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Richter transformation (RT) is a rare sequelae of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). The clonal relationship of the RT to the underlined CLL/SLL is an important prognostic factor as clonally related RT has a worse prognosis than that of clonally unrelated RT. The development of more than one RT in the same patient is exceedingly rare and prior reports have shown cases consisting of RT to diffuse large B‐cell lymphoma (DLBCL) and a subsequent or synchronous Hodgkin lymphoma. Here, we present a rare case of RT first to a clonally unrelated DLBCL and subsequently a clonally related DLBCL. Additionally, we retrospectively conducted next‐generation sequencing studies of both RT's and found different mutational landscapes, including more clinically aggressive mutations identified in the clonally related RT. To our knowledge, this is the first reported case of clonally related and clonally unrelated RT, both of which are DLBCL, in the same patient. [ABSTRACT FROM AUTHOR]

Background: Ewing sarcoma is a malignant round-cell tumor that primarily affects bones in children. It can also arise in extraosseous tissues, such as the lung, kidneys, and liver. The presentation symptoms of Ewing sarcoma may include cough, dyspnea, and chest pain. Case presentation: This report details the history of a 15-year-old Syrian boy with a previous diagnosis of Hodgkin lymphoma who presented with chronic shoulder pain. Imaging studies revealed an 80 mm mass in the apex of the left lung, which was confirmed through histopathological examination to be Ewing sarcoma following a computed-tomography-guided biopsy. The patient received multiple cycles of chemotherapy and subsequently underwent surgical resection of the remaining mass. Conclusions: This case highlights the rare occurrence of Ewing sarcoma in the lung and the unusual clinical presentation of shoulder pain without other accompanying symptoms. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article on the classification of mature B, T, and NK-cell neoplasms. The original article had errors in Table 1, which have been corrected in this document. The corrected table compares the classification of different types of lymphomas according to various classifications. The document provides a comprehensive overview of the different types of lymphomas, including subtypes of large B-cell lymphomas and other types associated with immune deficiency and dysregulation. [Extracted from the article]

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]

Background: Juvenile dermatomyositis (JDM) is a rare autoimmune myopathy whose main clinical manifestations include a characteristic rash, symmetrical proximal muscle weakness, and elevated muscle enzymes. While approximately one-third of adult patients with dermatomyositis (DM) develop malignancies, typically within a year of diagnosis, this phenomenon is not commonly observed in patients with JDM. In this study, we present a rare case of both JDM and Hodgkin's lymphoma (HL) diagnosed in an adolescent female patient. Case description: A 14-year-old girl with proximal muscle weakness and myalgia for 8 weeks was admitted to the hospital and ultimately received a diagnosis of DM. A thorough physical examination revealed enlarged lymph nodes on both sides of the cervical, and a lymph node biopsy was performed to diagnose HL. After she underwent radiotherapy and chemotherapy, her symptoms of both HL and DM were alleviated. Conclusion: The phenomenon of JDM as a paraneoplastic syndrome associated with HL is very rare. Thus, routine cancer screening for DM in adolescents is currently not recommended. The diagnosis of JDM requires a detailed physical examination, and further tumor screening is necessary for patients with unusual physical findings, such as atypical rashes, enlarged lymph nodes, and enlargement of the spleen and/or liver. Even if no malignancy is detected when JDM is diagnosed, long-term follow-up is necessary. [ABSTRACT FROM AUTHOR]

The article focuses on Google's recent chatbot enhancements and their impact on business communication and includes the introduction of new features to Google's chatbot, how these features aim to improve user interactions, and the potential effects on corporate productivity and efficiency.

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]

This case report describes a 16-year-old patient with refractory Hodgkin's lymphoma who developed bilateral anterior and intermediate uveitis as an adverse reaction to Brentuximab vedotin (BV). This is a rare case of an ocular adverse reaction potentially related to BV, with symptoms like blurred vision, decreased visual acuity, photophobia, and redness. Potential mechanisms include BV targeting CD30+ T cells in the uveal tissue or an immune response triggered by the microtubule-disrupting agent MMAE within BV. This highlights the need for vigilant monitoring of ocular adverse events in BV-treated patients and further research into their mechanisms and management. [ABSTRACT FROM AUTHOR]

Introduction: The current treatment regimens for Hodgkin's lymphoma (HL) are associated with high incidences of adverse events. Purpose: This study aimed to compare the efficacy and safety of doxorubicin + bleomycin + vincristine + dacarbazine (ABVD) and standard bleomycin + etoposide + doxorubicin + cyclophosphamide + vincristine + procarbazine + prednisone (BEACOPP) chemotherapy in the treatment of advanced stage HL. Methods: This multicenter, randomized, parallel, open, positive control noninferiority trial was conducted from 2016 to 2019 and comprised 93 subjects who were randomized in a 1:1 ratio between the treatment (BEACOPP; n = 44) and control (ABVD; n = 49) groups. Results: The primary efficacy endpoint of this trial was the objective response rate (ORR) after eight cycles of chemotherapy, which was 100.00% (36/36) in the treatment group and 95.74% (45/49) in the control group. The incidence of adverse reactions was 100% in both groups. Significant differences (P < 0.05) in the incidences of grade 3 (39/44 [88.64%] vs. 23/49 [46.94%]) and grade 4 (27/44 [61.36%] vs. 8/49 [16.94%]) adverse events were observed between the treatment and control groups, respectively. However, most of these reactions were manageable, with no serious consequences, and were reversible after discontinuation of the treatment. Conclusion: Both regimens had a similar ORR and were associated with a high number of adverse events. The ABVD regimen was better tolerated and safer than the standard BEACOPP regimen. This study indicates that the standard BEACOPP regimen may be considered as a treatment option for patients with advanced HL. [ABSTRACT FROM AUTHOR]

