Diseases of Infancy and Childhood Flashcards
1
Q
Time Frames for Development:
- Neonatal period =
- Infancy =
- Age 1 to 4 years =
- Age 5 to 14 years =
A
- Neonatal period = the first 4 weeks of life
- Infancy = the first year of life
- Age 1 to 4 years = toddler/preschool
- Age 5 to 14 years = school age
2
Q
Causes of Death For Younger than 1 Year:
A
- CONGENITAL MALFORMATIONS, DEFORMATIONS, AND CHROMOSOMAL ANOMALIES
- DISORDERS RELATED TO SHORT GESTATION AND LOW BIRTH WEIGHT (PREMATURITY)
- SUDDEN INFANT DEATH SYNDROME (SIDS)
- Newborn affected by maternal complications of pregnancy
- Accidents (unintentional injuries)
- Newborn affected by complications of placenta, cord, and membranes
- Bacterial sepsis of newborn
- RESPIRATORY DISTRESS OF NEWBORN
- Diseases of the circulatory system
- Neonatal hemorrhage
3
Q
Causes of Death For 1-4 Years:
A
- Accidents (unintentional injuries)
- CONGENITAL MALFORMATIONS, DEFORMATIONS, AND CHROMOSOMAL ABNORMALITIES
- Assault (homicide)
- MALIGNANT NEOPLASMS
- Diseases of the heart
4
Q
Causes of Death For 5-9 Years
A
- Accidents (unintentional injuries)
- MALIGNANT NEOPLASMS
- CONGENITAL MALFORMATIONS, DEFORMATIONS, AND CHROMOSOMAL ABNORMALITIES
- Assault (homicide)
- INFLUENZA AND PNEUMONIA
5
Q
Causes of Death For 10-14 Years
A
- Accidents (unintentional injuries)
- MALIGNANT NEOPLASMS
- Intentional self-harm (suicide)
- Assault (homicide)
- CONGENITAL MALFORMATIONS, DEFORMATIONS, AND CHROMOSOMAL ANOMALIES
6
Q
What represents primary errors of morphogenesis?
- Examples?
A
Malformations
- Ex. Extra fused thumb
- Ex. Cleft pallate
- Ex. Severe central mid face defect
7
Q
Result from secondary destruction of an organ or body region that was previously normal in development. (not usually heritable)
- Example?
A
Disruptions
- Ex. Amniotic band syndrome
8
Q
Localized or generalized compression of the growing fetus by abnormal biomechanical forces. This “uterine constraint” leads eventually to a variety of structural abnormalities.
- Example?
A
Deformations
(maternal, fetal, placental)
- Ex. Endometrial cavity obstructed with tumors
9
Q
Cascade of anomalies triggered by one initiating aberration
- Example?
A
Sequences
Ex. Oligohydramnios (potter sequence)
10
Q
Describes the absence of an opening, usually of a hollow visceral organ, such as the trachea and intestine
A
Atresia
11
Q
Refers to the complete absence of an organ and its associated primordium
A
Agenesis
12
Q
Refers to the absence of an organ but one that occurs due to failure of growth of the existing primordium
A
Aplasia
13
Q
What the 3 major categories of congenital anomalies?
A
- Genetic
- Environmental
- Multifactorial
14
Q
Frequencies of Congenital Anomalies:
Genetic:
- Chromosomal aberrations = ?
- Mendelian inheritance = ?
A
- Chromosomal aberrations = 10-15%
- Mendelian inheritance = 2-10%
15
Q
Frequencies of Congenital Anomalies:
Environmental:
- Maternal/Placental Infections = ?
- Maternal Disease States (Diabetes, PKU, Endocrinopathies) = ?
- Drugs and chemicals = ?
- Irradiations = ?
A
- Maternal/Placental Infections = 2-3%
- Maternal Disease States = 6-8%
- Drugs and chemicals = 1%
- Irradiations = 1%
16
Q
Frequencies of Congenital Anomalies:
Multifactorial: ?
A
Multifactorial = 20-25%
17
Q
Frequencies of Congenital Anomalies:
Unknown: ?
