• Clinical science

Wilms tumor (Nephroblastoma)

Summary

Wilms tumor (nephroblastoma) is the most common renal malignancy in children, typically affecting children between 2 and 5 years of age. A minority of cases are associated with specific syndromes (e.g., WAGR, Beckwith-Wiedemann) and gene mutations (e.g., WT1). Wilms tumor is typically an incidental finding that manifests as a large abdominal mass. Other signs and symptoms may occur, such as hematuria and abdominal pain, especially in tumors that are large, ruptured, or metastasized. Treatment consists of tumor resection and chemotherapy for all stages (except for very low-risk tumors), while radiation is predominantly used in advanced disease.

Epidemiology

  • Peak incidence: between 2 and 5 years
  • Most common malignant neoplasm of the kidney in children

References: [1]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

The exact etiology of Wilms tumor remains unknown; , but it is associated with several genetic mutations and syndromes.

Genetic predisposition [2][3]

Associated syndromes [5]

WAGR syndrome consists of Wilms tumor, Aniridia, Genitourinary anomalies, and Range of intellectual disability.

Denys-Drash syndrome is a mild form of WAGR without aniridia or intellectual disability.

Clinical features

Abdominal symptoms

  • Palpable abdominal mass (often found incidentally)
    • Non-tender
    • Unilateral and large but not crossing midline
    • Smooth and firm
  • Abdominal pain (∼ 40% of cases)

Other signs and symptoms

Wilms tumor should be suspected in a toddler with a non-tender abdominal mass, especially if it is firm, smooth, and associated with hematuria and/or hypertension.

Careless palpation of a Wilms tumor can result in rupture of the renal capsule and tumor spillage!

Stages

National Wilms Tumor Study (NWTS) system [8]
Stage Tumor location Tumor spread Surgery
I
  • Unilateral
  • Limited to the kidney
  • No renal sinus vessel involvement
  • Complete resection with no tumor beyond the excision margins
II
  • Unilateral
III
  • Unilateral
  • Incomplete resection with residual tumor remaining postoperatively (e.g., not resectable due to infiltration into vital structures)
IV
  • Unilateral
V
  • Bilateral

Diagnostics

Biopsy is usually reserved for assessing nodules that are suspected metastases, as tumor capsule rupture and spillage results in more advanced staging and intensive treatment.

Pathology

Overview

  • Wilms tumor consists of embryonic glomerular structures.
  • May include cysts, hemorrhage, or necrosis
  • Typically has a pseudocapsule

Histology

  • Classic type: consists of three cell types
    • Epithelial cells (i.e., glomeruli and tubules)
    • Stromal cells
    • Undifferentiated blastemal cells of metanephric origin
  • Anaplastic type
    • Contains multipolar polypoid mitotic figures
    • Marked hyperchromasia of nuclei

Differential diagnoses

Neuroblastoma

Differential diagnosis of Wilms tumor and neuroblastoma [9]
Wilms tumor Neuroblastoma
Clinical findings (e.g., fever, weight loss)
  • Less common
  • More common
CT/MRI findings (e.g., calcifications, vascular encasement, midline crossing)
  • Less common
  • More common
I-123 MIBG scan
  • Negative
  • Positive (∼ 90% of cases)
Catecholamine metabolites in urine (VMA, HVA)
  • Negative
  • Positive (∼ 70–90% of cases)

Other renal tumors

The differential diagnoses listed here are not exhaustive.

Treatment

Treatment of Wilms tumor according to stage
Treatment Stages I and II Stages III and IV Stage V (bilateral)
Surgery Renal parenchymal-sparing resection
  • No
  • Yes
Nephrectomy
  • Yes
  • No
Chemotherapy Preoperative chemotherapy
  • No
  • Yes
Doxorubicin
  • No
  • Yes
Dactinomycin and vincristine
  • Yes
Radiation
  • No
  • Possible
  • Yes

Prognosis

  • Good prognosis: survival rates are > 90% [10]
  • The majority of tumor recurrences happen within two years of treatment.

Prevention

  • Regular screening of children with associated syndromes (e.g., abdominal ultrasound every three months until the age of 8)
  • 1. American Cancer Society. Key Statistics for Wilms Tumors. https://www.cancer.org/cancer/wilms-tumor/about/key-statistics.html. Updated January 8, 2012. Accessed November 3, 2020.
  • 2. Cristy Ruteshouser E, Robinson SM, Huff V . Wilms Tumor Genetics: Mutations in WT1, WTX, and CTNNB1 Account for Only About One-Third of Tumors. Genes Chromosomes Cancer. 2008; 47(6): pp. 461–470. doi: 10.1002/gcc.20553.
  • 3. King-Underwood L, Pritchard-Jones K. Wilms' Tumor (WT1) Gene Mutations Occur Mainly in Acute Myeloid Leukemia and May Confer Drug Resistance. Blood. 1998; 91(8): pp. 2961–2968. url: http://www.bloodjournal.org/content/91/8/2961/tab-article-info.
  • 4. D. Dao. Multipoint analysis of human chromosome 11p15/mouse distal chromosome 7: inclusion of H19/IGF2 in the minimal WT2 region, gene specificity of H19 silencing in Wilms' tumorigenesis and methylation hyper-dependence of H19 imprinting. Hum Mol Genet. 1999; 8(7): pp. 1337–1352. doi: 10.1093/hmg/8.7.1337.
  • 5. Scott RH. Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour. J Med Genet. 2006; 43(9): pp. 705–715. doi: 10.1136/jmg.2006.041723.
  • 6. Fischbach BV. WAGR syndrome: a clinical review of 54 cases. Pediatrics. 2005; 116(4): pp. 984–988. doi: 10.1542/peds.2004-0467.
  • 7. National Organization for Rare Disorders. Denys-Drash Syndrome. https://rarediseases.info.nih.gov/diseases/5576/denys-drash-syndrome. Updated October 1, 2018. Accessed October 31, 2018.
  • 8. American Cancer Society. How Is Wilms Tumor Staged?. https://www.cancer.org/cancer/wilms-tumor/detection-diagnosis-staging/staging.html. Updated February 16, 2016. Accessed February 28, 2017.
  • 9. Dickson PV, Sims TL, Streck CJ et al. AVOIDING MISDIAGNOSING NEUROBLASTOMA AS WILMS TUMOR. J Pediatr Surg. 2008; 43(6): pp. 1159–1163. doi: 10.1016/j.jpedsurg.2008.02.047.
  • 10. Phelps H, Kaviany S, Borinstein S, Lovvorn H. Biological Drivers of Wilms Tumor Prognosis and Treatment. Children. 2018; 5(11): p. 145. doi: 10.3390/children5110145.
  • Neville H, Ritchey ML, Shamberger RC, Haase G, Perlman S, Yoshioka T. The occurrence of Wilms tumor in horseshoe kidneys: a report from the National Wilms Tumor Study Group (NWTSG). J Pediatr Surg. 2002; 37(8): pp. 1134–7. pmid: 12149688.
last updated 11/03/2020
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