Common Cutaneous T-cell Lymphoma Research Articles

Evaluation of mortality, prognostic parameters, and treatment efficacy in mycosis fungoides.

Mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, is characterized by a variable clinical course, presenting either as indolent disease or showing fatal progression due to extracutaneous involvement. Importantly, the lack of prognostic models and predominantly palliative therapy settings hamper patient care. Here, we aimed to define survival rates, disease prediction accuracy, and treatment impact in MF. Hundred-forty MF patients were assessed retrospectively. Prognosis and disease progression/survival were analyzed using univariate Cox proportional hazards regression model and Kaplan-Meier estimates. Skin tumors were linked to shorter progression-free, overall survival and a 3.48 increased risk for disease progression when compared to erythroderma. The Cutaneous Lymphoma International Prognostic Index identified patients at risk in early-stage disease only. Moreover, expression of Ki-67 >20%, CD30 >10%, CD20+, and CD7- were associated with a significantly worse outcome independent of disease stage. Only single-agent interferon-α and phototherapy combined with interferon-α or retinoids/bexarotene achieved long-term disease control in MF. Our data support predictive validity of prognostic factors and models in MF and identified further potential parameters associated with poor survival. Prospective studies on prognostic indices across disease stages and treatment modalities are needed to predict and improve survival.

Genetic predisposition to early mycosis fungoides: investigating genetic polymorphisms in tissue-resident memory T-cell genes.

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma; it arises from tissue-resident memory T-cells (TRM). In the present study, we investigated potential functional genetic variations that may predispose MF development. A case-control study was conducted using whole-exome sequencing, with a focus on genes that are essential to TRM function. We included 21 patients and 19 healthy subjects in the study. Single nucleotide polymorphisms in the following genes were significantly more common in patients than in healthy subjects: GZMB, HLA-DRB1, CD103, and NOTCH1. Moreover, the number of patients carrying single nucleotide polymorphisms in LAG3, NR4A2, and CD26L was significantly greater in the patient group than in the control group. The presence of genetic variations in one or more TRM functional gene may predispose patients to develop MF. Further studies involving a larger patient population and a comparative analysis of protein expression will be necessary to validate these findings.

MHC-I upregulation safeguards neoplastic T cells in the skin against NK cell-mediated eradication in mycosis fungoides

Cancer-associated immune dysfunction is a major challenge for effective therapies. The emergence of antibodies targeting tumor cell-surface antigens led to advancements in the treatment of hematopoietic malignancies, particularly blood cancers. Yet their impact is constrained against tumors of hematopoietic origin manifesting in the skin. In this study, we employ a clonality-supervised deep learning methodology to dissect key pathological features implicated in mycosis fungoides, the most common cutaneous T-cell lymphoma. Our investigations unveil the prominence of the IL-32β–major histocompatibility complex (MHC)-I axis as a critical determinant in tumor T-cell immune evasion within the skin microenvironment. In patients’ skin, we find MHC-I to detrimentally impact the functionality of natural killer (NK) cells, diminishing antibody-dependent cellular cytotoxicity and promoting resistance of tumor skin T-cells to cell-surface targeting therapies. Through murine experiments in female mice, we demonstrate that disruption of the MHC-I interaction with NK cell inhibitory Ly49 receptors restores NK cell anti-tumor activity and targeted T-cell lymphoma elimination in vivo. These findings underscore the significance of attenuating the MHC-I-dependent immunosuppressive networks within skin tumors. Overall, our study introduces a strategy to reinvigorate NK cell-mediated anti-tumor responses to overcome treatment resistance to existing cell-surface targeted therapies for skin lymphoma.

