Cut section showing two halves of a nephroblastoma specimen. Note the prominent septa subdividing the sectioned surface and the protrusion of tumor into the renal pelvis, resembling botryoid rhabdomyosarcoma.
ICD-10
C64
ICD-9
189.0
ICD-O:
M8960/3
OMIM
194070 607102
DiseasesDB
8896
MedlinePlus
001575
eMedicine
med/3093 ped/2440
MeSH
D009396
CT Scan of 11 cm Wilms' tumor of right kidney in 13-month-old patient.
Wilms' tumor or nephroblastoma is cancer of the kidneys that typically occurs in children, rarely in adults.[1] Its common name is an eponym, referring to Dr. Max Wilms, the German surgeon (1867–1918) who first described this kind of tumor.[2]
Approximately 500 cases are diagnosed in the U.S. annually. The majority (75%) occur in otherwise normal children; a minority (25%) are associated with other developmental abnormalities. It is highly responsive to treatment, with about 90% of patients surviving at least five years.
Contents
1Pathology
2Symptoms
3Diagnosis
4Prognosis
5Molecular biology
6Staging
6.1Definitions of stages
6.1.1Stage I (43% of patients)
6.1.2Stage II (23% of patients)
6.1.3Stage III (23% of patients)
6.1.4Stage IV (10% of patients)
6.1.5Stage V (5% of patients)
6.2Prognosis and treatment
7Risk factors
8See also
9References
10External links
Pathology
Micrograph showing the characteristic triphasic pattern consisting of tubules, solid sheets of small round cells, and stroma. H&E stain.
High magnification micrograph showing the epithelial component (tubules). H&E stain.
Most nephroblastomas are unilateral, being bilateral in less than 5% of cases, although patients with Denys-Drash syndrome mostly have bilateral or multiple tumors.[3] 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 hemorrhage 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.
Pathologically, a triphasic nephroblastoma comprises three elements:
blastema
mesenchyme
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, fibrous tissue. The tumor is compressing the normal kidney parenchyma.
The mesenchymal component may include cells showing rhabdomyoid differentiation. The rhabdomyoid component may itself show features of malignancy (rhabdomyosarcomatous Wilms).
Wilms' tumors may be separated into 2 prognostic groups based on pathologic characteristics:
Favorable - Contains well developed components mentioned above
Anaplastic - Contains diffuse anaplasia (poorly developed cells)
Symptoms
Typical symptoms are:
an abnormally large abdomen
abdominal pain
fever
nausea and vomiting
blood in the urine (in about 20% of cases)
high blood pressure in some cases
Diagnosis
The first sign is normally a painless abdominal tumor that can be easily felt by the doctor. An Ultrasound, Computed Tomography, or MRI are done first. A tumor biopsy is not typically performed due to the chance of upstaging the cancer and seeding the abdomen with malignant cells.
Prognosis
The overall 5-year survival is estimated to be approximately 90%,[4] 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.[5][6] Genome-wide copy number and LOH status can be assessed with virtual karyotyping of tumor cells (fresh or paraffin-embedded).
Molecular biology
Mutations of the WT1 gene on chromosome 11 p 13 are observed in approximately 20% of Wilms' tumors.[7][8] At least half of the Wilms' tumors with mutations in WT1 also carry mutations in CTNNB1, the gene encoding the proto-oncogene beta-catenin.[9]
A gene on the X chromosome, WTX, is inactivated in up to 30% of Wilms' tumor cases, according to research published in 2007.[10]
Most cases do not have mutations in any of these genes.[11]
Staging
Staging is determined by combination of imaging studies and pathology findings if the tumor is operable. Treatment strategy is determined by the stage:
Definitions of stages
Stage I (43% of patients)
For stage I Wilms' tumor, 1 or more of the following criteria must be met:
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.
Stage II (23% of patients)
For Stage II Wilms' tumor, 1 or more of the following criteria must be met:
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.
The tumor has been biopsied prior to removal or there is local spillage of tumor during surgery, confined to the flank.
Extensive tumor involvement of renal sinus soft tissue.
Stage III (23% of patients)
For Stage III Wilms' tumor, 1 or more of the following criteria must be met:
Unresectable 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.
Stage IV (10% of patients)
Stage IV Wilms' tumor is defined as the presence of hematogenous metastases (lung, liver, bone, or brain), or lymph node metastases outside the abdomenopelvic region.
