Distal‐type bronchiolar adenoma of the lung expressing p16^INK4a – morphologic, immunohistochemical, ultrastructural and genomic analysis – report of a case and review of the literature

Abstract

Bronchiolar adenoma (BA) of the lung is a rare benign neoplasm. Because of a chest abnormal shadow indicated by health checkup, a 77‐year‐old female nonsmoker underwent computed tomography, revealing an 8 mm ground glass nodule in the peripheral field of the right lower lobe. Wedge resection of the nodule was performed, with a frozen diagnosis of primary lung adenocarcinoma. The localized, 8 × 4 × 3 mm‐sized, jelly‐like mass microscopically revealed a lepidic‐growing lesion composed of ciliated columnar cells, mucous cells and basal cells surrounded by mucin pool. Neither nuclear atypia nor mitotic activity was noted. Immunohistochemically, the ciliated, mucous and basal cells were positive for TTF‐1 and p16INK4a. Mucous cells were positive for napsin A and focally expressed MUC5AC. MUC6 was negative. Basal cells were positive for CK5/6, p40, p63 and podoplanin. Human papillomavirus genome was undetectable by in situ hybridization. Ultrastructurally, the bronchiolar epithelial tubules consisted of two layers, the inner nonciliated microvillous cells and the outer basal‐like cells, and some of the inner cells were filled with mucin granules in cytoplasm. Molecular analysis of the tumor failed to show driver mutations. The final diagnosis was distal‐type BA. The postoperative course was uneventful for 6 months.

Mucin distribution in bronchiolar adenoma/ciliated muconodular papillary tumor reveals organoid differentiation simulating the normal lung

“…However, four cases were relatively proximally differentiated and three were relatively distally differentiated. Based on IHC, cases were largely negative or only weakly positive for MUC6, MUC2, and HIK1083, which is in line with previous reports 4–7 (Table 2).…”

“…A recent study extended the concept of CMPT and redefined it in the context of bronchiolar adenoma (BA): 3 these authors classified CMPT as proximal‐type BA, while lesions with luminal cell layers harboring cuboidal and club cells were categorized as distal‐type BA 3 . Previous reports have identified mucin types produced in BA/CMPT 4–7 . Based on these reports, immunohistochemistry (IHC) for MUC5AC in BA/CMPT is focally positive, while BA/CMPT tissues are largely negative for MUC6 and MUC2, and one study reported MUC5B production in BA/CMPT 4 .…”

Expression and role of p16 and GLUT1 in malignant diseases and lung cancer: A review

“…p16‐INK as well as p40 and p63 has been found to be overexpressed not only in malignant but also in benign lung adenoma 33 …”

“…32 p16-INK as well as p40 and p63 has been found to be overexpressed not only in malignant but also in benign lung adenoma. 33 Among the malignant lung diseases, abnormal expression of p16 has been found mainly in NSCLC in which methylation of p16 gene is frequently observed. [34][35][36] Hypermethylation of the p16 gene together with p53 and KRAS mutation has been reported to promote lung carcinogenesis in smokers.…”

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

“…Bronchiolar adenomas grow slowly and are usually detected when they are small. To date, no recurrence has been reported, 3–37 and its excellent prognosis suggests that BA is a benign tumor. The majority of BAs have driver mutations including BRAF V600E, unusual EGFR exon 19 deletions (e.g.…”