Liver Flashcards
Acute viral hepatitis: Changes in hepatocytes (3).
Swollen hepatocytes with rarified and granular cytoplasm.
Apoptotic bodies.
Replacement of lost hepatocytes by small clusters of lymphocytes and macrophages.
Acute hepatitis B: Classic histologic finding.
“Ground glass” hepatocytes.
Chronic viral hepatitis: Definition.
Persistent liver injury with positive viral serology and high serum aminotransferases for more than 6 months.
Chronic viral hepatitis: Location of inflammation.
Portal and periportal regions.
Characteristic features of ___.
A. Chronic hepatitis B.
B. Chronic hepatitis C (3).
A. Ground-glass hepatocytes.
B. Lymphoid aggregates, mild macrovesicular steatosis, damaged interlobular bile ducts.
Epstein-Barr viral hepatitis: Histology (2).
Single-file arrangement in lymphocytes and plasma cells in sinusoids.
Marked regeneration of hepatocytes.
Bacterial abscesses of the liver: Agents (3).
Staphylococcus aureus.
Salmonella typhi.
Treponema pallidum.
Syphilis of the liver: Gross lesions (2).
Gummata.
Hepar lobatum.
Syphilis of the liver: Histopathology.
Gummata are granulomatous abscesses that heal as dense scars.
Echinococcal infection of the liver: Local complication.
Secondary cholangitis.
Malaria of the liver: Histopathology (2).
Hyperplasia of Küpffer cells.
Phagocytosis of ruptured erythrocytes.
Hepatic leishmaniasis: Histopathology (2).
Hyperplasia of Küpffer cells.
Phagocytosis of organisms (Donovan bodies).
Hepatic leishmaniasis: Best special stain.
Giemsa.
Acetaminophen toxicity: Histopathology.
Hepatocellular necrosis in zone 3.
Drugs that cause a pattern mimicking acute viral hepatitis (3).
Antituberculosis drugs.
Anesthetics.
Aspirin (NSAIDs).
Drug that causes cholestasis with loss of bile ducts.
Augmentin (amoxicillin + clavulanic acid).
Drugs that cause the pattern of “vanishing bile ducts” (4).
Chlorpromazine.
Haloperidol.
Amoxicillin.
Flucloxacllin.
Drugs that cause microvesicular steatosis (4).
Valproic acid.
Tetracycline.
Nucleoside analogs.
Aspirin (Reye’s syndrome).
Drugs that cause veno-occlusive disease (2).
Pyrrholizidine alkaloids.
Chemotherapeutic agents.
Drugs that cause a steatohepatitis-like pattern (2).
Amiodarone.
Tamoxifen.
Hypervitaminosis A: Histopathology (2).
Hypertrophy of stellate cells.
Pericellular and perivenular fibrosis.
Histopathologic clues that drugs may be responsible for liver disease (3).
Many eosinophils.
Epithelioid granulomas.
Hepatitis together with cholestasis.
Alcoholic hepatitis: Location of histologic changes.
Zone 3.
Alcoholic hepatitis: Main histologic changes (5).
Steatosis.
Ballooning degeneration.
Lobular inflammatory infiltrates containing neutrophils.
Mallory bodies.
Peri cellular and perivenular (“chicken-wire”) fibrosis.
Alcoholic hepatitis vs. viral hepatitis: Location of inflammation.
Alcoholic: Mostly lobular.
Chronic viral: Mostly portal and periportal.
Ascariasis of the liver: Gross appearance.
Numerous foul-smelling cavities.
Alcoholic hepatitis vs. non-alcoholic steatohepatitis (2).
NASH:
− More glycogen aged nuclei.
− No sclerosing hyaline necrosis.
Non-alcoholic steatohepatitis: Risk factors (4).
Central obesity.
Insulin resistance / diabetes mellitus, type II.
Arterial hypertension.
Hypertriglyceridemia.
Mallory body: Composition.
Cytoskeletal intermediate filaments associated with ubiquitin.
Mallory body: Immunohistochemical stains (2).
p62.
Ubiquitin.
Indian childhood cirrhosis: Histopathology (3).
Mallory bodies.
No steatosis.
Marked overload of copper.
Acute fatty liver of pregnancy: Timing (2).
Onset: Third trimester.
Resolution: Upon delivery.
Acute fatty liver of pregnancy: Clinical presentation (4).
Bleeding.
Vomiting.
Jaundice.
Coma (occasionally).
