Wilms Tumor

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Original Editors - Students from Bellarmine University's Pathophysiology of Complex Patient Problems project.

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Definition/Description

Wilms’ Tumor, also known as nephroblastoma, is a solid tumor of the kidney that develops from immature kidney cells.¹ It is the most common cancer of the kidneys in children, and the fourth most common type of cancer in children.^1,2 Wilms’ tumors are most often unilateral, affecting only one kidney.³ 5-10% of children with Wilms’ tumors have more than one tumor in the same kidney, and approximately 5% of children with the cancer have bilateral Wilms’ tumors, affecting both kidneys.³

(Huszno)

Prevalence

Wilms’ tumor is most common in children ages 3 to 4 and becomes much less common after the age of 5.² Wilms’ tumor affects boys are girls equally, and can also be found in adults, though it is very rare.¹ On average, there are 460 new cases of Wilms’ tumor diagnosed in the United States every year. Approximately 1 in 8,000-10,000 children are affected.¹ About 5% of all cancers in children are Wilms’ tumors.³

Characteristics/Clinical Presentation

Wilms’ tumor is often hard to find early because the tumor can grow large without any signs or symptoms. These children may look and act normally.³ The most common first clinical sign is swelling or a hard mass in the abdomen. It is often firm and large enough to be palpated on both sides of the abdomen, and is usually not painful.³
Some children may also experience:^2,3
-Fever
-Loss of appetite
-Shortness of breath
-Constipation
-Nausea
-Blood in the urine
-Abdominal pain
Wilms’ tumors may also cause high blood pressure. The blood pressure can get high enough to cause bleeding in the eye or a change in consciousness in rare cases.³

Associated Co-morbidities

The types of secondary cancers include bone and soft tissue sarcomas, breast cancer, lymphoma, tumors of the digestive tract, melanoma and acute leukaemias. Certain birth defects and also correlated with Wilms tumor including Aniridia, hemihypertrophy, cryptorchidism, hypospadias. There are also several syndromes that are often associated with Wilms tumor including Sotos syndrome, Perlman syndrome, Simpson-Golabi-Behmel syndrome, Bloom syndrome, Frasier syndrome, Beckwith-Wiedemann Syndrome, Denys -Drash syndrome, and WAGR syndrome which are explained in further detail in differential diagnosis. (CANCER ORG)

Medications

The most effective chemotherapeutics in treatment of nephroblastoma are: actinomycin D (ACT), vincristine (VCR), doxorubicin (ADM), cyclophosphamide (ctx), ifosfamide (IFO), etoposide and carboplatin. (huszno) NWTS recommends polchemotherapy treatment (ACT, VCR, ADM) for a period of 15 weeks in stage III Less aggressive treatment using two medications (VCR and ACT) can be used in cancer stages I and II. (HUZON). It is important to note toxicity of such treatment is highger in adults than in children (HUS).

Toxicity: among vinicristine, dactinomycin and Adriamycin, the main acue toxicity was neuropathy due to vincristine. During chemotherapy with ICE (ifosfamide, carboplatin, etoposide) all patients had hematological toxicity such as neutropenia and thrombocytopenia in stage IV toxicity. The type, timing, and dosage of chemotherapy have been major risk factors in combined therapy. (HU)

Side Effects: Late side effects include cardiotoxicity, reproductive problems, renal dysfunction and the development of benign and malignant second tumors. (HUS) In some cases fertility may be impaired. (HUS) Other side effects of chemotherapy include: hair loss , mouth sores , loss of appetite , nausea and vomiting , diarrhea or constipation , increased chance of infections (from having too few white blood cells), Easy bruising or bleeding (from having too few blood platelets), Fatigue or extreme tiredness (from having too few red blood cells) (CANCer org)

Below are treatment protocols for the National Wilms' Tumor Study Group (NWTSG) and Society of Pediatric Oncology ( SIOP): (Huszno)

Diagnostic Tests/Lab Tests/Lab Values

A small percentage of Wilms tumors are caused by changes in the WT1 and WT2 genes, which are tumor suppressor genes on chromosome 11. Pathological diagnosis of adult nephroblastoma is based on criteria including: the presence of primitive blastemic spindle or round cell component; abortive or embryonal tubules or glomerular structures. Cytokeratin, vimentin,desmin,actin, and WTI allows to distinguish between other rare cancer types. An elevated serum IL-6 level has already been demonstrated to correlate with poor survival and unfavorable clinical outcome in some solid tissue cancers. (ZHANG). A urinalysis may also be performed to look for blood and other substances like catecholamines to rule out adrenal issues (Zhang). Recently research has shown that B7-H1 expression to be a favorable histology characteristic for  Wilms tumor and it is associated with an increased risk of failure of initial therapy. (Reference)

