Wilms' tumor

Typical signs and symptoms of Wilms' tumor include the following:{{citation needed|date=April 2021}}

• a painless, palpable abdominal mass
• loss of appetite
• abdominal pain
• fever
• nausea and vomiting
• blood in the urine (in about 20% of cases)
• high blood pressure in some cases (especially if synchronous or metachronous bilateral kidney involvement)
• Rarely as varicoceleErginel B, Vural S, Akın M, Karadağ CA, Sever N, Yıldız A. et al (2014) Wilms' tumor: a 24-year retrospective study from a single center. Pediatr Hematol Oncol 31: 409–414

File:Wilms tumor.jpg

File:Part of whole slide image of a Wilms' tumor of the kidney.jpg. The surrounding renal parenchyma is more eosinophilic (pink) than the rather grey tumor stroma.]]

Wilms' tumor has many causes, which can broadly be categorized as syndromic and non-syndromic. Syndromic causes of Wilms' tumor occur as a result of alterations to genes such as the Wilms Tumor 1 (WT1) or Wilms Tumor 2 (WT2) genes, and the tumor presents with a group of other signs and symptoms. Non-syndromic Wilms' tumor is not associated with other symptoms or pathologies.{{Citation|last=PDQ Pediatric Treatment Editorial Board|title=Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ®): Health Professional Version|date=2002|url=https://www.ncbi.nlm.nih.gov/books/NBK65842/|work=PDQ Cancer Information Summaries|publisher=National Cancer Institute (US)|pmid=26389282|access-date=2018-11-26}} Many, but not all, cases of Wilms' tumor develop from nephrogenic rests, which are fragments of tissue in or around the kidney that develop before birth and become cancerous after birth. In particular, cases of bilateral Wilms' tumor, as well as cases of Wilms' tumor derived from certain genetic syndromes such as Denys-Drash syndrome, are strongly associated with nephrogenic rests. Most nephroblastomas are on one side of the body only and are found on both sides in less than 5% of cases, although people with Denys-Drash syndrome mostly have bilateral or multiple tumors.{{cite journal | vauthors = Guaragna MS, Soardi FC, Assumpção JG, Zambaldi L, Cardinalli IA, Yunes JA, de Mello MP, Brandalise SR, Aguiar S | s2cid = 205860918 | title = The novel WT1 gene mutation p.H377N associated to Denys-Drash syndrome | journal = Journal of Pediatric Hematology/Oncology | volume = 32 | issue = 6 | pages = 486–8 | date = August 2010 | pmid = 20562648 | doi = 10.1097/MPH.0b013e3181e5e20d }} They tend to be encapsulated and vascularized tumors that do not cross the midline of the abdomen. In cases of metastasis it is usually to the lung. A rupture of Wilms' tumor puts the patient at risk of bleeding and peritoneal dissemination of the tumor. In such cases, surgical intervention by a surgeon who is experienced in the removal of such a fragile tumor is imperative.{{citation needed|date=June 2020}}

Pathologically, a triphasic nephroblastoma comprises three elements:{{cite book|last1=Popov|first1=Sergey D.|last2=Sebire|first2=Neil J.|last3=Vujanic|first3=Gordan M.|title=Wilms' Tumour – Histology and Differential Diagnosis|year=2016|pages=3–21|doi=10.15586/codon.wt.2016.ch1|pmid=27512769 |isbn=9780994438119 |s2cid=78834136 |url=https://discovery.ucl.ac.uk/id/eprint/10026140/ }}

• blastema
• mesenchyme (stroma)
• epithelium

Wilms' tumor is a malignant tumor containing metanephric blastema, stromal and epithelial derivatives. Characteristic is the presence of abortive tubules and glomeruli surrounded by a spindled cell stroma. The stroma may include striated muscle, cartilage, bone, fat tissue, and fibrous tissue. Dysfunction is caused when the tumor compresses the normal kidney parenchyma.{{citation needed|date=April 2021}}

The mesenchymal component may include cells showing rhabdomyoid differentiation or malignancy (rhabdomyosarcomatous Wilms).{{citation needed|date=April 2021}}

Wilms' tumors may be separated into two prognostic groups based on pathologic characteristics:{{citation needed|date=April 2021}}

