Nephroblastoma, also referred to as Wilms tumor, is the fifth most common malignancy in childhood and the most frequent renal tumor in the pediatric population [1] [2]. Additionally, its peak incidence is in early childhood between the ages of 3 to 4 [3]. Patients with trisomies 13 and 18, Beckwith-Wiedemann syndrome, and Drash syndrome are at risk for developing this tumor [3]. Due to advances in treatment, the survival rate is 80% to 90%.

Regarding the presentation, the majority of patients will have an asymptomatic abdominal mass [4] [5] while some will also develop manifestations such as malaise, abdominal pain, hematuria, and hypertension [5]. The mass may be discovered incidentally or during a workup following trauma, hematuria, or hypertension [4]. In rare cases, the tumor ruptures and causes fever, pain, and anemia [5]. Furthermore, respiratory symptoms are present in those with metastasis to the lungs.

Nephroblastoma adheres to the "rules of 10s," which relates that 10% of these cases are bilateral, 10% develop vascular invasion, 10% exhibit lung metastasis at initial presentation, 10% have histology suggestive of poor outcome, and 10% demonstrate calcifications on imaging [6].

Complications

There are adverse effects associated with various types of treatment. For example, radiation therapy poses danger to the remaining kidney while chemotherapy agents are harmful to the liver and other organs. Also, removal of one kidney will lead t0 hypertrophy of the remaining kidney.

Physical exam

Remarkable findings include an abdominal mass, which should be palpated carefully to avoid rupture. Other notable features will be those of associated syndromes.

• Splenomegaly

  It is also important to investigate “B” symptoms associated with any lymphadenopathy or splenomegaly. Laboratory tests can often be helpful in ambiguous cases. [aafp.org]

• Fever

  Your child is being treated for this condition and symptoms get worse or new symptoms develop, mainly cough, chest pain, weight loss, or persistent fevers. [medlineplus.gov]

  A six-month-old girl with persistent high fevers was found to have pyuria and bacteriuria. Ultrasonography revealed multilocular cysts in the right kidney. Right nephrectomy was performed with cyst wall rupture during surgery. [ncbi.nlm.nih.gov]

  However, parents must watch for signs of problems, like fever, nausea, vomiting, or diarrhea. A child with a high fever should see a doctor right away. [kidshealth.org]

• Anemia

  Tumor Children diagnosed with kidney tumors may have experienced the some following symptoms: A lump or mass in the abdomen of an otherwise well child Abdominal pain Blood in the urine High blood pressure Fever Diarrhea Weight loss Urogenital infections Anemia [curesearch.org]

  Typically, the tumor is first detected as a painless lump in the abdomen, found by a parent or by a pediatrician during a routine check-up, although it may be accompanied by symptoms such as blood in the urine, anemia (which may be accompanied by unusual [columbiadoctors.org]

  Tests include: Abdominal ultrasound Abdominal x-ray BUN Chest x-ray or CT scan Complete blood count (CBC), may show anemia Creatinine Creatinine clearance CT scan of the abdomen with contrast MRI Intravenous pyelogram MR angiography (MRA) Urinalysis Alkaline [mountsinai.org]

  Those include: blood in the urine anemia weight loss fever Risk Factors Most children develop Wilms’ tumor due to a random genetic mutation, not from an inherited genetic mutation. [mskcc.org]

  Patients sometimes experience abdominal pain (around 10% of cases), hypertension, fever (20% of cases), hematuria and anemia. [orpha.net]

• Weight Loss

  Later, symptoms may indicate fever, distortion of the kidney mass, evidence of secondary tumours elsewhere in the body, abdominal and flank pain, weight loss, nausea, loss of appetite, and vomiting. [britannica.com]

  loss Urogenital infections Anemia Shortness of breath A general feeling of being tired and unwell Nausea and vomiting News About Wilms Tumor [curesearch.org]

  Your child is being treated for this condition and symptoms get worse or new symptoms develop, mainly cough, chest pain, weight loss, or persistent fevers. [medlineplus.gov]

  weight loss, fever), and otherwise were healthy (80%). Twenty-six patients had IV or retrograde pyelograms. Twenty-three showed a nonspecific mass effect. [ajronline.org]

• Fatigue

  […] tumor is first detected as a painless lump in the abdomen, found by a parent or by a pediatrician during a routine check-up, although it may be accompanied by symptoms such as blood in the urine, anemia (which may be accompanied by unusual bleeding or fatigue [columbiadoctors.org]

  Some children may have bloody urine, abdominal pain, loss of appetite, fatigue or weight loss. If a tumor is suspected in your child's abdomen, don't apply pressure to this area. [ucsfbenioffchildrens.org]

