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The aim of this study was to assess the safety and efficacy of an ultrahypofractionated low-dose total skin electron beam therapy (TSEBT) regimen in patients with advanced mycosis fungoides (MF) or Sézary syndrome (SS). In this multicenter observational study from 5 German centers, 18 total patients with MF or SS underwent TSEBT with a total dose of 8 Gy in 2 fractions. The primary endpoint was the overall response rate. Fifteen of 18 patients with stage IIB-IV MF or SS were heavily pretreated with a median of 4 prior systemic therapies. The overall response rate was 88.9% (95% confidence interval [CI], 65.3-98.6), with 3 complete responses (16.9%; 95% CI, 3.6-41.4). At a median follow-up period of 13 months, the median time to next treatment (TTNT) was 12 months (95% CI, 8.2-15.8), and the median progression-free survival was 8 months (95% CI, 2-14). A significant reduction in the modified severity-weighted assessment tool, total Skindex-29 score (Bonferroni-corrected P <.005), and all subdomains (Bonferroni-corrected P <.05) was observed after TSEBT. Half of the irradiated patients (n = 9) developed grade 2 acute and subacute toxicities. One patient had confirmed grade 3 acute toxicity. Chronic grade 1 toxicity has been observed in 33% of patients. Patients with erythroderma/SS or prior radiation therapy appear at higher risk of skin toxicities. TSEBT with 8 Gy in 2 fractions achieves good disease control and symptom palliation with acceptable toxicity, greater convenience, and fewer hospital visits. [ABSTRACT FROM AUTHOR]

Cutaneous T-cell lymphoma (CTCL) is a group of non-Hodgkin lymphomas characterized by multiple erythematous patches, plaques, or even nodules on the skin. As the disease progresses, patients develop widespread pruritic skin lesions, leading to skin barrier dysfunction, which significantly impacts their quality of life, appearance, and social adaptation. The pathogenesis of CTCL is not fully understood. Recent studies have recognized the important role of skin barrier dysfunction in the development and progression of CTCL, yet a comprehensive review on this topic is lacking. This review summarizes recent findings on skin barrier dysfunction in CTCL, focusing on physical barrier dysfunction, chronic inflammation, and immune dysregulation. We also discuss current and potential therapies aimed at restoring barrier function in CTCL. By emphasizing the integration of barrier-centric approaches into CTCL management, this review provides valuable insights for improving treatment outcomes. [Display omitted] • Skin barrier dysfunction plays a critical role in the pathogenesis and progression of CTCL. • Physical barrier damage, chronic inflammation and immune dysregulation impair skin barrier in CTCL. • Barrier-centric therapies offer novel treatment options for CTCL patients. [ABSTRACT FROM AUTHOR]

The number of primary cutaneous lymphoma patients receiving low-dose radiotherapy is increasing, though controlled clinical trials defining the standard radiation dose for each specific entity have not yet been completed. Radiation oncologists are left with making highly individualized decisions that would be better enriched by additional clinical evidence. In this expert opinion, we aim to provide a clear recommendation to improve the current practice of radiation oncology. In addition, existing literature has been reviewed to develop recommendations for all types of primary cutaneous lymphoma. A prospective trial is urgently needed to identify the factors influencing patient outcomes following different radiation doses. • Reduced-dose RT is highly effective for patients with indolent types. • RT enhances the QoL in many patients with primary cutaneous lymphoma. • Radiation doses for primary cutaneous DLBCL range between 16 to 40 Gy. • There is still room for improvement in treating patients with cutaneous lymphoma. • The EORTC-CLTG provides radiotherapy dose recommendations to avoid overtreatment. [ABSTRACT FROM AUTHOR]

