Clinical Outcomes of COVID-19 in Mycosis Fungoides and Sezary Syndrome.

INTRODUCTION: Haemato-oncologic patients are more susceptible to severe infections with SARS-CoV-2. We aimed to assess the clinical outcomes of SARS-CoV-2 infection among patients with Mycosis Fungoides and Sezary Syndrome (MF/SS). METHODS: The data were retrieved from anonymized electronic medical records of Maccabi Healthcare Services (MHS), the second-largest healthcare organization in Israel. Patients diagnosed with MF/SS were included in the study. COVID-19 PCR test results together with sociodemographic and clinical data were extracted and analyzed to evaluate the association of COVID-19 with clinical outcomes. RESULTS: In the period of 2020-2022, 1,472 MF/SS patients were included in the study. Among them, 768 (52%) had SARS-CoV-2 infection. The hospitalization rate was 2.9% and infection by the Delta variant was associated with the highest hospitalization rate (7.7%). The hospitalization rate was lower among fully vaccinated patients (p = 0.032) but higher for patients older than 65 (p < 0.001) and patients with SS (vs. MF) (p < 0.001) or COPD (p = 0.024) diagnosis. There was a tendency for decreased hospitalization among patients treated with nirmatrelvir + ritonavir within 5 days of infection, with a 79% risk reduction, although it was not statistically significant (p = 0.164). CONCLUSION: Patients with MF/SS do not necessarily have worse COVID-19 outcomes compared to the general population.

Cutaneous T-cell lymphoma-Focus on some problems, and some solutions.

Cutaneous lymphomas are a heterogeneous group of several distinct entities of lymphoproliferative diseases. The diagnosis of a cutaneous lymphoma is a challenge, and it is always the result of a careful analysis of several information's consisting of clinical history, clinical picture, histological and molecular analyses. For this reason, experts taking care of patients with a skin lymphoma need to know all the peculiar diagnostic elements very well, in order not to run into mistakes. In this article, we will focus the discussion on some issues as the skin biopsy (when and where). In addition, we will discuss the approach to the erythrodermic patient, whose differential diagnoses include mycosis fungoides, and Sézary syndrome, beside more frequent inflammatory conditions. Finally, we will address the issue of quality of life and the possible support of the suffering patient with a cutaneous lymphoma, well knowing that the current therapeutic possibilities are unfortunately limited.

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.

Mycosis fungoides and Sézary syndrome - Review and outlook.

Mycosis fungoides and Sézary syndrome are the most important representatives of the heterogeneous group of cutaneous T-cell lymphomas. The diseases are rare and the diagnosis, which always requires a clinical-pathological correlation, is often delayed, especially in early forms of mycosis fungoides. The prognosis of mycosis fungoides depends on its stage and is usually favorable in the early stages. Clinically relevant prognostic parameters are missing and their development is the subject of current clinical research. Sézary syndrome, characterized by initial erythroderma and blood involvement, is a disease with a high mortality rate, in which good responses can now be achieved in many cases with new treatment options. The pathogenesis and immunology of the diseases is heterogeneous, with recent results pointing primarily to changes in specific signal transduction pathways that may be suitable as future treatment targets. Current therapy for mycosis fungoides and Sézary syndrome is primarily palliative with topical and systemic options either used alone or in combination. Only with allogeneic stem cell transplantation durable remissions can be achieved in selected patients. Similar to other areas of oncology, the development of new therapies for cutaneous lymphomas is currently changing from relatively untargeted empiricism to disease-specific, targeted pharmacotherapy based on knowledge from experimental research.

Development of Cutaneous T-Cell Lymphoma Following Biologic Treatment: A Systematic Review.

