Lymphocyte-rich Subtype Research Articles

Cytotoxic T-lymphocyte-associated 4 protein expression is associated with a high international prognostic score in advanced-stage classical Hodgkin lymphoma

ObjectiveTwenty percent of all classical Hodgkin lymphoma (CHL) cases relapse and recur, especially in advanced stages with a high International Prognostic Score (IPS). Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a regulatory molecule that can inhibit the immune response and is related to tumor aggressiveness. This study aimed to determine the relationship between CTLA-4 expression in advanced-stage CHL and IPS, identifying it as a potential therapy target.ResultsIn advanced-stage CHL, the group with a high IPS exhibited significantly higher mean CTLA-4 expression compared to the group with a low IPS (p = 0.003).The group with Hb level < 10.5 g/dl, leukocyte count > 15,000/µL, lymphocyte count < 8%, albumin level < 4 g/dl, and stage 4 exhibited higher CTLA-4 expression than the other group, although only leukocyte count and stage showed statistical significance (p = 0.004 and p = 0.020). Mean CTLA-4 expression was 239.84 ± 76.36 for nodular sclerosis, 293.95 ± 147.94 for mixed cellularity, 271.4 ± 23.56 for lymphocyte depleted, and 225.2 for lymphocyte-rich subtypes. The results suggest that CTLA-4 expression is associated with adverse prognostic factors in the IPS for advanced-stage CHL, supporting the notion that immune checkpoints play a role in cancer progression.

Epidemiologic and Clinical Patterns of Malignant Lymphoma in Qatar 2013–2017: A Population-Based Cohort Study

Introduction: Lymphoma, encompassing common non-Hodgkin lymphoma (NHL) and less common Hodgkin lymphoma (HL), represents significant hematological malignancies. Advancements in treatment modalities have reshaped survival rates, particularly in NHL. This complexity results in varying outcomes, some requiring extended observation periods and multiple chemotherapy treatments. The primary objective was to explore and compare the overall survival (OS) of HL and NHL at 1, 3, and 5-year follow-ups among adult lymphoma patients in Qatar during January 2013–December 2017. Further objectives encompass comparing the most prevalent histological types, clinical and epidemiological traits of HL and NHL, as well as secondary aims of assessing clinical features, treatment, response, disease-free survival, and OS. Methods: A retrospective, descriptive study of consecutive cases was conducted at Qatar’s NCCCR between 2013 and 2017. Inclusion criteria involved patients ≥18 years old, of any gender and clinical stage at diagnosis, who received chemotherapy and had known outcomes. Descriptive statistics were applied, and survival analysis utilized Kaplan-Meier curves. STATA version 13.0 facilitated data analysis. Results: Between 2013 and 2017, 414 individuals in Qatar were diagnosed with lymphoma. The median age at diagnosis was 49 years (IQR 36–95 years; p < 0.001) across all patients. Males exhibited a higher likelihood of developing HL and NHL, comprising 74% and 70% of cases, respectively, though this difference was statistically insignificant (p = 0.45). Among NHL-B subtypes, mature B-cell neoplasms (60%) predominated, while lymphocyte-rich subtype (49%) was prominent in HL cases. With a median follow-up of 17.3 months, OS rates at 1, 3, and 5 years were 99%, 82%, and 64%, respectively for all lymphoma patients. Subtype stratification revealed trends in 3-year follow-up OS (94 vs. 82%) for HL and NHL, with 5-year OS of 67% and 60%, respectively. HL demonstrated higher OS throughout the study period compared to NHL (p < 0.001), though median OS remained unreached. Conclusions: Diffuse large B-cell lymphoma emerged as the most prevalent subtype among lymphomas in Qatar. Generally, HL exhibited superior survival rates, at 67% compared to 60% for NHL. Minor deflation in survival rates, particularly for HL, might be attributed to Qatar’s immigration patterns.

Histopathology of hepatocellular carcinoma - when and what

When do you need to take biopsies of the liver, and what information will you get is the topic of this review on hepatocellular carcinoma (HCC). If, clinically, the differential diagnosis of HCC after imaging is suggested, a biopsy has become obligatory as a diagnostic confirmation of HCC in the non-cirrhotic liver prior to definitive therapeutic interventions, as well as in a palliative therapy concept. In the case of hepatic lesions with an uncharacteristic contrast uptake, a biopsy should be performed immediately to confirm the diagnosis of HCC. After diagnosing HCC, a treatment strategy is evaluated. Further, the biopsy, or in case of surgical treatment, the resected tissue, shows us the different subtypes of HCC, with the steatohepatitic subtype being the most common and the lymphocyte-rich subtype being the least common. Further, the histological grade of HCC is determined according to the grading system of the WHO or the Edmonson and Steiner System. Through biopsies, HCC can be differentiated from intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma or metastases of other malignant tumors, especially metastases of the gastrointestinal tract. In summary, biopsies are fundamental in the diagnosis of HCC.

