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Inherited Neuroendocrine Neoplasms

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The Spectrum of Neuroendocrine Neoplasia

Abstract

Inherited neuroendocrine neoplasms (NENs) represent a heterogeneous group of disorders that often present with subtle clinical or biochemical features. The well-recognized entities include a spectrum of associated neoplasms harboring various degrees of biologic aggressiveness, which often show variable degrees of genotype-phenotype correlations and penetrance. The rate of germline susceptibility in endocrine neoplasms is generally underestimated as most healthcare providers do not routinely consider the possibility of germline disease in a seemingly sporadic presentation in adults over the age of 50–60 years. Variations in disease penetrance and de novo pathogenic variants can lead to late-onset manifestations of inherited NENs that can simulate sporadic disease in the absence of family history. Some of these also manifest with a non-syndromic presentation as seen in patients with familial isolated hyperparathyroidism (FIHP), familial isolated pituitary adenoma (FIPA), as well as in a subset of multiple endocrine neoplasia type 2 (MEN2) patients manifesting only with medullary thyroid carcinoma (formerly known as familial isolated medullary thyroid carcinoma syndrome). The suspicion of an underlying germline susceptibility for NENs should be based on tumor multifocality and morphology including non-tumorous parenchyma, identification of hyperplasia-to-neoplasia progression sequence, early-onset, and coexistence of synchronous or asynchronous endocrinopathies, including endocrine neoplasias. The delivery of genetic care for hereditary inherited disorders is multifaceted and involves multiple healthcare practitioners, including laboratory geneticists, physician geneticists, and genetic counsellors.

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Authors and Affiliations

  1. Department of Pathology, University Health Network, Toronto, ON, Canada

    Ozgur Mete

  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

    Ozgur Mete

  3. Endocrine Oncology Site, Princess Margaret Cancer Centre, Toronto, ON, Canada

    Ozgur Mete & Raymond Kim

  4. Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

    Fady Hannah-Shmouni & Constantine A. Stratakis

  5. Departments of Medicine and Medical Oncology, University of Toronto, University Health Network, Toronto, ON, Canada

    Raymond Kim

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  2. Institute of Pathology, University Hospital of Lausanne, Lausanne, Vaud, Switzerland

    Stefano La Rosa

  3. Department of Pathology, University Health Network, Toronto, ON, Canada

    Ozgur Mete

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Mete, O., Hannah-Shmouni, F., Kim, R., Stratakis, C.A. (2021). Inherited Neuroendocrine Neoplasms. In: Asa, S.L., La Rosa, S., Mete, O. (eds) The Spectrum of Neuroendocrine Neoplasia. Springer, Cham. https://doi.org/10.1007/978-3-030-54391-4_18

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