TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: SZMON    
Sezary Monitoring Flow Cytometry, Blood

Useful For Suggests clinical disorders or settings where the test may be helpful

Monitoring response to therapy in patients with previously diagnosed Sezary syndrome or mycosis fungoides

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Sezary panel is ordered in cases with previously diagnosed Sezary syndrome or cutaneous T-cell lymphoma (CTCL) with peripheral blood involvement. For cases without a previously confirmed diagnosis or previously performed immunophenotyping at our laboratory, the ordered test will be changed to SZDIA / Sezary Diagnostic Flow Cytometry, Blood, which includes a triage panel to exclude a B-cell lymphoproliferative disorder and a Sezary panel. If there is a significant phenotypically distinct T-cell population detected, a V-beta panel for proof of clonality may be ordered by the signing pathologist.

 

The panel is charged based on number of markers tested (FIRST for first marker, ADD1 for each additional marker). In addition, reflex testing may occur to fully characterize a disease state or clarify any abnormalities from the screening test. Reflex tests will be performed at an additional charge for each marker tested (ADD1 if applicable).

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Sezary syndrome is a leukemic form of cutaneous T-cell lymphoma (CTCL). By definition, it is associated with systemic skin involvement (erythroderma) and the presence of at least 1000/microL of circulating cells with irregular nuclear features (Sezary cells). Morphologic assessment of the number of Sezary cells has been proven to have low reproducibility. Therefore, WHO/European Organization for Research and Treatment of Cancer (EORTC) classification of skin tumors adopted alternative methods to assess circulating T-cells in order to establish the diagnosis of Sezary syndrome. These include CD4:CD8 ratio of more than 10:1, and selective loss of CD7 and/or CD26 on 40% and 30% of the CD4-positiveT-cell population, respectively. It is important to recognize that the later criteria (fulfilled by peripheral blood flow cytometry immunophenotyping) are relative, and not in direct correlation with absolute counts of Sezary cells defined by morphology.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided. This test will be processed as a laboratory consultation. An interpretation of the immunophenotypic findings and, if available, morphologic features will be provided by a board-certified hematopathologist for every case.

Interpretation Provides information to assist in interpretation of the test results

Sezary cells typically show loss of CD7 and/or CD26. As loss of these markers is not completely sensitive or specific for Sezary cells, the WHO/European Organization for Research and Treatment of Cancer (EORTC) classification of skin tumors proposed cutoffs of 30% for CD26 loss and 40% for CD7 loss on CD4-positive T-cells, as diagnostic criteria for Sezary syndrome. In addition, CD4:CD8 ratio of greater than or equal to 10:1 in a gated T-cell population is also considered abnormal, and part of diagnostic algorithm for Sezary syndrome.

 

In mycosis fungoides staging studies the cutoffs are even less clearly defined. The clinical outcome was worse in patients with more than 5% of circulating lymphocytes showing Sezary-like morphology. However, flow cytometry immunophenotyping is deemed useful for relative quantification of these cells only if they can be separated by aberrant expression of other surface markers. In majority of cases, this cannot be accomplished to the proposed cutoff point (5% of circulating lymphocytes).

 

The test will be resulted as "No phenotypically aberrant T-cell population detected" if there is no specific phenotype that allows separation of potentially abnormal CD4-positive T-cells, loss of CD26 (and/or CD7) is present in less than 30% (40%), and CD4:CD8 ratio is less than 10:1. If any of the above aberrancies are present, the test will be resulted as "Phenotypically distinct T-cell population is detected" with a description of phenotype, percentage of total CD4-positive population and percentage of total analyzed events. In addition, the phenotype will be compared to that of any distinct T-cell population previously seen in the same patient by our laboratory.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Correlation with clinical features is necessary for diagnosis of Sezary syndrome. This analysis can only describe a cell population with aberrant phenotype, but the significance of this finding in isolation is uncertain.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Honra P, Deaver DM, Qin D, et al: Quantitative flow cytometric identification of aberrant T cell clusters in erythrodermic cutaneous T cell lymphoma. Implications for staging and prognosis. J Clin Pathol 2014;67:431-436

2. Vaughan J, Harrington AM, Hari PN, et al: Immunophenotypic stability of Sezary cells by flow cytometry: usefulness of flow cytometry in assessing response to and guiding alemtuzumab therapy. Am J Clin Patho. 2012 Mar;137(3):403-411

3. Kelemen K, Guitart J, Kuzel TM, et al: The usefulness of CD26 in flow cytometric analysis of peripheral blood in Sezary syndrome. Am J Clin Pathol 2008 Jan;129(1):146-156

4. Wilcox RA. Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol 2016;91:152-165 doi: 10.1002/ajh.24233

5. Olsen E, Vonderheid E, Pimpinelli N, et al: Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood 2007 Sep 15;110(6):1713-1722

6. Willemze R, Jaffe ES, Burg G, et al: WHO-EORTC classification for cutaneous lymphomas. Blood 2005;105:3768-3785