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

Abstract

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/p63À 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/TTF1À 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 NSCLC-NOS diagnostic category. Cancer 2011;117:3416-

Utility of small biopsies for diagnosis of lung nodules: doing more with less

“…However, recent immunohistochemical studies that have focused on poorly differentiated non-small cell carcinomas in small biopsies or cytology specimens with resected tumors as the gold standard have shown that some markers, especially when used in combination, are indeed useful and accurate in subclassifying poorly differentiated non-small cell lung carcinomas. [5][6][7][8] As subclassification using these markers shows excellent correlation with the gold standard H&E-based diagnosis on resected tumors, immunohistochemistry has become accepted as a reliable technique for subclassification when diagnostic features on H&E morphology are absent in a small biopsy. To summarize the current state of non-small cell lung carcinoma subclassification, H&E-based criteria remain the gold standard for subclassifying resected tumors.…”

“…Furthermore, although napsin A is slightly less sensitive for poorly differentiated adenocarcinomas than TTF-1, it is valuable in occasional adenocarcinomas that are napsin A-positive but TTF-1-negative. [8][9][10] Finally, napsin A stains adenocarcinomas but not small cell carcinomas, 9 a fact that can be helpful when the differential diagnosis of a TTF-1-positive poorly differentiated carcinoma includes small cell carcinoma. Similarly, although p63 is more sensitive for squamous cell carcinomas than CK5/6, the latter is useful when p63 staining is focal, weak or equivocal.…”

Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens

“…Although the optimal diagnostic algorithm is not firmly established, recent studies show that immunohistochemistry increases accuracy and reproducibility, and minimizes the rate of non-small cell carcinoma-not otherwise specified diagnoses in small specimens. [13][14][15][16][17] We recently showed that the rate of adenocarcinoma and squamous cell carcinoma unclassified by preoperative cytology in clinical practice with routine utilization of immunohistochemistry is low (3%). 18 Common markers used for non-small cell carcinoma subtyping include TTF-1 for adenocarcinoma vs p63 and high-molecular weight keratins (CK5/6 and 34bE12/CK903) for squamous cell carcinoma.…”

“…Given the recent insights into the clinical and biological significance of non-small cell carcinoma subtypes, several recent studies have analyzed the utility of various combinations of markers for the distinction of adenocarcinoma and squamous cell carcinoma. These studies were performed in small biopsies, [14][15][16] cytology, 17,23 and tissue microarrays, [24][25][26] and the proposed algorithms include between fourand six-marker panels. Although most studies agree on the inclusion of TTF-1 and p63 in the panel, there is no agreement on the role of additional markers.…”

Application of Immunohistochemistry in the Diagnosis of Pulmonary and Pleural Neoplasms

“…26 In the majority of pathology laboratories, the routine p63 antibody is 4A4, which recognizes both TAp63 and DNp63 isoforms. The p40 antibody, which exclusively recognizes the DNp63 isoform, may have a superior specificity 29 but inferior sensitivity [30][31][32] compared with p63 in the diagnosis of pulmonary SqCC.…”