2023 DBCS 324
Review for Exam 1
Pathology
M. Beth Miloro, DDS, MPH
Assistant Clinical Professor
University of Illinois at Chicago
Department of OMDS
Errors of Morphogenesis
Malformations
Disruptions
Deformations
Sequence
Malformation syndrome
Malformations
• Intrinsically abnormal developmental process
– Primary errors of morphogenesis
– Cause:
• Genetic
• Environmental
• Multifactorial
Malformation Causes
• Genetic diseases
– Down syndrome
– Turner/Klinefelter syndrome
• Environmental factors
– Viruses – rubella
– Drugs –
• Thalidomide - limb malformations
• Alcohol – fetal alcohol syndrome
• Smoking - low birth weight, SIDS
• Multifactorial - environment + genetic
– Cleft palate/lip, neural tube defects
Microcephaly and Zika
What we don’t know
• Causal relation between Zika virus and microcephaly or other
adverse pregnancy outcomes
• Full spectrum of phenotypes in affected infants
• Impact of timing of infection during pregnancy
• Impact of severity of maternal infection
• Magnitude of the possible risk of microcephaly and other adverse
pregnancy outcomes
Microcephaly
• Microcephaly is the clinical finding of a small head compared
with infants of the same sex and age, or gestational age if
measured at birth
• Head circumference is considered a reliable assessment of
the volume of the underlying brain
• Head circumference (HC) is also known as occipital-frontal
circumference (OFC)
• Anencephaly
•  Failure of the neural tube to close resulting in failure of
the brain and skull to form
• Spina bifida
•  Failure of neural tube closure resulting in an opening in
the spine
•  Can occur anywhere along the spine
Thalidomide malformation
FAS (Fetal Alcohol Syndrome)
• Low birth weight
• Heart septum defects
• #1 cause of acquired
mental impairment
• Short memory spans,
Impulsive behavior
Neural tube defects
Disruptions
• Extrinsic disturbance in morphogenesis
• Secondary destruction of an organ or body region that was
previously normal in development
• Ex: amniotic bands
– Rupture of amnion formation of “bands” compress/attach to
parts of developing fetus
• Environmental cause:
– Viral infections, drugs, and radiation
Pathogenesis
• Timing
– Embryonic period: 1st 9 weeks pregnancy
• Early – 1st 3 weeks after fertilization
• 3rd -9th weeks – very susceptible to teratogens (4-5 weeks organs
forming)
– Fetal period: 10 weeks – birth
• Susceptible to growth retardation/injury to already formed
organs
• Environment and genetic factors
Lymphangioma
• Benign tumor of dilated lymph vessels
• Present at birth or acquired
• Skin and deeper regions of neck, axilla, mediastinum,
and retroperitoneum
• Increase in size after birth
• Pediatric diseases
– SIDS
– Benign tumors
– Malignant tumors
• Neuroblastoma
• Retinoblastoma
• Wilms tumor
Malignant Tumors of Childhood
“small, round, blue cell tumors”
Neuroblastoma
• Second most common solid malignancy of
childhood after brain tumors
• Arise from primordial neural crest cells
• Most are sporadic but 1-2% familial
• Most arise in the adrenal medulla, others in
paravertebral region of abdomen
• In situ lesions are 40% more common than overt
tumors and most regress!
Neuroblastoma
• Histopath:
– primitive-appearing cells with dark nuclei, poorly defined
cells growing in solid sheets
– Mitosis
– Homer-Wright pseudo-rosettes
Neuroblastoma Prognosis
• Outlook for children younger than 18 months
more favorable than older children
• Amplification of the NMYC oncogene (25% of
cases has a profound affect - greater the
number of copies, the worse the prognosis
• Overexpression of telomerase – adverse
prognostic factors
Retinoblastoma
•
•
•
•
•
Intraocular malignancy
40% mutation in RB1 gene (heritable)
Neural in origin
Bilateral (familial) or unilateral (sporadic)
Familial cases have increased chance of
osteosarcoma
Retinoblastoma
• Clinical:
– Present at birth, presents ~ age 2
– Poor vision
– Strabismus
– Whitish hue to pupil (“cat’s eye reflex”)
– Pain and tenderness
• Histopath:
– Flexner-Wintersteiner rosettes (small round blue cells around a
central lumen
Retinoblastoma
• Prognosis:
– High survival rate with treatment
– Familial type has increased chance of osteosarcoma
Wilm’s Tumor (Nephroblastoma)
• Tumor of kidney
• 2-5 years of age
• Increased risk in 3 syndromes
– WAGR (Wilms tumor, aniridia, genital
abnormalities, mental retardation)
– BWS (Beckwith-Wiedemann syndrome) –
enlargement of tongue, kidneys or liver
– DDS (Denys-Drash syndrome)- gonadal dysgenesis
and renal abnormalities
• Presents as abdominal mass, abdominal pain
• Very good prognosis
