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Mycosis fungoides/Sézary syndrome
Background
Overview
Definition
Mycosis fungoides and Sézary syndrome are indolent types of cutaneous T-cell lymphomas that primarily affect the skin.
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Pathophysiology
Mycosis fungoides and Sézary syndrome arise from clonal proliferation of malignant T-cells, primarily CD4+ memory T-cells. In mycosis fungoides, these cells infiltrate the skin, causing characteristic patches, plaques, and potential tumor formation, while in Sézary syndrome, the malignant cells circulate in the blood, leading to erythroderma and lymphadenopathy. Molecular mechanisms implicated in these diseases include genetic and epigenetic alterations that disrupt normal T-cell signaling pathways. Mutations in genes such as STAT3, TNFRSF1B, STAT5B, and PLCG1 affect the JAK/STAT and T-cell receptor pathways, promoting uncontrolled cell growth. Additionally, alterations in chromatin-modifying genes, such as TET2 and DNMT3A, contribute to epigenetic dysregulation. Aberrant expression of certain molecules (such as PD-1, CTLA-4), chemokine receptors (such as CCR4, CCR7), and dysregulation of microRNAs also play roles in disease progression and dissemination.
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Epidemiology
Mycosis fungoides and Sézary syndrome are the most common subtypes of cutaneous T-cell lymphoma. The incidence of cutaneous T-cell lymphomas in the US is estimated at 6.4-9.6 per 1,000,000 person-year. The incidence of classic Sézary syndrome in Europe is estimated at 5 per 1,000,000 person-year.
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Disease course
Mycosis fungoides typically presents with skin lesions that progress through distinct stages. Initially, patients develop flat, scaly, red patches, often on sun-protected areas such as the buttocks and thighs. These patches can evolve into thicker, raised plaques and eventually form tumors that may ulcerate. Sézary syndrome, on the other hand, is characterized by a triad of generalized erythroderma, lymphadenopathy, and the presence of malignant Sézary cells in the blood. Patients with Sézary syndrome often experience severe pruritus, scaling, alopecia, and nail abnormalities. Both mycosis fungoides and Sézary syndrome have a chronic, relapsing course, with patients frequently undergoing multiple, consecutive therapies.
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Prognosis and risk of recurrence
Both mycosis fungoides and Sézary syndrome have a chronic, relapsing course, and patients frequently undergo multiple consecutive therapies. Mycosis fungoides typically presents in early-stage disease, which may progress to advanced disease over years. The 5-year overall survival in patients with stage IIB-IV mycosis fungoides/Sézary syndrome is estimated at 39-52%.
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Guidelines
Key sources
The following summarized guidelines for the evaluation and management of mycosis fungoides/Sézary syndrome are prepared by our editorial team based on guidelines from the American Society for Transplantation and Cellular Therapy & Cell Therapy Transplant Canada (ASTCT 2024), the United States Cutaneous Lymphoma Consortium (USCLC/ASTCT 2024), the British Association of Dermatologists (BAD 2019), and the European Society of Medical Oncology ...
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Screening and diagnosis
Diagnostic investigations
Initial assessment: as per ESMO 2018 guidelines, perform a complete physical examination and obtain a CBC with differential, routine serum biochemistry with LDH, and appropriate imaging studies in the initial evaluation of patients with primary cutaneous lymphoma.
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Imaging for staging
Diagnostic procedures
Medical management
General principles: as per ASTCT/USCLC 2024 guidelines, consider coordinating the care of patients with Sézary syndrome or advanced-stage mycosis fungoides (stage IIB or higher) as a multidisciplinary collaboration involving dermatology, hematology/oncology, radiation oncology, and dermatopathology/hematopathology.
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Management of early-stage disease (skin-directed therapy)
Management of early-stage disease (systemic therapy)
Management of early-stage disease (refractory disease)
Management of advanced-stage disease
Management of advanced-stage disease (allo-SCT)
Therapeutic procedures
Considerations for stem cell transplantation, preparation: as per ASTCT/USCLC 2024 guidelines, offer lower-intensity regimens, such as reduced-intensity conditioning or nonmyeloablative conditioning, in patients with mycosis fungoides/Sézary syndrome undergoing allogeneic hematopoietic cell transplantation conditioning.
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Considerations for stem cell transplantation (ASCT)
Considerations for stem cell transplantation (evaluation of post-transplantation rash)
Specific circumstances
Patients with primary cutaneous CD30-positive lymphoproliferative disorders: as per BAD 2019 guidelines, diagnose primary cutaneous CD30-positive lymphoproliferative disorders based on careful clinicopathological correlation. Obtain staging investigations for anaplastic large cell lymphoma and borderline cases.
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Patients with rare cutaneous T‐cell lymphoma variants
Patients with primary cutaneous B‐cell lymphomas (marginal zone and follicle centre lymphoma)
Patients with primary cutaneous B‐cell lymphomas (diffuse large B‐cell lymphoma)
Follow-up and surveillance
Follow-up
As per ESMO 2018 guidelines:
Individualize follow-up based on the clinical situation. Adjust the frequency of follow-up visits according to the type of primary cutaneous lymphoma and the stage of disease, ranging from every 6-12 months for patients with indolent types and stable disease or complete remission, to every 4-6 weeks for patients with active or progressive disease.
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Focus follow-up visits on eliciting history and performing physical examination, with additional testing only if necessary. Avoid obtaining routine imaging after treatment, as tumor responses are visible to the naked eye and recurrences are typically localized in the skin.
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Management of donor-specific anti-HLA antibodies (prevention)
Management of donor-specific anti-HLA antibodies (testing)
Management of donor-specific anti-HLA antibodies (desensitization therapy)
Management of donor-specific anti-HLA antibodies (follow-up)
Management of non-donor-specific anti-HLA antibodies