Peds Flashcards
Define malformations, disruptions, deformations and give and example of each
Malformation: Primary error of morphogenesis in which there is an intrinsically abnormal developmental process. Example congenital heart disease
Disruption: Secondary destruction of organ or body region that was previously normal. Example amniotic band
Deformation: Extrinsic disturbance of development rather than intrinsic error of morphogenesis. Example clubfoot due to oligohydramnios
Define hamartoma, choristoma, heterotopia, ectopia, sinus, fistula
Define sequence and malformation syndrome and give an example of each
Sequence - cascade of anomalies initiated by a single aberration. Example Potter’s sequence
Malformation syndrome: group of congenital anomalies that may be pathologically related but do not result from a single aberration. Example Down’s syndrome
Describe Potter squence
Chronic oligohydramnnios causes fetal compression.
Flattened facies
Small chest circumference with pulmonary hypoplasia
Talipes equinovarus/clubfeet
Hip dislocation
Amnion nodosum is characteristic
Pulmonary atresia
Oligo
Twisted skin/facies
Extremity deform
Renal agen
Define agenesis, aplasia, atresia, hypoplasia, hyperplasia, hypertrophy, hypotrophy
Agenesis: absence of organ primordium
Aplasia: Failure of organ primordium to develop beyond its primitive form
Atresia: abnormal absence of closure of an organ orifice or passage
Hypoplasia - under of incomplete development or decreased size due to decreased number of cells
Hyperplasia - increased size of an organ due to increased number of cells
Hypertrophy - increased size of organ due to increase size of cells
Hypotrophy - decreased organ size due to decreased cell size
Reasons to examine a placenta
Obtain information useful in management of mother, neonate, or future pregnancies
Identify pathology
Assess neonatal risk for sequelae
Exclude retained placenta
Explain adverse outcomes
How to differentiate between an artery and vein on chorionic plate at gross
Arteries cross over veins
Common causes of large placenta
Twin pregnancy
Placental edema
Maternal DM
Chronic intrauterine infection
Severe fetal anemia
Rh incompatibility
Fetal alpha-thal major
Placental chorangiomas
Metabolic storage disease
Common causes of small placenta
IUGR
Chromosomal anomalies
Intrauterine infection
Maternal vascular palperfusion
Gross and histologic findings of placenta infarct
Colour depends on age of infarct
Wedge-shaped but vili immediately beneath chorionic plate spared
Coagulative necrosis of group of vili
Intervillous spaces patent early but later filled by fibrin and obliterated
Adjacent villi have increase syncytial knots
Broad categories of organisms transmitted to fetuses by cervicovaginal (ascending route)
Mostly bacterial but some viral (eg HSV2)
Mechanism of ascending intrauterine infection
Inhalation of infected amniotic fluid
Passing through infected birth canal during delivery
Chronological sequence of placental histologic findings in ascending intrauterine infection
Acute subchorionitis
Acute chorionitis
Acute chorioamnionitis
Acute chorioamnionitis with acute chorionic vasculitis, umbilical cord vasculitis, and funisitis
What broad categories of maternal blood-borne infections can be transmitted to the fetus via the placenta? What is the main histological feature?
