Nephroblastoma also known as Wilms tumor, is the most common renal malignancy affecting one in 10,000 children <15 years old Children with bilateral disease are diagnosed at an earlier age (median age, girls at 31 months and boys at 24 months): Patients with associated congenital anomalies are also diagnosed at an earlier age Accounts for 6-7% of cases of childhood cancer in the developed world and 12% in South Africa In Tanzania the prevalence is 6.7% ( Mgaya E et al., 2000), “third from leukemia and lymphoma” (Shakilu J, 2017) The overall survival rate of nephroblastoma approaches 90% in the developed world but in developing countries the survival rates are much less and in some sub-Saharan countries it is only 40% at 8 months after diagnosis These may occur in 1% of infantile kidneys but typically regress during childhood Nephrogenic rests normally occur in 1% of newborn kidneys and regress early in childhood: in contrast, they are present in 35% of kidneys with unilateral Wilms tumor and almost 100% of kidneys with bilateral disease Nephrogenic rests normally occur in 1% of newborn kidneys and regress early in childhood: in contrast, they are present in 35% of kidneys with unilateral Wilms tumor and almost 100% of kidneys with bilateral disease Nephrogenic rests normally occur in 1% of newborn kidneys and regress early in childhood: in contrast, they are present in 35% of kidneys with unilateral Wilms tumor and almost 100% of kidneys with bilateral disease Nephrogenic rests normally occur in 1% of newborn kidneys and regress early in childhood: in contrast, they are present in 35% of kidneys with unilateral Wilms tumor and almost 100% of kidneys with bilateral disease Has been associated with loss of function mutations of a number of tumor suppressor and transcription genes These include mutations of the WT1, p53, FWT1, and FWT2 genes and at the 11p15.5 locus Histologically, the classic favorable histology Wilms tumor is comprised of three cell types: Blastemal cells – Undifferentiated cells Stromal cells – Immature spindle cells and heterologous skeletal muscle, cartilage, osteoid or fat Epithelial cells – Glomeruli and tubules Grossly, Wilms tumors are usually well-circumscribed and have a pseudo-capsule Histologically, Wilms is divided into "Favorable" and "Unfavorable" histologies "Favorable" Histology: 90% of Wilms tumors will demonstrate "favorable" histology which generally has a better prognosis Most children with Wilms tumor present with an abdominal mass or swelling without other signs or symptoms The definitive diagnosis of Wilms tumor is made by histologic confirmation at the time of either surgical excision or biopsy Stage I indicates the tumor was completely contained within the kidney without any breaks or spillage outside the renal capsule and no vascular invasion Stage II would be a tumor that has grown outside the kidney Stage IIIunresectable tumor Stage IV-Metastasis Stage V-bilateral kidney Surgery is the main treatment

1. NEPHROBLASTOMA
Presenter; Pendo Chaula MMED 1

2. INTRODUCTION
 Nephroblastoma also known as Wilms tumor, is the
most common renal malignancy affecting one in
10,000 children <15 years old
 it accounts for about 95% of all paediatric tumors
of the kidney with long term survival above 90% for
localised disease and 75% for metastatic disease
 In patients with unilateral involvement, the median
age at diagnosis is 43 months in girls and 37
months in boys
Bernstein L, Linet M, Smith MA, et al. Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995
SEER Program. Bethesda, MD, National Cancer Institute 1999. p.79
Breslow N, Olshan A, Beckwith JB, Green DM. Epidemiology of Wilms tumor. Med Pediatr Oncol 1993; 21:172

3.  The peak age is between 24 and 36 months and 75% of patients will
be less than 60 months of age at diagnosis and 95% of patients will
be less than 120 months of age at diagnosis
 Children with bilateral disease are diagnosed at an earlier age
(median age, girls at 31 months and boys at 24 months): Patients with
associated congenital anomalies are also diagnosed at an earlier age
• The overall survival rate approaches 90% in the developed world but
in developing countries the survival rates are much less and in some
sub-Saharan countries it is only 40% at 8 months after diagnosis
Bernstein L, Linet M, Smith MA, et al. Cancer incidence a
SEER Program. Bethesda, MD, National Cancer Institute 1999. p.79
Breslow N, Olshan A, Beckwith JB, Green DM. Epidemiology of Wilms tumor. Med nd survival
among children and adolescents: United States SEER Program 1975-1995 Pediatr Oncol 1993;

