eMedicine Specialties > Pediatrics: General Medicine > Oncology

Wilms Tumor: Differential Diagnoses & Workup

Author: Arnold C Paulino, MD, Associate Professor, Department of Radiology, Division of Radiation Oncology, Associate Professor of Pediatrics, Baylor College of Medicine; Consulting Staff, Methodist Hospital and Texas Children's Hospital
Coauthor(s): Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Contributor Information and Disclosures

Updated: Mar 3, 2009

Differential Diagnoses

Neuroblastoma
Polycystic Kidney Disease
Rhabdomyosarcoma

Other Problems to Be Considered

Mesoblastic nephroma (most common renal tumor in first month of life)7
Renal cell carcinoma
Clear cell sarcoma of the kidney (CCSK)
Rhabdoid tumor of the kidney (RTK)
Nonmalignant mass
Hydronephrosis
Multicystic kidney disease
Renal cyst
Renal thrombosis
Dysplastic kidney
Renal hemorrhage

Workup

Laboratory Studies

The following studies are indicated in patients with Wilms tumor:

  • CBC count
  • Chemistry profile, including kidney function tests and routine measurements of electrolytes and calcium
  • Urinalysis
  • Coagulation studies
  • Cytogenetics studies
    • Results may reveal an 11p13 deletion as in WAGR syndrome.
    • Studies may show a duplication of the paternal allele 11p15, as in Beckwith-Wiedemann syndrome (BWS).
    • Mutational analysis of the WT1 gene may be indicated when Denys-Drash syndrome (intersexual disorders, nephropathy, Wilms tumor) is suspected.

Imaging Studies

  • Renal ultrasonography
    • Often, the initial study as ultrasonography does not expose children to the detrimental effects of radiation.
    • Real-time ultrasonography is a relatively inexpensive way of helping determine the patency of the inferior vena cava. When tumor is identified in the vessel, the proximal extent of the thrombus must be established prior to surgery because of possible extension of tumor to the right atrium.
  • CT scanning8
    • Abdominal CT scanning helps in determining the origin of the tumor, involvement of the lymph nodes, bilateral kidney involvement, invasion into major vessels (eg, inferior vena cava), and liver metastases.

      CT scan in a patient with a right-sided Wilms tum...

      CT scan in a patient with a right-sided Wilms tumor with favorable histology.

      [ CLOSE WINDOW ]
      CT scan in a patient with a right-sided Wilms tum...

      CT scan in a patient with a right-sided Wilms tumor with favorable histology.


      CT scan of child with a stage IV Wilms tumor with...

      CT scan of child with a stage IV Wilms tumor with favorable histology. Note the bilateral pulmonary metastases.

      [ CLOSE WINDOW ]
      CT scan of child with a stage IV Wilms tumor with...

      CT scan of child with a stage IV Wilms tumor with favorable histology. Note the bilateral pulmonary metastases.

    • If chest CT findings are positive and chest radiographic findings are negative, diagnostic biopsy of the lesions noted on the chest CT scan is recommended.
  • MRI scanning
    • Abdominal MRI scanning has been reported to be the most sensitive imaging modality for determination of caval patency and may be important in determining whether the inferior vena cava is directly invaded by tumor.
    • Wilms tumor demonstrates low signal intensity on T1-weighted images and high signal intensity on T2-weighted images.
  • Four-field chest radiography
    • Images may depict lung metastases.
    • Patients with lung lesions on chest radiography have traditionally been given whole-lung radiation therapy.

