中国癌症杂志 ›› 2019, Vol. 29 ›› Issue (9): 715-722.doi: 10.19401/j.cnki.1007-3639.2019.09.006

• 论著 • 上一篇    下一篇

原发性胃弥漫大B细胞淋巴瘤临床病理学观察及预后因素分析

孙阳阳 1 ,耿 翔 2 ,周晓莉 1 ,王更方 1 ,顾文贤 1 ,张旭东 2   

  1. 1. 南京医科大学附属常州市第二人民医院病理科,江苏 常州 213000 ;
    2. 南京医科大学附属常州市第二人民医院普外科,江苏 常州 213000
  • 出版日期:2019-09-30 发布日期:2019-11-20
  • 通信作者: 耿 翔 E-mail: 874639437@qq.com
  • 基金资助:
    国家青年基金项目(81702323)。

Clinicopathologic observation and prognostic factor analysis of primary gastric diffuse large B-cell lymphoma

SUN Yangyang 1 , GENG Xiang 2 , ZHOU Xiaoli 1 , WANG Gengfang 1 , GU Wenxian 1 , ZHANG Xudong 2   

  1. 1. Department of Pathology, the Second People’s Hospital, Changzhou City, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China; 2. Department of General Surgery, the Second People’s Hospital, Changzhou City, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
  • Published:2019-09-30 Online:2019-11-20
  • Contact: GENG Xiang E-mail: 874639437@qq.com

摘要: 背景与目的:原发性胃弥漫大B细胞淋巴瘤(primary gastric diffuse large B-cell lymphoma,PG-DLBCL)是胃淋巴瘤最常见的组织学亚型,缺乏特异性临床表现,内镜检查易与胃癌、溃疡或其他炎症性病变混淆,病变组织学形态表现复杂,诊断困难。探索PG-DLBCL的临床病理学特征并分析患者的预后影响因素及生存率。方法:回顾性分析2008年1月—2018年7月南京医科大学附属常州市第二人民医院收治的104例PG-DLBCL患者的临床病理学资料。计数资料两组间比较采用χ 2 检验,应用Kaplan-Meier法计算生存率并绘制生存曲线,Log-rank检验和COX回归模型进行单因素及多因素预后影响分析。结果:104例PG-DLBCL患者,男性45例,女性59例,中位发病年龄68岁。104例患者均获得随访,随访时间6.0~103.0个月,中位随访时间71.0个月,患者中位生存时间56.8个月,1、3和5年总体生存率分别为90.1%、76.8%和47.6%。病理学分类:生发中心样B细胞(germinal center B cell-like,GCB)型40例,非生发中心样B细胞(non-germinal center B cell-like,non-GCB)型64例。荧光原位杂交技术(fluorescence in situ hybridization,FISH)检测结果显示:c-Myc基因异常27例(占26%,其中17例为多拷贝,10例为重排),B细胞淋巴瘤-2(B-cell leukemia/lymphoma 2,BCL-2)基因异常26例(占25.2%,其中17例为多拷贝,9例为重排),BCL-6基因异常32例(占31%,其中23例为多拷贝,9例为重排)。单因素分析结果显示,血清CA125水平、血清乳酸脱氢酶(lactate dehydrogenase,LDH)水平、淋巴瘤国际预后指数(international prognostic index,IPI)评分、改良Ann Arbor分期、骨髓侵犯、治疗方法、病理学类型non-GCB型、BCL-2/BCL-6/多发性骨髓瘤原癌基因-1(multiple myeloma protooncogene-1,MUM-1)/细胞分裂周期蛋白7(cell division cyclin 7,CDC7)/微小染色体维持蛋白2(minichromosome maintenance protein 2,MCM2)蛋白表达水平均是影响PG-DLBCL患者预后的相关因素(P<0.05)。多因素分析结果显示,改良Ann Arbor临床分期ⅢE~ⅣE期、IPI评分≥2、病理学类型非生发中心亚型、CDC7蛋白高表达、MCM2蛋白高表达、FISH检测BCL-2基因重排是影响PG-DLBCL患者预后的独立危险因素。结论:PG-DLBCL发病以老年人为主,临床表现无特殊性,内镜检出率较高,确诊依赖于病理学检查,R(利妥昔单抗)-CHOP(环磷酰胺+表多柔比星+长春新碱+泼尼松)化疗方案作为首选治疗方法。

Abstract: Background and purpose: Primary gastric diffuse large B-cell lymphoma (PG-DLBCL) is the most common histological subtype of gastric lymphoma, lacking specific clinical manifestations, and it is confused with gastric cancer, ulcer or other inflammatory lesions upon endoscopic examination. The pathological and histological manifestations are complex, and it is difficult to diagnose PG-DLBCL. This study aimed to explore the clinicopathological features of PG-DLBCL and analyze the prognostic factors and survival rate. Methods: The clinical and pathological data of 104 PG-DLBCL patients admitted to the Second People’s Hospital, Changzhou City from January 2008 to July 2018 were retrospectively analyzed. The chi-square test was used for the comparison of counting data between the two groups. Kaplan-Meier method was used to calculate the survival rate and draw the survival curve. The Log-rank test and COX regression model were used for the analysis of single and multiple prognostic factors. Results: There were 104 PG-DLBCL patients, including 45 males and 59 females. The median age of onset was 68 years. All 104 patients were followed up for 6.0-103.0 months. The median follow-up time was 71.0 months. The median survival time was 56.8 months. The 1-year, 3-year and 5-year overall survival rates were 90.1%, 76.8% and 47.6%, respectively. Pathological classification: 40 cases of germinal center B cell-like (GCB) and 64 cases of non-germinal center B cell-like (non-GCB). The results from fluorescence in situ hybridization (FISH) detection showed that there were 27 cases of c-Myc gene abnormality (accounting for 26%, among which 17 cases had multiple copies and 10 cases had rearrangements), 26 cases of B-cell leukemia/lymphoma 2 (BCL-2) gene abnormality (accounting for 25.2%, among which 17 cases had multiple copies and 9 cases had rearrangements), 32 cases of BCL-6 gene abnormality (accounting for 31%, among which 23 cases had multiple copies and 9 cases had rearrangements). The results of single-factor analysis showed that serum CA125 level, serum lactate dehydrogenase (LDH) level, international prognostic index (IPI) score, modified Ann Arbor stage, bone marrow invasion, treatment method, pathological non-germinal center subtype and BCL-2/ BCL-6/multiple myeloma protooncogene-1 (MUM-1)/cell division cyclin 7 (CDC7)/minichromosome maintenance protein 2 (MCM2) protein expression level were all related factors affecting the prognosis of PG-DLBCL patients (P<0.05). Multi-factor analysis results showed that the improved Ann Arbor clinical stage ⅢE-ⅣE, IPI grade 2 or more, pathological type of germinal center subtype, high CDC7 protein expression, MCM2 expression, FISH detection of the BCL-2 gene rearrangement were independent risk factors for the prognosis of patients with PG-DLBCL. Conclusion: The onset of PG-DLBCL is mainly in the elderly, with no particularity in clinical manifestations. Endoscopic detection rate is high, and the diagnosis depends on pathology. R-CHOP (rituximab, cyclophosphamide, hydroxydaunomycin, oncovin and prednisone) chemotherapy is the preferred treatment method.