childhood malignancies

1. Diseases of
Infancy
& Childhood

2. Diseases of Infancy
and Childhood
 Congenital Anomalies
 Birth Weight and Gestational Age
 Birth Injuries
 Perinatal Infections
 Respiratory Distress Syndrome (RDS)
 Necrotizing Enterocolitis
 Intraventricular Hemorrhage
 Hydrops
 Inborn Metabolic/Genetic Errors
 Sudden Infant Death Syndrome (SIDS)
 Tumors

3. INFANT MORTALITY
 USA 1970: 20
 USA 2000: 7
 USA WHITE: X
 USA BLACK: 2X
 SWEDEN 3
 INDIA 82

4. Major Time Spans
 Neonatal period
first four weeks of life
 Infancy
the first year of life
 Age 1 – 4 years (preschool)
 Age 5 – 14 years (school age)

5. MORTALITY by TIME SPAN
 NEONATE (0-4 WEEKS): CONGENITAL,
PREMATURITY
 UNDER ONE YEAR: CONGENITAL,
PREMATURITY/WEIGHT, SIDS
 1-4 YEARS: ACCIDENTS, CONGENITAL,
TUMORS
 5-14 YEARS: ACCIDENTS, TUMORS,
HOMICIDES
 15-24 YEARS: ACCIDENTS, HOMICIDE,
SUICIDE (NONE ARE “NATURAL” CAUSES)

6. Cause of Death Related
with Age
Causes1
Rate 2
Under 1 Year: All
Causes
727.4
1–4 Years: All
Causes
32.6
5–14 Years: All
Causes
18.5
15–24 Years: All
Causes
80.7
1Rates are expressed per 100,000 population
2Excludes congenital heart disease

7. Congenital Anomalies
Definitions
Causes
Pathogenesis

8. • Malformations
– primary errors of morphogenesis, usually multifactorial
– e.g. congenital heart defect
• Disruptions
– secondary disruptions of previously normal organ or body region
– e.g. amniotic bands
• Deformations
– extrinsic disturbance of development by biomechanical forces
– e.g. uterine constraint
• Sequence
– a pattern of cascade anomalies explained by a single localized
initiating event with secondary defects in other organs
– e.g. Oligohydramnios (Or Potter) Sequence
• Syndrome
– a constellation of developmental abnormalities believed to be
pathologically related
– e.g Turner syndrome

9. Malformations
Polydactyly &
syndactyly
Cleft Lip Severe Lethal Malformation

10. Disruption by an amniotic band

11. Oligohydramnios (Or Potter) Sequence
• Oligohydramnios (decreased amniotic
fluid)
– Renal agenesis
– Amniotic leak
• Fetal Compression
– flattened facies
– club foot (talipes equinovarus)
• Pulmonary hypoplasia
– fetal respiratory motions important for lung
development
• Breech Presentation

12. The Oligohydramnios “Sequence”

13. Infant with oligohydramnios
sequence

14. Organ Specific Anomalies
• Agenesis: complete absence of an organ
• Atresia: absence of an opening
• Hypoplasia: incomplete development or
under- development of an organ with decreased
numbers of cells
• Hyperplasia: overdevelopment of an organ
associated with increased numbers of cells
• Hypertrophy: increase in size with no change
in number of cells
• Dysplasia: in the context of malformations
(versus neoplasia) describes an abnormal
organization of cells

15. Implantation and the Survival of
Early Pregnancy
 Only 50-60% of all conceptions advance
beyond 20 weeks
 Implantation occurs at day 6-7
 75% of loses are implantation failures and
are not recognized
 Pregnancy loss after implantation is 25-40%
NEJM 2001; 345:1400-1408

16. Approximate Frequency of the More Common Congenital “Malformations” in
the United States
Malformation
Frequency per
10,000 Total
Births
Clubfoot without central nervous system anomalies 25.7
Patent ductus arteriosus 16.9
Ventricular septal defect 10.9
Cleft lip with or without cleft palate 9.1
Spina bifida without anencephalus 5.5
Congenital hydrocephalus without anencephalus 4.8
Anencephalus 3.9
Reduction deformity (musculoskeletal) 3.5
Rectal and intestinal atresia 3.4
Adapted from James LM: Maps of birth defects occurrence in the U.S., birth defects monitoring
program (BDMP)/CPHA, 1970–1987. Teratology 48:551, 1993.

