A 69–year–old Hispanic male, with a past history of diabetes and coronary artery disease, was admitted for fever, diarrhea and confusion of 4 weeks’ duration. Physical examination showed a disoriented patient with multiple ecchymoses, possible ascites and bilateral scrotal swelling. Hemoglobin was 6.7, PT 21.4 s with INR 2.1, PTT 55.6 s, fibrin split 10 mg/L, LDH 1231 IU/L. Except for a positive DNA test for EBV virus infection, extensive diagnostic work–up for infections (HIV and hepatitis, bacterial, fungal, AFB), malignancy (CT scans of brain, chest, abdomen, pelvis, scrotal ultrasound, bone marrow biopsy × 2) or a neurological cause (lumbar puncture) was negative. Mixing studies revealed a nonspecific inhibitor of PT and PTT but Factor VIII levels were normal. Patient was empirically treated with antibiotics but developed hypotension and died on day 27 of admission. At autopsy, patient was found to have intravascular diffuse large B–cell lymphoma involving testes, lung and muscles. The malignant cells were positive for CD20, CD791, Mum–1, Pax–5 and negative for CD3, CD5, CD10, CD30 and Bcl–6. The malignant cells were 100% positive for Ki–67.
Intravascular large cell B–cell lymphoma (IDLBCL) is rare form of diffuse large B–cell lymphoma, and tends to proliferate within small blood vessels, particularly capillaries and post–capillary venules. The cause of its affinity for vascular bed remains unknown. In many reports, IDLBCL was associated with HIV, HHV8 and EBV infections. The fact that our case showed evidence of EBV infection lends support to the association of this diagnosis to viral illness. The available literature on this subject is scant and in many cases, the diagnosis was made only at autopsy. The typical presentation of this disorder is with B symptoms, progressive neurologic deficits and skin findings. Bone marrow, spleen and liver are involved in a minority of patients. Nearly all patients have elevated LDH and about 65% are anemic. About 20% have hepatic and renal disfunction. The treatment consists of systemic chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone plus rituximab (CHOP–R) and CNS prophylaxis. Retrospective data suggests that, with treatment, 51–82% of the patients achieve a complete remission and 27 to 56% are alive at 2–year follow–up.
IDLBCL is a difficult diagnosis to make as the disease remains confined to vascular lumen. It may be associated with certain viral illnesses and this association needs to be explored further. It is important to consider this diagnosis in the appropriate settings because patients may achieve durable remissions with therapy.
Figure 1Skin biopsy showing malignant cells.