4. ASSOCIATED CONGENITAL
SYNDROMES
• Wagr syndrome- refers to the presence of Wilms tumor, aniridia,
genitourinary anomalies, and mental retardation
• Denys-Drash syndrome- This includes male pseudo-
hermaphroditism and progressive renal failure starting in infancy.
90% developes WT.
• Beckwith-wiedemann syndrome- hemihypertrophy, pancreatic
enlargement, hypertrophic kidneys, omphalocele, ear creases,
macrosomia, and macroglossia. 5% to 10% developes WT.
• Other congenital anomalies like Perlman syndrome, Setos
syndrome, Simpson-Golabi-Behmel syndrome, Trisomy 18
(Edward's syndrome), Frasier syndrome, Bloom syndrome, Li-
Fraumeni syndrome, etc.

5. EPIDEMIOLOGY
 The risk of developing Wilms tumor varies among ethnic
groups, with a greater risk in African-Americans and a lower
risk in the Asian population, Black – African children have an
increased prevalence of WT (11 cases per million children
 Accounts for 6-7% of cases of childhood cancer in the
developed world and 12% in South Africa
 In children less than 15 years of age, the annual prevalence
rate is about 7 to 10 cases per million USA.
Breslow N, Olshan A, Beckwith JB and Green DM. ‘Epidmiology of Wilms' tumor’, Med PediatrOncol. 1993; vol.21, pp.172-181.
Bernstein L, Linet M, Smith MA, Olshan AF. 1999, ‘Renal tumors’, In: Ries LAG, Smith MA, Gurney JG, et al (eds), Cancer Incidence and Survival among
Children and Adolescents: United States SEER Program 1975-1995, National Cancer Institute, SEER Program (Publication No. 99-4649), National Institutes of
Health, Bethesda.

6.  In Tanzania the prevalence is 6.7% ( Mgaya E et al., 2000), “third
from leukemia and lymphoma” (Shakilu J, 2017)
 The overall survival rate of nephroblastoma approaches 90% in the
developed world but in developing countries the survival rates are
much less and in some sub-Saharan countries it is only 40% at 8
months after diagnosis
 Wilms tumor is primarily a sporadic disease and only 1-2% of
individuals with Wilms tumor have a relative with the disease
Stiller CA, Parkin DM. Geographic and ethnic variations in the incidence of childhood cancer. Br Med Bull 1996; 52:682
Huff V. Wilms' tumours: about tumour suppressor genes, an oncogene and a chameleon gene. Nat Rev Cancer 2011; 11:111

7. Etiology
• The cause is not precisely known, but it is believed to be due
to genetic alterations that deal with the normal embryological
development of the genitourinary tract
• It is thought to develop from persistent metanephric tissue or
nephrogenic rests
• These may occur in 1% of infantile kidneys but typically
regress during childhood.
• These abnormal metanephric cells are found in up to 100% of
cases of bilateral Wilms but only 35% of unilateral tumors

8. PATHOGENESIS
 Caused by abnormal renal development, resulting in
proliferation of the metanephric blastema without normal
tubular and glomerular differentiation
 Is thought to arise from foci of persistent metanephric cells
referred to as nephrogenic rests or nephroblastomatosis
 Nephrogenic rests normally occur in 1% of newborn kidneys
and regress early in childhood: in contrast, they are present in
35% of kidneys with unilateral Wilms tumor and almost 100%
of kidneys with bilateral disease
Beckwith JB, Kiviat NB, Bonadio JF. Nephrogenic rests, nephroblastomatosis, and the pathogenesis of Wilms' tumor. Pediatr Pathol 1990;
10:1.
Beckwith JB. Precursor lesions of Wilms tumor: clinical and biological implications. Med Pediatr Oncol 1993; 21:158.

