Sézary Syndrome

  • Diagnosis
  • Algorithms
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

Indications for Testing

  • Undiagnosed chronic skin rash in patients >50 years

Laboratory Testing

  • Peripheral blood tests
    • 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 – may be unnecessary if skin biopsy is diagnostic
      • 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 dermopathologist 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
    • Panel should include CD2, CD3, CD4, CD7, CD8, CD20, CD25, CD30, CD58, TIA1, and granzymes B, BF1, TCR-CyM1

Differential Diagnosis

  • 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

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

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
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.

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

T-Cell Clonality by Next Generation Sequencing 2008409
Method: Massively Parallel Sequencing

Limitations 

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

Sezary Cell Exam 0049180
Method: Stain

Limitations 

Requires relatively large numbers of neoplastic cells (>15% of lymphocytes) due to morphological overlap with benign lymphocytes

CD3 by Immunohistochemistry 2003508
Method: Immunohistochemistry

CD8 by Immunohistochemistry 2003520
Method: Immunohistochemistry

CD20, L26 by Immunohistochemistry 2003532
Method: Immunohistochemistry

CD4 by Immunohistochemistry 2003511
Method: Immunohistochemistry

Comprehensive Metabolic Panel 0020408
Method: Quantitative Ion-Selective Electrode/Quantitative Enzymatic/Quantitative Spectrophotometry

Lactate Dehydrogenase, Serum or Plasma 0020006
Method: Quantitative Enzymatic

Guidelines

NCCN Clinical Practice Guidelines in Oncology, Non-Hodgkin's Lymphomas. National Comprehensive Cancer Network. Fort Washington: Pennsylvania [Accessed: 18 Jun 2015]

Olsen EA, Rook AH, Zic J, Kim Y, Porcu P, Querfeld C, Wood G, Demierre M, Pittelkow M, Wilson LD, Pinter-Brown L, Advani R, Parker S, Kim EJ, Junkins-Hopkins JM, Foss F, Cacchio P, Duvic M. Sézary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC). J Am Acad Dermatol. 2011; 64(2): 352-404. PubMed

Protocol for the Examination of Specimens From Patients With Hematopoietic Neoplasms Involving the Bone Marrow. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Jun 2012. College of American Pathologists (CAP). Northfield, IL [Accessed: Jun 2015]

Slater DN. The new World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas: a practical marriage of two giants. Br J Dermatol. 2005; 153(5): 874-80. PubMed

Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH, Ralfkiaer E, Chimenti S, Diaz-Perez JL, Duncan LM, Grange F, Harris NL, Kempf W, Kerl H, Kurrer M, Knobler R, Pimpinelli N, Sander C, Santucci M, Sterry W, Vermeer MH, Wechsler J, Whittaker S, Meijer CJ. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005; 105(10): 3768-85. PubMed

General References

Elenitoba-Johnson K, Lim M, Kjeldsberg C. Mature T-cell and NK-cell. In Kjeldsberg C and Perkins SL. Practical Diagnosis of Hematologic Disorders, 5th ed. Chicago: ASCP Press, 2010.

Jawed SI, Myskowski PL, Horwitz S, Moskowitz A, Querfeld C. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part I. Diagnosis: clinical and histopathologic features and new molecular and biologic markers. J Am Acad Dermatol. 2014; 70(2): 205.e1-16; quiz 221-2. PubMed

Jawed SI, Myskowski PL, Horwitz S, Moskowitz A, Querfeld C. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part II. Prognosis, management, and future directions. J Am Acad Dermatol. 2014; 70(2): 223.e1-17; quiz 240-2. PubMed

Lansigan F, Choi J, Foss FM. Cutaneous T-cell lymphoma. Hematol Oncol Clin North Am. 2008; 22(5): 979-96, x. PubMed

LeBoit P. Mycosis Fungoides and Sezary Syndrome. In Jaffe ES, et al. Hematopathology, St Louis, MO: Elsevier Saunders, 2011.

Matutes E. Adult T-cell leukaemia/lymphoma. J Clin Pathol. 2007; 60(12): 1373-7. PubMed

Prince M, Whittaker S, Hoppe RT. How I treat mycosis fungoides and Sézary syndrome. Blood. 2009; 114(20): 4337-53. PubMed

Song SX, Willemze R, Swerdlow SH, Kinney MC, Said JW. Mycosis fungoides: report of the 2011 Society for Hematopathology/European Association for Haematopathology workshop. Am J Clin Pathol. 2013; 139(4): 466-90. PubMed

Swerdlow S, Campo E, Harris N, Jaffe E, Pileri S, Harald S, Thiele J, Vardiman J. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th ed. Lyon, France: International Agency for Research on Cancer, 2008.

Vaughan J, Harrington AM, Hari PN, Kroft SH, Olteanu H. Immunophenotypic stability of Sézary cells by flow cytometry: usefulness of flow cytometry in assessing response to and guiding alemtuzumab therapy. Am J Clin Pathol. 2012; 137(3): 403-11. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Bahler DW, Hartung L, Hill S, Bowen GM, Vonderheid EC. CD158k/KIR3DL2 is a useful marker for identifying neoplastic T-cells in Sézary syndrome by flow cytometry. Cytometry B Clin Cytom. 2008; 74(3): 156-62. PubMed

Kadin ME, Pavlov IY, Delgado JC, Vonderheid EC. High soluble CD30, CD25, and IL-6 may identify patients with worse survival in CD30+ cutaneous lymphomas and early mycosis fungoides. J Invest Dermatol. 2012; 132(3 Pt 1): 703-10. PubMed

Nance D, Rodgers GM. Switching haemophilia products and inhibitor risk: a United States' perspective Eur J Haematol. 2015; 94(4): 283. PubMed

Medical Reviewers

Last Update: September 2016