To highlight the occurrence of granulomatous inflammation on neuropathology in a subset of patients with select neuronal autoantibody-associated paraneoplastic CNS syndromes.

Granulomatous inflammation has a broad range of potential causes, including infectious, primary inflammatory, and malignant etiologies. However, antibody-associated paraneoplastic neurologic syndromes have not traditionally been considered in the differential diagnosis of CNS granulomatous inflammation.

Case series from three specialty centers in the USA and France.

A man in his late 30s presented with months of progressive vertigo, ataxia, and a generalized seizure. MRI brain revealed pituitary, temporal lobe, and cerebellar vermis enhancement. CSF examination showed a mild pleocytosis, elevated IgG index, and +OCBs. Transsphenoidal pituitary biopsy revealed indistinct granuloma formation, chronic inflammation with lymphoid infiltrates, and architectural distortion. Despite initial improvement with glucocorticoids and treatment with infliximab and methotrexate for suspected neurosarcoidosis, there was insidious clinical progression. Kelch-like protein 11 antibodies were ultimately identified in CSF and serum, and testicular pathology revealed scarring and atrophy consistent with what was most likely a regressed germ cell tumor.  These observations build upon three previously published patients, two with Kelch-like 11 antibody-associated paraneoplastic neurological syndrome and non-necrotizing granulomatous inflammation in the brain (PubMed IDs 32744608 and 34557666) and one patient with anti-Ma2 antibodies (PubMed ID 20194918). Granulomatous inflammation on brain biopsy was also observed in a patient with subacute memory disturbances, a brain lesion that suggested glioblastoma, and anti-AK5 autoantibodies.

The differential diagnosis of CNS granulomatous inflammation should be broadened to include select paraneoplastic neurological syndromes, including when considering a diagnosis of isolated CNS parenchymal “neurosarcoidosis.”