9.  Has been associated with loss of function mutations of a
number of tumor suppressor and transcription genes
 These include mutations of the WT1, p53, FWT1, and FWT2
genes and at the 11p15.5 locus
 The role of these gene mutations in the pathogenesis of
Wilms tumor remains unknown
Coppes MJ, Haber DA, Grundy PE. Genetic events in the development of Wilms' tumor. N Engl J Med 1994; 331:586

10.  Most Wilms tumors are solitary lesions however 5-7% of
patients have bilateral renal involvement and 10% have
multifocal loci within a single kidney
 May include cysts, hemorrhage or necrosis
 The tumor is typically surrounded by a pseudocapsule, which
may help distinguish it from other renal tumors, which have
an infiltrative border
Fernandez C, Geller JI, Ehrlich PF, et al. Renal tumors. In: Principles and Practice of Pediatric Oncology, 6th ed, Pizzo P, Poplack D (Eds),
Lippincott Williams & Wilkins, St. Louis 2011. p.861

11.  Histologically, the classic favorable histology Wilms tumor is
comprised of three cell types:
 Blastemal cells – Undifferentiated cells
 Stromal cells – Immature spindle cells and heterologous skeletal muscle,
cartilage, osteoid or fat
 Epithelial cells – Glomeruli and tubules
 Some contain only one or two cell types: tumors with only
one cell type, it is often difficult to make the diagnosis of
Wilms tumor

12. Histopathology
• Grossly, Wilms tumors are usually well-circumscribed and
have a pseudo-capsule
• Histologically, Wilms is divided into "Favorable" and
"Unfavorable" histologies
• "Favorable" Histology: 90% of Wilms tumors will
demonstrate "favorable" histology which generally has a
better prognosis

13. • Classical histological features of a "favorable" Wilms tumor
include a triphasic pattern of blastema, epithelial, and stromal
tissues
• The blastema is the most undifferentiated

14. • malignant component. It consists of collections of small,
round blue cells with very active mitotic activity and
overlapping nuclei
• The epithelial component can demonstrate wide variations in
differentiation from an early tubular formation with primitive
epithelial rosette-like structures to differentiating tubules or
glomeruli-like structures, which represent nephrogenesis at
different developmental stages

15. • The stromal component may include densely packed
undifferentiated mesenchymal cells or loose cellular myxoid
areas
• The latter areas may be difficult to distinguish from non-
tumorous stroma associated with chemotherapy- induced
change
• Heterologous differentiation of neoplastic stroma in the form
of well-differentiated smooth or skeletal muscle cells, fat
tissue, cartilage, bone, and even glial tissue is present in some
cases, especially in tumors that have undergone preoperative
chemotherapy

16. CLINICAL PRESENTATION
 Most children with Wilms tumor present with an abdominal mass or
swelling without other signs or symptoms
• Abdominal pain 30-40%, hematuria 12-25%, fever and hypertension
25% (HTN will normalize after nephrectomy).
 Subcapsular hemorrhage can present with rapid abdominal
enlargement and anemia.
 Wilms tumor in boys may also present with cryptorchidism,
varicocele or hypospadias
Fernandez C, Geller JI, Ehrlich PF, et al. Renal tumors. In: Principles and Practice of Pediatric Oncology, 6th ed, Pizzo P, Poplack D (Eds),
Lippincott Williams & Wilkins, St. Louis 2011. p.861

17.  Although the lung is the most common metastatic site, children
rarely present with respiratory symptoms (dyspnea or tachypnea).
 10% of affected girls will have congenital uterine anomalies and
other renal congenital abnormalities such as duplication and renal
ectopia.
Fernandez C, Geller JI, Ehrlich PF, et al. Renal tumors. In: Principles and Practice of Pediatric Oncology, 6th ed, Pizzo P, Poplack D (Eds),
Lippincott Williams & Wilkins, St. Louis 2011. p.861

18. DIAGNOSIS
 The definitive diagnosis of Wilms tumor is made by histologic
confirmation at the time of either surgical excision or biopsy
 Laboratory testing: renal function, urinalysis, liver function, serum
calcium, complete blood count, coagulation studies and serum
electrolyte.
 Cytogenetics studies to look for 1p and 16q deletion.
 Abdominal imaging: USS, CT/MRI
 Chest imaging: CXR or chest CT scan for metastasis
https://www.ncbi.nlm.nih.gov/books/NBK442004/?report=printable 4/10

