Wilm's tumor, also known as nephroblastoma, is a malignant tumor of the kidneys that typically occurs in young children. It is the fifth most common pediatric malignancy. Max Wilms first described this tumor in 1899. Imaging tests such as ultrasound and CT scans are used to identify tumors in the kidneys and check for spread. Tissue samples are often obtained during surgery to confirm diagnosis. Treatment involves surgery, chemotherapy, and sometimes radiation therapy.

1. Wilm’s
tumor
Nephroblastoma

2. • Wilms' tumor or nephroblastoma is
malignant tumor of the kidneys that
typically occurs in children. Dr. Max Wilms
, the German surgeon (1867–1918) first
described this kind of tumor.
• Wilms tumor is the fifth most common
pediatric malignancy (7% of all childhood
tumors).
INTRODUCTION

3. HISTORY

4. • It was in 1899 when Max Wilms, a German surgeon and
pathologist, described a group of children with kidney
tumors and since that time his name has been applied to
pediatric nephroblastoma.
• In the early 1960s, a genetic basis of Wilms' tumor was
suggested for the first time. From retrospective analysis
of the first National Wilms' Tumor Study (NWTS)
(NWTS-1) in the mid-1970s, anaplasia was initially
recognized as an adverse prognostic feature.

5. EPIDEMIOLOGY, INCIDENCE, AND AGE AT
ONSET
• Wilms' tumor is the most common abdominal
malignancy observed in children and affects
approximately 1 in 10, 000 children before the age of
15 worldwide.
• Wilms' tumor is only exceptionally congenital but
primarily seen in infants, with 50 percent of cases
occurring before the age of 3 years and 90 percent
before the age of 6.
• Rarely, it is seen in adults aged 50 or older.

6. • Most commonly unilateral, but
• Approximately 5% to 10% of Wilms tumors
involve both kidneys,
• either simultaneously (synchronous)
or one after the other
(metachronous).

7. • The incidence in European populations ranges above
Asian but below Africans.
• The frequency in females may be slightly higher.
Wilms' tumor is primarily a disease of the kidney, but
occasionally extrarenal locations have been reported,
especially in the retroperitoneum, the sacrococcygeal
region, testis, uterus, inguinal canal, and mediastinum

8. RISK FACTORS
Age
• Wilms tumors are most common in young
children, with the average age being about 3
to 4 years. They are less common in older
children, and rare in adults.

9. Race/ethnicity
• In the United States, the risk of Wilms tumor
is slightly higher in African-American children
than in white children and is lowest among
Asian-American children. The reason for this is
not known.

10. Gender
• Wilms tumors are slightly more common in
girls than in boys

11. Family history of Wilms tumor
• About 1% to 2% of children with Wilms tumors have
one or more relatives with the same cancer. Scientists
think that these children inherit chromosomes with an
abnormal or missing gene from a parent that increases
their risk of developing Wilms tumor.
• Children with a family history of Wilms tumors are
slightly more likely to have tumors in both kidneys.
Still, in most children only one kidney is affected.

12. Certain genetic syndromes/birth defects
• There is a strong link between Wilms tumors
and certain kinds of birth defects.
• About 1 child in 10 with Wilms tumor also has
birth defects. Most birth defects linked to
Wilms tumors occur in syndromes. A
syndrome is a group of symptoms, signs,
malformations, or other abnormalities that
occur together in the same person

13. Syndromes linked to Wilms tumor
include:
WAGR syndrome
• WAGR stands for the first letters of the physical and
mental problems linked with this syndrome (although
not all children have all of them):
• Wilms tumor
• Aniridia (complete or partial lack of the iris [colored
area] of the eyes)
• Genitourinary tract abnormalities (defects of the
kidneys, urinary tract, penis, scrotum, clitoris, testicles,
or ovaries)
• Mental Retardation

14. • Children with this syndrome have about a 30% to
50% chance of having a Wilms tumor. The cells in
children with WAGR syndrome are missing part of
chromosome 11, where the WT1 gene is normally
found
• Children with WAGR tend to get Wilms tumors at an
earlier age and often have tumors in both kidneys.