  Prepare child and family for fatigue during recovery from surgery and with radiation treatments. Plan frequently rest periods between daily activities. [rnpedia.com]

  Children with Wilms’ tumor might display the following symptoms: constipation abdominal pain, swelling, or discomfort nausea and vomiting weakness and fatigue loss of appetite fever blood in their urine or discoloration of their urine high blood pressure [healthline.com]

  Wilms' tumor is characterized by: Abdominal swelling, often toward one side Fever Abdominal pain Constipation High blood pressure (hypertension) Large swollen veins across the abdomen Blood in the urine (hematuria) Fatigue Loss of appetite Weight loss [chop.edu]

• Wound Infection

  infection, hernia (4%) Vascular complications (2%) Splenic and intestinal injury (1.5%) Impaired renal function Bilateral Wilms tumor Approximately 5% of children with Wilms tumor will have bilateral involvement. [27] In these patients, the goals of [emedicine.com]

  Postoperative complications include intestinal obstruction (five percent), intussusception and wound infection. Children with retroperitoneal dissections are at increased risk of postoperative intussusception. [pedsurglibrary.com]

• Abdominal Pain

  We report a case of ERNB in a 4-year-old boy complaining of abdominal pain and vomiting. Imaging showed a retroperitoneal mass and left hydronephrosis. The mass was completely removed by surgery. [ncbi.nlm.nih.gov]

  Other children have abdominal pain or blood in the urine ( hematuria ). [healthanddisease.com]

  Signs and Symptoms of Wilms Tumor Children diagnosed with kidney tumors may have experienced the some following symptoms: A lump or mass in the abdomen of an otherwise well child Abdominal pain Blood in the urine High blood pressure Fever Diarrhea Weight [curesearch.org]

  Symptoms may include any of the following: Abdominal pain Abnormal urine color Constipation Fever General discomfort or uneasiness ( malaise ) High blood pressure Increased growth on only one side of the body Loss of appetite Nausea and vomiting Swelling [medlineplus.gov]

  […] malignancy of children Both kidneys affected synchronously or metachronously in 5-10% Peak incidence at 2.5-3 years More common in blacks than whites with an approximately equal gender distribution Clinical Findings Asymptomatic abdominal mass most common Abdominal [learningradiology.com]

• Abdominal Mass

  Nephroblastoma must be included in the differential diagnosis of hypertension associated with increased renin concentrations, even in the absence of an abdominal mass. [ncbi.nlm.nih.gov]

  Children who have Wilms tumor often present with an asymptomatic abdominal mass, found by caregivers or pediatricians. [pedsinreview.aappublications.org]

  On examination he was found to have an abdominal mass. An ultrasound and CT scan were performed. Caption: Sagittal image of the right kidney Description: A rounded solid appearing mass is seen in the interpolar region of the right kidney. [123sonography.com]

• Nausea

  Possible side effects include nausea, tiredness, skin irritation, or diarrhea. Treatment regimens vary depending on the Wilms tumor stage Stage I or II cancer. [plusmedical.ro]

  However, parents must watch for signs of problems, like fever, nausea, vomiting, or diarrhea. A child with a high fever should see a doctor right away. [kidshealth.org]

  The therapy might result in side effects, e.g. diarrhea, fatigue, nausea, and skin irritation. [junisa.ru]

• Abdominal Distension

  Abdominal distension was the most common clinical presentation (Figure 1). Discussion The Wilms tumor or Nephroblastoma is the commonest childhood cancer in Rwanda. [panafrican-med-journal.com]

• Pelvic Mass

  While the condition is extremely rare, it should be included in the differential diagnosis of a young child with bilateral renal pelvic masses. [ncbi.nlm.nih.gov]

• Hypertension

  An infant with severe hypertension who had a nephroblastoma which was secreting active renin is described. [ncbi.nlm.nih.gov]

• Hepatomegaly

  VOD is primarily a clinical diagnosis characterized by hepatomegaly or pain in the right upper quadrant, jaundice, ascites, and unexplained weight gain. [emedicine.medscape.com]

  Clinical Features• Opsoclonus-Myoclonus: " dancing eyes, dancing feet syndrome"—better prognosis 4%• Cervical involvement: - Horners syndromeThorax:- Respiratory distress• Abdomen: - Hard mass, fixed, abdominal Discomfort, Massive hepatomegaly 10. [slideshare.net]

• Hepatosplenomegaly

  Leukemia should be suspected if persistent vague symptoms are accompanied by evidence of abnormal bleeding, bone pain, lymphadenopathy or hepatosplenomegaly. [aafp.org]

