Pediatric Pathology

Question 1

Malformation

Answer 1

Primary errors of morphogenesis - intrinsically abnormal developmental process
Usually multifactorial rather than a result of a single gene or chromosomal defect

Question 2

Disruptions

Answer 2

Results from secondary destruction of an organ or body region that was previously normal in development
Arises from an extrinsic disturbance in morphogenesis
Amniotic bands – extrinsic causing defect

Question 3

Deformations

Answer 3

Also represent extrinsic disturbance of development leading to a variety of structural abnormalities
Fundamental to the pathogenesis is localized or generalized compression of the growing fetus by abnormal biomechanical forces - uterine constraint is the most common factor

Question 4

Potter’s sequence

Answer 4

Oligohydramnios
Wide set eyes with epicanthal folds
Low set ears
Broad, flattened nose and receding chin
Limb anomalies
Breech presentation – cannot turn around due to low fluid

Question 5

Sequence

Answer 5

A cascade of anomalies triggered by one initiating aberration

Question 6

Achondroplasia

Answer 6

the most common form of short-limb dwarfism, is caused by gain of function mutations in FGFR3. The FGFR3 protein is a negative regulator of bone growth, and the activation FGFR3 mutations are thought to exaggerate this physiologic inhibition, resulting in dwarfism.

Question 7

Trisomy 21 (Down’s syndrome)

Answer 7

Most common chromosomal disorder
Mental retardation, flat facial profile, prominent epicanthal folds, simian crease, duodenal atresia, and congenital heart defects
Increased Alzheimer’s disease in affected individuals >40 years old
Increased risk of acute lymphoblastic leukemia

Question 8

Trisomy 18 (Edward’s syndrome)

Answer 8

1 in 8,000
Severe mental retardation
Rocker bottom feet
Low set ears
Clenched hands with overlapping fingers
Micrognathia
Congenital heart defects
Renal abnormalities

Question 9

Trisomy 13 (Patau’s syndrome)

Answer 9

1 in 15,000
Severe mental retardation
Microcephaly
Cleft lip/cleft palate
Polydactyly
Congenital heart defects
Renal abnormalities

Question 10

Chromosome 5p- deletion (Cri-du-chat syndrome)

Answer 10

1 in 50,000
Severe mental retardation
High pitched crying/mewing – source of syndrome name
Epicanthal folds
Broad nasal bridge
Malformed ears
Congenital heart defects

Question 11

Klinefelter syndrome (XXY)

Answer 11

1:660 (500 – 1000)
Testicular atrophy
Tall stature
Long extremities
Gynecomastia 
Female hair and fat distribution

Question 12

Turner syndrome (XO)

Answer 12

1 in 3,000
Short stature
Ovarian dysgenesis – streak ovaries
Webbing of neck/Cystic hygromas (shield chest with wide spaced nipples)
Coarctation of aorta
Primary amenorrhea/Hypothyroidism/Insulin resistance

Question 13

AFP (alpha-fetoprotein)

Answer 13

a protein that is produced by the fetus
High levels of AFP suggest the possibility of a neural tube defect such as spina bifida or anencephaly
Low levels of AFP and abnormal levels of hCG and estriol suggest the possibility of Trisomy 21 or Trisomy 18 or another type of chromosome abnormality
However, the most common reason for elevated AFP levels is inaccurate dating of the pregnancy

Question 14

hCG (human chorionic gonadotropin)

Answer 14

a hormone produced within the placenta

Question 15

Estriol

Answer 15

an estrogen produced by both the fetus and the placenta

Question 16

Inhibin-A

Answer 16

a protein produced by the placenta and ovaries.

Question 17

Quad Screen

Answer 17

The quad screen measures levels of these four substances and the results are combined with the mother’s age and ethnicity in order to assess probabilities of potential genetic disorders
The quad screen test is performed between the 16th and 18th week of pregnancy testing AFP, hCG, Estriol, Inhibin-A

Question 18

Environmental induced injury Infections – TORCHES

Answer 18

Toxoplasmosis
Other infections (VZV, influenza, HIV, mumps)
Rubella
Cytomegalovirus (CMV, the most common fetal viral infection)
Herpes simplex virus (HSV)
Syphilis

Question 19

Congenital Toxoplasmosis

Answer 19

Hepatosplenomegaly
Diarrhea, vomiting and feeding problems
Retinitis, seizures and neurologic defects
Hearing loss
Low birth weight, jaundice and petechial rash

Question 20

Congenital Rubella

Answer 20

Cardiac defects (Patent ductus most common)
Cerebral defects
Ophthalmic defects (Cataracts and blindness)
Hearing loss
Prematurity, low birth weight, anemia, hepatitis and thrombocytopenia

Question 21

Congenital Cytomegalovirus infection

Answer 21

Prematurity, low birth weight, petechial rash and hepatosplenomegaly with jaundice
Microcephaly and seizures
Hearing and vision deficits
Mental retardation

Question 22

Congenital Herpes simplex infection

Answer 22

Localized form(birth canal exposure) = Lesions of skin, eyes and mouth 
Disseminated form (worse) = Involvement of internal organs, particularly the liver
CNS form (temporal lobes) = Seizures, tremors irritability, lethargy, encephalopathy

Question 23

Transplacental (hematologic/blood) infections

Answer 23

Most parasitic (toxoplasmosis, malaria) and viral infections and a few bacterial infections (Listeria and syphilis) gain access to the fetal bloodstream trans-placentally, via the chorionic villi

Question 24

Fetal alcohol spectrum disorders

(FASD’s)