15. Denys-Drash syndrome and Frasier
syndrome
• These rare syndromes have also been linked to changes
(mutations) in the WT1 gene.
• In Denys-Drash syndrome, the kidneys become diseased
and stop working when the child is very young.
• Wilms tumors usually develop in the diseased kidneys.
• The reproductive organs don’t develop normally, and
boys may be mistaken for girls.
• Because the risk of Wilms tumors is very high, doctors
often advise removing the kidneys soon after this
syndrome is diagnosed.

16. Beckwith-Wiedemann syndrome
• Children with this syndrome tend to be big for their age.
• They also have larger than normal internal organs and
often have an enlarged tongue.
• They may have an oversized arm and/or leg on one side
of the body (called hemihypertrophy), as well as other
medical problems.
• They have about a 5% risk of having Wilms tumors (or,
less often, other cancers that develop during childhood).
• This syndrome is caused by a defect in chromosome 11
that affects the WT2 gene.

17. Other syndromes
• Less often, Wilms tumor has been linked to
other syndromes, including:
• Perlman syndrome
• Sotos syndrome
• Simpson-Golabi-Behmel syndrome
• Bloom syndrome
• Li-Fraumeni syndrome
• Trisomy 18

18. Certain birth defects
• Wilms tumor is also more common in children
with certain birth defects (without known
syndromes):
• Aniridia (complete or partial lack of the iris
[colored area] of the eyes)
• Hemihypertrophy (an oversized arm and/or leg
on one side of the body)
• Cryptorchidism (failure of the testicles to
descend into the scrotum) in boys
• Hypospadias (defect in boys where the urinary
opening is on the underside of the penis)

19. ETIOLOGY
 Idiopathic
The exact etiology of the tumor
are still being investigated

20. Gene changes in Wilms tumors
• A small number of Wilms tumors have changes in or loss of
the WT1 or WT2 genes, which are tumor suppressor genes
found on chromosome 11. Changes in these genes and some
other genes on chromosome 11 can lead to overgrowth of
certain body tissues. This may explain why some other
growth abnormalities, like those described in Risk Factors
for Wilms Tumors, are sometimes found along with Wilms
tumors.
• In a small number of Wilms tumors there is a change in a
tumor suppressor gene known as WTX, which is found on
the X chromosome.
• Another gene that is sometimes altered in Wilms tumor cells
is known as CTNNB1, which is on chromosome 3.

21. • Tumor is exceedingly vascular, soft,
mushy, or gelatinous in character.
• Wilms tumor has capacity for rapid growth,
usually grows to a large size.

22. STAGING
• Children’s Oncology Group (COG) staging
system
• In the United States, the Children’s Oncology
Group staging system is used most often to
describe the extent of spread of Wilms
tumors. This system divides Wilms tumors into
5 stages using Roman numerals I through V.

23. • Stage I
• The tumor is contained within one kidney and
was removed completely by surgery. The
tissue layer surrounding the kidney (the renal
capsule) was not broken during surgery. The
cancer had not grown into blood vessels in or
next to the kidney. The tumor was not
biopsied before surgery to remove it.

24. • Stage II
• The tumor has grown beyond the kidney,
either into nearby fatty tissue or into blood
vessels in or near the kidney, but it was
removed completely by surgery without any
apparent cancer left behind. Nearby lymph
nodes (bean-sized collections of immune cells)
do not contain cancer.
• The tumor was not biopsied before surgery.

25. • Stage III
• This stage refers to Wilms tumors that most likely
have not have been removed completely. The cancer
remaining after surgery is limited to the abdomen
(belly). One or more of the following features may be
present:
• The cancer has spread to lymph nodes in the abdomen
or pelvis but not to more distant lymph nodes, such as
those inside the chest.
• The cancer has grown into nearby vital structures so
the surgeon could not remove it completely.
• Deposits of tumor (tumor implants) are found along
the inner lining of the abdominal space.

26. • Cancer cells are found at the edge of the sample
removed by surgery, a sign that some of the cancer
still remains after surgery.
• Cancer cells “spilled” into the abdominal space
before or during surgery.
• The tumor was removed in more than one piece – for
example, the tumor was in the kidney and in the
nearby adrenal gland, which was removed separately.
• A biopsy of the tumor was done before it was
removed with surgery.

27. Stage IV
• The cancer has spread through the blood to
organs away from the kidneys such as the
lungs, liver, brain, or bones, or to lymph nodes
far away from the kidneys.
Stage V
• Tumors are found in both kidneys at the time
of diagnosis.

