Adult Hodgkin lymphoma incidence trends in the United States from 2000 to 2020.

Hodgkin lymphoma (HL) is a rare malignancy affecting the lymphatic system. Our study examined the incidence rates of adult HL based on sex, race/ethnicity, age, and histological subgroups in the United States (US) from 2000 to 2020. Data for this study were extracted from the Surveillance, Epidemiology, and End Results 22 database. HL patients were identified utilizing the International Classification of Diseases for Oncology version 3 and categorized as classical HL, lymphocyte-rich/mixed cell/lymphocyte depleted, nodular sclerosis, classical HL, not otherwise specified, and nodular lymphocyte-predominant HL. The study reported average annual percent change (AAPC). All estimates were presented as counts and age-standardized incidence rates (ASIRs) per 100,000 individuals. Between 2000 and 2019, a total of 70,924 cases of HL were reported in the US. Classical HL was the predominant subtype (94.27%), and most incident cases were among non-Hispanic Whites (66.92%) and those aged 20-29 years (24.86%). The ASIR per 100,000 population was 3.83 for men and 2.92 for women. Both sexes showed declines in the AAPCs between 2000 and 2019 (- 0.64% [- 0.99, - 0.28] and - 0.40% [- 0.77, - 0.03] for men and women, respectively). There was a significant decrease in ASIRs after COVID-19 among both sexes (percent change: - 7.49% [- 11.58, - 3.40]). Throughout all age groups, men had a higher incidence rate compared to women, except for those aged 20-29 years. Although the overall HL incidence rate was lowered in the study period from 2000 to 2019, a dramatic decrease in ASIRs of HL patients following COVID-19 pandemic was observed.

SATB1 and p16 Expression and Prognostic Value in Croatian Hodgkin Lymphoma Patients: A Unicentric Study.

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.

terraFlow, a high-parameter analysis tool, reveals T cell exhaustion and dysfunctional cytokine production in classical Hodgkin's lymphoma.

Immune cells express an incredible variety of proteins; by measuring combinations of these, cell types influencing disease can be precisely identified. We developed terraFlow, a platform that defines cell subsets exhaustively by combinatorial protein expression. Using high-parameter checkpoint-focused and function-focused panels, we studied classical Hodgkin's lymphoma (cHL), where systemic T cells have not been investigated in detail. terraFlow revealed immune perturbations in patients, including elevated activated, exhausted, and interleukin (IL)-17+ phenotypes, along with diminished early, interferon (IFN)γ+, and tumor necrosis factor (TNF)+ T cells before treatment; many perturbations remained after treatment. terraFlow identified more disease-associated differences than other tools, often with better predictive power, and included a non-gating approach, eliminating time-consuming and subjective manual thresholds. It also reports a method to identify the smallest set of markers distinguishing study groups. Our results provide mechanistic support for past reports of immune deficiency in cHL and demonstrate the value of terraFlow in immunotherapy and biomarker studies.

Efficacy of escalating therapy with brentuximab vedotin-AVD in advanced stage Hodgkin lymphoma patients with positive interim positron emission tomography after ABVD.

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

Mature oocyte found during ovarian tissue cryopreservation in an early adolescent female. / 青春初期女性行卵巢组织冷冻过程中发现成熟卵母细胞一例.

A 15-year-old female with Hodgkin's lymphoma underwent ovarian tissue cryopreservation for preserving fertility in Reproductive Department of Sir Run Run Shaw Hospital, Zhejiang University School of Medical after receiving one course of chemotherapy. During the ovarian tissue cryopreservation, one MⅡmature oocyte and three germinal vesicle oocytes were found. The three immature oocytes underwent in vitro maturation but failed. Ultimately, one mature oocyte and 12 ovarian cortex slices were cryopreserved using vitrification. This case indicates that for patients with established gonadal axis feedback, ovarian tissue cryopreservation may not be the only method for fertility preservation. It is advisable to consider ovarian stimulation and oocyte retrieval for oocyte cryopreservation. Alternatively, for individuals in the ovulation phase of their menstrual cycle, attempting oocyte retrieval before ovarian tissue cryopreservation to obtain mature oocytes from the natural cycle, followed by oocyte cryopreservation, may enhance the likelihood of successful fertility preservation.

A rare development of classical Hodgkin lymphoma in the head and neck region: Case report and review of the literature.