Spectrum of common Hodgkin lymphoma and non-Hodgkin lymphomas subtypes in Zambia: a 3-year records review

BackgroundLymphomas usually present with different occurrence patterns across different geographical locations, but their epidemiology in Zambia is yet to be extensively explored.ObjectivesTo study the spectrum of lymphoma subtypes prevalent within the Zambian population.MethodsHistopathological records with suspected lymphoma at the University Teaching Hospital (UTH) in Lusaka from the year 2014 to 2016, diagnosed based on the 2008 World Health Organization (WHO) criteria were reviewed. The analysis was done in terms of type, sex, age, and site of biopsy; and Fisher’s exact test was used for significance testing.ResultsDuring the study period (2014-2016), there were more B cell neoplasms {222 (92.5%)} than T cell neoplasms {18 (7.5%)}. Non-Hodgkin’s lymphoma (NHL) was seen in 191 (79.6%) whereas classic Hodgkin’s lymphoma (CHL) was seen in 39 (16.3%). Burkitt’s lymphoma (BL) and diffuse large B cell lymphoma (DLBCL) showed equal proportions {17.5% of all lymphoma cases (42/240) each}, as the most prevalent subtypes of NHL whereas marginal zone B cell lymphoma was the rarest subtype with 1.4% (4/240). For CHL, mixed cellularity and lymphocyte rich subtypes (4.6% of all lymphoma cases) were the most common subtypes. There was a statistically significant difference in the occurrences of lymphoma subtypes across different age categories (p = 0.002).ConclusionZambia has a diverse lymphoma subtypes population, affecting a relatively young population. The data from this study will serve as a baseline for improved health care provision and more robust future studies.

Treatment of childhood Hodgkin lymphoma in sub-Saharan Africa: A report from the French-African Paediatric Oncology Group (GFAOP)

Background . Childhood Hodgkin lymphoma (HL) is typically treated by chemo- and radiotherapy, depending on the stage of the disease. Studies on the treatment of HL by chemotherapy alone have shown encouraging results. Objective. To evaluate the feasibility, epidemiological and therapeutic aspects of paediatric HL treated with only COPP/ABV hybrid chemotherapy (cyclophosphamide, vincristine, procarbazine, prednisone, adriamycin, bleomycin and vinblastine). Methods. This was a prospective multicentre study on the management of HL in paediatric oncology centres of the French-African Paediatric Oncology Group in sub-Saharan Africa, from 1 October 2006 to 30 November 2012. To be included in the study, patients had to be younger than 18 years at diagnosis, with histologically proven HL. Results. A total of 106 patients were included, with a median age of 10 years (range: 2 - 18 years). The sex ratio was 3.1, with a preponderance of male patients (male: n =80; female: n =26). The largest number of patients were in stage IIIB ( n =47), IIB ( n =18) and IVB ( n =15); other stages were represented to a lesser extent. More than 80% of patients had an unfavourable initial prognosis. On biopsy, the nodular sclerosis subtype was observed in 36% of patients ( n =38), followed by mixed cellularity ( n =21; 20%) and the lymphocyte-rich subtype ( n =17; 16%). Eighteen patients relapsed. The overall survival rate of treated patients was 82% at a median follow-up of 30 months. Conclusion. The treatment of childhood HL in sub-Saharan Africa is challenging. The use of a hybrid chemotherapy protocol alone can be effective at improving patient survival

Single Cell Transcriptome Analysis Reveals Disease-Defining T Cell Subsets in the Tumor Microenvironment of Classic Hodgkin Lymphoma

