To describe an interesting case of Mollaret meningitis with negative HSV-2 in lymphoma survivor

Retrospective review of clinical course, diagnostic workup, hospitalizations, and treatments.

A 46-year-old man with a history of diffuse large B-cell lymphoma without central nervous system involvement, previously treated with lenalidomide, obinutuzumab, and CHOP, had remained in remission for seven years. In November 2024, he presented to the hospital with recurrent episodes of fever and headache, accompanied by nausea and photophobia. Physical examination revealed nuchal rigidity, with negative Kernig's and Brudzinski's signs. The patient's clinical history included similar episodes of meningitis in 2020 and a subsequent recurrence in 2022. Cerebrospinal fluid (CSF) analysis demonstrated pleocytosis, with cell counts ranging from 14 cells in 2024 to 41 cells in 2020, predominantly eosinophilic and lymphocytic. CSF protein and glucose levels were within normal limits. Cytological examination identified monocytes with bilobed and cloverleaf-shaped nuclei and abundant cytoplasm, resembling Mollaret cells, negative for malignant cells. Extensive infectious workup, including HSV-2 PCR, HHV-6, varicella-zoster virus, enterovirus, Epstein–Barr virus, and cytomegalovirus, was negative. Due to eosinophilic predominance, additional testing for parasitic and fungal causes was negative. Autoimmune workup was unremarkable. MRI brain showed no meningeal enhancement. The patient experienced clinical improvement within one week without treatment. 

This case raises the possibility that immune dysregulation may contribute to the development of recurrent aseptic meningitis. In HSV-negative cases, particularly those presenting with atypical features, clinicians should consider immune-mediated mechanisms after excluding infectious and neoplastic etiologies.