Pulmonary cysts as a diagnostic indicator of Birt-Hogg-Dubé syndrome in patients with renal neoplasm

Abstract Objectives To assess the presence and CT features of pulmonary cysts (PCs) in patients with renal neoplasms (RN) as a hallmark of Birt-Hogg-Dubé syndrome (BHDS). Materials and methods Single institution retrospective study of all patients with histological RN between May 2014 and May 2020. Individuals with non-renal neoplasm, nephroblastoma, benign cysts, < 18 years old, or without thoracic CT were excluded. Demographics, history of smoking, pneumothorax and cutaneous fibrofolliculomas/trichodischomas, family history of pneumothorax or RN, and genetic testing were recorded. Number, location, distribution and morphology of PCs were assessed on thoracic CT. Differences between patients with positive (BHD+) and negative (BHD−) genetics were analysed. An independent cohort of 10 BHDS patients was added to calculate the diagnostic accuracy of cyst features. Results Of 1475 patients with RN, 127 (8.6%) had PCs; 40 underwent genetic testing (median age 56 [49–68], 28 men), and 6/127 (4.7%) individuals tested positive for BHDS. BHD+ had significantly more and larger cysts, affecting more lobes (p < 0.01). Higher prevalence of PCs with a perivascular (100% vs. 37%; p = 0.01) and interlobular septal location (100% vs. 16%; p < 0.001), and perilymphatic distribution (100% vs. 5%; p < 0.001) was found in BHD+. All BHD+ had elliptical, irregular, and variable shape PCs, compared to a lower prevalence of these in BHD− (p < 0.01). Traversing vein sign was more common in BHD+ (83% vs. 24%; p = 0.01). The highest accuracy was achieved for perilymphatic distribution (97%), followed by irregular shape (94%) and interlobular septal location (91%). Conclusion Specific CT features of PC in patients with RN can be highly indicative of BHDS. Critical relevance statement Radiologists can play a crucial role in the diagnosis of Birt-Hogg-Dubé syndrome (BHDS) by recognising specific CT features of pulmonary cysts; a diagnosis of BHDS has implications for family testing and timely, life-long screening for renal neoplasm. Key Points Birt-Hogg-Dubé syndrome (BHDS) should be considered in patients with renal neoplasms and multiple pulmonary cysts. A lower zone predominant, perilymphatic distribution of pulmonary cysts is a strong indicator of BHDS. Identifying specific CT features of pulmonary cysts can improve recognition of BHDS. Graphical Abstract