Wilms Tumor
(Nephroblastoma)
• Histopath
– triphasic – blastemal (small blue cells), epithelial (abortive
tubules),stromal (fibrous) anaplastic areas
– More anaplastic areas, worse prognosis
GI Pathology Outline
• Esophagus
• Stomach
• Intestine
• Liver
• Hepatitis
• Alcoholic liver disease
• Hemochromatosis
• Wilson disease
• Carcinoma
Viral Hepatitis
• Caused by Hepatitis A, B, or C viruses
• Some cases asymptomatic
• Some cases symptomatic:
• Acute (jaundice)
• Chronic (may lead to cirrhosis and liver failure)
• Fulminant (liver failure)
Hepatitis A
Hepatitis B
Hepatitis C
Transmission
Fecal-oral
Parenteral
Parenteral
Chronic
Hepatitis
None
5%
>85%
Fulminant
hepatitis
0.1%
0.1-1.0%
Rare
Carcinoma
No
Yes
Yes
Other stuff
50% of people
> 50 are +
Vaccine
effective
New drugs are
promising
Bottom line
Benign, selflimited disease
Most recover;
small % die
Nasty! Almost
10% die
Chronic viral hepatitis: ground-glass hepatocytes
Jaundice
• Yellow skin, eyes due to elevated bilirubin
• Conjugated hyperbilirubinemia
•  liver excretion (hepatitis)
•  bile flow (tumor blocking bile duct)
• Unconjugated hyperbilirubinemia
•  production (hemolytic anemia)
•  uptake (hepatitis)
Bilirubin metabolism
and elimination
Laboratory Tests
Serum aspartate aminotransferase (AST)
Hepatocyte integrity
Serum alanine aminotransferase (ALT)
Serum bilirubin (total and direct)
Biliary function
Serum alkaline phosphatase
Serum albumin
Hepatocyte function
Prothrombin time
Cirrhosis
• Fibrotic, nodular liver
• Causes: alcoholism, hepatitis
• Leads to portal hypertension and liver failure
• Increased risk of liver carcinoma
Portal Hypertension
• Decreased blood flow through liver
• Biggest cause: cirrhosis
• Symptoms
• ascites
• venous shunts (esophageal varices, hemorrhoids)
• congestive splenomegaly
• hepatic encephalopathy
Consequences of
portal hypertension
Liver Failure
• End point of severe liver disease
• Causes: fulminant hepatitis, cirrhosis,
drug overdose
• Symptoms: jaundice, edema, bleeding,
hyperammonemia
• Multiple organ-system failure
• Hepatic encephalopathy
• Hepatorenal syndrome
Oral Manifestations of Liver Injury
• Hematomas, gingival bleeding
• Jaundiced mucosa
• Glossitis (in alcoholic hepatitis)
• Reduced healing after surgery
Alcoholic Liver Disease
• 100,000 -200,000 deaths/year
• Effects on liver: steatosis, hepatitis, cirrhosis
• How much do you need to drink?
• Short-term ingestion of 8 beers/day 
reversible steatosis
• Long-term ingestion of 5 beers/day 
severe injury
• Beer and binge drinking are risky
Alcoholic liver disease
Alcoholic hepatitis: inflammation and Mallory bodies
Hereditary hemochromatosis
• Autosomal recessive disease:  body iron
• Cause: mutations in hemochromatosis gene
(regulates iron absorption)
• Cirrhosis, skin pigmentation, liver carcinoma
• Early detection and treatment (phlebotomy,
iron chelators) = normal life expectancy
Wilson Disease
• Autosomal recessive disease:  body copper
• Cause: mutation in gene regulating copper
excretion
• Symptoms: acute and chronic liver disease,
neuropsychiatric manifestations, KayserFleisher rings in cornea
• Treatment: copper chelation therapy
Hepatocellular Carcinoma
• Strongly associated with hepatitis B and C,
chronic liver disease, and aflatoxins
• Rapid increase in liver size, worsening
ascites, fever and pain
•  alpha fetoprotein level
• Median survival 7 months (death from
bleeding, liver failure, cachexia)
Metastatic Carcinoma
• Most common malignancy in the liver
• Usually multiple lesions
• Most common primaries: colon, lung,
breast, pancreas, stomach.
Cholelithiasis
• Common! (10% of adults in US)
• Cholesterol stones: Female, Fat, Fertile, Forty
• Pigment (bilirubin) stones: Asian countries,
hemolytic anemia and biliary infections
• Symptoms: None, or excruciating pain
• Complications: cholecystitis, empyema,
perforation, fistula, obstruction, pancreatitis
Acute Pancreatitis
• Acute inflammation and reversible destruction
•
•
•
•
of pancreas
Symptoms: abdominal pain radiating to back
Main causes: alcoholism, gallstones
Labs: elevated serum amylase and lipase
Prognosis: Most recover, but 5% die in first
week
Chronic Pancreatitis
• Longstanding, irreversible pancreatic destruction
• Most are alcohol related, some idiopathic
• Symptoms: silent, or bouts of jaundice and pain
• Prognosis: poor (50% mortality over 20 years)
Pancreatic Carcinoma
• 4th leading cause of cancer death in US
• Biggest risk factor: smoking
• Highly invasive
• Silent until late (especially tail); then
pain, jaundice
• Very high mortality: 5ys <5%