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目的探讨甲状腺胸腺样分化癌(carcinoma showing thymus-like differentiation,CASTLE)的组织学来源、诊断、鉴别诊断及治疗。方法对5例甲状腺CASTLE实施手术根治性切除及术后放射治疗,对手术切除的肿瘤组织进行免疫组化S-P法染色,检测肿瘤细胞CD5、CD117、细胞角蛋白-5/6(CK5/6)、P63蛋白、甲状腺转录因子-1(TTF-1)、癌胚抗原(CEA)、降钙素(CT)、抗原Ki-67、嗜铬粒蛋白A(Cg A)、甲状腺球蛋白(Tg)、氧化物酶增殖物激活受体γ(PPARγ)、钠碘转运体(NIS)以及促甲状腺激素受体(TSHR)的表达,并采用DNA测序法检测鼠类肉瘤滤过性毒菌致癌同源体B1(BRAF)基因和端粒酶逆转录酶(TERT)启动子突变情况。同时与同期收治的甲状腺低分化癌8例及甲状腺未分化癌6例患者的资料进行综合对比分析。结果甲状腺CASTLE肿瘤细胞的CD5、CD117、CK5/6以及P63均呈阳性表达,TTF-1、CT、Cg A、Tg、PPAR-γ、NIS以及TSHR均呈阴性表达;甲状腺低分化癌及未分化癌中CD5和CD117均呈阴性表达,CK5/6、P63、TTF-1、Cg A、Tg、NIS及TSHR显示部分病例呈阳性表达。甲状腺CASTLE中未发现BRAFV600E基因及TERT启动子突变,甲状腺低分化癌和未分化癌中均未发现BRAFV600E突变。甲状腺低分化癌存在TERT启动子突变4例(4/8),其中C228T位点突变3例,C250T位点突变1例;甲状腺未分化癌存在TERT突变2例(2/6),其中C228T位点突变1例,C250T位点突变1例。全部5例甲状腺CASTLE患者术后随访3~47个月(平均25.6个月)无复发及转移。结论甲状腺CASTLE的组织学来源可能与甲状腺无关。联合检测CD5、CD117、P63、TTF-1、Tg、NIS及TSHR,对甲状腺CASTLE的诊断及鉴别诊断具有重要的临床价值,检测BRAFV600E及TERT启动子突变,对甲状腺CASTLE诊断与鉴别诊断的意义尚需进一步研究。
Objective To investigate the histological origin, diagnosis, differential diagnosis and treatment of thyroid carcinoma with thymus-like differentiation (CASTLE). Methods Five cases of thyroid CASTLE were treated by radical resection and postoperative radiotherapy. The tumor tissues were excised by immunohistochemical SP method to detect the expression of CD5, CD117, CK5 / 6, , P63 protein, thyroid transcription factor-1 (TTF-1), CEA, CT, Ki-67, CgA, (PPARγ), sodium iodide transporter (NIS) and thyroid-stimulating hormone receptor (TSHR) were detected by enzyme linked immunosorbent assay (ELISA) and DNA sequencing was used to detect the oncogenic homology of murine sarcoid viral Body B1 (BRAF) gene and telomerase reverse transcriptase (TERT) promoter mutations. At the same time, the data of 8 cases with poorly differentiated thyroid carcinoma and 6 cases of undifferentiated thyroid carcinoma were analyzed and compared comprehensively. Results The expressions of CD5, CD117, CK5 / 6 and P63 in thyroid CASTLE tumor cells were all negative, and were negative in TTF-1, CT, Cg A, Tg, PPAR- The expression of CD5 and CD117 in carcinoma was negative, while CK5 / 6, P63, TTF-1, Cg A, Tg, NIS and TSHR showed positive expression in some cases. No mutation of BRAFV600E gene and TERT promoter was found in thyroid CASTLE. No BRAFV600E mutation was found in poorly differentiated thyroid carcinoma and undifferentiated carcinoma. There were 4 cases (4/8) of TERT promoter mutations in poorly differentiated thyroid cancer, including 3 cases of C228T mutation and 1 case of C250T mutation. There were 2 cases (2/6) of TERT mutations in undifferentiated thyroid carcinoma, in which C228T 1 case of point mutation and 1 case of C250T mutation. All 5 cases of thyroid CASTLE patients were followed up for 3 to 47 months (mean 25.6 months) without recurrence and metastasis. Conclusions The histological origin of thyroid CASTLE may not be related to thyroid. The combined detection of CD5, CD117, P63, TTF-1, Tg, NIS and TSHR has important clinical value in the diagnosis and differential diagnosis of thyroid CASTLE. The detection of mutations in BRAFV600E and TERT promoters is of great significance in the diagnosis and differential diagnosis of thyroid CASTLE Need further study