Diffuse Cystic Lung Diseases: Imaging Patterns and Differential Diagnosis

Abstract: Diffuse cystic lung diseases (DCLDs) comprise a heterogeneous group of disorders characterized by multiple pulmonary cysts with overlapping clinical and radiologic manifestations. Accurate diagnosis relies on recognizing characteristic imaging patterns in conjunction with clinical and extrapulmonary findings. High-resolution computed tomography (HRCT) plays a central role in distinguishing true pulmonary cysts from common cyst mimickers, including emphysema, bullae, cavities, pneumatoceles, cystic bronchiectasis, and honeycombing, thereby narrowing the differential diagnosis. This review summarizes the imaging features of the major DCLDs encountered in adults, including lymphocytic interstitial pneumonia, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, and folliculin deficiency-associated disease (formerly Birt-Hogg-Dubé syndrome). Emphasis is placed on cyst morphology, craniocaudal distribution, associated parenchymal abnormalities, and characteristic extrapulmonary manifestations that facilitate diagnosis. The underlying pathophysiologic mechanisms responsible for cyst formation and their relationship to imaging appearances are also discussed. In addition, the review highlights important clinical features, including smoking history, autoimmune disease, genetic predisposition, and systemic involvement, which help refine the differential diagnosis. An integrated pattern-recognition approach combining HRCT findings with clinical context allows confident differentiation of the major DCLDs in most patients while reducing the need for invasive diagnostic procedures. Awareness of ancillary imaging findings and less common cystic lung disorders is essential when the imaging pattern is atypical or overlaps with other diffuse pulmonary diseases. A systematic understanding of characteristic imaging appearances and associated extrapulmonary manifestations enables radiologists and clinicians to establish an accurate diagnosis, guide appropriate genetic and clinical evaluation, and optimize patient management.