Mixed Cellularity Hodgkin Lymphoma Research Articles

Stevens-Johnson Syndrome secondary to nivolumab in a patient with mixed cell variety classical Hodgkin Lymphoma

The immune checkpoint inhibitors (ICIs) nivolumab and pembrolizumab are some of the principal treatment options for relapsed or refractory classic Hodgkin lymphoma. However, immunotherapy has been related to dermatological adverse events (DAEs) and could lead to discontinuation of cancer treatment in severe cases. DAEs encompass entities such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS/TEN-like reactions, drug reaction with eosinophilia and systemic symptoms (DRESS). We reported a case of a 46-year-old- female with classic mixed cellularity Hodgkin lymphoma, Lugano IV, who underwent a hematopoietic cell transplant and subsequent relapse, currently with Stevens-Johnson Syndrome secondary to nivolumab.

A Real-World Single-Center Study of Adult Hodgkin's Lymphoma

To summarize the clinical characteristics, therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma (HL). A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled, and their clinical data, including sex, age, pathological type, Ann Arbor stage, ECOG score, blood test, β2-microglobulin, lactate dehydrogenase level, albumin level were collected. The clinical characteristics, therapeutic effect and long-term prognosis of the patients were summarized and analyzed. In classical HL, nodular sclerosis HL accounted for the highest proportion of 51.6%, followed by mixed cellularity HL (36.5%), lymphocyte-rich classical HL (3.2%), and lymphocyte depletion HL (0.7%), while nodular lymphocyte predominant HL accounted for 4.8%. The 3-year overall survival (OS) rate of HL patients was 89.8%, and 5-year OS was 85.0%. The 3-year progression-free survival (PFS) rate was 73.4%, and 5-year PFS was 63.1%. Multivariate regression analysis indicated that IPI score was an independent negative factor, while hemoglobin (Hb) level was an independent positive factor for OS in HL patients. When the mediastinal mass size was 9.2 cm, it was most significant to judge the survival status of HL patients. 5-year OS and 5-year PFS were 97.4% and 76.0% in early-stage HL patients without large mass, respectively, while in patients with advanced-stage HL was 83.4% and 55.9% (both P < 0.05). After 2-4 courses of treatment, the overall response rate (ORR) of patients who received chemotherapy combined with radiotherapy was 95.0%, while that was 89.6% in those with chemotherapy alone. The overall prognosis of patients with HL is satisfactory, especially those in early-stage without large mass. IPI score and Hb level are independent risk factors for the prognosis of HL patients. A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.

Hodgkin lymphoma: 2023 update on diagnosis, risk-stratification, and management.

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8540 new patients annually and representing approximately 10% of all lymphomas in the United States. HL is composed of two distinct disease entities: classical HL and nodular lymphocyte-predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography scan, are used to optimize therapy. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage, and the presence of poor prognostic features. Patients with early-stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced-stage disease receive a longer course of chemotherapy, often without radiation therapy. However, newer agents, including brentuximab vedotin and anti-programmed death-1 (PD-1) antibodies, are now being incorporated into frontline therapy. High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, non-myeloablative allogeneic transplant, or participation in a clinical trial should be considered.

Clinically Undetected Hodgkin Lymphoma Diagnosed Initially on Bone Marrow Biopsy: A Large Retrospective Observational Study from a Tertiary Care Center

