30例胸腺样分化甲状腺癌的回顾性分析及其机制研究

背景与目的：胸腺样分化甲状腺癌（carcinoma showing thymus-like differentiation，CASTLE）是非常罕见的甲状腺癌病理学类型，目前报道较少，相关诊疗经验及对该疾病的认知仍不足。方法：回顾并分析2007年9月1日—2021年9月1日复旦大学附属肿瘤医院收治的30例CASTLE患者的临床、病理学及预后资料。全基因组测序分析3例甲状腺癌及癌旁组织，转染构建MSH2过表达细胞株，并进行蛋白质印迹法（Western blot）、细胞活性及迁移实验等检测突变基因对细胞生物学行为的影响。结果：30例患者中，66.7%（20/30）的患者出现不同程度的外侵。平均随访60.6个月后，2例发生远处转移，无局部复发、进展或死亡病例。CD5、CD117呈阳性能对其进行有效的鉴别诊断。同时通过全基因检测和全基因组测序识别到MSH2、FBXW7及NOTCH1存在外显子突变，其中MSH2突变率最高，且可能参与提升甲状腺癌细胞的增殖及转移能力。结论：CASTLE恶性程度较低，进展缓慢，预后较好。根治性手术是CASTLE的首选治疗方式，术后放疗可能对减少局部复发有一定作用。MSH2基因可能参与CASTLE的发生、发展过程。

Review and mechanism research of 30 cases of carcinoma showing thymus-like differentiation

Background and purpose:?Carcinoma showing thymus-like differentiation (CASTLE) is a rare disease. There were few reports so far. The diagnosis and treatment experience and disease cognition are still insufficient. Methods: The clinical, pathological and prognostic data of 30 patients with CASTLE who received operation at Fudan University Shanghai Cancer Center from September 1, 2007 to September 1, 2021 were analyzed retrospectively. Three cases of thyroid carcinoma and adjacent tissues were analyzed by whole genome sequencing, and MSH2 gene overexpressed cells were transfected and constructed. The effects of mutant genes on cell biological behavior were detected by Western blot, cell activity and migration experiments. Results: 66.7% (20/30) of the 30 patients had different degrees of invasion. After an average follow-up of 60.6 months, distant metastasis occurred in 2 cases, and there was no local recurrence, progression or death. CD5 and CD117 could play important role in the diagnosis of CASTLE. Exon mutations in MSH2, FBXW7 and NOTCH1 were identified by whole gene detection and sequencing. The mutation rate of MSH2 was the highest, and may be involved in promoting the proliferation and metastasis of thyroid cells. Conclusion: CASTLE usually shows low malignancy, slow progression and good prognosis. Radical surgery is the preferred treatment for CASTLE. Postoperative radiotherapy may play a role in reducing local recurrence. MSH2 gene may be involved in the occurrence and development of CASTLE.