• Favorable – Contains well developed components mentioned above
• Anaplastic – Contains diffuse anaplasia (poorly developed cells)

Mutations of the WT1 gene which is located on the short arm of chromosome 11 (11p13) are observed in approximately 20% of Wilms' tumors, the majority of them being inherited from the germline, while a minority are acquired somatic mutations.{{cite journal | vauthors = Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH | s2cid = 29092372 | title = Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus | journal = Cell | volume = 60 | issue = 3 | pages = 509–20 | date = February 1990 | pmid = 2154335 | doi = 10.1016/0092-8674(90)90601-A }}{{cite journal | vauthors = Huff V | title = Wilms tumor genetics | journal = American Journal of Medical Genetics | volume = 79 | issue = 4 | pages = 260–7 | date = October 1998 | pmid = 9781905 | doi = 10.1002/(SICI)1096-8628(19981002)79:4<260::AID-AJMG6>3.0.CO;2-Q }} In addition at least half of the Wilms' tumors with mutations in WT1 also carry acquired somatic mutations in CTNNB1, the gene encoding the proto-oncogene beta-catenin.{{cite journal | vauthors = Maiti S, Alam R, Amos CI, Huff V | title = Frequent association of beta-catenin and WT1 mutations in Wilms tumors | journal = Cancer Research | volume = 60 | issue = 22 | pages = 6288–92 | date = November 2000 | pmid = 11103785 | url = http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11103785 }} This latter gene is found on short arm of chromosome 3 (3p22.1).

Most cases do not have mutations in any of these genes.{{cite journal | vauthors = Ruteshouser EC, Robinson SM, Huff V | title = Wilms tumor genetics: mutations in WT1, WTX, and CTNNB1 account for only about one-third of tumors | journal = Genes, Chromosomes & Cancer | volume = 47 | issue = 6 | pages = 461–70 | date = June 2008 | pmid = 18311776 | pmc = 4332772 | doi = 10.1002/gcc.20553 }}

An association with H19 has been reported.Coorens THH, Treger TD, Al-Saadi R, Moore L, Tran MGB, Mitchell TJ, Tugnait S, Thevanesan C, Young MD, Oliver TRW, Oostveen M, Collord G, Tarpey PS, Cagan A, Hooks Y, Brougham M, Reynolds BC, Barone G, Anderson J, Jorgensen M, Burke GAA, Visser J, Nicholson JC, Smeulders N, Mushtaq I, Stewart GD, Campbell PJ, Wedge DC, Martincorena I, Rampling D, Hook L, Warren AY, Coleman N, Chowdhury T, Sebire N, Drost J, Saeb-Parsy K, Stratton MR, Straathof K, Pritchard-Jones K, Behjati S (2019) Embryonal precursors of Wilms tumor. Science 366(6470):1247-1251 H19 is a long noncoding RNA located on the short arm of chromosome 11 (11p15.5).

Image:Wilms Tumor CTScan.OGG of 11 cm Wilms' tumor of right kidney in 13-month-old.]]

The majority of people with Wilms' tumor present with an asymptomatic abdominal mass which is noticed by a family member or healthcare professional.{{cite book | author =PDQ Pediatric Treatment Editorial Board|title=Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ®): Health Professional Version|date=2002|url=https://www.ncbi.nlm.nih.gov/books/NBK65842/|work=PDQ Cancer Information Summaries|publisher=National Cancer Institute (US)|pmid=26389282|access-date=2018-11-12}} Renal tumors can also be found during routine screening in children who have known predisposing clinical syndromes. The diagnostic process includes taking a medical history, a physical exam, and a series of tests including blood, urine, and imaging tests.{{Cite web|url=https://www.uptodate.com/contents/presentation-diagnosis-and-staging-of-wilms-tumor|title=Presentation, diagnosis, and staging of Wilms tumor }}

Once Wilms' tumor is suspected, an ultrasound scan is usually done first to confirm the presence of an intrarenal mass. A computed tomography scan or MRI scan can also be used for more detailed imaging. Finally, the diagnosis of Wilms' tumor is confirmed by a tissue sample.{{cite journal | vauthors = Szychot E, Apps J, Pritchard-Jones K | title = Wilms' tumor: biology, diagnosis and treatment | journal = Translational Pediatrics | volume = 3 | issue = 1 | pages = 12–24 | date = January 2014 | pmid = 26835318 | pmc = 4728859 | doi = 10.3978/j.issn.2224-4336.2014.01.09 }} In most cases, a biopsy is not done first because there is a risk of cancer cells spreading during the procedure. Treatment in North America is nephrectomy or in Europe chemotherapy followed by nephrectomy. A definitive diagnosis is obtained by pathological examination of the nephrectomy specimen.

