75例儿童淋巴瘤临床病理分析及EB病毒感染、c-myc基因改变的相关性研究
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摘要
目的
依据WH02008淋巴造血组织肿瘤分类对儿童淋巴瘤的临床病理资料进行分析,探讨儿童淋巴瘤的临床病理特点及EB病毒感染、c-myc基因改变与儿童淋巴瘤发生的关系。
方法
收集中国医科大学附属盛京医院病理科1996年至2009年14年间共75例儿童淋巴瘤病例。重新检查HE切片,应用免疫组织化学染色SP法标记CD20、CD79a、CD3、CD45RO、Ki67、CD21、TDT、CD10、BCL6、MUM1、ALK、CD30、EMA和CD15,结合临床病理特征及免疫组织化学染色结果进一步分型；应用原位杂交技术对75例儿童淋巴瘤进行EB病毒的检测；对初步诊断为伯基特淋巴瘤和弥漫大B细胞淋巴瘤的病例进行c-myc基因荧光原位杂交检测。结果
75例儿童淋巴瘤中男性57例,女性18例,男女性别之比为3.17：1,发病平均年龄8.74岁。75例儿童淋巴瘤发病部位：结内32例(42.7%,32/75),结外43例(57.3%,43/75),结外部位依次包括：胃肠道22例(29.3%,22/75),纵隔3例(4.0%,3/75),胸腺2例(2.7%,2/75),睾丸2例(2.7%,2/75),扁桃体2例(2.7%,2/75),骨髓2例(2.7%,2/75),脑2例(2.7%,2/75),软组织2例(2.7%,2/75),横纹肌2例(2.7%,2/75),椎体1例(1.3%,1/75),肝脾1例(1.3%,1/75),皮肤1例(1.3%,1/75),盆壁1例(1.3%,1/75)。75例儿童淋巴瘤包括：霍奇金淋巴瘤13例(17.3%,13/75),淋巴母细胞淋巴瘤16例(21.3%,16/75),间变性大细胞淋巴瘤12例(16.0%,12/75),伯基特淋巴瘤和弥漫大B细胞淋巴瘤33例(44.0%,33/75),小淋巴细胞性淋巴瘤1例(1.3%,1/75)。儿童淋巴瘤EBV感染的检测：75例儿童淋巴瘤中有14例EBER阳性,阳性率18.7%(14/75)。13例HL中有11例CHL阳性,阳性率84.6%(11/13),33例伯基特淋巴瘤和弥漫大B细胞淋巴瘤中有3例为阳性,阳性率9.1%(3/33)。通过对初步诊断为伯基特淋巴瘤和弥漫大B细胞淋巴瘤病例进行荧光原位杂交检测进行进一步诊断,结果显示,该组28例中存在c-myc基因改变的有18例。
结论
儿童淋巴瘤男性多见,发病平均年龄8.74岁。发病部位以淋巴结和胃肠道多见。最常见的组织学类型依次是伯基特淋巴瘤、淋巴母细胞淋巴瘤、霍奇金淋巴瘤、间变性大细胞淋巴瘤和弥漫大B细胞淋巴瘤。EBV感染在儿童霍奇金淋巴瘤中检出率较高,说明霍奇金淋巴瘤与EBV感染有相关性；在儿童伯基特淋巴瘤和弥漫大B细胞淋巴瘤中也检出EBV感染,EBV可能是儿童伯基特淋巴瘤和弥漫大B细胞淋巴瘤发生中的伴随现象或诱发因素。
Objective
By this study we hope to analysis the clinicopathology of childhood lymphoma according with the tumours of haematopoietic and lymphoid tissues of World Health Organization Classification of Tumours(2008).We hope to analysis the clinicopathologic features of childhood lymphoma and relationship with EBV infection and the genetic change of c-myc gene in childhood lymphoma.
Methods
75 cases of childhood lymphoma were selected from the files of Pathology Department,Chinese Medical University Shengjing Hospital in period of 1996 to 2009.Pathologic diagnosis was according to the WHO classification for tumors of hematopoietic and lymphoid tissue(2008).Immunophenotype analysis was performed by SP method.Antibodies selected were included CD20, CD79a, CD3, CD45RO, Ki67,CD21,TDT,CD10,BCL6,MUM1,ALK,CD30,EMA and CD15.ISH were used for detection of EBER in all the cases. FISH were used for detection of the segregation of c-myc gene in BL tumor and DLBCL tumor.
Results
Clinicopathologic features:there were 57 cases of males and 18 cases of females in 75 cases of childhood lymphoma, the ration of sex was 3.17:1, the average age was 8.74 years old.There were 32 cases (42.7%,32/75) in lymph node,43 cases (57.3%,43/75) in extra-node,including 22 cases (29.3%,22/75) in gastrointestinal tract, 3 cases (4.0%,3/75) in mediastinum,2 cases (2.7%,2/75) in thymus gland,2 cases (2.7%,2/75) in testis,2 cases (2.7%,2/75) in tonsil,2 cases (2.7%,2/75) in bone marrow,2 cases (2.7%,2/75) in brain,2 cases (2.7%,2/75) in soft tissues,2 cases (2.7%,2/75) in striated muscle,1 case (1.3%,1/75) in basivertebral,1 case (1.3%,1/75) in liver and spleen,l case (1.3%,1/75) in skin,l case (1.3%,1/75) in pelvic wall. The most common subtypes were Hodgkin lymphomas (17.3%,13/75),Lymphoblastic lymphoma (21.3%,16/75),Anaplastic large cell lymphoma (16.0%,12/75),Burkitt lymphoma and Diffuse Large B-cell Lymphoma (44.0%,33/75), Small lymphocytic lymphoma (1.3%,1/75). The detection of EBV:There were 14 cases were positive (18.7%,14/75),including 11 cases of Hodgkin lymphomas (84.6%,11/13),3 cases of Burkitt lymphoma and Diffuse Large B-cell Lymphoma (9.1%,3/33).The genetic change of c-myc gene was executived by FISH in cases of BL tumor and DLBCL tumor.18 cases of BL tumor exists the c-myc gene segregation in 28 cases of Burkitt lymphoma and Diffuse large B-cell lymphoma.
Conclusions
The cases of male was more than those of female,the average age was 8.74 years old.There were more cases in lymph node and gastrointestinal tract.The most common subtypes were Burkitt lymphoma, Lymphoblastic lymphoma, Hodgkin lymphomas, Anaplastic large cell lymphoma and Diffuse Large B-cell Lymphoma. The positive rate on EBV of Hodgkin lymphomas is as high as in the literature,showed childhood Hodgkin lymphoma was significantly associated with EBV infection.The positive rate on EBV is lower in BL and DLBCL,showed in childhood BL and DLBCL EBV were only the concomitant phenomenon or only a predisposing factor.
