Nephrogenic rest

Abstract: Nephrogenic rests consist of foci of primitive renal cells, typically microscopic, that are found within the normal kidney tissue of children with Wilms' tumour. To study the relationship between nephrogenic rests and the associated tumours, we screened these lesions for mutations in the 11p13 Wilms' tumour suppressor gene, WT1. In two cases in which the Wilms' tumour contained a somatic WT1 mutation, the nephrogenic rest had the identical mutation. Nephrogenic rests and Wilms' tumours are therefore topographically distinct lesions that are clonally derived from an early renal stem cell. Inactivation of WT1 appears to be an early genetic event which can lead to the formation of nephrogenic rests, enhancing the probability that additional genetic hits will lead to Wilms' tumour.

Abstract: Nephrogenic adenofibroma is a novel kidney tumor of young people (mean age of presentation, 13 years), who present with polycythemia, hypertension, or hematuria, which resolve following nephrectomy. The typical nephrectomy specimen contains a solitary, nonencapsulated, vaguely circumscribed, irregularly shaped or spherical, firm mass with either tan, gray-white, or pale yellow coloration. Cysts are sometimes present within the tumor. The histologic appearance is distinctive and characterized by a marked proliferation of spindled mesenchymal cells resembling the classical type of congenital mesoblastic nephroma, encasing discrete nodules of embryonal epithelium similar to the hyperplastic nephrogenic rests (nephroblastomatosis) usually associated with Wilms' tumor. The mesenchymal component consists of a fascicular proliferation of tightly interlaced, uniform, benign-appearing spindled cells that immunostatin for vimentin and fibronectin, but not desmin or actin. The epithelial component consists of discrete islands of blastemal cells that are partially or fully differentiated toward tubular, tubulopapillary, or papillary structures. Psammoma bodies are plentiful. Embryonal epithelium immunostains for cytokeratin but not epithelial membrane antigen. The overall histologic appearance of the mesenchymal and epithelial components is benign, and preliminary clinical data suggest that the tumor has a benevolent course. Two cases, however, contained small, well-circumscribed papillary lesions near the renal pelvis that resembled low-grade collecting duct carcinoma. The clinical implications of the latter finding are unclear.

Abstract: Nephrogenic rests are precursor lesions associated with about 40% of Wilms' tumors. This study identifies genetic steps occurring in the development of Wilms' tumor. Thirty-four Wilms' tumors with nephrogenic rests and/or areas of anaplasia were microdissected from paraffin sections to determine whether and at what stage loss of heterozygosity (LOH) occurred, using polymerase chain reaction-based polymorphic markers at 11p13, 11p15, and 16q. LOH at these loci have been identified in Wilms' tumors and are associated with identified or putative tumor suppressor genes. Three cystic nephromas/cystic partially differentiated nephroblastomas were also examined. LOH was detected in six cases at 11p13 and in six cases at 11p15, and two of these cases had LOH at both loci. All intralobar rests showing LOH also showed LOH in the tumor. A case with a small perilobar rest showed LOH of 11p13 only in the tumor. Five cases showing LOH at 16q were identified (this was identified only in the tumor, and not in the associated rest), and three of these had recurrence of the tumor. Two cases had a WT1 mutation (one germline and the other somatic), as well as LOH in both the intralobar rest and the tumor. A cystic partially differentiated nephroblastoma showed loss at 11p13 and 11p15, as well as at 16q. This study suggests that LOH at 11p13 and 11p15 and WT1 mutations are early events but that LOH at 16q occurs late in the pathogenesis of Wilms' tumor. Intralobar and perilobar nephrogenic rests are known to have different biological behaviors, and this study suggests that they are genetically different. A multistep model of Wilms' tumor pathogenesis is supported by these findings.

Abstract: Nephrogenic rests are the consequence of residual metanephric tissue in a fully developed kidney. They usually occur along the perimeter of a mature renal lobe (i.e., perilobar), within the lobe itself (i.e., intralobar), or both (i.e., combined). Nephrogenic rests can be grossly obvious or microscopically discrete. Nephroblastomatosis designates nephrogenic rests that are multifocal or diffuse, and implies more extensive disease. Universal (panlobar) nephroblastomatosis denotes complete replacement of the renal lobe by nephrogenic tissue. The fate of nephrogenic rests and nephroblastomatosis varies and includes obsolescence, sclerosis, dormancy, hyperplasia, or neoplasia. Evidence strongly suggests that neoplastic transformation of nephrogenic rests results in Wilms' tumor (nephroblastoma). Nephrogenic rests almost always occur in the setting of Wilms' tumor; perilobar rests show a strong association with synchronous bilateral Wilms' tumors, whereas intralobar rests are more strongly associated with metachronous tumors. Genetic studies have shown that nephrogenic rests often share many of the same chromosomal defects as Wilms' tumor, which provides further evidence that they are precursors to nephroblastoma. Thus, nephrogenic rests are recognized as clinically significant entities requiring adequate detection and close surveillance. Heightened awareness regarding the clinical relevance of nephrogenic rests and nephroblastomatosis (1) has led to improved detection of these precancerous lesions, (2) fostered more intensive investigation into their biologic behavior, and (3) initiated in-depth discussions about potentially new treatment regimens. The pathologists' ability to identify and detect nephrogenic rests has benefited from the more efficient Beckwith classification. Radiologists have deployed high-resolution radiologic/imaging modalities to improve detection of nephrogenic rests in situ. Clinicians and surgeons are more aware of the impact that nephrogenic rests have upon patient management. Despite this progress, more data is needed to further define these lesions.