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).