Beyond Infection and Malignancy: Diagnostic Pitfalls in Pulmonary Granulomatosis with Polyangiitis

Granulomatosis with polyangiitis (GPA) is a rare but potentially life-threatening antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis. It frequently presents with pulmonary manifestations that mimic infection or malignancy, leading to significant diagnostic delays. We describe three cases that illustrate the broad clinical, radiologic, and pathologic spectrum of GPA and highlight common diagnostic pitfalls. The first case involves a hypermetabolic cavitary lung mass initially suspected to represent primary lung cancer; the second highlights the development of lymphoproliferative malignancy in a patient with longstanding GPA receiving chronic immunosuppressive therapy; and the third demonstrates how partial responses to corticosteroids and empiric antibiotics can mask ongoing vasculitic activity, resulting in delayed diagnosis despite progressive cavitary lung disease. Across cases, nonspecific imaging findings, inconclusive or misleading biopsies, and delayed or incomplete serologic evaluation further complicated early recognition. This case series underscores that maintaining a high index of suspicion for GPA, together with a multidisciplinary approach to interpreting often ambiguous clinical, serologic, radiologic, and pathologic data, is critical to avoiding diagnostic delay and improving patient outcomes.