Virus de Epstein-Barr: más que una mononucleosis infecciosa / Epstein-Barr virus: more than infectious mononucleosis

El virus de Epstein-Barr (VEB) fue el primer virus asociado a neoplasias en humanos. Infecta el 95 % de la población mundial, y aunque usualmente es asintomático, puede causar mononucleosis infecciosa y se relaciona con más de 200.000 casos de neoplasias al año. De igual forma, se asocia con esclerosis múltiple y otras enfermedades autoinmunes. A pesar de ser catalogado como un virus oncogénico, solo un pequeño porcentaje de los individuos infectados desarrollan neoplasias asociadas a VEB. Su persistencia involucra la capacidad de alternar entre una serie de programas de latencia, y de reactivarse cuando tiene la necesidad de colonizar nuevas células B de memoria, con el fin de sostener una infección de por vida y poder transmitirse a nuevos hospederos. En esta revisión se presentan las generalidades del VEB, además de su asociación con varios tipos de neoplasias, como son el carcinoma nasofaríngeo, el carcinoma gástrico, el linfoma de Hodgkin y el linfoma de Burkitt, y la esclerosis múltiple. Adicionalmente, se describen los mecanismos fisiopatológicos de las diferentes entidades, algunos de ellos no completamente dilucidados

Epstein-Barr virus (EBV) was the first virus associated with human cancer. It infects 95% of the world's population, and although it is usually asymptomatic, it causes infectious mononucleosis. It is related to more than 200,000 cases of cancer per year, and is also associated with multiple sclerosis and other autoimmune diseases. Despite being classified as an oncogenic virus, only a small percentage of infected individuals develop EBV-associated cancer. Its persistence involves the ability to alternate between a series of latency programs, and the ability to reactivate itself when it needs to colonize new memory B cells, in order to sustain a lifelong infection and be able to transmit to new hosts. In this review, the general characteristics of EBV are presented, in addition to its association with various types of cancers, such as nasopharyngeal carcinoma, gastric carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma, and multiple sclerosis. Additionally, the pathophysiological mechanisms of the different entities are described, some of them not completely elucidated yet

A 51-Year-Old Man With a Large Posterior Mediastinal Mass.

CASE PRESENTATION: A 51-year-old White male never-smoker presented with intermittent cough and progressive dyspnea. His symptoms started after an exposure to bat guano while cleaning his attic approximately 9 months earlier. He has received several courses of antibiotic and corticosteroid for these symptoms, with short-term relief.

Gonadal Function Recovery in Patients With Advanced Hodgkin Lymphoma Treated With a PET-Adapted Regimen: Prospective Analysis of a Randomized Phase III Trial (AHL2011).

PURPOSE: The prospective, randomized AHL2011 trial demonstrated that the use of the doxorubicin, bleomycin, vinblastine, and dacarbazine regimen (ABVD) after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated) in early responders on the basis of a positron emission tomography (PET)-driven strategy was safe and minimized toxicity compared with standard 6 BEACOPPescalated cycles. This substudy investigated the benefit of this strategy in gonadal function and fertility in patients under 45 years old. METHODS: Ovarian function was assessed by serum measurement of follicle-stimulating hormone (FSH), estradiol, and anti-müllerian hormone in women, and semen analysis, FSH, and testosterone levels were used to evaluate testicular function in men at baseline, end of treatment, and during 5 years of follow-up. RESULTS: A total of 145 women and 424 men, enrolled between May 19, 2011, and April 29, 2014, were included. The risk of premature ovarian insufficiency (FSH > 24 IU/L) and of having a low ovarian reserve (anti-müllerian hormone < 0.5 ng/mL) was reduced after treatment in the PET-driven group (odds ratio [OR], 0.20; 95% CI, 0.08 to 0.50; P = .001 and OR, 0.15; 95% CI, 0.04 to 0.56, P = .005, respectively). Both parameters were correlated with age and dose of alkylating agents. However, no significant differences were observed in terms of pregnancy rates. Men in the PET-driven group had a higher recovery rate of sperm parameters after treatment compared with the standard BEACOPPescalated group, as well as a lower risk of severe testicular damage (OR, 0.26; 95% CI, 0.13 to 0.5; P < .0001) and a higher likelihood of achieving pregnancy (OR, 3.7; 95% CI, 1.4 to 9.3; P = .004). CONCLUSION: Although both treatments affected ovarian reserve and spermatogenesis, the PET-driven strategy decreased the risk of gonadal dysfunction and infertility in advanced Hodgkin lymphoma.

