Pathology 3.

6

Diseases of Infancy and Childhood

OUTLINE
I. Causes of death related with age
II. Congenital anomalies
III. Disorders of prematurity
IV. Perinatal infections
V. Fetal Hydrops
VI. Inborn Errors of Metabolism and other Genetic Disorders
VII. SIDS
VIII. Tumors


Dr. Padla
October 1, 2013

II.CONGENITAL ANOMALIES
Congenital anomalies are morphologic defects that are present at birth.
Malformations
o Disorder of morphogenesis that are intrinsic to the infant/fetus
o It is “within” the fetus (Genetically determined)

I.CAUSE OF DEATH RELATED WITH AGE
Table 1. Most Common Causes of Death in US
Under 1 year (Infancy)
1.

Congenital malformations, deformations,
chromosomal abnormalities

2.

Disorders related to short gestation & low
birth weight

3.
4.

Sudden infant death syndrome
Newborns affected by maternal
complications of pregnancy

5.
6.

Respiratory distress of newborn
Accidents (unintentional injuries)

7.
8.

Bacterial sepsis of newborn
Intrauterine hypoxia and birth asphyxia

9.

Diseases of the circulatory system

Rate /100,000

685.2

Figure 1.(L) syndactyly; (R) polydactyly
Syndactyly: two or more digits are fused together. Polydactyly: presence of
supernumerary digits on hand

Disruptions
o Results from secondary destruction of an organ or body region
that was previously normal in development.
o Arise from an extrinsic disturbance in morphogenesis

Under 1-4 year
1. Accidents and adverse effects
2.
3.

Congenital malformations, deformations,
chromosomal abnormalities
Malignant neoplasms

4.
5.

Homicide and legal intervention
Diseases of the heart

29.9

Note: Disruption and deformation are extrinsic to the fetus

6. Influenza and pneumonia
Under 5-14 year
1.

Accidents and adverse effects

2.

Malignant neoplasms

3.
4.

Homicide and legal intervention
Congenital malformations, deformations,
chromosomal abnormalities

5.

Suicide

6.

Diseases of the heart

Figure 2. Disruption of morphogenesis by amniotic band

16.8

Deformations
o Localized or generalized compression of the growing fetus by
abnormal biochemical factors
o Maternal

includes pregnancy, small uterus, malformed uterus, and
leiomyomas.
o Fetal (placental)

multiple fetuses and abnormal placental presentation

Under 15-24 year
1. Accidents and adverse effects
2.
3.
4.

Homicide
Suicide
Congenital malformations, deformations,
chromosomal abnormalities

5.

Malignant neoplasms

6.

Diseases of the heart

80.1

Source: (Minimo et al. National Vital Statistics 55:19,2007)
Note: Accidents and adverse effects are not so much common in infancy
but it becomes the most common cause of death in the succeeding age
groups.

Group # 6 | Manalo, Mangila, Maniego, Manlulu, Maralit

Figure 3. Malformation brought by homeobox gene.
Left: Cleft palate. Right: Cyclops eye
Sequence
o Effects of initial pathology; follows previous defects in
development(e.g. oligohydramnios)
o Cascade of anomalies triggered by one initiating aberration.
o Manifestations are related to each other
o “Domino effect”

