Intralobar Nephroblastematosis: Precursor Lesions of Nephroblastoma in the Sprague-Dawley Rat

Abstract

Abstract. Precursor lesions of spontaneous nephroblastoma (NB) in rats are here characterized for the first time, with a description of the progression of the tumor in prenatal, postnatal, and adult Sprague-Dawley rats (Upj:TUC[SD]spf.nb), which are genetically predisposed to the tumor. NB in the rat starts as a focal or multifocal interstitial accumulation of intensely basophilic immature (blastema) cells, invariably located in the deep renal cortex. Precursor lesions of NB (designated intralobar nephroblastematosis) and the early tumor do not overtly disrupt the overall structural organization and integrity of the kidney. However, with increasing size and neoplastic transformation, these lesions trap, compress, and displace/replace the existing renal tubules. Nephroblastematous foci occurred in one or both kidneys in tumor-bearing or non-tumor-bearing kidneys and in young and old rats. Like the precursor lesions, the early tumors in rats as young as 6 weeks of age were located in the inner cortex. Well-developed NB was comprised of blastema cells arranged in dense sheets or in ductular structures surrounded by mantles of blastema cells supported by varying amounts of fibromatous stroma. The stroma in one rat was hemangiosarcomatous (triphasic Wilms' tumor). Tumor cells were slightly pleomorphic and had varying amounts of granular cytoplasm with sparse organelles and showed junctional complexes and basal laminae whose frequency apparently depended upon whether the blastema cell tended to differentiate to epithelial or mesenchymal cells. NB in the rat was morphologically similar to immature preand postnatal kidneys, regardless of whether it occurred in young or old rats. The deep cortical location and interstitial infiltrative characteristics of precursor lesions of NB in the rat were analogous to intralobar nephrogenic rests, a variant of the precursor to Wilms' tumor in children.Key words: Intralobar nephroblastematosis; kidney; light microscopy; nephroblastoma; precursor; SpragueDawley rats; ultrastructure.Spontaneous nephroblastoma (NB), a common solid primary renal tumor in children, 11 occurs rarely in young adult rats, with an incidence of 0-0.4%. 8,12,17,19 Recently, a 14% incidence of NB was reported in a subline of Sprague-Dawley rat (Upj:TUC[SD]spf.nb) genetically predisposed to the tumor. 25 Although the progression of NB has been briefly described in a chemically induced tumor in the rat, 13 the evolution of the spontaneous tumor in animals has not been fully characterized because most of the published works are single case reports of tumors that were usually large and pseudoencapsulated and/or had displaced a substantial portion of the kidney at the time of evaluation. Precursor lesions of NB in children have been described under a variety of names, including persistent nodular blastoma, incipient Wilms' tumor, in situ nephroblastoma, Wilms' tumorelet, tubular adenoma, nephroblastic dysplasia, sclerosing hamartoma, and nephroblastomatosis. 22 A classification of precursor of NB in children has been...

Classification of Renal Proliferative Lesions in Rats and/or Mice and Their Diagnostic Problems: Report from the Working Group of the Japanese Society of Toxicologic Pathology.

“…These lesions are considered to be related to the tumorigenesis of nephroblastomas in human. The similar lesion was recently reported in the rats as "intralobar nephroblastematosis" 11 . The recognition that an intralobar nephroblastematosis is the precursor of the nephroblastomas is necessary.…”

Nephrogenic Rest in a Crl:CD (SD)IGS BR Rat

“…8 In other reports, the generic term nephrogenic rest has been used for a focus of abnormally persistent nephrogenic cells, retaining cells that can be induced to form a Wilms' tumor. 1 Lesions characteristic of nephrogenic rests have been reported in children, the Sprague-Dawley rat, 6 and the Mastiff dog. 11 When present in diffuse or multifocal distribution, nephroblastomatosis more specifically defines the morphologic change observed.…”

Nephroblastomatosis and nephroblastoma in nonhuman primates

“…They are usually well circumscribed and can range in size from several centimeters to masses weighing as much as 27 kg, and are usually found in pigs <1 year of age [10]. Although rare, these tumors have been reported in most other species including chickens, cattle, horses, sheep, deer, dogs, cats, rabbits, and rats [8, 10, 12, 16, 17].…”