17. #1
#2 #3

18. CAUSES OF ANOMALIES
Genetic
– karyotypic aberrations
– single gene mutations
• Environmental
– infection
– maternal disease
– drugs and chemicals
– irradiation
• Multifactorial
•Unknown

19. Causes of Congenital Anomalies in Humans
Cause
Frequency
(%)
Genetic
Chromosomal aberrations 10–15
Mendelian inheritance 2–10
Environmental
Maternal/placental infections 2–3
Maternal disease states 6–8
Drugs and chemicals 1
Irradiations 1
Multifactorial (Multiple Genes ?
Environment)
20–25
Unknown 40–60
Adapted from Stevenson RE, et al (eds): Human Malformations and Related Anomalies.
New York, Oxford University Press, 1993, p. 115.

20. Embryonic Development
 Embryonic period
 weeks 1- 8 of pregnancy
 organogenesis occurs in this period
 Fetal period
 weeks 9 to 38
 marked by further growth and maturation

21. Critical Periods Of Development

22. Genetic Causes
 Karyotypic abnormalities
 80-90% of fetuses with aneuploidy die in utero
 trisomy 21 (Down syndrome) most common
karyotypic abnormality (21,18,13)
 sex chromosome abnormalities next most
common (Turner and Klinefelter)
 autosomal chromosomal deletion usually lethal
 karyotyping frequently done with aborted
fetuses with repeated abortions
 Single gene mutations
 covered in separate chapters

23. Maternal Viral Infection
• Rubella (German measles) 1st TRIMESTER
– at risk period first 16 weeks gestation
– defects in lens (cataracts), heart, and CNS
(deafness and mental retardation)
– rubella immune status important part of prenatal
workup
• Cytomegalovirus 2nd TRIMESTER
– most common fetal infection
– highest at risk period is second trimester
– central nervous system infection predominates

24. Drugs and Chemicals
 Drugs
 13 cis-retinoic acid (acne agent)
 warfarin
 angiotensin converting enzyme inhibitors
(ACEI)
 anticonvulsants
 oral diabetic agents
 thalidomide
 Alcohol
 Tobacco

25. Teratogen Actions
 • Proper cell migration to predetermined locations that
influence the development of other structures
 • Cell proliferation, which determines the size and form of
embryonic organs
 • Cellular interactions among tissues derived from
different structures (e.g., ectoderm, mesoderm), which
affect the differentiation of one or both of these tissues
 • Cell-matrix associations, which affect growth and
differentiation
 • Programmed cell death (apoptosis), which, as we have
seen, allows orderly organization of tissues and organs
during embryogenesis
 • Hormonal influences and mechanical forces, which
affect morphogenesis at many levels

26. Diabetes Mellitus
 Fetal Macrosomy (>10 pounds)
 maternal hyperglycemia increases insulin
secretion by fetal pancreas, insulin acts with
growth hormone effects
 Diabetic Embryopathy
 most crucial period is immediately post
fertilization
 malformations increased 4-10 fold with
uncontrolled diabetes, involving heart and CNS
 Oral agents not approved in pregnancy
 Diabetics attempting to conceive should be
placed on insulin

27. Birth Weight and Gestational Age
 Appropriate for gestational age (AGA)
 between 10 and 90th percentile for gestational
age
 Small for gestational age (SGA) , <10%
 Large for gestational age (LGA) , >90%
 Preterm
 born before 37 weeks (<2500 grams)
 Post-Term
 delivered after 42 weeks

28. Prematurity
 Defined as gestational age < 37 weeks
 Second most common cause of neonatal
mortality (after congenital anomalies)
 Risk factors for prematurity
 Preterm Premature Rupture Of fetal
Membranes (PROM)
 Intrauterine infection
 Uterine, cervical, and placental abnormalities
 Multiple gestation

29. Fetal Growth Restriction
 At least 1/3 of infants born at term are < 2.5kg
 Undergrown rather than immature
 Commonly underlies SGA (small for gestational
age)
 Prenatal diagnosis: ultrasound measurements
 Classification
 Fetal
 Placental
Maternal

30. Fetal FGR
 Chromosomal abnormalities
 17% of FGR overall
 up to 66% of fetuses with ultrasound
malformations
 Fetal Infection
 Infection: TORCH (Toxoplasmosis, Other,
Rubella, Cytomegalovirus, Herpes)
 Characterized by symmetric growth
restriction – head and trunk proportionally
involved