Mycosis Fungoides: Case report of progression successfully treated with liposomal doxorubicin

Mycosis fungoides is the most common primary cutaneous T-cell lymphoma. It is a non-Hodgkin lymphoma that begins in the skin and is characterized by a slow clinical evolution of three stages: macules, plaques and tumors. The advanced stage includes lymph node, visceral, or blood involvement, and requires skin-directed therapy associated with systemic medications. The case of a 49-year-old female patient with a diagnosis of mycosis fungoides in the malar region since July 2019 is presented, initially treated between November 2019 and March 2020 with 3 cycles of the CHOP chemotherapy regimen - cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin) and prednisone without achieving any clinical response. Subsequently without follow-up or treatment. In February 2023, progression of the disease was documented due to worsening of the lesion in the malar region and involvement of the glutes and back, additionally with cervical lymphadenopathy but without bone marrow involvement. She is considered a candidate for liposomal doxorubicin, with which she has completed 5 cycles to date with excellent clinical response. Current reassessment studies using positron emission tomography show complete tumor response. A bone marrow transplant is the therapeutic option that is being considered at the moment.

Phototherapy and mycosis fungoides: what’s new?

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, clinically characterized by erythematous-scaly patches and erythematous-violaceous nodules. Phototherapy plays an important role in MF, currently used as first line treatment in the early stages. The aim of this study is to analyze and review the different options of phototherapy on cutaneous lymphoma.

Primary cutaneous T-cell lymphoma: a review of the most common entities with focus on recent updates

Cutaneous T-cell lymphomas are an heterogeneous group of uncommon lymphoid neoplasms that are challenging to diagnose and require close collaboration between dermatologists, pathologists and hematologists/oncologists. This article reviews the most common cutaneous T-cell lymphomas: mycosis fungoides (both classic and variant forms) as well as its leukemic counterpart Sézary syndrome, CD30+ T-cell lymphoproliferative disorders including the ever-expanding group of lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma, and primary cutaneous CD4+ small/medium lymphoproliferative disorder. We discuss the classic clinical and histopathologic features of these lymphomas and review how they can be distinguished from reactive entities. In particularly, updates to these diagnostic categories and current controversies in classification are highlighted. Moreover, we review the prognosis and treatment for each entity. These lymphomas exhibit variable prognosis, and therefore it is important to correctly classify atypical cutaneous T-cell infiltrates for appropriate patient treatment and prognosis. Cutaneous T-cell lymphomas are at the interface of several medical specialties; this review seeks to summarize key features of these lymphomas and highlight new and emerging insights into these lymphomas.

Primary Cutaneous Anaplastic Large Cell Lymphoma-A Review of Clinical, Morphological, Immunohistochemical, and Molecular Features.

Primary cutaneous anaplastic large cell lymphoma (ALCL) is the second most common cutaneous T-cell lymphoma after mycosis fungoides and belongs to the spectrum of cutaneous CD30+ T-cell lymphoproliferative disorders. Although primary cutaneous ALCL usually presents as a localized nodule or papule with or without ulceration, multifocal lesions may occur in up to 20% of cases. Histologically, primary cutaneous ALCL consists of a diffuse dermal infiltrate of medium to large anaplastic/pleomorphic cells with abundant amphophilic-to-eosinophilic cytoplasm, horseshoe-shaped nuclei, strong and diffuse expression of CD30, and with focal or no epidermotropism. The neoplastic infiltrate may show angiocentric distribution and may extend to the subcutis. Patients with localized or multifocal disease have a similar prognosis with a 10-year overall survival rate of 90%. Approximately 30% of primary cutaneous ALCLs harbor a DUSP22 (6p25.3) gene rearrangement that results in decreased expression of this dual-specific phosphatase, decreased STAT3 activation, and decreased activity of immune and autoimmune-mediated mechanisms regulated by T-cells.

