Isolated pulmonary IgG4-related disease mimicking infection and malignancy: clinical features and a proposed diagnostic approach.

OBJECTIVES: IgG4-related lung disease (IgG4-RLD) is a rare manifestation that often presents with nonspecific clinical and radiological findings, frequently mimicking pulmonary infection or malignancy. This case series aimed to characterize the clinical, serological, radiological, and pathological features of isolated pulmonary IgG4-RLD and to identify features that may facilitate its differentiation from pulmonary infection and malignancy. METHODS: We reviewed a case series of patients with isolated pulmonary IgG4-RLD diagnosed at the First Affiliated Hospital of Wenzhou Medical University between April 2014 and March 2025. Clinical characteristics, laboratory findings, chest computed tomography (CT) features, histopathological findings, treatment, and follow-up data were analyzed. RESULTS: Eight patients with isolated pulmonary IgG4-RLD were identified. All initially presented with nonspecific respiratory symptoms and were misdiagnosed as having other pulmonary diseases, most commonly pulmonary infection. Serum IgG4 concentrations were elevated in all patients, whereas microbiological investigations and serum tumor markers were negative. Radiologically, four patients presented with solitary pulmonary lesions that frequently mimicked lung malignancy, while the remaining four had multiple lesions suggestive of pulmonary infection. Histopathological examination revealed characteristic features of IgG4-RLD, supporting the diagnosis. Following glucocorticoid-based therapy, five of six treated patients showed radiological improvement, accompanied by decreased serum IgG4 levels, while one patient remained radiologically stable during follow-up. CONCLUSIONS: Isolated pulmonary IgG4-RLD may mimic pulmonary infection or malignancy because of its nonspecific clinical and radiological features. Solitary lesions may raise suspicion for lung malignancy, whereas multiple lesions may be mistaken for pulmonary infection. Diagnosis requires integration of clinical, serological, radiological, and histopathological findings, with tissue biopsy playing an important role when malignancy or infection cannot be reliably excluded. Key Points • Isolated pulmonary IgG4-RLD presents with nonspecific clinical manifestations and diverse radiological features, frequently mimicking pulmonary infection or lung malignancy. • Elevated serum IgG4 levels, negative microbiological investigations, and normal tumor markers may provide important diagnostic clues in patients with suspected disease. • Histopathological examination remains the cornerstone for confirming the diagnosis of isolated pulmonary IgG4-RLD. • Recognition of the characteristic clinical, serological, radiological, and pathological features may improve the differential diagnosis.