Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare subset of diffuse large B-cell lymphoma (DLBCL) exhibiting genetic features shared with LBCL of immune-privileged sites (notably the MYD88L265P mutation) and enriched in tumor associated macrophages (TAM) expressing M2 markers. Using a unique PCDLBCL-LT cell line (ARSI cell line) developed in our institute, we sought to mechanistically decipher the interplay between lymphoma cells and macrophages. We demonstrate that ARSI cells induce phenotypic, transcriptional and functional changes in macrophages obtained from primary monocytes and THP-1 cell line. These changes do not require cell-cell contact, and proteome analysis of ARSI secretome reveals high concentration of several cytokines and chemokines known to affect macrophages, including IL-10. We then demonstrate that IL-10/IL-10RA interaction blockade inhibits macrophage polarization induced by tumor cells. These findings are reproduced when macrophages are co-cultured with PCDLBCL-LT cells from different patient-derived xenografts. However, among 4 other DLBCL cell lines only the MYD88-mutated OCI-Ly3 cell line exhibits similar effects, which highlights the variability of macrophage interplays and led us to hypothesize that macrophage shaping, beyond the cutaneous localization, may rely on specific genetics of tumor cells. Finally, we reveal that macrophages enhance tumor cell proliferation and promote resistance to doxorubicin in co-culture. In conclusion, these results confirm the robustness of this model to study lymphoma cell and macrophage interplays, underline the critical role of IL-10 in lymphoma microenvironment modeling, and may contribute to better define its specificities in an era of rising microenvironment-targeted therapies.

Primary cutaneous lymphomas (CLs), comprising cutaneous T-cell lymphomas (CTCLs) and cutaneous B-cell lymphomas (CBCLs), are rare non-Hodgkin lymphomas with distinct epidemiological characteristics. How the incidence rates of CLs changed over the past decade has not been well documented. To assess changes in overall and subtype-specific CLs incidence rates in the US by sex, age and ethnic group. This study analyzed 13,126 CL cases diagnosed between 2010 and 2021 using data from the Surveillance, Epidemiology, and End Results Program. Age-adjusted incidence rates (IRs), five-year relative survival, and annual percent change were calculated. The overall CLs IR was 11.9 per 1,000,000 person-years, with 8.8 for CTCLs and 3.1 for CBCLs. Among CTCL subtypes, Mycosis fungoides had the highest IR of 5.2, whereas within CBCLs, primary cutaneous marginal zone lymphoma exhibited the highest IR of 1.4. Between 2014 and 2021, the incidence of CTCLs and CBCLs declined annually by 2.8% and 4.9%, respectively. In males, incidence rates for CTCLs and CBCLs decreased by 3.5% and 4.8% per year over the same period. Among individuals aged 60 years and older, CTCL incidence declined by 1.9% per year, while CBCL incidence decreased by 3.6% annually from 2010 to 2021. Five-year relative survival was 89.3% for CTCLs and 91.5% for CBCLs. The incidence of CLs has exhibited distinct patterns of decline among different population groups over the past decade. The continued disparities in both incidence and survival underscore the need for targeted research and interventions to mitigate demographic inequalities.

Integrated histomolecular approach to discriminate primary cutaneous follicle centre and marginal zone lymphoma of the scalp.

Rheumatologists and other nondermatologists often encounter patients with psoriatic arthritis (PsA) who present with cutaneous diseases that mimic psoriasis (PsO). Cutaneous disorders including tinea, seborrheic dermatitis, eczema, pityriasis rubra pilaris, syphilis, or cutaneous lymphoma are commonly mistaken for PsO. It is crucial for rheumatologists and other nondermatologists to recognize alternative conditions and to consider referral to dermatology when skin disease is not responding to therapy. Correct diagnosis is important when assessing disease severity in clinical practice as well. Although the Psoriasis Area and Severity Index (PASI) and the Dermatology Life Quality Index (DLQI) are gold standards for physician- and patient-reported outcomes in clinical trials, they are not practical to deploy in busy clinical practice. Use of a physician global assessment (PGA), body surface area using a handprint method, and informal patient-reported outcomes can be useful in documenting the burden of disease. A treat-to-target approach using a PGA of clear/almost clear is ideal. At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2024 annual meeting, a 2-part workshop was conducted for rheumatologists to first review skin disorders commonly mistaken for PsO, and second, to review outcome measures best suited for clinical practice.

