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From a 2DE-Gel Spot to Protein Function: Lesson Learned From HS1 in Chronic Lymphocytic Leukemia
Published on: October 19, 2014
Immunophenotype does not correlate with lymph node histology in chronic lymphocytic leukemia/small lymphocytic
Sheryl L Asplund1, Robert W McKenna, Michael S Howard
1University of Texas Southwestern Medical School, Dallas, Texas, USA. Sheryl.Asplund@UTSouthwestern.edu
Insights
Prominent proliferation centers in chronic lymphocytic leukemia/small lymphocytic lymphoma lymph nodes do not indicate distinct subtypes. Flow cytometry and morphology analysis showed no correlation with clinical features, challenging previous associations.
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- Prominent proliferation centers (PCs) in lymph nodes (LNs) of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) are linked to atypical morphology and poor outcomes.
- The clinical significance of abundant PCs in CLL/SLL LNs remains debated.
Purpose of the Study:
- To investigate the immunophenotypic features of CLL/SLL LNs based on PC prominence.
- To correlate these immunophenotypic findings with morphologic and clinical features.
Main Methods:
- Analyzed 54 CLL/SLL LNs using flow cytometry with antibody panels including CD5, CD19, CD20, CD23, CD38, FMC7, and surface immunoglobulin (sIg).
- Histologically classified LNs into Group I (scattered PCs) and Group II (prominent PCs).
- Scored marker intensity semi-quantitatively and calculated an immunophenotypic atypia score.
Main Results:
- No significant correlation was found between histologic group (PC prominence) and the intensity of individual marker expression.
- No association was observed between PC prominence or immunophenotype and clinical features.
- Immunophenotypic atypia scores did not correlate with the histologic classification based on PC prominence.
Conclusions:
- The prominence of proliferation centers in CLL/SLL LNs does not define biologically distinct subtypes.
- Current findings do not support the interpretation that abundant PCs in CLL/SLL LNs signify a different disease course or immunophenotype.
Abstract:
The presence of prominent proliferation centers (PCs) in lymph nodes (LNs) involved with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has been associated with atypical blood smear morphology. Atypical CLL has in turn been associated with variant immunophenotypes and poor outcome. However, the significance of abundant PCs remains controversial. We have analyzed the flow cytometric immunophenotypic features of 54 CLL/SLL LNs and correlated these findings with the morphologic and clinical features. The LN histology was assigned to one of two groups based on the prominence of PCs: Group I LNs contained scattered small, sometimes ill-defined PCs in a background of monotonous small round lymphocytes. Group II LNs had increased numbers and sizes of PCs resulting in an obviously nodular appearance at low magnification. Flow cytometry was performed using broad three- or four-color antibody panels that included anti-CD5, CD19, CD20, CD23, CD38, FMC7, and surface immunoglobulin (sIg). The intensity of expression of all markers was scored semi-quantitatively using isotypic controls and internal positive and negative populations as standards. There were 32 group I and 22 group II LNs that, by definition, expressed CD19, CD5, and CD23. Little variability was seen in the intensity of expression of CD19, and the majority of cases expressed CD23 brightly. CD5 varied from very dim to an intensity similar to that of normal T cells; the majority had an intermediate level of CD5 expression. FMC7 was expressed to a significant extent in 11 cases (21%). CD20 was relatively bright in 17 cases (32%). sIg was dim in 29 cases (55%) and moderate or bright in 24 cases (45%). CD38 was expressed significantly in 25 cases (47%). There was no correlation between histologic group and intensity of expression of any individual marker or with an immunophenotypic atypia score based on FMC7, CD20, and sIg. There was also no correlation between morphology or immunophenotype and clinical features. These findings do not support the interpretation that the prominence of proliferation centers in CLL/SLL LNs defines biologically distinct subtypes.
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