Background: 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. [ABSTRACT FROM AUTHOR]

A 30-year-old woman had 5 days of visual hallucinations, nystagmus, memory impairment and mutism. On examination, she was disorientated with reduced attention span, gazeevoked nystagmus, paratonia and abnormal frontal reflexes. Cerebrospinal fluid (CSF) showed 80 cells, protein 0.41 g/L and glucose 3.2 mmol/L (plasma glucose 5.0 mmol/L). MR scan of the brain showed involvement of limbic and extra-limbic regions and brainstem. Commercial cell-based assays were negative, but tissue-based assays showed neuropil staining, and cell-based assays for anti-metabotropic glutamate receptor 5 (mGluR5) antibodies were positive in serum and CSF. Six months later, she was diagnosed with Hodgkin's lymphoma. This case emphasises the broader clinical spectrum of anti-mGluR5 encephalitis, challenging its initial characterisation as Ophelia syndrome. It underscores the significance of interpreting commercial cell- based assays and advocates for tissue-based assay testing followed by cell-based assay testing in serum and CSF for diagnosing rare autoimmune encephalitis. [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]

The knowledge surrounding the application of immune checkpoint inhibitors (ICIs) in the treatment of pediatric cancers is continuously expanding and evolving. These therapies work by enhancing the body's natural immune response against tumors, which may have been suppressed by certain pathways. The effectiveness of ICIs in treating adult cancers has been widely acknowledged. However, the results of early phase I/II clinical trials that exclusively targeted the use of ICIs for treating different pediatric cancers have been underwhelming. The response rates to ICIs have generally been modest, except for cases of pediatric classic Hodgkin lymphoma. There seems to be a notable disparity in the immunogenicity of childhood cancers compared to adult cancers, potentially accounting for this phenomenon. On average, childhood cancers tend to have significantly fewer neoantigens. In recent times, there has been a renewed sense of optimism regarding the potential benefits of ICI therapies for specific groups of children with cancer. In initial research, individuals diagnosed with pediatric hypermutated and SMARCB1-deficient cancers have shown remarkable positive outcomes when treated with ICI therapies. This is likely due to the underlying biological factors that promote the expression of neoantigens and inflammation within the tumor. Ongoing trials are diligently assessing the effectiveness of ICIs for pediatric cancer patients in these specific subsets. This review aimed to analyze the safety and effectiveness of ICIs in pediatric patients with different types of highly advanced malignancies. [ABSTRACT FROM AUTHOR]

Classical Hodgkin lymphoma (cHL) is a common B-cell cancer and a significant health concern, especially in Western and Asian countries. Despite the effectiveness of chemotherapy, many relapse cases are being reported, highlighting the need for improved treatments. This study aimed to address this issue by discovering biomarkers through the analysis of gene expression data specific to cHL. Additionally, potential anticancer inhibitors were explored to target the discovered biomarkers. This study proceeded by retrieving microarray gene expression data from cHL patients, which was then analyzed to identify significant differentially expressed genes (DEGs). Functional and network annotation of the upregulated genes revealed the active involvement of matrix metallopeptidase 12 (MMP12) and C-C motif metallopeptidase ligand 22 (CCL22) genes in the progression of cHL. Additionally, the mentioned genes were found to be actively involved in cancer-related pathways, i.e., oxidative phosphorylation, complement pathway, myc_targets_v1 pathway, TNFA signaling via NFKB, etc., and showed strong associations with other genes known to promote cancer progression. MMP12, topping the list with a logFC value of +6.6378, was selected for inhibition using docking and simulation strategies. The known anticancer compounds were docked into the active site of the MMP12 molecular structure, revealing significant binding scores of −7.7 kcal/mol and −7.6 kcal/mol for BDC_24037121 and BDC_27854277, respectively. Simulation studies of the docked complexes further supported the effective binding of the ligands, yielding MMGBSA and MMPBSA scores of −78.08 kcal/mol and −82.05 kcal/mol for MMP12-BDC_24037121 and −48.79 kcal/mol and −49.67 kcal/mol for MMP12-BDC_27854277, respectively. Our findings highlight the active role of MMP12 in the progression of cHL, with known compounds effectively inhibiting its function and potentially halting the advancement of cHL. Further exploration of downregulated genes is warranted, as associated genes may play a role in cHL. Additionally, CCL22 should be considered for further investigation due to its significant role in the progression of cHL. [ABSTRACT FROM AUTHOR]

