Monocytic meningitis complicating histiocytosis and response to MEK-inhibitor: a case series

Central nervous system (CNS) involvement is common in histiocytosis, yet cerebrospinal fluid (CSF) analysis often yields normal results. We present three cases of monocytic meningitis associated with histiocytosis. The first patient was diagnosed with Erdheim-Chester disease (ECD) and exhibited evidence of a MAP2K1 mutation, concomitant with chronic myelomonocytic leukemia. Brain magnetic resonance imaging (MRI) revealed leptomeningitis and pachymeningitis. The presence of the same MAP2K1 mutation in CSF monocytes confirmed the clonal origin of neuromeningeal infiltration. Treatment with binimetinib rapidly improved the patient’s clinical condition. The second case involved CNS primary malignant histiocytosis (CNS-PMH) associated with myelodysplastic syndrome. However, treatment with binimetinib only led to a partial and time-limited response. The last patient was diagnosed with mixed histiocytosis ECD/Rosai-Dorfman disease (RDD). Cobimetinib also proved effective in managing CNS symptoms. CSF pleocytosis in CNS involvement of histiocytosis has been reported in a few published cases with neurological involvement. Given its rarity, the presence of monocytic meningitis should prompt immediate suspicion of histiocytosis, particularly if accompanied by typical manifestations. In cases of neurological involvement in histiocytosis, lumbar puncture and liquid biopsy can sometime overcome the need for a meningeal biopsy. The molecular characterization of histiocytosis is essential for considering the use of targeted therapy, but the lack of an identified mutation should not preclude the use of anti-MEK therapy.