Pediatric Pathology Flashcards
PERINATAL INFECTIONS
May be acquired transcervically (ascending) or transplacentally (hematologically)
- Transcervically (ascending)
- infection starts in vaginal canal in cervix, and then will enter the uterus with the amniotic fluid and then infect the baby - Transplacentally (hematologically)
- blood-borne infection will get through in a hematological route into the placenta and then involved in the developing fetus
PERINATAL INFECTIONS - transcervically (ascending)
- Spread of infection from cervicovaginal canal into uterus during birth
- In utero or during birth
- Bacterial infections most common (beta hemolytic streptococcal infections), but viral (herpes) also cause transcervical infection
- all pregnant women in Canada are screened during the third trimester for beta hemolytic streptococcal infections. If positive, they will receive antibiotic treatment before they deliver
- Fetus ‘inhales’ infected amniotic fluid into lungs or acquires infection when passing through infected
birth canal during delivery - Associated with chorioamnionitis and funisitis
Can result in premature birth
- can result in rupture of amniotic sac secondary to inflammation
- can also induce labour by releasing prostaglandins, which are released by neutrophils
- May cause pneumonia, sepsis, meningitis in the developing fetus
PERINATAL INFECTIONS - transplacentally (hematologically)
- Transplacental infection can occur via many methods, from: Viruses, parasites, some bacteria
Common ones are encompassed by acronym TORCH:
* TORCH: toxoplasma, rubella, CMV, herpes, and others (e.g., T. pallidum).
- toxoplasma can occur from cats
If the above TORCH things infect the baby, it can cause:
* Fever, encephalitis, chorioretinitis, hepatosplenomegaly, pneumonia, myocarditis, anemia
If acquired early in gestation, TORCH infections may cause:
- growth retardation
- intellectual disability
- cataracts
- congenital cardiac anomalies
- bone defects
RESPIRATORY DISTRESS SYNDROME OF THE NEWBORN
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 being around the neck
Most common cause of respiratory distress 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 (alveoli collapse) sets in
- 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; stimulates surfactant release by the baby), OR supportive ventilation of the newborn, OR aerosolized natural or recombinant surfactant can be used to help support ventilation of the infant.
Now it is uncommon for premature babies to die from RDS
SUDDEN INFANT DEATH SYNDROME
For Sudden Unexpected Death in Infancy (SUDI), there’s a number of causes:
- SIDS
- Infection
- Cardiovascular anomaly
- child abuse
- metabolic / genetic disorders
- covert homicide
Definition of SIDS:
“Sudden and unexpected death of an infant less than 1 year of age (between 1 month and 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”
- Leading cause of death during infancy in developed countries
- occurs 1 in 2000 live births in Canada each year
- 90% occur in less than 6 months (the peak is between 2 and 4 months)
- many have UTRI (upper respiratory tract infection) that precedes death
- Approx. 3000 deaths in USA annually
- Most babies between age 2-4 months
- Cause is unknown, but variety of maternal, infant and environmental risk factors identified
- “Back to sleep” has reduced SIDS by 40% in last 10 yrs
- pathogenesis is unknown
- autopsy shows no obvious cause of death
- Likely a heterogenous, multifactorial disorder
SIDS occurs in a vulnerable infant during a critical developmental period in homeostatic control affected by an exogenous stressor
Risk factors: maternal, infant, environment
Maternal factors:
* youth (<20 yrs age), unmarried, short intergestational intervals, low socioeconomic status (SES), smoking, drug abuse, alcohol abuse, Black race (SES?)
