Primary Cutaneous B-Cell Lymphomas - An Updated Portrait of Classification, Biology, and Clinical Management

Sep 30, 2026

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Primary cutaneous B-cell lymphomas (CBCL) are clinically and biologically heterogeneous extranodal non-Hodgkin lymphomas confined to the skin at diagnosis. Accounting for about 25% of primary cutaneous lymphomas, CBCL are subclassified by WHO–EORTC and ICC into PCFCL, PCMZL, PCDLBCL-LT, IVLBCL, and EBVMCU. These subtypes differ in clinical course, histopathology, molecular alterations, and prognosis. Indolent forms often use local therapy with excellent outcomes, while aggressive variants need systemic treatment and carry poorer survival. EBVMCU is typically self-limiting. This review updates diagnostic criteria, management strategies, and emerging molecular insights, highlighting multidisciplinary care and ongoing limits of innovative therapies, including prognostication challenges.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

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Introduction

Primary cutaneous B-cell lymphomas (CBCL) and classification

Entities within CBCL (PCFCL, PCMZL, PCDLBCL-LT, IVLBCL, EBVMCU)

Diagnostic and clinical management overview

Indolent versus aggressive subtypes

EBVMCU clinical course and implications

Molecular insights and emerging therapies

Multidisciplinary approach and prognostication challenges

European Journal of Haematology REVIEW OPEN ACCESS Primary Cutaneous B-Cell Lymphomas: An Updated Portrait of Classification, Biology, and Clinical Management A. Bernardelli1 | E. Carazzai2 | B. Bugnotto2 | F. Bellinato3 | M. Krampera1,2 | C. Visco1,2 1UOC di Ematologia e CTMO, DAI Medico Generale, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy | 2Hematology and Bone Marrow Transplant Unit, Section of Biomedicine of Innovation, Department of Engineering for Innovative Medicine (DIMI), University of Verona, Verona, Italy | 3Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy Correspondence: C. Visco ([carlo.visco@univr.it](carlo.visco@univr.it)) Received: 30 July 2025 | Revised: 29 September 2025 | Accepted: 7 October 2025 Funding: The authors received no specific funding for this work. Keywords: B-cell neoplasms | cutaneous B-cell lymphoma | multidisciplinary management | rare cutaneous lymphomas | targeted therapies ABSTRACT Primary cutaneous B-cell lymphomas (CBCL) represent a clinically and biologically heterogeneous group of extranodal nonHodgkin lymphomas confined to the skin at the time of diagnosis. They account for approximately 25% of all primary cutaneous lymphomas and are subclassified into distinct entities according to the World Health Organization—European Organization of Research and Treatment of Cancer (WHO–EORTC) classification and International Consensus Classification (ICC) . including primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), intravascular large B-cell lymphoma (IVLBCL) and Epstein– Barr virus–positive mucocutaneous ulcer (EBVMCU). These subtypes differ significantly in clinical behavior, histopathological features, molecular alterations, and prognosis. Indolent forms such as PCFCL and PCMZL are typically managed with local therapies and are associated with an excellent prognosis. In contrast, aggressive variants such as PCDLBCL-LT require systemic treatment and are linked to poorer outcomes. EBVMCU, despite its alarming histological appearance, generally follows a benign and self-limiting course. This review provides an updated overview of the current diagnostic criteria, clinical management strategies, and emerging molecular insights for each CBCL subtype. It also emphasizes the importance of a multidisciplinary approach and discusses the challenges of prognostication, along with the evolving but still limited role of innovative therapies. 1 | Introduction Primary cutaneous lymphomas represent a diverse and complex group of extranodal non-Hodgkin lymphomas affecting the skin, with no evidence of extracutaneous disease at the time of diagnosis. These malignancies are broadly categorized based on the lineage of the neoplastic cells, with the majority arising from T cells. However, approximately 25% of cases are of B-cell origin and are collectively referred to as primary cutaneous B-cell lymphomas (CBCL) [1–3](Table 1) . The incidence of CBCL has been steadily increasing and is currently estimated at approximately four cases per million individuals. Epidemiological data indicate that the highest incidence rates occur in males, individuals from Western populations, and adults over the age of 50 [4] . The classification and understanding of CBCLs have significantly evolved, particularly with the contributions of the 2018 joint World Health Organization (WHO)–European Organization for Research and Treatment of Cancer (EORTC) classification and the more recent International Consensus Classification (ICC) . These frameworks have established a standardized approach to diagnosis and nomenclature, recognizing four principal entities within CBCLs: primary cutaneous follicle center lymphoma (PCFCL)—typically presenting as slowly progressive lesions on the scalp, forehead, or trunk, and g

FAQs

What are primary cutaneous B-cell lymphomas (CBCL) and how are they defined at diagnosis?

They are extranodal non-Hodgkin lymphomas confined to the skin at the time of diagnosis, without evidence of extracutaneous disease initially. They form a clinically and biologically heterogeneous group.

Which subtypes are included in the updated CBCL portrait and how do they differ?

The review lists PCFCL, PCMZL, PCDLBCL-LT, IVLBCL, and EBVMCU. They differ in clinical behavior, histopathological features, molecular alterations, and prognosis.

How does treatment strategy differ between indolent and aggressive CBCL variants?

Indolent forms such as PCFCL and PCMZL are typically managed with local therapies and have excellent prognosis. Aggressive variants like PCDLBCL-LT usually require systemic treatment and are linked to poorer outcomes.

Sep 30, 2026

Uploaded by Ezra