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.

Impact of ABVD chemotherapy on ovarian reserve after fertility preservation in reproductive-aged women with Hodgkin lymphoma.

RESEARCH QUESTION: How is ovarian reserve affected by chemotherapy in patients with Hodgkin lymphoma (HL) who undergo fertility preservation (FP)? METHODS: A retrospective study was conducted by reviewing medical records of 105 HL patients referred to the FP unit before starting adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. Ovarian reserve was evaluated before chemotherapy and at the last follow-up using anti-Müllerian hormone (AMH) and antral follicle count (AFC) measurements. The decrease in AMH was compared with that expected from normograms. AMH was compared between patients who underwent cryopreservation of ovarian tissue and those who underwent cryopreservation of mature oocytes. RESULTS: After ABVD, 15% of patients required hematopoietic stem cell transplantation. At a median follow-up of 33 months, the median decrease in AMH was 0.88 ng/mL, which was significantly greater than that of the general population of this age group (p < 0.001). Of the 82 women who only had ABVD, 38 underwent FP by cryopreservation of mature oocytes and 44 underwent cryopreservation of the ovarian cortex. There was no significant difference in AMH or AFC at the last follow-up between FP techniques. CONCLUSION: Although ABVD is considered to be of low gonadotoxic risk, the decrease in AMH was greater than expected for patients' age, and 15% of patients needed more aggressive therapy during follow-up. Type of FP was not associated with decline in ovarian reserve. Reproductive-aged women with HL should have the opportunity for FP counseling before starting treatment.

The Incidence of Venous Thromboembolism and Impact on Survival in Hodgkin Lymphoma.

BACKGROUND: Thrombosis increase the acute and long-term morbidity and mortality in malignancy patients. We analyzed venous thromboembolism (VTE) in patients with Hodgkin lymphoma, the impact of VTE on survival, predisposing factors for VTE, and predicting value of Khorana and ThroLy score models. PATIENTS AND METHODS: We included 150 adult patients with Hodgkin lymphoma between January 2010 and 2018 at our university hospital. RESULTS: VTE was observed in 31 patients (20.7%). The types of VTE were 18 upper and 3 lower extremity deep vein thrombosis and 10 pulmonary embolism (1 with lower extremity deep vein thrombosis). Twenty-nine patients developed VTE during the treatment with a median time of episode as 5 months. In logistic regression analysis, a body mass index of >32 kg/m2, high fibrinogen levels, initial thrombocytosis and leukocytosis, splenic and extranodal involvement, presence of a central venous line, advanced stage, line of treatment status of thromboprophylaxis, VTE timing, and better Eastern Cooperative Oncology Group performance scores were observed to be related with VTE. Kaplan Meier survival analysis showed a negative impact of VTE on survival. Khorana and ThroLy risk assessment models were found predictive for VTE (P = .000 and P = .003, respectively), although only ThroLy score was associated with the survival. CONCLUSION: Thromboprophylaxis and precautions for VTE in patients with Hodgkin lymphoma according to validated risk assessment models can improve prognosis and quality of life owing to the impact of VTE on survival in the study.

Durable Response to Brentuximab Vedotin-Based Chemotherapy in Refractory Hodgkin Lymphoma with Central Nervous System (CNS) Involvement.

