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 toMYD88andCD79B. 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.
背景/目的：原发性皮肤B细胞淋巴瘤（PCBCL）是一组罕见且异质性的非霍奇金淋巴瘤，诊断时局限于皮肤，并表现出皮肤复发的倾向。世界卫生组织第五版分类与2022年国际共识分类确认了三种主要亚型：原发性皮肤滤泡中心淋巴瘤（PCFCL）、原发性皮肤边缘区淋巴瘤/淋巴增殖性疾病（PCMZL/LPD）以及原发性皮肤弥漫性大B细胞淋巴瘤，腿型（PCDLBCL,LT）。这些亚型在临床行为、组织病理学特征、免疫表型和分子改变方面存在差异。其诊断和治疗对临床医生仍具挑战性。本综述旨在全面概述PCBCL的定义特征及当前治疗策略。方法：本叙述性综述综合了当前关于PCBCL临床、形态学、免疫组织化学及分子特征的文献，并评估了免疫组织化学、基因表达谱和分子检测在诊断中的应用价值，特别是在区分原发性皮肤疾病与系统性淋巴瘤继发性皮肤受累方面。结果：PCFCL起源于生发中心B细胞，需与淋巴结滤泡性淋巴瘤相鉴别。PCMZL/LPD来源于生发中心后B细胞，常与慢性抗原刺激相关。PCFCL和PCMZL/LPD均呈惰性病程，预后良好。相比之下，PCDLBCL,LT是一种侵袭性淋巴瘤，其特征为激活NF-κB通路的基因改变，通常包括MYD88和CD79B基因突变。治疗策略因亚型而异，从针对惰性淋巴瘤的局部治疗到侵袭性PCBCL的全身性化学免疫治疗。针对复发/难治性疾病，布鲁顿酪氨酸激酶抑制剂和免疫调节剂等新兴疗法正在研究中。结论：PCBCL包含不同的临床病理实体，各亚型具有特定的诊断和治疗考量。虽然当前治疗以临床行为为指导，但关于皮肤趋向性、免疫逃逸和疾病进展的分子机制仍存在显著知识缺口。未来研究可侧重于完善分子特征分析，并开发个性化和基于免疫的疗法以改善预后。本综述整合了现有知识，并重点介绍了旨在推进PCBCL临床诊断与治疗创新的研究方向。
Unveiling Primary Cutaneous B-Cell Lymphomas: New Insights into Diagnosis and Treatment Strategies
肿瘤(癌症)患者之家