中国一位 RET M918T 种系突变的多发性内分泌腺瘤病 2B 相关混合性髓样和滤泡状甲状腺癌患者

Multiple Endocrine Neoplasia Type 2B Associated Mixed Medullary and Follicular Thyroid Carcinoma in A Chinese Patient with RET M918T Germline Mutation.

机构信息

Department of Oncologic and Urologic Surgery, The 903rd PLA Hospital, Wenzhou Medical University, 40 Jichang Road, Hangzhou 310004, Zhejiang Province, China.

Department of Urology, The Affiliated Wenling Hospital of Wenzhou Medical University, Chuan'an Nan Road, Chengxi Subdistrict, Wenling 317500, Zhejiang Province, China.

出版信息

Endocr Metab Immune Disord Drug Targets. 2021;21(3):554-560. doi: 10.2174/1871530320666200713092633.

DOI:10.2174/1871530320666200713092633

PMID:32660411

Abstract

BACKGROUND

Mixed medullary and follicular thyroid carcinoma (MMFC) displays heterogeneous morphological components and immunophenotypical features intermingled within the same lesion, which is rare and most described in the sporadic form. We report herein a Chinese patient with multiple endocrine neoplasia type 2B (MEN2B) harboring germline RET M918T and associated MMFC.

METHODS

A case of a 39-year-old male patient with MEN2B presented palpable neck masses in both thyroid lobes (maximum sizes: left, 3.9 cm; right, 5.4 cm) and a definitive phenotype. Serum levels of calcitonin (Ctn; >2000pg/mL), carcinoembryonic antigen (CEA; 719.27ng/mL), and thyroglobulin (Tg; 98.54ng/mL) were high. Fine-needle aspiration cytology showed features positive for malignancy, suggesting the possibility of medullary thyroid carcinoma (MTC). Total thyroidectomy, along with extending bilateral neck lymph nodes dissection, and subsequently, genetics family screening were performed.

RESULTS

The histopathological examination yielded a diagnosis of MMFC that showed immunohistochemical characteristic patterns of the component of MTC positive for Ctn and CEA, chromogranin A, and the follicular carcinoma components were positive for Tg. Lymph node metastasis was observed showing medullary tumoral cells positive for Ctn and follicular-like structures lacking tumor cells positive for Tg staining (T4bN1bM0). Genetics screening confirmed RET M918T (c.2753T>C) mutation manifested in the patient but was not detected in other family members. Follow up showed that the serum Ctn, CEA and Tg levels respectively dropped to 54.38pg/ml, 4.16ng/mL and 0.04ng/mL 16 months after the surgery.

CONCLUSION

Particular and diverse patterns of MMFC should be recognized with immunostaining features. MMFC occurring in a patient with MEN2B harboring RET M918T may be unique biological behavior and the treatment is mostly radical surgery.

摘要

背景

混合性髓样和滤泡状甲状腺癌（MMFC）在同一病变中呈现出异质性的形态学成分和免疫表型特征，这种情况较为罕见，且多发生于散发性病例。本文报告了一例中国患者，其患有多发性内分泌肿瘤 2B 型（MEN2B），携带种系 RET M918T，并伴有 MMFC。

方法

一位 39 岁男性患者，患有 MEN2B，双侧甲状腺叶均触及可触及的肿块（最大尺寸：左侧 3.9cm；右侧 5.4cm），并具有明确的表型。降钙素（Ctn；>2000pg/ml）、癌胚抗原（CEA；719.27ng/ml）和甲状腺球蛋白（Tg；98.54ng/ml）的血清水平升高。细针穿刺细胞学检查显示恶性特征阳性，提示甲状腺髓样癌（MTC）的可能性。进行了全甲状腺切除术，同时进行了双侧颈部淋巴结清扫术，随后进行了遗传家族筛查。

结果

组织病理学检查诊断为 MMFC，免疫组化特征显示 MTC 成分阳性，对 Ctn 和 CEA、嗜铬粒蛋白 A 呈阳性，滤泡癌成分对 Tg 呈阳性。观察到淋巴结转移，显示 Ctn 阳性的髓样肿瘤细胞和缺乏 Tg 染色（T4bN1bM0）的肿瘤细胞阳性的滤泡样结构。遗传筛查证实患者存在 RET M918T（c.2753T>C）突变，但未在其他家族成员中检测到。随访显示，手术后 16 个月，血清 Ctn、CEA 和 Tg 水平分别降至 54.38pg/ml、4.16ng/ml 和 0.04ng/ml。