INTRODUCTION: Classic Hodgkin lymphoma (cHL) is uniquely characterized by an extensively dominant microenvironment composed primarily of different types of non-cancerous immune cells with a rare population (~1%) of tumor cells. Detailed characterization of these cellular components and their spatial relationship is crucial to understand crosstalk and therapeutic targeting in the cellular ecosystem of the tumor microenvironment (TME). METHODS: In this study, we performed high dimensional and spatial profiling of immune cells in the TME of cHL. Single cell RNA sequencing (scRNA-seq) was performed with the 10x Genomics platform on cell suspensions collected from lymph nodes of 22 cHL patients, including 12 of nodular sclerosis subtype, 9 of mixed cellularity subtype and 1 of lymphocyte-rich subtype, with 5 reactive lymph nodes (RLNs) serving as normal controls. Illumina sequencing (HiSeq 2500) was performed to yield single-cell expression profiles for 127,786 cells. We also performed multicolor IHC and imaging mass cytometry (IMC) on TMA slides from the same patients. RESULTS: Unsupervised clustering using PhenoGraph identified 22 cell clusters including 12 T cell clusters, 7 B cell clusters and 1 macrophage cluster. While most immune cell populations were common between cHL and RLN, we observed an enrichment of cells from cHL in all 3 regulatory T cell (Treg) clusters. The most cHL-enriched cluster was characterized by high expression of LAG3, in addition to common Treg markers such as IL2RA (CD25) and TNFRSF18 (GITR), but lacked expression of FOXP3, consistent with a type 1 regulatory (Tr1) T cell population. LAG3+ T cells in cHL had high expression of immune-suppressive cytokines IL-10 and TGF-b . In vitro exposure of T cells to cHL cell line supernatant induced significantly higher levels of LAG3 in naïve T cells compared to co-culture with other lymphoma cell line supernatant or medium only. CD4+ LAG3+ T cells isolated by FACS also suppressed the proliferation of responder CD4+ T cells when co-cultured in vitro. Additionally, Luminex analysis revealed that cHL cell lines secrete substantial amounts of cytokines and chemokines that can promote Tr1 cell differentiation (e.g. IL-6). Our scRNA-seq analysis revealed that LAG3 expression was significantly higher in cHL cases with loss of major histocompatibility class II (MHC-II) expression on HRS cells as compared to MHC-II positive cases (P = 0.019), but was not correlated with EBV status or histological subtype. Strikingly, LAG3 was identified as the most up-regulated gene in cells from MHC-II negative cases compared to MHC-II positive cases. Topological analysis using multicolor IHC and IMC revealed that in MHC-II negative cases, HRS cells were surrounded by LAG3+ T cells. In these cases, the density of LAG3+ T cells in HRS cell-rich regions was significantly increased, and the average distance between an HRS cell and its closest LAG3+ T cell neighbor was significantly shorter. These associations were confirmed in an independent cohort of 166 cHL patients. Finally, we observed a trend towards an inferior disease-specific survival (DSS; P = 0.072) and overall survival (OS; P = 0.12) in cases with an increased number of LAG3+ T cells. A high proportion of LAG3+ T cells (&amp;gt; 20%) was identified as an independent prognostic factor for DSS by multivariate Cox regression. CONCLUSIONS: Our results reveal a diverse TME composition with inflammatory and immunosuppressive cellular components that are linked to MHC class II expression status on HRS cells (Figure). Unprecedented transcriptional and spatial profiling at the single cell level has established the pathogenic importance of HRS cell-induced CD4+ LAG3+ T cells as a mediator of immunosuppression in cHL, with potential implications for novel therapeutic approaches. Figure Disclosures Savage: Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding; BMS, Merck, Novartis, Verastem, Abbvie, Servier, and Seattle Genetics: Consultancy, Honoraria. Scott:Roche/Genentech: Research Funding; Celgene: Consultancy; Janssen: Consultancy, Research Funding; NanoString: Patents &amp; Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding. Steidl:Bristol-Myers Squibb: Research Funding; Nanostring: Patents &amp; Royalties: Filed patent on behalf of BC Cancer; Roche: Consultancy; Seattle Genetics: Consultancy; Bayer: Consultancy; Juno Therapeutics: Consultancy; Tioma: Research Funding.

Deficiency of Adenosine Deaminase 2 (DADA2) Presenting As Familial Hodgkin Lymphoma

