Plasma Cell Leukemia (PCL) is an aggressive form of myeloma in which the neoplastic plasma cells make up more than 20% of leukocytes in the peripheral blood. PCL may be present at the time of initial diagnosis (primary) or evolve later in an established case of myeloma (secondary). About 60% of PCL cases are primary and they account for 2% to 5% of myelomas. PCL vs Myeloma: When compared to multiple myeloma, the patients with PCL tend to be younger and more commonly have lymphadenopathy, organomegaly, renal complications, anemia and thrombocytopenia. On the other hand, lytic bone lesions and bone pain are less common. PCL is often CD56 negative in contrast to myeloma. PCL tends to be associated more frequently with IgD, IgE, and light-chain only myelomas in contrast to IgG or IgA myelomas. Abnormal karyotype and unfavorable cytogenetics are more frequently associated with PCL. PCL is a highly aggressive neoplasm with dismal prognosis. It does not respond well to therapy and the median survival is much shorter than with typical myelomas. The image shows a peripheral blood smear from a case of plasma cell leukemia. The center shows a plasmablast (black arrow). Nucleolus is prominent. Rouleaux of red cells is present in the background. Wright-Giemsa stain. 100X oil. Courtesy of: Jian-Hua Qiao, MD, FCAP, Los Angeles, CA, USA.