Wilms tumor

ウィルムス腫瘍

WordNet

1. an abnormal new mass of tissue that serves no purpose (同)tumour, neoplasm

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/07/07 01:57:25」(JST)

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Wilms' tumor
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.
Classification and external resources
Specialty	Oncology
ICD-10	C64
ICD-9-CM	189.0
ICD-O	M8960/3
OMIM	194070 607102
DiseasesDB	8896
MedlinePlus	001575
eMedicine	med/3093 ped/2440
MeSH	D009396

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CT Scan of 11 cm Wilms tumor of right kidney in 13-month-old patient.

Wilms (/vɪlmz/) tumor, Wilms' tumor, or nephroblastoma is a cancer of the kidneys that typically occurs in children, rarely in adults. It is named after Dr. Max Wilms, the German surgeon (1867–1918) who first described it.

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.

Signs and symptoms

Typical signs and symptoms of Wilms' tumor include the following:

• an abnormally large abdomen
• 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)

Pathogenesis

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 on one side of the body only and are found on both sides in less than 5% of cases, although patients with Denys-Drash syndrome mostly have bilateral or multiple tumors. 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.

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. Dysfunction is caused when the tumor compresses the normal kidney parenchyma.

The mesenchymal component may include cells showing rhabdomyoid differentiation or 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)

Molecular biology

Mutations of the WT1 gene on chromosome 11p13 are observed in approximately 20% of Wilms tumors. At least half of the Wilms tumors with mutations in WT1 also carry mutations in CTNNB1, the gene encoding the proto-oncogene beta-catenin.

A gene on the X chromosome, WTX, is inactivated in up to 30% of Wilms tumor cases, according to research published in 2007.

Most cases do not have mutations in any of these genes.

Diagnosis

The first sign is normally a painless abdominal tumor that can be easily felt by the doctor. An ultrasound scan, computed tomography scan, or MRI scan is done first. A tumor biopsy is not typically performed due to the risk of creating fragments of cancer tissue and seeding the abdomen with malignant cells.

Staging

Staging is a standard way to describe the extent of spread of Wilms tumors, and to determine prognosis and treatments. Staging is based on anatomical findings and tumor cells pathology.

Definitions of stages

Stage I (43% of patients)

Stage I Wilms tumor, all 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)

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.
  • Extensive tumor involvement of renal sinus soft tissue.

Stage III (20% of patients)

Stage III Wilms tumor, 1 or more of the following criteria must be met:

• 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 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

The overall 5-year survival is estimated to be approximately 90%, 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. Genome-wide copy number and LOH status can be assessed with virtual karyotyping of tumor cells (fresh or paraffin-embedded).

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 a stage IV tumor.

Stage	Histopathology	4 Year relapse-free survival (RFS) or event-free survival (EFS)	4 Year overall survival (OS)	Treatment
Stage I	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	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	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	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	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

Epidemiology

People of African descent have the highest rates of Wilms' tumor. Most instances of cancer occur among children between 3 and 3.5 years old. A genetic predisposition to Wilms' Tumor in individuals with aniridia has been established, due to deletions in the p13 band on chromosome 11.

History

Dr. 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 85 percent.

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

External links

• GeneReviews/NCBI/NIH/UW entry on Wilms Tumor Overview
• Information from National Cancer Institute
• Wilms' tumor at DMOZ
• Cancer.Net Wilms Tumor - Childhood

UpToDate Contents

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• 1. ウィルムス腫瘍の症状、診断、および病期分類 presentation diagnosis and staging of wilms tumor
• 2. ウィルムス腫瘍の治療および予後 treatment and prognosis of wilms tumor
• 3. 微細欠失症候群（1番～11番染色体） microdeletion syndromes chromosomes 1 to 11
• 4. ゲノム疾患：概要 genomic disorders an overview
• 5. 6ヵ月以下の乳幼児における体重減少の評価 evaluation of weight loss in infants six months of age and younger

English Journal

• Valsartan slows the progression of diabetic nephropathy in db/db mice via a reduction in podocyte injury, and renal oxidative stress and inflammation.

