Okoń Krzysztof
Department of Pathomorphology, Collegium Medicum Jagiellonian University, Kraków.
Pol J Pathol. 2008;59(3):129-76.
Malignant renal tumors constitute 3% of human cancers, although their frequency differs greatly in various areas. Since the fifties, the incidence of renal cancers has been increasing, but at the some time the prognosis has been improving. In particular, in the last years, several new treatment modalities have been introduced, relying on the understanding of renal cancer biology. The identified etiological factors include smoking, increased body mass, dietary factors and chronic renal disease. There are several renal tumor types differing in morphology, molecular genetics and biology. Inactivation of the VHL gene leads to formation of the most frequent form in adults, namely clear cell carcinoma. The VHL gene product, a component of an ubiquitin-ligase complex, regulates expression of several genes. Papillary carcinomas depend mainly on the HGF receptor gene (c-Met) activating mutations. At least two types of papillary carcinomas exist, which have different morphology and prognosis. The molecular biology of chromophobe carcinoma and oncocytoma is poorly understood. Differential diagnosis of these tumors is particularly difficult and may require extensive immunohistochemical and molecular studies. Collecting duct carcinoma and medullary carcinoma are extremely aggressive but rare tumors. Some renal tumors have been described or recognized only relatively recently; these newer entities include multilocular cystic clear cell carcinoma, spindle cell papillary mucinous carcinoma, tubulocystic carcinoma, renal epithelial and stromal tumor, epithelioid and oncocytic angiomyolipoma. Besides histological typing, the prognostic factors include tumor stage, grade and several immunohistochemical and molecular markers that are currently under elaboration. The improved prognosis in renal cancer depends on earlier detection, but also on refinement of therapeutic methods. Small tumors may currently be treated by partial nephrectomy or radiofrequency ablation and larger ones by a laparoscopic approach. All these methods seem to give satisfactory results with low morbidity and mortality rates. Renal carcinoma is notorious for its low sensitivity to chemotherapy and radiotherapy. For several years, immunological treatment with IL-2 and INF-alpha was the only adjuvant therapy method. However, recently several new drugs have been introduced; they act on tyrosine-kinase receptors, VEGF, c-Met or mTOR pathway. With this progress, perfect understanding of renal tumor biology and exact histological diagnosis have become of prime practical importance.
恶性肾肿瘤占人类癌症的3%，尽管其发病率在不同地区差异很大。自五十年代以来，肾癌的发病率一直在上升，但与此同时预后也在改善。特别是在过去几年中，基于对肾癌生物学的认识，引入了几种新的治疗方式。已确定的病因包括吸烟、体重增加、饮食因素和慢性肾病。有几种肾肿瘤类型在形态、分子遗传学和生物学方面存在差异。VHL基因的失活导致成人中最常见的肿瘤类型，即透明细胞癌的形成。VHL基因产物是泛素连接酶复合物的一个组成部分，可调节多个基因的表达。乳头状癌主要依赖于HGF受体基因（c-Met）的激活突变。至少存在两种类型的乳头状癌，它们具有不同的形态和预后。嫌色细胞癌和嗜酸细胞瘤的分子生物学了解较少。这些肿瘤的鉴别诊断特别困难，可能需要广泛的免疫组织化学和分子研究。集合管癌和髓样癌极具侵袭性但很罕见。一些肾肿瘤只是在相对较近的时期才被描述或认识到；这些较新的实体包括多房囊性透明细胞癌、梭形细胞乳头状黏液癌、微囊腺癌、肾上皮和间质肿瘤、上皮样和嗜酸细胞性血管平滑肌脂肪瘤。除了组织学分类外，预后因素还包括肿瘤分期、分级以及目前正在研究的几种免疫组织化学和分子标志物。肾癌预后的改善依赖于早期检测，也依赖于治疗方法的改进。目前小肿瘤可通过部分肾切除术或射频消融治疗，大肿瘤可通过腹腔镜手术治疗。所有这些方法似乎都能取得令人满意的结果，发病率和死亡率都很低。肾癌因其对化疗和放疗的低敏感性而声名狼藉。多年来，用IL-2和INF-α进行免疫治疗是唯一的辅助治疗方法。然而，最近引入了几种新药；它们作用于酪氨酸激酶受体、VEGF、c-Met或mTOR通路。随着这一进展，对肾肿瘤生物学的透彻理解和准确的组织学诊断已变得具有至关重要的实际意义。
