Pulmonary alveolar proteinosis with atypical clinical and bronchoscopic features

A man in his 40s presented with a 6-month history of progressive exertional dyspnoea. Initial evaluation, including high-resolution CT, which, while demonstrating some findings consistent with crazy-paving, was interpreted as a cellular non-specific interstitial pneumonia pattern when coupled with relative peripheral sparing. Furthermore, bronchoalveolar lavage yielded completely clear fluid with negative periodic acid-Schiff staining, leading to a working diagnosis of interstitial pneumonia with autoimmune features, a research classification. Treatment with prednisone and nintedanib proved ineffective, and his symptoms worsened. Subsequent transbronchial cryobiopsy confirmed pulmonary alveolar proteinosis (PAP). Crucially, anti-granulocyte-macrophage colony-stimulating factor antibodies were negative, establishing a diagnosis of idiopathic PAP. Inhaled recombinant human granulocyte-macrophage colony-stimulating factor led to significant clinical and radiological improvement. This case underscores the diagnostic challenges of PAP with atypical features and highlights the pivotal role of lung biopsy in unresolved interstitial lung disease.