Page 1 of 9

Mangila. It is found to be teratogenic that is why we do not give this to pregnant mothers nowadays. Without surfactant. Causes of Prematurity and Fetal growth restriction  Premature birth – occurs when the baby is delivered early than the full term age of 9 months or 37 to 42 weeks  PROM – Premature Rupture of Membrane o Occurs when the bag of water ruptures after 37 weeks of gestation but before 42 weeks o What happens during PROM? Amniotic sac contains amniotic fluid where baby floats inside the uterus. the fetus can progress to develop completely.Preterm Premature Rupture of Membrane  Occurs when the bag of water ruptures before the 37 weeks of gestation.9 week: embryo is extremely susceptible to teratogenesis. Babies who were born to mothers who were taking this drug have phocomelia (loss of extremeties). Note flattened facial features and deformed right foot Figure 5. cyst of the kidney. baby has no kidneys. organs are being crafted out of the germ cell layers. toxoplasmosis. The urine of the fetus contributes to the amniotic fluid inside the uterus that is why renal agenesis can be a factor causing oligohydramnios. Renal Agenesis (Baby doesn’t have kidneys) and others. They were given to pregnant mothers decades ago. This is termed as Potter sequence or Oligohydramnios sequence. o Causes can be fetal.  This will also lead to ascending infection  Fetal Growth Restrictions o There are various causes why the baby will be smaller than normal. Maniego. Oligohydramnios due to a very small amount of amniotic fluid It is characterized by inward and downward turning of the foot(Talipes equinovarus) and a flattened brain. GENETIC Chromosomal aberrations Frequency (%) 10-15 Mendelian inheritance ENVIRONMENTAL 2-10 Maternal/placental Infections (rubella. mental retardation). Figure 4. This is very dangerous before it will predispose to ascending infection and can cause compression of the fetus. CMV. presumably allowing the embryo to recover. thalidomide. o Manifestations are unrelated to each other Agenesis: absence of primordium (organ) usually due to infection and environmental factor during organogenesis Aplasia: primordium(organ) that fails to develop Atresia: absence of an opening usually of a hollow visceral organ Hypoplasia/Hyperplasia: lesser/greater number of cell Hypotrophy/Hypertrophy: lesser/greater size of cell Dysplasia: there is increase in the number of cells but the structural arrangement do not follow the normal configuration.DISORDERS OF PREMATURITY A. syphilis. o Fetal Period  Futher growth and maturation of the organs  Critical period: Reduced susceptibility to teratogens but the fetus is susceptible to growth retardation and injury  Complex interplay o Environment and genetic make-up III. folic acid antagonists. androgens. Herpes*) Maternal Disease States (diabetes. endocrinopathies) Drugs and Chemicals (alcohol. Maralit Pathogenesis of Congenital Anomalies  Timing o Early embryonic period st  1 3 weeks after fertilization: Injurious agent damages either enough cells to cause death and abortion or only few cells. Manlulu. phenylketonuria. since it is still too early.  There will be no congenital anomaly but abortion can happen.PATHOLOGY 3. May include:  Lack of proper nutrition. If the fetus survives. The most concern is infection. rd th  3 week. causing distress. Neonatal Respiratory Distress Syndrome  Characterized by prematurity of the lungs  Also called Hyaline Membrane Disease  The Alveolar Type 2 pneumocytes are immature and are not producing surfactant needed to reduce surface tension of lung fluid. hemangioma. when the mother goes to labor. the bag of water ruptures without labor or contraction of the uterus. In renal agenesis. etc) Irradiations MULTIFACTORIAL UNKNOWN 2-3 6-8 1 1 20-25 40-60 Group # 6 | Manalo. the bag of water spontaneously ruptures during labor and the baby comes out. Page 2 of 9 . During this period. During PROM. 13-cis-retinoic acid. the lung collapses. during the full term. Normally. o PPROM.  Maternal smoking  Inability of the placenta to provide sufficient blood and nutrient  Fetus can also be larger than normal such as in cases when the mother has diabetes.6 Note: Thalidomide – drug used to treat anxiety disorders as tranquilizers. Examples are adenoma of the liver. cataract.a complex cause of small for gestational age-fetus. B. Causes of Congenital Anomalies. This occurs because of the disruption in the signaling pathway of developmental genes (Wingless Signaling Pathway). fibroma and terratoma.        Syndrome: involvement of many organ that are not related sequentially (Rubella syndrome: congenital heart disease. It is also given as an anti-neoplastic drug. Pathogenesis of oligohydramnios The causes of hydramnios are Amniotic leak. Disorganization of cell that causes congenital anomaly Table 2. placental and maternal. Chromosomal aberration and Mendelian inheritance is an example of congenital malformation. phenytoin. warfarinj. therefore the fetus doesn’t produce urine.