Stage V (5% of patients)
Stage V Wilms’ tumor is defined as bilateral renal involvement at the time of initial diagnosis. Note: For patients with bilateral involvement, an attempt should be made to stage each side according to the above criteria (stage I to III) on the basis of extent of disease prior to biopsy.
Prognosis and treatment
Statistics may sometimes show more favorable outcomes for more aggressive stages than for less ones, 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 a stage IV tumor.
Stage[12]
Histopathology[12]
4 Year relapse-free survival (RFS) or event-free survival (EFS)[12]
4 Year overall survival (OS)[12]
Treatment[12]
Stage I [12]
Favorable histology in children younger than 24 months or tumor weight less than 550g
85%
98%
Surgery only (should be done only within the context of a clinical trial)
Favorable histology in children older than 24 months or tumor weight more than 550g
94% RFS
98%
Nephrectomy + lymph node sampling followed by regimen EE-4A
Diffuse anaplastic
68% EFS
80%
Nephrectomy + lymph node sampling followed by regimen EE-4A and radiotherapy
Stage II[12]
Favorable histology
86% RFS
98%
Nephrectomy + lymph node sampling followed by regimen EE-4A
Focal anaplastic
80% EFS
80%
Nephrectomy + lymph node sampling followed by abdominal radiotherapy and regimen DD-4A
Diffuse anaplastic
83% EFS
82%
Nephrectomy + lymph node sampling followed by abdominal radiotherapy and regimen I
Stage III[12]
Favorable histology
87% RFS
94%
Nephrectomy + lymph node sampling followed by abdominal radiotherapy and regimen DD-4A
Focal anaplastic
88% RFS
100% (8 people in study)
Nephrectomy + lymph node sampling followed by abdominal radiotherapy and regimen DD-4A
Focal anaplastic (preoperative treatment)
71% RFS
71%
Preoperative treatment with regimen DD-4A followed by nephrectomy + lymph node sampling and abdominal radiotherapy
Diffuse anaplastic
46% EFS
53%
Preoperative treatment with regimen I followed by nephrectomy + lymph node sampling and abdominal radiotherapy
Diffuse anaplastic
65% EFS
67%
Immediate nephrectomy + lymph node sampling followed by abdominal radiotherapy and regimen I
Stage IV[12]
Favorable histology
76% RFS
86%
Nephrectomy + lymph node sampling, followed by abdominal radiotherapy, bilateral pulmonary radiotherapy, and regimen DD-4A
Focal anaplastic
61% EFS
72%
Nephrectomy + lymph node sampling, followed by abdominal radiotherapy, bilateral pulmonary radiotherapy, and regimen DD-4A
Diffuse anaplastic
33% EFS
33%
Immediate nephrectomy + lymph node sampling followed by abdominalradiotherapy, whole-lung radiotherapy, and regimen I
Diffuse anaplastic (preoperative treatment)
31% EFS
44%
Preoperative treatment with regimen I followed by nephrectomy + lymph node sampling followed by abdominalradiotherapy, whole-lung radiotherapy
Stage V[12]
Overall
61% EFS
80%
Favorable histology
65%
87%
Bilateral renal biopsies and staging of each kidney followed by preoperative treatment with regimen EE-4A (if disease in both kidneys ≤ stage II) or regimen DD-4A (if disease in both kidneys > stage II), followed by second-look surgery and possibly more chemotherapy and/or radiotherapy
Focal anaplastic
76%
88%
Bilateral renal biopsies and staging of each kidney followed by preoperative treatment with regimen I, followed by second-look surgery and possibly more chemotherapy and/or radiotherapy
Diffuse anaplastic
25%
42%
Bilateral renal biopsies and staging of each kidney followed by preoperative treatment with regimen I, followed by second-look surgery and possibly more chemotherapy and/or radiotherapy
Risk factors
People of African descent have the highest rates of Wilms' tumor. Most instances of cancer occur among children between 3 to 3.5 years old.[citation needed]
See also
Beckwith-Wiedemann syndrome
Denys-Drash syndrome
Hemihypertrophy
National Wilms Tumor Study Group (NWTS)
Virtual Karyotype for 1p and 16q LOH