28. Table 12.2. Wilms' tumor staging
according to SIOP
•
• Stage I
• Tumor limited to kidney and completely excised
• Stage II
• Tumor extending outside kidney, but completely excised with
negative or invaded regional lymph nodes
• Stage III
• Incomplete excision, without hematogenous metastases,
extraregional lymph node infiltration, peritoneal metastases, tumor
rupture, or biopsy before or at surgery
• Stage IV
• Distant metastases.
• Stage V
• Bilateral tumor

29. CLINICAL PRESENTATION
• Wilms tumors occur most often in young
children. These tumors often grow quite large
before causing any symptoms. Children may
look healthy and act and play normally.

30. • Swelling or a large lump in the abdomen
(belly)
• This is often the first sign of a Wilms tumor.
Parents may notice swelling or hardness in the
belly while bathing or dressing the child. The
lump is sometimes large enough to be felt on
both sides of the belly. It’s usually not painful,
but it might be in some children.

31. • Patients usually present with a large (12 cm on
average), smooth, and non-tender flank mass on
palpation, usually noted by a parent.
• About 25 percent of cases experience (microscopic)
hematuria, dysuria, malaise, weight loss, anemia
• The tumor can rupture with or without abdominal
trauma and these patients present with acute
abdominal pain. Obstruction of the left spermatic vein
by the mass can result in a left-sided varicocele.

32. Other possible symptoms
• Some children with Wilms tumor may also have:
• Fever
• Nausea
• Loss of appetite
• Shortness of breath
• Constipation
• Blood in the urine
• Wilms tumors can also sometimes cause high blood
pressure. This doesn't usually cause symptoms on its
own, but in rare cases blood pressure can get high
enough to cause problems such as headaches, bleeding
inside the eye, or even a change in consciousness.

33. INVESTIGATIONS
• Medical history and physical exam
• Genetic testing

34. INVESTIGATIONS
• Routine sonographic imaging of the abdomen for
unspecific abdominal discomfort usually allows the
diagnosis even of small, non-palpable Wilms' tumors.
• A detailed description of anomalies of the urinary
tract and a check for the presence of aniridia should
be done.

35. Laboratory Tests
• A clinically useful biological serum marker specific for
Wilms' tumors providing early diagnosis, accurate therapy
monitoring, or both, has not been found yet
• (urinalysis) to see if there are problems with the kidneys.
Urine may also be tested for substances
called catecholamines.
• Recently, urinary basic Fibroblast Growth Factor (#FGF)
has been reported to be elevated preoperatively in
patients with Wilms' tumor.
• Tissue Polypeptide Specific antigen (TPS), a cytokeratin-
18 derived marker, which might be of clinical value in
monitoring the therapy of nephroblastoma

36. • Increased plasma prorenin and renin levels,
found by several investigators, could be the
cause of hypertension
• Endothelial growth factor (VEGF) production
• The serum level of Neuron-Specific Enolase
(NSE) and urinary catechol levels should
routinely be measured to exclude
neuroblastoma.

37. Imaging Studies
• Imaging tests might be done for a number of
reasons, including:
• To help find out if there is a tumor in the kidney(s),
and if so, if it's likely to be a Wilms tumor
• To learn if and how far the tumor has spread, both in
the kidney(s) and to other parts of the body
• To help guide surgery or radiation therapy
• To look at the area after treatment to help determine if
it has worked

38. Ultrasound (sonogram)
• Ultrasound is often the first imaging test done if the
doctor suspects child has a tumor in the abdomen.
This test is easy to have, does not use radiation, and
it gives the doctor a good view of the kidneys and
the other organs in the abdomen.
• shows if the tumor is growing into the main veins
coming out of the kidney. This can help in planning
for surgery, if it's needed.

39. – The extent of renal involvement (contralateral
kidney), the renal vein, the inferior vena cava (IVC)
and the liver can be assessed.
– Additionally, high-resolution sono-graphy may
detect areas of nephroblastomatosis usually
presenting as multiple solid, subcapsular,
hypovascular and hypoechogenic nodules or
cysts

40. Computed tomography (CT, CAT) scan
• The CT scan uses x-rays to make detailed cross-
sectional images of parts of your child’s body,
including the kidneys.
• This is one of the most useful tests to look for a
tumor inside the kidney.
• It’s also helpful for checking whether a cancer has
grown into nearby veins or has spread to organs
beyond the kidney, such as the lungs.

