Infiltration of Th1 and Th2 lymphocytes around Hodgkin and Reed-Sternberg (H&RS) cells in Hodgkin disease: Relation with expression of CXC and CC chemokines on H&RS cells

Hodgkin disease (HD) is characterized by the presence of Hodgkin and Reed-Sternberg cells (H&RS) and a prominent lymphocytic infiltration. Various CXC and CC chemokines [e.g., interferon-gamma-inducible protein-10 (IP10), monokine induced by interferon-gamma (MIG) and TARC] are expressed on H&RS cells. Our study was designed to investigate the expression of MIG, IP10 and TARC on H&RS cells and their relations on lymphocyte infiltration. Immunohistochemical staining was performed using antibodies for CXCR3 (a specific receptor for IP10 and MIG), which is characteristic of Th1 helper phenotype and CCR3, CCR4 and ST2, which are features of Th2 cells. We studied 15 cases of HD [lymphocyte predominance (LP) type, 2; mixed cellularity (MC) type, 6; and nodular sclerosis (NS) type, 7]. All 6 MC cases contained TARC-, IP10- and MIG-expressing H&RS cells, however only 2 of 5 NS cases contained TARC-expressing H&RS cells, 3 of 7 NS contained MIG-expressing H&RS cells and only 1 of 7 NS contained IP10-expressing H&RS cells. Neither of the 2 LP cases contained HR&S cells that expressed these chemokines. The chemokines were more frequently expressed by MC than by NS and LP types. IP10-, MIG- and TARC-positive HD cases contained higher numbers of Th2 lymphocytes (ST2- CCR3- or CCR4-positive lymphocytes), compared to IP10-, MIG- and TARC-negative HD cases (p < 0.05 or <0.5). The number of CXCR3 (MIG and IP10 receptor)-positive lymphocytes (Th1 lymphocytes) was not different between MIG- and IP10-positive and -negative HD. Lymphocytes surrounding MIG- and IP10-positive H&RS cells were more frequently CXCR3-positive, however, compared to MIG- and IP10-negative cases. The CCR4 (TARC receptor)-positive lymphocytes, surrounding H&RS cells, were minority and the surrounding lymphocytes were not different between TARC-positive and negative cases. Our results indicate that MIG, IP10 and TARC chemokines influenced the response of Th2 cells in HD. It is possible, however, that IP10 and MIG may locally influence Th1 cells via cell migration.     

Disease patterns in pediatric classical Hodgkin lymphoma: a report from a developing area in Brazil

Epidemiological patterns established about 20 years ago, divided classical Hodgkin lymphoma (cHL) in three entities with regard to Epstein–Barr virus (EBV) status and histological subtypes and suggested different epidemiological patterns associated with degree of economic development. Here, we investigated histopathological features and EBV association in 100 consecutive pediatric cHL cases occurring in Rio de Janeiro (Brazil). Age at diagnosis ranged from 3 to 18 years (median 14 years) with 27% of cases ≤10 years. Unexpectedly, we did not observe an early childhood peak with most cases occurring in the >10 years age group. Nodular sclerosis (NS) was the most frequent subtype (69%) and was more frequently observed in the >10 years age group, followed by mixed cellularity (MC, 23%) which was distributed equally between age groups. EBV was identified in 44.8% of cases, without preferential association with age groups (≤10 years vs. >10 years). MC cases were independently associated with EBV infection of tumour cells (p = 0.045) and with a CD4/CD20 ratio <1 in the microenvironment (p = 0.014). Our results suggest that a gradual shift from childhood peak to early adulthood peak may be observed in developing regions. The development of MC subtype may result from early exposure to EBV in the context of an impaired immune system reflected by a CD4/CD20 ratio <1. Conversely, it is possible that NS originates predominantly in the context of a better immune response against EBV and/or tumour antigens expressed in the neoplastic cells. Copyright © 2011 John Wiley & Sons, Ltd.     

