Search Results (244)

Introduction: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a very rare subtype of cutaneous T-cell lymphoma. It is characterized by the neoplastic infiltration of subcutaneous adipose tissue. Its clinical presentation, including subcutaneous nodules, fever, and systemic symptoms, often mimics inflammatory panniculitis, making diagnosis difficult. Case Presentation: This case report describes a 14-year-old female presenting with fever, limb pain, swelling, and subcutaneous nodules, who was ultimately diagnosed with SPTCL via punch biopsy and BIOMED-2 clonality assays, confirming positive T-cell receptor-γ chain gene rearrangement. Positron emission tomography–computed tomography revealed diffuse subcutaneous involvement across multiple body regions. Methylprednisolone and cyclosporine A treatment rapidly resolved her symptoms, with laboratory parameters, including ferritin and inflammatory markers, showing significant improvement. Next-generation sequencing identified a heterozygous C9 gene mutation (c.346C>T, p.Arg116Ter), adding a novel genetic dimension to the case. Following a tapered discontinuation of immunosuppressive therapy, the patient achieved sustained remission without relapse for over 1 year. Conclusions: We report a case of adolescent SPTCL treated with immunosuppressive therapy and suggest that immunosuppressive therapy should be considered before chemotherapy in pediatric patients with SPTCL but without HLH. Full article

Whether the spongiotic reaction caused by the interaction of keratinocytes, T-lymphocytes, inflammatory dendritic epidermal cells (IDECs), and Langerhans cells (LCs) observed in atopic dermatitis (AD) represents a common feature of spongiosis in various skin diseases remains unclear. We analyzed the characteristics of spongiosis in AD compared with those in other eczematous dermatitis and inflammatory skin diseases by using immunohistochemical methods. Infiltration of IDECs (CD11c+ cells and/or CD206+ cells) and T-lymphocytes, accompanied by degenerated keratinocytes and aggregated LCs (CD207+ cells), was frequently observed as a common feature of spongiosis in multiple conditions. However, IDECs expressing IgE were identified exclusively in IgE-mediated AD. Aggregation of IDECs was predominantly observed in the spongiosis of adaptive immune-mediated eczematous disorders, such as AD and allergic contact dermatitis. These IDEC aggregations constituted the major components of the epidermal dendritic cell clusters seen in AD and other eczematous or eczematoid dermatoses, and may serve as a useful distinguishing marker from Pautrier collections seen in cutaneous T-cell lymphoma. These findings suggest that IDECs, in cooperation with other immune cells, may play a pivotal role in spongiosis formation in AD and various skin diseases, although the underlying immunopathological mechanisms differ among these conditions. Full article

In this review, we explore the complexities of objectively assessing the response to immunotherapy in mycosis fungoides (MF), a prevalent form of cutaneous T-cell lymphoma. The core challenge lies in distinguishing between reactive and malignant lymphocytes amidst treatment, particularly given the absence of uniform pathological biomarkers for MF. We highlight the vital role of emerging histological technologies, such as multispectral imaging and spatial transcriptomics, in offering a more profound insight into the tumor microenvironment (TME) and its dynamic response to immunomodulatory therapies. Drawing on parallels with melanoma—another immunogenic skin cancer—our review suggests that methodologies and insights from melanoma could be instrumental in refining the approach to MF. We specifically focus on the prognostic implications of various TME cell types, including CD8+ tumor-infiltrating lymphocytes, natural killer (NK) cells, and histiocytes, in predicting therapy responses. The review culminates in a discussion about adapting and evolving treatment response quantification strategies from melanoma research to the distinct context of MF, advocating for the implementation of novel techniques like high-throughput T-cell receptor gene rearrangement analysis. This exploration underscores the urgent need for continued innovation and standardization in evaluating responses to immunotherapies in MF, a field rapidly evolving with new therapeutic strategies. Full article

Background: Lymphomatoid papulosis (LyP) is a primary cutaneous CD30-positive T-cell lymphoproliferative disorder presenting with self-healing erythematous papulonodular lesions that may ulcerate and scar. Treatment varies by lesion extent, location, and severity. Case Report: We describe a 57-year-old man with acral LyP successfully treated with chlormethine gel (CG). The patient experienced impaired second finger mobility for over 3 months due to an ulcerated nodular mass. After 3 months of CG treatment, complete remission, symptom resolution, and full joint recovery were achieved. Six months post-treatment, the patient remained in remission. Conclusions: This case underscores the effectiveness of CG in achieving sustained remission in acral LyP, suggesting its potential as a treatment option for this rare condition. Full article

