The Nature and Frequency of Atypical Phenotypic Features Detected by Flow Cytometry in CLL: Correlation with Prognostic Markers CD38 and ZAP70
NM Hassanein, E Kulbacki, E Wang, JB Weinberg, AS Lagoo. Duke University Medical Center, Durham, NC; Durham VA Medical Center, Durham, NC
Background: Prognostic markers in chronic lymphocytic leukemia (CLL) have garnered much attention in the past decade. Characteristically, CLL has a flow cytometric immunophenotype which includes dim surface Ig, dim/ heterogeneous CD20, co-expression of CD5 and CD23, and lack of CD123. Cases showing variation from this pattern are often referred to as “Atypical CLL.” The prognostic significance of these “atypical CLL” cases is unclear.
Design: A detailed retrospective re-analysis of flow cytometry findings was conducted in 194 CLL cases first examined in past five years in the Clinical Flow Cytometry Laboratory at our Institution.
Results: 72 of 194 cases (37.1%) had some atypical flow cytometric findings, which included 38 cases (52%) with strong surface immunoglobulin expression; 38 cases (52%) with uniform, moderate or bright CD20; 29 cases (40%) with partial expression of CD23; and 15 cases (21%) with partial CD5 expression. Aberrant expression of CD7 was found in 17 (23%), of CD123 in 12 (16%), and of CD8 in 6 (8.1%) cases. These phenotypic abnormalities were present as a single abnormality in 23 (31%) cases, and in combination in the remaining cases. In cases with multiple abnormalities, 21 (29%) had 2 abnormalities, 20 (27%) cases 3 abnormalities, 7 (9%) cases 4 abnormalities, and 1 (1%) had 5 abnormalities. Among the cases with atypical flow cytometric findings, CD38 was expressed in 38/72 (52.7%) cases, while ZAP -70 was positive in11/39 (28.2%) of examined cases, 26/39 (66.6%) cases were negative, and 2/39 (5.1%) were indeterminate. In 122 cases with typical flow cytometry findings, 30 of 93 (32.2%) cases were positive, 49 of 93 (52.6%) were negative, and 14 of 93 (15.1%) were indeterminate for ZAP70. For CD38 expression, 48 of 122 cases (39.3%) were positive, and 74 of 122 (60.6%) were negative.
Conclusions: CD38 expression is seen significantly more frequently in CLL cases with an atypical phenotype than in those with a classic phenotype (p = 0.023, Fisher exact test), but there is no significant difference in ZAP70 expression in typical and atypical CLL cases (p = 0.116, Fisher exact test). Additional information (e.g., immunoglobulin gene mutation status, cytogenetics, and patient survival) will help us further characterize these patients and determine whether patients with atypical CLL differ from typical CLL prognostically.
Monday, March 22, 2010 1:00 PM
Poster Session II # 155, Monday Afternoon