A
Unknown = 40-60%
18
Q
2 General Principles Affecting the Pathogenesis of Congenital Anomalies
A
- The timing of the prenatal teratogenic insult has an important impact on the occurrence and the type of anomaly produced.
(Embryonic vs fetal) - Interplay between environmental teratogens and intrinsic genetic defects is exemplified by the fact that features of dysmorphogenesis caused by environmental insults can often be recapitulated by genetic defects in the pathways targeted by these teratogens.
19
Q
Embryonic period when most congenital anomalies occur?
A
3rd to between the end of the 8th week
20
Q
Critical embryonic period for:
- CNS = ?
- Heart = ?
- Arms = ?
- Eyes = ?
- Legs = ?
- Teeth = ?
- Palate = ?
- External genitalia = ?
- Ears = ?
A
- CNS = 3- end of 5 weeks
- Heart = 3-6 week
- Arms = 4-7 weeks
- Eyes = 4-8 weeks
- Legs = 4 - end of 7 weeks
- Teeth = 6 - 8 weeks
- Palate = 6- 9 weeks
- External genitalia = 7-9 weeks
- Ears = 4-9 weeks
21
Q
Defined by a gestational age less than 37 weeks, is the second most common cause of neonatal mortality, behind only congenital anomalies
A
Prematurity
22
Q
Risk factors for prematurity?
A
- PPROM (preterm premature rupture of membrane)
- Intrauterine infection
- Uterus/cervix/placental abnormalities
- Multiple gestation
23
Q
Hazards of prematurity?
A
- RDS (respiratory distress syndrome/hyaline membrane disease)
- NEC (Necrotizing Enterocolitis)
- Sepsis
- Intraventricular and germinal matrix hemorrhage
24
Q
Small for GESTATIONAL age (SGA) = ?
1. Etiology (cause) –> maternal, fetal, placental
- Pathogenesis (infection, chromosomal, preeclampsia)
- Morphology (structural alterations specific to pathogenesis)
- Specific clinical manifestations/functional derangements related to this and prematurity
A
Fetal Growth Restriction
25
Fetal Growth Restriction:
Fetal influences are those that intrinsically reduce growth potential of the fetus despite an adequate supply of nutrients from the mother
- Prominent among such fetal conditions = ?
- Chromosomal disorders
- Congenital anomalies
- Congenital infections
26
Fetal Growth Restriction:
Placental influences:
- Adequate placental growth in the preceding mid trimester is important because during the third trimester, fetal growth places heavy demands on the uteroplacental blood supply
- Uteroplacental insufficiency is an important cause of growth restriction. This insufficiency may result from ?
- Placental causes of FGR tend to result in ASYMMETRIC growth retardation of the fetus with relative sparing of the brain
- Umbilical - placental vascular anomalies
- Placental abruption
- Placenta previa
- Placental thrombosis and infarction
- Placental infection
- Or multiple gestations
27
Fetal Growth Restriction:
Maternal Influences:
- The most common factors associated with SGA infants are the maternal conditions that result in decreased placental blood flow
- Vascular diseases like ? and ? are often the underlying cause
- Include thrombophilias such as ?
- Inherited diseases of hyper coagulability
- Narcotic abuse, alcohol intake, heavy cigarette smoking
- Malnutrition (esp prolonged hypoglycemia)
- Preclampsia and chronic hypertension
| - Acquired Antiphospholipid Antibody Syndrome
28
Neonatal Respiratory Distress Syndrome:
- Pathophysiology = ?
- Morphology = ?
- Clinical features = ?
• Pathophysiology
- Fundamental defect is deficiency of pulmonary surfactant. Congenital deficiency caused by mutations in SFTPB and SFTBC genes
- Treatment = glucocorticoids
• Morphology
- There is alternating atelectasis and dilation of the alveoli.
- Eosinophilic thick hyaline membranes lining the dilated alveoli
• Clinical features
- Tachypnea
- Grunting
- Peripheral cyanosis
- Retractions
- Hypoxemia
- Ground glass infiltrates (seen in lung radiology0 caused by reticulogranular densities
29
RDS:
- High concentration of ventilator administered oxygen for prolonged period is associated with 2 complications?
