Nodular Sclerosis Hodgkin Lymphoma Research Articles

Clinical Features and Prognostic Factors of Hodgkin's Lymphoma: A Single Center Experience.

Hodgkin's lymphoma (HL) is a B cell lymphoma characterized by the presence of Reed-Sternberg cells. HL comprises 1% of all cancer cases and 14% of all lymphoma cases. We designed a retrospective study to investigate the clinical features and prognostic factors of HL patients diagnosed at an experienced oncology centre. Retrospective study. Demographic characteristics, histopathological and clinical features, treatment modalities and response to treatment were obtained from hospital records. Dates of initial diagnosis, remission and relapse, last visit and death were recorded for survival analyses. We analysed data of 391 HL patients (61% male, 39% female; mean age 35.7±15.1 years). The most common classical HL histological subtype was nodular sclerosing HL (NSHL) (42.7%). The most common stage was II 50.4%. The most common chemotherapy regimen was doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) (70.6%). Five and 10-year survival rates were 90% and 84%, respectively. Early-stage patients with good prognostic factors had better overall and relapse-free survival rates. The presence of "B" symptoms, albumin level, Eastern Cooperative Oncology Group (ECOG) performance score, and LDH were prognostic factors that affect the survival in both univariate and multivariate analyses. This is the first study that demonstrates the demographic, clinical and prognostic features of HL patients in Turkey, and provides a general picture of the HL patients in our country.

Dose-Adjusted EPOCH-Rituximab Therapy in Primary Mediastinal B-Cell Lymphoma

BackgroundPrimary mediastinal B-cell lymphoma is a distinct subtype of diffuse large-B-cell lymphoma that is closely related to nodular sclerosing Hodgkin's lymphoma. Patients are usually young and present with large mediastinal masses. There is no standard treatment, but the inadequacy of immunochemotherapy alone has resulted in routine consolidation with mediastinal radiotherapy, which has potentially serious late effects. We aimed to develop a strategy that improves the rate of cure and obviates the need for radiotherapy.MethodsWe conducted a single-group, phase 2, prospective study of infusional dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (DA-EPOCH-R) and filgrastim without radiotherapy in 51 patients with untreated primary mediastinal B-cell lymphoma. We used results from a retrospective study of DA-EPOCH-R from another center to independently verify the outcomes.ResultsThe patients had a median age of 30 years (range, 19 to 52) and a median tumor diameter of 11 cm; 59% were women. During a median of 5 years of follow-up, the event-free survival rate was 93%, and the overall survival rate was 97%. Among the 16 patients who were involved in the retrospective analysis at another center, over a median of 3 years of follow-up, the event-free survival rate was 100%, and no patients received radiotherapy. No late morbidity or cardiac toxic effects were found in any patients. After follow-up ranging from 10 months to 14 years, all but 2 of the 51 patients (4%) who received DA-EPOCH-R alone were in complete remission. The 2 remaining patients received radiotherapy and were disease-free at follow-up.ConclusionsTherapy with DA-EPOCH-R obviated the need for radiotherapy in patients with primary mediastinal B-cell lymphoma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00001337.)

Latitude gradients for lymphoid neoplasm subtypes in Australia support an association with ultraviolet radiation exposure

