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Indian Journal of Dermatology 2023
PubMed: 38371587
DOI: 10.4103/ijd.ijd_270_23 -
Blood Advances Aug 2023Patients with relapsed/refractory (R/R) mature T- and natural killer (NK)-cell neoplasms lack effective treatments after failure of standard therapies. This phase 2...
Patients with relapsed/refractory (R/R) mature T- and natural killer (NK)-cell neoplasms lack effective treatments after failure of standard therapies. This phase 2 study evaluated the efficacy and safety of the programmed cell death protein 1 inhibitor tislelizumab in these patients. Seventy-seven patients were treated with 200 mg tislelizumab every 3 weeks. Twenty-two patients with extranodal NK-/T-cell lymphomas were enrolled in cohort 1; 44 patients with peripheral T-cell lymphoma (PTCL) were enrolled in cohort 2 (21 patients had PTCL not otherwise specified, 11 patients had angioimmunoblastic T-cell lymphoma, and 12 patients had anaplastic large-cell lymphoma). Cohort 3 comprised 11 patients with cutaneous T-cell lymphoma, of which 8 patients had mycosis fungoides (MF) and 3 had Sézary syndrome. Of the 77 patients, 76.6% had advanced-stage disease, 51.9% had refractory disease, and 49.4% received ≥3 prior systemic regimens. Promising efficacy was observed in cohort 3 (median follow-up [FU], 16.6 months; overall response rate [ORR], 45.5%; complete response [CR], 9.1%; median duration of response [DOR], 11.3 months; median progression-free survival, 16.8 months; median overall survival, not reached). Modest efficacy was observed in cohort 1 (median FU, 8.4 months; ORR, 31.8%; CR, 18.2%; median DOR, not reached) and cohort 2 (median FU, 9.3 months; ORR, 20.5%; CR, 9.1%; median DOR, 8.2 months). Most treatment-related adverse events were grade 1 or 2, and the safety profile was consistent with the known safety profile of tislelizumab. In conclusion, tislelizumab was well tolerated, achieving modest efficacy in R/R mature T- and NK-cell neoplasms, with some long-lasting remissions. This trial was registered at www.clinicaltrials.gov as #NCT03493451.
Topics: Humans; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Skin Neoplasms; Killer Cells, Natural
PubMed: 37276067
DOI: 10.1182/bloodadvances.2022009575 -
JCI Insight Oct 2023Malignant T lymphocyte proliferation in mycosis fungoides (MF) is largely restricted to the skin, implying that malignant cells are dependent on their specific cutaneous...
Malignant T lymphocyte proliferation in mycosis fungoides (MF) is largely restricted to the skin, implying that malignant cells are dependent on their specific cutaneous tumor microenvironment (TME), including interactions with non-malignant immune and stromal cells, cytokines, and other immunomodulatory factors. To explore these interactions, we performed a comprehensive transcriptome analysis of the TME in advanced-stage MF skin tumors by single-cell RNA sequencing. Our analysis identified cell-type compositions, cellular functions, and cell-to-cell interactions in the MF TME that were distinct from those from healthy skin and benign dermatoses. While patterns of gene expression were common among patient samples, high transcriptional diversity was also observed in immune and stromal cells, with dynamic interactions and crosstalk between these cells and malignant T lymphocytes. This heterogeneity mapped to processes such as cell trafficking, matrix interactions, angiogenesis, immune functions, and metabolism that affect cancer cell growth, migration, and invasion, as well as antitumor immunity. By comprehensively characterizing the transcriptomes of immune and stromal cells within the cutaneous microenvironment of individual MF tumors, we have identified patterns of dysfunction common to all tumors that represent a resource for identifying candidates with therapeutic potential as well as patient-specific heterogeneity that has important implications for personalized disease management.
Topics: Humans; Mycosis Fungoides; Skin; Skin Neoplasms; Administration, Cutaneous; Cytokines; Tumor Microenvironment
PubMed: 37669110
DOI: 10.1172/jci.insight.170015 -
The Journal of Investigative Dermatology Feb 2024Mycosis fungoides with large-cell transformation (MF-LCT) occurs in a minor proportion of aggressive lesions, which express CD30 similar to primary cutaneous anaplastic...
Mycosis fungoides with large-cell transformation (MF-LCT) occurs in a minor proportion of aggressive lesions, which express CD30 similar to primary cutaneous anaplastic large-cell lymphoma (pcALCL). We investigated the differences in spatially resolved transcriptome profiles of MF-LCT and pcALCL using CD30 morphology markers and 28 and 24 regions of interest (ROIs) in MF-LCT and pcALCL, respectively. Differentially expressed genes, pathway analysis, and immune-cell deconvolution by selective analysis of CD30-positive tumor cells and CD30-negative extratumoral areas were undertaken. In CD30-positive ROIs of MF-LCT, 190 differentially expressed genes were upregulated (29 were directly or indirectly associated with extracellular matrix remodeling), whereas 255 differentially expressed genes were downregulated, compared with those of pcALCL. Except for cornified envelope formation and keratinization, all six pathways enriched in CD30-positive ROIs of MF-LCT were associated with extracellular matrix remodeling. In CD30-positive ROIs in MF-LCT compared with those in pcALCL, immune-cell deconvolution revealed significantly increased fibroblasts and M2 macrophages (P = 0.012 and P = 0.023, respectively) but decreased M1 macrophages (P = 0.031). In CD30-negative ROIs in MF-LCT compared with those in pcALCL, memory B (P = 0.021), plasma (P = 0.023), and CD8 memory T (P = 0.001) cells significantly decreased, whereas regulatory T cells (P = 0.024) increased. Predomination of extracellular matrix remodeling pathways and immunosuppressive microenvironment in MF-LCT indicates pathophysiological differences between MF-LCT and pcALCL.
Topics: Humans; Lymphoma, Large-Cell, Anaplastic; Transcriptome; Ki-1 Antigen; Mycosis Fungoides; Skin Neoplasms; Tumor Microenvironment
PubMed: 37544586
DOI: 10.1016/j.jid.2023.05.030 -
Ophthalmology Dec 2023
Topics: Humans; Mycosis Fungoides; Skin Neoplasms
PubMed: 36925331
DOI: 10.1016/j.ophtha.2023.02.012 -
Frontiers in Immunology 2023Mycosis fungoides (MF) and Sézary syndrome (SS) are forms of cutaneous T cell lymphoma (CTCL) that pose significant challenges in their clinical management,... (Review)
Review
Mycosis fungoides (MF) and Sézary syndrome (SS) are forms of cutaneous T cell lymphoma (CTCL) that pose significant challenges in their clinical management, particularly in refractory and advanced-stage disease. With the emergence of novel therapeutic modalities however, there are increasing opportunities to exploit the current understanding of pathophysiologic mechanisms of MF/SS for treatment. This review summarizes recent advances in the treatment of MF/SS, with a focus on monoclonal antibodies, immunotherapies, and Janus kinase (JAK) inhibitors, including ongoing clinical trials.
Topics: Humans; Sezary Syndrome; Antibodies, Monoclonal; Janus Kinase Inhibitors; Skin Neoplasms; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Immunotherapy
PubMed: 38022633
DOI: 10.3389/fimmu.2023.1291259 -
Dermatologie (Heidelberg, Germany) Sep 2023Eczema encompass a wide range of dermatoses that can affect elderly patients in particular. Common differential diagnoses in elderly patients include asteatotic eczema,... (Review)
Review
Eczema encompass a wide range of dermatoses that can affect elderly patients in particular. Common differential diagnoses in elderly patients include asteatotic eczema, late-onset atopic dermatitis, allergic contact dermatitis, early phases of mycosis fungoides, eczematous and pruriginous variants of premonitory bullous pemphigoid, as well as eczematized scabies and post-scabietic eczema. Given the partly overlapping clinical presentations, accurate diagnosis plays a crucial role in the management of these conditions. Therapeutic options depend on the underlying disease and necessitate an individualized approach. This review presents relevant types of eczema in older adults together with diagnostic and therapeutic approaches. In addition to confirming the diagnosis and selecting the appropriate treatment, aspects relevant to the care of older patients should be incorporated into the tailored therapeutic approach.
Topics: Aged; Humans; Eczema; Dermatitis, Atopic; Mycosis Fungoides; Dermatitis, Allergic Contact; Scabies; Skin Neoplasms
PubMed: 37638989
DOI: 10.1007/s00105-023-05206-6 -
JAMA Dermatology Oct 2023There are limited prognostic statistics and data available on survival outcomes for patients with mycosis fungoides (MF) in Asia.
IMPORTANCE
There are limited prognostic statistics and data available on survival outcomes for patients with mycosis fungoides (MF) in Asia.
OBJECTIVE
To determine the prognostic factors and survival outcomes of patients with MF among a cohort in China.
DESIGN, SETTING, AND PARTICIPANTS
This was a retrospective cohort study of patients with MF who received treatment at a tertiary referral center for skin lymphoma (Peking University First Hospital, Beijing, China) from August 1, 2009, to August 31, 2021. Data were analyzed from September 1, 2021, to December 31, 2022.
MAIN OUTCOMES AND MEASURES
Overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS); for prognostic factors, hazard ratios (HRs), and adjusted HRs (aHRs; adjusted for sex, age, and overall TNMB [tumor, node, metastasis, blood] stage) determined using the Cox proportional hazards model.
RESULTS
The study cohort comprised 461 patients with MF (median [range] age at diagnosis, 46 [5-87] years; 275 [59.7%] men and 186 [40.3%] women; 461 [100%] Chinese). The overall 5-year rate was 82.2% for OS, 83.5% for DSS, and 79.6% for PFS. Stage-specific 5-year OS rates were 95.7% for stage IA, 93.2% for IB, 95.7% for IIA, 70.1% for IIB, 55.3% for III, and 23.6% for IV. Compared with a UK cohort, our Chinese cohort had a younger median age at diagnosis (46 years vs 54 years) and a more favorable 5-year OS (82.2% vs 75.0%); however, after adjusting for age, the discrepancy in the 5-year OS rate was diminished (77.3% vs 76.4%). Cox models revealed that unfavorable predictors of OS, PFS, and DSS, respectively, were: age older than 60 years (aHR [95% CI], 2.25 [1.28-3.96]; 2.09 [1.16-3.76]; 2.27 [1.39-3.72]); advanced TNMB stage; advanced overall stage; large-cell transformation (aHR [95% CI], 2.16 [1.17-3.99]; 2.29 [1.21-4.33]; 2.21 [1.26-3.86]); and elevated lactate dehydrogenase levels (aHR [95% CI], 3.92 [1.64-9.36]; 4.77 [1.86-12.22]; 5.05 [2.23-11.42]). Biological sex and plaque lesion type were not associated with prognosis among this study cohort.
CONCLUSION AND RELEVANCE
The findings of this retrospective cohort study of patients with MF in China suggest that Asian patients are diagnosed at a younger age and have a higher 5-year OS compared with patients of other races in studies in other countries (predominantly White). Prognostic factors were similar to those of previous studies, except for patient sex and plaque lesion type.
Topics: Male; Humans; Female; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Prognosis; Sezary Syndrome; Retrospective Studies; Neoplasm Staging; Disease Progression; Mycosis Fungoides; Skin Neoplasms; China
PubMed: 37585188
DOI: 10.1001/jamadermatol.2023.2634 -
Acta Dermato-venereologica Aug 2023Hypopigmented mycosis fungoides is a rare form of mycosis fungoides that is characterized by achromic lesions, early onset of disease, a predilection for darker skinned...
Hypopigmented mycosis fungoides is a rare form of mycosis fungoides that is characterized by achromic lesions, early onset of disease, a predilection for darker skinned populations, and a predominance of CD8+ T cells. Due to the rarity and heterogeneous presentation of hypopigmented mycosis fungoides, there are no criteria that clearly define the clinical characteristics and treatment regimens for this condition. This retrospective study of 44 paediatric patients with hypopigmented mycosis fungoides aimed to summarize their epidemiological and clinical characteristics and assess the effectiveness and safety of different treatment regimens. Clinical manifestations were further classified into 3 morphological groups: hypopigmented lesions, papules overlying hypopigmented lesions, and erythematous plaques overlying hypopigmented lesions. In addition, the results of this study suggest that interferon alpha might be an effective and well-tolerated therapy that could shorten the treatment time to complete response compared with other treatments. Maintenance therapy and long-term follow-up reduced the recurrence rate.
Topics: Humans; Child; Retrospective Studies; Mycosis Fungoides; CD8-Positive T-Lymphocytes; Patients; Skin Neoplasms
PubMed: 37606155
DOI: 10.2340/actadv.v103.6226 -
Cureus Apr 2024Primary cutaneous lymphomas, notably mycosis fungoides (MF), present diagnostic challenges in recognizing early mycosis fungoides (eMF) due to their diverse clinical and...
INTRODUCTION
Primary cutaneous lymphomas, notably mycosis fungoides (MF), present diagnostic challenges in recognizing early mycosis fungoides (eMF) due to their diverse clinical and histopathologic manifestations. The aim of our study was to use adjunctive histopathologic and immunohistochemical methods in eMF cases to make an early diagnosis and to facilitate differentiation from other dermatoses.
METHODS
This retrospective study analyzed 35 cases of eMF diagnosed at a single center. Demographic and clinicopathologic data were collected, and histopathologic features were assessed. Comparative analyses were conducted with conditions mimicking eMF, including large plaque parapsoriasis (LPP), psoriasis, and chronic dermatitis. Immunohistochemistry for T-cell markers (CD3, CD4, CD8, CD2, CD7) was performed.
RESULTS
With the scoring we applied in our study, a sensitivity of 91.43% (95% CI; 76.94% to 98.20%) and specificity of 85.71% (95% CI; 69.74% to 95.19%) for distinguishing eMF from LPP. Epidermotropism emerged as a crucial histopathologic marker, with a notable absence in most cases of cutaneous dermatitis (81.6% and 80% for CD and psoriasis, respectively) (P < 0.001). Immunohistochemistry revealed a T-helper phenotype (CD4+/CD8-) in the majority of eMF cases (78.1%), while CD4+/CD8+ and CD8+/CD4- patterns were less common (28.5% and 8.5%, respectively).
CONCLUSION
This study underscores the complexities in distinguishing eMF from inflammatory skin diseases, advocating for a comprehensive diagnostic approach.
PubMed: 38577165
DOI: 10.7759/cureus.57545