Sézary syndrome (SS) or ‘red man syndrome’ or ‘1’ homme rouge’ is the leukemic counterpart of cutaneous T-cell lymphoma mycosis fungoides (MF).
Aggressive cutaneous T-cell lymphoma (CTCL)
The distribution of patients with PCLs | Naeini, F. F., Abtahi-Naeini, B., Pourazizi, M., Sadeghiyan, H., & Najafian, J. (2015). Primary cutaneous lymphomas: A clinical and histological study of 99 cases in Isfahan, Iran. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences, 20(9), 827–831. doi:10.4103/1735-1995.170595
History
Jean-Louis-Marc Alibert (1768 – 1837) was a French dermatologist born in Villefranche-de-Rouergue, Aveyron. He was a pioneer of dermatology.
The first clinical description of mycosis fungoides (MF) was made in 1806 by Baron Jean-Louis Alibert, a French physician, who identified a 56-year-old man with skin tumors resembling mushrooms after having a desquamating rash over several months.
In 1975, Lutzner, Edelson, and associates introduced the term cutaneous T-cell lymphoma (CTCL) to describe the spectrum of skin-based lymphomas of T-cell origin, including classic MF and Sézary syndrome (SS).
Aetiology
Human T-cell lymphotropic virus type 1 & 2 (HTLV-1/2) (associated with Adult T cell leukaemia/lymphoma)
Pathophysiology
Leukemic phase of cutaneous T-cell lymphoma without any bone marrow compromise.
Leukaemic seeding of blood by malignant T cells from the skin (CD4+)
Clinical features
Triad of manifestations:
Erythroderma (diffuse erythema and scaling of the entire body) with pruritus
Lymphadenopathy
Sezary or Lutzner cells (atypical circulating lymphocytes)
Patient with erythroderma (SS stage IVA1). | Sean Whittaker, Richard Hoppe, H. Miles Prince; How I treat mycosis fungoides and Sézary syndrome. Blood 2016; 127 (25): 3142–3153. doi: https://doi.org/10.1182/blood-2015-12-611830
Associated clinical manifestations:
Lagophthalmos
Alopecia
Palmoplantar hyperkeratosis
Onycodystrophy
Diagnosis
Diagnostic criteria:
Erythroderma involving > 80% BSA
Clonal TCR rearrangement (confirmed by PCR/Southern blot)
Absolute Sezary cell count of at least 1000 cells/microL, or one of the following 2 criteria:
Increased CD4+ or CD3+ with CD4/CD8 ratio of 10 or more
Increased CD4+ cells with abnormal phenotype: CD4+CD7 ratio of 40% or more or CD4+CD26 ratio of 30% or more.
Sézary syndrome is a rare aggressive subtype of cutaneous T-cell lymphoma. It is closely related to mycosis fungoides and is presented with erythroderma, generalised lymphadenopathy and circulating malignant T cells (Sézary cells). This peripheral blood smear shows two typical Sézary cells. The cells are medium-sized to large with abundant, irregularly shaped and basophilic cytoplasm. The shape of the nucleus is very irregular, hyperconvoluted with a cerebriform pattern. Nuclear chromatin is condensed, nucleoli are not visible. Cerebriform appearance of the nucleus is a typical finding in Sézary syndrome. | Cell – Atlas Of Haematological Cytology. (2020) Sézary syndrome – CELL – Atlas of Haematological Cytology. Retrieved February 03, 2020, from http://www.leukemia-cell.org/atlas/index.php?pg=images–mature-t-and-nk-cell-neoplasms–sezary-syndrome#1
Excisional skin biopsy (same as mycosis fungoides):
Pautrier microabscesses: tumor cells invade epidermis as single cells and small clusters
Epidermotropism
A, B, Pautrier microabscesses containing atypical lymphocytes and apoptotic cells (arrows) [hematoxylin and eosin, original magnification (OM): 3200]. For comparison, the inset in (B) (OM: 340) shows 2 typical microabscesses of MF without apoptotic cells. C, Apoptotic debris in the context of a dense infiltrate of atypical lymphocytes (OM: 3100). | Kim, N.H., Torchia, D., Miteva, M., Rongioletti, F., & Romanelli, P.L. (2011). Prominent apoptosis in pautrier microabscesses: a distinctive finding in adult T-cell leukemia/lymphoma? The American Journal of dermatopathology, 33 5, 530-1 .
Differential diagnosis
Mycosis fungoides
Psoriasis
Pityriasis rubra pilaris
Atopic dermatitis
Hypereosinophilic syndrome
Adult T-cell leukaemia
Clinical appearance of patient with Sézary syndrome (a) and atopic dermatitis (b). | Saulite, I., Hoetzenecker, W., Weidinger, S., Cozzio, A., Guenova, E., & Wehkamp, U. (2016). Sézary Syndrome and Atopic Dermatitis: Comparison of Immunological Aspects and Targets. BioMed research international, 2016, 9717530. doi:10.1155/2016/9717530
Staging
Tumor-node-metastasis-blood (TNMB) staging:
ISCL/EORTC revision of the classification of mycosis fungoides and Sézary syndrome | Last, First. (2020) cmar-138661_T002.jpg (JPEG Image, 988 × 529 pixels). Retrieved February 03, 2020, from https://www.dovepress.com/cr_data/article_fulltext/s138000/138661/img/cmar-138661_T002.jpg
ISCL/EORTC revision of mycosis fungoides and Sézary syndrome staging | Last, First. (2020) cmar-138661_T002.jpg (JPEG Image, 988 × 529 pixels). Retrieved February 03, 2020, from https://www.dovepress.com/cr_data/article_fulltext/s138000/138661/img/cmar-138661_T002.jpg
Management
Skin-directed therapy:
Topical/systemic steroids
Topical nitrogen mustard
Phototherapy (UVB and PUVA)
Total skin electron beam therapy (TSEBT)
Patient No. 32 with Sézary syndrome (SS) (a) before and (b) after treatment with bexarotene. The patient is now on maintenance treatment with 75 mg/day (stable disease). This patient was initially treated for ultraviolet B (UVB)-photosensitivity (and actinic reticuloid), which still persists in the neck and face area. | Ten-year Experience of Bexarotene Therapy for Cutaneous T-cell Lymphoma in Finland – Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Patient-No-32-with-Sezary-syndrome-SS-a-before-and-b-after-treatment-with_fig4_225283518 [accessed 3 Feb, 2020]
