老年人EB病毒阳性弥漫性大B细胞淋巴瘤的临床病理特征

目的 探讨老年人EB病毒阳性弥漫性大B细胞淋巴瘤(简称老年人EBV阳性DLBCL)的临床病理特征。方法 回顾性分析496例DLBCL,应用EBV原位杂交技术,检测病变组织中EBV感染情况,免疫组织化学检测EBV阳性病例中CD10、CD20、CD30、CD79a、bcl-6、bcl-2、MUM-1、CD5、CD3、T细胞内抗原1(TIA-1)以及Ki-67蛋白表达水平;并结合临床病理资料,分析它们之间的相关性。结果 59例DLBCL的EBER阳性,其中48例为老年人。老年人EBV阳性DLBCL患者中位年龄为73岁,绝大部分( 42/48)年龄＞60岁,男女比为1.4∶1;淋巴结病变11例,结外病变18例,39.6％ (19/48)可见淋巴结病变及结外病变;Ann ArborⅠ～Ⅱ期与Ⅲ～Ⅳ期之比为13/35,33.3％ (16/48)的患者肿瘤累及了2个或以上的结外部位,13.9％ (5/36)的患者体能状态较差,23.3％ (7/30)的患者血清乳酸脱氢酶(LDH)增高;国际预后指数(IPI)3 ～5的18例,IPI 0～2的12例;中位生存期为35个月。镜下观察：淋巴结结构或累及的组织结构完全破坏,在不同程度的炎性反应性背景上,可见中心母细胞、免疫母细胞、H/RS细胞样巨细胞弥漫性浸润或散在分布;老年人EBV阳性DLBCL包括大细胞亚型33例,多形性亚型14例,混合亚型1例。免疫表型上几乎全部表达C D20( 47/48)和（或）CD79a (45/45),绝大部分病例(44/47)可见MUM-1的表达,少量病例表达CDI0或bcl-6;bcl-2及CD30的表达率分别为80.0％ (28/35)及28.9％( 11/38)。大多数(33/39)老年人EBV阳性DLBCL都有很高的增殖指数。与非老年人EBV阳性DLBCL相比,除了年龄偏高及bcl-6的表达较低外,其他临床、病理及免疫表型特征差异均无统计学意义。结论 老年人EBV阳性DLBCL是具有一定独特临床病理特征的DLBCL亚型,但与非老年人EBV阳性DLBCL相类似,在病理诊断上还需结合临床、免疫学等资料去鉴别于其他类型的淋巴瘤。

Clinicopathological features of Epstein-Barr virus-positive diffuse large B-cell lymphoma in elderly

Objective To investigate the clinicopathological features of EB virus positive diffuse large B-cell lymphomas ( EBV+ DLBCL) of the elderly. Methods Four hundred and ninety-six cases of DLBCLs were retrospectively studied by in situ hybridization ( ISH ) to detect the EBV in tumor cells, and by immunohistochemistry to evaluate the expression of CD10, CD20, CD30, CD79a, bcl-6, bcl-2, MUM-1,CD5, CD3, TIA-1 and Ki-67 protein. Their clinicopathological correlations were analyzed. Results Of the 59 cases of EBV+ DLBCL, 48 cases were EBV positive. The median age of these EBV+ DLBCLs was 73 years with male predominance ( 1.4∶1 ). There were 11 cases with nodal presentation only, 18 cases with extra-nodal presentation and 19 cases with both lymph nodal and extra-nodal involvements, whereas about one third cases with more than one extra-nodal involvement. Thirty-five patients presented with advanced disease (Ann Arbor stage Ⅲ/Ⅳ ). A performance status was available in 36 cases and 5 cases had performance status of more than 1. Seven of 30 patients were found with high lactate dehydrogenase value ( more than twice of the normal). An IPI-score was calculated in 30 cases and 18 cases had an intermediate/high IPI-score ( 3 - 5 ). The median survival for these patients was 35 months. Morphologically, EBV+ DLBCLs of the elderly generally showed a diffuse and polymorphic proliferation of large lymphoid cells with varying degrees of reactive components including small lymphocytes, plasma cells, histiocytes, and epithelioid cells. These tumor cells were frequently characterized by a broad range of B-cell maturation, containing centroblasts, immunoblasts, and Hodgkin- and Reed-Sternberg (HRS)-like giant cells. The study cohort was further morphologically divided into large cell lymphoma subtypes (n =33 ) and polymorphic lymphoma subtypes (n =14) and one case with mixed subtype. Immunohistochemical studies showed that tumor cells were positive for CD20 (47/48) and/or CD79a (45/45) in almost cases. Tumor cells were MUM-1-positive in the majority of the cases (44/47) and were stained for CD10 or bcl-6 in a few cases. Expression of bcl-2 and CD30 was observed in 80. 0％ ( 28/35 ) and 28.9％ ( 11/38 ) cases,respectively, and most of the cases (33/39) had a high proliferative index ( by Ki-67 with a 50％ cut-off point). Compared with other EBV+ DLBCLs, except the older age and low frequency of bcl-6 staining, no other significant differences were observed in EBV+ DLBCLs of the elderly. Conclusions EBV+ DLBCLs of the elderly constitute a distinct clinicopathologic subtype of DLBCL, although many clinical and histological features with EBV+ lymphomas are similar with that of younger ages. Differential diagnosis from other types of lymphomas should also be considered.