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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

The Clinicopathology of 75 Cases of Childhood Lymphoma and the Relation among Epstein-Barr Virus Infection and the C-myc Gene Abnormality

【作者】 辛小川

【导师】 杨向红;

【作者基本信息】 中国医科大学 , 病理学与病理生理学, 2010, 硕士

【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。

【Abstract】 ObjectiveBy 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.Methods75 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.ResultsClinicopathologic 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.ConclusionsThe 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.

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