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The aim of the present study was to evaluate the occurrence of synchronous or metachronous hematologic and gynecologic malignancies. The medical database of the pathology department at a tertiary center was searched from 2016 to 2024 for cases involving both hematologic and gynecologic tumors. A literature search using Google Scholar and PubMed was also conducted between May and June 2024. Articles reporting surgical pathology data were included, while radiologic studies and those lacking pathology data were excluded. Cases involving one gynecologic cancer and one hematologic malignancy were analyzed. Three cases from our center and 25 cases from 15 English‐language articles were identified. The mean age of the cases at diagnosis was 61.4 ± 9.4 years. A total of 19 patients (68%) were diagnosed with synchronous cancers, while the rest had metachronous diagnoses. Endometrial cancer was seen in 20 cases (71.4%): 14 synchronous and five metachronous endometrioid adenocarcinomas, and one unspecified metachronous endometrial cancer. This was followed by five cases of ovarian cancer (17.9%): three synchronous serous ovarian carcinomas, one metachronous serous ovarian carcinoma, and one synchronous ovarian adenocarcinoma. Additionally, there were two cases of cervical cancer (7.1%): one synchronous adenosquamous carcinoma and one metachronous invasive squamous carcinoma, and one case of carcinosarcoma (3.6%). Involvement of more than one site is possible for hematolymphoid cancer, commonly affecting the pelvic or para‐aortic lymph nodes in 16 patients (57.1%), with other sites including the cervix (4 cases, 14.3%), ovary (4 cases, 14.3%), uterus (2 cases, 7.1%), iliac/inguinal lymph nodes (2 cases, 7.1%), fallopian tube (1 case, 3.6%), vagina (1 case, 3.6%), liver (1 case, 3.6%), abdomen (1 case, 3.6%), and appendix (1 case, 3.6%). Two cases were unspecified. Non‐Hodgkin lymphoma (NHL), primarily of B cell lineage, was the most common hematologic malignancy (25 cases, 89.3%, with 22 cases being B cell lineage). In contrast, Hodgkin lymphoma was observed in two cases (7.1%), and acute leukemia in one case (3.6%). Among 21 patients with available follow‐up data, eight died during the follow‐up period. The co‐occurrence of NHL, Hodgkin lymphoma, and acute leukemia with gynecologic cancers is rare. However, during surgery for gynecologic cancers, the potential of synchronous lymphoma should be considered, particularly in cases with unusual retroperitoneal lymphadenopathy. [ABSTRACT FROM AUTHOR]

Purpose:In vitro maturation (IVM) of oocytes obtained from ovarian tissue during ovarian tissue cryopreservation (OTC) is a technique for fertility preservation in patients with cancer obviating the need to postpone chemotherapy initiation. Little is known about IVM outcomes in hematological malignancies, especially post-chemotherapy. The purpose of this study was to evaluate the effect of cytotoxic treatment on the potential to retrieve immature oocytes and mature them in vitro and examine the association between serum inflammatory markers and these results. Methods: In this retrospective study, we evaluated inflammation markers, including B symptoms and IVM outcomes of 78 chemotherapy-naive and exposed patients diagnosed with Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), or acute myeloid leukemia (AML). Results: The mean number of oocytes found was 7.2 ± 7.2. The average number of oocytes matured by IVM was 2.8 ± 3.5, and a mean IVM rate was 32.1 ± 27.7%. All patients in the ALL and AML groups had previous exposure to chemotherapy before OTC, compared with 50.0% (7/14) and 31.9% (15/47) in the NHL and HL groups, respectively. Among patients with lymphoma, chemotherapy exposure was associated with the reduced number of retrieved oocytes (9.8 ± 7.7 vs. 5.3 ± 5.7 oocytes, p = 0.049) in the HL group but not with the number of mature oocytes or IVM rate. B symptoms were not associated with IVM outcomes. Lymphocyte count (ß = 1.584; p = 0.038) and lactate dehydrogenase (ß = 0.009; p = 0.043) were the only significant parameters associated with the number of matured oocytes in a linear regression model. Conclusion: IVM is a promising assisted reproductive technology, which holds great potential for patients in need of urgent fertility preservation or those who cannot receive hormonal stimulation. Our results demonstrate the feasibility of the technique even in the presence of B symptoms and elevated inflammation markers and in patients with previous exposure to chemotherapy. [ABSTRACT FROM AUTHOR]

ABSTRACT Risk of cardiovascular disease (CVD) in patients with classical Hodgkin lymphoma (cHL) undergoing contemporary treatment is unclear. cHL patients ≥ 18 years at diagnosis treated with doxorubicin‐containing chemotherapy between 2000 and 2022 were matched 1:5 with comparators on birth year, sex, and Charlson Comorbidity Index at time of matching (score of 0 or ≥ 1). Cause‐specific cumulative incidence of a composite of CVDs with corresponding 95% confidence intervals (CIs) were computed with death and lymphoma relapse as competing events (i.e., by censoring individuals at such occurrences) using the Aalen‐Johansen estimator. A total of 1905 patients and 9525 comparators with a median follow‐up of 10 years (interquartile range, [IQR]: 5.9–17.4). Median age was 39 years (IQR: 27–56), median cumulative doxorubicin dose was 250 mg/m2 (IQR: 200–300). The CVD cumulative incidences were 4.7% (95% CI: 3.6–5.7) for patients versus 2.6% (95% CI: 2.3–2.9) for comparators at 5 years, 8.9% (95% CI: 7.2–10.5) versus 5.5% (95% CI: 4.9–6.0) at 10 years, and 17.0% (95% CI: 14.1–19.9) versus 8.2% (95% CI: 7.4–9.0) at 15 years. CVD remains a substantial effect after contemporary treatment for cHL, suggesting that awareness of symptoms and a low threshold for referral to diagnostic examination are still important measures during survivorship. [ABSTRACT FROM AUTHOR]

Since their initial approval as single agent therapy for multiply relapsed/refractory Hodgkin lymphoma (HL), the PD-1 inhibitors nivolumab and pembrolizumab have been incorporated into second-line salvage regimens, and they are being investigated in upfront therapy of newly diagnosed patients. As second-line therapy in combination with brentuximab vedotin or multi-agent chemotherapy, nivolumab and pembrolizumab provide high complete remission rates and durable progression-free survival after consolidative autologous stem cell transplant. Incorporation of these agents into frontline chemotherapy regimens is feasible, and early results from a Phase III trial of nivolumab-AVD compare favorably with the existing standard for advanced stage HL, brentuximab vedotin plus AVD. As nivolumab and pembrolizumab move into earlier lines of HL therapy, open research questions include the efficacy of checkpoint inhibitor regimens in patients who relapse after frontline exposure to nivolumab or pembrolizumab; the selection of patients with relapsed HL who can achieve durable remissions without autologous stem cell transplant; and the efficacy of the PD-1 inhibitors in the frontline therapy of patients with early stage Hodgkin lymphoma. [ABSTRACT FROM AUTHOR]

Introduction: Hodgkin lymphoma (HL) is deficient in major histocompatibility complex class I, rendering it susceptible to antitumoral immunity by natural killer (NK) cells. Despite the functional impairment of PD-1+ NK cells in HL, the underlying mechanisms of NK cell dysfunction remain unclear. Methods: This study involved 14 HL patients and SNK10/KHYG-1 cell lines to assess NK cell activation against cancer cells. Activation was measured through transcript (PCR) and protein expression (flow cytometry). Regulatory mechanisms associated with IRE1α activation were validated through knockdown and luciferase reporter assays. Results: Our findings reveal a novel role for IRE1α-endonuclease in fine-tuning NK cell effector functions by orchestrating the XBP1s/microRNA-34a-5p/PD-1 axis. When NK cells encounter cancer cells, IRE1α endonuclease activates the decay of microRNA-34a-5p, resulting in increased expression of XBP1s and PD-1. IRE1α-endonuclease activation enhances NK cell functions while promoting PD-1 expression. In turn, PD-1 is directly regulated by microRNA-34a-5p, which binds to the 3′UTR of PD-1 transcript to repress PD-1 protein on the NK cell surface. Importantly, IRE1α-pathway activation is impaired in NK cells from HL patients. Conclusion: The IRE1α endonuclease emerges as a key player, simultaneously regulating the XBP1s/microRNA-34a-5p/PD-1 axis in NK cells, a process disrupted in HL. Targeting the IRE1α-pathway holds promise as a therapeutic strategy to optimize NK cell functions in Hodgkin lymphoma treatments. Plain Language Summary: Natural killer (NK) cells play a critical role in our innate immune defense against tumors without prior exposure to cancer cells and, therefore, make an attractive instrument to harness antitumoral immunity as novel immunotherapies. Hodgkin lymphoma (HL) typically lacks major histocompatibility complex class I which is a requirement for an antigen-specific recognition of effector T cells but not for the NK cell antitumoral function. NK cells are dysfunctional in HL patients mainly due to upregulation of immune checkpoint PD-1 expression that inhibits immune cells effector functions. However, the mechanisms underpinning PD-1 expression and NK cell dysfunction remain unknown. In this study, we uncovered the mechanism by which immune checkpoint PD-1 expression is upregulated upon activation of the endonuclease IRE1α to rapidly change the abundance of key regulatory molecules including a small noncoding regulatory RNA (microRNA-34a) and the transcription factor XBP1. The IRE1α endonuclease plays a dual role in regulating the XBP1/miRNA-34a axis and PD-1 expression within NK cells, which is disrupted in patients with HL. IRE1α pathway in NK cells represents a potential target to optimize NK cell immune functions in future HL treatments. [ABSTRACT FROM AUTHOR]