1. Retrolental Fibroplasia
| 2. Bronchopulmonary Dysplasia
30
RDS:
Bronchopulmonary dysplasia (BPD) --> ? cytokines --> Arrest ? development
- Proinflammatory cytokines (TNF, IL-1B, IL-6, IL-8)
| - Alveolar
31
RDS:
Retrolental fibroplasia (ROP) --> ?
VEGF
- phase I = hyperoxic phase where VEGF is decreased causing endothelial cell apoptosis
- phase II= VEGF levels rebound after return to relatively hypoxic room air ventilation inducing retinal vessel proliferation characteristic of lesions in the retina
32
Necrotizing Enterocolitis (NEC)
• Involves what organs?
- The involved segment is distended, friable, and congested, or it can be frankly gangrenous; intestinal perforation with accompanying peritonitis may be seen.
• What do you see microscopically?
* Typically involves the terminal ileum, cecum, and right colon, although any part of the small or large intestines may be involved.
* Microscopically
- mucosal or transmural coagulative necrosis
- ulceration
- bacterial colonization
- submucosal gas bubbles may be seen
33
What is the most common diagnostic sign occurring in 98% of patients with Necrotizing Enterocolitis?
Pneumatosis Intestinalis (gas in the intestinal wall)
34
NEC
- Pathogenesis = ?
- Most cases associated with = ?
- Inflammatory mediator = ?
- Probably multifactorial
- Prematurity and enteral feeding (postnatal insult like bacteria) set in motion the cascade culminating in tissue destruction
- PAF (platelet activating factor) - increased mucosal permeability and found in increased amounts in stool and serum samples
35
The accumulation of edema fluid in two or more fetal compartments during intrauterine growth (pleural, peritoneal, ascites, skin)
Fetal hydrops
36
Fetal hydrops
1. Immune
2. Nonimmune
-Accumulation of fluid can be variable:
~ ? = generalized (2 or more compartments)
~ ? – localized
~ Hydrops fetalis
~ Cystic hygroma
37
Non-immune Hydrops:
| 3 major etiologies
1. Cardiovascular defects – structural and functional anomalies
2. Chromosomal anomalies – 45, X, and trisomies 21 and 18
3. Fetal anemia (not Rh or ABO) – alpha thalassemia, transplacental Parvo
B19, twin-twin transfusion
38
Hemolytic disease caused by blood group antigen incompatibility between mother and fetus (Rh antigens and ABO blood groups)
Immune Hydrops
39
Immune Hydrops
- Pathogenesis = ?
- Of the antigens included in the Rh system, only the ? antigen is a major cause of Rh incompatibility
- The incidence of maternal Rh isoimmunization has decreased since the use of ?
- The initial exposure to Rh antigen evokes the formation of IgM antibodies, that unlike IgG antibodies, do not cross the placenta. Thus, Rh disease is uncommon with the first pregnancy.
- D antigen is a major cause of Rh incompatibility
- Rhesus immune globulin (RhIg) containing anti-D antibodies
40
Immune Hydrops:
- Pathogenesis for ABO incompatibility = ?
- ABO hemolytic disease occurs almost exclusively in infants of group A or B who are born of group O moms.
- For unknown reasons, certain group O women possess IgG antibodies directed against group A or B antigens (or both) even without prior sensitization.
- So the firstborn MAY BE AFFECTED
41
Immune Hydrops:
- Consequences of excessive destruction of red cells in the neonate = ?
- Anemia
| - Jaundice (causing kernicterus- CNS damage with yellow discoloration)
42
Nonimmune Hydrops
- Clinical features for mild and severe = ?
1. Mild
- Pallor
- Hepatomegaly
2. Severe
- Intense jaundice
- Generalized edema
- Signs of neurologic injury
43
Nonimmune Hydrops
- Histo/morpholgy = ?
- Numerous islands of EXTRAMEDULLARY HEMATOPOIESIS are scattered among mature hepatocytes in the liver
44
Immune Hydrops
- Histo/morphology = ?
