A 72-year-old man with history of smoking, cholangiocarcinoma, and urothelial carcinoma underwent a left upper lung lobectomy for invasive adenocarcinoma. An additional tumor, 0.3 x 0.3 x 0.2 cm, was identified in the lobe. H&E photomicrographs of the second tumor are provided below (Figures 1-2). Immunohistochemical studies revealed that the tumor cells stained positive for p40 (staining the basal cell layer, Figure 3), TTF-1 (staining the luminal cell layer, Figure 4) and CK7 (staining both layers).
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Bronchiolar adenomas (BA) are rare, benign lung tumors composed of bronchiolar-type epithelium with continuous basal cell layer. They are located peripherally in the lung and involve the peribronchiolar lung parenchyma. The term bronchiolar adenoma was proposed in 2018 for the entire spectrum of bilayered bronchiolar-type lesions, encompassing the previously described classical and nonclassical ciliated muconodular papillary tumors (CMPT). Like in this case, BA are typically incidental findings and affect middle-aged to elderly patients.
BA can appear as solid, ground-glass or mixed solid/ground-glass on computed tomography (CT). Grossly, they are well-circumscribed, tan-white to grey, with firm, cystic or mucoid cut surface. Histologically, BA are divided into proximal and distal types, based on similarity to normal proximal and distal bronchiolar epithelium. Proximal BA correspond to classic CMPT, and distal BA correspond to nonclassical CMPT. Proximal type BA are composed of mucinous and ciliated luminal cells. They can have a spectrum of architectural patterns, ranging from predominantly papillary to flat. Abundant intratumoral or intraalveolar mucin is characteristic. Distal type BA are predominantly composed of non-ciliated luminal cells, resembling type II pneumocytes, and club cells. They are mostly flat. The basal cell layer is highlighted by basal cell markers, p40, p63 or CK5/6. The luminal cells in distal type BA are more likely to be positive for TTF-1 than in proximal type BA.
The etiology of BA is unknown. Studies have shown BRAF V600E being the most common driver mutation with KRAS being the second most common. The detection of driver mutations, however, is not necessary for diagnosis.
The diagnosis of BA can be challenging during intraoperative consultation and on small biopsies. The distinction from adenocarcinoma is important and can be difficult with limited samples. The differential diagnosis of BA depends on the predominant cell type of the lesion (proximal vs. distal). The most useful features in differentiating BA from mucinous and non-mucinous adenocarcinoma of the lung are the continuous basal cell layer (that can be highlighted by basal cell markers p40, p63 or CK5/6), ciliated cells, and the lack of nuclear atypia. Location and presence of well-defined borders can help differentiate BA from other benign lesions such as bronchial papillomas and peribronchial metaplasia.
Alma Oskarsdottir, M.D.
Resident, Anatomic & Clinical Pathology
Joanne (Eunhee) Yi, M.D.
Consultant, Anatomic Pathology
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science