Mycosis Fungoides Research Articles

Predicting Prognosis of Early-Stage Mycosis Fungoides with Utilization of Machine Learning

Mycosis fungoides (MF) is the most prevalent type of cutaneous T cell lymphomas. Studies on the prognosis of MF are limited, and no research exists on the potential of artificial intelligence to predict MF prognosis. This study aimed to compare the predictive capabilities of various machine learning (ML) algorithms in predicting progression, treatment response, and relapse and to assess their predictive power against that of the Cox proportional hazards (CPH) model in patients with early-stage MF. The data of patients aged 18 years and over who were diagnosed with early-stage MF at Ankara University Faculty of Medicine Hospital from 2006 to 2024 were retrospectively reviewed. ML algorithms were utilized to predict complete response, relapse, and disease progression using patient data. Of the 185 patients, 94 (50.8%) were female, and 91 (49.2%) were male. Complete response was observed in 114 patients (61.6%), while relapse and progression occurred in 69 (37.3%) and 54 (29.2%) patients, respectively. For predicting progression, the Support Vector Machine (SVM) algorithm demonstrated the highest success rate, with an accuracy of 75%, outperforming the CPH model (C-index: 0.652 for SVM vs. 0.501 for CPH). The most successful model for predicting complete response was the Ensemble model, with an accuracy of 68.89%, surpassing the CPH model (C-index: 0.662 for the Ensemble model vs. 0.543 for CPH). For predicting relapse, the decision tree classifier showed the highest performance, with an accuracy of 78.17%, outperforming the CPH model (C-index: 0.782 for the decision tree classifier vs. 0.505 for CPH). The results suggest that ML algorithms may be useful in predicting prognosis in early-stage MF patients.

A woman with mycosis fungoides, vitiligo, and a new hand nodule.

A 70-year-old African American female with a history of stage IV mycosis fungoides in remission presented with a gradually enlarging, red, ulcerated nodule on her right dorsal hand. The lesion was biopsied, and it showed intraepidermal proliferation with cytologic atypia and increased vasculature in the papillary dermis. Immunohistochemical staining indicated a yes-associated protein 1 (YAP1) rearrangement, confirmed by RNA sequencing, revealing a YAP1::MAML2 (mastermind-like transcriptional coactivator 2) fusion. The lesion was diagnosed as an eccrine porocarcinoma (EPC). The occurrence of EPCs following radiotherapy or trauma has been documented. This case highlights the importance of considering EPCs in patients with extensive skin treatments and immunosuppression history.

Review of Treatment Algorithms in Mycosis Fungoides and Sezary Syndrome

Review of Treatment Algorithms in Mycosis Fungoides and Sezary Syndrome

A retrospective study comparing PUVA therapy with and without maintenance therapy in patients with mycosis fungoides in a real‐word clinical practice

A retrospective study comparing PUVA therapy with and without maintenance therapy in patients with mycosis fungoides in a real‐word clinical practice

Multidisciplinary and personalized approach to the management of mycosis fungoides with chlormethine gel: a collection of clinical experiences.

Topical chlormethine (CL) gel formulation was approved by the EMA in 2017 for the treatment of adult patients with mycosis fungoides (MF). To expand the knowledge on the management of MF, this paper provides an overview of clinical practice evidence about the MF diagnostic phase and a collection of clinical experiences to better characterize the use of CL gel in daily practice. Collected cases underline the importance of the concomitant biopsy and clinical evaluation in the diagnostic phase, with the contribution of a multidisciplinary team, and support the use of CL gel as a first-line or adjuvant treatment in selected patients.

