Clinical manifestations and outcomes of patients with intravascular large B-cell lymphoma with neurological involvement: highlighting longitudinally extensive myelopathy as a distinct feature

Abstract

Objective: This study aimed to elucidate the clinical manifestations, laboratory findings and outcomes of patients with intravascular large B cell lymphoma (IVLBCL) with neurological involvement and to differentiate IVLBCL with and without neurological involvement.

Methods: A cohort study was conducted at Siriraj Hospital, Mahidol University, Thailand, between January 2005 and September 2024. Clinical data, laboratory values and central nervous system imaging results were analysed. Categorical variables were compared using the χ² or Fisher's exact test, while continuous variables were analysed with the Mann-Whitney U test, as appropriate.

Results: Of the 30 patients with IVLBCL, 10 had neurological involvement and 20 without neurological symptoms, including myelopathy (5 patients, 50%); cognitive impairment (3 patients, 30%); seizures (2 patients, 20%); optic neuropathy, hemiparesis, homonymous hemianopia, vertigo and global aphasia (each affecting 1 patient, 10%). 60% of IVLBCL with neurological involvement had systemic symptoms, including prolonged fever, anaemia, anorexia and weight loss. MRI showed hyperintense lesions in the supratentorial, infratentorial and spinal cord with the prominent findings being longitudinally extensive cord lesions (four patients, 40.0%). The median survival time of the IVLBCL with neurological involvement was 4.1 months (95% CI: 0.0 to 17.1 months), with a 1-year survival rate of 37.5% and a 2-year survival rate of 25.0%.

Interpretation: This study highlights the distinct clinical, laboratory features and imaging of IVLBCL with neurological involvement and compares it to IVLBCL without neurological involvement. Early recognition of these findings is crucial for accurate diagnosis and improved patient outcomes despite the aggressive nature of IVLBCL.

Keywords: CLINICAL NEUROLOGY; LYMPHOMA; NEURO-ONCOLOGY.

Figure 1. Neurological symptoms in patients with intravascular large B cell lymphoma.

Figure 2. MRI features of patients 1–3 with IVLBCL. (A) Patient 1: This patient presented with non-convulsive status epilepticus, left homonymous hemianopia and left hemiparesis. MRI revealed bilateral asymmetrical hypointense signals on T1-weighted (T1W) images and hyperintense signals on T2/FLAIR images in the bilateral subcortical regions and periventricular white matter without restricted diffusion. T1-weighted imaging with gadolinium (Gd) enhancement revealed punctate and curvilinear enhancement with multiple foci of blooming artefacts within these lesions (SWI not shown). (B) Patient 2: This patient presented with rapid cognitive decline. MRI revealed multifocal hypointense and hyperintense signals on T1W and T2/FLAIR images, with restricted diffusion suggesting multistage intraparenchymal infarction (white arrow) and haemorrhage. Two Gd-enhanced lesions in the occipital region were compatible with subacute infarction. (C) Patient 3: This patient presented with chronic progressive thoracic myelopathy and prolonged fever. MRI revealed hyperintense signals on T2/FLAIR images with faint enhancement from T7 to the conus medullaris (white arrow). IVLBCL, intravascular large B cell lymphoma, ADC, Apparent diffusion coefficient; DWI, Diffusion-weighted imaging; FLAIR, Fluid-attenuated inversion recovery; SWI, Susceptibility-weighted imaging.

Figure 3. MRI features of patients 4–7 with IVLBCL. (A) Patient 4: This patient presented with subacute thoracic myelopathy and optic neuropathy. Spinal MRI revealed isointense T1-weighted (T1W) signals and hyperintense T2-weighted (T2W) signals from T2 to T7 without gadolinium (Gd) enhancement. Brain MRI revealed a hyperintense FLAIR signal in the splenium without restricted diffusion or Gd enhancement. (B) Patient 5: This patient presented with rapid cognitive decline, recurrent stroke and behavioural changes. MRI showed multifocal cortical/subcortical white matter hyperintensities on T2/FLAIR images with restrictive diffusion (white arrow) and punctate Gd enhancement. (C) Patient 6: This patient presented with longitudinally extensive transverse myelopathy and prolonged fever. MRI revealed multifocal hyperintense signals on T2/FLAIR images with restricted diffusion in bilateral periventricular lesions and Gd enhancement. Extensive long-segment spinal enlargement with high signal intensity was observed on T2-weighted images and enhancement from T1 to the conus medullaris (head arrow). (D) Patient 7: This patient presented with conus medullaris syndrome, prolonged fever and significant weight loss. MRI showed no abnormal signal change on T2/FLAIR or T1W images with Gd enhancement. IVLBCL, intravascular large B cell lymphoma, ADC, Apparent diffusion coefficient; DWI, Diffusion-weighted imaging; FLAIR, Fluid-attenuated inversion recovery.

Figure 4. MRI features of patients 8–9 with IVLBCL and pathology of patient 8. (A) Patient 8: This patient presented with longitudinally extensive transverse myelopathy and vertigo. Spinal MRI revealed long segmental intramedullary cord lesions at C2 to T2 levels. (white arrow). (B) Patient 9: presented with cognitive impairment and aphasia. MRI demonstrated a diffuse patchy hyperintense signal in T2 at the bilateral midbrain, pons, bilateral thalamus, bilateral posterior limb of the internal capsule, left basal ganglion and a few small enhancements at the left splenium. (C) Pathological findings of bone marrow patient 8 revealed that H&E-stained showed no cluster or aggregate of lymphoid cells. PAS stain highlighted the large abnormal cell (red arrow) within the vascular lumen (blue arrow). CD20+large lymphoma B-cell (red arrow) flanked by endothelial cells (blue arrow). Gd, gadolinium; IVLBCL, intravascular large B cell lymphoma.