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

Takeda-Miyata, Naoko; Miyagawa‐Hayashino, Aya; Hamada, Shinshichi; Nagamine, Michiko; Fujii, Tomomi; Imura, Tetsuya; Tsunezuka, Hiroaki; Shimomura, Manabu; Yamaguchi, Tadanori; Yanada, Masashi; Inoue, Masayoshi; Konishi, Eiichi

doi:10.1111/pin.13213

Cited by 6 publications

(7 citation statements)

References 45 publications

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“…5 Compared to solitary CMPT/BA series without LC, CMPT/BA with LC (including our cohort) showed slightly different genetic characteristics. (Supporting Information: Table S2) According to previous reports [3][4][5]7,[22][23][24][25][26][27][28][29][30][31] and our case series, the incidence of BRAF/EGFR/KRAS mutations in solitary CMPT/BA was 32%/16%/14%: on the other hand, 60%/0%/20% in CMPT/BA with LC, respectively. Although the number of cases is small, the incidence of BRAF mutations tends to be higher in CMPT/BA with LC than in solitary CMPT/BA.…”

Section: Discussionsupporting

confidence: 60%

Clinicopathological characteristics and molecular analysis of lung cancer associated with ciliated muconodular papillary tumor/bronchiolar adenoma

Higashiyama

Motoi

Yotsukura

et al. 2023

Pathology International

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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 speci c 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 identi ed 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-xed para n-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 speci c trend in driver gene mutations. In conclusion, our study revealed differences in the gene mutation pro les 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.

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Section: Discussionsupporting

confidence: 60%

Clinicopathological characteristics and molecular analysis of lung cancer associated with ciliated muconodular papillary tumor/bronchiolar adenoma

Higashiyama

Motoi

Yotsukura

et al. 2023

Pathology International

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“…This entity includes the classical ciliated muconodular papillary tumor (CMPT) (Proximal type) and the non-classical CMPT (Distal type). 38 Our series included two (2) bronchiolar adenomas, with none of them being identified appropriately based on their cytologic features only. In one case, the smears were hypocellular with scattered ciliated cells and mucus in the background, hence it was interpreted as "favor NN" (Proximal type).…”

Section: Discussionmentioning

confidence: 99%

“…Bronchiolar adenomas are benign pulmonary neoplasms that may have different sizes of solid or subsolid radiologic features. This entity includes the classical ciliated muconodular papillary tumor (CMPT) (Proximal type) and the non‐classical CMPT (Distal type) 38 . Our series included two (2) bronchiolar adenomas, with none of them being identified appropriately based on their cytologic features only.…”

Section: Discussionmentioning

confidence: 99%

Scrape cytology and radiological solid size correlation can be used in the intraoperative management of subsolid lung nodules

Bulutay

Atasoy

Erus

et al. 2022

Diagnostic Cytopathology

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Background The term radiologic subsolid lung nodule (SLN) represents a heterogeneous group of non‐neoplastic and neoplastic lesions. Intraoperative evaluation (IO) is often required to differentiate and diagnose. The current study aims to investigate the feasibility and reliability of scrape cytology (SC) and radiologic solid size correlation for the IO diagnosis of SLNs. Methods Sixty‐eight patients with SLN signs were eligible to take part in the study due to intraoperatively prepared SC slides. We managed to complete the blind radiologic solid size measurement and cytologic evaluation retrospectively. Cases were grouped into three categories based on their cytological features: Group‐0 (Benign), Group‐1 (mild atypical features), and Group‐2 (severe atypical features/unequivocally carcinoma). IO diagnoses were given by combining the radiologic solid size and cytological findings. Results Cytological features of Group‐1 were observed in 100%, 93%, 32.5%, and 17% of the AIS, MIA, IA, and benign lesions, respectively. Cytological features of Group‐2 were observed in 67.5%, and 7% of the IA and MIA, respectively. By combining cytology with radiologic solid size, 100%, 85%, 71%, and 83% of the AIS, IA, MIA, and benign lesions respectively were diagnosed correctly. Fifteen (15%) percent of the IA cases were underdiagnosed as MIA since their radiological solid sizes were less than 0.5 cm with cytological features of Group‐1. Conversely, 29% of the MIA cases were overdiagnosed as IA since their radiological solid sizes were greater than 0.5 cm. Conclusion SLNs should be handled with caution in terms of IO management. SC and radiologic solid size correlation both provide a practical and tissue‐protecting approach for the IO evaluation of SLNs, ensuring a high consistency between IO and definitive diagnosis.

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“…In general, BA is slow‐growing, without reported recurrence. A few variants of BA have been described 5,7,8 …”

Section: Introductionmentioning

confidence: 99%

“…A few variants of BA have been described. 5,7,8 To date, there are only a few articles that describe the squamous metaplasia of BA. 9 In the present study, we identified a novel type of BA, bronchiolar adenoma with squamous metaplasia (BASM), where basal cells overgrow and undergo the squamous metaplasia.…”

Section: Introductionmentioning

confidence: 99%

Bronchiolar adenoma with squamous metaplasia: a distinct phenotype

et al. 2023

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Aims: Pulmonary bronchiolar adenoma is a benign lung tumour characterised by nodular proliferation of bilayered bronchiolar-type epithelium with a continuous layer of basal cells. The aim of this study was to describe a distinct and rare histological type of pulmonary bronchiolar adenoma: bronchiolar adenoma with squamous metaplasia. Methods and results: We examined the clinicopathological, immunohistochemical, and molecular characteristics of five cases (two cases from the same patient). The samples were histopathologically characterised by bilayered bronchiolar-type cells with sheets like spindle-oval and polygonal cells. Immunohistochemistry analysis revealed that columnar surface cells of the tumour were diffusely positive for TTF-1 and Napsin A, while basal cells were positive for P40 and P63. Moreover, the squamous metaplastic cells in the stroma were positive for P40, and P63, while being negative for TTF-1, Napsin A, S100, and SMA. Genomic analyses uncovered that all five samples had BRAF V600E mutations. Notably, both squamous metaplastic and basal cells were positive for BRAF V600E staining. Conclusion:We discovered a distinct subtype of pulmonary bronchiolar adenoma termed bronchiolar adenoma with squamous metaplasia. It is composed of columnar surface cells, basal cells, and sheet-like spindle-oval cells with squamous metaplasia in the stroma. All five samples harboured the BRAF V600E mutation. Importantly, BASM may be misdiagnosed as pulmonary sclerosing pneumocytoma upon frozen sections analysis. It may need further immunohistochemistry staining.

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

Cited by 6 publications

References 45 publications

Clinicopathological characteristics and molecular analysis of lung cancer associated with ciliated muconodular papillary tumor/bronchiolar adenoma

Clinicopathological characteristics and molecular analysis of lung cancer associated with ciliated muconodular papillary tumor/bronchiolar adenoma

Scrape cytology and radiological solid size correlation can be used in the intraoperative management of subsolid lung nodules

Bronchiolar adenoma with squamous metaplasia: a distinct phenotype

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