The bi- or multinucleated Reed–Sternberg cell (RS) is the diagnostic cornerstone of Epstein–Barr Virus (EBV)-positive and EBV-negative classical Hodgkin lymphoma (cHL). cHL is a germinal center (GC)-derived B-cell disease. Hodgkin cells (H) are the mononuclear precursors of RS. An experimental model has to fulfill three conditions to qualify as common pathogenic denominator: (i) to be of GC-derived B-cell origin, (ii) to be EBV-negative to avoid EBV latency III expression and (iii) to support permanent EBV-encoded oncogenic latent membrane protein (LMP1) expression upon induction. These conditions are unified in the EBV-, diffuse large B-Cell lymphoma (DLBCL) cell line BJAB-tTA-LMP1. 3D reconstructive nanotechnology revealed spatial, quantitative and qualitative disturbance of telomere/shelterin interactions in mononuclear H-like cells, with further progression during transition to RS-like cells, including progressive complexity of the karyotype with every mitotic cycle, due to BBF (breakage/bridge/fusion) events. The findings of this model were confirmed in diagnostic patient samples and correlate with clinical outcomes. Moreover, in vitro, significant disturbance of the lamin AC/telomere interaction progressively occurred. In summary, our research over the past three decades identified cHL as the first lymphoid malignancy driven by a disturbed telomere/shelterin/lamin AC interaction, generating the diagnostic RS. Our findings may act as trailblazer for tailored therapies in refractory cHL. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Materials and Methods Results Conclusion Hodgkin lymphoma (HL) constitutes 10% of all lymphoma diagnoses and accounts for 5% of lymphoma‐related deaths. Accurate prognostication in HL remains crucial, particularly given that 10%–20% of patients may receive either insufficient or excessive treatment. This study investigates the effect of hemoglobin, albumin, lymphocyte, and platelet (HALP) score, which is a marker of inflammation status and nutrition, at the time of diagnosis for the patients with HL on prognosis.A total of 147 patients diagnosed with cHL were included in the study, and their data were analyzed retrospectively. The significance of the HALP score and hematological indices [neutrophil‐lymphocyte ratio (NLR), lymphocyte‐monocyte ratio (LMR), and platelet‐lymphocyte ratio (PLR)] as predictors of overall survival (OS) and disease‐free survival (DFS) was evaluated.Patients were grouped according to median values for the HALP score and hematological indices. High HALP score (p = 0.034), low NLR (p = 0.033), high LMR (p = 0.003), and low PLR (p = 0.014) were statistically significant in the early‐stage favorable group. DFS and OS were not statistically significant according to the HALP score NLR, LMR, and PLR groups.The need for readily applicable, reliable prognostic markers in cHL, where immunotherapy treatments have led to significantly improved survival outcomes, remains persistent. [ABSTRACT FROM AUTHOR]

Introduction: Prurigo nodularis is a highly pruritic chronic dermatosis, characterized by the appearance of hyperkeratotic skin nodules in middle-aged adults. Sometimes it can be the initial manifestation of a lymphoproliferative disease. Objective: To present the case of a patient with a history of prurigo nodularis as a paraneoplastic manifestation of mediastinal Hodgkin lymphoma. Case presentation: A 48-year-old patient with a history of prurigo nodularis. Three years after diagnosis, she presented with an increase in volume of the anterior region of the thorax. Imaging studies demonstrated a tumor in the anterosuperior mediastinum, which was concluded in the histological study to be nodular sclerosis variant Hodgkin’s lymphoma. Conclusions: Chronic skin lesions can be manifestations of internal neoplasms. [ABSTRACT FROM AUTHOR]

Summary: Osteonecrosis (ON) is a common complication of glucocorticoid‐based Hodgkin lymphoma (HL) treatment, but the natural evolution and prognosis of ON lesions remain poorly understood. We describe the radiological evolution of ON lesions identified in a Nordic population‐based cohort of paediatric HL patients. Magnetic resonance images of suspected ON lesions were centrally reviewed to confirm ON diagnosis and grade the ON lesions according to the Niinimäki classification. The study included 202 ON lesions in 46 patients, of which 77 were joint lesions. Follow‐up images were available for 146/202 lesions, with a mean follow‐up time of 28 months. During follow‐up, 71% of the lesions remained stable, 26% improved or resolved, and 3% progressed. A higher ON grade at diagnosis was associated with a lower likelihood of spontaneous resolution. The likelihood for resolution of ON decreased by 50% for each year of added patient age, when adjusted for sex, ON location, and symptoms. Hip ON showed less spontaneous improvement compared with other joints, and the risk for surgery was 13‐fold in hip ON. Grades 3–4 joint ON has the potential to either progress or resolve, warranting follow‐up in patients with severe symptoms. Research on secondary prevention should be directed at grade 3–4 joint ON. [ABSTRACT FROM AUTHOR]

Summary: We demonstrated that dose‐densified and dose‐intensified ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine; ABVDDD‐DI) was safe and effective. Here, we present a post hoc long‐term analysis of the 82 patients enrolled in the original study. The median observation time was 175 months (IQR 159–197). At 15 years, progression‐free and overall survival rates were 81.2% (95% CI, 69.9%–88.7%) and 92.7% (95% CI, 82.6%–97.0%), respectively. Four patients with multiple cardiovascular risk factors experienced delayed G3 cardiac events. The cumulative incidence of second malignancies at 20 years was 6.1%. Fertility and childbearing potential were unaffected. Data support an ongoing benefit for ABVDDD‐DI without uneven late toxicities. [ABSTRACT FROM AUTHOR]

Background: With conventional standard treatment modalities, children and adolescents with Hodgkin lymphoma (HL) have long-term overall survival rates of over 90%. However, primary refractory disease may occur in 5%-10% of HL patients, while relapse occurs in 5%--10% of patients with early stage disease and up to 30% in an advanced stage. This retrospective study evaluated patient characteristics in cases of HL relapse and refractory and their response to second-line treatment of standalone chemotherapy or in combination with radiotherapy. Methodology: A retrospective study was conducted by Indus Hospital and Health Network to determine the outcomes of paediatric patients with first and second relapses of HL between 2013 and 2022. Results: A total of 742 patients were diagnosed with HL at Indus Hospital & Health Network. Of these, 48 (6.5%) patients presented with relapse and 35 (4.7%) with refractory disease after initial chemotherapy. In HL relapse patients, 57% were stage IV at initial diagnosis with the most common pathology being nodular sclerosis constituting 42.9% of patients. The most common age group was 6--10 years, 45.8%. B symptoms were experienced by 25 (52%) patients. A time to relapse of >12 months following diagnosis was seen in 69% and 3-12 months was seen in 31%. After receiving second-line treatment, complete remission was achieved by 34 (70.8%) patients, partial remission (PR) was seen in 5 (10.4%), disease progression in 5 (10.4%), 3 (6.3%) patients left during treatment and 1 (2.1%) had a treatment-related mortality. Reradiation in second-line treatment was only required for 2 patients. The second relapse was seen in 11 (28.2%) of 39 complete and PR patients. Conclusion: Major limitations in the treatment of HL relapse in a low-resource setting are the non-availability of immunotherapy and autologous stem cell transplantation due to extreme financial burden and lack of capacity in facilities. Dedicated efforts are required to provide these facilities free of cost in low--middle income countries (LMICs). [ABSTRACT FROM AUTHOR]