Background: Mycosis fungoides (MF), the most prevalent cutaneous T cell lymphoma, features clonal CD4⁺ T cell proliferation within a Th2-dominant microenvironment. Interleukin-4 (IL-4) promotes disease progression while Brentuximab Vedotin (BV), an anti-CD30 antibody–drug conjugate, shows efficacy but faces resistance challenges. Methods: We conducted a narrative literature review (2010–2024) synthesizing evidence on IL-4 signaling and BV’s efficacy in MF to develop a theoretical framework for combination therapy. Results: IL-4 may modulate CD30 expression and compromise BV’s effectiveness through immunosuppressive microenvironment remodeling. Theoretical mechanisms suggest that IL-4 pathway inhibition could reprogram the microenvironment toward Th1 dominance and restore BV sensitivity. However, no direct experimental evidence validates this combination, and safety concerns including potential disease acceleration require careful evaluation. Conclusions: The proposed IL-4/BV combination represents a biologically compelling but unproven hypothesis requiring systematic preclinical validation and biomarker-driven clinical trials. This framework could guide future research toward transforming treatment approaches for CD30-positive MF by targeting both malignant cells and their immunologically permissive microenvironment. Full article

Background/Objectives: We examined the in vivo effects of successive treatments with the histone deacetylase (HDAC) inhibitor romidepsin in patients with cutaneous T-cell lymphoma (CTCL), using changes in gene expression in peripheral blood mononuclear cells (PBMCs). Methods: Exploiting data from a highly responsive CTCL patient through 12 months of treatment, we identified a malignant cell predictor (MCP), a gene signature associated with the diminishing numbers of circulating malignant cells. Results: The MCP was successfully validated in the patient’s relapse sample 9 months after treatment was terminated and via an independent set of CTCL patient samples. Conclusions: The MCP set of genes contained novel CTCL markers, including membrane-associated proteins not normally expressed in lymphocytes. A subclass of those markers was also detectable in residual malignant cells undetected by flow cytometry in remission samples from a patient who relapsed 10 months later. We identified a subset of transcriptional regulators, miRNAs and methylation patterns associated with the effect of progressive treatments revealing potential mechanisms of transcriptional dysregulation and functional effects in the malignant cells. We demonstrate a role for transcriptional activator HLF, over-expressed in malignant cells, and downregulated transcriptional-suppressor and immune-modulator NFIL3, as regulators of CTCL-specific genes. Full article

Intravascular lymphoma (IVL) is a rare, aggressive subtype of non-Hodgkin lymphoma (NHL) characterized by the selective proliferation of neoplastic lymphoid cells within small and medium-sized blood vessels, most frequently of B-cell origin (IVLBCL). Its protean clinical presentation, lack of pathognomonic findings, and absence of tumor masses or lymphadenopathies often lead to diagnostic delays and poor outcomes. IVLBCL can manifest in classic, hemophagocytic syndrome-associated (HPS), or cutaneous variants, with extremely variable organ involvement including the central nervous system (CNS), skin, lungs, and endocrine system. Diagnosis requires histopathologic identification of neoplastic intravascular lymphoid cells via targeted or random tissue biopsies. Tumor cells are highly atypical and display a non-GCB B-cell phenotype, often expressing CD20, MUM1, BCL2, and MYC; molecularly, they frequently harbor mutations in MYD88 and CD79B, defining a molecular profile shared with ABC-type DLBCL of immune-privileged sites. Therapeutic approaches are based on rituximab-containing chemotherapy regimens (R-CHOP), often supplemented with CNS-directed therapy due to the disease’s marked neurotropism. Emerging strategies include autologous stem cell transplantation (ASCT) and novel immunotherapeutic approaches, potentially exploiting the frequent expression of PD-L1 by tumor cells. A distinct but related entity, intravascular NK/T-cell lymphoma (IVNKTCL), is an exceedingly rare EBV-associated lymphoma, showing unique own histologic, immunophenotypic, and molecular features and an even poorer outcome. This review provides a comprehensive overview of the current understandings about clinicopathological, molecular, and therapeutic landscape of IVL, emphasizing the need for increased clinical awareness, standardized diagnostic protocols, and individualized treatment strategies for this aggressive yet intriguing malignancy. Full article

Background/Objectives: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare and aggressive cutaneous lymphoma, often misdiagnosed due to nonspecific clinical features. Early diagnosis and treatment remain challenging. Methods: We report the case of a 31-year-old female with a chronic non-healing gluteal wound initially treated as an abscess. The lack of improvement prompted repeated investigations, culminating in the diagnosis of SPTCL with an alpha–beta T-cell phenotype. Results: Management involved combined chemotherapy and surgical wound reconstruction. Six cycles of CHOEP-21 chemotherapy led to complete clinical remission. A soft tissue defect superinfected with multidrug-resistant organisms was successfully reconstructed using Integra Dermal Regeneration Template followed by split-thickness skin grafting. Conclusions: This case highlights the diagnostic complexity of SPTCL and the therapeutic potential of dermal matrix application in complex wound management, especially in immuno-compromised patients. Full article

