digestive pathology lecture 6 · circulatory disorders 11. hepatic disease in pregnancy 12. nodular...
TRANSCRIPT
![Page 1: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/1.jpg)
Digestive Pathology Lecture 6
Reproduction Prohibited
This file contains original text and images as well as materials adapted from copyrighted sources
For use only as a temporary educational aid
Partially or completely copying or distributing the contents of this file may constitute an infringement of the fair use exception
for teaching faculty of the U.S. Copyright Law
LSUHSC-New Orleans, 2015
Last updated on September 30, 2015
--
![Page 2: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/2.jpg)
The liver III
11. Inborn errors of metabolism
– Wilson disease
– Alpha1-antitrypsin deficiency
– Hemochromatosis12. Intrahepatic biliary tract diseases
13. Circulatory disorders
14. Hepatic disease in pregnancy
15. Nodular hyperplasias
16. Benign neoplasms
17. Malignant neoplasms
![Page 3: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/3.jpg)
Wilson disease (hepatolenticular degeneration)
Autosomal recessive
Progressive copper accumulation
Oxidative injury Commonly manifest in late adolescence Hepatic manifestations
– Chronic hepatitis, cirrhosis– Massive necrosis, fulminant failure
![Page 4: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/4.jpg)
Wilson disease: Chronic hepatitis, copper stains
![Page 5: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/5.jpg)
Wilson’s disease, glycogenated nuclei
Glycogenated nuclei are a common but nonspecific finding in Wilson’s diseaseGastrointestinal and Liver Pathology. C. Iacobuzio-Donahue
![Page 6: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/6.jpg)
Wilson disease: Mallory bodies
Numerous Mallory bodies (arrowheads)Scheuer’s Liver Biopsy Interpretation
![Page 7: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/7.jpg)
Wilson, cirrhosis, acute failure
Cirrhotic nodules (N) are surrounded by inflamed fibrous septa Scheuer’s Liver Biopsy Interpretation
![Page 8: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/8.jpg)
Wilson disease: chronic hepatitis, cirrhosis
![Page 9: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/9.jpg)
Wilson disease (hepatolenticular degeneration)
Neurologic manifestations– Injury of basal ganglia– Incoordination, dystonia
• muscle spasms/cramps, involuntary twisting, jerking, speech and gait disturbances
– Psychiatric disorders• Depression, bipolar disorder, psychosis
![Page 10: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/10.jpg)
Wilson disease: basal ganglia degeneration, atrophy, cavitation
![Page 11: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/11.jpg)
Wilson disease (hepatolenticular degeneration)
Hematologic manifestations– Hemolytic anemia
Ophthalmologic manifestations– Kayser-Fleischer rings (corneal limbus)
![Page 12: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/12.jpg)
Kayser-Fleischer ring
D. Huster. Wilson disease. Research Clinical Gastroenterology Volume 24, Issue 5 2010 531 - 539
![Page 13: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/13.jpg)
Kayser-Fleischer ring, slit lamp
![Page 14: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/14.jpg)
Wilson disease
In hepatocytes copper is:
– Transported into the golgi apparatus where it is incorporated into apo-ceruloplasmin to form ceruloplasmin which is SECRETED into circulation (90-95% of plasma copper)
– Transported into bile (canaliculi) to be EXCRETED
ATP7B gene codes for a copper-transporting ATPase required for both functions
Defect in the ATP7B gene interferes with both secretion and excretion
![Page 15: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/15.jpg)
ATP7B-mediated copper export in the hepatocyte
Copper entrance: copper transporter CTR1. Copper is delivered to ATP7B in the golgi apparatus by the copper chaperone ATOX1. In the golgi apparatus copper is incorporated in various cuproenzymes including ceruloplasmin. When copper levels rise, ATP7B redistributes to a vesicular compartment and participates in copper excretion in the bile via an unknown mechanism that probably involves COMMD1
