Immunohistochemical and molecular characterization of clear cell carcinoma of the lung

The diagnostic entity of clear cell carcinoma of the lung (CCCL) is controversial, with many investigators arguing against its inclusion in the World Health Organization classification of lung carcinoma. Because of its rarity and questions regarding its histogenesis, I studied 3 groups of carcinomas with immunohistochemical and molecular assays, including 6 cases of CCCL, 7 cases of adenocarcinoma with clear cell change, and 11 cases of squamous carcinomas with prominent clear cell change. CCCL tended to be present in older individuals with an adenocarcinoma immunophenotype (cytokeratin 7 and TTF1 positivity). Molecular analysis by Sanger sequencing revealed KRAS mutations in 5 of 6 cases of CCCL, 2 of 7 adenocarcinomas with clear cell change, and 2 of 11 squamous carcinomas with clear cell change. Although perhaps not a distinct pathologic entity, in this pilot study, CCCL has an immunophenotype similar to solid-type adenocarcinoma with clear cell change and displays more frequent and unusual KRAS mutations than expected in most adenocarcinomas of the lung.