Anaplastic Large Cell Lymphoma (ALCL) represents a diverse group of mature T-Cell Lymphomas unified by strong CD30 expression but with different molecular and clinical subtypes. This review summarizes recent molecular advances in ALCL, highlighting key discoveries that have refined its classification, diagnosis, and therapeutic strategies. ALCL comprises four major entities: systemic ALK-positive ALCL, systemic ALK-negative ALCL, Breast Implant-Associated ALCL (BIA-ALCL), and primary cutaneous ALCL. Each subtype exhibits unique phenotypes, along with cytogenetic and molecular alterations that affect clinical outcomes. Nevertheless, different oncogenic mechanisms mediate STAT3 activation. In ALK-positive ALCL, ALK fusion proteins drive oncogenesis via constitutive activation of STAT3 and other signaling pathways. ALK-negative ALCL comprises heterogeneous genetic subtypes, in which JAK/STAT3 pathway alterations and novel gene fusions are gaining recognition as potential therapeutic targets. This review emphasizes the need for integrative molecular diagnostics to improve stratification of ALCL subtypes and targeted treatment approaches. Future research should focus on elucidating the biological mechanisms underlying these alterations and on translating molecular insights into clinical practice. Full article

Mogamulizumab is a humanized monoclonal antibody that targets C-C chemokine receptor 4 (CCR4) present on certain T cells in lymphomas and leukemias. This antibody-based therapy has demonstrated efficacy in treating various cutaneous T cell lymphomas (CTCLs), including mycosis fungoides and Sézary syndrome, through the depletion of CCR4-expressing T cells by antibody-dependent cellular cytotoxicity (ADCC). However, the precise epitope and binding mode of mogamulizumab responsible for its augmented ADCC activity remain undisclosed. Here, X-ray crystallographic studies of mogamulizumab in complex with a 28-residue N-terminal peptide indicated that SIYSNYYLYES (residues 14–24) would constitute the antibody epitope. Another high-resolution structure, using a short core peptide of these 11 residues, has elucidated unambiguous electron density for the bound peptide, confirming consistent binding for both peptides. This linear epitope is located in the membrane-proximal region of CCR4, facilitating the Fc-mediated effector functions, including ADCC. The structures also provide insights into the molecular basis for the resistance of the CCR4 L21V variant to mogamulizumab, which is due to a lack of structural complementarity with mogamulizumab binding. Understanding the structural basis for the mechanism of action of mogamulizumab is crucial for optimizing anti-CCR4 therapeutics to improve treatment outcomes for patients with these challenging diseases. Full article

This report describes two cases of solitary subcutaneous nodular lymphoid lesions in dogs. Case 1 involved a 6-year-old male Maltese and Case 2 a 5-year-old female Yorkshire Terrier. Both presented with firm, non-ulcerated dorsal subcutaneous nodules and were unresponsive to corticosteroids. Surgical excision was performed for diagnosis. Histopathology and immunohistochemistry revealed distinct patterns. Case 1 exhibited well-formed lymphoid follicles with CD20⁺/PAX5⁺ B cells and strong BCL6 but absent BCL2 expression, consistent with B-cell pseudolymphoma. Case 2 demonstrated diffuse CD3⁺ T-cell infiltrates with adipocyte rimming and minimal BCL2/BCL6 expression, diagnostic for SPTCL. Despite their similar clinical presentation, these two lesions were histopathologically and immunophenotypically distinct. These findings underscore the importance of histologic and immunophenotypic correlation in accurately distinguishing benign from malignant subcutaneous lymphoid proliferations in dogs. Full article

Non-Hodgkin lymphomas (NHLs) encompass a diverse group of neoplasms arising from the clonal proliferation of B-cell progenitors, T-cell progenitors, mature B-cells, mature T-cells, and natural killer (NK) cells. These malignancies account for over 90% of lymphoid neoplasms. The link between the gut microbiome and neoplasms has been extensively studied in recent years. Growing evidence suggests that the gut microbiome may be involved not only in the development of the disease, but also in modulating the efficacy of implemented therapies. In this review, we summarize the current knowledge on the potential involvement of the gut microbiome in the development of diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mucosa-associated lymphoid tissue (MALT) lymphoma, and NK/T-cell lymphoma, including cutaneous T-cell lymphoma (CTCL). Moreover, we discuss the relationship between gut microbiome changes before and after treatment and their association with treatment outcomes, focusing on chemotherapy and CAR T-cell therapy. Full article

