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Cancers
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Cutaneous Lymphomas: From Pathology to Treatment
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Cutaneous Lymphomas: From Pathology to Treatment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 7072

Special Issue Editors

Dr. Weiyun Z. Ai

E-Mail Website
Guest Editor
Department of Medicine, Divison of Hematology and Oncology, University of California, San Francisco, CA, USA
Interests: Hodgkin and non-Hodgkin lymphoma; cutaneous lymphoma; pre-clinical models and targeted therapy for mycosis fungoides and Sezary syndrome
Dr. Christiane Querfeld

E-Mail Website
Guest Editor
Division of Dermatology, City of Hope, Duarte, CA 91010, USA
Interests: tumor microenvironment in cutaneous lymphoma; advancing novel biologic therapies for cutaneous lymphoma; dermatopathology; mycosis fungoides; Sezary syndrome; lymphoma

Special Issue Information

Dear Colleagues,

This Special Issue of Cancers will focus on primary cutaneous lymphomas, a heterogenous group of non-Hodgkin lymphomas that includes both T-cell and B-cell subtypes. These lymphomas primarily involve the skin at the time of diagnosis. Mycosis fungoides and Sezary syndrome are the most common subtypes, accounting for approximately 60% of all primary cutaneous lymphomas.

In recent years, there has been remarkable progress in this field. Revisions to the classification systems have improved diagnosis, prognostication, and treatment. The application of state-of-the-art molecular and genetic techniques has provided insights into the potential genetic drivers and therapeutic targets. In addition, a deeper understanding of epigenetic modulation and the tumor microenvironment has opened new avenues for drug discovery and the development of strategies to overcome drug resistance. Insights into the mechanisms of action and treatment responses to novel agents, along with the identification of biomarkers, are accelerating the shift toward personalized therapeutic approach.

We therefore welcome the submission of original research and review articles that highlight recent advances and address ongoing challenges in the diagnosis, biological insights, and treatment of primary cutaneous lymphomas. Our goal is to foster cross-disciplinary dialogue and accelerate progress in the care of patients with these rare and complex diseases.

Dr. Weiyun Z. Ai
Dr. Christiane Querfeld
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cutaneous T cell lymphoma
  • mycosis fungoides and Sezary syndrome
  • pathogenesis/biomarker discovery
  • tumor microenvironment
  • pre-clinical and clinical studies
  • biological insights

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Published Papers (5 papers)

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Research

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16 pages, 1223 KiB  
Article
Clinical Features and Outcomes of Primary Cutaneous Peripheral T-Cell Lymphoma, Not Otherwise Specified, Treated with CHOP-Based Regimens
by Ge Hu, Zheng Song, Chao Lv, Yifei Sun, Yidan Zhang, Xia Liu, Xue Han, Lanfang Li, Lihua Qiu, Zhengzi Qian, Shiyong Zhou, Wenchen Gong, Bin Meng, Jin He, Xianhuo Wang and Huilai Zhang
Cancers 2025, 17(10), 1673; https://doi.org/10.3390/cancers17101673 - 15 May 2025
Viewed by 203
Abstract
Background: Primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS), is a rare and aggressive form of lymphoma. Its characteristics and treatment outcomes remain poorly understood. Methods: We identified 15 patients who were diagnosed with pcPTCL-NOS between January 2014 and August 2024 at [...] Read more.
Background: Primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS), is a rare and aggressive form of lymphoma. Its characteristics and treatment outcomes remain poorly understood. Methods: We identified 15 patients who were diagnosed with pcPTCL-NOS between January 2014 and August 2024 at Tianjin Medical University Cancer Institute and Hospital (TMUCIH) in this retrospective study. The clinical and immunophenotypic features, treatment regimens, and outcomes of these patients were investigated. Results: All patients (4 men, 11 women; median age 54 years) presented with skin lesions, including five stage T1, four stage T2 and six stage T3 lesions. pcPTCL-NOS manifests clinically either with solitary or disseminated rapidly growing nodules/tumors and papules and, less often, ulcers. The lesion sites in patients presenting with solitary/localized tumors (stage T1 and T2) were the head and limbs, and those in patients presenting with disseminated lesions (stage T3) were the trunk, head, and limbs. The CD4/CD8 immunophenotypic characteristics were as follows: CD4+/CD8− 53.33%; CD4+/CD8+ 26.67%; CD4−/CD8− 13.33%; and CD4−/CD8+ 6.67%. One patient had a T follicular helper (TFH) phenotype. Five patients had aberrant expression of the B-cell marker CD20 by tumor cells. All patients received CHOP or CHOP-like regimens as the initial treatment, with three patients undergoing complete lesion resection before chemotherapy, seven patients receiving treatment combined with chidamide (tucidinostat), two patients receiving treatment combined with brentuximab vedotin, two patients receiving treatment combined with mitoxantrone liposomes (Lipo-Mit), three patients receiving treatment combined with radiotherapy, and two patients receiving ASCT after the first-line treatment. The OS rates at 1 year, 2 years, and 3 years were 80%, 77.8%, and 77.8%, respectively; the PFS rates were 60%, 44.4%, and 33.3%, respectively. With a median follow-up of 40 months, the median PFS was 21 months, and the median OS was not reached. Univariate analyses revealed that patients with B symptoms and the CD4−/CD8− phenotype had inferior outcomes (p < 0.05). Age, sex, tumor stage, PIT score, Ki-67 index, elevated β2-MG levels, expression of CD20 or PD1, and treatment selection were not associated with the prognosis. A trend of a survival benefit in patients with solitary (T1) tumors compared with patients with disseminated (T2, T3) tumors was observed, suggesting that it is possible to reduce the intensity of treatment in patients with T1 tumors in the future. Conclusions: pcPTCL-NOS is an aggressive but poorly characterized lymphoma that may require early and active systemic treatment. However, for patients with T1 tumors, reducing the intensity of treatment with CHOP should be appropriately considered. Full article
(This article belongs to the Special Issue Cutaneous Lymphomas: From Pathology to Treatment)
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Review

