Wilms Tumor

Abstract

Wilms tumor (WT) is the most common neoplasm of the kidney in children. It is an embryologic tumor that histologically mimics renal embryogenesis and is composed of a variable mixture of stromal, blastemal, and epithelial elements. Nephrogenic rests, generally considered to be precursor lesions of the WT, are foci of the embryonic metanephric tissue that persist after the completion of renal embryogenesis. These are classified as perilobar and intralobar based on their location and maybe present as single or multiple foci. Intralobar and perilobar rests and the tumors arising from these rests differ morphologically and are characterized by 2 different sets of genetic abnormalities involving 2 adjacent foci, WT1 and WT2, on the short arm of chromosome 11. WTs arising in the intralobar rests tend to be stromal predominant and have a mutation or deletion of WT1. Germline mutation in WT1 may be associated with syndromic conditions such as WAGR and Denys-Drash syndromes. Perilobar rests and their corresponding tumors usually have loss of imprinting/loss of heterozygosity involving WT2, which contains several parentally imprinted genes. Loss of function of these genes, if present constitutionally, may be associated with Beckwith-Wiedemann syndrome or may result in isolated hypertrophy. Abnormalities in several other genes may also be seen in WT. These include WTX, (on chromosome X), CTNNB1 (chromosome 3), and TP53 (chromosome 17) among others. WT with loss of heterozygosity at 1p and 16q may have poor prognosis, requiring aggressive therapy. Treatment modalities for WT have evolved over many decades, primarily through the efforts of Dr J Bruce Beckwith at National WT study. This work is now being carried out by Children Oncology Group in North America and International Society of Pediatric Oncology in Europe. Although their therapeutic approaches are somewhat different, both have reported excellent results with equally high cure rates.

Identification of proteins associated with pediatric bilateral Wilms tumor

“…WT is the most common abdominal solid cancer of children, mostly discovered by parents during bathing or while dressing the children (7). BWT is rare, accounting for ~5% of all patients with WT, and is more complex in its diagnosis and treatment compared with UWT (7).…”

“…BWT is rare, accounting for ~5% of all patients with WT, and is more complex in its diagnosis and treatment compared with UWT (7). In addition, according to WT staging criteria formulated by the Children Tumor Institute based on surgery and histopathology, BWT was confirmed as stage V and was worse than stages I–IV of WT in prognosis (8).…”

A unified pathogenesis for kidney diseases, including genetic diseases and cancers, by the protein-homeostasis-system hypothesis

“…Also, it is proposed that tumorigenesis in Wilms tumor is associated with embryonal cells in the nephrogenic rests. These cell clusters have a genetic defect, including Wilms tumor gene ( WT1 ), which may sustain additional mutations and transform into tumour cells [55]. In the PHS hypothesis, a cancer cell also originates from a gene defect in an intracellular protein which may be essential for cell survival.…”

“…Some malignancies are associated with genetic diseases, such as familial adenomatous polyposis in colorectal cancers or WAGR syndrome and Denys-Drash syndrome that predispose to Wilms tumor [55,62]. It is possible that various tissue cells which are affected with chronic infections or genetic defects may have a short turn-over time of replication with subsequent fragility in a genetic variation, although chronic infections may induce epigenetic changes such as gene methylation and activation of microRNAs in the infected cells.…”

An unusual Wilms tumor with urethral recurrence: rare case report and literature review

“…This is not unusual, as the majority of WT cases are classified as sporadic [22] , with germline mutation thought to only account for about 10%-15% of WT [21] .…”