Distinct Hodgkin lymphoma subtypes defined by noninvasive genomic profiling.

The scarcity of malignant Hodgkin and Reed-Sternberg cells hampers tissue-based comprehensive genomic profiling of classic Hodgkin lymphoma (cHL). By contrast, liquid biopsies show promise for molecular profiling of cHL due to relatively high circulating tumour DNA (ctDNA) levels1-4. Here we show that the plasma representation of mutations exceeds the bulk tumour representation in most cases, making cHL particularly amenable to noninvasive profiling. Leveraging single-cell transcriptional profiles of cHL tumours, we demonstrate Hodgkin and Reed-Sternberg ctDNA shedding to be shaped by DNASE1L3, whose increased tumour microenvironment-derived expression drives high ctDNA concentrations. Using this insight, we comprehensively profile 366 patients, revealing two distinct cHL genomic subtypes with characteristic clinical and prognostic correlates, as well as distinct transcriptional and immunological profiles. Furthermore, we identify a novel class of truncating IL4R mutations that are dependent on IL-13 signalling and therapeutically targetable with IL-4Rα-blocking antibodies. Finally, using PhasED-seq5, we demonstrate the clinical value of pretreatment and on-treatment ctDNA levels for longitudinally refining cHL risk prediction and for detection of radiographically occult minimal residual disease. Collectively, these results support the utility of noninvasive strategies for genotyping and dynamic monitoring of cHL, as well as capturing molecularly distinct subtypes with diagnostic, prognostic and therapeutic potential.

Spatial and molecular profiling of the mononuclear phagocyte network in classic Hodgkin lymphoma.

Classic Hodgkin lymphoma (cHL) has a rich immune infiltrate, which is an intrinsic component of the neoplastic process. Malignant Hodgkin Reed-Sternberg cells (HRSCs) create an immunosuppressive microenvironment by the expression of regulatory molecules, preventing T-cell activation. It has also been demonstrated that mononuclear phagocytes (MNPs) in the vicinity of HRSCs express similar regulatory mechanisms in parallel, and their presence in tissue is associated with inferior patient outcomes. MNPs in cHL have hitherto been identified by a small number of canonical markers and are usually described as tumor-associated macrophages. The organization of MNP networks and interactions with HRSCs remains unexplored at high resolution. Here, we defined the global immune-cell composition of cHL and nonlymphoma lymph nodes, integrating data across single-cell RNA sequencing, spatial transcriptomics, and multiplexed immunofluorescence. We observed that MNPs comprise multiple subsets of monocytes, macrophages, and dendritic cells (DCs). Classical monocytes, macrophages and conventional DC2s were enriched in the vicinity of HRSCs, but plasmacytoid DCs and activated DCs were excluded. Unexpectedly, cDCs and monocytes expressed immunoregulatory checkpoints PD-L1, TIM-3, and the tryptophan-catabolizing protein IDO, at the same level as macrophages. Expression of these molecules increased with age. We also found that classical monocytes are important signaling hubs, potentially controlling the retention of cDC2 and ThExh via CCR1-, CCR4-, CCR5-, and CXCR3-dependent signaling. Enrichment of the cDC2-monocyte-macrophage network in diagnostic biopsies is associated with early treatment failure. These results reveal unanticipated complexity and spatial polarization within the MNP compartment, further demonstrating their potential roles in immune evasion by cHL.

Hodgkin lymphoma: A review and update on recent progress.