South Africa has a high burden of human immune deficiency virus (HIV)-associated Hodgkin lymphoma (HL) which is typically Epstein–Barr virus (EBV) infected, detected by histological stains. Circulating plasma EBV derived from apoptotic EBV infected tumour cells is a potential biomarker. This study aimed to evaluate the role of plasma EBV load testing in newly diagnosed HL patients and correlate pretreatment plasma EBV levels, HIV status and EBV tumour status with overall survival (OS). Untreated HL patients were prospectively included. Polymerase chain reaction measured EBV plasma viral loads. Kaplan–Meier curves with log-rank tests estimated the impact of HIV, EBV tumour status and plasma EBV viral loads on OS. Multivariable analysis was performed using a Cox proportional hazards model. Receiver operative characteristic curve analysis determined cutoff plasma EBV DNA levels with optimal sensitivity, specificity and concordance with tumour EBV status. The 68 patients included 21 (31%) HIV +ve and 33 (49%) EBV tumour +ve. EBV plasma ≥ 10 000 IU/ml (P = 0.008), EBV +ve tumour (P = 0.014), HIV +ve status (P = 0.009) and age ≥ 45 years (P = 0.018) predicted poorer OS on univariate analysis. Plasma EBV levels > 762 IU/ml had 89.29% sensitivity and 96.77% specificity for detecting EBV +ve HL. High plasma EBV levels ≥ 10 000 IU/ml, HIV +ve status and EBV tumour +ve status predicted poorer OS. Plasma EBV levels > 762 IU/ml predicted EBV +ve tumour status with high sensitivity and specificity. Plasma EBV viral DNA testing is a promising biomarker for EBV +ve HL. [ABSTRACT FROM AUTHOR]

Abstract Background Prospective data from sub-Saharan Africa suggests that treatment outcomes for people living with HIV (PWH) with Hodgkin lymphoma (HL) are similar to those without HIV. However, real-world data from high-resource settings and retrospective studies from sub-Saharan Africa, suggest inferior outcomes. We set out to evaluate the real-world treatment outcomes for HL in South Africa to better understand the disparate outcomes. Methods We established a prospective, observational cohort of newly diagnosed, adult (≥ 18 years) HL cases recruited from Chris Hani Baragwanath Academic and Netcare Olivedale Hospitals in Johannesburg, South Africa between March 2021 and March 2023. Participants were followed for up to 18 months after enrollment with data censored on December 23rd, 2023. The primary endpoint was 1-year overall survival. Results We enrolled 47 participants with HL including 31 PWH and 16 HIV-negative. Advanced stage disease and B symptoms were common at time of diagnosis irrespective of HIV status. Bone marrow biopsy, performed during the work-up and evaluation of cytopenias, provided the initial diagnosis of HL in 16/31 (52%) PWH. HIV status and bone marrow involvement were associated with early mortality (within 3 months of diagnosis) and a poorer 1-year overall survival from diagnosis (HIV: 55% vs. 88%; p = 0.03; bone marrow involvement: 50% vs. 80%; p = 0.02). Among evaluable participants, those that received at least 6 cycles of chemotherapy and underwent response assessment, there was no difference between those with and without HIV. Conclusion Traditional laboratory markers of poor prognosis including anemia, lymphopenia and hypoalbuminemia were more common among PWH and those with bone marrow involvement and suggest high risk disease. A better understanding of the drivers of these aggressive presentations is warranted to ensure more PWH are able to tolerate chemotherapy.

Abstract Rationale Warthin tumor (WT) is the second most common benign tumor in salivary gland. It has a slow growth rate and most frequently occurs in the parotid gland. Most patients present with an incidental finding of a painless mass inferior/anterior to the ear. Besides the epithelial component of the tumor, WT is characteristically associated with lymphoid stroma that is considered benign. While there have been a few reports of malignant transformation of the lymphoid components in WT, cases of WT concomitant with mantle cell lymphoma (MCL) are extremely rare. To the best of our knowledge, two cases have been described in the English literature. Herein, we report a case of WT concomitant with MCL in a 70-year-old female patient, and emphasize the importance of careful examination of lymphoid stroma in WT so that concurrent lymphoma is not missed. Patient concerns A 70-year-old Chinese woman with a 40-year history of cigarette smoking presented with a one year history of a right submaxillary mass with recent enlargement. Diagnosis Cervical ultrasound (US) and computed tomography (CT) scans of the neck revealed a well-circumscribed mass in the right parotid with a maximum diameter of 3.1 cm. Surgical resection of the mass was performed. Histopathological examination revealed a characteristic double-layer of neoplastic epithelium with prominent lymphoid stroma, suggesting WT. In addition, morphology and immunohistochemistry studies confirmed the coexistence of MCL. Thereafter, the final diagnosis of this case was WT concomitant with MCL. Interventions The patient was staged as stage I after clinical assessment. Due to the slow growth of parotid lesions, close observation was decided with periodic clinical and radiological monitoring. Outcomes Currently, the patient demonstrates a stable disease by clinical evaluation. Lessons To the best of our knowledge, reported cases of WT concomitant with MCL are very rare. This case highlights the importance of a comprehensive assessment of the lymphoid stroma of WT to avoid missed diagnosis of a lymphoma component in a collision tumor.

Amaylia Oehadian,1 Andini Kartikasari,2 Lusi Mersiana,1 Stephanie Victoria Gunadi,3 Gusti Fungani,1 Putri Vidyaniati,1 Dimmy Prasetya,1 Indra Wijaya,1 Pandji Irani Fianza,1 Trinugroho Heri Fadjari,1 Nanny Natalia Sutedjo4 1Division of Hematology and Oncology Medic, Internal Medicine Department, Faculty of Medicine, Padjadjaran University/ Dr. Hasan Sadikin General Hospital, Bandung, Indonesia; 2Bandung City Regional General Hospital, Bandung, Indonesia; 3Internal Medicine Department, Faculty of Medicine, Padjadjaran University/ Dr. Hasan Sadikin General Hospital, Bandung, Indonesia; 4Endocrinology and Metabolism Division, Internal Medicine Department, Faculty of Medicine, Padjadjaran University/ Dr. Hasan Sadikin General Hospital, Bandung, IndonesiaCorrespondence: Amaylia Oehadian, Department of Internal Medicine, Padjadjaran University/ Dr. Hasan Sadikin General Hospital, Jl. Pasteur No. 38, Pasteur, Bandung, West Java, 40161, Indonesia, Email amaylia.oehadian@unpad.ac.idBackground: No specific data have been systematically collected regarding lymphoma patient characteristics, while non-Hodgkin lymphoma (NHL) is identified as the 7th most common cancer and Hodgkin lymphoma (HL) is the 28th. Inflammation plays an important role in the pathogenesis and progression of lymphoma. Malnutrition is an adverse prognostic factor in lymphoma. Systemic Inflammatory Index (SII), Prognostic Nutritional Index (PNI), and Advanced Lung Cancer Inflammation Index (ALI) were biomarkers depicting inflammation and nutritional status. This study aims to describe the clinical and biomarker characteristics of both HL and NHL patients.Methods: This descriptive study used a cross-sectional design, and data were collected from Hasan Sadikin Hospital lymphoma registry from January 2020 to November 2023. Demographic, staging, and histopathological data were extracted. Three biomarkers were evaluated. Survival curves were drawn using Kaplan–Meier curve analysis, and the log rank test was used for comparison of survival between early and advanced stage.Results: A total of 271 patients were recruited as participants, and the majority (80.5%) had NHL, with diffuse large B-cell lymphoma (DLBCL) being the most common histopathological type (50.5%). Early disease was observed in two-thirds of patients, and low-risk International Prognostic Index (IPI) score was the most common prognostic score found (95%). SII was slightly higher in early compared to advanced stages. Treatment response was evaluated from 101 patients, and complete response was observed in 44.5%. Two-year overall survival (OS) was 93.1%, with median survival 22.7 (95% CI 21.9– 23.5) months. In early stage, the median survival was slightly longer than in advanced stage [23.0 (95% CI 22.2– 23.8) vs 21.6 (95% CI 19.3– 23.8) months, P= 0.09].Conclusion: Hodgkin lymphoma and DLBCL had similar clinical and biomarker characteristics. There were slight differences between the three biomarkers SII, ALI, and PNI based on the disease stage. Almost all patients still survived at 2-year follow-up.Keywords: lymphoma, non-Hodgkin lymphoma, Hodgkin lymphoma, registry