Genetic alterations of class I HLA in cutaneous T-cell lymphoma

Abnormalities involving class I HLA are frequent in many lymphoma subtypes but have not yet been extensively studied in cutaneous T-cell lymphomas (CTCL). We characterized the occurrence of class I HLA abnormalities in 65 patients with advanced mycosis fungoides (MF) or Sézary syndrome (SS). Targeted DNA sequencing including coverage of HLA loci revealed at least one HLA abnormality in 26/65 patients (40%). Twelve unique somatic HLA mutations were identified across nine patients, and loss of heterozygosity or biallelic loss of HLA was found to affect 24 patients. Although specific HLA alleles were commonly disrupted, these events did not associate with decreased total class I HLA expression. Genetic events preferentially disrupted HLA alleles capable of presentation of greater numbers of putative neoantigens. HLA abnormalities co-occurred with other genetic immune evasion events and were associated with worse progression-free survival. Single-cell analyses demonstrated HLA abnormalities were frequently subclonal. Through analysis of serial samples, we observed disrupting class I HLA events change dynamically over the disease course. The dynamics of HLA disruption are highlighted in a patient receiving pembrolizumab, where resistance to pembrolizumab was associated with elimination of an HLA mutation. Overall, our findings show that genomic class I HLA abnormalities are common in advanced CTCL and may be an important consideration in understanding the effects of immunotherapy in CTCL.

RUNX2 as a novel biomarker for early identification of patients progressing to advanced-stage mycosis fungoides.

The majority of patients with mycosis fungoides (MF) have an indolent disease course, but a substantial fraction (20-30%) of patients progress to advanced stages - usually with a grave prognosis. Early differentiation between indolent and aggressive types of MF is important for the choice of treatment regimen and monitoring of the individual patient. Good biomarkers are therefore desired. Here, we used spatial transcriptomics on skin samples at time-of-diagnosis to enable prediction of patients who later progressed to advanced stages of MF. Formalin-fixed, paraffin-embedded skin biopsies at time of diagnosis from six patients with MF who progressed to advanced stages of disease within 4 months to 12 years after diagnosis, and nine patients who remained in early-stage disease over 9 to 27 years were analyzed using the GeoMx Digital Spatial Profiler to capture spatially resolved high-plex RNA gene expression data. Five different regions of interest (the epidermis, the basal layer of epidermis, CD4+ T-cells and neighboring cells, and Pautrier's microabscesses) were profiled for further assessment. Interestingly, RUNX2, SHMT2, and MCM7 were upregulated in the enriched population of malignant T-cells in Pautrier's microabscesses in patients who later developed advanced stages of disease. Expression of RUNX2, SHMT2 and MCM7 in malignant T-cells was confirmed in a subset of patients in MF skin using scRNA-seq datasets across multiple studies and correlating with stage of disease. Taken together, we provide first evidence that RUNX2 has potential as a biomarker to identify MF patients progressing to advanced stage disease. As RUNX2 has not previously been linked to MF, our data also shows the analytical strength of combining spatial transcriptomics with scRNA-seq analysis.

Surcharges cutanées endogènes

As in other organs, the diagnosis of endogenous cutaneous overload diseases is based on histopathological analysis of the lesions using special stainings, even if the clinical appearance is sometimes very suggestive. The lesions are sometimes very subtle and can be included in the group of "invisible" dermatoses, such as primary macular cutaneous amyloidosis or calciphylaxis. Superficial dermal melanosis or pigmentary incontinence generally reflects the post-inflammatory stage of a chronic or recurrent interface dermatitis. Section levels should be systematically performed to look for active lesions of diagnostic interest: Alcian blue staining to identify dermal mucinosis (connectivitis) and pan-T markers (fixed pigmented erythema, lichenoid mycosis fungoides, and vitiligo). Some pathologies have a prognostic impact, either because they reflect an underlying disease, monoclonal gammopathies, in particular myeloma, being one of the most common conditions in this context (AL amyloidosis, xanthoma and xanthogranuloma, scleromyxedema), or because they can be associated with visceral damage (AL amyloidosis, scleromyxedema). The clinical-pathological comparison is mandatory to rule out differential diagnoses, especially for life-threatening diseases: nodular amyloidosis and primary cutaneous amyloidosis versus systemic AL amyloidosis, papular mucinosis versus scleromyxedema and calcific panniculitis versus calciphylaxis.

