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American Journal of Pathology, Vol 113, 8-18, Copyright © 1983 by American Society for Investigative Pathology

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Histologic characterization of renal tumors (nephroblastomas) induced transplacentally in IIIVO/J and WH/J rabbits by N-ethylnitrosourea

GC Hard and RR Fox

The histologic features of 63 renal tumors induced in 39 rabbits of two partially inbred strains, IIIVO/J and WH/J, by transplacental exposure to N-ethylnitrosourea (ENU) were analyzed. All tumors in the series conformed to nephroblastoma, permitting the establishment of histologic standards for this neoplasm in the rabbit as well as observations on tumor progression. Essentially, nephroblastoma proved to be predominantly an epithelial tumor identifying with metanephrogenic blastema, which was presumed to be the tissue of origin during fetal development. The outstanding features comprised clusters or sheets of undifferentiated blastemalike tissue and differentiation along the epithelial pathway into tubular profiles and structures suggestive of primitive, nonvascularized glomeruli. The latter were frequently of a complex nature, with a papillary configuration. On the other hand, no definitive evidence of bipotential differentiation into malignant secondary mesenchyme was found, there being no recognizable areas of fibrosarcomatous elements or specialized connective tissue such as smooth or striated muscle, adipose tissue, cartilage, or osteoid. Mesenchymelike fascicular disposition of neoplastic cells between blastemal clusters was an acquired feature seen in advanced tumors but not in small early lesions. By light microscopy alone it was not possible to determine whether this represented a conformational change of tumor cells or true bipotential differentiation into neoplastic secondary mesenchyme. However, the reticulin pattern was not characteristic of sarcoma. A conspicuous feature accompanying the growth and development of tumors was the magnitude of host fibrous reaction discernible only as a simple ramifying stroma in the earliest lesions but attaining impressive proportions both within and around the tumor with advancing age. Increasing collagen formation appeared to be associated with ischemic necrosis of tumor tissue. Other features of advanced tumors were the presence of discrete foci of differentiated tubular structures suggestive of mature medullary elements and small islands of squamoid differentiation. Metastases occurred only in rabbits of strain IIIVO/J, which had been subjected to a single dose of the carcinogen, representing an incidence in this subgroup of 25%. Nephroblastomas resulting from transplacental induction in IIIVO/J rabbits, particularly by single, high doses of ENU, appear to provide a suitable model for the predominant histologic form of the Wilms' tumor complex in man.