Intravascular large B-cell lymphoma (IVLBCL) is a rare entity characterized by growth of neoplastic lymphocytes in the lumina of small blood vessels. Hallmarks of the disease include poor performance status, elevated lactate dehydrogenase levels, anemia, B symptoms and variable clinical presentation. In this study, we conducted a retrospective analysis of all identified cases of intravascular lymphoma that presented within a large integrated healthcare delivery system, reviewing clinical presentation, laboratory findings, pathological features and outcomes.
Kaiser Permanente Northern California (KPNC) provides care to approximately 3.2 million members and maintains centralized database of all hospital and ambulatory visits, laboratory, pathology, radiology, and pharmacy records. We utilized electronic pathology record databases to identify all cases of intravascular lymphoma, defined by the World Health Organization from January 1995 - July 2010 using the following search terms: intravascular lymphoma, intravascular B-cell lymphoma, intravascular T-cell lymphoma, intra vascular lymphoma, malignant angioendotheliomatosis, and angiotropic large-cell lymphoma.
Twelve cases of IVLBCL were identified. Median age was 70 years, female to male ratio of 2 to 1. 50% were diagnosed in vivo. The median time of diagnosis from onset of symptoms was 1.5 months. Four patients underwent multiple biopsies prior to diagnosis. Of the six patients with in vivo diagnosis, three were made by bone marrow biopsy, one by small bowel resection, one by muscle biopsy, and one by abdominal fat pad biopsy.
At the time of diagnosis, ten (83%) patients had B symptoms and seven (58%) patients had ECOG≥4. Other common organ systems involved on presentation included neurological (58%) and gastrointestinal symptoms or hepatic involvement (58%).
Increased serum lactate dehydrogenase was seen in 92% of patients, anemia in 92% of patients and thrombocytopenia in 75% of patients. Elevated erythrocyte sedimentation rate seen in 67% of patients and elevated C-reactive protein in 58% of patients.
Extremely low subnormal high density lipoprotein cholesterol level (HDL-C) was present in 10 of 11 patients with measured lipoprotein profiles. The median HDL-C was 22 mg/dl (range <4–56 mg/dl). Levels of low density lipoprotein cholesterol, total cholesterol and triglyceride levels were all within the normal range (median 61 mg/dl, 117 mg/dl and 230 mg/dl respectively).
All patients had biopsy proven involvement of at least one organ. Four patients had complete autopsy. The sites of disease involvement included bone (4), gastrointestinal tract (4), renal (4), lymph node (3), spleen (3), central nervous system (2), liver (2), peripheral blood (1), hemophagocytosis syndrome (1).
Four patients received chemotherapy. CHOP (1), R-CHOP (3). Overall survival was 8 days (CHOP); 38 days to >5 years (R-CHOP). The one patient in our cohort who achieved complete remission had localized bowel IVLBCL, treated with resection and three cycles of R-CHOP.
Our cases represent a population-based ascertainment of IVLBCL within a large unselected clinic population. The clinical presentation and organ system involvement is variable. The disease is aggressive with poor outcomes. The unique finding in our series was the low HDL-C prior to diagnosis of IVLBCL. HDL-C may represent a possible preclinical indicator of this rare lymphoma.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.