Abstract Introduction Hodgkin lymphoma (HL) involving the bone marrow (BM) is relatively rare with an incidence ranging from 4% to 18%. The incidence of primary HL of marrow is 0.25%. To the best of our knowledge, the present study is the largest study on HL diagnosed initially on marrow biopsy. Objective To establish diagnostic criteria based on clinicopathological and histological features in HL diagnosed first on the marrow. Materials and Methods This was a retrospective study done from January 2012 to December 2020 that included 36 cases of HL diagnosed initially on BM. Based on the presence of large mononuclear or binucleate Reed–Sternberg (RS)-like cells in a polymorphous inflammatory background, HL was suspected and immunohistochemistry (IHC) with CD15 and CD30 was done. Correlation with subsequent lymph node biopsies was done, wherever possible. Results Fever (94.4%) was the most common symptom, followed by loss of weight (66.7%). Twenty-one cases (58.4%) had uni/bicytopenia and 15 cases (41.6%) had pancytopenia. Only one case showed suspicious mononuclear RS cells on aspirates and the rest of the cases were diagnosed on trephine biopsy alone. Trephine imprints showed variable cellularity in 13 (36%) cases. Diffuse involvement was seen in 24 cases (66.7%), and focal nodular aggregates were seen in 12 cases (33.3%). Out of 36 cases, 26 cases (19 cases on marrow and 7 cases on lymph node) were confirmed as HL with IHC. Immunophenotype of the RS cells on the marrow was CD30+/CD15+ in (6/29) (20.7%) cases, CD30+/CD15− in (7/29) (24.1%) cases and CD30−/CD15+ in (6/29) (20.7%) cases. Seven cases (26.9%) were diagnosed on subsequent lymph node biopsy as mixed cellularity HL with IHC confirmation. Marrow fibrosis was seen in 16 cases (44.4%), and granulomas were seen in 8 cases (22.2%). Conclusion In cases presenting with long-standing fever and cytopenias, HL must always be suspected, even if there are no palpable lymph nodes. Bone marrow biopsy is preferable over aspiration in such cases and IHC plays a major role in diagnosing the cases.

Incidence and survival of Hodgkin lymphoma patients treated at a national cancer center in a middle-income country from 1999-2018: A report of 1,382 cases.

e19523 Background: Hodgkin lymphoma (HL) is classically described as a malignancy with a good prognosis and bimodal pattern. We aim to describe the incidence and survival of HL patients treated at the National Cancer Institute (NCI) in Peru. Methods: We evaluated the database at the NCI Epidemiology Department in Peru from 1999-2018. The international classification of diseases (ICD)-10 codes C810-C813, C817, C819 and ICD for Oncology (version 3) codes 96503-96533, 96573-96593, 96533-96553, 96573, 99903 were used to classify both nodal and extra-nodal HL. The estimate of overall survival (OS) curves was performed by the Kaplan-Meier method, and the difference was computed by the log-rank test. Results: During the study period 12,092 patients with lymphoma were found, of which 1,382 (11.4%) were HL. The median age was 24 years (range 2-88). Male patients were 62.4%. Patients of ≤14 years were 32.9%, with the most frequent 5-year interval group those aged 5-9 years-old representing 16.7% of patients. The adolescent and young adults (AYA) (15-39 years) group represented 38.4%. A total of 1,360 (98.4%) were classified as nodal HL. The classification according to the subtypes was as follows: 1,148 (83.1%) were one of the five subtypes [classical HL (cHL) and nodular lymphocyte-predominant HL (NLPHL)], 196 (14.2%) were HL, not otherwise specified, and 38 (2.7%) were HL without pathological confirmation. The classifiable 1,148 patients were categorized as follows: 1,107 patients (96.4%) were cHL and 41 (3.6%) were NLPHL. The cHL patients were classified as mixed cellularity HL (MCHL) in 52.3%, nodular sclerosis HL (NSHL) in 36.7%, lymphocyte-rich HL (LRHL) in 8.1%, and lymphocyte-depleted HL (LDHL) in 2.9%. The whole classifiable cohort (n = 1,148) showed a trimodal pattern. The MCHL subtype was most frequent in the 5-9 years group and in the 60-64 years group. The NSHL subtype was most frequent in the 20-24 years group. The median 5-year OS of the entire cohort (n = 1,382) was 86.3% (95%CI, 83.9-88.5). The OS according to the interval age groups were as follows: for the 0-14 years group the 5-yr OS was 94.9% (95%CI, 91.8-96.8), for the 15-39 years was 84% (95%CI, 79.5-87.68), for the 40-64 years group was 82.5% (95%CI, 75.2-87.8), and for the ≥65 years group was 58.6% (95%CI, 43.4-71.1). The OS according to age range showed a statistically significant difference p &lt; 0.01. Conclusions: In our study, patients with HL are younger compared to those in developed countries. The most frequent 5-year interval group is the 5-9 years group. HL incidence had a trimodal pattern. Extra-nodal presentation was extremely rare. NLPHL was also rare. The most frequent subtype was MCHL, however, in AYA patients the most frequent subtype was NSHL. Better OS was seen in the 0-14 year group, this being statistically significant compared to the older groups. Worse OS was observed in patients aged 65 and older.

