CD5-negative, CD10-negative small B-cell leukemia: variant of chronic lymphocytic leukemia or a distinct entity?

CD5- and CD10-negative chronic lymphocytic leukemias are quite uncommon as compared to the CD5-positive CLL. We reviewed 250 sequential cases of peripheral blood lymphocytosis to characterize cases of small B-cell lymphoproliferative disorders, submitted with a clinical diagnosis of chronic lymphocytic leukemia exhibiting a non-classic immunophenotypic profile. Six cases of CD5-, CD10-negative chronic lymphocytic leukemias and no tissue involvement were identified that revealed high-density surface-membrane immunoglobulin and CD20 expression, with variable expression of CD11c, CD23, and CD25. Most had a profound leukocytosis (mean WBC 180 x 10(9)/L) with proliferation of mature-appearing lymphocytes. Subsequent bone marrow biopsies showed diffuse infiltration by neoplastic cells in all evaluated patients. The clinical course appeared indolent, with follow-up revealing three patients alive (survival time 38-68 months), while two died of unrelated causes and one was lost to follow-up soon after diagnosis. These cases may represent somewhat unusual chronic lymphoproliferative disorders, with morphologic features and immunophenotypic profile not readily classifiable, but which are certainly atypical for classic chronic lymphocytic leukemia. Some of these features are reminiscent of those seen in marginal-zone lymphoma. However, it is most unusual for this known to be tissue-based disease to present primarily as leukemia rather than lymphoma.