Predictors for the use of systemic therapy in stage IB Mycosis fungoides.

BACKGROUND: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is aprospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) inpatients with newly diagnosed mycosis fungoides (MF). OBJECTIVES: To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB)staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures. METHODS: In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centresin 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review. RESULTS: The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smallerpercentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariateanalysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA,20%; IA-IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs.T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first-line SDT was 73%,while the ORR to first-line systemic treatments was lower (57%) (P = 0·027). Health-related QoL improvedsignificantly both in patients with responsive disease and in those with stable disease. CONCLUSIONS: Disease characteristics such as presence of plaques and FMF influence physician treatment choices,and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, futuretreatment guidelines for early-stage MF need to address these issues.

Estimation of the tissue and serum levels of IL-35 in Mycosis fungoides: a case-control study.

Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma (CTCL) with its etiology not yet fully understood. Interleukin (IL)-35 is an inhibitory cytokine that belongs to the IL-12 family. Elevated IL-35 in the plasma and the tumor microenvironment increases tumorigenesis and indicates poor prognosis in different types of malignancies. The objective of this study is to estimate the expression levels of IL-35 in tissue and serum of MF patients versus healthy controls. This case-control study included 35 patients with patch, plaque, and tumor MF as well as 30 healthy controls. Patients were fully assessed, and serum samples and lesional skin biopsies were taken prior to starting treatment. The IL-35 levels were measured in both serum and tissue biopsies by ELISA technique. Both tissue and serum IL-35 levels were significantly higher in MF patients than in controls (P < 0.001) and tissue IL-35 was significantly higher than serum IL-35 in MF patients (P < 0.001). Tissue IL-35 was significantly higher in female patients and patients with recurrent MF compared to male patients and those without recurrent disease (P < 0.001). Since both tissue and serum IL-35 levels are increased in MF, IL-35 is suggested to have a possible role in MF pathogenesis. IL-35 can be a useful diagnostic marker for MF. Tissue IL-35 can also be an indicator of disease recurrence.

The Impact of Primary Tumor Site on Survival in Mycosis Fungoides.

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL), but little is known about the influence of anatomic location of the primary disease site on overall survival (OS) and disease-specific survival (DSS). The purpose of this study was to examine the significance of primary tumor site on survival in MF. A search of the Surveillance, Epidemiology, and End Results (SEER) database was conducted for patients with a diagnosis of MF with a specified primary site from 2000 to 2019. Prognostic factors including demographic and tumor characteristics were examined using Cox regression models. Further research is needed to fully investigate primary disease site as a prognostic indicator, including a deeper dive into MF of all stages and subtypes.

Milia en plaque on the shoulder as an early manifestations of mycosis fungoides.

Milia en plaque (MEP) is an uncommon skin condition identified as retroauricular confluent milium by Boulzer and Fouqet in 1903 [1]. It can be mistaken for other dermatoses like Favre-Racouchot nodular elastosis, steatocystoma multiplex, and nevus comedonicus. Milia en plaque can either be primary or secondary and is typically benign, often triggered by dermatological procedures like cryotherapy, as reported in this journal. In some cases, MEP can arise as a secondary manifestation of other diseases, including folliculotropic mycosis fungoides (FMF). Despite this association, there are few documented cases in the literature. Herein, we present a patient in whom MEP served as the initial clinical presentation of FMF; the treatment involved oral retinoids and phototherapy. Furthermore, we highlight distinctive features of both conditions. It is important to emphasize that early diagnosis and treatment of FMF are vital for the patient's quality of life. The presence of MEP can serve as a valuable indicator for identifying it.

Genomic profiling of mycosis fungoides identifies patients at high risk of disease progression.

ABSTRACT: Mycosis fungoides (MF) is the most prevalent primary cutaneous T-cell lymphoma, with an indolent or aggressive course and poor survival. The pathogenesis of MF remains unclear, and prognostic factors in the early stages are not well established. Here, we characterized the most recurrent genomic alterations using whole-exome sequencing of 67 samples from 48 patients from Lille University Hospital (France), including 18 sequential samples drawn across stages of the malignancy. Genomic data were analyzed on the Broad Institute's Terra bioinformatics platform. We found that gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), or mutations in JUNB and TET2 are associated with high-risk disease stages. Furthermore, gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), and del6q16.3 (TNFAIP3) are coupled with shorter survival. Del6q16.3 (TNFAIP3) was a risk factor for progression in patients at low risk. By analyzing the clonal heterogeneity and the clonal evolution of the cohort, we defined different phylogenetic pathways of the disease with acquisition of JUNB, gain10p15.1 (IL2RA and IL15RA), or del12p13.1 (CDKN1B) at progression. These results establish the genomics and clonality of MF and identify potential patients at risk of progression, independent of their clinical stage.