Familial Hodgkin Lymphoma (HL) accounts for 4.5% of HL. Both genetic susceptibility and shared environmental factors can play a role. The usual presentation of HL is cervical lymphadenopathy/ mediastinal mass. Subdiaphragmatic presentation is rare and hepatosplenomegaly is associated with advanced HL.Adenosine deaminase 2 (ADA2) act as an outside extracellular growth factor for integrity of endothelial cells and in the development of certain immune cells. Deficiency of ADA2 (DADA2) is a recently described inborn error of immunity caused by biallelic mutations in adenosine deaminase 2 (ADA2) gene (formerly known as CECR1). It is an auto-inflammatory disorder with a spectrum of vascular, inflammatory, hematological and immunodeficiency phenotypes. The condition is inherited in an autosomal recessive pattern.The association of DADA2 with lymphoproliferation such asT-LGL like condition and ALPS like disease have been reported, however, HL has not previously been reported in DADA2.Herein we describe two siblings with DADA2 who presented with Hodgkin Lymphoma. The first patient is the third child of Saudi first degree related parents. He is known to have bronchial asthma on bronchodilators. At the age of 5 years, he was referred from primary care clinic for investigation of hepatosplenomegaly. He was otherwise well with growth along the fifth centile. His complete blood count (CBC) showed mild lymphopenia, other lab results including liver function tests were within normal. Few months later, he developed non-tender mobile cervical lymph nodes enlargement. Viral serology including EBV was negative based on PCR testing. Lymph node biopsy revealed the diagnosis of HL, mixed cellularity type, EBV negative (Figure 1). Whole exome analysis sequencing identified a homozygous variant in ADA2 gene c.1447_1451del. This variant has been confirmed by Sanger sequencing. Plasma assay of ADA2 enzyme activity revealed undetectable levels compatible with ADA2 deficiency.The patient started on prednisone 2 mg/kg/day, which showed good response in the form of being off blood support and regression of splenomegaly. Few months later, the course was complicated by recurrent infections. The patient remained stable for three years on small dose of prednisone, monthly IVIG due to hypogammaglobulinemia. Recently, etanercept was started to control disease progression.Nine months after the diagnosis of first patient, his younger brother who is known to have mild bronchial asthma on bronchodilators presented at the age of five years with hepatosplenomegaly and generalized lymphadenopathy. Lymph node biopsy revealed the diagnosis of classical HL, lymphocyte-rich subtype. Similar to his sibling, whole exome analysis identified the same mutation (a homozygous variant in ADA2 gene c.1447_1451del). This variant has been confirmed by Sanger sequencing and plasma level of ADA2 enzyme activity was undetectable. After the diagnosis of DADA2, screening for serum immunoglobulin levels showed hypogammaglobulinemia. The patient continues to be off treatment. Both patients were treated with chemotherapy with or without radiotherapy showing good response and they remained in remission at respectively and months after cessation of chemotherapy.This study is important for several reasons. First, this is the first report of HL in the context of DADA2. This again widens the clinical spectrum of DADA2. Interestingly, the boys presented two different forms of HL at the cellular level with no evidence of viral infection. The reported siblings presented with subdiaphragmatic diseases, which is uncommon in HL but in line with the sites of lymphoproliferation in DADA2. In addition, the age of presentation in the two siblings is uncommon in HL (less than 10 years).Second, we report an novel mutation in ADA2 gene. It creates a shift in the reading frame starting at codon Ser483. The new reading frame ends in a stop codon 4 positions downstream. This description and the description of the HL occurrence further expands the spectrum of DADA2. Our data, call for judicious exclusion of ADA2 deficiency in the HL patient with an aberrant course and additional symptoms / signs.In summary, we report familial HL in two patients with a novel deleterious mutation in ADA2 gene. This expands the spectrum of this disease to include cancer and should alert the hemato-oncologist to the possibility of DADA2 as an underlying diagnosis in HL. DisclosuresNo relevant conflicts of interest to declare.

Rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin in the treatment of secondary hemophagocytic lymphohistiocytosis with classical Hodgkin lymphoma: a case report and review of the literature

BackgroundHemophagocytic lymphohistiocytosis is becoming an increasingly recognized disorder in adults. Classical Hodgkin lymphoma is a relatively uncommon etiology of hemophagocytic lymphohistiocytosis and may complicate treatment options. Rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin are discussed here as a treatment regimen. Case presentationA 66-year-old Hispanic man previously in good health presented with a 1-month history of recurrent fevers, chills, and night sweats and a 3-week history of new onset jaundice. A bone marrow biopsy revealed a normocellular bone marrow with increased histiocytes with areas of hemophagocytic activity. He met five out of eight criteria for hemophagocytic lymphohistiocytosis diagnosis including fevers, pancytopenia, hemophagocytosis, ferritin of 23,292 ng/mL (>500 ng/mL), and soluble-CD25 of 15,330 pg/mL (>1033 pg/mL). A right cervical lymph node biopsy revealed CD15, CD30, MUM-1, and Epstein–Barr virus-encoded small ribonucleic acid-positive cells with morphologic findings of classical Hodgkin lymphoma, lymphocyte-rich subtype. He completed 2 weeks of hemophagocytic lymphohistiocytosis-directed therapy with etoposide and dexamethasone, but then was switched to rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin due to minimal improvement in his pancytopenia and hepatic impairment. He completed one full cycle of rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin with notable improvement in serial hepatic function panels and had an undetectable Epstein–Barr virus viral load. However, he eventually died due to complications of Enterococcus faecalis bacteremia and colonic microperforation in the setting of persistent pancytopenia.ConclusionsThis case discusses the challenges facing treatment of adult malignancy-associated hemophagocytic lymphohistiocytosis. Rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin may be a viable option for patients with secondary hemophagocytic lymphohistiocytosis and Hodgkin lymphoma who cannot tolerate standard therapies due to hepatic impairment. Targeted therapy and immunotherapy are promising new areas of developing treatments.

