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

Background 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. 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.

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

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.

Detection of a novel gene mutation, ERBB2 exon 20 insertion, in bronchial adenoma using next-generation sequencing and a review of the literature

Objectives: Ciliated muconodular papillary tumor (CMPT) is a rare peripheral lung tumor and is a subtype of bronchial adenoma (BA). Although recent studies have suggested that BA is a neoplastic disease, the complete histogenesis of BA is not fully understood and molecular data are limited. Methods: We examined the clinicopathological features of four patients with BA and performed immunohistochemical analysis and next-generation sequencing to characterize the molecular features of BA. A review of the previous literature was also undertaken to comprehensively conclude the molecular characteristics of this disease. Results: From previous studies and the present study, 99 BA /CMPT cases have been reported to date, with most of the patients from East Asia (77/99, 77.8%). The median age was 64 years old and the ages ranged from 19 to 84 years. The proportion of males and females was close, being approximately 1:1.3. From the computed tomography images, the BA /CMPT tumor usually presented as a peripheral solid mass, part-solid nodules, or ground-glass opaque with an irregular border and occasional central cavities. ERBB2, EGFR, BRAF, and AKT1 mutations were found on the computed tomography images of the BAs. To the best of our knowledge, this is the first study to report about ERBB2 exon 20 insertion in BA. Conclusion: BA /CMPT is a rare pulmonary disease that mainly affects elderly Asian patients. Many abnormal molecular changes were found, which confirmed the neoplastic nature of BA /CMPT. However, it also added to the debate regarding the biological behavior of BA /CMPT.