Given the uncertainty surrounding solar ultraviolet radiation (UVR) exposure and risk of lymphoid neoplasms, we performed an ecological analysis of national Australian data for incident cases diagnosed between 2002 and 2006. Subtype-specific incidence was examined by latitude band (<29°S, 29-36°S, ≥37°S), a proxy for ambient UVR exposure, using multiple Poisson regression, adjusted for sex, age-group and calendar year. Incidence increased with distance from the equator for several mature B-cell non-Hodgkin lymphomas, including diffuse large B-cell [incidence rate ratio (IRR) = 1.37; 95% confidence interval (CI): 1.16-1.61 for latitude ≥37°S relative to <29°S], lymphoplasmacytic (IRR = 1.34; 95% CI: 1.12-1.61), mucosa-associated lymphoid tissue (IRR = 1.32; 95% CI: 0.97-1.80) and mantle cell lymphoma (IRR = 1.29; 95% CI: 1.05-1.58), as well as plasmacytoma (IRR = 1.52; 95% CI: 1.09-2.11) and plasma cell myeloma (IRR = 1.15; 95% CI: 1.03-1.27). A similar pattern was observed for several mature cutaneous T-cell neoplasms, including primary cutaneous anaplastic large cell lymphoma (IRR = 4.26; 95% CI: 1.85-9.84), mycosis fungoides/Sézary syndrome (IRR = 1.72; 95% CI: 1.20-2.46), and peripheral T-cell lymphoma not otherwise specified (NOS) (IRR = 1.53; 95% CI: 1.17-2.00). Incidence of mixed cellularity/lymphocyte-depleted (IRR = 1.60; 95% CI: 1.16-2.20) and nodular sclerosis Hodgkin lymphoma (IRR = 1.57; 95% CI: 1.33-1.85) also increased with distance from the equator. Many of these subtypes have a known association with infection or immune dysregulation. Our findings support a possible protective effect of UVR exposure on the risk of several lymphoid neoplasms, possibly through vitamin D-related immune modulation critical in lymphomagenesis.

Chromosomal integration of the HHV‐6 genome in a patient with nodular sclerosis Hodgkin lymphoma

Chromosomal integration of the <scp>HHV</scp>‐6 genome in a patient with nodular sclerosis Hodgkin lymphoma

GLUT1 expression patterns in different Hodgkin lymphoma subtypes and progressively transformed germinal centers

BackgroundIncreased glycolytic activity is a hallmark of cancer, allowing staging and restaging with 18F-fluorodeoxyglucose-positron-emission-tomography (PET). Since interim-PET is an important prognostic tool in Hodgkin lymphoma (HL), the aim of this study was to investigate the expression of proteins involved in the regulation of glucose metabolism in the different HL subtypes and their impact on clinical outcome.MethodsLymph node biopsies from 54 HL cases and reactive lymphoid tissue were stained for glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA) and lactate exporter proteins MCT1 and MCT4. In a second series, samples from additional 153 HL cases with available clinical data were stained for GLUT1 and LDHA.ResultsMembrane bound GLUT1 expression was frequently observed in the tumor cells of HL (49% of all cases) but showed a broad variety between the different Hodgkin lymphoma subtypes: Nodular sclerosing HL subtype displayed a membrane bound GLUT1 expression in the Hodgkin-and Reed-Sternberg cells in 56% of the cases. However, membrane bound GLUT1 expression was more rarely observed in tumor cells of lymphocyte rich classical HL subtype (30%) or nodular lymphocyte predominant HL subtype (15%). Interestingly, in both of these lymphocyte rich HL subtypes as well as in progressively transformed germinal centers, reactive B cells displayed strong expression of GLUT1. LDHA, acting downstream of glycolysis, was also expressed in 44% of all cases. We evaluated the prognostic value of different GLUT1 and LDHA expression patterns; however, no significant differences in progression free or overall survival were found between patients exhibiting different GLUT1 or LDHA expression patterns. There was no correlation between GLUT1 expression in HRS cells and PET standard uptake values.ConclusionsIn a large number of cases, HRS cells in classical HL express high levels of GLUT1 and LDHA indicating glycolytic activity in the tumor cells. Although interim-PET is an important prognostic tool, a predictive value of GLUT1 or LDHA staining of the primary diagnostic biopsy could not be demonstrated. However, we observed GLUT1 expression in progressively transformed germinal centers and hyperplastic follicles, explaining false positive results in PET. Therefore, PET findings suggestive of HL relapse should always be confirmed by histology.

Clinical Significance of Tumor-Associated Macrophages in Early-Stage Hodgkin's Lymphoma.

