Abstract Introduction Granulomatosis with polyangiitis (GPA), a rare systemic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, is characterized by necrotizing granulomatous inflammation and vasculitis predominantly affecting small- to medium-sized vessels in the upper and lower respiratory tracts, with frequent renal involvement. Diagnosis integrates clinical, radiographic, histopathological, and serologic features; however, pulmonary-dominant manifestations can radiologically simulate malignancy, posing substantial diagnostic challenges. Case Report A 67-year-old woman with hypertension presented with dyspnea, hemoptysis, sinus congestion, and pleuritic chest pain. Contrast-enhanced chest computed tomography angiography (CTA) demonstrated more than 20 bilateral pulmonary nodules, the largest measuring 5.9 cm, alongside bulky mediastinal lymphadenopathy. Subsequent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) exhibited intense FDG avidity (maximum standardized uptake value SUVmax 11.6) in the pulmonary nodules and lymph nodes, heightening suspicion for metastatic pulmonary malignancy. Bronchoscopic biopsies of lung parenchyma and mediastinal lymph nodes revealed granulomatous inflammation with associated multinucleated giant cells, fibrinous organizing pneumonia and focal acute inflammation, microabscesses, focal increased eosinophils and acute lung injury without any demonstrable necrotizing vasculitis. Comprehensive serologic evaluation confirmed positivity for cytoplasmic-ANCA (c-ANCA), perinuclear-ANCA (p-ANCA), and anti-proteinase 3 (PR3) antibodies. In the absence of cutaneous or renal involvement, the constellation of clinical, radiographic, histopathologic, and serologic findings supported a diagnosis of limited GPA. The patient exhibited rapid clinical improvement and near-complete radiographic resolution of pulmonary nodules and lymphadenopathy following initiation of corticosteroids, with subsequent transition to rituximab for induction and maintenance therapy. Discussion This case exemplifies an atypical, organ-limited presentation of GPA without its characteristic mucocutaneous or glomerulonephritic features, manifesting instead as multifocal bilateral pulmonary nodules and mediastinal lymphadenopathy with exceptionally high FDG uptake mimicking metastatic carcinoma. Although 18F-FDG PET/CT demonstrates high sensitivity for detecting metabolically active lesions, its limited specificity precludes differentiation between neoplastic and inflammatory etiologies in GPA. The histopathological findings of inflammation, necrosis, eosinophils, and giant cells—without overt necrotizing vasculitis—further underscore sampling challenges in granulomatous vasculitides, where focal lesions may evade definitive vascular involvement on biopsy. Prompt recognition of GPA within the differential diagnosis for FDG-avid pulmonary masses is imperative to avert misdiagnosis and expedite targeted immunosuppression. This report highlights the pivotal role of multidisciplinary evaluation, including ANCA serologies and therapeutic trial response, in resolving diagnostic ambiguity and optimizing outcomes in such masquerading vasculitides. This abstract is funded by: None
Kaur et al. (2026) studied this question.