O'Keefe R J, Rosier R N, Teot L A, Stewart J M, Hicks D G
Department of Pathology, University of Rochester, NY, USA.
Iowa Orthop J. 1998;18:26-34.
Pigmented villonodular synovitis (PVNS) is characterized by hypervascular proliferative synovium containing multinucleated giant cells, macrophages, and hemosiderin. The destruction of articular cartilage and erosion of periarticular bone is thought to be mediated by matrix metalloproteinases (MMPs). Expression of MMPs in some tumors appears to be stimulated through local production of cytokines, and several specific cytokines (TNF alpha, IL-1, and IL-6) play an important role in the stimulation of osteoclastic bone resorption. The role of cytokine secretion and regulation of MMP production in PVNS has not been investigated.
In the present study, ten specimens from eight patients (ages 19 to 80) were evaluated histologically according to a modified Mirra classification and immunohistochemically (IHC) for the expression of MMP-9 (92 kDa gelatinase B), tumor necrosis factor alpha (TNF alpha), interleukin 1-beta (IL-1 beta), and interleukin 6 (IL-6). Localization of IL-6 and TNF alpha production was confirmed by in situ hybridization (ISH) for mRNA.
All specimens, regardless of location (six knees, one ankle, one subtalar joint), showed diffuse and intense immunoreactivity for cytokines in the giant cells and synovial cells, and less intense and diffuse staining in the activated macrophages. Staining in the fibroblastic elements was minimal. In situ hybridization for TNF alpha and IL-6 mRNA mirrored the immunohistochemistry results, although the IL-6 staining was weaker than that for TNF alpha. Immunoreactivity for MMP-9 was diffuse and strong in giant cells, diffuse and moderate in synovial cells, and focal and moderate to strong in macrophages. In contrast, normal synovium demonstrated focal, moderate immunoreactivity for IL-1 beta, IL-6, TNF alpha and MMP-9 localized in the synovial lining cells.
These findings suggest that periarticular bone resorption and cartilage destruction which characterize PVNS may be related to the expression of inflammatory cytokines, which in turn stimulate MMP production.
色素沉着绒毛结节性滑膜炎（PVNS）的特征是富含多核巨细胞、巨噬细胞和含铁血黄素的血管增生性滑膜。关节软骨破坏和关节周围骨侵蚀被认为是由基质金属蛋白酶（MMPs）介导的。MMPs在一些肿瘤中的表达似乎是通过细胞因子的局部产生来刺激的，几种特定的细胞因子（肿瘤坏死因子α、白细胞介素-1和白细胞介素-6）在刺激破骨细胞骨吸收中起重要作用。细胞因子分泌和MMP产生的调节在PVNS中的作用尚未得到研究。
在本研究中，根据改良的米拉分类法对来自8例患者（年龄19至80岁）的10个标本进行组织学评估，并通过免疫组织化学（IHC）检测基质金属蛋白酶-9（92 kDa明胶酶B）、肿瘤坏死因子α（TNFα）、白细胞介素1-β（IL-1β）和白细胞介素6（IL-6）的表达。通过mRNA原位杂交（ISH）证实IL-6和TNFα的产生部位。
所有标本，无论位置（6个膝关节、1个踝关节、1个距下关节）如何，在巨细胞和滑膜细胞中均显示出细胞因子的弥漫性强免疫反应性，在活化的巨噬细胞中染色较弱且弥漫。成纤维细胞成分中的染色极少。TNFα和IL-6 mRNA的原位杂交反映了免疫组织化学结果，尽管IL-6染色比TNFα弱。MMP-9的免疫反应性在巨细胞中弥漫且强，在滑膜细胞中弥漫且中等，在巨噬细胞中呈局灶性且中等至强。相比之下，正常滑膜在滑膜衬里细胞中显示出IL-1β、IL-6、TNFα和MMP-9的局灶性中等免疫反应性。
这些发现表明，PVNS特征性的关节周围骨吸收和软骨破坏可能与炎性细胞因子的表达有关，而炎性细胞因子反过来又刺激MMP的产生。