Lymphomatoid papulosis (LYP), the most common primary cutaneous CD30-positive lymphoproliferative disorder, is heralded by multiple papular and nodular lesions at anatomically discontiguous cutaneous sites. The histologic patterns are protean. An uncommon form of LYP is one that is anatomically confined. Cases of unilesional LYP, regional LYP, and persistent agmination of LYP were encountered in the routine and consultative practices of Weill Cornell Medicine, Division of Dermatopathology. The clinical presentation, outcomes, light microscopic findings, and phenotypic profile are reviewed. There were 10 cases of LYP presenting as solitary plaques or nodules primarily occurring in older patients and without a relevant medical history in most. Most cases occurred at an acral site with many localized to the foot; the morphology was one of a necrotizing angiocentric type E pattern and borderline type C morphology. Two of the unilesional patients in our series went on to develop mycosis fungoides, one at the initial site of unilesional type A LYP, and the other at a discontiguous site. Excluding one case, the solitary lesions underwent complete regression; after the lesions regressed, some cases had no apparent recurrence. The second anatomically confined variant of LYP in our series was regional LYP exhibiting a type E morphology in two cases and a hybrid type A and granulomatous eccrinotropic morphology in one case. There was no subsequent development of lymphoma, nor was there any spread to additional anatomic sites. The final category was persistent agmination of LYP, whereby the agminated papules of LYP were superimposed on a plaque of cutaneous T-cell lymphoma represented by mycosis fungoides in two and follicular helper T-cell lymphoma in one. In conclusion, anatomically confined LYP defines an uncommon form of LYP, but it is an important one to recognize because the histology can be worrisome despite an indolent clinical course. The clinical presentation, the infrequent association with lymphoma/leukemia, and histology are similar to conventional LYP, although there appears to be a greater tendency for complete regression without recurrence, excluding cases of persistent agmination of LYP whereby the clinical course warrants categorization as a form of cutaneous T cell lymphoma cutaneous T cell lymphoma (CTCL). [ABSTRACT FROM AUTHOR]

Anti-interferon (IFN)-γ autoantibody-positive syndrome is one of the acquired non-HIV cellular immunodeficiencies, caused by abnormalities in the IFN-γ/interleukin (IL)-12 pathways. It is often diagnosed alongside the onset of disseminated mycobacterium infection, and requires continuous antimycobacterial chemotherapy; however, the detailed pathological mechanisms underlying this syndrome, including its prognosis, are not known. To the best of our knowledge, this is the first reported case of intravascular large B-cell lymphoma complicated by anti-IFN-γ autoantibody syndrome, presented in an 82-year-old woman. The patient had been diagnosed with anti-IFN-γ autoantibody immunodeficiency ten years ago. She had repeated subacute fever of undetermined origin for 13 months that made us suspect infections, such as disseminated mycobacterium disease and other viral and fungal infections, despite receiving prophylactic antimycobacterial chemotherapy with rifampicin and clarithromycin. However, all the screenings performed showed no evidence of infectious diseases; thus, she was finally diagnosed with intravascular large B-cell lymphoma via a random skin biopsy. Unfortunately, the patient debilitated rapidly and died. Evidence supporting a correlation between anti-IFN-γ autoantibody syndrome and carcinogenesis is still lacking, although it is known that patients with anti-IFN-γ autoantibody syndrome are at risk of persistent viral infection-related and T-cell lineage-related carcinogenesis. This case demonstrated that patients with anti-IFN-γ autoantibody syndrome are also at risk of developing B-cell lymphoma, such as intravascular lymphoma. This emphasizes that caution should be paid to increased risk of developing malignancy during the long-term management of anti-IFN-γ autoantibody syndrome with cellular immunodeficiency. [ABSTRACT FROM AUTHOR]

• We report a fatal case of breakthrough infection with the SARS-CoV-2 Delta variant after the first vaccination course. • Patients with hematologic malignancies are vulnerable to COVID-19 viral infection. • Surveillance of mixed alleles could help detect unknown aggravating factors. Although messenger ribonucleic acid vaccines are substantially effective toward SARS-CoV-2 infection, patients with hematologic malignancies are still prone to the virus. Herein, we report a fatal case of breakthrough SARS-CoV-2 Delta variant infection in a patient with mucosa-associated lymphoid tissue lymphoma with remission by bendamustine-rituximab (BR) therapy completed a year ago. The serologic study revealed impaired responsiveness toward vaccines and prolonged high viral load after infection. BR therapy seemingly induced an immune escape. Prevention and treatment strategies for such vulnerable patients should be clarified immediately. [ABSTRACT FROM AUTHOR]

Sézary syndrome (SS) is a rare and aggressive T-cell lymphoma with a poor prognosis in advanced stages. Allogeneic hematopoietic cell transplantation (allo-HCT) offers a potential cure, but complications such as graft-versus-host disease (GvHD) remain a clinical challenge. Mogamulizumab, a humanized anti-CC chemokine receptor 4 (CCR4) antibody, is sometimes used as a bridge to transplantation, but its potential interactions with allo-HCT are unclear. This report describes the case of a 37-year-old man with advanced SS who received mogamulizumab therapy followed by allo-HCT from an HLA-identical sibling donor. The patient developed severe gastrointestinal acute GvHD, which was treated with steroids and infliximab. However, the condition rapidly progressed to severe intestinal symptoms and life-threatening haemorrhagic shock, ultimately resulting in the patient's death. This case highlights a potential link between mogamulizumab and severe acute GvHD promoted by drug-induced suppression of regulatory T cells. Further research is required to fully understand the interaction between mogamulizumab and allo-HCT and to determine whether it is an optimal approach as a bridge to transplant therapy. This paradigmatic case suggests the need of personalizing transplant strategies by selecting appropriate conditioning therapy and GvHD prophylaxis to minimize potential toxicity. [ABSTRACT FROM AUTHOR]

