An 81-year-old man presented with a 4-week nonhealing plaque on the right lower leg following minor trauma. Despite wound care and systemic antibiotics, the lesion persisted and progressed. Histopathological evaluation of a punch biopsy led to a rare and unexpected diagnosis.

BACKGROUND:Primary cutaneous lymphomas (PCLs) are uncommon in children, with mycosis fungoides (MF), lymphomatoid papulosis (LyP), and primary cutaneous small/medium CD4+ T-cell lymphoproliferative disorder (PCSM-TCLPD) representing the most frequent entities. Due to their rarity, available data derive mainly from case reports and small series, and diagnostic delays are frequent. This study aimed to describe the clinical, histopathological, and therapeutic features of pediatric PCLs in a single Italian referral centre and compare them with the literature evidence. METHODS:We conducted a single-center, retrospective observational study including patients aged ≤16 years with a histologically confirmed diagnosis of PCLs, followed for at least six months at the Dermatology Unit of the University Hospital of Bologna between 2002 and 2024. Clinical, histological, therapeutic, and follow-up data were collected and analyzed. RESULTS:Among 354 PCL patients, 10 pediatric cases were identified: six MF, three LyP, and one PCSM-TCLPD. The mean age at diagnosis was 9.1 years. MF cases were mostly early-stage (IA, 5/6), with folliculotropic (67%), hypopigmented (50%), and classic (50%) variants; all were treated with topical corticosteroids and/or PUVA, with good long-term outcomes (67% complete remission). LyP patients presented at younger ages (mean 5.7 years) with type A (N.=2) and D (N.=1) subtypes; all achieved complete remission despite recurrences, one requiring methotrexate. The single PCSM-TCLPD case was cured with surgical excision. After a mean follow-up of 8.2 years, all patients were alive, most disease-free. CONCLUSIONS:Pediatric PCLs are rare but generally indolent, with an excellent prognosis. However, their clinical heterogeneity and diagnostic delay highlight the importance of early biopsy, integrated clinicopathological assessment, and long-term follow-up. Multicenter studies are needed to establish tailored treatment algorithms for children.

ABSTRACT Background Juvenile mycosis fungoides (JMF) is a rare cutaneous T‐cell lymphoma with onset in childhood or adolescence. Diagnosis is often delayed due to clinical resemblance to benign dermatoses. Compared to adult‐onset disease, JMF may exhibit distinct clinicopathological and immunophenotypic features. Management typically relies on skin‐directed therapies, though paediatric‐specific treatment guidelines are lacking. Objectives To characterise the clinical, histopathological, and immunophenotypic features of JMF, evaluate treatment responses, and assess long‐term outcomes in an Italian multicenter cohort. Methods We conducted a retrospective observational study involving five tertiary dermatology centres in Italy. Patients with biopsy‐confirmed MF and disease onset ≤ 20 years were included. Clinical, histological, immunophenotypic, treatment and follow‐up data were collected. Patients were stratified by age at onset (< 14 vs. ≥ 14 years) for subgroup analysis. Results Twenty‐nine patients were included (median age at onset: 12 years). Twenty‐nine patients were included (median age at onset: 12 years). The most common clinical variants were classic erythematous MF (41%) and hypopigmented MF (28%), the latter associated with longer diagnostic delay. A CD8⁺‐predominant phenotype was found in 52% of evaluable cases. A personal or familial atopic diathesis was reported in 44% of patients, including a personal history of atopic dermatitis in 31%, which was significantly more frequent in children under 14 years (p = 0.027). Most patients presented with stage IA disease (79%) and received skin‐directed therapies. The overall response rate to first‐line treatment was 90% (59% complete remission, 31% partial remission), with no cases of progression. At final follow‐up (median 8.1 years), patients with disease onset before 14 years were more likely to be disease‐free (65% vs. 22%, p = 0.044). Conclusions JMF typically presents with early‐stage disease and responds well to skin‐directed therapy. Hypopigmented variants and CD8⁺ immunophenotype are frequent. A younger age at onset may predict better long‐term disease control.