Primary cutaneous lymphomas (PCLs) constitute a heterogeneous group of rare diseases. Previously, few studies have focused on the aspect of scalp involvement by PCLs. The objective of this study was to analyze the clinical presentation, diagnostic pathways, and treatment methods in patients diagnosed with scalp PCLs. A comprehensive literature review was conducted using the PubMed database, with the search terms “scalp” AND “cutaneous lymphoma”, “folliculotropic mycosis fungoides” AND “scalp”, “trichoscopy” AND “lymphoma”, and “dermoscopy” AND “scalp” AND “lymphoma.” The search was limited to articles published from database inception to May 2, 2024. Based on the title and abstract analysis, we included articles on PCLs involving the scalp. After a thorough review of the full manuscripts, several were excluded due to irrelevance, the absence of essential clinical data, discrepancies in patient age, gender, and diagnosis, and a lack of information pertinent to scalp PCLs. The literature search identified 1482 patients with scalp involvement in PCLs. Of the total number of cases, 1096 were diagnosed with B-cell PCLs, 384 with T-cell PCLs, and two cases lacked a precise PCL diagnosis. Primary cutaneous follicle center lymphoma was the most frequently reported B-cell PCL of the scalp, while mycosis fungoides was the most common T-cell PCL. Alopecia was observed in 69.0% of the patients analyzed, with the most prevalent form being non-scarring focal alopecia. It is imperative to consider the scalp in patients with PCLs, particularly in light of the knowledge that some lymphomas affecting the scalp exhibit a higher degree of aggressiveness. Full article

Background: Primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS), is a rare and aggressive form of lymphoma. Its characteristics and treatment outcomes remain poorly understood. Methods: We identified 15 patients who were diagnosed with pcPTCL-NOS between January 2014 and August 2024 at Tianjin Medical University Cancer Institute and Hospital (TMUCIH) in this retrospective study. The clinical and immunophenotypic features, treatment regimens, and outcomes of these patients were investigated. Results: All patients (4 men, 11 women; median age 54 years) presented with skin lesions, including five stage T1, four stage T2 and six stage T3 lesions. pcPTCL-NOS manifests clinically either with solitary or disseminated rapidly growing nodules/tumors and papules and, less often, ulcers. The lesion sites in patients presenting with solitary/localized tumors (stage T1 and T2) were the head and limbs, and those in patients presenting with disseminated lesions (stage T3) were the trunk, head, and limbs. The CD4/CD8 immunophenotypic characteristics were as follows: CD4+/CD8− 53.33%; CD4+/CD8+ 26.67%; CD4−/CD8− 13.33%; and CD4−/CD8+ 6.67%. One patient had a T follicular helper (TFH) phenotype. Five patients had aberrant expression of the B-cell marker CD20 by tumor cells. All patients received CHOP or CHOP-like regimens as the initial treatment, with three patients undergoing complete lesion resection before chemotherapy, seven patients receiving treatment combined with chidamide (tucidinostat), two patients receiving treatment combined with brentuximab vedotin, two patients receiving treatment combined with mitoxantrone liposomes (Lipo-Mit), three patients receiving treatment combined with radiotherapy, and two patients receiving ASCT after the first-line treatment. The OS rates at 1 year, 2 years, and 3 years were 80%, 77.8%, and 77.8%, respectively; the PFS rates were 60%, 44.4%, and 33.3%, respectively. With a median follow-up of 40 months, the median PFS was 21 months, and the median OS was not reached. Univariate analyses revealed that patients with B symptoms and the CD4−/CD8− phenotype had inferior outcomes (p < 0.05). Age, sex, tumor stage, PIT score, Ki-67 index, elevated β2-MG levels, expression of CD20 or PD1, and treatment selection were not associated with the prognosis. A trend of a survival benefit in patients with solitary (T1) tumors compared with patients with disseminated (T2, T3) tumors was observed, suggesting that it is possible to reduce the intensity of treatment in patients with T1 tumors in the future. Conclusions: pcPTCL-NOS is an aggressive but poorly characterized lymphoma that may require early and active systemic treatment. However, for patients with T1 tumors, reducing the intensity of treatment with CHOP should be appropriately considered. Full article

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most prevalent forms of cutaneous T-cell lymphoma (CTCL) and are characterized by the proliferation of CD4⁺ T-helper cells. The pathogenesis of CTCLs involves a critical interaction between neoplastic cells and the tumor microenvironment. This interaction is driven not only by cytokines but also by surface proteins that mediate cell–cell contact. One such protein, OX40 (also known as CD134), is a member of the TNF receptor superfamily and serves as an induced costimulatory molecule that facilitates the interaction between T-cells and antigen-presenting cells. In this narrative review, we explore the literature surrounding the OX40–OX40L interaction in CTCLs, highlighting its pathogenic and prognostic significance. Additionally, we compare the expression and function of OX40–OX40L in chronic inflammatory skin diseases, such as atopic dermatitis and psoriasis, with their role in CTCLs. Finally, we provide an overview of the current state of therapeutic research, discussing the potential of targeting the OX40–OX40L axis in CTCL treatment. Full article