Suitability of thoracic cytology for new therapeutic paradigms in non-small cell lung carcinoma: high accuracy of tumor subtyping and feasibility of EGFR and KRAS molecular testing.

Introduction: The two essential requirements for pathologic specimens in the era of personalized therapies for non-small cell lung carcinoma (NSCLC) are accurate subtyping as adenocarcinoma (ADC) versus squamous cell carcinoma (SqCC) and suitability for EGFR and KRAS molecular testing. The aim of this study was to comprehensively review the performance of cytologic specimens for the above two goals in a high-volume clinical practice.

Methods: Subtyping of primary lung carcinomas by preoperative cytology was correlated with subsequent resection diagnoses during a 1-year period (n = 192). The contribution of various clinicopathologic parameters to subtyping accuracy and utilization of immunohistochemistry (IHC) for NSCLC subtyping were analyzed. In addition, the performance of cytologic specimens submitted for EGFR/KRAS molecular testing during a 1-year period (n = 128) was reviewed.

Results: Of the 192 preoperative cytology diagnoses, tumor subtype was definitive versus favored versus unclassified in 169 (88%) versus 15 (8%) versus 8 (4%) cases, respectively. Overall accuracy of cytologic tumor subtyping (concordance with histology) was 93% and accuracy of definitive diagnoses 96%. For a group of patients with ADC and SqCC (n = 165), the rate of unclassified cytologic diagnoses was 3% and overall accuracy 96%. IHC was used for subtyping of 9% of those cases, yielding 100% accuracy. The strongest predictors of difficulty in subtyping of ADC and SqCC were poor differentiation (p = 0.0004), low specimen cellularity (p = 0.019), and squamous histology (p = 0.003). Of 128 cytologic specimens submitted for molecular testing, 126 (98%) were suitable for analysis, revealing EGFR and KRAS mutations in 31 (25%) and 25 (20%) cases, respectively.

Conclusions: Cytologic subtyping of NSCLC is feasible and accurate, particularly when morphologic assessment is combined with IHC. Furthermore, routine cytologic specimens can be successfully used for EGFR/KRAS mutation analysis. Our data strongly support the suitability of cytologic specimens for the new therapeutic paradigms in NSCLC.