Anti-DNER antibody is associated with paraneoplastic cerebellar degeneration (PCD) and Hodgkin's disease (HD). However, recent studies reported cases absence of HD and that non-tumor anti-DNER antibody-associated ataxia was not well characterized. We present a case of acute cerebellar ataxia and nystagmus with detected anti-DNER antibody. Brain magnetic resonance imaging (MRI) showed cerebellar atrophy. High titer of anti-DNER antibody was detected in CSF and serum. Positron emission tomography (PET) scanning was unremarkable at a 10-month follow up. The patient improved significantly after immunosuppressive therapy with intravenous steroids, immunoglobulin followed by rituximab. Our study suggest that the presence of such anti-neuronal antibodies might not come along with malignancy and that early onset non-tumor patients are more likely to have a better outcome after immunotherapy. Early diagnosis and timely immunosuppressive therapy may prove beneficial for these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Using the Proton Therapy Collaborative group registry, we describe the impact of pencil beam scanning (PBS) proton beam therapy (PBT) for Hodgkin lymphoma patients who require radiation to both mediastinal and axillary targets. We performed dosimetric comparisons between delivered PBS plans and photons with butterfly volumetric arc therapy (BVMAT). Compared to BVMAT, PBS had greater target coverage, better conformity, and lower dose heterogeneity while achieving a lower dose to the lungs and heart. Nearly half of the BVMAT plans exceeded the lung V5 constraint (>55%). PBS was well tolerated without any pneumonitis or grade 3+ acute toxicity. We show here that patients requiring both mediastinal and axillary treatment may be another subgroup of lymphoma patients who may benefit from PBT. Because proton beam therapy (PBT) can lower the dose of radiation to the heart, lungs, and breast, it is an established radiation modality for patients with Hodgkin lymphoma (HL). Pencil beam scanning (PBS) PBT facilitates the treatment of more extensive targets. This may be especially of value for lymphoma patients who require RT to both mediastinal and axillary targets, defined here as extended target RT (ETRT), given the target distribution and need to minimize the lung, heart, and breast dose. Using the Proton Collaborative Group registry, we identified patients with HL treated with PBT to both their mediastinum and axilla, for which DICOM-RT was available. All patients were treated with PBS. To evaluate the dosimetric impact of PBS, we compared delivered PBS plans with VMAT butterfly photon plans optimized to have the same target volume coverage, when feasible. Between 2016 and 2021, twelve patients (median 26 years) received PBS ETRT (median 30.6 Gy (RBE)). Despite the large superior/inferior (SI, median 22.2 cm) and left/right (LR, median 22.8 cm) extent of the ETRT targets, all patients were treated with one isocenter except for two patients (both with SI and LR > 30 cm). Most commonly, anterior beams, with or without posterior beams, were used. Compared to photons, PBS had greater target coverage, better conformity, and lower dose heterogeneity while achieving lower doses to the lungs and heart, but not to the breast. No acute grade 3+ toxicities were reported, including pneumonitis. Proton ETRT in this small cohort was safely delivered with PBS and was associated with an improved sparing of the heart and lungs compared to VMAT. [ABSTRACT FROM AUTHOR]

