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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.

SUBMITTER: Yang X

PROVIDER: S-EPMC7550676 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Yang Xinxin X Hou Yunjing Y Geng Jiashi J Geng Jingshu J Meng Hongxue H

Frontiers in genetics 20200929

<h4>Introduction</h4>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.<h4>Methods</h4>Molecular features of 5 CMPTs cases (one case with mucinous adenocarcinoma simultaneously) were observed by whole exon gene detection. ...[more]

PMID: 33133167

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Project description:We have identified 25 lesions involving alveolar lung parenchyma characterized by nodular proliferation of bland bilayered bronchiolar-type epithelium containing a continuous layer of basal cells. These lesions shared some histologic features with the recently described entity of ciliated muconodular papillary tumor (CMPT); however, the majority did not fit all diagnostic criteria in that they exhibited only focal or absent papillary architecture, and they had variable number of ciliated and mucinous cells, with some lesions entirely lacking 1 or both of these components. The morphologic and immunohistochemical features ranged from those resembling proximal bronchioles (proximal-type: moderate to abundant mucinous and ciliated cells; negative or weak TTF1 in luminal cells; n=8) to those resembling respiratory bronchioles (distal-type: scant or absent mucinous and ciliated cells; positive TTF1 in luminal cells; n=17). The hallmark of all lesions was a continuous layer of basal cells (p40 and CK5/6-positive). We provisionally designated these lesions as bronchiolar adenomas (BAs) and analyzed their clinicopathologic and molecular features. All BAs were discrete, sharply circumscribed lesions with a median size of 0.5 cm (range, 0.2 to 2.0 cm). Most lesions were either entirely flat (n=14) or contained focal papillary architecture (n=7); only 4 lesions, all proximal-type, were predominantly papillary, fitting the classic description of CMPT. Notably, of 9 lesions submitted for frozen section evaluation, 7 were diagnosed as adenocarcinoma. No postsurgical recurrences were observed for any lesions (median follow-up, 11 mo). Twenty-one BAs underwent next-generation sequencing and/or immunohistochemistry for BRAF V600E, revealing mutation profiles similar to those previously described for CMPTs, including BRAF V600E mutations (n=8, 38%), unusual EGFR exon 19 deletions (n=2, 10%), EGFR exon 20 insertions (n=2, 10%), KRAS mutations (n=5, 24%), and HRAS mutations (n=1, 5%). The mutation profiles were similar in proximal-type and distal-type lesions. In conclusion, we describe a family of putatively benign clonal proliferations with a spectrum of morphology recapitulating various levels of the bronchiolar tree, of which only a minor subset fits the classic description of CMPT. Comparable mutation profiles and partially overlapping morphologic features across the spectrum of these lesions support their nosological relationship. We propose designating this entire family of lesions as BAs, and that lesions currently designated CMPTs represent a subgroup of this family.

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Dataset Information

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

Publications

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

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