组织细胞坏死性淋巴结炎84例的临床病理和免疫表型特点

Clinicopathologic characteristics and immunophenotypes of histiocytic necrotizing lymphadenitis： an analysis of 84 cases

目的探讨组织细胞坏死性淋巴结炎（HNL）临床病理特点、免疫表型，寻找可以作为HNL诊断依据的生物分子标志物，为进一步研究HNL的发病机制奠定基础。方法对2005年至2014年间收集的84例HNL患者的临床表现、病理形态及免疫组织化学特点进行回顾性分析，应用免疫组织化学EliVision法检测CD20、PAX5、CD3、CD45RO、CD4、CD8、CD56、CD68、CD123、颗粒酶B、T细胞胞质内抗原1（TIA1）和髓过氧化酶（MPO）等蛋白质表达水平；同时应用原位杂交方法检测EB病毒在HNL中的表达。结果免疫组织化学染色显示病变区增生细胞主要为组织细胞（CD68＋）、浆样树突状细胞（CD123＋）和T淋巴细胞（CD3和CD45RO＋）。其中CD68阳性的组织细胞成簇聚集，弥漫且强表达MPO；浆样树突状细胞呈CDl23阳性表达；在增生的T淋巴细胞中，CD4和CD8阳性的T淋巴细胞均有表达，且两者表达量在增生型和坏死型HNL中差异无统计学意义；CD56标记的NK细胞和CD20、PAX5标记的B细胞则在病变区内很少见。在HNL的T淋巴细胞胞质内可见到与凋亡有关物质，如TIM、颗粒酶B等；应用原位杂交方法检测EB病毒，阳性检出率仅为10．0％。结论HNL的临床表现和实验室检查结果缺乏特异性，淋巴结活检特征性的组织病理学改变是诊断HNL的主要依据。病变区域的细胞呈CD20、PAX5、CD56阴性和CD3、CD4（或CD8）、MPO、CD123、颗粒酶B及TIA1阳性的免疫表型对HNL鉴别诊断有很大的帮助。

Objective To study the clinical manifestation, pathologic features and immunophenotype of histioeytic necrotizing lymphadenitis （HNL）. Methods The elinicopathologic data of 84 patients with HNL from 2005 to 2014 were retrospectively studied. Immunohistochemical staining using EliVision method for CD20, PAX5, CD3, CD45RO, CD4, CD8, CD56, CD68, CD123, granzyme-B, TIA1 and MPO was carried out. In-situ hybridization for Epstein-Barr virus RNA was performed on archival lymph node biopsy tissue. Results hnmunohistochemical study showed that the lesional cells were predominantly histioeytes （CD68 ＋ ） , plasmaeytoid dendritic cells （ CD123 ＋ ） and T lymphoeytes （ CD3 ＋ and CD45RO ＋ ）. Clusters of CD68-positive cells with strong and diffuse MPO expression were identified. T lymphocytes with CD4 and CD8 positivity were noted. CD56 ＋ natural killer cells and CD20 ＋/PAX5 B cells were rare. Apoptosis-related markers, including TIA1 and granzyme B were expressed by T lymphocytes and histiocytes in lymph nodes of HNL. In-situ hybridization for Epstein-Barr virus RNA was positive in only 10. 0% of the cases. Conclusions HNL shows no specific clinical and laboratory findings. Recognition of the characteristic histopathologic changes in lymph node biopsy of HNL is the key to correct diagnosis. hnmunohistochemical study using a panel of markers, including CD3, CD4, CD8, MPO, CD123, grauzyme-B and TIA1, is helpful in the differential diagnosis of HNL.