expressed in some types of normal tissue including placenta and neonatal testis. It is also present in certain types of germ cell tumors, especially seminomas. One study using a cultured cell line demonstrated that PLAP is expressed in endometrial carcinoma cells, but not in normal endometrial cells. To our best knowledge, the immunohistochemical (IHC) profile of PLAP in human benign and malignant endometrial tissues has not been studied. Our study was to assess the IHC staining pattern of PLAP in benign, hyperplastic, and malignant endometrium.
Design: Four endometrial categories were included in this study, including normal endometrium (n = 67), simple hyperplasia (n = 14), complex hyperplasia (n = 8), and endometrial carcinoma, endometrioid type (n = 41). Immunostain of PLAP using anti-PLAP mouse monoclonal antibody (clone 8A9, Leica) was performed for all the cases with proper positive and negative controls. The results were interpreted by 2 attending pathologists and the data were analyzed. A positive immunostaining result was defined as strong membranous and cytoplasmic staining of at least 10% of epithelial cells. Weak staining, less than 10% positivity in epithelial cells, or only apical staining were interpreted as negative.
Results: See Table.
Conclusions: 1. Our study demonstrated that normal endometrium and simple hyperplasia does not express PLAP. 2. PLAP was only identified in complex hyperplasia or endometrial carcinoma. 3. The differential expression of PLAP in simple and complex (atypical) hyperplasia could reflect their different molecular pathways. 4. PLAP cannot be used as a marker to differentiate complex hyperplasia from endometrial cancer.
Clinical Presentation of Uterine Serous Carcinoma in an Urban Setting—A Shift in Paradigm?: (Poster No. 88)
Context: Emerging evidence has linked obesity with type II endometrial carcinoma, specifically uterine serous carcinoma (USC). The aim of this study is to evaluate morbidly obese patients with USC.
Design: Women with USC diagnosed from 1996 to 2013 at a single institution were identified in our pathology database. Electronic medical records were reviewed for clinicopathologic information. A pathologist reviewed cases to confirm USC diagnosis. Patients were stratified based on their BMI. Morbidly obese (BMI = 40 kg/m2) patients were compared to those with normal BMI (25 kg/m2)
Results: Included in the study were 140 cases of USC. Seventeen patients (12%) had BMI 25 kg/m2 and 27 (19%) had BMI 40 kg/m2. Median age at presentation was 70 and 64 years respectively (P = .04). Median survival was 28 months in normal BMI and 21 months in morbidly obese. Amajority of the morbidly obese women (78%) presented with early-stage disease at diagnosis (FIGO stage I and II) compared to 35% with normal BMI (P = .01). The background endometrium was predominantly atrophic in both BMI categories, with the only exceptions being 1 normal-BMI and 5 morbidly obese patients, all of whom had proliferative endometrium (P >.05). Other clinicopathologic parameters were not statistically significant (Table).
Conclusions: Morbidly obese women with USC appear to present at an earlier age and earlier stage compared to normal-BMI women. This may represent differences in accessing medical attention by the 2 groups, resulting in earlier detection. Larger studies are needed to understand the impact of obesity in USC.
Adult Ovarian Granulosa Cell Tumor With Anaplastic Features: (Poster No. 97)
Ovarian granulosa cell tumors are rare sex-cord neoplasm derived from granulosa cells. Adult granulosa cell tumor (AGCT) is a low-grade malignant neoplasm with potential for recurrence and metastases and overall good prognosis. These tumors are composed of small, bland, polygonal monomorphic cells with prominent grooves (“coffee bean”) arranged in different patterns and low mitotic count (rarely >1–2/10 high-power fields). We report a rare case of adult granulosa cell tumor with anaplastic features. A 41-year-old woman presented with abdominal pain. Magnetic resonance imaging showed a large complex mass in the left ovary. The removed mass (19 ×18 × 11 cm) was well-encapsulated, soft, fleshy, and grey-tan with solid, cystic, and necrotic areas with hemorrhage on cut surface (Figure 144). Histologically the tumor architecture was consistent with that of AGCT (microfollicules with Call-Exner bodies, macrofollicules, insular, trabecular, watered-silk, cystic, and solid patterns). However, tumor cytomorphology was unusual for the high-grade nuclear atypia, marked pleomorphism, brisk and abnormal mitoses (up to 16 mitoses per 1 high-power field), necrosis, and lack of prominent nuclear grooving. The tumor was positive for inhibin, calretinin, CD56, and CKAE1/AE3 (punctate pattern), weakly positive for EMA in rare cells, and negative for CK7, synaptophysin, and chromogranin. The tumor histology and immunostain profile were consistent with the diagnosis of AGST (pT1aNx) with anaplastic histologic features. Although the most important prognostic indicator in AGCT is tumor stage, the presence of marked anaplasia and large tumor size (as in our case) in stage 1 disease portend aggressive tumor behavior and adversely affect survival warranting closer and long-term follow-up.
Evaluation of Histologic Features Predictive of Serous Carcinoma in Scant Endometrial Samples: A Study of 125 Patients: (Poster No. 99)
Context: Endometrial serous carcinoma tends to occur in elderly patients. When encountering scant endometrial biopsy/endometrial curettage (EMB/EMC) samples, diagnosing this entity can be a challenge. We studied 125 cases with the goal of finding histologic features highly predictive of serous carcinoma in scant samples.
Design: The demographic features of 125 patients were collected. Specimens from their preoperative EMB/EMC as well as postoperative hysterectomy slides were reviewed.
Results: The age range of patients was 50–90 years (median 65). The common clinical presentation was postmenopausal bleeding. Serous carcinoma was confined to polyps in 20 cases (16%). The preoperative EMB/EMC diagnoses are shown in the Table. 75% of cases had abundant material for diagnoses while 25% had a very limited sample, causing diagnostic difficulty. In the latter scenario, the most useful histologic features predictive of serous carcinoma included glandular cells with marked nuclear pleomorphism, tight papillae structure, and necrotic debris. Positive p53 immunostain was observed in one third of the cases. The most common pitfalls included (1) incorrectly designating samples as nondiagnostic, (2) mistaking them as reactive atypia, and (3) misclassifying them as low-grade endometrioid adenocarcinoma owing to the villoglandular architecture (10% of cases).
Conclusions: Our study demonstrated that certain histologic features are highly predictive of malignancy, including rare pleomorphic cells, small papillae, and necrotic debris. In an otherwise scant endometrial sample, these are strong indicators for serous carcinoma in postmenopausal bleeding patients.
Umbilical Cord Hemangioma Versus Other Vascular Lesions: A Comparative Clinicopathologic Study: (Poster No. 102)
Tumors of the umbilical cord are extremely rare. Hemangioma of the umbilical cord is a benign vascular tumor associated with congenital anomalies and increased perinatal mortality. Differential diagnoses include angiomyxoma, hematoma, and aneurysm. We report a case of umbilical cord hemangioma and a case of umbilical cord organizing hematoma/dissecting aneurysm to compare these 2 entities clinically and histologically. The case of umbilical cord hemangioma was diagnosed in a full-term female neonate born to a 31-year-old G1P0 mother with omphalocele discovered on prenatal sonography. Surgical repair of the omphalocele after birth identified an urachal cyst tracing down to the bladder. Histologic examination revealed a 3-vessel umbilical cord associated with small capillary–type vascular proliferation positive for factor VIII immunostaining, consistent with hemangioma (Figure 145, A). In the second case, a large umbilical cord mass with a highly vascular solid portion clinically suggestive of hemangioma or angiomyxoma was discovered on prenatal ultrasonography in a 42-year-old G4P2 mother with elevated amniotic fluid AFP level. Other abnormalities in the fetus detected by ultrasonography included the absence of bladder, hypoplastic lower extremities, enlarged heart, and separation of amnion from chorion. Fetal demise occurred at 21 weeks. Histologic examination revealed small pools of blood in the umbilical cord dissecting through the Wharton jelly with no endothelial lining (Figure, B), as confirmed by negative factor VIII staining. This led to a diagnosis of organizing hematoma or dissecting aneurysm, instead of hemangioma. Our work highlights the importance of histopathologic examination in correlation with ultrasound imaging and clinical presentations.
Monoclonal PAX-8 in Mucinous Ovarian Tumors: A Study of 59 Cases of Primary and Metastatic Tumors: (Poster No. 105)
Context: PAX-8 is a clinically useful marker in the evaluation of most ovarian nonmucinous carcinomas including serous, endometrioid, and clear cell lesions. However, in studies using polyclonal PAX-8 antibodies, 50% or less of primary ovarian mucinous tumors are positive. The aim of this study was to test a PAX-8 monoclonal antibody in a series of primary and metastatic mucinous tumors in the ovary.
Design: Immunohistochemistry with PAX-8 monoclonal antibody (clone BC12, Biocare Medical, Concord, California) was performed in 59 ovarian mucinous tumors, including 10 primary ovarian mucinous carcinomas, 22 borderline mucinous tumors, and 27 metastatic mucinous tumors to the ovary. The percentage of positive cells and the intensity of the staining (using a 2-tier system: weak 1+, strong 2+) were evaluated.
Results: PAX-8 was positive in 50% of primary ovarian carcinomas, in most cases with strong intensity in more than 50% of the cells. It was positive in 57% of borderline tumors intestinal type (with variable range of percentage of cells positive and variable intensity). It was positive in all endocervical types of borderline tumors in 100% of cells with strong intensity. All metastases were negative (Table).
Conclusions: Monoclonal PAX-8 has similar sensitivity and specificity to polyclonal PAX-8 in mucinous ovarian tumors. It is positive in 50% of primary ovarian carcinomas, 57% of borderline tumors intestinal type, 100% of borderline tumors endocervical type, and it is negative in metastatic tumors (100% of metastases in this series were negative). PAX-8 positivity may be useful in the differential diagnosis of primary versus metastatic mucinous ovarian tumors.
PAX8 Immunohistochemical Staining in Mucinous Neoplasms Involving Ovary: A Critical Evaluation Including Comparison of Monoclonal Versus Polyclonal Antibodies: (Poster No. 107)
Context: Distinction of primary mucinous tumors of ovary (PMO) from metastatic carcinoma involving ovary (MCO) is challenging. Immunohistochemical (IHC) stains including PAX8 have been used recently to aid in differential diagnosis. The aims of this study were (1) to evaluate PAX8 IHC expression in MCO particularly from the lower GIT; and (2) to compare staining patterns of the monoclonal (MC) versus polyclonal (PC) antibody (AB).
Design: From the pathology database we retrieved 25 MCOs (2 stomach, 1 jejunum, 7 appendix, 10 colon, and 5 clinically unknown but suggestive of primary GIT, on the basis of other IHC findings), 10 PMOs, and 1 primary mucinous carcinoma of ovary. PAX8 IHC staining using MC and PC AB was performed and nuclear staining was evaluated.
