IgG4-Related Disease and Synchronous Marginal Zone Lymphoma Evaluated by 99mTc-iFAP SPECT/CT and [18F]-FDG PET/CT: A Case Report

IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory condition that can mimic malignancy due to its tumorous lesions. Marginal zone lymphoma (MZL), a low-grade B cell lymphoma, may occasionally arise in the context of chronic immune stimulation. The synchronous occurrence of IgG4-RD and MZL is rare and diagnostically challenging. We report the case of a 39-year-old male with right hemiplegia and aphasia, initially suspected to have a meningioma based on magnetic resonance imaging (MRI) findings. Histopathology following surgical resection revealed features consistent with IgG4-RD. Subsequently, [18F]-FDG PET/CT ([18F]-fluorodeoxyglucose positron emission tomography/computed tomography) demonstrated a metabolically inactive extra-axial supratentorial lesion, as well as a hypermetabolic triangular consolidation in the left lower lung lobe. Lung biopsy confirmed bronchus-associated lymphoid tissue MZL. Immunohistochemistry supported the dual diagnosis. Complementary 99mTc-iFAP SPECT/CT (single photon emission computed tomography/CT) demonstrated focal uptake in the central nervous system lesion but not in the pulmonary lesion. Multimodal image fusion with brain MRI facilitated precise anatomical and functional correlation. The coexistence of IgG4-RD and MZL raises important considerations regarding shared immunopathogenic mechanisms. Dual molecular imaging with FDG and FAPI (fibroblast activating protein inhibitor)-based radiotracers proved essential in discriminating between inflammatory and neoplastic components of disease, enabling accurate diagnosis and guiding appropriate management. This case highlights the value of [18F]-FDG PET/CT and 99mTc-iFAP SPECT/CT in the evaluation of complex systemic diseases. fibroblast activation protein–targeted imaging may play a key role in the diagnostic workup of IgG4-RD and in distinguishing it from coexisting lymphoproliferative disorders.