Neurolymphomatosis: an International Primary CNS Lymphoma Collaborative Group report

Abstract

Neurolymphomatosis (NL) is a rare clinical entity. The International Primary CNS Lymphoma Collaborative Group retrospectively analyzed 50 patients assembled from 12 centers in 5 countries over a 16-year period. NL was related to non-Hodgkin lymphoma in 90% and to acute leukemia in 10%. It occurred as the initial manifestation of malignancy in 26% of cases. The affected neural structures included peripheral nerves (60%), spinal nerve roots (48%), cranial nerves (46%), and plexus (40%) with multiple site involvement in 58%. Imaging studies often suggested the diagnosis with 77% positive magnetic resonance imaging, and 84% (16 of 19) positive computed tomography-positron emission tomography studies. Cerebrospinal fluid cytology was positive in 40%, and nerve biopsy confirmed the diagnosis in 23 of 26 (88%). Treatment in 47 patients included systemic chemotherapy (70%), intra-cerebrospinal fluid chemotherapy (49%), and radiotherapy (34%). Response to treatment was observed in 46%. The median overall survival was 10 months, with 12- and 36-month survival proportions of 46% and 24%, respectively. NL is a challenging diagnosis, but contemporary imaging techniques frequently detect the relevant neural invasion. An aggressive multimodality therapy can prevent neurologic deterioration and is associated with a prolonged survival in a subset of patients.

Figure 1

Imaging studies in NL. (A-B) FDG-PET imaging of a patient with neurolymphomatosis (NL). (A) Multiple sites of involvement, including the brachial and lumbosacral plexi (arrows). (B-C) Bilateral involvement of the brachial plexus in the same patient clearly detected by both FDG-PET (B) and by MRI (C) T2 short T1 inversion recovery imaging. (D-E) Enhanced MRI imaging (T1-weighted with gadolinium) of a patient with NL that affected multiple cranial nerves. (D) Bilateral abnormal enhancement of the oculomotor nerves that corresponded to the clinical presentation of bilateral ophthalmoplegia. (E) Complete resolution of abnormal enhancement after 2 cycles of treatment with intravenous high-dose methotrexate and intra-CSF treatment with cytarabine. These imaging findings matched the marked neurologic improvement observed under treatment. (F-G) FDG-PET imaging of a patient with NL who presented with severe painful sensorimotor neuropathy and bilateral brachial plexus involvement. (F) FDG-PET findings at diagnosis of NL compatible with bilateral brachial plexus involvement by lymphoma. (G) Complete resolution of abnormal tracer uptake after 2 courses of treatment with systemic high doses of methotrexate and cytarabine. The treatments lead to clear neurologic improvement and good control of the painful neuropathy.

Figure 2

Survival of patients with NL. (A) Overall survival of the 50 patients from the date of diagnosis of NL (median, 10 months). Vertical lines indicate censored observations. (B) Survival of patients with either primary NL (median, 20 months; 13 patients) or secondary NL (median, 8 months; 37 patients). Vertical lines indicate censored observations.