Outcome of Elderly Patients with Hodgkin's Disease-Single Centre Experience from Riyadh, Saudi Arabia

Background: Hodgkin's disease accounts for approximately 10% of all lymphoma cases. There is a bimodal distribution with initial peak in second decade and a later peak in sixth decade. There is paucity of date on outcome of elderly patients with Hodgkin's disease. There is hardly any data from middle eastern patients.Materials and Methods: We retrospectively analyzed 168 consecutive patients diagnosed with Hodgkin's disease at our centre from 2006 to 2015 (age>14 years) and found 16 patients to be over the age of 60 years.Results: Out of 16 patients 6 were females, 10 were males and the median age was 70 years (range 61-86).All patients had classical Hodgkin's disease out of which 12 had nodular sclerosis subtype, 2 had mixed cellularity subtype and 1 had lymphocyte rich subtype. 4 patients had early stage disease (IA-IIA) while rest 12 had advanced stage disease. 15 were treated with ABVD based regimen, the other was treated with chlorambucil based regimen.3 out of 16 were given radiation in addition to chemotherapy. Out of the 14 evaluable patients (two were lost to follow up) 13 completed treatment and all of them achieved complete remission (93%).9 of 16 patients were given reduced dose doxorubicin. Three patients died (one due to sepsis, the other due cardiomyopathy 2 years after treatment, third one due secondary cancer).None of the alive patients have relapsed yet. One patient developed secondary cancer who later died with the same. At a median follow up of 35 months (range 1-72) even free survival and overall survival were 79% and 86% respectively.Discussion: As per our study unlike in western world, older patients are less frequently affected with Hodgkin's disease. The remission rates and survival data are very encouraging despite dose reductions, however further data from this part of the world is needed to confirm our results. ABVD appears feasible, effective treatment option for elderly patients although frail patients who cannot tolerate ABVD may be candidates for anti CD30 antibody based regimens. DisclosuresNo relevant conflicts of interest to declare.

Hodgkin's disease in adults: the royal medical services experience

Background: The aim of this study to examine our experience in the presentation and management and to determine the factors that potentially influenced the outcome in 96 patients with Hodgkin’s lymphoma. Methods: A retrospective study done at oncology unit in royal medical services hospitals, a total 96 patient whom diagnosed with Hodgkin’s lymphoma between 2005 and 2013, data include age, sex of patients, presenting and duration of symptoms, staging of disease, and prognosis of disease. Results: 66 males and 30 females, the most common enlarged lymph node was at cervical region. The most common histopathology subtype was nodular sclerosis. Most of our patients were staged as stage 4. Systemic symptoms developed in 50 (52%) patients. The most common site of extralymphatic involvement was lung. Complete remission was noted in all 29 patients whom presented with early stages of disease and less in advanced stages. Failure of remission post treatment was noticed more in mixed cellularity and lymphocyte rich subtypes. On regular follow up of patients 8 patients whom were in complete remission developed relapse of disease; mean time of relapse was 9 months post remission. Conclusion: Hodgkin’s lymphoma has high rates of cure. Epidemiological, clinical, histological and therapeutic results in our series are similar to those Western series. Long term evaluation is necessary to assess relapse and late toxicity treatment.