Procedures

  • Histopathologic confirmation of Wilms tumor is essential.
    • In North America, patients with suspected Wilms tumor undergo nephrectomy immediately. During this procedure, the contralateral kidney is explored to ensure that the disease is indeed unilateral, and lymph node biopsy samples are obtained for staging purposes. Lymph node dissection is not indicated.
    • In contrast to immediate surgery, most European centers make a presumptive diagnosis of Wilms tumor based on imaging findings alone. Clinicians in Europe prefer to administer chemotherapy before nephrectomy without survival compromise.9,10
    • In North America, immediate nephrectomy is not performed in patients with bilateral disease at presentation when sparing of the renal tissue becomes important.
    • Transcutaneous biopsy is not usually recommended and may in fact complicate treatment by causing preoperative tumor spill, requiring whole abdominal radiotherapy.
  • Patients with negative findings on chest radiography and positive findings on CT of the lungs require tissue diagnosis of the lung nodules because several conditions (eg, histoplasmosis, atelectasis, pseudotumor, intrapulmonary lymph node, pneumonia) can mimic pulmonary metastases. Studies from the NWTS have not shown any survival benefit by treating nodules that have negative chest radiograph findings but positive CT scan findings with whole lung radiotherapy. In one study, patients treated with whole lung radiotherapy had fewer lung relapse but had higher treatment-related deaths.11

Histologic Findings

  • The classic histologic pattern is triphasic and composed of epithelial, blastemal, and stromal elements.
    • Approximately 90% of all renal tumors have favorable histology.
    • About 3-7% of Wilms tumors are characterized by anaplastic changes. If these changes are present diffusely throughout the tumor, they are predictive of a poor outcome. Wilms tumors with anaplastic changes have unfavorable histology.
    • Two tumor types previously included in the category with unfavorable histology are, in fact, clearly separate malignant entities. These types are clear cell sarcoma of the kidney (CCSK) and rhabdoid tumor of the kidney (RTK).
  • The improved histopathologic classification of childhood renal tumors has not only helped to define appropriate treatment strategies for these patients but has also contributed to the understanding of the molecular genetic events underlying the Wilms tumor.
    • For instance, nephrogenic rests, dysplastic lesions of metanephric origin, are now believed to represent precursor lesions. These lesions are observed in approximately one third of kidneys affected by Wilms tumors.
    • The relationship between the pathology of the nephrogenic rests, the tumor, and the congenital disorders is of particular interest. These associations have been helpful in evaluating a potential correlation between a Wilms tumor phenotype in one regard and molecular genetic events leading to the development of that same tumor in another.
    • Children younger than 12 months diagnosed with perilobar nephrogenic rests have a markedly increased risk of developing a contralateral Wilms tumor.12

Staging

The current Children's Oncology Group (COG) staging for Wilms tumor is as follows:

  • Stage I: Tumor is limited to kidney and is completely resected. The renal capsule is intact. The tumor was not ruptured or biopsied prior to removal. The vessels of the renal sinus are not involved. No evidence of tumor is present at or beyond margins of resection.
  • Stage II: The tumor is completely resected, and no evidence of tumor at or beyond the margins of resection is noted. The tumor extends beyond the kidney (penetration of renal capsule, involvement of renal sinus).
  • Stage III: A residual nonhematogenous tumor is present following surgery and is confined to the abdomen. Positive lymph nodes in abdomen or pelvis are noted. Penetration through peritoneal surface is observed. Peritoneal implants are present. Gross or microscopic tumor remains postoperatively, including positive margins of resection. Tumor spillage is noted. The tumor is treated with preoperative chemotherapy. The rumor is removed in more than one piece.
  • Stage IV: Hematogenous metastases (eg, lung, liver, bone, brain) or lymph node metastases beyond abdomen or pelvis is noted.
  • Stage V: Bilateral renal involvement by tumor is present at diagnosis.

More on Wilms Tumor

Overview: Wilms Tumor
Differential Diagnoses & Workup: Wilms Tumor
Treatment & Medication: Wilms Tumor
Follow-up: Wilms Tumor
Multimedia: Wilms Tumor
References
[ CLOSE WINDOW ]

References

  1. Coppes MJ, Pritchard-Jones K. Principles of Wilms' tumor biology. Urol Clin North Am. Aug 2000;27(3):423-33, viii. [Medline].