Abstract 2638Although patients with early-stage Hodgkin's lymphoma (HL) overall have a high rate of cure, they cannot be considered as a homogeneous group. In fact, a portion of these patients are resistant to or may relapse after standard treatment. Current prognostic criteria based on clinical and laboratory parameters at diagnosis do not allow to accurately identify the subset of patients with less favorable clinical outcome. In a study aimed at defining new biomarkers for risk stratification, an increased number of tumor-associated macrophages was found to be strongly associated with shortened survival in patients with classic Hodgkin's lymphoma [N Engl J Med. 2010 Mar 11;362(10):875-85].The aim of this study was to evaluate the clinical significance of the proportion of CD68-positive infiltrating macrophages in patients with early-stage Hodgkin’s lymphoma. By using an immunohistochemistry method, we analyzed diagnostic biopsies of 63 patients followed at our institution between 2006 and 2010, and uniformly treated with ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy. Thirty-nine (62%) patients were males and 24 (38%) were females; median age at diagnosis was 30 years (range 17–85). Histological subtype was nodular sclerosis HL in 55 cases, mixed cellularity HL in 3 cases, lymphocyte-rich HL in 3 cases, and not classified in 2 cases. Five patients had subdiaphragmatic disease while 58 had supradiaphragmatic localizations. Forty-four patients with supradiaphragmatic disease were classified in the EORTC unfavorable subset: in detail, 25 patients had B symptoms and ESR ≥30, or ESR ≥50 despite the absence of B symptoms, 29 patients had bulky disease, 7 patients were older than 50 years, and 6 patients had more than 3 nodal areas involved. Thirty-six out of 63 (59%) patients received radiotherapy as a consolidation treatment after chemotherapy. After completion of the therapeutic program, 54 out of 63 (86%) patients obtained complete remission, while 9 (14%) had refractory disease; 15 out of 54 (28%) patients in complete remission relapsed during follow up.Diagnostic biopsies were reviewed by expert hematopathologists and classified into 3 groups according to the intensity of CD68 expression [N Engl J Med. 2010 Mar 11;362(10):875-85]. CD68-positive infiltrate was lower than 5% in 14 patients (group A), between 5 and 25% in 43 patients (group B), and greater than 25% in 6 patients (group C).Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method with observation time calculated from diagnosis. Comparison between survival curves was performed by means of the Gehan-Wilcoxon test. The 2-year OS and PFS in the entire cohort were 98% and 79%, respectively. There was a difference in the 2-year PFS between patients with favorable and those with unfavorable prognosis according to the EORTC risk criteria (100% vs 72%, P<.05). CD68 expression had a significant effect on 2-year PFS, which was 86%, 84% and 33% in group A, B and C, respectively (P<.004). After merging group A and B, there was a significant difference in 2-year PFS between patients having up to 25% and those with more than 25% CD68-positive infiltrating macrophages (84% vs 33%, P<.002). All patients with favorable EORTC criteria had CD68 expression lower than or equal to 25%. Within those with unfavorable EORTC criteria, patients with CD68 expression greater than 25% had a worse 2-year PFS compared with patients having values up to 25% (33% vs 77%, P<.012).In conclusion, the findings of this study suggest that a proportion of CD68-positive infiltrating macrophages greater than 25% is associated with unfavorable clinical outcome in patients with early-stage Hodgkin's lymphoma. However, for CD68 expression to be used as a prognostic factor in these patients, both technical standardization of the immunohistochemistry method and prospective validation of the prognostic biomarker in a clinical trial are clearly required. Disclosures:No relevant conflicts of interest to declare.

The Difference in the Incidence and the Trend of Malignant Lymphomas in Japan and the United States.

