Lecca S, Pilloni L, Ambu R, Flore C, Callea F, Faa G
Dipartimento di Citomorfologia, Università degli Studi di Cagliari.
Pathologica. 1998 Dec;90(6):771-5.
Conflicting results have been reported on the usefulness of histochemistry for copper in the diagnosis of Wilson's Disease (W.D.). In spite of the high number of methods proposed in the literature, no-one has shown to have the characteristics typical of a good histochemical method: high sensitivity associated with high specificity. On this basis, it seemed of interest to evaluate, in a large series of patients with W.D., the diagnostic value of the most commonly used histochemical methods for copper (rhodanine, orcein and Timm's method). To this end, 74 liver needle biopsies from patients affected by W.D., 39 males and 35 females, aged 4-60 years (mean age 28.5 years), were stained with rhodanine (R), orcein (O) and Timm's (T) methods. On the basis of the histological picture, liver biopsies were subdivided in four evolutive stages: stage I = steatosis; stage II = interface hepatitis; stage III = bridging fibrosis; stage IV = cirrhosis. In stage I, histochemistry for copper was positive in 11 out of 21 cases: 6 cases were T+; 1 case R+ and 2 cases O+; 2 cases were T+, R+, O+. In stage II, 11 out of 14 cases were positive for copper staining: 4 T+, 2 R+ and 2 O+; 3 cases were contemporary positives for T, R, O. In stage III, 22 out of 25 cases resulted positive: 8 T+, 3 R+ and 1 O+; 10 cases were positives, in the mean time, for more of one method. In stage IV, 12 of 14 cases were positives: 5 T+, 2 R+, 2 O+ and 3 cases were contemporaneously positives for multiple methods. Our data show that: 1) the percentage of positivity obtained using three histochemical methods for copper is higher than using only one method. From a practical point of view, it is mandatory to utilize, in clinical practice, multiple histochemical stains in order to increase the diagnostic utility of histochemistry for copper; 2) the Timm's method appears to be the most sensitive method for the demonstration of copper in all stages of W.D.; 3) even though hepatic copper already abounds in the early stages of W.D., this pool of intrahepatic copper is not yet demonstrable with any of the three histochemical techniques utilized.
关于组织化学检测铜在威尔逊病（W.D.）诊断中的作用，已有相互矛盾的结果报道。尽管文献中提出了大量方法，但没有人证明其中任何一种具有良好组织化学方法的典型特征：高灵敏度与高特异性相关。在此基础上，评估一系列大量W.D.患者中最常用的铜组织化学方法（罗丹宁法、地衣红法和蒂姆法）的诊断价值似乎很有意义。为此，对74例W.D.患者的肝穿刺活检组织进行了检测，其中男性39例，女性35例，年龄4 - 60岁（平均年龄28.5岁），分别采用罗丹宁法（R）、地衣红法（O）和蒂姆法（T）进行染色。根据组织学表现，肝活检组织分为四个演变阶段：I期 = 脂肪变性；II期 = 界面性肝炎；III期 = 桥接纤维化；IV期 = 肝硬化。在I期，21例中有11例铜组织化学检测呈阳性：6例蒂姆法阳性（T +）；1例罗丹宁法阳性（R +），2例地衣红法阳性（O +）；2例为蒂姆法、罗丹宁法和地衣红法均阳性。在II期，14例中有11例铜染色阳性：4例蒂姆法阳性，2例罗丹宁法阳性，2例地衣红法阳性；3例为蒂姆法、罗丹宁法和地衣红法同时阳性。在III期，25例中有22例呈阳性：8例蒂姆法阳性，3例罗丹宁法阳性，1例地衣红法阳性；10例同时有不止一种方法呈阳性。在IV期，14例中有12例呈阳性：5例蒂姆法阳性，2例罗丹宁法阳性，2例地衣红法阳性，3例同时有多种方法呈阳性。我们的数据表明：1）使用三种铜组织化学方法获得的阳性率高于仅使用一种方法。从实际角度来看，在临床实践中必须使用多种组织化学染色方法，以提高铜组织化学检测的诊断效用；2）蒂姆法似乎是在W.D.各阶段检测铜最敏感的方法；3）尽管在W.D.早期肝铜就已大量存在，但使用的这三种组织化学技术均无法检测到肝内铜池。
