Patient Presentation
A 4-year-old male came to clinic for his well-child evaluation. He was doing well and would start pre-school in the fall. The past medical history showed that after birth he had a history of macroglossia and possible hemihypertrophy, both of which he outgrew. Genetic consultation had recommended testing for Beckwith-Wiedemann syndrome which was done and was negative. Because of the variance in the testing though, genetics also offered to continue to screen the patient as if he did have Beckwith-Wiedemann with an increased risk of Wilms tumor with q3-4 month abdominal ultrasound examinations; all returned negative to date. The family history was non-contributory.

The pertinent physical exam showed a happy male with normal vital signs and growth parameters.
His examination was normal.

The diagnosis of of a healthy male was made. The pediatrician reminded the parent that there were standing orders for the ultrasound examinations. “I already have 2 more scheduled. I just have them arranged and we just go. Each time the ultrasound is negative I am very grateful, and when he’s 7 years old, I’m going to be thrilled that we should have this behind us,” the mother commented.

Figure 142: Sagittal US of the left kidney (upper left) shows a round hyperechoic lesion in the lower pole of the kidney. Axial T2 MRI without contrast of the abdomen (upper right) and coronal T1 MRI without (lower left) and with (lower right) contrast of the abdomen shows a well-circumscribed, solid T1 hypointense and T2 isointense mass in the lower pole of the left kidney that enhances minimally.

Discussion
Wilms Tumor (WT) is a malignancy embryonal renal tumor and the most common pediatric renal tumor. It is ~ 5% of all pediatric malignancies. WT most commonly occurs in young children particularly those < 2 years, with most occurring under 5 years of age. It is uncommon after age 6-7 years. It is more common in girls than boys. It usually occurs in one kidney but can be multifocal (7%) or bilateral (5-9%). Bilateral disease is more common in patients with underlying genetic syndromes.

Most patients are asymptomatic when diagnosed. Parents notice a hard abdominal mass when bathing, dressing or holding their child. It is also commonly found on routine physical examination when the child is brought to the physician for an unrelated problem. Some patients present with fever, flank pain, hematuria or hypertension. Evaluation usually includes ultrasound of the mass and may include computed tomography and/or magnetic resonance imaging. Biopsy is often used but may not be performed in particular circumstances.

Treatment depends on the staging and also the protocols followed. Treatment consists of surgery to remove the tumor and kidney (and potentially adjacent structures) usually along with lymph node biopsies. Radiation and chemotherapy are used for higher risk patients.

Overall prognosis is good with 92% survival. However about 20% will recur most within 2 years of treatment, with an overall survival decreasing to 50%.

• *Tumor histology – + anaplasia and changes in chromosome 1p or 16q have poor prognosis
• *Tumor extension – metastasis (usually to the lung) and bilateral disease have poor prognosis. Tumor weight is considered in treatment stratification.
• Age – increasing age (especially > 2 years) has poorer prognosis
• Response to treatment

* – key prognostic factors

Survivors have increased overall early mortality and morbidity, usually relating to cancer recurrence, secondary malignancies and cardiac abnormalities secondary to chemotherapy side effects.
A review of common pediatric malignancies can be found here.

Learning Point
The etiology for most patients is unknown. “Up to 17% of WT occur as part of a recognizable malformation syndrome, 10% of which are associated with known WT predisposition.”
Several of these syndromes associated with WT have overgrowth, eye abnormalities or renal/genitourinary abnormalities as common features.

• Denys-Drash
  • Clinical: Nephrotic syndrome, ambiguous genitalia
  • Risk for WT: 75%
• Mosaic Variegated Aneuploidy
  • Clinical: microcephaly, cataracts, heart defects, intellectual disability
  • Risk for WT: > 70%
• WAGR
  • Clinical: acronym stands for WT, Aniridia, genitourinary abnormalities, range of developmental delays
  • Risk for WT: 45-60%
• Perlman
  • Clinical: Prenatal overgrowth, facial dysmorphism, cryptorchidism, renal dysplasia, developmental delay
  • Risk for WT:64%
• Fanconi Anemia
  • Clinical: Short stature, bone marrow failure, radial ray defects, may have normal appearance
  • Risk for WT: 20-40%
• Beckwith Wiedemann
  • Clinical: Overgrowth, organomegaly, hemihypertrophy, ear creases and/or pits, neonatal hypoglycemia
  • Risk for WT: 0.2-24%

Other syndromes with <10% risk of WT association include Mulibrey nanism (6-8%), Bloom (3%), Simpson-Golabi-Behmel (3%), Frasier syndrome (case report), Trisomy 18 (case report), Li-Fraumeni (case report), and Hyperparthyroid-jaw tumor (case report).

Preventative screening can be undertaken and can vary but is often considered when the risk of WT is 1-5%. Screening with abdominal ultrasound occurs every 3 months until age 7 when the risk of WT markedly decreases because of age.

Questions for Further Discussion
1. What are common oncologic emergencies? A review can be found here
2. What is in the differential diagnosis of an abdominal mass? A review can be found here
3. What are some of the communication techniques to help families when delivering bad news?

Related Cases

Disease: Wilms’ Tumor | Kidney Cancer

Symptom/Presentation: Health Maintenance and Disease Prevention

Specialty: Oncology | Genetics

Age: Preschooler

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.
Information prescriptions for patients can be found at MedlinePlus for these topics: Wilms Tumor and Kidney Cancer.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Pater L, Melchior P, Rube C, et al. Wilms tumor. Pediatric Blood & Cancer. 2021;68(S2):e28257. doi:10.1002/pbc.28257

Nelson MV, van den Heuvel-Eibrink MM, Graf N, Dome JS. New Approaches to Risk Stratification for Wilms Tumor. Curr Opin Pediatr. 2021;33(1):40-48. doi:10.1097/MOP.0000000000000988

Spreafico F, Fernandez CV, Brok J, et al. Wilms tumour. Nat Rev Dis Primers. 2021;7(1):1-21. doi:10.1038/s41572-021-00308-8

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa