摘要目的：探讨肺基底细胞样鳞癌（ BSC ）与小细胞癌的细胞形态学特点及免疫组织（细胞）化学染色在鉴别诊断中的意义。方法收集经组织学证实的肺BSC及小细胞癌各17例，包括支气管刷片、细针穿刺涂片及肺泡灌洗液。对两组涂片中的细胞团和单个细胞的比例、细胞团的排列及形态、拉丝及挤压假象、细胞核最大径、细胞质、细胞核形态、核染色质分布、核仁、单个角化细胞、坏死、凋亡小体及核分裂象等17个形态学特征进行观察和比较；免疫组织（细胞）化学染色采用EnVision法，对两组25个病例进行了标记，其中10例BSC穿刺样本采用扩增阻滞突变系统（ ARMS）进行了表皮生长因子受体（ EGFR）基因外显子18、19、20、21突变的检测。结果 BSC组15／17呈黏附紧密的细胞团，小细胞癌组14／17呈现单个散在或三五成群、排列松散的细胞簇；BSC的细胞核相对于小细胞癌要略大一些，15／17的BSC细胞核最大径为9～11μm；而13／17的小细胞癌细胞核最大径为7～9μm；小细胞癌具有特征性胡椒盐样核（15／17），核铸型（17／17），挤压及拉丝现象明显（14／17），而BSC 16／17可见针尖大小核仁；此外BSC较小细胞癌更易出现单细胞角化（9／17）。 BSC组与小细胞癌组之间上述细胞形态学特点的比较差异均有统计学意义（ P＜0．05）。细胞块的免疫组织化学染色显示BSC特征性表达CK5、p40和p63，而小细胞癌则表达甲状腺转录因子（TTF）1、嗜铬粒素A（CgA）、突触素和CD56，PAX5在小细胞癌也有局灶阳性表达。10例BSC未检测出EGFR基因突变，均为野生型。结论细胞多黏附成团、细胞核较小、细胞略增大，少见拉丝、挤压现象及显著的核铸型，具有针尖大小的小核仁，可以出现单细胞角化是BSC区别于小细胞癌的重要细胞形态学特点；免疫组织化学染色对于细胞病理学鉴别二者很有帮助，推荐TTF1配合2个鳞癌标志物（ CK5、p40或p63）和2个神经内分泌标志物（突触素、CgA或CD56）共5个抗体作为BSC与小细胞癌鉴别诊断的一线抗体；建议BSC行EGFR基因突变检测。

abstractsObjective To evaluate the roles of cytomorphology and immunohistochemistry in distinguishing between basaloid squamous cell carcinoma ( BSC) and small cell carcinoma ( SCC) of lung. Methods The direct smears and/or liquid-based cytology preparation ( ThinPrep) of bronchial brushing/washing and fine-needle aspiration ( FNA ) specimens from 17 cases of biopsy-proven BSC of lung were retrospectively reviewed and compared with those from 17 cases of SCC.The cytomorphologic parameters analyzed included proportion of cohesive cell clusters, cell palisades/rosettes, adenoid cystic features, crushing artifact, nuclear maximum diameter, nuclear molding, scantiness of cytoplasm,“salt-and-pepper”nuclei, distinct nucleoli, spindly configuration, individual cell keratinization, necrosis, hyaline material, apoptosis and mitotic activity.Immunocytochemical/immunohistochemical study of 25 cases was performed. Ten FNA samples of basaloid squamous cell carcinoma were also analyzed for epidermal growth factor receptor mutations in exons 18, 19, 20 and 21 using amplification refractory mutation system.Results Most of the 17 BSC cases ( 15/17 ) showed a predominance of tightly cohesive tumor cell clusters.The&nbsp;proportion of isolated tumor cells was high in SCC ( more than 60% in 14 cases ) .The nuclear maximum diameter of BSC was slightly larger than that of SCC (9 to 11μm in BSC versus 7 to 9μm in SCC).“Salt-in-pepper” nuclei, nuclear molding and crushing artifact were detected in all SCC cases (15/17, 17/17 and 14/17, respectively).These features were only occasionally found in BSC group.Nucleoli were present in BSC and rarely ( 2/17 ) in SCC. Only 9 of 17 BSC cases showed individual cell keratinization. The differences in the above-mentioned cytomorphologic features were statistically significance (P<0.05).The results of immunohistochemistry performed on the cell block sections and immunocytochemistry performed on the ThinPrep slides were identical to that performed on the corresponding biopsy specimens.The tumor cells in BSC were consistently positive for CK5, p40 and p63.TTF1, chromogranin A, synaptophysin and CD56 were positive in most of SCC.One of SCC cases showed focal PAX5 expression.No EGFR mutations were detected in the 10 BSC cases studied.Conclusions Selected cytomorphologic features, including presence of cohesive cell clusters, larger nuclear size, distinct nucleoli, lack of crushing artifact, absence of nuclear molding and presence of individual cell keratinization, are helpful in diagnosing BSC on cytology specimens. Immunohistochemistry using a panel of TTF1, CK5, p40/p63 and chromogranin A/synaptophysin/CD56 provides further clues in differential diagnosis between BSC and SCC.EGFR mutation study is often negative in lung BSC.