Case Report: Hypothalamic demyelinating lesion preceding lymphoma arising outside the central nervous system

Nonneoplastic demyelinating brain lesions, known as sentinel lesions, occasionally precede primary central nervous system lymphomas (PCNSL). However, cerebral sentinel lesions associated with lymphoma "outside" the central nervous system (CNS) have not been reported. Here, we describe the case of a 76-year-old female who presented with rapidly progressive visual field disturbances. Magnetic resonance imaging revealed a hypothalamic lesion, and a biopsy demonstrated inflammatory demyelination with T-lymphocyte and macrophage infiltration, but no evidence of lymphoma. Steroid therapy was initiated only after biopsy. The lesions responded well to steroids and almost disappeared, and the patient was discharged with improvement in all symptoms except for diabetes insipidus. Three months later, the patient developed systemic symptoms, including osteolytic bone and skull lesions and multiple organ failure. A second biopsy of a skull lesion revealed diffuse large B-cell lymphoma (DLBCL), a non-germinal center B-cell-like subtype. Despite initiating chemotherapy, the patient died five months after the initial biopsy, although no recurrence of the brain lesion was observed. This case is the first to document a brain sentinel lesion preceding systemic DLBCL without associated cerebral lymphoma. It highlights the similarities with previously reported sentinel lesions in PCNSL, such as inflammatory demyelination and steroid responsiveness, while raising questions regarding the underlying mechanisms and challenges of early diagnosis. We emphasize the importance of considering sentinel lesions in patients with tumefactive inflammatory demyelination characterized by T-lymphocyte-dominant infiltration.