Hodgkin lymphoma (HL) is a unique hematopoietic neoplasm characterized by cancerous Reed-Sternberg cells in an inflammatory background. Patients are commonly diagnosed with HL in their 20s and 30s, and they present with supradiaphragmatic lymphadenopathy, often with systemic B symptoms. Even in advanced-stage disease, HL is highly curable with combination chemotherapy, radiation, or combined-modality treatment. Although the same doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapeutic regimen has been the mainstay of therapy over the last 30 years, risk-adapted approaches have helped de-escalate therapy in low-risk patients while intensifying treatment for higher risk patients. Even patients who are not cured with initial therapy can often be salvaged with alternate chemotherapy combinations, the novel antibody-drug conjugate brentuximab, or high-dose autologous or allogeneic hematopoietic stem cell transplantation. The programmed death-1 inhibitors nivolumab and pembrolizumab have both demonstrated high response rates and durable remissions in patients with relapsed/refractory HL. Alternate donor sources and reduced-intensity conditioning have made allogeneic hematopoietic stem cell transplantation a viable option for more patients. Future research will look to integrate novel strategies into earlier lines of therapy to improve the HL cure rate and minimize long-term treatment toxicities. CA Cancer J Clin 2018;68:116-132. © 2017 American Cancer Society.

HLH and Recurrent EBV Lymphoma as the presenting manifestation of MAGT1 Deficiency: A Systematic Review of the Expanding Disease Spectrum.

Magnesium transporter 1 (MAGT1) gene loss-of-function variants lead to X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-glycosylation defect (XMEN), a condition with a variety of clinical and immunological effects. In addition, MAGT1 deficiency has been classified as a congenital disorder of glycosylation (CDG) due to its unique role in glycosylation of multiple substrates including NKG2D, necessary for viral protection. Due to the predisposition for EBV, this etiology has been linked with hemophagocytic lymphohistiocytosis (HLH), however only limited literature exists. Here we present a complex case with HLH and EBV-driven classic Hodgkin lymphoma (cHL) as the presenting manifestation of underlying immune defect. However, the patient's underlying immunodeficiency was not identified until his second recurrence of Hodgkin disease, recurrent episodes of Herpes Zoster, and after he had undergone autologous hematopoietic stem cell transplant (HSCT) for refractory Hodgkin lymphoma. This rare presentation of HLH and recurrent lymphomas without some of the classical immune deficiency manifestations of MAGT1 deficiency led us to review the literature for similar presentations and to report the evolving spectrum of disease in published literature. Our systematic review showcased that MAGT1 predisposes to multiple viruses (including EBV) and adds risk of viral-driven neoplasia. The roles of MAGT1 in the immune system and glycosylation were highlighted through the multiple organ dysfunction showcased by the previously validated Immune Deficiency and Dysregulation Activity (IDDA2.1) score and CDG-specific Nijmegen Pediatric CDG Rating Scale (NPCRS) score for the patient cohort in the systematic review.

A gene expression-based model predicts outcome in children with intermediate-risk classical Hodgkin lymphoma.

Classical Hodgkin lymphoma (cHL) is a common malignancy in children and adolescents. Although cHL is highly curable, treatment with chemotherapy and radiation often come at the cost of long-term toxicity and morbidity. Effective risk-stratification tools are needed to tailor therapy. Here, we used gene expression profiling (GEP) to investigate tumor microenvironment (TME) biology, to determine molecular correlates of treatment failure, and to develop an outcome model prognostic for pediatric cHL. A total of 246 formalin-fixed, paraffin-embedded tissue biopsies from patients enrolled in the Children's Oncology Group trial AHOD0031 were used for GEP and compared with adult cHL data. Eosinophil, B-cell, and mast cell signatures were enriched in children, whereas macrophage and stromal signatures were more prominent in adults. Concordantly, a previously published model for overall survival prediction in adult cHL did not validate in pediatric cHL. Therefore, we developed a 9-cellular component model reflecting TME composition to predict event-free survival (EFS). In an independent validation cohort, we observed a significant difference in weighted 5-year EFS between high-risk and low-risk groups (75.2% vs 90.3%; log-rank P = .0138) independent of interim response, stage, fever, and albumin. We demonstrate unique disease biology in children and adolescents that can be harnessed for risk-stratification at diagnosis. This trial was registered at www.clinicaltrials.gov as #NCT00025259.

