Pediatric Pathology

Question 1

How are perinatal infections acquired?

Answer 1

Transcervically (ascending) or transplacentally (hematologically)

Question 2

Transcervical Perinatal Infections

Answer 2

“Ascending”
Spread of infection from cervicovaginal canal into uterus

Cause: Bacterial (beta hemolytic streptococcal infections) and viral (herpes)
Women are screened in 3rd trimester for beta hemolytic streptococcus

In utero or during birth
Fetus ‘inhales’ infected amniotic fluid into lungs or acquires infection when passing through infected birth canal during delivery (common with herpes)

Results in premature birth
Rupture of amniotic sac secondary to inflammation
Induction of labour by prostaglandins released by neutrophils

Associated with chorioamnionitis and funisitis
May cause meningitis, pneumonia, sepsis,

Question 3

Transplacental Perinatal Infection

Answer 3

“Hematological”
Occur from multiple organisms
Viruses, parasites, some bacteria
TORCH infections: toxoplasma (from cats), others, rubella, CMV, and herpes (e.g., T. pallidum).
Effects: Anemia, chorioretinitis, encephalitis, fever, hepatosplenomegaly, myocarditis, pneumonia
If acquired early in gestation, TORCH infections may cause: Bone defects, cataracts, Congenital cardiac anomalies, Growth retardation, Intellectual disability

Question 4

What is the difference between a normal placenta and acute chorioamnionitis?

Answer 4

More neutrophils in the infected one.

Question 5

Neonatal HSV (herpes simplex virus)

Answer 5

Affects skin, eyes, mucous membranes (skin lesions)
Complications include blindness and encephalitis
Antiviral treatment → much improved outcome

Question 6

Causes of respiratory distress

Answer 6

Aspiration of blood or amniotic fluid
Excessive maternal sedation during delivery
Fetal head injury during delivery
Intrauterine hypoxia from nuchal cord (cord around the neck)

Question 7

Identify and describe the most common cause of respiratory distress

Answer 7

Most common cause is: respiratory distress syndrome (RDS), aka “hyaline membrane disease”
Approx 60,000 cases of RDS/yr in USA; 5,000 deaths
Main risk factor of RDS is prematurity (born before 36 wks gestation)
Other contributors: maternal diabetes, C-section before onset of labour, twin gestation, male infants
Immature lungs cannot synthesize sufficient surfactant, which is made by type II pneumocytes
Alveoli tend to collapse; infant rapidly tires from breathing; atelectasis sets in (alveoli collapse)
Hypoxia leads to epithelial and endothelial damage, leading to formation of hyaline membranes
Treatments include
Corticosteroids for the mother if early delivery is unavoidable (increases surfactant synthesis)
Supportive ventilation
Aerosolized natural or recombinant surfactant.
Now uncommon for babies to die from RDS

Question 8

Describe the pathway of respiratory distress syndrome

Answer 8

1. Decreased surfactant
2. Increases atelectasis (collapse of the lung)
3. Increases hypoventilation and uneven perfusion
4. Hypoxemia and CO2 retention
5. Acidosis
6. Pulmonary vasoconstriction
7. Pulmonary hypoperfusion
8. Endothelial and epithelial damage
9. Plasma leak into alveoli
10. Fibrin + necrotic cells (hyaline membrane)
11. Increased diffusion gradient

Question 9

What is the difference between type I and type II pneumocytes?

Answer 9

Type II pneumocytes are larger and produce surfactant

Question 10

What are the causes of SUDI?

Answer 10

Cardiovascular anomaly
Child abuse
Cover homicide
Infection
Metabolic/genetic disorders
SIDS

Question 11

What is SIDS?

Answer 11

SIDS: “Sudden and unexpected death of an infant less than 1 year of age whose death remains unexplained after the performance of a complete autopsy, examination of the scene of death, and review of the case history”
SIDS occurs in a vulnerable infant during a critical developmental period in homeostatic control affected by an exogenous stressor
Pathogenesis: cause is unknown, but variety of maternal, infant, and environmental risk factors identified
Autopsy: no obvious cause of death
Leading cause of death during infancy in developed countries
Healthy infants 1 month to 1 year old
Approx. 3000 deaths in USA annually
Kills 1 in 2000 live births in Canada each year
90% occur < 6 months (peak 2-4 months)
Many have URTI (upper respiratory tract infection) preceding death
Likely a heterogeneous, multifactorial disorder

“Back to sleep” campaign
Reduced SIDS by 40% in last 10 yrs
Launched in Canada 1999
50% decrease in rate of SIDS worldwide

Question 12

What are the maternal risk factors of SIDS?

Answer 12

Youth (<20 yrs age)
Unmarried
Short intergestational intervals
Low socioeconomic status (SES)
Smoking (including during pregnancy)
Drug abuse
Black race

Question 13

What are the infant risk factors of SIDS?

Answer 13

Prematurity
Low birth weight
Male
Ethnicity
Multiple birth
Not 1st sibling
SIDS in prior sibling (history of SIDS)

Question 14

What are the environmental risk factors of SIDS?

Answer 14

Prone sleeping position (sleeping on belly)
Sleeping on soft surface (too many pillows and blankets)
Hyperthermia (too many clothes/too warm)
Postnatal passive smoking (someone smokes in the house)

Question 15

How does cancer relate to infant mortality?

