Peripheral Nerve Involvement (Neurolymphomatosis) as a Manifestation of Intravascular Large B-Cell Lymphoma

Intravascular large B-cell lymphoma (IVL) is characterised by proliferation of lymphoma cells only in the lumina of small vessels in various organs, a high incidence of neurological symptoms associated with central nervous system (CNS) involvement has been reported, but its association with peripheral nerve involvement (neurolymphomatosis, NL) has rarely described previously. We recently encountered 2 patients with IVL who relapsed as a NL shortly after the completion of chemotherapy. Because both NL and IVL is extremely rare clinical condition, its occurrence led us to explore the predilection of NL in patients with IVL.

We reviewed the medical records of patients with diagnosis of IVL over the past 4 years. Diagnosis of IVL was made by the definition of WHO classification of hematopoietic tumours. The diagnosis of NL required: 1) clinical symptoms and neurological findings related to the peripheral neuropathy of cranial or spinal nerves; and 2) histological confirmation of lymphoma cells within the peripheral nerve, nerve root/plexus, or cranial nerve; or 3) CT/MRI demonstration of nerve enhancement and/or enlargement of peripheral nerve(s) that were also demonstrated by accumulation of FDG by FDG-PET/CT.

We identified 5 patients of NL among 12 IVL patients. NL occurred as an initial manifestation in one patient and relapse disease in the remaining 4 patients. All 5 patients had neurologic symptoms corresponding to the NL of cranial and/or peripheral nerve. Comparison of clinical and laboratory features could not disclose the difference in IVL patients with or without NL in terms of presence or absence of haemophagocytosis, bone marrow infiltration, neurological symptoms, cytopenia, soluble interleukin 2 receptor level, and skin lesions. All of the 4 patients with NL as a relapse disease occurred during or shortly after R-CHOP chemotherapy. Brain MRI and whole-spine MRI with thin sliced coronal image could reveal the nerve infiltration by gadolinium enhancement and enlargement of nerve structure, it might not always sensitive enough for its detection because of patchy distribution and small lesion. In contrast, FDG-PET/CT successfully revealed the involved lesions as a linear or nodular FDG-uptake which was anatomically correlated with cranial nerves, nerve plexus, spinal nerve root, or peripheral nerves in all of the 5 cases. In addition FDG-PET/CT was useful for evaluating the therapeutic responses. Treatment with high-dose methotrexate with or without systemic chemotherapy appeared beneficial, however one of the 5 patient needed additional localized irradiation for relapse disease.

Considering the extreme rarity of both IVL and NL, there may be a strong predilection of NL in patients with IVL. As IVL has a high frequency of CNS involvement, it may also have a high frequency of peripheral nerve involvement. Early recognition and familiarity of the disease and prompt institution of aggressive chemotherapy incorporating high-dose MTX with or without involved field radiation might be useful, although further studies are still warranted.

No relevant conflicts of interest to declare.