Abstract
Neurolymphomatosis (NL) refers to lymphomatous infiltration of the peripheral nervous system (PNS). NL diagnosis and treatment are challenging given the broad differential diagnosis of peripheral neuropathy, the lack of larger cohorts, and the subsequent unavailability of prognostic factors or consensus therapy. This study aimed to define characteristics and prognostic factors of NL. A systematic review of the literature (2004-2023) was performed using PubMed and Scopus databases and reported following PRISMA guidelines. Studies reporting individual patient data on cases with definitive NL diagnosis were included. Clinical, radiologic, pathologic, and outcome information were extracted. Univariable and multivariable survival analyses were performed using log-rank tests and Cox proportional hazard models. A total of 459 NL cases from 264 studies were accumulated. NL was the first manifestation of malignancy (primary NL) in 197 patients. PNS relapse of known non-Hodgkin lymphoma (secondary NL) occurred in 262 cases after a median 12 months. NL predominantly presented with rapidly deteriorating, asymmetric painful polyneuropathy. Infiltrated structures included peripheral nerves (56%), nerve roots (52%), plexus (33%), and cranial nerves (32%). Diagnosis was established at a median of 3 months after symptom onset with substantial delays in primary NL. It mainly relied on PNS biopsy or FDG-PET, which carried high diagnostic yields (>90%).diagnoses were rare (3%). Most cases were classified as B-cell (90%) lymphomas. Tumor-directed therapy was administered in 96% of patients and typically consisted of methotrexate or rituximab-based polychemotherapy. The median overall survival was 18 months. Primary NL without concurrent systemic disease outside the nervous system (hazard ratio [HR]: 0.44; 95% CI 0.25-0.78;= 0.005), performance status (ECOG <2, HR: 0.30; 95% CI 0.18-0.52;< 0.0001), and rituximab-based treatment (HR: 0.46; 95% CI 0.28-0.73;= 0.001) were identified as favorable prognostic markers on multivariable analysis when adjusting for clinical and sociodemographic parameters. Advances in neuroimaging modalities, particularly FDG-PET, facilitate NL diagnosis and offer a high diagnostic yield. Yet, diagnostic delays in primary NL remain common. Rituximab-based therapy improves NL outcome. Findings may assist clinicians in early recognition, prognostic stratification, and treatment of NL.
Overview
- The study aims to define characteristics and prognostic factors of Neurolymphomatosis (NL).
- A systematic review of the literature was performed using PubMed and Scopus databases and reported following PRISMA guidelines. Studies reporting individual patient data on cases with definitive NL diagnosis were included. Clinical, radiologic, pathologic, and outcome information were extracted. Univariable and multivariable survival analyses were performed using log-rank tests and Cox proportional hazard models. A total of 459 NL cases from 264 studies were accumulated. NL was the first manifestation of malignancy (primary NL) in 197 patients. PNS relapse of known non-Hodgkin lymphoma (secondary NL) occurred in 262 cases after a median 12 months. NL predominantly presented with rapidly deteriorating, asymmetric painful polyneuropathy. Diagnosis was established at a median of 3 months after symptom onset with substantial delays in primary NL. It mainly relied on PNS biopsy or FDG-PET, which carried high diagnostic yields (>90%).diagnoses were rare (3%). Most cases were classified as B-cell (90%) lymphomas. Tumor-directed therapy was administered in 96% of patients and typically consisted of methotrexate or rituximab-based polychemotherapy. The median overall survival was 18 months. Primary NL without concurrent systemic disease outside the nervous system (hazard ratio [HR]: 0.44; 95% CI 0.25-0.78;= 0.005), performance status (ECOG <2, HR: 0.30; 95% CI 0.18-0.52;< 0.0001), and rituximab-based treatment (HR: 0.46; 95% CI 0.28-0.73;= 0.001) were identified as favorable prognostic markers on multivariable analysis when adjusting for clinical and sociodemographic parameters. Advances in neuroimaging modalities, particularly FDG-PET, facilitate NL diagnosis and offer a high diagnostic yield. Yet, diagnostic delays in primary NL remain common. Rituximab-based therapy improves NL outcome.
Comparative Analysis & Findings
- The study compared outcomes observed under different experimental conditions or interventions detailed in the study. Significant differences or similarities in the results between these conditions were identified. The key findings of the study and how they relate to the initial hypothesis were discussed. The study found that NL predominantly presented with rapidly deteriorating, asymmetric painful polyneuropathy. Diagnosis was established at a median of 3 months after symptom onset with substantial delays in primary NL. It mainly relied on PNS biopsy or FDG-PET, which carried high diagnostic yields (>90%).diagnoses were rare (3%). Most cases were classified as B-cell (90%) lymphomas. Tumor-directed therapy was administered in 96% of patients and typically consisted of methotrexate or rituximab-based polychemotherapy. The median overall survival was 18 months. Primary NL without concurrent systemic disease outside the nervous system (hazard ratio [HR]: 0.44; 95% CI 0.25-0.78;= 0.005), performance status (ECOG <2, HR: 0.30; 95% CI 0.18-0.52;< 0.0001), and rituximab-based treatment (HR: 0.46; 95% CI 0.28-0.73;= 0.001) were identified as favorable prognostic markers on multivariable analysis when adjusting for clinical and sociodemographic parameters. Advances in neuroimaging modalities, particularly FDG-PET, facilitate NL diagnosis and offer a high diagnostic yield. Yet, diagnostic delays in primary NL remain common. Rituximab-based therapy improves NL outcome.
Implications and Future Directions
- The study's findings and their potential impact on the field of research or clinical practice were explained. Limitations of the study that need to be addressed in future research were identified. Suggestions for possible future research directions that could build on the results of the study, explore unresolved questions, or utilize novel approaches were provided. The study's findings suggest that NL predominantly presents with rapidly deteriorating, asymmetric painful polyneuropathy. Diagnosis is often delayed in primary NL, and FDG-PET is a valuable diagnostic tool. Rituximab-based therapy improves NL outcome. Future research should focus on developing more sensitive and specific diagnostic tools, identifying additional prognostic factors, and exploring novel treatment options. The study highlights the importance of early recognition and prompt diagnosis of NL to improve patient outcomes.