Erythroblastosis fetalis (left shift of RBC)
45
2 primary routes by which Perinatal infections are acquired?
1. Transcervically (Ascending)
- Fetus acquires the infection either by inhaling infected amniotic fluid into the lungs before birth OR by passing through an infected birth canal during delivery
2. Transplacental (Hematologic) (via the chorionic villi)
- May occur at any time during gestation OR occassionally at the time of delivery via maternal-to-fetal transfusion (like Hep B and HIV)
46
Most inborn errors of metabolism are genetically inherited as ?
Autosomal recessive or X-linked traits
47
3 bigs inborn errors of metabolism?
- PKU
- Classic Galactosemia (GALT)
- Cystic Fibrosis (CF)
48
Abnormalities Suggesting Inborn Errors of Metabolism:
1. General = ?
2. Neurologic = ?
3. GI = ?
4. Eyes = ?
5. Muscle, Joints = ?
1. General
- Dysmorphic features
- Deafness
- Self-mutilation
- Abnormal hair
- Abnormal body or urine odor (“sweaty feet”; “mousy or musty”; “maple syrup”)
- Hepatosplenomegaly; cardiomegaly
- Hydrops
2. Neurologic
- Hypotonia or hypertonia
- Coma
- Persistent lethargy
- Seizures
3. GI
- Poor feeding
- Recurrent vomiting
- Jaundice
4. Eyes
- Cataract
- Cherry red macula
- Dislocated lens
- Glaucoma
5. Muscles, Joints
- Myopathy
- Abnormal mobility
49
Enzyme deficiency in PKU?
Phenylalanine Hydroxylase (PAH)
| autosomal recessive
50
Clinical presentation of PKU?
- Severe mental retardation by 6 months
- Seizures
- Decreased pigmentation of hair and skin
- Eczema
51
Enzyme deficiency in Galactosemia?
Galactose-1-phosphate uridyl transferase
| autosomal recessive
52
Clinical presentation of Galactosemia?
- Most damage to liver, eyes and brain
- Hepatomegaly
- Opacification of the lens (cataracts) within a few weeks
- CNS: loss of nerve cells, gliosis, and edema in cerebellum and medulla
- Vomiting and diarrhea with milk ingestion
- Jaundice and hepatomegaly during the first week
- Mental retardation within the first 6 to 12 months
53
Incidence of Cystic Fibrosis
The most common lethal genetic disease that affects Caucasian populations
(1/2500 live births).
54
An inherited disorder of ion transport that affects fluid secretion in exocrine glands and in the epithelial lining of the respiratory, gastrointestinal, and
reproductive tracts.
Cystic Fibrosis
55
Clinical Features of CF = ?
- Chronic lung disease secondary to recurrent infections
- Pancreatic insufficiency **
- Steatorrhea
- Malnutrition
- Hepatic cirrhosis
- Intestinal obstruction
- Male infertility
- Bronchiectasis
56
CF:
The most common mutation in the ? gene results in defective protein folding in the Golgi/endoplasmic reticulum and degradation of ? before it reaches the cell surface.
CFTR
57
The pathogenesis of respiratory and intestinal complications in cystic fibrosis seems to stem from an isotonic but low-volume surface fluid layer.
- In the lungs, this dehydration leads to defective mucociliary action and the accumulation of hyperconcentrated, viscid secretions that obstruct the air passages and predispose to ?
Recurrent pulmonary infections
58
CF:
| Pancreatic insufficiency causes ?
- Impaired fat absorption
- Vit A deficiency (squamous metaplasia)
- Meconium ileus (small bowel obstruction)
59
CF:
Three most common organisms responsible for lung infections?
Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa
60
Clinical features of CF?
* Can appear at birth - meconium ileus in 5-10%
* Intussusception
• Years later (table 10-5) –
- Exocrine pancreatic insufficiency
- Cardiorespiratory – recurrent nasal polyps 10-25%
- Liver disease – puberty
- Infertility --> obstructive azoospermia
61
How to diagnose CF?
characteristic clinical findings, sweat chloride test, IRT, CFTR sequencing
62
Defined as “the 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.
