摘要目的 探讨胃肠道侵袭性B细胞淋巴瘤即弥漫性大B细胞淋巴瘤(DLBCL)、Burkitt淋巴瘤(BL)、特征介于DLBCL和BL之间不能分类型的淋巴瘤(DLBCL/BL)的组织学特点,及其临床病理参数、免疫组织分型与预后的相关性.重点讨论c-myc抗体在胃肠道侵袭性B细胞淋巴瘤中的表达特点,及预测其基因易位的价值和意义.方法 对54例胃肠道侵袭性B细胞淋巴瘤的临床资料、组织学、免疫组织化学(EnVision法)进行观察分析并随访;荧光原位杂交(FISH)检测所有病例c-myc和部分病例的bcl-2的基因状态;免疫组织化学检测c-myc、Tcl-1及CD38 3种c-myc基因预测抗体的表达;统计分析各临床病理参数间及其与预后的关系,并对基因易位预测指标c-myc进行准确性检验(ROC曲线).结果 54例胃肠道侵袭性B细胞淋巴瘤,包括49例DLBCL(免疫分型:生发中心B细胞型11例,活化B细胞型38例)、4例DLBCL/BL、1例BL,中位年龄56岁,男女之比为1.6:1.0,中位生存时间42个月,其中11例在97个月内死亡.组织学观察可见异型的大细胞弥漫浸润胃肠道壁全层,部分伴有核碎裂及星空现象(18/54).瘤细胞CD20、CD79a均阳性,CD43(4/54)、CD5 (7/54)、bcl-2 (26/54)、Tcl-1 (17/54)、CD38(15/54)部分阳性,CD3、CD30均阴性,Ki-67阳性指数40％ ～ 100％.FISH检测显示部分病例出现bcl-2(1/19)和c-myc(4/54)易位,后者免疫组织化学c-myc均阳性(阳性百分数为80％ ～ 100％).单因素分析显示B症状、行为状态、乳酸脱氢酶、国际预后指数、远处转移、临床分期、c-myc阳性百分数90％以上、c-myc易位在内的8个因素与预后相关,CD5阳性的DLBCL预后不良,其中乳酸脱氢酶、远处转移、c-myc易位是独立的预后因素.ROC曲线显示c-myc抗体阳性百分数预测c-myc基因易位的最佳阈值为75％.结论 胃肠道侵袭性B细胞淋巴瘤预后受多方面临床病理因素影响;DLBCL(多为生发中心B细胞型)、DLBCL/BL可出现c-myc易位,组织学上可伴有Burkitt样的形态学特征和Ki-67高表达,且该基因易位是影响预后的独立因素,其检测对于患者的治疗和预后的判断均有重要意义;较高的c-myc抗体阳性百分数有助于预测c-myc易位.

abstractsObjective To study the histological features,diagnosis,differential diagnoses of aggressive B-cell lymphomas of the gastrointestinal tract and to correlate clinical prognosis with pathologic parameters and immunophenotypes with an emphasis on c-myc,Tcl-1 and CD38 expression and their values in predicting the status of c-myc gene translocation.Methods Fifty-four cases of aggressive B-cell lymphomas of the gastrointestinal tract with complete clinical and pathologic data were retrospectively collected.The clinical data,histologic and immunohistochemical findings and follow-up results were analyzed.Predictive immunohistochemical stains including c-myc,Tcl-1 and CD38 were performed and ROC curve analysis was used to confirm the accuracy of these markers in predicting c-myc translocation.Results Of54 cases,there were 33 males and 21 females with median age of 56 years.Histological types of lymphomas included 49 cases of DLBCL (11 cases of germinal central B cell like and 38 cases of activated B cell like by Hans classification),4 cases of DLBCL/BL and 1 case of BL.Eleven of 54 patients died within 97 months,with median survival of 42 months.Histologically,full-thickness infiltration of the gastrointestinal tract by large atypical cells with evident phagocytosis of karyorrhexis by macrophages (“ starry sky”) were seen in 18/54 cases.The lymphoma cells were positive for CD20 (54/54),CD79a (54/54),CD43 (4/54),CD5 (7/54),bcl-2 (26/54),Tcl-1 (17/54) and CD38 (15/54),but all negative for CD3 and CD30.The proliferative index by Ki-67 ranged from 40％ to 100％.The univariate survival analysis indicated that B symptoms,general performance,high LDH,high IPI,distant metastasis,high clinical stage and tumors with over 90％ of cells positive for c-myc were negative predictors for the patient's survival.In addition,cases of DLBCL positive for CD5 had an unfavorable prognosis.Cox regression analysis showed c-myc translocation,distant metastasis and high LDH were independent predictors for unfavorable prognosis.ROC curve revealed the percentage of c-myc positivity predicted the presence of c-myc gene translocation,with 75％ as the optimal threshold.Conclusions Aggressive B-cell lymphomas of the gastrointestinal tract with a prognosis influenced by variable clinicopathologic factors.DLBCL and DLBCL/BL may possess c-myc translocation and tend to be Burkitt-like or atypical Burkitt lymphoma.As independent prognostic indicator,c-myc expression may be used for selection of therapeutic regimens and prognostication.High percentage of tumor cells with c-myc positivity may be used to predict the presence of c-myc gene translocation.