Pulmonary Peripheral Glandular Papilloma and Mixed Squamous Cell and Glandular Papilloma Frequently Harbor the BRAF V600E Mutation

AIMS: Pulmonary peripheral glandular papilloma (GP) and mixed squamous cell and glandular papilloma (MP) have very similar histological features to pulmonary ciliated muconodular papillary tumor (CMPT) /bronchiolar adenoma (BA). The underlying genetic relationships between GP/MP and CMPT/BA have rarely been characterized. We aimed to reveal the relationship between them. METHODS AND RESULTS: We performed a clinicopathologic review and next-generation sequencing (NGS) study of 2 GPs and 5 MPs. Histologically, GPs/MPs showed similar cellular and architectural features to CMPTs/BAs, such as bilayered epithelium, bronchiole-associated lesions and skipping (discontinuous) growth pattern. One MP showed partial and inconspicuous endobronchiolar growth and more glandular structures, which was very similar to the appearance of CMPT/BA. The BRAF V600E mutation was detected in 4 papillomas (57.1%, 1 GP and 3 MPs). CONCLUSIONS: Overlapping morphologic features and comparable mutation profiles support that peripheral GPs/MPs and CMPTs/BAs are on the same disease spectrum. We propose expanding the concept of CMPT/BA and including GP and MP in the CMPT/BA family.