Survival Varies By Age and Histology in Classical Hodgkin Lymphoma: A Report from the Children's Oncology Group

Introduction While 5-year event-free (EFS) and overall survival (OS) in Hodgkin lymphoma (HL) generally exceed 85% and 95%, respectively, outcomes may not be as favorable in adolescents and young adults (15 - 39 years [y]) compared to children. Small clinical trials have reported better outcomes for pediatric but not adult patients with mixed cellularity (MC) vs. nodular sclerosing (NS) histology, suggesting the possibility of biologic differences across the age-spectrum in HL. We examined survival by age and histology in patients receiving risk-based, response-adapted therapy for de novo HL on contemporary Children's Oncology Group (COG) trials. Methods This was a pooled analysis of individual-level data from 1,907 patients enrolled on three Phase 3 COG clinical trials for treatment of low-risk (AHOD0431), intermediate risk (AHOD0031) and high-risk (AHOD0831) HL between 2002 and 2012. Histologic subgroups included MC, NS and classical HL, not-otherwise-specified (cHL, NOS). Five-year cumulative incidence of relapse, EFS and OS were compared by age group (&amp;lt;15 y vs. ≥15 y) in the pooled cohort, and in histologic subgroups (MC and non-MC) using the Kaplan-Meier method. Effect modification was confirmed between age and histology. Cox proportional hazards regression models were used to examine the influence of age on EFS and OS, adjusted for race/ethnicity, Ann Arbor stage, B symptoms, bulky disease, receipt of radiation therapy (RT), and the interaction between age and histology; COG study was also included in the model, given that the criteria for response adaptation differed across the trials. Results Between 2002 and 2012, N= 2155 patients 1 - 21 y enrolled on three COG trials, 1,907 (88%) of whom were included in this analysis. Mean age of the cohort was 14.6 y (± 3.5) with N= 871 (46%) &amp;lt;15 y and N= 1,036 (54%) ≥15 y. In total, N= 1,547 patients (81%) had NS histology, N= 108 (6%) had cHL, NOS, and N= 196 (10%) had MC histology; by age, MC histology was present in N= 66 patients (7%) ≥15 y and N= 130 patients (15%) &amp;lt;15 y (p&amp;lt; 0.01). A significantly higher proportion of those ≥15 y vs. younger had B-symptoms at diagnosis (29% vs. 21%, p&amp;lt; 0.01), however the presence of bulky disease did not differ by age. Finally, patients ≥15 y (vs. &amp;lt;15 y) were significantly more likely to receive RT as part of their treatment (72% vs. 63%, p&amp;lt;0.01). Survival: Median follow up was 6.9 years. In unadjusted analyses, 5-year EFS and OS were 83% and 97%, respectively. The 5-year EFS was lower for patients ≥15 y vs. &amp;lt;15 y (85% vs 89%, p&amp;lt;0.01), as was the 5-year OS (96% vs. 99%, p&amp;lt; 0.01). In multivariable models, age ≥15 y (vs. younger) was associated with a 1.4-fold increased risk of EFS (HR: 1.4, 95% CI: 1.1, 1.8, p&amp;lt; 0.01), and more than a 3-fold increased risk of death (OS: HR: 3.1, 95% CI: 1.5, 6.4, p&amp;lt; 0.01). The effect of age on EFS varied by histologic subgroup. Among those with non-MC histology, cumulative incidence of relapse did not significantly differ by age in unadjusted models (Figure A), however 5-year EFS was significantly worse in the older group (Figure B). In multivariable analyses, age ≥15 y (vs. younger) was associated with a 1.3-fold increased risk of EFS (HR: 1.3; 1.03 - 1.7, p= 0.03) (Table). Among patients with MC histology, age ≥15 y (vs. younger) was associated with significantly higher relapse rate (22% vs. 5%, p&amp;lt; 0.01) (Figure C) and significantly worse 5-year EFS (75% vs. 94%, p&amp;lt; 0.01) (Figure D). This remained significant in multivariable models: patients with MC histology who were ≥15 y (vs. younger) had a 3.7-fold increased risk of EFS (HR: 3.7, 95% CI: 1.6, 8.9, p&amp;lt; 0.01) (Table). Conclusion In patients receiving response-adapted therapy for de novo HL on contemporary COG trials, adolescents ≥15 y had worse EFS and OS compared to younger groups. The magnitude of the effect of age was higher in patients with MC disease. Although recent pediatric trials in HL have indicated better survival for some children with MC histology, alternative approaches or novel therapies should be considered for older adolescents with MC disease, whose outcomes appear more like adults. Disclosures No relevant conflicts of interest to declare.