依据WH02008淋巴造血组织肿瘤分类对儿童淋巴瘤的临床病理资料进行分析,探讨儿童淋巴瘤的临床病理特点及EB病毒感染、c-myc基因改变与儿童淋巴瘤发生的关系。
方法
收集中国医科大学附属盛京医院病理科1996年至2009年14年间共75例儿童淋巴瘤病例。重新检查HE切片,应用免疫组织化学染色SP法标记CD20、CD79a、CD3、CD45RO、Ki67、CD21、TDT、CD10、BCL6、MUM1、ALK、CD30、EMA和CD15,结合临床病理特征及免疫组织化学染色结果进一步分型；应用原位杂交技术对75例儿童淋巴瘤进行EB病毒的检测；对初步诊断为伯基特淋巴瘤和弥漫大B细胞淋巴瘤的病例进行c-myc基因荧光原位杂交检测。结果
75例儿童淋巴瘤中男性57例,女性18例,男女性别之比为3.17：1,发病平均年龄8.74岁。75例儿童淋巴瘤发病部位：结内32例(42.7%,32/75),结外43例(57.3%,43/75),结外部位依次包括：胃肠道22例(29.3%,22/75),纵隔3例(4.0%,3/75),胸腺2例(2.7%,2/75),睾丸2例(2.7%,2/75),扁桃体2例(2.7%,2/75),骨髓2例(2.7%,2/75),脑2例(2.7%,2/75),软组织2例(2.7%,2/75),横纹肌2例(2.7%,2/75),椎体1例(1.3%,1/75),肝脾1例(1.3%,1/75),皮肤1例(1.3%,1/75),盆壁1例(1.3%,1/75)。75例儿童淋巴瘤包括：霍奇金淋巴瘤13例(17.3%,13/75),淋巴母细胞淋巴瘤16例(21.3%,16/75),间变性大细胞淋巴瘤12例(16.0%,12/75),伯基特淋巴瘤和弥漫大B细胞淋巴瘤33例(44.0%,33/75),小淋巴细胞性淋巴瘤1例(1.3%,1/75)。儿童淋巴瘤EBV感染的检测：75例儿童淋巴瘤中有14例EBER阳性,阳性率18.7%(14/75)。13例HL中有11例CHL阳性,阳性率84.6%(11/13),33例伯基特淋巴瘤和弥漫大B细胞淋巴瘤中有3例为阳性,阳性率9.1%(3/33)。通过对初步诊断为伯基特淋巴瘤和弥漫大B细胞淋巴瘤病例进行荧光原位杂交检测进行进一步诊断,结果显示,该组28例中存在c-myc基因改变的有18例。
结论
儿童淋巴瘤男性多见,发病平均年龄8.74岁。发病部位以淋巴结和胃肠道多见。最常见的组织学类型依次是伯基特淋巴瘤、淋巴母细胞淋巴瘤、霍奇金淋巴瘤、间变性大细胞淋巴瘤和弥漫大B细胞淋巴瘤。EBV感染在儿童霍奇金淋巴瘤中检出率较高,说明霍奇金淋巴瘤与EBV感染有相关性；在儿童伯基特淋巴瘤和弥漫大B细胞淋巴瘤中也检出EBV感染,EBV可能是儿童伯基特淋巴瘤和弥漫大B细胞淋巴瘤发生中的伴随现象或诱发因素。
Objective
By this study we hope to analysis the clinicopathology of childhood lymphoma according with the tumours of haematopoietic and lymphoid tissues of World Health Organization Classification of Tumours(2008).We hope to analysis the clinicopathologic features of childhood lymphoma and relationship with EBV infection and the genetic change of c-myc gene in childhood lymphoma.
Methods
75 cases of childhood lymphoma were selected from the files of Pathology Department,Chinese Medical University Shengjing Hospital in period of 1996 to 2009.Pathologic diagnosis was according to the WHO classification for tumors of hematopoietic and lymphoid tissue(2008).Immunophenotype analysis was performed by SP method.Antibodies selected were included CD20, CD79a, CD3, CD45RO, Ki67,CD21,TDT,CD10,BCL6,MUM1,ALK,CD30,EMA and CD15.ISH were used for detection of EBER in all the cases. FISH were used for detection of the segregation of c-myc gene in BL tumor and DLBCL tumor.
Results
Clinicopathologic features:there were 57 cases of males and 18 cases of females in 75 cases of childhood lymphoma, the ration of sex was 3.17:1, the average age was 8.74 years old.There were 32 cases (42.7%,32/75) in lymph node,43 cases (57.3%,43/75) in extra-node,including 22 cases (29.3%,22/75) in gastrointestinal tract, 3 cases (4.0%,3/75) in mediastinum,2 cases (2.7%,2/75) in thymus gland,2 cases (2.7%,2/75) in testis,2 cases (2.7%,2/75) in tonsil,2 cases (2.7%,2/75) in bone marrow,2 cases (2.7%,2/75) in brain,2 cases (2.7%,2/75) in soft tissues,2 cases (2.7%,2/75) in striated muscle,1 case (1.3%,1/75) in basivertebral,1 case (1.3%,1/75) in liver and spleen,l case (1.3%,1/75) in skin,l case (1.3%,1/75) in pelvic wall. The most common subtypes were Hodgkin lymphomas (17.3%,13/75),Lymphoblastic lymphoma (21.3%,16/75),Anaplastic large cell lymphoma (16.0%,12/75),Burkitt lymphoma and Diffuse Large B-cell Lymphoma (44.0%,33/75), Small lymphocytic lymphoma (1.3%,1/75). The detection of EBV:There were 14 cases were positive (18.7%,14/75),including 11 cases of Hodgkin lymphomas (84.6%,11/13),3 cases of Burkitt lymphoma and Diffuse Large B-cell Lymphoma (9.1%,3/33).The genetic change of c-myc gene was executived by FISH in cases of BL tumor and DLBCL tumor.18 cases of BL tumor exists the c-myc gene segregation in 28 cases of Burkitt lymphoma and Diffuse large B-cell lymphoma.
Conclusions
The cases of male was more than those of female,the average age was 8.74 years old.There were more cases in lymph node and gastrointestinal tract.The most common subtypes were Burkitt lymphoma, Lymphoblastic lymphoma, Hodgkin lymphomas, Anaplastic large cell lymphoma and Diffuse Large B-cell Lymphoma. The positive rate on EBV of Hodgkin lymphomas is as high as in the literature,showed childhood Hodgkin lymphoma was significantly associated with EBV infection.The positive rate on EBV is lower in BL and DLBCL,showed in childhood BL and DLBCL EBV were only the concomitant phenomenon or only a predisposing factor.
