Search Results (79)

Background and Objectives: Mycosis fungoides (MF) is the predominant subtype of cutaneous T-cell lymphoma, whereas large plaque parapsoriasis (LPP) closely resembles early-stage MF, making differential diagnosis challenging. Immune markers, such as CD47, CD163, and B7-H3, play crucial roles in tumor immune evasion and macrophage polarization. However, their expression profiles and potential diagnostic or prognostic implications in early-stage MF and LPP remain poorly defined. Therefore, this study aimed to evaluate the expression of CD47, CD163, and B7-H3 in early-stage MF and LPP and analyze their associations with clinicopathological characteristics and patient outcomes. Materials and Methods: This retrospective study evaluated the immunohistochemical expression of CD47, CD163, and B7-H3 in 46 patients with early-stage mycosis fungoides (MF) and 46 patients with large plaque parapsoriasis (LPP). Expression levels were assessed using an immunoreactivity scoring system and analyzed for their associations with clinical parameters and disease-free survival (DFS). The study included patients diagnosed and followed at Sivas Cumhuriyet University between 1 March 2015 and 31 March 2025. Results: High CD47 expression was detected in 72.7% of MF patients, high B7-H3 expression in 45.7%, and high CD163 expression in 46.7% compared with LPP patients (p < 0.001). These markers showed positive correlations, and elevated expression, especially of B7-H3 and CD163, was associated with shorter disease-free survival in univariate analysis. Conclusions: The higher expression of CD47, CD163, and B7-H3 in early-stage MF compared with LPP suggests that these markers may contribute to the differential diagnosis and could represent potential therapeutic targets; however, their independent prognostic value requires confirmation in larger studies. Full article

CD19-directed chimeric antigen receptor (CAR) T-cell therapies have been instrumental in improving outcomes of refractory or relapsed B-cell malignancies. However, there have been safety concerns due to recent reports of second primary malignancies (SPMs) related to CAR T-cell therapies. We reviewed articles from Embase, PubMed, and Cochrane Library records and included SPM case reports as well as cohort studies. Across published cohorts, secondary cutaneous or peripheral T-cell lymphoma (PTCL) after diffuse large B-cell lymphomas (DLBCLs) have been reported at low incidence (generally in the low single-digit percentage range). While CAR T-cell therapy is associated with these rare secondary malignancies and lineage-switch events primarily described in acute leukemia, they are clinically significant and have resulted in increased surveillance. The currently available evidence suggests that most secondary malignancies after CAR T-cell therapy are due to background risk and prior treatment exposures rather than direct CAR T-cell therapy induced oncogenesis. However, rare CAR T-cell therapy-associated second primary T-cell malignancies have been reported. To properly define incidence, mechanisms, and risk factors for CAR T-cell therapy-associated malignancies, continued prospective registry follow-up and additional research will be needed. Full article

Primary cutaneous lymphomas (PCLs) are a heterogeneous group of extranodal T- and B-cell neoplasms confined to the skin at diagnosis, characterised by distinct biological drivers, clinical behaviour, and therapeutic challenges compared with systemic lymphomas. Over the past decade, advances in genomic profiling, single-cell and spatial transcriptomics, and tumour microenvironment analysis have substantially refined the understanding of PCL pathogenesis, highlighting immune evasion, clonal heterogeneity, and compartment-specific disease dynamics as key determinants of outcome and treatment response. These insights have coincided with a rapidly evolving therapeutic landscape that includes immunomodulatory agents, targeted therapies, and ADCs, while also exposing persistent limitations related to diagnostic delay, response heterogeneity, resistance, and lack of validated predictive biomarkers. In this review, we provide a dermatology-focused synthesis of primary cutaneous lymphomas, integrating contemporary classification and clinicopathologic features with molecular pathogenesis and tumour microenvironmental insights of direct clinical relevance. We discuss current diagnostic and staging approaches, critically appraise established and emerging therapeutic strategies in cutaneous T- and B-cell lymphomas, and highlight unresolved clinical challenges and unmet needs, including biomarker integration, longitudinal disease monitoring, and translation of molecular advances into routine practice. Full article

Background: Primary cutaneous B-cell lymphomas (CBCLs) are a rare and heterogeneous group of lymphomas, among which the anaplastic variant of diffuse large B-cell lymphoma (A-DLBCL) represents an exceptionally rare entity. Although they typically present as painless and non-ulcerated skin lesions, rare variants may exhibit atypical clinical features. Pyoderma gangrenosum (PG) is a rare inflammatory ulcerative disease that may overlap clinically with other ulcerative dermatoses and pose diagnostic challenges due to the absence of standardized differential algorithms. Methods: An 85-year-old male presented with multiple rapidly progressive, painful, ulcerative lesions, initially misdiagnosed as PG and treated with oral cyclosporine with no clinical response. Skin biopsy specimens underwent detailed histopathological and immunohistochemical evaluation. Results: The analyses revealed dense infiltration of atypical large lymphoid cells, with CD20, CD45, and CD30 positivity, and a Ki-67 proliferation index of approximately 90%, consistent with primary cutaneous A-DLBCL. Owing to the delayed correct diagnosis, the patient’s condition deteriorated rapidly, leading to his death before appropriate therapy could be initiated. Conclusions: The case documents an exceptionally rare cutaneous presentation of A-DLBCL, expanding the extremely limited literature on this enigmatic entity. Furthermore, it underscores the fundamental role of early skin biopsy in the differential diagnosis of non-specific ulcerative lesions, which is critical for ensuring appropriate treatment administration within the therapeutic window in cases of malignancy. Full article

