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

  Doctors don’t know what causes Wilms tumor, but children who have certain health problems at birth are more likely to get it Children with Wilms tumor have a lump in their belly and may throw up and have belly pain, fever, poor appetite, and upset stomach [msdmanuals.com]

  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]

  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

  겸상적혈구빈혈(sickle cell anemia),                     선천혈구감소성빈혈(congenital thrombocytopenic anemia, CDA), 판코니빈혈(Fanconi anemia),                     지중해빈혈(thalassemia), 무거대핵세포혈소판감소증(amegakaryocytic thrombocytopenia) 등 선천성 대사질환 헐러증후군(Hurler syndrome) 등 선천성 [lifeline.co.kr]

  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]

  In rare cases, the tumor ruptures and causes fever, pain, and anemia. Furthermore, respiratory symptoms are present in those with metastasis to the lungs. [symptoma.com]

  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]

• Weight Loss

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

  Each patient presented with a large, rapidly growing, abdominal mass (average duration of symptoms, less than 2 months), had no constitutional symptoms (e.g., weight loss, fever), and otherwise were healthy (80%). [ajronline.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]

  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]

• Weakness

  Blood in the urine Fever for no known reason High blood pressure (headache, feeling very tired, chest pain, or trouble seeing or breathing) Hypercalcemia -- high calcium levels in the blood, which can lead to a loss of appetite, nausea and vomiting, weakness [aacrfoundation.org]

  […] which causes no tenderness, in the abdomen Pain in the abdomen from pressure on other organs near the tumor Swelling of the abdomen Veins that appear distended or large across the abdomen Blood in the urine Decreased appetite Fever High blood pressure Weakness [ucsfbenioffchildrens.org]

  The inadequacy of orderly solutions to such speculative problems merely reflects the position of human weakness and insufficiency which inspires such investigations. [dictionary.cambridge.org]

  These include swelling of the abdomen, veins that appear distended or large across the abdomen, pain in the abdomen from pressure on other organs near the tumor, blood in the urine (hematuria), decreased appetite, weakness or fatigue, fever and high blood [cincinnatichildrens.org]

  Symptoms may include: A nontender mass, or lump, felt or seen in the abdomen Swelling of the abdomen Blood in the urine (hematuria) Pain in the abdomen from pressure on other organs near the tumor Decreased appetite and weakness or tiredness Constipation [stanfordchildrens.org]

• Malaise

  Regarding the presentation, the majority of patients will have an asymptomatic abdominal mass while some will also develop manifestations such as malaise, abdominal pain, hematuria, and hypertension. [symptoma.com]

  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]

  Symptoms 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 [mountsinai.org]

  Symptoms that may be indicative of Wilms Tumor include: Abdominal pain and swelling Constipation Fever Hypertension Loss of appetite Malaise Nausea Urine discoloration Vomiting There may also be a growth localized to one side of the body in the abdominal [news-medical.net]

• Cough

  […] swollen belly (sometimes parents notice that a young child suddenly needs a larger-sized diaper) Belly pain, fever, poor appetite, upset stomach, and throwing up Blood in the urine High blood pressure If the cancer spreads to the lungs, it may cause coughing [msdmanuals.com]

  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]

  Abdominal and pelvic CT scans Cough Cough is prolonged (> 2 weeks) and has no identifiable cause. Chest radiograph Bone or muscle pain Pain is prolonged (> 2 weeks) and has no identifiable cause. [aafp.org]

  […] or breathing) Hypercalcemia -- high calcium levels in the blood, which can lead to a loss of appetite, nausea and vomiting, weakness, or feeling very tired Wilms tumor that has spread to the lungs or liver may cause the following signs and symptoms: Cough [aacrfoundation.org]

• Dyspnea

  As the tumor enlarges, pressure may cause constipation, vomiting, abdominal distress, anorexia, weight loss and dyspnea. Less common manifestation are hypertension, fever, hematuria, and anemia. [rnpedia.com]

  For masses in the chest, the presenting symptoms are usually persistent cough or dyspnea. Extremity lesions usually present with pain subsequent to trauma. [aafp.org]

  The rationale of omitting pulmonary RT for the majority of the patients is prevention of midterm and long-term morbidity, such as exercise-induced dyspnea, interstitial pneumonia, diminished lung volumes, and other respiratory disorders. 3 – 8, 15 – 17 [jco.ascopubs.org]

  […] features include: Abdominal pain Gross hematuria Urinary tract infections Varicocele Hypertension or hypotension (Up to 1/3 of Wilms patients will demonstrate hypertension which normalizes after nephrectomy) Fever Anemia If the patient has lung metastases, dyspnea [ncbi.nlm.nih.gov]