CD123 "expression" is common in hematological malignancies, including acute lymphoblastic leukemia (ALL). Flotetuzumab is a novel, investigational CD3/CD123 DART®. We conducted a phase 1 study evaluating safety and efficacy of flotetuzumab in relapsed/refractory ALL (Cohort A) and other advanced CD123-positive hematological malignancies (excluding myeloid malignancies) (cohort B). Thirteen patients (9 in Cohort A and 4 in Cohort B) were treated at dose level 1 (500 ng/kg/day) before early closure due to discontinuation of drug development by sponsor. Two dose limiting toxicities (Grade 4 thrombocytopenia and neutropenia) occurred in one patient in Cohort B. Cytokine release syndrome occurred in most patients (85%), all being grade ≤2. Responses only occurred in Cohort B, with a partial response in one patient with Hodgkin's lymphoma and morphological complete remission in the bone marrow in one patient with blastic plasmacytoid dendritic cell neoplasm. In conclusion, flotetuzumab had a manageable safety profile in advanced CD123-positive hematological malignancies. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the impact of the EuroNet-PHL-C2 treatment protocol for children with classical Hodgkin lymphoma (cHL) on gonadal function in girls, based on assessment of serum anti-Müllerian hormone (AMH)? SUMMARY ANSWER Serum AMH levels decreased after induction chemotherapy and increased during subsequent treatment and 2 years of follow-up, with lowest levels in patients treated for advanced stage cHL. WHAT IS KNOWN ALREADY Treatment for cHL, particularly alkylating agents and pelvic irradiation, can be gonadotoxic and result in premature reduction of primordial follicles in females. The current EuroNet-PHL-C2 trial aims to reduce the use of radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. This study aims to assess the gonadotoxic effect of the EuroNet-PHL-C2 protocol. STUDY DESIGN, SIZE, DURATION This international, prospective, multicenter cohort study is embedded in the EuroNet-PHL-C2 trial, an European phase-3 treatment study evaluating the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) versus intensified OEPA-DECOPDAC-21 (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide) in a randomized setting. Participants were recruited between January 2017 and September 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS Female patients aged ≤18 years, treated according to the EuroNet-PHL-C2 protocol for cHL were recruited across 18 sites in the Netherlands, Belgium, Germany, Austria, and Czech Republic. All parents and patients (aged ≥12 years old) provided written informed consent. Serum AMH levels and menstrual cycle characteristics were evaluated over time (at diagnosis, one to three times during treatment and 2 up to 5 years post-diagnosis) and compared between treatment-levels (TL1, TL2, and TL3) and treatment-arms (OEPA-COPDAC-28 and OEPA-DECOPDAC-21). Serum samples obtained from patients after receiving pelvic radiotherapy were excluded from the main analyses. MAIN RESULTS AND THE ROLE OF CHANCE A total of 104 females, with median age at diagnosis of 15.6 years (IQR 13.7; 17.0), were included in the analysis. Ninety-nine were (post)pubertal. Eighteen girls were diagnosed with an early stage of cHL (TL1) and 86 with intermediate or advanced stage disease (50 TL2 and 36 TL3, 66% received COPDAC-28 and 34% DECOPDAC-21). Five patients received pelvic radiotherapy. Median AMH level at diagnosis was 1.7 µg/l (IQR 0.9; 2.7). After two courses of OEPA chemotherapy, AMH levels decreased substantially in all patients (98% <0.5 µg/l), followed by a significant increase during the consolidation treatment and follow-up. After 2 years, 68% of patients reached their baseline AMH value, with overall median recovery of 129% (IQR 75.0; 208.9) compared to baseline measurement. Five patients (7%) had AMH <0.5 µg/l. In patients treated for advanced stage disease, AMH levels remained significantly lower compared to early- or intermediate stage disease, with median serum AMH of 1.3 µg/l (IQR 0.8; 2.1) after 2 years. Patients who received DECOPDAC-21 consolidation had lower AMH levels during treatment than patients receiving COPDAC-28, but the difference was no longer statistically significant at 2 years post-diagnosis. Of the 35 postmenarchal girls who did not receive hormonal co-treatment, 19 (54%) experienced treatment-induced amenorrhea, two girls had persisting amenorrhea after 2 years. LIMITATIONS, REASONS FOR CAUTION The studied population comprises young girls with diagnosis of cHL often concurring with pubertal transition, during which AMH levels naturally rise. There was no control population, while the interpretation of AMH as a biomarker during childhood is complex. The state of cHL disease may affect AMH levels at diagnosis, potentially complicating assessment of AMH recovery as a comparison with baseline AMH. The current analysis included data up to 2–5 years post-diagnosis. WIDER IMPLICATIONS OF THE FINDINGS The current PANCARE guideline advises to use the cyclophosphamide-equivalent dose score (CED-score, as an estimation of cumulative alkylating agent exposure) with a cut-off of 6000 mg/m2 to identify females aged <25 years at high risk of infertility. All treatment-arms of the EuroNet-PHL-C2 protocol remain below this cut-off, and based on this guideline, girls treated for cHL should therefore be considered low-risk of infertility. However, although we observed an increase in AMH after chemotherapy, it should be noted that not all girls recovered to pre-treatment AMH levels, particularly those treated for advanced stages of cHL. It remains unclear how our measurements relate to age-specific expected AMH levels and patterns. Additional (long-term) data are needed to explore clinical reproductive outcomes of survivors treated according to the EuroNet-PHL-C2 protocol. STUDY FUNDING/COMPETING INTEREST(S) The fertility add-on study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M-K. D.K. W.H.W. D.H. M.C. A.U. and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors indicated no potential conflicts of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Context.--: It is known that a subset of cases of classic Hodgkin lymphoma (CHL) with B-cell-rich nodules (lymphocyte-rich CHL) exhibits morphologic and immunophenotypic features that overlap with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), raising diagnostic difficulties that can be resolved in most cases by performing an adequate battery of immunohistochemical studies. Objective.--: To fully characterize cases of T-cell-rich Hodgkin lymphoma where a specific diagnosis of NLPHL (ie, pattern D) or CHL could not be made even after complete immunophenotypic investigation. Design.--: The clinical, immunomorphologic, and molecular (when applicable) presentation of 3 cases of T-cell-rich Hodgkin lymphoma was thoroughly investigated. Results.--: These 3 cases harbored lymphocyte-predominant-like and Hodgkin and Reed-Sternberg-like cells that partially expressed B-cell and CHL markers and were negative for Tiftein-Barr virus-encoded small RNA, in a T-cell-rich background with residual follicular dendritic cell meshworks; 1 case had frequent and the other 2 cases scant/absent eosinophils and plasma cells. Two patients with advanced-stage (III or IV) disease presented with axillary and supraclavicular lymphadenopathy, respectively, and without B symptoms. These patients underwent NLPHL-like therapeutic management with 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride [hydroxydaunorubicin], vincristine sulfate [Oncovin], and prednisone) chemotherapy; both are in complete remission 7 years posttherapy. One patient presented with stage I disease involving an internal mammary lymph node without B-symptoms and was treated with surgical excision alone; this patient is also in complete remission 1 year later. Conclusions.--: These cases illustrate overlapping features of T-cell-rich NLPHL and CHL with neoplastic cells expressing both B-cell program and CHL markers. This underrecognized overlap has not been fully illustrated in the literature, although it portrays a therapeutic challenge. These neoplasms may deserve in-depth investigation in the future that may bring up diagnostic or theragnostic implications. [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]

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]

Classic Hodgkin lymphoma (CHL) can arise in patients with low-grade B-cell lymphoma. The features of CHL arising in follicular lymphoma (FL) and its outcome are still unclear, mainly due to the very few cases reported. This study compares 17 patients with CHL and FL to 2 control groups: 1 of 26 patients with FL and a second of 60 patients older than 40 when diagnosed with CHL. Of the FL and CHL patients, 8 had simultaneous FL and CHL, while 9 had FL first, followed by CHL 4.7 years later on average. The age at the diagnosis of FL was 61 years for patients with synchronous FL and CHL and of 60 years for FL, followed by CHL at 65 years. Patients with FL only were, on average, 59 years old at presentation, while CHL patients were 61. FL was grade 1-2 in 75% of FL and CHL patients and 67% of FL first and CHL second patients, lower proportions than in the FL control group-92%. Epstein-Barr virus (EBV) was detected in a lower fraction (29%) of the FL and CHL group than in CHL-only controls (46%). BCL2 translocations were detected in 4 of the 7 cases with FL, but in positive cases, the rearrangement was also present in the CHL component, indicating a clonal relationship between FL and CHL. Patients with FL and CHL treated for CHL had an initial outcome more similar to FL than to CHL controls. [ABSTRACT FROM AUTHOR]

