Distinct Populations of CD8+/CD57+ Large Granular Lymphocytes Are Associated with T-Cell Monoclonality and Define a Subset of Clinically and Pathologically Significant Patients: A Case-Control Study of 70 Patients with Large Granular Lymphocytic Proliferations.
Robert S Ohgami, Irma T Pereira, James L Zehnder, Daniel A Arber. Stanford University Medical Center, CA
Background: Large granular lymphocytic (LGL) leukemia is a disease with chronic elevations of LGLs for > 6 months associated with a T-cell clone and often cytopenias. While a defined classification has been established in the 2008 WHO, the clinical and pathologic diagnosis often remains elusive, as significant polyclonal or oligoclonal proliferations of LGLs can be seen in reactive conditions.
Design: In an attempt to identify flow cytometry patterns associated with monoclonality, we performed a retrospective review of patients at our institute between 2003-2010 with significant populations of LGLs and concurrent T-cell clonality tests. 70 cases were identified and were divided impartially by time into a study set (2008-2010) and an experimental set (2003-2007).
Results: In the study set (2008-2010), 33 flow cytometry cases were identified, which stratified into 18 cases with monoclonal T-cell populations and 15 with oligoclonal or polyclonal populations. Comparing flow cytometry scatter-plots, we identified that cases with distinct CD8+(dim)/CD57+ populations were significantly associated with T-cell monoclonality (P = 0.0026) as well as lower neutrophil counts (average ANC= 1.55, p < 0.001) (See Figure 1). Such a preliminary analysis suggested that identification of patients with specific CD8+(dim)/CD57+ populations might define patients with not only monoclonal proliferations, but also with clinically and pathologically significant disease. To further evaluate this hypothesis, we used these criteria (discrete CD8+(dim)/CD57+ populations) to examine, in a blinded analysis, our experimental set of 37 consecutive cases of large granular lymphocytosis from 2003-2007. 12 cases were identified which demonstrated significant CD8+(dim)/CD57+ populations. Yet again, we observed that distinct populations of CD8+(dim)/CD57+ populations were associated with T-cell monoclonality (P =0.0174), as well as neutropenia (average ANC=1.55; P =0.026).
Conclusions: These findings demonstrate and define a major subset of clinically and pathologically significant patients through the use of flow cytometry immunophenotyping.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 173, Monday Morning