IgG4-related pulmonary disease masquerading as lung cancer: a case report and literature review

Abstract Background: Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory condition that can involve the lungs (IgG4-RPD). Its clinical and radiological presentation often mimics malignancies, leading to diagnostic challenges. Case Presentation: A 57-year-old man presented with a six-month history of intermittent cough, whitish sputum, chest tightness, and exertional dyspnea. Initial chest CT revealed a right hilar soft tissue mass concerning for malignancy with mediastinal lymphadenopathy and obstructive pneumonia. Histopathological examination of initial lung biopsy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of lymph nodes were non-diagnostic for malignancy, showing only chronic inflammation. His symptoms progressed over the following month. Laboratory investigation revealed elevated serum IgG4 (1460 mg/dL), IgE, and C-reactive protein. Pulmonary function tests showed moderate obstructive ventilatory dysfunction with a positive bronchodilator response. PET-CT demonstrated intense FDG uptake in the right hilar mass and multiple lymph nodes, highly suspicious for advanced lung cancer. A subsequent percutaneous lung biopsy revealed organizing pneumonia with focal fibroinflammation and a prominent perivascular plasma cell infiltrate. Immunohistochemistry confirmed an IgG4+ plasma cell count of >10/HPF and an IgG4+/IgG+ ratio of >40%, establishing the diagnosis of IgG4-RPD. The patient was also diagnosed with comorbid bronchial asthma. He showed marked clinical and radiological improvement after initiation of prednisone (0.5 mg/kg/day). Discussion: This case underscores that IgG4-RPD can closely simulate lung cancer both radiologically (e.g., hilar mass, lymphadenopathy, high FDG avidity on PET-CT) and clinically. A high index of suspicion is crucial in middle-aged men presenting with such findings, especially when tissue sampling is repeatedly negative for malignancy. Key diagnostic clues include elevated serum IgG4 and IgE, but definitive diagnosis relies on characteristic histopathology. Corticosteroids are the first-line treatment and typically yield excellent responses. Pathologist-clinician communication and specific IgG4 immunostaining are essential to avoid misdiagnosis and unnecessary interventions. Conclusion: IgG4-RPD is an important differential diagnosis for a lung mass with lymphadenopathy. Integration of clinical, serological, and meticulous histopathological findings is critical for accurate diagnosis and appropriate management.