Infections - parasitic and viral, few bacterial (syphilis, listeria)
Histology - chronic villitis, multifocal
- plasma cells suggest CMV
- Listerosis = multifocal acute villitis with microabscesses
Types of twin placentation
Dichorionic diamniotic, 2 discs or 1 fused disc
Monochorionic diamniotic
MonoMono
Gross findings of twin placentation
1 or 2 discs
Dividing membrane - thick and opaque (dichorionic) or thin and translucent (monochorionic)
Monochorionic - look for twin to twin transfusion syndrome (arteriovenous vascular anastamosis)
Histology of dividing membrane of monochorionic vs dichorionic placenta
Monochorionic - no chorionic tissue in dividing membrane
Dichorionic - amnion chorion amnion
Zygosity determination
Twins different sex - dizygotic
Placenta monochorionic - monozygotic
Placenta dichorionic - 80% dizygotic
Features of chronic histiocytic intervillositis
Infiltrate of histiocyte-predominant mononuclear cells in intervillous space
Represents abnormal cell-mediated immune response at maternal-fetal surface
Associated with adverse fetal outcome, including first and second trimester miscarriage and impaired growth
25% recurrence rate
Sometimes with massive perivillous fibrin deposition
Massive perivillous fibrin deposition vs maternal floor infarct
Massive perivillous fibrin deposition - >50% of placenta, tends to be thick, firm, pale
Maternal floor infarction - layer of fibrin deposition surrounding basal villi with other villi spared
Both associated with second trimester fetal loss, IUGR, and chronic histiocytic intervillositis, tend to recur
Gross and microscopic features and clinical significance of chorangiomas
Gross - well demarcatd, firm round nodules, may be in placental slices or bulging/pedunculated on surface. Often dark red
Microscopic - capillary-sized vessels and scanty stroma, may have foci of infarction
Clinical significance - small ones are insignificany, large ones may cause polyhydramnios, obstruction, fetal cardiomegaly or anemia
Gross and microscopic features and clinical significance of velamentous cord insertion
Gross - umbilical cord inserts into and traverses the free membranes
Micro - chorionic vessels seen in membrane roll
Clinical significance - susceptible to tearing during labor and delivery, associated with SGA babies
Gross and microscopic features and clinical significance of circumvallate placenta
Gross - placental membranes fold in on themselves forming a raised white ring at the junction of extraplacental membranes and fetal surface. Can be complete or partial
Micro - fibrin and infarcted chorionic villi folded over surface with double membranes
clinical significance - Increased frequency of low birth weight, perinatal mortality, antepartum bleeding, premature labour, fetal hypoxia
Clinical manifestations of preeclampsia
Pregnancy-induced hypertension and proteinuria develop after 20GW
Subcutaneous edema
Epigastric pain/liver tenderness common in preeclampsia pts with HELLP syndrome
Placental gross and histologic findings in preeclampsia
Small placental size
Multiple infarcts due to maternal vascular malperfusion
Decidual arteriopathy
Accelerated villous maturation
Why do cytogenetic analysis of abortus tissue
~50% of early pregnancy losses have chromosomal anomalies
Analysis may provide insight for parents regarding recurrence
Usually only medically indicated when 3 or more pregnancy losses
Limitations of cytogenetic analysis for abortus tissues
Fetal tissue may be contaminated by maternal cells
Needs viable tissue for karyotyping as that requires tissue culture - recently largely replaced by RAD
Pathologist’s role in cytogenetic analysis for abortus tissue
Examine to select appropriate tissue
Can submit representative tissue to confirm viability
Value of performing autopsies on macerated stillborn fetuses
Demonstrate presence or absence of malformations which may suggest an inheritable condition
Demonstrate present or absence of infection
Presence or absence of intrauterine stress - thymic involution, mec aspiration, pseudofollicular changes in adrenal cortex
Determine approx age of fetus, IUGR
Status of fetus when infection started - eg presence of fetal response indicates fetus was alive
