Deceptive initial presentation of systemic DLBCL with CNS progression following Oligometabolic PET/CT: case report.

We present a diagnostically challenging case of a 51-year-old woman with systemic diffuse large B-cell lymphoma (DLBCL) that progressed to secondary central nervous system (CNS) involvement. The initial presentation was notable for a whole-body PET/CT scan showing only subtle, diffuse fluorodeoxyglucose uptake in lymph nodes and bone marrow (SUVmax <5.0), below conventional thresholds for malignancy. Four months later, the patient developed an acute encephalopathic illness accompanied by multiorgan dysfunction and a severe hyperinflammatory state consistent with hemophagocytic lymphohistiocytosis. Hallmark laboratory features included refractory lactic acidosis, extreme hyperferritinemia, markedly elevated lactate dehydrogenase, and profound CD4+ lymphopenia. Cranial imaging revealed rapidly progressive, non-specific parenchymal lesions. A definitive diagnosis of the non-germinal center B-cell (non-GCB) subtype of DLBCL was secured via biopsy of a readily accessible facial lymph node-rather than high-risk brain biopsy-illustrating a pivotal diagnostic principle. This case highlights that unexplained persistent lactic acidosis, extreme hyperferritinemia, and even subthreshold PET/CT findings can be sentinel signs of an underlying aggressive lymphoma. It emphasizes the need for high clinical suspicion and the pursuit of safe, extracranial biopsy sites to enable early diagnosis and intervention in such diagnostically elusive cases.