![Page 16: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/16.jpg)
Wilson disease
Diagnosis– LOW serum ceruloplasmin
– HIGH non-ceruloplasmin serum copper
– HIGH urinary copper
– HIGH hepatic copper
– Ophthalmologic evaluation
– Genetic testing is now available• Sequencing of the ATP7B gene, more than 500
different mutations identified
![Page 17: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/17.jpg)
Alpha1-antitrypsin deficiency
Autosomal recessive disorder with codominant expression
The most common genetic cause of liver disease in children
The most common genetic cause of emphysema in adults
![Page 18: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/18.jpg)
Alpha1-antitrypsin deficiency A1AT is a serine protease inhibitor (Pi, SERPINA1)
– Inhibition of neutrophil elastase and other proteases
SERPINA1 gene, has more than 100 allelic variants
Each gene allele provides half of the enzyme level
The normal gene product is PiM
Most common deficiency alleles are:
– PiS (50-60% enzyme levels)
– PiZ (10-20% enzyme levels)
Most common carrier genotypes: PiMS, PiMZ
Most common deficiency genotypes: PiSS, PiSZ, PiZZ
![Page 19: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/19.jpg)
Alpha-1-antitrypsin deficiency
A single amino acid substitution
Alpha-1 antitrypsin abnormally folded
Cannot move from ER
Form large aggregates that resist normal degradation including autophagy
Appear as PAS-positive cytoplasmic globes
![Page 20: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/20.jpg)
Alpha1-antitrypsin deficiency, biopsy, PAS stain
![Page 21: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/21.jpg)
Alpha-1-antitrypsin deficiency
Defective degradation of the misfolded protein appears to induce apoptosis, inflammation
Only 10% of PiZZ individuals develop clinical disease
Other genetic/environmental factors must play a role
![Page 22: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/22.jpg)
Alpha-1-antitrypsin deficiency
Liver manifestations
– Neonatal (giant cell) hepatitis
– Chronic hepatitis (adolescents)
– Cirrhosis (adults)
– Hepatocellular carcinoma
Lung manifestations:
– Emphysema
![Page 23: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/23.jpg)
Alpha-1-antitrypsin deficiency
Diagnosis
– Serum levels of A1AT, used for screening
– Protein electrophoresis (phenotype)
– DNA analysis (genotype)
– Liver biopsy
Underdiagnosed
– PiZZ, present in 1/1800 live births
![Page 24: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/24.jpg)
Hemochromatosis
![Page 25: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/25.jpg)
Iron metabolism Absorbed in duodenum and proximal jejunum
No natural mechanism of excretion
Amount absorbed must balance out losses: epithelial exfoliation, minor hemorrhages, menstruation
Ferroportin, an iron channel, controls the release of iron into the circulation from: enterocytes, macrophages, hepatocytes
Hepcidin, produced in the liver, binds ferroportin which is then internalized and degraded preventing the release of iron
![Page 26: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/26.jpg)
Hepcidin, ferroportin
Low iron, low hepcidin: ferroportin exports iron into the circulation
High iron, high hepcidin: hepcidin binds to ferroportin inducing its internalization and degradation; iron remains in the cells
![Page 27: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/27.jpg)
Iron transport and storage Iron is transported in blood by TRANSFERRIN
Iron is stored as:– FERRITIN (circulation, readily available)
– HEMOSIDERIN (macrophages, tissues, poorly available)
![Page 28: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/28.jpg)
Dietary Iron
Enterocyte
Hemoglobin
SpleenRES
Ferritin
Hemosiderin
Bone Marrow
Blood Losses
EpithelialShed
Transferrin
![Page 29: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/29.jpg)
Hemosiderosis, hemochromatosis
HEMOSIDEROSIS: generic term, excessive accumulation of iron
HEMOCHROMATOSIS: the disease state caused by the generation of free radicals and oxidative injury
![Page 30: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/30.jpg)
Hemochromatosis Secondary, acquired
– Ineffective erythropoiesis (the most common cause)
