Introduction: Real-world evaluation of diffuse cystic lung diseases is essential to improve clinical recognition and guide management strategies.

Objectives: To comprehensively evaluate the clinical characteristics of patients diagnosed with cystic lung diseases in a single-center cohort.

Materials and Methods: This retrospective study included patients diagnosed with lymphangioleiomyomatosis (LAM), pulmonary Langerhans cell histiocytosis (PLCH), Birt–Hogg–Dubé (BHD) syndrome, and lymphocytic interstitial pneumonia (LIP). Data regarding demographics, clinical presentation, treatment modalities, history of pneumothorax, pleural effusion and pleurodesis, as well as survival outcomes were systematically collected.

Results: A total of 35 patients (female/male: 27/8; mean age: 35.8±11.3 years; mean follow-up duration: 73.4±54.6 months) were analyzed. The distribution of diagnoses was PLCH (n=15), LAM (n=12), BHD syndrome (n=5), and LIP (n=3). A positive family history was identified in 5 patients, while 6 reported environmental exposure. Smoking status revealed that 48.6% (n=17) were current smokers and 20% (n=7) were former smokers. Comorbid conditions were present in 37.1% (n=13), with hypertension being the most frequent.

The majority of patients presented with chronic respiratory symptoms (n=24), whereas 7 presented with pneumothorax and 3 with extrapulmonary manifestations (all abdominal pain); only one patient was asymptomatic. Diagnosis was established based on clinical–radiological findings in 14 patients and histopathological confirmation in 21. Among patients with suspected BHD, genetic mutations were identified in 2 of 4 cases.

Pneumothorax developed in 13 patients (11 recurrent), and pleural effusion occurred in 3 (including one chylothorax). Pleurodesis was performed in 11 patients using surgical, talc, or autologous blood techniques. Immunosuppressive therapy was initiated in 16 patients (sirolimus or corticosteroids ± hydroxychloroquine), and one patient received nintedanib. Four patients required long-term oxygen therapy, and seven were referred for lung transplantation. During follow-up, four patients died.

Conclusions: Increasing case series and sharing clinical experience will enhance disease awareness and contribute to the optimization of diagnostic and therapeutic strategies.