31. Placental FGR
 Vascular
 umbilical cord anomalies (single artery,
constrictions, etc)
 thrombosis and infarction
 multiple gestation
 Confined placental mosaicism
 mutation in trophoblast
 trisomy is common
 Placental FGR tends to cause
asymmetric growth with relative
sparing of the head

32. Maternal FGR
 Most common cause of FGR by far
 Vascular diseases
 preeclampsia (toxemia of pregnancy)
 hypertension
 Toxins
 ethanol
 narcotics and cocaine
 heavy smoking

33. Organ Immaturity
 Lungs
 alveoli differentiate in 7th month
 surfactant deficiency
 Kidneys
 glomerular differentiation is incomplete
 Brain
 impaired homeostasis of temperature
 vasomotor control unstable
 Liver
 inability to conjugate and excrete bilirubin

34. Evaluation Of The Newborn Infant
Sign 0 1 2
Heart rate Absent Below 100 Over 100
Respiratory
effort
Absent Slow, irregular Good, crying
Muscle tone Limp Some flexion of
extremities
Active motion
Response to
catheter in
nostril (tested
after
oropharynx is
clear)
No
response
Grimace Cough or
sneeze
Color Blue, pale Body pink,
extremities blue
Completely
pink
Data from Apgar V: A proposal for a new method of evaluation of the
newborn infant. Anesth Analg 32:260, 1953.
APGAR (Appearance, Pulse, Grimace, Activity, Respiration)

35. Apgar Score and 28 Day Mortality
 Score may be evaluated at 1 and
5 minutes
 5 minute scores
 0-1, 50% mortality
 4, 20% mortality
 ≥ 7, nearly 0% mortality

36. Perinatal Infection
• Transcervical (ascending)
– inhalation of infected amniotic fluid
• pneumonia, sepsis, meningitis
• commonly occurs with PROM
– passage through infected birth canal
• herpes virus– caesarian section for active herpes
• Transplacental (hematogenous)
– mostly viral and parasitic
• HIV—at delivery with maternal to fetal transfusion
• TORCH-Toxo, Other, Rubella, Cmv, Herpes
• parvovirus B19 (Fifth), erythema infectiosum
– bacterial
• Listeria monocytogenes

37. Fetal Lung Maturation

38. Neonatal Respiratory Distress
Syndrome (RDS)
• 60,000 cases / year in USA with 5000
deaths
• Incidence is inversely proportional to
gestational age
• The cause is lung immaturity with decreased
alveolar surfactant
– surfactant decreases surface tension
– first breath is the hardest since lungs must be
expanded
– without surfactant, lungs collapse with each
breath

39. RDS Risk Factors
1) Prematurity
 by far the greatest risk factor
 affected infants are nearly always premature
 2) Maternal diabetes mellitus
 insulin suppresses surfactant secretion
 3) Cesarean delivery
 normal delivery process stimulates surfactant
secretion

40. RDS Pathology
Gross
 solid and airless (no crepitance)
 sink in water
 appearance is similar to liver tissue*
Microscopic
 atelectasis and dilation of alveoli
 hyaline membranes composed of fibrin and
cell debris line alveoli (HMD former name)
 minimal inflammation

43. V/Q
Mismatch

44. RDS Prevention and Treatment
 Delay labor until fetal lung is mature
 amniotic fluid phospholipid levels are useful in
assessing fetal lung maturity
 Induce fetal lung maturation with antenatal
corticosteriods
 Postnatal surfactant replacement therapy
with oxygen and ventilator support

45. Treatment Complications
 Oxygen toxicity
 oxygen derived free radicals damage tissue
 Retrolental fibroplasia
 hypoxia causes ↑ Vascular Endothelial Growth Factor
(VEGF) and angiogenesis
 Oxygen Rx suppresses VEGF and causes endothelial
apoptosis
 Bronchopulmonary “dysplasia”
 oxygen suppresses lung septation at the saccular stage
 mechanical ventilation
 epithelial hyperplasia, squamous metaplasia, and peribronchial
and interstitial fibrosis were seen with old regimens of ventilator
usage and no surfactant use, but are now uncommon
 lung septation is still impaired

46. Necrotizing Enterocolitis
 Incidence is directly proportional to
prematurity, like RDS
 approaches 10% with severe prematurity
 2000 cases yearly in USA
 Pathogenesis
 not fully understood
 intestinal ischemia
 inflammatory mediators
 breakdown of mucosal barrier

