1

PREFACE
Thanks God,i had finished my paper about THE CORRELLATION BETWEEN WILLMS
TUMOR AND HEMATURIA. I thanks to God, for all of the amazing things which have been given
to me.
I also want to express my great appreciation to dr. Alvina, as my supervisor, whose
gave me a lot of constructive input to me and this paper.
And of course, I want to express my gratitude to my parents and my friends for all of the
support, interests, and partnership, so I could finish my paper.
I hope this paper may give a lot of information about hematuria and wilms tumor. I
want to say great apologizes for my paper contents as if described mistakes. I am very pleased if
reader can give some inputs, so that I can make better writing for other paper. Thank you.


Jakarta, June 2012

Herman Malondong


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TABLE OF CONTENTS


Preface..................................................................................................................................1
Table of Contents .................................................................................................................2
Chapter I: Abstract............................................................................................................3
Background ..................................................................................................3
Introduction ..................................................................................................4
Chapter II: Contents..........................................................................................................5
Definition .....................................................................................................5
Etiology ........................................................................................................5
The Development & Deployment ................................................................6
Stadiums Of Wilms Tumor ..........................................................................6
Symptoms ....................................................................................................7
Causes And Risk Factors .............................................................................7
Diagnosis......................................................................................................9
Physical Examinations .................................................................................9
Pathophysiology Of Hematuria..................................................................10
Treatments..................................................................................................10
Chapter III: Conclusions .................................................................................................12
References ..........................................................................................................................13

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CHAPTER I
ABSTRACT
BACKGROUND
The objectives of this paper are to explain the pathophysiology of hematuria in
wilms tumor. Wilms tumor is the most common primary malignant renal tumor of
childhood and the paradigm for multi-modal treatment of a pediatric malignant solid
tumor. Developments in surgical techniques and postoperative care, recognition of the
sensitivity of Wilms tumor to irradiation, and the availability of several active
chemotherapeutic agents have led to a dramatic change in the prognosis for most patients
with this once uniformly lethal malignancy.
Children with Wilms tumor may have associated anomalies, including aniridia,
hemihypertrophy, cryptorchidism, and hypospadias.
1,2
The constellation of Wilms
tumor, aniridia, ambiguous genitalia, and mental retardation (WAGR syndrome) occurs
in association with an interstitial deletion on chromosome 11 (del [11p 13]).
3
Children
with pseudohermaphroditism and/or renal disease (glomerulonephritis or nephrotic
syndrome) who develop Wilms tumor may have the Denys-Drash or Frasier syndrome,
which are associated with mutations in the WT1 gene at chromosome 11p13.
4,5

Hemihypertrophy may occur as an isolated abnormality or as a component of
Beckwith- Wiedemann syndrome (BWS), which includes macroglossia, omphalocele,
visceromegaly, and a predisposition to embryonal tumors including Wilms tumor.
6

The role of parental environmental exposures in the etiology of Wilms tumor is
unknown. No consistent positive findings have emerged from a series of case-control
studies.
79

Key words :
Wilms, Hematuria, Nephroblastoma, Kidney, Tumor, Children

4

INTRODUCTION
Wilms tumor is a malignant kidney tumors highest in infants and children. About
80% of these tumors occur in children under 6 years, with a peak incidence at age 2-4
years. Wilms tumor can also be found in neonates. Wilms tumor accounting for 6% of all
malignant disease in children.
The incidence of this disease is almost the same in every country, because there is
no distinction of race, climate and environment, that is an estimated 8 per 1 million
children under the age of 15. Comparison of the incidence of men and women are almost
equal. Location of the tumor is usually unilateral, more often on the left, could also
bilateral (about 5%).
Hematuria, is the presence of red blood cells (erythrocytes) in the urine. It may be
idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the
urinary tract (kidneys, ureters, urinary bladder, prostate-(In males only), and urethra),
ranging from trivial to lethal. If white blood cells are found in addition to red blood cells,
then it is a signal of urinary tract infection.