BACKGROUND: Cutaneous T-cell lymphoma following biologic therapy is extremely rare. OBJECTIVE: The aim of this systematic review was to investigate the development of cutaneous T-cell lymphoma (CTCL) following treatment with a biologic agent. METHODS: A systematic literature review was performed for patients who developed CTCL after exposure to biologic therapy. Works were limited to English language and excluded animal studies, guidelines, and protocols. Potentially eligible titles were identified using controlled vocabulary in tandem with key words. The search strategy was peer-reviewed prior to execution. RESULTS: Twenty-eight total studies revealed sixty-two patients who developed CTCL following exposure to a biologic agent. Of these, 44% were Caucasian, and the median age at diagnosis was 56 years. Seventy-six percent of patients received biologic therapy for a primary inflammatory skin condition. Dupilumab was the most reported (42%) agent amongst the cohort. The median time from initiation of the biologic agent to diagnosis of CTCL in these cases was 4 months (range: 0-84). Mycosis fungoides (65%) and Sézary syndrome (10%) were the most common subtypes of CTCL diagnosed. Twenty-one (34%) patients were reported to be alive with disease, outcome was not reported in 21 patients (34%), ten patients (16%) were alive and in complete remission, eight patients (13%) died of disease and two patients (3%) died due to other causes. CONCLUSION: While biologic agents may have a role in the development of CTCL, in order to definitively elucidate their role, more methodologically robust studies (such as those that utilize population databases) would need to occur.

Cutaneous T-cell lymphomas: 2023 update on diagnosis, risk-stratification, and management.

DISEASE OVERVIEW: Cutaneous T-cell lymphomas are a heterogenous group of T-cell neoplasms involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary Syndrome (SS). DIAGNOSIS: The diagnosis of MF or SS requires the integration of clinical and histopathologic data. RISK-ADAPTED THERAPY: TNMB (tumor, node, metastasis, blood) staging remains the most important prognostic factor in MF/SS and forms the basis for a "risk-adapted," multidisciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin-directed therapies is preferred, as both disease-specific and overall survival for these patients is favorable. In contrast, patients with advanced-stage disease with significant nodal, visceral or the blood involvement are generally approached with systemic therapies, including biologic-response modifiers, histone deacetylase inhibitors, or antibody-based strategies, in an escalating fashion. In highly-selected patients, allogeneic stem-cell transplantation may be considered, as this may be curative in some patients.

Sézary syndrome: Report of a rare case with perioral manifestation and review of the literature.

This report aimed to describe a rare case of Sézary syndrome (SS) diagnosed in an Oral Medicine service. A 54-year-old female presented a generalized pruritus and erythema of the skin of 2 years in duration, which had been treated with antihistamines, corticosteroids, and hydrating creams, without resolution. Extra-oral examination showed a painful lymphadenopathy on the right supraclavicular region. Ultrasound-guided fine-needle aspirationbiopsy did not detect any abnormalities. The patient's skin was remarkably dry and thickened, with erythroderma, fissures, and ulcerations. The perioral region exhibited extreme peeling and angular cheilitis. Immunophenotyping of peripheral blood revealed proliferation of undifferentiated T-cells and a massive proportion of TCD4+ cells relative to TCD8+ cells. PET/CT examination demonstrated multiple lymphadenopathies, and bone marrow biopsy was negative for neoplastic cell infiltration. A diagnosis of SS was established, and the patient is currently being treated with UVB phototherapy, methotrexate, doxepin, and folic acid, with mostly complete regression of signs and symptoms.

Clinical Presentation and Outcome Differences Between Black Patients and Patients of Other Races and Ethnicities With Mycosis Fungoides and Sézary Syndrome.

Importance: Mycosis fungoides and Sézary syndrome (MF/SS) has an increased incidence in Black patients, but clinical characteristics, treatments, and outcomes have been poorly characterized. Objective: To assess racial differences in presentation and outcome and identify drivers for racial disparities in MF/SS. Design, Setting, and Participants: A retrospective cohort analysis was conducted of 566 patients with MF/SS diagnosed from 1990 to 2020 and seen at the Winship Cancer Institute of Emory University and Grady Memorial Hospital, both in Atlanta, Georgia. Self-reported race and ethnicity were obtained from patient medical records and analyzed as 2 groups: non-Hispanic Black (Black) and all other races and ethnicities, including Asian, Hispanic, White, and unknown/undeclared (non-Black). Main Outcomes and Measures: Univariate and multivariable models and Kaplan-Meier assessments were analyzed for overall survival and time to next treatment. The primary outcome was to assess differences in overall survival by racial and ethnic group. The hypotheses were formulated prior to data collection. Results: Of the 566 patients with MF/SS identified (mean [SD] age 55 [16.4] years; 270 (47.7%) female), 257 were Black and 309 were non-Black. Black race was associated with increased rates of progression to a higher TNMB stage (39.8% in Black patients vs 29.1% in non-Black patients; P < .001) but not survival. Black patients were younger and had increased female predominance, higher TNMB stage, higher tumor stage, nodal involvement, and higher lactate dehydrogenase level compared with non-Black patients with MF/SS. Hypopigmented MF (HMF) was found in 62 patients, who were mostly Black (n = 59). Hypopigmented MF was significantly associated with survival on univariate and multivariable models, with 10-year survival of 100% in patients with HMF compared with 51.8% in patients without HMF. Black race was only associated with inferior outcomes after excluding patients with HMF who were younger than 60 years (hazard ratio [HR], 1.61; 95% CI, 1.02-2.55; P = .04), but not in patients older than 60 years (HR, 1.20; 95% CI, 0.80-1.81; P = .37). On multivariate analysis, among the cohort without HMF who were younger than 60 years, Black race remained statistically significant when controlling for cancer stage and large-cell transformation (HR, 1.27; 95% CI, 1.08-2.87; P = .43). Conclusions and Relevance: In this cohort study, Black patients with MF/SS showed distinct clinical presentations and patterns of progression with heterogeneous outcomes depending on age at presentation and presence of HMF.