引文
1 李冰.中国恶性肿瘤的死亡情况和分布特点.中华肿瘤学杂志.1980；2(1)：5-7.
2 Cho EY,Kim KH,Kim WS,et al.The spectrum of Epstein-Barr virus-associated lymphoproliferative disease in Korea:incidence of disease entities by age groups.J Korean Med Sci.2008;23(2):185-192.
3 Trimeche M, Bonnet C, Korbi S, et al. Association between Epstein-Barr virus and Hodgkin's lymphoma in Belgium:a pathological and virological study. Leuk Lymphoma.2007; 48(7): 1323-1331.
4 Hayday AC,gillies SD,Saito H,et al.Activation of translocated human c-myc gene by an enhancer in the immunoglobulin heavy-chain locus.Nature.1984;307:334-340.
5 Ar Rushdi A,Nishikura K,Erikson J,et al.Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma.Science.1983;222:390-393.
6 Jonathan L,Hecht,Jon C Aster.Molecular Biology of Burkitt's lymphoma.J Clin Oncol.2000; 18(21):3707-3721.
7 奚政君,张忠德,王燕,等.200例儿童恶性淋巴瘤临床病理分析.临床儿科杂志.2004；22(3)：161-163.
8 宪莹,徐酉华.儿童恶性淋巴瘤79例临床分析.重庆医科大学学报.2001；26(2)：204-205.
9 Al-Samawi AS,Aulaqi SM,AI-Thobhani AK.Childhood lymphomas in Yemen. Clinicopathological study.Saudi Med J.2009;30(9):1192-1196.
10 Hochberg J,Waxman IM,Kelly KM,et al.Adolescent non-Hodgkin lymphoma and Hodgkin lymphoma:state of the science.Br J Haematol.2009;144(1):24-40.
11 Maeda E,Akahane M,Kiryu S,Kato N,et al.Spectrum of Epstein-Barr virus-related diseases:a pictorial review.Jpn J Radiol.2009; 27(1):4-19.
12 Gottschalk S, Rooney CM, Heslop HE. Post-transplant lymphoproliferative disorders. Annu Rev Med.2005; 56:29-44.
13 Saito N,Courtois G,Chiba A,et al.Two Carboxyl-terminal activation regions of Epstein-Barr virus latentmembrane protein 1 activate NF-κB through distinct signaling pathways in fibroblast cell lines. J Biol Chem.2003;278(47):46565-46575.
14 Thompson MP,kurzrock R.Epstein-Barr virus and cancer.Clin Cancer Res.2004;10(3): 803-821.
15 Young LS,Rickinson AB.Epstein-Barr virus:40 years on.Nat Rev Cancer.2001;4(10):757-768.
16 王志伟,邓国华.EB病毒感染与淋巴瘤内科理论与实践.2007；2(4)：275-276.
17 藏素红,王莉,陈波,等.新疆维吾尔族霍奇金淋巴瘤与EB病毒感染的关系.临床与实验病理学杂志.2008；24(1)：80-82.
18 Keegan TH,Glaser SL,Clarke CA,et al.Epstein-barr virus as a marker of survival after Hodgkin's lymphoma:a population-based study.J Clin Oncol.2005;23(30):7604-7613.
19 李佩娟,周小鸽,刘姝荣,等.82例小儿何杰金淋巴瘤与EB病毒相关的研究.中华病理学杂志.1994；23：224-226.
20 Zhou XG, Sandvej K, Li PJ, et al.Epstein-Barr virus in Chinese pediatric Hodgkin disease: Hodgkin disease in young children is a distinct Epstein-Barr virus related lymphoma. Cancer. 2001;92:1621-1631.
21 谢正德,王琳,路娣.EB病毒感染与儿童淋巴瘤的相关性研究.中华肿瘤杂志.2008；30(5)：365-367.
22 Kim D,Ko Y,Suh Y,et al.Characteristics of Epstein-Barr virus associated childhood non-Hodgkin's lymphoma in the Republic of Korea.Virchows Arch.2005;447:593-596.
23 Chabay PA, De M EN,Aversa L,et al. Assessment of Epstein-Barr virus association with pediatric non-Hodgkin lymphoma in immunocompetent and in immunocompromised patients in Argentina.Arch Pathol Lab Med.2002;126(3):331-335.
24 Talkada k. Role of Epstein-Barr virus in Burkitt's lymphoma.Curr Topics Microbiol Immunol. 2001;258:141-151.
25 Patte C,Auperin A,Michon J,et al.The Societe Francaise d'Oncologie Pediatrique LMB89 protocol:highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphoma and L3 leukemia.Blood.2001; 97:3370-3379.
26 Mbulaiteye SM,Biggar RJ,Bhatia K,et al.Sporadic childhood Burkitt lymphoma incidence in the United States during 1992-2005.Pediatr Blood Cancer.2009; 53(3):366-370.
27 Banthia B,Jen A,Kacher A.Sporadic Burkitt's lymphoma of the head and neck in the pediatric population.Int J Pediatr Otorhinolaryngol.2003;67(l):59-65.
28 Ohnishi K.Clinicopathological characteristics of Burkitt lymphoma.Nippon Rinsho.2000; 58(3):635-638.
29 黄远洁,刘翠苓,宫丽平,等.散发性Burkitt淋巴瘤的病理学特点.白血病·淋巴瘤.2009；18(1)：18-20.
30 于亚平.儿童弥漫大B细胞淋巴瘤研究进展.实用儿科临床杂志.2009；24(15)：1197-1200.
31 周倩,张正祥,施红旗,等.散发性伯基特及伯基特样淋巴瘤临床病理分析.诊断学理论与实践.2008；7(6)：633-636.
32 Poirel HA,Cairo MS,Heerema NA,et al.Specific cytogenetic abnomalities are associated with a significantly inferior outcome in children and adolescemts with mature B-cell non-Hodgkin's lymphoma:Results of the FAB/LMB 96 intenational study.Leukemia.2009;23(2):323-331.
33 Karajannis MA,Hummel M,Oschlies I,et al.Epstein-Barr virus infection in Western European pediatric non-Hodgkin lymphomas.Blood.2003;102(12):4244.
34 Sevilla DW,Gong JZ,Goodman BK,et al.Clinicopathblogic findings in high-grade B-cell lymphomas with typical Burkitt morphologic features but lacking the MYC translocation.AM J Clin Pathol.2007; 128(6):981-991.
35 Haralambieva E,Boerma EJ,van imhoff GW,et al.Clinical,immunophenotypic,and genetic analysis of adult lymphomas with morphologic features of Burkitt lymphoma.Am J Surg Pathol.2005;29(8):1086-1094.
