肺原发玻璃样变透明细胞癌临床病理特点及活检诊断中的陷阱

Clinicopathological features of primary pulmonary hyalinizing clear cell carcinoma and its diagnostic pitfalls in biopsy specimens

目的:探讨肺原发玻璃样变透明细胞癌(hyalinizing clear cell carcinoma,HCCC)的诊断及鉴别诊断,特别是活检诊断中的陷阱。方法:收集上海市胸科医院病理科2019年8月至2023年12月肺原发HCCC 5例,总结其临床病理特点、免疫组织化学、EWSR1基因易位及融合,复习相关文献并总结诊断及鉴别诊断要点。结果:5例HCCC男性2例,女性3例;年龄36~74岁,肿物位于气管或支气管腔内,呈息肉样生长。肿瘤最大径范围1.3~5.0 cm。镜下观察:肿瘤细胞为中等大小圆形,胞质透亮或嗜酸性,排列呈条带状、巢团状及不规则片状,瘤细胞异型性小,核分裂象罕见,间质为相互连接、宽窄不均的玻璃样变或硬化性纤维间质。免疫表型:所有病例均表达常见鳞状上皮标志物广谱细胞角蛋白、细胞角蛋白(CK)5/6、p40、p63,也表达CK7,不表达常见的肌上皮标志物S-100蛋白、平滑肌肌动蛋白、Calponin,以及肺泡上皮标志物甲状腺转录因子1、Napsin A,Ki-67阳性指数均小于10%。分子特征:5例荧光原位杂交检测均有EWSR1基因易位,3例二代测序检测显示EWSR1::ATF1基因融合。结论:肺原发HCCC的小活检标本因表达鳞状上皮标志物容易误诊,具有挑战性。正确认识肺原发HCCC的形态学特征,结合免疫组织化学和分子检测有助于正确诊断。

Objective To investigate the clinicopathological features and differential diagnosis of primary pulmonary hyalinizing clear cell carcinoma(HCCC),as well as its diagnostic pitfalls in assessing biopsy specimens.Methods Five cases of primary pulmonary HCCC diagnosed in the Department of Pathology,Shanghai Chest Hospital,Shanghai,China from August 2019 to December 2023 were collected.The clinicopathological characteristics,immunohistochemistry,and the EwsR1 gene related translocation and fusion were summarized,and relevant literature was reviewed.Results Among the five cases of HcCC,two were males and three were females,with ages ranging 36-74 years.The tumors were located in the lumen of the bronchus or trachea and showed an exophytic polypoid growth pattern.The maximum diameter of the tumors ranged from 1.3 to 5.0 cm.Histologically,the tumor cells showed transparent cytoplasm and slight cellular atypia,with medium-sized round cells arranged in cords,nests,and trabecula.Small nucleoli were noted,while mitotic figures were rare.The interstitial bands of the tumor in various thickness were anastomosed with hyalining and sclerosing fibrous tissues.All the tumor cells were positive for CKpan,CK7,p40,p63 and CK5/6,but negative for S-100,SMA,Calponin,TTF1 and Napsin A;Ki-67 proliferation index was less than 10%(1%-10%).FISH testing showed EWSR1 gene translocation in all cases,three of which were confirmed by next generation sequencing to have EWSR1:ATF1 gene fusion.Conclusions Biopsy specimens of primary HCCC in the lungs are prone to misdiagnosis due to the expression of squamous cell carcinoma biomarkers,which poses a unique challenge.A complete understanding of the morphological characteristics of primary pulmonary HCCC,combined with immunohistochemistry and molecular testing,is helpful to reach accurate diagnosis.