Background. The COVID-19 pandemic, which swept the world in 2020–2021, had a significant impact on the epidemiological picture of hematological malignancies. Aim. To study the dynamics of epidemiological indicators of five chronic hemoblastoses in Moscow over a 12-year period, and also to assess the impact of the COVID-19 pandemic on these indicators. Materials and methods. A population-based study was conducted for five types of oncohematological diseases: multiple myeloma, Hodgkin's lymphoma, follicular lymphoma, chronic lymphocytic leukemia, chronic myeloid leukemia. The annual rates of morbidity, mortality, prevalence of these nosologies, overall survival, and expected overall survival were calculated. Gender and age characteristics for each disease were determined. Results and discussion. The present study showed a uniform increase in the incidence and prevalence of five hematological malignancies between 2012 and 2019. Convincing evidence of an increase in mortality and a decrease in the number of diagnosed cases in comparison with the expected figures for these hematological malignancies in 2020–2021 was presented. A greater reduction was shown for cases diagnosed at early stages compared to later ones. During the pandemic, a significant increase in mortality was recorded among patients with chronic lymphocytic leukemia and multiple myeloma, while in cohorts of patients with chronic myeloid leukemia and Hodgkin lymphoma it increased slightly. The return of morbidity, mortality and prevalence rates to the original dynamics in 2022–2023 has been demonstrated. Conclusion. This study demonstrated the features of the regional pattern of incidence, mortality, prevalence and gender-age characteristics of five hematological malignancies and provided the changes in the indicators dynamics of different hematological malignancies during the COVID-19 pandemic.

Abstract Objective Twenty percent of all classical Hodgkin lymphoma (CHL) cases relapse and recur, especially in advanced stages with a high International Prognostic Score (IPS). Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a regulatory molecule that can inhibit the immune response and is related to tumor aggressiveness. This study aimed to determine the relationship between CTLA-4 expression in advanced-stage CHL and IPS, identifying it as a potential therapy target. Results In advanced-stage CHL, the group with a high IPS exhibited significantly higher mean CTLA-4 expression compared to the group with a low IPS (p = 0.003).The group with Hb level 15,000/µL, lymphocyte count

Abstract Hodgkin lymphoma (HL) represents a neoplasm primarily affecting adolescents and young adults, necessitating the development of precise diagnostic and monitoring tools. Specifically, classical Hodgkin lymphoma (cHL), comprising 90% of cases, necessitating tailored treatments to minimize late toxicities. Although positron emission tomography/computed tomography (PET/CT) has enhanced response assessment, its limitations underscore the urgency for more reliable progression predictive tools. Genomic characterisation of rare Hodgkin Reed-Sternberg (HRS) cells is challenging but essential. Recent studies employ single-cell molecular analyses, mass cytometry, and Next-Generation Sequencing (NGS) to unveil mutational landscapes. The integration of liquid biopsies, particularly circulating tumor DNA (ctDNA), extracellular vesicles (EVs), miRNAs and cytokines, emerge as groundbreaking approaches. Recent studies demonstrate ctDNA's potential in assessing therapy responses and predicting relapses in HL. Despite cHL-specific ctDNA applications being relatively unexplored, studies emphasize its value in monitoring treatment outcomes. Overall, this review underscores the imperative role of liquid biopsies in advancing HL diagnosis and monitoring.

Background: Prospective data from sub-Saharan Africa suggests that treatment outcomes for people living with HIV (PWH) with Hodgkin lymphoma (HL) are similar to those without HIV. However, real-world data from high-resource settings and retrospective studies from sub-Saharan Africa, suggest inferior outcomes. We set out to evaluate the real-world treatment outcomes for HL in South Africa to better understand the disparate outcomes. Methods: We established a prospective, observational cohort of newly diagnosed, adult (≥ 18 years) HL cases recruited from Chris Hani Baragwanath Academic and Netcare Olivedale Hospitals in Johannesburg, South Africa between March 2021 and March 2023. Participants were followed for up to 18 months after enrollment with data censored on December 23rd, 2023. The primary endpoint was 1-year overall survival. Results: We enrolled 47 participants with HL including 31 PWH and 16 HIV-negative. Advanced stage disease and B symptoms were common at time of diagnosis irrespective of HIV status. Bone marrow biopsy, performed during the work-up and evaluation of cytopenias, provided the initial diagnosis of HL in 16/31 (52%) PWH. HIV status and bone marrow involvement were associated with early mortality (within 3 months of diagnosis) and a poorer 1-year overall survival from diagnosis (HIV: 55% vs. 88%; p = 0.03; bone marrow involvement: 50% vs. 80%; p = 0.02). Among evaluable participants, those that received at least 6 cycles of chemotherapy and underwent response assessment, there was no difference between those with and without HIV. Conclusion: Traditional laboratory markers of poor prognosis including anemia, lymphopenia and hypoalbuminemia were more common among PWH and those with bone marrow involvement and suggest high risk disease. A better understanding of the drivers of these aggressive presentations is warranted to ensure more PWH are able to tolerate chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction: The identification of baseline prognostic factors in Classical Hodgkin Lymphoma could help in tailoring a risk-based approach as the therapeutic landscape expands. Currently, the International Prognostic Score (IPS) represents the most used prediction tool in clinical practice, but other potential baseline risk predictors have been identified. Methods: We performed a retrospective analysis in a cohort of 274 patients treated with 18FDG-PET/CT-guided ABVD to assess the prognostic significance of the IPS risk factors, and to validate the impact of the peripheral blood lymphocyte to monocyte (LMR) and neutrophil to lymphocyte (NLR) ratios on prognosis definition. Results: Among the considered risk factors, stage IV disease (HR 1.83), leukocytosis (HR 2.28), anemia (HR 3.23) and low LMR (HR 2.01) significantly predicted PFS, whereas male sex (HR 2.93), stage IV disease (HR 3.00) and lymphopenia (HR 7.84) significantly predicted OS. A 4 variable and a 3 variable prognostic system was subsequently proposed for PFS and OS, respectively. In both cases, a stark decrease in the survival probability was documented as the score increased. Moreover, by selecting only the significant IPS items and considering a more recently proposed prognostic factor (LMR) we were able to better identify patients at higher risk of relapsing after PET/CT-guided ABVD. Discussion: Although the IPS was still able to identify a subgroup of high-risk patients within our cohort of individuals treated with PET/CT-guided ABVD, not all the risk factors that it considers were found to have an impact on survival times. Moreover, by selecting only the significant IPS items and considering a more recently proposed prognostic factor (LMR) we were able to better identify patients at higher risk of relapse, in an effort to contribute to the building of a modern risk prediction tool that can help guide treatment choices. [ABSTRACT FROM AUTHOR]

AbstractAs the integration of novel agents in the frontline therapy has primarily impacted upfront therapy of advanced stage classic Hodgkin lymphoma (cHL), this review will outline current management of advanced stage cHL at first line and at progression and relapse, focusing on the biology, clinical features, and therapeutic approaches. Due to S1826, HD21, and ECHELON-1, the first-line treatment of advanced cHL has dramatically changed, with novel agents part of standard frontline therapy. BV-AVD, BrECADD, and Nivo-AVD are now standard first-line regimens for patients with stage III-IV cHL, with improved outcomes compared to historical data in cHL. The addition of BV and PD-1 inhibitors to relapsed/refractory (r/r) cHL chemotherapy regimens improved outcomes in this population. Now, there is a paradigm shift with PD-1 moving into frontline therapy, so new studies to evaluate the role of these novel agents in salvage will be required to determine the optimal salvage approach in r/r cHL. [ABSTRACT FROM AUTHOR]

Simple Summary: The first Onco Summit: The Latin American (LATAM) Chapter was held from 19–20 May 2023, in Rio de Janeiro, Brazil. This educational initiative aimed to discuss the current challenges in cancer care, both globally and in LATAM, and foster the exchange of best practices to address these challenges. The Summit brought together more than 30 international and regional experts and more than 300 oncology specialists to deliberate on the advancements and barriers in oncology, with a focus on strategies tailored to the specific needs of LATAM. This report provides an overview of the key discussions among cancer specialists at the Summit. The Onco Summit 2023: The Latin American (LATAM) Chapter took place over two days, from 19–20 May 2023, in Brazil. The event aimed to share the latest updates across various oncology disciplines, address critical clinical challenges, and exchange best practices to ensure optimal patient treatment. More than 30 international and regional speakers and more than 300 oncology specialists participated in the Summit. The Summit discussions centered on common challenges and therapeutic advances in cancer care, with a specific focus on the unique obstacles faced in LATAM and examples of adaptable strategies to address these challenges. The Summit also facilitated the establishment of a network of oncologists, hematologists, and scientists in LATAM, enabling collaboration to improve cancer care, both in this region and globally, through drug development and clinical research. This report summarizes the key discussions from the Summit for the global and LATAM oncology community. [ABSTRACT FROM AUTHOR]