"Alterations in the Skin Microbiota Are Associated With Symptom Severity in Mycosis Fungoides".

Cutaneous T cell lymphoma (CTCL), a non-Hodgkin lymphoma, is thought to arise from mature tissue-resident memory T cells. The most common subtypes include Mycosis Fungoides and Sezary Syndrome. The role of skin microbiota remains unclear in the symptom manifestation of MF. Among 39 patients with MF, we analyzed bacteria colonizing MF lesions and non-lesional skin in the contralateral side and characterized regional changes in the skin microbiota related to MF involvement using the difference in relative abundance of each genus between lesional and contralateral non-lesional skin. We investigated the relationship between these skin microbiota alterations and symptom severity. No statistically significant difference was found in bacterial diversity and richness between lesional and non-lesional skin. Different skin microbiota signatures were associated with different symptoms. More pronounced erythema in the lesions was associated with an increase in Staphylococcus. Pain and thick skin in the lesions were associated with a decrease in Propionibacterium. The results of this pilot study suggest that the skin microbiota plays an important role in changing skin phenotypes among patients with MF. Larger skin microbiota studies are needed to confirm these findings and support the use of antibiotic treatment to mitigate CTCL symptoms.

CD200 expression on Sezary cells: A valuable tool for flow cytometric assessment of peripheral blood T-cell neoplasms.

BACKGROUND: CD200 (OX-2) is a valuable marker in the diagnosis of B-cell neoplasms and is commonly used in the screening panels for assessment of peripheral blood B-cell lymphoproliferative disorders. However, there is limited understanding about CD200 expression in T-cell neoplasms. A previous study has shown that CD200 is expressed on the neoplastic cells of angioimmunoblastic T-cell lymphoma (AITL) by immunohistochemistry, but no study has evaluated CD200 expression in T-cell neoplasms by flow cytometry. METHODS: We assessed CD200 expression in peripheral blood T-cell lymphoproliferative disorders by retrospective analysis of our institutional flow cytometry screening database over a 6-year period. RESULTS: In addition to AITL, we identified CD200 expression in a significant number of mycosis fungoides/Sezary syndrome cases (58%, 19 of 33 samples), while most other T-cell neoplasms were negative for CD200. These findings were confirmed by CD200 immunohistochemical staining of tissue specimens from our patient cohort. CONCLUSIONS: CD200 is commonly expressed on circulating Sezary cells, a feature that can potentially improve the diagnostic value of flow cytometry for assessment of T-cell neoplasms.

Morphology of Mycosis Fungoides and Sézary Syndrome in Skin of Color.

Although mycosis fungoides (MF) and Sézary syndrome (SS) commonly affect Black patients, dermatologic educational resources primarily describe the appearance of these conditions in lighter skin types. Skin of color (SoC) patients with Fitzpatrick skin types (FSTs) IV to VI tend to have variable morphologies compared to the erythematous patches, plaques, or tumors in non-sun-exposed areas seen in non-SoC patients (FSTs I-III). We performed a single-institution review of clinical photographs of patients with FSTs I to VI with the primary outcome of determining the frequency of various morphologic features of MF/SS in SoC vs non-SoC patients. Providers need to be familiar with the differences in morphologic features across skin types to ensure early diagnosis and treatment.

