Mycosis Fungoides, Sézary Syndrome, and Cutaneous B-Cell Lymphomas: 2025 Update on Diagnosis, Risk-Stratification, and Management

Abstract

Disease Overview: Primary cutaneous lymphomas are a rare and heterogeneous group of extranodal lymphomas that require the integration of clinical and histopathologic data for classification and treatment. Diagnosis: Diagnosis and disease classification is based on histopathologic review and immunohistochemical staining of an appropriate skin biopsy. Pathologic review and appropriate clinical and staging evaluations are necessary to distinguish primary cutaneous and systemic lymphomas. Risk-Stratification: Disease histopathology remains the most important prognostic determinant in primary cutaneous B-cell lymphomas, whereas staging remains an important prognostic determinant in cutaneous T-cell lymphomas. Risk-Adapted Therapy: PCFCL and PCMZL patients with solitary or relatively few skin lesions may be effectively managed with local radiation therapy. While single-agent rituximab may be employed for patients with more widespread skin involvement, multiagent chemotherapy is rarely appropriate. In contrast, the management of patients with PCDLBCL, LT is comparable to the management of patients with systemic DLBCL. Clinical staging forms the basis for a “risk-adapted,” multi-disciplinary approach to CTCL treatment. For patients with disease limited to the skin, disease-specific and overall survival is measured in years, if not decades, and skin-directed therapies are preferred. In contrast, patients with advanced-stage disease, including cutaneous tumors or significant nodal, visceral, or blood involvement, are approached with systemic therapies in an escalating fashion. In selected patients, allogeneic stem-cell transplantation may be considered, as this is curative in some patients.