Primary cutaneous T-cell lymphoma: a review of the most common entities with focus on recent updates

Cutaneous T-cell lymphomas are an heterogeneous group of uncommon lymphoid neoplasms that are challenging to diagnose and require close collaboration between dermatologists, pathologists and hematologists/oncologists. This article reviews the most common cutaneous T-cell lymphomas: mycosis fungoides (both classic and variant forms) as well as its leukemic counterpart Sézary syndrome, CD30+ T-cell lymphoproliferative disorders including the ever-expanding group of lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma, and primary cutaneous CD4+ small/medium lymphoproliferative disorder. We discuss the classic clinical and histopathologic features of these lymphomas and review how they can be distinguished from reactive entities. In particularly, updates to these diagnostic categories and current controversies in classification are highlighted. Moreover, we review the prognosis and treatment for each entity. These lymphomas exhibit variable prognosis, and therefore it is important to correctly classify atypical cutaneous T-cell infiltrates for appropriate patient treatment and prognosis. Cutaneous T-cell lymphomas are at the interface of several medical specialties; this review seeks to summarize key features of these lymphomas and highlight new and emerging insights into these lymphomas.

SOHO State-of-the-Art Updates and Next Questions: A Modern Approach to the Systemic Treatment of Advanced CTCL.

The term cutaneous T-cell lymphoma (CTCL) is a general term for T-cell lymphomas that are found primarily in skin. The most common CTCL entities, mycosis fungoides and Sezary syndrome are incurable diseases with a plethora of conventional treatment options. In the past treatment options have been selected primarily according to stage. Given newer targeted therapies with varied response in different body compartments, we suggest a compartment-guided algorithm that may enhance response rates directing the selection of the most efficacious treatment options.

Primary cutaneous lymphomas: exploration of 10-year data from supraregional mutlidisciplinary team meetings in Glasgow, UK.

Primary cutaneous lymphomas (PCLs) are non-Hodgkin lymphomas, presenting in the skin. They are classified into cutaneous B-cell lymphomas (CBCLs) or cutaneous T-cell lymphomas (CTCLs). The most common CTCL subtypes are mycosis fungoides (MF) and Sézary syndrome (SS). All patient's cases should be discussed at a specialist multidisciplinary team (MDT) meeting. This is the first published review, to our knowledge, of PCL MDT case discussion in the UK. Patient cases between 2008 and 2019 were reviewed to assess: frequency of PCL subtype, documentation of CTCL staging and management of MF/SS. Of 356, 103 (29%) were CBCLs and the majority (n = 200, 56%) were CTCLs. MF/SS was the diagnosis in 120 (34%). Staging was documented in 44% (n = 53) of patients with MF/SS. Management largely followed guidelines for MF/SS, topical corticosteroids were the most common treatment (n = 93, 78%). Frequency of PCL subtype is largely comparable with previously published data. Documentation of CTCL staging is low, but higher than other reports. Our work begins to address the gap in real-world data on CTCLs. A standardized approach to data collection would inform clinical practice.

Risk of skin cancers in mycosis fungoides patients receiving PUVA therapy: A real-life experience from a single tertiary center.

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Skin-directed therapies, including phototherapy, are the first-line treatment modalities. Psoralen plus ultraviolet A light photochemotherapy (PUVA) is quite effective in controlling the disease; however, long-term adverse effects, particularly carcinogenesis, are the cons of this treatment. There are various studies on the negative impact of PUVA on skin cancer in patients with autoimmune skin diseases. The data on the long-term effects of phototherapy on MF patients are scarce. All MF cases that received PUVA alone or combined with other treatments at a single tertiary center were analyzed. This study compared the development of non-melanoma skin cancers, melanoma, and solid organ tumors in MF patients with at least 5-year follow-up data with age- and sex-matched controls. A total of 104 patients were included in the study. Ninety-two malignancies were detected in 16 (15.4%) patients, and six developed multiple malignancies. Skin cancers consisted of 56 basal cell carcinomas, 16 Bowen's disease, four squamous cell carcinomas, three melanomas, two basosquamous cell carcinomas, one Kaposi sarcoma, and one keratoacanthoma were found in nine (8.7%) patients. Eight patients developed three solid cancers and six lymphomas. The risk of developing skin cancer was associated with the total number of PUVA sessions (<250 vs ≥250 sessions; hazard ratio (HR) 4.44, 95% confidence interval (CI) 1.033-19.068; p = .045). 9 (13.2%) of 68 patients who had follow-ups for at least 5 years developed skin cancer. Compared to an age- and sex-matched cohort, the prevalence of new skin cancer was considerably greater (p = .009). Patients with MF are predisposed to develop secondary malignancies, and continual exposure to PUVA may potentiate this risk. Annual digital dermoscopic follow-up in MF patients treated with UVA is advised for early diagnosis and treatment of secondary cutaneous malignancies.