36 CHUANG SS,Ye H,Du MQ,et al.Histopathology and immunohistochemistry in distinguishing Burkitt lymphoma from diffuse large B-cell lymphoma with very high proliferation index and with or without starry-sky pattern:a comparative study with EBER and FISH.Am J Clin Pathol.2007; 128:558-564.
37 Lossos IS.Molecular pathogenesis of diffuse large B-cell lymphoma.J Clin Oncol.2005; 23: 6351-6357.
38 Gurbuxani S,Anastasi J,Hyjek E.Diffuse large B-cell lymphoma-more than a diffuse collection of large B cells:an entity in search of a meaningful classification.Arch Pathol Lab Med.2009;133(7):1121-1134.
39 Sunderl M,Kolman OK,Chen YB.B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements are aggressive neoplasms with clinical and pathologic features distinct from Burkitt lymphoma and diffuse large B-cell lymphoma.Am J Surg Pathol.2010;34(3):327-340.
40 Poirel HA,Cairo MS,Heerema NA,et al.Cytogenetics and fluorescence in situ hybridization studies of diffuse large B-cell lymphoma in children and young adults.Cancer Genet Cytogenet. 2004;153(2):115-121.
1 Head DR,Behm FG.Acute lymphoblastic leukemia and the lymphoblastic lymphomas of childhood.Semin Diagn Patho.1995;12:325-334.
2 Maitra A,Mckenna RW,Weinberg AG,et al.Precursor B-cell lymphoblastic lymphoma.A study of nine cases lacking blood and bone marrow involvement and review of the literature.Am J Clin Pathol.2001;115(6):868-875.
3 Goldsby RE,Carroll WL.The molecular biology of pediatric lymphomas.J Pediatr Hematol Oncol.1998;20:282-296.
4 Ma SK,Wan TS,Cheruk AT,et al.Characterization of additional genetic events in childhood acute lymphoblastic leukemia with TEL/AML1 gene fusion:a molecular cytogenetics studys. 2001; 15(9):1442-1447.
5 Rubnitx JE,Downing JR,Pui CH,et al.TEL gene rearrangement in acute lymphoblastic leukemia:a new genetic marker with prognostic significance.J Clin Oncol.1997;15:1150-1157.
6 Brown L,Cheng JT,Chen Q,et al.Site-specific recombination of the TAL-1 gene is a common ocurrence in human T cell leukemia.EMBO J.1990;9(10):3343-3351.
7 Carrol AJ,Crist WM,Link MP,et al.The t(1;14)(p34;q11) is nonrandom and restricted to T-cell acute lymphoblastic leukemia:a Pediatric Oncology Group study.Blood.1990;76:1220-1224.
8 Wan Zutven LJ,Velthuizen SC,Wolvers-Tettero IL,et al.Two dual-color split singal fluorescence in situ hybridization assays to detect t(5;14) involving HOX11L2 or CSX in T-cell acute lymphoblastic leukemia.Haemotologica.2004;89:671-678.
9 Hyjed E,Chadbum A,Liu YE,et al.BCL6 protein is expressed in precursor T-cell lymphoblastic lymphoma and in prenatal and postnatal thymus. Blood.2001;97(1):270-276.
10 Brune V,Tiacci E,Pfeil I,et al.Origin and pathogenesis of nodular lymphocyte predominant hodgkin lymphoma as revealed by global gene expression analysis.J Exp Med.2008; 205(10): 2251-2268.
11 Szymanowska N.Klapper W,Gesk S,et al.BCL2 and BCL3 are recurrent translocation parters of the IGH locus.Cancer Genet Cytogenet.2008;186(2):110-114.
12 Boerma EG,Van Imhoff GW,Appel IM,et al.Gender and age-related differences in burkitt lymphoma--epidemiological and clinical data from the Netherlands.Eur J Cancer.2004; 40(18): 2781-2787.
13 Cairo MS,Sposto R,Perkins SL,et al.Burkitt-like lymphoma in children and adolescents:a review of the children's Cancer Group experience.Br J haematol.2003;120(4):660-670.
14 Durant E,Diaz S,Greenaway s,et al.A novel cytogenetic abnormality in Burkitt lymphoma associated with treatment resistant disease.Clin Lab Haem.2005;27:328-330.
15 Chuang SS,Huang WT,Hsien PP,et al.Sporadic paediatric and adult Burkitt lymphomas share similar phenotypic and genotypic features. Histopathology.2008;52(4):427-435.
16 Ar Rushdi A,Nishikura K,Erikson J,et al.Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma.Science.1983;222:390-393.
17 Hayday AC,gillies SD,Saito H,et al.Activation of translocated human c-myc gene by an enhancer in the immunoglobulin heavy-chain locus. Nature.1984;307:334-340.
18 Jonathan L,Hecht,Jon C Aster.Molecular Biology of Burkitt's lymphoma.J Clin Oncol.2000; 18(21):3707-3721.
19 Boerma EG,Siebert R,Kluin PM,et al.Translocations involving 8q24 in Burkitt lymphoma and other malignant lymphomas:a historical review of cytogenetics in the ligth of today knowledge. Leukemia,2009;23(2):225-34.
20 Sandlund JT,Kastan MB,Kennedy W,et al.A subtle t(3;8) results in plamsible juxtaposition of myc and bcl6 in a child with burkitt lymphoma/leukemia and ataxia-telangiectasia.Cancer Genet Cytogenet.2006;168(1):69-72.
21 Moon Y,Kim M,Park G.Burkitt lymphoma with dual translocation of chromosome 14:a novel chromosomal abnormality of t(8;14) t(14;15).Ann Clin Lab Sci.2008;38(1):75-79.
22 Drexler HG,Gignac SM,Von Wasielewski R,et al.Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphoma. Leukemia.2000; 14(9): 1533-1559.
23 Shin HJ,Thorson P,Gu J,et al.Detection of subset of CD30+ anaplastic large cell lymphoma by interphase fluorescence in situ hybridization. Diagn Cytopathol.2003;29(2):61-66.
24 Gascoyne,Aoun P,Wu D,et al.Prognostic significance of anaplastic lymphoma kinase(ALK) protein expression in adults with anaplastic large cell lymphoma. Blood.1999; 93(11): 3913-3921.
25 Rimokh R,Maguad JP,Berger F,et al.A translocation involving a specific breakpoint (q35) on chromosome 5 is characteristic of anaplastic large cell lymphoma ("Ki-1 lymphoma").Br J Haematol.1989:71:31-36.
26 Kaneko Y,Frizzera G,Edamura S,et al.A novel translocation t(2;5)(p23;q35) in childhood phagocytic large T-cell lymphoma mimicking malignant histiocytosis.Blood.1989;73:806-813.