AbstractAbstract 2695 Background:Malignant lymphomas (ML) are heterogeneous groups that the detailed classification is evolving dramatically. An incidence of malignant disease in certain population reflects cumulative exposure to environment, genetics and their combination overtime. Therefore, a comparison of incidences in various population and their secular trends is very helpful to understand etiology of disease. The aim of this study is to assess the incidence and the trend of each ML subtypes and to evaluate the difference between Japan and US. Materials and Methods:We used the data from a population-based cancer registry in Japan and from the Surveillance Epidemiology and End Results (SEER) program 9. Registry data of the US, SEER 9 included 95,155 cases and the data of Japan included 48,658 cases. The period covered in this analyses was 1993 to 2006 in Japan and 1993 to 2008 in the US. Rates of sex-specific, age-standardized incidence with 95% confidence intervals were estimated and standardized by age-adjustment according to the world standard population. We also estimated the annual percent change using joinpoint regression analysis and evaluated the significance of the trend. Results:The overall age-standardized incidence rate of all malignant lymphomas per 100,000 in 2006 was 22.4 for males and 16.0 for females in the US, 7.4 for males and 4.9 for females in Japan. The incidence is higher in the US than Japan with most of the subtypes especially for the nodular sclerosis HL, CLL/SLL and FL. In general, B-cell lymphomas showed large difference in incidence while T-cell lymphomas (TCL) showed similar incidence between Japan and the US. The total numbers of ML are constantly increasing in Japan but not in the US as shown in the figure {annual percent change (95%CI), Japan; +2.6% (2.1, 3.1), US; +0.2% (−0.0, 0.4)}. As for details, follicular lymphoma, mantle cell lymphoma, Burkitt lymphoma and the total numbers of TCL are constantly increasing in both countries. Conclusion:In conclusion, we showed the marked difference in the incidence and the trend of hematologic malignancies between Japan and the US. The incidence of hematologic malignancies is lower in Japan than the US, but is increasing significantly. The most remarkable difference in the incidence was seen with nodular sclerosis HL, CLL/SLL and FL which was consistent with previous reports. Even with the TCL, the incidence seems to be similar to higher in the US except for the ATLL. The improvement in the quality of cancer registry systems and the organization of these registries between countries enables us to unite the data worldwide that will bring us new insights. [Display omitted] Solid line and circle are the data of the US. Dashed line and hollow circle are the data of Japan. Disclosures:No relevant conflicts of interest to declare.

Hodgkin lymphoma: 2012 update on diagnosis, risk‐stratification, and management

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 9,000 new patients annually and representing approximately 11% 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 are used to optimize therapy for patients with limited or advanced stage disease. 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 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. 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, palliative chemotherapy, non-myeloablative allogeneic transplant or participation in a clinical trial should be considered.

Using biologic predictive factors to direct therapy of diffuse large B-cell lymphoma

While diffuse large B-cell lymphoma (DLBCL) was once considered to be a single disease entity, recent biological insights have demonstrated that it can be divided up into at least three molecular subtypes. Gene expression profiling has revealed that DLBCL consists of a germinal center B-cell like subtype (GCB), an activated B-cell like subtype (ABC) and a primary mediastinal B-cell lymphoma subtype (PMBL). These three entities arise from different stages of B-cell differentiation and are characterized by distinct mechanisms of oncogenic activation. In GCB DLBCL, the BCL6 transcription factor may play an important role in tumor survival and treatment resistance and strategies that target this are under investigation. ABC DLBCL is characterized by high expression of target genes of the nuclear factor kappa B (NF-κB)/Rel family of transcription factors and strategies that target NF-κB are in clinical trials. PMBL is a distinct clinicopathologic entity that shares many molecular features with nodular sclerosis Hodgkin lymphoma (HL) and may benefit from dose intensity approaches and inhibition of the Janus kinases. Other biologic predictive factors such as MYC and BCL2 may be overexpressed in both the GCB and ABC subtypes and strategies that target these complexes are also being tested.

Human herpesvirus 6 positive Reed–Sternberg cells in nodular sclerosis Hodgkin lymphoma

Classical Hodgkin lymphoma (HL) exhibits a bi-modal age distribution that suggests an infectious aetiology. However, most cases of nodular sclerosis HL (NSHL) are Epstein-Barr virus (EBV) negative (60-90%). Previous studies regarding human herpesvirus 6 (HHV-6) positivity of HL have led to conflicting results. In order to clarify this situation, we examined NSHL biopsies for the presence and distribution of HHV-6 by immunohistochemistry (IHC), polymerase chain reaction (PCR), and fluorescence in situ hybridization (FISH). PCR identified HHV-6 DNA in 86% of NSHL cases. As HHV-6 DNA was also identified in most cases of reactive lymphoid hyperplasia, we sought to localize the virus to specific cells by IHC, which detected HHV-6 in Reed-Sternberg (RS) cells of nearly half (48%) of NSHL cases. Dual CD30/HHV-6 immunostaining confirmed HHV-6 immunoreactivity in CD30+ RS cells, and HHV-6 PCR positivity was confirmed in laser capture microdissection-isolated CD30+ RS cells. FISH demonstrated multiple copies of HHV-6 genome in scattered cells. In contrast, EBV+ RS cells were identified in only 24% of the cases. HHV-6+ cases trended toward a younger age than EBV+ cases. These results conclusively demonstrate that RS cells in many cases of NSHL are HHV-6 positive, and suggest that HHV-6 may play a role in NSHL pathogenesis, particularly in younger patients with EBV-negative disease.

