Multiple endocrine neoplasia type 2B：a case report and literature review Multiple endocrine neoplasia type 2B：a case report and literature review

Objective To explore the clinical features and genetic characteristics of the multiple endocrine neoplasia type 2B (MEN 2B). Methods Comprehensive medical history was obtained from one patient with MEN 2B and his other 8 family members in a 3-generation southeast Chinese family. Systematic family screening including biochemical testing, imaging examinations and germline RET proto-oncogene screening. Results A 34-year old male patient was first admitted to our hospital due to neck masses for two years. The patient had two palpable masses in thyroids of both sides and also had lip hypertrophy, multiple mucosal neuroma and Marfanoid body habitus. Serum calcitonin level was over 2 000 ng/L at admission. Doppler ultrasound scanning indicated multi-centric hypoechoic nodules with calcifications in both thyroid lobes with bilateral cervical lymph nodes enlargement. The patient underwent total thyroidectomy plus lateral cervical lymph node dissection. Histopathology revealed multicentric thyroid medullary carcinoma (MTC) with lymph node metastases (T4aN1bM0, ⅣA). Five months later, the patient presented a left cervical mass and high calcitonin level (1 090 ng/L), and received second left cervical lymph node dissection. The patient had been follow-up for 17 months after initial operation, the calcitonin level was still elevated (1 541 ng/L); but the result of Doppler ultrasound scanning was normal, and there was no evidence showing pheochromocytoma, primary hypoparathyroidism or hypocalcemia. Family screening was performed, and other family members were all normal. RET screening showed heterozygous missense mutation of ATG to ACG (c.2753T>C) at codon 918 in exon 16 in the proband, but there was no corresponding mutation in other family members. Domestic literature was reviewed, the results showed that 9 of 10 reported MEN2B cases based on RET screening (including this case) had de novo p. M918T mutation or the mutation existed in a parental germ cell mosaicism, which was similar as reported in English literature that the de novo occurrence rate of MEN2B was more than 90%. Conclusions De novo RET proto-oncogene mutation that p. M918T, is also a common mutation of MEN2B in China. The early diagnosis and normalize surgery facilitate to improve the prognosis of this disease. Key words: Multiple endocrine neoplasia type 2b; Proto-oncogenes; Review literature