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20 pages, 13696 KiB  
Review
Unveiling Primary Cutaneous B-Cell Lymphomas: New Insights into Diagnosis and Treatment Strategies
by Zachary R. Barbati and Yann Charli-Joseph
Cancers 2025, 17(7), 1202; https://doi.org/10.3390/cancers17071202 - 1 Apr 2025
Viewed by 791
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Cutaneous Lymphomas: From Pathology to Treatment)
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17 pages, 792 KiB  
Review
Therapeutic Targeting of the Janus Kinase/Signal Transducer and Activator of Transcription Pathway in Cutaneous T-Cell Lymphoma
by Alisha Kashyap, Julia Dai and Xiao Ni
Cancers 2025, 17(4), 568; https://doi.org/10.3390/cancers17040568 - 7 Feb 2025
Cited by 1 | Viewed by 1879
Abstract
Background/Objectives: Cutaneous T-cell lymphoma (CTCL) is a rare group of non-Hodgkin lymphomas characterized by the clonal expansion of malignant T cells. While current treatments can alleviate symptoms and significant progress has been made in treating leukemic CTCL, a definitive cure remains elusive. [...] Read more.
Background/Objectives: Cutaneous T-cell lymphoma (CTCL) is a rare group of non-Hodgkin lymphomas characterized by the clonal expansion of malignant T cells. While current treatments can alleviate symptoms and significant progress has been made in treating leukemic CTCL, a definitive cure remains elusive. Dysregulation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is a key driver of CTCL pathogenesis. As a result, therapeutic strategies targeting JAK/STAT signaling have gained momentum, with the increasing use of JAK inhibitors and other agents that effectively suppress this pathway. These immune-modulating therapies have broad effects on physiological processes, inflammation, and the pathological changes associated with both inflammatory diseases and cancers. Several JAK inhibitors, originally FDA-approved for inflammatory conditions, are now being investigated for cancer treatment. Methods: In this paper, a brief review of the literature on JAK/STAT pathway dysregulation in CTCL is provided, highlighting both clinical and preclinical studies involving JAK inhibitors and other agents that target this pathway. Results: Specifically, we focus on six JAK inhibitors currently under clinical investigation—golidocitinib, ruxolitinib, cerdulatinib, tofacitinib, upadacitinib, and abrocitinib. Additionally, we discuss preclinical studies that explore the mechanisms underlying JAK/STAT pathway inhibition in CTCL. Furthermore, we review reported cases in which CTCL relapsed or emerged following JAK inhibitor treatment. Conclusions: Collectively, these findings support the potential clinical utility of targeting the JAK/STAT pathway in CTCL. However, further research is needed to evaluate safety risks, minimize adverse effects, and optimize these therapeutic strategies. Full article
(This article belongs to the Special Issue Cutaneous Lymphomas: From Pathology to Treatment)
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17 pages, 908 KiB  
Review
Antibody–Drug Conjugates Targeting CD30 in T-Cell Lymphomas: Clinical Progression and Mechanism
by Yi Jiang, Sai Dong and Yang Wang
Cancers 2025, 17(3), 496; https://doi.org/10.3390/cancers17030496 - 2 Feb 2025
Viewed by 1232
Abstract
CD30 is overexpressed in many T-cell lymphoma (TCL) entities, including subsets of peripheral T-cell lymphomas (PTCL) and cutaneous T-cell lymphomas (CTCL). The antibody–drug conjugate brentuximab vedotin (BV), targeting CD30-positive cells, has been approved for the treatment of relapsed or refractory (R/R) systemic anaplastic [...] Read more.