Results: One of 25 MCOs showed PAX8 nuclear positivity (50%) PAX8 positivity, while 1 case of primary ovarian mucinous carcinoma was negative. Endocervical type of PMO showed diffuse strong staining, and the intestinal-type PMO showed variable degrees of staining (Table).
Conclusion: (1) Most MCOs (96%) were negative for PAX8 and the 1 positive case showed less than 5% staining. (2) The sensitivity of PAX8 for diagnosing PMO is low (63.6%), particularly in the intestinal-type PMO, but any nuclear positivity is strongly suggestive of this diagnosis over MCO. (3) PC AB for PAX8 is very difficult to assess owing to the background cytoplasmic staining, unlike the MC AB, which can be evaluated without ambiguity even on low-power microscopic evaluation.
A Case of Uterine Lipofuscinosis in a Patient With Progressive Cerebellar Ataxia and Dystonia: (Poster No. 109)
Lipofuscinosis is a rare condition with excessive accumulation of lipopigments (lipofuscin) in tissue. More commonly, it is seen in neuronal cells (neuronal ceroid lipofuscinosis). Rare cases of lipofuscinosis in liver, intestine (brown bowel syndrome), and kidney have been found in literature. Here we report a case of lipofuscinosis in the uterus. A 36-year-old woman with progressive dystonia and cerebellar ataxia for the past 23 years and menorrhagia and dysmenorrhea for the past 12 years had a hysterectomy. Grossly, the uterus (72 g, 8.5 ×5 ×4 cm) showed marked brown discoloration in the endomyometrium. Microscopically, the light brown green granular pigments are seen in smooth muscle cells. Adenomyosis and endometriosis were ruled out. Iron and copper special stains are negative. Uterine lipofuscinosis is extremely rare. By literature search, to date, only 2 cases have been reported: 1 is related to vitamin E deficiency and 1 is associated with brown bowel syndrome and Friedreich ataxia. The etiology of uterine lipofuscinosis remains unclear. It may be related to vitamin E deficiency, which leads to mitochondrial myopathy in smooth muscle cell, which may explain at least partially the intestinal symptoms in brown bowel syndrome and menorrhagia. Vitamin E deficiency can be secondary to malabsorption. However, isolated vitamin E deficiency was also reported in a case with progressive spinocerebellar syndrome, which was improved upon the correction of the deficiency. This patient had no gastrointestinal symptoms and there is no serum vitamin E report so far. Serum vitamin E level should be recommended (Figure 146).
Presence and Potential Diagnostic Utility of Microphthalmia-Associated Transcription Factor Staining in Normal Myometrium, Uterine Leiomyoma, and Leiomyosarcoma: (Poster No. 114)
Context: Microphthalmia-associated transcription factor (MITF) plays a key role in melanocytic differentiation and has been used for more than 10 years as a melanoma marker. MITF is also expressed in a variety of normal tissues (eg, muscles of the stomach and colon), as well as in some tumors (eg, angiomyolipoma). However, its expression in normal myometrium, uterine leiomyoma, and uterine leiomyosarcoma has not been well studied. Our study aimed to assess the MITF immunohistochemical (IHC) staining profile in normal myometrium, uterine leiomyoma, and uterine leiomyosarcoma, and evaluate its potential diagnostic utility in myometrial neoplasms.
Design: Cases of normal myometrium (n = 24), uterine leiomyoma (n= 37), and uterine leiomyosarcoma (n = 16) were included. Immunostaining for MITF was performed by using a mouse monoclonal antibody (clone C5/D5, Ventana) with proper positive and negative controls. For the purpose of this study, a positive result was defined as nuclear staining of at least 10% of total relevant cells. The slides were read by 2 attending pathologists and the data were analyzed with Fisher exact test.
Results: See Table. The difference between the MITF immunostain positivity of benign cases (normal myometrium or leiomyoma) and uterine leiomyosarcoma was statistically significant (P <.001). We did not identify any significant histologic differences between uterine leiomyosarcomas that did express MITF and those that did not.
Conclusion: We found that MITF is consistently expressed in normal myometrium and uterine leiomyomas, while its expression is lost in most uterine leiomyosarcomas. Our data indicated a limited diagnostic usefulness for MITF in the differential diagnosis between uterine leiomyomas and leiomyosarcomas.
Umbilical Artery Thrombosis and Vascular Smooth Muscle Necrosis With Associated Single Umbilical Artery in a Live Birth: (Poster No. 115)
Umbilical vessel thrombi are associated with increased perinatal morbidity and mortality. Clinical sequelae include diverse or potentially catastrophic outcomes for the child, including cerebral palsy, fetomaternal hemorrhage, fetal organ infarction, growth restriction, and demise. Incidence is 1:1300 deliveries with most cases involving solely the umbilical vein. However, single umbilical artery thrombosis (UAT) is rare (1:4000) and most diagnoses are established at postmortem. We present clinicopathologic features and literature review of UAT in a live birth. A 36-year-old woman (gravida 3, para 0-2-0-2) at 34 and 3/7 weeks gestational age with a history of thrombophilia, bicornuate septate uterus, and abruptio placentae presented for repeated cesarean section after abnormal Doppler study findings. A 2165-g live birth with a tight nuchal cord in respiratory distress and thrombocytopenia (83 000 platelets/μL) was delivered. Gross placental examination revealed an oval 465-g disc measuring 16.5 × 14.0 × 1.5–3.0 cm with focal lacerated cotyledons; meconium was not observed. Serial sections were congested and spongy with a 0.6-cm solid tan subchorionic lesion. Umbilical cord was 60 × 1.0–1.1 cm, left-hypercoiled. Microscopic examination exhibited a single occlusive UA thrombus with complete vascular smooth muscle necrosis consistent with thrombosis remote to delivery (Figure 147). A mural thrombus was embedded deep into a large chorionic plate vessel wall. Multifocal avascular villi and prominent syncytial knotting and basophilia were observed. Several mechanisms have been implicated: cord pathology (knots, hypercoiling, prolapse, funisitis), fetal thrombophilia, and meconium-induced vascular necrosis; however, oftentimes the etiology is unknown. Antenatally, such lesions can be clinically silent, and thus careful pathologic examination may be the only method to identify UAT.
Multifocal Serous Carcinoma of the Cervix and Fallopian Tube in a Patient With Turner Syndrome: (Poster No. 116)
Patients with Turner syndrome are at increased risk for gonadoblastoma, cancers of the uterine corpus, and other nongynecologic neoplasms. To date, there are no reports of Turner syndrome associated with cervical carcinoma or serous carcinoma of the fallopian tube in the English literature. We report a case of multifocal serous carcinoma of the cervix and fallopian tube in a patient with a confirmed diagnosis of Turner syndrome. The patient was a 46-year-old woman taking combined oral contraceptives who presented with pelvic pain. Pelvic ultrasonography revealed a small uterus and bilateral complex adnexal cysts. The patient underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy with radical tumor debulking. The hysterectomy specimen consisted of uterus and bilateral fallopian tubes. The ovaries were absent, and a disrupted cystic mass was present on the posterior surface of the uterus. The entire cervix, lower uterine segment, and endometrium were submitted for histologic examination. Sections showed serous intraepithelial carcinoma and invasive poorly differentiated serous carcinoma of the endocervix and left fallopian tube (Figure 148), with involvement of the left fallopian tube serosa and uterine serosa. The endometrium was atrophic and no ovarian tissue was identified. Metastatic tumor was present in the omentum and colon. The tumor was immunoreactive with WT-1 and ER, and negative for PR, EGFR, and CEA. The tumor cells were completely negative for p53, suggesting p53 mutation. The patient was treated with 6 cycles of carboplatin and taxol and has no evidence of disease at 11 months after surgery.
Vanishing Endometrial Cancer in Hysterectomy Specimens: A Myth or a Fact: (Poster No. 119)
Context: Occasional cases of endometrial cancer (EC) diagnosed on biopsy have no residual cancer (RC) identified in the hysterectomy specimen. The incidence of these cases is not well studied. The aim of our study was to analyze this “vanishing cancer” phenomenon.
Design: Cases of EC on dilation and curettage and biopsy with no RC on hysterectomy were identified. The endometrium was entirely submitted in each case. Clinicopathologic variables analyzed included patient demographics; tumor type, grade, and stage; biopsy method; treatment; surgical procedure; recurrence; and disease-specific survival.
Results: We identified 24 biopsies of EC with no RC on hysterectomy specimen. The median age of patients was 58.5 years (32–76 years). Of the 24 patients, 15 (62.5%) had endometrioid, 6 (25%) serous, 1 (4.2%) clear cell, 1 (4.2%) serous intraepithelial carcinoma and 1 (4.2%) low-grade adenosarcoma. Of the endometrioid carcinoma cases, 12 (50%) were FIGO grade I, 2 (8.3%) were grade II, and 1 (4.2%) was grade III. Eighteen of 24 patients underwent dilation and curettage and 6 had endometrial biopsy as primary procedure. Median follow-up was 8.8 years (SD = 0.617 year). Two patients with serous carcinoma underwent adjuvant chemotherapy. One patient died of disease. This patient was diagnosed as having FIGO grade II endometrioid carcinoma, later developed recurrence, and died within 31 months of diagnosis (Table).
Conclusions: The inability to identify cancer in a hysterectomy specimen for biopsy confirmed that carcinoma does not indicate technical failure, as all cases in our cohort underwent complete endometrial sampling and evaluation. Although there is no standard treatment for patients with vanishing endometrial cancer, the prognosis is excellent.
A Pure Sex Cord Proliferation Arising in 46,XY Dysgenic Gonads: (Poster No. 120)
Patients with 46,XY complete gonadal dysgenesis (Swyer syndrome) are externally and internally female with dysgenic streak gonads. The disorder is often due to a mutation in the SRY gene on the Y chromosome, which is responsible for the initiation of male sex determination. The gonads are composed of fibrous stroma without sex cord development or germ cells. There is a significant risk of developing neoplasia within these gonads. Gonadoblastoma is the most commonly reported benign tumor, while germ cell tumors, especially dysgerminomas, are the most common malignant tumors. We present a case of a previously unreported sex cord proliferation in the streak gonads of a patient with Swyer syndrome. A 13-year-old patient with Swyer syndrome and a SRY gene mutation underwent surgical exploration that revealed bilateral small streak gonads and an undeveloped uterus. Microscopically, numerous small, simple, hollow tubules were dispersed throughout the fibrous stroma of the left and right streak gonads. The tubules were lined by columnar cells with minimal cytoplasm and bland, oval nuclei, with no appreciable mitotic activity. The tubular cells were positive for inhibin, confirming a sex cord derivation. Germ cells were not identified histologically or by placental alkaline phosphatase immunostain. The proliferations are favored to be hamartomatous owing to their bilaterality, distribution, and intermingling with gonadal fibrous tissue, but a benign neoplastic origin cannot be excluded. This case highlights a unique finding in streak gonads, not previously reported in the medical literature, which may pose a diagnostic dilemma (Figure 149).