19. Tanzania treatment guideline 2021

20. DIFFERENTIAL DIAGNOSIS
Imaging studies and tissue histology differentiate Wilms tumor from
other disorders:
 Neuroblastoma-patients who are post-radiation and post-chemotherapy are
at increased risk.
 Clear cell sarcoma of the kidney-high mortality and relapse rate. Metastasize
to bone. Histologically similar to WT.
 Rhabdoid tumor of the kidney-seen before age of 2yrs almost never in
children older than 5yrs. Metastatic at initial presentation. 80% mortality rate.
 Congenital mesoblastic nephroma-typically found in the first year of life, most
often by USS. Hypertension and elevated renin levels usually accompany it.
 Renal cell carcinoma- is rare in the pediatric age group. However, when
present, it is often at a more advanced stage than in adults.
 Renal medullary carcinoma-very aggressive and dangerous cancer that is
found almost exclusively in individuals with sickle cell disease, usually trait. It
tends to be highly locally-invasive and metastasizes early.

21. STAGES
 Staging criteria for Wilms tumor are based upon the anatomic
extent of the tumor without consideration for genetic,
histologic or biological markers:
 National Wilms Tumor Study (NWTS): The NWTS system is
based upon surgical evaluation prior to the administration of
chemotherapy
 International Society of Pediatric Oncology (SIOP): The SIOP
system is based upon post-chemotherapy surgical evaluation
Metzger ML, Dome JS. Current therapy for Wilms' tumor. Oncologist 2005; 10:815

22. Staging
 Stage I indicates the tumor was completely contained within
the kidney without any breaks or spillage outside the renal
capsule and no vascular invasion.
 This stage accounts for 40% to 45% of all Wilms tumors.
 Stage II would be a tumor that has grown outside the kidney
to some degree, such as into surrounding fatty tissue.
 Usually, the tumor would be completely removable by
surgery, and regional lymph nodes are negative, About 20% of
all Wilms tumors are at this stage.

23.  Stage III comprises about 20% to 25% of all Wilms tumors and
indicates a tumor which could not be completely removed
surgically such as the following:
 Cancer has spread to the regional lymph nodes but not to
more distant nodes, such as in the chest
 Cancer has grown into nearby vital structures so it could not
be surgically removed completely
 Deposits of the tumor (tumor implants) are found in the
peritoneum, or there are positive surgical margins

24.  Cancer cells were accidentally “spilled” into the abdominal
cavity during surgery
 The tumor was removed in separate pieces surgically; such as
one piece from the kidney and another from the
 adrenal gland
 A renal biopsy of the tumor was done before it was surgically
removed

25.  Stage IV tumors are those that have spread through the
vascular system to distant organs such as the lungs, liver,
brain, or bones, or to distant lymph nodes. These account for
about 10% of all Wilms tumors.
 Stage V are those cases where both kidneys are involved with
tumor at the time of initial diagnosis. About 5% of all Wilms
tumors are at this stage. Individual staging of each renal unit is
needed as well.

26. TREATMENT
 Surgery is the main treatment for Wilms tumor
 Radical nephrectomy for unilateral: cancer along with the
entire kidney, surrounding lymphnodes and tissues are
removed and partial nephrectomy on the contralateral side
 Lymphnodes sampling is performed to assess degree of
spread within the abdomen
 Neoadjuvant treatment shrinks the tumor and adjuvant
therapy prevents recurrence

27. Chemotherapy
• Give vincristine IV,
• actinomycin D IV,
• doxorubicine IV,
• carboplatin IV,
• etoposide IV,
• cyclophosphamide IV,
• doxorubicin IV
6/23/2021 Wilms Tumor - StatPearls - NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK442004

28. Treatment / Management
 chemotherapy first and do the nephrectomy later. The
opposite kidney may be explored to ensure that cancer has
not spread although this is not necessary for low stage tumors
with favorable histology if imaging is negative.
 Lymph nodes around the aorta are sampled for staging and to
improve survival.
 Open surgery, however, typically provides more lymph nodes
in the surgical specimen.
 Routine biopsies are not recommended except in unusual
circumstances as a biopsy automatically increases tumor
staging to Stage III. This stage requires radiation and
chemotherapy.