Acute fatty liver of pregnancy: Histopathology (3).
Microvesicular steatosis.
Cholestasis may be seen.
Possibly much inflammation in the portal tracts.
Acute fatty liver of pregnancy: Pathogenesis.
Defective oxidation of fatty acids in the mitochondria.
Acquired hemochromatosis: Causes (3).
Blood transfusions.
Porphyria cutanea tarda.
Bantu hemosiderosis.
Hereditary hemochromatosis:
− Inheritance.
− Classic clinical triad.
− Autosomal recessive.
− Cirrhosis, skin pigmentation, diabetes mellitus.
Hereditary hemochromatosis: Lethal complication.
Hepatocellular carcinoma.
Hereditary hemochromatosis, early: Histopathology.
Hemosiderin granules in periportal hepatocytes.
Hereditary hemochromatosis, intermediate: Histopathology (3).
Hemosiderin granules in lobular hepatocytes, bile-duct epithelium, Kupffer cells.
Portal inflammation.
Portal and bridging fibrosis.
Hereditary hemochromatosis, late: Histopathology.
Fibrous septa progressing to cirrhosis.
Hepatic iron index: Calculation.
Micromoles of Fe per gram of dry liver ÷ patient’s age.
Hepatic iron index: Values.
Normal: Less than 1.
Homozygotes: Greater than 2.
Heterozygotes: Less than 2.
Hemochromatosis: Pathogenesis in liver.
Iron is directly hepatotoxic.
Ballooned hepatocytes: Immunohistochemistry.
Loss of cytokeratin 8/18.
Steps of metabolism of copper (4).
Absorbed in stomach and duodenum.
Bound to albumin and carried to hepatocytes.
Bound to α₂-globulin to form ceruloplasmin.
Re-secreted into the plasma.
Steps of excretion of copper (3).
Senescent ceruloplasmin is taken up by the hepatocytes, degraded in the lysosomes, and excreted in the bile.
Defective gene in Wilson’s disease:
− Name and location.
− Product.
ATP7B on chromosome 13.
Canalicular transmembrane copper-transporting ATPase.
Wilson’s disease: Laboratory findings (3).
Decreased serum ceruloplasmin.
Increased urinary copper.
Increased hepatic copper.
Wilson’s disease: Ocular finding.
Kayser-Fleischer ring due to deposition of copper in Descemet’s membrane.
Wilson’s disease: Inflammatory changes (2).
Acute hepatitis.
Chronic hepatitis progressing to cirrhosis.
Wilson’s disease: Changes in the hepatocytes (4).
Fatty change.
Focal necrosis.
Glycogenated nuclei.
Mallory bodies.
Wilson’s disease: Special stains (2).
Rhodanine: Copper.
Orcein: Copper-associated protein.
Wilson’s disease: Diagnostic concentration of hepatic copper.
More than 250 μg per gram of dry liver.
Wilson’s disease: Treatment.
D-penicillamine.
Defective gene in α₁-antitrypsin deficiency: Location and function.
Chromosome 14; inhibits neutrophil elastase in the lungs.
α₁-Antitrypsin deficiency: Pathogenesis of liver disease.
Abnormally folded protein gets trapped in the endoplasmic reticulum.
α₁-Antitrypsin deficiency: Variant presentation.
Liver disease without pulmonary emphysema.
α₁-Antitrypsin deficiency: Presentation in neonates.
Hepatitis with cholestatic jaundice.
Eosinophilic globules of α₁-antitrypsin deficiency:
− Location.
− Staining.
Mainly in periportal hepatocytes.
PAS positive, diastase resistant.
α₁-Antitrypsin: Most significant alleles (3).
M: Normal.
Z: Clinically most significant.
S: Reduced concentration of α₁-antitrypsin but no disease.
α₁-Antitrypsin deficiency: Mutation in Z allele.
Glu to Lys.
Autoimmune hepatitis: Antibodies (4).
ANA.
ASMA.
Anti-soluble liver antigen.
Anti-LKM1.
Autoimmune hepatitis: Suggestive histologic findings (2).
Inflammatory infiltrate rich in plasma cells.
Hepatitic rosettes.
Autoimmune hepatitis: Location of inflammatory infiltrate.
Portal, periportal, lobular.
Autoimmune hepatitis: Other histologic findings (3).
Interface hepatitis.
Lobular apoptotic bodies.
Syncytial giant hepatocytes.
