CAJ | 학술논문

目的探讨家族性甲状腺髓样癌(FMTC)的临床诊治特点及RET原癌基因检测的意义.方法对1个FMTC家系进行系统的家系调查,提取外周血进行RET原癌基因和降钙素检测,并绘制家系图.结果基因检测该家系为RET原癌基因第10外显子第618位点TGC→TAC杂合错义突变,即p.C618Y突变,与临床完全符合.7例MTC中,男1例,女6例；首次诊断平均年龄49.6(24 ～78)岁；临床均表现为颈部肿块；肿瘤最大直径1.4～4.4 cm,平均2.6 cm;7例均伴颈部淋巴结转移.除1例(78岁)拒绝手术外,1例行右侧甲状腺全切除术+左侧甲状腺次全切除术,1例行右侧甲状腺全切除术(既往左侧甲状腺因“良性肿瘤”已全切除),其余4例行双侧甲状腺全切除术；6例均+至少双侧颈部Ⅵ区淋巴结清扫或+单/双侧颈部改良淋巴结清扫术.接受手术的6例患者首次术后降钙素仍升高:其中1例首次术后64个月因MTC转移死亡；3例在首次术后6个月行再次手术,2例降钙素降至正常,1例降钙素仍升高；另外2例分别在首次术后214、60个月,影像学检查示双侧甲状腺叶残留、局部淋巴结肿大并降钙素升高.2例无症状中的1例因术前血清降钙素高,行双侧甲状腺全切除术,术后病理诊断为双侧甲状腺C细胞增生；另1例已随访10个月,未发现影像学和降钙素异常.结论基于家系调查并整合RET基因和降钙素检测,有利于早期诊断以改善预后；对无症状的RET基因突变携带者,应根据其降钙素水平,实施个体化的预防性甲状腺全切除或严密随访观察.
목적 탐토가족성갑상선수양암(FMTC)적림상진치특점급RET원암기인검측적의의.방법 대1개FMTC가계진행계통적가계조사,제취외주혈진행RET원암기인화강개소검측,병회제가계도.결과기인검측해가계위RET원암기인제10외현자제618위점TGC→TAC잡합착의돌변,즉p.C618Y돌변,여림상완전부합.7례MTC중,남1례,녀6례；수차진단평균년령49.6(24 ～78)세；림상균표현위경부종괴；종류최대직경1.4～4.4 cm,평균2.6 cm;7례균반경부림파결전이.제1례(78세)거절수술외,1례행우측갑상선전절제술+좌측갑상선차전절제술,1례행우측갑상선전절제술(기왕좌측갑상선인“량성종류”이전절제),기여4례행쌍측갑상선전절제술；6례균+지소쌍측경부Ⅵ구림파결청소혹+단/쌍측경부개량림파결청소술.접수수술적6례환자수차술후강개소잉승고:기중1례수차술후64개월인MTC전이사망；3례재수차술후6개월행재차수술,2례강개소강지정상,1례강개소잉승고；령외2례분별재수차술후214、60개월,영상학검사시쌍측갑상선협잔류、국부림파결종대병강개소승고.2례무증상중적1례인술전혈청강개소고,행쌍측갑상선전절제술,술후병리진단위쌍측갑상선C세포증생；령1례이수방10개월,미발현영상학화강개소이상.결론 기우가계조사병정합RET기인화강개소검측,유리우조기진단이개선예후；대무증상적RET기인돌변휴대자,응근거기강개소수평,실시개체화적예방성갑상선전절제혹엄밀수방관찰.
Objective To explore the clinical characteristics,therapeutic and clinical significance for RET proto-oncogene screening in a pedigree with familial medullary thyriod carcinoma.Methods 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.Results 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 thyriod 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.Conclusions 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.