BACKGROUND CNS involvement in Hodgkin lymphoma is rare. Despite various treatment options, median overall survival is only 13 months after diagnosis of CNS involvement in relapsed/refractory HL. CASE REPORT A 29-year-old woman with classical HL (mixed cellularity) in clinical stage IIB was treated with multilineage chemotherapy and radiotherapy without achieving a sustained complete remission. Systemic and CNS progression of HL occurred at the age of 32 years and the patient received 2 cycles of brentuximab vedotin with bendamustine alternating with 2 cycles of high-dose methotrexate-based treatment and achieved partial remission. She then underwent autologous stem cell transplantation followed by brentuximab vedotin consolidation. The disease progressed and the patient died 6 months after the last dose of brentuximab vedotin. CONCLUSIONS We demonstrated a durable response to brentuximab vedotin-based chemotherapy in a patient with refractory Hodgkin lymphoma with CNS involvement. Prognosis of these patients is poor and new treatment options are needed.

Linfoma anaplásico de grandes células relacionado ao implante mamário: revisão sistemática da literatura / Breast implant-associated anaplastic large-cell lymphoma: a systematic literature review

O linfoma anaplásico de grandes células associado ao implante de mama (Breast Implant Associated Anaplastic Large Cell Lymphoma - BIA-ALCL) é uma doença maligna recentemente descoberta, rara e possivelmente associada aos implantes mamários texturizados. Essa revisão da literatura teve como objetivo trazer novas atualizações acerca da epidemiologia, fisiopatologia e fatores de risco para desenvolvimento do BIAALCL. Foi realizado o levantamento de dados do período de dezembro de 2018 a fevereiro de 2019, através das bases de dados PUBMED, LILACS e Scielo sendo selecionados 10 artigos publicados entre 2016 e 2018. Foi encontrada uma incidência variando entre 2,8:100.000 a 1:3 milhões de pacientes com implantes mamários. Os dados coletados corroboram para a teoria de que não há uma relação direta de causa e efeito entre os implantes mamários, mormente os texturizados, e o desenvolvimento do BIA-ALCL, podendo esses ser considerados somente como fatores de risco e não agentes causadores. A teoria fisiopatológica mais aceita é a de que os implantes mamários com maior área de superfície levariam a formação de maior biofilme por maior adesão bacteriana gerando inflamação crônica mais proeminente, levando ao gatilho para a transformação maligna das células T. As informações explicitadas nessa revisão devem auxiliar na ampliação de estudos acerca da doença e criação de políticas públicas para a prevenção e diagnóstico precoce de tal enfermidade. Pelos dados encontrados há necessidade de que cirurgiões plásticos realizem acompanhamento mais próximo de seus pacientes, assim como orientem os pacientes antes das cirurgias sobre a existência da doença.

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a newly discovered and rare cancer possibly associated with textured breast implants. This literature review investigates its epidemiology, pathophysiology, and risk factors. PubMed, LILACS, and SciELO databases were searched from December 2018 to February 2019, and 10 articles published between 2016 and 2018 were selected. The incidence of BIA-ALCL ranged from 2.8:100,000 to 1:3 million breast implants. The obtained data corroborate the hypothesis that there is no direct cause and effect relationship between breast implants, especially textured implants, and BIA-ALCL, and these implants can be considered risk factors but not causative factors. The most accepted hypothesis on disease pathophysiology is that breast implants with larger surface areas may promote bacterial adhesion and biofilm formation, leading to severe chronic inflammation, triggering the malignant transformation of T cells. This review provides knowledge on BIA-ALCL and helps develop and implement public policies for disease prevention and timely diagnosis. The data highlight that long-term follow up is necessary and that surgeons should advise patients of the potential risk of developing BIA-ALCL before performing the implant surgery.

Hodgkin-like adult T-cell leukemia/lymphoma that developed during the follow-up of HTLV-1 associated myelopathy/tropical spastic paraparesis.