  2. Knudson AG, Strong LC. Mutation and cancer: a model for Wilms' tumor of the kidney. J Natl Cancer Inst. Feb 1972;48(2):313-24. [Medline].

  3. Coppes MJ, Haber DA, Grundy PE. Genetic events in the development of Wilms' tumor. N Engl J Med. Sep 1 1994;331(9):586-90. [Medline].

  4. Coppes MJ, Huff V, Pelletier J. Denys-Drash syndrome: relating a clinical disorder to genetic alterations in the tumor suppressor gene WT1. J Pediatr. Nov 1993;123(5):673-8. [Medline].

  5. Grundy PE, Breslow NE, Li S, et al. Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor: a report from the National Wilms Tumor Study Group. J Clin Oncol. Oct 10 2005;23(29):7312-21. [Medline].

  6. Breslow N, Olshan A, Beckwith JB, Green DM. Epidemiology of Wilms tumor. Med Pediatr Oncol. 1993;21(3):172-81. [Medline].

  7. van den Heuvel-Eibrink MM, Grundy P, Graf N, et al. Characteristics and survival of 750 children diagnosed with a renal tumor in the first seven months of life: A collaborative study by the SIOP/GPOH/SFOP, NWTSG, and UKCCSG Wilms tumor study groups. Pediatr Blood Cancer. Jun 2008;50(6):1130-4. [Medline].

  8. Refaie HD, Sarhan M, Hafez A. Role of CT in assessment of unresectable Wilms' tumor response after preoperative chemotherapy in pediatrics. ScientificWorldJournal. Jul 13 2008;8:661-9. [Medline].

  9. Mitchell C, Pritchard-Jones K, Shannon R, et al. Immediate nephrectomy versus preoperative chemotherapy in the management of non-metastatic Wilms' tumour: results of a randomised trial (UKW3) by the UK Children's Cancer Study Group. Eur J Cancer. Oct 2006;42(15):2554-62. [Medline].

  10. Reinhard H, Semler O, Burger D, et al. Results of the SIOP 93-01/GPOH trial and study for the treatment of patients with unilateral nonmetastatic Wilms Tumor. Klin Padiatr. May-Jun 2004;216(3):132-40. [Medline].

  11. Meisel JA, Guthrie KA, Breslow NE, Donaldson SS, Green DM. Significance and management of computed tomography detected pulmonary nodules: a report from the National Wilms Tumor Study Group. Int J Radiat Oncol Biol Phys. Jun 1 1999;44(3):579-85. [Medline].

  12. Coppes MJ, Arnold M, Beckwith JB, et al. Factors affecting the risk of contralateral Wilms tumor development: a report from the National Wilms Tumor Study Group. Cancer. Apr 1 1999;85(7):1616-25. [Medline].

  13. D'Angio GJ, Breslow N, Beckwith JB, et al. Treatment of Wilms' tumor. Results of the Third National Wilms' Tumor Study. Cancer. Jul 15 1989;64(2):349-60. [Medline].

  14. Kalapurakal JA, Li SM, Breslow NE, et al. Influence of radiation therapy delay on abdominal tumor recurrence in patients with favorable histology Wilms' tumor treated on NWTS-3 and NWTS-4: a report from the National Wilms' tumor Study Group. Int J Radiat Oncol Biol Phys. 2003;57:495-9. [Medline].

  15. Green DM, Breslow NE, Beckwith JB, et al. Treatment with nephrectomy only for small, stage I/favorable histology Wilms tumor: a report from the National Wilms Tumor Study Group. J Clin Oncol. Sep 1/ 2001;19:3719-24. [Medline].

  16. D'Angio GJ, Rosenberg H, Sharples K, et al. Position paper: imaging methods for primary renal tumors of childhood: costs versus benefits [published erratum appears in Med Pediatr Oncol 1993;21(9):695]. Med Pediatr Oncol. 1993;21(3):205-12. [Medline].

  17. Green DM, Donckerwolcke R, Evans AE, D'Angio GJ. Late effects of treatment for Wilms tumor. Hematol Oncol Clin North Am. Dec 1995;9(6):1317-27. [Medline].