HL-287: An Unusual Presentation of Discordant Classical Hodgkin and Non-Hodgkin Lymphoma in a Young Adult

Introduction Discordant lymphoma is the condition in which two subtypes of lymphoma occur synchronously in different anatomical sites. The objective is to highlight this exceptionally rare combination in order to prevent inaccurate diagnosis. Case Presentation A 20-year-old female presented with typical signs of diffuse supraclavicular and mediastinal lymph node enlargement. Based on the characteristic histological appearance of lymph nodes, she was diagnosed with classical mixed cellularity Hodgkin Lymphoma. Treatment was initiated with ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy. Following four cycles of therapy, the patient underwent a PET scan that revealed partial remission with persistence of mediastinal lymph nodes. Two additional cycles of ABVD were initiated, followed by a repeat PET scan that revealed new anterior and mediastinal lymph nodes with a necrotic center. Radiotherapy was done with a dose of 36 Gy in 20 fractions. Three months later following therapy, the patient underwent a PET scan that showed new onset sub-diaphragmatic lymph nodes with necrotic centers, although it showed a major decrease in the mediastinal lymph nodes previously described. A biopsy was performed on the new appearing nodes and was in favour of diffuse large B cell lymphoma, most likely of non-germinal center cell of origin, and was expressing CD30. Following this discovery, additional cycles of R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and cisplatin) were administered, resulting in a significant decrease in sub-diaphragmatic lymph nodes. Conclusion Even if strict guidelines are followed, we must remain aware that several types of lymphoma can coexist simultaneously, and discordant lymphoma should be considered, especially when new lymph nodes appear despite adequate therapy, and a biopsy is always recommended. Identifying this rare entity can offer a survival benefit.

Hodgkin lymphoma.

Hodgkin lymphoma (HL) is a B cell lymphoma characterized by few malignant cells and numerous immune effector cells in the tumour microenvironment. The incidence of HL is highest in adolescents and young adults, although HL can affect elderly individuals. Diagnosis is based on histological and immunohistochemical analyses of tissue from a lymph node biopsy; the tissue morphology and antigen expression profile enable classification into one of the four types of classic HL (nodular sclerosis, mixed cellularity, lymphocyte-depleted or lymphocyte-rich HL), which account for the majority of cases, or nodular lymphocyte-predominant HL. Although uncommon, HL remains a crucial test case for progress in cancer treatment. HL was among the first systemic neoplasms shown to be curable with radiation therapy and multiagent chemotherapy. The goal of multimodality therapy is to minimize lifelong residual treatment-associated toxicity while maintaining high levels of effectiveness. Recurrent or refractory disease can be effectively treated or cured with high-dose chemotherapy followed by autologous haematopoietic stem cell transplantation, and prospective trials have demonstrated the potency of immunotherapeutic approaches with antibody-drug conjugates and immune checkpoint inhibitors. This Primer explores the wealth of information that has been assembled to understand HL; these updated observations verify that HL investigation and treatment remain at the leading edge of oncological research.