• Zhou G, Cheung AK, Liu X1, Huang Y1.Author information 1†Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108, U.S.A.AbstractHigher doses of AngII (angiotensin II) blockers are intended to optimize albuminuria reduction rather than for blood pressure control in chronic kidney disease. However, the long-term renoprotection of high-dose AngII blockers has yet to be defined. The present study sought to determine whether doses of ARB (AngII receptor blocker) that maximally reduce proteinuria could slow the progression of glomerulosclerosis in the uninephrectomized db/db mouse, a model of Type 2 diabetes. Untreated uninephrectomized db/db mice had normal blood pressure, but developed progressive albuminuria and mesangial matrix expansion between 18 and 22 weeks of age, which was associated with increased renal expression of TGFβ1 (transforming growth factor β1), PAI-1 (plasminogen-activator inhibitor-1), type IV collagen and FN (fibronectin). Treatment with valsartan in the drinking water of db/db mice from 18 to 22 weeks of age, at a dose that was determined previously to maximally reduce proteinuria, prevented the increases in albuminuria and the markers of renal fibrosis seen in untreated db/db mice. In addition, WT-1 (Wilms tumour protein-1)-immunopositive podocyte numbers were found to be lower in the untreated glomeruli of mice with diabetes. The expression of podocin and nephrin were continually decreased in mice with diabetes between 18 and 22 weeks of age. These changes are indicative of podocyte injury and the administration of valsartan ameliorated them substantially. Renal expression of TNFα (tumour necrosis factor α), MCP-1 (monocyte chemoattractant protein-1), Nox2 (NADPH oxidase 2), p22phox and p47phox and urine TBARS (thiobarbituric acid-reacting substance) levels, the markers of renal inflammation and oxidative stress, were increased during disease progression in mice with diabetes. Valsartan treatment was shown to reduce these markers. Thus high doses of valsartan not only reduce albuminuria maximally, but also halt the progression of the glomerulosclerosis resulting from Type 2 diabetes via a reduction in podocyte injury and renal oxidative stress and inflammation.
• Clinical science (London, England : 1979).Clin Sci (Lond).2014 May;126(10):707-20. doi: 10.1042/CS20130223.
• Higher doses of AngII (angiotensin II) blockers are intended to optimize albuminuria reduction rather than for blood pressure control in chronic kidney disease. However, the long-term renoprotection of high-dose AngII blockers has yet to be defined. The present study sought to determine whether dose
• PMID 24195695

• Clear cell sarcoma of the kidney demonstrates an embryonic signature indicative of a primitive nephrogenic origin.

• Karlsson J1, Holmquist Mengelbier L, Ciornei CD, Naranjo A, O'Sullivan MJ, Gisselsson D.Author information 1Department of Clinical Genetics, Lund University, University and Regional Laboratories, Lund, Sweden.AbstractClear cell sarcoma of the kidney (CCSK) is a tumor affecting children with a median age of 3 years at diagnosis. The cell of origin of CCSK is unknown and data on the molecular changes giving rise to CCSK is scarce. This has hindered the identification of positive diagnostic markers and development of molecularly targeted treatment protocols for CCSK. We have characterized a panel of CCSK to gain information regarding its molecular profile and possible origin. High-resolution genomic analysis with single nucleotide polymorphism array of 37 tumors did not reveal any clues to the mechanisms behind tumor development as remarkably few genetic imbalances were found. Gene expression analysis revealed a highly characteristic gene signature, enriched for pathways involved in embryonic development, including kidney formation. The presence of markers for two different developmental lineages in the embryonic kidney was therefore investigated in the tumor cells. FOXD1 which identifies cells giving rise to stromal elements, and CITED1, a marker for cells primed for nephrogenic epithelial differentiation, were both highly expressed in CCSK. In addition, the early embryonic marker OSR1 was expressed at higher levels in CCSK than in Wilms tumor, normal fetal kidney or adult kidney. As this marker discriminates the intermediate mesoderm from other mesodermal structures, our study could suggest that CCSK arises from a mesodermal cell type that retains the capacity to initiate differentiation towards both nephrons and stroma, but remains locked in a primitive state. © 2014 Wiley Periodicals, Inc.
• Genes, chromosomes & cancer.Genes Chromosomes Cancer.2014 May;53(5):381-91. doi: 10.1002/gcc.22149. Epub 2014 Feb 1.
• Clear cell sarcoma of the kidney (CCSK) is a tumor affecting children with a median age of 3 years at diagnosis. The cell of origin of CCSK is unknown and data on the molecular changes giving rise to CCSK is scarce. This has hindered the identification of positive diagnostic markers and development
• PMID 24488803

• Non-activated protein C rescue treatment in Wilms tumour associated hepatic sinusoidal obstructive syndrome.

