摘要目的：探讨原发中枢神经系统弥漫性大B细胞淋巴瘤（ DLBCL）的临床病理、免疫表型、与EB病毒相关性及分子遗传学改变，并分析相关预后因素。方法回顾性分析30例原发中枢神经系统DLBCL临床资料；采用HE染色及免疫组织化学EnVision法染色观察肿瘤组织病理学特点和免疫表型特征；原位杂交技术检测肿瘤EB病毒编码mRNA表达情况；荧光原位杂交技术检测肿瘤组织中bcl-2、bcl-6和C-MYC基因重排，并对所有患者进行随访。结果30例患者，男性18例，女性12例，男女比例1.5∶1.0。中位年龄53（24～76）岁。患者以局灶性神经功能缺损为主要临床表现。形态学以中心母细胞型为主，可见凝固性坏死及血管中心性-血管破坏性生长，有较多核分裂象和凋亡小体，常见血管周淋巴细胞套。免疫表型：生发中心（ GCB）型6例，非GCB型24例，bcl-2、bcl-6、C-MYC蛋白表达率分别为53.3％（16／30）、80.0％（24／30）、20.0％（6／30）。荧光原位杂交检测bcl-2、bcl-6、C-MYC基因重排阳性率分别为3.3％（1／30）、16.7％（5／30）、6.7％（2／30）。仅1例检测出EBER阳性。国际预后指数（IPI）评分：0～1分19例（63.3％），2～3分11例（36.7％）。患者性别、民族、初次就诊时存在B症状、发病部位、血清乳酸脱氢酶、血沉、β2微球蛋白含量、bcl-2蛋白表达、bcl-6蛋白表达、Ki-67阳性指数及分子遗传学改变与预后均无统计学意义；发病年龄≤60岁组、功能状态（PS）评分0～1分组及IPI评分0～1分组患者预后较好（P＜0.05）；免疫分型GCB型组预后优于非GCB型组（ P＝0.013）；术后加用大剂量甲氨蝶呤或阿糖胞苷化疗组的预后优于其他治疗方式组（P＝0.006），术后电话随访，平均随访时间13.6个月，中位生存时间10个月，其中16例在1年内死亡，1年生存率为46.7％。结论年龄、临床功能状态评分、IPI评分、免疫分型及治疗方式与预后相关，原发中枢神经系统DLBCL患者病程进展迅速，1年内为死亡的高发时间，手术切除加用大剂量甲氨蝶呤或阿糖胞苷化疗是目前最佳的治疗方式。

abstractsObjective To investigate clinicopathologic characteristics, immunophenotype and EB virus-related molecular genetic alterations in primary central nervous system diffuse large B cell lymphoma ( DLBCL) along with correlation with clinical prognosis.Methods A total of 30 cases of primary central nervous system DLBCL were retrospectively studied by retrieving clinical data, histological evaluation and immunophenotyping by EnVision two steps methods.The expression of EBER mRNA was detected by in situ hybridization and bcl-2, bcl-6 and C-MYC gene abnormalities were analyzed by interphase fluorescence in situ hybridization.Results The cases included 18 males and 12 females ( sex ratio of 1.5∶1.0) with an age ranging from 24 to 78 years ( average age of 52 years, the median age of 53 years) .The single primary clinical presentation was focal neurologic deficits.Tumor locations were supratentorial ( 21 cases ) , subtentorial (7 cases), involving both locations in 2 cases.Diffuse growth pattern was observed with large lymphoid cells mostly resembling centroblasts with abundant basophilic cytoplasm with oval to round, vesicular nuclei containing fine chromatin.An angiocentric and angiodestructive growth pattern was also present.Other features included perivascular space invasion.Immunohistochemical staining using a panel of CD10, bcl-6 and MUM1, six cases were germinal center-like ( GCB) and 24 cases were non-germinal central-like (non-GCB).The positive rates of bcl-2, bcl-6 and C-MYC were 53.3% (16/30), 80.0%(24/30) and 20.0% (6/30), respectively.Genetic alterations were detected by FISH and the gene arrangement rates of bcl-2, bcl-6 and C-MYC were 3.3% (1/30), 16.7% (5/30) and 3.3% (1/30), respectively.There were 19 cases in stage 0-1 disease and 11 cases had stage 2-3 disease.Postoperative follow-up for average 13.6 months showed the median survival of 10 months, one-year survival of 46.7%and 16 patients died within a year.Conclusions The clinical prognosis of primary central nerve system DLBCL depends on age, clinical performence status score, IPI score, immune classification and treatment.Patients typically progress rapidly with the high mortality within one year of diagnosis.Surgical resection combined with high-dose methotrexate or cytarabine chemotherapy offer the best treatment option.