Predict outcome of future pregnancies
Inheritable condition
Infection
Fetal stress
Status of fetus visavis inf
Estimation of duration of fetal death before delivery
Degree of maceration
- mild 0-1 day: red skin with slippage and peeling
- mod 2-7day: extensive peeling and red serous fluid in chest and abdomen, calvarial slippage
- severe >14d: yellow-brown liver +/- mummification
Presence of diffuse avascular villi and obliteration of stem vessels >2 weeks
Common autopsy findings in intrauterine/neonatal death in trisomy 13
Patau syndrome
- microphthalmia, iris coloboma, incomplete forebrain
- microcephaly, cleft lip/palate, cyclopia and proboscis
- polydactyly
- VSD, PDA, ASD
- SGA, inguinal hernia, single umbilical artery
Common autopsy findings in intrauterine/neonatal death in trisomy 18
Edward syndrome
- small mouth, micrognathia, low set ears
- overlapped fingers, short dorsiflexed toe
- valvular abnormalities, ASD, VSD, PDA
- SGA, short sternum
Common autopsy findings in intrauterine/neonatal death in trisomy 21
Down syndrome
- open operculum
- flat facies, oblique palpebral fissues, epicanthal folds
- simian crease, short metacarpals and phalanges, sandal deformity
- AVSD, VSD
- SGA
Common autopsy findings in intrauterine/neonatal death in monosomy X
Turner syndrome
- nuchal cystic hygroma
- marked edema or dorsal surfaces
- Coarctation of aorta
- SGA, generalized hydrops, normal ovaries at birth
Genetic abnormalities in turner syndrom
50% of cases - complete monosomy X
50% of cases - partial monosomy X or mosaics
Manifestations of turner syndrome in adolescents
Short stature
hypogonadism
streak ovaries
failure to develop 2ary sex characteristics
short webbed neck
broad chest with widely spaced nipples
congenital heart disease
melanocytic nevi
Genetic abnormalities in down syndrome
95% T21 (meiotic nondisjunction)
3% translocations
2% mosaics
Main autopsy findings in congenital herpes
Microcephaly, hydrocephaly, microphthalmia
Main autopsy findings in congenital CMV
Microcephaly, hydrocephaly, microphthalmia
necrotizing meningoencaphalitis
arterial and periventricular calcs
giant cell hepatitis, cholangitis
viral inclusions in lungs, kidneys
Main autopsy findings in Congenital toxoplasmosis
Mostly asymptomatic
Severe: hydrocephaly, microcephaly, intracranial calcs, hepatosplenomegaly, jaundice, chorioretinitis
Visible organisms in multiple organs and tissues
Impact of timing of exposure to teratogens on severity of fetal anomalies
0-3wk GA: severe insult will result in abortion, less severe no apparent effect
3-9wk GA: organogenesis = very susceptible
>9wk: organogenesis complete, already formed organs susceptible to growth retardation and damage
Well documented tertogens
Thalidomide
Folate antagonists
Ethanol
Androgenic hormones
Warfarin
Retinoid acid
Valproic acid
Classic findings in fetal alcohol syndrome
Growth retardation
Microcephaly
ASD
Short palpebral fissures
maxillary hypoplasia
Phenotype of excessive and deficiency in retinoic acid during embryogenesis
Excess - cleft lip/palate, CND defects, cardiac defects
Deficiency - ocular, GU, CV, pulmonary malformations
Characteristic findings in congenital rubella
Tetrad - cataracts, congenital heart defects, deafness, mental retardation
At risk period for congenital rubella
Shortly before conception to 16th wk GA, highest first 8 weeks
Main autopsy findings in neonatal death following intrapatrum HSV infection
Hepatoadrenal necrosis
Vesicular skin rash
Vesciular/ulcerated stomatitis, esophagitis
Necrotizing pneumonitis
Chorioretinitis
Consequences of Parvovirus B19 infection during pregnancy vs childhood
Pregnancy - mostly normal, rarely congeital anemia, hydrops fetalis, spontaneous abortion
Childhood - erythema infectiosum
Most severe and lesser severity forms of fetal hydrops
Most severe = hydrops fetalis
Less severe = pleural effusion, ascites, cystic hygroma
3 major broad categories of nonimmune hydrops and example of each
Structural/functional cardiovascular defects
Chromosomal (turner)
Fetal anemia (homozygous alpha-thal, parvo)
Less common causes of nonimmune hydrops
Infections other than parvo (CMV, syph, toxo)
Malformations esp thoracic and urinary tract