  Affected males typically have intellectual disability, macrosomia, cardiac, skeletal, gastrointestinal and genitourinary anomalies, hepatosplenomegaly, and distinctive facial features that include macrocephaly, macrostomia (large, wide mouth), and macroglossia [invitae.com]

• Aniridia

  Patients with bilateral tumors, aniridia, cryptorchism/hypospadias, Beck-with-Wiedemann syndrome, or intralobar nephrogenic rests tend to be diagnosed much younger than average (median 17-27 months). [ncbi.nlm.nih.gov]

  Wilms' tumor occurs more frequently in children with certain abnormalities or syndromes present at birth, including: Aniridia. In aniridia (an-ih-RID-e-uh), the iris — the colored portion of the eye — forms only partially or not at all. [mayoclinic.org]

  Population-based risk estimates of Wilms tumor in sporadic aniridia. A comprehensive mutation screening procedure of PAX6 identifies 80% of mutations in aniridia. Hum. Genet. 2001; 109(1):11-8. PMID: 11479730 Muto, R, et al. [invitae.com]

  Sporadic aniridia mutations may affect the WT1 region adjacent to the AN2 aniridia region, causing a kidney cancer called nephroblastoma (Wilms tumor). [diki.pl]

• Hematuria

  Large tumor size and gross hematuria were associated with risk of a poorer outcome. [ncbi.nlm.nih.gov]

  Urine specimens show hematuria; no increase in vanillylmandelic acid and homovanillic acid levels as occurs with neuroblastoma. [rnpedia.com]

  Less frequent findings include abdominal pain, hematuria, fever, anorexia, nausea, and vomiting. Hematuria can be microscopic or gross. Hypertension may occur and is of variable severity. [msdmanuals.com]

  Constipation Fever General discomfort or uneasiness ( malaise ) High blood pressure Increased growth on only one side of the body Loss of appetite Nausea and vomiting Swelling in the abdomen ( abdominal hernia or mass ) Sweating (at night) Blood in urine (hematuria [medlineplus.gov]

  movement of the mass during respiration, looking for signs of overgrowth, peripheral lymph nodes, edemas, hypertension, passing stool/urine, macroscopic hematuria. [telemedicina.med.muni.cz]

• Macroscopic Hematuria

  movement of the mass during respiration, looking for signs of overgrowth, peripheral lymph nodes, edemas, hypertension, passing stool/urine, macroscopic hematuria. [telemedicina.med.muni.cz]

Any child with an abdominal mass warrants a full workup consisting of a patient and family history, complete physical exam, and the appropriate studies.

Laboratory tests

The clinician must obtain a complete blood count (CBC), complete metabolic panel (CMP) including renal function tests, and a coagulation panel. Urinalysis is also important.

Cytogenetic testing

Chromosomal analysis for associated syndromes is indicated.

Imaging

Ultrasonography of the kidneys is the initial diagnostic modality since it is widely available, inexpensive, and safe. Renal ultrasonography determines the location and characteristic of the mass as it differentiates solid from cystic lesions [5]. This study also detects thrombi in the inferior vena cava (IVC).

Abdominal computed tomography (CT) scan provides critical details regarding the tumor's origin, vascular and lymph nodal invasion, bilateral renal involvement, and metastatic disease [7]. Moreover, CT with contrast enhancement demonstrates a greater sensitivity for vascular involvement [8].

Experts advocate that contrast-enhanced magnetic resonance imaging (MRI) is the preferred diagnostic study [3]. This modality exhibits the most sensitivity for ascertaining caval patency and invasion. Generally, a nephroblastoma has low signal intensity on a T1 weighted image and high intensity on T2 [9].

Chest radiography and CT scan are performed to investigate lung metastasis.

Histology

The diagnosis is confirmed by histologic analysis of the tumor, which is characterized by epithelial, stromal, and blastemal embryonic elements [4]. Very importantly, histology also determines the prognosis [10].

