Search Results (123)

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

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: Extranodal NK-/T-cell lymphoma (ENKTCL) is a rare and highly aggressive lymphoma with a bad prognosis. The aim of our analysis is to evaluate existing research on the potential usefulness of fluorine-18-fluorodeoxyglucose positron emission tomography or positron/computed tomography (2-[18F]FDG PET or PET/CT) in the management of patients with ENKTCL. Methods: A complete search of the literature was conducted across Scopus, PubMed/MEDLINE, and Embase databases, focusing on articles published up to March 2025. Results: A total of 21 studies that investigated the role of 2-[18F]FDG PET or PET/CT in ENKTCL were included in our analysis. The main findings from the literature analysis were (1) 2-[18F]FDG PET/CT seems to be helpful in staging settings, showing a better diagnostic performance than conventional imaging and a positive impact on clinical stage; (2) 2-[18F]FDG PET/CT had excellent negative predictive value for detecting bone marrow involvement, especially in early-stage disease; and (3) qualitative and semiquantitative PET parameters might predict prognosis. Conclusions: Despite several limitations affecting this analysis, especially related to the heterogeneity of the studies included, 2-[18F]FDG PET/CT seems to be a useful tool for the evaluation of ENKTCL. Full article

Nasal-type extranodal natural killer/T-cell lymphoma (ENKTL) is a rare, aggressive non-Hodgkin lymphoma associated with the Epstein–Barr virus (EBV). It predominantly affects middle-aged men and is most common in East Asia and Latin America. Due to its nonspecific symptoms, including nasal obstruction and discharge, ENKTL is frequently misdiagnosed as chronic rhinosinusitis or fungal infection, leading to delays in diagnosis and treatment. This case report presents a 46-year-old Algerian male with persistent nasal obstruction, foul-smelling nasal discharge, and progressive midfacial destruction. Multiple biopsies initially suggested chronic rhinosinusitis with fungal infection, delaying the definitive diagnosis. Subsequent deep biopsies confirmed ENKTL through histopathological and immunohistochemical analysis. ENKTL is characterized by its locally invasive nature, leading to necrotizing lesions and midfacial destruction. Histopathological confirmation through multiple well-targeted biopsies is crucial to prevent misdiagnosis. However, the prognosis remains poor, with a 5-year survival rate ranging from 20% to 65%. 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

Disease eponyms can be confusing, difficult to remember, scientifically non-robust, and lacking in implications on and relationships with cell lineage, histogenesis, and pathogenesis. This review is geared toward revisiting hematolymphoid diseases with eponyms in light of recent advances in technology and science by searching the past fifty years of the literature using Scopus and Google Scholar with the keywords “eponyms, hematolymphoid, diseases, lymphoma, benign, malignant, lymph node, spleen, liver, bone marrow, leukemia”. With advances in science and technology, there is accumulation of information on the morphologic nuances and immunologic, immunophenotypic, and genetic features of various hematolymphoid eponymic diseases, thus shedding light on important issues of etiology and pathogenesis with implications on therapy in various non-neoplastic (Castleman, Evans syndrome Kikuchi–Fujimoto, IgG4-related diseases) and neoplastic (Hodgkin, Burkitt, NK/T-cell lymphomas, dendritic/histiocytic neoplasms, and Sezary syndrome) diseases. This contributes to modern nomenclature, classification, subtyping, prognostication, and discoveries on new treatment strategies of hematolymphoid eponymic diseases. Full article

