[Clinical and molecular characteristics of bronchial adenoma: an analysis of 88 cases]

Objective: To investigate the clinicopathological features, gene mutations, and distribution of bronchial adenoma (BA). Methods: Eighty-eight cases of BA diagnosed via routine section diagnosis between May 2015 and February 2024 were collected at the Pathology Departments of Zhongshan Hospital Affiliated to Fudan University (71 cases), Shanghai, China and Jining No.1 People's Hospital (17 cases), Jining, China. Clinical data, image features, histopathological sections, immunohistochemical stains, and genetic testing results were reviewed. Results: Among the 88 patients with BA, there were 36 males and 52 females. The incidence of proximal-type BA was the same in both genders (50%, 28/56), while distal-type BA was more commonly found in females (75%, 24/32, P=0.022). BA predominantly affected middle-aged and elderly adults, with an age range of 30-78 years (median, 61 years). Clinically, BA generally presented without obvious symptoms. Radiologically it mainly manifested as peripheral lung ground-glass nodules, mixed ground-glass nodules, or solid nodules, primarily located in the lower lobes of the lungs (72.7%, 64/88). Proximal-type BA was characterized by solid nodules (53.6%, 30/56), while distal-type BA by ground-glass nodules (56.3%, 18/32), with a statistically significant difference between the two types (P<0.01). The tumor was non-encapsulated, with a gray-white cut surface, and some areas were gray-brown. In 18.2% (16/88) of cases, the cut surface was slippery, with soft to medium-firm consistency and poorly defined margins. The smooth texture was predominantly found in proximal-type BA (14/16), whose tumor diameters ranged from 0.2 to 4.6 cm. Microscopically, the lesions exhibited glandular, papillary, or relatively flat patterns, with the main cellular components consisting of basal cells, ciliated columnar cells, mucinous cells, and alveolar epithelial cells in various proportions. Proximal-type BA resembled the morphology of proximal bronchioles and commonly contained mucinous and ciliated cells, while distal-type BA typically lacked mucinous and ciliated cells. The frequency of ciliated cell micropapillae in proximal-type BA (64.3%, 36/56) was significantly higher than that in distal-type BA (31.3%, 10/32, P=0.003). The morphological manifestation of glandular duct dilation was more commonly noted in proximal-type BA (98.2%, 55/56) than that in distal-type BA (81.25%, 26/32, P=0.009). Overall, the disagreement rate between frozen-section and routine diagnoses was 19.5% (17/87). Immunohistochemistry for cytokeratin 5/6 (CK5/6) and p40 showed that basal cell continuity in proximal-type BA (82.1%, 46/56) was significantly higher than that in distal-type BA (56.2%, 18/32, P=0.009). Molecular testing showed an accumulative gene mutation rate of 60.5% (23/38) in BA, including mutations in BRAF V600E (34.2%, 13/38), KRAS (18.4%, 7/38), ALK (5.3%, 2/38), and EGFR (2.6%, 1/38). Proximal-type BA was associated with BRAF V600E mutations, while distal-type BA with KRAS mutations (P=0.025). Conclusions: BA is a rare benign bronchial tumor and has a high diagnostic error-rate on intraoperative frozen section. Proximal-type BA often presents with ciliated cell micropapillae, which supports the diagnosis, while distal-type BA frequently shows a partial reduction or absence of basal cells, increasing the diagnostic difficulty. The different subtypes of BA exhibit distinct genetic (mutation) profiles that may assist in its diagnosis and histological classification.