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66 - Multiple endocrine neoplasia type 2 (MEN2)

from Part 3.4 - Molecular pathology: endocrine cancers

Published online by Cambridge University Press:  05 February 2015

By
Jo W. M. Höppener  and
C. J. M. Lips
Edited by
Edward P. Gelmann ,
Charles L. Sawyers  and
Frank J. Rauscher, III
Jo W. M. Höppener
Affiliation:
Department of Molecular Cancer Research, University Medical Center Utrecht, University Hospital, the Netherlands
C. J. M. Lips
Affiliation:
Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
Edward P. Gelmann
Affiliation:
Columbia University, New York
Charles L. Sawyers
Affiliation:
Memorial Sloan-Kettering Cancer Center, New York
Frank J. Rauscher, III
Affiliation:
The Wistar Institute Cancer Centre, Philadelphia
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Summary

Introduction

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominantly inherited disorder characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PC), and primary parathyroid hyperplasia (PPH). While the penetrance of MTC is nearly 100%, there is much inter- and intra-family variability in the other clinical manifestations of this disorder. An MEN2 syndrome is often first suspected when a patient is found to have one or more of these tumors and especially at a young age. MEN2 is subclassified into three distinct syndromes: MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC). Although these syndromes are rare, early identification enables adequate treatment and evaluation of family members. Because the predisposing gene is known (the RET proto-oncogene), molecular testing by DNA mutation analysis is now available for detecting pre-symptomatic patients with MEN2. Early detection and treatment improves life expectancy and quality of life.

Medullary thyroid carcinoma (MTC)

MTC is a neuroendocrine tumor of the parafollicular or C-cells of the thyroid gland, accounting for approximately 3 to 5% of all thyroid carcinomas. C-cells are neuroendocrine cells derived from the ultimobranchial bodies (transient embryonic structures), which fuse with the posterior lobes of the thyroid; C-cells make up only about 0.1% of the thyroid mass. Multi-centric hyperplasia of the parafollicular C-cells is the hallmark of MEN2, with a penetrance approaching 100%. C-cell hyperplasia (CCH) clearly is a precursor lesion of MTC (see Figure 66.1). Nearly all MEN2 patients develop clinically apparent MTC, often early in life (1). A characteristic feature of thyroid C-cells and MTC is the production of the blood calcium-lowering peptide hormone calcitonin (2–4). The diagnoses of CCH and MTC are based upon microscopy criteria (histopathology, see Figure 66.1; 5). Neoplastic CCH and MTC in MEN2 are caused by a germline mutation in the RET proto-oncogene; MTCs in MEN2 patients are multi-centric and concentrated in the upper third of the thyroid gland (see Figure 66.2), reflecting the normal distribution of parafollicular thyroid C-cells.

Type
Chapter
Information
Molecular Oncology
Causes of Cancer and Targets for Treatment
 , pp. 720 - 730
Publisher: Cambridge University Press
Print publication year: 2013

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