Diagnostic Considerations for Neurolymphomatosis: A Natural History Analysis

Neurolymphomatosis (NL), a rare manifestation of non-Hodgkin’s lymphoma affecting the peripheral nervous system, remains a diagnostic challenge. This study aimed to define an optimal diagnostic approach for timely and effective identification of NL. We analyzed 559 NL cases from 231 articles published from 1951 to 2022, examining how patient outcomes correlated with various diagnostic modalities, including magnetic resonance imaging (MRI), computed tomography (CT), [18F]fluorodeoxyglucose positron emission tomography (FDG-PET), electromyography-nerve conduction studies (EMG-NCS), ultrasound, and tissue biopsy when used individually or in combination. Separate analyses were performed in a mutually exclusive fashion to minimize confounding effects from multiple modalities. The results of this investigation revealed that patients with biopsies had a longer time interval from first treatment to progression (Kruskal–Wallis p < 0.0001), survival from diagnosis (overall survival) (p < 0.0001), and survival from symptom onset (p < 0.0001), but not symptom onset to diagnosis (p = 0.2134). Pairwise comparisons of biopsy plus 2, 3, or 4 diagnostic modalities revealed a positive trend for the combination of biopsy + PET + MRI + EMG-NCS. A majority of patients without biopsy had secondary NL. In this non-biopsied population, no diagnostic modality had a significant correlation with outcome. The data collectively indicate that histological confirmation of NL from biopsy was associated with a positive patient outcome. Management of NL patients requires timely testing using PET, MRI, and EMG-NCS to quickly identify a site for image-guided nerve biopsy.