SIDS
63
Many cases of sudden death in infancy may have an unexpected anatomic or biochemical basis discernible at autopsy
SUID (sudden unexpected infant death)
64
- SIDS is the leading cause of death between age ?
- The ? leading cause of death overall in infancy, after congenital anomalies and diseases of prematurity and low birth weight
- 1 month and 1 year (90% occur in first 6 months of
life) in this country
- Third
65
Morphological findings of SIDS?
- Petechiae on Lungs, Thymus, and Heart
| - Congested lungs and vascular engorgement with or without pulmonary edema
66
Some Risk Factors for SIDS (table 10-6)
- Parental = ?
- Infant = ?
- Environment = ?
1. Parental
- Young maternal age (less than 20 years)
- Smoking
- Drug use in either parent
- Short intergestational intervals
- Late or no prenatal care
- Low socioeconomic group
- AA or American Indian
2. Infant
- Brain stem abnormalities associated with delayed development of arousal and cardiorespiratory control *
- Premature and low birth weight
- Male sex
- Product of a multiple birth
- SIDS in a prior sibling
- Antecedent Respiratory infections
- Germline polymorphisms
3. Environment
- Prone or side sleep position
- Sleeping on a soft surface
- Hyperthermia
- Co-sleeping in first 3 months of life
67
Benign Tumors:
| normal cells in abnormal location
Heterotopia (choristoma)
68
Benign Tumor:
| excessive focal overgrowth of tissue native to the organ
Hamartoma
69
The most common tumor of infancy
- Examples?
Hemangioma
- Ex. Capillary hemangioma; Port wine stain
(Benign tumor)
70
What kind of benign tumor are lymphangioma and lymphangiectasia?
lymphatic tumors
71
What kind of benign tumors can look like adult type fibrosarcoma in adults but do better?
Fibrous tumors
72
What kind of benign tumor are 2 peaks of age, more histologically mature = better prognosis
Teratoma
73
Most common teratoma
| - F>M, 4:1
Sacrococcygeal teratoma
74
Common Malignant Neoplasms of Infancy and Childhood:
| - Leukemia involves what age groups?
- 0 to 4 years
| - 5 to 9 years
75
Common Malignant Neoplasms of Infancy and Childhood:
| - Retinoblastoma involves what age groups?
- 0 to 4 Years
| - 5 to 9 Years
76
* *Common Malignant Neoplasms of Infancy and Childhood:
| - Neuroblastoma involves what age groups?
- 0 to 4 years
| - 5 to 9 years
77
* **Common Malignant Neoplasms of Infancy and Childhood:
| - Wilms tumor involves what age groups?
- 0 to 4 Years
78
Common Malignant Neoplasms of Infancy and Childhood:
- Hepatoblastoma age group?
- Hepatocellular carcinoma age group?
- Hepatoblastoma = 0 to 4 years
| - Hepatocellular carcinoma = 5 to 9 years; 10 to 14 Years
79
Common Malignant Neoplasms of Infancy and Childhood:
- Soft tissue sarcoma (esp rhabdomyosarcoma) ages?
- Soft tissue sarcoma ages?
- Soft tissue sarcoma (esp rhabdomyosarcoma) = 0 to 4 Years
| - Soft tissue sarcoma = 5 to 9 Years; 10 to 14 years
80
Common Malignant Neoplasms of Infancy and Childhood:
| - Teratoma age group?
0 to 4 years
81
```
Common Malignant Neoplasms of Infancy and Childhood:
Age Groups of:
- CNS tumors?
- Ewing sarcoma?
- Lymphoma?
- Osteogenic sarcoma?
- Thyroid carcinoma?
- Hodgkin disease ?
```
- CNS tumors = 0 to 4 years; 5 to 9 Years
- Ewing sarcoma = 5 to 9 years
- Lymphoma = 5 to 9 years
- Osteogenic sarcoma = 10 to 14 Years
- Thyroid carcinoma = 10 to 14 years
- Hodgkin disease = 10 to 14 years
82
Only 2% of all malignant tumors occur in infancy and childhood; nonetheless, cancer (including leukemia) accounts for about ?% of deaths in the United States in children older than age 4 and up to age 14 years, and only ? cause significantly more deaths.