Immune checkpoint proteins including PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT regulate T-cell functions, which are essential for anti-tumor immunity. Over-expression of these immune checkpoint proteins leads to T-cell exhaustion and a significant impairment of anti-tumor immunity. Rejuvenation of effector T-cell function with immune checkpoint inhibitors (ICI) restores anti-tumor immunity, which translates into clinical efficacy in the frontline and salvage treatment of various hematological malignancies. Efficacy of ICIs is highest in classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, and NK/T-cell lymphomas, and modest in immune-privileged-site lymphomas and cutaneous T-cell lymphoma. However, in myeloid malignancies and multiple myeloma, the efficacy of ICIs remains doubtful. In addition to being used as single agents, ICIs have also been combined with other ICIs; as well as chemotherapy, antibody drug conjugates, and epigenetic agents (histone deacetylase inhibitors and hypomethylating agents). More innovative strategies include the use of ICIs in the context of allogeneic haematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapy. This review synthesizes current evidence for the use of ICI in different haematological malignancies, and highlights future directions toward biomarker-driven, rationally designed therapeutic combinations. Full article

Cutaneous lymphomas are a heterogeneous group of extranodal non-Hodgkin lymphomas with distinct clinical and biological features, broadly classified into cutaneous T-cell lymphomas (CTCL) and cutaneous B-cell lymphomas (CBCL). With improved survival due to early detection and therapeutic advances, the emergence of second primary malignancies (SPMs) has become a clinical concern. SPMs, defined as new, distinct malignant neoplasms arising synchronously or metachronously with the index cancer, can significantly impair prognosis and quality of life. In this narrative review, we meticulously examine the current literature, to synthesize evidence on SPMs’ incidence and risk factors in patients with primary cutaneous lymphomas. Evidence from population-based and institutional studies consistently demonstrates elevated risks of hematologic and solid tumors in CTCL. By contrast, data on CBCL remain limited, though recent population-based analyses suggest increased risks of certain hematologic malignancies and solid tumors. We further propose development mechanisms for SPMs, including treatment-related mutagenesis, shared genetic susceptibilities, chronic antigenic stimulation, and immune dysregulation. Lastly, we highlight the clinical implications of these findings, underscoring the need for vigilant surveillance, patient education, and tailored screening strategies. Future research should prioritize large-scale, prospective, and molecularly integrated studies to refine risk stratification and guide personalized survivorship care of this vulnerable population. Full article

Immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 antibodies, have significantly improved outcomes in a variety of solid tumors, including urothelial carcinoma. However, their use is frequently associated with immune-related adverse events (irAEs) which frequently affect the skin and mucous membranes. Among these, plasma-cell-rich infiltrates are exceptionally rare. Circumorificial plasmacytosis (COP) is a rare, predominantly reactive condition typically involving mucosal transition zones, with histologic features characterized by dense, polyclonal plasma cell infiltrates and a benign clinical course. Only two case reports have described COP in association with ICI therapy and, to date, transformation or overlap with lymphoproliferative disorders such as marginal zone lymphoma has not been documented. We report the case of an 86-year-old male with urothelial carcinoma who developed a progressive, ulcerated, bleeding lesion of the lower lip during adjuvant nivolumab therapy. Histologic examination revealed a dense subepithelial infiltrate of mature plasma cells and lymphocytes. Direct and indirect immunofluorescence studies were negative, excluding autoimmune blistering disorders. Immunohistochemistry showed a predominance of CD138-positive plasma cells with a moderate kappa light-chain shift, CD19 expression, and absence of CD56, Cyclin-D1, and CD117, arguing against a plasma cell neoplasm. Molecular analysis via multiplex PCR revealed a clonal B-cell population with distinct IgH rearrangements, and some EBV-positive cells were also identified by EBER in situ hybridization. The histopathologic and molecular findings suggested a marginal zone lymphoma-like, plasmacytic proliferation arising in the setting of COP. This case illustrates a rare and diagnostically challenging constellation at the intersection of reactive and clonal B-cell proliferations in the context of ICI therapy. Although the lesion demonstrated features of clonality, the overall low B-cell content, indolent clinical course, and lack of systemic involvement support a reactive, immunodeficiency-associated lymphoproliferation rather than overt lymphoma. This case expands the known spectrum of mucocutaneous irAEs and highlights the need for careful clinicopathologic correlation, including immunophenotyping and molecular diagnostics. Awareness of such rare presentations is essential to avoid overdiagnosis and unnecessary systemic treatment in patients with otherwise indolent lesions. Full article

