Neurolymphomatosis: A Comprehensive Review of Clinical and Imaging Features.

Abstract

Neurolymphomatosis (NL) is a rare condition characterized by infiltration of the peripheral nervous system by malignant lymphocytes. It most commonly occurs in the setting of hematologic malignancy, particularly non-Hodgkin lymphoma, where neural involvement represents a distinct form of extranodal disease. It may also occur as a manifestation of primary central nervous system lymphoma. This review aims to summarize the clinical presentation, diagnostic challenges, and imaging characteristics of NL and to highlight the role of MRI and fluorine 18 (¹⁸F) fluorodeoxyglucose (FDG) PET/CT in detection, diagnosis, and assessment of disease extent. Two clinical patterns are recognized: Primary NL manifests with neuropathy as the initial disease manifestation, with or without concomitant nodal or extranodal disease at the time of lymphoma diagnosis, whereas secondary NL occurs as a site of progression or relapse in patients with a prior history of lymphoma. NL demonstrates diverse clinical presentations, which often leads to misdiagnosis. Clinical red flags, particularly in patients presenting with polyneuropathy, include severe pain, asymmetric distribution, subacute onset, and rapid clinical progression. The brachial plexus, lumbosacral plexus, sciatic nerve, and trigeminal nerve are the most commonly involved sites. Although nerve biopsy remains the diagnostic reference standard, it carries a high risk of irreversible nerve damage. MR neurography and ¹⁸F-FDG PET/CT provide high diagnostic yield and facilitate early detection and diagnosis of NL, particularly when interpreted in the appropriate clinical context. In addition, they are essential for evaluating disease extent, guiding targeted biopsy when needed, and supporting clinical management and treatment monitoring. Keywords: PET/CT, Nervous-Peripheral, Lymphoma, MR Imaging, Neuro-Oncology, Neurolymphomatosis, Lymphoma, Peripheral Nervous System, Neuropathy, Nerve Biopsy, MRI, FDG/PET © RSNA, 2026.