Presentation of B-cell lymphoma in childhood and adolescence: a systematic review and meta-analysis.

BACKGROUND: The diagnosis of B-cell lymphoma, one of the commonest cancers seen in childhood and adolescence, is challenging. There is a crucial need to identify and delineate the prevalence of associated symptoms in order to improve early diagnosis. AIMS: To identify clinical presentations associated with childhood and adolescent B-cell lymphomas and estimate symptom prevalence. METHODS: A systematic review of observational studies and meta-analysis of proportions was carried out. Medline and EMBASE were systematically searched, with no language restrictions, from inception to 1st August 2022. Observational studies with at least 10 participants, exploring clinical presentations of any childhood and adolescent lymphoma, were selected. Proportions from each study were inputted to determine the weighted average (pooled) proportion, through random-effects meta-analysis. RESULTS: Studies reported on symptoms, signs and presentation sites at diagnosis of 12,207 children and adolescents up to the age of 20. Hodgkin's lymphoma most frequently presented with adenopathy in the head-and-neck region (79% [95% CI 58%-91%]), whilst non-Hodgkin's lymphoma presented abdominally (55% [95% CI 43%-68%]). Symptoms associated with lymphoma included cervical lymphadenopathy (48% [95% CI 20%-77%]), peripheral lymphadenopathy (51% [95% CI 37%-66%]), B-symptoms (40% [95% CI 34%-44%]), fever (43% [95% CI 34%-54%]), abdominal mass (46% [95% CI 29%-64%]), weight loss (53% [95% CI 39%-66%]), head-and-neck mass (21% [95% CI 6%-47%]), organomegaly (29% [95% CI 23%-37%]), night sweats (19% [95% CI 10%-32%]), abdominal pain (28% [95% CI 15%-47%]), bone pain (17% [95% CI 10%-28%]) and abnormal neurology (11% [95% CI 3%-28%]). CONCLUSION: This systematic review and meta-analysis of proportions provides insight into the heterogeneous clinical presentations of B-cell lymphoma in childhood and adolescence and provides estimates of symptom prevalence. This information is likely to increase public and clinical awareness of lymphoma presentations and aid earlier diagnosis. This review further highlights the lack of studies exploring childhood and adolescent lymphoma presentations in primary care, where patients are likely to present at the earliest stages of their disease.

Vogt-Koyanagi-Harada disease developed during chemotherapy for Hodgkin lymphoma: a case report.

BACKGROUND: Ocular manifestations are known for non-Hodgkin lymphoma, but are rare for Hodgkin lymphoma. We report a case of Vogt-Koyanagi-Harada (VKH) disease presenting as serous retinal detachment and uveitis in both eyes in a child undergoing chemotherapy for Hodgkin lymphoma. CASE PRESENTATION: The patient was a 7-year-old boy with stage IIB Hodgkin lymphoma (nodular lymphocyte predominant type) who was undergoing chemotherapy, including 2 cycles of the OEPA regimen and 1 cycle of the COPDAC regimen. Two days after the end of the COPDAC regimen, the patient complained of headache and of blurred and decreased vision in both eyes. On the basis of optic symptoms, such as uveitis and serous retinal detachment in both eyes, increased cell counts in cerebrospinal fluid, and positivity for human leukocyte antigen (HLA)-DR4 in peripheral blood cells, incomplete VKH disease was diagnosed. Intravenous treatment with high-dose prednisolone (60mg/m2/day) for 7 days improved both visual acuity and serous retinal detachment and enabled the remains of the COPDAC chemotherapy cycle to be administered. With prednisolone treatment, visual acuity improved from 20/500 to 20/20 in the right eye and from 20/63 to 20/25 in the left eye. Because multiple vitiligo lesions later appeared in the abdomen, complete VKH disease was finally diagnosed. CONCLUSION: The onset of VKH disease occurred during chemotherapy for Hodgkin lymphoma. The patient was HLA-DR4-positive and might have had a predisposition to develop autoimmune diseases, including VKH disease. However, the anticancer drugs administered to this patient have not been reported to cause uveitis. Whether Hodgkin lymphoma triggered the development of VKH remains unclear. Early diagnosis of VKH disease and prompt treatment with high-dose prednisone enabled the patient to maintain good visual function despite chemotherapy for Hodgkin lymphoma.

Liquid biopsy: A promising tool for driving strategies and predicting failures in patients with classic Hodgkin lymphoma.

Classic Hodgkin lymphoma (cHL) consists of a heterogeneous group of haematological disorders that covers undifferentiated B cell neoplasms originating from germinal centre B cells. The HL molecular characterization still represents an ongoing challenge due to the low fraction of tumour Hodgkin and Reed-Sternberg cells mixed with a plethora of non-tumour haematological cells. In this scenario, next generation sequencing of liquid biopsy samples is emerging as a useful tool in HL patients' management. In this review, we aimed to overview the clinical and methodological topics regarding the implementation of molecular analysis in cHL, focusing on the role of liquid biopsy in diagnosis, follow-up, and response prediction.

Lymphoma as an Exclusion Criteria for CVID Diagnosis Revisited.

PURPOSE: Hypogammaglobulinemia in a context of lymphoma is usually considered as secondary and prior lymphoma remains an exclusion criterion for a common variable immunodeficiency (CVID) diagnosis. We hypothesized that lymphoma could be the revealing symptom of an underlying primary immunodeficiency (PID), challenging the distinction between primary and secondary hypogammaglobulinemia. METHODS: Within a French cohort of adult patients with hypogammaglobulinemia, patients who developed a lymphoma either during follow-up or before the diagnosis of hypogammaglobulinemia were identified. These two chronology groups were then compared. For patients without previous genetic diagnosis, a targeted next-generation sequencing of 300 PID-associated genes was performed. RESULTS: A total of forty-seven patients had developed 54 distinct lymphomas: non-Hodgkin B cell lymphoma (67%), Hodgkin lymphoma (26%), and T cell lymphoma (7%). In 25 patients, lymphoma developed prior to the diagnosis of hypogammaglobulinemia. In this group of patients, Hodgkin lymphoma was overrepresented compared to the group of patients in whom lymphoma occurred during follow-up (48% versus 9%), whereas MALT lymphoma was absent (0 versus 32%). Despite the histopathological differences, both groups presented with similar characteristics in terms of age at hypogammaglobulinemia diagnosis, consanguinity rate, or severe T cell defect. Overall, genetic analyses identified a molecular diagnosis in 10/47 patients (21%), distributed in both groups and without peculiar gene recurrence. Most of these patients presented with a late onset combined immunodeficiency (LOCID) phenotype. CONCLUSION: Prior or concomitant lymphoma should not be used as an exclusion criteria for CVID diagnosis, and these patients should be investigated accordingly.

Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma.

Pembrolizumab, a humanized IgG4 monoclonal antibody targeting programmed death-1 protein, has demonstrated efficacy in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the complete metabolic response (CMR) rate and safety of pembrolizumab monotherapy in newly diagnosed cHL, we conducted a multicenter, single-arm, phase 2 investigator-initiated trial of sequential pembrolizumab and doxorubicin, vinblastine, and dacarbazine (AVD) chemotherapy. Patients ≥18 years of age with untreated, early, unfavorable, or advanced-stage disease were eligible for treatment. Thirty patients (early unfavorable stage, n = 12; advanced stage, n = 18) were treated with 3 cycles of pembrolizumab monotherapy followed by AVD for 4 to 6 cycles, depending on stage and bulk. Twelve had either large mediastinal masses or bulky disease (>10 cm). After pembrolizumab monotherapy, 11 patients (37%) demonstrated CMRs, and an additional 7 of 28 (25%) patients with quantifiable positron emission tomography computed tomography scans had >90% reduction in metabolic tumor volume. All patients achieved CMR after 2 cycles of AVD and maintained their responses at the end of treatment. With a median follow-up of 22.5 months (range, 14.2-30.6) there were no changes in therapy, progressions, or deaths. No patients received consolidation radiotherapy, including those with bulky disease. Therapy was well tolerated. The most common immune-related adverse events were grade 1 rash (n = 6) and grade 2 infusion reactions (n = 4). One patient had reversible grade 4 transaminitis and a second had reversible Bell's palsy. Brief pembrolizumab monotherapy followed by AVD was both highly effective and safe in patients with newly diagnosed cHL, including those with bulky disease. This trial was registered at www.clinicaltrials.gov as #NCT03226249.