CD30 is overexpressed in many T-cell lymphoma (TCL) entities, including subsets of peripheral T-cell lymphomas (PTCL) and cutaneous T-cell lymphomas (CTCL). The antibody–drug conjugate brentuximab vedotin (BV), targeting CD30-positive cells, has been approved for the treatment of relapsed or refractory (R/R) systemic anaplastic large cell lymphoma (sALCL), and primary cutaneous anaplastic large cell lymphoma or mycosis fungoides in patients who have received previous systemic therapy. However, many patients still experience disease progression after BV monotherapy. Extensive efforts have been dedicated to investigating effective combinations of BV. A phase III clinical study demonstrated that the combination of BV with cyclophosphamide, doxorubicin, and prednisone (CHP) is superior to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for CD30-positive PTCL. This study led to the approval of BV with CHP as the first-line therapy for CD30-positive PTCL (sALCL in Europe). We summarize the encouraging combination applications of BV in this review. Ongoing studies on combination therapies of BV are also listed, highlighting potential directions for the future application of BV. We focus on dissecting the underlying mechanisms of BV, discussing its effects on both tumor cells and the tumor microenvironment. Exploring resistance mechanisms in TCL provide valuable insights for optimizing BV-based therapies in the future. Full article
(This article belongs to the Special Issue Cutaneous Lymphomas: From Pathology to Treatment)
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18 pages, 1579 KiB  
Review
The Tumor Microenvironment as a Therapeutic Target in Cutaneous T Cell Lymphoma
by Louis Boafo Kwantwi, Steven T. Rosen and Christiane Querfeld
Cancers 2024, 16(19), 3368; https://doi.org/10.3390/cancers16193368 - 1 Oct 2024
Cited by 1 | Viewed by 2169
Abstract
Cutaneous T cell lymphomas (CTCLs) are a heterogeneous group of non-Hodgkin lymphomas, with mycosis fungoides and Sézary syndrome being the two common subtypes. Despite the substantial improvement in early-stage diagnosis and treatments, some patients still progress to the advanced stage with an elusive [...] Read more.
Cutaneous T cell lymphomas (CTCLs) are a heterogeneous group of non-Hodgkin lymphomas, with mycosis fungoides and Sézary syndrome being the two common subtypes. Despite the substantial improvement in early-stage diagnosis and treatments, some patients still progress to the advanced stage with an elusive underpinning mechanism. While this unsubstantiated disease mechanism coupled with diverse clinical outcomes poses challenges in disease management, emerging evidence has implicated the tumor microenvironment in the disease process, thus revealing a promising therapeutic potential of targeting the tumor microenvironment. Notably, malignant T cells can shape their microenvironment to dampen antitumor immunity, leading to Th2-dominated responses that promote tumor progression. This is largely orchestrated by alterations in cytokines expression patterns, genetic dysregulations, inhibitory effects of immune checkpoint molecules, and immunosuppressive cells. Herein, the recent insights into the determining factors in the CTCL tumor microenvironment that support their progression have been highlighted. Also, recent advances in strategies to target the CTCL tumor micromovement with the rationale of improving treatment efficacy have been discussed. Full article
(This article belongs to the Special Issue Cutaneous Lymphomas: From Pathology to Treatment)
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