Clinicopathologic study of 40 cases of mediastinal tumours of haematopoietic and lymphoid tissues

To study clinical and histopathological features, and diagnosis of mediastinal tumours of haematopoietic and lymphoid tissues (MTHL). Forty cases of MTHL were analyzed for clinicopathology by microscopy and immunohistochemical staining and in situ hybridization, according to the updated 2008 WHO classification of tumours of haematopoietic and lymphoid tissues. In 40 cases of MTHL, there were 20 males and 20 females. The ratio of male/female was 1:1. The mean age was 31.8 years and median age was 29 years (range, 12 - 70 years).Superior vena cava syndrome was observed in 28 cases. The specimens of 4 cases were obtained by lumpectomy, whereas 36 cases by biopsy (25 cases by thoracoscopy, 1 by core needle aspiration). Twenty cases lay in anterior mediastinum, and 2 in posterior, 1 in superior, 8 in anterior and superior, 2 in posterior and superior, 2 in anterior and middle, 1 in middle and anterior mediastinum.Frozen section were performed in 28 cases, and 17 cases were diagnosed as tumours of haematopoietic and lymphoid tissues (consistency ratio was 60.7%). Twelve cases were classical Hodgkin lymphomas (cHL) (8 were nodular sclerosis subtype, and 3 were mixed cellarity, 1 was lymphocyte-rich subtype), and 10 were primary mediastinal (thymic) large B cell lymphoma (PMBCL), 10 were precursor lymphocyte neoplasm [8 were T lymphoblastic leukemia/lymphomas (T-LBL), 2 were B-LBL], 1 was MALT lymphoma, 1 was composite lymphoma (PMBCL and cHL), 2 were myeloid sarcomas, 4 were gray zone lymphomas (GZL) (3 had morphology reminiscent of cHL, and 1 of DLBCL, all cases were positive for CD20, PAX5, CD30 and CD15).EBER were detected in 11 cases by in situ hybridization, 2 of which were positive (18.2%), and the 2 positive cases were cHL. MTHLs occur predominantly in adolescents and young adults, mainly present as superior vena cava syndrome and anterior mediasinal masses. cHL, PMBCL, T-LBL were the most common MTHLs.GZLs mainly occur in young adults, those whose morphology reminiscent of cHL, immunohistochemistry reminiscent of PMBCL, and vice versa. Thoracoscopy, frozen section and a suitable panel of antibodies were practical approaches to MTHL.

Hodgkin lymphoma at the paediatric oncology unit of Gabriel-Touré teaching Hospital Bamako (Mali): 3 years experience

Approximately 20 000 new cases of Hodgkin lymphoma are diagnosed each year in North America and Europe. However in Africa, the incidence of this condition is almost unknown. While publications from western countries and the rest of world are numerous in the literature, few data from Africa about this malignancy are available. The aim of this retro and prospective, unicentric study over 3 years is to describe the epidemiologic, pathologic, clinical and therapeutic aspects of children treated for Hodgkin lymphoma in our paediatric oncology unit of Gabriel-Toure Hospital, Bamako (Mali). From January 2005 to December 2007, all children under 18 years of age, with histologically proven Hodgkin lymphoma, not previously treated by chemotherapy and HIV negative, were included in this study. Informed consent was obtained from parents. The treatment protocol was the GFAOP (Groupe franco-africain d’oncologie pediatrique) Hodgkin lymphoma treatment protocol: COPP/ABV (Cyclophosphamid, Vincristin, Prednisone, Procarbazin, Adriamycine, bleomycin and vinblastine). During the study period, 217 cancer cases were diagnosed in our centre. Of these cases, 7 were Hodgkin Lymphoma (0.04%). The average age was 11.7 years. The sex-ratio was 6/1 in favor of boys. 6.71% (5/7) of the patients were stage IIB and 28.6 % (2/7) of the patients were stage IIIB of the Ann-Arbor classification. Histologically, there were 42.8% cases of sclero-nodular subtype, 28.6% of lymphocyte-rich subtype, 14.3 % of mixed cellularity and 14.3% of lymphocyte depleted subtype. After 4 years follow-up, 5 patients (71.4 %) were alive, and 2 patients (28.6 %) had died from drug toxicity. Hodgkin lymphoma is a relatively rare condition in African children which can be cured. Broader multicentric studies are needed for more accurate data on this malignancy.

