Sézary Syndrome

Diagnosis

Indications for Testing

  • Undiagnosed chronic skin rash in patients >50 years

Laboratory Testing

  • CBC with manual differential
    • Sézary cells >12 μm in diameter and ≥20%/100 lymphocytes are diagnostic
    • Morphological analysis of small populations of Sézary cells is relatively insensitive due to morphological overlap with benign cells
  • Flow cytometry analysis – phenotyping
    • Detect and quantify phenotypically abnormal T-cell population
      • Typically characterized by CD4+, CD5+, CCR4+, CD45RO+, and dim CD2+, CD3+ neoplastic T-cell population
        • Usually lack T-cell markers CD7 and CD26; may also lack CD2, CD3, and CD5
      • CD4/CD8 ratio >10; 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 cytometry using V-beta testing

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 be unnecessary but recommended when patient has unexplained hematological 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 – 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 is the disseminated, erythrodermic, leukemic form of mycosis fungoides (primary cutaneous T-cell lymphoma). It is characterized by significant marrow involvement and lymphadenopathy. 

Epidemiology

  • Incidence – <1/100,000
    • ~2-4% of all non-Hodgkin lymphomas
    • 3% of cutaneous T-cell lymphomas (WHO 2008)
  • Age – median onset in 50s
  • Sex – M>F, 2:1
  • Ethnicity – occurs more frequently in African Americans

Classification

  • 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, pruritus, +/- generalized adenopathy
  • 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
  • Increased risk for second malignancies – most commonly, Hodgkin and other T-cell lymphomas

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 Follow Up
Leukemia/Lymphoma Phenotyping by Flow Cytometry 2008003
Method: Flow Cytometry

Aid in evaluation of 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 by Next Generation Sequencing 2008409
Method: Massive Parallel Sequencing

Diagnosis and monitoring of T-cell lymphoproliferative disorders

Clonal TCRG gene rearrangements below the limit of detection will not be reported

 
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 morphological 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 NumberComments
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

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