Etiology/Causes

Wilms’ tumor is typically seen in otherwise healthy children, and the exact cause in most children is unknown.^4,5 However, approximately 10% of patients with the tumor have a congenital anomaly, including certain birth defect syndromes and genetic changes.5 Wilms’ tumor, whether hereditary or sporadic, shows evidence of changes in one or more of at least ten different genes.⁴
Common syndromes that are associated with Wilms’ tumor include the following:
WAGR Syndrome: WAGR stands for Wilms tumor, Aniridia (lack of the iris of the eyes), Genitourinary tract abnormalities, and mental retardation. Children who have WAGR syndrome have approximately 30-50% chance of developing a Wilms’ tumor, and often have them bilaterally. In this syndrome, cells are missing part of chromosome 11, which involves the WT1 gene.^3,6
Beckwith-Wiedemann sydrome: These children are at a 5% risk of having a Wilms’ tumor. This syndrome is caused by a malformation of chromosome 11.³
Denys-Drash Syndrome: This syndrome is also caused by mutations to the WT1 gene. The risk for Wilms’ tumor in these patients is greater than 90%.⁶

Systemic Involvement

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Medical Management (current best evidence)

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Physical Therapy Management (current best evidence)

There are several long-term side effects of chemotherapy. Childhood cancers tend to respond better to chemotherapy than adult cancers. Children’s bodies also tend to tolerate it better than adults do. Patients do not undergo physical therapy to a large extent but it is a field of healthcare that should be stressed to patients and family members to increase overall strength and decrease fatigability.

(http://www.cancer.org/acs/groups/cid/documents/webcontent/003149-pdf.pdf) ↑ 13.0 13.1

Kidney Cancer Association. Living with kidney cancer. http://www.kidneycancer.org/knowledge/live/living-with-kidney-cancer/ (accessed 8 Feb 2013).

Alternative/Holistic Management (current best evidence)

Complementary medicine is treatment used in combination with regular medical care. Alternative treatments are used instead of the traditional medical treatment. Although there is not any alternative medicine instead of surgery, radiation or chemotherapy, there are complementary treatments including art therapy or play therapy to reduce stress, peppermint tea to relieve nausea and acupuncture to help relieve pain. (CANCER ORG)

Differential Diagnosis

There is a strong link between Wilms tumors and certain kinds of birth defects. Infact, 1 in 10 children with Wilms tumor have birth defects (Cancer org).

WAGR syndrome:
WAGR stands for Wilms tumor, Aniridia, Genitourinary tract abnormalities, and Mental Retardation. Children with this syndrome have about a 30-50% of having a wilms tumor. With this syndrome part of chromosome 11 is missing. Children with this syndrome tned to get Wilms tumor earlier and they are often bilateral.

Denys- Drash Syndrome
This is a rare syndrome linked to genetic mutation in WT1 gene. The kidneys become diseased and stop working in which most children will then develop Wilms tumors if the kidneys are not removed.

Beckwith-Wiedemann Syndrome:
These children are often of a larger size for their age. This includes organs and is also caused by a defect in chromosome 11. There is a 5% chance of having a Wilms tumor.

Other syndromes Wilms tumor have been linked to include:
-Sotos syndrome
-Perlman syndrome
-Simpson-Golabi-Behmel syndrome
-Bloom syndrome
-Frasier syndrome
- Li- Fraumeni syndrome
-Trisomy 18

Case Reports/ Case Studies

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Routh J, Grundy P, Anderson J, Retik A, Kurek K. B7-h1 as a biomarker for therapy failure in patients with favorable histology Wilms tumor. The Journal Of Urology [serial online]. April 2013;189(4):1487-1492. Available from: MEDLINE, Ipswich, MA. Accessed March 24, 2014.

Resources

Huszno J, Starzyczny-Slota D, Jaworska M, Nowara E. Adult Wilms’ tumor-diagnsis and current therapy. Cent Eur J Urol. 2013. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921847/pdf/CEJU-66-00262.pdf. Accessed March 2, 2014.

American Cancer Society: Wilms Tumor. 2013. Accessed March 2, 2014.
http://www.cancer.org/acs/groups/cid/documents/webcontent/003149-pdf.pdf

Recent Related Research (from Pubmed)

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References

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