• Respiratory Distress

  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]

  Nonetheless, preoperative complications during NAC such as pulmonary embolism or ARDS (acute respiratory distress syndrome) can occur, but remain rarities [ 14 ]. [karger.com]

  In a report by Shamberger et al. 5 out of 69 patients receiving neoadjuvant chemotherapy had complications, among which one ended up in fatality due to acute respiratory distress syndrome (ARDS). [numonthly.com]

  Large masses often cause respiratory distress. Children with high thoracic and cervical tumors may present with Horner's syndrome. [aafp.org]

• Tachypnea

  Abdominal pain Gross hematuria Urinary tract infections Varicocele Hypertension or hypotension (Up to 1/3 of Wilms patients will demonstrate hypertension which normalizes after nephrectomy) Fever Anemia If the patient has lung metastases, dyspnea or tachypnea [ncbi.nlm.nih.gov]

• Abdominal Pain

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

  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]

  Children usually have a lump in the abdomen, and they may also have abdominal pain, fever, poor appetite, nausea, and vomiting. An imaging test is done to determine the nature and size of the lump. [merckmanuals.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]

• Abdominal Mass

  Regarding the presentation, the majority of patients will have an asymptomatic abdominal mass while some will also develop manifestations such as malaise, abdominal pain, hematuria, and hypertension. [symptoma.com]

  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]

  Rarely, anaemia or polycythaemia (secondary to production of erythropoeitin by the tumour) On examination, the most common finding is an abdominal mass. [ozradonc.wikidot.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]

  Children usually have a lump in the abdomen, and they may also have abdominal pain, fever, poor appetite, nausea, and vomiting. An imaging test is done to determine the nature and size of the lump. [merckmanuals.com]

• Loss of Appetite

  As a result, these medicines may have side effects such as nausea, vomiting, loss of appetite, hair loss. Most side effects will blur after the treatment is stopped. Radiation therapy - Radiation uses radiation to destroy cancer cells. [plusmedical.ro]

  Short-term (or temporary) effects may include: nausea and vomiting loss of appetite mouth sores tiredness hair loss a weakened immune system bleeding or bruising Long-term (or late) effects may include: the development of secondary cancers (like leukemia [kidshealth.org]

  Choose the appropriate responses and click “search. “ Symptoms of Kidney Tumors Symptoms can include: a lump, swelling, and/or pain in the abdomen abnormal urine color or blood in the urine constipation loss of appetite fever of unknown origin high blood [acco.org]

  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]

• 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]

• 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]

  Beckwith-Wiedemann syndrome: 4–10% risk for Wilms tumor, excessive growth at the cellular level, organ level (macroglossia, nephromegaly, hepatomegaly) or body segment level (hemihypertrophy), WT2 mutations (see below). [urology-textbook.com]

• 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]

• Hypertension

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

  The mass may be discovered incidentally or during a workup following trauma, hematuria, or hypertension. In rare cases, the tumor ruptures and causes fever, pain, and anemia. [symptoma.com]

  Additionally, a physical exam will need to be conducted in order to find the indicative presence of an abdominal mass or hypertension. [news-medical.net]

• Aniridia

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

  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]

  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]

• Irritability

  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]

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

  Clinical Features• Appears chronically ill- Fever, irritability, FTT• Bone pain• Bluish subcutaneous nodules-blueberry muffins - mainly in neonates and infants• Periorbital ecchymosis – Racoon eye & proptosis 8. [slideshare.net]

• Hematuria

  The mass may be discovered incidentally or during a workup following trauma, hematuria, or hypertension. In rare cases, the tumor ruptures and causes fever, pain, and anemia. [symptoma.com]

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

  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. [merckmanuals.com]

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

• 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].

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 histology of the tumor affects the prognosis and the treatment of Wilms tumor. The histology may be favorable or "anaplastic" (unfavorable). [aacrfoundation.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]

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

Certain genetic changes in the tumor cells are associated with a less favorable prognosis. [aacrfoundation.org]

In a multivariate analysis, PDGF-α protein expression by epithelial cells was an independent prognostic marker of a favourable prognosis. [ncbi.nlm.nih.gov]

Etiology of Wilms' tumor (nephroblastoma) : mutations of WT1 gene on chromosome 11 and nephroblastematosis (persistence of renal blastema in kidney tissue). Wilms' tumor (nephroblastoma). [pathologyatlas.ro]

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]

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]

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

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]

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

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]

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.