Navigating a cyst-astrophe: the diagnostic challenge of cystic lung disease

SESSION TITLE: Diffuse Lung Disease: It's Not What You Think SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/10/2023 09:40 am - 10:25 am INTRODUCTION: Diffuse cystic lung diseases (DCLDs) refer to a group of conditions characterized by the presence of thin-walled, air-filled lucencies within the pulmonary parenchyma. The differential diagnosis for DCLDs encompasses a variety of diseases categorized by underlying pathophysiology and patterns observed on computed tomography (CT). Early focus on narrowing the differential diagnosis has important prognostic and treatment-related implications.1-2 CASE PRESENTATION: A 32-year-old female never-smoker presented with pleuritic chest pain one year after delivering her second child and was subsequently diagnosed with a spontaneous pneumothorax. Her family history was negative for pulmonary, renal, or dermatologic disorders. She denied sicca symptoms and exhibited no abnormal cutaneous or pulmonary exam findings. Results of a serologic rheumatologic evaluation, including ANA and anti-SSA/SSB, were negative. A CT chest revealed bilateral, lower lobe-predominant perivascular and subpleural cysts (Figure 1); CT of the abdomen and pelvis showed no signs of angiomyolipoma, other renal masses, or uterine lesions. Serum VEGF-D level was normal. The patient subsequently underwent a video-assisted thoracic surgery with pleurodesis, bullectomy, and wedge biopsy (Figure 2). Histopathology did not reveal the presence of lymphangioleiomyomatosis (LAM) cells (Figure 3), and genetic testing of the tissue did not yield mutations in TSC or FLCN; however, serum genetic testing identified a pathogenic variant in the FLCN gene, which confirmed a diagnosis of Birt-Hogg-Dubé (BHD) syndrome. DISCUSSION: This case report highlights the presentation of a premenopausal woman with no relevant family history who developed a spontaneous pneumothorax and bilateral lower lobe-predominant pulmonary cysts postpartum. These findings initially raised the clinical pre-test probability for LAM, as her presentation was consistent with a typical phenotype for this condition; however, serum VEGF-D testing and histopathologic staining of her lung tissue for Melan A—a LAM cell marker—were both negative. Serum genetic testing subsequently revealed a pathogenic FLCN gene mutation, leading to a diagnosis of BHD syndrome.BHD syndrome is an inherited autosomal dominant disorder caused by mutations in the FLCN gene. It can present clinically with recurrent spontaneous pneumothorax, diffuse pulmonary cysts, renal tumors, and cutaneous fibrofolliculomas. Up to 80% of BHD patients exhibit multiple bilateral pulmonary cysts and, less commonly, present with absent cutaneous or renal involvement, which was the case in this report.3 CONCLUSIONS: It is essential to consider BHD syndrome as a potential diagnosis for patients presenting with multiple bilateral pulmonary cysts and recurrent pneumothoraces, even in the absence of hallmark cutaneous and renal manifestations. This consideration is especially critical as early recognition and diagnosis of BHD syndrome may facilitate appropriate patient management, including screening for renal tumors and genetic counseling. REFERENCE #1: Gupta N, Vassallo R, Wikenheiser-Brokamp KA, McCormack FX. Diffuse Cystic Lung Disease. Part II. Am J Respir Crit Care Med. 2015 Oct 1;192(7):17-29. doi: 10.1164/rccm.201503-0461CI. PMID: 25906202. REFERENCE #2: Gupta N, Vassallo R, Wikenheiser-Brokamp KA, McCormack FX. Diffuse Cystic Lung Disease. Part I. Am J Respir Crit Care Med. 2015 Oct 1;192(7):750-761. doi: 10.1164/rccm.201503-0453CI. PMID: 25906201. REFERENCE #3: Daccord C, Good JM, Morren MA, Bonny O, Hohl D, Lazor R. Birt-Hogg-Dubé syndrome. Eur Respir Rev. 2020 Sep 30;29(157):200042. doi: 10.1183/16000617.0042-2020. PMID: 32998969. DISCLOSURES: No relevant relationships by Jane Dematte D Amico No relevant relationships by Anthony Esposito No relevant relationships by Kevin Grudzinski No relevant relationships by Anjana Yeldandi