• Thalassemia
• Sideroblastic anemia
• Pyruvate kinase deficiency
• Other
– Parenteral administration• Transfusions, injections
– Increased oral intake• Bantu siderosis
Primary, hereditary– Excessive intestinal iron absorption
![Page 31: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/31.jpg)
Hereditary hemochromatosis Adult form Autosomal recessive Mutations in proteins that regulate hepcidin
synthesis in response to iron levels– HFE (the most common)– Transferrin receptor 2 (TfR-2)– Hemojuvelin (HJV)
These mutations result in:– Lower hepcidin levels– Greater ferroportin levels– Greater transport of iron into the circulation
![Page 32: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/32.jpg)
Hereditary hemochromatosis HFE mutations cause most cases of adult
hemochromatosis Two mutations: C282Y, H63D, account for
more than 90% of HH cases C282Y is the most common Common among whites (Northern European)
– Homozygotes, 1 of every 200– Heterozygotes, 1 of every 8 (accumulate less iron)
![Page 33: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/33.jpg)
Hereditary hemochromatosis Men predominate 5:1
Occurs earlier in men (40’s) than in women (50’s)
Classic triad:– Cirrhosis (micronodular)
– Diabetes mellitus (pancreatic fibrosis, atrophy)
– Bronze skin pigmentation
Other manifestations:– Joint pain (arthropathy), the most common presenting
complaint, may precipitate pseudogout
– Cardiomyopathy: arrhythmia, heart failure
– Thyroid and adrenal insufficiency
– Hypogonadism: impotence, amenorrhea, early menopause
![Page 34: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/34.jpg)
![Page 35: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/35.jpg)
Hemochromatosis, bronze skin pigmentation
![Page 36: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/36.jpg)
Hemochromatosis, liver, pancreas, lymph nodes
![Page 37: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/37.jpg)
HemochromatosisA, Hereditary hemochromatosis, iron accumulates in hepatocytes before spilling over to Kupffer cells. Accumulation in periportal hepatocytes in early stages of the disease, becomes panlobular later on. B, Prussian blue stain. C,Secondary hemochromatosis, heavy iron deposition may be seen in Kupffer cells (arrow). Gastrointestinal and liver pathology. C. Iacobuzio-Donahue
![Page 38: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/38.jpg)
Hemochromatosis
Diagnosis
– Elevated serum iron
– Increased transferrin saturation
– Elevated serum ferritin
– Increased iron concentration in liver
– Genetic analysis (HFE gene)
Hepatocellular carcinoma 200-fold risk
![Page 39: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/39.jpg)
The liver III11. Inborn errors of metabolism
12. Intrahepatic biliary tract diseases
– Congenital abnormalities
– Primary and secondary biliary cirrhosis
– Primary sclerosing cholangitis13. Circulatory disorders
11. Hepatic disease in pregnancy
12. Nodular hyperplasias
13. Benign neoplasms
14. Malignant neoplasms
![Page 40: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/40.jpg)
Congenital Abnormalities of the Intrahepatic Biliary Tree
![Page 41: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/41.jpg)
von Meyenburg’s complexes (bile duct micro-hamartomas)
![Page 42: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/42.jpg)
von Meyenburg’s complexes, MRI
![Page 43: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/43.jpg)
Polycystic liver diseaseAutosomal DOMINANT polycystic (kidney) disease
![Page 44: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/44.jpg)
Congenital hepatic fibrosis, broad fibrous septa Autosomal recessive polycystic (kidney) disease
![Page 45: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/45.jpg)
Caroli diseaseSegmental cystic dilatation of bile ducts
RadioGraphics, 2006, 26:715-731
![Page 46: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/46.jpg)
Caroli disease, cystically dilated bile ducts
![Page 47: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/47.jpg)
Caroli’s disease, bile duct dilatation, cholangitis
![Page 48: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/48.jpg)
Caroli disease and congenital hepatic fibrosis