A High Programmed Cell Death Protein 1 Hormone Receptor Score on Skin Biopsy is Associated with Sézary Syndrome Diagnosis: A Study of 91 Patients with Erythroderma.

Erythroderma is challenging to diagnose. The aim of this single-centre retrospective study was to identify factors that can be used to improve the diagnosis of erythroderma. Among 91 patients with erythroderma, 21 were diagnosed with eczema, 17 with psoriasis, 20 with drug-induced erythroderma, 13 with erythrodermic mycosis fungoides and 20 with Sézary syndrome. Nail alterations, ear involvement, and severe scaling were significantly associated with psoriasis (p = 0.044). Fever and hypereosinophilia were associated with drug-induced erythroderma. Expression of programmed cell death protein 1 was observed in all skin biopsies. However, with Sézary syndrome, programmed cell death protein 1 expression was significantly higher than with other aetiologies. A programmed cell death protein 1 hormone receptor score (H-score) >50 was associated with Sézary syndrome (p < 0.001, sensitivity 75%, specificity 92%) as well as CXCL13 expression (p < 0.044). CD7 loss was more frequent with erythrodermic mycosis fungoides and Sézary syndrome (p = 0.022). This study reports the importance of programmed cell death protein 1 expression for the differential diagnosis of Sézary syndrome and other aetiologies, including erythrodermic mycosis fungoides.

Cutaneous T-cell lymphoma: diagnosing subtypes and the challenges.

Cutaneous T-cell lymphoma is a rare type of extranodal non-Hodgkin's lymphoma that primarily affects the skin. The uncertain pathogenesis and variable clinical presentation make the diagnosis and management of cutaneous T-cell lymphoma a challenge. Cutaneous T-cell lymphoma is a chronic, relapsing illness with treatment aimed at symptomatic relief and improving patient related quality of life. Early-stage cutaneous T-cell lymphoma typically follows an indolent course, often being mistaken for benign dermatological conditions which can lead to a diagnostic delay. Advanced stage cutaneous T-cell lymphoma has a poor prognosis with significant morbidity. Accurate diagnosis and early involvement of a specialist team is paramount to ensure correct management and improved patient outcomes. Promising advances are being made to develop novel agents which could improve prognosis and quality of life. This article provides an overview of the two main subtypes of cutaneous T-cell lymphoma: mycosis fungoides and Sézary syndrome. Clinical presentation, histopathological correlation and diagnostic challenges are reviewed alongside example case studies.

Care structure of patients with mycosis fungoides and Sézary syndrome in Germany - Care research based on SHI claims data.

BACKGROUND: Cutaneous T-cell lymphomas (CTCLs) are rare forms of non-Hodgkin's lymphoma of T-cell origin that occur mainly in the skin. The most common form is mycosis fungoides (MF), but Sézary syndrome (SS), a more aggressive form of CTCL, is another relevant subgroup. Due to the rare nature of the disease, population-based studies of the epidemiology and disease burden and insights into care delivery are limited. PATIENTS AND METHODS: Based on an anonymized, age and sex-adjusted routine dataset comprising approximately five million people with statutory health insurance, a retrospective, longitudinal healthcare research study was conducted over a six-year period (2012-2017). RESULTS: In 55 % of patients with MF and SS, the initial diagnosis was documented in an outpatient setting; in 59 % of cases by a dermatologist. Immunophenotyping by flow cytometry is considered an important investigative tool for the detection and follow-up surveillance of blood involvement of cutaneous lymphomas, as the disease stage is the most important prognostic factor in MF and SS; this was performed in only 10 % of patients. The first-line treatment was topical (76 %), in particular with corticosteroids (66 %). CONCLUSIONS: The findings from this healthcare research point to the need for increased guideline-based care.

[A patient with erythroderma and pruritus: Sézary syndrome]. / Een man met jeuk en roodheid van de huid.