Primary biliary cirrhosis: Laboratory findings (3).
Antimitochondrial antibody (directed against subunit E2 of pyruvate dehydrogenase).
Elevated alkaline phosphatase.
Hyperbilirubinemia.
Primary biliary cirrhosis: Stages (4).
I. Florid duct lesion.
II. Ductular reaction.
III. Scarring.
IV. Cirrhosis.
Florid duct lesion of primary biliary cirrhosis: Inflammatory cells.
Granulomas.
Lymphocytes, macrophages, plasma cells, eosinophils.
Ductular reaction of primary biliary cirrhosis: Histologic findings (4).
Small bile ducts: Loss.
Medium-sized bile ducts: Scarring.
Bile ductules in portal tracts: Proliferation.
Periportal inflammation and interface hepatitis.
Scarring stage of primary biliary cirrhosis: Histologic findings (2).
Small and medium-sized bile ducts are replaced by lymphoid aggregates that may contain PAS-positive remnants of basement membrane.
Otherwise little inflammation.
Primary biliary cirrhosis: Treatment.
Liver transplantation.
Primary sclerosing cholangitis: Radiologic finding.
ERCP: Beaded appearance of intrahepatic bile ducts.
Primary sclerosing cholangitis: Association with ulcerative colitis (2).
Present in 70% of patients with PSC.
Only 4% of patients with UC have PSC.
Primary sclerosing cholangitis: Association with carcinoma.
Cholangiocarcinoma occurs in 10% of patients with PSC.
Primary sclerosing cholangitis: Stages.
I: Portal.
II: Periportal.
III: Septal.
IV: Cirrhotic.
Portal stage of primary sclerosing cholangitis: Histologic features (2).
Concentric periductal fibrosis.
Lymphocytic inflammation of portal tracts.
Periportal stage of primary sclerosing cholangitis: Histologic features (3).
Extension of periportal parenchyma.
Interface hepatitis.
Bile-ductular reaction.
Septal stage of primary sclerosing cholangitis: Histologic features (2).
Obliteration of bile ducts.
Bridging fibrosis.
Primary sclerosing cholangitis: Another frequent histologic feature.
Pseudoxanthomatous change due to chronic cholestasis.
Primary sclerosing cholangitis: Histologic mimic.
Secondary sclerosing cholangitis due to obstruction of extrahepatic bile ducts or of large bile ducts.
Primary sclerosing cholangitis: Treatment.
Liver transplantation.
Acute (cellular) rejection of liver transplant: Characteristic histologic triad.
Portal inflammation.
Bile-duct damage.
Endotheliitis.
Acute (cellular) rejection of liver transplant: Composition of inflammatory infiltrates (5).
Lymphocytes, plasmacytoid cells, macrophages, neutrophils, eosinophils.
Chronic (ductopenic) rejection of liver transplant: Histopathology (3).
Loss of interlobular bile ducts.
Aggregates of foam cells in the intima of arteries.
Centrilobular necrosis.
Chronic (ductopenic) rejection of liver transplant: Definitive diagnosis.
At least 50% of at least 20 portal tracts show loss of bile ducts.
Cirrhosis: Histopathology in biliary-type diseases.
Irregular nodules (“jigsaw” pattern).
High-grade dysplastic nodule: Histopathology (2).
Hepatocytes form plates more than two cells thick or pseudoglandular structures.
Cytologic atypia in hepatocytes.
Congenital hepatic fibrosis: Histopathology (2).
Bands of collagen divide liver tissue into geographic areas.
Usually no inflammation or hepatocellular regeneration.
Nodular regenerative hyperplasia: Histopathology.
Diffuse disease consisting of hyperplastic parenchymal nodules without significant fibrosis.
Nodular regenerative hyperplasia: Associations (4).
Myeloproliferative disorders.
Autoimmune diseases.
Chronic venous congestion.
Drugs.
Focal nodular hyperplasia:
− Radiological finding.
− Laboratory finding.
Hypervascularity on arteriography.
Normal tests of liver function.
Focal nodular hyperplasia: Association with oral contraceptives.
No apparent association.
Focal nodular hyperplasia: Classic gross and histologic finding.
Central stellate scar.
Focal nodular hyperplasia: Other histologic features (2).
Presence of all components of the normal liver lobule.
Chronic cholestatic (pseudoxanthomatous) change in hepatocytes next to the fibrous septa.
Focal nodular hyperplasia: What is found in the fibrous septa (3)?