  18. Egeler RM, Wolff JE, Anderson RA, Coppes MJ. Long-term complications and post-treatment follow-up of patients with Wilms' tumor. Semin Urol Oncol. Feb 1999;17(1):55-61. [Medline].

  19. Evans AE, Norkool P, Evans I, et al. Late effects of treatment for Wilms' tumor. A report from the National Wilms' Tumor Study Group. Cancer. Jan 15 1991;67(2):331-6. [Medline].

  20. Paulino AC, Wen BC, Brown CK, et al. Late effects in children treated with radiation therapy for Wilms' tumor. Int J Radiat Oncol Biol Phys. Mar 15 2000;46(5):1239-46. [Medline].

  21. Green DM. The treatment of stages I-IV favorable histology Wilms' tumor. J Clin Oncol. Apr 15 2004;22(8):1366-72. [Medline].

  22. Montgomery BT, Kelalis PP, Blute ML, et al. Extended followup of bilateral Wilms tumor: results of the National Wilms Tumor Study. J Urol. Aug 1991;146(2 ( Pt 2)):514-8. [Medline].

  23. Paulino AC, Wilimas J, Marina N, et al. Local control in synchronous bilateral Wilms tumor. Int J Radiat Oncol Biol Phys. Oct 1 1996;36(3):541-8. [Medline].

  24. Paulino AC, Thakkar B, Henderson WG. Metachronous bilateral Wilms' tumor: the importance of time interval to the development of a second tumor. Cancer. Jan 15 1998;82(2):415-20. [Medline].

  25. Dome JS, Cotton CA, Perlman EJ, et al. Treatment of anaplastic histology Wilms' tumor: results from the fifth National Wilms' Tumor Study. J Clin Oncol. May 20 2006;24(15):2352-8. [Medline].

  26. Green DM, Cotton CA, Malogolowkin M, et al. Treatment of Wilms tumor relapsing after initial treatment with vincristine and actinomycin D: a report from the National Wilms Tumor Study Group. Pediatr Blood Cancer. May/ 2007;48:493-9. [Medline].

  27. Malogolowkin M, Cotton CA, Green DM, et al. Treatment of Wilms tumor relapsing after initial treatment with vincristine, actinomycin D, and doxorubicin. A report from the National Wilms Tumor Study Group. Pediatr Blood Cancer. Feb 2008;50(2):236-41. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

Wilms tumor, Wilms' tumor, nephroblastoma, synchronous bilateral Wilms tumor, metachronous bilateral Wilms tumor, National Wilms Tumor Study, NWTS, National Wilms Tumor Study Group, NWTSG, International Society of Pediatric Oncology, SIOP, WAGR syndrome, Beckwith-Wiedemann syndrome, BWS, Denys-Drash syndrome, Denys-Drash syndrome, visceromegaly, macroglossia, hyperinsulinemic hypoglycemia, urinary tract infection, varicocele, hypertension, hypotension, cryptorchidism, horseshoe kidney, hypospadias

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Arnold C Paulino, MD, Associate Professor, Department of Radiology, Division of Radiation Oncology, Associate Professor of Pediatrics, Baylor College of Medicine; Consulting Staff, Methodist Hospital and Texas Children's Hospital
Arnold C Paulino, MD is a member of the following medical societies: American College of Radiology, American Medical Association, American Radium Society, American Society for Therapeutic Radiology and Oncology, Children's Oncology Group, Connective Tissue Oncology Society, and Radiological Society of North America
Disclosure: Nothing to disclose.

Coauthor(s)

Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Kathleen M Sakamoto, MD, PhD, Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA and California Nanosystems Institute and Molecular Biology, UCLA
Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, Society for Pediatric Research, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Steven K Bergstrom, MD, Assistant to the Chairman, Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland
Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and International Society for Experimental Hematology
Disclosure: Nothing to disclose.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine
Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.