The value of thymus and activation related chemokine immunohistochemistry in classic Hodgkin lymphoma diagnostics.

AIMS: Classic Hodgkin lymphoma (cHL) should be distinguished from its wide variety of histological mimics, including reactive conditions and mature B and T cell neoplasms. Thymus and activation-related chemokine (TARC) is produced in extremely high quantities by the Hodgkin/Reed-Sternberg (HRS) tumour cells and is largely responsible for the attraction of CD4+ T cells into the cHL tumour micro-environment. In the current study we evaluated the diagnostic potential of TARC immunohistochemistry in daily practice in a tertiary referral centre in the Netherlands. METHODS AND RESULTS: A total of 383 cases, approximately half of which were cHL mimics, were prospectively evaluated in the period from June 2014 to November 2020. In 190 cHL cases, 92% were TARC-positive and the majority of cases showed strong and highly specific staining in all HRS cells (77%). In most cases, TARC could discriminate between nodular lymphocyte-predominant and lymphocyte-rich Hodgkin lymphoma. HRS-like cells in mature lymphoid neoplasms were rarely positive (6.4%) and there was no TARC staining at all in 64 reactive lymphadenopathies. CONCLUSIONS: TARC immunohistochemistry has great value in differentiating between cHL and its mimics, including nodular lymphocyte-predominant Hodgkin lymphoma, reactive lymphadenopathies and mature lymphoid neoplasms with HRS-like cells.

Prognostic value of baseline metabolic tumor volume (MTV) for forecasting chemotherapy outcome in early-stage unfavorable Hodgkin lymphoma: Data from the phase III HD17 trial.

OBJECTIVES: The prognostic relevance of metabolic tumor volume (MTV) having recently been demonstrated in patients with early-stage favorable and advanced-stage Hodgkin lymphoma. The current study aimed to assess the potential prognostic value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in early-stage unfavorable Hodgkin lymphoma patients treated within the German Hodgkin Study Group HD17 trial. METHODS: 18 F-FDG PET/CT images were available for MTV analysis in 154 cases. We used three different threshold methods (SUV2.5 , SUV4.0 , and SUV41% ) to calculate MTV. Receiver-operating-characteristic analysis was performed to describe the value of these parameters in predicting an adequate therapy response. Therapy response was evaluated as PET negativity after 2 cycles of eBEACOPP followed by 2 cycles of ABVD. RESULTS: All three threshold methods analyzed for MTV showed a positive correlation with the PET response after chemotherapy. Areas under the curve (AUC) were 0.70 (95% CI 0.53-0.87) and 0.65 (0.50-0.80) using the fixed thresholds of SUV4.0 and SUV2.5 , respectively, for MTV- calculation. The calculation of MTV using a relative threshold of SUV41% showed an AUC of 0.63 (0.47-0.79). CONCLUSIONS: MTV does have predictive value after chemotherapy in early-stage unfavorable Hodgkin lymphoma, particularly when the fixed threshold of SUV4.0 is used for MTV calculation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01356680.

Comparison of outcomes between Hodgkin's lymphoma patients treated in and outside clinical trials: A study based on the EORTC-Dutch late effects cohort-linked data.

