Is There a Better Way to Diagnose and Treat Mycosis Fungoides and Sézary Syndrome?

🔍 Key Finding Mycosis fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas with MF being the most common type and having an indolent course, while SS is a rare, aggressive, leukemic variant; skin biopsy with histopathology and immunohistochemistry is essential for diagnosis, and treatment is based on disease stage and may include skin-directed therapies or systemic treatments for advanced disease.

🔬 Methodology Overview

• Design: Narrative review.
• Data Sources: Published literature on mycosis fungoides (MF) and Sézary syndrome (SS). References cited include epidemiological studies, clinical trials, and reviews.
• Selection Criteria: Focus on clinical presentation, diagnosis, staging, and therapeutic management of MF/SS. Includes discussion of histopathology, immunohistochemistry, prognosis, and various treatment modalities.
• Analysis Approach: Qualitative synthesis of information from the selected literature.
• Scope: Comprehensive overview of MF/SS for clinicians and researchers. Includes discussion of different subtypes and variants, as well as recent advances in understanding and managing these conditions.

📊 Results

• Mycosis fungoides (MF) accounts for nearly 50% of all primary cutaneous lymphomas, with an annual incidence of 2.0-4.1 cases per 1,000,000 individuals. Sézary syndrome (SS) is rarer, with an annual incidence of 0.1-0.3 cases per 1,000,000.
• Classic Alibert-Bazin MF presents with patches (71.4%), plaques (36.3%), and tumors (13.5%), with erythroderma developing in 16.6% of cases. Lesions often appear on sun-protected areas.
• Folliculotropic MF, the most common MF variant, can be divided into advanced (infiltrated plaques and tumors, poorer prognosis) and early (patches and thin plaques, better prognosis) forms.
• SS presents with erythroderma, generalized lymphadenopathy, and circulating Sézary cells. Peripheral blood involvement is confirmed by >1000 Sézary cells/µL, CD4/CD8 ratio ≥ 10, CD4+CD7- ≥ 40%, and/or CD4+CD26- ≥ 30%.
• Skin biopsy with histopathology and immunohistochemistry is essential for diagnosis. Epidermotropism of atypical lymphocytes is a key feature.
• Staging follows the modified TNMB system. Advanced stage, older age, male gender, specific histopathological features (folliculotropism in advanced disease), large cell transformation, and elevated LDH are associated with poorer prognosis.
• Treatment includes skin-directed therapies (topical steroids, phototherapy, radiotherapy) for early-stage disease and systemic therapies (biological response modifiers, targeted therapies, chemotherapy) for advanced-stage disease. Allogeneic bone marrow transplantation and extracorporeal photopheresis are used in selected cases.

💡 Clinical Impact This review comprehensively discusses the clinical presentation, diagnosis, staging, and treatment of mycosis fungoides (MF) and Sézary syndrome (SS), aiming to improve early recognition and appropriate management of these cutaneous T-cell lymphomas. The information provided may aid clinicians in differentiating MF/SS from other skin conditions, leading to earlier diagnosis and optimized treatment strategies, ultimately improving patient outcomes.

🤔 Limitations

• No single gold standard test exists for diagnosing MF or SS.
• Histopathology may not always show folliculotropism even in lesions with clinical features of folliculotropic MF.
• Follicular accentuation may be due to follicular mucinosis rather than neoplastic cell infiltration.
• In erythrodermic MF, epidermotropism may be less evident, making diagnosis difficult.
• TCR gene rearrangement can show monoclonal T-cell proliferation in inflammatory dermatoses.
• Phenotypic variations of neoplastic cells can occur in the same patient.
• Peripheral blood involvement in early MF may not indicate true hematologic involvement.
• T-cell clones in the blood can be found in healthy individuals and those with benign dermatoses.
• Bone marrow biopsy’s role in MF/SS is not well established, and studies on its prognostic impact are conflicting.
• Visceral involvement may be more frequent than detected, but its impact on prognosis is unknown.
• Studies on prognostic factors are mostly retrospective and have conflicting results.

✨ What It Means For You This review emphasizes the complexity of diagnosing and staging MF/SS, urging clinicians to integrate clinical, histopathological, and molecular findings, and consider the heterogeneity of these diseases. The summarized treatment options, ranging from skin-directed therapies for early stages to systemic approaches for advanced disease, guide physicians in tailoring individualized treatment plans based on disease stage and prognostic factors.

Reference Miyashiro D, Sanches JA. Mycosis fungoides and Sézary syndrome: clinical presentation, diagnosis, staging, and therapeutic management. Front Oncol. 2023;13:1141108. https://doi.org/10.3389/fonc.2023.1141108