27 Morris SW,Kirstein MN,Valentine MB,et al.Fusion of a kinase gene,ALK,to a nucleolar protein gene,NPM,in non-hodgkin's lymphoma. Science.1997;263:1281-1284.
28 Stein H,Foss HD,Durkop H,et al.CD30+ anaplastic largecell lymphoma:a review of its histopathologic,genetic,and clinical features.Blood.2000;96(12):3681-3692
29 Amin HM,Lai R.Pathobiology of ALK+ anaplastic large cell lymphoma. Blood.2007; 110(7): 2259-2267.
30 Falini B,Pileri S,Zinzani PL,et al.ALK+ lymphoma:clinicopathological findings and outcome. Blood.1999;93:2697-2706.
31 Morris SW,Xue L,Ma Z,et al.ALK+ CD30+ lymphomas:a distinct molecular genetic subtype of non-Hodgkin's lymphoma.Br J Haematol.2001;113:275-295.
32 Chiarle R,Voena C,Ambrogio C,et al.The anaplastic lymphoma kinase in the pathogenesis of cancer.Nat Rev Cancer.2008;8(1):11-23.
33 Swerdlow SH,Campo E,Harris NL,et al.WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue. IARC,LYON 2008.
34 曹军宁.弥漫大B细胞淋巴瘤临床研究进展.中国肿瘤影像学.2009；2(3)：87-89.
35 Hochberg J,Waxnan M,Kelly KM,et al.Adolescent non-Hodgkin lymphoma and Hodgkin lymphoma:State of the science.Br J Haematol.2009;144(1):24-40.
36 于亚平.儿童弥漫大B细胞淋巴瘤研究进展.实用儿科临床杂志.2009；24(15)：1197-1200.
37 Hans CP,Weisenburger DD,Greiner TC,et al.Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004; 103(1):275-282.
38 schlies I,Klapper W,Zimmermann M,et al.Diffuse large B-cell lymphoma in pediatric patients belongs predominantly to the germinal-center type B-cell lymphomas:A clinicapathologic analysis of cases included in the German BFM (Berlin-Frankfurt-Munster) Multicenter Trial. Blood.2006;107(10):4047-4052.
39 Iqbal J.Neppalli VT,Wright G,et al.BCL2 expression is a prognostic marker for the activated B-cell-like type of diffuse large B-cell lymphoma.J Clin Oncol,2006;24(6):961-968.
40 Gurbuxani S,Anastasi J,Hyjek E.Diffuse large B-cell lymphoma-more than a diffuse collection of large B cells:an entity in search of a meaningful classification.Arch Pathol Lab Med.2009; 133(7):1121-1134.
41 李义,王国平,郗彦凤.弥漫大B细胞淋巴瘤3q27染色体状态和不同亚型与预后的关系.中华病理学杂志.2009；38(4)：231-236.
42 Poirel HA,Cairo MS,Heerema NA,et al.Cytogenetics and fluorescence in situ hybridization studies of diffuse large B-cell lymphoma in children and young adults.Cancer Genet Cytogenet. 2004; 153(2):115-121.
43 Poirel HA.Cairo MS,Heerema NA,et al.Specific cytogenetic abnormalities are associated with mature B-cell non-Hodgkin's lymphoma:Results of the FAB/LMB 96 international study. Leukemia.2009;23(2):323-331.
44 Kuppers R.The biology of Hodgkin's lymphoma.Nat Rev Cancer.2009;9(1):15-27.
45 Anagnostopoulos I, Hansmann ML, Franssila K, et al.European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease:histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes.Blood.2000;96(5):1889-1899.
46 Chang KC,Khen NT,Jones D,et al. Epstein-Barr virus is associated with all histological subtypes of Hodgkin lymphoma in Vietnamese children with special emphasis on the entity of lymphocyte predominance subtype.Hum Pathol.2005;36(7):747-755.
47 Dolcetti R,Boiocchi M,Gloghini A,et al.Pthogenetic and histogenetic features of HIV-associated Hodgkin's disease.Eur J Cancer.2001;37(10):1276-1287.
48 Kutok JL,Wang F.Spectrum of Epstein-Barr Virus-associated diseases. Annu. Rev. Pathol. 2006; 1:375-404.
49 KR, Birgersdotter A, Reynolds GM, Wei W, et al. Expression of the Epstein-Barr virus-encoded Epstein-Barr virus nuclear antigen 1 in Hodgkin's lymphoma cells mediates Up-regulation of CCL20 and the migration of regulatory T cells.Am J Pathol.2008; 173(1): 195-204.
50 Flavell JR, Baumforth KR, Wood VH, et al. Down-regulation of the TGF-beta target gene, PTPRK, by the Epstein-Barr virus encoded EBNA1 contributes to the growth and survival of Hodgkin lymphoma cells.Blood.2008;111(1):292-301.
51 Kulwichit W,Edwards RH,Davenport EM,et al.Expression of the Epstein-Barr virus latent membrane protein 1 induces B cell lymphoma in transgenic mice.Proc Natl Acad Sci USA.1998;95(20):11963-11968.
52 Kilger E, Kieser A, Baumann M, Hammerschmidt W,et al.Epstein-barr virus-mediated B-cell proliferation is dependent upon latent membrance protein 1,which simulates an activated CD40 receptor.EMBO J.1998; 17(6):1700-1709.
53 Young LS,Murray PG.Epstein-Barr virus and oncogenesis:from latent genes to tumours. Oncogene.2003;22(33):5108-5121.
54 Alber G,Kim KM.Molecular mimicry of the antigen receptor signalling motif by transmembrane proteins of the Epstein-Barr virus and the bovine Leukaemia virus.Curr Biol. 1993;3(6):333-339.
55 Caldwell RG.Wilson JB,Anderson SJ,et al.Epstein-barr virus LMP2A drives B cell development and survival in the absence of normal Bcell receptor signals. Immunity.1998; 9(3):405-411.
56 Keeqan TH,Glaser SL,Clarke CA,et al.Epstein-Barr virus a marker of survival after Hodgkin's lymphoma:a population-based study.J Clin Oncol.2005; 23(30):7604-7613.
57 Thorley Lawson DA,Allday MJ.The curious case of the tumour virus:50 years of Burkitt's lymphoma.Nat Rev Microbiol.2008;6(2):913-924.
58 Bellan C,Lazzi S,Falco DG,et al.Burkitt's lymphoma:new sights into molecular pathogenesis.J Clin Pathol.2003;56:188-193.
59 Lindahl T,Adams A,Bjursell G,et al.Covalently closed circular duplex DNA of Epstein-Barr virus in human lymphoid cell line.J Mol Biol.1976; 102(3):511-530.
60 de-The G,Geser A,Day NE,et al.Epidemiological evidence for causal relationship between Epstein-Barr virus and Brukitt's lymphoma from Ugandan Prospective study. Nature.1978; 274(5673):756-761.