The article discusses a case of a 27-year-old male with lepromatous leprosy and chronic type 2 lepra reaction who developed cryptococcosis involving the skin and bone. The patient had received multiple courses of systemic steroids and other medications for the lepra reaction. Treatment with antifungal medications led to the healing of the skin lesions. The case highlights the importance of considering cryptococcosis in leprosy patients on immunosuppressive therapy to prevent serious complications. [Extracted from the article]

Intensified systemic chemotherapy has the highest primary cure rate for advanced-stage, classical Hodgkin lymphoma but this comes with a cost of severe and potentially life long, persisting toxicities. With the new regimen of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD), we aimed to improve the risk-to-benefit ratio of treatment of advanced-stage, classical Hodgkin lymphoma guided by PET after two cycles. This randomised, multicentre, parallel, open-label, phase 3 trial was done in 233 trial sites across nine countries. Eligible patients were adults (aged ≤60 years) with newly diagnosed, advanced-stage, classical Hodgkin lymphoma (ie, Ann Arbor stage III/IV, stage II with B symptoms, and either one or both risk factors of large mediastinal mass and extranodal lesions). Patients were randomly assigned (1:1) to four or six cycles (21-day intervals) of escalated doses of etoposide (200 mg/m2 intravenously on days 1–3), doxorubicin (35 mg/m2 intravenously on day 1), and cyclophosphamide (1250 mg/m2 intravenously on day 1), and standard doses of bleomycin (10 mg/m2 intravenously on day 8), vincristine (1·4 mg/m2 intravenously on day 8), procarbazine (100 mg/m2 orally on days 1–7), and prednisone (40 mg/m2 orally on days 1–14; eBEACOPP) or BrECADD, guided by PET after two cycles. Patients and investigators were not masked to treatment assignment. Hierarchical coprimary objectives were to show (1) improved tolerability defined by treatment-related morbidity and (2) non-inferior efficacy defined by progression-free survival with an absolute non-inferiority margin of 6 percentage points of BrECADD compared with eBEACOPP. An additional test of superiority of progression-free survival was to be done if non-inferiority had been established. Analyses were done by intention to treat; the treatment-related morbidity assessment required documentation of at least one chemotherapy cycle. This trial was registered at ClinicalTrials.gov (NCT02661503). Between July 22, 2016, and Aug 27, 2020, 1500 patients were enrolled, of whom 749 were randomly assigned to BrECADD and 751 to eBEACOPP. 1482 patients were included in the intention-to-treat analysis. The median age of patients was 31 years (IQR 24–42). 838 (56%) of 1482 patients were male and 644 (44%) were female. Most patients were White (1352 [91%] of 1482). Treatment-related morbidity was significantly lower with BrECADD (312 [42%] of 738 patients) than with eBEACOPP (430 [59%] of 732 patients; relative risk 0·72 [95% CI 0·65–0·80]; p<0·0001). At a median follow-up of 48 months, BrECADD improved progression-free survival with a hazard ratio of 0·66 (0·45–0·97; p=0·035); 4-year progression-free survival estimates were 94·3% (95% CI 92·6–96·1) for BrECADD and 90·9% (88·7–93·1) for eBEACOPP. 4-year overall survival rates were 98·6% (97·7–99·5) and 98·2% (97·2–99·3), respectively. BrECADD guided by PET after two cycles is better tolerated and more effective than eBEACOPP in first-line treatment of adult patients with advanced-stage, classical Hodgkin lymphoma. Takeda Oncology. [ABSTRACT FROM AUTHOR]

Background: Lymphoid neoplasm is a common disease, arising from lymphoid cells. It is divided into Hodgkin lymphoma and non-Hodgkin lymphoma. Non-Hodgkin lymphoma can be intranodular or extranodular, which happens in 25% of primary cases. The most common locations of extranodular non-Hodgkin lymphoma are the skin and gastrointestinal tract. The genital tract is a rare location; most lymphomas arise from the cervix and vagina, while the uterine corpus is an extremely rare location. In our case, the patient was diagnosed with primary extranodular non-Hodgkin lymphoma in different locations of her genital tract. Case presentation: A 48-year-old nonparous Syrian woman complained of diffuse abdominal pain, fatigue, debility, high fever, vomiting, and urinary retention for a week. The last menstrual period of the patient was 5 years previously. The physical examination showed periodic abdominal pain with severe fatigue and increased abdominal size. The laboratory investigations were within normal limits except for a low level of hemoglobin and a high level of cancer antigen 125. The radiological investigations showed a uterine sizable lobulated mass with irregular borders and high and heterogeneous density, extending to the right and left ovaries, enlargement lymph nodes around the abdominal aortic and right iliac vessels, and severe right pleural effusion with right inferior lobe atelectasis. A total hysterectomy and oophorectomy were done. The histopathological examination showed that the patient had non-Hodgkin lymphoma (primary tumor). Conclusion: Primary non-Hodgkin lymphoma in the female genital tract is an extremely rare disease. Fast diagnosis and treatment can improve the outcomes, so this differential diagnosis should be in our minds even in the absence of systematic manifestations of lymphoma. More studies are needed to explain the pathology of this disease and to put guidelines that determine the perfect methods for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Hodgkin lymphoma (HL) is an uncommon malignancy that is characterized by Hodgkin or Reed–Sternberg cells. Cardiac implications of HL remain one of the least investigated subjects. There are few case reports in the literature of cardiac tamponade in HL patients. We describe a case of a 21‐year‐old female patient who presented with cardiac tamponade as an initial presentation of HL. Any pericardial effusion significant for tamponade requires immediate drainage and fluid analysis for thorough investigation. Prompt identification and timely intervention are crucial in effectively addressing these complex situations. Therefore, clinicians should maintain heightened awareness in such cases. [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]

