Sézary Syndrome

Dx
Monitor
Background
Lab Tests
Algorithm

Diagnosis

Indications for Testing

Abnormal chronic skin rash in patient >50 years

Laboratory Testing

CBC with manual differential
- Sézary cells >12 μm in diameter and ≥20%/100 lymphocytes are diagnostic
- Morphologic analysis of small populations of Sézary cells is relatively insensitive due to morphologic overlap with benign cells
Flow cytometric analysis – phenotyping
- Detect and quantify phenotypically abnormal T-cell population
  - Typically characterized by CD2+, CD3+, CD4+, CD5+, CCR4+, CD45RO+ neoplastic T-cell population
    - Often lack T-cell markers CD7 and CD26; may also lack CD2, CD3, and CD5
  - CD4/CD8 ratio >10:1; able to detect small T-cell neoplastic populations
  - Rare cases are CD8+
T-cell clonality studies
- Presence of T-cell clone (TCR gene) confirms diagnosis of Sézary syndrome in proper clinical context
- T-cell clonality may also be detected by flow cytometric approaches using V-beta testing
Nonspecific tests
- Metabolic panel
- Lactate dehydrogenase

Histology

Skin biopsy may show no diagnostic features
- Slides should be reviewed by pathologist with experience in cutaneous lymphomas
Bone marrow or lymph node biopsy – may not be necessary but recommended when patient has unexplained hematologic abnormality or significant adenopathy
Immunohistochemistry – may demonstrate selective loss of pan-T-cell antigens, particularly in CD3, CD8, and CD20
- May show alteration in CD4/CD8 ratio; however, calculation is not as accurate as flow cytometry
- Other possible T-cell antigens include CD2, CD5, CD7, CD30, CD26, and CD56

Differential Diagnosis

Monitoring

Neoplastic mature T-cell testing can be used to monitor treatment responses and follow disease levels in peripheral blood specimens for most patients with Sézary syndrome

Clinical Background

Sézary syndrome represents the disseminated, erythrodermic, leukemic form of mycosis fungoides, a primary cutaneous T-cell lymphoma; it is characterized by significant blood involvement and lymphadenopathy.

Epidemiology

Incidence – <0.5/100,000
- ~2% of all non-Hodgkin lymphomas
- 5% of cutaneous T-cell lymphomas
Age – median onset in 50s
Sex – M>F, 2:1
Ethnicity – occurs more frequently in African Americans

WHO Classification of Mature T- and NK-cell Neoplasms (2008)

Precursor T-cell neoplasm
T-cell prolymphocytic leukemia
T-cell large granular lymphocytic leukemia
Chronic lymphoproliferative disorder of NK-cells (provisional entity)
Aggressive NK-cell leukemia
Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorder of childhood
Adult T-cell leukemia/lymphoma (ATLL)
Extranodal NK/T-cell lymphoma, nasal type
Enteropathy-associated T-cell lymphoma
Hepatosplenic T-cell lymphoma
Subcutaneous panniculitis-like T-cell lymphoma
Mycosis fungoides
Sézary syndrome
Primary cutaneous CD30-positive T-cell lymphoproliferative disorders
Primary cutaneous gamma-delta T-cell lymphoma
Peripheral T-cell lymphoma, NOS (not otherwise specified)
Angioimmunoblastic T-cell lymphoma
Anaplastic large-cell lymphoma (ALCL), ALK positive
ALCL, ALK negative (provisional entity)

Pathophysiology

Considered to be caused by malignant T-helper cells in dynamic equilibrium between the skin and vascular compartments
Sézary cells are abnormal lymphocytes that undergo nuclear, but not cytoplasmic, division
- Benign cells that morphologically resemble Sézary cells can be seen in small numbers in normal peripheral blood

Clinical Presentation

Erythroderma, edema, pruritus, adenopathy, ectropion, keratoderma
Most commonly, signs and symptoms arise de novo but can follow nonspecific dermatitis or, rarely, mycosis fungoides
Patients diagnosed with Sézary syndrome generally have a more advanced disease stage and worse prognosis than those diagnosed with classic mycosis fungoides localized to skin

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations
Click on number for test-specific information in the ARUP Laboratory Test Directory