Staging is a standard way to describe the extent of spread of Wilms' tumors{{Cite web|title = How is Wilms tumor staged?|url = http://www.cancer.org/cancer/wilmstumor/detailedguide/wilms-tumor-staging|website = www.cancer.org|access-date = 2015-11-15}} and to determine prognosis and treatments. Staging is based on anatomical findings and tumor cells pathology.{{Cite web|title = Wilms Tumor - Childhood - Stages|url = http://www.cancer.net/cancer-types/wilms-tumor-childhood/stages|website = Cancer.Net| date=25 June 2012 |access-date = 2015-11-15}}{{Cite web|title = Treatment by type and stage of Wilms tumor|url = http://www.cancer.org/cancer/wilmstumor/detailedguide/wilms-tumor-treating-by-stage|website = www.cancer.org|access-date = 2015-11-13}} According to the extent of tumor tissue at the time of initial diagnosis, four stages are considered, with a fifth classification for bilateral involvement.{{citation needed|date=April 2021}}

In Stage I Wilms' tumor (43% of cases), all of the following criteria must be met: {{citation needed|date=April 2021}}

• Tumor is limited to the kidney and is completely excised .
• The surface of the renal capsule is intact.
• The tumor is not ruptured or biopsied (open or needle) prior to removal.
• No involvement of extrarenal or renal sinus lymph-vascular spaces
• No residual tumor apparent beyond the margins of excision.
• Metastasis of tumor to lymph nodes not identified.

In Stage II (23% of cases), 1 or more of the following criteria must be met: {{citation needed|date=April 2021}}

• Tumor extends beyond the kidney but is completely excised.
• No residual tumor apparent at or beyond the margins of excision.
• Any of the following conditions may also exist:
• Tumor involvement of the blood vessels of the renal sinus and/or outside the renal parenchyma.
• Extensive tumor involvement of renal sinus soft tissue.

In Stage III (20% of cases), 1 or more of the following criteria must be met: {{citation needed|date=April 2021}}

• Inoperable primary tumor.
• Lymph node metastasis.
• Tumor is present at surgical margins.
• Tumor spillage involving peritoneal surfaces either before or during surgery, or transected tumor thrombus.
• The tumor has been biopsied prior to removal or there is local spillage of tumor during surgery, confined to the flank.

Stage IV (10% of cases) Wilms' tumor is defined by the presence of hematogenous metastases (lung, liver, bone, or brain), or lymph node metastases outside the abdominopelvic region.{{citation needed|date=April 2021}}

5% of Wilms' tumor cases at the time of initial diagnosis are bilateral involvements, which pose unique challenges to treatment. An attempt should be made {{according to whom|date=November 2018}} to stage each side according to the above criteria (stage I to III) on the basis of extent of disease prior to biopsy. Bilateral Wilms' tumors are as a whole placed in Stage V.

