儿童非霍奇金氏淋巴瘤（non-Hodgkin's lymphoma，NHL）是高度恶性、侵袭性强的恶性肿瘤。

非霍奇金淋巴瘤占儿童恶性淋巴瘤的60%以上。最常好发10岁以上青少年，诊断时中位年龄大约10岁，3岁以下罕见。随着年龄增长，发生率逐渐增高。

根据WHO 2008淋巴瘤分类标准：儿童青少年NHL的主要病理类型为前驱B和前驱T淋巴母细胞淋巴瘤、伯基特淋巴瘤、弥漫大B细胞淋巴瘤和间变性大细胞淋巴瘤。几乎都是高度恶性侵袭性的淋巴瘤。

本文主要介绍儿童非霍奇金淋巴瘤的实验室检查及预后评估。

一、实验室检查

1.血常规

早期NHL外周血象正常。晚期患者可有贫血。晚期淋巴母细胞淋巴瘤或伯基特淋巴瘤如侵犯骨髓可伴有外周血白细胞升高，贫血、血小板下降等白血病血象。间变大细胞淋巴瘤可伴有外周血白细胞数增高，以中性粒细胞为主，类似类白血病反应血象。晚期和进展期间变大细胞淋巴瘤可伴有血小板下降。

2.生化常规

血乳酸脱氢酶（LDH）升高提示肿瘤负荷大。骨和肝脏受侵犯常伴有碱性磷酸酶升高。晚期伯基特淋巴瘤常伴有肿瘤自发溶解综合征，水、电解质紊乱，肾功能受损。尿酸升高、肌酐和尿素氮升高、高钾、高磷和低钙。

3.骨髓检查

所有NHL患者均有可能侵犯骨髓。淋巴母细胞淋巴瘤和伯基特淋巴瘤最常伴有骨髓侵犯。骨髓流式细胞术检测有助于区别白血病和淋巴瘤。淋巴母细胞淋巴瘤骨髓形态学和流式细胞术检测与急性淋巴细胞白血病相似，而其他类型淋巴瘤属于淋巴细胞发育后期的肿瘤，流式细胞术进行免疫分型可以与急淋白血病相鉴别。NHL骨髓侵犯可为局灶性侵犯，多部位取材和行骨髓活检有助于骨髓侵犯的诊断。

4.影像学检查

所有NHL患者治疗前需要进行全身CT检查，明确肿瘤侵犯范围。全身氟脱氧葡萄糖正电子发射断层扫描（fluorodeoxyglucose PDG-PET），有助于更准确分期和治疗后残留病灶鉴别，PDG-PET扫描在淋巴瘤敏感性为71%～96%，结合CT扫描更有助于进一步提高其确诊率。

二、鉴别诊断

浅表淋巴结肿大应与淋巴结其他疾病相鉴别：如：结核性淋巴结炎、慢性淋巴结炎、传染性单核细胞增多症、白血病和转移癌等鉴别。凡直径＞1cm的淋巴结肿大且观察6周以上仍不消退。均应活检明确诊断。

纵隔、肺门和后腹膜淋巴结肿大，需要与结核、胸部肿瘤（胸腺癌、纵隔生殖细胞瘤等）和腹膜后肿瘤（生殖细胞瘤、横纹肌肉瘤、神经母细胞瘤和肾母细胞瘤等）鉴别。必要时行肿块穿刺明确病理诊断。

对于常规治疗无效的淋巴结肿大或肿块结节或发热原因不明的患者，需要详细全身检查包括胸腹部的影像学检查，对肿大的淋巴结或包块结节行活检病理检查是最重要的鉴别诊断手段。

三、临床分期

儿童NHL临床分期不采用Ann Arbor分期系统。目前广泛接受的是St Jude Children's Research Hospital Staging System。即：Murphy Staging。此分期系统将原发部位和肿瘤侵犯范围结合起来共同考虑（表1）。

表1 St Jude Children's Research Hospital Staging System（Murphy Staging）

注：（1）骨髓侵犯定义　骨髓有5%的恶性肿瘤细胞伴外周血细胞计数和血涂片正常。淋巴母细胞淋巴瘤骨髓恶性细胞＞25%定义为白血病。
（2）此分期系统目前广泛用于儿童NHL分期，但是在临床实践中仍发现有不足之处。特别对于肝脏、肺、多发骨、肾脏和皮肤侵犯难以根据此分期系统进行分期。中山大学肿瘤防治中心则参照An Arbor分期系统，将弥漫性或播散性结外侵犯，即：骨髓、中枢、肝脏、肺、多发骨、肾脏和皮肤等器官侵犯定义为Ⅳ期。