Primary Intraosseous Malignant Myoepithelioma of Mandible With EWSR1 Translocation: A Case Report and Review of the Literature: (Poster No. 121)
Myoepithelial cells have a unique potential for divergent differentiation along both epithelial and mesenchymal lineages. Outside the salivary gland, myoepithelial tumor (MET) is a newly introduced concept and only recently have such lesions in the soft tissues been established. Primary intraosseous MET is extremely rare. Only 19 cases have been reported in the English literature, and only 6 cases occurred in the maxilla and mandible. We report a case of a 24-year-old woman presenting with left temporomandibular joint pain. Computed tomography showed a 4.8-cm expansile mass centered in the left mandibular condyle, involving vertical ramus. Histologically, the tumor was composed of predominantly spindle cells embedded in a fibrotic and hyalinized stroma, with vesicular or coarse chromatin, prominent nucleoli, and high mitosis (5–10 per high-power fields). Focal epithelioid cells with scant clear cell cytoplasm were also present. Both components were diffusely positive for AE1/3, S100, and FLI-1 and were focally positive for EMA, SMA, calponin, TLE-1, and CD99. Electromiscoscopy showed both desmosome, dense body and filaments in the same cell, supporting epithelial and mesenchymal differentiation. Molecular studies revealed a unique EWSR1 translocation (Figure 150). For the first time, we report a case of intraosseous malignant MET of the mandible with EWSR1 translocation, therefore extending the spectrum of clinicopathologic and molecular characteristics of this lesion. This finding supports its primary bone origin, and not accessory intra-mandibular salivary gland origin. The partner gene of EWSR1 is now under investigation.
Hyaline Vascular Castleman Disease Associated With a Calcifying Fibrous Pseudotumor in a Pediatric Neck Mass: (Poster No. 122)
Castleman disease (CD), although well-described, remains a relatively rare lymphoproliferative disorder. There is a known association of CD with exposure to human herpesvirus-8 and HIV. Histologically, CD is divided into the hyaline vascular, plasma cell, transitional/mixed, and plasmablastic subtypes. The hyaline vascular subtype is by far the most common variant, typically presenting as a unicentric mass involving the lymph nodes of the mediastinum, neck, abdomen, or axilla. We present the case of a 9-year-old boy with a slowly enlarging, radiologically heterogeneous, 10-cm neck mass. Upon resection of the mass, classic features of hyaline vascular CD were observed to be enveloped by a densely sclerotic zone punctuated by scattered dystrophic calcifications. The lesion was ultimately diagnosed as hyaline vascular CD with associated calcifying fibrous (pseudo) tumor. While CD has been associated with other neoplastic entities, its association with calcifying fibrous pseudotumor has only rarely been reported in the literature. Calcifying fibrous pseudotumors are exceptionally rare, benign soft tissue processes, the pathogenesis of which has yet to be elucidated. One theory postulates a connection with a traumatic or scarring process; this same reactive mechanism—namely, an exaggerated response by follicular dendritic cells to tissue injury—is believed by some to contribute to the development of hyaline vascular CD. Our case is unique in that it features the intimate association of these entities within the neck without an established history of trauma or surgical intervention; thus, the stimulus in this child remains unknown (Figure 151).
Mycobacterium avium Infection of Nasal Septum in a Diabetic Adult: (Poster No. 126)
A 69-year-old man with diabetes mellitus was admitted with a 2-month history of left lateral frontal headache. The pain was fluctuating and partially relieved by pain medications. He also had complaint of chronic cough, but the chest x-ray was unremarkable. Intranasal examination revealed a sessile polypoid lesion (1.5 cm in diameter) on the right anterior nasal septum. Bilateral turbinates showed atrophic changes. A biopsy was performed. The gross examination revealed tan-yellow polypoid soft tissue fragments. Microscopic examination showed stratified squamous epithelium overlying numerous foamy histiocytes with admixed inflammatory cells. An acid-fast stain highlighted numerous bacilli within the foamy histiocytes. There was no evidence of caseating granulomas. Biopsy tissue culture was positive for Mycobacterium avium. As the patient's incision had healed well, no antibiotics were initiated. The patient was followed up at 6 months with intranasal examination showing a scar without evidence of a mass or other abnormality. M avium complex is an unusual cause of extrapulmonary infection, with most examples presenting in immuno-compromised adults. The current case illustrates both an atypical anatomic location, the nasal cavity, and an often overlooked cause of immune compromise, diabetes mellitus. Chronic inflammation with foamy histiocytes should prompt consideration of M avium complex, especially in patients with diabetes mellitus. Acid-fast bacilli on stains and growth on culture can be used to confirm the diagnosis of M avium infection (Figure 152).
Unusual Granulomatous Vocal Cord Nodules: Two Rare Cases: (Poster No. 127)
The most common vocal cord lesions are vocal cord nodules/polyps. Both occur as the result of vocal cord irritation, can be bilateral or unilateral, and can develop anywhere along the vocal cords. These lesions show little variation grossly. They are identified grossly as white or gray protuberances covered by intact squamous epithelium and may be sessile or pedunculated. Histopathologically, the most distinctive feature is myxoid stromal change with fibrin deposition. The differential diagnoses include recurrent laryngeal papillomatosis, contact granuloma (ulcer), amyloidosis, myxoma, hemangioma, granular cell tumor, paragangliomas, and squamous cell carcinoma. We present 2 unusual cases of vocal cord nodular granulomatous lesions. The first involves a 66-year-old woman who presented with 1.5 years of hoarseness and hilar adenopathy. On biopsy, there were well-defined, noncaseating granulomas that were negative for microorganisms when stained with acid-fast bacilli and Grocott methenamine silver, consistent with sarcoid granulomas (Figure 153, A). The second case involves a 49-year-old woman with known history of rheumatoid arthritis who presented with a left vocal cord nodule. On biopsy, there were multiple foci of fibrinoid necrosis surrounded by palisading histiocytes and multinucleated giant cells. There was an associated lymphoplasmacytic connective tissue infiltrate. These findings, taken in conjunction with the patient's history, were quite typical of rheumatoid nodule of the vocal cord (Figure, B). A review of the literature shows few reported cases of these lesions, since they are rare and unusual in this particular location.
Gnathic, Intraosseous (Central) Sebaceous Adenocarcinoma of Salivary Gland Differentiation: (Poster No. 129)
Primary intraosseous salivary malignancies are rare. Adenoid cystic adenocarcinoma, adenocarcinoma NOS, acinic cell adenocarcinoma, and epithelial-myoepithelial carcinoma have all been reported within the jaws, but the mucoepidermoid carcinoma is by far the most common tumor in this setting, accounting for 2% to 4% of all mucoepidermoid carcinomas. Sebaceous adenocarcinoma has never been reported in this location. Here, we document a sebaceous adenocarcinoma of the maxilla in a 56-year-old woman presenting with a painful swelling of the right face. Computed tomography scans showed an expansile, osteolytic tumor of the right maxilla (Figure 154, A). An exploratory biopsy revealed the tumor to be expanding and eroding the cortical plates including the floor of the sinus. The histopathology was consistent with a sebaceous adenocarcinoma (Figure, B and C). The sebocytes expressed EMA and CD15. The basaloid cells were CD15− (Figure, D). The tumor was treated with a wide local resection. The healing process was uneventful and the patient is being monitored regularly for recurrences. Sebaceous adenocarcinoma of the parotid gland is an intermediate-grade to aggressive malignancy with a guarded prognosis. This is the first report of a central sebaceous adenocarcinoma, and prognostication of parotid tumors may not be applicable in this setting.
MicroRNA Expression Profiling of Papillary Thyroid Carcinomas: (Poster No. 132)
Context: MicroRNAs (miRNAs) are small endogenous molecules involved in the posttranscriptional regulation of genes. Papillary thyroid carcinoma (PTC) is the commonest thyroid cancer with rising incidence in the United States. Its incidence and mortality differ by race, with the increasing burden occurring among African Americans. We hypothesize that in PTC (1) identification of altered miRNAs can improve diagnosis, prognosis, and treatment; and (2) differentially expressed miRNAs by race would help in overcoming race disparities.
Design: RNA was extracted from PTC (n = 27; 16 white Americans + 11 African Americans) and normal thyroids (n = 27). miRNA expression profiling was performed by using microfluidic biochip microarrays (LC Sciences). Data were statistically analyzed by using the Student t test.
Results: Of the 2555 miRNAs profiled, PTC revealed overexpression of miR-146, miR-21, miR-221, miR-222, miR-31, and miR-4267 and low expression of miR-138, miR-451, and miR-143, compared to normal thyroid (P < .001). In African Americans there was upregulation of miR-31 and in white Americans there was upregulation of miR-4267 (Figure 155) with down-regulation of miR-138 (P <.001).
Conclusions: Overexpression of miR-146, miR-21, miR-221, miR-222, miR-31, and miR-4267 and low expression of miR-138, miR-45, and miR-143 can serve as a molecular “signature” for PTC. Upregulation of miR-31 in African Americans and down-regulation of miR-138 with upregulation of miR-4267 in white Americans could explain race disparities in PTC. Our findings may have significant clinical impact, since these can be used to improve diagnostic accuracy; determine prognosis; and with the use of antagomirs (chemically modified oligonucleotides), serve as novel targets for therapy to achieve the goals of precision medicine.
Histopathology of Lemierre Syndrome: (Poster No. 133)
Lemierre syndrome is caused by a necrotizing infection of the head and neck. This can become complicated by septic thrombophlebitis with ensuing sepsis. The histopathology of this forgotten syndrome has previously not been well characterized. We describe the case of a 20-year-old man who developed a left tonsillar abscess, septic thrombophlebitis of his left jugular vein, and septic shock. Fusobacterium was isolated from his blood cultures. The patient underwent internal jugular vein excision. Grossly, the vein was occluded by clot and the thickened blood vessel wall was adherent to adjacent soft tissue. Microscopic examination showed an organizing thrombus with acute and chronic inflammatory cells (Figure 156, A). The wall of the vein was also infiltrated by acute and chronic inflammatory cells (Figure, B; higher magnification). Circumferential granulation tissue with fibrosis extended from the media into perivascular soft tissue. Masson trichrome and Verhoeff-Van Gieson elastic stain showed interruption of the vessel wall with inflammation and fibrosis. Intramural granulation tissue was highlighted by using CD31, CD34, and FLI-1 immunostains. Smooth muscle actin stained proliferating myofibroblasts and CD68-admixed histiocytes. No organisms were identified with special stains, perhaps because the patient was previously treated with antibiotics. As depicted in this case, the histopathology of Lemierre syndrome is characterized by septic thrombophlebitis. Albeit rare, this is an important diagnosis because these necrotizing infections of the head and neck can have a lethal outcome.