41. Computed tomography scan demonstrating a large
Wilms' tumor originating from the left kidney

42. Computed tomography scan showing
a bilateral Wilms' tumor

43. Magnetic resonance imaging (MRI)
scan
• An MRI scan creates detailed images using radio
waves and strong magnets instead of x-rays, so there
is no radiation involved.
• This test might be done if the doctor needs to see very
detailed images of the kidney or nearby areas.
• For example, it might be done if there’s a chance that
a kidney tumor might have reached a major vein (the
inferior vena cava) in the abdomen.
• An MRI might also be used to look for possible
spread of cancer to the brain or spinal cord if doctors
are concerned the cancer may have spread there.

44. Chest x-ray
• Chest x-rays may be done to look for any
spread of Wilms tumor to the lungs, as well as
to have a baseline view of the lungs to
compare with other x-rays that might be done
in the future. This test might not be needed if
a CT scan of the chest is done.

45. • Pre-treatment kidney scintigraphy,
echocardiography and an audiogram should
be performed in patients planned to receive
cardio-, nephro- or ototoxic chemotherapy.
• Patients with clear cell sarcoma or rhabdoid
tumor of the kidney additionally need skeletal
radiographs, radionuclide bone scans, and
MRIs of the cranium.

46. Kidney biopsy/surgery
• Most often, a sample is removed
during surgery to treat the tumor.
• Sometimes if the doctors are less certain
about the diagnosis or if they aren’t sure the
tumor can be removed completely, a sample
of the tumor may be taken during a biopsy as
a separate procedure before surgery.

47. Tumor Suppressor Genes
 WT1
• The Wilms' tumor gene 1 (WT1, on chromosome
11p13)
• mutations in WT1 form only part of the genetic
complexity of Wilms' tumors. Loss of one copy of
WT1 allele may confer genitourinary defects in
addition to constituting the first hit required for the
development of Wilms' tumor.

48.  WT2
• DNA loss on 11p15 has been designated as WT2
and seems to be involved much more commonly
that WT1 in Wilms' tumor but also in other
embryonal tumors. The locus has been linked to
the familial form of the Beckwith-Wiedemann
Syndrome.

49.  p53
• The presence of structural anomalies of the
chromosome 17 in approximately 15 percent of
tumors and the observation of an individual with
Wilms' tumor in a Li-Fraumeni family (a cancer
susceptibility syndrome with germline mutations of
p53) suggested a role for the p53 tumor suppressor
gene

50. • Surgery is the main treatment for nearly all
children with Wilms tumors
– Removing the tumor (Resection)
– The main goal of surgery is to remove the entire
Wilms tumor in one piece, if possible. This is to keep
the cancer cells from spreading in the abdomen
(belly)
– The entire tumor can’t be removed safely, other
treatments may be used first. If these treatments
shrink the tumor enough, surgery can then be done
more safely.

51. Excision of left-sided Wilms' tumor:
• The colon and mesocolon
have been dissected free
from the tumor's anterior
surface and reflected over
the opposite kidney.
• The renal vein and artery
are identified and ligated
.
• Then the posterior aspect of
the kidney is mobilized by
establishing a retro-renal
plane of dissection

52. Radical nephrectomy
• A radical nephrectomy removes the entire kidney and
some nearby structures. This is the most common
surgery for a Wilms tumor that’s only in one kidney,
as it provides the best chance of making sure all of
the tumor is removed.
• During this operation, the surgeon makes an incision
(cut), usually down the middle of the belly, and
removes the cancer along with the whole kidney, the
adrenal gland that sits on top of the kidney, the
surrounding fatty tissue, and the ureter (tube that
carries urine from the kidney to the bladder). Most
children do very well with only one kidney.

53. Partial Nephrectomy(nephron-sparing
surgery)
• Left-sided Wilms'
tumor:
• The kidney is fully
mobilized and lifted out
of the abdomen; the
ureter, left renal artery
and vein are identified
and elevated with
vascular slings

54. (SURGICAL EXPLORATION)
regional lymphadenectomy.
• When either radical or partial nephrectomy is
done, another main goal of surgery is to
determine the extent of the cancer and
whether or not it can all be removed.
• Lymph nodes near the kidney will be removed
during surgery to look for cancer cells in them.
• Cancer often spreads to lymph nodes (bean-
sized collections of immune cells).