New and emerging therapies in cutaneous T-cell lymphoma

Mycosis Fungoides (MF) is the most common cutaneous T-cell lymphoma that typically presents in the early phase as inflammatory erythematous patches or plaques, with epidermotropism as the histopathological hallmark of the disease. Traditionally, in the early stages, non-aggressive options represent the first-line strategy: topical corticosteroids, phototherapy, radiotherapy and occasionally adopting a 'wait-and-see' approach for minimally symptomatic patients. In patients with advanced or recurrence disease, good results can be achieved with immune modifiers, chemotherapeutic agents, total skin irradiation or extracorporeal photochemotherapy and maintenance therapy is often required. The past decade has seen an expansion of therapies that can be used in this setting by increasing new therapeutic strategies. Herein are resumed the key advancements coming from recently published trials.

Pegylated interferon-α2a in cutaneous T-cell lymphoma - a multicenter retrospective data analysis with 70 patients.

Interferon-alpha is an important therapeutic option for the treatment of the cutaneous T-cell lymphomas (CTCL). Since the approved recombinant interferon-α-2a(IFN-α2a) has no longer been produced sinceJanuary 2020, pegylated interferon-α2a (pegIFN-α2a) can be used as an alternative treatment, even though it is not approved for the treatment of CTCL. The aim of this multicentre study was to generate comprehensive data on the efficacy and tolerability of pegIFN-α2a in the treatment of CTCL. A multicenter retrospective study was conducted with 70 patients with CTCL from twelve German skin centers. In total, 70 patients were included in the study, with 57.2% male and a mean age of 58.8 ±14.9 years. Mycosis fungoides was present in 71.4% of cases and Sézary Syndrome in 28.6%. An overall response rate of 55.2% was observed with pegIFNα-2a therapy. In 50% of cases, therapy was discontinued after 63.6 ±33.5 weeks. The most common reason for discontinuation was adverse events, which occurred in 68.6% of cases and which were classified as severe in 29.2%. Blood count changes, fatigue and liver toxicity occurred most frequently. Our analysis provides comprehensive data on the efficacy and tolerability of pegIFNα-2a therapy in patients with CTCL. In terms of response rates and side effect profile, pegIFNα-2a appears to be comparable to IFN-α2a therapy.

Real-world Use of Mogamulizumab Among Patients With Mycosis Fungoides and Sézary Syndrome Before and During COVID-19 in the United States

During the coronavirus disease 2019 (COVID-19) pandemic, professional organizations suggested extending dosing intervals for systemic cancer therapies to limit in-person visits. Mogamulizumab, indicated for adults with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after ≥1 prior systemic therapy, should be administered every 7 days of the first 28-day cycle (loading) and every 14 days of each subsequent cycle (maintenance) according to the approved prescribing information in the United States (US). This study examined the real-world use of mogamulizumab before and during the COVID-19 pandemic in the US. Using Symphony Health's Integrated Dataverse (IDV) database, adults with ≥1 diagnosis of MF or SS and ≥1 mogamulizumab claim between October 1, 2018 and December 22-, 2022 were identified. Patients in MF and SS cohorts were divided into 3 subgroups based on the date they initiated mogamulizumab treatment: pre-COVID-19 (October 1, 2018-March 31, 2020), COVID-19 Phase 1 (April 1, 2020-July 31, 2021), and COVID- 19 Phase 2 (August 1, 2021-December 22, 2022). During the study, 270 patients with MF and 337 patients with SS initiated mogamulizumab. The pre-COVID-19, COVID-19 Phase 1, and COVID-19 Phase 2 subgroups included 95, 81, and 94 patients with MF and 124, 119, and 94 patients with SS, respectively. In the MF cohort, mean loading dosing intervals were 13, 12, and 9 days for the pre-COVID-19, COVID-19 Phase 1, and COVID-19 Phase 2 subgroups, respectively, and mean maintenance dosing intervals were 16, 16, and 16 days, respectively. In the SS cohort, mean loading dosing intervals were 16, 11, and 11 days, and mean maintenance dosing intervals were 19, 18, and 16 days, respectively. For both cohorts, more patients in the COVID-19 Phase 1 and Phase 2 subgroups than in the pre-COVID-19 subgroup had gaps of ≤10 days between loading doses and ≤21 days between maintenance doses. In patients with MF and SS, loading dosing intervals in the pre-COVID-19 period were longer than the loading schedule per the approved prescribing information, but there was a trend towards closer concordance in the COVID-19 periods. Maintenance dosing intervals in patients with MF were consistently similar to the approved schedule across treatment periods, and in patients with SS became more closely aligned over time. Thus, dosing intervals for mogamulizumab in both loading and maintenance cycles do not appear to have been extended during the COVID-19 Phase 1 and Phase 2 periods compared with the pre-COVID-19 period, despite recommendations to extend dosing intervals for systemic cancer therapies during COVID-19.