Papillary Thyroid Carcinoma, Follicular Variant, Arising Within a Thyroglossal Duct Cyst: (Poster No. 134)
The incidence of carcinoma arising in a lingual thyroid is very rare, less than 1%, with approximately 45 reported cases since its first discovery in 1910. To date, fewer than 5 cases of papillary thyroid carcinoma, follicular variant, arising from a lingual thyroid have been reported in the literature. We report the case of a 23-year-old woman who presented with a right neck mass and a hyoid mass of 10 years' duration with a slow growth rate. The right neck mass was excised and consisted of a 2.6-cm cystic mass filled with spongy brown material. Microscopic examination showed benign ectopic thyroid tissue with cystically dilated colloid follicles, fibrosis, hemosiderinladen macrophages, and aggregates of foreign body cells with cholesterol clefts. Interestingly, there were a few small foci of cells with papillary nuclear features, but this was favored to represent degenerative atypia. However, the possibility of a metastatic carcinoma was not entirely excluded. The hyoid mass was excised and consisted of a 4-cm, lobulated, pink-tan rubbery mass with attached hyoid bone. Microscopic examination showed papillary thyroid carcinoma, follicular variant, 1.7 cm, involving the hyoid bone and adjacent skeletal muscle (Figure 157). The tumor was admixed with ectopic thyroid tissue and surrounded by a thick fibrous capsule. The patient subsequently underwent a total thyroidectomy, in which no focus of carcinoma was identified. We present a detailed examination of our case and literature review.
Intranodal Parotid Nonsebaceous Lymphadenoma: (Poster No. 135)
We present the case of a 58-year-old man with a history of pancreatic neuroendocrine tumor who presented with presyncope. A magnetic resonance imaging of the brain showed no intracranial abnormalities and an incidentally noted enlarged upper right cervical lymph node. A follow-up computed tomography and magnetic resonance imaging showed a heterogeneous, 2.4-cm, well-circumscribed right parotid mass with radiographic features of a pleomorphic adenoma (benign mixed tumor). The patient was asymptomatic with no facial pain or numbness and was unaware of the lesion. A fine-needle aspiration showed basaloid epithelial cells with a prominent lymphoid component, which was favored to be a low-grade parotid neoplasm. Given the low-grade impression based on imaging and fine-needle aspiration, the nodule was removed conservatively without sacrificing facial nerve branches (superficial parotidectomy). The resection specimen was well circumscribed and encapsulated, grossly resembling a lymph node. Microscopically, it was an encapsulated, well-circumscribed basaloid epithelial proliferation containing areas of ductal differentiation set within a follicular lymphoid background (Figure 158). The specimen was diagnosed as a nonsebaceous lymphadenoma, a rare benign parotid tumor that may be confused with basal cell adenoma or metastatic carcinoma. Sebaceous lymphadenomas have been speculated to arise within intraparotid lymph nodes. The etiology of nonsebaceous lymphadenomas is less well understood, and it has been proposed that the lymphocytic component represents a tumor-associated lymphoid proliferation, lacking features of a lymph node. We present a case of nonsebaceous lymphadenoma that demonstrates features suggestive of lymph node derivation.
Crohn Disease: An Unusual Cause of Sinonasal Granulomatous Disease: (Poster No. 138)
A 27-year-old woman presented with sinus symptoms, intermittent epistaxis, and discomfort. Significant past medical history includes Crohn disease. Examination showed a nasal septal perforation as well as bilateral turbinate hypertrophy. A partial reduction of the inferior turbinates was performed. Histopathologic examination shows sinonasal mucosa with prominent involvement by granulomatous inflammation. The submucosa is expanded by noncaseating granulomas composed of both mononuclear histiocytes and multinucleated, Langerhans-type giant cells. The granulomas are dispersed within a dense lymphoplasmacytic infiltrate. Special stains for microorganisms are negative (acid-fast [Ziehl-Neelsen], Gomori methenamine silver, Brown and Brenn; Figure 159). Vasculitis is not observed. Many patients with Crohn disease have extraintestinal manifestations, but sinonasal involvement has been reported in only 8 patients, including this case. Studies of sinonasal symptoms in patients with Crohn disease suggest that the prevalence may be much higher than currently appreciated. Presenting symptoms in histologically documented cases have included chronic sinonasal congestion, nasal obstruction, intermittent epistaxis, and septal perforation. Histopathologic findings are nonspecific; the findings reported in this patient are characteristic. The differential diagnosis includes infectious disorders, various forms of vasculitis, lymphoma, trauma, cocaine use, and sarcoidosis. The diagnosis requires a high index of suspicion, and correlation with the clinical, imaging findings, and other laboratory findings. Perhaps underrecognized, Crohn disease should be considered in the differential diagnosis of granulomatous sinonasal disease.
A Case of Mammary Analog Secretory Carcinoma of Salivary Gland With High-Grade Histology: (Poster No. 139)
Mammary analog secretory carcinoma (MASC) of salivary gland is a recently recognized malignancy that strikingly resembles secretory carcinoma of the breast in histology and bears the same balanced translocation of t(12;15)(p13;q25) that creates a ETV6-NTRK3 fusion. MASC occurs most commonly in parotid and uncommonly in minor salivary glands, has low-grade histology, and follows a relatively benign course. Metastasis to lymph node is uncommon and high-grade histology is only rarely reported. MASC is often confused with acinic tumor and adenocarcinoma not otherwise specified and less commonly with other salivary gland tumors. Here we report a rare case with high-grade histology and metastasis to cervical lymph nodes. The tumor occurred in the hard palate of a 41-year-old adult and confirmed with ETV6-NTRK3 translocation. It was histologically composed of a minor glandular component with pale eosinophilic secretion (Figure 160, A and B) commonly seen in MASC and a dominant solid component (Figure, C and D) with mitotically active (arrows in Figure, D) solid cell nests separated by fibrovascular septa. Both components had enlarged nuclei with prominent nucleoli. Expression of cytokeratin 7 and 8/18 was patchy in the glandular component but diffuse in the solid component. Both components were diffusely immunoreactive for S100 and vimentin but negative for calponin, cytokeratin 5/6, epithelial membrane antigen, GCDFP-15, and p63. The solid component has higher Ki-67 labeling index. This case emphasizes the importance of molecular pathology in distinguishing this tumor from other high-grade tumors of salivary gland.
Parathyroid Lipoadenoma: An Entity Linking to Multiple Endocrine Neoplasia?: (Poster No. 142)
Parathyroid lipoadenoma is an extremely rare cause of hyperparathyroidism. There were fewer than 50 cases reported in the English literature, none of which was associated with multiple endocrine neoplasia (MEN). Reporting bias may exist owing to its rarity and the limited number of case reports. The characteristic histologic feature of parathyroid lipoadenoma is an increased parathyroid parenchymal mass with abundant stromal fat in a patient with primary hyperparathyroidism. The paradoxical increase in stromal fat poses significant challenges in preoperative imaging and intraoperative frozen diagnoses. We report 2 cases involving elderly women (58 and 66 years old) who underwent parathyroidectomy for primary hyperparathyroidism. Gross examination revealed completely and partially encapsulated masses weighing 2.64 and 5.07 g, respectively. Histologically, the masses, with thin rims of normal parathyroid (Figure 161, A), are composed of abundant mature adipose tissue (30% and 40%, respectively) and follicular pattern predominant chief cells intermingled with nested and trabecular areas and scattered oxyphilic cells (Figure, B). The first patient had a concurrent incidental finding of stage IV thyroid medullary carcinoma, in the context of a family history of MEN type II. The second patient has a rather strong family history of hyperparathyroidism clinically suggestive of MEN. In summary, we present 2 cases of parathyroid lipoadenomas in the context of a family history of MEN, suggesting an association of this rare tumor to MEN syndrome. A large-scale study needs to be conducted to confirm this correlation.
Oncocytic Mucoepidermoid Carcinoma Arising Within Warthin Tumor of the Parotid Gland: (Poster No. 145)
Oncocytic salivary gland carcinomas are uncommon salivary gland neoplasms, among which the oncocytic variant of mucoepidermoid carcinoma (OMEC) is very rare. We report a case of OMEC arising in a Warthin tumor of the parotid gland. A 66-year-old man had a 6-month history of left neck mass, which on fine-needle aspiration showed rare atypical cells. Computed tomography scan showed a cystic parotid mass. Left superficial parotidectomy revealed a 2.5-cm, partially solid, partially cystic, tan-red mass. Microscopically, it was a well-circumscribed mass with a morphology characteristic of Warthin tumor. However, the major component of the tumor was more solid with frequent mucocytes and also composed of large, slightly atypical oncocytic cells with a back-to-back glandular arrangement. In some areas, the tumor cells were pseudostratified and focally showed various degrees of squamous metaplasia. The oncocytic cells in the solid area were positive for p63, and the Ki-67 proliferation index was approximately 10% to 15%. All these findings support a diagnosis of Warthin tumor, which contains low-grade mucoepidermoid carcinoma with oncocytic features. The differential diagnoses of OMEC include other salivary oncocytic neoplasms, which usually can be differentiated by immunostains. Positive p63 and presence of mucocytes are the features of OMEC. In conclusion, it is important to recognize OMEC and distinguish this entity from other high-grade oncocytic carcinoma, since OMECs are usually a low-grade malignancy with low recurrence rate after complete excision (Figure 162).
A Rare Case of Respiratory Epithelial Adenomatoid Hamartoma: (Poster No. 147)
Respiratory epithelial adenomatoid hamartoma (REAH) is a rare lesion of the sinonasal tract and nasopharynx. The case described here is from a 71-year-old man who presented with sneezing, anosmia, and nasal block. Endoscopic examination revealed bilateral nasal polyps. On surgical operation, multiple polyps were arising from nasal septum and all sinuses. The clinical diagnosis was bilateral sinonasal polyps and inverted papilloma. Microscopic examination revealed REAH with irregular glandular proliferation composed of widely spaced, small to medium glands lined by multilayered, ciliated respiratory epithelium. The glands were in direct continuity with surface epithelium in some areas. Characteristic stromal hyalinization was present with envelopment of glands by a thick, eosinophilic basement membrane (Figure 163). Multiple sinonasal polyps were also present. A search of medical literature showed approximately 54 cases of REAH, including the 31 cases first described by Wenig and Heffner in 1995. REAH preferentially involves 1 side of the posterior nasal septum but can occur at other sites also. The etiology of REAH is unknown but appears to be associated with inflammation and polyposis. REAH appears to be a benign lesion, since no recurrence or metastasis has been reported. Surgical excision is the treatment of choice. However, some studies suggest that REAH may be associated with sinonasal adenocarcinoma.