Tape stripped stratum corneum samples are suitable for diagnosis and comprehensive proteomic investigation in mycosis fungoides.

Mycosis Fungoides (MF) is a common cutaneous T-cell lymphoma. It can sometimes be challenging to diagnose MF using current clinico-histopathological criteria. Non-invasive molecular profiling analysis has the potential to aid the diagnosis and understanding of MF. Lesional and body site matched normal stratum corneum samples were obtained from the same MF patients (n=28) using adhesive discs, followed by proteomic analyses using data-independent acquisition mass spectrometry (DIA-MS). Differential abundance analyses and bioinformatic analyses were performed to identify differentially abundant proteins and altered biofunctions between the MF and normal stratum corneum samples. In total, 1303 proteins were identified, of which 290 proteins were significantly changed in the MF cohort compared to the normal stratum corneum. Ingenuity pathway analysis (IPA) predicted the significant inhibition of cell death of cancer cells and significant activation of immune-related activities and viral infection in the MF lesions. MF lesions were also associated with upstream regulators relating to immuno-oncologic dysfunctions. The top-250 variating proteins efficiently separated normal stratum corneum from matched MF samples. Non-invasive proteomic analysis could transform the diagnosis of MF by reducing the need for invasive biopsy. The identification of altered biological functions may serve as useful biomarkers to predict MF progression.

Multidisciplinary Approach to the Diagnosis and Therapy of Mycosis Fungoides

Mycosis fungoides is the most common primary cutaneous T-cell lymphoma, characterized by skin-homing CD4+ T cells derivation, indolent course, and low-grade of malignancy. Mycosis fungoides's classic type typically onsets with cutaneous erythematous patches, plaque, and tumor. In WHO-EORTC classification, folliculotropic mycosis fungoides, pagetoid reticulosis, and granulomatous slack skin are recognized as distinct variants of mycosis fungoides, because of their clinical and histological features, behavior, and /or prognosis. Mycosis fungoides often shows diagnostic difficulties, due to its absence of specific features and lesional polymorphism. A patient's treatment requires staging. In about 10% of cases, mycosis fungoides can progress to lymph nodes and internal organs. Prognosis is poor at advanced stage and management needs a multidisciplinary team approach. Advanced stage disease including tumors, erythroderma, and nodal, visceral, or blood involvement needs skin directed therapy associated with systemic drugs. Skin directed therapy includes steroids, nitrogen mustard, bexarotene gel, phototherapy UVB, and photochemiotherapy, i.e., total skin electron radiotherapy. Systemic therapies include retinoids, bexarotene, interferon, histone deacetylase inhibitors, photopheresis, targeted immunotherapy, and cytotoxic chemotherapy. Complexity of mycosis fungoides associated with long-term chronic evolution and multiple therapy based on disease stage need a multidisciplinary team approach to be treated.

Evaluation of Oxidative Stress by Thiol/Disulphide Homeostasis in Patients with Mycosis Fungoides: A Prospective Double-Centre Study.

