リンパ脈管筋腫症

BACKGROUND: Diffuse cystic lung disease (DCLD) in women of reproductive age is often attributed to lymphangioleiomyomatosis (LAM), but malignancy should be considered when atypical features are present. CASE DESCRIPTION: We report the case of a 27-year-old never-smoking woman initially diagnosed with LAM based on high-resolution computed tomography (HRCT) findings, who was subsequently found to have metastatic lung adenocarcinoma on supraclavicular lymph node biopsy. Her first HRCT showed diffuse thin-walled lung cysts, and in 6 months, the second HRCT showed diffuse cysts (2-14 mm) with heterogeneous cyst-wall thickness plus a left upper-lobe patchy opacity, as well as beaded pleural-based fissural nodules in the right lung. Meanwhile, her serum carcinoembryonic antigen (CEA) was 21.96 ng/mL and the supraclavicular node biopsy confirmed metastatic lung adenocarcinoma (cT4N3M1a, stage IVA). DNA-based next-generation sequencing (NGS) identified an EZR-ROS1 rearrangement. After 8 months of crizotinib therapy, she achieved a partial response (PR) with CEA normalization. As of 77 months after treatment initiation, the patient maintains a PR without progression or documented acquired resistance. CONCLUSIONS: In a LAM-like cystic background, the presence of superimposed focal opacities or nodules, fissural beading, and heterogeneous cyst-wall thickness should prompt an expedited malignancy work-up rather than an HRCT-only diagnosis, as this case demonstrates that systematic evaluation of atypical features in presumed LAM can identify treatable oncogene-driven malignancies amenable to highly effective targeted therapy.

Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant disorder characterized by a classic triad of cutaneous fibrofolliculomas, bilateral pulmonary cysts and renal tumours. Pulmonary manifestations may occur in isolation, posing a significant diagnostic challenge. We report a 50-year-old non-smoking woman with recurrent pneumothorax referred to our pulmonology clinic for dyspnoea on exertion. Chest CT revealed multiple bilateral pulmonary cysts with lower-lobe predominance. Review of prior wedge resection specimens showed subpleural and parenchymal cysts lined by flattened epithelium. Negative immunohistochemical staining for HMB-45 and GPNMB excluded lymphangioleiomyomatosis. Given the characteristic cyst pattern, germline whole-exome sequencing identified a pathogenic heterozygous FLCN frameshift variant, confirming the diagnosis. Because of the lifetime risk of renal malignancy, early recognition is important and genetic testing is recommended when BHD is suspected.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder characterized by multiple pulmonary cysts, predisposing individuals to spontaneous pneumothorax, cutaneous lesions-specifically fibrofolliculomas-and an increased risk of renal malignancies. Although diagnosing BHD is difficult due to the variable presentation of the disease, identification is crucial for proper management, which includes lifelong screening for renal malignancies and management of recurrent pneumothoraces. Despite its rarity, maintaining awareness of BHD in the differential diagnosis of pulmonary cysts is essential. CASE PRESENTATION: We present the case of a nonsmoking male veteran in his 60s whose BHD diagnosis surfaced many years after a history of recurrent pneumothoraces, leading to 1 pleurodesis in each lung. Genetic testing of the FLCN gene confirmed the BHD diagnosis. A shave biopsy of a skin lesion confirmed a histologic pattern of fibrofolliculoma/trichodiscoma. Annual magnetic resonance imaging surveillance was initiated to monitor for potential renal malignancies. CONCLUSIONS: BHD is a rare and complex disease. Early recognition and diagnosis play a pivotal role in preventing potentially severe complications such as renal malignancies. Suspicion for a genetic disorder such as BHD, lymphangioleiomyomatosis, or pulmonary Langerhans cell histiocytosis should arise in patients who experience spontaneous pneumothorax, especially in the presence of multiple cystic lesions or a family history of pneumothoraces. Early consideration of pleurodesis after the first spontaneous pneumothorax is recommended. The complex presentation of BHD may delay recognition, which can be exacerbated by variable continuity of care.

BACKGROUND: Pleural complications remain a major source of morbidity after lung transplantation, with chylothorax posing particular therapeutic challenges. When complicated by fibrinous septation, effective drainage becomes difficult, often necessitating intrapleural fibrinolytic therapy (IPFT). However, in the early post-transplant period, blind fibrinolysis carries substantial risks, including hemorrhage and disruption of fragile bronchial anastomoses or lymphatic vessels. CASE DESCRIPTION: We report a 31-year-old woman with pulmonary lymphangioleiomyomatosis (PLAM) who developed refractory loculated chylothorax 39 days after bilateral lung transplantation. Initial chemical pleurodesis was ineffective and subsequently induced a honeycomb-like, non-communicating pleural effusion that was not amenable to conventional drainage. To balance the need for septation lysis against the risk of bleeding, contrast-enhanced ultrasound (CEUS) was integrated as a real-time guidance tool. CEUS facilitated the precise differentiation between avascular fibrin septa and vascularized pleural tissue, allowing targeted low-dose urokinase injection into isolated locules. The restoration of inter-locule communication was directly visualized, permitting early termination of fibrinolytic exposure. Subsequent drainage and repeat pleurodesis resulted in full lung re-expansion without recurrence. CONCLUSIONS: To our knowledge, this is the first case utilizing CEUS to guide precision fibrinolysis in a lung transplant recipient. This case provides a proof-of-concept that CEUS-guided precision fibrinolysis can transform a traditionally blind and high-risk intervention into a controlled, visualization-driven procedure. By enabling targeted intervention and real-time efficacy assessment, this approach offers a safer salvage strategy for high-risk patients.

Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease that primarily affects women of reproductive age. The disease may involve extrapulmonary sites, including the lymphatic system, and can present with a lymphocyte-predominant pleural effusion mimicking tuberculosis. We report a 35-year-old woman who presented with a three-year history of progressive dyspnea and recurrent lymphocyte-predominant exudative pleural effusions. She was empirically started on anti-TB therapy at a local hospital but showed no clinical improvement. Upon evaluation at a tertiary center, there was decreased air entry over the posterior third of the chest. Repeat pleural fluid analysis demonstrated a milky appearance with elevated triglyceride levels, consistent with chylous effusion. High-resolution CT showed diffuse, bilateral, thin-walled pulmonary cysts and bilateral pleural effusion with retroperitoneal lymphatic involvement, which confirmed the diagnosis of LAM. Treatment with sirolimus was started and showed significant clinical improvement, but the patient discontinued therapy after two months due to financial constraints. In this patient, LAM presented as tuberculous pleuritis that delayed the definitive diagnosis. This should alert clinicians in high TB burden settings to consider this rare disease in reproductive-aged women who present with progressive dyspnea and a lymphocyte-predominant pleural effusion, particularly when there is no response to anti-TB therapy.