5

CHAPTER II
CONTENTS
DEFINITION
Wilms tumor is a malignant tumor derived from embryonal kidney metanefros.
Another name of this tumor is Nefroblastoma or renal embrioma. The tumor was first
reported by Runce in 1814, but the name of the tumor "Wilms" comes from a surgeon
(Max Wilms), which revealed a complete classical description of the disease in 1899.
The incidence of this disease is almost the same in every country, because there is
no distinction of race, climate and environment, that is an estimated 8 per 1 million
children under the age of 15. Comparison of the incidence of men and women are almost
equal. Location of the tumor is usually unilateral, more often on the left, could also
bilateral (about 5%).
ETIOLOGY
Wilms tumor derived from pathological proliferation of blastema metanefron due
to the absence of normal stimulation of the duct metanefron tubuli and glomeruli to
produce a differentiated good. The development of renal blastema to form kidney
structures occur at 8-34 weeks gestation. So that it is estimated that the ability of
primitive blastema to blaze the trail toward the formation of Wilms tumor, whether as a
germ or somatic mutations, that occurred at 8-34 weeks gestation.
Approximately 1.5% of patients had siblings or other family members who also
suffer from Wilms tumor. Almost all cases of unilateral non-hereditary tumors are
different from the case bilateral. Approximately 70-10% of cases of Wilms tumor in an
autosomal dominant inherited. Genetic mechanisms associated with this disease, not yet
fully known. In patients with WAGR syndrome (Wilms tumor, aniridia, genital
malformations and mental retardation) shows the presence of cytogenetic deletions on
chromosome 11, region p13. In some patients, found WT1 gene on the short arm of
chromosome 11, region pl3. WT1 gene expression specifically in the kidney and is
known as transcription factors that are allegedly responsible for the development of
Wilms tumor.
6

THE DEVELOPMENT AND DEPLOYMENT
These tumors form pseudocapsule, so that these tumors have a clear macroscopic
boundaries covered by the kidney tissue. In the development of this tumor is pressing
pseudocapsule, followed by infiltration into the kidney tissue itself, then spread to the
perirenal tissue and begin to spread or metastasis:
Perkontinuitatum: direct spread through the perirenal fat tissue and the peritoneum and
abdominal organs (the contralateral kidney, liver, etc.).
Haematogenous: occurs after the growth of tumor into the renal vasa, then spread
through the bloodstream to the lungs (90%), brain and bones.
Lymphogenous: Lymphogenous deployment occurs in regional lymph around vasa
para-aortal or in the mediastinum.
STADIUM (GRADATION) OF WILMS TUMOR
The National Wilms' Tumor Siudy (NWTS) dividing the 5-stage Wilms tumor,
namely:
Stage I
tumors confined to the kidney tissue without penetrating the capsule. These tumors can
be resected completely.
Stage II
penetrate the tumor capsule and extends into the tissue surrounding the kidney and
perirenal tissue of the kidney, the renal hilum, renal vein and para-aortal lymph nodes.
Tumors can still be in with a complete resection.
Stage III
tumor spread to the abdominal cavity (perkontinuitatum), for example to the liver,
peritoneum, etc..
7

Stage IV
hematogenous tumor spread to the organs such as lungs, brain, and bones.
SYMPTOMS
The existence of mass in stomach (abdominal tumors) are the symptoms of Wilms
tumor most frequently (75-90%), most of which was first known by a parent or patient's
family. Sometimes found by chance by a physician during a physical examination. Wilms
tumors can grow very quickly, which in some circumstances due to the occurrence of
bleeding. Hematuri (macroscopic) present in about 25% of cases, due to tumor infiltration
into the system Calix.
Hypertension was found in about 60% of cases, presumably due to suppression of
tumor or a hematoma on the blood vessels that supply blood to the kidneys, resulting in
tissue ischemia which would stimulate the release of renin, or renin remove the tumor
itself.
Other symptoms of anemia, weight loss, urinary tract infection, fever, malaise and
anorexia. Can be found in some patients who are colicky abdominal pain, as a result of
blood clots in the urinary tract.
Wilms tumor is rarely found with other congenital abnormalities, such as aniridia,
hemihiperttofi, urinary tract or genital anomalies and mental retardation.
CAUSES AND RISK FACTORS
The exact causes why certain children develop Wilms tumor are not known yet,
but medical researchers have made progress in understanding some of the mechanisms
that lead to Wilms' tumor (nephroblastoma).
Wilms tumors form when undifferentiated kidney cells do not correctly mature
and remain as fetal kidney cells. These cells can collect in clusters, grow and divide
abnormally causing tumors to form. In some cases, the impaired maturation process of
the kidney cells, that lead to Wilms tumors, is caused by a mutation that occurs in two
8