Twin to twin transusion
Metabolic disorders
Define immune hydrops
Hemolytic disorder caused by blood group antigen incompatibility between mother and fetus
Etiology and pathogenesis of immune hydrops
Rh+ fetus Rh- mother
Rh+ RBCs pass to maternal blood, starts to develop anti-D Abs, which can cross placenta and cause lysis of fetal RBCs
Why is Rh disease uncommon in first pregnancy
Maternal exposure to fetal RBCs doesn’t happen til last trimester when placental villi cytotrophoblasts are absent or during delivery. Initial exposure is IgM which doesn’t cross placenta
Prophylaxis for immune hydrops
Rh- mothers receive rhesus immune globulin containing anti-D antibodies at 28 wk gestation and within 72h of delivery
Difference between fetal hemolysis in maternal-fetal ABO incompatibility and Rh incompatibility
ABO incompatibility usually has no adverse effect - most Anti-A and anti-B Abs are IgM and don’t cross placenta
Neonatal RBCs express A and B antigens poorly
Fetal cells other than RBCs can express A and B and can absorb transferred antibodies
Under what circumstances is ABO hemolytic disease of the newborn most likely to occur
Group A or B infants born to group O mothers who possess preformed A/B IgG Abs
Changes in incidence of immune hydrops
Formerly most common cause of fetal hydrops but not nonimmune has surpassed it
2 common signs/symptoms of destruction of RBCs in neonates
Anemia
Jaundice
Define SIDS
death of infant <1y that cannot be explained by clinical hx, examination of death scene, or autopsy
Distinction between SIDS and SUID
SUID - sudden unexpected infant death - subset of these are SIDS
Discovery of a cause of death makes the death SUID
Triple risk model of SIDS
SIDS happens when three overlapping factors intersect
1. Vulnerable infant
2. critical developmental period in homeostatic control
3. exogenous stressor
Risk factors for SIDS
Young maternal age
maternal smoking during pregnancy
drug abuse in either parent
short intergestational intervals
late or no prenatal care
poverty
brainstem abnormalities with associated defective arousal and cardiorespiratory control
Prematurity and/or low birth weight
male sex
Product of multiple birth
SIDS in prior subling
Germlind polymorphisms in autonomic nervous system genes
Antecedent respiratory infections
Prone or side sleeping position
Sleeping on a soft surface
Cosleeping in first three months of life
Hyperthermia
Most common pediatric age range for leukemia
0-9
Most common pediatric age range for retinoblastoma
0-4
Most common pediatric age range for neuroblastoma
0-9
Most common pediatric age range for Wilms tumor
0-4
Most common pediatric age range for hepatoblastoma
0-4
Most common pediatric age range for HCC
5-14
Most common pediatric age range for soft tissue sarcoma
all ages
Most common pediatric age range for teratoma
0-4
Most common pediatric age range for CNS tumors
0-9
Most common pediatric age range for Ewing sarcoma
5-14
Most common pediatric age range for Osteogenic sarcoma
10-14
Most common pediatric age range for thyroid CA
10-14
Most common pediatric age range for lymphoma
5-14
Most common pediatric age range for Hodgkin lymphoma
10-14
DDx of pediatric SRBCTs of the head
Medulloblastoma, ATRT, neuroblastoma, retinoblastoma, olfactory neuroblastoma, rhabdomyosarcoma
DDx of pediatric SRBCTs of the thorax
Ewings family, rhabdomyosarcoma, lymphoma, pleuropulmonary blastoma
DDx of pediatric SRBCTs of the abdomen
Neuroblastoma, rhabdomyosarcoma, lymphoma, wilms, Ewing sarcoma, DSRCT
Histologic features of neuroblastoma
Nesting pattern - ill-defined organoid nests with thin fibrovascular septae
Neuroblasts at varying stages of differentiation
Schwannian stroma <50% of the tumor
DDx of neuroblastoma
Lymphoma
Ewing sarcoma
Rhabdomyosarcoma
Desmoplastic small round cell tumor
Wilms tumor
INPC classification of neuroblastoma
Distinguishes two prognostic groups - FH and UH
Classified by amount of schwannian stroma, nodular vs non, ganglionic differentiation, mitotic rate and karyorrhectic index (MKI) and pt age
- Neuroblastoma schwannian stroma poor: undiff, poorly diff, differentiating
- Ganglioneuroblastoma, nodular
- Ganglioneuroblastoma, intermixed
- Ganglioneuroma