Background: Classical Hodgkin Lymphomas (HL) are a unique malignant growth with an excellent initial prognosis. However, 10–30% of patients will still relapse after remission. One primary cellular function that has been the focus of tumor progression is autophagy. This process can preserve cellular homeostasis under stressful conditions. Several studies have shown that autophagy may play a role in developing HL. Therefore, this review aimed to explore chemotherapy's effect on autophagy in HL, and the effects of autophagy on HL. Methods: A scoping review in line with the published PRISMA extension for scoping reviews (PRISMA-ScR) was conducted. A literature search was conducted on the MEDLINE database and the Cochrane Central Register of Controlled Trials (CENTRAL). All results were retrieved and screened, and the resulting articles were synthesized narratively. Results: The results showed that some cancer chemotherapy also induces autophagic flux. Although the data on HL is limited, since the mechanisms of action of these drugs are similar, we can infer a similar relationship. However, this increased autophagy activity may reflect a mechanism for increasing tumor growth or a cellular compensation to inhibit its growth. Although evidence supports both views, we argued that autophagy allowed cancer cells to resist cell death, mainly due to DNA damage caused by cytotoxic drugs. Conclusion: Autophagy reflects the cell's adaptation to survive and explains why chemotherapy generally induces autophagy functions. However, further research on autophagy inhibition is needed as it presents a viable treatment strategy, especially against drug-resistant populations that may arise from HL chemotherapy regimens. [ABSTRACT FROM AUTHOR]

Background: Hodgkin's lymphoma (HL) is an extremely rare cause of ocular inflammation that is usually not considered in the typical workup of uveitis and other eye diseases. A few cases of ocular inflammation were reported previously showcasing HL with absence of typical symptoms of HL at presentation. Acknowledging the potential ocular inflammation associated with HL can prompt ophthalmologists to broaden their diagnostic approach and collaborate with internal medicine departments to investigate this rare yet significant etiology. Case presentation: A 17-year-old Caucasian woman presenting unilateral panuveitis was later diagnosed with HL. The ocular findings were non-necrotizing scleritis, anterior uveitis, vitritis, white/yellowish chorioretinal lesions, papillitis and vasculitis. A left supra-clavicular lymph node biopsy confirmed the diagnosis of nodular sclerosing Hodgkin's lymphoma stage IIB. Other causes of uveitis were excluded. Chemotherapy led to remission of the disease and the ocular lesions became quiescent with persistent pigmented chorioretinal scars. Conclusions: Hodgkin's lymphoma should be considered in the differential diagnosis of diseases that can occasionally be revealed by unilateral ocular inflammation. A comprehensive, multidisciplinary approach is key to properly assessing such cases. [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]

The relevance of this study arises from the pressing need for a deeper investigation into the morphological aspects of identifying focal and localised lesions in the spleen. The spleen performs several vital functions, including immune, haematological, storage, metabolic, haemostatic, hormonal, and antiblastic roles, among others. Therefore, this study aimed to determine the clinical characteristics of splenic tumour lesions and their structural changes, as well as to identify the macroscopic appearance of the organ post-splenectomy. In diagnosing splenic diseases, a key instrumental method was employed - ultrasound examination with Doppler imaging - which enabled comprehensive investigation, analysis, and characterisation of parenchymal pathologies. Animals underwent clinical examinations during routine health checks or upon presentation of symptoms. When a splenic neoplasm was detected, surgical treatment was carried out, specifically through an open laparotomy and splenectomy. The surgery was performed under combined general anaesthesia (using both non-inhalational and inhalational anaesthetics). The intraoperatively collected material from the affected organ was subjected to histological examination. It was found that the pathomorphosis of splenic lesions varies, and the author's pathological and histological studies highlight the key morphological characteristics of the neoplasms. Accordingly, any splenic neoplasm can pose a life-threatening condition for several reasons: organ rupture and haemorrhage, organ torsion, and malignancy, among others. The findings are crucial for verifying splenic pathology, enabling the establishment of a definitive clinical diagnosis, facilitating treatment of the animal, and extending its lifespan. The practical significance of the results lies in identifying the need for comprehensive clinical and morphological investigations in diagnosing splenic diseases, as well as examining histological preparations for cellular and tissue changes. In veterinary medicine, the method of surgical treatment for splenic lesions in animals may be a subject of debate. In contrast, in human medicine, established protocols exist for performing organ-destructive operations such as splenectomy (by open or laparoscopic approach), organ-preserving procedures like splenic resection or splenectomy with autotransplantation of splenic tissue into the greater omentum (by open or laparoscopic approach), and percutaneous punctures for splenic cysts. [ABSTRACT FROM AUTHOR]