Interstitial mycosis fungoides: A rare presentation of mycosis fungoides with overlapping granulomatous and folliculotropic features.

BACKGROUND: Interstitial mycosis fungoides (IMF) is a rare subtype of mycosis fungoides (MF) characterized by atypical lymphocytes infiltrating the reticular dermis between collagen bundles with limited epidermotropism and variable granulomatous features. METHODS: Retrospective single institution review of 31 cases of IMF including clinical characteristics, disease course and pathological features. RESULTS: Our cohort was predominately male (19; 61%, M:F 1.6:1) with a mean age at diagnosis of 43 years (range 11-85), mean signs/symptoms duration of 7 years prior to diagnosis, and 6 years mean follow-up duration. Clinically, patients often exhibited symmetric ill-defined patches/plaques involving intertriginous regions with tan-yellow hyperpigmentation and follicular-based papules, wrinkling, and alopecia. Lymphadenopathy was noted in seven patients. Fifteen (52%) patients were in near or complete clinical remission at the latest follow-up. T-cell receptor gene rearrangement was positive in 23/24 (96%) cases. Histopathologically, atypical cells were small-medium, CD4+ (29; 94%) or rarely CD4+/CD8+ (1; 3%) lymphocytes infiltrating the reticular dermis with thickened collagen bundles (27; 87%), multinucleated giant cells (12; 39%), and often tracing along adnexa with subtle folliculotropism (12/20; 60%). CONCLUSIONS: Our study demonstrates IMF is an indolent subtype of MF with distinct features, including frequent granulomatous and subtle follicular involvement resulting in alopecia.

Diagnostic Validation of Anti-TOX Antibody for Early-Stage Mycosis Fungoides Through Digital Analysis of Tissue Samples.

ABSTRACT: Mycosis fungoides (MF) has become one of the most difficult diagnostic challenges for both dermatologists and dermatopathologists because its clinical presentation and microscopic findings may mimic benign reactive processes, specifically those displaying histopathological features of interface dermatitis. The goal of our study was to prove with digital scanning and automated sample methodology through algorithmic analysis, combined with the utility of TOX marker a more precise, faster, and objective evaluation of each sample. Moreover, this would offer high levels of reproducibility with the possibility of establishing cut-off points, allowing us to distinguish between inflammatory dermatoses (ID) and MF. A retrospective longitudinal-descriptive and observational study was conducted to compare the diagnostic criteria (immunohistochemical studies of anti-TOX stain) in patients with clinical suspicion of MF by dividing them into 2 groups: samples with a positive biopsy for MF (MF group) and those with a negative biopsy, therefore diagnosed as an ID (control group). The algorithm assessed 5 selected areas with lymphocytic representative cellularity, and based on the intensity, nuclear staining was classified as 0 (negative), 1+ (weak/yellow), 2+ (moderate/orange), and 3+ (strong/scarlet red) nuclei. The results showed statistically significant differences ( P = 0.040) between the mean number of (2+) nuclei in the positive final diagnosis group (MF group) and the negative final diagnosis group (ID group).

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

BACKGROUND AND OBJECTIVES: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Incidence and survival rates of primary cutaneous malignancies in Korea, 1999-2019: A nationwide population-based study.

