Case 5 -

Poorly differentiated neuroendocrine carcinoma of the pancreas producing somatostatin Dr. Günter Klöppel

Case history: 48-year-old male patient. Admission to hospital because of continuously increasing jaundice of one-week duration. Laparotomy because of suspected carcinoma in the head of the pancreas. Removal of tumor tissue. Case 5 - Figure 1 Click to view with ImageScope Click to view with a Web-Based Viewer Macroscopy: Multiple lymph node metastases in the tissue between the pancreatic head and the hilus of the liver. The individual lymph nodes have a diameter of up to 2 cm. Microscopy: Lymph node tissue that is almost totally replaced by solid and anastomosing tumor cell complexes. The tumor cell have round to oval nuclei and sparse eosinophilic cytoplasm. The chromatin of the nuclei is dense, but a distinct nucleus is rarely seen. There are many mitoses in multiple necrotic areas. The tumor tissue is supported by cords of connective tissue. Immunohistochemistry: The tumor cells stain for synaptophysin and chromogranin. They also express cytokeratin 8 and 18 to a variable extent, occasionally with a dotlike staining pattern. Somatostatin is expressed in about 50% of the cells, while there is no staining for gastrin and serotonin. Diagnosis: Poorly differentiated neuroendocrine carcinoma of the pancreas producing somatostatin. Differential diagnosis: The differential diagnosis of poorly differentiated neuroendocrine carcinomas includes all poorly differentiated and undifferentiated solid carcinomas of nonneuroendocrine tissues. The most important are undifferentiated pancreatic carcinoma, leiomyosarcoma, gastrointestinal stromal tumor (GIST), peripheral neuroectodermal tumor (PNET), malignant peripheral nerve sheath tumor (MPNST) and metastases of malignant melanoma. All these tumors are negative for neuroendocrine markers such as synaptophysin and chromogranin. This makes the differential diagnosis rather easy. The only ones that may show some positivity for synaptophysin are PNET, MPNST and GIST; however, this never as strong and even as it is for the neuroendocrine carcinoma. Moreover, they consistently lack chromogranin positivity. Comments: The WHO classification of endocrine tumors of the pancreas distinguishes between well differentiated endocrine tumors with benign or uncertain behavior, low grade malignant well differentiated endocrine carcinomas and high grade malignant poorly differentiated endocrine carcinomas. Most pancreatic endocrine tumors (PET) belong to the groups of well differentiated endocrine tumors and well differentiated endocrine carcinomas. They account for at least 95% of cases. Poorly differentiated endocrine carcinomas are very rare. They are usually carcinomas with a solid pattern, small necrotic areas, mitotic activity >10/10 HPF and proliferative activity of 30-50%. When stained for the neuroendocrine markers synaptophysin and chromogranin, they show distinct positivity for synaptophysin and no or only very weak positivity for chromogranin. The expression of cytokeratin 8 and 18, which is always found in these tumor cells, occasionally shows a dotlike staining pattern, which is seen in neuroendocrine carcinomas such as small cell lung carcinomas or Merkel cell carcinomas of the skin, but may also be observed in poorly differentiated neuroendocrine carcinomas of the pancreas. In contrast to well differentiated PET, they often show nuclear expression of p53. Poorly differentiated neuroendocrine carcinomas rarely express hormones. Therefore the production of somatostatin in this tumor is an exception. Since the patient had no symptoms of a somatostatinoma syndrome (diabetes, cholelithiasis, steatorrhea), the term somatostatinoma cannot be applied. Poorly differentiated neuroendocrine carcinomas follow a rapid course, with early metastases to the lymph nodes, the liver and extrahepatic organs. They usually respond to chemotherapy. Patients with poorly differentiated neuroendocrine carcinomas usually fare better than patients with undifferentiated carcinomas of the exocrine pancreas. References DeLellis RA, Lloyd RV, Heitz PU, Eng C (2004) Pathology and genetics: tumours of endocrine organs. WHO classification of tumors. IARC Press, Lyon Klöppel G, Heitz PU (2000) Tumors of the endocrine pancreas. In: CDM Fletcher (ed) Diagnostic histopathology of tumors, 2nd ed. Churchill Livingstone, London, pp 1083-1098 Solcia E, Capella C, Klöppel G (1997) Tumors of the pancreas. AFIP Atlas of Tumor Pathology, third series, fascicle 20. Armed Forces Institute of Pathology, Washington, D.C.