Sinonasal Eosinophilic Angiocentric Fibrosis: (Poster No. 149)
Eosinophilic angiocentric fibrosis (EAF) is a rare benign condition. EAF is a tumefactive lesion of the orbit and upper respiratory tract, with progressive upper airway obstruction in association with submucosa inflammation, fibrosis, and tumorlike growth. Histologic features include different stages of fibrosis, inflammatory cell infiltration with predominance of eosinophils, lymphocytes, and plasma cells. The distinctive morphologic feature is the perivascular fibrosis (“onion skinning”). The fibrosis in EAF has various appearances as the disease progresses. Predominant fibrotic tissue with minimal onion skinning, as seen in our present case, represents an early stage of the disease course. Biopsy from the nasal cavity of our 36-year-old male patient is composed of multiple fragments of fibrous tissue with inflammatory cell infiltrate including eosinophils, plasma cells, and lymphocytes. Small foci of characteristic “onion skinning” are appreciated with careful evaluation of the specimen. The ratio of IgG4 to IgG by immunohistochemical study is 0.18. This case represents another example of the unique and characteristic histologic picture of this rare entity, which will serve to increase the awareness of the entity and lead to the correct diagnosis. In addition, our case, in line with the previous 3 reported cases, demonstrates a possible IgG4 involvement in the pathogenesis of EAF (Figure 164).
A Novel Association of Biventricular Cardiac Noncompaction and Diabetic Embryopathy: (Poster No. 151)
Diabetic embryopathy (DE) refers to a constellation of congenital malformations arising in the setting of poorly controlled maternal diabetes. Cardiac abnormalities are the most frequently observed findings in this syndrome, with a 5-fold risk over normal pregnancies. While a diverse spectrum of cardiac defects has been documented, cardiac noncompaction morphology has not been associated with this syndrome. In this report, we describe a novel case of biventricular cardiac noncompaction in a neonate born to a mother with pregestational diabetes. The patient is a late preterm female neonate with nonspecific facial dysmorphism, caudal regression syndrome, bilateral bilobed lungs, multiple cardiac septal and arch defects, heterotaxy with left atrial isomerism, as well as biventricular cardiac noncompaction. Gross examination of both ventricles demonstrated marked spongy myocardium (Figure 165, A and B). Histologic sections by Masson trichrome staining showed increased myocardial trabeculation greater than 50% left ventricular thickness and greater than 75% right ventricular thickness, consistent with noncompaction morphology (Figure, C and D). Additionally, noncompaction was noted on postdelivery echocardiogram (Figure, E). The pathogenesis of DE and cardiac noncompaction are not well understood. DE may arise secondarily to cellular organelle stress in a hyperglycemic environment in utero. Cardiac noncompaction, commonly seen isolated to the left ventricle, has been associated with a number of genetic defects that arrest normal embryologic compaction of the developing myocardium. In this case, we postulate that the development of noncompaction morphology may also arise as a result of metabolic derangements secondary to gestational hyperglycemia, perhaps through epigenetic modification of genes critical for normal myocardial compaction.
Eosinophilic Coronary Periarteritis With Arterial Dissection: The Mast Cell Hypothesis: (Poster No. 154)
A subset of coronary arterial dissections is associated with eosinophilic coronary periarteritis (ECPA); however, the pathogenesis of the process remains unclear. Mast cells normally reside in coronary arterial adventitia and are known mediators of eosinophilic inflamma-tory conditions such as type I hypersensitivity reactions. It has recently been proposed that mast cells may help recruit eosinophils in cases of ECPA. We report 2 cases in which coronary arterial dissection with ECPA was detected at autopsy (Figure 166, A and B). Tryptase, CD68, CD4, CD8, and CD1a immunohistochemical staining was performed to better characterize inflammation. Mucicarmine and elastin stains were used to assess for underlying structural vasculopathy such as cystic medial necrosis. While eosinophils represented a prominent cell population (median: 100 and 133 in cases 1 and 2, respectively), median numbers of T cells (CD4+ and CD8+ lymphocytes) were slightly higher (median: 104 and 156; Figure, C). This finding is in contrast to previous reports of an eosinophil predominance in ECPA. The ratio of CD4+/CD8+ lymphocytes did not suggest a clonal population. There were moderate numbers of macrophages, and few neutrophils or dendritic cells. Tryptase staining for mast cells in dissected coronaries revealed median numbers of 3 and 4.5 in case 1 and 2, respectively (Figure, D). Numbers of mast cells in dissected versus nondissected coronary sections were compared: adventitial mast cell densities were 3-fold higher in dissected portions and showed a trend toward increased degranulation. These findings suggest that mast cells may play a role in orchestrating inflammation in cases of ECPA.
Immunohistochemical Evaluation of Ber-EP4, MOC-31, TAG-72, and CEA in Various Carcinomas: (Poster No. 2)
Context: Ber-EP4, MOC-31, TAG-72, and CEA are the commonly used immunomarkers to identify carcinomas (CAs), especially in cytologic specimens; however, data were inconsistent. In this study, we evaluated their expressions in CAs from various organs.
Design: Immunohistochemical evaluation of the expressions of Ber-EP4 and MOC-31 (DakoCytomation, Glostrup, Denmark), TAG-72 (Cell Marque, Rocklin, California), and CEA (BioGenex, San Ramon, California) was performed on 797 CAs on tissue microarray sections. The staining results were recorded.
Results: The positive staining results (%) and the total number of cases for each entity (N) are summarized in the Table. MOC-31 had the highest sensitivity (74%) and TAG-72 the lowest (18%). Urothelial CAs showed the lowest expression of all 4 markers. CEA was often expressed in colorectal, pancreatic, and endocervical adenocarcinomas; in contrast, it lacked or had low expression in ovarian serous CAs, and endometrial and prostatic ADCs.
Conclusions: Our data suggest that (1) MOC-31 and Ber-EP4 are reasonably sensitive markers for CAs and should be used as the first choice; (2) TAG-72 has very limited utility owing to its low sensitivity; (3) CEA is sensitive for adenocarcinomas of colon, pancreas, and endocervix; however, it has limited utility for ovarian serous CA, and endometrial and prostatic ADCs; and (4) if UCAs are the differential considerations, the utility of these markers is limited.
A Case of Renal Mucinous Tubular and Spindle Cell Carcinoma in a Patient With Metastatic Colonic Adenocarcinoma: (Poster No. 4)
Renal mucinous tubular and spindle cell carcinoma is a rare low-grade renal epithelial neoplasm recently described as a subtype of renal cell carcinoma in the 2004 World Health Organization classification. It is considered a low-grade malignancy carrying a relatively favorable prognosis. We report fine-needle aspiration (FNA) and core biopsy findings in a 67-year-old man with metastatic colonic adenocarcinoma. A follow-up computed tomography scan showed a 3.2-cm hyperdense cystic renal mass. Cytology smears revealed crowded clusters and sheets of cells with round nuclei and pinpoint nucleoli associated with mucinous material in the background (Figure 167). On cell block these cells were arranged in a tubular pattern. Core biopsy revealed several small fragments of tumor cells with uniform low-grade nuclei that formed microacinar and nested patterns. Tumor cells were positive for PAX8, CK7, and AMACR, and negative for CD10. This immunophenotype, along with morphology, was consistent with the diagnosis of mucinous tubular and spindle cell carcinoma. As this is a rare newly described entity, limited experience with renal mucinous tubular and spindle cell carcinoma may pose a diagnostic challenge on FNA, particularly in the presence of a second malignancy, for which the differential diagnosis includes metastasis to the kidney. To our knowledge, this is the first case of renal mucinous tubular and spindle cell carcinoma in a patient with colonic adenocarcinoma.
A Splenule Disguised as a Pancreatic Mass—Endoscopic Ultrasound-Guided, Fine-Needle Aspiration Cytology Raises the Curtain and Steals the Show: Review of Cytologic Features and Differential Diagnoses: (Poster No. 5)
Intrapancreatic accessory spleens (IPAS) are rarely encountered in endoscopic ultrasound-guided, fine-needle aspirations (EUS-FNA). However, as incidentally discovered IPAS can radiologically mimic a pancreatic neoplasm, a definitive diagnosis made by EUS-FNA can avert an unnecessary surgical intervention or additional radiologic follow-up. A 77-year-old African American woman with history of diverticulitis and thyroid cancer was found to have a pancreatic tail mass (18 × 13 mm) on computed tomography. She underwent EUS-FNA to rule out an endocrine neoplasm. Cytology slides showed a mixed population of inflammatory cells present both embedded in a vascular meshwork and loosely dispersed throughout the aspirate smears. We did not observe the presence of large platelet aggregates, a feature recently described in IPAS. Immunocytochemical analysis on cell block material showed lack of staining for synaptophysin, chromogranin, CD56, CAM 5.2, CK7, and CK20, and a mixed B- and T-cell population without evidence of a lymphoproliferative process. Ki-67 showed low proliferation (<10%). The primary cytologic differential diagnosis was neuroendocrine neoplasm, as the typically dispersed, predominantly single-cell population of inflammatory cells seen in IPAS can be mistaken for a monotonous population of neuroendocrine cells. The neoplastic cells of PanNET, however, typically have more cytoplasm than inflammatory cells, show eccentric round to oval nuclei, and finely dispersed chromatin. The differential diagnosis also included solid pseudopapillary neoplasm, but its blood vessels are typically larger than in IPAS and form fibrovascular cores surrounded by uniform epithelioid cells. Recognizing the cytologic features of IPAS on EUS-FNA and correct classification is important to avoid unnecessary surgery (Figure 168).
Can Patterns of Conversion From a Negative Initial Urine Cytology Finding to a Positive Finding on Either Subsequent Cytology or Biopsy Be Used as a Benchmark for Surveillance in the Diagnosis of Urothelial Carcinoma?: (Poster No. 6)
Context: As part of a greater study on the accuracy of urine cytology, we explored patterns of conversion from negative to positive urine cytology finding.
Design: A laboratory information system–based search was conducted in the surgical pathology database from January 2008 to December 2010. There were 587 subjects (694 biopsy and cytology pairs), including only those with histologic follow-up that had occurred within 2 years of urine cytology. We examined a subset of 180 subjects that had positive biopsy findings after an initial negative cytology finding in the past 2 years.