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

Distressed personality is associated with late adverse effects in long-term survivors of Hodgkin lymphoma.

BACKGROUND AND PURPOSE: There are few studies of personality traits in long-term Hodgkin lymphoma survivors (HLSs) treated according to contemporary stage-and risk-adapted approaches. The Distressed Personality (DP) Scale covers negative affectivity and social inhibition. We examined differences in self-reported late adverse effects (LAEs) between HLSs with and without DP and other explanatory variables. MATERIAL AND METHODS: This cross-sectional questionnaire-based study included a population-based cohort of HLSs treated from 1997 to 2006, aged 8-49 years at diagnosis, and alive in 2016. Among 518 eligible HLSs, 303 responded (58%), and 294 completed the DP scale. DP was defined by scores above cut-off on both the negative affectivity and social inhibition subscales. LAEs studied were major depression, posttraumatic stress disorder, sleep problems, obesity, neuropathy, fatigue, memory problems, and general health. DP and 10 other explanatory variables were tested against LAEs as dependent variables in multivariable regression analyses. RESULTS: The mean age at survey was 45.9 years (standard deviation [SD] 4.6), mean follow-up time 16.7 years (SD 3.0), and 48% were females. Eighty-two HLSs had DP (28%, 95% confidence interval 23% - 33%). All LAEs except obesity were significantly more common/had higher mean score in HLSs with DP. In multivariable analyses, presence of DP was significantly associated with all LAEs except obesity. INTERPRETATION: The presence of DP is common among HLSs. The presence of DP was associated with most self-report LAEs examined. Including assessment of personality traits in the survivorship care plans of HLSs should be considered. Prospective studies assessing the influence of pretreatment DP on LAEs are warranted.

Posterior reversible encephalopathy syndrome (PRES) in classic Hodgkin's lymphoma, complicated by anthracycline-induced cardiomyopathy.

A woman in her 20s with no medical history was diagnosed with bulky stage II classic Hodgkin's lymphoma after an 8-week history of shortness of breath, cough and lethargy. A regimen of doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) was commenced with six cycles planned. During the first cycle, the patient was profoundly hypertensive. She then suffered two self-terminating tonic-clonic seizures.Examination and investigations diagnosed posterior reversible encephalopathy syndrome (PRES), which resolved completely in 11 days with strict blood pressure control and withholding chemotherapy. Treatment was further complicated by anthracycline-induced cardiomyopathy, requiring a switch in regimen to gemcitabine BVD.The patient made a full recovery from neurology and cardiology perspectives and completed six cycles of chemotherapy, achieving a complete metabolic response by the tumour. We illustrate the case, describe differential diagnoses and management of PRES, its association with chemotherapy and the successful chemotherapy rechallenge.

Association of both BCL2 positive and negative follicular lymphoma to clasical Hodgkin lymphoma and/or gray zone lymphoma.

We present a series of 9 follicular lymphomas that progressed/transformed into classical Hodgkin lymphoma (CHL). Three cases of CHL showed a syncytial pattern (SCHL) making the differential diagnosis to Gray zone lymphoma (GZL) challenging. None of these three cases presented in the mediastinum. Based in all molecular data analyzed (BCL2/BCL6 FISH studies, IgH PCR and TNGS with a customized gene panel) we did find clonal relationship between the BCL2-positive FL cases and their CHL components in all cases. The three SCHL/GZL cases showed an activated phenotype according to Hans algorithm, presented the t(14; 18)(q32; q21), two out of three showed B cell markers and all expressed CD30 and p53. Interestingly, we identified three BCL2-negative FL cases with a further diagnosis of CHL expanding the spectrum of these association. In one of these three cases a different mutational profile was found in both the FL and the CHL components. All this data together suggests that CHL associated to BCL2-positive FL could be originated in a common progenitor cell (CPC) that give rise to both FL and CHL, acquiring this last component further genetic events in a linear fashion. On the other hand, no clonal relationship between CHL and BCL2-negative FL could be found, suggesting a fortuity association. Nevertheless, ample series of cases studied with more sensitive techniques are needed to confirm our hypothesis.

Management of Hodgkin Lymphoma during pregnancy, review of the literature and description of an homogenous expectative attitude associated with excellent outcome.