Purpose: Lymphomas are generally radiosensitive; therefore, disease volume tends to shrink during radiotherapy courses. As MRI-linac provides excellent soft tissue definition and allows daily re-contouring of gross tumor volume and clinical target volume, its adoption could be beneficial for the treatment of lymphomas. Nonetheless, at this time there is a lack of literature regarding the use of MR-linac in this context. Methods: A prospective observational study was conducted on patients affected by non-Hodgkin lymphoma (NHL) involving head and neck (H&N) sites and treated with Elekta Unity^® MR-Linac. The clinical and dosimetric data of the first eight patients were collected and integrated with relevant data from medical records. Results: Seven patients had B-cell lymphoma (three DLBCL, two MALT, one follicular, and one mantle-cell) and one T-cell/NK lymphoma. The intent of RT was radical for four patients, salvage treatment for three, and CAR-T bridging for one. Two patients presented orbital localizations and six cervical lymphonodal sites. Median GTV was 5.74 cc, median CTV 127.01 cc, and median PTV 210.37 cc. The prescribed dose was 24–50 Gy in 2 Gy fractions for seven patients and 24 Gy in 3 Gy fractions for one patient. All the patients experienced acute toxicity, the maximum grade was G1 for five patients and G2 for three at the end of RT. One month after radiotherapy seven patients still experienced G1 toxicity, but no toxicity grade ≥ 2 was reported. First radiological assessment was performed for all the patients after a median of 101.5 days, reporting complete response in all the cases. After a median follow up of 330 days, no patient experienced local disease progression, while one patient developed distant progression. Conclusions: radiotherapy for NHL with H&N localization using a 1.5 T MR-linac was feasible, with no >G2 toxicity and optimal response rate and disease control. Full article

Background/Objectives: The primary objective of this study was to investigate clinical manifestations, time to diagnosis, and number of biopsies in patients with extranodal natural killer T-cell lymphoma (ENKTL). The secondary objectives were to determine response rates, survival outcomes, prognostic factor for overall survival (OS), and validation of the Prognostic Index of Natural Killer Lymphoma (PINK), Ann Arbor staging system (AASS), and the CA system. Methods: This retrospective study included data pertaining to patients with newly diagnosed ENKTL in Chiang-Mai University Hospital from 2004 to 2020. Comparisons between the areas under the receiver operating characteristic curve (AUC) of prognostic models (PINK, AASS, and CA system) were made. Results: Sixty patients were enrolled (n = 60) with a mean age of 49.1 ± 13.4 years. The most frequent symptom of ENKTL was nasal obstruction (66%). The median time to diagnosis was 22 days (ranging from 3 to 84 days), with 36.7% requiring more than one biopsy for diagnosis. Most patients presented with limited stage disease (75%). The median OS was 49 months. Factors associated with increased mortality were advanced stage, bone marrow involvement, gastrointestinal tract involvement, and receiving chemotherapy. Following prognostic model validation, the CA system model scored the highest level of accuracy (AUC 0.61), followed by AASS (AUC 0.58) and PINK (AUC 0.54). Conclusions: Patients with ENKTL commonly presented with nasal obstruction, with 36.7% requiring more than one biopsy for diagnosis. An advanced stage, bone marrow involvement, or gastrointestinal tract involvement were associated with poor OS. The CA system model has the highest level of accuracy for prognostic determination. Full article

In B-cell malignancies, the overexpression of MYC is associated with poor prognosis, but its mechanism underlying resistance to immunochemotherapy remains less clear. In further investigations of this issue, we show here that the pharmacological inhibition of MYC in various lymphoma and multiple myeloma cell lines, as well as patient-derived primary tumor cells, enhances their susceptibility to NK cell-mediated cytotoxicity induced by conventional antibodies targeting CD20 (rituximab) and CD38 (daratumumab), as well as T cell-mediated cytotoxicity induced by the CD19-targeting bispecific T-cell engager blinatumomab. This was associated with upregulation of the target antigen only for rituximab, suggesting additional escape mechanisms. To investigate these mechanisms, we targeted the MYC gene in OCI-LY18 cells using CRISPR-Cas9 gene-editing technology. CRISPR-Cas9-mediated MYC targeting not only upregulated CD20 but also triggered broader apoptotic pathways, upregulating pro-apoptotic PUMA and downregulating anti-apoptotic proteins BCL-2, XIAP, survivin and MCL-1, thereby rendering tumor cells more prone to apoptosis, a key tumor-lysis mechanism employed by T-cells and NK-cells. Moreover, MYC downregulation boosted T-cell activation and cytokine release in response to blinatumomab, revealing a MYC-mediated T-cell suppression mechanism. In conclusion, MYC overexpressing tumor cells mitigated the efficacy of therapeutic antibodies through several non-overlapping mechanisms. Given the challenges associated with direct MYC inhibition due to toxicity, successful modulation of MYC-mediated immune evasion mechanisms may improve the outcome of immunotherapeutic approaches in B-cell malignancies. Full article

