Lymphangioleiomyomatosis is a rare disease characteristically found in women of childbearing age, presenting with shortness of breath, cough, recurrent pneumothoraces, and chylothorax. Patients demonstrate accumulation of atypical or immature smooth muscle cells along lung and pleural lymphatics. Lymph nodes in the mediastinum, abdomen, and lower cervical chain may also be involved. Clinical history and radiologic features are typically helpful in the diagnosis. Pathogenesis is unknown, and most patients die due to progressive respiratory failure within 10 years. Similar histologic findings occur in women with tuberous sclerosis, and approximately 30% of tuberous sclerosis patients have lymphangioleiomyomatosis.

Lymphangioleiomyomatosis is most frequently identified on wedge biopsy, but even then the lesions may be subtle and easily overlooked. Occasionally, though, lymphangioleiomyomatosis can be diagnosed on transbronchial biopsy. Characteristic lesions composed of a disorderly proliferation of atypical, spindled, or occasionally epithelioid smooth muscle cells involve alveolar septa, bronchioles, vessels, or lymphatic spaces. The smooth muscle cells may form nodules, with associated air trapping and cyst formation; and blood vessel involvement may cause hemorrhage with associated hemosiderin-laden macrophages. Any of these features may dominate the biopsy findings. When air trapping and cysts predominate and the smooth muscle proliferation is subtle, the findings may suggest emphysema.

If the diagnosis of lymphangioleiomyomatosis is clinically suspected, immunostains may help diagnose lymphangioleiomyomatosis when the transbronchial biopsy is without diagnostic features on hematoxylin and eosin (H&E) stain. HMB-45 selectively stains the abnormal smooth muscle cells but not normally occurring smooth muscle. Estrogen receptor, progesterone receptor, desmin, actin, and MART1 immunopositivity also may occur in the lesions.