• Human Papillomavirus

  The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle. Proc Natl Acad Sci U S A 2000 ; 97 : 10002 –7. Saunders W. [doi.org]

Recurrent Wilms tumor The prognosis and treatment for children with Wilms tumor that recurs (comes back after treatment) depends on their prior treatment, the cancer’s histology (favorable or anaplastic), and where it recurs. [cancer.org]

[…] leading to precise diagnoses and the selection of the optimal treatment. [ncbi.nlm.nih.gov]

The first step in treatment is to stage the tumor. Staging helps the provider determine how far the cancer has spread and to plan for the best treatment. Surgery to remove the tumor is planned as soon as possible. [medlineplus.gov]

CONCLUSIONS: The absence of RGS4 and P16 in pediatric nephroblastoma tissue is correlated with poor prognosis of patients. RGS4 and P16 are of significance for the prognosis of pediatric nephroblastoma. [ncbi.nlm.nih.gov]

Your child’s treatment and prognosis (outlook) depend, to a large extent, on the cancer’s stage. [cancer.org]

Prognostic factors The 2 most important factors that predict the prognosis of a child with a Wilms tumor are: The histology of the tumor. This is what the tumor cells look like under a microscope. [cancer.net]

It is unlikely that such environmental exposures play a major role in the etiology of Wilms tumor. The median age-at-onset of Wilms tumor is 38 months in the U.S. [ncbi.nlm.nih.gov]

Most early reports suggest that hepatic irradiation is the major etiologic factor in hepatic injury. [emedicine.medscape.com]

The epidemiologic features suggest that somatic mosaicism, rather than a germline mutation, may be responsible for some of the bilateral and multicentric cases. [ncbi.nlm.nih.gov]

Hung, Wilms' tumour: a systematic review of risk factors and meta‐analysis, Paediatric and Perinatal Epidemiology, 24, 5, (449-469), (2010). [doi.org]

The pathophysiology and clinical aspects of both tumours including associated risk factors and pathologies are discussed. [ncbi.nlm.nih.gov]

[…] including FNA) and removal of tumor in 1 piece Stage IV (10%): Hematogenous metastases or spread beyond abdomen Stage V (5%): Bilateral renal involvement (substage each tumor separately according to above criteria) Reference: American Cancer Society Pathophysiology [pathologyoutlines.com]

Original Editors - Students from Bellarmine University's Pathophysiology of Complex Patient Problems project. [physio-pedia.com]

Multicellular spheroid, which is an aggregated form of cells in a spherical shape, provides a relevant pathophysiological gradients of various chemicals that reflects the environment of tumors, since the 3D structure acts as a barrier against chemical [library.kaist.ac.kr]

Acquired von Willebrand syndromes: clinical features, aetiology, pathophysiology, classification and management. Best Pract Res Clin Haematol. 2001;14(2):401-36. [PMID:11686107] Ritchey ML, Shamberger RC, Haase G, et al. [pedsurglibrary.com]

Simultaneous thoraco-abdominal surgery with total circulatory arrest is advocated to remove the cardiac and caval tumor together with the primary tumor in order to prevent sudden hemodynamic and embolic complications. [ncbi.nlm.nih.gov]

Chemotherapy given before the surgery is also effective in preventing complications. Outlook (Prognosis) Children whose tumor has not spread have a 90% cure rate with appropriate treatment. [mountsinai.org]

Prevention Wilms' tumor can't be prevented by anything you or your child can do. [mayoclinic.org]

1. Breslow N, Olshan A, Beckwith JB, et al. Epidemiology of Wilms tumor. Med Pediatr Oncol. 1993;21(3):172–81.
2. Pastore G, Znaor A, Spreafico F, et al. Malignant renal tumours incidence and survival in European children (1978–1997): report from the Automated Childhood Cancer Information System project. Eur J Cancer. 2006;42(13):2103–2114.
3. Dumba M, Jawad N, McHugh K. Neuroblastoma and nephroblastoma: a radiological review. Cancer Imaging. 2015;15(1):5.
4. Lonergan GJ, Martinez-Leon MI, Agrons GA, Montemarano H, Suarez ES. Nephrogenic rests, nephroblastomatosis, and associated lesions of the kidney. Radiographics. 1998;18(4):947–68.
5. Davidoff AM. Wilms tumor. Adv Pediatr. 2012;59(1):247–67.
6. Dahnert W. Urogenital tract. In: Radiology Review Manual. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011: 895-1012.
7. Refaie HD, Sarhan M, Hafez A. Role of CT in assessment of unresectable Wilms' tumor response after preoperative chemotherapy in pediatrics. ScientificWorldJournal. 2008; 8:661-69.
8. Khanna G, Rosen N, Anderson JR, et al. Evaluation of diagnostic performance of CT for detection of tumour thrombus in children with Wilms tumour: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2012;58(4):551–55.
9. Lowe HL, Isuani BH, Heller RM, Stein SM, Johnson JE, Navarro OM, et al. Pediatric Renal Masses: Wilms Tumor and Beyond. Radiographics. 2000;20(6):1585–1603.
10. Beckwith JB, Palmer NF. Histopathology and prognosis of Wilms tumor results from the first National Wilms’ Tumor Study. Cancer. 1978;41(5):1937–48.