genes called WT1 and WT2. These mutations cause an overgrowth in certain tissues.
However, these mutations can either be inherited, or are acquired early in the children's
life or even before birth. In other cases (11 to 17 percent), the Wilms tumors display an
abnormality in the chromosome 1 or chromosome 16. Unfortunately, these tumors are
more likely to spread or to relapse after treatment.
Some of the risk factors that are associated with Wilms' tumor include:
Age: Children between the age of 3 and 5 are at higher risk to develop Wilms' tumor.
Gender: The risk of developing Wilms' tumor is slightly higher in girls than in boys.
Races: For the US population, the risk for developing Wilms' tumor is slightly higher
among African Americans that Caucasians, and is lower among Asian Americans.
family history of Wilms' tumor: Between 1 to 3 percent of the children that suffer from
Wilms tumor have one or more relatives with this type of kidney cancer. In these
cases, researchers believe that the children inherited a mutated gene from one of the
parents, a mutation which has increased the risk for cancer.
Displaying certain birth defects: There is a high connection between Wilms tumor and
birth defects specific to certain syndromes, such as:
WAGR - This acronym stands for (1)Wilms tumor, (2) aniridia (complete or
partial missing of the iris -the colored portion - of the eyes) (3) genitourinary
abnormalities (such as kidneys, urinary tract, penis, scrotum, testicles, clitoris, or
ovaries defects), and (4) mental retardation. Children that suffer from this
syndrome have a 3 percent chance for developing Wilms' tumor.
Beckwith-Wiedemann syndrome - This is a congenital growth disorder (present
at birth) that causes larger body size, large organs, and impaired body functions.
Children with this symptom have larger internal organs (larger than normal), a
larger tongue, an oversized arm or leg, or other parts of the body (condition called
9

hemibinhypertrophy). Children with Beckwith-Wiedemann syndrome are at
higher risk for developing Wilms' tumor.
Denys-Drash syndrome -This syndrome is characterized by the absence of the
penis, testicles, and scrotum. Children that suffer from this syndrome develop
kidney problems and the kidney may fail to function.
Abnormalities of the genitals or urinary system:
Cryptorchidism is a medical condition where one or both testicles do not
descend from the scrotum.
Hypospadias is a medical condition where the urethral (the urinary opening) is
not in its normal position at the tip of the penis, but underneath.
DIAGNOSIS
Wilms tumor diagnosis based on clinical symptoms, radiological examinations
(IVP and ultrasound), laboratory and confirmed by examination of tumor tissue
histopathology. Clinical symptoms for diagnosis are as described above, especially the
presence of tumor in the abdomen (abdominal tumors).
With IVP examination seemed distortion pielokalises system (changes in shape
pielokalises system) and at the same examination is useful to know the renal function.
Ultrasound is a noninvasive examination that can differentiate solid tumors with tumor-
containing fluid. With ultrasound, Wilms tumor appears as solid tumors in the kidney
area. Laboratory findings that support essential for Wilms tumor is the level of lactic
dehydrogenase (LDH) rises and Vinyl atid mandelic (VMA) within normal limits.
PHYSICAL EXAMINATIONS
The physician should perform a careful examination of the abdomen to look for
abdominal or flank masses. The most common renal tumor seen in young children (aged
14 years) is Wilms tumor, although other types do occur [21]. Hydronephrosis or
enlarged cystic kidneys may be palpable. Suprapubic pain may isolate the source of
bleeding and indicate possible infection, stone, or other bladder pathology. Blood
10

pressure measurement should be performed to look for hypertension and may indicate
glomerulonephritis or renal insufficiency, especially in the presence of edema. Growth
should be assessed. Failure to thrive may indicate a chronic renal disease. Presence of
pallor, fever, skin rashes or musculoskeletal findings may give clues to systemic disease,
such as systemic lupus erythematosus with glomerulonephritis.
10
As the history or
symptoms dictate, the genitalia should be inspected for a foreign body or tears and
lacerations caused by abuse or accidents.
PATHOPHYSIOLOGY OF HEMATURIA
The pathophysiology of hematuria depends on the anatomic site in the urinary
tract from which blood loss occurs. A distinction has conventionally been drawn between
glomerular and extraglomerular bleeding, separating nephrologic and urologic disease.
Blood originating from the nephron is termed glomerular or nephronal
hematuria.
11
RBCs can enter the urinary space from the glomerulus or, rarely, from the
renal tubule. Disruption of the filtration barrier in the glomerulus may result from
inherited or acquired abnormalities in the structure and integrity of the glomerular
capillary wall. These RBCs can be trapped in Tamm-Horsfall mucoprotein and will be
manifest in the urine by RBC casts. Finding casts in the urine represents significant
disease at the glomerular level. However, in disease of the nephron, casts can be absent
and isolated RBCs may be the only finding. The presence of proteinuria helps support a
glomerular source of blood loss.
Hematuria without proteinuria or casts is termed isolated hematuria. Although a
few glomerular diseases may produce isolated hematuria, this finding is more consistent
with extraglomerular bleeding. Anything that disrupts the uroepithelium, such as
irritation, inflammation, or invasion, can result in normal-appearing RBCs in the urine.
Such insults may include malignancy, renal stones, trauma, infection, and medications.
Also, nonglomerular renal causes of blood loss, such as tumors of the kidney, renal cysts,
infarction, and arteriovenous malformations, can cause blood loss into the urinary space.
TREATMENTS
The treatment of children with renal tumors begins with the removal of the kidney
and tumor and is determined by the stage and histology of the tumor. The histologic
11