Introduction. In rare cases, chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma may transform into Hodgkin lymphoma, with about a hundred cases reported in the literature so far. We present a case of the Hodgkin variant of Richter transformation. Case report. After a oneyear watch and wait period, a 60-year-old male with CLL developed B symptoms, generalized lymphadenopathy, and splenomegaly. Upon initial staging (Binet B/Rai 3), he was started on fludarabine, cyclophosphamide, and rituximab (FCR) regimen. After the third cycle of treatment, the rightsided axillary lymphadenopathy persisted and became painful, while the dimensions of the remaining organs affected by the disease decreased. Upon the finalization of the final sixth FCR cycle, the painful right-sided axillary lymphadenopathy persisted (though partially decreasing in size), with the development of local redness and swelling. A biopsy of the residual axillary node was performed, which revealed disease transformation into Hodgkin lymphoma. Upon multislice computed tomography-based s taging ( IV E c linical stage) and prognostic assessment (unfavorable prognosis), it was decided that the treatment be continued with doxorubicin, vinblastine, dacarbazine (AVD) regimen. The presented patient died two months after the diagnosis of Hodgkin transformation (HT) was established during the initial cycle of AVD. Conclusion. Although CLL is an indolent malignancy, in rare cases of HT, the prognosis is largely dismal. The available treatment strategies demonstrate suboptimal results, although novel immunotherapies may change the landscape of HT therapy in the near future. [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]

This article discusses the case of a 73-year-old woman with rheumatoid arthritis who developed a lymphoproliferative disorder after discontinuing immunosuppressive drugs. The patient initially showed improvement but later experienced a relapse of symptoms. The article highlights the importance of closely monitoring rheumatoid arthritis patients with lymphoproliferative disorders and promptly initiating chemotherapy. It also discusses the classification and prognosis of these disorders and the significance of monitoring lymphocyte counts and serum markers. The article provides case reports and references to support its findings. [Extracted from the article]

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]

Summary: Combination checkpoint inhibitor (CPI) and chemotherapy is an effective and safe treatment strategy for patients with untreated classic Hodgkin lymphoma. Recent studies of programmed cell death protein 1 inhibitors combined with doxorubicin, vinblastine and dacarbazine have demonstrated high overall and complete response rates. This combination has a unique toxicity profile that should be managed appropriately so as not to compromise treatment efficacy. Common toxicities include rash, hepatoxicity, neutropenia and thyroid dysfunction. Here, we present four cases and the management strategies around such toxicities. In addition, we highlight key clinical decision‐making around the administration of subsequent doses of CPI and chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Hodgkin lymphoma (HL) management varies throughout developing nations. This observational study aims to present the results of children having HL who received various combinations of chemotherapy treatment. The response-based method was used regardless of the risk classification. Materials and Methods: We recruited patients≤ 18 years of age diagnosed with HL in an Iraqi cancer center between January 2014 and December 2021. By stratifying patients, three risk categories were identified. Every patient initially received two cycles of ABVD as induction chemotherapy. Following induction chemotherapy, patients showing a full radiological response continued on ABVD chemotherapy for 4-6 cycles without receiving radiotherapy. Patients showing a modest initial response received three additional courses of COPDac next to the third cycle of ABVD, followed by radiotherapy. Results: This study included fifty-nine patients with a median age of 7 years. Stage III patients accounted for 33.9% (n=20), then stage II (32.2%). B symptoms were present in 25 patients. Eleven children had initial splenic involvement. Fifty-two individuals (n = 19; 32.2%) had bulky disease. Mixed cellularity was the most prevalent histology (n=44). The median duration of follow-up was 2.7 years. EFS was 78% ±10%, and survival was 92% at 5-year estimation. Bulky disease was the only factor with a substantial unfavorable impact on the result. Conclusion: Response-based approach is a valuable strategy in nations with limited resources to prevent long-term sequelae from unnecessary radiotherapy. [ABSTRACT FROM AUTHOR]

Cost-effectiveness analyses are required for therapies within Canada's universal healthcare system, leading to delays relative to U.S. healthcare. Patients with Hodgkin lymphoma (HL) generally have an excellent prognosis, but those who relapse after or are ineligible for transplant benefit from novel therapies, including brentuximab vedotin (BV). BV was FDA-approved in 2011 but not Canadian-funded until 2014. To assess the impact of access delays, we compared changes in survival for U.S. (by insurer) and Canadian patients in periods pre/post-U.S. approval. Patients were 16–64 years, diagnosed with HL in 2007–2010 (Period 1) and 2011–2014 (Period 2) from the U.S. SEER and Canadian Cancer Registries. Approval date (surrogate) was utilized as therapy was unavailable in registries. Kaplan-Meier survival curves and adjusted Cox regression models compared survival between periods by insurance category. Among 12,003 U.S. and 4210 Canadian patients, survival was better in U.S. patients (adjusted hazard ratio (aHR) 0.87 (95%CI 0.77–0.98)) between periods; improvement in Canadian patients (aHR 0.84 (95%CI 0.69–1.03) was similar but non-significant. Comparisons between insurers showed survival was significantly worse for U.S. uninsured and Medicaid vs. U.S. privately insured and Canadian patients. Given the increasingly complex nature of oncologic funding, this merits further investigation to ensure equity in access to therapy developments. [ABSTRACT FROM AUTHOR]

