Unveiling Primary Cutaneous B-Cell Lymphomas: New Insights into Diagnosis and Treatment Strategies
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Department of Pathology and Laboratory Medicine, University of California San Francisco, San Francisco, CA 94107, USA
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Dermatology and Dermatopathology Private Practice, Mexico City 01090, Mexico
*
Author to whom correspondence should be addressed.
Cancers 2025, 17(7), 1202; https://doi.org/10.3390/cancers17071202
Submission received: 20 January 2025
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Revised: 23 March 2025
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Accepted: 26 March 2025
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Published: 1 April 2025
(This article belongs to the Special Issue Cutaneous T Cell Lymphomas: From Pathology to Treatment)
Simple Summary
This review discusses the diagnosis and management of B-cell lymphomas of the skin, which can be primary (originating in the skin) or secondary (spreading from other areas, often lymph nodes). The focus is on the three key subtypes of primary cutaneous B-cell lymphomas: follicle center lymphoma and marginal zone lymphoma, which are indolent with excellent prognoses, and diffuse large B-cell lymphoma, leg type, which is aggressive and has a high mortality rate. Each subtype has distinct clinical, microscopic, and molecular features that guide diagnosis and treatment. Indolent subtypes are treated with localized therapies like radiation or skin surgery, while aggressive subtypes require chemotherapy and/or immunotherapy. The authors highlight emerging treatments targeting cancer-specific molecules or enhancing the immune response, and discuss medical knowledge gaps that remain for these rare cancers. They also emphasize the need for further research and emphazise the importance for inclusive studies to improve outcomes and health equity for diverse patient populations.
Abstract
Background/Objectives: Primary cutaneous B-cell lymphomas (PCBCL) are a rare and heterogeneous group of non-Hodgkin lymphomas that are confined to the skin at diagnosis and exhibit a tendency for cutaneous recurrence. The 5th edition of the World Health Organization and the 2022 International Consensus Classification recognize three main subtypes: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma/lymphoproliferative disorder (PCMZL/LPD), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL,LT). These subtypes differ in clinical behavior, histopathologic features, immunophenotype, and molecular alterations. Diagnosis and management remain challenging for clinicians. This review aims to provide a comprehensive overview of the defining features and current treatment strategies for PCBCL. Methods: This narrative review synthesizes current literature on the clinical, morphologic, immunohistochemical, and molecular characteristics of PCBCL. It also evaluates the diagnostic utility of immunohistochemistry, gene expression profiling, and molecular assays, particularly in distinguishing primary cutaneous disease from secondary cutaneous involvement by systemic lymphomas. Results: PCFCL arises from germinal center B-cells and must be differentiated from nodal follicular lymphoma. PCMZL/LPD is derived from post-germinal center B-cells and is often linked to chronic antigenic stimulation. Both PCFCL and PCMZL/LPD are indolent and associated with favorable outcomes. By contrast, PCDLBCL,LT is an aggressive lymphoma characterized by genetic alterations activating the NF-κB pathway, commonly including mutations to MYD88 and CD79B. Treatment strategies vary by subtype, ranging from localized therapies for indolent lymphomas to systemic chemoimmunotherapy for aggressive PCBCL. Emerging therapies, such as Bruton tyrosine kinase inhibitors and immunoregulatory agents, are being investigated for relapsed/refractory disease. Conclusions: PCBCL encompass distinct clinicopathologic entities with subtype-specific diagnostic and therapeutic considerations. While current management is guided by clinical behavior, significant knowledge gaps remain regarding the molecular mechanisms underlying skin tropism, immune evasion, and disease progression. Future research could focus on improving molecular characterization and developing personalized and immune-based therapies to enhance outcomes. This review consolidates current knowledge and highlights innovations aimed at advancing the diagnosis and treatment of PCBCL in clinical practice.
