Immunoglobulin G4 (IgG4)-Related Lung Disease Mimicking Pulmonary Malignancy: A Case Report With Histopathological Characterisation and Review of Diagnostic Criteria.

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a systemic fibroinflammatory condition with highly variable pulmonary manifestations that frequently overlaps clinically, radiologically, and metabolically with primary malignancy, granulomatous disease, and vasculitis. Tissue diagnosis with immunohistochemical quantification of IgG4-positive plasma cells remains the diagnostic cornerstone. A 50-year-old male ex-smoker presented with a two-month history of progressive cough, dyspnoea, chest pain, and 8 kg of unintentional weight loss. Examination revealed digital clubbing and bilateral crepitations. Laboratory investigations showed mild normocytic anaemia, leukocytosis with neutrophilic predominance, and a markedly elevated erythrocyte sedimentation rate of 109 mm/h. Serum IgG4 was elevated at 2.23 g/L (reference range <1.35 g/L). Total IgG and comprehensive autoimmune and infectious serology were unremarkable. Positron Emission Tomography-Computed Tomography (PET-CT) demonstrated multiple bilateral pulmonary nodules (some cavitating) with an exceptionally high maximal standardised uptake value (SUVmax 20.1) and mediastinal lymphadenopathy, prompting strong initial suspicion of primary pulmonary malignancy. CT-guided lung biopsy revealed dense storiform fibrosis, a lymphoplasmacytic infiltrate rich in eosinophils, and features of fibroinflammatory change; however, immunohistochemistry did not demonstrate an increased number of IgG4-positive plasma cells, and formal histopathological criteria for IgG4-related disease were not fulfilled. In the context of compatible clinical, radiological, and serological findings, a diagnosis of probable IgG4-related lung disease was considered. Oral prednisolone at 0.6 mg/kg/day produced substantial clinical and radiological improvement, with near-complete resolution of opacities and reduction in nodule size by six months. This case illustrates the diagnostic pitfalls of IgG4-related lung disease, which can produce exceptionally high 18F-fluorodeoxyglucose (FDG) avidity on PET-CT, cavitating nodules, and constitutional features indistinguishable from malignancy. Histopathological evaluation with formal IgG4 cell quantification and ratio calculation is essential for accurate diagnosis; however, cases with supportive clinicoradiological features but non-diagnostic immunostaining may still pose significant diagnostic challenges. Early corticosteroid treatment yields excellent outcomes and prevents unnecessary oncological intervention.