Key prognostic parameters in neuroblastoma
Tumor stage and extent of disease
- Stage L1: localized and not involving vital structures
- Stage L2: locoregional tumor with presence of at least one image-defined risk factors
- Stage M: distant metastatic disease except stage MS
- Stage MS: metastatic disease in children <18mo with mets confined to skin, liver, bone marrow
Genomic characteristics of neuroblastic tumors
MYCN amplification: most prognostically relevant - associated with high risk neuroblastic tumors and poor pt prognosis
ALK mutation and amplification: seen in pts with familial predisposition to neuroblastic tumors - associated with higher risk and worse prognosis
ATRX: 2-3% - majority of high-stage tumors in older children
DNA index: near diploid/tetraploid unfavourable, hyperdiploid better prognosis
IHC in neuroblastoma
PGP9.5+, NB84+, synaptophysin and NSE
Biochemical markers for neuroblastoma
VMA, HVA
Catecholamines may not be increased in undifferentiated neuroblastoma
Histologic features in Wilms and how histologic impacts prognosis
Classic triphasic appearance: blastema, stroma, epithelial components, percentage of each highly variable. May have heterologous elements
Prognosis - Presence of anaplasia (giant cells and abnormal mitoses) correlates with p53 mutations and chemo resistance, even with no extrarenal spread
Define nephrogenic rests
Abnormally persistent clusters of embryonal kidney cells, putative precursor lesions of wilms tumor. Seen adjacent to 25-40% of unilateral tumors and nearly 100% of bilateral
Significance of nephrogenic rests
Patients have increased risk of developing wilms in contralateral kidney
Sites of predilection for Ewing sarcoma
Long bones
Pelvis
Likes to arise in medullary cavities
Radiologic findings in Ewing sarcoma
Destructive lytic tumor extending into soft tissue
Elevation of periosteum
“Onionskin” layering
Histologic features of Ewing sarcoma
Sheets of uniform small round blue cells
Homer-wright rosettes
Sparse intercellular stroma
Few or no mitoses
Intracytoplasmic glycogen
CD99+, vimentin+
Cytogenetics of Ewing sarcoma
95% involve t(11;22) translocation EWSR1-FLI1, some involve EWSR1-ERG
Tumors with involvement of EWSR1 gene
Ewing sarcoma family of tumors
Desmoplastic small round cell tumor
Angiomatoid fibrous histiocytoma
Clear cell sarcoma of soft parts
Extraskeletal myxoid chondrosarcoma
Extraskeletal chondrosarcoma
Myoepithelioma
Presentation and treatment for aneurysmal bone cyst
Occurs in first two decades of life
Rapid onset of pain and swelling
Common treatment is curettage and bone graft
Where does aneurysmal bone cyst commonly arise
Long bones (metaphysis) in 50-60%
Vertebrae and sacrum in 20-30%
Radiologic findings of ABC
x-ray: sharply defined, expansile osteolytic lesion with thin sclerotic borders
CT: fluid-fluid levels
Gross and histologic findings of ABC
Honeycombing and cystic spaces
Septi of solid and hemorrhagic tissue
Cystic spaces filled with blood and separated by septa containing fibroblasts, osteoclast-like giant cells and woven bone
Numerous hemosiderin-laden macrophages
Reactive bone formation
DDx of ABC
Telangiectatic osteosarcoma
Giant cell tumor
Pathogenesis of ABC
Rearrangements of chromosome 17 lead to USP6 overexpression
Secondary ABC (non-neoplastic) do not have USP6 rearrangements
Diseases associated with EBV infection
Infectious mononucleosis
Burkitt lymphoma
Nasopharyngeal carcinoma
Chronic active EBV infection
Hodgkin lymphoma (mixed cellularity 70%, lymphocyte poor 40%)
Primary CNS lymphoma
PTLD
Oral hairy leukoplakia
EBV-associated smooth muscle tumor
Extranodal NK/T cell lymphoma, nasal type
Angioimmunoblastic T cell lymphoma
EBV-associated gastric carcinoma
Histologic features of desmoplastic small round cell tumor
Well defined nests of small round cells separated by desmoplastic stroma
Uniform cells with small hyperchromatic nuclei, inconspicuous nucleoli, scant cytoplasm and indistinct cytoplasmic borders
IHC of desmoplastic small round cell tumor
WT1+ (C terminus)
Desmin+ (dot-like perinuclear cytoplasmic)
Keratin+ (dot like cytoplasmic)
Vimentin+ (dot like cytoplasmic)
Genetic anomaly in desmoplastic small round cell tumor
EWSR1-WT1