Studies have shown higher survival rates for patients with Hodgkin lymphoma (HL) treated within clinical trials compared to patients treated outside clinical trials. However, endpoints are often limited to overall survival (OS). In this retrospective cohort study, we investigated the effect of trial participation on OS, the incidence of relapse, second cancer, and cardiovascular disease (CVD). The study population consisted of patients with HL, aged between 14 and 51 years at diagnosis, who started their treatment between 1962 and 2002 at three Dutch cancer centres. Patients were either included in the EORTC Lymphoma Group trials (H1-H9) or treated according to standard guidelines at the time. After adjusting for differences in baseline characteristics, trial participation was associated with longer OS (median OS: 29.4 years [95%CI: 27.0-31.6] for treatment inside trials versus 27.4 years [95%CI: 26.0-28.5] for treatment outside trials, p = .046), a lower incidence of relapse (HR = 0.79, 95%CI: 0.63-0.98, p = .036) and a higher incidence of CVD (HR = 1.49, 95%CI: 1.23-1.79, p < .001). The trial effect for CVD was present only for patients treated before 1983. No evidence of differences in the incidence of second cancer was found. Consequently, essential results from clinical trials should be implemented into standard practice without undue delay.

Chronic fatigue in long-term survivors of Hodgkin's lymphoma after contemporary risk-adapted treatment.

BACKGROUND: Chronic fatigue (CF), substantial fatigue for ≥ six months, can manifest as a late effect (LE) after cancer treatment, and may affect several aspects of life. In a Norwegian cohort of Hodgkin's lymphoma survivors (HLS), more than a decade after contemporary risk-adapted treatment regimens with limited use of radiotherapy (RT), we assessed: (1) Prevalence of, (2) factors associated with (3) and implications of CF on socioeconomic status (SES) and work ability (WA). MATERIAL AND METHODS: HLS treated between 1997-2006, aged 8-49 years at diagnosis, were invited to participate in a population-based cross-sectional study on late effects in 2018-2019. In a mailed questionnaire, HLS responded to a fatigue questionnaire (FQ), work ability score (WAS) and short-form health survey (SF-36). Disease- and treatment data were extracted from hospital records. Factors associated with CF were identified by uni- and multivariate analysis. To study the implications of CF on SES and WA, a multinomial regression analysis was performed. RESULTS: Invitations were extended to 518 HLS and 298 (58%) responded to FQ, of whom 42% had CF with mean (standard deviation [SD]) physical- and mental fatigue scores of 10.2 (4.3) and 5.5 (2.1) respectively. Median age at survey was 45 years, 47% were females. In multivariate analysis female sex (p = 0.03), lower education (p = 0.03), body mass index ≥30 kg/m2 (p = 0.04), and an increasing number of comorbidities (p = 0.01) were associated with CF. No association with disease stage, chemotherapy or RT was found. CF was associated with poorer WAS scores at survey (p < 0.001), unemployment (p = 0.03), and receiving disability pension (p = 0.003). CONCLUSION: After risk-adapted treatment, CF is still a frequent LE among long-term HLS, without apparent association with disease or treatment-related parameters. CF is associated with reduced WA and SES. As no apparent risk reduction is seen with contemporary treatment, further studies should emphasize etiological factors of CF and treatment to alleviate this common LE.

Maternal and perinatal outcomes following a diagnosis of Hodgkin lymphoma during or prior to pregnancy: A systematic review.