Hodgkin-like adult T-cell leukemia/lymphoma (ATLL) is a rare variant of ATLL, which represents the early neoplastic phase of ATLL that follows an indolent clinical course compared with typical ATLL. Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurological disorder characterized by the paralysis of lower limbs and urinary disturbance. Although these diseases are caused by HTLV-1 infection, there are no reports describing the coexistence of Hodgkin-like ATLL and HAM/TSP. Here, we report the first case of Hodgkin-like ATLL complicated by HAM/TSP. The patient was a 56-year-old man with right inguinal lymphadenopathy who had been using the neurology outpatient service for 13 years after being diagnosed with HAM/TSP. He was unable to receive intensive chemotherapy or allogeneic stem cell transplantation due to a poor performance status, but his condition was stable for approximately two years.

Early chemotherapy de-escalation strategy in patients with advanced-stage Hodgkin lymphoma with negative positron emission tomography scan after 2 escalated BEACOPP cycles.

INTRODUCTION Escalated BEACOPP (escBEACOPP: bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) significantly improves overall response rates (ORRs) and prolongs progression­free survival (PFS) in patients with advanced­stage Hodgkin lymphoma (HL). However, 6 to 8 cycles of escBEACOPP are associated with increased acute toxicity and late complications. OBJECTIVES We aimed to determine the role of early positron emission tomography-computed tomography (PET­CT) response assessment in a de­escalation strategy. PATIENTS AND METHODS We retrospectively analyzed 188 consecutive patients with advanced­stage HL treated at diagnosis. Patients received 2 cycles of escBEACOPP followed by an early PET­CT response assessment performed after 2 cycles of chemotherapy (PET2). Patients with an active disease continued therapy with escBEACOPP, while those with negative PET2 were de­escalated to ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). Radiotherapy was allowed in patients with stage IIBX. RESULTS PET2 allowed for de­escalation of therapy in 141 patients (75%). Their ORR was 92.2%, with a complete remission (CR) rate of 91.5%; 10­year PFS and overall survival (OS) were 87.2% and 95%, respectively. In the whole cohort, ORR was 87.8% (CR, 85.6%), while the 10­year PFS and OS were 79.3% and 89.4%, respectively. Hematological and thromboembolic complications were significantly more frequent in patients treated with 6 escBEACOPP cycles, including febrile neutropenia (25 patients, [53.2%] vs 7 [5%]), serious anemia (35 [74.5%] vs 11 [7.8%]), or thrombocytopenia (16 [34%] vs 7 [5%]) (P <0.001 for all comparisons with de­escalation strategy) as well as pulmonary embolism (3 [6.4%] vs 0) (P = 0.02). CONCLUSIONS The early de­escalation strategy allows for effective treatment of advanced HL, with a comparable efficacy to that of 6 to 8 cycles of escBEACOPP, but with significantly reduced toxicity.

Epstein-Barr virus LMP2A utilizes Syk and PI3K to activate NF-κB in B-cell lymphomas to increase MIP-1α production.

The incidence of Hodgkin's lymphoma (HL) is growing due to an increase in Epstein-Barr virus (EBV)-associated HL in AIDS patients. The HL tumor microenvironment is vital for the survival of the malignant Hodgkin-Reed Sternberg (HRS) cells of HL, which express the EBV protein latent membrane protein 2A (LMP2A). While previous work shows that LMP2A mimics B-cell receptor (BCR) signaling to promote the survival of HRS cells, the ability of LMP2A to establish and maintain the tumor microenvironment through the production of chemokines remains unknown. Since BCR signaling induces the production of the chemokine macrophage inflammatory protein-1α (MIP-1α), and since LMP2A is a BCR mimic, we hypothesized that LMP2A increases MIP-1α levels. A comparison of multiple LMP2A-negative and -positive cell lines demonstrates that LMP2A increases MIP-1α. Additionally, LMP2A-mutant cell lines and pharmacologic inhibitors indicate that LMP2A activates a Syk/PI3K/NF-κB pathway to enhance MIP-1α. Finally, based on the finding that an NF-κB inhibitor decreased MIP-1α RNA/protein in LMP2A-positive cells, we are the first to demonstrate that LMP2A increases the nuclear localization of the NF-κB p65 subunit using DNA-binding assays and confocal microscopy in human B cells. These findings not only have implications for the treatment of HL, but also other LMP2A-expressing B-cell tumors that overexpress NF-κB.