2 Cho EY,Kim KH,Kim WS,et al.The spectrum of Epstein-Barr virus-associated lymphoproliferative disease in Korea:incidence of disease entities by age groups.J Korean Med Sci.2008;23(2):185-192.
3 Trimeche M, Bonnet C, Korbi S, et al. Association between Epstein-Barr virus and Hodgkin's lymphoma in Belgium:a pathological and virological study. Leuk Lymphoma.2007; 48(7): 1323-1331.
4 Hayday AC,gillies SD,Saito H,et al.Activation of translocated human c-myc gene by an enhancer in the immunoglobulin heavy-chain locus.Nature.1984;307:334-340.
5 Ar Rushdi A,Nishikura K,Erikson J,et al.Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma.Science.1983;222:390-393.
6 Jonathan L,Hecht,Jon C Aster.Molecular Biology of Burkitt's lymphoma.J Clin Oncol.2000; 18(21):3707-3721.
7 奚政君,张忠德,王燕,等.200例儿童恶性淋巴瘤临床病理分析.临床儿科杂志.2004；22(3)：161-163.
8 宪莹,徐酉华.儿童恶性淋巴瘤79例临床分析.重庆医科大学学报.2001；26(2)：204-205.
9 Al-Samawi AS,Aulaqi SM,AI-Thobhani AK.Childhood lymphomas in Yemen. Clinicopathological study.Saudi Med J.2009;30(9):1192-1196.
10 Hochberg J,Waxman IM,Kelly KM,et al.Adolescent non-Hodgkin lymphoma and Hodgkin lymphoma:state of the science.Br J Haematol.2009;144(1):24-40.
11 Maeda E,Akahane M,Kiryu S,Kato N,et al.Spectrum of Epstein-Barr virus-related diseases:a pictorial review.Jpn J Radiol.2009; 27(1):4-19.
12 Gottschalk S, Rooney CM, Heslop HE. Post-transplant lymphoproliferative disorders. Annu Rev Med.2005; 56:29-44.
13 Saito N,Courtois G,Chiba A,et al.Two Carboxyl-terminal activation regions of Epstein-Barr virus latentmembrane protein 1 activate NF-κB through distinct signaling pathways in fibroblast cell lines. J Biol Chem.2003;278(47):46565-46575.
14 Thompson MP,kurzrock R.Epstein-Barr virus and cancer.Clin Cancer Res.2004;10(3): 803-821.
15 Young LS,Rickinson AB.Epstein-Barr virus:40 years on.Nat Rev Cancer.2001;4(10):757-768.
16 王志伟,邓国华.EB病毒感染与淋巴瘤内科理论与实践.2007；2(4)：275-276.
17 藏素红,王莉,陈波,等.新疆维吾尔族霍奇金淋巴瘤与EB病毒感染的关系.临床与实验病理学杂志.2008；24(1)：80-82.
18 Keegan TH,Glaser SL,Clarke CA,et al.Epstein-barr virus as a marker of survival after Hodgkin's lymphoma:a population-based study.J Clin Oncol.2005;23(30):7604-7613.
19 李佩娟,周小鸽,刘姝荣,等.82例小儿何杰金淋巴瘤与EB病毒相关的研究.中华病理学杂志.1994；23：224-226.
20 Zhou XG, Sandvej K, Li PJ, et al.Epstein-Barr virus in Chinese pediatric Hodgkin disease: Hodgkin disease in young children is a distinct Epstein-Barr virus related lymphoma. Cancer. 2001;92:1621-1631.
21 谢正德,王琳,路娣.EB病毒感染与儿童淋巴瘤的相关性研究.中华肿瘤杂志.2008；30(5)：365-367.
22 Kim D,Ko Y,Suh Y,et al.Characteristics of Epstein-Barr virus associated childhood non-Hodgkin's lymphoma in the Republic of Korea.Virchows Arch.2005;447:593-596.
23 Chabay PA, De M EN,Aversa L,et al. Assessment of Epstein-Barr virus association with pediatric non-Hodgkin lymphoma in immunocompetent and in immunocompromised patients in Argentina.Arch Pathol Lab Med.2002;126(3):331-335.
24 Talkada k. Role of Epstein-Barr virus in Burkitt's lymphoma.Curr Topics Microbiol Immunol. 2001;258:141-151.
25 Patte C,Auperin A,Michon J,et al.The Societe Francaise d'Oncologie Pediatrique LMB89 protocol:highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphoma and L3 leukemia.Blood.2001; 97:3370-3379.
26 Mbulaiteye SM,Biggar RJ,Bhatia K,et al.Sporadic childhood Burkitt lymphoma incidence in the United States during 1992-2005.Pediatr Blood Cancer.2009; 53(3):366-370.
27 Banthia B,Jen A,Kacher A.Sporadic Burkitt's lymphoma of the head and neck in the pediatric population.Int J Pediatr Otorhinolaryngol.2003;67(l):59-65.
28 Ohnishi K.Clinicopathological characteristics of Burkitt lymphoma.Nippon Rinsho.2000; 58(3):635-638.
29 黄远洁,刘翠苓,宫丽平,等.散发性Burkitt淋巴瘤的病理学特点.白血病·淋巴瘤.2009；18(1)：18-20.
30 于亚平.儿童弥漫大B细胞淋巴瘤研究进展.实用儿科临床杂志.2009；24(15)：1197-1200.
31 周倩,张正祥,施红旗,等.散发性伯基特及伯基特样淋巴瘤临床病理分析.诊断学理论与实践.2008；7(6)：633-636.
32 Poirel HA,Cairo MS,Heerema NA,et al.Specific cytogenetic abnomalities are associated with a significantly inferior outcome in children and adolescemts with mature B-cell non-Hodgkin's lymphoma:Results of the FAB/LMB 96 intenational study.Leukemia.2009;23(2):323-331.
33 Karajannis MA,Hummel M,Oschlies I,et al.Epstein-Barr virus infection in Western European pediatric non-Hodgkin lymphomas.Blood.2003;102(12):4244.
34 Sevilla DW,Gong JZ,Goodman BK,et al.Clinicopathblogic findings in high-grade B-cell lymphomas with typical Burkitt morphologic features but lacking the MYC translocation.AM J Clin Pathol.2007; 128(6):981-991.
35 Haralambieva E,Boerma EJ,van imhoff GW,et al.Clinical,immunophenotypic,and genetic analysis of adult lymphomas with morphologic features of Burkitt lymphoma.Am J Surg Pathol.2005;29(8):1086-1094.
