Clinicopathologic spectrum and diagnostic insights from IgG4-related disease of the CNS

IgG4-related disease (IgG4-RD) of the central nervous system (CNS) is a recently recognized entity, often misdiagnosed as neoplastic or inflammatory conditions. We present the largest retrospectively analysed Indian cohort of nine cases histologically diagnosed as CNS IgG4-RD from 2021 to 2024, integrating clinical, serological, pathological, treatment, radiological, and follow-up details. The mean age of the cohort was 25.9 ± 8.8 years (range: 11–41 years), with a male-to-female ratio of 2:1. Headache (5/9) and seizures (3/9) were the most common presentations, with lesions involving the frontal/frontotemporal dura (3/9), cerebellopontine angle (2/9), and tentorium (1/9), among others (3/9). Radiological impressions included hypertrophic pachymeningitis or inflammatory disease (4/9), meningioma (3/9), vestibular schwannoma (1/9), and IgG4-RD (1/9). Preoperative, serum IgG4 levels testing was done in 4/9 cases, and levels exceeded 1.35 g/L in 3/4 patients. Following the 2020 revised comprehensive diagnostic criteria for IgG4-RD, three cases were classified as definite and six as probable for IgG4-RD. Histopathological findings of dense lymphoplasmacytic infiltrates with storiform fibrosis, with >10 IgG4-positive plasma cells per high-power field and an IgG4/IgG-positive plasma-cell ratio >40% were present in all cases, while obliterative phlebitis was seen in only 2/9 cases. All patients received and responded to corticosteroid-based therapy and were alive without documented clinical recurrence or radiological progression at a mean follow-up of 30.6 months. This study highlights the distinctive clinico-radiological and serological profiles of CNS IgG4-RD correlating with histopathology and immunophenotyping in differentiating it from mimics such as neoplastic or other infectious pathologies, especially in patients where serum IgG4 testing remains limited. Not applicable.