中国癌症杂志 ›› 2021, Vol. 31 ›› Issue (11): 1096-1103.doi: 10.19401/j.cnki.1007-3639.2021.11.008

• 论著 • 上一篇    下一篇


刘 伟 1 ,王晓江 2 ,张 静 1 ,朱伟峰 1 ,彭凤英 1 ,王健超 1 ,肖伟进 1 ,胡 丹 1   

  1. 1. 福建医科大学附属肿瘤医院,福建省肿瘤医院病理科,福建 福州 350014 ;
    2. 福建医科大学附属肿瘤医院,福建省肿瘤医院分子病理研究室,福建 福州 350014
  • 出版日期:2021-11-30 发布日期:2021-12-03
  • 通信作者: 刘 伟 E-mail:
  • 基金资助:

Clinicopathological characteristics and prognostic analysis of medullary thyroid carcinoma in children and adolescents

LIU Wei 1 , WANG Xiaojiang 2 , ZHANG Jing 1 , ZHU Weifeng 1 , PENG Fengying 1 , WANG Jianchao 1 , XIAO Weijin 1 , HU Dan   

  1. 1. Department of Pathology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou 350014, Fujian Province, China; 2. Department of Molecular Pathology Laboratory, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou 350014, Fujian Province, China
  • Published:2021-11-30 Online:2021-12-03
  • Contact: LIU Wei E-mail:

摘要: 背景与目的:儿童青少年甲状腺髓样癌(medullary thyroid carcinoma,MTC)少见,国内报道甚少。探讨儿童青少年MTC临床病理学特征、诊断及预后因素,以提高对其认识。方法:收集2007年1月—2021年5月在福建省肿瘤医院确诊的儿童青少年MTC共10例,对其临床特征、形态学、免疫表型、基因突变及预后进行分析。结果:散发病例6例,有家族史者4例,年龄10~20岁,平均17岁,均有血清降钙素(calcitonin,CT)和癌胚抗原(carcinoembryonic antigen,CEA)升高。9例为双侧甲状腺病变,肿瘤直径0.2~3.5 cm,中位直径1.5 cm。镜下肿瘤呈片状、巢状或梁状分布,侵袭性生长模式,伴有卫星结节病灶,部分病例可见乳头及滤泡结构,肿瘤细胞以圆形、卵圆形细胞为主,混杂有梭形/纺锤状细胞及浆样细胞,可见少量瘤巨细胞及核内假包涵体。间质不同程度纤维化/淀粉样沉积,偶见钙化和砂粒体。肿瘤细胞呈突触素(synaptophysin,Syn)、嗜铬素A(chromogranin A,CgA)、分化簇(cluster of differentiation,CD)56、CT、CEA、甲状腺转录因子-1(thyroid transcription factor-1,TTF-1)及刚果红染色阳性表达,甲状腺球蛋白(thyroglobulin,Tg)阴性。RET基因M918T突变为MTC最常见的基因改变。8例患者术后血清CT和CEA降至正常水平,随访时间27~98个月,平均为62个月,无复发、转移(生化治愈);1例患者生化未愈,且于术后第75和108个月行两次颈部转移淋巴结清扫。另外1例患者术后6个月因肿瘤死亡。该死亡病例的肿瘤细胞呈现高级别核(细胞多形、核仁明显,核分裂象>3个/10HPF),Ki-67增殖指数较高(20%),并可见大量脉管内癌栓及局灶性坏死。结论:儿童青少年MTC绝大多数为双侧甲状腺病变,双侧甲状腺全切是清除潜在隐性病灶和防止复发的最佳治疗方式。血清CT和CEA升高是其重要临床特征。高级别核、高Ki-67增殖指数、脉管内癌栓及坏死,为其重要不良预后指标。

关键词: 甲状腺髓样癌, 儿童青少年, 免疫组织化学, 降钙素, 预后

Abstract: Background and purpose: Medullary thyroid carcinoma (MTC) is a rare disease in children and adolescents, which is seldom reported in China. The purpose of this study was to explore its clinicopathological features, diagnosis and prognostic factors, and to improve the understanding of MTC. Methods: Data of 10 cases of MTC in children and adolescents were collected from Fujian Cancer Hospital from January 2007 to May 2021, and clinical features, morphology, immunophenotype, gene mutation, and outcome were analyzed. Results: There were 6 sporadic cases, and 4 cases with family history, aged 10-20 years with a mean of 17 years. All showed elevated serum calcitonin (CT) and carcinoembryonic antigen (CEA). Bilateral thyroid lesions were found in 9 patients. The tumor diameter was 0.2-3.5 cm, with a median diameter of 1.5 cm. Microscopically, the tumor presented a patchy, nest- shaped, or beamlike distribution, with invasive growth pattern and surrounding satellite nodules. Papillary and follicular structures were also observed in some cases. The cells were round and oval, mixed with some spindle cells and plasmacytoid cells. A few giant cells and intranuclear pseudo-inclusions were also found. Different degrees of fibrosis/amyloid deposition were observed in the tumor stroma, with occasional calcification and sand bodies. Synaptophysin (Syn), chromogranin A (CgA), cluster of differentiation (CD56), CT, CEA, thyroid transcription factor-1 (TTF-1) and Congo red staining were positive for tumor cells, while thyroglobulin (Tg) was negative. The M918T mutation in RET gene was the most common genetic change in MTC. Among all of the 10 cases, the serum CT and CEA of 8 cases were reduced to normal levels after operation, without recurrence/metastasis (biochemical cure) during the follow-up period (27-98 months, with an average of 62 months). One patient was non-biochemical cure, and cervical lymph node dissection was performed twice at 75 and 108 months postoperatively. Another patient died of tumor 6 months after surgery, which presented high-grade nuclei (polymorphic, prominent nucleoli, mitotic  > 3/10HPF), high proliferation index (Ki- 67 was 20%), numerous intravascular tumor thrombi and focal coagulant necrosis. Conclusion: The majority of MTC in children and adolescents have bilateral thyroid involvement. Bilateral thyroidectomy is the best therapeutic theatment for removing potential hidden lesions and prevent recurrence. The elevation of serum CT and CEA is an important clinical feature. High nuclear grade, high Ki-67 proliferation index, intravascular tumor thrombus and necrosis are important prognostic indicators.

Key words: Medullary thyroid carcinoma, Children and adolescents, Immunohistochemistry, Calcitonin, Prognosis