Infant factors:
* prematurity, low birth weight, male, multiple birth (like twins or triplets), not 1st sibling, SIDS in prior sibling, certain ethnicities
Environmental factors:
* prone sleeping position (sleeping on belly), sleeping on soft surface with too many pillows or blankets, hyperthermia (too warm), postnatal passive smoking (lives in environment with smoker)
Back to sleep campaign
- has helped decrease rate of SIDS
- launched in Canada in 1999
- resulted in 50% decrease of SIDS worldwide
TUMOURS AND TUMOUR-LIKE LESIONS
Heterotopia or choristoma
Hamartoma
Teratoma
Heterotopia or choristoma
Microscopically normal cells or tissues present in abnormal locations e.g., pancreatic tissue found in wall of stomach
i.e. adrenal cells found in kidneys, lungs, ovaries
Hamartoma
Excessive but focal overgrowth of cells and tissues native to the organ in which it occurs e.g., pulmonary hamartoma is a nodule made up of cartilage, smooth muscle, respiratory epithelium in the lung
Teratoma
Greek word for “Monster tumour”
* consists of tissue from all 3 germ (or more than 1) layers (ectoderm, mesoderm, endoderm)
* may be benign, of indeterminate malignant potential, or frankly malignant
* locations: testis, ovary, midline locations (sacrococcygeal, mediastinum, retroperitoneum, head/neck)
Under microscope…
- can see histologically many diff tissue types in mature teratoma (gastrointestinal epithelium, bone and cartilage, skin and hair, brain tissue, respiratory epithelium, cystic lesion with multiple tissue types)
Types:
- mature (benign): 75%, well differentiated cystic lesions
- immature: 13%, more often immature neural tissue that can be malignant, indeterminate potential, malignant potential correlates with amount of immature tissue present
- malignant: 12%, malignancy develops in a specific tissue type
BENIGN TUMOURS
Hemangioma
Lymphangioma
Hemangioma
- Most common tumour of infancy
- Benign tumours consisting of blood vessels
- Common locations: skin of face and scalp
- flat/irregular red-blue masses
- larger flat lesions (port-wine stains)
- Capillary or cavernous
- Skin as well as within internal organs
Under microscope (size of blood vessels will vary):
- capillary hemangioma: multiple small capillary channels, poorly formed capillary structures, too many capillary structures that form a complex mass
- cavernous hemangioma: large tortuous dilated vascular spaces
- May enlarge with growth of child
- often spontaneously regress, so are often not treated until a certain age just in case they regress on their own
- rarely, when located in liver and soft tissues, can become malignant
- may be associated with von Hippel-Lindau disease
— people with this disease have increased risk of renal cell carcinoma, adrenal pheochromocytoma, and cerebellar vascular tumours
Hemangiomas are treated with surgery if it interferes with sight, hearing, speech/eating
Lymphangioma
- Cystic or cavernous spaces
- Skin, deeper regions of neck, axilla, mediastinum, retroperitoneum, abdominal
MALIGNANT TUMOURS
- Most common malignant neoplasms involve hematopoietic system, neural tissue, and soft tissues
- In contrast to adults, in whom tumours are epithelial and involve lung, prostate, colon, breast most
frequently - Pediatric malignancies often look primitive histologically, hence the name “small blue round cell
tumours”
3 common small blue round cell tumours:
1. Neuroblastoma
2. Retinoblastoma
3. Wilms Tumour
Other important malignant neoplasms of infancy and childhood include leukemia, rhabdomyosarcoma (skeletal muscle), hepatoblastoma (liver), and CNS tumours.
Neuroblastoma
- Neural crest origin, may arise anywhere in sympathetic nervous system from head to pelvis;
- Most arise in abdomen: adrenal glands
- 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
- Mets to liver, lungs, bone, skin (blueberry muffin baby)
- average 5 yr survival 55%
- 1 in 7000 live births
- most common extracranial solid malignancy in children
- Tumours of the sympathetic ganglia and adrenal medulla
– paravertebral region of abdomen
– posterior mediastinum
– head and neck
– brain - median age at diagnosis is 18 months
- 1-2% is familial
— germline mutations in the ALK gene - the rest is sporadic
Low risk and intermediate risk is 80-90% long term survival
High risk is only 40% long term survival
Molecular features:
- N-myc gene amplification (automatic high risk category): if there is amplification of this gene, it will be put into the high risk category
These tumours can metastasize to…
- lung, liver, bone
- skin can have blueberry muffin baby appearance
Under microscope:
- cells form rosettes
- made up of small round blue cells
Retinoblastoma
Most common malignant eye tumour of childhood
Often congenital; can be multifocal and bilateral; may undergo spontaneous regression!
It was one of the first tumours to highlight a genetic basis of cancer
RB first and prototypic tumour suppressor gene to be discovered in 1950s
Both normal alleles need to be mutated for disease to develop
- this brought up the 2 hit hypothesis for tumour suppressor gene
Familial: usually multiple and bilateral
Sporadic: unilateral and unifocal
Mutation in tumour suppressor gene, retinoblastoma (RB) gene, chromosome 13; both normal alleles must be inactivated (two hits) for development of disease
Increased risk for osteosarcoma
Most are sporadic (60%)
- unifocal
- unilateral
- need to lose both alleles of the retinoblastoma tumour suppressor
Familial is 40%
- multiple
- bilateral
- inherit one defective allele for the retinoblastoma tumour suppressor, so they only have to lose the 1 other allele in order to develop the tumour. so they often have multiple and bilateral retinoblastomas
- Familial case patients at increased risk for osteosarcoma and other cancers
Usually arises in posterior retina
- nodular mass forms
- small round blue cells that form a rosette: seen under microscope