Hodgkin lymphoma with co-existing extramedullary haematopoiesis in a Thalasaemia Major patient: Killing two birds with one stone using PET-CT.

Hodgkin lymphoma is a high grade lymphoma which is usually confined to the lymphnodes. Extranodal involvement of the Hodgkin lymphoma is uncommon but any organ can be involved.. Extramedullary haematopoiesis is the production of red cells outside the medullary cavity in response to failure of erythrogenesis in bone marrow which can occur due to many diseases with thalassaemia and myelofibrosis being most common. We present a case of a 21 year old patient who underwent PET-CT scan for the staging of Hodgkin lymphoma and revealed co-existing extramedullary haematopoiesis secondary to known thalassaemia.

Physical fitness in survivors of childhood Hodgkin lymphoma: A report from the St. Jude Lifetime Cohort.

BACKGROUND: There are limited data describing fitness and associated health-related quality of life (HRQoL) in survivors of childhood Hodgkin lymphoma (HL). PROCEDURE: Fitness was evaluated among 336 adult survivors of childhood-onset HL treated at St. Jude Children's Research Hospital and 327 controls who never had childhood cancer. The controls were frequency matched on age, sex, and race. Associations were examined between chronic disease and fitness and between fitness and HRQoL using a multivariable linear and logistic regression. RESULTS: Male survivors had lower endurance (6-min walk [6MW] distance 604.4 ± 7.9 m vs 637.0 ± 7.5 m, P < 0.01), and worse neuropathy (modified Total Neuropathy Score [mTNS] 2.7 ± 0.2 vs 1.4 ± 0.2, P < 0.01) compared to controls. Female survivors had lower endurance (6MW distance 564.5 ± 6.9 m vs 590.6 ± 7.0 m, P < 0.01), quadriceps strength (145.7 ± 4.0 vs 163.4 ± 4.0 N·m per kilogram, P < 0.01), and worse neuropathy (mTNS 3.2 ± 0.2 vs 1.4 ± 0.3, P < 0.01) compared to controls. Moderate, severe/disabling, or life-threatening (grades 2-4) neurological conditions were associated with impaired quadriceps strength (odds ratio [OR] 2.94, 99% confidence interval [CI] 1.24-6.96) and impaired endurance (OR 2.96, 99% CI 1.28-6.69). Cardiovascular (OR 2.36, 99% CI 1.00-5.61) and pulmonary (OR 2.78, 99% CI 1.30-5.94) conditions were associated with impaired endurance. Quadriceps strength (ß -6.44 ± 2.01, P < 0.01), endurance (ß -4.63 ± 1.54, P < 0.01), and neuropathy (ß -4.98 ± 1.14, P < 0.01) were associated with a lower physical component summary on the HRQoL. CONCLUSION: Survivors of childhood HL, particularly those with neurological, cardiac, and pulmonary chronic conditions, are at risk for impaired fitness and HRQoL.

Clinical practice: hepatitis C virus infection, cryoglobulinemia and cryoglobulinemic vasculitis.

Cryoglobulins are circulating immunoglobulins that reversibly precipitate at temperatures below 37 °C. Type-II cryoglobulins consist of monoclonal IgM/polyclonal IgG immune complexes (ICs), whereas in type-III cryoglobulins both IgM and IgG are polyclonal. The clinical condition resulting from the presence of cryoglobulins in the blood is called mixed cryoglobulinemia (MC), which can be asymptomatic or manifest as cryoglobulinemic vasculitis (CV). Type-I cryoglobulins, consisting of a single monoclonal isotype, are detected in patients with lymphoproliferative disorders. It is now established that > 90% of MCs are associated with HCV infection. Clinically, the spectrum of symptoms may range in severity from occasional purpuric eruptions to life-threatening features. In addition to the development of liver cirrhosis and hepatocellular carcinoma, the possible progression of HCV-positive CV patients to B-cell non-Hodgkin lymphoma (B-NHL) has been reported. The pathogenetic role played by HCV infection in the onset of B-NHL is suggested by regression of the latter following the achievement of a sustained virologic response (SVR). For several years, interferon-α alone or combined with ribavirin has been the standard of care. However, the rates of clinical, biochemical, and virologic responses have been low, and the occurrence of relapse frequent. The addition of rituximab has resulted in a higher rate of responses. With the advent of direct-acting antiviral agents, SVR has been achieved in ~ 95% of CV patients. However, in a minority of patients, despite SVR, CV may persist or reappear over variable lengths of time from the completion of therapy. The eventual appearance of B-NHL is also possible.

