We report a diagnostically challenging case of a 79-year-old man who presented with mediastinal lymphadenopathy, hepatosplenomegaly, and renal enlargement, raising suspicion for clinical lymphoma. However, the histological evaluation of a submandibular gland excision revealed fibrosis, a dense IgG4-positive plasma cell infiltrate (>100/HPF), and an IgG4:IgG ratio > 40%, supportive of IgG4-related disease (IgG4-RD) in the appropriate clinicopathologic context. This case illustrates an important but well-recognised diagnostic pitfall in which IgG4-RD may clinically and radiologically mimic lymphoma. PET-CT demonstrated multiorgan involvement with diffuse FDG uptake, but definitive diagnosis required the integration of clinical, radiologic, serologic, and pathologic findings. The patient’s laboratory profile, including hypocomplementemia and elevated inflammatory markers, supported the proliferative phenotype of IgG4-RD—recently proposed in the literature as a clinically distinct subgroup with systemic involvement and steroid responsiveness. Rather than representing a novel presentation, this case reinforces the importance of integrated assessment in distinguishing IgG4-RD from haematolymphoid malignancy. PET-CT served as a useful adjunct for identifying multiorgan disease and guiding diagnostic evaluation, but tissue evaluation remained essential to avoid misdiagnosis and inappropriate treatment. Recognition of this entity is vital to avoid misdiagnosis and inappropriate treatment.
Fan et al. (2026) studied this question.