Evaluation of demographic and clinical characteristics of 728 patients with mycosis fungoides and their relationship with systemic comorbidities: multicenter, registry-based (MF-TR) study from Türkiye.

Mycosis fungoides (MF) is the most common cutaneous lymphoma with a chronic disease course. MF patients may also suffer from systemic comorbidities such as cardiovascular and metabolic diseases. In this study, we aimed to evaluate the demographic and clinical features of MF patients registered in the MF-TR registry system and to examine the relationship of these features with systemic comorbidities. We collected the data from the medical files of the patients via the MF-TR registry system. Our study included 728 patients with MF, of which 396 (54.40%) were male and 332 (45.60%) were female. The most common additional systemic disease observed was hypertension, affecting 124 (17.03%) patients. This was followed by multinodular goiter in 66 (9.06%) patients, and diabetes mellitus type 2 in 61 (8.37%) patients. Twenty-two (3.02%) patients had a history of another secondary malignancy, with lung cancer being the most common type, affecting 5 (0.68%) patients. Female gender and high BMI were statistically higher in MF patients with asthma (P=0.019 and P=0.031, respectively). In patients with hypertension and hypercholesterolemia, the duration of diagnosis was significantly longer (P=0.013 and P=0.047, respectively). Dermatologists should be aware of these accompanying comorbidities in patients with MF. Multidisciplinary evaluation should be performed in the follow-up, if necessary.

A-209 Utility of TCR-β and TCR-γ gene rearrangement to distinguish between tumour-stage mycosis fungoides and early-stage mycosis fungoides associated with CD30+ lymphoproliferative disorders

A-209 Utility of TCR-β and TCR-γ gene rearrangement to distinguish between tumour-stage mycosis fungoides and early-stage mycosis fungoides associated with CD30+ lymphoproliferative disorders

A-167 Durable disease control with low-dose total skin electron beam therapy combined with maintenance treatment for patients with erythrodermic mycosis fungoides and Sézary syndrome

A-167 Durable disease control with low-dose total skin electron beam therapy combined with maintenance treatment for patients with erythrodermic mycosis fungoides and Sézary syndrome

A-240 Mogamulizumab-Associated Rash in Patients with Mycosis Fungoides or Sezary Syndrome: A Real-World Analysis

A-240 Mogamulizumab-Associated Rash in Patients with Mycosis Fungoides or Sezary Syndrome: A Real-World Analysis

A-152 Dissecting the role of CXCR4 in mycosis fungoides: from gene editing to therapeutic molecule

A-152 Dissecting the role of CXCR4 in mycosis fungoides: from gene editing to therapeutic molecule

A-182 Phase 2a Study of Topical 0.25% Hypericin in Mycosis Fungoides: Results and Review of the FLASH Study

A-182 Phase 2a Study of Topical 0.25% Hypericin in Mycosis Fungoides: Results and Review of the FLASH Study

The Tumor Microenvironment as a Therapeutic Target in Cutaneous T Cell Lymphoma.

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.

A-188 Correlation of skin barrier function, bacterial colonization, and inflammation in Mycosis Fungoides and Sézary Syndrome

A-188 Correlation of skin barrier function, bacterial colonization, and inflammation in Mycosis Fungoides and Sézary Syndrome

A-278 Assessing Inter-Rater Reliability in Mycosis Fungoides: Impact of Clinician Experience on Skin Involvement Assessments

A-278 Assessing Inter-Rater Reliability in Mycosis Fungoides: Impact of Clinician Experience on Skin Involvement Assessments