Answer 15

Cancer is a leading cause of death for children aged 4-14 years in developed countries
In kids <1 year, other things like perinatal conditions/infections → majority of deaths in the age group (also SIDS)
In kids older than that, neoplasms are a common cause of mortality
Common adult malignant tumours
Carcinomas (epithelial - skin, bowel, breast, lung)
Melanoma
Leukemia
Lymphomas
Sarcomas
Common child tumours
Lymphomas and sarcomas (soft tissue, bone)
Carcinomas infrequent in children

Question 16

Describe benign tumors

Answer 16

Benign Tumours/not true tumours:
Heterotopia or choristoma
Microscopically normal cells or tissues present in abnormal locations e.g., pancreatic tissue found in wall of stomach, adrenal tissue in lungs
Hamartoma
Excessive but focal overgrowth of cells and tissues native to the organ in which it occurs e.g., pulmonary hamartoma made up of cartilage, smooth muscle, respiratory epithelium
Teratoma
Greek word for “Monster tumour”
Consists of tissue from all 3 germ layers (ectoderm, mesoderm, endoderm)
May be benign, of indeterminate malignant potential, or frankly malignant
Locations: sacrococcygeal, testis, ovary, mediastinum, retroperitoneum, head/neck
Types:
Mature (benign) -75%
Well-differentiated cystic lesions
Immature - 13%
Indeterminate potential
Malignant potential correlates with amount of immature tissue present
Immature neural tissue
Malignant - 12%
Malignancy develops in a specific tissue type
Mature tissue can develop a tumour in it (tumour within a tumour; squamous cell carcinoma)

Question 17

What are benign tumours in children?

Answer 17

Hemangioma and lymphangioma

Question 18

Hemangioma

Answer 18

Most common tumour of infancy
Benign tumour made up of blood vessels
Characterized by flat/irregular red-blue masses and larger flat lesions (port-wine stains)
Common locations: skin of face, scalp, and internal organs

Size of blood vessels can vary greatly
Capillary hemangioma: multiple small capillary channels (cells look bland)
Cavernous hemangioma: large tortuous dilated vascular spaces

May enlarge with growth of child but often spontaneously regresses
Can become malignant in liver and soft tissues in rare cases
May be associated with von Hippel-Lindau (VHL) disease
Risk of adrenal pheochromocytoma, cerebral vascular tumours, and renal cell carcinoma

Treated with surgery if it interferes with sight, hearing, speech/eating

Question 19

Lymphangioma

Answer 19

Cystic or cavernous spaces
Abdominal, Axilla, deeper regions of neck, mediastinum retroperitoneum, skin

Question 20

What are the most common benign tumours in children?

Answer 20

Most common tumours are ‘soft tissue’ tumours (e.g. mesenchymal differentiation)

Question 21

What are the most common benign tumours in adults?

Answer 21

Tumors of epithelial origin

Question 22

What are the most common malignant tumors in children?

Answer 22

Most common malignant neoplasms involve hematopoietic system, neural tissue, and soft tissues (typically sarcomas)
Renal tumours
Soft tissue and bone
Nervous tissue (central and sympathetic nervous system, adrenal, retina)
Hematopoietic system
Leukemia accounts for more deaths in kids <15 years than all other tumours combined

Question 23

List the tumours that peak in incidence at ages below ten

Answer 23

They end in blastoma
Hepatoblastoma (liver)
Medulloblastoma
Nephroblastoma (Wilms tumour)
Neuroblastoma
Retinoblastoma

Ewing sarcoma
Rhabdomyosarcoma (skeletal muscle)

Ependymoma
Juvenile astrocytoma
Leukemia (ALL)
Posterior fossa neoplasms
Teratoma

Question 24

What are the most common malignant tumors in adults?

Answer 24

Tumours are epithelial and involve lung, prostate, colon, breast most frequently

Question 25

What are the 3 common small blue round cell tumours?

Answer 25

Neuroblastoma, Nephroblastoma (Wilms tumour), retinoblastoma

Question 26

Neuroblastoma

Answer 26

Most common extracranial solid malignancy in children
Tumours of the adrenal medulla and sympathetic ganglia and adrenal medulla: Brain, head and neck, paravertebral region of abdomen, posterior mediastinum
Neural crest origin, may arise anywhere in sympathetic nervous system from head to pelvis; most arise in the adrenal glands in the abdomen

Many factors influence prognosis, most importantly stage of disease and age of patient
May have deletion of part of chromosome 1, abnormal tumour suppressor gene
N-myc gene amplification → automatic high risk category
Germline mutation in the ALK gene

1 in 7000 live births affected
Median age of diagnosis is 18 months
1-2% familial, rest is sporadic
Average 5 yr survival 55%
Low and intermediate risk: 80-90% chance long-term survival
High risk: 40% chance long-term survival

Metastasizes to bone, liver, lung, skin (blueberry muffin baby)

Question 27

Retinoblastoma

Answer 27

Most common malignant eye tumors in children
Arise in the posterior retina
Characterized by small round blue cells and nodular masses
Often congenital; can be multifocal and bilateral; may undergo spontaneous regression!

RB first and prototypic tumour suppressor gene to be discovered (1950s)
Both normal alleles must be mutated (inactivated) for disease to develop
Mutation in tumour suppressor gene, retinoblastoma (RB) gene, chromosome 13

Familial (40%): usually multifocal and bilateral
Familial cases at increased risk for osteosarcoma and other cancers
Sporadic (60%): usually unifocal and unilateral

Question 28

Wilms Tumor (Nephroblastoma)

Answer 28

Most common primary tumour of the kidney in children
AKA nephroblastoma
4th most common pediatric malignancy
Often presents as abdominal mass, noticed by parent holding baby

May be associated with other congenital malformations: Beckwith-Wiedemann syndrome, Denys-Drash syndrome, and WAGR

Triphasic tumour
Blastemal (small round blue cells)
Epithelial
Stromal (spindle cells)

90% long term survival