An increase in myocardial 18-fluorodeoxyglucose uptake is associated with left ventricular ejection fraction decline in Hodgkin lymphoma patients treated with anthracycline.

BACKGROUND: Doxorubicin (DOX)-based chemotherapy for Hodgkin lymphoma (HL) yields excellent disease-free survival, but poses a substantial risk of subsequent left ventricular (LV) dysfunction and heart failure, typically with delayed onset. At the cellular level, this cardiotoxicity includes deranged cardiac glucose metabolism. METHODS: By reviewing the hospital records from January 2008 through December 2016, we selected HL patients meeting the following criteria: ≥ 18 year-old; first-line DOX-containing chemotherapy; no diabetes and apparent cardiovascular disease; 18-fluoro-deoxyglucose positron emission tomography (18FDG-PET) scans before treatment (PETSTAGING), after 2 cycles (PETINTERIM) and at the end of treatment (PETEOT); at least one echocardiography ≥ 6 months after chemotherapy completion (ECHOPOST). We then evaluated the changes in LV 18FDG standardized uptake values (SUV) during the course of DOX therapy, and the relationship between LV-SUV and LV ejection fraction (LVEF), as calculated from the LV diameters in the echocardiography reports with the Teicholz formula. RESULTS: Forty-three patients (35 ± 13 year-old, 58% males) were included in the study, with 26 (60%) also having a baseline echocardiography available (ECHOPRE). LV-SUV gradually increased from PETSTAGING (log-transformed mean 0.20 ± 0.27) to PETINTERIM (0.27 ± 0.35) to PETEOT (0.30 ± 0.41; P for trend < 0.001). ECHOPOST was performed 22 ± 17 months after DOX chemotherapy. Mean LVEF was normal (68.8 ± 10.3%) and only three subjects (7%) faced a drop below the upper normal limit of 53%. However, when patients were categorized by median LV-SUV, LVEF at ECHOPOST resulted significantly lower in those with LV-SUV above than below the median value at both PETINTERIM (65.5 ± 11.8% vs. 71.9 ± 7.8%, P = 0.04) and PETEOT (65.6 ± 12.2% vs. 72.2 ± 7.0%, P = 0.04). This was also the case when only patients with ECHOPRE and ECHOPOST were considered (LVEF at ECHOPOST 64.7 ± 8.9% vs. 73.4 ± 7.6%, P = 0.01 and 64.6 ± 9.3% vs. 73.5 ± 7.0%, P = 0.01 for those with LV-SUV above vs. below the median at PETINTERIM and PETEOT, respectively). Furthermore, the difference between LVEF at ECHOPRE and ECHOPOST was inversely correlated with LV-SUV at PETEOT (P < 0.01, R2 = - 0.30). CONCLUSIONS: DOX-containing chemotherapy causes an increase in cardiac 18FDG uptake, which is associated with a decline in LVEF. Future studies are warranted to understand the molecular basis and the potential clinical implications of this observation.

Hodgkin Lymphoma in Adults.