![Page 49: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/49.jpg)
Primary Biliary Cirrhosis Autoimmune
– Destruction of small and medium-size intrahepatic bile ducts
– Chronic hepatitis
– Biliary cirrhosis
Antimitochondrial antibodies– E2 component of pyruvate dehydrogenase
Association with other autoimmune conditions
Female predominance > 6:1
Peak incidence, 40-50 years
Family and geographic clustering
Symptoms: those associated with cholestasis and portal hypertension
![Page 50: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/50.jpg)
Small and medium size ducts infiltrated by lymphocytes
![Page 51: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/51.jpg)
Ducts, granulomatous inflammation
![Page 52: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/52.jpg)
Primary biliary cirrhosis, jigsaw puzzle pattern
![Page 53: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/53.jpg)
Biliary cirrhosis, micronodular, green
![Page 54: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/54.jpg)
Secondary biliary cirrhosis
In adults:
– Choledocholithiasis
– Malignant neoplasms (head of the pancreas, biliary tree)
– Biliary strictures from surgical procedures
In children:
– Biliary atresia
– Choledochal cysts
– Cystic fibrosis
![Page 55: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/55.jpg)
Primary Sclerosing Cholangitis Immune-mediated SEGMENTAL inflammation, fibrosis
and obliteration of LARGE intrahepatic and extrahepatic bile ducts, and pancreatic ducts
Males predominate 2:1
Third through fifth decades of life
Ulcerative colitis, 70% of patients
p-ANCA antibodies
Toxins released by inflamed gut may cause injury in the biliary tree
T cells and antibodies cross-reactivity between intestinal or bacterial antigens and bile ducts
Genetic predisposition
![Page 56: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/56.jpg)
Primary sclerosing cholangitis, onion-skin fibrosis
![Page 57: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/57.jpg)
Primary sclerosing cholangitis, fibrous obliteration
![Page 58: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/58.jpg)
PSC, gross fibrosis of intrahepatic bile ducts
![Page 59: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/59.jpg)
Primary sclerosing cholangitis, chain of lakes
![Page 60: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/60.jpg)
Primary Sclerosing Cholangitis Inflammation (cholangitis) and stone
formation (hepatolithiasis) in dilated ducts
May involve gallbladder (cholecystitis) and pancreatic ducts (pancreatitis)
Risk for cholangiocarcinoma
Many progress to cirrhosis and liver failure and need liver transplantation
May recur after transplantation
![Page 61: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/61.jpg)
The liver III11. Inborn errors of metabolism
12. Intrahepatic biliary tract diseases
13. Circulatory disorders
– Passive congestion
– Infarcts
– Portal hypertension
– Budd-Chiari syndrome
– Veno-occlusive disease14. Hepatic disease in pregnancy
15. Nodular hyperplasias
16. Benign neoplasms
17. Malignant neoplasms
![Page 62: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/62.jpg)
Nutmeg liver, passive congestion
![Page 63: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/63.jpg)
Passive congestion, histology
![Page 64: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/64.jpg)
Hemorrhagic necrosis, cardiac sclerosis
![Page 65: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/65.jpg)
Hepatic artery obstruction, infarcts
Liver infarcts are rare
Double blood supply
– Hepatic artery 30 -40%
– Portal vein 60 -70%
Interruption of the main hepatic artery can be tolerated
– Except in transplanted liver: thrombosis of the hepatic artery a major cause of graft loss
![Page 66: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/66.jpg)
Liver infarcts, shock, gross
![Page 67: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/67.jpg)
Infarct of Zahn
Thrombosis of a portal vein radicle
Results in:
– Ischemia
– Dilatation and congestion of sinusoids
– Flattening of the surrounding hepatocytes
– No necrosis (pseudoinfarct)
Grossly visible as sharply demarcated area of congestion
