Case Presentation: A 76-year-old woman, presented with seven months of progressive exertional dyspnea, 20-pound weight gain, and worsening left lower extremity edema . Past medical history is notable for acute myeloid leukemia status post allogeneic stem cell transplant (2015), complicated by chronic graft-versus-host disease (GVHD) involving the eyes, mouth, and liver, autoimmune hepatitis, chronic kidney disease, and type 2 diabetes. Pulmonary function tests revealed decreased FEV1, FVC, and DLCO (45% from 84% four years prior). Chest CT demonstrated bilateral diffuse ground-glass opacities. Bronchoscopy with bronchoalveolar lavage was negative for infection and malignancy. Cryobiopsy was obtained to rule out GVHD.While pathology results were pending, an Echocardiogram was obtained to evaluate for possible cardiac contribution, which revealed right ventricular enlargement, tricuspid regurgitation, and IVC dilation. BNP was also elevated. These changes were believed to be secondary to her pulmonary disease. Cryobiopsy revealed intra-alveolar accumulations of periodic acid–Schiff–positive proteinaceous material, confirming the diagnosis of pulmonary alveolar proteinosis. GM-CSF antibodies were obtained to differentiate primary versus secondary PAP. While awaiting results, the patient was started on inhaled recombinant GM-CSF (administered every other week) pending GM-CSF antibody testing. Ultimately, GM-CSF testing was negative, confirming secondary PAP. She initially reported symptomatic improvements while on the inhaled GM-CSF, but five months later, she continued to have dyspnea, with worsening DLCO (35%) and progression of bilateral ground-glass opacities on CT. A whole lung lavage (WLL) was successfully performed, resulting in symptomatic improvement.
Discussion: Secondary pulmonary alveolar proteinosis (PAP) is a rare but serious complication of hematologic malignancies. Because radiographic and bronchoalveolar lavage findings are frequently nonspecific, diagnosis relies on maintaining a high index of suspicion and obtaining tissue confirmation. Management primarily focuses on treating the underlying disorder. Whole lung lavage (WLL) can provide symptomatic relief and has shown benefit in selected patients; however, responses are variable and often limited in those with advanced disease or ongoing immunosuppression. Unlike autoimmune PAP, secondary PAP does not arise from GM-CSF dysfunction, and evidence does not support the use of inhaled GM-CSF in this setting. This case highlights the importance of multidisciplinary collaboration to ensure timely diagnosis and optimizing outcomes for patients with secondary PAP.
Conclusions: Secondary PAP should be considered in patients with a history of hematologic malignancy with unexplained progressive dyspnea and diffuse ground-glass opacities. Early recognition and intervention are crucial to optimizing outcomes and preventing respiratory failure.