Chromosome 16q deletion and loss of E-cadherin expression in Hodgkin and Reed-Sternberg cells

Hodgkin and Reed-Sternberg (H&RS) cells are generally considered to be the neoplastic cells of Hodgkin's disease (HD); however, such H&RS cells are a few in number due to the numerous reactive cells. Very few data have so far been published on the cytogenetic abnormalities in HD. We have previously used the analysis of comparative genomic hybridization (CGH), employing sorted H&RS cells. The most commonly observed genetic aberrations were a loss on 16q11/21, a gain on 1p13 and a gain on 7q35/36. To confirm the loss of 16q, we analyzed the loss of heterozygosity (LOH) using the regions D16S3075 (16p13), D16S3068 (16q11), D16S3136 (16q12), D16S503 (16q13), D16S515 (16q21), D16S3091 (16q23) and D16S520 (16q24). A total of 100 sorted H&RS cells were compared with a similar number of sorted reactive T cells in 15 cases with HD, including 5 cases with nodular sclerosis (NS) type and 10 cases with mixed cellularity (MC) type. LOHs of 16q, especially 16q21-23, were frequently detected, but 16p deletions were infrequent. Analysis of 16q21 showed LOH in 12 of 15 cases with HD (80%), including 9 cases with MC type (90%) and 3 cases with NS type (60%). 16q23 showed LOH in 9 of 15 cases with HD (60%), including 5 cases with MC type (50%) and 4 cases with NS (80%). On the other hand, 16p13 showed LOH in 3 of 15 cases with HD (20%). Immunohistochemical staining showed that H&RS cells rarely expressed E-cadherin, which is located on 16q. Our findings suggest that 16q deletion, especially 16q21-23, is probably involved in H&RS giant cell formation and tumorigenesis.     

Measles virus and classical Hodgkin lymphoma: no evidence for a direct association

A proportion of Hodgkin lymphoma (HL) cases are causally associated with the Epstein-Barr virus (EBV) but the aetiology of the remaining cases remains obscure. Over the last 3 decades several studies have found an association between HL and measles virus (MV) including a recent cohort study describing the detection of MV antigens in Hodgkin and Reed-Sternberg cells, the tumour cells in HL. In the present study we looked at the relationship between history of MV infection and risk of developing HL in a population-based, case/control study of HL. In addition we used immunohistochemistry and RT-PCR to look for direct evidence of MV in HL biopsies. There was no significant difference in the proportion of cases reporting previous measles compared to controls in the entire data set or when young adults were considered separately. Using a robust immunohistochemical assay for MV infection, we failed to find evidence of MV in biopsies from 97 cases of HL and RT-PCR studies similarly gave negative results. This study therefore provides no evidence that MV is directly involved in the development of HL. However, when age at first reported MV infection was investigated, significant differences emerged with children infected before school-age having higher risk, especially of EBV-ve HL, when compared with children infected at older ages; the interpretation of these latter results is unclear.     

Antibody titers against EBNA1 and EBNA2 in relation to Hodgkin lymphoma and history of infectious mononucleosis

A role for Epstein Barr virus (EBV) in Hodgkin lymphoma (HL) pathogenesis is supported by the detection of EBV genome in about one-third of HL cases, but is not well defined. We previously reported that an elevated prediagnosis antibody titer against EBV nuclear antigens (EBNA) was the strongest serologic predictor of subsequent HL. For the present analysis, we measured antibody levels against EBNA components EBNA1 and EBNA2 and computed their titer ratio (anti-EBNA1:2) in serum samples from HL cases and healthy siblings. We undertook this analysis to examine whether titer patterns atypical of well-resolved EBV infection, such as an anti-EBNA1:2 ratio ≤ 1.0, simply reflect history of infectious mononucleosis (IM), an HL risk factor, or independently predict HL risk. Participants were selected from a previous population-based case-control study according to their history of IM. We identified 55 EBV-seropositive persons with a history of IM (IM+; 33 HL cases, 22 siblings) and frequency-matched a comparison series of 173 IM history-negative, EBV-seropositive subjects on HL status, gender, age and year of blood draw (IM-; 105 cases, 58 siblings). In multivariate logistic regression models, an anti-EBNA1:2 ratio ≤ 1.0 was significantly more prevalent in HL cases than siblings (odds ratio, 95% confidence interval = 2.43, 1.05-5.65); similar associations were apparent within the IM+ and IM- groups. EBNA antibodies were not significantly associated with IM history in HL cases or siblings. These associations suggest that chronic or more severe EBV infection is a risk factor for HL, independent of IM history.     