55. Placing a central venous catheter
(port)
• This might be done during the surgery to
remove the tumor, or as a separate operation
(especially if chemo is going to be given before
the surgery).

56. CHEMOTHERAPY AND
RADIOTHERAPY
• The goal of both study groups is to improve survival
by identifying high-risk patients for more intense
therapy while minimizing therapy and thus short- and
long-term side effects for low-risk patients.

57. • Except for patients younger than 6 months,
therapeutic protocols include a
• 4-week-period of preoperative chemotherapy
(vincristine and actinomycin D), followed by
• nephrectomy and postoperative
chemotherapy

58. Stage Surgery Radiotherapy Chemotherapy
I Nephrectomy None
AMD (18 wk)
VCR, Pulse-
intensive
II Nephrectomy None VCR, Pulse-
intensive
AMD (18 wk)
II-IV Nephrectomy 10.8 Gy VCR, Pulse-
intensive
AMD and DOX (24
wk)
III/IV Nephrectomy 10.8 Gy VCR, Pulse-
intensive
AMD and DOX (24
wk)

59. II-IV Nephrectomy Yes vincristine;
doxorubicin;
cyclophosphamide;
etoposide
I-IV Nephrectomy Yes Carboplatin, ETP and
CPP

60. LONG-TERM COMPLICATIONS
“Renal failure” was most often caused by
bilateral nephrectomy , followed by radiation
nephritis and surgical complications.
Congestive Heart Failure
• The cumulative rate of patients treated with
doxorubicin in NWTS 2/3 that developed
cardiac disease at 15 years after diagnosis is
1.7 percent

61. • Lung Damage
• Both chemotherapeutic agents and total lung-
irradiation can cause severe changes in pulmonary
function. Radiation pneumonitis is dose dependent,
and is reported from 13 percent (NWTS-3) up to 23
and 25 percent, respectively, in patients receiving
actinomycin D

62. • Liver Damage
• Studies reported a dose-related incidence of
hepatotoxicity in patients receiving
chemotherapy
• hepatic irradiation (above 30 Gy) also
increases the risk for hepatotoxicity and veno-
occlusive disease as characterized by hepato-
megaly, elevated liver enzymes,
hyperbilirubinemia, and ascites

63. • Infertility
• Damage to the reproductive systems may
represent one of the main late sequelae of
both, gonadal radiation or chemotherapeutic
agents.

64. • Musculoskeletal Function
• Ionizing radiation (megavoltage/orthovoltage)
has well been documented to interfere with
epipyseal growth. Soft tissue hypoplasia and
diminished bone growth is followed by
scoliosis and other orthopedic abnormalities
with a frequency of 60 to 80 percent of
patients treated with radiation.

65. Second Malignant Neoplasms
• Generally, it is believed, that children with a
history of malignancy have a 10–20 times
higher risk of developing a second malignancy,
indicating the need for careful follow-up of
these patients.
RECURRENCE

66. PROGNOSIS
• The cumulative survival rate for infants with
bilateral tumors is approximately 65 to 70
percent at 10 years.

67. Cut section of the excised specimen

68. REFERENCES
• M. Wilms Die Mischgeschwulste der Nieren. Arthur Georgi, Leipzig, 1899.
•
• W. Ladd “Embryoma of the kidney (Wilms' tumor).” Ann surg 1938;108:885.
•
• NE, Breslow A, Olshan JB, Beckwith et al. “Ethnic variation in the incidence,
diagnosis, prognosis, and follow-up of children with Wilms' tumor.” J Natl Cancer
Inst 1994;86:49–51.
• NE, Breslow JB, Beckwith M, Ciol et al. “Age distribution of Wilms' tumor: report
from the National Wilms' Tumor Study.” Cancer Res 1988;48:1653–7.
• DJ, Roberts D, Haber J, Sklar et al. “Extrarenal Wilms' tumors. A study of their
relationship with classical renal Wilms' tumor using expression of WT1 as a
molecular marker.” Lab Invest 1993;68:528–36.
• RY, Lin PA, Argenta KM, Sullivan et al. “Urinary hyaluronic acid is a Wilms' tumor
marker.” J Pediatr Surg
• 1995;30:304–8.