Results: The median number of urine cytologies before a positive cytology diagnosis was 2.0 (Figure 169). The median time from the initial negative to the first observed positive cytology finding was 1.4 months (IQR: 5.0 months). The median time from the first negative cytology finding until positive biopsy finding was 5.5 months (IQR: 11.0 months). Only 62 subjects (34.4%) had conversion from negative to positive urine cytology finding.
Conclusions: Our study suggests that greater than 3 cytology samples may lower the likelihood of finding malignancy. Furthermore, the median time for conversion of negative cytology to positive cytology finding is much shorter than that from negative cytology to positive biopsy finding. This shorter time interval is helpful in identification of earlier recurrences of urothelial carcinoma and underscores the importance of cytology as a more sensitive and efficient test. While cytology may not be the sole determinant in the triage of management, our study substantiates the currently accepted 3 monthly follow-up with cytology as a posttreatment urothelial carcinoma surveillance regimen.
Effusion Cytology of Myeloid Sarcoma in a Patient With Myelodysplastic Syndrome: An Unusual Clinical Scenario: (Poster No. 7)
Pericardial myeloid sarcoma is uncommon and is even rarer as a primary presentation, indicating acute leukemic transformation in a patient with a history of myelodysplastic syndrome with no other evidence of increased myeloblasts. We report the case of a 71-year-old woman with a history of transfusion-dependent myelodysplastic syndrome (RAEB-2), with good response to 4 cycles of Vidaza, who presented with dyspnea on exertion and intermittent chest tightness. Chest x-rays revealed large pleural and pericardial effusions, which were drained and collected. Cytologic examination of the pleural effusion identified large immature hematopoietic cells with high N/C ratio, scant basophilic cytoplasm, open chromatin, distinct nucleoli, and occasional binucleation in a background of abundant reactive mesothelial cells. Immunohistochemical studies demonstrated that these cells were positive for CD34 and myeloperoxidase. The pericardial fluid also showed similar atypical cells. Tissue from a therapeutic pericardial window confirmed the diagnosis of pericardial myeloid sarcoma. At this time, flow cytometry performed on the peripheral blood and the bone marrow showed no evidence of acute myeloid leukemia. To the best of our knowledge, this is the first reported case in the literature. Myeloid sarcoma is a rare extramedullary myeloid tumor. Owing to its rarity, the diagnosis on effusion cytology can be very challenging. However, as a devastating complication of myelodysplastic syndrome, it is important for cytopathologists and surgical pathologists to be vigilant and recognize this entity when evaluating specimens from patients with myelodysplastic syndrome (Figure 170).
Lobular Carcinoma of the Breast Presenting as a Metastatic Melanoma to the Axilla on Fine-Needle Aspiration and Core Biopsy: Report of a Case and Review of the Literature: (Poster No. 8)
An 84-year-old woman with a history of infiltrating lobular carcinoma (status post right mastectomy) and endometrial adenocarcinoma presented for excision of a right upper back, irregular, multihued, pigmented lesion. The lesion was diagnosed as malignant melanoma extending to the lateral margin. Two weeks later, she returned to the hospital with a right axillary mass. Sonography demonstrated a 1.5-cm region of ill-defined mixed echogenicity corresponding with a firm palpable right axillary nodule. The patient underwent a fine-needle aspiration and core biopsy of the right axillary soft tissue with the preprocedure differential diagnosis of melanoma, scar tissue, and carcinoma. Cytology slides revealed a hypercellular specimen with numerous malignant single cells and rare crowded groups displaying anisonucleosis, eccentric nuclei, dark dense cytoplasm, and small conspicuous nucleoli. The core biopsy showed an infiltrating solid tumor composed of single malignant cells with eccentric nuclei. These findings were highly suggestive of melanoma. The case was diagnosed as cytomorphologically consistent with malignant neoplasm with immunostains pending for further characterization (Figure 171, A and B). Immunocytochemistry results were negative for S100, HMB-45, Melan-A, and E-cadherin, with positive staining in AE1.3 cytokeratin (Figure, C), high-molecular-weight cytokeratin 903, and estrogen receptor (>90%) (Figure, D). These findings confirmed the presence of invasive lobular carcinoma. Metastatic melanoma of the breast is an uncommon finding but must be considered in cases with cytomorphologic features of melanoma presenting in breast cytology specimens. Despite the recent history of melanoma in our patient, it was important to consider the possibility of recurrence or metastasis from a prior carcinoma (endometrial or lobular).
Mesothelioma—Hiding Behind the “Community Border”: Case Report and Literature Review: (Poster No. 9)
Differentiation of malignant cells from reactive benign cells in ascitic and pleural effusions can be challenging and may lead to diagnostic errors. Even after malignant cells are identified, it is equally challenging to differentiate malignant mesothelial from malignant epithelial cells. In addition, coexistence of malignant mesothelioma and pulmonary carcinoma, although rare, has been reported. In our case, immunohistochemical studies were essential to establish the correct diagnosis that would have been missed by using cytomorphology alone. A 44-year-old man presented with ascites, peritoneal implants, and questionable lung nodules. Although initial cytomorphologic evaluation of the pleural fluid was negative for malignancy, a subsequent fine-needle aspiration of peritoneal implants showed characteristic cell clusters with smooth outlines (community borders) that suggested adenocarcinoma (Figure 172, A). Immunohistochemical characterization of the tumor was not possible owing to the lack of diagnostic material in the cell block. A subsequent pleural biopsy showed solid nodules of moderately pleomorphic epithelioid cells with rare mitoses and prominent nucleoli. The concomitant ascitic fluid aspiration displayed crowded 3-dimensional groups and single malignant cells with enlarged nuclei and prominent nucleoli (Figure, C). Morphology and immunohistochemical profile established a diagnosis of malignant mesothelioma: positive mesothelial markers were WT-1 (Figure, B), CK5/6 (Figure, D), calretinin, and GLUT-1; negative epithelial markers were MOC-31, BerEP4, and TTF-1; nonspecific CEA positivity was noted, as was negative histiocytic marker (CD163). Mesothelioma is a rare and aggressive malignant neoplasm of the serosal membranes, posing diagnostic challenges. Our case highlights the importance of using immunohistochemical studies in effusions even in the presence of strong cytomorphologic features.
Diagnostic Pitfalls of Effusion Cytology for Early Diagnosis of Primary Pleural Angiosarcoma: Two Case Reports: (Poster No. 10)
Primary pleural angiosarcoma (PPA) is rare and often presents as pleural effusion without other symptoms, which makes effusion cytology diagnosis very important. We present 2 cases of PPA in which atypical cells were first identified in effusion cytology. Our first case involved a 31-year-old man with chest pain who developed pleural effusion. Fluid cytology revealed single and clusters of large cells with nuclear abnormalities and benign-appearing mesothelial cells (Figure 173, A and B). The negative-for-malignancy finding was diagnosed in an outside hospital, since the cells of interest were negative for Ber-EP4 on immunohistochemistry. Later, pleural biopsy and additional immunohistochemistry panel for fluid showed that the atypical cells were positive for CD31 and CD34, consistent with angiosarcoma (Figure, C and D). Diagnosis of PPA was established after clinically ruling out other primaries. Our second case involved a 65-year-old woman who presented with left pleural effusion and had past history of breast cancer. Single and irregular clusters of atypical cells were identified on fluid cytology with final diagnosis of atypical cells. Imaging revealed pleural mass and biopsy showed angiosarcoma with expression of CD31 and CD34. In both our patients with PPA, pleural effusion was the early presenting symptom and the definite diagnosis was established by biopsies after atypical cells were first identified on fluid cytology. Immunohistochemistry panel in effusion cytology usually includes mesothelial and epithelial cell markers. We report these 2 cases to emphasize the importance of identifying atypical cells by using adjunctive endothelial markers for an early diagnosis of PPA.
A Rare Case of Adult Ewing Sarcoma Diagnosed by Cytology: (Poster No. 12)
Ewing sarcoma is a primary bone tumor that more commonly occurs in children but can arise in any age group. In adults older than 40 years, Ewing sarcoma is very rare, and although little is known about this disease in this age group, the prognosis is thought to be even worse. The common sites of metastasis include the chest and bone, and the less common sites include the central nervous system and lymph nodes. Localized disease is treated with chemotherapy and has a more favorable prognosis. We present the case of a 49-year-old man with a right sacral bone lesion without any prior history of malignancy. The patient underwent a computed tomography–guided fine-needle aspiration (FNA) biopsy, and core biopsy samples were also taken at the same time. The cytology smears, cell block, and core biopsy samples showed scattered groups and isolated cells with small round blue cell (SRBC) morphology (Figure 174, A through C). Diagnosis of extraskeletal Ewing sarcoma or other SRBC neoplasms, such as lymphoma, neuroblastoma, and other soft-tissue sarcomas, cannot be made solely on the basis of morphologic features. Immunocytochemical studies were performed and the cells were positive for vimentin, CD99 (Figure, D), and Fli-1. Ki-67 showed high proliferation index (>40%), consistent with Ewing/PNET sarcoma. Molecular studies demonstrated Ewing sarcoma gene translocation, t(11;22)(q24;q12), confirming the diagnosis. In summary, FNA is a quick procedure that may be used in the diagnosis of Ewing sarcoma. As in our case, accurate diagnosis can be made in deep-seated tumors by procuring adequate material under radiologic guidance.
A Case of Peripheral T-Cell Lymphoma With Unusual Presentation in a HTLV-II–Positive Patient: (Poster No. 13)
Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a rare neoplasm that typically presents as generalized lymphadenopathy. PTCL-NOS presenting as malignant ascites is rare. A 61-year-old African American man with past medical history of HCV, cryoglobulinemia, and cryptococcal pneumonia was admitted for dyspnea on exertion during a period of 1 month and new onset of abdominal distension. Ascites, splenomegaly, hepatomegaly, and extensive lymphadenopathy were found by imaging. Paracentesis obtained 1.3 L of abdominal fluid. The cytologic evaluation of Romanowsky and Papanicolaou stains of abdominal fluid revealed a monomorphic population of intermediate-sized lymphocytes with irregular to convoluted nuclear contours, with some cells morphologically mimicking “flower cells” (Figure 175). Abdominal fluid sent for flow cytometry showed an abnormal T-lymphocyte population expressing CD4, CD5, weak surface CD3, but no expression of CD7. Polymerase chain reaction studies of ascitic fluid detected a clonal T-lymphocyte population with T-cell receptor γ gene rearrangement. Serologic testing for human T lymphotropic virus (HTLV) was positive for HTLV II, and Western blot confirmed antibodies against HTLV II antigens. Subsequent bone marrow biopsy revealed lymphomatous involvement. Immunotaining with CD30 and ALK-1 immunostaining was negative. This case was classified as PTCL-NOS. PTCL-NOS can have an unusual clinical presentation, such as ascites and pleural effusion, and may also occur as a complication of immunodeficiency state. Cytomorphology may mimic adult T-cell lymphoma/leukemia. Further studies are needed to determine if HTLV II viral infection is associated with PTCL.