• Cutaneous T-cell lymphomas are a diverse group of malignant blood disorders characterized by initial skin infiltration. • These diseases are characterized by the plasticity and heterogeneity of the tumor cells in different tissue compartments. • Recent advancements in understanding the pathophysiology of CTCL have improved diagnostic and therapeutic strategies. Cutaneous T-cell lymphomas (CTCL) are a diverse group of malignant blood disorders characterized by initial skin infiltration, and sometimes, tumor spreading to lymph nodes, blood, and viscera. Mycosis fungoides is the most common form. Sézary syndrome is a distinctive form of CTCL marked by a significant presence of circulating tumor cells in peripheral blood. These diseases are characterized by the plasticity and heterogeneity of the tumor cells in the different tissue compartments, and a difficulty in identifying these tumor cells for diagnostic purposes and therapeutic monitoring. Progress has been made in the understanding of the pathophysiology of these diseases in recent years, and we provide here a review of these advancements. [ABSTRACT FROM AUTHOR]

Le syndrome de Sésary (SS) est une forme rare et de mauvais pronostic de lymphome T cutané (LTC) se présentant sous la forme d'une érythrodermie. Nous rapportons le cas d'une patiente présentant au diagnostic de SS, un syndrome néphrotique secondaire, consécutif à une glomérulopathie par lésions glomérulaires minimes associées à des dépôts mésangiaux d'immunoglobulines A, se manifestant sous la forme d'une anasarque. Dans les rares cas rapportés dans la littérature, l'atteinte rénale apparaît au cours de l'évolution du tableau cutané, à l'introduction du traitement immunomodulateur, ou lors de sa décroissance, sans lien de causalité établi entre le LTC et la néphropathie. Dans le cas de notre patiente, la présence de cellules de Sézary dans les urines et sur la biopsie rénale, l'apparition synchrone des deux pathologies ainsi que la résolution de la néphropathie après le traitement du LTC, supportent l'hypothèse d'une imputabilité du SS dans l'atteinte rénale. L'atteinte glomérulaire associée au syndrome de Sézary doit être connue. The Sézary syndrome (SS) is an aggressive form of cutaneous T-cell lymphoma (CTCL) requiring a rapid diagnosis due to its poor prognosis. We report the first case of an eighty-nine-year-old woman who presented with concomitant Sezary syndrome and anasarca, revealing a nephrotic syndrome caused by a minimal change nephropathy associated with immunoglobulin A (IgA) deposits. Scarce literature described rare cases associating these two entities (nephrotic syndrome and nephropathy). However, the nephrotic syndrome was delayed from disease onset, secondary to immunosuppressive treatment of SS, or due to the weaning of SS therapy. Thus, the direct link between the glomerular lesion and the cutaneous lymphoma was difficult to establish. However, the synchronous occurrence of both SS and glomerulopathy in our patient, along with Sezary cells in both urines (urinary cytology) and biopsy, and resolution of nephropathy after treatment of SS, support the likely attributability of SS in glomerulopathy. Practitioners must acknowledge the possible occurrence of glomerular involvement in SS. [ABSTRACT FROM AUTHOR]

Primary cutaneous T-cell lymphomas (CTCLs) other than mycosis fungoides (MF) and Sézary syndrome (SS) encompass a heterogenous group of non-Hodgkin lymphomas with variable clinical courses, prognoses, and management approaches. Given the morphologic and histologic overlap among the CTCL subtypes and other T-cell lymphomas with cutaneous manifestations, thorough evaluation with clinicopathologic correlation and exclusion of systemic involvement are essential prior to initiating therapy. Staging and treatment recommendations vary, depending on the subtype, clinical behavior, and treatment response. Generally, for subtypes in which staging is recommended, Ann Arbor or tumor, node, metastasis staging specific to CTCL other than MF or SS are used. For many subtypes, there is no standard treatment to date. Available recommended treatments range widely, from no active or minimal intervention with skin-directed therapy to aggressive systemic therapies that include multi-agent chemotherapy with consideration for hematopoietic stem cell transplant. Emerging targeted therapies, such as brentuximab, a chimeric antibody targeting CD30, show promise in altering the disease course of non-MF/SS CTCLs. [ABSTRACT FROM AUTHOR]