Hodgkin Lymphoma of the Oral Mucosa

In this report, we describe a rare case of relapsed nodular sclerosing Hodgkin lymphoma presenting as a lesion of the oral mucosa. Although this is an uncommon clinical scenario, health care professionals should be aware of this possibility. A brief differential diagnosis and review of Hodgkin lymphoma is discussed.

Postpartum maternal death associated with undiagnosed Hodgkin's lymphoma

The authors describe the case of a 28-year-old patient who died from an extensive intracerebral haemorrhage due to disseminated intravascular coagulation (DIC) which occurred a few days after delivery. Access to an emergency department of gynaecology on three separate occasions in the three days preceding hospitalization made judicial evaluation of the case necessary. The case was studied with a methodological approach based on the following steps: (1) examination of clinical records; (2) autopsy; (3) study of the placenta; (4) anatomo-histopathological observations concerning particular organs and structures potentially involved in postpartum maternal death; and (5) evaluation of physicians' behaviour, in the light of necroscopic findings and a review of the literature. The causes of death most frequently described in the postpartum period were excluded; a mediastinal nodular sclerosing Hodgkin's lymphoma with transdiaphragmatic diffusion, not diagnosed in life, was demonstrated. The cause of death was identified as intracerebral haemorrhage following DIC, Hodgkin's disease and recent delivery by caesarean section. Analysis of the physicians' conduct, together with a review of the literature, revealed a medical error. However, no causal relationship between the error and the death of the patient was considered to exist. The interest of the case lies in the unusual cause of DIC discussed in relation to a hypothesis of obstetric-gynaecological liability.

A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32

Nodular sclerosing Hodgkin lymphoma (NSHL) is a distinct, highly heritable Hodgkin lymphoma subtype. We undertook a genome-wide meta-analysis of 393 European-origin adolescent/young adult NSHL patients and 3315 controls using the Illumina Human610-Quad Beadchip and Affymetrix Genome-Wide Human SNP Array 6.0. We identified 3 single nucleotide polymorphisms (SNPs) on chromosome 6p21.32 that were significantly associated with NSHL risk: rs9268542 (P = 5.35 × 10(-10)), rs204999 (P = 1.44 × 10(-9)), and rs2858870 (P = 1.69 × 10(-8)). We also confirmed a previously reported association in the same region, rs6903608 (P = 3.52 × 10(-10)). rs204999 and rs2858870 were weakly correlated (r(2) = 0.257), and the remaining pairs of SNPs were not correlated (r(2) < 0.1). In an independent set of 113 NSHL cases and 214 controls, 2 SNPs were significantly associated with NSHL and a third showed a comparable odds ratio (OR). These SNPs are found on 2 haplotypes associated with NSHL risk (rs204999-rs9268528-rs9268542-rs6903608-rs2858870; AGGCT, OR = 1.7, P = 1.71 × 10(-6); GAATC, OR = 0.4, P = 1.16 × 10(-4)). All individuals with the GAATC haplotype also carried the HLA class II DRB1*0701 allele. In a separate analysis, the DRB1*0701 allele was associated with a decreased risk of NSHL (OR = 0.5, 95% confidence interval = 0.4, 0.7). These data support the importance of the HLA class II region in NSHL etiology.

