BA is a term introduced by Chang et al. , which is an expansion of the concept of CMPT, characterized by benign tumors corresponding to the anatomic epithelium of bronchioles. The hallmark of BA is a continuous layer of basal cells, the basis for BA to be identified as a benign neoplasm , and is key to distinguishing between BA and lung adenocarcinoma. At low power, it may be misdiagnosed as preinvasive or invasive lesions of carcinoma, especially in frozen sections. However, ciliated cells and basal cells can be identified when sections are examined at high power, thus avoiding misdiagnosis . In the present case, flat, papillary, and glandular structures in the epithelial neoplasm were observed in the frozen sections making it difficult to distinguish the benign lesions from malignancy.
The diagnosis of BA should refer to its morphological and immunohistochemical characteristics. Chang et al.  showed that BA reproduced a spectrum of morphologic features ranging from proximal bronchioles to distal respiratory bronchioles. The proximal type was characterized by a bilayered epithelium comprising continuous basal cells and luminal epithelial cells (mucinous cells and ciliated columnar cells), with bilayered bronchiolar proliferation presenting a papillary structure. TTF-1/Napsin A staining in luminal cells was negative or weakly positive, whereas p63, p40, and CK5/6 were continuously expressed in basal cells. In contrast, the distal-type BA occurs in respiratory bronchioles with the absence of ciliated cells or mucinous cells and may have no papillary structure. TTF-1/Napsin A staining in luminal cells is positive, whereas p63, p40, and CK5/6 are expressed in the basal cells in a skipping growth pattern. In our case, the tumor was 17.0 mm in diameter with a continuous basal cell layer in certain areas. Significant ciliated differentiation was observed in luminal cells, accompanied by abundant mucinous cells. However, in certain areas, the markers of basal cells were expressed in a skipping pattern with no definite papillary structure and the luminal cells were cubic/low columnar cells, which were positive for TTF-1/Napsin A. Thus, the morphological and immunohistochemical lesion features were consistent with continuous changes in the components of mucosal epithelial cells from the proximal to distal bronchioles.
To date, BA/CMPT has been recognized as a benign or low-grade inert malignant tumor based on the results of previous studies [1, 3–9]. The high prevalence of driver gene mutations (EGFR, BRAF, ALK, and KRAS) [1, 4, 8, 10, 11] supports the notion that these lesions are neoplastic rather than reactive or metaplastic. BA is a tumor rather than a reactive or cytoplastic lesion, however, the relationship of these mutated genes with the pathogenesis and prognosis of BA remains unclear and needs to be further explored. Several cases of BA/CMPT with malignant transformation have been reported [12–15]. Miyai et al.  reported a case of CMPT with malignant transformation of basal cell components, and Chen et al.  described a case of MA caused by canceration from CMPT, speculating that CMPT was a precancerous lesion of MA. Han et al.  reported a particular case with the loss of continuity of the basal cell layer in the junctional zone between BA and IMA, and BA, in this case, had the same KRAS mutation as the adjacent IMA. Wang et al.  also reported a case of malignant CMPT. All of the above cases featured the absence of a basal cell layer in histology. The present case was diagnosed as MA caused by malignant transformation of BA based on HE staining and immunohistochemistry, providing histological evidence for the malignant potential of BA. The clinicopathological findings of the reported cases are shown in Table 1 [see Additional file 1].
Several driver gene mutations of lung adenocarcinoma have been found in BA, among which the high incidence of BRAF mutations (50%)  contrasts with that of EGFR mutations in lung adenocarcinoma. Meanwhile, EGFR mutation, ALK gene rearrangement , AKT1 mutation, and KRAS mutation were also validated in BA . As reported by Zheng et al. , CMPT characterized by tripartite cellular components of ciliated columnar cells, mucinous cells, and basal cells with predominantly papillary architecture is termed “classic CMPT”. Compared to non-classic CMPT, BRAF mutations are more common in classic CMPT. However, Chang et al.  believed that the BRAF mutation was more frequent and common in distal-type BA.
In conclusion, the postoperative pathological results confirmed the diagnosis of BA accompanied by MA, the underlying reason for which may be related to the malignant potential of BA. Therefore, it is of great significance to further improve our understanding of BA and report similar cases due to the rarity of the disease.