Pulmonary alveolar proteinosis diagnosed during leuprorelin acetate therapy for ovarian endometrioma: a case report

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disorder characterized by impaired surfactant clearance due to alveolar macrophage dysfunction. Leuprorelin acetate, a gonadotropin-releasing hormone agonist, is widely used in the treatment of ovarian endometriosis; however, pulmonary findings associated with this therapy have not been well characterized. We report a case of PAP diagnosed during leuprorelin acetate therapy for ovarian endometrioma and describe its temporal relationship with treatment.

A 29-year-old woman underwent laparoscopic surgery for an ovarian endometrioma in August 2025 and initiated leuprorelin acetate therapy three days postoperatively. A routine chest computed tomography (CT) performed one month later revealed scattered bilateral ground-glass opacities (GGOs), which persisted on repeat CT in November 2025. Although the patient remained asymptomatic, video-assisted thoracoscopic surgery (VATS) lung biopsy was performed to obtain a histopathological diagnosis and confirmed PAP. Serum anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody testing was negative (3.2 µg/mL; reference range, ≤ 5 µg/mL), not supporting autoimmune PAP. During treatment, the patient developed transient Common Terminology Criteria for Adverse Events (CTCAE) grade 2 leukopenia (white blood cell nadir, 2.94 × 10⁹/L), which resolved spontaneously after completion of leuprorelin acetate therapy without intervention. Hematological evaluation did not suggest an underlying clonal disorder, including myelodysplastic syndrome. Because baseline chest imaging was unavailable, pre-existing subclinical PAP could not be excluded. Follow-up CT performed three months after completion of therapy showed regression of GGOs.

This case shows a temporal relationship between leuprorelin acetate therapy and non-autoimmune PAP. However, causality cannot be inferred in the absence of baseline imaging. Only a temporal association can be observed. This observation is hypothesis-generating and highlights a potential rare pulmonary finding observed in the context of gonadotropin-releasing hormone agonist therapy.