36 CHUANG SS,Ye H,Du MQ,et al.Histopathology and immunohistochemistry in distinguishing Burkitt lymphoma from diffuse large B-cell lymphoma with very high proliferation index and with or without starry-sky pattern:a comparative study with EBER and FISH.Am J Clin Pathol.2007; 128:558-564.
37 Lossos IS.Molecular pathogenesis of diffuse large B-cell lymphoma.J Clin Oncol.2005; 23: 6351-6357.
38 Gurbuxani S,Anastasi J,Hyjek E.Diffuse large B-cell lymphoma-more than a diffuse collection of large B cells:an entity in search of a meaningful classification.Arch Pathol Lab Med.2009;133(7):1121-1134.
39 Sunderl M,Kolman OK,Chen YB.B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements are aggressive neoplasms with clinical and pathologic features distinct from Burkitt lymphoma and diffuse large B-cell lymphoma.Am J Surg Pathol.2010;34(3):327-340.
40 Poirel HA,Cairo MS,Heerema NA,et al.Cytogenetics and fluorescence in situ hybridization studies of diffuse large B-cell lymphoma in children and young adults.Cancer Genet Cytogenet. 2004;153(2):115-121.
1 Head DR,Behm FG.Acute lymphoblastic leukemia and the lymphoblastic lymphomas of childhood.Semin Diagn Patho.1995;12:325-334.
2 Maitra A,Mckenna RW,Weinberg AG,et al.Precursor B-cell lymphoblastic lymphoma.A study of nine cases lacking blood and bone marrow involvement and review of the literature.Am J Clin Pathol.2001;115(6):868-875.
3 Goldsby RE,Carroll WL.The molecular biology of pediatric lymphomas.J Pediatr Hematol Oncol.1998;20:282-296.
4 Ma SK,Wan TS,Cheruk AT,et al.Characterization of additional genetic events in childhood acute lymphoblastic leukemia with TEL/AML1 gene fusion:a molecular cytogenetics studys. 2001; 15(9):1442-1447.
5 Rubnitx JE,Downing JR,Pui CH,et al.TEL gene rearrangement in acute lymphoblastic leukemia:a new genetic marker with prognostic significance.J Clin Oncol.1997;15:1150-1157.
6 Brown L,Cheng JT,Chen Q,et al.Site-specific recombination of the TAL-1 gene is a common ocurrence in human T cell leukemia.EMBO J.1990;9(10):3343-3351.
7 Carrol AJ,Crist WM,Link MP,et al.The t(1;14)(p34;q11) is nonrandom and restricted to T-cell acute lymphoblastic leukemia:a Pediatric Oncology Group study.Blood.1990;76:1220-1224.
8 Wan Zutven LJ,Velthuizen SC,Wolvers-Tettero IL,et al.Two dual-color split singal fluorescence in situ hybridization assays to detect t(5;14) involving HOX11L2 or CSX in T-cell acute lymphoblastic leukemia.Haemotologica.2004;89:671-678.
9 Hyjed E,Chadbum A,Liu YE,et al.BCL6 protein is expressed in precursor T-cell lymphoblastic lymphoma and in prenatal and postnatal thymus. Blood.2001;97(1):270-276.
10 Brune V,Tiacci E,Pfeil I,et al.Origin and pathogenesis of nodular lymphocyte predominant hodgkin lymphoma as revealed by global gene expression analysis.J Exp Med.2008; 205(10): 2251-2268.
11 Szymanowska N.Klapper W,Gesk S,et al.BCL2 and BCL3 are recurrent translocation parters of the IGH locus.Cancer Genet Cytogenet.2008;186(2):110-114.
12 Boerma EG,Van Imhoff GW,Appel IM,et al.Gender and age-related differences in burkitt lymphoma--epidemiological and clinical data from the Netherlands.Eur J Cancer.2004; 40(18): 2781-2787.
13 Cairo MS,Sposto R,Perkins SL,et al.Burkitt-like lymphoma in children and adolescents:a review of the children's Cancer Group experience.Br J haematol.2003;120(4):660-670.
14 Durant E,Diaz S,Greenaway s,et al.A novel cytogenetic abnormality in Burkitt lymphoma associated with treatment resistant disease.Clin Lab Haem.2005;27:328-330.
15 Chuang SS,Huang WT,Hsien PP,et al.Sporadic paediatric and adult Burkitt lymphomas share similar phenotypic and genotypic features. Histopathology.2008;52(4):427-435.
16 Ar Rushdi A,Nishikura K,Erikson J,et al.Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma.Science.1983;222:390-393.
17 Hayday AC,gillies SD,Saito H,et al.Activation of translocated human c-myc gene by an enhancer in the immunoglobulin heavy-chain locus. Nature.1984;307:334-340.
18 Jonathan L,Hecht,Jon C Aster.Molecular Biology of Burkitt's lymphoma.J Clin Oncol.2000; 18(21):3707-3721.
19 Boerma EG,Siebert R,Kluin PM,et al.Translocations involving 8q24 in Burkitt lymphoma and other malignant lymphomas:a historical review of cytogenetics in the ligth of today knowledge. Leukemia,2009;23(2):225-34.
20 Sandlund JT,Kastan MB,Kennedy W,et al.A subtle t(3;8) results in plamsible juxtaposition of myc and bcl6 in a child with burkitt lymphoma/leukemia and ataxia-telangiectasia.Cancer Genet Cytogenet.2006;168(1):69-72.
21 Moon Y,Kim M,Park G.Burkitt lymphoma with dual translocation of chromosome 14:a novel chromosomal abnormality of t(8;14) t(14;15).Ann Clin Lab Sci.2008;38(1):75-79.
22 Drexler HG,Gignac SM,Von Wasielewski R,et al.Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphoma. Leukemia.2000; 14(9): 1533-1559.
23 Shin HJ,Thorson P,Gu J,et al.Detection of subset of CD30+ anaplastic large cell lymphoma by interphase fluorescence in situ hybridization. Diagn Cytopathol.2003;29(2):61-66.
24 Gascoyne,Aoun P,Wu D,et al.Prognostic significance of anaplastic lymphoma kinase(ALK) protein expression in adults with anaplastic large cell lymphoma. Blood.1999; 93(11): 3913-3921.
25 Rimokh R,Maguad JP,Berger F,et al.A translocation involving a specific breakpoint (q35) on chromosome 5 is characteristic of anaplastic large cell lymphoma ("Ki-1 lymphoma").Br J Haematol.1989:71:31-36.
26 Kaneko Y,Frizzera G,Edamura S,et al.A novel translocation t(2;5)(p23;q35) in childhood phagocytic large T-cell lymphoma mimicking malignant histiocytosis.Blood.1989;73:806-813.
27 Morris SW,Kirstein MN,Valentine MB,et al.Fusion of a kinase gene,ALK,to a nucleolar protein gene,NPM,in non-hodgkin's lymphoma. Science.1997;263:1281-1284.