Primary cutaneous lymphomas (PCLs), including cutaneous T-cell lymphomas (CTCL) and primary cutaneous B-cell lymphomas (PCBCL), are a diverse group of non-Hodgkin lymphomas that primarily affect the skin. Radiotherapy (RT) plays a pivotal role in the treatment of these lymphomas, particularly for localized disease, due to its ability to deliver precise, skin-directed treatment. Mycosis fungoides (MF) and Sézary syndrome (SS), the most common subtypes of CTCL, often require skin-directed therapies such as electron beam therapy and superficial brachytherapy to manage localized lesions. Electron beam therapy, including total skin electron beam therapy (TSEBT), has been utilized for decades, offering high response rates but with the risk of cumulative skin toxicity. Recently, low-dose radiotherapy (LDRT) has gained attention as an effective alternative that reduces toxicity while maintaining durable responses. Superficial brachytherapy is another modality that delivers radiation through custom molds, allowing for homogeneous dosing over complex anatomical areas like the face. Both teleradiotherapy and brachytherapy have demonstrated high complete response rates, with low recurrence rates observed when higher doses are used. In the context of primary cutaneous B-cell lymphomas, such as primary cutaneous marginal zone lymphoma (PCMZL) and primary cutaneous follicle center lymphoma (PCFCL), radiotherapy also offers excellent local control, particularly for indolent subtypes. However, more aggressive subtypes, such as diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), may require systemic therapies in addition to radiation. Overall, teleradiotherapy and brachytherapy are essential components of the therapeutic arsenal for primary cutaneous lymphomas, offering effective disease control with manageable toxicity, while ongoing research focuses on optimizing treatment strategies and exploring novel combinations with systemic therapies. Full article

Introduction: X-linked agammaglobulinemia (XLA) is a prototypical inborn error of immunity (IEI) caused by mutations in the BTK gene, leading to a profound deficiency of mature B cells and severe pan-hypogammaglobulinemia. The Epstein-Barr virus (EBV), which primarily infects B lymphocytes, is believed to be unable to establish persistence in these patients due to the lack of its natural reservoir. Indeed, current evidence supports that EBV infection is typically refractory in individuals with XLA. Methods: We describe the clinical and molecular characterization of a 10-year-old male patient with genetically confirmed XLA who developed EBV viremia, hemophagocytic lymphohistiocytosis (HLH), and EBV-positive cutaneous T cell lymphoma. Diagnosis was supported by flow cytometry, serology, quantitative PCR, EBER in situ hybridization, histopathology, and whole-exome sequencing. Results: Despite the complete absence of peripheral B cells, EBV was detected in leukocytes and multiple tissues, indicating active infection. The patient developed HLH and a T cell lymphoma with EBER-positive infiltrates. Genetic analysis revealed a nonsense mutation in BTK (1558C>T, R520*), confirming XLA. The clinical course included multiple episodes of neutropenia, viral and bacterial infections, and severe systemic inflammation. Conclusions: This is the first documented case of an XLA patient with confirmed BTK mutation presenting with clinical features more consistent with chronic active EBV infection. These findings challenge the prevailing paradigm that XLA confers protection against EBV-related diseases and further support the possibility of EBV noncanonical reservoirs leading to immune dysregulation. EBV should also be considered in the differential diagnosis of XLA patients presenting with systemic inflammation or lymphoproliferative disease. 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

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

Background/Objectives: Primary cutaneous lymphomas (CLs) are a group of skin-limited lymphoproliferative disorders, including cutaneous T-cell (CTCLs) and B-cell lymphomas (CBCLs). Photodynamic therapy (PDT), a non-invasive, light-activated treatment, has gained attention as a skin-directed therapy for early-stage CLs due to its selectivity and favorable safety profile. This systematic review evaluates the current evidence on the clinical use of PDT in managing CLs. Methods: A systematic literature search was conducted in PubMed, Scopus, and Embase through 1 September 2024 following PRISMA guidelines. Search terms included “primary cutaneous skin lymphoma”, “CTCL”, “CBCL”, “mycosis fungoides”, “lymphomatoid papulosis”, and “photodynamic therapy”. After screening 1033 records, 30 studies were included. Data were extracted and categorized by lymphoma subtype and clinical outcomes. Results: Of the included studies, 23 focused on mycosis fungoides (MF), 5 on lymphomatoid papulosis (LyP), and 2 on CBCL. PDT demonstrated notable clinical efficacy in early-stage and localized disease, particularly MF, using methyl aminolevulinate (MAL) or 5-aminolevulinic acid (5-ALA) as photosensitizers. Adjunctive techniques like microneedling and laser-assisted delivery improved treatment outcomes. PDT was generally well tolerated, with mild, transient side effects; rare complications such as localized neuropathy were reported. Conclusions: PDT is a promising, non-invasive treatment for early-stage CLs, especially MF and indolent CBCL variants. While current evidence supports its safety and effectiveness, further comparative and prospective studies are needed to refine protocols, evaluate long-term efficacy, and compare different photosensitizers. Full article