Pediatric pathology

Question 1

What are perinatal infections? What are the methods of transfer?

Answer 1

Infections that can be transmitted to the neonate from the mother during pregnancy, during labor or shortly after birth.
Can be acquired transcervically (ascending) or transplacentally (hematologically)

Question 2

Describe the transcervical method of perinatal infection, common infections, and what it may cause

Answer 2

• Spread of infection from cervicovaginal canal
• Starts in vaginal canal in the cervix then will get into the uterus with the amniotic fluid and will infect the baby. In utero or during birth
• Common infections:
  -> Bacterial (beta hemolytic streptococcal infections) - all pregnant women in Canada are screened during their 3rd trimester
  -> Viral (herpes)
• Fetus ‘inhales’ infected amniotic fluid into lungs or acquires infection when passing through infected birth canal during delivery (commonly herpes)
• Associated with chorioamnionitis and funisitis
• May cause pneumonia, sepsis, meningitis
• Can result in premature birth
  -> Rupture of amniotic sac secondary to inflammation
  -> Induction of labour by prostaglandins released by neutrophils

Question 3

Describe the transplacental method of perinatal infection, the common infectors, and what they may cause

Answer 3

• Blood borne infection
• Viruses, parasites, some bacteria
• TORCH: toxoplasma, rubella, CMV, herpes, and other (e.g. T. pallidum)
  -> If acquired early in gestation, TORCH infections may cause
  ~ Growth retardation
  ~ Intellectual disability
  ~ Cataracts
  ~ Congenital cardiac anomalies
  ~ Bone defects
  -> Fever, encephalitis, chorioretinitis, hepatosplenomegaly, pneumonia, myocarditis, anemia
• Neonatal HSV (Herpes)
  -> Affects skin, eyes, mucous membranes.
  -> Complications include blindness and encephalitis
  -> Anti–viral treatment allows for much improved results

Question 4

What does TORCH stand for? What is it?

Answer 4

Toxoplasma, rubella, CMV, herpes, and other
-> transplacental perinatal infections

Question 5

What are the causes of respiratory distress syndrome of the newborn?

Answer 5

• Many causes of respiratory distress: excessive maternal sedation during delivery, fetal head injury during delivery, aspiration of blood or amniotic fluid, intrauterine hypoxia from nuchal cord (cord around the neck)
• Most common cause is: respiratory distress syndrome (RDS), aka “hyaline membrane disease)
• Approximately 60,000 cases of RDS/year in US; 5,000 deaths
• Main risk factor of RDS is prematurity (born before 36 weeks gestation)
• Other contributors: maternal diabetes, C-section before onset of labor, twin gestation, male infants
  *not uncommon for premature babies to die from RDS

Question 6

What occurs in respiratory distress syndrome of the newborn?

Answer 6

• Immature lungs cannot synthesize sufficient surfactant which is made by type II pneumocytes
• Alveoli tend to collapse (atelectasis - collapse of the lung); infant rapidly tires from breathing - more work to keep open the lung
• Hypoxia leads to epithelial and endothelial damage, leading to formation of hyaline membranes

Question 7

What are the treatments of respiratory distress syndrome of the newborn?

Answer 7

Treatments include corticosteroids for the mother if early delivery is unavoidable (increases/ stimulates surfactant synthesis/ release by baby), supportive ventilation of newborn, aerosolized natural or recombinant surfactant

Question 8

What is SUDI? What causes it?

Answer 8

Sudden unexpected death in infancy
- SIDS
- Infection
- Cardiovascular anomaly
- Child abuse
- Metabolic/ genetic disorders
- Covert homicide

Question 9

What is SIDS?

Answer 9

Sudden infant death syndrome: “sudden and unexpected death of an infant less than 1 year of age (1 month to 1 year) whose death remains unexplained after the performance of a complete autopsy, examination of the scene of death and review of the case history” - cause is unexplained
-> leading cause of death during infancy (in healthy infants) in developed countries
-> Approximately 3000 deaths in US annually, 1 in 2000 live births in Canada each year
-> 90% occur < 6 months (peak 2-4 months of age)

Question 10

What is the pathogenesis and cause of SIDS?

