Frequent BRAF or EGFR Mutations in Ciliated Muconodular Papillary Tumors of the Lung

Abstract

Introduction: Ciliated muconodular papillary tumors (CMPTs) are recently characterized, rare peripheral nodules of the lung. These small tumors are histologically comprised of a vaguely organized mixture of nonatypical ciliated columnar cells, mucous cells, and basal cells, and consistently follow a benign clinical course. However, the histogenesis of CMPTs remains uncertain.

Methods: We performed detailed genomic analyses of 10 archived CMPT cases, using next-generation sequencing and high-resolution melting analysis.

Results: Mutations were identified in eight of the 10 cases (80%); four cases harbored the BRAF-V600E mutation, one case harbored the BRAF-G606R mutation, and three cases harbored deletions in exon 19 of EGFR. All of the deletions in EGFR were of the E746-T751/S752V subtype.

Conclusions: The high prevalence of driver gene mutations in CMPTs supports the notion that these lesions are neoplastic rather than reactive or metaplastic.

Keywords: BRAF; Ciliated muconodular papillary tumors; EGFR; Histogenesis; Next-generation sequencing.