Multiple Bronchiolar Adenomas With Malignant Transformation and CCNE1 Mutation: a Case Report and Literature Review

Abstract

Background: Bronchiolar adenoma (BA) is a recently proposed diagnostic terminology, which is considered as the expansion of the concept of ciliated muconodular papillary tumors (CMPT). BA is considered to be a benign neoplasm, but a few previous cases have been reported with the possibility of malignant transformation. Therefore，the genetic and histological nature of BA is controversial so far. We describe a rare case of multiple BAs with malignant transformation and CCNE1（cyclin E1）mutation to increase the understanding of this disease.Case description: A 56-year-old woman was admitted to our hospital due to two ground-glass nodules (GGNs) in the left lung detected by chest CT without symptom. The pure GGN located in the upper lingual segment about 6 mm in diameter and another mixed GGN located in the dorsal segment about 7 mm. The two GGNs have been found a year ago without treatment, and the mixed GGN become larger to 8 mm with vacuole sign in the next year health checkup. We performed a wedge resection of the two nodules completely by video-assisted thoracoscopy (VATS). Postoperative pathology indicated that the pure GGN was atypical bronchial adenoma, while the mixed GGN was atypical bronchial adenoma with malignant transformation which was missed in frozen section. Gene mutations analysis by next-generation sequencing (NGS) showed CCNE1 gene mutation in both lesions, and her-2 mutation was identified in the mixed GGN. The programmed cell death 1 ligand 1 (PD-L1) expression analysis of tumor cells showed 0% and less than 1% in the pure GGN and the mixed GGN, respectively. Conclusion: BA is generally considered to be a benign tumor. The present study indicated that BA may be carcinogenic in atypical cases with some driver genes mutation and we should be vigilant for its potentiality of malignant transformation in clinical practice.

Bronchiolar adenoma/ciliated muconodular papillary tumor mixed with adenocarcinoma in situ in the same tumor

“…7 According to previous studies, driver mutations or malignant transformation in BA/CMPT have been reported in several cases. [1][2][3][4][5][8][9][10][11] It is therefore controversial whether BA/CMPT is benign or malignant. In reported cases that showed malignant transformation, the lack of continuity of basal cells and the recognition of the same driver mutation were considered to be grounds for malignant transformation of BA/CMPT.…”

“…Recently, some cases with driver mutations or malignant transformation have been observed. [1][2][3][4][5] Thus, whether BA/CMPT is benign or malignant is considered controversial. We herein report an extremely rare case of a 68-year-old woman with a CMPT accompanied by adenocarcinoma in situ (AIS).…”

“…Bronchiolar adenoma (BA)/ciliated muconodular papillary tumor (CMPT) is defined as a benign tumor composed of epithelial and basal cells. Recently, some cases with driver mutations or malignant transformation have been observed 1–5 . Thus, whether BA/CMPT is benign or malignant is considered controversial.…”

Proximal bronchiolar adenoma with malignant transformation to invasive mucinous adenocarcinoma with 4 years follow-up: A case report

“…Interestingly, the high mutation frequency of BA driver genes, the skip growth pattern, characteristic micropapillary structure, and the simultaneous coexistence with IMA with the same driver gene mutation [5,6,12,13], which makes whether BA can act as a precancerous lesion as a hot topic for current discussion. In this case, we report the simultaneous presence of mutations in KRAS (G12V) in the BA and IMA regions.…”

“…Supporting the evidence of BA as a precancerous lesion there are some the published literatures (Table 2), Han [6] et al found that sequencing analysis of the region of BA and IMA showed that KRAS mutation (G12V) occurred in both parts, so it is further inferred that IMA originate from BA, in other words BA malignant transformation to IMA. Li [13] et al reported a case of CCNE1 (Exon7, c.476A > G) mutation in mixed GGN and pure GGN with mutation abundances of 48.83% and 45.41%, respectively.…”