![Page 68: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/68.jpg)
Infarct of Zahn, gross
![Page 69: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/69.jpg)
Posthepatic– Right-sided heart failure
– Hepatic veins thrombosis• Budd-Chiari syndrome
Intrahepatic– Cirrhosis (the most common cause)
– Nodular regenerative hyperplasia
– Sinusoidal obstruction syndrome
Prehepatic– Portal vein obstruction
• Pylephlebitis (portal thrombophlebitis)
Portal Hypertension, causes:
![Page 70: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/70.jpg)
Portosystemic shunts, manifestations
Coronary VeinsEsophageal Varices
Splenic veinSplenomegaly
Inferior Mesenteric VeinHemorrhoids
Umbilical VeinCaput Medusae
Ascites
![Page 71: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/71.jpg)
Caput medusae
![Page 72: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/72.jpg)
Budd-Chiari syndrome Thrombosis of 2 or more major hepatic veins
Massive enlargement of the liver
Severe portal hypertension
Severe ascites
Etiology:– Hypercoagulable states
• Pregnancy, oral contraceptives
• Postoperative, postpartum states
• Deficiencies in antithrombin III, protein S or protein C
• Polycythemia vera, sickle cell disease
– Hepatocellular carcinoma
– Idiopathic, 10%
![Page 73: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/73.jpg)
Budd-Chiari, hepatic vein thrombosis
![Page 74: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/74.jpg)
Budd-Chiari, centrizonal congestion/necrosis
![Page 75: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/75.jpg)
Sinusoidal obstruction syndrome
Also called veno-occlusive disease– Toxic damage of sinusoidal endothelial cells
– Desquamation, embolization into the terminal hepatic venules
– Extravasation of red blood cells
– Marked centrizonal congestion, necrosis, fibrosis
Etiology:– Acute: After bone marrow transplantation
– Subacute or chronic: Chemotherapy, herbal remedies (Jamaican bush tea, pyrrolizidine alkaloids found in many plants)
![Page 76: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/76.jpg)
Veno-occlusive disease, centrizonal congestion/necrosis
![Page 77: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/77.jpg)
The liver III11. Inborn errors of metabolism
12. Intrahepatic biliary tract diseases
13. Circulatory disorders
14. Liver disease in pregnancy– Preeclampsia-Eclampsia
– Acute fatty liver of pregnancy
– Intrahepatic cholestasis of pregnancy
15. Nodular hyperplasias
16. Benign neoplasms
17. Malignant neoplasms
![Page 78: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/78.jpg)
Preeclampsia-Eclampsia
Hypertension, proteinuria, edema, coagulation disorders
Hyperreflexia, seizures
HELLP syndrome
– Hemolysis, elevated liver enzymes, low platelets
Unknown etiology
Periportal fibrin deposits
Periportal coagulative necrosis
Parenchymal hemorrhage and infarcts
Subcapsular hematoma, catastrophic rupture
![Page 79: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/79.jpg)
Eclampsia, periportal fibrin deposits, necrosis
![Page 80: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/80.jpg)
Eclampsia, subcapsular hematoma, CT scan
![Page 81: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/81.jpg)
Eclampsia, subcapsular hematoma
![Page 82: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/82.jpg)
Acute Fatty Liver of Pregnancy
Third trimester
Jaundice
Acute liver failure
Microvesicular steatosis
Parental/fetal defect in mitochondrial oxidation of long-chain fatty acids that accumulate and cause liver toxicity
20-40% coexistent preeclampsia
![Page 83: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/83.jpg)
Acute fatty liver, microvesicular steatosis
![Page 84: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/84.jpg)
Intrahepatic Cholestasis of Pregnancy
Conjugated hyperbilirubinemia, < 5 mg/dl Pruritus and jaundice Third trimester More common in multiple pregnancies,
Scandinavia, Chile Resolve rapidly after delivery, may recur Increased incidence of fetal distress,
stillbirths, prematurity Pathogenesis not entirely clear:
– Estrogen/progesterone inhibit bile secretion– Mutation in genes encoding biliary transport
proteins
