摘要
目的探讨多发性内分泌腺瘤2B型（MEN2B）患者的临床特点及其遗传学特征。方法分析1例临床诊治为MEN2B患者的临床资料，并进行家系调查，收集患者及其家系成员外周血DNA标本进行RET原癌基因突变检测，并结合文献复习讨论。结果患者男34岁，于32岁时以颈部肿块就诊，体检发现双侧甲状腺占位伴双唇肥厚、舌黏膜下多发性神经瘤和类马凡征体形。I血清基础降钙素〉2000ng／L；彩超检查示双侧甲状腺多发结节伴钙化，双颈部淋巴结肿大。患者先后分2次行全甲状腺切除＋双侧颈部淋巴结清扫术，术后病理诊断：双侧多发性甲状腺髓样癌（MTC）伴淋巴结转移（T4aNIbM0-IVA）。术后5个月，患者因再发左颈部局部肿块伴降钙素升高（1090ng／L），再次行左颈部淋巴结清扫术。首次术后至今随访17个月，血清降钙素示1541ng／L；彩超检查颈部未发现异常肿块；均未发现嗜铬细胞瘤、原发性甲状旁腺功能亢进。基因检测仅见患者存在RET原癌基冈P．M918T突变（C．2753T〉C，ATG→AcG）；家系其他成员未见类似病症和其他内分泌肿瘤疾病，也无RET原癌基因突变。复习国内文献报告的包括本例在内的经基因检测诊断的10例MEN2B病例，其中9例为自身新发（Denovo）的RET基因P．M918T突变或其父母一方为P．M918T突变镶嵌体，与围外文献报告一致。结论DenovoRET原癌基因P．M918T突变也是国内MEN2B发病的一种常见形式。提高对MEN2B的认识，早期、规范诊治有利于提高MEN2B—MTC的远期疗效。
Objective To explore the clinical features and genetic characteristics of the multiple endocrine ncoplasia 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 gennline 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, nmltiple mucosal neuroma and Maffanoid body habitus. Seialm 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 muhicentric thyroid medullary carcinoma （ MTC ） with lymph node metastases （T4aNlbM0, ⅣA）. Five months later, the patient presented a left cervical mass and high ealcitonin 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 l＇lypocalcemia. Family screening was performed, and other family members were all normal. RET screening showed heterozygous missense mutation of AT（; to ACG （c. 2753T 〉 C） at codon 918 in exon 16 in the probmM, 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 simi
出处
《中华全科医师杂志》
2015年第3期194-199,共6页
Chinese Journal of General Practitioners
基金
国家自然科学基金项目（81472861）
南京军区医学科技创新课题基金重点项目（092038,102036）
关键词
多发性内分泌瘤病2b型
原癌基因
文献综述
Multiple endocrine neoplasia type 2b
Proto-oncogenes
Review literature
