淋巴结内外弥漫大B细胞淋巴瘤分化谱系及异质性的比较性研究

Comparative study of heterogeneity of extranodal and nodal diffuse large B cell lymphoma

目的:对原发于淋巴结内、外的弥漫大B细胞淋巴瘤(DLBCL)进行病理形态学分化谱系以及免疫表型异质性的比较性研究,并探讨其与临床分期的相关性。同时对转录因子E2F1作为一种新的生发中心B细胞(GCB)型DLBCL的判断指标的可行性进行探讨。方法:收集1996年至2005年北京大学第一医院病理科诊断为DLBCL的病检存档蜡块98例,应用组织芯片、通过免疫组化方法进行肿瘤病理形态学以及免疫表型分类研究。结果:经病理形态学分型后,中心母细胞型占88.7%(87/98),免疫母细胞型占5.1%(5/98),间变型占3.1%(3/98),富于T的B细胞型占3.1%(3/98)。98例DLBCL中,GCB型共31例(31.6%),淋巴结外组中GCB型占42%(21/50),高于其在淋巴结内组中所占的比例20.8%(10/48),二者的差异有统计学意义(P=0.024)。淋巴结内、外Ⅰ/Ⅱ期DLBCL所占的比例分别为45.8%和70%,两者差异有统计学意义(P=0.015)。Ⅰ/Ⅱ期和Ⅲ/Ⅳ期DLBCL中,CD10的阳性表达率分别为36.8%和17.1%,二者的差异有统计学意义(P=0.033)。CD10在淋巴结内、外的阳性率分别为18.8%和38%,二者的差异有统计学意义(P=0.035)。Ⅰ/Ⅱ期在GCB型DLBCL中占74.2%,在非GCB型DLBCL中占50.7%,两者差异有统计学意义(P=0.029)。GCB型DLBCL中E2F1的阳性表达率为38.8%,在非GCB型DLBCL中为16.5%,两者间差异有统计学意义(P=0.016)。且E2F1的阳性表达与CD10及Bcl-6的表达呈正相关(P<0.05)。结论:98例DLBCL中,中心母细胞型最多,占88.8%。GCB型DLBCL在淋巴结外的发生率显著高于淋巴结内。GCB型DLBCL的预后比非GCB型DLBCL要好。CD10可以作为预后判断指标。E2F1的阳性表达可作为判断GCB型DLBCL的辅助指标。

Objective： Primary nodal and extranodal diffuse large B-cell lymphoma （DLBCL） were investigated for the heterogeneity of histopathology and immunophenotype, and their relation to clinical stage, comparatively. Whether E2F1 can be used as a germinal center B cell （GCB） DLBCL marker was also discussed. Methods： Classification of histopathology and immunophenotype of 98 cases were studied by immunohistochemistry in tissue microarray. Results： Histopathologic morphology presented as： centroblastic （ CB, 88. 8%, 87/98 ）, immunoblastic （ IB, 5. 1%, 5/98 ）, anaplastic （ ALCL, 3. 1%, 3/98）, and T cell rich B cell lymphoma （TCRBCL,3. 1%, 3/98）. Of which, 31 cases were GCB DLBCL, 10 （20.8%, 10/48） nodal, and 21 extranodal （42%, 21/50,P =0.024）. The rates of Sta- ges Ⅰ/Ⅱin nodal and extranodal area were 48.5% and 70%, respectively （P =0. 015）. The rate of StageⅠ / Ⅱ in GCB DLBCL （74.2%） were higher than in non-GCB DLBCL （50.7%, P = 0. 029）. The CD10 positive rates were 36.8% and 17.1% in Stages Ⅰ / Ⅱ and Ⅰ/Ⅳ, respectively, and had significant differences （P =0.033 ）. The CD10 positive rates were 18.8% and 38% in nodal and extranod- al area, respectively （P =0.035）. The positive rates of E2F1 were 38.8% and 16.5% in GCB and non-GCB DLBCL, respectively, and had significant differences （P = 0.016）. The positive rate of E2F1 had positive relation with the expression of CD10 and Bcl-6 （P 〈0.05 ）. Conclusion： CB is the most type in 98 cases of DLBCL. The rate of GCB DLBCL was significant higher in extranodal than in nodal areas. CD 10 can be used as a prognostic marker. The prognosis of GCB DLBCL is better than that of non-GCB DLBCL. The positive expression of E2F1 can be used as a marker of GCB DLBCL.