![Page 85: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/85.jpg)
Intrahepatic cholestasis of pregnancy
![Page 86: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/86.jpg)
The liver III11. Inborn errors of metabolism
12. Intrahepatic biliary tract diseases
13. Circulatory disorders
14. Liver disease in pregnancy
15. Nodular hyperplasias
– Focal nodular hyperplasia
– Nodular regenerative hyperplasia16. Benign neoplasms
17. Malignant neoplasms
![Page 87: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/87.jpg)
Focal nodular hyperplasiaHyperplastic nodule with central stellate scar
![Page 88: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/88.jpg)
Focal nodular hyperplasiaFibrous scar with misshaped vessels and bile ducts, hyperplastic lobular parenchyma
Robbins, Cotran
![Page 89: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/89.jpg)
Focal nodular hyperplasia
Hyperplastic response to focal increased blood flood (vascular malformations)
More common in females
Questionable association with oral contraceptives
![Page 90: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/90.jpg)
Nodular regenerative hyperplasiaRegenerative nodules, absence of fibrosis
![Page 91: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/91.jpg)
Nodular regenerative hyperplasia, reticulumNodules surrounded by rims of compressed cords
![Page 92: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/92.jpg)
Nodular regenerative hyperplasia
May be subclinical, no liver dysfunction
Presents with portal hypertension
Uncertain etiology
Associated with : toxic/drug vascular injury, autoimmune, infectious, hematologic/thrombotic conditions.
Obstructive vasculopathy with global decrease of the (low-pressure) venous portal blood supply and compensatory increase of the (high pressure) arterial blood supply
![Page 93: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/93.jpg)
The liver III11. Inborn errors of metabolism
12. Intrahepatic biliary tract diseases
13. Circulatory disorders
14. Liver disease in pregnancy
15. Nodular hyperplasias
16. Benign neoplasms
– Hemangiomas
– Adenomas17. Malignant neoplasms
![Page 94: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/94.jpg)
Cavernous hemangiomas
The most common liver neoplasm
Red-blue soft nodules
Usually less than 2 cm
Often directly beneath the capsule
Significance:
– Mistaken for metastatic tumors
– Percutaneous biopsies may cause profuse bleeding
![Page 95: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/95.jpg)
Cavernous hemangiomas
![Page 96: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/96.jpg)
Hepatic adenoma Well-demarcated proliferation of hepatocytes
– No bile ducts
Often subcapsular
Young women
Related to the use of oral contraceptives and anabolic steroids
May regress on discontinuance
Significance:– Mistaken for hepatocellular carcinoma
– Rupture, bleeding
– May undergo malignant transformation
![Page 97: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/97.jpg)
Hepatic adenoma
![Page 98: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/98.jpg)
Adenoma subtypes
HNF1α mutation, fatty, almost no malignant transformation
β-catenin mutation, cytologic atypia, highest-risk for malignant transformation
Inflammatory, associated with non-alcoholic fatty liver disease, small risk of malignant transformation
![Page 99: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/99.jpg)
The liver III11. Inborn errors of metabolism
12. Intrahepatic biliary tract diseases
13. Circulatory disorders
14. Liver disease in pregnancy
15. Nodular hyperplasias
16. Benign neoplasms
17. Malignant neoplasms
– Hepatoblastoma
– Angiosarcoma
– Hepatocellular carcinoma
– Cholangiocarcinoma
– Metastases
![Page 100: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/100.jpg)
Hepatoblastoma
Infants
More common in boys
Immature hepatocytes
Some have mesenchymal elements (cartilage, bone, striated muscle)
Survival has improved
Only chance for cure: total resection
![Page 101: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/101.jpg)
Hepatoblastoma, fetal-like or embryonic-like hepatocytes
Odze & Goldblum Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas
