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Correlation of cytomorphology and molecular findings in EGFR+, KRAS+, and ALK+ lung carcinomas.

OBJECTIVES
There is increasing emphasis on the subclassification of non-small cell lung carcinomas (NSCLCs) and molecular features to guide treatment. Histologic studies have suggested some morphologic features predominating in tumors. Our aim was to determine if mutated cases had distinct cytomorphology.


METHODS
A retrospective study was designed to retrieve all cytopathology cases of NSCLC that had mutation studies for EGFR or KRAS or fluorescence in situ hybridization studies for ALK between 2007 and 2012. All slides from available mutation-positive cases were reviewed, and cytomorphologic features were correlated to mutation status.


RESULTS
Of the cases with molecular testing, 62 (39%) of 160 were positive for mutation, including 39 (31%) positive for KRAS, 20 (14%) for EGFR, and 4 (3%) for ALK (one case positive for both EGFR and ALK). More of ALK+ and KRAS+ cases had a diagnosis of NSCLC-favor adenocarcinoma or NSCLC not otherwise specified than did EGFR+ cases (25; 51% vs 5%). Eosinophilic granular cytoplasm was seen in more ALK and KRAS cases than in EGFR cases (100; 32% vs 6%).


CONCLUSIONS
Cytologic features of ALK+ and KRAS+ tumors included more nuclear pleomorphism, necrosis, and a less vacuolated cytoplasm than did EGFR+ tumors, which may explain the less definitive subclassification in ALK+ and KRAS+ tumors.