Classical Hodgkin lymphoma: Differential diagnosis and tumour microenvironment

Hodgkin lymphoma (HL) accounts for approximately 15% to 30% of all malignant lymphomas. according to current diagnostic criteria, approximately 90% to 95% of HLs fall into the Classical Hodgkin lymphoma (CHL) category; the remaining cases are nodular lymphocyte-predominant subtype of Hodgkin’s lymphoma (NLPHL) which is recognized as a separate entity in the World Health Organization (WHO) classification1. WHO classification is based on the fact that there are clear and consistent histologic, epidemiologic, immunologic, and genetic differences between NLPHL and CHL. NLPHL is an indolent germinal center (GC) B-cell malignancy, that represents a nodular proliferation comprised of a minority of large neoplastic centroblasts with multilobated nuclei, the so-called popcorn or lymphocyte-predominant (LP) cells. Immunohistochemically LP cells are Cd20+, PaX5+, BCL6+, EBV-LMP1-, Cd30and Cd15-. Background inflammatory infiltrate represent mixture of small B and T lymphocytes1. This type of tumour is characterised clinically by a relatively indolent course and a very good response to standard therapy in cases with low stage disease. Unfortunately, the prognosis is unfavourable for advanced stages2. CHL is also a clonal, malignant lymphoproliferation originating from germinal center B cells3. CHL has a bimodal age curve in western countries, showing a peak at 15-35 years of age and a second peak later in life at 45-60 years1. a histopathologic diagnosis of CHL is based on the identification of diagnostic reed-sternberg (rs) cells in an appropriate inflammatory background of mixed infiltrate by histiocytes, small lymphocytes, eosinophils, neutrophils, plasma cells, fibroblasts and colagen. Based on characteristics of the reactive infiltrate and the specific features of neoplastic cells, cases may be subclassified into one of four subtypes: nodular sclerosis (NsCHL), lymphocyte-rich (LrCHL), mixed cellularity (MCCHL) and lymphocyte-depleted classical Hodgkin lymphoma (LdCHL)1,4. although most cases can be diagnosed on the basis of morphology alone, diagnostic criteria include the characteristic immunophenotype of the neoplastic population. rs cells and variants express the Cd30 and Cd15 antigens in the majority of cases and lack the common leukocyte antigen Cd455,6. The LMP-1 protein of EBV is expressed in approximately 25% to 50% of CHLs depending on the histologic subtype and patient age7. The staining is membranous and cytoplasmic, and usually most neoplastic cells are positive. Etiology of CHL is still questionable, but due to the unique epidemiologic and clinical features of the disease, an infectious cause has long been suspected. Currently, immunohistochemistry for the EBV latent membrane protein-1 (LMP-1) and nonradioactive in situ hybridization for EBV-encoded early rNas (EBErs) are the methods of choice for the detection of EBV in routinely fixed, paraffin-embedded tissues8. recent data suggest that the EBV status of tumour cells in classical HL could have prognostic significance for patients with this heterogenous disease9.

Isolated intracranial relapse of hodgkin lymphoma in a child

Introduction: Although involvement of the central nervous system (CNS) is well described in non­Hodgkin lymphoma (NHL) at diagnosis and/or at relapse, there are few reports in the pediatric literature of primary or relapsed CNS Hodgkin lymphoma (HL). Case Report: We report dural disease as the only site of relapse of HL in an immunocompetent seven­year­old child, presenting with diplopia. Imaging demonstrated a well­circumscribed dural­based mass at the base of the skull involving the clivus and enveloping the pituitary. Restaging did not show disease elsewhere, with normal bone marrow trephine biopsies and cytological examination of the cerebrospinal fluid. Biopsy of the dural­based tumor confirmed classical HL. Eleven months before, he was diagnosed with stage IIIA HL nodular sclerosis subtype and underwent four courses of combination chemotherapy with a complete metabolic response on early response assessment. Forty­ eight months after completing treatment for relapsed HL, he remains well in complete remission, although future relapse of HL cannot be excluded. Conclusion: There were no specific risk factors predictive of relapse in this child. He had responded well to standard chemotherapy as early response assessment after two courses showed complete metabolic response. Treatment of this child at relapse was challenging, since standard salvage chemotherapy regimens comprise drugs not well known to traverse the blood brain barrier. This case highlights the rarity of intracranial HL in children and difficulty with regards to the diagnosis, evidence based treatment and overall prognosis. We suggest that irrespective of any imaging abnormality, histological confirmation should be sought before commencement of definitive treatment.

