Bronchiolar adenoma-like lesions with atypical features beyond the classic morphological spectrum: integrating histomorphology and molecular profiles.

Bronchiolar adenoma (BA) is a rare benign pulmonary neoplasm defined by a bilayered architecture with a continuous basal cell layer. Increasingly, BA-like lesions with atypical features have been recognized, challenging established diagnostic boundaries and raising questions regarding their malignant potential. In this study, we investigated the clinicopathological and molecular characteristics of such lesions. We retrospectively analyzed 19 BA-like lesions that retained at least focal classic BA morphology and exhibited one or more predefined atypical features, including basal cell hyperplasia (with or without squamous dysplasia), partial-to-complete loss of the basal cell layer, stromal-like growth, cytological atypia exceeding classic BA, or morphologically contiguous carcinoma components. Patients showed a broad age distribution with a slight female predominance, and all cases with available follow-up remained disease-free following complete surgical resection (median 29.6 months; range 5-64 months). Histologically, atypical changes involved both basal and luminal compartments, resulting in mixed biphasic and monolayered areas, stromal-like growth, squamous metaplasia or dysplasia, and variable degrees of cytological atypia. Whole-exome sequencing (10 cases) and targeted profiling (two cases) revealed heterogeneous genetic alterations, including driver events involving BRAF, EGFR, and MET, as well as recurrent mutations affecting HRAS, PIK3CA, MTOR, DNA repair genes, and epigenetic regulators. Pathogenic TP53 mutations were confined to lesions with marked epithelial atypia. At the pathway level, MAPK alterations, including HRAS mutations, were enriched in basal-hyperplasia lesions, whereas PI3K/AKT/mTOR alterations were more frequent in basal-deficient lesions. These findings support the concept that BA-like lesions with atypical features represent a morphological continuum ranging from benign BA to malignant lesions. We further propose a pragmatic framework for diagnosis and clinical management, although validation in larger cohorts with longer follow-up is required. © 2026 The Pathological Society of Great Britain and Ireland.