-Case Reports-

The Reality of Multiple Endocrine Neoplasia Type 2B Diagnosis: Awareness of Unique Physical Appearance Is Important

Ryuta Nagaoka, Iwao Sugitani, Marie Sanada, Tomoo Jikuzono, Ritsuko Okamura, Takehito Igarashi, Haruki Akasu and Kazuo Shimizu

Department of Endocrine Surgery, Nippon Medical School, Tokyo, Japan

Background: Multiple endocrine neoplasia type 2B (MEN2B) is an extremely rare syndrome mainly caused by RET918 germline mutations. MEN2B typically causes medullary thyroid carcinoma (MTC), pheochromocytoma, and unique physical characteristics including mucosal neuroma, distinctive facial appearance, and Marfanoid habitus. Most patients have abdominal symptoms such as bloating, intermittent constipation, and diarrhea. MTC is the most important determinant of mortality in patients with MEN2B. Establishing the diagnosis of MEN2B at a curative stage of MTC is crucial.
Case Presentation: We have encountered four patients with MEN2B. Two were hereditary cases from the same family, and two were considered de novo cases with phenotypically normal parents. Mean age at diagnosis was 25.5 years (range, 13-39 years). Although all patients had shown mucosal neuroma on the lips and tongue, in addition to gastrointestinal symptoms from infancy, diagnoses were made from symptomatic MTC even for the hereditary patients (our index case was a 14-year-old girl, whose mother was subsequently diagnosed with advanced MTC). Genetic tests for RET mutations revealed the M918T mutation in all patients. Two patients developed pheochromocytoma, two died from distant metastases of MTC, and two received treatment for multiple metastases of MTC (one with vandetanib).
Conclusions: In our patients with MEN2B, prophylactic or early thyroidectomy could not be performed. The characteristic phenotype associated with MEN2B is almost always seen prior to detection of MTC or pheochromocytoma. Knowledge about the non-endocrine manifestations of MEN2B needs to be shared among pediatricians and gastroenterologists.

J Nippon Med Sch 2018; 85: 178-182

Keywords
multiple endocrine neoplasia, medullary thyroid carcinoma, mucosal neuroma, prophylactic thyroidectomy, megacolon

Correspondence to
Ryuta Nagaoka, Department of Endocrine Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
ryuta-n@nms.ac.jp

Received, September 23, 2017
Accepted, December 19, 2017