Answer 24

Growth retardation
Microcephaly
Atrial septal defect
Short palpebral fissures
Maxillary hypoplasia
Mental retardation and behavioral problems

Question 25

Phenytoin (Dilantin)

Answer 25

A common anti-epileptic and anti-arrhythmic medication Can cause broadened nasal bridge, cleft lip/palate and microcephaly Can also cause mild mental retardation Similar to FAS – has been called the “Fetal hydantoin syndrome” (FHS)

Question 26

Warfarin – Coumadin and anti-coagulants

Answer 26

Hypoplastic nose Stippled epiphyses Other skeletal abnormalities Ocular abnormalities

Question 27

Iodine

Answer 27

Congenital goiter or hypothyroidism

Question 28

13-cis-retinoic acid – Isotretinoin or Accutane, an anti-acne medication

Answer 28

Abnormalities of the face, eyes, ears, skull, CNS, CV system, thymus and parathyroid glands

Question 29

Angiotensin-converting-enzyme (ACE) inhibitors

Answer 29

Renal defects as angiotensin II necessary for normal renal development

Question 30

Cocaine

Answer 30

Premature delivery Birth defects Attention deficit disorder Fetal/neonate addiction (Crack babies)

Question 31

Maternal hyperglycemia and diabetes

Answer 31

Causes hyperinsulinemia in fetus resulting in increased insulin and IGF release Increased body fat Organomegaly (macrosomia) – big babies Cardiac anomalies Neural tube defects, and other CNS malformations Hypertrophy of pancreatic islets, puts infant at risk for significant post-natal hypoglycemia

Question 32

Radiation (cervical cancer radiation)

Answer 32

Exposure to heavy doses of radiation during organogeneis leads to malformations such a microcephaly, blindness, skull defects, and spina bifida

Question 33

Fetal hydrops

Answer 33

Defined as the accumulation of widespread fetal edema during pregnancy Generally classified into immune and non-immune forms, based on the underlying etiology

Question 34

Immune hydrops

Answer 34

Secondary to maternal IgG antibodies capable of transplacental distribution. Causes intravascular hemolysis in the infant with resulting anemia (direct result of RBC loss), jaundice (hemolysis produces unconjugated bilirubin), hypoproteinemia (decreased RBCs results in ischemia and damages heart & liver leading to decreased plasma proteins) Most commonly seen with Rh disease

Question 35

Non-immune hydrops

Answer 35

Cardiovascular defects with intrauterine congestive heart failure (CHF) Chromosomal anomalies Turner syndrome with large cystic hygromas NoHemangiomasn-immune fetal anemia Hemoglobinopathies such as thalassemia Parvovirus B19 infection

Question 36

Neonatal respiratory distress

Answer 36

Excessive sedation of mother, fetal head injury, fetal aspiration, intrauterine hypoxia, autosomal recessive polycystic renal disease, diaphragmatic hernia, etc. Most common cause is hyaline membrane disease (Respiratory distress syndrome, RDS) - Ground glass pulmonary infiltrates on chest radiograph deficiency of surfactant, Surfactant is synthesized by Type II pneumocytes and is abundantly after 35 weeks and surfactant can be deficient at earlier ages

Question 37

Hemangiomas

Answer 37

most common tumors of infancy Most located on the face and scalp, can see in any organ May enlarge with growth of child, but some forms may also regress  strawberry hemangiomas

Question 38

Lymphangiomas

Answer 38

often in deeper regions of the neck, axilla, mediastinum and retroperitoneal Cystic hygromas, as seen in Turner syndrome, are one manifestation of this neoplasm

Question 39

Fibrous tumors

Answer 39

range from pauci-cellular benign fibromatosis to richly cellular lesions malignancies such as congenital infantile fibrosarcoma

Question 40

acute lymphoblastic leukemia (ALL)

Answer 40

The most common malignancy in children

Question 41

Malignant neoplasms

Answer 41

The most frequent childhood cancers arise in the hematopoietic system, nervous system, adrenal medulla, soft tissues, bone and kidney

Question 42

Malignant CNS neoplasms

Answer 42

Most common solid malignancy in children In childhood, 70% are below tentorium (posterior fossa, e.g. cerebellum) (adults are above tentorium) Incidence: astrocytoma > medulloblastoma > ependymoma

Question 43

Neuroblastoma

Answer 43

Second most common solid malignancy of childhood (after brain tumors) Account for 7-10% pediatric neoplasms ~50% of malignancies diagnosed in infancy Derived from primordial neural crest cells In childhood 40% arise in the adrenal medulla and the remaining occur along the sympathetic chain (paravertebral area and posterior mediastinum)~90% produce catecholamines Elevated blood levels of catecholamines and elevated urine levels of metabolites Usually present with large abdominal mass, fever and weight loss

Question 44

Wilm tumor (WT)

Answer 44

Nephroblastoma Most common primary renal tumor of childhood Usually diagnosed between the ages of 2-5 years 5-10% involved both kidneys Usually presents with large abdominal mass and possibly hematuria WAGR syndrome (WT, aniridia, genital anomalies, and mental retardation) - 33% chance of developing a WT Germline mutations in WT1 gene (Chromosome 11p13) Denys-Drash syndrome (gonadal dysgenesis, and early onset nephropathy leading to renal failure - 90% chance of develop WT) tumor (WT) - risk factors Beckwith -Wiedemann syndrome (organomegaly, hemihypertrophy, macroglossia, omphalocele) Mutation in locus distant to WT1 called WT2