Primary cutaneous malignancies are among the most commonly diagnosed types of cancer worldwide. We aimed to examine the incidence and 5-year survival rates of all types of primary cutaneous malignancies in the Korean population. Data from the Korean Nationwide Cancer Registry from 1999 to 2019 were analyzed. The crude incidence rates, age-standardized incidence rates, and 5-year relative survival rates of each type of skin cancer were calculated. A total of 89 965 patients were diagnosed with primary cutaneous malignancies, which was a 7-fold increase from 1999 to 2019. The age-standardized incidence rates increased 3.4-fold in basal cell carcinoma (3.7/100 000 person-years), 2.0-fold in squamous cell carcinoma (1.6/100 000 person-years), 12.0-fold in Bowen disease (1.2/100 000 person-years), and 1.8-fold in malignant melanoma (0.7/10 000 person-years) in 2019. Average annual percentage changes in age-standardized incidence rates were statistically significant in basal cell carcinoma (15.8%), Bowen disease (5.8%), squamous cell carcinoma (5.1%), malignant melanoma (1.2%), melanoma in situ (1.1%), dermatofibrosarcoma protuberans (1.2%), mycosis fungoides (0.5%), primary cutaneous CD30+ T-cell proliferations (0.5%), adnexal and skin appendage carcinoma (0.4%), extramammary Paget's disease (0.2%), and Merkel cell carcinoma (0.2%). The 5-year relative survival rates were the highest in basal cell carcinoma (103.3%), followed by dermatofibrosarcoma protuberans (99.7%) and mycosis fungoides (96.6%), and lowest in angiosarcoma (24.7%). The 5-year relative survival rates steadily increased in extramammary Paget's disease (23.6%), cutaneous B-cell lymphoma (21.3%), mycosis fungoides (20.2%), extranodal NK/T-cell lymphoma, nasal type (18.1%), and malignant melanoma (16.1%) from 1996-2000 to 2015-2019. Most primary cutaneous malignancies have increased in incidence and survival rates in the Korean population, but to varying extents depending on the type of skin cancer.

Computational Flow Cytometry Accurately Identifies Sezary Cells Based on Simplified Aberrancy and Clonality Features.

Flow cytometric identification of circulating neoplastic cells (Sezary cells) in patients with mycosis fungoides and Sezary syndrome is essential for diagnosis, staging, and prognosis. Although recent advances have improved the performance of this laboratory assay, the complex immunophenotype of Sezary cells and overlap with reactive T cells demand a high level of analytic expertise. We utilized machine learning to simplify this analysis using only 2 predefined Sezary cell-gating plots. We studied 114 samples from 59 patients with Sezary syndrome/mycosis fungoides and 66 samples from unique patients with inflammatory dermatoses. A single dimensionality reduction plot highlighted all TCR constant ß chain-restricted (clonal) CD3+/CD4+ T cells detected by expert analysis. On receiver operator curve analysis, an aberrancy scale feature computed by comparison with controls (area under the curve = 0.98) outperformed loss of CD2 (0.76), CD3 (0.83), CD7 (0.77), and CD26 (0.82) in discriminating Sezary cells from reactive CD4+ T cells. Our results closely mirrored those obtained by exhaustive expert analysis for event classification (positive percentage agreement = 100%, negative percentage agreement = 99%) and Sezary cell quantitation (regression slope = 1.003, R squared = 0.9996). We demonstrate the potential of machine learning to simplify the accurate identification of Sezary cells.

A case report of acute promyelocytic leukemia with mycosis fungoides.

RATIONALE: Acute promyelocytic leukaemia (APL) is a rare subtype of acute myelogenous leukaemia. With advances in treatment regimens, namely, introduction of all-trans-retinoicacid, outcomes have drastically improved, its side effects should not be ignored. Mycosis fungoides is one of the side effects of all-trans-retinoicacid treatment, but it may also be a clinical manifestation before disease progression. However, it rarely appears and is easily overlooked. This leads to being easily misled during the treatment process, affecting the treatment plan, and resulting in adverse consequences. Therefore, early identification and judgment can not only provide appropriate treatment options, but also prevent and treat further disease progression. PATIENT CONCERNS: The patient was hospitalized for pancytopaenia. After completing the examination, the patient was finally diagnosed with acute promyelocytic leukaemia (acute myelogenous leukaemia-M3). We administered tretinoin and arsenous acid. Evaluation of the treatment effect on the 7th day after chemotherapy showed that the bone marrow morphology showed complete remission. After the second course of chemotherapy, the patient developed red miliary macular papules, which gradually worsened. After completing relevant inspections, Considering that the cases was complicated with skin mycosis fungoides, the patient was treated with budesonide ointment and methylprednisolone as chemotherapy. DIAGNOSES: Upon examination, the patient was initially diagnosed with acute promyelocytic leukaemia. Evaluation of the treatment effect on the 7th day after chemotherapy showed that the bone marrow morphology showed complete remission. After the second course of chemotherapy, we discovered the patient was diagnosed with skin mycosis fungoides. INTERVENTIONS: Systemic chemotherapy is first given when a patient was diagnosed with acute promyelocytic leukaemia. After the patient happened skin mycosis fungoides, We have adjusted the treatment plan and supplemented it with other treatment plans based on the original chemotherapy, After 2 months of treatment, his condition gradually improved. OUTCOMES: All-trans-retinoicacid in the treatment of APL must be given attention because mycosis fungoides should not only be distinguished from infectious diseases but also be further assessed with regard to disease progression and metastasis. LESSONS: Acute promyelocytic leukemia needs to be treated with arsenic trioxide. All-trans-retinoicacid in the treatment of APL must be given attention mycosis fungoides. Early diagnosis can guide accurate treatment, which is of great help in alleviating the pain of patients and improving the cure rate.