Polymorphisms in the interleukin-10 and interferon gamma genes in Hodgkin lymphoma

Genetic factors are known to be important in the development of Hodgkin lymphoma (HL). Interleukin-10 (IL-10) secretion by both malignant and reactive cells is thought to be important in the pathogenesis of HL especially Epstein-Barr virus (EBV) positive cases. Polymorphisms of the IL-10 gene have been reported to be associated with susceptibility to EBV infection. The cytotoxic response to EBV is determined by a Th1 biased immune response which is characterised by interferon gamma (IFNγ) secretion. We therefore investigated polymorphisms in the IL-10 (-1082 G/A and -592 C/A) and IFNγ (intron 1 CA repeat) genes as predisposing factors in the development 147 cases of HL. A difference of borderline statistical significance was demonstrated for the IFNγ gene polymorphism but significance was lost when analysis was restricted to the common genotypes. No significant differences in the distributions of genotypes were found for the IL-10 gene polymorphisms. IL-10 and IFNγ levels were also measured on 26 patients with HL. No statistically significant differences were detected when the results were analysed by genotype. We found little evidence IL-10 and IFNγ genotypes predispose to the development of HL or influence the inflammatory host response.     

Epstein-Barr virus latent membrane protein-1 upregulates autophagy and promotes viability in Hodgkin lymphoma: Implications for targeted therapy

Hodgkin lymphoma (HL) is composed of neoplastic Hodgkin and Reed-Sternberg cells in an inflammatory background. The neoplastic cells are derived from germinal center B cells that, in most cases, are infected by Epstein-Barr virus (EBV), which may play a role in tumorigenesis. Given that EBV-latent membrane protein 1 (LMP1) regulates autophagy in B cells, we explored the role of autophagy mediated by EBV or LMP1 in HL. We found that EBV-LMP1 transfection in HL cells induced a modest increase in autophagy signals, attenuated starvation-induced autophagic stress, and alleviated autophagy inhibition- or doxorubicin-induced cell death. LMP1 knockdown leads to decreased autophagy LC3 signals. A xenograft mouse model further showed that EBV infection significantly increased expression of the autophagy marker LC3 in HL cells. Clinically, LC3 was expressed in 15% (19/127) of HL samples, but was absent in all cases of nodular lymphocyte-predominant and lymphocyte-rich classic HL cases. Although expression of LC3 was not correlated with EBV status or clinical outcome, autophagic blockade effectively eradicated LMP1-positive HL xenografts with better efficacy than LMP1-negative HL xenografts. Collectively, these results suggest that EBV-LMP1 enhances autophagy and promotes the viability of HL cells. Autophagic inhibition may be a potential therapeutic strategy for treating patients with HL, especially EBV-positive cases.     

Characterization of Hodgkin's lymphoma-like undifferentiated carcinoma of the nasopharyngeal type as a particular UCNT subtype mimicking Hodgkin's lymphoma

Undifferentiated carcinoma of the nasopharyngeal type (UCNT) that histologically mimics Hodgkin's lymphoma (HL) ("Hodgkin's lymphoma-like UCNT"--HL-like UCNT) is known as a diagnostic pitfall. Using immunohistochemistry, Western blot and cDNA array technology, we wanted to document its phenotypical and molecular characteristics. We report herein 5 cases of UCNT that morphologically mimic HL and 3 classical UCNT cases. We compared the expression profiles of a thousand selected genes in HL-like UCNT and in classical UCNT cases. No difference in the profile of EBV infection was noted between the HL-like UCNT and control cases. Significant differences were detected in the expression of genes involved in the matrix modelling, angiogenesis, apoptosis and regulation of the Th-2 interleukins. The eosinophil chemoattractant eotaxin was expressed in the stroma of HL-like UCNT, but not in the control cases. The eotaxin receptor CCR3 was expressed in both stromal and carcinoma cell populations of HL-like UCNT, this pattern being similar to the one observed in HL. These results show that UCNT morphologically resembling HL share also some specific phenotypical and molecular features with HL, and might deserve to be isolated as a particular UCNT subtype.     

Changing patterns in the frequency of Hodgkin lymphoma subtypes and Epstein-Barr virus association in Taiwan

