Multiple Endocrine Neoplasia, Type IIB

Alternative Names

  • MEN2B
  • MEN IIB
  • Neuromata, Mucosal, with Endocrine Tumors
  • Wagenmann-Froboese Syndrome
  • Multiple Endocrine Neoplasia, Type III
  • MEN3
  • Mucosal Neuroma Syndrome
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WHO-ICD-10 version:2010

Neoplasms

Malignant neoplasms

OMIM Number

162300

Mode of Inheritance

Autosomal dominant

Gene Map Locus

10q11.21

Description

Medullary thyroid cancers (MTC) are rare tumors of neuroendocrine origin that arise from parafollicular C cells which secrete calcitonin and other peptides and hormones.  Sporadic MTC accounts for 75% of cases, and inherited MTC constitutes the rest.  Inherited MTC occurs in association with multiple endocrine neoplasia (MEN) type 2A and 2B syndromes, but non-MEN familial MTC also occurs.

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant syndrome, characterized by the occurrence of medullary thyroid carcinoma (MTC), pheochromocytoma, in one variant, primary hyperparathyroidism (PHPT).  MEN2 can be classified into three forms: MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC).  MEN 2B syndrome accounts for 5% of all MEN2 cases.

MTC typically occurs in childhood in MEN 2B.  The diagnosis of MTC is based on history, physical examination, calcitonin and CEA levels, imaging, and fine needle aspiration biopsy.  MEN 2B is diagnosed clinically by the presence of additional features including mucosal neuromas of the lips and tongue, distinctive facies with enlarged lips, ganglioneuromatosis of the gastrointestinal tract, and an asthenic ‘marfanoid’ body habitus.  Every patient with MTC should undergo DNA analysis for the presence of the RET mutation.

The best treatment for MEN 2B is surgery.  A prophylactic thyroidectomy is recommended for all patients with an identified RET mutation at the first year of life.  Also, lifelong thyroid hormone supplementation is needed.  The prognosis of MTC depends on the stage at which it is diagnosed and the quality of initial surgical treatment.

Mutations in the RET proto-oncogene, at the chromosomal region 10q11.2, account for the clinical subtypes of MEN2.  The RET protein is a receptor tyrosine kinase.  About 98% of individuals with MEN 2B are identifiable through RET testing.  FMTC, including families with fewer than four cases, is more accurately considered a matter of penetrance.

Epidemiology in the Arab World

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Other Reports

Saudi Arabia

Abu-Amero et al. (2006) sequenced the entire coding region of mitochondrial DNA for 26 MTC patients and 119 normal population controls.  Of the MTC patients, 13 were sporadic, nine had MEN 2A, one had MEN 2B, and three had FMTC.  In 20 MTC samples, 41 nonsynonymous mutations were detected; nine were from sporadic MTC and 11 were from familial MTC and MEN2.  Also, 15 synonymous mtDNA sequence variants were found in MTC samples, seven of them were novel.  Twenty seven mutations were transversions; 22 nonsynonymous and six synonymous.  These transversion variants were only detected in FMTC/MEN2 and transition variants were mainly in sporadic MTC.  None of these mutations were present in the normal controls, suggesting that mtDNA mutations may be involved in MTC tumorigensis and progression.

Tunisia

Charfi et al. (2008) reported the case of a 27-year-old woman with marfanoid habitus and numerous mucosal neuromas of the oral cavity and the eyelids.  Clinical investigations revealed a left adrenal medullary tumor and bilateral thyroid nodules. Histologic examination confirmed the presence of typical pheochromocytoma with large areas of ganglioneuroma and multifocal medullary carcinoma with cervical lymph nodes metastases.  Charfi et al. (2008) considered their case to be the first comorbid occurrence of pheochromocytoma with multiple endocrine neoplasia 2B.

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