So-called “non-classic” ciliated muconodular papillary tumors: a comprehensive comparison of the clinicopathological and molecular features with classic ciliated muconodular papillary tumors

Abstract

Ciliated muconodular papillary tumors (CMPTs) are characterized by tripartite cellular components of ciliated columnar cells, mucinous cells, and basal cells with predominantly papillary architecture. Some peripheral lung nodules may not demonstrate papillary architecture and tripartite cells that show bronchiolar differentiation; these nodules are termed "CMPTs with non-classic morphology" by some authors. To validate the rationality of "non-classic" CMPTs and to analyze the clinicopathological features of CMPTs, we enrolled 21 cases of lung nodules, comprising classic CMPTs (n = 11) and so-called non-classic CMPTs (n = 10). The status of driver mutations, including those in EGFR, BRAF, ALK, and KRAS, was examined by molecular tests. Clinical and radiological follow-up was performed (3-27 months). Cilia as well as the mucinous and papillary components are usually present throughout classic CMPTs but may be absent in their non-classic counterparts. However, both entities present a bi-layer architecture with evidence of bronchiolar differentiation. Driver mutations involved the BRAF (n = 6), EGFR (n = 1) and ALK (n = 1), were identified in 8 of 11 (73%) classic CMPTs, whereas driver mutations, comprising BRAF (n = 2), EGFR (n = 1) and KRAS (n = 1), were identified in 4 of 10 (40%) non-classic lesions. Since it contains the largest series of Chinese patients with CMPTs, this study may expand the morphologic and molecular spectrum of CMPTs: a hallmark of CMPTs is bi-layer architecture with a continuous basal layer that can harbor high-frequency driver mutations. Recognition of the non-classic morphology of CMPTs may be helpful to avoid misdiagnosis and unnecessary treatment.