Associations between
bronchioloalveolar carcinoma (BAC), mucinous differentiation, and
epidermal growth factor receptor (EGFR) and KRAS mutations have been previously reported in studies of surgical specimens. We present the cytomorphology of
lung adenocarcinomas, including
metastases that were diagnosed by cytologic methods and the relationship to both EGFR and KRAS mutational status. We retrospectively reviewed the clinical and cytomorphologic features of 50
lung adenocarcinomas that were tested for both EGFR and KRAS mutations. Cytomorphologic features evaluated included cell size, architectural pattern, nucleoli, intranuclear cytoplasmic inclusions (INCI),
mucin,
necrosis, squamoid features, lymphocytic response, and histologic features of BAC differentiation.
DNA was extracted from a
paraffin-embedded cell block or frozen needle core fragments. Exon 19 deletions and the L858R mutation in exon 21 of EGFR were detected using PCR followed by capillary electrophoresis for fragment sizing. KRAS mutational analysis was performed by real-time PCR using a set of seven different Taqman(r) allelic discrimination assays to detect six mutations in
codon 12 and one mutation in
codon 13. Six cases (12%) showed EGFR mutations, 12 (24%) showed KRAS mutations, and 38 (62%) contained neither EGFR nor KRAS mutations. The majority of patients had stage IV disease (78%); 20 samples (40%) were from metastatic sites. The presence of prominent INCI (P = 0.036), papillary fragments (P = 0.041), and histologic features of BAC on
paraffin block (P = 0.039) correlated with the presence of EGFR mutations. The presence of
necrosis (P = 0.030), squamoid features (P = 0.048), and poorly differentiated
tumors (P = 0.025) were more likely to be identified in the KRAS positive group.