Primary cutaneous T-cell lymphomas (CTCLs) are defined as lymphomas with a T-cell phenotype that present in the skin without evidence of systemic or extracutaneous disease at initial presentation. CTCLs other than mycosis fungoides and Sézary syndrome (SS) account for approximately one third of CTCLs and encompass a heterogenous group of non-Hodgkin lymphomas, ranging from indolent lymphoproliferative disorders to aggressive malignancies with a poor prognosis. The spectrum of CTCLs continues to broaden as new provisional entities are classified. Given the morphologic and histologic overlap among CTCLs and other diagnoses, a thorough clinical history, physical evaluation, and clinicopathologic correlation are essential in the work up and diagnosis of these rare entities. This article will summarize the epidemiologic, clinical, pathologic, and diagnostic features of CTCLs other than mycosis fungoides and SS. [ABSTRACT FROM AUTHOR]

Adoptive cell therapy (ACT) is an emerging powerful cancer immunotherapy, which includes a complex process of genetic modification, stimulation and expansion. During these in vitro or ex vivo manipulation, sensitive cells are inescapability subjected to harmful external stimuli. Although a variety of cytoprotection strategies have been developed, their application on ACT remains challenging. Herein, a DNA network is constructed on cell surface by rolling circle amplification (RCA), and T cell-targeted trivalent tetrahedral DNA nanostructure is used as a rigid scaffold to achieve high-efficient and selective coating for T cells. The cytoprotective DNA network on T-cell surface makes them aggregate over time to form cell clusters, which exhibit more resistance to external stimuli and enhanced activities in human peripheral blood mononuclear cells and liver cancer organoid killing model. Overall, this work provides a novel strategy for in vitro T cell-selective protection, which has a great potential for application in ACT. T cell-selective coating and protection strategy with a flexible DNA network was formed by rolling circle amplification, which promotes T-cell aggregation and activation for anti-tumor therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Cutaneous T cell lymphomas (CTCLs) are malignancies of skin-trafficking T cells. Patients with advanced CTCL manifest immune dysfunction that predisposes to infection and suppresses the antitumor immune response. Therapies that stimulate immunity have produced superior progression-free survival compared with conventional chemotherapy, reinforcing the importance of addressing the immune deficient state in the care of patients with CTCL. Recent research has better defined the pathogenesis of these immune deficits, explaining the mechanisms of disease progression and revealing potential therapeutic targets. The features of the malignant cell in mycosis fungoides and Sézary syndrome are now significantly better understood, including the T helper 2 cell phenotype, regulatory T cell cytokine production, immune checkpoint molecule expression, chemokine receptors, and interactions with the microenvironment. The updated model of CTCL immunopathogenesis provides understanding into clinical progression and therapeutic response. [ABSTRACT FROM AUTHOR]

In the past few decades, immunotherapy has emerged as an effective therapeutic option for patients with cutaneous T cell lymphoma (CTCL). CTCL is characterized by progressive impairment of multiple arms of the immune system. Immunotherapy targets these deficits to stimulate a more robust antitumor response, thereby both clearing the malignant T cells and repairing the immune dysfunction. By potentiating rather than suppressing the immune system, immunotherapy can result in longer treatment responses than alternatives such as chemotherapy. In recent years, advances in our understanding of the pathogenesis of CTCL have led to the development of several new agents with promising efficacy profiles. The second article in this continuing medical education series describes the current immunotherapeutic options for treatment of CTCL, with a focus on how they interact with the immune system and their treatment outcomes in case studies and clinical trials. We will discuss established CTCL immunotherapies, such as interferons, photopheresis, and retinoids; emerging therapies, such as interleukin-12 and Toll-like receptor agonists; and new approaches to targeting tumor antigens and checkpoint molecules, such as mogamulizumab, anti-programmed cell death protein 1, anti-CD47, and chimeric antigen receptor T cell therapy. We also describe the principles of multimodality immunotherapy and the use of total skin electron beam therapy in such regimens. [ABSTRACT FROM AUTHOR]