While antibody-based immunotherapeutic strategies have revolutionized the treatment of B-cell lymphomas, progress in T-cell lymphomas has suffered from suboptimal targets, disease heterogeneity, and limited effective treatment options. Nonetheless, recent advances in our understanding of T-cell biology, the identification of novel targets, and the emergence of new therapies provide hope for the future. In this review, we explore four areas of current and evolving antibody-based strategies for the treatment of peripheral T-cell lymphoma (PTCL): monoclonal antibodies (mAbs), bispecific antibodies (BsAs), chimeric antigen receptor T-cell therapy (CAR-T), and antibody–drug conjugates (ADCs). As part of this discussion, we will also include limitations, lessons learned, and potential future directions. Full article

Early lymphocyte recovery as manifested by an absolute lymphocyte count at d+15 (ALC-15) ≥ 0.5 × 10⁹/L after autologous hematopoietic stem cell transplantation (AHCT) has been associated with a better outcome. This prospective multicenter study aimed to clarify factors associated with ALC-15 ≥ 0.5 × 10⁹/L after AHCT among 178 patients with non-Hodgkin lymphoma. The mobilization capacity, as manifested by peak blood CD34⁺ cell numbers > 45 × 10⁶/L correlated with higher ALC-15 levels (p = 0.020). In addition, the amount of CD3⁺CD4⁺ T cells > 31.8 × 10⁶/kg in the infused graft predicted ALC-15 ≥ 0.5 × 10⁹/L (p < 0.001). Also, the number of infused graft CD3⁺CD8⁺ T cells > 28.8 × 10⁶/kg (p = 0.017) and NK cells > 4.4 × 10⁶/kg was linked with higher ALC-15 (p < 0.001). The two-year progression-free survival after AHCT was significantly better in patients with ALC-15 ≥ 0.5 × 10⁹/L (74 vs. 57%, p = 0.027). The five-year OS in patients with higher ALC-15 was 78% vs. 60% in those with lower ALC-15 (p = 0.136). To conclude, the mobilization capacity of CD34⁺ cells and detailed measures of graft cellular content mark prognostic tools that predict ALC-15 ≥ 0.5 × 10⁹/L, which is associated with a better outcome in NHL patients after AHCT. Full article

Diffuse large B cell lymphoma (DLBCL) is a multifaceted condition characterized by significant diversity in its molecular and pathological subtypes and clinical manifestation. Despite the progress made in the treatment of DLBCL through the development of novel drugs, an estimated one-third of patients encounter relapse or acquire refractory disease. The tumor microenvironment (TME) of DLBCL, a complex network consisting of cellular and noncellular components that engage in interactions with the tumor, is a parameter that is gaining increasing attention. The TME comprises both the immune and nonimmune microenvironments. The immune microenvironment comprises natural killer (NK) cells, dendritic cells (DCs), tumor-associated macrophages (TAMs), neutrophils, myeloid-derived suppressor cells (MDSCs), and T and B lymphocytes. The nonimmune microenvironment consists of the extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), mesenchymal stromal cells, and other molecules that are secreted. Despite ongoing research, the exact impact of these components and their interaction on the progression of the disease remains elusive. A comprehensive review of significant discoveries concerning the cellular and noncellular constituents, molecular characteristics, and treatment response and prognosis of the TME in DLBCL, as well as the potential targeting of the TME with novel therapeutic approaches, is provided in this article. Full article

