Ciliated Muconodular Papillary Tumors of the Lung: Distinct Molecular Features of an Insidious Tumor

Abstract

Introduction Ciliated muconodular papillary tumors (CMPTs) are rare special peripheral pulmonary nodule composed of different cell proportions, characterized by papillary structures and significant alveolar mucus. Because of their rarity, underrecognized processes, the full range clinical course and histogenesis of CMPTs remains uncertain. Methods Molecular features of 5 CMPTs cases (one case with mucinous adenocarcinoma simultaneously) were observed by whole exon gene detection. The histological features of CMPTs and the development trends of three major constituent cells were studied by immunohistochemistry and PCR. Results NGS revealed 77 gene mutations in the patient’s tumor tissue and 31 mutations in the border tissue. TMB of CMPT tends to TMB of cancer tissues, and both are higher than normal tissues, CMPT share the same phylogenetic tree with cancer tissues. Moreover, PDL1, B7H3, and B7H4 were overexpressed in high columnar cells and eosinophilic ciliated cells of CMPT, tends to cancer tissues, while LAG3 and siglec15 were not found in CMPT. Conclusion The high prevalence of driver gene mutations in CMPTs, similar TMB and phylogenetic tree with cancer tissues indicate their malignant potential. Distinct molecular and immune check point features of each component support the notion that ciliated columnar cells in CMPT are insidious with immune escape.

A clinicopathologic and molecular analysis of five cases of bronchiolar adenoma with rare mutations

“…Of the 134 BA/CMPT lesions, a total of 14 cases had coexistent lung adenocarcinomas 3,18,32 . Five of these lung adenocarcinomas underwent NGS studies, and in all cases, the molecular profiles were entirely distinct from the BAs 3 .…”

“…A total of 134 BA/CMPT lesions were found in the literature from 2010 to 2021; 53 BAs in nine reports (nine lesions were excluded because of duplicates, and 13 lesions that did not meet the definition of BA wereexcluded, 3,[28][29][30][33][34][35][36][37] and 81 CMPTs in 26 reports (11 lesions were excluded because of duplicates). [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][20][21][22][23][24][25][26][27]31,32 Of these, 94 (70.1%) were interpreted as proximal-type BA, and 25 (18.6%) were interpreted as distal-type BA, whereas 15 lesions (11.1%) could not be categorized as either of them. 18,32 Thirtythree lesions were not noted to have genetic abnormalities or failed to undergo genetic analysis.…”

“…Bronchiolar adenomas grow slowly and are usually detected when they are small. To date, no recurrence has been reported, 3–37 and its excellent prognosis suggests that BA is a benign tumor. The majority of BAs have driver mutations including BRAF V600E, unusual EGFR exon 19 deletions (e.g.…”

“…The majority of BAs have driver mutations including BRAF V600E, unusual EGFR exon 19 deletions (e.g. p.E746_S752delinV, p.L747_S752del), EGFR exon 20 insertions, KRAS and HRAS mutations, and ALK rearrangement 3,8,9,13–19,22,24,32–35 . Although dozens of case reports and small case series have been reported, the molecular profile of BA is still incompletely understood because of its low incidence.…”

“…p.E746_S752-delinV, p.L747_S752del), EGFR exon 20 insertions, KRAS and HRAS mutations, and ALK rearrangement. 3,8,9,[13][14][15][16][17][18][19]22,24,[32][33][34][35] Although dozens of case reports and small case series have been reported, the molecular profile of BA is still incompletely understood because of its low incidence.…”