47. Necrotizing Enterocolitis

48. Hydrops Fetalis
 Chromosomal abnormalities
 Turner syndrome with cystic hygromas
 other
 Cardiovascular with heart failure
 anemia with high output failure
 immune hemolytic anemia
 hereditary hemolytic anemia (α-thalassemia)
 parvovirus B19 infection
 twin to twin in utero transfusion
 congenital heart defects

49. Hydrops Fetalis

50. Immune Hydrops
 Fetus inherits red cell antigens from the
father that are foreign to the mother
 Mother forms IgG antibodies which cross
the placenta and destroy fetal RBCs
 Fetus develops severe anemia with CHF
and compensatory ↑ hematopoiesis
(frequently extramedullary)
 Most cases involve Rh D antigen
 mother is Rh Neg and fetus is Rh Pos
 ABO and other antigens involved less often

51. Pathogenesis of Sensitization
 Fetal RBCs gain access to maternal
circulation largely at delivery or upon
abortion
 Since IgM antibodies are involved in
primary response and prior sensitization is
necessary, the first pregnancy is not
usually affected
 Maternal sensitization can be prevented in
most cases with Rh immune globulin
(Rhogam) given at time of delivery or
abortion (spontaneous or induced)

52. Treatment of Immune Hydrops
 In utero
 identification of at risk infants via blood typing
by amniocentesis, (Chorionic Villi Sampling)
CVS, or fetal blood sampling
 fetal transfusions via umbilical cord
 early delivery
 Live born infant
 monitoring of hemoglobin and bilirubin
 exchange transfusions

54. Kernicterus

55. Pathogenesis of Immune Hydrops

56. Inborn Errors of Metabolism
(Genetic)
PhenylKetonUria (PKU)
Galactosemia
Cystic Fibrosis (CF)
(Mucoviscidosis)

57. PHENYLKETONURIA (PKU)
• Ethnic distribution
– common in persons of Scandinavian descent
– uncommon in persons of African-American and
Jewish descent
• Autosomal recessive
• Phenylalanine hydroxylase deficiency leads to
hyperphenylalaninemia, brain damage, and
mental retardation
• Phenylananine metabolites are excreted in the
urine
• Treatment is phenylalanine restriction
• Variant forms exist

58. GALACTOSEMIA
• Autosomal recessive
• Lactose → glucose + galactose
• Galactose-1-phosphate uridyl transferase (GALT)
– GALT is involved in the first step in the transformation of
galactose to glucose
– absence of GALT activity → galactosemia
• Symptoms appear with milk ingestion
– liver (fatty change and fibrosis), lens of eye (cataracts),
and brain damage involved (mechanism unknown)
• Diagnosis suggested by reducing sugar in urine
and confirmed by GALT assay in tissue
• Treatment is removal of galactose from diet for at
least the two first years of life

59. Cystic Fibrosis
 Normal Gene
 Mutational Spectra
 Genetic/Environmental Modifiers
 Morphology
 Clinical Course

60. Cystic Fibrosis (Mucoviscidosis)
 Autosomal recessive
 Most common lethal genetic disease
affecting Caucasians (1 in 3,200 live births in
the USA)
 2-4% of population are carriers
 Uncommon in Asians and African-Americans
 Widespread disorder in epithelial chloride
transport CFTR affecting fluid secretion in
exocrine glands, (SWEAT)
 epithelial lining of the respiratory,
gastrointestinal, and reproductive tracts
 Abnormally viscid mucus secretions

61. Cellular Metabolism Of The Cystic Fibrosis
Transmembrane Regulator (CFTR)
Harrison’s Internal Med, 16th Ed

62. CFTR Gene: Normal
 Cystic Fibrosis Transmembrane Conductance
Regulator (CFTR)
 CTFR → epithelial chloride channel protein
 agonist induced regulation of the chloride channel
 interacts with epithelial sodium channels (ENaC)
 Sweat gland
 CTFR activation increases luminal Cl− resorption
 ENaC increases Na+ resorption
 sweat is hypotonic
 Respiratory and Intestinal epithelium
 CTFR activation increases active luminal secretion of
chloride
 ENaC is inhibited

63. CFTR Gene: Cystic Fibrosis
 Sweat gland
 CTFR absence decreases luminal Cl− resorption
 ENaC decreases Na+ resorption
 sweat is hypertonic
 Respiratory and Intestinal epithelium
 CTFR absence decreases active luminal secretion of
chloride
 lack of inhibition of ENaC is opens sodium channel with
active resorption of luminal sodium
 secretions are decreased but isotonic