![Page 102: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/102.jpg)
Hepatoblastoma, bone (osteoid) and undifferentiated mesenchyme
Odze & Goldblum Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas
![Page 103: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/103.jpg)
Angiosarcoma
Exposure to
– Poly-vinyl chloride (PVC) industry
– Arsenic
– Thorotrast
The latency period several decades
Highly aggressive, metastasize widely
![Page 104: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/104.jpg)
Angiosarcoma
![Page 105: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/105.jpg)
Liver carcinomas, mayor types
Hepatocellular carcinoma (hepatoma)
– 90% of all primary cancers
Cholangiocarcinoma
Mixed forms
![Page 106: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/106.jpg)
Liver and intrahepatic bile duct cancer incidence rates
![Page 107: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/107.jpg)
Hepatocellular carcinoma
Uncommon in the US
Cirrhosis present in > 85%
Male predominance 3:1
Rare before age 60
![Page 108: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/108.jpg)
Hepatocellular carcinoma
HBV endemic regions
20-40% of all cancers
Vertical transmission (200-fold risk)
Cirrhosis may not be present
Male predominance 8:1
Younger age (20-40 years)
![Page 109: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/109.jpg)
Risk factors
Cirrhosis
HBV
HCV
Alcohol, NASH
Primary hemochromatosis, A1AT deficiency, Wilson disease
Hereditary tyrosinemia (40%)
Aflatoxins– Food spoilage molds (Aspergillus flavus)
– Activated in hepatocytes
![Page 110: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/110.jpg)
Hepatocellular carcinoma
Background cirrhosis and chronic hepatitis
May be preceded by hepatocellular dysplasia
Unifocal, multifocal or diffusely infiltrative
Strong propensity for vascular invasion
– Extensive intrahepatic metastases
– Extension to portal vein, inferior vena cava
– Hematogenous metastases to other organs tend to occur late
Poor prognosis
Elevated alpha-fetoprotein, 60-75%
![Page 111: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/111.jpg)
Hepatocellular carcinoma
![Page 112: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/112.jpg)
Hepatocellular carcinoma
![Page 113: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/113.jpg)
Fibrolamellar carcinoma
Young adults (20 to 40 years of age)
Equal male and female incidence
No association with underlying liver disease or cirrhosis
No elevation of alpha-fetoprotein
Better prognosis, 76% alive at 5 years
![Page 114: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/114.jpg)
Fibrolamellar carcinoma, fibrous bands, tumoral
cells with abundant eosinophilic cytoplasm
![Page 115: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/115.jpg)
Cholangiocarcinomas
Resemble adenocarcinomas arising in the pancreas
Characteristically desmoplastic (fibrous)
Not commonly associated with cirrhosis
Preceded by biliary intraepithelial neoplasia
Usually detected late
Death within 6 months
![Page 116: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/116.jpg)
Cholangiocarcinoma
![Page 117: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/117.jpg)
Cholangiocarcinoma
![Page 118: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/118.jpg)
Cholangiocarcinoma
![Page 119: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/119.jpg)
Cholangiocarcinoma, risk factors
Primary sclerosing cholangitis
Congenital hepatic fibrosis
Caroli disease
Choledochal cysts
Hepatolithiasis, liver flukes
Thorotrast
HCV
![Page 120: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/120.jpg)
Metastatic tumors Far more common than primary neoplasia Most common:
– Breast– Lung– Colon– Pancreas
Multiple implants– Cannon balls with central necrosis
Striking hepatomegaly Nodularity palpable on the free edge Extensive involvement may be silent
![Page 121: Digestive Pathology Lecture 6 · Circulatory disorders 11. Hepatic disease in pregnancy 12. Nodular hyperplasias 13. Benign neoplasms 14. Malignant neoplasms. Congenital Abnormalities](https://reader035.vdocuments.us/reader035/viewer/2022081405/5f0949397e708231d4261914/html5/thumbnails/121.jpg)
Metastatic tumors