15例血管免疫母细胞T细胞淋巴瘤的临床病理、免疫组织化学及分子分析

Clinicopathologic,immunohistochemical and molecular analysis in 15 cases of angioimmunoblastic T-cell lymphomas

目的:对血管免疫母细胞T细胞淋巴瘤(AITL)的组织病理学、特征性免疫标记、抗原受体基因重排及EB病毒(EBV)感染情况进行全面认识及评价。方法:选择具有淋巴结结构破坏、分支状高内皮血管增生、多形性细胞浸润和/或透明异型T淋巴细胞增生的15例典型AITL病例,进行临床和组织学特点分析,行CD3、CD20、CD4、CD21、CXCL13、CD10和BCL6免疫组化染色,PCR分析免疫球蛋白重链(IgH)及T细胞受体(TCR)基因重排,原位杂交检测EBV。结果:组织学检查示8例滤泡萎缩、6例滤泡消失、1例滤泡增生,病变位于滤泡间。8例伴有片状透明细胞聚集,4例伴有大型淋巴细胞,5例富于上皮样组织细胞,CD20染色示4例伴有大B细胞增生,CD21染色显示11例(73.3%)滤泡外滤泡树状突细胞(FDC)网络,部分有围绕血管分布的趋势。CXCL13的阳性率为73.3%,CD10的阳性率为6.7%,TCRγ的重排阳性为6/15(40%),均为单克隆;IgH的重排阳性为7/15(46.7%),其中5例单克隆,2例寡克隆。EBV阳性率为8/15(53.3%)。伴大B细胞增生的4例中,3例EBV阳性。结论:AITL在临床和病理学上的表现异常复杂多样,深入认识这些多样性、合理应用及正确评价免疫标记和分子技术可以提高诊断准确率。

Objective：To evaluate angioimmunoblastic T-cell lymphoma（AITL） completely, we gave in-depth investigation of histopathological features, specific immunochemical markers, antigen receptor gene rearrangements and in situ hybridization for Epstein-Barr virus （EBV）. Methods： 15 cases of typical AITL displayed effacement of the normal lymph node architecture partially or completely, abundance of arborizing high endothelial vessels, infiltration of polymorphic cells and hyperplastic atypical T lymphocytes with or without clear cytoplasm. Clinical characteristics, histological manifestations, and immunohistochemical staining for CD3, CD20, CD4,CD21, CXCL13, CD10, and BCL6 were analyzed. Polymerase chain reaction for immunoglobulin heavy chain （IgH） and T cell receptor γ（TCRγ） rearrangements and in situ hybridization for Epstein-Barr virus encoded RNA （ EBER-1 ） were performed. Results： Histologically, we found eight cases with regressed lymphoid follicles, six with absence of follicles and one with hyperplastic follicles with interfollicular lesions. We also found eight cases displaying aggregation of clear cells, four infiltration of large lymphoid cells, five abundant epithelioid histiocytes. CD20 staining showed hyperplasia of large B cells in four cases. CD21 expression exihibited extrafollicular expansion of follicular dendritic cell meshworks in 11 cases （73.3%）, partially with a tendency of perivascular distribution. Positive rate for CXCL13 and CD10 are 73.3% and 6.7% respectively. Monoclonal rearrangements of TCRγ were detected in 6/15 （40%） of cases, IgH rearrangements in 7/15 （46. 7% ）, of which five were monoclonal, while two oligoclonal. 8 out of 15 cases （53.3%） contained EBV-positive cells. Among the four cases with large B cell proliferation, three were EBV-positive. Conclusion. AITL display great complexity and diversity clinicopathologically. Only when we recognize such diversity, can we reasonably apply and properly evaluate immunochemical markers and molecular techniques, and thus give a correct diagnosis.