patterns of the renal tumors that occur in children include Wilms tumor with favorable
histology, Wilms tumor with focal or diffuse anaplasia, CCSK, and RTK.
The transperitoneal approach to the tumor has become the standard procedure
because it allows inspection of the regional lymph nodes, a very important criterion for
staging.
12,13
It also permits mobilization of the opposite kidney, which should be
inspected on all surfaces for tumor or nephrogenic rests which may not be identified on
preoperative imaging studies. Radical or modified radical nephrectomy is employed to
remove the affected kidney. Heroic attempts to excise all or parts of adjoining organs that
might be invaded are not warranted because such procedures are associated with an
increased risk of surgical complications.
12
Wedge resection of an infiltrated portion of the
liver is advisable, however, if the lesion can be removed into, since this converts a stage
III tumor to stage II.
13
Attempts at primary surgical excision of the tumor with vena caval
extension at or above the liver are associated with increased surgical morbidity.
12

Preoperative chemotherapy should be administered to such patients, making the standard
transabdominal approach subsequently feasible and avoiding thoracoabdominal incisions,
cardiac bypass, and the other maneuvers necessary to extract the tumor from the heart.
14

Preoperative chemotherapy may also be advisable in selected children but prevailing.
North American practice has been to perform an initial nephrectomy because
treatments can best be modulated in their intensity according to accurate histopathologic
and staging criteria, which are obscured when preoperative treatments are given.

12

CHAPTER III
CONCLUSIONS

Wilms tumor is the most common primary malignant renal tumor of childhood
and the paradigm for multi-modal treatment of a pediatric malignant solid tumor.
Developments in surgical techniques and postoperative care, recognition of the sensitivity
of Wilms tumor to irradiation, and the availability of several active chemotherapeutic
agents have led to a dramatic change in the prognosis for most patients with this once
uniformly lethal malignancy.
Wilms tumor diagnosis based on clinical symptoms, radiological examinations
(IVP and ultrasound), laboratory and confirmed by examination of tumor tissue
histopatology. Clinical symptoms for diagnosis are as described above, especially the
presence of tumor in the abdomen (abdominal tumors).
Modality treatment consist of tumor surgery (surgery), chemotherapy and
radiotherapy. Treatment of Wilms tumor almost always begins with surgery. Surgery is
performed to remove the tumor or reduce the period of renal tumors. It has long been
known that Wilms tumor is sensitive to radiation. Similarly obtained several types of
chemotherapy provide effective results in these tumors, namely daktinomisin, vincristine,
doxorubicin and cyclophosphamide. Information about the type and spread of tumor cells
is needed to determine treatment strategies.

13

REFERENCES

1. Miller RW, Fraumeni JF, Manning MD. Association of Wilms tumor with
aniridia, hemihypertrophy and other congenital anomalies. N Engl J Med
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2. Pendergrass TW. Congenital anomalies in children with Wilms tumora new
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3. Riccardi VM, Hittner HM, Francke U, et al. The aniridia-Wilms tumor
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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
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5. Koziell AB, Grundy R, Barratt TM, Scambler P. Evidence for the genetic
heterogeneity of nephropathic phenotypes associated with Denys-Drash and
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6. Beckwith JB. Macroglossia, omphalocele, adrenal cytomegaly, gigantism, and
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Intercontinental; 1969. p. 188196.

7. Sanders BM, White GC, Draper GJ. Occupations of fathers of children dying
from neoplasm. J Epidemiol Commun Health 1981;35:245250.

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8. Olshan AF, Breslow NE, Daling JR, et al. Wilms tumor and paternal occupation.
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10. Alterations in Urinary Function and Electrolytes: Harrison's Principles of Internal
Medicine. 13th ed. 1994; ;New York.

11. Hematuria. Emerg Med Clin North Am. 19: 2001; 621-632.

12. Ritchey ML, Kelalis PP, Breslow N, et al. Surgical complications after
nephrectomy for Wilms tumor. Surg Gynecol Obstet 1992;175:507514.

13. Thomas PRM, Tefft M, DAngio GJ, Norkool P. Validation of radiation dose
reductions used in the Third National WilmsTumor Study (NWTS-3). Proc Am
Assoc Cancer Res 1988;29:227.

14. Nakayama DK, Norkool P, deLorimier AA, et al. Intracardiac extension of
Wilms tumor. Ann Surg 1986;204:693697.