396 Spatially dissecting the role of macrophages in cutaneous lymphoma

413 Primary cutaneous follicle center lymphoma spans yet unrecognised subtypes including polyclonal reactions

Surgical treatment of facial single primary cutaneous marginal zone B-cell lymphoma: A case report

Primary cutaneous T-cell lymphomas (CTCLs) are rare extranodal non-Hodgkin lymphomas, especially in children. Diagnosing CTCL in pediatric patients is challenging due to its clinical resemblance to inflammatory dermatoses and infections. We report a 15-year-old girl who presented with multiple erythematous to violaceous papulonodular, non-pruritic lesions over the face, abdomen, and extremities for 6 months, preceded by low-grade fever. The initial clinical impression was sarcoidosis. Hematological examination revealed microcytic hypochromic anemia. Fine needle aspiration cytology of the cutaneous lesion showed atypical lymphoid proliferation. Histopathology revealed a non-epidermotropic, folliculocentric, deep dermal infiltrate of atypical lymphoid cells. Immunohistochemistry showed CD45+, CD3+, CD5+, CD4−, CD8−, CD20−, CD30−, confirming primary CTCL of double-negative (CD4/CD8) phenotype. Primary CTCL in childhood is extremely rare and often misdiagnosed. High clinical suspicion and integration of histopathology with immunophenotyping are essential. Reporting such cases contributes to understanding their varied presentation and aids early diagnosis.

The diagnostics of B-cell cutaneous lymphomas is difficult because of its clinical manifestations’ nonspecificity. Since 2015 dermoscopy has been used as an additional method for diagnostics of B-cell cutaneous lymphomas. Dermoscopy is an inexpensive, non-invasive, painless diagnostic method that allows to quickly get additional information about the disease. Currently known dermatoscopic signs in conjunction with anamnestic and clinical data may indicate a diagnosis of B-cell cutaneous lymphoma. Capabilities of dermatoscopy in the diagnosis of B-cell cutaneous lymphomas are demonstrated in this article. However, dermatoscopy cannot replace histological and immunohistochemical examinations of skin which are the “gold standard” necessary for diagnosis of B-cell cutaneous lymphoma. The molecular genetic research using PCR-method is necessary in some cases of primary cutaneous marginal zone lymphoma with rich T-cells microenvironment.

Accurate blood staging in mycosis fungoides (MF)/Sézary syndrome (SS) is essential for precise diagnosis, prognostication, and effective management. Through 3 illustrative cases, we highlight the complexity of blood staging of MF/SS caused by expanded CD4-positive T-cell large granular lymphocyte (T-LGL) populations that mimic malignant involvement and complicate accurate disease assessment. We identified 3 patients with MF/SS and more than 250/µL of CD4-positive, CD7-negative and/or CD4-positive, CD26-negative T cells in blood but with discordant T-cell receptor profiles between blood and skin samples. We also analyzed 100 consecutive T-cell blood flow cytometry panels ordered for patients evaluated in our cutaneous lymphoma clinic to determine the frequency of such populations. Each case demonstrated expanded CD4-positive T-LGL populations in the blood characterized by at least partial CD8, CD56, and CD57 expression and absent or decreased CD26 and/or CD7 expression. Blood from these patients exhibited distinct clonotypes from skin lesions, suggesting a reactive rather than malignant origin. Analysis of 100 consecutive cutaneous lymphoma staging blood flow cytometry cases identified similar CD4-positive, CD57-positive T cells of 250/μL or more in 3 of 100 cases, plus 1 atypical case of SS with partial, dim CD57 expression. The presence of expanded T-LGL populations in blood can confound accurate staging of MF/SS, potentially leading to misclassification and ineffective or unnecessary treatment. These cases exemplify how comprehensive molecular and immunophenotypic profiling, including multicolor flow cytometry and T-cell receptor comparisons, along with morphologic evaluation of blood ensure accurate disease assessment to inform better clinical decision-making in MF/SS.

