Seronegative pachymeningitis

Surgical pathology specimens from patients with hypertrophic pachymeningitis are infrequently encountered. After excluding infectious and neoplastic causes, autoimmune conditions should be considered, especially neurosarcoidosis, rheumatoid arthritis, granulomatosis with polyangiitis (GPA), and IgG4-related disease (IgG4-RD) before the case is designated "idiopathic". However, even if histological findings strongly favor one of these conditions, clinical and serological correlation is mandatory. Further complicating the issue is evolving thinking that suggests there may be overlap between GPA and IgG4-RD.

We report clinical, histological, serological, and follow-up data on 2 seronegative cases of pachymeningitis with histological features identical to GPA, providing comparison with a seropositive pachymeningitis case from the author's files.

Two men, ages 73 and 75 years, presented with blurred vision and focal seizures, respectively; neuroimaging revealed dural thickening. Surgical resection specimens of hypertrophic dura proved histologically identical to GPA, with extensive non-storiform fibrosis, dense lymphoplasmacytic and histiocytic infiltrates, multinucleated giant cells, and dirty necrosis. Tumor, rheumatoid nodules with palisading histiocytes, and small compact granulomas were absent; stains for microorganisms were negative. Case 2 additionally showed medium-sized vessel vasculitis with fragmented elastic lamina, as seen in GPA. IgG4 cells were increased in each (170/HPF, IgG4 : IgG ratio = 26%, 65/HPF, IgG4 : IgG ratio = 10 - 15%), respectively.

Hypertrophic pachymeningitis cases are challenging. Pathologists should offer likely differential diagnoses based on histological features, but refrain from rendering a definitive diagnosis pending clinical-serological correlation. Whether seronegative examples represent a GPA variant, a new disease, or, in the case of high IgG4+ cells, two coincident disorders is unknown.