Epstein Barr Virus in Hodgkin’s Lymphoma a Path Less Treaded: An Observational Study

Background: Epstein-Barr virus (EBV) is a ubiquitous virus belonging to γ-Herpesvirus subfamily, infecting B cells, T cells, Natural killer (NK) cells &amp; causes both benign and malignant diseases. It has been detected in large subset of Hodgkin lymphoma (HL) cases around the world, especially in countries with poor socioeconomic conditions and among younger age. Limited studies are available reflecting the Indian scenario of HL and EBV association. EBV positivity in Indian HL varies from 28-97% Majority of these studies employed Immunohistochemistry (IHC) for LMP1, a few performed In Situ Hybridisation (ISH) for EBER.&#x0D; Objective: To study the association of EBV in classical HL by immunohistochemical expression of latent membrane protein 1 (LMP1) antigen in North Indian population and to correlate it with different demographic variables &amp; subtypes of HL.&#x0D; Materials and Methods: Observational study including 26 untreated HL cases diagnosed on lymph node excision biopsy. IHC was performed for EBV LMP1, CD15, CD30, CD45, CD3, CD20.&#x0D; Results: Patients ranged in age from 5-55years (median 18yrs), with M:F ratio of 3.3:1. Palpable lymphadenopathy was found in all cases followed by pallor (64%), B symptoms (50%), nodal pain (30.8%) &amp; bulky disease (19.2%). Maximum number of patients were in Stage I (65.4%) followed by stage II&amp;III (15.4% each) &amp; stage IV (3.8%). Mixed cellularity HL comprised 77%, lymphocyte depleted 11.5%, nodular sclerosis 7.7% &amp; lymphocyte rich 3.8%. IHC for EBV LMP1 was positive in 73.1% cases. Mixed cellularity HL showed an association in 70% cases.&#x0D; Conclusions: HL in India is a disease of young males, with mixed cellularity as the commonest subtype, highly associated with EBV and presentation at an early stage.

Hodgkin lymphoma: A 2020 update on diagnosis, risk-stratification, and management.

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8480 new patients annually and representing approximately 10% of all lymphomas in the United States. Hodgkin lymphoma is composed of two distinct disease entities: classical HL and nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography (PET) scan, are used to optimize therapy. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy, followed by involved-field radiation therapy. Patients with advanced stage disease receive a longer course of chemotherapy, often without radiation therapy. However, newer agents including brentuximab vedotin and anti-PD-1 antibodies are now being incorporated into frontline therapy. High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, non-myeloablative allogeneic transplant or participation in a clinical trial should be considered.

Analysis of 153 115 patients with hematological malignancies refines the spectrum of familial risk

AbstractEstimating familial cancer risks is clinically important in being able to discriminate between individuals in the population at differing risk for malignancy. To gain insight into the familial risk for the different hematological malignancies and their possible inter-relationship, we analyzed data on more than 16 million individuals from the Swedish Family-Cancer Database. After identifying 153 115 patients diagnosed with a primary hematological malignancy, we quantified familial relative risks (FRRs) by calculating standardized incident ratios (SIRs) in 391 131 of their first-degree relatives. The majority of hematological malignancies showed increased FRRs for the same tumor type, with the highest FRRs being observed for mixed cellularity Hodgkin lymphoma (SIR, 16.7), lymphoplasmacytic lymphoma (SIR, 15.8), and mantle cell lymphoma (SIR, 13.3). There was evidence for pleiotropic relationships; notably, chronic lymphocytic leukemia was associated with an elevated familial risk for other B-cell tumors and myeloproliferative neoplasms. Collectively, these data provide evidence for shared etiological factors for many hematological malignancies and provide information for identifying individuals at increased risk, as well as informing future gene discovery initiatives.