Herein, we report a case of a 16-year-old girl who presented with an episode of shortness of breath while playing sports. Upon radiologic workup, she was found to have a large multicystic anterior mediastinal mass. The cystic appearance of mass and lack of constitutional symptoms contributed to favoring a benign cystic process and deferring surgical resection until the end of sport season. When surgery was performed 3 months later, microscopic examination showed findings diagnostic of classic Hodgkin lymphoma arising in a thymic cyst. Despite the rarity of such cases, it is important to remember that the cystic nature of an anterior mediastinal mass does not exclude lymphoma. Definitive diagnosis is not possible without examination of representative tissue. [ABSTRACT FROM AUTHOR]

Introduction: Lymphoma, encompassing common non-Hodgkin lymphoma (NHL) and less common Hodgkin lymphoma (HL), represents significant hematological malignancies. Advancements in treatment modalities have reshaped survival rates, particularly in NHL. This complexity results in varying outcomes, some requiring extended observation periods and multiple chemotherapy treatments. The primary objective was to explore and compare the overall survival (OS) of HL and NHL at 1, 3, and 5-year follow-ups among adult lymphoma patients in Qatar during January 2013–December 2017. Further objectives encompass comparing the most prevalent histological types, clinical and epidemiological traits of HL and NHL, as well as secondary aims of assessing clinical features, treatment, response, disease-free survival, and OS. Methods: A retrospective, descriptive study of consecutive cases was conducted at Qatar's NCCCR between 2013 and 2017. Inclusion criteria involved patients ≥18 years old, of any gender and clinical stage at diagnosis, who received chemotherapy and had known outcomes. Descriptive statistics were applied, and survival analysis utilized Kaplan-Meier curves. STATA version 13.0 facilitated data analysis. Results: Between 2013 and 2017, 414 individuals in Qatar were diagnosed with lymphoma. The median age at diagnosis was 49 years (IQR 36–95 years; p < 0.001) across all patients. Males exhibited a higher likelihood of developing HL and NHL, comprising 74% and 70% of cases, respectively, though this difference was statistically insignificant (p = 0.45). Among NHL-B subtypes, mature B-cell neoplasms (60%) predominated, while lymphocyte-rich subtype (49%) was prominent in HL cases. With a median follow-up of 17.3 months, OS rates at 1, 3, and 5 years were 99%, 82%, and 64%, respectively for all lymphoma patients. Subtype stratification revealed trends in 3-year follow-up OS (94 vs. 82%) for HL and NHL, with 5-year OS of 67% and 60%, respectively. HL demonstrated higher OS throughout the study period compared to NHL (p < 0.001), though median OS remained unreached. Conclusions: Diffuse large B-cell lymphoma emerged as the most prevalent subtype among lymphomas in Qatar. Generally, HL exhibited superior survival rates, at 67% compared to 60% for NHL. Minor deflation in survival rates, particularly for HL, might be attributed to Qatar's immigration patterns. [ABSTRACT FROM AUTHOR]

Classical Hodgkin lymphoma (CHL) is characterized by a proliferation of malignant cells of the lymphoreticular system and often involves lymph nodes, spleen, liver, and bone marrow; it is rare in the head and neck region. A 58-year-old man had an enlargement with ulceration in the left palatine tonsil that was causing dysphagia. Microscopic examination revealed an infiltrate of large, atypical lymphoid cells positive for cluster of differentiation 30, cluster of differentiation 15, PAX5, and Epstein-Barr virus. Complementary tests initially ruled out other sites of the disease. The results led to diagnosis of a rare development of CHL in the palatine tonsil, which was staged as IIEB. Before therapy was initiated, nodal lesions developed in the neck and the CHL was restaged as IIB. The patient was treated successfully with a regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine. After a review of the literature, the authors found only 3 cases with the clinical, imaging, and microscopic features of primary CHL of the palatine tonsil. Despite being a rare event, CHL may first develop in extranodal sites, such as the palatine tonsil. In this context, the role of the dentist is pivotal for early diagnosis of the disease. Investigations into the development of primary tonsillar CHL in the oropharynx are needed because the disease has a different clinical course than nodal lesions. [ABSTRACT FROM AUTHOR]

Patients with advanced‐stage Hodgkin lymphoma treated with ABVD who have a positive interim FDG‐PET (iPET) have a poor prognosis. Escalation to BEACOPP has been shown to improve progression‐free survival (PFS). However, randomized trials are lacking to determine the best strategy for intensification. We report on A‐AVD escalation treatment outcomes for 15 iPET‐positive patients post‐ABVD. Overall response and complete response rates were 80% and 60%, respectively. Four patients underwent salvage therapy followed by autologous stem cell transplantation. At a median 17‐month follow‐up, all patients are alive, 87% in complete remission, and 1‐year PFS was 57.8%. For patients ineligible for BEACOPP due to age, comorbidities, or preference, A‐AVD escalation may be a viable alternative. [ABSTRACT FROM AUTHOR]

Diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS) is the most common type of non-Hodgkin lymphoma (NHL). Significant efforts have been focused on utilizing advanced genomic technologies to further subclassify DLBCL, NOS into clinically relevant subtypes. These efforts have led to the implementation of novel algorithms to support optimal risk-oriented therapy and improvement in the overall survival of DLBCL patients. The pathogenesis of DLBCL at the molecular level indicates copy number variation (CNV) as one of the major forms of genetic alterations in the somatic mutational landscape. Random deregulation that results in complex breaks of chromosomes and restructuring of shattered chromosomal segments is called chromothripsis. Gene expression changes influenced by chromothripsis have been reported in cancer and congenital diseases. This chaotic phenomenon results in complex CNV, gene fusions, and amplification and loss of tumor suppressor genes. We present herein a summary of the most clinically relevant genomic aberrations, with particular focus on copy number aberrations in a case that highlights DLBCL, NOS arising from relapsed Hodgkin lymphoma. The focus of our study was to understand the relationship between the clinical, morphological, and genomic abnormalities in DLBCL, NOS through multiple techniques for therapeutic considerations. [ABSTRACT FROM AUTHOR]

Rationale: Warthin tumor (WT) is the second most common benign tumor in salivary gland. It has a slow growth rate and most frequently occurs in the parotid gland. Most patients present with an incidental finding of a painless mass inferior/anterior to the ear. Besides the epithelial component of the tumor, WT is characteristically associated with lymphoid stroma that is considered benign. While there have been a few reports of malignant transformation of the lymphoid components in WT, cases of WT concomitant with mantle cell lymphoma (MCL) are extremely rare. To the best of our knowledge, two cases have been described in the English literature. Herein, we report a case of WT concomitant with MCL in a 70-year-old female patient, and emphasize the importance of careful examination of lymphoid stroma in WT so that concurrent lymphoma is not missed. Patient concerns: A 70-year-old Chinese woman with a 40-year history of cigarette smoking presented with a one year history of a right submaxillary mass with recent enlargement. Diagnosis: Cervical ultrasound (US) and computed tomography (CT) scans of the neck revealed a well-circumscribed mass in the right parotid with a maximum diameter of 3.1 cm. Surgical resection of the mass was performed. Histopathological examination revealed a characteristic double-layer of neoplastic epithelium with prominent lymphoid stroma, suggesting WT. In addition, morphology and immunohistochemistry studies confirmed the coexistence of MCL. Thereafter, the final diagnosis of this case was WT concomitant with MCL. Interventions: The patient was staged as stage I after clinical assessment. Due to the slow growth of parotid lesions, close observation was decided with periodic clinical and radiological monitoring. Outcomes: Currently, the patient demonstrates a stable disease by clinical evaluation. Lessons: To the best of our knowledge, reported cases of WT concomitant with MCL are very rare. This case highlights the importance of a comprehensive assessment of the lymphoid stroma of WT to avoid missed diagnosis of a lymphoma component in a collision tumor. [ABSTRACT FROM AUTHOR]

