From the Guidelines
Sézary syndrome is a rare and aggressive type of cutaneous T-cell lymphoma, characterized by erythroderma, generalized lymphadenopathy, and the presence of clonally related neoplastic T cells with cerebriform nuclei (Sézary cells) in skin, lymph nodes, and peripheral blood, requiring systemic treatment and often a combination approach for management 1.
Key Features of Sézary Syndrome
- Erythroderma: a widespread red, itchy rash covering most of the body
- Generalized lymphadenopathy: enlargement of lymph nodes
- Presence of Sézary cells in skin, lymph nodes, and peripheral blood
Treatment Approach
- Systemic treatment is required, with options including extracorporeal photopheresis (ECP), interferon (IFN), retinoids, and chemotherapy 1
- Skin-directed therapies like PUVA or potent topical steroids may be used as adjuvant therapy
- Mogulizumab has shown significant clinical efficacy in MF/SS, particularly in patients with blood involvement 1
Management Considerations
- Patients often need supportive care to manage intense itching and skin infections
- The disease primarily affects older adults, with most patients diagnosed after age 60
- Ongoing management by specialists in dermatology and oncology is required
- Treatment should be individualized, considering the patient's overall health, disease stage, and response to previous treatments 1
From the Research
Definition and Characteristics of Sézary Syndrome
- Sézary syndrome (SS) is a rare and aggressive type of cutaneous T cell lymphoma (CTCL) characterized by an intensely pruritic, exfoliative rash, known as erythroderma, with cutaneous and systemic dissemination of clonal CD4+ T cells into the blood and lymph nodes 2.
- It is a primary cutaneous T-cell lymphoma (CTCL) characterized by erythroderma, lymphadenopathy, and leukemic involvement of the peripheral blood 3.
- SS is a rare form of cutaneous T-cell lymphoma characterized by erythroderma and the presence of Sézary cells in the skin, lymph nodes, and peripheral blood 4.
Genetic Alterations and Biomarkers
- Genetic alterations in SS include monosomy 10, losses of 10q and 17p, gains of 8q24 and 17q, and diverse structural alterations involving these regions 4.
- The mutational landscape of SS includes somatic copy number alterations, such as chromosomal deletions involving the TP53, RB1, PTEN, DNMT3A, and CDKN1B tumor suppressors 5.
- Biomarkers implicated in the development of SS include a wide spectrum of genes involved in epigenetic regulation and signaling, such as TET2, CREBBP, KMT2D, and MAPK1 3, 5.
Diagnosis and Detection
- The diagnosis of SS can be aided by the evaluation of TCR-Vβ2 levels, which can identify the presence of a clone in the peripheral blood of patients affected by SS 6.
- A "two-step" procedure in the detection of the malignant T cell clone in CTCLs is suggested, involving TCR-Vβ2 assessment and further confirmation by means of T cell gene rearrangement evaluation 6.