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

Background 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. Case presentation 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. Similar content being viewed by others Abbreviations - AKA: - Anti-keratin antibody - Alb: - Albumin - ALP: - Alkaline phosphatase - ALT: - Alanine aminotransferase - ANA: - Antinuclear antibody - Anti-CCP: - Anti-cyclic citrullinated peptide antibody - Anti-CENP-B: - Anti-centromere protein B antibody - Anti-dsDNA: - Anti–double-stranded DNA antibody - Anti-Jo-1: - Anti–histidyl-tRNA synthetase antibody - Anti-P0: - Anti-ribosomal P0 antibody - Anti-PM-Scl: - Anti–polymyositis/scleroderma antibody - Anti-Ro52: - Anti-Ro52 antibody - Anti-Scl70: - Anti–scleroderma 70 antibody (anti–topoisomerase I) - Anti-Sm: - Anti-Smith antibody - Anti-SSA: - Anti–Sjögren’s-syndrome-related antigen A antibody (anti-Ro) - Anti-SSB: - Anti–Sjögren’s-syndrome-related antigen B antibody (anti-La) - Anti-U1-RNP: - Anti–U1 small nuclear ribonucleoprotein antibody - ASO: - Antistreptolysin O - AST: - Aspartate aminotransferase - BAL: - Bronchoalveolar lavage - BPI: - Bactericidal/permeability-increasing protein - C3: - Complement component 3 - C4: - Complement component 4 - CEA: - Carcinoembryonic antigen - CG: - Cathepsin G - Cl: - Chloride - Cre: - Creatinine - CRP: - C-reactive protein - CT: - Computed tomography - CTCAE: - Common Terminology Criteria for Adverse Events - CYFRA: - Cytokeratin 19 fragment (CYFRA 21-1) - ELISA: - Enzyme-linked immunosorbent assay - ESR: - Erythrocyte sedimentation rate - GGOs: - Ground-glass opacities - GM-CSF: - Granulocyte-macrophage colony-stimulating factor - GnRH agonist: - Gonadotropin-releasing hormone agonist - HBG: - Hemoglobin - H&E: - Hematoxylin and eosin - IgA: - Immunoglobulin A - IgG: - Immunoglobulin G - IgM: - Immunoglobulin M - IgE: - Immunoglobulin E - K: - Potassium - LF: - Lactoferrin - MPO: - Myeloperoxidase - Na: - Sodium - PAP: - Pulmonary alveolar proteinosis - PAS: - Periodic acid-Schiff - PLT: - Platelet count - PR3: - Proteinase 3 - RBC: - Red blood cell count - RF: - Rheumatoid factor - T-Bil: - Total bilirubin - TB-IGRA: - Tuberculosis interferon-gamma release assay - TP: - Total protein - Urea: - Urea - VATS: - Video-assisted thoracoscopic surgery - WBC: - White blood cell count Funding This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors. Author information Authors and Affiliations Corresponding author Ethics declarations Ethics approval and consent to participate Not applicable. Consent for publication Written informed consent for publication of this case report and any accompanying images was obtained from the patient. A copy of the written consent is available for review by the Editor of this journal. Competing interests The authors declare no competing interests. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. About this article Cite this article Gao, X., Wang, L., Li, Z. et al. Pulmonary alveolar proteinosis diagnosed during leuprorelin acetate therapy for ovarian endometrioma: a case report. BMC Pulm Med (2026). https://doi.org/10.1186/s12890-026-04507-5 Received: Accepted: Published: DOI: https://doi.org/10.1186/s12890-026-04507-5