Clinical Spectrum, Diagnosis, and Treatment Outcome in Individuals With Intravascular Large B-cell Lymphoma Affecting the Nervous System: A Case Series

Abstract

We treated five patients, three females, and two males, with intravascular lymphoma that affected the central or peripheral nervous systems. We reviewed their clinical, laboratory, neuro-imaging, and pathological data and treatment outcomes. The median age of onset was 60 years, with a range of 39 to 69 years. Three patients presented with central nervous system symptoms only, such as confusion, aphasia, seizure, stroke, and ataxia. Three patients presented with systemic lymphoma stage B symptoms, one with peripheral nervous system symptoms, and one with multi-organ failure. Brain imaging revealed white matter lesions, infarcts, hemorrhages, or combinations. Histology showed CD20-positive B-lymphocytes confined to small-size vessels in autopsy or biopsy specimens from the brain or muscle, confirming the diagnosis of intravascular large B-cell lymphoma (IVLBL). The patient with multi-organ failure had diffuse infiltration to the spleen, liver, and kidney. Three patients died within three to four months after the clinical presentation and were diagnosed at autopsy. The other two were diagnosed by biopsy and underwent chemotherapy CHOP-R (cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisone) or MTX (methotrexate)+Rituximab. The median survival of the chemotherapy patients was 17.5 months, compared to three to four months in those who did not receive chemotherapy. Although IVLBL has distinct pathological features, its clinical presentation can be variable. The patient's best chance for survival depends on the early pathological diagnosis and prompt, aggressive chemotherapy.

Keywords: central nervous system; cerebro-vascular accident (stroke); intravascular large b-cell lymphoma; myopathy; rituximab.

Figure 1. Dynamic progression of different types of brain lesions in a patient who did not receive chemotherapy (case 4). (A) SAH (red arrow), IPH (red arrow), and cerebral edema (yellow arrow) in the patient with a different clinical stage, (B) multi-foci of restrict diffusion representing acute ischemic infarct (light green arrow), (C) progression of T2/FLAIR hyperintensity lesions in a different clinical stage.

SAH - Subarachnoid Hemorrhage; IPH - Intraparenchymal Hemorrhage

Figure 2. Resolved gadolinium-enhanced lesion after chemotherapy (case 5). (A) Prior to therapy (yellow arrow); (B) three months after the induction therapy.

Figure 3. Pathological findings of IVLBL (case 1). (A) Gross anatomy of autopsied brain showed scattered parenchymal hemorrhages (dark green arrow) present in bilateral cerebral hemisphere, brain stem and cerebellum; (B) multifocal subtotal necrosis with small patches of incomplete neuronal loss, reactive astrocytes, and microhemorrhage (purple arrow); (B, C) H-E staining showed that cerebral and leptomeningeal vessels were plugged by numerous neoplastic large lymphoid cells, which were noncohesive and free in the lumina, and confined to the vessels (red arrow). Lymphoma cells in all cases were confirmed as B-cell lineage by immunohistochemistry staining using anti-CD20 (blue arrow).