Immunohistochemical subtyping of nonsmall cell lung cancer not otherwise specified in fine-needle aspiration cytology

BACKGROUND: Histopathological subtyping of nonsmall cell lung cancer (NSCLC) is currently relevant in treatment decision because of a differential activity of specific therapeutic agents. Immunohistochemistry highlights cell differentiation lineages and, in this study, it was applied to maximize the proportion of accurately subtyped NSCLC not otherwise specified (NOS) on fine-needle aspiration cytology (FNAC) samples. METHODS: Cell blocks from 103 FNAC samples with a morphological diagnosis of NSCLC-NOS were immunostained for cytokeratin (CK) 7, CK5, TTF1, and p63, whereas p40, napsin A (Naps-A), and desmocollin-3 (DSC-3) were only assessed in a subgroup of cases with discordant (CK7 and TTF1þ for nonsquamous, CK5 and p63þ for squamous) findings. Results were correlated with surgical specimens evaluated by morphology alone. RESULTS: Thirty-seven (36%) tumors with CK7/TTF1þ and CK5/p63� corresponded to 35 cases of adenocarcinoma (ADC) and 2 cases of large cell carcinoma, whereas 9 (9%) cases with the reverse immunoprofile were squamous cell carcinoma (SQCC) at surgery (P < .001). Although the remaining 57 cases had different marker combinations, a correlation was found with ADC histology for TTF1þ samples (independent of other markers) and with SQCC for p63þ/TTF1� immunophenotype (P < .001). p40 was never expressed in p63þ ADC, whereas Naps-A was restricted to ADC and DSC-3 to SQCC lineage. The percentage of unclassified NSCLC-NOS decreased from 36% to 14%. Combinations of 2 antibodies (TTF1/DSC-3 or p63/Naps-A) in the same section allowed diagnostic optimization in scant cytological samples. CONCULSIONS: This 4-antibody panel approach may contribute to refine lung cancer classification in FNAC cell blocks, remarkably reducing the NSCLCNOS diagnostic category. Cancer 2011;000:000–000. V C 2011 American Cancer Society.