INTRODUCTION:Bruton's tyrosine kinase inhibitors (BTKi) have transformed the management of B-cell malignancies by selectively targeting signaling pathways essential for malignant B-cell survival, thereby reducing the systemic toxicity of conventional chemotherapy. However, with their expanding use, cutaneous adverse events are increasingly recognized as clinically relevant complications that may affect quality of life and treatment adherence. AREAS COVERED:This review provides an updated overview of first- and second-generation BTKi, including ibrutinib, acalabrutinib, zanubrutinib, and pirtobrutinib, with a specific focus on dermatologic toxicities. A comprehensive literature search was conducted using PubMed, Embase, and Scopus, covering publications up to February 2025. Clinical studies, case series, and case reports describing skin-related adverse events associated with BTKi therapy were reviewed. EXPERT OPINION:Cutaneous toxicities related to BTKi are often underrecognized but clinically significant, ranging from xerosis and bruising to lichenoid eruptions and vasculitis. First-generation agents, particularly ibrutinib, are associated with a broader spectrum of dermatologic adverse events, whereas newer BTKi show improved selectivity and potentially reduced skin toxicity. Early recognition, standardized dermatologic evaluation, and proactive multidisciplinary management are essential to minimize patient discomfort, preserve quality of life, and prevent unnecessary treatment discontinuation.

Abstract Lymphocyte activation gene 3 (LAG-3; CD223) is an inhibitory immune checkpoint receptor that regulates T-cell activation and contributes to immune tolerance. In cancer, LAG-3 is frequently coexpressed with programmed cell death protein-1 (PD-1) on exhausted tumour-infiltrating lymphocytes, and its blockade has emerged as a promising immunotherapeutic strategy. Cutaneous T-cell lymphomas (CTCLs), including mycosis fungoides (MF) and Sézary syndrome (SS), are characterized by profound immune dysregulation, T-cell exhaustion and tumour microenvironment-­driven immune escape, providing a strong rationale for checkpoint-based therapies. However, clinical responses to PD-1 inhibition in CTCL remain limited, prompting interest in alternative or complementary targets such as LAG-3. This review summarizes current evidence on the expression, regulation and functional role of LAG-3 in CTCL. Available data indicate that LAG-3 expression is heterogeneous and highly context dependent. In MF, LAG-3 is detectable on subsets of CD4+ and CD8+ tumour-infiltrating lymphocytes and regulatory T cells, where it may contribute to local immunosuppression within skin lesions. In contrast, SS is characterized by systemic downregulation of LAG-3 in peripheral blood T cells, despite upregulation of other inhibitory receptors, highlighting distinct compartment-specific immune landscapes. Genetic studies further suggest that germline LAG-3 variants may influence MF susceptibility by modulating tissue-resident memory T-cell function. Overall, LAG-3 does not appear to be a dominant checkpoint in CTCL but rather a modulatory component of a complex, multicellular exhaustion network shaped by microenvironmental cues. Its inducible expression in defined contexts supports the potential for patient-stratified and combinatorial immunotherapeutic approaches. Future mechanistic and protein-level studies are needed to clarify the therapeutic relevance of LAG-3 targeting in CTCL.

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive haematological malignancy commonly involving the skin. Haematopoietic stem cell transplantation (HSCT) is the only potentially curative treatment, yet the prognostic relevance of skin-limited disease and disease status at HSCT remains unclear. We aimed to evaluate the association between HSCT and survival in BPDCN, and to assess whether disease status at transplantation provides prognostically relevant information. We performed a retrospective multicentre cohort study across 10 European tertiary centres. Patients diagnosed with BPDCN from 2008 onward were included. Overall survival was analysed using Kaplan–Meier methods and Cox regression, with HSCT modelled as a time-­dependent covariate to account for immortal time bias. Post-transplant survival was assessed according to disease status at HSCT. Forty-seven patients were included (median age 60 years, 74% male), of whom 26 (55%) underwent HSCT. In time-­dependent Cox analysis, HSCT was strongly associated with improved overall survival (adjusted hazard ratio 0.17, 95% confidence interval 0.05–0.55; P = 0.003). Among transplanted patients, those transplanted in complete remission or with skin-limited residual disease tended to have better post-transplant outcomes than those with active systemic disease. In this pan-European real-world cohort, HSCT was associated with improved survival in BPDCN when analysed using a time-dependent approach. Disease status at the time of transplantation, rather than initial disease presentation, appears to provide clinically relevant prognostic information and supports the importance of achieving deep remission before HSCT whenever feasible.