BACKGROUND: Erythroderma could be the first sign of a cutaneous T-cell lymphoma (CTCL), such as Sézary syndrome. Causes of erythroderma include inflammatory dermatosis, toxicoderma, paraneoplastic erytroderma, and CTCL. Hence, diagnosing Sézary syndrome can be difficult. Sézary syndrome is a rare, aggressive disease characterized by erythroderma, generalized lymphadenopathy and the presence of clonally related neoplastic T-cells in skin, peripheral blood, and lymph nodes. Treatment consists of photochemotherapy (PUVA), radiotherapy, immunomodulatory agents, low dose cytotoxic agents, and intensive chemotherapy. Immunotherapy directed against CCR4 and PD1 are new, promising developments. CASE DESCRIPTION: A 51-year-old man presented with a 1-year history of progressive, itchy erythroderma and lymphocytosis. After extensive cytomorphological, histopathological and molecular examination the diagnosis of Sézary syndrome could be established. Combination treatment of interferon and photochemotherapy (PUVA) was started. CONCLUSION: Diagnostic delay in Sézary syndrome is common. Integrated cytomorphological, immunological, and molecular evaluation of peripheral blood in patients with unexplained erythroderma non-responsive to (topical) treatment is warranted.

PD-1 improves accurate detection of Sezary cells by flow cytometry in peripheral blood in mycosis fungoides/Sezary syndrome.

BACKGROUND: Accurate Sezary cell detection in peripheral blood of mycosis fungoides/Sezary syndrome (MF/SS) patients by flow cytometry can be difficult due to overlapping immunophenotypes with normal T cells using standard markers. We assessed the utility of programmed death-1 (PD-1/CD279), a transmembrane protein expressed in some hematopoietic cells, for identification and quantitation of circulating Sezary cells among established markers using flow cytometry. METHODS: 50 MF/SS and 20 control blood samples were immunophenotyped by flow cytometry. Principal component analysis (PCA) assessed contributions of antigens to separation of abnormal from normal T cell populations. PD-1 was assessed over time in blood and bone marrow of available MF/SS cases. RESULTS: Normal CD4+ T cells showed dim/intermediate to absent PD-1 expression. PD-1 in Sezary cells was informatively brighter (≥1/3 log) than internal normal CD4+ T cells in 39/50 (78%) cases. By PCA, PD-1 ranked 3rd behind CD7 and CD26 in population separation as a whole; it ranked in the top 3 markers in 32/50 (64%) cases and 1st in 4/50 (8%) cases when individual abnormal populations were compared to total normal CD4+ T cells. PD-1 clearly separated Sezary from normal CD4+ T cells in 15/26 (58%, 30% of total) cases with few and subtle alterations of pan-T cell antigens/CD26 and was critical in 6 (12% of total), without which identification and quantification were significantly affected or nearly impossible. PD-1 remained informative in blood/bone marrow over time in most patients. CONCLUSIONS: PD-1 significantly contributes to accurate flow cytometric Sezary cell assessment in a routine Sezary panel.

[Mycosis fungoides and Sézary syndrome : a systematic review]. / Mycosis fongoïde et syndrome de Sézary : revue systématique.

The two main subtypes of primary cutaneous T-cell lymphomas include the most frequent, mycosis fungoides (MF), and the rare leukemic variant, Sézary syndrome (SS). MF presents as cutaneous patches and can progress to plaques, tumors and erythroderma. SS is characterized by the presence of erythroderma, generalized lymphadenopathy and clonal T cells in the peripheral blood, consistent with a poorer prognosis. Histologically, early CTCL lesions are sometimes indistinguishable from more common inflammatory skin diseases and a clinico-pathological correlation is essential for an accurate diagnosis. Except for allogenic stem-cell transplantation, therapy is generally palliative and aims to improve patient quality of life.

Les deux principaux sous-types de lymphomes cutanés primaires à cellules T (LCCT) sont le mycosis fongoïde (MF) et le syndrome de Sézary (SS). Le MF se présente sous forme de patchs, pouvant évoluer en plaques, en tumeurs ou en érythrodermie. Le SS, bien plus rare et de mauvais pronostic, est caractérisé par la présence d'une érythrodermie, d'adénopathies généralisées et de cellules T clonales dans le sang périphérique. Histologiquement, les lésions précoces de LCCT sont parfois impossibles à distinguer des maladies inflammatoires et une corrélation clinico-pathologique est essentielle pour un diagnostic précis. Excepté la transplantation allogénique de cellules souches hématopoïétiques, le traitement du MF/SS est généralement palliatif et vise à contrôler au mieux la maladie pour améliorer la qualité de vie du patient.