BACKGROUND: The initial peak incidence of Hodgkin lymphoma (HL) occurs during reproductive years. OBJECTIVES: Synthesise published literature on the relationship between HL and maternal and perinatal outcomes. SEARCH STRATEGY: Systematic search of PubMed/Medline, Cochrane Library, Scopus, Embase and Science Direct from inception to June 2022, supplemented by hand-searching reference lists. SELECTION CRITERIA: Two reviewers independently reviewed titles, abstracts and full-text articles. Published studies containing original data were eligible. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and appraised study quality. Outcomes for pregnant women with a previous/current diagnosis of HL were compared separately with women never diagnosed with HL. Where data permitted, meta-analyses of odds ratios and proportions were performed. Certainty of evidence was determined using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. MAIN RESULTS: Of the 5527 studies identified, 33 met the inclusion criteria. In the groups with HL before pregnancy and HL during pregnancy, adjusted odds ratios were not statistically significant for congenital malformation (aOR 1.7, 95% CI 0.9-3.1, and aOR 1.84, 95% CI 0.81-4.15, respectively), preterm birth (PTB) (aOR 0.99, 95% CI 0.65-1.51, and aOR 6.74, 95% CI 0.52-88.03, respectively) and miscarriage (aOR 0.78, 95% CI 0.55-1.10, and aOR 0.38, 95% CI 0.05-2.72, respectively). The aORs for all other outcomes were not statistically significant, except for blood transfusion (aOR 1.38, 95% CI 1.05-1.82) and venous thromboembolism (VTE) (aOR 7.93, 95% CI 2.97-21.22) in the group for HL during pregnancy. The proportion of anaemia was also increased in this group (69%, 95% CI 57%-80% vs 4%, 95% CI 4%-5%, respectively). The GRADE certainty of findings ranged from low to very low. CONCLUSIONS: Rates of most adverse pregnancy outcomes among women with a previous/current HL diagnosis are not increased significantly compared with the general pregnant population. Women with HL diagnosed during pregnancy may have a higher PTB rate and increased likelihood of VTE, anaemia and blood transfusion; however, small study numbers and the low to very low GRADE certainty of findings preclude firm conclusions.

Unfavorable early-stage Hodgkin lymphoma: assessment of patient characteristics in a real-world setting.

Aim: Unfavorable prognostic factors among classical Hodgkin lymphoma (cHL) patients in the real-world setting have yet to be fully characterized. Methods: In this retrospective study using the ConcertAI Oncology Dataset, patient characteristics, unfavorable prognostic factors and treatment patterns were evaluated among patients diagnosed with cHL. Results: Among 324 adult cHL patients diagnosed 2016-2021, 16.1% were classified as early favorable, 32.7% early unfavorable and 51.2% advanced disease. Early unfavorable patients were younger and had a larger nodal mass. The prognostic factor B symptoms was most frequently documented in early unfavorable patients (59.4%), followed by bulky disease (46.2%), >3 involved lymph node regions (31.1%), and erythrocyte sedimentation rate ≥50 (25.5%). Conclusion: In this analysis of real-world data, we found that nearly a third of newly diagnosed cHL patients had early unfavorable disease. Our analysis also showed differences in the proportion of patients for each unfavorable factor among patients with early-stage unfavorable cHL.

What is this article about? Lymphoma is a type of blood cancer that develops when white blood cells grow out of control. This study looked at a certain type of lymphoma called classical Hodgkin lymphoma (cHL). Patients with cHL are put into groups based on risk factors. Risk factors mean the cancer had certain characteristics that make it more likely to spread to other body parts and more difficult to treat. These can be symptoms like drenching night sweats, unexplained fever, sudden weight loss, or large swellings of the infection fighting glands of the body.What did we do? We studied the risk factors of patients with cHL, using data from electronic medical records. What were the results? About a third of the patients in this study had early stage cHL with unfavorable risk factors, and over half of the patients had advanced stage cHL. The patients who had early stage cHL with unfavorable risk factors were younger and had a larger lump in a lymph node. More than half of the patients experienced drenching night sweats, unexplained fever, or weight loss of more than 10%. What do the results mean? We found that nearly a third of new cHL patients had early-stage cHL with unfavorable risk factors. We also showed differences in the number of patients with each unfavorable risk factor among patients with early-stage unfavorable cHL. This study can help doctors and researchers group patients and determine the best treatment or research study for patients who have cHL.

