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Neuroendocrine Carcinoma : Immunostains

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Neuroendocrine tumors arising at various body sites are a heterogenous group of tumors with diverse clinical, biological, and pathologic features. The common underlying thread that connects them is characteristic histology, the presence of neurosecretory granules by electron microscopy, and demonstration of neuroendocrine markers by immunohistochemistry or in-situ hybridization.

Immunohistochemical markers useful in the diagnosis of gastrointestinal neuroendocrine tumors include: synaptophysin (most sensitive), chromogranin (most specific), CD56/NCAM1, Leu7, PGP9.5, and neuron specific enolase. Glucagon, somatostatin, gastrin, and serotonin are variably positive.

Most gastrointestinal NETs also express CDX-2 and CEA. Transcription factors such as pancreatic and duodenal homeobox 1 (PDX1), islet 1 (ISL-1), and PAX8 are considered to be pancreas specific. Metastatic NETs with an unknown primary site should be evaluated with a panel of CDX-2 (+ in gastrointestinal), ISL-1 or PDX1 (pancreas specific), and thyroid transcription factor 1 (TTF-1; favors lung origin). Rectal well-differentiated neuroendocrine tumors (Carcinoids) frequently express prostate-specific acid phosphatase.

Poorly-differentiated neuroendocrine carcinomas show BCL2 overexpression, loss of RB expression, and abnormal p53 expression (total loss or overexpression). This pattern is rarely observed in well-differentiated NETs.

The image shows immunoreactivity for CDX-2, villin, synaptophysin, and NSE in a neuroendocrine carcinoma of sigmoid colon. Image courtesy of: Jian-Hua Qiao, MD, Los Angeles, California, USA. Used with permission.

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