Knoess M, Krukemeyer M G, Kriegsmann J, Thabe H, Otto M, Krenn V
Department of Pathology, Institute of Pathology, Max-Planck-Strasse 18+20, Trier, Germany.
Pathol Res Pract. 2008;204(6):373-8. doi: 10.1016/j.prp.2008.01.009. Epub 2008 Mar 14.
Rheumatoid nodule (RN) represents a palisading granuloma with central fibrinoid necrosis, which is not only a classical manifestation of rheumatoid arthritis (RA) and part of the American College of Rheumatology (ACR)-criteria, but also is its diagnostic hallmark. The pathogenesis of RN is still not fully understood. At present, only data on serum analyses indicating a complement-mediated pathogenesis in the development of RA are available. Equivalent examinations for RN have not yet been performed. Granuloma annulare (GA) represents another type of palisading granuloma. A special subtype of GA, subcutaneous GA (SGA), is an important differential diagnosis to RN. Therefore, our aim was to examine RN and SGA regarding the complement deposition (C4d) by immunohistochemical means. All RN and GA were stained by hematoxylin/eosin and different special stains. In addition, all specimens were stained immunohistochemically with antibodies against CD68. Five GA and five RN were analyzed immunohistochemically with antibodies against C4d and CD68, and evaluated using single- and doublestaining immunohistochemistry. All RN and GA displayed depositions of C4d within their central necroses and between the surrounding palisading macrophages. Most importantly, C4d/CD68 double staining was visible in the palisading macrophages next to the necroses, while macrophages in the periphery were negative for C4d but positive for CD68. The main difference between RN and GA was a quantitative phenomenon with less positively reacting macrophages in a more incomplete palisade in GA. The positive reactions of all central necroses to C4d and colocalization of CD68 and C4d suggest that a complement-mediated mechanism may be operative in the formation of fibrinoid necrosis. This mechanism may be involved in any form of "fibrinoid necrosis", since no different patterns of C4d/CD68 expression could be observed in GA. This may explain why RG/GA are not distinguishable morphologically.
类风湿结节（RN）表现为一种具有中央纤维蛋白样坏死的栅栏状肉芽肿，它不仅是类风湿关节炎（RA）的典型表现且是美国风湿病学会（ACR）标准的一部分，也是其诊断标志。RN的发病机制仍未完全阐明。目前，仅有血清分析数据表明补体介导的发病机制参与RA的发展过程。尚未对RN进行类似检查。环状肉芽肿（GA）代表另一种类型的栅栏状肉芽肿。GA的一种特殊亚型，即皮下GA（SGA），是RN的重要鉴别诊断对象。因此，我们的目的是通过免疫组化方法检测RN和SGA中的补体沉积（C4d）情况。所有RN和GA均用苏木精/伊红及不同特殊染色进行染色。此外，所有标本均用抗CD68抗体进行免疫组化染色。对5个GA和5个RN用抗C4d和抗CD68抗体进行免疫组化分析，并采用单染和双染免疫组化进行评估。所有RN和GA在其中央坏死灶内及周围栅栏状巨噬细胞之间均显示C4d沉积。最重要的是，在坏死灶旁的栅栏状巨噬细胞中可见C4d/CD68双染，而周边巨噬细胞C4d呈阴性但CD68呈阳性。RN和GA之间的主要差异是一种数量现象，GA中栅栏状结构更不完整，阳性反应性巨噬细胞较少。所有中央坏死灶对C4d的阳性反应以及CD68和C4d的共定位表明补体介导的机制可能在纤维蛋白样坏死的形成中起作用。该机制可能参与任何形式的“纤维蛋白样坏死”，因为在GA中未观察到C4d/CD68表达的不同模式。这可能解释了为什么RG/GA在形态学上无法区分。
