1. Clinicopathological characteristics and molecular analysis of lung cancer associated with ciliated muconodular papillary tumor/bronchiolar adenoma
- Author
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Masahiro Higashiyama, Noriko Motoi, Masaya Yotsukura, Yukihiro Yoshida, Kazuo Nakagawa, Shigehiro Yagishita, Masayuki Shirasawa, Tatsuya Yoshida, Kouya Shiraishi, Takashi Kohno, Yuichiro Ohe, and Shun-ichi Watanabe
- Subjects
General Medicine ,Pathology and Forensic Medicine - Abstract
Ciliated muconodular papillary tumor/bronchiolar adenoma (CMPT/BA) is a benign tumor with a high frequency of BRAF or EGFR mutations. It remains unclear whether CMPT/BA is associated with a specific type of lung cancer. Thus, we studied the clinicopathological and genetic characteristics of cases with coexisting CMPT/BA and primary lung cancer to explore this relationship. Among 1945 patients with resected stage 0-III primary lung cancer between 2015–2018, we identified eight patients with concurrent CMPT/BA (lung cancer associated with CMPT/BA; LCCM). We compared the gene mutation status of each lesion according to the target sequence using macro-dissected formalin-fixed paraffin-embedded specimens. Whole-exon sequencing (WES) was performed for six lung cancer cases. The LCCM cohort was male-dominant (male:female = 6:2); the median age was 72 years (range 66–81); and most were smokers (six smokers). The most common histological type corresponding to LCCM was adenocarcinoma; however, two squamous cell carcinomas and one small cell carcinoma were also detected. CMPT/BA lesions in LCCM showed a median size of 0.5 cm (range 0.3–1.1). The mutational test revealed no shared mutations between CMPT/BA and lung cancer, except for one invasive mucinous adenocarcinoma (IMA) harboring an HRAS mutation (I46N, c.137T > A). HRAS (I46N) is a rare variant, and all tumors showed an approximately 50% variant allele frequency, suggesting a single nucleotide polymorphism. Other driver gene alterations in lung cancer included EGFR (InDel, n = 2), BRAF (V600E) (n = 1), KRAS (n = 2), GNAS (n = 1), and TP53 (n = 2) mutations. BRAF (V600E) was the most frequent mutation in CMPT/BA. In contrast, lung cancer showed no specific trend in driver gene mutations. In conclusion, our study revealed differences in the gene mutation profiles of CMPT/BA and lung cancer in coexisting cases, suggesting a mostly independent tumorigenesis of CMPT/BA from lung cancer, except for one IMA with a rare HRAS SNV.
- Published
- 2023