28 Stein H,Foss HD,Durkop H,et al.CD30+ anaplastic largecell lymphoma:a review of its histopathologic,genetic,and clinical features.Blood.2000;96(12):3681-3692
29 Amin HM,Lai R.Pathobiology of ALK+ anaplastic large cell lymphoma. Blood.2007; 110(7): 2259-2267.
30 Falini B,Pileri S,Zinzani PL,et al.ALK+ lymphoma:clinicopathological findings and outcome. Blood.1999;93:2697-2706.
31 Morris SW,Xue L,Ma Z,et al.ALK+ CD30+ lymphomas:a distinct molecular genetic subtype of non-Hodgkin's lymphoma.Br J Haematol.2001;113:275-295.
32 Chiarle R,Voena C,Ambrogio C,et al.The anaplastic lymphoma kinase in the pathogenesis of cancer.Nat Rev Cancer.2008;8(1):11-23.
33 Swerdlow SH,Campo E,Harris NL,et al.WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue. IARC,LYON 2008.
34 曹军宁.弥漫大B细胞淋巴瘤临床研究进展.中国肿瘤影像学.2009；2(3)：87-89.
35 Hochberg J,Waxnan M,Kelly KM,et al.Adolescent non-Hodgkin lymphoma and Hodgkin lymphoma:State of the science.Br J Haematol.2009;144(1):24-40.
36 于亚平.儿童弥漫大B细胞淋巴瘤研究进展.实用儿科临床杂志.2009；24(15)：1197-1200.
37 Hans CP,Weisenburger DD,Greiner TC,et al.Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004; 103(1):275-282.
38 schlies I,Klapper W,Zimmermann M,et al.Diffuse large B-cell lymphoma in pediatric patients belongs predominantly to the germinal-center type B-cell lymphomas:A clinicapathologic analysis of cases included in the German BFM (Berlin-Frankfurt-Munster) Multicenter Trial. Blood.2006;107(10):4047-4052.
39 Iqbal J.Neppalli VT,Wright G,et al.BCL2 expression is a prognostic marker for the activated B-cell-like type of diffuse large B-cell lymphoma.J Clin Oncol,2006;24(6):961-968.
40 Gurbuxani S,Anastasi J,Hyjek E.Diffuse large B-cell lymphoma-more than a diffuse collection of large B cells:an entity in search of a meaningful classification.Arch Pathol Lab Med.2009; 133(7):1121-1134.
41 李义,王国平,郗彦凤.弥漫大B细胞淋巴瘤3q27染色体状态和不同亚型与预后的关系.中华病理学杂志.2009；38(4)：231-236.
42 Poirel HA,Cairo MS,Heerema NA,et al.Cytogenetics and fluorescence in situ hybridization studies of diffuse large B-cell lymphoma in children and young adults.Cancer Genet Cytogenet. 2004; 153(2):115-121.
43 Poirel HA.Cairo MS,Heerema NA,et al.Specific cytogenetic abnormalities are associated with mature B-cell non-Hodgkin's lymphoma:Results of the FAB/LMB 96 international study. Leukemia.2009;23(2):323-331.
44 Kuppers R.The biology of Hodgkin's lymphoma.Nat Rev Cancer.2009;9(1):15-27.
45 Anagnostopoulos I, Hansmann ML, Franssila K, et al.European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease:histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes.Blood.2000;96(5):1889-1899.
46 Chang KC,Khen NT,Jones D,et al. Epstein-Barr virus is associated with all histological subtypes of Hodgkin lymphoma in Vietnamese children with special emphasis on the entity of lymphocyte predominance subtype.Hum Pathol.2005;36(7):747-755.
47 Dolcetti R,Boiocchi M,Gloghini A,et al.Pthogenetic and histogenetic features of HIV-associated Hodgkin's disease.Eur J Cancer.2001;37(10):1276-1287.
48 Kutok JL,Wang F.Spectrum of Epstein-Barr Virus-associated diseases. Annu. Rev. Pathol. 2006; 1:375-404.
49 KR, Birgersdotter A, Reynolds GM, Wei W, et al. Expression of the Epstein-Barr virus-encoded Epstein-Barr virus nuclear antigen 1 in Hodgkin's lymphoma cells mediates Up-regulation of CCL20 and the migration of regulatory T cells.Am J Pathol.2008; 173(1): 195-204.
50 Flavell JR, Baumforth KR, Wood VH, et al. Down-regulation of the TGF-beta target gene, PTPRK, by the Epstein-Barr virus encoded EBNA1 contributes to the growth and survival of Hodgkin lymphoma cells.Blood.2008;111(1):292-301.
51 Kulwichit W,Edwards RH,Davenport EM,et al.Expression of the Epstein-Barr virus latent membrane protein 1 induces B cell lymphoma in transgenic mice.Proc Natl Acad Sci USA.1998;95(20):11963-11968.
52 Kilger E, Kieser A, Baumann M, Hammerschmidt W,et al.Epstein-barr virus-mediated B-cell proliferation is dependent upon latent membrance protein 1,which simulates an activated CD40 receptor.EMBO J.1998; 17(6):1700-1709.
53 Young LS,Murray PG.Epstein-Barr virus and oncogenesis:from latent genes to tumours. Oncogene.2003;22(33):5108-5121.
54 Alber G,Kim KM.Molecular mimicry of the antigen receptor signalling motif by transmembrane proteins of the Epstein-Barr virus and the bovine Leukaemia virus.Curr Biol. 1993;3(6):333-339.
55 Caldwell RG.Wilson JB,Anderson SJ,et al.Epstein-barr virus LMP2A drives B cell development and survival in the absence of normal Bcell receptor signals. Immunity.1998; 9(3):405-411.
56 Keeqan TH,Glaser SL,Clarke CA,et al.Epstein-Barr virus a marker of survival after Hodgkin's lymphoma:a population-based study.J Clin Oncol.2005; 23(30):7604-7613.
57 Thorley Lawson DA,Allday MJ.The curious case of the tumour virus:50 years of Burkitt's lymphoma.Nat Rev Microbiol.2008;6(2):913-924.
58 Bellan C,Lazzi S,Falco DG,et al.Burkitt's lymphoma:new sights into molecular pathogenesis.J Clin Pathol.2003;56:188-193.
59 Lindahl T,Adams A,Bjursell G,et al.Covalently closed circular duplex DNA of Epstein-Barr virus in human lymphoid cell line.J Mol Biol.1976; 102(3):511-530.
60 de-The G,Geser A,Day NE,et al.Epidemiological evidence for causal relationship between Epstein-Barr virus and Brukitt's lymphoma from Ugandan Prospective study. Nature.1978; 274(5673):756-761.