64. Chloride Channel Defect and Effects

65. CFTR Gene: Mutational Spectra
 More than 800 mutations are known
 These are grouped into six classes
 mild to severe
 Phenotype is correlated with the
combination of these alleles
 correlation is best for pancreatic disease
 genotype-phenotype correlations are less
consistent with pulmonary disease
 Other genes and environment further
modify expression of CFTR

66. Clinical Manifestations Of Mutations In The Cystic
Fibrosis Gene

67. Organ Pathology
 Plugging of ducts with viscous mucus and loss of
ciliary function of respiratory mucosa
 Pancreas
 atrophy of exocrine pancreas with fibrosis
 islets are not affected
 Liver
 plugging of bile canaliculi with portal inflamation
 biliary cirrhosis may develop
 Genitalia
 Absence of vas deferens and azoospermia
 Sweat glands
 normal histology

70. Lung Pathology in CF
• More than 95% of CF patients die of
complications resulting from lung infection
• Viscous bronchial mucus with obstruction
and secondary infection
– S. aureus
– Pseudomonas
– Hemophilus
• Bronchiectasis
– dilatation of bronchial lumina
– scarring of bronchial wall

72. Cystic Fibrosis
Clinical Manifestations

73. CF Diagnosis
 Clinical criteria
 sinopulmonary
 gastrointestinal
 pancreatic
 intestinal
 salt loss
 male genital tract
 Sweat chloride analysis
 Nasal transepithelial potential difference
 DNA Analysis
 gene sequencing

74. Clinical Course and Treatment
 Highly variable – median life expectance is
30 years
 7% of patients in the United States are
diagnosed as adults
 Clearing of pulmonary secretions and
treatment of pulmonary infection
 Transplantation
 lung
 liver-pancreas

75. Sudden Infant Death
Syndrome (SIDS)
Epidemiology
Morphology
Pathogenesis

76. Sudden Infant Death Syndrome
 NIH Definition
 sudden death of an infant under 1 year of age
which remains unexplained after a thorough
case investigation, including performance of a
complete autopsy, examination of the death
scene, and review of the clinical history
 “Crib” death
 another name based on the fact that most die
in their sleep

77. Epidemology of SIDS
 *Leading cause of death in USA of
infants between 1 month and 1 year of
age
 90% of deaths occur ≤ 6 months age,
mostly between 2 and 4 months
 In USA 2,600 deaths in 1999 (down from
5,000 in 1990)

78. Risk Factors for SIDS
• Parental
– Young maternal age (age <20 years)
– Maternal smoking during pregnancy
– Drug abuse in either parent, specifically paternal marijuana and
maternal opiate, cocaine use
– Short intergestational intervals
– Late or no prenatal care
– Low socioeconomic group
– African American and American Indian ethnicity (? socioeconomic
factors)
• Infant
– Brain stem abnormalities, associated defective arousal, and
cardiorespiratory control
– Prematurity and/or low birth weight
– Male sex
– Product of a multiple birth
– SIDS in a prior sibling
– Antecedent respiratory infections
• Environment
– Prone sleep position
– Sleeping on a soft surface
– Hyperthermia
– Postnatal passive smoking

79. Morphology of SIDS
 SIDS is a diagnosis of exclusion
 Non-specific autopsy findings
 Multiple petechiae
 Pulmonary congestion ± pulmonary edema
 These may simply be agonal changes as they
are found in non-SIDS deaths also
 Subtle changes in brain stem neurons
 Autopsy typically reveals no clear
cause of death

80. Pathogenesis of SIDS
 Generally accepted to be multifactorial
 Triple risk model
 Vulnerable infant
 Critical development period in homeostatic
control
 Exogenous stressors
 Brain stem abnormalities, associated
defective arousal, and cardio-respiratory
control

81. Prevention of SIDS
 Maternal factors
 attention to risk factors previously mentioned
 redress problems in medical care for underprivileged
 Environmental
 avoid prone sleeping
 back to sleep program: infant should sleep in supine position
 Avoid sleeping on soft surfaces
 no pillows, comforters, quilts, sheepskins, and stuffed toys
 Sleeping clothing (such as a sleep sack) may be used in
place of blankets.
 Avoid hyperthermia
 no excessive blankets
 set thermostat to appropriate temperature
 avoid space heaters

82. Diagnosis of SIDS
 SIDS is a diagnosis of exclusion
 Complete autopsy
 Examination of the death scene
 Review of the clinical history
 Differential diagnosis
 child abuse
 intentional suffocation