Classification of malignant lymphoma subtypes in Korean patients: a report of the 4th nationwide study

To determine the relative frequency and change of malignant lymphoma in Korea according to the 4th World Health Organization (WHO) classification and compare with previous reports. Between 2015 and 2016, 7737 new patients with malignant lymphoma were enrolled from 31 institutes, with their clinicopathologic information obtained, and evaluated for the relative frequency of lymphoma subtypes. The relative frequency of non-Hodgkin lymphoma (NHL) was 94.8%, and that of Hodgkin lymphoma (HL) was 5.2%. B cell lymphomas accounted for 83.1% of all NHLs; T/natural killer (NK) cell lymphomas, 16.4%; and immunodeficiency-associated lymphoproliferative disorders, 0.5%. The most common NHL subtypes were diffuse large B cell (41.5%), extranodal marginal zone (MALT, 19.8%), follicular (7.5%), NK/ T cell (4.2%), and peripheral T cell lymphomas, not otherwise specific (PTCL, NOS, 3.4%). Nodular sclerosis was the predominant HL subtype (48.5%), followed by mixed cellularity (28.7%), lymphocyte-rich (6.8%), lymphocyte-depleted (1.5%), lymphocyte-predominant (2.8%), and unclassified HL (11.8%). Compared with a previous report, increased B cell lymphomas (77.6–83.1%) and slightly decreased NK/T cell lymphomas and PTCL were observed. The incidence of follicular lymphoma increased by more than 2.5-fold (2.9–7.5%). Incidence rates of newly diagnosed lymphomas were lower for HL and higher for extranodal NHL, MALT, and nasal type NK/T cell lymphomas in Korea than those in Western countries. A slight increase in the relative frequency of B cell lymphoma and a prominent increase in follicular lymphoma may be attributed to refined diagnostic criteria and Westernized disease patterns.

Childhood use of antimicrobials and risk of Hodgkin lymphoma: a Danish register–based cohort study

AbstractThe peculiar bimodal age distribution of Hodgkin lymphoma (HL), together with other epidemiological findings, inspired the so-called “late infection hypothesis” in the 1970s. Under this model, HL in young adults is caused by delayed infection with a relatively common agent, with HL risk increasing with age at infection. We time-dependently tallied prescriptions filled, for a broad spectrum of antimicrobials, at age 0 to 9 years for all Danish HL patients diagnosed in 1997 to 2015 at age 10 to 25 years (n = 296) and up to 10 controls for each of these, individually matched for sex and birthdate (n = 2688). Antimicrobial use was taken as a proxy for general infectious disease pressure. Analyses were also stratified by the 2 main histological subtypes: nodular sclerosis HL (NSHL) (n = 206) and mixed cellularity HL (MCHL) (n = 47). We compared antimicrobial use at ages 0 to 9 years between cases and comparators using stratified Cox regressions with repeated follow-up for a next prescription, to produce hazard ratios (HRs) of antimicrobial use according to (future) HL status. Reverse causation was mitigated by disregarding risk time <2 years before HL (pseudo)diagnosis. Analyses were adjusted for number of older and younger siblings. NSHL patients had received statistically significantly fewer antimicrobials than comparators early in life (HR0-2 years, 0.79; 95% confidence interval, 0.66-0.95), whereas patients with MCHL had received statistically significantly more antimicrobials than comparators throughout the first 10 years of life (HR0-9 years, 1.53; 95% confidence interval, 1.33-1.76). The late infection hypothesis was supported in NSHL, whereas immune dysfunction seemed more prominent in MCHL etiology.

Incidence of Hodgkin lymphoma in HIV-positive and HIV-negative patients at a tertiary hospital in South Africa (2005 - 2016) and comparison with other African countries.