BACKGROUND: Hodgkin lymphoma is the most common neoplasm in young adults, with an incidence of 2 to 3 cases per 100 000 persons per year. Risk-adapted chemotherapy and radiotherapy usually lead to cure. Finding ways to lessen the treatment- associated morbidity and mortality is a major goal of current research. METHODS: For the creation of an updated guideline (DKH grant number 111778), a systematic literature search was carried out in medical databases (MEDLINE, CENTRAL) and guideline databases (GIN) (search dates: January 2012 to June 2017). RESULTS: Results from 10 meta-analyses, 89 randomized and controlled trials, and 81 prospective or retrospective trials were evaluated. The use of positron emission tomography (PET) is strongly recommended in the initial diagnostic evaluation, as well as for the guidance of treatment in advanced stages. In early stages, two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and involved-site radiotherapy (IS-RT) at a dose of 20 Gy are recommended. For the treatment of intermedi- ate stages, two cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) + two cycles of ABVD and 30 Gy IS-RT are recommended. In advanced stages, two cycles of escalated BEACOPP are administered, and then PET is performed for the guidance of further treatment: two further cycles of escalated BEACOPP are recommended if the PET is negative and four further cycles if it is positive, followed by radiotherapy of PET- positive residual tumor tissue. The five-year survival of patients with Hodgkin lymphoma is 95%. In case of disease recurrence, high-dose chemotherapy followed by autologous stem-cell transplantation is performed, and targeted drugs including brentuxi- mab vedotin, nivolumab, and pembrolizuab are used. CONCLUSION: The highly favorable long-term prognosis of HL necessitates careful consideration of the intensity of treatment as well as thorough follow-up to enable the detection of late sequelae, such as second tumors or organ damage.

Anterior mediastinal Hodgkin lymphoma presenting as an extremely hypervascular tumor on computed tomography: A case report.

RATIONALE: In the thorax, Hodgkin lymphoma (HL) most frequently involves the anterior mediastinal and paratracheal regions and tends to spread to contiguous nodal groups. Enlarged lymph nodes typically have homogeneous soft tissue attenuation similar to that of muscle tissue on computed tomography (CT). PATIENT CONCERNS: A contrast-enhanced CT examination of a 19-year-old man with right-sided chest pain showed an intense, heterogeneously enhancing mass with organization of serpentine and dilated blood vessels in the right anterior mediastinum that had invaded the upper lobe of the right lung. DIAGNOSES: Following a wedge resection, histopathological examination showed Reed-Sternberg cells that were positive for CD-15 and CD-30, which is typical of HL. INTERVENTIONS: The patient was started treatment with 6 cycles of doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD) regimen. OUTCOMES: After chemotherapy, the patient had shown a partial response to the treatment. LESSONS: This presentation of HL as an extremely hypervascular anterior mediastinal mass on CT imaging has not been previously reported in the literature. This case suggests that HL should be included in the differential diagnosis of a hypervascular anterior mediastinal mass, especially if the patient is a young adult.

Lifetime physical inactivity is associated with increased risk for Hodgkin and non-Hodgkin lymphoma: A case-control study.

BACKGROUND: Although physical activity is a well-established risk factor for several cancer types, studies evaluating its association with lymphoma have yielded inconclusive results. In such cases where physical activity is not clearly associated with cancer risk in a dose-dependent manner, investigators have begun examining physical inactivity as an independent exposure of interest. METHODS: Associations of self-reported, lifetime physical inactivity with risk of developing Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) were evaluated in a hospital-based case control study using data from the Patient Epidemiology Data System at Roswell Park Comprehensive Cancer Center. Participants included 87 patients with HL and 236 patients with NHL as well as 348 and 952 cancer-free controls, respectively. Multivariable-adjusted logistic regression models were fit to calculate odds ratios (OR) and 95% confidence intervals (CI) estimating the association between physical inactivity and lymphoma risk. RESULTS: We observed significant, positive associations between lifetime recreational physical inactivity and risk of both HL (OR = 1.90, 95% CI: 1.15-3.15) and NHL (OR = 1.35, 95% CI: 1.01-1.82). CONCLUSIONS: The current analysis provides evidence for a positive association between physical inactivity and risk of both HL and NHL. These results add to a growing body of research suggesting that lifetime physical inactivity may be an important independent, modifiable behavioral risk factor for cancer.