Focal Versus Diffuse Anaplasia in Wilms Tumor—New Definitions with Prognostic Significance

Abstract

Anaplasia, defined by the presence of extreme nuclear and mitotic atypia, is a potent marker of adverse prognosis in Wilms tumor (WT). Anaplastic WT cells apparently have increased resistance to therapy rather than increased aggressiveness. The distribution of anaplasia should therefore have critical prognostic relevance. The original definitions for focal anaplasia (FA) and diffuse anaplasia (DA) were based on quantitative rather than topographical criteria and lacked prognostic significance. A new definition was developed based on the distribution of anaplastic changes within the tumor: FA applies only to tumors with anaplasia confined to one or a few discrete loci within the primary tumor, with no anaplasia or marked nuclear atypia elsewhere. This revised definition 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 free of relapse; 22 of 23 children with stage IV DA WT died of tumor. This new definition reinforces the importance of carefully documenting the exact site from which each tumor section is obtained.

Rationale for the treatment of Wilms tumour in the UMBRELLA SIOP–RTSG 2016 protocol

“…In rare instances in which the diagnosis of Wilms tumour is histologically proven before surgery, preoperative chemotherapy is recommended, similar to treatment strategies for Wilms tumour diagnosed in childhood. In contrast to the histological classification of childhood Wilms tumours, both focal and diffuse ana plasia are considered high-risk subtypes in adults, as no evidence exists that patients with focal anaplasia have better outcomes 50 . Adult patients often experience considerable delays before starting postoperative chemotherapy, owing to the time needed to verify histology [46][47][48][49] .…”

Current Therapy for Wilms’ Tumor

“…A retrospective study of pathology samples from the first National Wilms' Tumor Study (NWTS-1) showed that anaplasia (irregular mitotic figures, large nuclear size, and hyperchromasia) is associated with adverse outcome [4]. Anaplasia may be diffuse or focal; focal anaplasia portends a prognosis between that of tumors without anaplasia (a so-called "favorable" or "standard" histologic feature) and that of tumors with diffuse anaplasia [5,6]. Clear-cell sarcoma of the kidney and malignant rhabdoid tumor of the kidney, initially believed (a) The tumor extends beyond kidney or penetrates through the renal capsule and/or fibrous pseudocapsule into perirenal fat but is completely resected (resection margins "clear") (b) The tumor infiltrates the renal sinus and/or invades blood and lymphatic vessels outside the renal parenchyma but is completely resected (c) The tumor infiltrates adjacent organs or vena cava but is completely resected…”

Prognóstico de pacientes com tumor de Wilms unilateral no Rio de Janeiro, 1990-2000

“…This finding is thus characterized as a marker of "unfavorable histology" and one of the most relevant indicators of poor prognosis. 1,11 A study by the NWTSG 9 showed that tumors presenting diffuse anaplasia had worse prognosis than those with focal anaplasia. Furthermore, some studies have reported that local recurrence of the disease is more frequent in patients with local or diffuse rupture of the tumor during surgery, or in cases where there was microscopic involvement of the surgical resection margins.…”