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Hereditary Endocrine Tumor Syndromes

The Clinical and Predictive Role of Molecular Histopathology

Duan, Kai MD*†; Mete, Ozgur MD, FRCPC*†‡

doi: 10.1097/PCR.0000000000000206

Hereditary tumor syndromes are increasingly recognized in the development of endocrine neoplasms. Depending on the tumor type, 10% to 40% of cases are associated with genetic disorders, including the classic multiple endocrine neoplasia syndromes (MEN1 and MEN2), hyperparathyroidism–jaw tumor syndrome, SDH-related familial paraganglioma-pheochromocytoma syndromes, von Hippel-Lindau syndrome, neurofibromatosis type 1, Carney complex, McCune-Albright syndrome, and familial nonmedullary thyroid cancer syndromes, as well as newer entities (MEN4, DICER1 syndrome, glucagon cell hyperplasia and neoplasia syndrome). Although some features commonly seen in familial disease (early onset, family history, multifocal neoplasia, multiorgan involvement) may alert one to the possibility of an underlying genetic predisposition, endocrine neoplasia syndromes tend to be phenotypically complex and heterogeneous and present variably with de novo mutations, making it difficult to recognize and classify on clinical grounds alone. In an era of precision medicine, pathologists play a central role in the diagnosis of familial cancer syndromes, by leading the way toward screening and molecular histopathology prediction models. In particular, the identification of “pathognomonic” morphologic and immunohistochemical “clues” is crucial to raise the possibility of an inherited genetic disorder and to guide further management, including gene testing, counseling, and targeted therapy. This review highlights the important genotype-phenotype correlations to consider in hereditary endocrine tumor syndromes and their associated clinical implications.

From the *Department of Pathology, University Health Network; †Department of Laboratory Medicine and Pathobiology, University of Toronto; and ‡Endocrine Oncology Site Group, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

Reprints: Ozgur Mete, MD, FRCPC, 200 Elizabeth St, 11th Floor, Department of Pathology, University Health Network, Toronto, Ontario, Canada M5G 2C4. E-mail:

The authors have no funding or conflicts to declare.

© 2017 Lippincott Williams & Wilkins, Inc.