间变性淋巴瘤激酶阳性肺腺癌细胞病理学特点初探

Anaplastic lymphoma kinase-positive adenocarcinoma of lung ： a cytopathologic analysis

目的探讨间变性淋巴瘤激酶（ALK）基因重排阳性肺腺癌的细胞病理学特点。方法回顾性分析2011年9月至2015年4月在复旦大学附属肿瘤医院用细胞学标本进行AIⅨ基因重排和／或ALK融合蛋白检测的肺腺癌连续病例153例，包括胸水34例，经气管镜超声引导针吸活检术（EBUS．TBNA）40例，体表肿块穿刺79例。结果经荧光原位杂交（FISH）和免疫组织化学VentanaALK（D5F3）证实的ALK阳性病例共39例（25．5％），其中单独由FISH法确定的3例，经两者共同证实的36例。中位年龄50岁，较ALK阴性者（60岁）年轻（P=0．002）。39例ALK阳性患者中只有4例为吸烟者，明显少于阴性组（P〈0．01）。ALK阳性病例中3例可见筛孑L状结构和明显的核仁，3例见筛孔状结构和黏液细胞，8例见细胞外黏液和黏液细胞，出现率显著高于ALK阴性病例（均P〈0．01）。结论细胞学标本（常规涂片和细胞块）可以显示ALK阳性肺腺癌的一些形态学特征如筛孔状结构、明显的核仁、黏液细胞和细胞外黏液等，结合患者临床特征，对于筛选潜在ALK阳性的肺腺癌患者有一定帮助。

Objective To study the cytomorphologic features of anaplastic lymphoma kinase （ALK）-rearranged pulmonary adenocarcinoma. Methods The morphologic features in 153 pulmonary adenocarcinoma cytology specimens encountered during the period from September, 2011 to April, 2015 in Shanghai Cancer Hospital were retrospectively reviewed. Fluorescence in-situ hybridization （FISH） and/or immunohistochemistry （Ventana DSF3） for ALK gene rearrangement were carried out. The samples studied included 34 pleural effusion specimens, 40 endobronchial ultrasound-guided transbronchial needle aspirates （EBUS-TBNA） and 79 fine needle aspirates of palpable masses on body surface. Results Thirty-nine cases （25.5%） of ALK-rearranged samples were identified by FISH and/or immunohistochemistry, including 3 cases diagnosed by FISH and 36 cases by both technologies. The median age of the ALK-positive group was 50 years, significantly younger than that of the ALK-negative group （60 years old,P = 0. 002）. Only 4 of the ALK-positive patients were smokers, which was significantly less than that of the ALK-negative group （P 〈0. 01 ）. In ALK-positive group, 3 cases showed cribriform pattern with prominent nucleoli, 3 cases showed cribriform pattern with mucin-rich cells and 8 cases showed extracellular mucus with mucin-rich cells. The above cytomorphologic patterns were significantly less common in ALK-negative tumors （P 〈 0.01）. Conclusions ALK-rearranged lung adenocarcinoma is associated with certain distinctive morphologic patterns, including cribriform architecture, presence of prominent nucleoli, mucin-rich cells and extracellular mucus, which can be observed in cytology specimens （ including conventional smears and cell block sections）. These findings, when combined with clinical features, may give clues to detection of ALK- positive cases.