四、疗效评估

基本上同成人淋巴瘤。

五、预后因素

采用现代标准治疗，儿童青少年NHL 5年生存率超过80%。许多因素影响治疗结果，包括临床分期和组织学亚型。主要预后因素如下：

1.年龄
婴儿NHL罕见，回顾性分析显示婴儿NHL生存率低于儿童NHL。BFM协作组研究显示青少年NHL生存率比儿童NHL低（EFS 79%与85%），尤其是在T淋巴母细胞淋巴瘤和弥漫大B细胞淋巴瘤患者中年龄影响因素更明显。

2.疾病部位
早期患者（即：单个肿瘤位于腹部或胸腔以外，或者腹部肿瘤完整切除）有极好的预后，不考虑组织学亚型，5年生存率大约90%。骨的NHL也有极好的预后。睾丸侵犯不影响预后。非淋巴母细胞淋巴瘤的纵隔侵犯预后较差。原发纵隔弥漫大B细胞淋巴瘤与其他NHL相比较预后稍差。起病时中枢侵犯预后也较差。间变大细胞淋巴瘤侵犯骨髓预后较差。

3.染色体异常
虽然NHL细胞遗传学资料不如白血病多，但是，某些染色体异常与预后有关。肿瘤组织存在13号染色体（13q）和22号染色体异常（22q）的儿童高危晚期伯基特淋巴瘤患者预后差。T淋巴母细胞瘤染色体6q杂合子丢失的患者有较高复发风险，而Notch1突变有较好疗效和预后。

4.肿瘤负荷
乳酸脱氢酶（LDH）升高与不良预后相关。骨髓和外周血微小残留病灶与预后关系仍待研究。

5.化疗疗效
伯基特淋巴瘤对前期化疗的疗效与预后相关，前期化疗肿瘤缩小低于20%预后差。

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来源：《淋巴瘤诊疗学》

专家简介：孙晓非教授现任中山大学肿瘤防治中心儿童肿瘤科教授，主任医师。神经母细胞瘤首席专家。长期从事儿童肿瘤内科治疗（化学治疗、靶向治疗和生物治疗）及抗癌药物临床研究。擅长儿童、青少年恶性肿瘤综合诊治。包括恶性淋巴瘤、白血病、神经母细胞瘤、中枢神经系统肿瘤、肾母细胞瘤、横纹肌肉瘤等软组织肿瘤、骨肉瘤、肝母细胞瘤、生殖细胞肿瘤、视网膜母细胞瘤和朗格罕组织细胞增生症等各种儿童恶性肿瘤的诊疗。对儿童肿瘤诊治有很深的造诣。临床治疗和研究经验丰富。

孙晓非教授于1982年12月毕业于中山医学院医疗系。1982-1986年在中山医学院附属第三医院任儿科医生。1986-1989年中山医科大学儿科血液学研究生，从事儿童白血病研究。1989年研究生毕业至今在中山大学肿瘤防治中心从事儿童肿瘤诊治和研究工作。曾赴日本、香港和美国等著名的儿童血液/肿瘤中心进修学习和访问交流。

孙晓非教授创建和发展了中山大学肿瘤防治中心儿童肿瘤科。积极引进国际上先进的儿童肿瘤诊疗策略和方案，牵头组建和发展了本中心儿童肿瘤多学科诊疗团队，带领团队积极规范儿童肿瘤的诊疗，促进和提高了儿童肿瘤诊疗水平，明显改善了本中心儿童肿瘤的生存率。将本中心儿童非霍奇金淋巴瘤生存率从1998年前40% 提高到目前80%以上。此研究成果获得2008年度广东省科学技术三等奖。儿童实体肿瘤生存率也获得明显改善。孙晓非教授牵头中山大学儿童肾脏肿瘤5010项目研究获得国际同行高度评价，目前受邀并带领本中心和广东儿童肿瘤团队加入国际儿童肾脏肿瘤全球多中心规范诊疗研究。
 

来源：人民卫生出版社《临床知识》约稿
作者：孙晓非教授，中山大学肿瘤防治中心儿童肿瘤科
编辑：环球医学资讯常路