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Wilms tumour

Nature Reviews Disease Primers volume 7, Article number: 75 (2021) Cite this article

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Abstract

Wilms tumour (WT) is a childhood embryonal tumour that is paradigmatic of the intersection between disrupted organogenesis and tumorigenesis. Many WT genes play a critical (non-redundant) role in early nephrogenesis. Improving patient outcomes requires advances in understanding and targeting of the multiple genes and cellular control pathways now identified as active in WT development. Decades of clinical and basic research have helped to gradually optimize clinical care. Curative therapy is achievable in 90% of affected children, even those with disseminated disease, yet survival disparities within and between countries exist and deserve commitment to change. Updated epidemiological studies have also provided novel insights into global incidence variations. Introduction of biology-driven approaches to risk stratification and new drug development has been slower in WT than in other childhood tumours. Current prognostic classification for children with WT is grounded in clinical and pathological findings and in dedicated protocols on molecular alterations. Treatment includes conventional cytotoxic chemotherapy and surgery, and radiation therapy in some cases. Advanced imaging to capture tumour composition, optimizing irradiation techniques to reduce target volumes, and evaluation of newer surgical procedures are key areas for future research.

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Fig. 1: Timeline of key clinical advances that established the modern clinical management of children with Wilms tumour.
Fig. 2: The estimated mortality for kidney cancers according to geographical area.
Fig. 3: The incidence of Wilms tumour according to geographical area and ethnicity.
Fig. 4: Age-specific incidence of Wilms tumour according to gender, laterality and geographical area.
Fig. 5: Biology of paediatric renal tumours.
Fig. 6: Different histological patterns of Wilms tumour.

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Acknowledgements

The authors thank both the SIOP Renal Tumour Study Group and the Children’s Oncology Group Renal Tumour Committee for their collective expertise. Their work laid the foundations for this Review article. The authors also thank parents and survivors of childhood Wilms tumour for their contribution to setting research priorities.

Author information

Authors and Affiliations

  1. Department of Medical Oncology and Hematology, Paediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Filippo Spreafico

  2. Department of Paediatrics, IWK Health, Dalhousie University, Halifax, Nova Scotia, Canada

    Conrad V. Fernandez

  3. Department of Paediatric Haematology and Oncology, Rigshospitalet, Copenhagen, Denmark

    Jesper Brok

  4. Cancer Control Center, Osaka International Cancer Institute, Osaka, Japan

    Kayo Nakata

  5. Department of Pathology, Sidra Medicine, Doha, Qatar

    Gordan Vujanic

  6. Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Cincinnati, OH, USA

    James I. Geller

  7. Theodor-Boveri-Institute, Developmental Biochemistry, and Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg, Germany

    Manfred Gessler

  8. Research Center, Boldrini Children’s Hospital, Genetics and Molecular Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil

    Mariana Maschietto

  9. Wellcome Sanger Institute, Hinxton, UK

    Sam Behjati

  10. Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

    Sam Behjati

  11. Department of Paediatrics, University of Cambridge, Cambridge, UK

    Sam Behjati

  12. National Cancer Research Institute Children’s Group Consumer Representative, London, UK

    Angela Polanco

  13. Department of Child Health, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana

    Vivian Paintsil

  14. Division of Hematology, Oncology and Bone Marrow Transplantation, Department of Paediatrics, University of Colorado, Aurora, CO, USA

    Sandra Luna-Fineman

  15. Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK

    Kathy Pritchard-Jones

Authors
  1. Filippo Spreafico
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  2. Conrad V. Fernandez
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  3. Jesper Brok
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  4. Kayo Nakata
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  5. Gordan Vujanic
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  6. James I. Geller
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  7. Manfred Gessler
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  8. Mariana Maschietto
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  9. Sam Behjati
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  10. Angela Polanco
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  11. Vivian Paintsil
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  12. Sandra Luna-Fineman
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  13. Kathy Pritchard-Jones
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Contributions

Introduction (F.S. and K.P.-J.); Epidemiology (F.S., K.P.-J. and K.N.); Mechanisms/pathophysiology (F.S., K.P.-J., M.G., M.M. and S.B.); Diagnosis, screening and prevention (F.S., K.P-J., C.V.F., J.B., S.L.-F. and G.V.); Management (F.S., C.V.F., K.P.-J., S.L.-F. and V.P.); Quality of life (F.S., K.P.-J. and A.P.); Outlook (F.S., K.P.-J., C.V.F., J.B., M.G., S.L.-F. and J.I.G.); Overview of the Primer (F.S. and K.P.-J.).

Corresponding author

Correspondence to Filippo Spreafico.

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All authors declare no competing interests.

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Peer reviewer information

Nature Reviews Disease Primers thanks R. Furtwängler, N. Cost, J. Kalapurakal and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Glossary

Nephron-sparing surgery

An operation to remove a kidney tumour by removing only part of the surrounding normal renal parenchyma.

Nephrogenic rests

Abnormally persistent foci of embryonal cells regarded as precursor lesions of Wilms tumour. Rests are subdivided into two main types: perilobar, confined to the periphery of the renal lobe, and intralobar, found anywhere within the renal lobe.

Overgrowth syndromes

A heterogeneous group of disorders in which the main characteristic is that weight, height or head circumference is two to three standard deviations above the mean for sex and age. The different presentations are dependent on the developmental pathways and organ systems affected.

Aniridia

A rare condition characterized by a partial or complete absence of the iris of the eye.

Nephrotic syndrome

A rare clinical disorder defined by massive proteinuria (>40 mg/m2 per hour) responsible for hypoalbuminaemia (<25 g/l), with resulting hyperlipidaemia, oedema, and various complications.

WAGR syndrome

A rare contiguous gene deletion syndrome (Wilms tumour (WT), aniridia, genitourinary anomalies, and range of developmental delays) associated with a 45–60% risk of developing WT.

Hypospadias

An anatomical congenital malformation of the male external genitalia, characterized by abnormal development of the urethral fold and the ventral foreskin of the penis that causes abnormal positioning of the urethral opening.

Cryptorchidism

The absence of at least one testicle from the scrotum.

Denys–Drash syndrome

A rare condition caused by mutations in the tumour-suppressor gene WT1, characterized by a triad of disorders: ambiguous genitalia, nephrotic syndrome leading to end-stage renal disease, and Wilms tumour.

Frasier syndrome

A rare autosomal recessive disorder that presents with male pseudohermaphroditism with gonadal dysgenesis, renal failure in early adulthood and increased risk of developing gonadoblastoma.

Chromothripsis

A catastrophic chromosomal shattering event associated with random rejoining.

Li–Fraumeni syndrome

An inherited autosomal dominant cancer predisposition disorder that is usually associated with abnormalities in TP53 located on chromosome 17p13.

Anaplasia

Cells with hyperchromatic, pleomorphic nuclei that are three times larger than adjacent cells and have abnormal mitotic figures. Anaplasia is associated with a poor response to chemotherapy.

Oophorectomy

A surgical procedure to remove one or both ovaries.

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Spreafico, F., Fernandez, C.V., Brok, J. et al. Wilms tumour. Nat Rev Dis Primers 7, 75 (2021). https://doi.org/10.1038/s41572-021-00308-8

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