- 9%
| - accidents
83
Histologically, many of the malignant non-hematopoietic pediatric neoplasms are unique.
- Tend to have a more primitive (embryonal) ? appearance, are often characterized by sheets of cells with small, ? nuclei, and frequently show features of organogenesis specific to the site of tumor origin. Because of this latter characteristic, these tumors are frequently designated by the suffix - ?
- Because of their primitive histological appearance many childhood tumors are collectively called ?
- UNDIFFERENTIATED
- ROUND
- blastoma
- small round blue cell tumors
84
There is a tendency of fetal and neonatal malignancies to regress or differentiate ?
Spontaneously
85
? survival or cure of many childhood tumors, so that more attention is now being devoted to minimizing the adverse delayed efforts of chemotherapy and radiation therapy in survivors, including the development of second malignancies
Improved
86
Most common EXTRACRANIAL SOLID TUMOR OF CHILDHOOD,
| and the most frequently diagnosed tumor of infancy
Neuroblastoma
87
Neuroblastoma Prevalence:
| - approximately ? cases diagnosed each year in the United States
700
88
Neuroblastoma:
- Median age at diagnosis is ?; approximately ?% of cases are diagnosed in
infancy
- 18 months
| - 40%
89
most neuroblastomas occur sporadically, but ?% to ?% are familial (ALK gene =
anaplastic lymphoma kinase)
1% to 2%
90
Morphological features of Neuroblastoma
- In childhood, about 40% arise in the adrenal medulla
- Histo = Neuropil; Homer-Wright pseudorosette
- GANGLIONEUROMAS, arising from spontaneous or therapy-induced maturation of neuroblastomas, are characterized by clusters of large cells with vesicular nuclei and abundant eosinophilic cytoplasm, representing neoplastic ganglion cells. Spindle-shaped Schwann cells are present in the background stroma.
91
Clinical Features of Neuroblastoma?
* >2 y.o. may present with mets (blood and lymphatic)
* periorbital region a common metastatic site
* <2 y.o. with large abdominal mass, fever, +/- weight loss
* Infants with multiple cutaneous mets “blueberry muffin baby”
92
Important diagnostic feature of neuroblastoma?
Catecholamines (i.e., elevated blood levels of catecholamines and elevated urine levels of the metabolites vanillylmandelic acid [VMA] and homovanillic acid [HVA])
93
Neuroblastoma Prognostic Factors:
Stage:
1. Favorable = ?
2. Unfavorable = ?
1. Favorable = Stage 1, 2A, 2B, 4S
| 2. Unfavorable = Stage 3, 4
94
Neuroblastoma Prognostic Factors:
Age:
1. Favorable = ?
2. Unfavorable = ?
1. Favorable = <18 months
| 2. Unfavorable = >18 months
95
```
Neuroblastoma Prognostic Factors:
Histology:
A.) Evidence of schwannian stroma and gangliocytic differentiation
1. Favorable =?
2. Unfavorable = ?
```
B) Mitosis-karyorrhexis index
1. Favorable = ?
2. Unfavorable = ?
A) Evidence of schwannian storm and gangliocytic differentiation
1. Favorable = Present
2. Unfavorable = Absent
B) Mitosis-karyorrhexis index
1. Favorable = <200/5000 cells
2. Unfavorable = >200/5000 cells
96
Neuroblastoma Prognostic Factors:
DNA ploidy:
1. Favorable = ?
2. Unfavorable = ?
1. Favorable = Hyperdiploid (whole chromosomal gains)
| 2. Unfavorable = Near-diploid (Segmental chromosomal losses; chromothripsis)
97
Neuroblastoma Prognostic Factors:
MYCN:
1. Favorable = ?
2. Unfavorable = ?
1. Favorable = Not amplified
| 2. Unfavorable = Amplified
98
- ? uses DNA probes that recognize sequences specific to particular chromosomal regions.
- Gene amplification (i.e. ? amplification in neuroblastomas).
