Section 3 -

Less Common Solid Tumors of the Pancreas Toshio Morohoshi and Nobuyuki Ohike Showa University Tokyo, Japan

Although the majority of solid tumors of the pancreas are ductal adenocarcinomas, various types of less common solid pancreatic tumors are often found in surgical pathology practice and in the rapidly developing field of imaging techniques. It may be practical to summarize the common and less common solid mass-forming pancreatic lesions in a list as below. Here we would like to present the histopathological features of some of the less common tumors, including acinar cell carcinoma, pancreatoblastoma, solid-pseudopapillary neoplasm, non-epithelial tumors, secondary tumors, and solid variants of cystic tumors. Solid Neoplasms and Lesions of the Pancreas Solid Tumors Ductal adenocarcinoma and its variants Other less common neoplasms Acinar cell carcinoma and its variants Pancreatoblastoma Solid-pseudopapillary neoplasm Endocrine neoplasms Non-epithelial tumors Secondary tumors Pseudotumors Solid Variants of Primarily Cystic Neoplasms Solid variant of serous cystic neoplasm Intraductal papillary-tubular tumor (a variant of intraductal papillary-mucinous neoplasm) Acinar Cell Carcinoma and its Variants Acinar cell carcinoma (ACC) This neoplasm may show several histological patterns, such as an acinar, solid, glandular, or trabecular pattern, but most common are acinar and/or solid structures. The former consist of well-developed acini having small lumina with basally oriented nuclei, and the latter are characterized by sheets or cords of cells separated by delicate fibrovascular stroma. This neoplasm usually shows expansive growth and forms nodes that are well demarcated from the surrounding pancreatic tissues, often with pseudocystic changes at the center. The diagnosis is based on immunohistochemical staining for pancreatic acinar cell markers such as trypsin (most reliable) and ultrastructural examination, which reveals zymogen granules. Mixed acinar-endocrine carcinoma (MAEC) MAEC is a variant of ACC that is so named when endocrine cells comprise at least 30% of the tumor. Endocrine differentiation is determined by immunohistochemical labeling using antisera to synaptophysin, chromogranin A, and pancreatic hormones., In MAECs the endocrine cells are either scattered among the exocrine cells or form islet-like clusters of neoplastic cells with relatively sparse granular eosinophilic cytoplasm. Pancreatoblastoma Pancreatoblastomas are composed predominantly of various epithelial components, which mainly consist of cells in acinar arrangement next to solid or sheet-like cell populations and squamoid corpuscles. Ductular structures may also be seen, but well-formed ductules with tall columnar lining cells containing mucin are uncommon. Endocrine components are also often found. The stroma may be hypercellular and include neoplastic bone and cartilage. Solid-pseudopapillary Neoplasm The non-cohesive neoplastic cells are cuboidal to polygonal and have eosinophilic, somewhat granular cytoplasm, similar to endocrine cells. In well-preserved areas, solid growth and pseudopapillary or pseudorosette patterns with delicate microvasculature are seen. In the degenerated and cystic areas, which are probably exposed to various ischemic and regressive changes, cytoplasmic vacuolization of tumor cells, aggregates of foamy cells, hemorrhage, calcification, and cholesterol clefts are usually recognized. At the periphery, tumor tissue intermingled with adjacent normal pancreatic tissue is seen. The pseudopapillary pattern with hyalinized or myxoid fibrovascular stroma, one of the hallmarks of this tumor, results from dyscohesion of tumor cells. Electron microscopically, zymogen- and endocrine-like granules and apoptotic bodies are often detected in tumor cells. These neoplasms label with antibodies to CD10 and show an abnormal nuclear pattern of labeling for beta-catenin. Non-epithelial Tumors A review of reported cases reveals various rare primary non-epithelial tumors of the pancreas. It may be difficult to distinguish some sarcomas histologically from undifferentiated (anaplastic) carcinoma of the pancreas. Mesenchymal tumors Benign or low-risk: neurofibroma, schwannoma, neuroma, leiomyoma, solitary fibrous tumor (SFT), GIST, granular cell tumor, benign fibrous histiocytoma, hemangioma, hemangioblastoma, lymphangioma, paraganglioma, angiomyolipoma and sugar tumor. High-risk: leimyosarcoma, GIST, MFH, fibrosarcoma, sclerosing epithelioid fibrosarcoma, liposarcoma, SFT, MPNST, PNET, malignant hemangiopericytoma, angiosarcopma, rhabdomyosarcoma. Malignant lymphoma Primary pancreatic lymphomas are usually of B phenotype, including low-grade MALT lymphoma, follicular lymphoma, and large B-cell lymphoma. Secondary Tumors Secondary involvement of the pancreas by a malignant tumor is due to metastasis from a distant site such as lung, breast, or prostate, to systemic spread of lymphoma/leukemia, or to invasion from an adjacent organ, such as the stomach, liver, or retroperitoneum. It is difficult to distinguish pancreatic adenocarcinoma from metastatic adenocarcinoma showing a solitary mass and involvement of the pancreatic duct epithelium. Renal cell carcinoma is notorious for delayed metastasis and its difficult differential diagnosis from several tumors with clear cell appearance (see next paragraph). Solid Variants of Cystic Tumors Solid Variant of Serous Cystadenoma Serous cystadenomas usually have a microcystic spongy or an oligolocular gross appearance, but on occasion the cystic spaces are absent in some areas or in the entire neoplasm. Histologically, the neoplastic cells are similar to those of conventional serous cystadenoma and are polygonal to cuboidal with clear to pale cytoplasm. However, they lack a cystic arrangement with nests resembling small ducts or acinar structures, sheets, and a trabecular pattern separated by fibrovascular stroma. Immunohistochemically, the tumor cells are positive for cytokeratins 7, 8, 18 and 19 and CA19-9. The differential diagnosis includes clear-cell "sugar" tumor, clear cell adenocarcinoma, clear cell endocrine tumor, hemangioblastoma, and metastatic renal cell carcinoma. References Hamilton SR, Aaltonen LA (Eds. ) (2000) WHO Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System. IARC Press: Lyon. Morohoshi T, Kanda M, Horie A, Chott A, Dreyer T, Kloppel G, Heitz PU (1987) Immunocytochemical markers of uncommon pancreatic tumors. Acinar cell carcinoma, pancreatoblastoma, and solid cystic (papillary-cystic) tumor. Cancer 59:739-747. Morohoshi T, Sagawa F, Mitsuya T (1990) Pancreatoblastoma with marked elevation of serum alpha-fetoprotein. An autopsy case report with immunocytochemical study. Virchows Arch A Pathol Anat Histopathol. 416:265-270. Lack EE (eds) (2003) Pathology of the pancreas, gall bladder, extrahepatic biliary tract, and ampullary region. Oxford University Press: New York. Klöppel G, Bogomoletz WV (2000) Tumors of the exocrine pancreas. In: CDM Fletcher (ed) Diagnostic histopathology of tumors, vol. 1. Churchill Livingstone, London , pp 461-474