but returns to distress after a while. Pathophysiology of RDS. o Increase in the chemical mediators of inflammation particularly Platelet Activating Factor (PAF). o PATHWAY of INFECTION:  The mother has infectionThe maternal blood enters the placenta through openings in the endometrium of the uterus surrounding the fetus At the placental implantation in the endometrium. o The infecting agent (e.6   Classical manifestation of the disease: o A Premature infant manifests with distress immediately after birth. Two(2) ways by which the root of infection may infect the fetus during perinatal infections: Transplacental (hematologic) o The infection crosses the placental barrier from the mother to the fetus. The APGAR score. If the baby survives the critical 3-day period. This is why Neonatal Respiratory Distress Syndrome is also called Hyaline Membrane Disease. (Note that there is no direct between fetal and maternal circulation. solid instead of spongy. Maralit  1. Group # 6 | Manalo. is very low. Transplacental/Hematologic Spread of Infection Figure 6. Necrotizing Enterocolitis o The premature baby is given enteral feeding (tube feeding) in which bacteria or infection is introduced. alveolar ducts and alveolar sacs. IV.. This shows atelectiasis and dilation in the alveoli. around the chorionic vili. the hyaline resorbs and normal breathing ensues. Figure 8. Figure 7. This shows how the hyaline membrane develops in the respiratory passages. (Note: Chorionic villi are blood capillaries/ vessels of the fetus in the placenta. The lungs become collapsed and atelectiatic. there is still no exchange of CO2 and O2.PATHOLOGY 3. The alveolar sacs disappear and are replaced by cells. Other causes of respiratory distress in newborn: a) Excessive sedation of the mother b) Fetal head injury during the delivery c) Aspiration of blood of amniotic fluid d) Intrauterine hypoxia C. PERINATAL INFECTIONS Figure 6.g. which describes how live or sick the baby is. it has a characterized appearance called Pneumatosis Intestinalis. the exchange of gas and nutrient happens between the maternal blood circulating the placenta and the chorionic vili which contains the fetal blood. If the baby survives the critical 3-day period. Hyaline Membrane Disease. o This usually happens for three days. Those alveolar sacs which remain are hyperinflated or overdilated (compensatory emphysema) because the baby is struggling to inhale.)  In summary:  MotherPlacentaChorionic ViliUmbilicusBaby Page 3 of 9 . They are used by pathologists as histologic markers of placental tissue during cases such as abortion.)  The mother’s blood is also inside the placenta. Manlulu. The baby requires resuscitation and initially responds. The PAF increases permeability of the tight junctions between the epithelial cells. Mangila. So. The hyaline membrane lines the alveolar sacs. the pneumocytes will recover and be able to produce surfactant. bacteria. Necrotizing enterocolitis  Manifestations of the infection: o Presence of blebs or air sacs within the mucosa of the intestine o On Xray. leading to entry of bacteria and possible progression to gangrene. If the baby does not survive. the maternal blood enters the placenta  The fetal blood also enters the placenta and circulates around the chorionic vili. virus) enters through the chorionic vili to the fetus. There are also other forms of management such as giving of surfactant or oxygen therapy. Because of the hyaline membrane. Maniego. the autopsy will show collapsed lung with hyaline membrane.

