Zhao Jian-qiang, Guo Liang, Qi Xiao-ping, Chen Zhen-guang, Wang Ke-jing, Lou Jian-lin, Yu Xiu-hua, Cheng Jun, Jin Hang-yang, Li Xiao-long, Ying Rong-biao, Zhang Xian-ning
Department of Head & Neck Surgery, Zhejiang Cancer Hospital, Hangzhou, China.
Zhonghua Yi Xue Za Zhi. 2013 Feb 5;93(6):440-4.
To explore the clinical characteristics, therapeutic and clinical significance for RET proto-oncogene screening in a pedigree with familial medullary thyroid carcinoma.
Comprehensive medical history was obtained from 19 members in a 4-generate southern Chinese family. Systemic clinical investigations including biochemical testing, imaging examinations and germline RET screening.
RET screening showed heterozygous missense mutations of TGC to TAC at codon 618 on exon 10 in 8 cases (p.C618Y) completely consistent with the clinical manifestations. The clinical data of 7 patients with medullary thyroid carcinoma (MTC) and 2 carriers of asymptomatic RET mutation from were analyzed. Single/bilateral multi-centric MTC with lymph node metastases was confirmed in 6 cases by histopathology and 1 case by clinical examination. There were 1 male and 6 females with an initial mean diagnostic age was 49.6 years (range: 24 - 78). All had palpable neck masses. And the mean maximum diameter of MTC was 2.6 cm (range 1.4 - 4.4). Seven patients underwent thyroidectomy except a 78-year-old female patient: right total and left subtotal thyroidectomy (n = 1), right total thyroidectomy (previous left total thyroidectomy for benign mass) (n = 1) and total thyroidectomy (n = 4) were performed. All procedures were accompanied by at least bilateral level VI lymph node dissection and/or with modified single/bilateral neck dissection. After the first operation, 6 patients still presented a high value of calcitonin: 1 patient died of metastasis 64 months postoperatively; 3 patients underwent reoperation at 6 months after initial operation, the calcitonin levels dropped to normal in 2/3 cases and stayed higher in 1 case; another two cases presented bilateral thyroid gland residua, local lymph node enlargement on imaging examination and elevated levels of calcitonin at 214 and 60 months postoperation respectively. However, 1/2 asymptomatic with elevated pre-operative calcitonin subjects underwent total thyroidectomy and histopathological examination showed bilateral C cell hyperplasia. The other carriers, without surgery, with normal neck images, close monitoring and a 10-month follow-up, still presented undetectable calcitonin.
Based on family survey, integrated RET screening and serum levels of calcitonin facilitate an early diagnosis and normalize surgery to improve the prognosis. For asymptomatic RET mutation carriers, their levels of calcitonin shall guide the individualized regimen of prophylactic thyroidectomy or strict monitoring and follow-ups.
探讨家族性甲状腺髓样癌家系中RET原癌基因筛查的临床特征、治疗方法及临床意义。
收集一个四代中国南方家族中19名成员的完整病史。进行包括生化检测、影像学检查和种系RET筛查在内的系统临床调查。
RET筛查显示，8例患者第10外显子618密码子处存在TGC突变为TAC的杂合错义突变（p.C618Y），与临床表现完全一致。分析了7例甲状腺髓样癌（MTC）患者和2例无症状RET突变携带者的临床资料。6例经组织病理学确诊为单/双侧多中心MTC伴淋巴结转移，1例经临床检查确诊。患者共7例，男性1例，女性6例，初始诊断平均年龄为49.6岁（范围：24 - 78岁）。所有患者均可触及颈部肿块。MTC平均最大直径为2.6 cm（范围1.4 - 4.4 cm）。除1例78岁女性患者外，7例患者均接受了甲状腺切除术：行右全甲状腺切除及左次全甲状腺切除术（n = 1）、右全甲状腺切除术（既往因良性肿块行左全甲状腺切除术）（n = 1）和全甲状腺切除术（n = 4）。所有手术均至少伴有双侧Ⅵ区淋巴结清扫和/或改良单侧/双侧颈部清扫。首次手术后，6例患者降钙素水平仍较高：1例患者术后64个月死于转移；3例患者在初次手术后6个月再次手术，2/3病例降钙素水平降至正常，1例仍较高；另外2例患者术后214个月和60个月分别出现双侧甲状腺残留、影像学检查显示局部淋巴结肿大及降钙素水平升高。然而，1/2术前降钙素升高的无症状受试者接受了全甲状腺切除术，组织病理学检查显示双侧C细胞增生。其他未手术的携带者颈部影像学检查正常，密切监测并随访10个月，降钙素仍未检出。
基于家系调查，综合RET筛查和降钙素血清水平有助于早期诊断并规范手术，从而改善预后。对于无症状RET突变携带者，其降钙素水平应指导预防性甲状腺切除术的个体化方案或严格的监测及随访。