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma with unknown etiopathogenesis. Oxidant and antioxidant balance is important for cell function and normal metabolism. An imbalance between pro-oxidants and antioxidants causes oxidative stress. A recent focus has been on thiol/disulphide homeostasis as a novel marker of oxidative stress. This study aimed to evaluate the role of oxidative stress in MF by analysing thiol/disulphide homeostasis. A total of 103 patients (48 female, 55 male) and a control group of 120 healthy individuals (48 female, 72 male) from two tertiary care hospitals were included in our study. Serum native thiol, total thiol and disulphide levels were evaluated using novel method developed by Erel and Neeliolu. Native thiol levels were 340.30 ± 87.44 in the patient group and 401.62 ± 69.45 in the control group. Total thiol value was 374.17 ± 87.78 in the patient group and 428.54 ± 70.05 in the control group. Native thiol and total thiol levels were significantly lower in the patient group compared to the control group (P < 0.001 and P < 0.001). The disulphide value was 16.93 ± 6.46 in the patient group and 13.46 ± 5.06 in the control group. Disulphide levels were found to be significantly higher in the patient group compared to the control group (P < 0.001). In our study, thiol/disulphide balance shifted towards disulphide which indicates the presence of oxidative stress especially in the early stage while 93.2% of our patients had early-stage MF. We think that this may have pathogenetic and prognostic significance.

Water bolus in photon-beam therapy of irregular skin lesions of extremities: a case report

Background: Mycosis fungoides (MF) represents the most common cutaneous T-cell lymphoma and approximately 4% of non-Hodgkin lymphomas. Treatment of skin lesions includes external beam radiation therapy which often provides adequate local control and symptom relief. Case presentation: A 39-year-old male with the diagnosis of MF presents with infiltrative and pruriginous plaques comprising the plantar, interdigital, lateral and posterior surfaces of the foot. A protocol using a water tank was used to provide uniform coverage to an irregular target volume. By creating a tissue-equivalent and homogenous bolus material a total dose of 8Gy in 2 fractions of photon-beam therapy was prescribed. After one month of treatment there was a partial response with minimal toxicity, achieving complete response in most lesions after six months. Conclusion: Photon-beam therapy for irregular surfaces such as extremities is a valid alternative to conventional electron-beam radiation by attaining uniform coverage while minimizing hotspots. Treatment utilizing a water tank is well-tolerated and has good clinical outcomes even in the presence of extensive skin lesions.

Rapidly progressive tumor stage mycosis fungoides: A case report from Syria

Mycosis Fungoides, the most common type of cutaneous T-cell lymphomas (CTCLs), has typically an indolent course over years or decades. Patches grow into infiltrated plaques which may turn eventually into tumors. The tumor stage represents advanced lymphoma, but this occurs in a minority (∼10%) of cases. we present a rare case of mycosis fungoides in a 30-year-old woman showing rapid progression to tumor stage, unlike the indolent clinical course seen classically. Mycosis Fungoides (MF) is the most common primary cutaneous T-cell lymphoma, representing less than 1% of the total number of non-Hodgkin lymphoma. Patients with a classical type of MF progress from patch stage to plaque stage and finally to tumor stage disease, and they have a protracted clinical course over years or even decades. Although mycosis fungoides is a rare disease, it requires a high degree of suspicion clinically. The disease can have an excellent prognosis when identified and treated promptly.

437 Single-cell RNA sequencing reveals specific T cell and fibroblast populations that can distinguish early mycosis fungoides from parapsoriasis and atopic dermatitis lesions

The diagnosis of early mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, is often delayed due to clinical and histopathological similarities with benign inflammatory dermatoses. Moreover, its clear delineation from the spectrum of so-called “parapsoriasis” is still controversial. For further insight on a molecular level, we performed single-cell RNA sequencing to profile skin biopsies from patients presenting clinically with small- or large-patch dermatitis and compared them to atopic dermatitis (AD) lesions and healthy control (HC) individuals.