• De Leonardis F1, Koronica R, Bruno SD, Santoro N.Author information 1Division of Paediatric Haematology-Oncology, Department of Pediatrics, Bari, Italy.AbstractHepatic sinusoidal obstructive syndrome (HSOS) is a frequent complication in patients undergoing haematopoietic stem cell transplant (HSCT), and more rarely, in paediatric patients receiving conventional chemotherapy for solid tumours. Its diagnosis relies on a combination of clinical signs and symptoms such as hepatomegaly, jaundice, weight gain and fluid retention. HSOS treatment is primarily based on supportive care and anti-fibrinolytic agents. Here we report two patients affected by Wilms tumour who developed life-threatening HSOS that failed to respond to conventional treatment. Both patients recovered after receiving aggressive supportive treatment that included administration of non-activated protein C (Ceprotin®-Baxter). Pediatr Blood Cancer 2014;61:940-941. © 2013 Wiley Periodicals, Inc.
• Pediatric blood & cancer.Pediatr Blood Cancer.2014 May;61(5):940-1. doi: 10.1002/pbc.24859. Epub 2013 Nov 26.
• Hepatic sinusoidal obstructive syndrome (HSOS) is a frequent complication in patients undergoing haematopoietic stem cell transplant (HSCT), and more rarely, in paediatric patients receiving conventional chemotherapy for solid tumours. Its diagnosis relies on a combination of clinical signs and symp
• PMID 24281860

Japanese Journal

• WT1ペプチドがんワクチン (特集 がん免疫療法 : がん完治に向けての新たな治療法の探索) -- (がんペプチドワクチン)

• 日本臨床 = Japanese journal of clinical medicine 75(2), 263-269, 2017-02
• NAID 40021132038

• 放射線照射後40年を経て発生した乳頭状腎細胞癌の1例

• 泌尿器科紀要 = Acta urologica Japonica 63(2), 69-73, 2017-02
• NAID 120005997734

• Differential detection of cytoplasmic Wilms tumor 1 expression by immunohistochemistry, western blotting and mRNA quantification

• International journal of oncology 50(1), 129-140, 2017-01
• NAID 120006313439

Related Links

• Wilms Tumor

PRESENTATION Children with Wilms tumor typically present with an asymptomatic abdominal mass. It is not uncommon for the tumor to be discovered by a parent while bathing the child or by a relative who notices a protuberant ...

• Wilms tumor - National Library of Medicine - PubMed Health

Wilms tumor is a type of kidney cancer that occurs in children. ... Calling your health care provider Call your health care provider if you discover a lump in your child's abdomen, blood in the urine, or other symptoms of ...

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★リンクテーブル★

リンク元	「ウィルムス腫瘍」
拡張検索	「teratoid Wilms tumor」
関連記事	「tumor」

「ウィルムス腫瘍」

　　[★]

英

Wilms tumor

同

Wilms腫瘍、腎芽細胞腫、腎芽腫 nephroblastoma

関

WT1

病因

• 第11番染色体短腕の変異・欠失
• WT1：11p13
• WT2：11p15

• 腎・生殖器系組織が正常に発達するのに重要な役割を果たす転写因子。増殖抑制に作用

• 予後不良因子

• 第1番染色体短腕：1p
• 第16番染色体長腕：16q

疫学

• 神経芽腫についで多い小児悪性固形腫瘍。小児腫瘍の約5%を占める。
• 1case/8,000/year
• 男女比はほぼ同じ。
• 両側性もありうる
• 3歳が最多。成人でもありうる
• 98%が10才以下。80%は5歳以下。

症状

• 無虹彩症、片側肥大、Beckwith-Wiedemann症候群を合併することがある。
• 腹部膨満、肉眼的血尿、肺転移をきたしやすい。

「teratoid Wilms tumor」

　　[★] 胎児性横紋筋腫型腎芽腫

「tumor」

　　[★]

• n.

• 腫瘍、腫瘤、腫脹