Simple Summary: Three-dimensional (3D) telomere analysis using TeloView v 2.2 has shown promise in quantifying genomic instability and predicting therapy response. In a study of 156 Classic Hodgkin's lymphoma (cHL), we identified significant 3D telomere parameters that predict patient outcomes. A predictive model using four 3D telomere parameters, including the proportion of t-stumps (very short telomeres), achieved an area under curve (AUC) of 0.83, with a sensitivity and specificity of 0.82 and 0.78, respectively. Classic Hodgkin's lymphoma (cHL) is a curable cancer with a disease-free survival rate of over 10 years. Over 80% of diagnosed patients respond favorably to first-line chemotherapy, but few biomarkers exist that can predict the 15–20% of patients who experience refractory or early relapsed disease. To date, the identification of patients who will not respond to first-line therapy based on disease staging and traditional clinical risk factor analysis is still not possible. Three-dimensional (3D) telomere analysis using the TeloView® software platform has been shown to be a reliable tool to quantify genomic instability and to inform on disease progression and patients' response to therapy in several cancers. It also demonstrated telomere dysfunction in cHL elucidating biological mechanisms related to disease progression. Here, we report 3D telomere analysis on a multicenter cohort of 156 cHL patients. We used the cohort data as a training data set and identified significant 3D telomere parameters suitable to predict individual patient outcomes at the point of diagnosis. Multivariate analysis using logistic regression procedures allowed for developing a predictive scoring model using four 3D telomere parameters as predictors, including the proportion of t-stumps (very short telomeres), which has been a prominent predictor for cHL patient outcome in a previously published study using TeloView® analysis. The percentage of t-stumps was by far the most prominent predictor to identify refractory/relapsing (RR) cHL prior to initiation of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) therapy. The model characteristics include an AUC of 0.83 in ROC analysis and a sensitivity and specificity of 0.82 and 0.78 respectively. [ABSTRACT FROM AUTHOR]

Hodgkin lymphoma (HL) is a rare lymphoid neoplasm in which Hodgkin/Reed–Stenberg (HRS) cells are admixed with a population of non-neoplastic inflammatory cells and fibrosis. Dysregulated expressions of cell cycle regulators and transcription factors have been proven as one of the hallmarks of HL. In that context, SATB1 and p16 have been reported as potential regulators of HL progression and survival. However, to date, no studies have assessed the expression levels of SATB1 and p16 in HL in Croatian patients or their prognostic values. Therefore, we investigated the expression pattern of SATB1 and p16 in paraffin-embedded lymph node biopsies using standard immunohistochemistry. We found that 21% of the patients stained positive for SATB1, while 15% of the patients displayed positive staining for p16. Furthermore, we aimed to understand the prognostic value of each protein through the analysis of the overall survival (OS) and progression-free survival (PFS). SATB1 showed a significantly positive correlation with better OS and PFS, while p16 expression had no impact. Interestingly, when patients were stratified by a combination of the two studied markers, we found that patients in the SATB1+/p16- group tended to have the best prognosis in HL, according to statistical significance. In conclusion, SATB1 and p16 might be potentially useful as diagnostic and prognostic markers for HL. [ABSTRACT FROM AUTHOR]

Bleomycin is an antibiotic with cytotoxic properties that is commonly used in combination regimens for the treatment of Hodgkin lymphoma. The inconsistency in the dosage nomenclature of bleomycin appears universally, which increases the risk of medication errors. However, to the best of our knowledge, no such cases have been reported. Herein, we present a rare case report of a medication error caused by a bleomycin overdose. At the third cycle of chemotherapy, a 25‐year‐old patient with stage II Hodgkin lymphoma received a 10 times higher dose of bleomycin (150 USP) than that usually used as part of the doxorubicin, bleomycin, vindesine and dacarbazine protocol (ABVD). After the medication error was discovered, the patient was immediately treated with intravenous rehydration and furosemide to promote drug clearance. Additionally, methylprednisone and acetylcysteine were administered to prevent lung injury. However, the patient developed slight nausea and mild rash, which gradually improved after treatment. After evaluation with positron emission spectrometry‐computed tomography (PET‐CT), the patient received four cycles of AVD chemotherapy. No other obvious abnormalities were observed during the treatment and 1‐year follow‐up period. Hence, the toxicities, clinical management and selection of further chemotherapy after bleomycin overdose in such cases deserved serious attention. More importantly, management measures after this error may be used as a reference in other hospitals. [ABSTRACT FROM AUTHOR]

Summary: Late toxicities can impact survivorship in patients with classical Hodgkin lymphoma (cHL) with pulmonary toxicity after bleomycin‐containing chemotherapy being a concern. The incidence of pulmonary diseases was examined in this Danish population‐based study. A total of 1474 adult patients with cHL treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or BEACOPP (bleomycin, vincristine, etoposide, doxorubicin, cyclophosphamide, procarbazine and prednisone) between 2000 and 2018 were included along with 7370 age‐ and sex‐matched comparators from the background population. Median follow‐up was 8.6 years for the patients. Patients with cHL had increased risk of incident pulmonary diseases (HR 2.91 [95% CI 2.30–3.68]), with a 10‐year cumulative risk of 7.4% versus 2.9% for comparators. Excess risks were observed for interstitial lung diseases (HR 15.84 [95% CI 9.35–26.84]) and chronic obstructive pulmonary disease (HR 1.99 [95% CI 1.43–2.76]), with a 10‐year cumulative risk of 4.1% and 3.5% respectively for patients. No excess risk was observed for asthma (HR 0.82 [95% CI 0.43–1.56]). Risk factors for interstitial lung diseases were age ≥60 years, the presence of B‐symptoms and low albumin. These findings document a significant burden of pulmonary diseases among patients with cHL and emphasize the importance of diagnostic work‐up of pulmonary symptoms. [ABSTRACT FROM AUTHOR]

Secondary breast cancer is a frequent late adverse event of mediastinal Hodgkin lymphoma radiotherapy. Secondary breast cancers overwhelmingly correspond to ductal carcinoma and develop from the glandular mammary tissue. In addition, during childhood, radiation overexposure of the glandular tissue may lead to a late breast hypotrophy at adult age. The aim of this study was to evaluate the radiation exposure to the glandular tissue in patients treated for mediastinal Hodgkin lymphoma with intensity-modulated proton therapy, in order to evaluate the potential dosimetric usefulness of its delineation for breast sparing. Sixteen consecutive intermediate-risk mediastinal female patients with Hodgkin lymphoma treated with consolidation radiation with deep inspiration breath hold intensity-modulated proton therapy to the total dose of 30 Gy were included. Breasts were delineated according to the European Society for Radiotherapy and Oncology guidelines for treatment optimization ("clinical organ at risk"). The glandular tissue ("glandular organ at risk") was retrospectively contoured on the initial simulation CT scans based on Hounsfield unit (HU) values, using a range between −80 HU and 500 HU. The mean and maximum doses delivered to the glandular organ at risk were significantly lower than the mean and maximum doses delivered to the clinical organ at risk, but were statistically correlated. Glandular organ at risk volumes were significantly smaller. Optimizing the treatment plans on the clinical breast contours will systematically lead to overestimation of the dose received to the glandular tissue and, consequently, to an indistinct and involuntary improved glandular tissue sparing. As such, our findings do not support the consideration of the glandular tissue as an additional organ at risk when planning intensity-modulated proton therapy for mediastinal Hodgkin lymphoma in female patients. [ABSTRACT FROM AUTHOR]

Current studies describing younger children with Hodgkin lymphoma are limited by geographical region, small sample sizes and variable age groups. Although published data is lacking, there appears to be a trend toward a higher male to female ratio and a higher proportion of mixed cellularity subtype when compared to older cohorts. We performed a retrospective multicenter study utilizing the Pediatric Health Information System® database to evaluate patients aged 0–39 years with Hodgkin lymphoma. We identified 3,034 unique patients who met inclusion criteria. Younger age groups had a larger proportion of males, Hispanic/Latino ethnicity, and mixed cellularity subtype. Treatment-related complications, including mucositis, pain, bacterial infections, and thrombosis, were documented more frequently in older cohorts. We also found significant age-related differences in medical management. This study is the largest study evaluating age-related differences in patients with Hodgkin lymphomaand the first study to evaluate for differences in complicationsand supportive care management. [ABSTRACT FROM AUTHOR]

Angioimmunoblastic T-cell lymphoma was reclassified a subtype of nodal T-follicular helper cell lymphoma (nTFHL-AI) in the 5th Edition of the World Health Organization Classification of Haematolymphoid Tumours. It is now grouped with related entities upon recent discovery of a shared T-follicular helper (TFH) cell origin. Numerous studies attest to the many peculiar presentations that impede recognition of the disease. Surgical biopsy is often required to secure a diagnosis though is rarely the first-line intervention. Delayed or missed diagnosis has a high price. Advanced stage of disease at presentation is common and rates of relapse are high. There is an unmet need for earlier detection and improved outcomes. Here we present a case which showed some quintessential clinicopathologic features of nTFHL-AI, and an approach to discerning these is discussed. [ABSTRACT FROM AUTHOR]