29.  Postoperative radiation may or may not be administered
depending on tumor histology and extent of spread.
 For patients without metastases who will be receiving
radiation, initiation of therapy within 14 days of surgery
appears to improve overall survival
 Chemotherapy is usually administered for more aggressive
disease. In children with bilateral disease, immediate
nephrectomy is not performed. Some experts attempt high-
dose chemotherapy to kill the tumor cells and hopefully
salvage the kidney.

30. • Repeat biopsies are required to determine if the tumor is
responding to therapy.
• Patients who relapse after initial combined therapy tend to
have a worse prognosis than newly discovered Wilms.

31. PROGNOSIS
 Several prognostic factors at the time of initial diagnosis are
associated with an increased risk of tumor recurrence or
death:
 The most important determinants of outcome in children
with WT are the histopathology and tumor stage.
 Tumor histology: anaplastic histology, blastemal type
histology
 Tumor stage
 Molecular and genetic markers: e.g. loss of heterozygosity at
chromosome 16q, 1p, 11p15; and 1q gain
 Age >2 years
Dome JS, Graf N, Geller JI, et al. Advances in Wilms Tumor Treatment and Biology: Progress
Through International Collaboration. J Clin Oncol
2015; 33:2999

32. The prognosis varies by tumor stage and histology.
 Favorable histology has survival rates of 99% to 86% while
unfavorable histology survival ranges from 84% to 38%
depending on the stage.
 A poorer prognosis is associated with the following
characteristics:
 Anaplastic histology in stage II to IV tumors
 Diffuse anaplasia is worse than focal
6/23/2021 Wilms Tumor - StatPearls - NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK442004/?report=printable 6/10

33.  A poorer prognosis has been linked to TP53 and with the loss
of heterozygosity at chromosomes 1p, 1q, 11p15 and 16q.
 Loss of heterozygosity at chromosomes 1p, 1q, 11p15 and 16q
or presence of TP53
 Higher stage (most epithelial predominant tumors are stage I;
 most blastema predominant tumors are stage III and IV)

34.  Age older than two years
 Higher positive lymph node density
 Large tumor size
 Even small tumor foci can be associated with a poorer
prognosis due to resistance to chemotherapy

35. complications
 Increased risk of secondary malignancies years later in life due
to Radiation and chemotherapy
 It is well established that radiation therapy will increase the
risk for bone, breast, colon and thyroid cancers later on in life
 It will also increase the risk of osteoporosis
Islam M, Saltzman AF, Amini A, Carrasco A, Cost NG. Factors Influencing Overall Survival of Children, Adolescents, and Young Adults With High-risk Renal
Tumors. Urology. 2018 Oct;120:222-230. [PubMed: 30076944] Islam M, Saltzman AF, Amini A, Carrasco A, Cost NG. Factors Influencing Overall Survival
of Children, Adolescents, and Young Adults With High-risk Renal Tumors. Urology. 2018 Oct;120:222-230. [PubMed: 30076944] ,

36.  Chemotherapy with dactinomycin, doxorubicin and
vincristine contributes to a higher risk of secondary
malignancies as well as specific toxicities such as hearing
(carboplatin), cardiac function (adriamycin) and peripheral
neuropathy (vincristine)
 About 5% to 10% of Wilms patients will present with Von
Willebrand's disease which can complicate treatment
Baxter PA, Nuchtern JG, Guillerman RP, Mahoney DH, Teruya J, Chintagumpala M, Yee DL. Acquired von
Oostveen RM, Pritchard-Jones K. Pharmacotherapeutic Management of Wilms Tumor: An Update. Paediatr Drugs. 2019 Feb;21(1):1-
13. [PubMed: 30604241]

37. RECOMMENDATION
 Advocate early health care seeking behavior in the
communities for early diagnosis and management
 Networking with pediatric cancer charity organizations to
assist parents with financial constraints for timely
investigations
 Therapeutic foods program establishment at different
hospitals eg Benjamin Mkapa hospital

38. TAKE HOME MESSAGE
 Early and thorough diagnosis thus treatment helps reduce
morbidity and mortality