Microglandular carcinoma of the pancreas: immunohistochemical and ultrastructural study of an unusual variant of pancreatic carcinoma that may closely resemble a neuroendocrine neoplasm.

Two cases are described of an unusual form of primary adenocarcinoma of the pancreas characterized histologically by their striking resemblance with a neuroendocrine neoplasm. The tumors were composed of a population of relatively small, uniform cells arranged in sheets admixed with small microglandular structures resulting in a cribriform pattern of growth. The tumor cells displayed scant cytoplasm with indistinct cell borders and round to oval nuclei with irregular clumping of chromatin and small, inconspicuous nucleoli. Immunohistochemical studies in both cases showed positivity of the neoplastic cells with CAM 5.2 antibodies and negative staining with a battery of neuroendocrine-related markers including chromogranin, NSE and synaptophysin, as well as with a variety of peptide hormones including insulin, glucagon, vasoactive intestinal polypeptide, gastrin and serotonin. Ultrastructural examination revealed a cohesive population of cells forming abortive glandular lumens lined by imperfectly formed microvilli and showing well-developed junctional complexes. No dense core neurosecretory granules or zymogen granules could be identified in any of the cells, supporting a ductal type of differentiation for these tumors. The main importance of recognizing this rare variant of pancreatic adenocarcinoma lies in avoiding misdiagnosis with other primary and metastatic neuroendocrine neoplasms of this organ. Immunohistochemical and ultrastructural examination will be of value in such cases for differential diagnosis.