In advanced-stage cutaneous T-cell lymphoma (CTCL), the current therapeutic options rarely provide long-lasting responses, leaving allogenic stem-cell transplantation the only potentially curative option for highly selected patients. Until today, there are no standardised strategies for maintenance therapy in patients with CTCL who achieved disease control. Moreover, evidence-based treatment options or drugs that are approved for maintenance treatment in advanced stages after remission induction are still lacking. Patients require maintenance options that provide a good safety profile, are convenient to apply and do not negatively affect their health-related quality of life. However, carrying out large-scale, controlled studies is challenging in CTCL. In addition to information on the concept of maintenance therapy, this review provides an update on current and emerging approaches that target maintenance treatment in advanced-stage CTCL. After all, the group of potentially interesting maintenance therapy candidates, especially for patients in advanced stage, includes not only immunomodulating and phototherapeutic modalities that have been used already for many decades but also newer systemic therapies, including epigenetic modifiers. • Short therapeutic response rate with chemotherapy is limited to a few months. • Maintenance therapy must be selected, effective, available, and well tolerated. • Treatment in advanced MF, SS between USA/non USA did not influencing survival outcome. • Besides classical end-points SD, PR, CR, HRQol the length of TTNT is of relevance. [ABSTRACT FROM AUTHOR]

• Patients with early stage (Stage IA-IB) mycosis fungoides (MF) report poor quality of life on Skindex-29 questionnaire. • Regardless of the extent of skin involvement or the type of treatment received, early stage MF patients reported comparable scores on Skindex-29. • Patients with no active disease scored significantly higher on questions pertaining to anger and fatigue. • Early stage MF patients with minimal or no skin involvement can still be significantly impacted by poor quality of life. • There is a need to develop quality of life surveys that fully encompass common concerns of MF patients. Questionnaire tools are increasingly being used to assess health related quality of life (HRQOL) in mycosis fungoides (MF) patients. However, a thorough understanding of the factors that lead to poor HRQoL in early stage disease and their distribution across patient subgroups is lacking. To characterize factors affecting HRQoL as assessed by Skindex-29 in subgroups of patients with early stage MF seen at a multidisciplinary cutaneous lymphoma clinic. Skindex-29, a multidimensional survey that evaluates HRQoL (emotions, symptoms, function), was distributed to early stage MF patients. Overall and component scores were analyzed in three groups: no evidence of disease (NED), active disease with limited early stage (AD-T1), and active disease with more extensive early stage (AD-T2). Scores were also compared among patients receiving different treatment modalities. 56 patients (9 NED, 36 AD-T1, and 11 AD-T2) were enrolled in the study. Overall Skindex-29 scores and scores for individual dimensions were comparable among the three sub-groups. Similarly, these scores did not significantly differ among treatment groups or after removal of patients with previous staging higher than IB. Analysis of individual questions revealed that NED patients reported higher scores for questions pertaining to anger and fatigue. Early stage MF patients enrolled in this study had high overall Skindex-29 scores. Surprisingly, Skindex-29 scores of NED patients were comparable to those of patients with active disease, T1 and T2, mostly due to anger and fatigue. Even when skin involvement is minimal or absent, MF patients continue to report impaired HRQoL. [ABSTRACT FROM AUTHOR]

La peau est l'organe le plus fréquemment atteint par la maladie des emboles de cristaux de cholestérol (MECC) qui peut parfois se manifester initialement uniquement par des symptômes dermatologiques. Nous rapportons l'observation d'une MECC associée à une érythrodermie à l'origine d'un diagnostic erroné de syndrome d'hypersensibilité médicamenteuse (HM). Une femme de 66 ans présentait une érythrodermie à la suite de l'introduction d'allopurinol quelques mois plus tôt. On notait une dégradation récente de la fonction rénale avec une créatininémie à 523 μmol/L et une hyperéosinophilie (HE) à 5666/mm3. Les critères n'étaient finalement pas suffisants pour retenir le diagnostic d'HM. En examinant les anciennes numérations il était constaté une HE fluctuante remontant à plus de 10 mois avant l'introduction d'allopurinol. La biopsie rénale permettait de diagnostiquer une MECC. Nous rapportons une présentation évocatrice d'une HM dans une MECC, dont les symptômes cliniques sont liés à l'HE et non pas aux emboles. Clinical presentation of cholesterol crystal embolism (CCE) can be dermatologic when cholesterol crystals become lodged in small cutaneous arteries resulting in ischemia. We report a case of CCE with erythroderma misleading to a diagnostic of drug reaction with eosinophilia and systemic symptoms (DRESS). A 66 year-old woman presented with erythroderma few months after initiation of allopurinol. Acute renal failure was present with elevation in plasma creatinine concentration (523 μmol/L) and hypereosinophilia (HE) (5666/mm3). Finally, the REGISCAR score helped to rule out DRESS diagnostic. Past blood-count tests were analyzed revealing chronic HE present before allopurinol initiation. Renal biopsy identified CCE. This case is the first to report a DRESS like presentation of CCE. Clinical findings are secondary to HE and not to occlusion of cutaneous arteries. [ABSTRACT FROM AUTHOR]