METHODS. Clinical and pathologic features of 8 malignant tumors from 6 TSC patients ranging in age from 22 months to 21 years are reviewed. Six tumors were renal, one was from the inguinal region, and one was from the brain. The tumors were analyzed for loss of heterozygosity (LOH) in the chromosomal regions of the TSC1, TSC2, and VHL genes.

RESULTS. Three patients (ages 7, 8, and 20 years) had renal cell carcinomas (RCCs). Two of these patients had multifocal RCCs. All three patients with RCC also had prominent multifocal dysplasia of renal cyst epithelium. Two patients (ages 20 and 21 years) had malignant angiomyolipomas (1 renal and 1 inguinal). One patient (age 22 months) had a Grade 4 giant cell astrocytoma (glioblastoma multiforme). LOH in the region of the TSC2 gene was found, either in the malignant tumor or in benign tumors, in all five patients whose DNA could be analyzed.

CONCLUSIONS. Children with TSC, as well as adults with the disease, are at risk for developing malignant tumors. Two types of renal malignancy occur in TSC: RCC, which appears to arise from dysplastic renal cyst epithelial cells, and malignant angiomyolipoma. Tumors cytologically similar to malignant angiomyolipomas also may occur at extrarenal sites. LOH analyses suggest that the majority of patients with TSC who develop malignant tumors have germline TSC2, rather than TSC1, gene mutations. Cancer 1998;83:2208-16. (C) 1998 American Cancer Society.