Breast Adenocarcinoma Metastasis to the Thyroid Mimicking Papillary Thyroid Carcinoma: A Potential Diagnostic Pitfall in Fine-Needle Aspiration: (Poster No. 14)
Metastases of malignant tumors to the thyroid gland are rare compared to primary thyroid neoplasms. Most thyroid nodules are initially evaluated by fine-needle aspiration and diagnosed by using the Bethesda System nomenclature. We present the case of a 59-year-old woman with a history of breast cancer who underwent a fine-needle aspiration of her thyroid gland that showed two >1-cm nodules on ultrasonography. Isthmic nodule cytology smears were interpreted as “suspicious for follicular variant of papillary thyroid carcinoma” (Bethesda V). Suspicious features included nuclear enlargement, elongation, crowding, clearing, and rare grooves (Figure 176). The cells were arranged in small clusters and sheets, forming microfollicular and macrofollicular structures. The patient underwent a total thyroidectomy, with a frozen section diagnosis consistent with papillary thyroid carcinoma. Further examination of the permanent sections showed a multifocal, bilateral neoplastic cell proliferation. Histologically, these cells formed nests and glandular structures between the thyroid follicles and stained positively for ER and negatively for TTF-1 and thyroglobulin. These results were consistent with metastatic breast carcinoma, ductal type. A literature review showed that adenocarcinoma metastasis to the thyroid is very rare, and rarer still for breast carcinoma. In patients with a prior history of malignancy, metastasis to the thyroid gland can mimic a primary thyroid neoplasm and may represent a diagnostic pitfall in fine-needle aspiration. It is important to recognize the possibility of metastatic malignancy when performing aspiration biopsies on this patient population.
Cytomorphologic Features of “Intrathyroid Follicular Lesion” of Parathyroid Origin: (Poster No. 16)
Context: Intrathyroidal parathyroid adenoma/hyperplasia is rare but a challenging lesion to distinguish from a follicular neoplasm of thyroid origin on cytology especially when submitted as “thyroid FNA.”
Design: We present 3 cases of intrathyroid parathyroid adenoma/ hyperplasia diagnosed on fine-needle aspiration (FNA). All 3 lesions underwent FNA on the basis of ultrasonographic suspicion of follicular neoplasm of thyroid origin. In the first case, initially diagnosed as suggestive of follicular neoplasm on the basis of cytomorphologic features, the patient underwent total thyroidectomy that revealed a parathyroid adenoma in a normal thyroid. Cytologic features of these cases were retrospectively reviewed at the time of cytohistologic correlation. Subsequently, the other 2 cases were diagnosed as parathyroid adenoma/hyperplasia on the basis of cytologic features and confirmed by immunohistochemistry (negative TTF-1 and positive PTH stain), thereby avoiding thyroid surgery.
Results: The radiologic findings, clinical indications, and significant clinical histories of the 3 cases are presented in the Table. Evaluation of direct smears (Figure 177, A) and cell block (Figure, B) of all 3 cases revealed tightly packed, branching trabeculae of cellular fragments of monomorphic round cells with prominent nuclear overlapping. Microfollicle formation, single cells in the background, and presence of colloidlike material were variable in their presence. Follicular adenomas, in contrast, are composed of uniform follicular cells in microfollicles, loose clusters, and monolayered sheets (Figure, C and D).
Conclusions: Presence of crowded, uniform cells arranged in thick trabeculae on “thyroid FNA” should raise a suspicion of parathyroid origin that can be easily confirmed by immunohistochemistry, thereby avoiding unnecessary thyroidectomy.
Fine-Needle Aspiration Biopsy Diagnosis of Oncocytic Carcinoma of the Pancreas: (Poster No. 17)
Oncocytic carcinoma is a very rare type of pancreatic adenocarcinoma, associated with intraductal papillary oncocytic neoplasm of the pancreas. It harbors genetic changes distinct from those of pancreatic ductal adenocarcinoma. Therefore, correct preoperative diagnosis is important in this era of personalized medicine. Here we report a case of oncocytic carcinoma diagnosed at Moffitt Cancer Center and discuss the cytologic and histologic features, differential diagnosis, utility of ancillary studies, and the recently updated knowledge about this entity. A 65-year-old woman presented with a mass in the head of the pancreas that was biopsied by fine-needle aspiration on 2 separate occasions. The smears were hypercellular with necrosis. The malignant cells showed oncocytic cytoplasm or less visible cytoplasm with rounded nuclei and prominent nucleoli or rounded nuclei with pale chromatin, focal intranuclear inclusions, and grooves. The cells were arranged in crowded groups, irregular sheets, and papillary clusters (Figure 178, A). Oncocytic carcinoma diagnosis was rendered on the basis of these distinct cytomorphologic features. Subsequent pancreatoduodenectomy demonstrated an invasive oncocytic carcinoma with an intraductal component involving the main pancreatic duct (Figure, B through D). The carcinoma was negative for HER2/neu, AFP, HepPar, CDX2, CD56, synaptophysin, and chromogranin by immunohistochemistry. This case demonstrates that oncocytic carcinoma can be diagnosed preoperatively by fine-needle aspiration biopsy on the basis of its unique cytomorphologic features. The differential diagnosis includes other neoplasms occurring in the pancreas with oncocytic features, particularly neuroendocrine tumors. Ancillary studies are beneficial for a definitive diagnosis. This carcinoma variant lacks the KRAS mutations common to pancreatic ductal adenocarcinomas.
CDX2 in Metastatic Prostatic Adenocarcinoma—Potential for Diagnostic Dilemma: Report of 2 Cases: (Poster No. 19)
Diagnosis of metastatic prostatic adenocarcinoma is generally straightforward, using hematoxylineosin and immunohistochemistry. CDX2 is commonly positive in colorectal cancer and not usually associated with prostate cancer. However, a subset of mucinous/signet-ring prostate carcinomas can show reactivity. Colorectal carcinoma is in the differential diagnosis of metastatic/primary prostate carcinoma. A positive CDX2 finding without a known history of prostate carcinoma and lack of prostate-specific antigen (PSA) staining can present diagnostic difficulties. We present 2 cases of metastatic nonmucinous prostate carcinomas with diffuse CDX2 positivity. Case 1 involved an 86-year-old man with a history of prostate carcinoma who presented with multiple lytic bone lesions. A computed tomography (CT)–guided biopsy of a left sixth rib lytic lesion showed metastatic prostatic adenocarcinoma (Figure 179, A). The tumor was positive for prostatic markers (Table). CDX2 showed diffuse nuclear positivity (Figure, B). Case 2 involved a 66-year-old man with elevated PSA levels who had transrectal ultrasound-guided biopsies, which showed extensive prostatic adenocarcinoma, predominately Gleason pattern 4+4. A CT of the chest, abdomen, and pelvis a year later showed extensive metastatic disease and no gastrointestinal tract lesions. A supraclavicular mass was biopsied, showing metastatic prostatic adenocarcinoma. CDX2 (Figure, C) and P504S stains were positive, while PSA and PAP were negative (Table). Immunohistochemistry of the original prostate biopsy (Table) showed strong diffuse positivity for PSA and CDX2 focal positivity (Figure, D). Pathologists need to be aware of possible CDX2 staining in prostate carcinoma, especially in metastatic disease. This unusual finding in conjunction with other immunohistochemistry and clinical history is crucial in establishing the correct diagnosis.
Suboccipital Malignant Solitary Fibrous Tumor Diagnosed on Fine-Needle Aspiration and Core Biopsy: Report of an Uncommon Tumor in a Rare Location and Review of the Literature: (Poster No. 20)
A 61-year-old man presented with an enlarged suboccipital heterogeneous soft tissue mass in the suboccipital region that had increased in size from 6.8 to 9.8 cm as compared with 6 months prior. The possibility of a soft tissue sarcoma was raised. Therefore, the patient underwent a fine-needle aspiration and core needle biopsy of the mass. Cytology slides showed sheets, clusters, and single cells with bland cytomorphologic features and prominent plasmacytoid morphology (Figure 180, A through C). The core biopsy showed solid sheets of plasmacytoid-like cells with bland cytomorphology, predominantly in perivascular arrangements. Rare mitoses and no necrosis were noted. The differential diagnosis included solitary fibrous tumor (SFT), PEComa, and hemangioendothelioma owing to the perivascular arrangement of bland cells, nerve sheath tumors as well as smooth muscle tumors, melanoma and even squamous cell carcinoma. An extended immunocytochemistry panel was performed for tumor characterization. The only antibodies with strong/positive staining were CD34 and CD99 (Figure, D) with focal weak/positive chromogranin staining. Negative stains included S100, HMB-45, Melan-A, EMA, AE1/ AE3, CAM 5.2, HMW-CK903, p40, CD31, GFAP, CD163, desmin, SMA, and synaptophysin Ki-67 (<2%). A diagnosis of low-grade mesenchymal neoplasm, hemangiopericytoma/SFT was made. Excision of the entire mass revealed the final diagnosis of malignant SFT. In cytology it is crucial to correlate the cytomorphologic features with the clinical presentation and the radiologic findings. Although uncommon, SFTs should be included in the differential diagnosis of suboccipital masses in adults. Our case report adds to the very limited existing literature on cytologic diagnosis of SFT.
Malignant Pulmonary Neoplasm With Papillary Features, Not Otherwise Specified—Does It Belong to the Current Lung Tumor Classification? Report of 2 Unusual Cases: (Poster No. 21)
Malignant pulmonary neoplasm with papillary features, not otherwise specified (NOS), is not part of the current classification of lung tumors; however, such cases do appear in daily practice. A 37-year-old woman presented with chest pain. Imaging revealed a large left lung mass, and a computed tomography–guided fine-needle aspiration followed. Smears and cell block showed a neoplasm with prominent papillary architecture, bland-looking columnar cells with increased nuclear to cytoplasmic ratio, regular nuclei, and inconspicuous nucleoli (Figure 181, upper images). Differential diagnosis included sclerosing hemangioma, papillary adenoma, adenocarcinoma, and papillary metastatic neoplasm. Immunohistochemical stains supported lung origin and excluded metastatic thyroid carcinoma (Table). The absence of a dual-cell population pointed to a well-differentiated adenocarcinoma. The MIB-1 (Ki-67) showed intermediate proliferation rate (10%–20%). In a second case a 53-year-old woman with a past medical history of lung cancer presented with dyspnea and a subphrenic/pleural mass. Cytopathology specimen showed a malignant neoplasm with papillary features. Immunohistochemistry suggested a poorly differentiated carcinoma, and pulmonary, mesothelial, renal, gastrointestinal, or müllerian primaries were excluded (Table). Another fine-needle aspiration and biopsy performed 1 month later recapitulated the initial hypercellular specimen: groups, sheets, clustered or single malignant cells, with enlarged nuclei and prominent nucleoli, vacuolated cytoplasm, and atypical mitoses (Figure, lower images). The proliferation index was 10% to 20%. In both of these instances the final diagnosis was malignant neoplasm with papillary features, NOS. These cases underscore the invaluable help of immunohistochemistry in challenging situations. With continued reporting of additional similar cases, their classification as a separate entity may be warranted.