Epstein–Barr virus (EBV) infection is a risk factor for Hodgkin lymphoma (HL). To test whether the frequency of HL subtypes and their association with EBV has shifted with rising socioeconomic status in Taiwan, we compared the pathological features and EBV status, detected by in situ hybridization, of HL diagnosed between 1996 and 2007 (99 cases) and 1982 and 1995 (74 cases). The male-to-female ratio was 121:52 (2.3:1) and the mean age at presentation was 41.5 years. The overall EBV positivity rate was 50% (86/173 cases). Comparing the distribution of HL cases diagnosed at two different time periods, we found an increased frequency of the nodular sclerosis (NS) subtype (53 vs 68%, P  = 0.045), a decreased frequency of the mixed cellularity subtype (35 vs 13%, P  < 0.001), a reduced male-to-female ratio (2.9:1 compared to 1.4:1) and mean age (42.4 vs 36.6 years) in the NS subtype, and a significant decrease in EBV positivity rates among the NS and lymphocyte-depletion subtypes (61 vs 39%, P  = 0.03). These data indicate shifts in the frequency of histological subtype and EBV association for HL in Taiwan over the last decade, with a trend closer to that seen in Western countries and Japan. ( Cancer Sci 2008; 99: 345–349)     

In vitro EBV-infected subline of KMH2, derived from Hodgkin lymphoma, expresses only EBNA-1, while CD40 ligand and IL-4 induce LMP-1 but not EBNA-2

In about 50% of classical Hodgkin lymphomas, the Hodgkin/Reed Sternberg (H/RS) cells carry Epstein-Barr virus (EBV). The viral gene expression in these cells is restricted to EBNA-1, EBERs, LMP-1 and LMP-2 (type II latency). The origin of H/RS cells was defined as crippled germinal center B cells that escaped apoptosis. In spite of numerous attempts, only few typical Hodgkin lymphoma (HL) lines have been established. This suggests that the cells require survival factors that they receive in the in vivo microenvironment. If EBV is expected to drive the cells for growth in culture, the absence of EBNA-2 may explain the incapacity of H/RS cells for in vitro proliferation. In EBV carrying B lymphocytes, functional EBNA-2 and LMP-1 proteins are required for in vitro growth. For analysis of the interaction between EBV and the H/RS cells, we infected the CD21-positive HL line KMH2 with the B958 and Akata viral strains. Only EBNA-1 expression was detected in a few cells in spite of the fact that all cells could be infected. Using a neomycin-resistance-tagged recombinant EBV strain (Akata-Neo) we established an EBV-positive subline that was carried on selective medium. In contrast to the type II EBV expression pattern of H/RS cells in vivo, the KMH2 EBV cells did not express LMP-1. The EBV expression pattern could be modified in this type I subline. LMP-1 could be induced by the histone deacetylase inhibitors TSA and n-butyrate, by 5-AzaC, a demethylating agent, and by phorbol ester. None of these treatments induced EBNA-2. Importantly, exposure to CD40 ligand and IL-4 induced LMP-1 without EBNA-2 expression and lytic replication. The KMH2 EBV cells expressed LMP-2A, but not LMP-2B mRNAs. This result is highly relevant for the type II expression pattern of H/RS cells in vivo, since these stimuli can be provided by the surrounding activated T lymphocytes.     

Racial/ethnic variation in EBV-positive classical Hodgkin lymphoma in California populations

Epstein-Barr virus (EBV) is detected in the tumor cells of some but not all Hodgkin lymphoma (HL) patients, and evidence indicates that EBV-positive and -negative HL are distinct entities. Racial/ethnic variation in EBV-positive HL in international comparisons suggests etiologic roles for environmental and genetic factors, but these studies used clinical series and evaluated EBV presence by differing protocols. Therefore, we evaluated EBV presence in the tumors of a large (n = 1,032), racially and sociodemographically diverse series of California incident classical HL cases with uniform pathology re-review and EBV detection methods. Tumor EBV-positivity was associated with Hispanic and Asian/Pacific Islander (API) but not black race/ethnicity, irrespective of demographic and clinical factors. Complex race-specific associations were observed between EBV-positive HL and age, sex, histology, stage, neighborhood socioeconomic status (SES), and birth place. In Hispanics, EBV-positive HL was associated not only with young and older age, male sex, and mixed cellularity histology, but also with foreign birth and lower SES in females, suggesting immune function responses to correlates of early childhood experience and later environmental exposures, respectively, as well as of pregnancy. For APIs, a lack of association with birth place may reflect the higher SES of API than Hispanic immigrants. In blacks, EBV-positive HL was associated with later-stage disease, consistent with racial/ethnic variation in certain cytokine polymorphisms. The racial/ethnic variation in our findings suggests that EBV-positive HL results from an intricate interplay of early- and later-life environmental, hormonal, and genetic factors leading to depressed immune function and poorly controlled EBV infection.     

