BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal non-Hodgkin lymphoma with highly heterogeneous clinical and imaging manifestations. Its atypical manifestations often lead to critical differential diagnosis challenges, resulting in high rates of misdiagnosis and delayed diagnosis.

CASE REPORT: We report a case of PCNSL in a 55-year-old male patient. The patient was a chronic hepatitis B virus carrier, with a history of consumption of medicinal wine with unknown ingredients 1 month prior to onset. He presented with progressive somnolence and generalized fatigue as the core initial symptoms, accompanied by other non-focal neurological deficits, including fever, altered mental status and cognitive impairment. Brain magnetic resonance imaging (MRI) revealed abnormal signals around the third ventricle and midbrain aqueduct, with a rare “wine glass” sign. In contrast, multiple contrast-enhanced MRI scans showed no typical homogeneous enhancement signals. Tumor cells were found in the third cerebrospinal fluid analysis, and he was definitively diagnosed with PCNSL after stereotactic biopsy. The patient’s symptoms improved following a single fraction of radiotherapy treatment.

CONCLUSIONS: The insidious onset and atypical features of PCNSL increase the risk of delaying diagnosis, which may negatively impact patient outcomes. Here, we present a case of PCNSL exhibiting atypical clinical manifestations and imaging findings, while differentiating it from other neurological disorders with overlapping features. It also highlights the critical value of serial cerebrospinal fluid cytology and early biopsy for timely diagnosis, providing a clinical reference for managing similar cases.

Keywords: Lymphoma, Primary Central Nervous System, Neurology, Somnolence, Asthenia, Magnetic Resonance Imaging, Case Reports