Mycosis Fungoides in Skin of Color

ABSTRACT Mycosis fungoides is the most common primary cutaneous T-cell lymphoma. Although mycosis fungoides affects patients of all skin tones, mycosis fungoides has a higher incidence in patients with skin of color. Patients with skin of color who are diagnosed with mycosis fungoides have worse outcomes and poor prognosis compared with patients with lighter skin tones. Mycosis fungoides is difficult to diagnose in patients with skin of color as rare subtypes or clinical presentations are commonly seen in these populations. Increased awareness of the presentation of mycosis fungoides in skin of color and early detection could address the higher rates of morbidity and mortality in these populations.

Unraveling the Structural Variations of Early-Stage Mycosis Fungoides-CD3 Based Purification and Third Generation Sequencing as Novel Tools for the Genomic Landscape in CTCL.

Simple SummaryMycosis fungoides is the most common cutaneous T-cell lymphoma, but knowledge of the genetic alterations, particularly of the early stages, is limited. A major problem is that biopsies from early stages contain few tumor cells and many “healthy” skin cells, making accurate analysis of tumor cells difficult. Here, we demonstrate a workflow to enrich tumor cells and thereby obtain better results for mutation detection, especially for deletions and amplifications. For the same sample, we also demonstrate the advantages of long-read sequencing for a more comprehensive elucidation of genetic alterations in early stages of mycosis fungoides.Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL). At present, knowledge of genetic changes in early-stage MF is insufficient. Additionally, low tumor cell fraction renders calling of copy-number variations as the predominant mutations in MF challenging, thereby impeding further investigations. We show that enrichment of T cells from a biopsy of a stage I MF patient greatly increases tumor fraction. This improvement enables accurate calling of recurrent MF copy-number variants such as ARID1A and CDKN2A deletion and STAT5 amplification, undetected in the unprocessed biopsy. Furthermore, we demonstrate that application of long-read nanopore sequencing is especially useful for the structural variant rich CTCL. We detect the structural variants underlying recurrent MF copy-number variants and show phasing of multiple breakpoints into complex structural variant haplotypes. Additionally, we record multiple occurrences of templated insertion structural variants in this sample. Taken together, this study suggests a workflow to make the early stages of MF accessible for genetic analysis, and indicates long-read sequencing as a major tool for genetic analysis for MF.

33870 Mechlorethamine gel as a maintenance treatment regimen in patients with mycosis fungoides

Background: Cutaneous T-cell lymphomas (CTCLs) are malignant proliferations in the skin that can invade blood, lymph nodes, or viscera. Mycosis fungoides (MF), the most common CTCL, is treated with topical agents, such as mechlorethamine gel 0.016%, in skin-limited stages. Currently, no data exist on maintenance therapy for patients in remission. Thomas Jefferson University has developed a unique protocol to use mechlorethamine as a maintenance regimen after total skin electron beam therapy. Purpose: To determine progression-free survival and efficacy of mechlorethamine as maintenance and active treatment regimens for MF. Methods: A retrospective review of MF patients seen at Thomas Jefferson University from 2012 to 2020 was conducted. Patients of all stages treated with mechlorethamine as maintenance or active treatment with 2 consecutive mSWATs (modified Severity Weighted Assessment Tool) documented were included. Treatment outcomes were assessed by change in mSWAT and progression-free survival. Dermatology Life Quality Index surveys before and after treatment were analyzed. Results: Of 186 MF patients, 44 met inclusion criteria. Patients on maintenance therapy had a 65.22% progression-free survival rate with median time to progression of 29.45 months. By-time analysis for responders on active and maintenance treatment showed an increased response over time. Peak responses were seen at last mSWAT recorded. Both cohorts experienced improved quality-of-life scores from initiation to discontinuation of mechlorethamine. Conclusions: Patients on maintenance and active mechlorethamine treatment regimens demonstrated improvement in mSWAT and quality-of-life. Mechlorethamine treatment showed progression-free survival for a median of 29.45 months, indicating this therapy may be an effective maintenance regimen.