83. TUMORS
Benign
Malignant

84. BENIGN
Hemangiomas
Lymphatic Tumors
Fibrous Tumors
Teratomas (also can be
malignant)

85. Hemangioma
 Benign tumor of blood vessels
 Are the most common tumor of infancy
 Usually on skin, especially face and scalp
 Regress spontaneously in many cases

86. Congenital Capillary Hemangioma
At birth At 2 years
After spontaneous regression

87. Teratomas
 Composed of cells derived from more than
one germ layer, usually all three
 Sacrococcygeal teratomas
 most common childhood teratoma
 frequency 1:20,000 to 1:40,000 live births
 4 times more common in boys than girls
 Aproximately 12% are malignant
 often composed of immature tissue
 occur in older children

88. Sacrococcygeal Teratoma

89. MALIGNANT
Neuroblastic Tumors
Wilms Tumor
Incidence and Types

90. TABLE 10-9 -- Common Malignant Neoplasms of Infancy and Childhood
0 to 4 Years 5 to 9 Years 10 to 14 Years
Leukemia Leukemia
Retinoblastoma Retinoblastoma
Neuroblastoma Neuroblastoma
Wilms tumor
Hepatoblastoma Hepatocarcinoma Hepatocarcinoma
Soft tissue sarcoma (especially
rhabdomyosarcoma)
Soft tissue sarcoma Soft tissue sarcoma
Teratomas
Central nervous system tumors Central nervous system
tumors
Ewing sarcoma
Lymphoma Osteogenic sarcoma
Thyroid carcinoma
Hodgkin disease

91. Small Round Blue Cell Tumors
 Frequent in pediatric tumors
 Differential diagnosis
 Lymphoma
 Neuroblastoma
 Wilms tumor
 Rhabdomyosarcoma
 Ewings tumor
 Diagnostic procedures
 immunoperoxidase stains
 electron microscopy
 chromosomal analysis and molecular markers

92. Neuroblastomas
 Second most common malignancy of
childhood (650 cases / year in USA)
 Neural crest origin
 adrenal gland, medulla, like a pheo – 40 %
 sympathetic ganglia – 60%
 In contrast to retinoblastoma, most are
sporadic but familiar forms do occur
 Median age at diagnosis is 22 months

93. Neuorblastoma Morphology
 Small round blue cell tumor
 neuorpil formation
 rosette formation
 immunochemistry – neuron specific enolase
 EM – secretory granules (catecholamine)
 Usual features of anaplasia
 high mitotic rate is unfavorable
 evidence of Schwann cell or ganglion
differentiation favorable
 Other prognostic predictors are used by
pathologists and oncologists

94. Neuorblastoma
*Neuropil **Homer-Wright Rosettes
*
**

97. Clinical Course and Prognosis
 Hematogenous and lymphatic metastases to liver,
lungs and bone
 90% produce catecholamines, but hypertension is
uncommon
 Age and stage are most important prognostically
 < 1 year age: good prognosis regardless of stage
 Amplification of N-myc oncogene
 present in 25-30% of cases and is unfavorable
 up to 300 copies on N-myc has been observed
 Risk Stratification
 low risk: 90% cure rate
 high risk 20% cure rate

98. Wilms Tumor
 Most common primary renal tumor of
childhood
 Incidence 10 per million children < 15 years
 Usually diagnosed between age 2-5
 5 – 10 % are multi-focal, i.e., bilateral
 synchronous
 metachronous

99. Clinical Features
 Most children present with a large
abdominal mass
 Treatment
 nephrectomy and combination chemotherapy
two year survival up to
90% even with spread
beyond the kidney

100. Pathogenesis of Wilms Tumor
 10% of Wilms tumors arise in one of three
congenital malformation syndromes with
distinct chromosomal loci
 Familial disposition for Wilms is rare, and most
of these patients have de novo mutations
 Nephrogenic rests of adjacent parenchyma
 present in 40% of unilateral tumors, 100% of
bilateral tumors
 if found in one kidney, these rests predict an
increased risk for tumor in the contralateral
kidney

101. Pathology of Wilms Tumor
 Gross
 well circumscribed fleshy tan tumor
 areas of hemorrhage and necrosis
 Microscopic: triphasic appearance
 Blastema: small blue cells
 Epithelial elements: tubules & glomeruli
 Stromal elements
 Anaplasia
 correlates with p53 mutation and poor
prognosis and resistance to chemotherapy

102. Wilms Tumor