Multiple bronchiolar adenomas with malignant transformation and CCNE1 mutation: a case report and literature review

Bronchiolar adenoma (BA) is a recently proposed diagnostic terminology, which is considered as the expansion of the concept of ciliated muconodular papillary tumors. 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.

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.

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.