Hodgkin lymphoma (HL) occuring during pregnancy is a rare condition, and management relies on sparse literature. The specificity of pregnancy requires the clinician to take into account the clinical emergency, the stage of the lymphoma, the trimester of pregnancy, and the patient's choices. The main objective is twofold: to limit the risk of toxicity and adverse events for both mother and fetus, without reducing the chances of a successful outcome. Current literature data suggest that the use of ABVD-type polychemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine) is associated with obstetrical events and long-term fetal toxicity. We report here the results of a homogeneous management considering wait-and-see, vinblastine monotherapy and ABVD polychemotherapy options. The outcomes in terms of obstetrical complications, response rate, and overall survival (100 %) reinforce the idea that strategies that do not involve the use of multidrug therapy are possible and are associated with very good results.

Ewing sarcoma presenting in the lung: a case report.

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.

Efficacy and safety of standard BEACOPP regimen versus ABVD regimen for treatment of advanced Hodgkin's lymphoma.

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.

The Effect of Diagnostic and Therapeutic Changes on the Survival of Hodgkin's Lymphoma Patients (1980-2019).

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.

Radiation exposure of the glandular mammary tissue in women patients with mediastinal Hodgkin lymphoma treated with protons.

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

[Hodgkin lymphoma - pain at alcohol consumption as the only symptom]. / Diagnostik och behandling av klassiskt Hodgkins lymfom.

The authors Lanke and Relander describe a patient with classical Hodgkin lymphoma (cHL) stage IIA, who had pain at alcohol consumption as the only symptom at diagnosis. The patient was treated with 4 cycles of ABVD chemotherapy and proton therapy 29.75 Gy (RBE). Apart from FDG-PET/CT the course of the disease was followed with serum-TARC. The case illustrates the value of knowing also rare symptoms at the general practice, the usefulness of TARC as a tumour marker in cHL, and the use of proton therapy in order to further reduce late radiotherapy side effects.

Multiplex spatial analysis reveals increased CD137 expression and m-MDSC neighboring tumor cells in refractory classical Hodgkin Lymphoma.

The Hodgkin and Reed - Sternberg (HRS) cells in classical Hodgkin Lymphoma (cHL) actively modify the immune tumor microenvironment (TME) attracting immunosuppressive cells and expressing inhibitory molecules. A high frequency of myeloid cells in the TME is correlated with an unfavorable prognosis, but more specific and rare cell populations lack precise markers. Myeloid-derived suppressor cells (MDSCs) have been identified in the peripheral blood of cHL patients, where they appear to be correlated with disease aggressiveness. TNFRSF9 (CD137) is a T cell co-stimulator expressed by monocytic and dendritic cells. Its expression has also been described in HRS cells, where it is thought to play a role in reducing antitumor responses. Here, we perform qualitative and quantitative analyses of lymphocytic and MDSC subtypes and determine the CD137 cell distribution in cHL primary tumors using multiplex immunofluorescence and automated multispectral imaging. The results were correlated with patients' clinical features. Cells were stained with specific panels of immune checkpoint markers (PD-1, PD-L1, CD137), tumor-infiltrating T lymphocytes (CD3, PD-1), and monocytic cells/MDSCs (CD68, CD14, CD33, Arg-1, CD11b). This approach allowed us to identify distinct phenotypes and to analyze spatial interactions between immune subpopulations and tumor cells. The results confirm CD137 expression by T, monocytic and HRS cells. In addition, the expression of CD137, T exhausted cells, and monocytic MDSCs (m-MDSCs) in the vicinity of malignant HRS cells were associated with a worse prognosis. Our findings reveal new elements of the TME that mediate immune escape, and confirm CD137 as a candidate target for immunotherapy in cHL.

CD137-expressing immune cells and HRS cells are more abundant and in closer proximity in refractory patients than in responders.Monocytic myeloid-derived suppressor cells (m-MDSCs) are associated with unfavorable outcomes and relapse in cHL, unlike granulocytic MDSCs (g-MDSCs), which are located far from HRS cells in non-responders.The cHL tumor microenvironment promotes immune escape in refractory patients by holistically driving polarization and/or recruitment of several cell types with increased expression of CD137 and PD-L1 checkpoints.

Insights into the Gene Expression Profile of Classical Hodgkin Lymphoma: A Study towards Discovery of Novel Therapeutic Targets.

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.