Canine epitheliotropic cutaneous T-cell lymphoma (ECTCL) is a malignant neoplasm exhibiting various skin lesions. Metastasis to the lymph nodes and distant organs contributes to the poor prognosis of ECTCL; however, the underlying molecular mechanisms remain unclear. In the present study, the roles of chemokine receptors, such as CC chemokine receptor (CCR) 4 and CCR7, in the migration of tumor cells were examined using a canine cutaneous lymphoma model. Three mouse groups were prepared and xenografted with wild-type (WT), CCR4 knockout (KO), or CCR7KO canine ECTCL (EO-1) cells. The proportion of EO-1 cells in tissues and blood was significantly lower in the CCR4KO and CCR7KO groups than in the WT group. Only the iliac lymph node, a sentinel lymph node for the xenograft site, was enlarged with the infiltration of EO-1 cells in all groups. The size of the iliac lymph node was smaller in the KO groups than in the WT group. All mice developed a subcutaneous nodule at the xenograft site, which was smaller in the KO groups. In the cell proliferation assay, chemokine ligands stimulated an increase in EO-1 cells in the WT group, but not in the KO groups. These results suggest that CCR4 or CCR7 plays a vital role in the initial migration to sentinel lymph nodes and proliferation in a canine cutaneous lymphoma model.

BackgroundBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy originating from precursors of plasmacytoid dendritic cells. This study aimed to understand the relationship between malignant clones in different tissues and determine new biomarkers to improve the management of BPDCN.MethodsWe conducted a comprehensive analysis by integrating single-cell transcriptomic data from bone marrow (BM)-derived cells, peripheral blood mononuclear cells (PBMCs), and skin-derived cells from one BPDCN patient and matched healthy controls (HCs). Validation was performed in two independent cohorts consisting of 12 BPDCN patients and control groups, including common skin tumors, cutaneous lymphomas, inflammatory skin diseases and HCs.ResultsOur study revealed that malignant cells in the skin exhibited greater maturity and differentiation compared with those from BMs, suggesting that the BM is a more likely origin for BPDCN. Additionally, malignant cells across different tissues in the BPDCN patient displayed significant transcriptional heterogeneity. The multiplex immunohistochemistry (mIHC) analysis revealed that the expression of PLD4 was significantly elevated in the dermis of BPDCN patients compared with the control groups. Furthermore, most PLD4-positive cells were found to co-localize with CD123 in BPDCN skin lesions.ConclusionsThis study suggested a potential clonal origin of tumor cells, and revealed the transcriptional heterogeneity among malignant cells across different tissues in BPDCN. PLD4 was identified as a specific marker of malignant cells, aiding in the diagnosis of BPDCN and showing potential as a therapeutic target.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12935-025-04038-9.

Since the publication of the Japanese guidelines for the management of cutaneous lymphomas in 2020, the WHO classification of hematolymphoid neoplasms has been updated, and a number of novel systemic drugs for cutaneous T-cell lymphoma have been approved in Japan. In 2025, we revised the Japanese guidelines for the management of cutaneous lymphomas in consideration of recent advances in our understanding of the pathophysiology and classification of cutaneous lymphomas, together with the update in treatment strategies reflecting the advent of novel drugs. This revision was also conducted under the Japanese Dermatological Association's commission, incorporating expert reviews and public comments. In addition to a brief explanation of the epidemiology, diagnosis, staging system, prognosis, and management of the different types of cutaneous lymphomas, we herein provide recommendations for 12 clinical questions (CQs) regarding treatment options that may vary even among experts. A systematic review process and the selection of recommendations to individual CQs were conducted in accordance with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) scheme by a multidisciplinary expert panel consisting of dermatologists, hematologists, and a radiation oncologist. In these guidelines, we present outlines of the revised Japanese guidelines for the management of cutaneous lymphomas.

Implementation of a patient-reported outcome assessment during radiotherapy for mycosis fungoides and other cutaneous lymphomas

A new prognostic index (CLIPI) stratifies risk in advanced cutaneous lymphomas: Associations with treatment pathways, quality of life and survival

Outcomes of primary cutaneous anaplastic large cell lymphoma across u.S. cancer care settings: A national cancer database analysis.

Determinants of survival in primary cutaneous anaplastic large cell lymphoma (pcALCL): Analysis of a real-world pooled database

Lymphoma are the most frequent secondary hematologic malignancies following solid tumors: A large cohort study from the german cancer registry nrw

Pharmacologic activators of immunoproteasomes unmask actionable public and private neoantigens in multiple myeloma patients

AI-based diagnosis of cutaneous lymphoma and lymphoproliferative disorders via H&E morphology and LLM-assisted cohort curation