A Unique Case of Fibrolamellar Hepatocellular Carcinoma Presenting With Altered Mental Status and Elevated Liver Enzymes Diagnosed by Cytology of Peritoneal Fluid: (Poster No. 22)
Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare malignant primary liver neoplasm that typically arises in young individuals lacking a background of chronic liver disease and other risk factors for hepatocellular carcinoma. Distinct pathologic features include presence of tumor cells with deeply eosinophilic cytoplasm and macronucleoli surrounded by abundant fibrous bands. On immunohistochemistry, FL-HCC shows both hepatocellular and bile duct differentiation. Metastasis significantly influences patient survival. The overall 5-year mortality rate for patients without metastasis at time of presentation is 86%, whereas it is 39% in cases with metastasis. We report the case of a 25-year-old white woman with history of deep venous thrombosis and without known chronic liver disease who presented with altered mental status. Liver enzymes (AST/ALT) were markedly elevated; CT scan revealed a 13×9-cm mass with focus of calcification in the left lobe of the liver and diffuse ascites. Ascitic fluid yielded dyshesive large tumor cells with abundant eosinophilic/oncocytic cytoplasm and large prominent nucleoli. Immunohistochemical stains were positive for CK7, EMA, and HepPar1, consistent with a metastatic FL-HCC. To our knowledge, this is the first documented FL-HCC that presented with altered sensorium and elevated liver enzymes. Metastatic FL-HCC can pose several diagnostic challenges owing to its uncommonness and the wide range of differential diagnoses. Extensive effort should be made in evaluating the patients' demographic and clinical history, as well as laboratory and radiologic findings. Awareness of this tumor with emphasis on cytologic features, along with aid of immunohistochemical stains, is the key in clinching a diagnosis (Figure 182).
Metaplastic Carcinoma of the Breast Diagnosed by Fine-Needle Aspiration Biopsy: Diagnostic Pitfalls in Cytopathology: (Poster No. 24)
Metaplastic carcinoma of the breast is a rare, highly aggressive variant of ductal carcinoma. This heterogenous neoplasm is characterized by the presence of adenocarcinoma admixed with squamous and/or mesenchymal components, and presents several diagnostic challenges in fine-needle aspiration cytology. We report a case of metaplastic carcinoma with chondroid differentiation in an 88-year-old woman with a left breast mass originally diagnosed as phyllodes tumor by fine-needle aspiration. The cytologic diagnosis was based on the finding of abundant atypical stromal cells admixed with scattered aggregates of epithelial cells and chondroid matrix. Subsequent excision revealed a highly cellular neoplasm with extensive chondroid differentiation and associated ductal carcinoma in situ, which was categorized as metaplastic carcinoma. Upon careful retrospective review, the cytology revealed epithelial atypia, most compatible with the diagnosis of metaplastic carcinoma (Figure 183). Metaplastic carcinoma is a challenging cytologic diagnosis because of its variable cytomorphology and potential to mimic numerous benign and malignant conditions. The most likely alternate diagnosis is that of malignant phyllodes tumor owing to its similar stromal cells and potential for matrix-producing sarcomatous differentiation. Other possible diagnoses include fat necrosis, pleomorphic adenoma, primary sarcomas, and metastatic disease. Fine-needle aspiration may not adequately sample both epithelial and mesenchymal components essential for the diagnosis of either metaplastic carcinoma or malignant phyllodes tumor. We conclude that it is necessary to consider the rare possibility of metaplastic carcinoma in the setting of fibroepithelial lesions, particularly in the presence of atypical stromal and epithelial cells.
Herpes Simplex Viral Cytopathic Changes Detected by Urine Cytology: (Poster No. 25)
Urinary tract cytopathology is a key component of the hematuria workup and surveillance of urothelial carcinoma. When reviewing these specimens, rarely infectious agents could be encountered. We present a rare finding of cellular changes consistent with herpes simplex virus (HSV) infection in a bladder barbotage specimen collected from a 68-year-old woman with recurrent urinary tract infections resulting in multiple hospital admissions. The patient had a past medical history of chronic kidney disease and was taking immunosuppressive agents owing to her liver transplant for alcoholic cirrhosis. Urology was consulted for cystourethroscopy to evaluate her bladder and upper urinary tract and placement of a suprapubic catheter. Cytomorphologic examination of the bladder barbotage specimen revealed an unexpected finding of multinucleated cells with glassy intranuclear inclusions, molding of nuclei, and margination of chromatin. This finding was consistent with the viral cytopathic effects of HSV (Figure 184, A) and was further supported by a positive HSV stain on the cell block section (Figure, B). Biopsies were obtained as well, but were negative for HSV. Without cytologic examination of our specimen, the asymptomatic HSV infection in our immunosuppressed patient may have otherwise gone unnoticed, which may have presented in the future with dissemination and potentially devastating consequences. Therefore, our case highlights the vast importance of urine cytopathology in the identification and management of disease, including infectious agents such as HSV. Our case also displays the sampling advantage of urine cytology, as biopsies are only a focal sampling and failed to yield the HSV infection recognized in our bladder barbotage specimen.
High-Grade Malignant Germ Cell Tumor With Initial Presentation as Metastatic Liver Lesions: Case Report and Literature Review: (Poster No. 27)
Metastatic germ cell tumors (MGCTs) are relatively uncommon, but represent 1% to 5% of all GCTs. MGCTs are found in a variety of anatomic locations, but most commonly affect the mediastinal, retroperitoneal, and sacrococcygeal region, and other areas of the head and neck region. Fine-needle aspiration biopsy (FNAB) was performed on 2 male patients, ages 24 and 48 years, who both presented with multiple liver lesions and mediastinal masses. Neither patient had a prior history of malignancy or any scrotal or testicular masses. Cytology smeared slides (Figure 185, A) and cell block (Figure, B) in both cases showed a moderately cellular specimen displaying disorganized crowded groups and single-lying malignant cells showing marked pleomorphism, anisonucleosis, irregular chromatin, and prominent nucleoli in a background of necrotic debris. Preliminary diagnosis was high-grade malignant neoplasm with prominent pleomorphic features. Additional studies were needed for a more specific diagnosis. Serum tumor markers revealed high human chorionic gonadotropin (HCG) and negative α-fetoprotein. Immunohistochemical studies revealed positive staining for AE1/AE3 (Figure, C) and b-HCG (Figure, D), but negative staining for CK5/6, synaptophysin, and S100. A final diagnosis of high-grade MGCT was rendered. MGCTs should be included in the differential diagnosis of liver lesions, as the criteria for MGCT are similar to those of other high-grade tumors such as hepatocellular carcinoma, neuroendocrine tumors, sarcoma, and melanoma. FNAB cytology, together with clinical history, imaging studies, and specific tumor markers, is crucial to the early diagnosis and subsequent management of patients with MGCTs.
Epithelioid Hemangioendothelioma and Angiosarcoma—Is There Something In Between? Malignant Epithelioid Hemangioendothelioma Diagnosed on Fine-Needle Aspiration and Core Biopsy: Case Report and Review of the Literature: (Poster No. 28)
A 58-year-old woman with a history of hepatic hemangiomas and liver resection presented with multiple liver lesions. Before presentation, the patient experienced 2 months of low-grade fevers as well as generalized fatigue and body aches. The patient's primary medical doctor referred her for a magnetic resonance imaging scan, which revealed multiple lesions in the liver. Radiologically guided fine-needle aspiration was performed. Cytology slides showed limited diagnostic material (Figure 186, A). The concurrent core biopsy showed an infiltrating tumor displaying short cords and small nests, with some foci showing well-demarcated nodules infiltrating the preexisting hepatocytes and bile ducts (Figure, B and C). The tumor cells showed abundant eosinophilic cytoplasm with focal cytoplasmic vacuolization. The cells showed marked nuclear atypia, mitotic activity >3 mitoses per 10 high-power fields, and focal spindling of cells. Necrosis could not be evaluated in the limited sample. These features can be seen in up to one-third of epithelioid hemangioendotheliomas, which show atypical histologic features and confer with a more aggressive course. All hepatic and epithelial markers were negative (Hep-Par1, TTF-1, AE1.3, CK7, CAM 5.2, EMA), while mesenchymal and vascular markers were strongly positive (vimentin, CD31, CD34, factor VIII) (Figure, D). The morphologic and immunohistochemical features prompted the diagnosis of malignant epithelioid hemangioendothelioma. Our case showed predominantly low proliferation (<10% nuclear staining), with focal nodular areas showing high proliferation. Angiosarcoma also expresses endothelial markers, but it is more destructive and often has a greater degree of nuclear atypia and mitosis. This diagnosis may represent a morphologic continuum with epithelioid angiosarcoma.
Cytologic Diagnosis of Intrapancreatic Accessory Spleen During Intraoperative Consultation: (Poster No. 30)
Accessory spleens are found in approximately 10% of the population, 17% of which occur in the tail of the pancreas. Intrapancreatic accessory spleens are usually found incidentally on computed tomography (CT) imaging and may mimic a malignant pancreatic neoplasm. We report a case of intrapancreatic accessory spleen with emphasis on cytologic material obtained at the time of intraoperative consultation. A 58-year-old white man presented with symptoms of heart failure. An abdominal CT scan demonstrated an incidental solid, enhancing mass in the tail of the pancreas. A laparoscopic distal pancreatectomy and splenectomy was subsequently performed. The surgical specimen was received for intraoperative consultation. Within the pancreas was a well-circumscribed, 2.6-cm, red-brown homogeneous mass. Scrape cytology demonstrated hypercellular smears with cohesive, papillary groups of bland, epithelioid cells with round to oval nuclei, associated with traversing vessels; a heterogeneous lymphoid population of cells was noted in the background. Permanent sections show histologic features of splenic parenchyma and a diagnosis of intrapancreatic accessory spleen was rendered. The use of scrape cytology can be a fast and effective way of identifying both endothelial and hematopoietic elements when intrapancreatic accessory spleen is in the differential diagnosis of a pancreatic mass (Figure 187).