Hodgkin lymphoma (HL) is the most common non-AIDS-defining cancer in HIV-positive patients. Studies on South African (SA) populations have described the prevalence as 7 - 17% of all lymphomas, 8 - 27% of head and neck lymphomas, 9% of lymph node biopsies and 4% of HIV-related malignancies. To describe the incidence of HL at our centre between 2005 and 2016 by year, gender, HIV status, histological subclassification and bone marrow involvement, and compare these findings with similar SA and African studies. This was a retrospective study of all incident HL cases diagnosed in the Department of Pathology, National Health Laboratory Service, Tygerberg Academic Hospital, Cape Town. Follow-up, relapsed and referral cases were excluded. A positive diagnosis of HL was confirmed by either lymph node or bone marrow biopsy and was based on morphological and immunohistochemical findings in accordance with the World Health Organization classification. There were 303 incident cases of HL diagnosed. The incidence increased from 2005 to 2011, with a spike in cases in 2008 and a subsequent decline overall after 2011. The highest proportion of cases was in the 25 - 49-year-old age category (51.1%). There were 77 HIV-positive patients (25.4%), of whom 53 (68.8%) had CD4+ counts &lt;500 cells/µL. In keeping with other African studies, the main subtypes were nodular sclerosis HL (49.8%) and mixed-cellularity HL (23.1%). Bone marrow biopsy following lymph node diagnosis of HL confirmed involvement in 23.7% of patients. Absolute numbers of cases of HL at our centre have increased since the roll-out of antiretroviral therapy (ART) to the public sector. The recent change in policy to make ART available to all HIV-positive patients independent of CD4+ count suggests that patients will survive longer and are therefore at increased risk of developing HL. We anticipate that numbers of HL cases will increase or remain high in the coming years, and we need to prepare for this.

Hodgkin lymphoma: 2018 update on diagnosis, risk-stratification, and management.

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8500 new patients annually and representing approximately 10.2% of all lymphomas in the United States. HL is composed of two distinct disease entities: classical HL and nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography scan, are used to optimize therapy. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. Newer agents including brentuximab vedotin are now being incorporated into frontline therapy and these new combinations are becoming a standard of care. High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, nonmyeloablative allogeneic transplant or participation in a clinical trial should be considered.

Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility

Several susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all classical Hodgkin lymphoma at 6q22.33 (rs9482849, P = 1.52 × 10−8) and for nodular sclerosis Hodgkin lymphoma at 3q28 (rs4459895, P = 9.43 × 10−17), 6q23.3 (rs6928977, P = 4.62 × 10−11), 10p14 (rs3781093, P = 9.49 × 10−13), 13q34 (rs112998813, P = 4.58 × 10−8) and 16p13.13 (rs34972832, P = 2.12 × 10−8). Additionally, independent loci within the HLA region are observed for nodular sclerosis Hodgkin lymphoma (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity Hodgkin lymphoma (rs1633096, rs13196329, Val86 in HLA-DRB1). The new and established risk loci localise to areas of active chromatin and show an over-representation of transcription factor binding for determinants of B-cell development and immune response.

Survival Pattern of Hodgkin Lymphoma Patients in the Last 25 Years in Lebanon.

After the emergence of combination chemotherapy in 1960s, survival of patients with Hodgkin lymphoma (HL) has dramatically improved worldwide. We lack studies that document the favorable evolution of survival regarding this disease in Lebanon. To compare the overall survival in HL over 3 different decades in Lebanon. We retrospectively reviewed the charts of 196 patients diagnosed with HL, treated and followed from 1990 to 2015 in our center. Patients were divided into 3 groups according to period of analysis: group A (1990-1999), group B (2000-2009), and group C (2010-2015). We studied the characteristics and survival patterns of patients in each group. The male-to-female sex ratio was 1.06. The median age at diagnosis was 33 years in group A, 30.4 in group B, and 33.12 in group C (P= .6). Results showed variations in the subtypes of the disease according to the following: nodular-sclerosis HL 59.5% in group A, 76.2% in group B, and 85.4% in group C. Mixed cellularity HL 21.6% in group A, 2.4% in group B, and 73.7% in group C (P= .0001). Patients presented with localized disease in 58.6%, 73.7%, and 56.4% in groups A, B, and C, respectively (P= .173). Complete remission was achieved in 76.5% in group A, 85.3% in group B, and 69.5% in group C (P= .007). The survival rate at 5 years in group A was 91%, 94% in group B, and 100% in group C. The survival of patients with HL has dramatically improved over the past 25 years in Lebanon. These results resemble those achieved in Western countries due to the fast adoption of new molecular imaging technologies at diagnosis and follow-up and the rapid approval of new drugs for relapse in the Lebanese market.