Thick-walled blood vessels, many bile ductules, inflammatory cells.
Focal nodular hyperplasia: Immunohistochemistry.
Glutamine synthetase:
− Stains clusters of hepatocytes in a geographic pattern.
− Shows perivenular staining in the adjacent liver tissue.
Hepatic adenoma: Risk factors (3).
Oral contraceptives.
Obesity.
Ethanol.
Hepatic adenoma: Complications (2).
Rupture.
Progression to hepatocellular carcinoma.
Hepatic adenoma: Definition of adenomatosis.
More than 10 adenomas.
Hepatic adenoma: Possible changes within hepatocytes (3).
Glycogen-rich cytoplasm.
Fatty change.
Intracellular bile.
Hepatic adenoma: Architectural features (3).
No portal tracts.
Arteries without their veins.
No thickened hepatocellular plates; no pseudoglandular structures.
Immunohistochemistry of hepatic adenoma: Stains common to all types (4).
HepPar-1, arginase-1, glypican-3.
Glutamine synthetase in perivenular pattern.
Immunohistochemistry of hepatic adenoma: Stains used in classifying (4).
LFABP (liver fatty-acid-binding protein).
Glutamine synthetase.
β-Catenin.
SAA/CRP.
Immunohistochemistry of hepatic adenoma: HNF-1α-mutated type.
Negative for all stains (absence of staining for LFABP is abnormal).
Immunohistochemistry of hepatic adenoma: β-Catenin-activated type.
Staining for all except SAA/CRP.
Immunohistochemistry of hepatic adenoma: Inflammatory type.
Staining for LFABP and for SAA/CRP.
Immunohistochemistry of hepatic adenoma: Unclassified type.
Staining for LFABP only.
Hepatic adenoma: Association with cirrhosis (2).
Absent by definition.
An adenoma-like lesion in the setting of cirrhosis is called low-grade dysplasia (macroregenerative nodule).
Hepatocellular carcinoma: In how many is serum AFP elevated?
In about 60-80%.
Hepatocellular carcinoma: Diagnostic level of serum AFP.
More than 100 times normal (in the absence of a germ-cell tumor).
Hepatocellular carcinoma: Associated protein of hepatitis B virus.
The product of the gene Hbx.
Hepatocellular carcinoma: Most strongly associated type of hepatic adenoma.
The β-catenin-activated type.
Hepatocellular carcinoma: Appearance of trabecular pattern.
Hepatocytic cords are more than 3 cells thick and are lined y flat endothelial cells but lack Kupffer cells.
Hepatocellular carcinoma: Appearance of the acinar pattern.
Degeneration of solid trabecula results in pseudoglandular spaces filled with colloid-like matter or bile.
Hepatocellular carcinoma: Least common pattern.
The solid pattern.
Hepatocellular carcinoma: Possible nuclear features (4).
Vesicular nuclei.
Eosinophilic inclusions.
Bizarre shape.
Prominent nucleoli.
Hepatocellular carcinoma, fibrolamellar variant: Appearance of hepatocytes (3).
Abundant oncocytic-appearing cytoplasm.
Cytoplasmic pale bodies.
Prominent nucleoli.
Hepatocellular carcinoma, fibrolamellar variant: Immunohistochemistry.
Malignant cells are positive for CD68.
Hepatocellular carcinoma, fibrolamellar variant: Association with cirrhosis.
The tumor occurs in the absence of cirrhosis and other liver disease.
Hepatocellular carcinoma: Utility of stain for AFP.
Highly specific but positive in less than 25% of cases.
HepPar-1:
A. Biological function.
B. Cells that stain positively.
A. Mitochondrial enzyme of the urea cycle.
B. Hepatocytes, metaplastic and neoplastic intestinal.
Patterns of staining for markers of HCC:
A. TTF-1.
B. CK8/18.
C. Glutamine synthetase.
A. Cytoplasmic.
B. Sub-plasmalemmal.
C. Diffuse.
Immunohistochemical stains for HCC:
A. CK19.
B. EMA.
C. CD34.
A. Positivity predicts poor outcome.
B. Usually negative.
C. May stain sinusoids (abnormal).
Immunohistochemical staining of hepatocellular carcinoma for CEA:
A. Patterns.
B. Markers that give a similar pattern (4).
A. Polyclonal CEA highlights canaliculi; monoclonal CEA is negative.
B. CD10, multidrug-resistant p-glycoprotein, and (occasionally) villin mark the canaliculi.
Other immunohistochemical markers for HCC (3).