The (arrows) indicate 2 large erythroid precursors with large nucleus. Maniego. Anemia: Direct result of red cell loss. o 2 Mechanisms: 1. This is due to the compensation to restore the normal amount of blood due to hemolysis. pneumonia and sepsis o Late Onset – When the baby manifest the disease after 7 days of life  Listeria and Monilla fungal infections are more common  Characterized by long latent period   V. o For example: Rh incompatibility (Mother: Rh. FETAL HYDROPS Fetal hydrops refers to the accumulation of edema fluid in the fetus during intrauterine growth. re-exposure to same antigen produces IgG Antibodies that cross placental barrier. and a peripheral rim of residual chromatin. which is lypophilic. Figure 7. Hence. nd  During 2 pregnancy. no hemolytic destruction of RBC. NON IMMUNE HYDROPS (Parvovirus B19) o Suprresion of RBC proliferation Anemia Compensatory increase in rate of pumping by heart Increase blood volume Increase Hydrostatic pressure Edema Fetal Hydrops Figure 8. Pathogenesis of immune hydrops fetalis Note: On the subsequent pregnancy. causing hemolytic destruction of fetal RBC. due to viral intranuclear inclusions. Destruction of this region will lead to fetal consequences in the baby Figure 11. creating amnionitis The infection contaminates the amniotic fluid The baby inhales the infection into the lungs  TYPES OF SEPSIS BASED ON ONSET OF DISEASE o Early Onset – When the baby manifests the disease within 7 days of life  Group B Streptococcus is the most common infective agent causing meningitis.PATHOLOGY 3. Maralit Figure 10.6 2. Kernicterus. Islands of extramedullary hematopoeisis.and Fetus: Rh+) st  Mother is sensitized by fetal Rh+ antigen during 1 pregnancy producing IgM Antibodies that does not pass placental barrier. Page 4 of 9 .  IMMUNE HYDROPS o Destruction of RBC o Hemolytic disease caused by blood group incompatibility between mother and fetus. Liver.  Hemolytic Anemia Compensatory increase in rate of pumping by heart Increase blood volume Increase Hydrostatic pressureEdema Fetal Hydrops 2. Transcervical (Ascending) o PATHWAY of INFECTION  The infection goes through the cervix and then ultimately to the amniotic sac The amniotic sac becomes infected. Figure 9. (A) hydrops fetalis (B) cystic hygroma – fluid accumulation is particularly prominent in the soft tissues of the neck. Manlulu. Jaundice: Develops because hemolysis produces unconjugated bilirubin. Mangila. because of non-development of lymphatic channels.  Can produce Kernicterus if bilirubin passes blood-brain barrier Hypoalbuminemia Decrease in Oncotic pressureExtravasation of fluid Edema Fetal Hydrops Group # 6 | Manalo. Bone marrow from infant with parvovirus B19. the IgG crosses the placenta attaching to the Rh+ erythrocyte causing hemolysis. crosses the blood brain barrier and causes kernicterus causing CNS manifestation. respiratory and cardiocvascular function. Unconjugate bilirubin. This is the a picture of midbrain that controls the vegetative.

Asians. Page 5 of 9 .2 CFTR regulates multiple additional ion channels and cellular processes. Metabolites are produced from this which causes symptoms such as mental retardation (due to metabolic derangement) o Phenyl acetic acid accumulation – excreted in urine and sweat which gives the infant a mousy odor which is distributed throughout the body o Screening fos this condition is important – early diagnosis can prevent the occurrence and further complications of the disease by not giving phenyalanine rich food to the baby Figure 14. This is responsible for the salty taste of the baby. Chloride channel defect in sweat duct. Immune Hydrops and Non-immune hydrops Reason Characteristic Immune Hydrops Rh Incompatibility Destruction of RBC NonImmune Hydrops Parvovirus B19 Suppression of RBC proliferation Hematopoeitic Response Bone Marrow Hypercellularity/ Hyperplasia With Extramedullary hematopoesis Bone Marrow Aplasia/ Hypoplasia Without Extramedullary hematopoeisis VI. o Caucasian> African Americans. Phenylalanine hydroxylase system  Galactosemia: autosomal recessive disorder of galactose metabolism. gastrointestinal. it does not cause mental retardation. Maralit Cystic fibrosis associated gene: Normal Structure  The primary defect in cystic fibrosis results from the abnormal function of an epithelial chloride channel protein ecroded by the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7q31. Maniego.INBORN ERRORS OF METABOLISM AND OTHER GENETIC DIISORDERS  Phenylketonuria: Abnormalities of phenylalanine metabolism o Phenylalanine hydroxylase deficient (nausea. o Most common and severe: Reaction 2 will not take place o Lacks the enzyme that digest galactose present in themilk leading to Galactose 1. at least in the first two years. It is not so much important in the metabolic reaction during brain development thus.  mutations result in loss or reduction of chloride secretion into the lumen. Hispanics Figure 12. Functions of CFTR are tissue specific therefore mutations are also tissue specific. ENaC activity decreases therefore a hypertonic luminal fluid containing high sweat chloride and high sodium content is formed (salty sweat). Manlulu.yhis is due to the accumulation of the metabolites produced  Cataract (eye)  Hepatomegaly (liver) o Don’t give galactose in the diet in the first 2 years of life. Thus other sources of nutrition should be considered. In human sweat ducts. Galactosemia in liver causing fibrosis and fatty change thus causing hepatomegaly. o Milk of the mother contains lactose that will be broken down by lactase to become galactose and lactose which will worsen the manisfestation. and reproductive tracts. Figure 15. o Cystic Fibrosis Gene regulates the chloride and other ions that pass through the ion channel. mental retardation) – error in metabolizing phenylalanine protein leading to its accumulation in the system. Mangila. In cystic fibrosis. vomiting.PATHOLOGY 3. Interaction of CFTR with epithelial sodium channel (ENaC) has possibly the most pathophysiologic relevance in cystic fibrosis. Pathway of galactose metabolism Group # 6 | Manalo. o o o o o Figure 13.  Cystic Fibrosis (Mucoviscidosis): Disorder of ion transport in epithelial cells that affects fluid secretion in exocrine glands and the epithelial lining of the respiratory.6 Table 3. Respiratory and intestinal epithelium  CFTR is an avenue for active luminal excretion of chloride. ENaC is responsible for sodium uptake from the luminal fluid rendering it hypotonic. ENaC activity increases markedly augmenting sodium uptake across the apical membrane.phosphate accumulation o Manifestations:  Mental retardation (brain) .

