Sézary syndrome

Sézary & Bouvrain 1938.

Aggressive, leukemic cutaneous T-cell lymphoma.

• First manifestation usually between 5-7 decades of life.
• Men > Women.

• Unknown.
• Under certain circumstances it is the erythrodermal variant of Mycosis fungoides.

• Size-progressive, slightly scaly, pruriginous erythema, which in the course of time leads to erythroderma. The skin lesions tend to be hyperpigmentated, which is why they are referred to as melanoerythrodermia.

• Typically, light, skin-colored maculae are localized in the skin lesions.. They are called nappes claires (note differential diagnosis pityriasis rubra pilaris).

• Edema (anasarca)

• Facies-leontina

• Palmoplantar hyperkeratoses are visible in almost half of all patients.

• Diffuse alopecia and onychodystrophy may occur.

• Loco-regional lymphadenopathy

• Bone marrow infestation (rare).

• Clinical features
• Laboratory

  • ESR/CRP, differential blood count (leukocytosis, relative lymphocytosis), liver and kidney values, LDH, electrolytes.

  • Sézary cells (= Lutzner cells) 

    • Sézary syndrome suspected at > 1000 cells/μL

  • FACS analysis, CD4/CD8 ratio, determination of CD4+CD7 cells

  • Clonality detection in blood

  • A bone marrow biopsy is usually not indicated

  • If necessary, immune electrophoresis

  • HTLV serology, if applicable

  • If necessary, Lyme disease serology

• Biopsy 
• Dermatopathology
• Immunohistology: 

  • CD4+/CD7- T cells > 40% or CD4/CD8 ratio > 10

  • T-helper phenotype: CD3+, CD4+, CD8-.

  • Molecular biology: Clonal rearrangement of T cell receptor genes

Staging --> consult most recent SOP, currently being updated.

Generalized.

• Routine histology and immunopathology similar to MF.
• In 40% of cases histology is not diagnostic.
• Monoclonal T-cell population, which is visible subepidermally.
• Atypical lymphocytes with a strongly lobed nucleus (Lutzner cells) are characteristic. 
• Pautrier abscesses may be visible.

1. Erratum in Olsen 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;110:1713-1722. Blood, 2008. 111(9): p. 4830-4830.
2. Beylot-Barry, M., et al., Is bone marrow biopsy necessary in patients with mycosis fungoides and Sezary syndrome? A histological and molecular study at diagnosis and during follow-up. Br J Dermatol, 2005. 152(6): p. 1378-1379.
3. Booken, N., et al., Die Kombinationstherapie mit extrakorporaler Photopherese, Interferon-α, PUVA und lokalen Glukokortikoiden in der Behandlung des Sézary-Syndroms. JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 2010. 8(6): p. 428-438.
4. Bunn, P.A., Systemic Therapy of Cutaneous T-Cell Lymphomas (Mycosis Fungoides and the Sezary Syndrome). Annals of Internal Medicine, 1994. 121(8): p. 592.
5. Caprini, E., et al., Identification of Key Regions and Genes Important in the Pathogenesis of Sezary Syndrome by Combining Genomic and Expression Microarrays. Cancer Research, 2009. 69(21): p. 8438-8446.
6. Dummer, R., et al., Aktuelle Aspekte zur Pathogenese von Sézary-Syndrom und Mycosis fungoides. Der Hautarzt, 2001. 52(3): p. 189-192.
7. Introcaso, C.E., et al., Total skin electron beam therapy may be associated with improvement of peripheral blood disease in Sézary syndrome. Journal of the American Academy of Dermatology, 2008. 58(4): p. 592-595.
8. Kim, Y.H., et al., TNM classification system for primary cutaneous lymphomas other than 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. 110(2): p. 479-484.
9. Prince, H.M., S. Whittaker, and R.T. Hoppe, How I treat mycosis fungoides and Sezary syndrome. Blood, 2009. 114(20): p. 4337-4353.
10. Richardson, S.K., et al., High Clinical Response Rate with Multimodality Immunomodulatory Therapy for Sézary Syndrome. Clinical Lymphoma and Myeloma, 2006. 7(3): p. 226-232.
11. Scarisbrick, J.J., et al., Secondary Malignant Neoplasms in 71 Patients With Sézary Syndrome. Arch Dermatol, 1999. 135(11).
12. Schappell, D.L., Treatment of Advanced Mycosis Fungoides and Sézary Syndrome With Continuous Infusions of Methotrexate Followed by Fluorouracil and Leucovorin Rescue. Arch Dermatol, 1995. 131(3): p. 307.
13. Talpur, R., R. Bassett, and M. Duvic, Prevalence and treatment of Staphylococcus aureus colonization in patients with mycosis fungoides and Sézary syndrome. Br J Dermatol, 2008. 159(1): p. 105-112.
14. Trautinger, F., et al., EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome. European Journal of Cancer, 2006. 42(8): p. 1014-1030.
15. Trotter, M.J., et al., Cutaneous histopathology of Sézary syndrome: a study of 41 cases with a proven circulating T-cell clone. Journal of Cutaneous Pathology, 1997. 24(5): p. 286-291.
16. van Doorn, R., et al., Oncogenomic analysis of mycosis fungoides reveals major differences with Sezary syndrome. Blood, 2008. 113(1): p. 127-136.
17. Vermeer, M.H., et al., Novel and Highly Recurrent Chromosomal Alterations in Sezary Syndrome. Cancer Research, 2008. 68(8): p. 2689-2698.
18. Whittaker, S.J. and F.M. Foss, Efficacy and tolerability of currently available therapies for the mycosis fungoides and Sezary syndrome variants of cutaneous T-cell lymphoma. Cancer Treatment Reviews, 2007. 33(2): p. 146-160.
19. Wood, G.S., et al., Detection of Clonal T-Cell Receptor γ Gene Rearrangements in Early Mycosis Fungoides/Sezary Syndrome by Polymerase Chain Reaction and Denaturing Gradient Gel Electrophoresis (PCR/DGGE). Journal of Investigative Dermatology, 1994. 103(1): p. 34-41.
20. Stadler, R., et al., Short German guidelines: cutaneous lymphomas. J Dtsch Dermatol Ges, 2008. 6 Suppl 1: p. S25-31.