Ciliated Muconodular Papillary Tumor of the Lung: A New Entity Formerly Regarded as a Well-Differentiated Adenocarcinoma

Ciliated muconodular papillary tumor (CMPT) of the lung is a newly defined distinct entity in the spectrum of mucinous tumors of the peripheral lung. Previously regarded as a low-grade adenocarcinoma, CMPT is currently considered an indolent neoplasm with characteristic tubulopapillary, glandular, or papillary architecture showing tripartite morphology including basal cells, mucinous cells, and ciliated cells. The diagnosis can be made by identifying a tumor that shows proliferation of basal cells, mucinous cells, and ciliated cells without nuclear atypia or mitotic activity and demonstrating a continuous layer of p40/p63 or CK5/6 staining basal cells. These tumors were shown to harbor BRAF (V600E), EGFR (E746-T751/S752V), AKT1 (E17K), and rarely KRAS (G12C) mutations. The diagnosis of this entity may be particularly difficult on small biopsies, fine-needle aspirates, and frozen sections. The prognosis is excellent after limited resection. We present a case of CMPT incidentally identified in a lung explant with emphysema; review the clinical, histopathologic, and molecular features of CMPT and its differential diagnosis; and explore the controversial aspects regarding diagnosis, origin, and classification of these neoplasms.