Cyst-predominant nonfibrotic hypersensitivity pneumonitis mimicking Birt-Hogg-Dubé syndrome.

Hypersensitivity pneumonitis (HP) is classified into fibrotic and nonfibrotic phenotypes. Rarely, nonfibrotic HP presents radiologically with multiple cysts. Histologically, nonfibrotic HP is characterized by cellular interstitial pneumonia, cellular bronchiolitis, and poorly formed non-necrotizing granulomas; however, the histopathological features and mechanisms underlying cyst formation remain poorly understood. We report a rare case of cyst-predominant nonfibrotic HP. A 42-year-old woman underwent pulmonary surgery for enigmatic lung cysts complicated by spontaneous pneumothorax. Histological examination revealed subpleural cystic lesions mimicking those of Birt-Hogg-Dubé syndrome and an absence of cellular interstitial pneumonia, a feature considered mandatory in current HP guidelines. Despite this, the presence of cellular bronchiolitis, microgranulomas, and supportive clinical findings led to a diagnosis of nonfibrotic HP following multidisciplinary discussion. This case underscores a significant diagnostic pitfall, as cyst-predominant nonfibrotic HP may be overlooked by clinicians and pathologists and misdiagnosed as Birt-Hogg-Dubé syndrome or other cystic lung diseases.