Different histopathological subtypes of Hodgkin lymphoma show significantly different levels of FDG uptake

Positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) enables quantitative analysis of metabolic activity. This study investigated standardized uptake value (SUV) levels in the different histopathological subtypes of Hodgkin lymphoma (HL). Sixty patients with newly diagnosed HL underwent staging FDG-PET/CT after lymph node biopsy. Maximum SUV in each patient (SUV(max/total)) and in each affected region or organ (SUV(max)) were recorded. Mean SUV(max/total) was 9.3 g/ml in seven nodular lymphocyte predominance (NLP) patients, 16.3 g/ml in 38 nodular sclerosis (NS) patients, 20.8 g/ml in 11 mixed cellularity (MC) patients, and 19.5 g/ml in four patients with unclassified classical HL (CHL-NOS), (ANOVA, p = 0.011). Out of 780 sites (600 lymph node regions plus 180 organs), 208 sites were found to be affected with HL. Mean SUV(max) was 8.3 g/ml in the 12 sites with NLP, 11.2 g/ml in the 147 sites affected with NS, 14.6 g/ml in the 36 sites with MC, and 13.1 g/ml in the 13 sites with CHL-NOS (ANOVA, p = 0.002). There is a significant difference in FDG/glucose uptake between the different histopathological subtypes of HL.     

Hodgkin lymphoma in Pakistan: an analysis of subtypes and their correlation with Epstein Barr virus

The epidemiology of Hodgkin lymphoma (HL) shows a wide geographic variation with regard to age, gender, histological subtypes and their association with Epstein-Barr virus. The proportion of EBV positive cases appears higher in developing than in developed countries. EBV is a common infection in Pakistan due to poor socioeconomic conditions, but reports regarding HL subtypes have been rather selective. Our aims were to establish the relative frequencies of the five subtypes of Hodgkin lymphoma, to determine their associations with Epstein-Barr virus, and finally to establish whether such association follows patterns seen in developing or developed countries. Among 100 cases, the male: female ratio was 4.5:1, with an age range of 4-82 years and an average of 26.6 years. Similar to the subtype distribution in developing countries, mixed cellularity was the commonest 57%, followed by nodular sclerosis 35%, lymphocyte rich 6% and nodular lymphocyte predominant 2%. EBV-LMP1 staining was demonstrated in 41/57 (71%) of the mixed cellularity and the 19/35 (54.2%) of nodular sclerosis subtypes. All 6 cases of lymphocyte rich and 2 cases of nodular lymphocyte predominant were negative for EBV-LMP 1. Speculation about prognostic effects of EBV infection on the course of HL are tempting. Thus the EBV-positive HL could in the future prove to be an excellent candidate for targeted cellular immunotherapy.     

Infectious,autoimmune and allergic diseases and risk of Hodgkin lymphoma in children and adolescents: A Children's Oncology Group study

An infectious origin for pediatric Hodgkin lymphoma (HL) has long been suspected and Epstein‐Barr virus (EBV) has been implicated in a subset of cases. Increased HL incidence in children with congenital and acquired immunodeficiencies, consistent associations between autoimmune diseases and adult HL and genome‐wide association and other genetic studies together suggest immune dysregulation is involved in lymphomagenesis. Here, healthy control children identified by random digit dialing were matched on sex, race/ethnicity and age to HL diagnosed in 1989–2003 at 0–14 years at Children's Oncology Group institutions. Parents of 517 cases and 784 controls completed telephone interviews, including items regarding medical histories. Tumor EBV status was determined for 355 cases. Using conditional logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for risk of HL. Cases were more likely to have had an infection >1 year prior to HL diagnosis (OR = 1.69, 95% CI: 0.98–2.91); case siblings were also more likely to have had a prior infection (OR = 2.04, 95% CI: 1.01–4.14). Parental history of autoimmunity associated with increased EBV+ HL risk (OR = 2.97, 95% CI: 1.34–6.58), while having a parent (OR = 1.47, 95% CI: 1.01–2.14) or sibling (OR = 1.62, 95% CI: 1.11–2.36) with an allergy was associated with EBV ? HL. These results may indicate true increased risk for infections and increased risk with family history of autoimmune and allergic conditions that varies by tumor EBV status, or they may be attributable to inaccurate recall. In addition to employing biomarkers to confirm the role of immune‐modulating conditions in pediatric HL, future studies should focus on family based designs.     