abnormal hair. JOINTS o myopathy. cherry red macula. The acid will extravasate in the surrounding gland causing fibrosis. lowering the water content of the surface fluid layer coating mucosal cells. and hypovitaminosis. glaucoma  MUSCLE. a history of cystic fibrosis in sibling o OR. including 3.Reduced abundance  reduced amount of normal protein  Class VI – Altered regulation of separate ion channels  affect regulatory role of CFTR Figure 16. chronic metabolic acidosis 4. Male urogenital abnormalities resulting in obstructive azoospermia (congenital bilateral absence of vas deferens) Criteria for diagnosis of cystic fibrosis  One or more characteristic features.Defective regulation  prevent activation of CFTR by preventing ATP binding and hydrolysis  Class IV – Decreased conductance  reduced function of CFTR  Class V . o or. mostly in the prone or side position (crib death or cot death) Diagnosis of exclusion – you should examine the scene of death of the baby to rule out the possibility of child abuse or no harm was inflicted on the baby Epidemiology o It is the leading cause of death between age 1 month and 1 year in the USA o third leading cause of death overall in infancy o 90% of deaths occur during first 6 months of life (specifically 2 to 6 mos. deafness. Group # 6 | Manalo. cardiomegaly. viscid secretions.  In the lungs. Gastrointestinal and nutritional abnormalities. Clinical features of cystic fibrosis. visceral and parietal pleura and epicardium are common Page 6 of 9 . abnormal body and urine odor. Clinical manifestations of mutations in CFTR gene. malabsortion. 1. CF changes in pancreas. Manlulu. recurrent vomiting. Maralit  VII. identification of 2 cf mutations o or. This will result in digestive enzyme insufficiency. abnormnal motility      Figure 17. hepatosplenomegaly. trafficking  defective processing of the protein from the endoplasmic reticulum to the Golgi apparatus. a positive newborn screening test result AND  An increased sweat chloride concentration on 2 or more occasions. dislocated lens. Hyperconcentrated fluid will cause the obstruction of the duct causing dilatation of exocrine glands (digestive glands) which contains acids that are corrosive. Chronic sinopulmonary disease manifested by 2. processing. jaundice  EYES o cataract.SUDDEN INFANT DEATH SYNDROME (SIDS) This is a phenomenon which is known as the killer in the young infant Autopsy (no clear cause of death) usually dies while asleep. marked change in color or muscle tone and choking or gagging are considered risk factors. dehydration leads to defective mucociliary action and the accumulation of hyperconcentrated. Maniego.) o Prolonged apnea. coma.Abnormal protein folding.6  o increase passive water reabsorption from the lumen. persistent lethargy.PATHOLOGY 3. Two severe mutations are associated with the classic cystic fibrosis phenotype while the presence of a mild mutation on one or both alleles results in a less severe type. seizures  GASTROINTESTINAL o poor feeding. malnutrion. Mangila. This will result to the fibrous thickening in the interspaces of the dilated glands. demonstration of abnormal epithelial nasal ion transport Abnormalities suggesting inborn errors of metabolism  GENERAL o dysmorphic features. o OR.  Does not become fully folded and glycosylated  Class III . Morphology o Multiple petechiae on the thymus. Lungs The chloride channel and some other electrolyte will lead to the dehydration of the lungs thus will increase the lungs susceptibility to infection. hydrops  NEUROLOGIC o hypotonia or hypertonia. Gene: CFTR  Class I – Defective protein synthesis  complete lack of CFTR protein  Class II . Figure 18. self-mutilation. Salt-loss syndromes: acute salt depletion.

