Expression of calretinin, marker of mesothelial differentiation, in pancreatic ductal adenocarcinoma: A potential diagnostic pitfall

Objective: Pancreatic ductal adenocarcinoma is one of the most common causes of "peritoneal carcinomatosis" and has an insidious growth pattern. Thus, it falls into the differential diagnosis of other peritoneal malignancies including malignant mesothelioma. Recently, we have encountered an undifferentiated pancreatic carcinoma presenting with peritoneal disease and exhibiting immunoreactivity to calretinin, mimicking mesothelioma. In this study, we explored the incidence of calretinin expression in pancreatic ductal adenocarcinoma. Materials and Methods: Calretinin immunohistochemical staining was performed on the tissue microarrays (TMAs), which were created using three 0.6 mm diameter punches per tumor (n=113). Distribution and intensity of expression were evaluated. Results: The TMAs contained 86 well/moderately differentiated and 27 poorly differentiated/undifferentiated carcinomas. Calretinin was positive in nine tumors (8%); six with diffuse and strong staining, three with focal and/or weak staining. The incidence of calretinin expression was 15% in poorly differentiated/undifferentiated carcinomas (vs. 6% in well/moderately differentiated carcinomas, p=0.03). Conclusions: Pancreatic ductal adenocarcinomas, especially when poorly differentiated/undifferentiated, may be diffusely and strongly positive for calretinin creating a potential diagnostic challenge with malignant mesothelioma. Therefore, caution should be exercised when using this marker to explore a diagnosis of malignant mesothelioma. Tumors expressing calretinin without other mesothelial markers should prompt a careful evaluation of the morphologic and immunohistochemical features to exclude other malignancies. If the diagnosis of pancreatic ductal adenocarcinoma is considered, ductal differentiation can be demonstrated by using additional immunohistochemical markers such as mucin-related glycoproteins (MUC1, MUC5AC) and/or oncoproteins (CEA, B72.3, CA125)

Mesenchymal tumors involving the pancreas: A clinicopathologic analysis and review of the literature

Objective: Most pancreatic tumors are epithelial, and, among these, more than 90% are of ductal origin. However, a variety of mesenchymal tumors may involve the pancreas and may manifest different clinicopathological characteristics. The literature on mesenchymal tumors in the pancreas is largely limited to individual case reports or analyses of small series, predominantly focusing on radiologic features. Material and Method: Authors' institutional and consultation databases were reviewed to identify the mesenchymal tumors involving the pancreas. Results: Forty cases were identified; twenty-five (63%) tumors were benign/borderline, and the remaining fifteen (37%) were malignant. Of the benign/borderline tumors; 9 were solitary fibrous tumors, 6 gastrointestinal stromal tumors (GISTs), 4 schwannomas, 2 desmoid type fibromatosis, 1 lymphangioma, 1 ganglioneuroma, 1 inflammatory myofibroblastic tumor, and 1 low grade mesenchymal neoplasm. Malignant tumors included 6 cases of leiomyosarcomas, 4 liposarcomas, 2 rhabdomyosarcomas, 1 epithelioid angiosarcoma, 1 malignant peripheral nerve sheet tumor, and 1 undifferentiated pleomorphic sarcoma. Four cases (multicystic schwannoma, desmoid fibromatosis, lymphangioma and inflammatory myofibroblastic tumor) were preoperatively misdiagnosed as a primary epithelial tumor of the pancreas. Conclusion: Mesenchymal tumors rarely involve the pancreas. They are usually benign/borderline neoplasms but may be diagnostically challenging, especially clinically/radiologically, as they may form cystic and/or large lesions in the pancreas. Mesenchymal tumors should be considered in both the clinical/radiological and pathological differential diagnosis of pancreatic lesions

Intraductal Neoplasms of the Pancreas: An Update

With improvements in imaging to detect silent pancreatic lesions and increases in the number of centers now performing pancreatic surgery, more surgeries have been performed for indications other than invasive carcinoma. This has enormously added to our knowledge of the intraductal neoplasms of the pancreas. In addition, our understanding of the genetics of these lesions has expanded with the introduction of routine molecular genetic analyses. In this review, we provide an update into the most common intraductal neoplasms, namely intraductal papillary mucinous neoplasm and intraductal tubulopapillary neoplasm. We first focus on their clinicopathologic and molecular features of relevance to the practicing pathologist and then discuss their differential diagnoses