What is your diagnosis? Cervical mass in a cat

An 8-year-old female spayed domestic shorthair cat was presented for several months of weight loss, decreased appetite, and 2 bilateral, ventral cervical masses. Initial cytologic samples were interpreted as reactive lymphoid hyperplasia. Evaluation of subsequent mass aspirates revealed small numbers of large binucleated and multinucleated cells resembling Reed-Sternberg cells admixed with more numerous small and intermediate-sized lymphocytes. In histopathologic sections, the normal architecture of the lymph node was largely effaced by a slightly heterogeneous mass composed of round cells arranged in densely cellular sheets with a minor population of large (25-microm diameter) mononuclear cells and a few very large (30-40-microm diameter) binucleated or multinucleated cells interpreted as Reed-Sternberg-like cells. Immunohistochemically, the large neoplastic (Reed-Sternberg-like) cells were negative for CD18, CD3, CD20, and CD79a while the background population consisted of about 70% T cells and 30% B cells. This pattern of immunohistochemical staining along with cytologic and histopathologic findings supported a diagnosis of Hodgkin's-like lymphoma, specifically, the lymphocyte-rich subtype. Hodgkin's-like lymphoma has been reported previously in cats and should be suspected when Reed-Sternberg-like cells are observed in cytologic preparations of lymph node aspirates. Histopathology and immunohistochemistry are necessary for a definitive diagnosis.

Expression of Epstein–Barr virus in Hodgkin lymphoma in a population of United Arab Emirates nationals

Hodgkin lymphoma (HL) shows wide geographic variation in histological subtypes and in its association with the Epstein–Barr virus (EBV). HL has three main epidemiological patterns (I, II and III). Type I pattern, which is prevalent in developing countries, shows a relatively high incidence in male children, a low incidence in the third decade and a second peak of high incidence in older age groups. Type III, which is usually seen in developed countries, is characterised by a low rate in children and a pronounced initial peak in young adults. The third pattern (Type II), which is described in many Asian countries, is intermediate and reflects a transition between types I and III. In this pattern there is both a childhood and a third decade peak. The proportion of EBV positive HL is low in industrialised countries, high in non-industrialised countries and intermediate in early-industrialised countries. Reports from the Arabian Gulf and Middle East are few. The aim of this study is to determine the epidemiology of HL in a population of United Arab Emirates (UAE) nationals, an early industrialised country in the Arabian Gulf, and to delineate the extent of its association with EBV. In total, 88 cases of HL were diagnosed in native patients during the period 1988 through 2004 at Tawam hospital. Forty-five paraffin blocks were available for this study. Five-micrometer sections were prepared and stained with hematoxylin and eosin and the immunohistochemical streptavidin–biotin methods for CD45, CD3, CD20, CD15 and CD30. Other sections were examined for the presence of EBV using the immunohistochemical streptavidin–biotin method for the latent membrane protein 1 and in situ hybridisation for EBV encoded RNA to determine the prevalence of EBV in Hodgkin cells and its possible role in the pathogenesis of HL. Nodular sclerosis (NS) subtype was the most common type of HL among UAE nationals followed by mixed cellularity (MC), lymphocytic predominant (LP), unclassified, lymphocytic depletion (LD) and lymphocyte rich (LR) subtypes, respectively. EBV was seen in 17 of 45 (38%) cases of HL and was predominately seen in the MC subtype followed by NS, LD and LR subtypes, respectively. EBV was more frequently expressed in HL in the pediatric age group than the adult age group. These data indicate that the epidemiology of HL in a native population of the UAE is suggestive of a type II epidemiologic pattern in terms of age distribution, and histopathologic subtypes, whereas the frequency of EBV expression is more suggestive of a type III epidemiologic pattern. The significant association between EBV and HL that we have found further strengthens the suggestion that all cases of HL should be assessed for EBV status, because its presence may have a significant impact on prognosis and response to therapy.

Who is WHO and what was REAL?

The principles of the new WHO classification of haematopoietic and lymphoid tumours are based on those defined in the Revised European American classification of Lymphoid neoplasms (REAL), published by the International Lymphoma Study Group (ILSG) in 1994. Thus, the new WHO classification may be considered an updated version of the REAL classification rather than of the old WHO classification published in 1976. Disease entities are defined on the basis of morphological, phenotypic, genotypic, and clinical data. The relative impact of these characteristics varies among different diseases and there is "no gold standard". Thus, the strict hierarchy among diagnostic criteria, headed by morphology and followed by immunohistochemistry and genetics, has been discontinued. The WHO classification not only encompasses lymphoid tumours but extends to myeloid, mast cell and histiocytic/dendritic cell malignancies. Neoplasms are primarily stratified according to their tumour cell lineage. For each neoplasm a cell of origin is postulated. The classification of lymphoid malignancies recognises three major categories, B-cell neoplasms, T-/NK-cell neoplasms, and Hodgkin lymphomas. B-cell and T-cell lymphomas are further divided into precursor neoplasms and mature neoplasms, the latter being subdivided according to their clinical manifestation into disseminated/leukaemic, extranodal and nodal malignancies. In contrast to previous classifications, the neoplasms are grouped neither according to their histological grade (Kiel classification) nor according to their clinical aggressiveness (International Working Formulation). However, the histological grade is considered a prognostic factor which enters into the description of each disease entity. Hodgkin's disease, now more appropriately termed Hodgkin lymphoma, comprises nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphomas of nodular sclerosis, mixed cellularity, lymphocyte-depleted and lymphocyte-rich subtype. For practical purposes this minireview disregards the description of myeloid, macrophage/histiocytic, dendritic cell and mast cell disorders. Furthermore, the present paper is restricted to those lymphoid tumours that are not already identically described in the REAL classification, in order to focus on what is really new in the WHO classification.