Arginase.
Glypican-3.
CK7.
High-grade dysplasia in cirrhosis: Histologic distinction from HCC (2).
High-grade dysplasia:
− Cords are generally no more than 3 cells thick.
− Portal elements are retained.
High-grade dysplasia in cirrhosis: Immunohistochemistry (2).
Staining for Ki-67 and TGF-α is intermediate between that of cirrhosis and that of HCC.
Cholangiocarcinoma: Positive stains (5).
CEA, mucicarmine, EMA.
CK19, CK8/18.
Hepatoblastoma:
A. How many are associated with a syndrome?
B. Examples of syndromes (2).
A. About one third.
B. Beckwith-Wiedemann syndrome; FAP.
Hepatoblastoma: Possible clinical presentation.
Virilization, infrequently with sexual precocity in boys.
Hepatoblastoma: Laboratory findings (2).
Elevated serum AFP (frequent) or hCG (infrequent).
Hepatoblastoma: Main histologic types.
Epithelial.
Mixed epithelial and mesenchymal.
Hepatoblastoma, epithelial type: Components.
Fetal and embryonal.
Hepatoblastoma, epithelial type: Appearance of fetal component.
Large cells with clear or granular cytoplasm and a single nucleolus.
Extramedullary hematopoiesis sometimes.
Hepatoblastoma, epithelial type: Appearance of embryonal component.
Smaller, elongated cells with hyperchromatic nuclei and scant cytoplasm.
Solid pattern.
Hepatoblastoma, epithelial type: Variants (2).
Anaplastic small-cell variant resembles neuroblastoma.
Macrotrabecular variant resembles HCC.
Hepatoblastoma, epithelial-mesenchymal type: Histology.
Mixture of fetal component, embryonal component, and mesenchymal component consisting of osteoid, cartilage, or undifferentiated spindle cells.
Hepatoblastoma, epithelial-mesenchymal type: Immunohistochemical staining of the osteoid.
Positive for keratin.
Hepatoblastoma: Positive “non-hepatocellular” immunohistochemical markers (4).
Often: NSE, S-100, chromogranin.
Variable: Bcl-2.
Cytogenetic abnormalities in hepatoblastoma:
A. Overall (3).
B. In Beckwith-Wiedemann syndrome.
A. +2q, +20, +X.
B. Loss of heterozygosity at 11p15.
Immunohistochemical distinction of hepatoblastoma from
A. Wilms’ tumor.
B. Neuroblastoma.
A. Wilms’ tumor: Positive for WT-1.
B. Neuroblastoma lacks keratin; neuroendocrine markers are not helpful.
Hepatoblastoma: Clinical predictors of poor outcome (3).
Age less than 1 year.
Large size.
Involvement of vital structures.
Hepatoblastoma: Pathological predictors of poor outcome (2).
Predominance of anaplastic small-cell or macrotrabecular pattern.
Aneuploidy.
Bile-duct hamartoma:
A. Synonym.
B. Embryology.
C. Associations (2).
A. Von Meyenburg’s complex.
B. Malformation of ductal plate.
C. Polycystic disease of liver or of kidney.
Bile-duct hamartoma: Gross pathology.
Scattered small white nodules, mimicking metastatic tumor.
Bile-duct hamartoma: Histopathology.
Variably dilated, sometimes bile-filled ductal structures in a hyalinized stroma.
Mesenchymal hamartoma: Gross pathology.
Usually solitary, unlike bile-duct hamartoma.
Mesenchymal hamartoma: Histopathology (3).
Myxoid stroma.
Islands of hepatocytes.
Bile rarely present within the ducts.
Peribiliary-gland hamartoma: Synonym.
Bile-duct adenoma.
Peribiliary-gland hamartoma: Architectural features (3).
Closely packed tubules with a single epithelial layer.
Fibrous stroma that may be cellular or hyalinized.
No connection with interlobular bile ducts.
Peribiliary-gland hamartoma: Contents (2).
Lumens: No bile.
Lining cells may contain mucin.
Mucinous cystic neoplasm of the liver:
A. Epidemiology.
B. Other locations (2).
A. Found almost exclusively in women.
B. Extrahepatic biliary tree, gallbladder.
Mucinous cystic neoplasm: Gross pathology (2).
Forms lobules of variable size.
No connection with the biliary tree.