Dedifferentiated Liposarcoma of the Gastroesophageal Junction

Liposarcoma is one of the most common sarcomas in adults, but very rarely presents as a primary in the upper gastrointestinal system. Herein, we present a 71-year-old male patient who underwent wedge excision biopsy twice and then fine needle aspiration and total gastrectomy for a recurrent gastroeosophageal junction mass. In microscopic sections, both well-differentiated and dedifferentiated components were seen. Tumor cells were positive for MDM2, CDK4 and negative for CD117, DOG1, CD34, SMA, Desmin, S-100, HMB45, SOX10, AE1/AE3, CAM5.2, CK18. Fluorescence in situ hybridization (FISH) was performed and MDM2 gene (12q15) amplification was detected. According to these findings, a diagnosis of dedifferentiated liposarcoma was supported. We believe this is the first reported case of dedifferentiated liposarcoma of the gastroesophageal junction

Is it justifiable to move the grade-1 ki67 index cut-off from 3% to 5% for pancreatic neuroendocrine tumors as has been proposed? The cases that fall to 3-5% category have clinicopathologic characteristics closer to those > 5%

Background: Grading of linear parameters into meaningful (clinically relevant) clusters is a well-known challenge. Recently several groupshave proposed to change the Ki67 index cut-off for grade 1 (G1) category for PanNETs from 3%).United States & Canadian Academy of Patholog

A proposal for improved t-staging of pancreatic ductal adenocarcinoma by using microscopic examination as the basis for determining the size and t-stage

Background: Stage remains as the most helpful prognosticator in pancreatic ductal adenocarcinoma (PDAC). However, accurate grossmeasurement of PDAC tumor size, the main stage parameter, is a well-known challenge due to its notoriously ill-defined nature. It hasbeen well documented that there are often satellite microtumor foci beyond the grossly appreciated tumor (PMID: 26832882), which in factmay represent intraparenchymal metastases. This becomes a bigger challenge if the gross room personnel are not experienced enough forthe subtleties of PDAC

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A proposal for improved t-staging of pancreatic ductal adenocarcinoma by using microscopic examination as the basis for determining the size and t-stage

Background: Stage remains as the most helpful prognosticator in pancreatic ductal adenocarcinoma (PDAC). However, accurate grossmeasurement of PDAC tumor size, the main stage parameter, is a well-known challenge due to its notoriously ill-defined nature. It hasbeen well documented that there are often satellite microtumor foci beyond the grossly appreciated tumor (PMID: 26832882), which in factmay represent intraparenchymal metastases. This becomes a bigger challenge if the gross room personnel are not experienced enough forthe subtleties of PDAC

Epithelial inclusions in the gallbladder: cytoisospora belli organisms or degenerative intracytoplasmic pas-positive hyaline globules

Background: Lai et al. reported 18 cases of Cystoisospora belli in the gallbladders (GBs), detected incidentally in 0.5% ofimmunocompetent patients (PMID: 27158759). However, a recent molecular study failed to confirm this observation at molecular level(PMID: 30020094). Although Lai et al. indicated that Cystoisospora in the GB is quiescent in immunocompetent patients, this diagnosisnevertheless has major implications, resulting in extensive patient workup for undetected immunosuppression.United States & Canadian Academy of Patholog

Epithelial inclusions in the gallbladder: cytoisospora belli organisms or degenerative intracytoplasmic pas-positive hyaline globules

Background: Lai et al. reported 18 cases of Cystoisospora belli in the gallbladders (GBs), detected incidentally in 0.5% ofimmunocompetent patients (PMID: 27158759). However, a recent molecular study failed to confirm this observation at molecular level(PMID: 30020094). Although Lai et al. indicated that Cystoisospora in the GB is quiescent in immunocompetent patients, this diagnosisnevertheless has major implications, resulting in extensive patient workup for undetected immunosuppression.United States & Canadian Academy of Patholog