and Colon Cancer).6 o Recent infection in the upper respiratory tract o astrogliosis of the brain stem and cerebellum o hypoplasia of the arcuate nucleus  Pathogenesis o Vulnerable infant  delayed development of “arousal” and cardiorespiratory control o Maternal Risk factors  born before term or low birth weight o Environment  side sleeping positions. Sacrococcideal teratoma  MALIGNANT Table 4. Group # 6 | Manalo. scant cytoplasm and poorly defined cell borders Figure 21.congenital capillary hemangioma at birth (A). Manlulu. it is EPITHELIAL (e. at age 2 years (B) Benign hemangioma will resolve as the baby ages. composed of small. Staging. associated defective arousal.diffuse swelling of part or all or an extremity Fibrous fibromatosis  Fibromatosis. Maralit Page 7 of 9 . He only mentioned few facts regarding the morphology of Neuroblastoma and Wilm’s Tumor. sleeping on sofa surfaces and thermal stress *if the cause of death is not clear then it is known as unclassified infant death syndrome and not a condition of sudden infant death syndrome RISK FACTORS ASSOCIATED WITH SIDS  PARENTAL o Young maternal age (<20yo) o Maternal smoking during pregnancy o Drug abuse in either parent o Short intergestational intervals o Late or no prenatal care o Low socioeconomic status o African American and American Indialn ethnicity  INFANT o Brain stem abnormalities. Breast. and cardiorespiratory control o Prematurity and/or low birth weight o Male sex o Product of multiple birth o SIDS in a prior sibling o Antecedent respiratory infections o Gastroesophageal reflux  ENVIRONMENT o Prone sleep position o Sleeping on soft surface o Hyperthermia o Postnatal passive smoking     VIII. Clinical feautures.PATHOLOGY 3. Note: The following were not thoroughly discussed by Dr.g. primitive appearing cells with dark nuclei. In adults. Maniego.flat larger lesions o o o Lymphatic  Lymphangiomas  Lymphangectiasis. NEUROBLASTOMA Prognosis o most common extracranial solid tumor of childhood and the most frequent diagnosed tumor of infancy o Germline mutations in the anaplastic lymphoma kinase gene is a major cause of familial predisposition o 5 year survival in the range of 40% o children younger than 18 months of age tend to have a significantly better prognosis Morphology o Most arise in the adrenal medulla o Size from minute nodules to large masses o Often sharply demarcated by a fibrous pseudo-capsule o Histologically.TUMORS/TUMOR-LIKE LESIONS There is better prognosis in childhood malignancy than adults In childhood malignancy there is a a tendency to regress and cells to differentiate to its normal structure Special feauture in the young: no clear distinction between tumors and tumor-like lesions BENIGN o Hemangioma  most common tumors of infancy  most are located in the skin. and Pathogenesis were retained from 2015A Transcription. Common Malignant Neoplasms of Infancy and Childhood COMMON MALIGNANT NEOPLASMS OF INFANCY AND CHILDHOOD 0-4 years 5-9 years 10-14 years Leukemia (Topnotcher) Neuroblastoma nd (2 challenger) Wilm’s tumor (3rd placer) Hepatoblastoma Leukemia Neuroblastoma Hepatoblastoma Hepatoblastoma Soft tissue sarcoma (rhabdomyosarcoma) Teratomas Soft tissue sarcoma Soft tissue sarcoma CNS tumors CNS tumors Ewing’s sarcoma Lymphoma Osteogenic sarcoma Thyroid carcinoma Hodgkin’s disease Note: In the young the most common origin of malignancy is MESENCHYMAL. particularly on the face and scalp  Port-wine stains. Lung.   A.cellular proliferations of spindle shaped cells  congenital-infantile fibrosarcomas – richly cellular lesions Teratoma Figure 19. Mangila. Morphlogy. Details of Prognosis. Padla.

