Acute blast crisis with EBV-infected blasts, in a patient with chronic myeloid leukemia, and vasculitis.

Unless they undergo transplantation, all patients with chronic myeloid leukemia (CML) will eventually develop a late phase of acute blast crisis (ABC). Although additional chromosomal abnormalities to the Philadelphia (Ph) chromosome may herald ABC in many CML cases, the mechanisms leading to this fatal event are obscure. Viral etiology, including the Epstein-Barr virus (EBV) has never been implicated in the pathogenesis of ABC in CML. Iloprost is an analogue of epoprostenol (prostacyclin; PGI2) commonly used for the treatment of peripheral vascular diseases and acts via inhibition of platelet activation, and by vasodilation. A case of ABC with blasts of undetermined lineage showing EBV infection in a male patient with Ph positive CML is described here. This unusual event developed during a course of treatment with the prostacyclin analogue, iloprost administered for vasculopathic leg ulcers. The proliferating blasts stained positively by immunohistochemistry only for the leukocyte common antigen (LCA/CD-45), and the EBV-latent membrane protein 1 (LMP-1). The only chromosomal abnormality detected by cytogenetic analysis was the conventional Ph-chromosome. It is suggested that ABC in this case of CML, was associated with EBV-activated blasts of undetermined lineage.

Lymphoproliferative disorders of natural killer cells.

Natural killer (NK) cells are a distinct non-T, non-B lineage of lymphocytes that mediate major histocompatibility complex-unrestricted cytotoxicity. Morphologically they are large granular lymphocytes, and phenotypically they commonly express CD16 and CD56 antigens, without expressing cell surface CD3. Although the developmental pathway of NK cells is not fully understood, they arise from CD34+ hematopoietic stem cells and, at least in part, differentiate in the bone marrow. They gain byctoplasmic CD3 gamma delta epsilon zeta antigens during maturation, and lose cytoplasmic CD3 gamma delta epsilon thereafter until the terminal maturation. Lymphoproliferative disorders of NK cells include NK cell-lineage granular lymphocyte-proliferative disorders (NK-GLPD), NK-cell lymphoma, and acute leukemia of NK-cell lineage. NK-GLPD are relatively rare. Most patients exhibit a chronic indolent clinical course, and do not require specific treatment. However, some patients exhibit an aggressive clinical course, and die of the disease despite extensive chemotherapy. This aggressive type NK-GLPD is caused by Epstein-Barr virus (EBV). Patients with NK-cell lymphoma are rare, and often exhibit necrotic lesion and angiocentric morphology. This tumor is mainly found in the nasal tract, but the true incidence of NK-cell lymphoma in nasal lymphomas is not known. Probably many lymphomas arising from the nasal cavity, but not from paranasal sinuses, are of NK-cell lineage. NK-cell lymphoma is also caused by EBV, and is resistant to combination chemotherapy. Acute leukemia of NK-cell lineage is very rare. Several cases of acute lymphoblastic leukemia and a single case of blast crisis of chronic myelogenous leukemia have been documented to have leukemic blasts characteristic of NK cells. However, the precise lineage and differentiation stage of the leukemic blasts have not been delineated.