Cytology of basaloid squamous cell carcinoma and small cell carcinoma of lung: a comparative study

Abstract

To evaluate the roles of cytomorphology and immunohistochemistry in distinguishing between basaloid squamous cell carcinoma (BSC) and small cell carcinoma (SCC) of lung. 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. Most of the 17 BSC cases (15/17) showed a predominance of tightly cohesive tumor cell clusters. The 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 11 μm in BSC versus 7 to 9 μm 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. 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.