FOCAL VERSUS DIFFUSE ANAPLASIA IN WILMS-TUMOR - NEW DEFINITIONS WITH PROGNOSTIC-SIGNIFICANCE - A REPORT FROM THE NATIONAL WILMS-TUMOR STUDY-GROUP

Anaplasia, defined by the presence of extreme nuclear and mitotic atyp ia, is a potent marker of adverse prognosis in Wilms tumor (WT). Anapl astic WT cells apparently have increased resistance to therapy rather than increased aggressiveness. The distribution of anaplasia should th erefore have critical prognostic relevance. The original definitions f or focal anaplasia (FA) and diffuse anaplasia (DA) were based on quant itative rather than topographical criteria and lacked prognostic signi ficance. A new definition was developed based on the distribution of a naplastic changes within the tumor: FA applies only to tumors with ana plasia confined to one or a few discrete loci within the primary tumor , with no anaplasia or marked nuclear atypia elsewhere. This revised d efinition was evaluated in 165 cases with anaplastic WT entered on the third and fourth National Wilms Tumor Study. Only three relapses and one death occurred among 39 cases with FA, regardless of tumor stage, a result comparable to that for nonanaplastic WT. Eight children with metastases at diagnosis and FA in the primary tumor were alive and fre e of relapse; 22 of 23 children with stage IV DA WT died of tumor. Thi s new definition reinforces the importance of carefully documenting th e exact site from which each tumor section is obtained.