and/or bone marrow. Ganglioneuroma Characterized by clusters of large cells with vesicular nuclei and abundant eosinophllic cytoplasm . or 2B) with dissemination limited to skin. which are negative for tumor microscopically. representing neoplastic ganglion cells (arrow)— cells are more mature Figure 20. The hemorrhagic partially encapsulated tumor has displaced the opened left kidney and is impinging on the aorta and left renal artery. liver. Maniego. Mangila. (Fluorescence in-situ hybridization) Page 8 of 9 . Manlulu. Ploidy of the tumor cells correlates with outcome in children less than 2 years of age but loses its independent prognostic significance in older children. 2A. Morphology is an independent prognostic variable in neuroblastic tumors Amplification of the N-myc oncogene in neuroblastomas is a molecular event that has possibly the most profound impact on prognosis. bone marrow. Maralit Figure 24. Enlarged contralateral lymph nodes. with or without microscopic residual disease o Stage 2A: Localized tumor with incomplete gross resection. o Stage 4: Any primary tumor with dissemination to distant lymph nodes. skin. liver.  Figure 21. Clinical Course and Prognostic factors Figure 22. Circular (Homer-wright rosette) Figure 23. o Stage 3: Unresectable unilateral tumor infiltrating across the midline with or without regional lymph node involvement. Adrenal neuroblastoma in a 6 month old child. Clusters of cells (Zellballen). Adrenal Neuroblastoma Presence of small rounded blue cells. o Stage 4S ("S" = special): Localized primary tumor (as defined for Stages 1. Group # 6 | Manalo. bone. o Stage 2B: Localized tumor with or without complete gross excision.6  Staging o Stage 1: Localized tumor with complete gross excision. Stage 4S is limited to infants <1 yr. Infants younger than age 1 year have an excellent prognosis regardless of the stage of the neoplasm. or localized unilateral tumor with contralateral regional lymph node involvement. Neuroblastoma. Representative ipsilateral nonadherent lymph nodes negative for tumor microscopically.PATHOLOGY 3. and/or other organs (except as defined for stage 4S). Prognostic factors in Neuroblastoma o o o o Age and stage are the most important determinants of outcome. ipsilateral nonadherent lymph nodes positive for tumor.

WILM’S TUMOR Pathogenesis & Genetics o WT1 encodes a DNA-binding transcription factor that is expressed within several tissues during embryogenesis. Maniego. macroglossia.are putative precursor lesions of Wilms tumors and seen in the renal parenchyma. Maralit Page 9 of 9 . all you who are weary and burdened. Figure 25. hemihypertrophy. Wilm’s tumor. He places His arms underneath you.PATHOLOGY 3. Phase 3: spindle shaped mesenchymal cells …Because your SMILE is my LIFE  Edited by: Rei Israel Manlulu When God places a burden upon you. It is critical for normal renal and gonadal development o Children with Beckwith-Wiedemann syndrome  characterized by enlargement of body organs. and abnormal large cells in the adrenal cortex. “Come to me. Phase 2: Epithelial cell that leads to abortive tubules. o Hematuria. omphalocele. Take my yoke upon you and learn from me. Morphology o Nephrogenic rests. Triphasic Histology of Wilm’s tumor Phase 1: Small blue rounded cells/blastimal cells. Manlulu. for I am gentle and humble in heart. gross  Clinical Features o large abdominal mass that may be unilateral or may extend across the midline and down into the pelvis. and I will give you rest. For My yoke is easy and My burden is light. Mangila.6   B. abdominal pain o Anaplastic histology remains a critical determinant of adverse prognosis Figure 26.” (Matthew 11:28-30) Group # 6 | Manalo. and you will find rest for your souls.