Eosinophilia as a first sign of Hodgkin´s lymphoma: A case report

Introduction. It is well known that eosinophilia appears in a malignant disease. Frequency of all Hodgkin`s lymphoma patients is estimated to about 15%. Prognostic importance of this phenomenon is not completely investigated. Therefore we decided to present a female patient with eosinophilia, six months before lymphoma appearance. Case report. We presented a 51- years old female, from Serbia, who had eosinophilia (1,530?2,040 eosinophils per ?L of blood), six months before Hodgkin's lymphoma appearance. Eosinophilic granuloma was confirmed by tumor?s biopsy and histopathologic examination, from the right femoral region. As eosinophilia was increasing, lymph nodes became enlarged (120 ? 65 mm diameter), in the right parailiac region. All infectious and allergic examinations did not reveal eosinophilia's cause. Histopathologic revision was made with added immunohistochemical stains 17 months after tumor's biopsy. The diagnosis was changed from eosinophilic granuloma to mixed cellularity Hodgkin's lymphoma. After conducted Ann Arbor staging classification, II B clinical stage was established. The treatment was done by chemotherapy according to adriamycin, bleomycin, vinblastine, dacarbarine (ABVD) protocol, with 6 courses. Complete remission of the disease was achieved after 4 courses. Eosinophils number dropped to 640 per ?l blood. Conclusion. Eosinophilia without revealed cause can precede Hodgkin's lymphoma. We suggest careful search for enlarged lymph nodes, anywhere in the patients? body who suffer from eosinophilia. Timely and accurate histopathologic diagnostic is a right way to resolve such conditions.

Hodgkin lymphoma: 2016 update on diagnosis, risk-stratification, and management.

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 9,050 new patients annually and representing approximately 11.2% of all lymphomas in the United States. HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups under the designation of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography (PET) scan, are used to optimize therapy. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. Management of relapsed/refractory disease: High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, nonmyeloablative allogeneic transplant or participation in a clinical trial should be considered.

Immunohistochemical Profile of Hodgkin and Non-Hodgkin Lymphoma.

To analyze the frequencies of histological types of lymphoma, diagnosed with complete immunohistochemical profile in younger and older age group. Cross-sectional analytical study. Dow Diagnostic Research and Reference Laboratory, Dow University of Health Sciences, Karachi, from January 2009 to September 2013. Consecutive cases of lymphomas, which were diagnosed using immunohistochemistry, were analyzed according to WHO classification. Frequency and percentages for different types of lymphomas were calculated. Hodgkin and non-Hodgkin lymphomas characteristics in two age groups of less than and more than 40 years were compared, applying chi-square test. Out of the 318 cases, 79 (25%) were Hodgkin Lymphomas (HL) and 239 (75%) were Non-Hodgkin Lymphomas (NHL). Mixed Cellularity Hodgkin Lymphoma (MCHL) was the commonest (n=48). Amongst the NHL, 215 (89.95%) were B cell lymphomas and 24 (10.05%) were T-cell lymphomas. Diffuse Large B-Cell Lymphoma (DLBCL) was the commonest lymphoma (n=165, 69.95% of NHL). Anaplastic T-Cell Lymphoma (ALCL, n=10) was the commonest T-cell lymphoma. The frequency of HLwas significantly higher in the younger age group and that of NHLwas higher in the older age group (p < 0.001). Primary lymph node involvement was reported in 175 (55%) and cervical lymph node was the most frequent site. Extra nodal involvement was seen in 93 (29%) of all cases and was reported in 87 (36.4%) of NHLand 6 (7.5%) of HL. The most common extra nodal site was the gastrointestinal tract. Hodgkin lymphoma comprises 25% and non-Hodgkin lymphoma comprises 75% of all lymphomas. Both occur in younger age groups than reported in the West. B-cell NHLis three times more common than T-cell lymphoma. DLBCLis the most frequent lymphoma. ALCLis the most common T-cell, and mixed cellularity is the most common Hodgkin lymphoma.