Answer 10

• cause/ pathogenesis is unknown, autopsy = no obvious cause of death, but variety of maternal, infant and environmental factors identified
• likely a heterogenous, multifactorial disorder
• maternal factors -> youth (<20 years), unmarried, short intergestational intervals, low socioeconomic status (SES), smoking, drug abuse, black race
• infant factors -> prematurity, low birth weight, male, multiple birth, not 1st sibling, SIDS in prior sibling, - many have URTI (upper respiratory tract infection) preceding death
• environmental factors -> prone sleeping position (sleeping on belly), sleeping on soft surface, hypothermia, postnatal passive smoking, too many pillows/ blankets

Question 11

Define heterotopia or choristoma

Answer 11

Microscopically normal cells or tissues present in abnormal locations e.g. pancreatic tissue found in wall of stomach

Question 12

Define hamartoma

Answer 12

Excessive but focal overgrowth of cells and tissues to the organ in which it occurs e.g. pulmonary hamartoma made up of cartilage, smooth muscle, respiratory epithelium (all normally found in lung, just growing in an abnormal way)

Question 13

Define teratoma

Answer 13

Greek word for monster tumour, consists of tissue from all 3 germ layers (ectoderm, mesoderm, endoderm), may be benign (mostly), of indeterminate malignant potential or frankly malignant.
- locations: testis, ovaries, midline locations (mediastinum, retroperitoneum, head/neck, sacrococcygeal)
-> 75% mature (benign) - well differentiated cystic lesions
-> 13% immature - malignant potential correlates with amount of immature tissue present
-> 12% malignant -malignancy develops in a specific tissue type - can be a tumor inside a tumor

Question 14

Define hemangioma

Answer 14

Most common tumor of infancy, can be capillary (multiple small capillary channels) or cavernous (large tortuous dilated vascular spaces), found in skin as well as within internal organs
- Benign tumor consisting of blood vessels. Common locations: skin of face and scalp. Flat / irregular red-blue masses. Larger flat lesions (port-wine stains).
- May enlarge with the growth of the child. Often spontaneously regress. Rarely, when located in liver and soft tissues, can become malignant. May be associated with von Hippel-Lindau disease.
- At increased risk for renal cell carcinoma, cerebral vascular tumors.
- Treated with surgery if it interferes with sight, hearing speech / eating

Question 15

Define lymphangioma

Answer 15

Cystic or cavernous spaces, skin, deeper regions of neck, axilla, mediastinum, retroperitoneum, abdominal - benign tumour

Question 16

What are the common malignant tumours in children?

Answer 16

• Most common malignant neoplasms involve hematopoietic system, neural tissue, and soft tissues *leukemia accounts for more death in kids <15 years than all other tumors combined
  -> Most common malignant childhood tumors are lymphomas
• In contrast to adults, in whom tumors are epithelial and involve lung, prostate, colon, breast most frequently
• Pediatric malignancies often look primitive (embryonal) histologically, hence the name “small blue round cell tumors”. Sheets of cells with small round nuclei. ‘-blastoma’.
• Tumours which peak in incidence <10 years: leukemia (ALL), neuroblastoma, Wilm’s tumour (nephroblastoma), hepatoblastoma (liver), retinoblastoma, rhabdomyosarcoma (skeletal muscle), teratoma, Ewing sarcoma, posterior fossa neoplasms (juvenile astrocytoma, medulloblastoma, ependymoma)

Question 17

What are the 3 common small blue cell tumours?

Answer 17

1. Neuroblastoma
2. Retinoblastoma
3. Wilms tumour (nephroblastoma)

Question 18

Describe neuroblastoma

Answer 18

• Neural crest origin, may arise anywhere in sympathetic nervous system from head to pelvis;
• Most arise in abdomen: adrenal glands
• Tumours of the sympathetic ganglia and adrenal medulla (paravertebral region of abdomen, posterior mediastimum, head & neck, brain)
• Most common extracranial solid malignancy in children; 1 in 7000 live births
• Median age at diagnosis 18 months
• 1-2% familial (germline mutations in ALK gene), rest are sporadic
• Many factors influence prognosis, most importantly stage of disease and age of patient
  -> Low risk = 80-90% long term survival
  -> Intermediate risk
  -> High risk = 40% long term survival
• Molecular features: may have deletion of part of chromosome 1, abnormal tumor suppressor gene, n-myc amplification (this puts patient automatically into high risk category)
• Mets to liver, lungs, bone, skin (blueberry muffin baby)
• Average 5 year survival 55%

Question 19

Describe retinoblastoma

Answer 19

• Most common malignant eye tumor of childhood
• Often congenital; can be multifocal and bilateral; may undergo spontaneous regression (both normal alleles must be mutated for disease to develop)
• Familial: usually multiple and bilateral = 40% - familial cases at increased risk for osteosarcoma and other cancers
• Sporadic: unilateral and unifocal = 60%
• Mutation in tumor suppressor gene, retinoblastoma (RB) gene, chromosome 13; both normal alleles must be inactivated (two hits) for development of disease
  -> RB first and prototypic tumor suppressor gene to be discovered (1950s, chr.13)
• Increased risk for osteosarcoma

Question 20

Describe Wilms tumour (nephroblastoma)

Answer 20

• Most common primary renal tumor of the kidney in children; AKA nephroblastoma
  -> 4th most common pediatric malignancy
• May be associated with other congenital malformations (WAGR, Denys-Drash, Beckwith-Wiedemann syndromes)
• Often presents as abdominal mass, noticed by parent holding baby
• 90% long term survival