- FISH
| - NMYC
99
Unfortunately, most (60% to 80%) children present with stage ? tumors, and only 20% to 40% present with stage ? neuroblastomas. The staging system is of paramount importance in determining prognosis.
- 3 or 4
| - 1, 2A, 2B, or 4S
100
One peculiar form of segmental aberration described recently in aggressive neuroblastomas is called?
- Characterized by extensive ? and an oscillating pattern of DNA copy number levels, all curiously restricted to one or a few chromosomes.
chromothripsis
- genomic rearrangements
101
Prevalence of Wilms Tumor:
Afflicts about 1 in every ?children in the US , making it the most common ? tumor of childhood and the ? most common pediatric malignancy in the US
- 10,000
- renal
- fourth
102
Many children with Wilms tumor present with?
- Large abdominal mass (either unilateral or when large can extend into the pelvis) ***
- Hematuria
- Pain in the abdomen after some traumatic incident
- Intestinal obstruction
- Hypertension
- Pulmonary metastases
103
Morphology of Wilms Tumor
- 5% show ANAPLASIA = ? mutation
• Large solitary well circumscribed mass although are either 10% bilateral or multicentric
- The cut surface is soft, homogeneous, tan-grey
- Can have necrosis, cysts formation or hemorrhage
•Classic triphasic combination of blastemal, stromal, and epithelial cell types is observed in the vast majority of lesions
- Blastemal = small blue cells
- Epithelial = tubules
- Stromal = fibrocytic or myxoid
• 5% show ANAPLASIA = TP53 mutation
- Lack of differentiation, or anaplasia, is considered a
hallmark of malignancy (pleomorphism, abnormal
nuclear morphology, mitoses, loss of polarity)
• Can have heterologous elements
104
The risk of Wilms tumor is increased with at least 3 recognizable groups of congenital malformations associated with distinct chromosomal loci
1. ?
2. ?
3. ?
1. WAGR/WAGI syndrome
2. Denys-Drash syndrome
3. Beckwith-Wiedeman syndrome
105
Wilms Tumor: WAGR syndrome (33% risk)
- What does WAGR stand for?
- Germline deletion of ?
- ? = Wilms tumor-associated gene
- ? = provides instructions for making a protein that is involved in the early development of the eyes, brain, spinal cord and pancreas
- Germline ? deletion is first hit, second hit is frameshift or nonsense mutation in second allele
- Wilms tumor, Aniridia, Genital anomalies, mental Retardation
- 11p13
- WT1
- PAX6
- WT1
106
Wilms Tumor: Denys-Drash syndrome (90% risk)
• Gonadal dysgenesis (male ?)
• Early onset nephropathy
--> ?
• Increased risk of ?
- pseudohermaphrodism
- renal failure
- gonadoblastoma
107
Wilms Tumor: Beckwith-Wiedemann syndrome
- Clinical features?
- Example of ? - 11p15.5 (WT2 – IGF2)
- Some have ? mutation - a cell cycle regulator (p57) that broadly inhibits
multiple CDKs
- Increased risk of ?
- Organomegaly, macroglossia, hemihypertrophy, omphalocele, adrenal cytomegaly
- genomic imprinting
- CDKN1C
- hepatoblastoma, pancreatoblastoma, adrenal cortical tumors, rhabdomyosarcoma
108
Wilms Tumor
- Putative precursor lesions of Wilms tumors and are seen in the renal parenchyma and adjacent to approximately 25% to 40% of unilateral tumors; this frequently rises to 100% in cases of bilateral Wilms tumor = ?
- It is important to document the presence of these in the resected specimen, because these patients are at an increased risk of developing Wilms tumors in the ? kidney and require regular and frequent surveillance for many years
NEPHROGENIC RESTS
- contralateral
109
The time lag between the first and second malignant transformation is variable. Two or more primary carcinomas can coexist at the time of diagnosis (?), or develop consequently (?), sometimes years after resection of the first primary.
- synchronous
| - metachronous
110
Clinical features of Fetal Alcohol Syndrome Disorder
- prenatal and postnatal growth retardation
- facial anomalies (microcephaly, short palpebral fissures, maxillary hypoplasia)
- psychomotor disturbances