Who is WHO and what was REAL?

The principles of the new WHO classification of haematopoietic and lymphoid tumours are based on those defined in the Revised European American classification of Lymphoid neoplasms (REAL), published by the International Lymphoma Study Group (ILSG) in 1994. Thus, the new WHO classification may be considered an updated version of the REAL classification rather than of the old WHO classification published in 1976. Disease entities are defined on the basis of morphological, phenotypic, genotypic, and clinical data. The relative impact of these characteristics varies among different diseases and there is "no gold standard". Thus, the strict hierarchy among diagnostic criteria, headed by morphology and followed by immunohistochemistry and genetics, has been discontinued. The WHO classification not only encompasses lymphoid tumours but extends to myeloid, mast cell and histiocytic/dendritic cell malignancies. Neoplasms are primarily stratified according to their tumour cell lineage. For each neoplasm a cell of origin is postulated. The classification of lymphoid malignancies recognises three major categories, B-cell neoplasms, T-/NK-cell neoplasms, and Hodgkin lymphomas. B-cell and T-cell lymphomas are further divided into precursor neoplasms and mature neoplasms, the latter being subdivided according to their clinical manifestation into disseminated/leukaemic, extranodal and nodal malignancies. In contrast to previous classifications, the neoplasms are grouped neither according to their histological grade (Kiel classification) nor according to their clinical aggressiveness (International Working Formulation). However, the histological grade is considered a prognostic factor which enters into the description of each disease entity. Hodgkin's disease, now more appropriately termed Hodgkin lymphoma, comprises nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphomas of nodular sclerosis, mixed cellularity, lymphocyte-depleted and lymphocyte-rich subtype. For practical purposes this minireview disregards the description of myeloid, macrophage/histiocytic, dendritic cell and mast cell disorders. Furthermore, the present paper is restricted to those lymphoid tumours that are not already identically described in the REAL classification, in order to focus on what is really new in the WHO classification.

WHO classification of Hodgkin's lymphoma and its molecular pathological relevance

The current WHO classification of Hodgkin's lymphoma (HL) generally distinguishes the relatively rare variant (approximately 5% of all cases of HL) of nodular lymphocyte predominant type from a second group, which comprises classical HL and is separated into four subtypes: lymphocyte rich type, nodular sclerosis type, mixed cellularity type and lymphocyte depleted type. The classical lymphocyte rich subtype is a new entity and based on the typical morphology, can be recognized by definition only by the immunohistochemical characteristics of the Hodgkin and Reed/Sternberg cells (HRS) (CD30+, CD15+, CD20-). Molecular single cell studies are consistent with the dichotomy of HL in nodular lymphocyte predominant and classical types and stress the exceptional position of the former, which shows similarities with non-Hodgkin's lymphomas in several aspects. On the molecular biology level the tumor cells of all kinds of HL turn out to be clonal B cells derived from germinal center cells. However, tumor cells of nodular lymphocyte predominant HL differ from those of classical HL by the pattern of somatic mutations. Considering the inability of HRS cells of classical HL to express a B cell receptor, they should perish under normal conditions. However, they escape from apoptosis by mechanisms so far only partially understood, such as genomic mutations of the l-kappa B gene and the fas receptor gene or probably by down-regulation of B cell markers. In rare cases, HRS cells of HL can also be derived from T cells, as could be demonstrated by single cell analysis. Also, it could be shown by single cell PCR that HL and non-Hodgkin's lymphoma of both B and T cell types can arise from a common precursor. These results suggest that future classifications of HL will not only take into account the morphological and phenotypical profile, but also mechanisms of transformation yet to be discovered.