An Atypical Presentation of Hodgkin Lymphoma Invading the Myocardium.

Pericardial involvement by Hodgkin lymphoma has been found in up to 20% of children at presentation, but disease of the myocardium itself is rare. We describe an 18-year-old male with HL who presented with a large mediastinal mass, pericardial effusion, and tumor invasion of both atrial walls with intra-atrial extension. A PubMed search of publications between 1989 and 2022 was conducted and additional older references were identified among these publications. While pericardial disease is described in numerous case series, myocardial involvement by HL, diagnosed clinically rather than at autopsy, is distinctly unusual.

Endobronchial Presentation of Hodgkin Lymphoma Responding to Pembrolizumab: A Case Report.

An endobronchial localization of Hodgkin lymphoma is rare, and few experiences since the 1900s have been reported in the literature. Here we report the first case of a relapsed/refractory Hodgkin lymphoma with a critical vegetative mass at the level of the trachea successfully treated with pembrolizumab.

Primary CNS EBV-positive post-transplant lymphoproliferative disorder with polymorphic and classic Hodgkin lymphoma features: A case report and literature review.

Post-transplant lymphoproliferative disorders (PTLD) are typically Epstein-Barr virus (EBV)-associated lymphoid or plasmacytic proliferations that occur when immunosuppressed after transplantation. Only 2 cases of primary central nervous system (PCNS) classic Hodgkin lymphoma PTLD and 1 case of PCNS Hodgkin lymphoma-like PTLD have been previously reported. A 59-year-old male presented with malaise, headaches, and dizziness; neuroimaging revealed a 1.7-cm right cerebellar mass and a 0.6-cm right frontal mass. Microscopic examination demonstrated a perivascular and parenchymal polymorphous infiltrate composed of lymphocytes (CD3-positive T cells and CD20-positive B cells), plasma cells, and macrophages. Focally, macrophages had a spindled morphology with a fascicular arrangement amounting to poorly formed granulomata. Mitoses were seen. Scattered large atypical cells were visualized with irregular hyperchromatic nuclei, reminiscent of lacunar cells, mononuclear Hodgkin and binucleate Reed-Sternberg (RS) cells. EBV in situ highlighted a significant number of small lymphoid cells as well as many large atypical forms. Large atypical cells were seen to co-express CD15 and CD30. To our knowledge, this is the first such case with hybrid polymorphic PTLD and classic Hodgkin lymphoma features and the first such case to arise following liver transplantation. This case highlights the histological and immunophenotypic spectrum of these lymphoid proliferations and the resulting challenges in diagnosis and definitive subtyping.

Classic Hodgkin lymphoma in young people.

Classic Hodgkin lymphoma (CHL) is a unique form of lymphoid cancer featuring a heterogeneous tumor microenvironment and a relative paucity of malignant Hodgkin and Reed-Sternberg (HRS) cells with characteristic phenotype. Younger individuals (children, adolescents and young adults) are affected as often as the elderly, producing a peculiar bimodal age-incidence profile that has generated immense interest in this disease and its origins. Decades of epidemiological investigations have documented the populations most susceptible and identified multiple risk factors that can be broadly categorized as either biological or environmental in nature. Most risk factors result in overt immunodeficiency or confer more subtle alterations to baseline health, physiology or immune function. Epstein Barr virus, however, is both a risk factor and well-established driver of lymphomagenesis in a significant subset of cases. Epigenetic changes, along with the accumulation of somatic driver mutations and cytogenetic abnormalities are required for the malignant transformation of germinal center-experienced HRS cell precursors. Chromosomal instability and the influence of endogenous mutational processes are critical in this regard, by impacting genes involved in key signaling pathways that promote the survival and proliferation of HRS cells and their escape from immune destruction. Here we review the principal features, known risk factors and lymphomagenic mechanisms relevant to newly diagnosed CHL, with an emphasis on those most applicable to young people.