Acute viral hepatitis: Type and location of inflammation.
Mainly lymphocytic; zone 3.
Mucinous cystic neoplasm of the liver: Lining cells (2).
Columnar but may become flatter or form papillae.
Intestinal metaplasia with goblet cells may occur.
Mucinous cystic neoplasm of the liver: Stroma.
Ovarian-like.
Mucinous cystic neoplasm of the liver: Grading of dysplasia.
Adenoma: Low-grade dysplasia.
Borderline: Intermediate-grade dysplasia.
Carcinoma in situ: High-grade dysplasia.
Mucinous cystadenocarcinoma of the liver:
A. Origin.
B. Signs of malignancy (3).
A. Most arise from a non-malignant mucinous cystic neoplasm.
B. Nuclear atypia, epithelial stratification, invasion.
Intraductal papillary neoplasm of the bile duct: Gross pathology (2).
Dilated bile ducts containing papillary excrescences.
May spread throughout the biliary tree, even to the gallbladder.
Intraductal papillary neoplasm of the bile duct: Lining cells (3).
May mimic biliary epithelial cells.
May show gastric or intestinal metaplasia.
May produce mucin.
Intraductal papillary neoplasm of the bile duct: Grading of dysplasia.
Same as for mucinous cystic neoplasm.
Cholangiocarcinoma: Types.
Intrahepatic.
Extrahepatic.
Hilar (Klatskin’s) tumor: Generally considered extrahepatic.
Cholangiocarcinoma: Possible precursors lesions (4).
Biliary hyperplasia.
Biliary dysplasia.
Intraductal papillary neoplasm of the bile ducts.
Mucinous cystic neoplasm.
Cholangiocarcinoma: Laboratory findings (2).
Elevated serum CEA.
Normal serum AFP.
Cholangiocarcinoma: Presentation (3).
Intrahepatic: Abdominal pain, weight loss.
Extrahepatic: Jaundice, ascites, large mass.
Hilar: Jaundice, small mass.
Cholangiocarcinoma: Gross pathology (3).
Intrahepatic: Infiltrating gray-white, scirrhous mass.
Extrahepatic: Deep invasion into wall of bile duct.
Hilar: Large, green liver; collapsed gallbladder.
Cholangiocarcinoma: Cytologic clues to malignancy (3).
Heterogeneity of cells within the same gland.
Increased N:C ratio.
Large nucleoli.
Cholangiocarcinoma: Architectural clues to malignancy (2).
Marked desmoplasia.
Spread within sinusoids and along bile ducts and nerves.
Cholangiocarcinoma: Pertinently infrequent histologic features (2).
Necrosis.
Vascular invasion.
Cholangiocarcinoma: Keratin stains.
Positive for CK19 and CK7.
Cholangiocarcinoma: Mutated genes (3).
C-Ras.
β-Catenin: Underexpressed
COX-2: Overexpressed.
Cholangiocarcinoma: Most helpful feature on frozen section.
Perineural invasion.
Cholangiocarcinoma: Diagnostic pitfall.
Confusion with the periluminal sacculi of Beale (small acini normally found within the walls of extrahepatic bile ducts).
Carcinoma of the gallbladder: Geography.
Most common in Latin American countries.
Carcinoma of the gallbladder: Associated cancer syndrome.
Familial adenomatous polyposis / Gardner’s syndrome.
Carcinoma of the gallbladder: Laboratory finding.
Elevated alkaline phosphatase.
Carcinoma of the gallbladder: Growth patterns by gross pathology (2).
Diffuse.
Polypoid or papillary.
Carcinoma of the gallbladder: Pitfall of gross pathology.
Diffuse pattern may be confused with cholecystitis, especially when there is much fibrosis.
Carcinoma of the gallbladder: Pitfall of microscopic pathology.
Mistaking carcinoma in situ in Rokitansky-Aschoff sinuses for invasive carcinoma.
Carcinoma of the gallbladder: Epithelial changes frequently found near invasive carcinoma (4).
Hyperplasia.
Metaplasia: Gastric or intestinal.
Dysplasia.
Carcinoma in situ.
Carcinoma of the gallbladder: Histopathlogic clues to malignancy (2).
Cytologic atypia.
Concentric desmoplasia.
*By contrast, the glands are typically well formed.
Carcinoma of the gallbladder: Spread (2).
Follows nerves.
Spreads to regional lymph nodes.
Carcinoma of the gallbladder: Less common types (5).