Non-Hodgkin lymphomas (NHLs) encompass a diverse group of malignancies arising from B cells, T cells, and natural killer (NK) cells at various stages of differentiation. Conversely, classical Hodgkin lymphomas (cHLs) primarily feature Reed-Sternberg cells (RSCs) amid a background of reactive immune cells. Immunomodulatory pathways, notably the PD-1/PD-L1 axis, play pivotal roles in tumor immune evasion across both NHLs and cHLs. Elevated expression of PD-1 and PD-L1 is observed in a spectrum of lymphomas, influencing prognosis and treatment response. Therapeutically, immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have revolutionized lymphoma management, particularly in relapsed/refractory cases. Nivolumab and pembrolizumab, among others, have demonstrated efficacy in various B-cell lymphomas, with promising outcomes in cHL. Combination strategies incorporating ICIs with conventional chemotherapy or targeted agents show enhanced efficacy and are being explored extensively. In this review we discuss the most important features of the tumor microenvironment of NHLs and cHLs, address the therapeutic approaches with ICIs and try to outline future perspectives. [ABSTRACT FROM AUTHOR]

Thymic regulatory lymphocytes (Tregs) are rare in the normal periphery where they mediate immune tolerance but accumulate in the tumor immune microenvironment (TIM), reducing the antitumor response. Subtypes of classical Hodgkin lymphoma (CHL) are characterized by a minority of malignant Hodgkin and Reed–Sternberg cells (HRS) and an abundant TIM that plays a key role in modulating the disease. CHL is related to the Epstein–Barr virus (EBV), whose oncogenes influence the growth of HRS. We analyzed the number of T lymphocytes expressing the regulatory marker FOXP3 in CHL with regard to EBV status. The tumor tissue of 182 patients was stained by double immunohistochemistry for FOXP3, CD4, and CD8, and the number of different phenotypes was analyzed microscopically. EBV status was determined by EBER in situ hybridization. EBV-positive CHL was confirmed in 28% of patients and was associated with mixed cellularity (MC) (p < 0.001), older age (p < 0.001), and unfavorable outcomes (p = 0.038). The number of CD8+ T lymphocytes differed according to the EBV status of MC and nodular sclerosis (NS), and was the lowest in EBV-negative NS (p = 0.001). Likewise, the numbers for FOXP3 and FOXP3/CD4 were different, and were the lowest in EBV-negative MC (p = 0.035 and p = 0.041, respectively). Values above a median of FOXP3 and CD4 are associated with longer progression-free survival (p = 0.039 and p < 0.001, respectively). EBV impacts the composition of T cell phenotypes in TIM, among which the amount of CD4 and FOXP3 is prognostically valuable. [ABSTRACT FROM AUTHOR]

Despite the high rate of cure in classical Hodgkin Lymphoma (cHL), some patients experienced a refractory disease, sometimes, hardly curable. In the pathogenesis of cHL, Reed Sternberg Cells (HRSC), which represent only less than 1% of tumor cells, are not the only protagonist; in fact, the role of tumor microenvironment is essential in survival, tumor growth, and progression of the disease due to the interaction between immune cells, chemokines, and cytokines. In this review, the current significant literature was discussed. Many studies demonstrated the role of macrophages CD68+ as 'protumor', especially in supporting HRSC survival through cell-to-cell and paracrine interactions. Increased infiltration of CD68 macrophages correlate with a poor prognosis. This review examines the interaction between CD68 macrophages, HRSC and cHL milieu, and the consequent clinical impact, providing an up-do-date portrait of these immune cells with possible translational and therapeutic applications. We can suggest that a high baseline CD68 macrophages in cHL patients could contribute to the identification of high-risk patients and help clinicians to choose the best treatment, in the context of refractory disease. A macrophage target strategy in association with chemotherapy or biological therapy could represent a promising approach for future studies and investigations. [ABSTRACT FROM AUTHOR]

Background and Objectives: The overall- and progression-free survival rates of Hodgkin's lymphoma patients have improved. Our goal was to examine the changes in our treatment results and their causes depending on the daily diagnostic and therapeutic practice. Materials and Methods: We analysed data of 776 classical Hodgkin lymphoma patients treated between 1980 and 2019. Patient data were investigated in ten-year periods (first period: 1980–1989, second period: 1990–1999, third period: 2000–2009, and fourth period: 2010–2019). Results: Radiotherapy alone as a first-line treatment was used progressively less often, and in the 4th period it was no longer used before or without chemotherapy. The use of combined chemo- and radiotherapy decreased in the last period, and the number of those patients who received only chemotherapy increased significantly. The 10-year overall survival improved significantly from 1990 to 1999 compared to 2010 to 2019 (74.9% vs. 86.9%). About 30% of patients relapsed after or were refractory to first-line therapy in each period. The incidence of relapse in the last period did not increase after two years, but there was no significant difference between the periods. Conclusions: Overall survival rates of HL patients have improved significantly in recent decades, which is due to improved diagnostic methods and modern therapies. Progression-free survival is unchanged; one-third of patients relapse or are refractory to first-line treatment within the first two years. Early recognition of R/R patients, the early application of newer and already available innovative therapies, and the finding of additional new and effective therapies are of particular importance. [ABSTRACT FROM AUTHOR]

Objective: Twenty percent of all classical Hodgkin lymphoma (CHL) cases relapse and recur, especially in advanced stages with a high International Prognostic Score (IPS). Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a regulatory molecule that can inhibit the immune response and is related to tumor aggressiveness. This study aimed to determine the relationship between CTLA-4 expression in advanced-stage CHL and IPS, identifying it as a potential therapy target. Results: In advanced-stage CHL, the group with a high IPS exhibited significantly higher mean CTLA-4 expression compared to the group with a low IPS (p = 0.003).The group with Hb level < 10.5 g/dl, leukocyte count > 15,000/µL, lymphocyte count < 8%, albumin level < 4 g/dl, and stage 4 exhibited higher CTLA-4 expression than the other group, although only leukocyte count and stage showed statistical significance (p = 0.004 and p = 0.020). Mean CTLA-4 expression was 239.84 ± 76.36 for nodular sclerosis, 293.95 ± 147.94 for mixed cellularity, 271.4 ± 23.56 for lymphocyte depleted, and 225.2 for lymphocyte-rich subtypes. The results suggest that CTLA-4 expression is associated with adverse prognostic factors in the IPS for advanced-stage CHL, supporting the notion that immune checkpoints play a role in cancer progression. [ABSTRACT FROM AUTHOR]

Hodgkin lymphoma (HL) represents a neoplasm primarily affecting adolescents and young adults, necessitating the development of precise diagnostic and monitoring tools. Specifically, classical Hodgkin lymphoma (cHL), comprising 90% of cases, necessitating tailored treatments to minimize late toxicities. Although positron emission tomography/computed tomography (PET/CT) has enhanced response assessment, its limitations underscore the urgency for more reliable progression predictive tools. Genomic characterisation of rare Hodgkin Reed-Sternberg (HRS) cells is challenging but essential. Recent studies employ single-cell molecular analyses, mass cytometry, and Next-Generation Sequencing (NGS) to unveil mutational landscapes. The integration of liquid biopsies, particularly circulating tumor DNA (ctDNA), extracellular vesicles (EVs), miRNAs and cytokines, emerge as groundbreaking approaches. Recent studies demonstrate ctDNA's potential in assessing therapy responses and predicting relapses in HL. Despite cHL-specific ctDNA applications being relatively unexplored, studies emphasize its value in monitoring treatment outcomes. Overall, this review underscores the imperative role of liquid biopsies in advancing HL diagnosis and monitoring. [ABSTRACT FROM AUTHOR]

Background. Tuberculosis (TB) remains the most common infectious disease that kills people worldwide. The occurrence of cancer and Tuberculosis is rare, yet they are the major causes of illness and mortality worldwide. Case presentation. We present four cases of female patients with primary malignancy and Tuberculosis (TB). The first case was diagnosed histopathologically as TB and nodular sclerosis subtype Hodgkin lymphoma. The other two cases were invasive breast carcinoma with TB, and the final case was nasopharyngeal carcinoma with TB. All four patients received six months of antituberculosis medication, followed by anticancer treatment. Conclusion. The probability of coexisting TB and cancer necessitates a thorough histological evaluation to minimize diagnostic failure and hence treatment errors. [ABSTRACT FROM AUTHOR]