Wound edge assessment is a key component of chronic wound evaluation, but it remains highly subjective and affected by inter-observer variability, particularly when performed on two-dimensional clinical photographs. We retrospectively analysed 1 860 wound images acquired during routine clinical practice and independently annotated by four expert clinicians. An automated image-analysis pipeline was used to segment the wound, standardise the peri-wound border region, and estimate the three-dimensional profile of the wound edge. We first tested whether geometry-derived edge profiles alone could reproduce clinical wound edge categories. We then evaluated whether adding global visual descriptors of wound shape, colour appearance, and surface pattern improved agreement with clinicians. Inter-clinician agreement was low, confirming the intrinsic subjectivity of wound edge classification. Geometry-based analysis identified coherent edge-profile patterns but showed poor correspondence with clinical annotations. In contrast, a supervised classifier incorporating both geometric and visual features achieved agreement comparable to, and in some comparisons higher than, the agreement observed among clinicians. Clinical wound edge assessment is not driven by edge geometry alone. Visual cues such as wound shape, colour appearance, and surface pattern appear to influence expert classification and may contribute to variability. Automated image-based analysis may support more reproducible wound edge assessment, provided that it is externally validated in diverse clinical settings.

BACKGROUND:Brentuximab vedotin (BV) is a targeted therapy for CD30-expressing lymphomas, including Hodgkin lymphoma (HL) and cutaneous T-cell lymphoma (CTCL). While peripheral neuropathy is the most common adverse event, BV-induced skin rashes are less frequent and not well characterized. PATIENTS AND METHODS:This study analyzed the clinical and histologic features of BV-induced skin rashes over the past 5 years, focusing on patterns and severity across lymphoma types. We retrospectively reviewed cases from the Dermatology and Hematology Departments at Bologna and Ancona Universities, and we identified 20 eligible patients (13 males, 7 females, median age 59 years) with a Naranjo score ≥ 5. Six had CTCL, and 14 had systemic lymphoma. RESULTS:Rashes appeared after a median of 3.5 BV cycles, presenting as eczematous (n = 11 patients), maculopapular (n = 3), or lichenoid (n = 6). Histology showed cytotoxic lichenoid infiltrates in lichenoid cases and spongiotic dermatitis in eczematous ones. CTCL patients experienced more severe reactions (50 % grade ≥ 3) compared to systemic lymphoma patients (36.3 %). BV was discontinued in 10 cases, while others continued with dose adjustments and corticosteroids. CONCLUSIONS:Lichenoid reactions were more common in CTCL, possibly due to BV's effects on the tumor microenvironment. Recognizing rash patterns may optimize care and minimize unnecessary treatment interruptions.

Cutaneous involvement in multiple myeloma is rare and may present as nodules mimicking other lymphoid neoplasms. It typically occurs late in the course of the disease and is associated with an aggressive clinical course and poor prognosis.

Mycosis fungoides (MF) and Sezary syndrome (SS) are the most prevalent cutaneous T-cell lymphomas, classified separately in the 2022 WHO Classification due to their distinct features. Despite advances, the mechanisms underlying disease progression—from early patch and plaque lesions to advanced tumor stages—remain incompletely understood. Chemokines and their receptors play crucial roles in the migration and survival of malignant T cells, influencing tissue invasion, immune evasion, and dissemination. This review highlights the altered expression of chemokine receptors like CCR4, CCR7, CCR8, CCR10, CXCR3, and CXCR4 in MF/SS and their contribution to disease evolution. It also explores the transition from a Th1 to a Th2 immune profile, linked to tumor progression. The dual role of chemokines in physiology and pathology is examined, with emphasis on their therapeutic potential in CTCL.

This retrospective case series compares vitiligo resulting from immune checkpoint inhibitor (ICI) therapy vs preexisting vitiligo among patients receiving ICI treatment for cancer.

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.