Diffusion‐weighted MRI compared to FDG PET‐CT in the staging and response assessment of Hodgkin lymphoma

A 29-year-old man presented with a large right supraclavicular mass, weight loss and night sweats. A diagnosis of stage 4B nodular sclerosis Hodgkin lymphoma was made. F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET-CT) and whole-body magnetic resonance imaging with diffusion-weighting (DW-MRI) were performed before and after escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) chemotherapy. The pre-treatment FDG PET-CT (top left) demonstrated extensive nodal disease above and below the diaphragm, including the right supraclavicular fossa. Post-treatment FDG PET-CT (top right) showed physiological FDG uptake only. The pre-treatment DW-MRI (bottom left) showed extensive nodal disease in the same distribution as the pre-treatment FDG PET-CT. DW-MRI revealed a bone lesion (arrow) not diagnosed on the FDG PET-CT, confirmed on the source axial images. Post-treatment morphological MRI (not shown) demonstrated residual nodal disease in the right lower neck and upper abdomen but this was all inactive on DW-MRI (bottom right). FDG PET-CT and DW-MRI independently established a complete response. FDG PET-CT is a recommended imaging method for determining disease activity in residual masses after treatment for Hodgkin lymphoma. There is an increasing body of evidence to support its use in the assessment of early response to chemotherapy and it has been established as reliable for staging Hodgkin lymphoma. However, it involves radiation exposure for both the CT and FDG components of the test. MRI does not use ionizing radiation and offers higher soft tissue contrast compared with CT. The reduction of exposure to ionizing radiation is of particular significance in patients with lymphoma who have a high chance of cure, especially in younger patients. Water diffusion whole body MRI also allows functional assessment of lymphoma response. DW-MRI relies on measuring the random motion of water molecules in tissues. Many malignant tumours, including lymphomas, are more cellular than benign/normal tissue and therefore show more restricted water diffusion, appearing bright on normal images or dark on inverted images such as those shown above. The disadvantages of MRI include the exclusion of patients with pacemakers, implantable defibrillators or significant claustrophobia. In addition, bulk tissue movements and physiological water motion can sometimes affect DW-MRI image quality. In general, FDG PET-CT is accurate for diagnosis of marrow and bone involvement in Hodgkin lymphoma but, in this case, DW-MRI revealed bone disease not diagnosed on FDG PETCT. Further research is needed to compare the relative merits of DW whole-body MRI with FDG PET-CT in the staging and monitoring of lymphoma.

Hodgkin's Lymphoma (HL) Presenting As An Abnormal Mammogram: A Case Report

Abstract 4865 Background:Although not a common presentation, Hodgkin's lymphoma (HL) can first manifest as an enlarged axillary lymph node. We report a case of a patient diagnosed with nodular sclerosing HL, presenting as an abnormal axillary lymph node incidentally noted during routine mammogram. Case report:A 79 year-old asymptomatic female was referred to our center after being discovered a 3 cm left axillary lymph node detected during a routine screening mammogram. Except from the enlarged left axillary lymphadenopathy, the remaining physical exam was within normal limits. An ultrasound-guided fine needle biopsy revealed histologic features consistent with Hodgkin's lymphoma, nodular sclerosing type. Immunostains confirmed the presence of Reed Sternberg cells that were positive for CD 30, focally positive for CD 15, and negative for CD 20 and EMA. Bilateral bone marrow showed no evidence of HL involvement. A positron-emission tomography detected abnormal uptake in multiple enlarged lymph nodes above and below the diaphragm, and in the thoracic spine, at T9, T11 and T12 vertebral body levels. The patient was successfully treated with doxorubicin-based combination chemotherapy regimen. Conclusion:There are multiple clinical presentations for Hodgkin's lymphoma. Routine mammograms can aid in the detection of cancer types other than breast cancer. Disclosures:No relevant conflicts of interest to declare.

