Abstract Background Spontaneous pneumothorax, ranging from minor to life-threatening, is a common hospital presentation, yet the underlying etiology is often overlooked. Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease that primarily affects women of reproductive age and can present with recurrent pneumothorax or progressive dyspnea. Case Presentation A 42-year-old female with no significant PMH presented with acute-onset, pleuritic left-sided chest pain and exertional dyspnea. She denied trauma or recent long-distance travel. Vitals were stable, with absent breath sounds in the left upper lung field. Chest imaging showed a large pneumothorax occupying one-third of the hemithorax with diffuse cystic lung disease and scattered emphysematous blebs. A chest tube was placed, resulting in symptom resolution. She denied smoking, toxic exposures, or a family history of lung disease. Autoimmune panel, alpha-1 antitrypsin, HIV, and sweat chloride testing were negative. Repeat CT showed diffuse thin-walled cysts in all lung lobes. CT abdomen was negative for renal angiomyolipoma. PFTs and echocardiogram were normal. Her serum VEGF-D level was 444 pg/ml. Given that her serum VEGF-D level was not diagnostic, she underwent wedge resection of her left upper lobe. Immunohistochemistry demonstrated cystic spindle cell proliferation positive for smooth muscle actin and patchy HMB-45 staining. These findings were consistent with LAM. Given preserved lung function and symptom resolution, a conservative approach was adopted. She was referred to a cystic lung disease center to assess the need for mTORC1 inhibitor therapy. Discussion Lymphangioleiomyomatosis is characterized by the proliferation of abnormal smooth muscle-like cells that cause cystic lung destruction and may occur sporadically or with tuberous sclerosis complex. Although dyspnea is common, pneumothorax may be the initial presentation, especially in women aged 30-50. A definitive diagnosis can be made radiographically without biopsy if accompanied by elevated VEGF-D (≥800 pg/mL), renal angiomyolipoma, lymphangioleiomyoma, or chylous effusions. However, in cases where VEGF-D is nondiagnostic (600 pg/ml) or imaging findings are indeterminate, lung biopsy remains the gold standard for confirmation. Histopathology typically demonstrates cystic remodeling with abnormal spindle-shaped or epithelioid smooth muscle cells expressing markers such as HMB-45, smooth muscle actin, and desmin, as seen in this patient. The clinical course of LAM is highly variable and requires individualized management. mTORC1 inhibitors are the current standard of care, shown to reduce lung function decline, chylous accumulation, and angiomyolipoma growth. Early identification of LAM as the etiology of spontaneous pneumothorax is critical and should be considered at initial presentation, not only after recurrence. This abstract is funded by: None
Karn et al. (Fri,) studied this question.