Pruritus and Cutaneous Lesions: Granuloma Annulare vs. Mycosis Fungoides in a Pa-tient with Comorbidities. Case Report

Introduction: Pruritus is a common symptom in dermatological practice. Affecting patients with a wide range of cutaneous and systemic diseases. It can be caused by cutaneous disorders, systemic diseases, neurological disorders, psychological disorders, medications, among others. When assessing individuals with pruritus and cutaneous lesions, it is essential to consider mycosis fungoides and granuloma annulare as noteworthy differential diagnoses. Case presentation: A 51-year-old female patient exhibited symptoms of pruritus and two occurrences of pruritic skin lesions. Accompanied by a low-grade fever measuring 37.7 ºC, as well as asthenia and myalgia. Physical examination revealed two rounded plaques with erythematous borders and multiple non-confluent papular lesions. Discussion: Differentiating between mycosis fungoides and granuloma annulare can be challenging due to the similarities in their clinical presentations. However, performing a biopsy is essential to reach a definitive diagnosis.Conclusions: A biopsy is being suggested for the front part of the left lower limb. The application of mometasone furoate twice a day for two weeks was prescribed. Subsequently, a meeting has been arranged to conduct a review and to carefully analyze the biopsy findings within thirty days.

Introducción: El prurito es un síntoma frecuente en la práctica dermatológica, que afecta a pacientes con una amplia gama de enfermedades cutáneas y sistémicas. Puede estar causado por trastornos cutáneos, enfermedades sistémicas, trastornos neurológicos, trastornos psicológicos y medicamentos, entre otros. En la evaluación de personas con prurito y lesiones cutáneas, es fundamental tener en cuenta la micosis fungoide y el granuloma anular como diagnósticos diferenciales destacables. Presentación del caso clínico: Una paciente de 51 años de edad presentaba síntomas de prurito y dos apariciones de lesiones cutáneas pruriginosas, acompañadas de fiebre baja de 37.7 ºC, así como astenia y mialgias. El examen físico reveló dos placas redondeadas con bordes eritematosos y múltiples lesiones papulares no confluentes. Discusión: Diferenciar entre micosis fungoide y granuloma anular puede ser un reto debido a las similitudes en sus presentaciones clínicas. Sin embargo, la realización de una biopsia es esencial para llegar a un diagnóstico definitivo. Conclusiones:Se sugiere la realización de una biopsia en la parte anterior del miembro inferior izquierdo. Se prescribe la aplicación de furoato de mometasona dos veces al día durante dos semanas. Posteriormente, se ha concertado una reunión para realizar una revisión y deliberar sobre los resultados de la biopsia en un plazo de treinta días

Racial Disparities in Mycosis Fungoides/Sézary Syndrome-A Single-Center Observational Study of 292 Patients.

BACKGROUND: Clinical presentation of Mycosis fungoides/Sézary syndrome (MF/SS) in Black and African American (AA) patients can be heterogeneous with poor survival reported in AA/black patients. In this study, we aim to characterize differences between AA/black and white patients with MF/SS. PATIENTS AND METHODS: A retrospective single-center hospital-based case-control study including 292 MF/SS patients (146 AA/black matched with 146 white patients). We analyzed demographic, clinical and survival differences. RESULTS: AA/black patients were diagnosed at an earlier age (9 years younger), were predominantly females, had higher rates of Medicaid/Medicare insurance and lower income compared to matched white patients (P <.001). Adjusting for age, sex, insurance type, and income bracket, AA/black patients had significantly worse overall survival (hazard ratio [HR] 2.88, 95%CI 1.21-6.85, P = .017). Association of clinical MF phenotype with survival showed that hypopigmentation was associated with survival in AA/black patients but not in white patients. Erythroderma and ulceration were associated with worse survival risk in AA/black patients. CONCLUSIONS: AA/black patients with MF/SS have a significant worse survival outcome compared to white patients. The association between clinical phenotypes and survival differed between these groups. Further studies are required to investigate whether race-specific pathogenesis or genetic factors may explain these differences.