Smoking and Hodgkin Lymphoma Risk in Women United States

OBJECTIVE: Smoking has received little consideration as a risk factor for Hodgkin lymphoma (HL) in women, despite recent significant findings in men and gender differences in HL incidence. We investigated the association of HL with lifetime cigarette smoking and household environmental tobacco smoke (ETS) exposure in women. METHODS: In data from a population-based case-control study in women ages 19-79, we analyzed HL risk associated with self-reported smoking and household ETS exposure in 312 diagnostically re-reviewed cases and 325 random-digit dialing controls using logistic regression. Epstein-Barr virus (EBV) presence was determined in tumors of 269 cases. RESULTS: In 253 cases compared to 254 controls ages 19-44, risks of HL overall, and of nodular sclerosis and EBV-negative HL, were increased 50% with ETS exposure in childhood; for 11 cases of mixed cellularity (MC) HL, current smoking and adult ETS exposure also increased risk; for 24 cases of EBV-positive HL, risk was elevated for current smoking, greater smoking intensity and duration, and ETS exposure. In 59 cases and 71 controls ages 45-79, most smoking characteristics did not appear to affect risk. CONCLUSIONS: Apparent effects of current smoking on risks of MC HL and EBV-positive HL and of household ETS on risk of all HL in young adult females may broaden the evidence implicating tobacco smoke exposures in HL etiology.     

Upregulation of CC chemokine ligand 18 and downregulation of CX3C chemokine receptor 1 expression in human T-cell leukemia virus type 1-associated lymph node lesions: Results of chemokine and chemokine receptor DNA chip analysis

Adult T-cell leukemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukemia virus type 1 (HTLV-1). The pathological features of the lymph nodes of ATLL change from those of lymphadenitis to Hodgkin's-like features and those of lymphoma. Chemokines and their receptors are closely associated with T-cell subgroups and immune responses. To clarify the relationship between chemokines and their receptor expression, as well as the development of ATLL, 17 cases with ATLL were analyzed using DNA chips of chemokines and their receptors. All cases showed a varied and mixed pattern of upregulated and downregulated gene expression of Th1, Th2 , naïve, and cytotoxic cell-associated chemokine genes. As CC chemokine ligand 18 (CCL18) accounted for the most upregulated gene and CX3C chemokine receptor 1 (CX3CR1) for the most downregulated gene, they were selected for immunohistochemical analysis. Immunohistochemical staining showed expression of the two genes in immunological cells, with a positive expression for reticulum cells, but not for ATLL cells. HTLV-1-associated lymphadenitis type ( n  = 13) and Hodgkin's-like type ( n  = 12) cases showed significantly higher CCL18 expression than the non-specific lymphadenitis cases ( n  = 10) ( P <  0.05). However, all HTLV-1-associated cases showed significantly lower CX3CR1 expression than the non-specific lymphadenitis cases ( P <  0.05). These results suggest that upregulation of CCL18 expression and downregulation of CX3CR1 expression play a role in immune responses against the ATLL cells. ( Cancer Sci 2007; 98: 1875–1880)     

儿童霍奇金淋巴瘤83例临床研究

目的 探讨儿童霍奇金淋巴瘤(HL)的病理及临床特点,初步分析患者EB病毒感染状态,总结根据危险度分层治疗即化疗联合低剂量受累野放疗的疗效及相关不良反应.方法 回顾性分析2003年1月至2013年3月接受规范化治疗的83例HL患儿的临床资料.全部行活组织检查病理形态及免疫组织化学检查,参照世界卫生组织(WHO)2001病理分型标准诊断,按HL Ann Arbor分期标准分期.根据不同的危险因素及对治疗的反应,将患儿分成低危、中危、高危3个治疗组.结果 83例患儿中,男性69例,女性14例;Ⅲ～Ⅳ期59例(71.1％).1例为结节性淋巴细胞为主型,其余82例均为经典型HL,其中64例(77.1％)为经典混合细胞型.侵犯部位广泛,巨大瘤块34例(41.0％),大于4个淋巴结区受累26例,有B组症状35例.70例行EB病毒感染指标[潜伏膜蛋白(LMP)和(或)EB病毒编码RNA(EBER)染色]检测,65例(92.9％)阳性.随访时间(72±32)个月.低危组3例,中危组27例,高危组53例.总体生存率97.5％,5年无事件生存率92.8％.结论 儿童HL男性多于女性,与EB病毒相关,病理以混合细胞型居多,预后相对较好.根据疾病危险度进行联合化疗及低剂量受累野放疗的近期疗效可靠,但随访时间尚短,需进一步观察远期不良反应.