Pulmonary peripheral glandular papilloma and mixed squamous cell and glandular papilloma frequently harbour the BRAF V600E mutation

Histopathology. 2020 Jun;76(7):997-1004. doi: 10.1111/his.14098. Epub 2020 May 11.

Abstract

Aims: Pulmonary peripheral glandular papilloma (GP) and mixed squamous cell and glandular papilloma (MP) have very similar histological features to pulmonary ciliated muconodular papillary tumour (CMPT)/bronchiolar adenoma (BA). The underlying genetic relationships between GP/MP and CMPT/BA have rarely been characterised. We aimed to reveal the relationship between them.

Methods and results: We performed a clinicopathological review and next-generation sequencing (NGS) study of two GPs and five 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. BRAF V600E mutation was detected in four papillomas (57.1%, one GP and three MPs).

Conclusions: Overlapping morphological 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.

Keywords: bronchiolar adenoma; ciliated muconodular papillary tumour; glandular papilloma; mixed squamous cell and glandular papilloma.

MeSH terms

  • Aged
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Mutation
  • Papilloma / genetics*
  • Papilloma / pathology*
  • Proto-Oncogene Proteins B-raf / genetics*

Substances

  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf