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Cells Aug 2020Sézary syndrome (SS), an aggressive cutaneous T-cell lymphoma (CTCL) with poor prognosis, is characterized by the clinical hallmarks of circulating malignant T cells,... (Review)
Review
Sézary syndrome (SS), an aggressive cutaneous T-cell lymphoma (CTCL) with poor prognosis, is characterized by the clinical hallmarks of circulating malignant T cells, erythroderma and lymphadenopathy. However, highly variable clinical skin manifestations and similarities with benign mimickers can lead to significant diagnostic delay and inappropriate therapy that can lead to disease progression and mortality. SS has been the focus of numerous transcriptomic-profiling studies to identify sensitive and specific diagnostic and prognostic biomarkers. Benign inflammatory disease controls (e.g., psoriasis, atopic dermatitis) have served to identify chronic inflammatory phenotypes in gene expression profiles, but provide limited insight into the lymphoproliferative and oncogenic roles of abnormal gene expression in SS. This perspective was recently clarified by a transcriptome meta-analysis comparing SS and lymphocytic-variant hypereosinophilic syndrome, a benign yet often clonal T-cell lymphoproliferation, with clinical features similar to SS. Here we review the rationale for selecting lymphocytic-variant hypereosinophilic syndrome (L-HES) as a disease control for SS, and discuss differentially expressed genes that may distinguish benign from malignant lymphoproliferative phenotypes, including additional context from prior gene expression studies to improve understanding of genes important in SS.
Topics: Biomarkers; Gene Expression; Humans; Hypereosinophilic Syndrome; Sezary Syndrome
PubMed: 32872487
DOI: 10.3390/cells9091992 -
Blood Advances Mar 2022Sezary syndrome (SS) is a rare leukemic form of cutaneous T-cell lymphoma. Diagnosis mainly depends on flow cytometry, but results are not specific enough to be...
Sezary syndrome (SS) is a rare leukemic form of cutaneous T-cell lymphoma. Diagnosis mainly depends on flow cytometry, but results are not specific enough to be unequivocal. The difficulty in defining a single marker that could characterize Sezary cells may be the consequence of different pathological subtypes. In this study, we used multivariate flow cytometry analyses. We chose to investigate the expression of classical CD3, CD4, CD7, and CD26 and the new association of 2 markers CD158k and PD-1. We performed lymphocyte computational phenotypic analyses during diagnosis and follow-up of patients with SS to define new SS classes and improve the sensitivity of the diagnosis and the follow-up flow cytometry method. Three classes of SS, defined by different immunophenotypic profiles, CD158k+ SS, CD158k-PD-1+ SS, CD158k and PD-1 double-negative SS, showed different CD8+ and B-cell environments. Such a study could help to diagnose and define biological markers of susceptibility/resistance to treatment, including immunotherapy.
Topics: Biomarkers, Tumor; Humans; Programmed Cell Death 1 Receptor; Receptors, KIR2DL2; Receptors, KIR3DL2; Sezary Syndrome; Skin Neoplasms
PubMed: 34570200
DOI: 10.1182/bloodadvances.2021005147 -
Turkish Journal of Haematology :... Mar 2018Transformed mycosis fungoides (T-MF) is a rare variant of MF with an aggressive course. In this study, we aimed to describe characteristics of MF/Sezary syndrome (SS)...
OBJECTIVE
Transformed mycosis fungoides (T-MF) is a rare variant of MF with an aggressive course. In this study, we aimed to describe characteristics of MF/Sezary syndrome (SS) patients with transformation.
MATERIALS AND METHODS
Patients diagnosed with T-MF among MF/SS patients between 2000 and 2014 in a tertiary single center were evaluated retrospectively. Demographic data, clinical data, laboratory data, immunophenotype features, response to treatment, survival, and histopathologic features were analyzed.
RESULTS
Among 254 MF patients, 25 patients with T-MF were identified (10.2%) and included in the study. The male-to-female ratio was 2.6/1. The median time between MF diagnosis and transformation was 32 months (range: 0-192). Nine (36%) patients were diagnosed initially with T-MF. Advanced disease stage and high serum lactate dehydrogenase (LDH) levels were indicators of poor prognosis and treatment response. Five of the 18 patients with progressive disease had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT resulted in complete remission in three (60%) patients. Ten (40%) patients died as a result of disease progression. Mean survival time was 25.2±14.9 (2-56) months after transformation.
CONCLUSION
Advanced stage, high serum LDH levels, and loss of CD26 and CD7 expression in the peripheral blood are poor rognostic factors in T-MF. Treatment-resistant tumors and nodules should be cautionary for T-MF. Patients with T-MF have a shortened survival. Some patients may respond to first-line treatments. However, the majority of patients who do not respond to first-line therapies also are unresponsive to second or third-line therapies. Allo-HSCT may be an alternative option in patients with T-MF.
Topics: Adult; Aged; Biomarkers; Combined Modality Therapy; Female; Humans; Immunophenotyping; Kaplan-Meier Estimate; Male; Middle Aged; Mycosis Fungoides; Neoplasm Staging; Prognosis; Retrospective Studies; Risk Factors; Sezary Syndrome; Skin; Skin Neoplasms
PubMed: 28533196
DOI: 10.4274/tjh.2016.0502 -
Best Practice & Research. Clinical... Sep 2019Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of cutaneous lymphoma, accounting for approximately 60% of cutaneous T-cell lymphomas.... (Review)
Review
Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of cutaneous lymphoma, accounting for approximately 60% of cutaneous T-cell lymphomas. Diagnosis requires correlation of clinical, histologic, and molecular features. A multitude of factors have been linked to the aetiopathogenesis, however, none have been definitively proven. Erythrodermic MF (E-MF) and SS share overlapping clinical features, such as erythroderma, but are differentiated on the degree of malignant blood involvement. While related, they are considered to be two distinct entities originating from different memory T cell subsets. Differential expression of PD-1 and KIR3DL2 may represent a tool for distinguishing MF and SS, as well as a means of monitoring treatment response. Treatment of E-MF/SS is guided by disease burden, patients' ages and comorbidities, and effect on quality of life. Current treatment options include biologic, targeted, immunologic, and investigational therapies that can provide long term response with minimal side effects. Currently, allogeneic stem cell transplantation is the only potential curative treatment.
Topics: Humans; Immunologic Memory; Mycosis Fungoides; Neoplasm Proteins; Programmed Cell Death 1 Receptor; Receptors, KIR3DL2; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes
PubMed: 31585624
DOI: 10.1016/j.beha.2019.06.004 -
International Journal of Molecular... Jan 2022Sézary syndrome is an aggressive leukemic variant of cutaneous T-cell lymphomas, characterized by erythroderma, lymphadenopathy, and peripheral blood involvement by... (Review)
Review
Sézary syndrome is an aggressive leukemic variant of cutaneous T-cell lymphomas, characterized by erythroderma, lymphadenopathy, and peripheral blood involvement by CD4+ malignant T-cells. The pathogenesis of Sézary syndrome is not fully understood. However, the course of the disease is strongly influenced by the tumor microenvironment, which is altered by a combination of cytokines, chemokines, and growth factors. The crosstalk between malignant and reactive cells affects the immunologic response against tumor cells causing immune dysregulation. This review focuses on the interaction of malignant Sézary cells and the tumor microenvironment.
Topics: CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Humans; Sezary Syndrome; Skin Neoplasms; Tumor Microenvironment
PubMed: 35055124
DOI: 10.3390/ijms23020936 -
Cells Oct 2021Mycosis fungoides (MF) and Sezary Syndrome (SS) are the most common cutaneous T-cell lymphomas. It has been hypothesized that the interaction between the immune system,... (Review)
Review
BACKGROUND
Mycosis fungoides (MF) and Sezary Syndrome (SS) are the most common cutaneous T-cell lymphomas. It has been hypothesized that the interaction between the immune system, cutaneous cells, and neoplastic elements may play a role in MF/SS pathogenesis and progression.
METHODS
This paper aims to revise in a narrative way our current knowledge of the microenvironment's role in MF/SS.
RESULTS AND CONCLUSIONS
Literature data support a possible implication of microenvironment cells in MF/SS pathogenesis and progression, opening up new therapeutic avenues.
Topics: Animals; Disease Progression; Humans; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms; Tumor Microenvironment
PubMed: 34685762
DOI: 10.3390/cells10102780 -
Journal of the European Academy of... Aug 2019Limited information exists regarding survival of Asian patients with mycosis fungoides (MF) and Sézary syndrome (SS). (Review)
Review
BACKGROUND
Limited information exists regarding survival of Asian patients with mycosis fungoides (MF) and Sézary syndrome (SS).
OBJECTIVE
To evaluate the epidemiology, outcome and prognostic factors of these patients.
METHODS
A retrospective review of MF/SS cases diagnosed from 2000 to 2011 at a tertiary referral dermatology centre in Singapore was performed.
RESULTS
Of 246 patients, 63% were male and the median age at diagnosis was 49 years. 73.2% were Chinese, 12.6% Indian, 6.9% Malay and 7.3% Caucasian. A total of 239 patients (97.2%) had MF and seven had SS. Median follow-up duration was 6.3 years, and median duration of symptoms at diagnosis was 13 months. For patients with MF, the majority had early disease (92.8% stage IA-IIA). 3.8% were stage IIB, 1.7% stage III and 1.7% stage IV. Complete response to treatment occurred in 78.2%, partial response in 9.6%, persistent but non-progressive disease in 10.0% and disease progression in 4.1% of patients. Large cell transformation occurred in 4.1% of patients. Mean overall survival during this study was 12.7 years, with death occurring in 2.5% of patients (all ≥stage IIB at diagnosis). For patients with SS, 71.4% presented with stage IVA disease, 28.6% stage IVB. Complete response to treatment occurred in 14.2%, persistent but non-progressive disease in 28.6% and disease progression in 57.2% of patients. Mean overall survival was 3.3 years within this study, with death occurring in 42.9% of SS patients. Prognostic factors associated with favourable recurrence-free survival were male gender (P = 0.008), early disease stage (T1) at diagnosis (P < 0.001) and absence of maintenance treatment after remission (P = 0.01).
CONCLUSION
Compared to Caucasian and East Asian cohorts, MF in South-East Asians was diagnosed at a younger age and associated with lower mortality, largely due to greater prevalence of hypopigmented MF.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asian People; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Mycosis Fungoides; Prognosis; Retrospective Studies; Sezary Syndrome; Young Adult
PubMed: 30801779
DOI: 10.1111/jdv.15526 -
Seminars in Cutaneous Medicine and... Mar 2018Sézary syndrome (SS) is a rare subtype of cutaneous T-cell lymphoma marked by erythroderma, circulating neoplastic T cells, and poor prognosis. Its low incidence has... (Review)
Review
Sézary syndrome (SS) is a rare subtype of cutaneous T-cell lymphoma marked by erythroderma, circulating neoplastic T cells, and poor prognosis. Its low incidence has made the study of its etiology, immunologic/molecular pathways, and effective treatments difficult. Because histopathology may be nonspecific in SS, microscopic findings must be correlated with the clinical presentation and the results of blood evaluation in order to make the diagnosis. Treatments that preserve, rather than compromise, the immune system are preferred.
Topics: Humans; Sezary Syndrome; Skin Neoplasms
PubMed: 29719016
DOI: 10.12788/j.sder.2018.005 -
BMC Health Services Research Feb 2021Information about health care use and costs of cutaneous T-cell lymphoma (CTCL) patients is limited, particularly in a European setting.
BACKGROUND
Information about health care use and costs of cutaneous T-cell lymphoma (CTCL) patients is limited, particularly in a European setting.
METHODS
In this population-wide study we set out to investigate prevalence, and trends in health care use in two CTCL subtypes, mycosis fungoides (MF) and Sézary syndrome (SS) over a time period of 19 years in 1998-2016 by using a nation-wide patient register containing data on all diagnosed MF and SS cases in Finland.
RESULTS
The prevalence of diagnosed MF and SS rose from 2.04 to 5.38/100000, and from 0.16 to 0.36/100000 for MF and SS respectively during 1998-2016. We found a substantial decrease in inpatient treatment of MF/SS in the past two decades with a mean of 2 inpatient days/patient/year due to MF/SS in 2016, while the mean numbers of MF/SS related outpatient visits remained stable at 8 visits/year/patient. Most MF/SS-related outpatient visits occurred in the medical specialty of dermatology. In a ten-year follow-up after MF/SS diagnosis, the main causes for outpatient visits and inpatient stays were MF/SS itself, other cancers, and other skin conditions. Also cardiovascular disease and infections contributed to the number of inpatient days. Mean total hospital costs decreased from 11,600 eur/patient/year to 3600 eur/patient/year by year 4 of the follow-up, and remained at that level for the remainder of the 10-year follow-up. MF/SS accounted for approximately half of the hospital costs of these patients throughout the follow-up.
CONCLUSIONS
The nearly 3-fold increase in prevalence of diagnosed MF/SS during 1998-2016 puts pressure on the health care system, as this is a high-cost patient group with a heavy burden of comorbidities. The challenge can be in part answered by shifting the treatment of MF/SS to a more outpatient-based practice, and by adapting new pharmacotherapy, as has been done in Finland.
Topics: Delivery of Health Care; Finland; Humans; Mycosis Fungoides; Prevalence; Sezary Syndrome; Skin Neoplasms
PubMed: 33618714
DOI: 10.1186/s12913-021-06109-9 -
The Journal of Dermatology Feb 2022Mycosis fungoides (MF) and Sézary syndrome (SS) are representative cutaneous lymphomas. In their early stage, a small number of tumor cells and a large number of... (Review)
Review
Mycosis fungoides (MF) and Sézary syndrome (SS) are representative cutaneous lymphomas. In their early stage, a small number of tumor cells and a large number of non-malignant cells form a Th1-dominant tumor microenvironment. Increase in malignant T cells is accompanied by a decrease in CD8-positive T cells, with a shift toward a Th2-dominant milieu in advanced-stage lesions. The etiologies of MF/SS are diverse, and the underlying pathogenetic mechanisms are yet to be elucidated. Advanced MF/SS is known to be highly sensitive to Staphylococcus aureus, and the majority of deaths are caused by severe infections. The susceptibility to infection is associated with barrier dysfunction and immunosuppression, which are the main symptoms of MF. In recent years, skin-colonizing S. aureus has been identified to not only cause severe infections but also play an important role in the pathogenesis of MF/SS. Staphylococcal superantigens activate the proliferation of tumor cells and induce CD25 upregulation, FOXP3 expression, IL-17 expression, and miR-155 expression. Alpha-toxin eliminates non-neoplastic CD4-positive cells and CD8-positive cells and plays a major role in tumor cell selection. Lipoprotein may also be associated with the induction of Th2-dominant milieu. Antibiotic therapy for S. aureus eradication has been reported to cause considerable clinical improvement in the majority of individuals with advanced cutaneous T-cell lymphoma. Therefore, S. aureus may be a novel target for the treatment of advanced-stage MF/SS in the future.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms; Staphylococcus aureus; Tumor Microenvironment
PubMed: 34927279
DOI: 10.1111/1346-8138.16288