The overall 5-year survival is estimated to be approximately 90%,{{cite journal | vauthors = Stewénius Y, Jin Y, Øra I, de Kraker J, Bras J, Frigyesi A, Alumets J, Sandstedt B, Meeker AK, Gisselsson D | title = Defective chromosome segregation and telomere dysfunction in aggressive Wilms' tumors | journal = Clinical Cancer Research | volume = 13 | issue = 22 Pt 1 | pages = 6593–602 | date = November 2007 | pmid = 18006759 | doi = 10.1158/1078-0432.CCR-07-1081 | doi-access = | s2cid = 17036977 }}{{cite journal | vauthors = Tournade MF, Com-Nougué C, de Kraker J, Ludwig R, Rey A, Burgers JM, Sandstedt B, Godzinski J, Carli M, Potter R, Zucker JM | title = Optimal duration of preoperative therapy in unilateral and nonmetastatic Wilms' tumor in children older than 6 months: results of the Ninth International Society of Pediatric Oncology Wilms' Tumor Trial and Study | journal = Journal of Clinical Oncology | volume = 19 | issue = 2 | pages = 488–500 | date = January 2001 | pmid = 11208843 | doi = 10.1200/jco.2001.19.2.488 | author12 = International Society of Pediatric Oncology Nephroblastoma Trial Study Committee }} but for individuals the prognosis is highly dependent on individual staging and treatment. Early removal tends to promote positive outcomes.

Tumor-specific loss-of-heterozygosity (LOH) for chromosomes 1p and 16q identifies a subset of Wilms' tumor patients who have a significantly increased risk of relapse and death. LOH for these chromosomal regions can now be used as an independent prognostic factor together with disease stage to target intensity of treatment to risk of treatment failure.{{cite journal | vauthors = Messahel B, Williams R, Ridolfi A, A'hern R, Warren W, Tinworth L, Hobson R, Al-Saadi R, Whyman G, Brundler MA, Kelsey A, Sebire N, Jones C, Vujanic G, Pritchard-Jones K | title = Allele loss at 16q defines poorer prognosis Wilms tumour irrespective of treatment approach in the UKW1-3 clinical trials: a Children's Cancer and Leukaemia Group (CCLG) Study | journal = European Journal of Cancer | volume = 45 | issue = 5 | pages = 819–26 | date = March 2009 | pmid = 19231157 | doi = 10.1016/j.ejca.2009.01.005 | author16 = Children's Cancer Leukaemia Group (CCLG) }}{{cite journal |vauthors=Grundy PE, Breslow NE, Li S, Perlman E, Beckwith JB, Ritchey ML, Shamberger RC, Haase GM, D'Angio GJ, Donaldson M, Coppes MJ, Malogolowkin M, Shearer P, Thomas PR, Macklis R, Tomlinson G, Huff V, Green DM |date=October 2005 |title=Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor: a report from the National Wilms Tumor Study Group |journal=Journal of Clinical Oncology |volume=23 |issue=29 |pages=7312–21 |doi=10.1200/JCO.2005.01.2799 |pmid=16129848 |doi-access=free |author19=National Wilms Tumor Study Group}} Genome-wide copy number and LOH status can be assessed with virtual karyotyping of tumor cells (fresh or paraffin-embedded).{{citation needed|date=April 2021}}

Statistics may sometimes show more favorable outcomes for more aggressive stages than for less aggressive stages, which may be caused by more aggressive treatment and/or random variability in the study groups. Also, a stage V tumor is not necessarily worse than, but nevertheless comparable in prognosis to a stage IV tumor.{{citation needed|date=April 2021}}

In case of relapse of Wilms' tumor, the 4-year survival rate for children with a standard-risk has been estimated to be 80%.{{cite journal | vauthors = Spreafico F, Pritchard Jones K, Malogolowkin MH, Bergeron C, Hale J, de Kraker J, Dallorso S, Acha T, de Camargo B, Dome JS, Graf N | s2cid = 207212698 | title = Treatment of relapsed Wilms tumors: lessons learned | journal = Expert Review of Anticancer Therapy | volume = 9 | issue = 12 | pages = 1807–15 | date = December 2009 | pmid = 19954292 | doi = 10.1586/era.09.159 }}

Wilms tumor is the most common malignant renal tumor in children.{{cite journal | vauthors = Sonn G, Shortliffe LM | s2cid = 23599363 | title = Management of Wilms tumor: current standard of care | language = En | journal = Nature Clinical Practice. Urology | volume = 5 | issue = 10 | pages = 551–60 | date = October 2008 | pmid = 18836464 | doi = 10.1038/ncpuro1218 }} There are a number of rare genetic syndromes that have been linked to an increased risk of developing Wilms Tumor.{{cite journal | vauthors = Kalish JM, Doros L, Helman LJ, Hennekam RC, Kuiper RP, Maas SM, Maher ER, Nichols KE, Plon SE, Porter CC, Rednam S, Schultz KA, States LJ, Tomlinson GE, Zelley K, Druley TE | title = Surveillance Recommendations for Children with Overgrowth Syndromes and Predisposition to Wilms Tumors and Hepatoblastoma | journal = Clinical Cancer Research | volume = 23 | issue = 13 | pages = e115–e122 | date = July 2017 | pmid = 28674120 | pmc = 5538793 | doi = 10.1158/1078-0432.CCR-17-0710 }} Screening guidelines vary between countries; however health care professionals are recommending regular ultrasound screening for people with associated genetic syndromes.