French Guiana is a French Overseas territory with singular features: it has a high prevalence of HIV and HTLV-1, its population is ethnically mixed, with widespread poverty, and up to 20% of the population lives in geographic isolation. In this context, we used registry data to estimate incidence and mortality due to hematological malignancies and to compare them with France and tropical Latin America. ICD codes C90 and C88 were compiled between 2005 and 2014. The direct standardization of age structure was performed using the world population. Survival analysis was performed, and Kaplan–Meier curves were drawn. The overall standardized incidence rate was 32.9 per 100,000 male years and 24.5 per 100,000 female years. Between 2005 and 2009, the standardized incidence rate was 29.6 per 100,000 among men and 23.6 per 100,000 among women, and between 2010 and 2014, it was 35.6 per 100,000 among men and 25.2 per 100,000 among women. Multiple myeloma/plasmocytoma and mature t/NK cell lymphomas, notably adult t-cell lymphoma/leukemia due to HTLV-1 infection, were the two most common hematologic malignancies and causes of death. Non-Hodgkin’s lymphoma incidence estimates were greater than global estimates. After adjusting for age, sex, and type of malignancy, people born in a foreign country independently had a poorer case-fatality rate, presumably reflecting difficulties in accessing care. The epidemiology of hematological malignancies in French Guiana has features that distinguish it from mainland France or from Latin America. The incidence of multiple myeloma and adult t-cell lymphoma/leukemia was significantly greater in French Guiana than in France or other Latin American countries. Full article

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by the uncontrolled activation of cytotoxic T lymphocytes, NK cells, and macrophages, resulting in an overproduction of pro-inflammatory cytokines. A primary and a secondary form are distinguished depending on whether or not it is associated with hematologic, infectious, or immune-mediated disease. Clinical manifestations include fever, splenomegaly, neurological changes, coagulopathy, hepatic dysfunction, cytopenia, hypertriglyceridemia, hyperferritinemia, and hemophagocytosis. In adults, therapy, although aggressive, is often unsuccessful. We report the case of a 41-year-old man with no apparent history of previous disease and an acute onset characterized by fever, fatigue, and weight loss. The man was from Burkina Faso and had made trips to his home country in the previous five months. On admission, leukopenia, thrombocytopenia, increased creatinine and transaminases, LDH, and CRP with a normal ESR were found. The patient also presented with hypertriglyceridemia and hyperferritinemia. An infectious or autoimmune etiology was ruled out. A total body CT scan showed bilateral pleural effusion and hilar mesenterial, abdominal, and paratracheal lymphadenopathy. Lymphoproliferative disease with HLH complication was therefore suspected. High doses of glucocorticoids were then administered. A cytologic analysis of the pleural effusion showed anaplastic lymphoma cells and bone marrow aspirate showed hemophagocytosis. An Epstein–Barr Virus (EBV) DNA load of more than 90000 copies/mL was found. Bone marrow biopsy showed a marrow localization of peripheral T lymphoma. The course was rapidly progressive until the patient died. HLH is a rare but usually fatal complication in adults of hematologic, autoimmune, and malignant diseases. Very early diagnosis and treatment are critical but not always sufficient to save patients. Full article

EBV-positive nodal T- and NK-cell lymphoma (EBV+ NT/NKCL) is a recently recognized entity in the 5th edition of the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. Notably, CD30 positivity is frequently observed in (EBV+ NT/NKCL), creating diagnostic challenges to distinguish it from ALK-negative anaplastic large cell lymphoma (ALCL). Furthermore, cases of EBV+ ALCL have been documented in the literature, predating the inclusion of EBV+ nodal cytotoxic T-cell lymphoma as a variant of peripheral T-cell lymphoma. We present a case of a 47-year-old male presenting with multiple lymphadenopathies. The histomorphologic and immunophenotypic features of the lymph node closely resemble ALK-negative ALCL, characterized by uniform CD30 expression and a subcapsular distribution of lymphoma cells. However, the lymphoma cells exhibit diffuse positivity for EBV, consistent with EBV+ NT/NKCL. A case of ALK-negative ALCL with an immunophenotype identical to the EBV-positive case is included for comparison. Given that EBV+ NT/NKCL represents an aggressive neoplasm requiring unique clinical management compared to ALK-negative ALCL, it is critical to accurately differentiate EBV+ NT/NKCL from ALK-negative ALCL with a cytotoxic T-cell immunophenotype. Full article