Simple Summary: Autoantibodies against the metabotropic glutamate receptor 5 (mGluR5) have been linked to Ophelia syndrome, a combination of limbic encephalitis and Hodgkin lymphoma (HL). We studied mGluR5 expression in 57 pediatric HL and NHL by immunohistochemistry to explore the relationship between mGluR5 antibody formation and HL. All lymphoma tissues displayed mGluR5 staining, especially HL Reed–Sternberg cells. There was no staining in age-matched healthy lymph nodes, and we did not find GRM5 transcripts in RNA-sequencing data from normal lymphocytes. Lower mGluR5 levels in HL correlated with younger patients and EBV-positive tumors. Cases of paraneoplastic and neurological symptoms were found exclusively in the HL cohort. The frequent presence of mGluR5 in lymphoma tissue suggests a possible role in tumor development. This finding is in line with reports that glutamatergic signaling affects the outcome in other cancers. However, further studies in larger cohorts are needed to evaluate the impact of mGluR5 on HL severity. Autoantibodies targeting the neuronal antigen metabotropic glutamate receptor 5 (mGluR5) have been identified in patients with Ophelia syndrome, which describes a co-occurrence of paraneoplastic limbic encephalitis and Hodgkin lymphoma (HL). Little data exist regarding frequency and function of mGluR5 in HL and its potential role in causing seropositive paraneoplastic disease. We studied a representative cohort of pediatric HL and NHL patients (n = 57) using immunohistochemistry and fluorescence staining to investigate mGluR5 expression. All lymphoma tissues displayed positive mGluR5 staining, with focus on Hodgkin–Reed–Sternberg (H-RS) cells. We did not detect any mGluR5 staining in tumor-free lymph nodes, which is consistent with the absence of GRM5 transcripts in RNA-sequencing data from non-malignant B and T cells. The frequent presence in pediatric lymphoma falls in line with reports of mGluR5 expression and associated tumor progression in other malignancies. We tested for correlation with clinical features, focusing on disease progression and neurological symptoms. Low mGluR5 expression in H-RS cells correlated with young patient age (<15 years) and positive histology for EBV infection. Paraneoplastic or neurological symptoms were found exclusively in HL patients. While an impact of mGluR5 on HL severity remains possible, a prognostic value of mGluR5 expression levels requires further investigation. [ABSTRACT FROM AUTHOR]

The article reports on a case of cardiac metastasis of renal carcinoma in the absence of invasion of the inferior vena cava. The case of a 67-year-old woman with a history of Chagas disease, Hodgkin's lymphoma, thyroid carcinoma, and hypertension is described. Several studies were performed confirming the presence of metastasis in the heart, lungs, adrenal gland, and kidney. Immunomodulatory treatment was initiated, but after six cycles of treatment, no reduction in metastasis or the primary tumor was observed. The article highlights the importance of performing diagnostic tests such as echocardiography, magnetic resonance imaging, or positron emission tomography to characterize the lesions. It also mentions that first-line treatment for advanced clear cell renal carcinoma is the administration of immunomodulators. [Extracted from the article]

Introduction: Distinguishing the cellular origin of lung cancer is essential for tailored patient care. This pioneering pilot study explores the synergy of ¹HMagnetic Resonance Spectroscopy (¹H-MRS) and 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) in the differentiation of primary squamous cell carcinoma (SCC) of the lung from Hodgkin's lymphoma (HL) metastases. Methods: Ethically approved, the study enrolled 21 participants with confirmed lung lesions (10 SCC, 11 HL). [18F]FDG PET/CT and ¹H-MRS were conducted, and analyses were performed to assess diagnostic potential. Results: Significant differences in [18F]FDG PET/CT parameters (SUVmax BSA, SUVmax LBM, and ID%) between SCC and HL were observed. Metabolite concentrations (Cho, Lac, Cr) from ¹H-MRS also exhibited distinctions. Correlations between PET values and metabolite concentrations hinted at links between glucose metabolism and molecular composition. Conclusion: This study presents an innovative approach, integrating ¹H-MRS and [18F]FDG PET/CT to distinguish primary from metastatic lung lesions. The results hold promise for improving non-invasive diagnostic accuracy and guiding targeted therapies. Future research should validate these findings and explore the potential for clinical integration. [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]

Post-transplant lymphoproliferative disorder (PTLD) is a common secondary malignancy after transplantation, which has been recognized as a life-threatening complication. Hodgkin lymphoma (HL)-type PTLD is the rarest of four subtypes of PTLD, which has no treatment guideline due to its rarity. HL-type PTLD includes classical HL-type PTLD (cHL-PTLD) and HL-like PTLD. In our study, we reported the case of successful treatment using brentuximab vedotin (BV) plus sirolimus for a patient with classical HL-type PTLD in detail. Lymph node biopsy showed a picture of classical HL with mixed cellularity subtype, and immunophenotyping suggested CD30 strong positivity. Due to his impaired physical condition, we decided against intensive chemotherapy and started BV treatment with immunosuppressive agents switched to sirolimus. The 66-year-old patient with cHL-PTLD had achieved a durable complete remission for over a 1-year follow-up period. Additionally, we analyzed the clinical profile and outcomes in PTLD patients who used BV monotherapy or combined therapy by literature review. In summary, this case-based review might provide clues that treatment of cHL-PTLD with new modalities such as BV monotherapy or combination therapy, together with improvements in the immunosuppressive regimens like sirolimus, might be a feasible and chemotherapy-free approach, but warrants further evaluation in a larger patient cohort. [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]