The natural history of intravascular lymphomatosis

Abstract

Intravascular lymphomatosis (IVL) is a rare and clinically devastating form of extranodal B-cell non-Hodgkin's lymphoma. We performed a comprehensive analysis of the literature on IVL's published between 1959 and 2011 and evaluated the natural history as well as identified prognostic and predictive factors in patients. Nonparametric two-tailed Mann–Whitney U-test and Mantel–Cox log rank test were used to evaluate the survival intervals and prognostic factors. Multivariate analysis of variance (MANOVA) and chi-squared statistics were carried out to examine treatment-related predictive factors. Of the 740 patients with IVL, 651 (88%) had a diagnosis of B-cell lymphoma, 45 (6%) with T-cell lymphoma, and 12 patients (2%) with NK cell lymphoma. Central nervous system (CNS) IVL had the highest proportion of postmortem diagnosis, 250 (60%) compared to 21 (8%) of skin, 28 (11%) of bone marrow (BM) and spleen, and 17 (7%) of lung IVL's. Age <70 years (P = 0.0073), non-CNS site of initial diagnosis (P = 0.0014), lactate dehydrogenase (LDH) <700 (P = 0.0112), and rituximab treatment (P < 0.0001) were favorable prognostic factors. Gender, ethnicity, hemoglobin, BM biopsy, and the type of imaging studies used were not significant. Rituximab and doxorubicin treatment worked significantly better in patients with age >71 and LDH >577 compared to nonrituximab, nondoxorubicin regimens (MANOVA 2 degrees of freedom, P = 0.0345), with a median time from treatment to death of 20.0 (95% confidence interval [CI] 14.0–N/A, n = 14) months versus 2.0 (95%CI 0.5–N/A, n = 5) (χ2 = 4.7, P = 0.0304). Patients with CNS IVL relapsed primarily in the CNS (88%) while same-organ relapse occurred less frequently in skin (23%), BM and spleen (50%) and lung (20%) IVL's. Our results indicate that IVL is primarily a disease of B-lymphoma cells. Timely diagnosis and treatment with rituximab-based chemotherapy improve patient survival. The pattern of recurrence is different between CNS IVL and IVL's in other organs.

A 58-year-old lady with progressive neurological syndrome: Presence of an intravascular lymphoma

“…[14] The geographic variation is possibly caused by genetic and epigenetic differences in the production of inflammatory cytokines. [4,10] Majority of the reported cases are single cases or short series with very few large cohorts, making it difficult to draw conclusions regarding its natural history, prognostic factors and best treatment options. A large meta-analysis of IVL involving 740 cases from 431 publications addresses this issue systematically.…”

“…A large meta-analysis of IVL involving 740 cases from 431 publications addresses this issue systematically. [10] IVL was initially diagnosed in the CNS (41%), skin (20%), bone marrow and spleen (17%) and lungs (7%) and occasionally in the other organs. The in vivo diagnosis was often delayed and was established only at the post-mortem studies in as high as 34% of the cases.…”

“…[7] Supporting these hypotheses is the aberrant expression of adhesion molecules CD11a and CD49d (VLA-4) on lymphoma cells and the absence of CD29 and CD54 (ICAM-1) markers, both of which are regarded as essential for lymphocyte homing and transvascular migration. [8,9] Classically, IVL is of B cell type (88%), [10] with B cell-associated antigen-positive CD19+CD20+CD22+CD79a+. The Han's algorithm classifies DLBCL into germinal centre B type [GCB] (CD10+) and non-GCB subtypes (CD10-BCL6-or CD10-BCL6+MUM1+).…”

“…This was more so in CNS-IVL (cIVL), where the post-mortem assessment established the diagnosis in 60% of the cases. [10] Patients with neurologic disease usually have one or more of the following presentations: (1) Progressive, multifocal cerebrovascular events, (2) spinal cord and nerve root vascular syndromes, (3) subacute encephalopathy, or (4) peripheral or cranial neuropathies. [15] Other manifestations include dementia, seizures, conus syndrome, myopathy and ocular difficulties.…”

“…Rarely, IVL with T-cell (6%) and NK (2%) cell phenotypes have also been identified. [10] The potentially widespread intravascular involvement of nearly every organ results in a multitude of clinical presentations. The absence of lymphadenopathy, hepatosplenomegaly or circulating cells in the peripheral blood makes accurate and timely diagnosis difficult.…”