Test Name and Number	Recommended Use	Limitations
CBC with Platelet Count and Automated Differential 0040003 Method: Automated Cell Count/Differential	Manual differential may detect Sézary cell changes in order to rule out leukemic cell disorders
Manual Differential 0040005 Method: Microscopy	Use to detect Sézary cells	Requires relatively large numbers of neoplastic cells (>20% of lymphocytes) due to morphologic overlap with benign lymphocytes
Leukemia/Lymphoma Phenotyping by Flow Cytometry 2008003 Method: Flow Cytometry	Initial test when evaluating hematopoietic neoplasms (ie, leukemia, lymphoma) Monitor therapy in patients with established diagnosis of hematopoietic neoplasms Specimens include peripheral blood, bone marrow, and tissue Markers selected based on clinical history, previous flow studies, and pathologist interpretation Available markers: T cell: CD1, CD2, CD3, CD4, CD5, CD7, CD8, TCR alpha-beta, TCR gamma-delta, cytoplasmic CD3 B cell: CD10, CD19, CD20, CD22, CD23, CD103, kappa, lambda, FMC7, cytoplasmic kappa, cytoplasmic lambda Myelo/Mono: CD11b, CD13, CD14 (Mo2), CD14 (MY4), CD15, CD33, CD64, CD117, myeloperoxidase Misc: CD11c, CD16, CD25, CD30, CD34, CD38, CD41, CD42b, CD45, CD56, CD57, CD61, HLA-DR, glycophorin, TdT, bcl-2, ALK-1, CD123, CD138, CD200, CD26, CD45
T-Cell Clonality Screening by PCR 0055567 Method: Polymerase Chain Reaction/Capillary Electrophoresis	Characterize abnormal T cells Confirm results from phenotyping testing	“Not detected” PCR screening results should be terminally analyzed by restriction fragment Southern blot hybridization (RF-SBH) to definitively exclude T-cell monoclonality
T-Cell Clonality by Flow Cytometry Analysis of TCR V-Beta 0093199 Method: Flow Cytometry	Further characterize phenotypically abnormal T-cell populations identified by flow cytometry and identify evidence of monoclonality based on expression of T-cell antigen receptor beta chain variable regions (TCR V-Beta) Suggest ordering along with Neoplastic Mature T-Cell Evaluation flow cytometry
Sezary Cell Exam 0049180 Method: Stain	Suggestive of Sézary syndrome in patient with mycosis fungoides Not a first-line test in diagnosis; flow cytometry is the preferred method of testing due to sensitivity and specificity	Requires relatively large numbers of neoplastic cells (>15% of lymphocytes) due to morphologic overlap with benign lymphocytes
CD3 by Immunohistochemistry 2003508 Method: Immunohistochemistry	Aid in histologic diagnosis of Sézary syndrome Stained and returned to client pathologist for interpretation; consultation available if needed
CD8 by Immunohistochemistry 2003520 Method: Immunohistochemistry	Aid in histologic diagnosis of Sézary syndrome Stained and returned to client pathologist for interpretation; consultation available if needed
CD20, L26 by Immunohistochemistry 2003532 Method: Immunohistochemistry	Aid in histologic diagnosis of Sézary syndrome Stained and returned to client pathologist for interpretation; consultation available if needed
CD4 by Immunohistochemistry 2003511 Method: Immunohistochemistry	Aid in histologic diagnosis of Sézary syndrome Stained and returned to client pathologist for interpretation; consultation available if needed
Comprehensive Metabolic Panel 0020408 Method: Quantitative Ion-Selective Electrode/Quantitative Enzymatic/Quantitative Spectrophotometry	Assess visceral organ involvement
Lactate Dehydrogenase, Serum or Plasma 0020006 Method: Quantitative Enzymatic	Determine bone involvement

Additional Tests Available

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
CD2 by Immunohistochemistry 2003505 Method: Immunohistochemistry
CD5 by Immunohistochemistry 2003514 Method: Immunohistochemistry
CD7 by Immunohistochemistry 2003517 Method: Immunohistochemistry
CD30 (Ki-1) by Immunohistochemistry 2003547 Method: Immunohistochemistry
CD56 (NCAM) by Immunohistochemistry 2003589 Method: Immunohistochemistry