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Immunophenotypic identification of Sezary cells in peripheral blood
S A Bogen1, D Pelley, M Charif
1Department of Pathology and Laboratory Medicine, Boston University Medical Center, MA 02118, USA.
Insights
The CD4+ CD7- immunophenotype accurately identifies Sezary cells in most Sézary syndrome/mycosis fungoides patients, offering a simpler alternative to nuclear contour analysis for diagnosing this T-cell leukemia.
Area of Science:
- Immunology
- Dermatology
- Oncology
Background:
- Current Sezary cell identification relies on nuclear contour analysis, a complex and inaccessible method.
- Anecdotal evidence suggests the CD4+ CD7- immunophenotype may identify Sezary cells, but lacks formal validation.
Purpose of the Study:
- To validate the accuracy of CD4+ CD7- subset quantitation for identifying Sezary cells.
- To assess the utility of this immunophenotype as a diagnostic tool for Sézary syndrome and mycosis fungoides.
Main Methods:
- Quantitation of the CD4+ CD7- cell subset.
- Comparison with nuclear contour analysis for Sezary cell enumeration.
- Correlation with other aberrant immunophenotypes (CD3low, CD4low) and clonal T lymphocytes (V beta TCR).
- Analysis of CD4/CD8 ratios in patients.
Main Results:
- Elevated percentages of CD4+ CD7- cells were observed in many Sézary syndrome/mycosis fungoides patients compared to healthy individuals.
- CD4+ CD7- enumeration correlated with nuclear contour analysis in most patients with elevated CD4/CD8 ratios (11/15).
- The CD4+ CD7- subset correlated with CD3low, CD4low expression, and clonal T lymphocytes.
- Caveats include uninformative results with normal CD4/CD8 ratios and CD7+ Sezary cells in ~25% of patients with elevated ratios.
Conclusions:
- CD4+ CD7- subset quantitation is a highly accurate method for identifying Sezary cells in most Sézary syndrome/mycosis fungoides patients.
- This immunophenotype offers a more accessible and potentially simpler alternative to nuclear contour analysis for clinical and research purposes.
- Clinical utility requires consideration of CD4/CD8 ratios and the possibility of CD7+ Sezary cells in a subset of patients.
Abstract:
Despite anecdotal literature that Sezary cells express the CD4+ CD7- immunophenotype, no formal validation has been published establishing the use of this immunophenotype for clinical or experimental purposes. Consequently, the only method presently available for Sezary cell identification is nuclear contour analysis, a labor-intensive procedure not generally available at most major medical centers. In this study, the accuracy of CD4+ CD7- subset quantitation for the identification of Sezary cells was examined. The study found that the percentage of CD4+ CD7- cells is elevated in many Sezary syndrome/MF patients relative to normal, healthy individuals. In addition, CD4+ CD7- enumeration correlates with enumeration by nuclear contour analysis in most patients (11 of 15) with elevated CD4/CD8 ratios. The CD4+ CD7- subset also correlates with the expression of other aberrant immunophenotypes, such as CD3low or CD4low. Lastly, CD4+ CD7- subset quantitation correlates with the number of clonal T lymphocytes, as measured using V beta-specific T-cell receptor monoclonal antibodies. The study found this method to be exceptionally accurate, with two caveats: (1) the absence of an expanded CD4+ CD7- subset in patients with a normal CD4/CD8 ratio is uninformative; and (2) in approximately 25% of patients with an elevated CD4/CD8 ratio, the Sezary cells are CD7+.