Wilms' tumor affects approximately one person per 10,000 worldwide before the age of 15 years.{{cite journal | vauthors = Breslow N, Olshan A, Beckwith JB, Green DM | title = Epidemiology of Wilms tumor | journal = Medical and Pediatric Oncology | volume = 21 | issue = 3 | pages = 172–81 | date = 1993 | pmid = 7680412 | doi = 10.1002/mpo.2950210305 }} People of African descent may have slightly higher rates of Wilms' tumor. The peak age of Wilms' tumor is 3 to 4 years and most cases occur before the age of 10 years.{{cite journal | vauthors = Breslow NE, Beckwith JB, Perlman EJ, Reeve AE | title = Age distributions, birth weights, nephrogenic rests, and heterogeneity in the pathogenesis of Wilms tumor | journal = Pediatric Blood & Cancer | volume = 47 | issue = 3 | pages = 260–7 | date = September 2006 | pmid = 16700047 | pmc = 1543666 | doi = 10.1002/pbc.20891 }} A genetic predisposition to Wilms' tumor in individuals with aniridia has been established, due to deletions in the p13 band on chromosome 11.{{cite journal | vauthors = Pritchard-Jones K, Fleming S, Davidson D, Bickmore W, Porteous D, Gosden C, Bard J, Buckler A, Pelletier J, Housman D | s2cid = 4350729 | title = The candidate Wilms' tumour gene is involved in genitourinary development | journal = Nature | volume = 346 | issue = 6280 | pages = 194–7 | date = July 1990 | pmid = 2164159 | doi = 10.1038/346194a0 | bibcode = 1990Natur.346..194P }}

Sidney Farber, founder of Dana–Farber Cancer Institute, and his colleagues achieved the first remissions in Wilms' tumor in the 1950s. By employing the antibiotic actinomycin D in addition to surgery and radiation therapy, they boosted cure rates from 40 to 89 percent.Mukherjee, Siddhartha, The Emperor of All Maladies, pg. 123

The use of computed tomography scan for the diagnosis of Wilms' tumor began in the early 1970s, thanks to the intuition of Mario Costici, an Italian physician. He discovered that in the direct radiograms and in the urographic images, determining elements for a differential diagnosis with the Wilms' tumor can be identified. This possibility was a premise for starting a treatment.Nephroblastoma in childhood: current possibilities for an early radiographic diagnosis, Italian Journal of Surgery 1969

• Hemihypertrophy
• National Wilms Tumor Study Group (NWTS)
• Perlman syndrome
• Virtual Karyotype for 1p and 16q LOH

{{Reflist}}

{{Medical resources

| DiseasesDB = 8896

| ICD10 = {{ICD10|C|64||c|64}}

| ICD9 = {{ICD9|189.0}}

| ICDO = {{ICDO|8960|3}}

| OMIM = 194070

| OMIM_mult = {{OMIM|607102||none}}

| MedlinePlus = 001575

| eMedicineSubj = med

| eMedicineTopic = 3093

| eMedicine_mult = {{eMedicine2|ped|2440}}

| MeshID = D009396

| SNOMED CT = 302849000

}}

• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=wilms-ov GeneReviews/NCBI/NIH/UW entry on Wilms' Tumor Overview]
• [http://www.cancer.gov/cancertopics/pdq/treatment/wilms/Patient Information] from National Cancer Institute
• [http://www.cancer.net/cancer-types/wilms-tumor-childhood Cancer.Net Wilms' Tumor – Childhood]

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{{Soft tissue tumors and sarcomas}}

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