Silvia Uccella, Claudio Luchini, Atsuko Kasajima, Günter Klöppel, Stefano La Rosa
About 10% of neuroendocrine tumors (NETs) can occur in the context of several different hereditary tumor syndromes, and, in a not negligible number of cases, their diagnosis precedes the clinical identification of the hereditary syndrome. In this context, the role of a pathologist can be crucial in identifying these sentinel cases. Indeed, early recognition of inherited NETs has significant clinical value, both for guiding therapeutic strategies and for managing at-risk family members. Modern pathologists play a central role not only in the accurate diagnosis and subtyping of NETs but also in recognizing specific morphologic features that may point to a germline etiology. When morphology does not show peculiar features suggestive of a hereditary context, integrating morphology with clinical context may, however, help identify appropriate genetic testing. In the present paper, we provide an organ-based overview of the most important morphologic and immunohistochemical features, along with their molecular correlates, of pituitary, parathyroid, thoracic, and digestive NETs arising in the context of hereditary tumor syndromes.