False positive serum vascular endothelial growth factor-D in a patient with Birt-Hogg-Dubé syndrome

Diffuse cystic lung diseases (DCLDs) are a heterogeneous group of disorders requiring careful evaluation due to distinct management and prognostic implications. A 32-year-old woman presented with dyspnea and chest pressure following a coughing episode and was found to have a right-sided pneumothorax. CT chest showed bilateral, small, round-elliptiform, basal-predominant cysts. Workup, including autoimmune serologies and abdominal imaging, was unrevealing. Serum vascular endothelial growth factor (VEGF)-D was elevated at 839pg/ml, supporting a clinical diagnosis of lymphangioleiomyomatosis (LAM). However, critical re-evaluation of cyst morphology was more suggestive of Birt-Hogg-Dubé syndrome (BHD). Genetic testing revealed a pathogenic folluculin gene mutation, thus confirming the diagnosis of BHD. Surgical lung biopsy, obtained afterwards at the time of elective pleurodesis, did not reveal features of LAM. This case represents a rare instance of falsely elevated VEGF-D in patient with non-LAM DCLD and highlights the importance of critical review of chest radiology in the diagnostic evaluation of patients with cystic lung disease.