Previously, we showed that quantification of lymphoma‐associated miRNAs miR‐155‐5p, ‐127‐3p and let‐7a‐5p levels in plasma extracellular vesicles (EVs) report treatment response in patients with classic Hodgkin lymphoma (cHL). Prior to clinical implementation, quality control (QC) steps and validation are required to meet international regulatory standards. Most published EV‐based diagnostic assays have yet to meet these requirements. In order to advance the assay towards regulatory compliance (e.g., IVDR 2017/746), we incorporated three QC steps in our experimental EV‐miRNA quantitative real‐time reverse‐transcription PCR (q‐RT‐PCR) assay in an ISO‐13485 certified quality‐management system (QMS). Liposomes encapsulated with a synthetic (nematode‐derived) miRNA spike‐in controlled for EV isolation by automated size‐exclusion chromatography (SEC). Additional miRNA spike‐ins controlled for RNA isolation and cDNA conversion efficiency. After deciding on quality criteria, in total 107 out of 120 samples from 46 patients passed QC. Generalized linear mixed‐effect modelling with bootstrapping determined the diagnostic performance of the quality‐controlled data at an area under the curve (AUC) of 0.84 (confidence interval [CI]: 0.76–0.92) compared to an AUC of 0.87 (CI: 0.80–0.94) of the experimental assay. After the inclusion of QC steps, the accuracy of the assay was determined to be 78.5% in predicting active disease status in cHL patients during treatment. We demonstrate that a quality‐controlled plasma EV‐miRNA assay is technically robust, taking EV‐miRNA as liquid biopsy assay an important step closer to clinical evaluation. [ABSTRACT FROM AUTHOR]

Aim: To describe a rare case of primary refractory Hodgkin lymphoma nodular sclerosis syncytial variant in a child and review immunotherapy in relapsed/refractory Hodgkin lymphoma. Methods: We described the treatment course of a child with primary refractory classic Hodgkin lymphoma and discussed different options for salvage therapy, with an emphasis on immunotherapy. We searched PubMed for all published clinical trials investigating immunotherapy in classic Hodgkin lymphoma written in English until 31 June, 2023. The reference list of each identified paper was searched for additional publications. Results: Our patient was salvaged with anti‐programmed cell death 1 (PD‐1) antibody therapy followed by high‐dose chemotherapy with autologous stem cell rescue. Radiotherapy was avoided. We identified five one‐armed phase II trials investigating anti‐PD‐1 therapy in first relapse/refractory disease in a total of 254 patients aged 9–71 years, of which one included 31 children. The complete remission rate before high‐dose chemotherapy was 59%–95% overall and 67%–89% among those with refractory disease. Conclusion: Although it remains to be proven in randomised trials, anti‐PD‐1 therapy may provide higher complete response rates than traditional chemotherapy. Anti‐PD‐1 therapy has the potential to increase the chance of cure while decreasing the risk of late effects from chemotherapy and radiotherapy. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess thyroid function and lesions after radiotherapy to the head and neck region in children with Hodgkin lymphoma (HL) or central nervous system (CNS) tumors. Material and Methods: The study included children diagnosed with HL or CNS tumors who were in complete remission at least one year after completion of chemotherapy (CT) and who had all received radiotherapy (RT) to the head and/or neck. All patients were requested to undergo thyroid function tests and thyroid ultrasonography (USG). Results: A total of 37 patients were included. The mean age was 13.7±3.8 years. The mean follow-up time was 5.09±2.5 years. All patients had CT and RT. Seven (18.9%) patients had subclinical hypothyroidism, and 7 (18.9%) had thyroid USG abnormalities. None of the patients had thyroid malignancy. Age under 10 years at diagnosis, follow-up time of 3 years or more, and an RT dose of 25 Gy or more were found as effective factors for subclinical hypothyroidism development. Only an RT dose of 25 Gy or more was found to be related to thyroid USG abnormalities. Conclusion: Thyroid function tests and thyroid imaging should be routinely examined in any patient who has been treated for cancer to evaluate thyroid dysfunction regardless of clinical findings and the follow-up of these patients should be lifelong. [ABSTRACT FROM AUTHOR]

In oncological imaging, the use of metabolic tumor volume (MTV) for further prognostic differentiation and the development of risk adapted strategies appears promising. The aim of this analysis was to evaluate ultra-high definition (UHD) and ordered subset expectation maximization (OSEM) PET/CT reconstructions for their potential impact on different methods of MTV measurement. We analyzed positron emission tomography combined with computed tomography (PET/CT) scans of 40 Hodgkin lymphoma patients before first-line treatment who had undergone fluorodeoxyglucose (FDG) PET/CT. The MTVs were determined taking an SUV of 4.0 (MTV4.0) as a fixed threshold or 41% of the single hottest voxel (MTV41%) as an adaptive threshold for automated lymphoma delineation in both UHD and OSEM reconstructions. We then compared the absolute and relative differences between MTV4.0 and MTV41% in UHD and OSEM reconstructions. The relative distribution of MTV4.0 and MTV41% in relation to the reconstruction method applied was recorded and respective differences were tested for statistical significance using the paired sample t-test. A comparison of MTV4.0 and MTV41% showed smaller relative and absolute differences in MTV between different reconstruction settings for the MTV4.0 method. Conversely, the absolute as well as the relative differences between MTVs obtained from different reconstructions settings were significantly greater when the MTV41% method was applied (p < 0001). MTV4.0 brings higher robustness between different reconstruction settings, while with MTV41% the deviation between volumes obtained with different reconstruction settings is greater. For clinical routine and for multicenter settings, the MTV4.0 therefore appears most promising. [ABSTRACT FROM AUTHOR]

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Hodgkin lymphoma is histologically characterised by the presence of Hodgkin (H) and Reed‐Sternberg (RS) cells originating from germinal centre B‐cells rearranged in the IgV gene. The formation of multinucleated RS cells is a product of telomere organisation in a process initiated by telomere aggregate accumulation in mononuclear H cells and may be mediated by latent membrane protein 1 (LMP‐1) expression. LMP‐1 is the main oncoprotein of EBV and supports several tumourigenic processes. LMP‐1 may rescue proapoptotic B‐cells through downregulation of B‐cell receptor (BCR) components, mimicking and inducing multiple distinct B‐cell signalling pathways to promote proliferation and survival, such as Janus kinase‐signal transducer and activator of transcription (JAK‐STAT), nuclear factor‐kappa b (NF‐кB), and cellular MYC (c‐MYC), and inducing telomere instability mainly through Telomere repeat binding factor 2 (TRF2) downregulation to promote the formation of multinucleated RS cells. This review presents recent discoveries regarding the influence of LMP‐1 on the surviving cellular signalling, genomic instability and mecanical formation of HRS cells. [ABSTRACT FROM AUTHOR]

Most patients with classic Hodgkin lymphoma (cHL) are cured with combination chemotherapy, but approximately 10-20% will relapse, and another 5-10% will have primary refractory disease. The treatment landscape of relapsed/refractory (R/R) cHL has evolved significantly over the past decade following the approval of brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, and the PD-1 inhibitors nivolumab and pembrolizumab. These agents have significantly expanded options for salvage therapy prior to autologous hematopoietic cell transplantation (AHCT), post-transplant maintenance, and treatment of relapse after AHCT, which have led to improved survival in the modern era. In this review, we highlight our approach to the management of R/R cHL in 2023 with a focus on choosing first salvage therapy, post-transplant maintenance, and treatment of relapse after AHCT. We also discuss the management of older adults and transplant-ineligible patients, who require a separate approach. Finally, we review novel immunotherapy approaches in clinical trials, including combinations of PD-1 inhibitors with other immune-activating agents as well as novel antibody-drug conjugates, bispecific antibodies, and cellular immunotherapies. Ongoing studies assessing biomarkers of response to immunotherapy and dynamic biomarkers such as circulating tumor DNA may further inform treatment decisions and enable a more personalized approach in the future.

Patients diagnosed with Hodgkin lymphoma (HL) have improved survival because of the early use of effective therapies and positron emission tomography (PET) – adapted strategies. However, long-term observational studies have shown that HL survivors have an increased risk of secondary cancers and other complications, which include cardiovascular disease, infertility and endocrinopathies. Therefore, long-term follow-up and screening of HL survivors is important. Contribution: We report a case of a 22-year-old female with chondroblastic osteosarcoma following treatment of HL. We have devised a simple screening algorithm to ensure comprehensive long-term surveillance of HL survivors.