A molecular pathological study of four cases of ciliated muconodular papillary tumors of the lung

Abstract

Ciliated muconodular papillary tumors (CMPTs) are a recently categorized benign or low-grade malignant neoplasm that develops in the peripheral lung. Only about 40 cases have been reported to date, and the clinicopathological characteristics have yet to be defined in detail. Here, we present four cases of CMPTs with a focus on their immunohistochemical profiles and driver gene mutations. These tumors were a papillary proliferation of a mixture of ciliated, mucous, and basal cells located in the peripheral lung. Ciliated, mucous and basal cells were positive for TTF-1 when using the clone SPT24, but negative for HNF-4α. Basal cells were positive for p40. Mucous cells in some tumors were positive for MUC5AC and MUC6. The Ki-67 index was less than 5%, and strong expression of p53 was not detected. Three of the four tumors had a BRAF (V600E) driver mutation, an EGFR (del E746-T751/S752V) driver mutation, or driver mutations in both EGFR (E709G) and KRAS (G12V). These mutation types are rare for any histological type of lung cancer. The present results confirmed that CMPT is a neoplasm with immunohistochemical features and driver gene mutations that are distinct from those of common lung tumors.

Distal‐type bronchiolar adenoma of the lung expressing p16INK4a – morphologic, immunohistochemical, ultrastructural and genomic analysis – report of a case and review of the literature

“…Ishikawa 1 reported the first case in 2002, and named it ciliated muconodular papillary tumor. Literature review indicated a total of 68 cases reported to date 1–10 . The clinicopathological features of the previously reported cases are summarized in Table 1.…”

“…Literature review indicated a total of 68 cases reported to date. [1][2][3][4][5][6][7][8][9][10] The clinicopathological features of the previously reported cases are summarized in Table 1. The tumor size ranged from 2 to 15 mm.…”

Ciliated muconodular papillary tumors of the lung: Cytologic features and diagnostic pitfalls in intraoperative examinations

“…The first report of a CMPT as a new entity was by Ishikawa in the Japanese literature in 2002 . Although CMPTs are rare, with only about 50 cases reported so far, their recognition is increasing as more and more cases are documented . Most CMPT cases involved middle‐aged or elderly patients in East Asia, with a few cases in Western countries …”

“…Histologically, they are composed of tripartite elements (eg, ciliated columnar cells, mucous cells, and basal cells) surrounded by an intra‐alveolar mucin pool. According to recent molecular analyses, they frequently contain driver oncogenes ( EGFR , BRAF , ALK , and KRAS ) and are neoplastic rather than reactive lesions . CMPTs always lack nuclear atypia and mitotic activity.…”

“…and are neoplastic rather than reactive lesions. [11][12][13][14][15][16][17][18] CMPTs always lack nuclear atypia and mitotic activity. Moreover, all previous reported cases followed an indolent clinical course without recurrence or metastasis even after limited resection.…”