–Visceromegaly

–Associated with WT2 (see below) on chromosome 11p15 at a rate of 15%

•Isolated hemihypertrophy

•In neurofibromatosis, Perlman syndrome, Simpson–Golabi–Behmel syndrome

•Familial occurrence:

–1–2% of nephroblastomas with chromosomal anomalies and familial gene loci (familial WT-1, familial WT-2; see below)

–Sometimes bilateral nephroblastoma

–Increased risk in homozygous twins

11.4Pathology

11.4.1Macroscopic Features

•High variation in tumor size and tissue morphology

•Tumor often with lobular structure of gray to pink color and with a capsule

•Occasionally with cysts and hemorrhages

•Tumor growth into the renal vein

•Bilateral 5–7.5%, multifocal 12% spread in one kidney

11.4.2Microscopic Features

•Mostly mixed form of epithelial blastemic and stromal cellular components as well as with various degrees of cell differentiation

•In well-differentiated forms, glandular acini or glomerular structures separated by stroma elements which arrange cells in cords or nests

•Stroma with fibroblastic or myxomatous components, containing smooth muscle, skeletal muscle, cartilage, and fatty tissue

•Nephrogenic residual tissue:

–In 1% of all autopsies of small children: in 35% of children with unilateral nephroblastoma and in the majority of children with bilateral nephroblastoma

–Hyperplastic nephrogenic tissue with differentiation and disappearance under chemotherapy

•Minority with undifferentiated histology:

–Anaplastic nephroblastoma at a rate of 5%: focal or diffuse anaplasia with large and atypical nuclei, hyperchromatism and abnormal mitosis

–Clear-cell sarcoma (3%): polygonal cells with crystal-clear cytoplasm, separated into nests by thin spindle-cell septa containing blood vessels; high incidence of bone or lung metastases; high rate of relapse; age less than 2 years in 85% of children; occasionally deletion 22q11–12