Hodgkin Lymphoma in Jordan; A Retrospective Analysis of 477 Cases in King Hussein Cancer Centre

Abstract 4862 BACKGROUNDJordan is a small country with an estimated mid year population in 2008 of 5 850 000, 3015000 of whom are males and 2 835 000 are females (male: female ratio 1.06: 1). (Department of Statistics Jordan, 2008).About 12.7 % of the population is under 5 years old, and 37.3 % under 15 years old. 11%if the population are 15–19 year old, with a M:F ratio 1.06:1 as well) Only 3.3 % of the total population is above the age of 65 years old (sex ratio of 1.01 male per 1 female in this age group).According to the Jordan Cancer Registry Report for 2008, Lymphoma is the fourth most common Cancer in the country. A total of (4606 ) new cases of cancer were recorded among Jordanians in the year 2008, 333 (7.2%) of whom had a diagnosis of lymphoma.111 (2.4%) were diagnosed as Hodgkin's lymphoma (HL), and 222 (4.8%) as Non Hodgkin Lymphoma(NHL). OBJECTIVEIn this study, we aim to characterize some of the clinico-pathological features of Hodgkin lymphoma in Jordan by analyzing the data available for patients referred to King Hussein Cancer Center over a seven year period. PATIENTS AND METHODSA retrospective analysis was conducted of adults (>18 years) lymphoma patients referred to KHCC, between 1/1/2003 and 31/12/2010. Clinical features and histological subtypes were prospectively established for all patients registered in the Lymphoma Service Database. Pathology review and original paraffin block were mandated for all patients. RESULTSOver the 8 year period of 2003–2010,1329 lymphoma patients were referred to KHCC and registered in the Lymphoma Service Database, of whom 477 (35.9%) were diagnosed with Hodgkin’s lymphoma. Among this group all 477 patients were adults 18 years or older (100%), as children are treated in a different department. The median age was 35 years, (with an age range of 18–77), and 5% of patients were above the age of 60. 290 (61 %) of the patients were males, 187 (39%) were females, with a male to female (M:F) ratio of 1.55:1.276 (57.8%) of the HL cases had a diagnosis of nodular sclerosis Hodgkin lymphoma (HDNS), making it the most common histological subtype. 120(25.2%) had mixed cellularity Hodgkin lymphoma (HDMC), 9 (1.9%) had lymphocyte-rich Hodgkin lymphoma (HDLR), and 6 (1.2%) had lymphocyte-depleted Hodgkin (HDLD). Nodular lymphocyte predominance Hodgkin lymphoma (NLPHD) cases were 33, and constituted 6.9% of the HL cohort. CONCLUSIONHodgkin lymphoma appears to constitute a bigger share of the lymphoma burden in Jordan, as opposed to Europe and the US. Clinico-pathological features, however, appear to be closer to those described in Western countries, with similar incidence of HDNS, and HDMC subtypes, but possibly with less incidence of HDLR and HDLD subtypes. Disclosures:No relevant conflicts of interest to declare.

Identification of stromal proteins overexpressed in nodular sclerosis Hodgkin lymphoma

Hodgkin lymphoma (HL) represents a category of lymphoid neoplasms with unique features, notably the usual scarcity of tumour cells in involved tissues. The most common subtype of classical HL, nodular sclerosis HL, characteristically comprises abundant fibrous tissue stroma. Little information is available about the protein composition of the stromal environment from HL. Moreover, the identification of valid protein targets, specifically and abundantly expressed in HL, would be of utmost importance for targeted therapies and imaging, yet the biomarkers must necessarily be accessible from the bloodstream. To characterize HL stroma and to identify potentially accessible proteins, we used a chemical proteomic approach, consisting in the labelling of accessible proteins and their subsequent purification and identification by mass spectrometry. We performed an analysis of potentially accessible proteins in lymph node biopsies from HL and reactive lymphoid tissues, and in total, more than 1400 proteins were identified in 7 samples. We have identified several extracellular matrix proteins overexpressed in HL, such as versican, fibulin-1, periostin, and other proteins such as S100-A8. These proteins were validated by immunohistochemistry on a larger series of biopsy samples, and bear the potential to become targets for antibody-based anti-cancer therapies.

Hodgkin lymphoma: 2011 update on diagnosis, risk‐stratification, and management

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8,500 new patients annually and representing approximately 11% 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 are used to optimize therapy for patients with limited or advanced stage disease. 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 treated with combined modality strategies using 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. 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, palliative chemotherapy, nonmyeloablative allogeneic transplant, or participation in a clinical trial should be considered.