Isolated central nervous system involvement in blastic plasmacytoid dendritic cell neoplasm: a rare case of relapse during systemic remission with diagnostic and therapeutic implications

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, highly aggressive hematologic malignancy characterized by frequent involvement of the skin and bone marrow. Central nervous system (CNS) infiltration is uncommon and may be clinically occult, thereby posing diagnostic challenges. We report the case of a 74 year-old man who initially presented with progressively enlarging cutaneous masses on the trunk. Histopathological examination of skin biopsy demonstrated BPDCN with a characteristic immunophenotype, and subsequent bone marrow studies confirmed extensive marrow involvement. The patient was treated with a combination of azacitidine and low-dose cytarabine to achieve sustained hematologic remission with marked regression of skin lesions and splenomegaly, despite intermittent treatment-related myelosuppression. After several months of stable disease, he was readmitted with new-onset paroxysmal occipital headache and blurred vision. Peripheral blood counts, bone marrow evaluation, and systemic imaging were unremarkable, and brain and orbital magnetic resonance imaging showed no abnormalities. Cerebrospinal fluid (CSF) analysis revealed marked pleocytosis with abundant atypical cells. Flow cytometry identified BPDCN cells accounting for 97.6% of nucleated cells, establishing the diagnosis of CNS involvement. Intrathecal methotrexate combined with cytarabine led to the rapid resolution of neurologic and visual symptoms. This case study demonstrates that BPDCN may lead to isolated CNS involvement despite ongoing systemic remission, highlighting the importance of cerebrospinal fluid evaluation in patients with unexplained neurologic manifestations.