WAGR syndrome
Perlman syndrome
References
^EBSCO database verified by URAC; accessed from Mount Sinai Hospital, New York
^WhoNamedIt.com: Max Wilms
^Guaragna, M. S.; et al., Fernanda Caroline; Assumpção, Juliana Godoy; Zambaldi, Lílian de Jesus Girotto; Cardinalli, Izilda Aparecida; Yunes, José Andrés; De Mello, Maricilda Palandi; Brandalise, Silvia Regina et al. (2010). "The Novel WT1 Gene Mutation p. H377N Associated to Denys-Drash Syndrome". Journal of Pediatric Hematology/Oncology32 (6): 486–488. doi:10.1097/MPH.0b013e3181e5e20d. PMID 20562648.|displayauthors= suggested (help)
^Stewenius, Y.; Jin, Y.; Ora, I.; De Kraker, J.; Bras, J.; Frigyesi, A.; Alumets, J.; Sandstedt, B. et al. (2007). "Defective Chromosome Segregation and Telomere Dysfunction in Aggressive Wilms' Tumors". Clinical Cancer Research13 (22): 6593–6602. doi:10.1158/1078-0432.CCR-07-1081. PMID 18006759.|displayauthors= suggested (help)edit, in turn citing Tournade, M. F.; Com-Nougué, C.; De Kraker, J.; Ludwig, R.; Rey, A.; Burgers, J. M.; Sandstedt, B.; Godzinski, J. et al. (2001). "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 of clinical oncology : official journal of the American Society of Clinical Oncology19 (2): 488–500. PMID 11208843.|displayauthors= suggested (help) edit
^Messahel, B.; Williams, R.; Ridolfi, A.; et al., Roger; Warren, William; Tinworth, Lorna; Hobson, Rachel; Al-Saadi, Reem et al. (2009). "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". Eur J Cancer45 (5): 819–826. doi:10.1016/j.ejca.2009.01.005. PMID 19231157.|displayauthors= suggested (help)
^Grundy, P. E.; Breslow, N. E.; Li, S.; et al., E; Beckwith, JB; Ritchey, ML; Shamberger, RC; Haase, GM et al. (2005). "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". J Clin Oncol23 (29): 7312–7321. doi:10.1200/JCO.2005.01.2799. PMID 16129848.|displayauthors= suggested (help)
^Call K, Glaser T, Ito C, Buckler A, Pelletier J, Haber D, Rose E, Kral A, Yeger H, Lewis W (1990). "Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus". Cell60 (3): 509–20. doi:10.1016/0092-8674(90)90601-A. PMID 2154335.
^Huff V (1998). "Wilms tumor genetics". Am J Med Genet79 (4): 260–7. doi:10.1002/(SICI)1096-8628(19981002)79:4<260::AID-AJMG6>3.0.CO;2-Q. PMID 9781905.
^Maiti S, Alam R, Amos CI, Huff V (2000). "Frequent association of beta-catenin and WT1 mutations in Wilms tumors". Cancer Res60 (22): 6288–92. PMID 11103785.
^Rivera M, Kim W, Wells J, Driscoll D, Brannigan B, Han M, Kim J, Feinberg A, Gerald W, Vargas S, Chin L, Iafrate A, Bell D, Haber D (2007). "An X chromosome gene, WTX, is commonly inactivated in Wilms tumor". Science315 (5812): 642–5. doi:10.1126/science.1137509. PMID 17204608.
^Ruteshouser EC, Robinson SM, Huff V (June 2008). "Wilms tumor genetics: mutations in WT1, WTX, and CTNNB1 account for only about one-third of tumors". Genes Chromosomes Cancer47 (6): 461–70. doi:10.1002/gcc.20553. PMID 18311776.
^ abcdefghijUnless otherwise specified in boxes, then reference is: Treatment of Wilms Tumor at National Cancer Institute. Last Modified: 03/29/2012
External links
GeneReviews/NCBI/NIH/UW entry on Wilms Tumor Overview
5. 癌が疑われる小児の臨床的評価 clinical assessment of the child with suspected cancer
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Spontaneous Nephroblastoma with Lung Metastasis in a Rat
ITO Yuko,MATSUSHITA Kohei,TSUCHIYA Takuma,KOHARA Yukari,YOSHIKAWA Tsuyoshi,SATO Makoto,KITAURA Keisuke,MATSUMOTO Satoshi
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… This report describes a spontaneous nephroblastoma with lung metastasis in a 10-week-old male Crl:CD(SD) rat. … Thus, the case was diagnosed as a nephroblastoma with lung metastasis. …
neph·ro·blas·to·ma (n f r-bl-st m) n. See Wilms' tumor. nephroblastoma. See Wilms' tumor. nephroblastoma nephroblastoma An older term for Wilms tumour. tumor [too´mor] 1. swelling or morbid enlargement; this is one of the ...