High-grade endocrine (small-cell).
Low-grade endocrine.
Squamous.
Adenosquamous.
Sarcomatoid.
Carcinoma of the gallbladder: Keratins.
CK19, CK7,
More likely than cholangiocarcinoma to express CK20.
Carcinoma of the gallbladder: Immunohistochemical pitfall.
May express AFP.
Carcinoma of the gallbladder: Mutation.
Overexpression of TP53.
Carcinoma of the gallbladder: Most important prognostic indicator.
Stage.
Metastasis to the liver: Typical gross pathology (3).
Well-circumscribed.
Hyperemic rim.
Single or multiple.
Metastasis to the liver: Mimics of benign disease (3).
Metastases from the breast, prostate, or stomach can form punctuate lesions that mimic cirrhosis.
Metastasis to the liver: Gross appearance of colonic metastases.
Multiple, large, umbilicated nodules on the surface.
Source of hepatic metastasis suggested by this immunohistochemical profile:
+: CK20, villin (brush border), CDX2 (uniform).
−: CK7.
Lower intestinal tract.
Immunohistochemical profile suggestive of metastasis from the upper gastrointestinal / pancreaticobiliary tract (3,2).
+: CK7, villin (brush border), CK17 or CK19.
v: CK20, CDX2.
Immunohistochemical profile suggestive of metastasis from the lung (4,3).
+: CK7, TTF-1, napsin, surfactant A.
−: CK20, villin, CDX2.
Immunohistochemical profile suggestive of metastasis from urothelium (5,1).
+: CK7, CK20, HMW-CK, p63, GATA-3.
-: CDX2.
Immunohistochemical profile suggestive of metastasis of conventional renal-cell carcinoma (4,2).
+: CD10, EMA, PAX2, PAX8.
-: CK7, CK20.
Immunohistochemical profile suggestive of metastasis from the prostate gland (2,4).
+: PSA, prostatic alkaline phosphatase.
-: CK7, CK20, HMW-CK, p63.
Immunohistochemical profile suggestive of metastasis from the thyroid gland (4,1).
+: TTF-1, thyroglobulin, PAX2, PAX8.
-: Surfactant A.
Immunohistochemical profile suggestive of metastasis from the breast (5).
+: GCDFP-15, mammaglobin, S-100, ER, PR.
Immunohistochemical profile suggestive of metastasis from a salivary ductal carcinoma (3,1).
+: GCDFP-15, S-100, AR.
-: ER.
Immunohistochemical profile suggestive of metastasis from a non-mucinous müllerian tumor (6,1).
+: CK7, p53, CA125, WT-1, PAX8, ER.
-: CEA.
Immunohistochemical profile suggestive of metastasis from a mucinous müllerian tumor (1,3).
Similar to that of an intestinal tumor.
-: CA125, WT-1, PAX8.
Causes of peliosis hepatis:
A. Drugs (4).
B. Pathogen.
A. Anabolic steroids, danazol, oral contraceptives, thiopurines.
B. Bartonella henselae.
Histopathology of peliosis hepatis: Common features (2).
Blood lakes surrounded by hepatocytes but without lining cells.
Disrupted sinusoids.
Histopathology of peliosis hepatis: Bartonella-associated cases.
Myxoid perisinusoidal stroma containing clumps of granular matter.
Peliosis hepatis: Helpful stains (2).
Reticulin: Disrupted sinusoids.
Warthin-Starry: Bartonellids.
Hemangioma: Types (2).
Capillary.
Cavernous.
Hemangioma: Variable histologic finding.
Thrombosis.
Infantile hemangioendothelioma: Epidemiology (2).
Mostly diagnosed in the first year of life.
Mostly in males.
Infantile hemangioendothelioma: Lethal complications (2).
Arteriovenous shunt leading to high-output heart failure.
Rupture.
Infantile hemangioendothelioma: Treatment.
Excision, unless multiple.
Vascular ligation.
Embolization.
Infantile hemangioendothelioma: Distinctive gross feature.
Central scar.
Infantile hemangioendothelioma: Histopathology (2).
Center: Necrosis, calcification, few vessels.
Periphery: Proliferation of capillary-like vessels with plump, focally epithelioid endothelial cells and occasional mitotic figures.
Epithelioid hemangioendothelioma: Epidemiology (3).
Middle age; females.
Epithelioid hemangioendothelioma: Radiography.
Calcifications.
Epithelioid hemangioendothelioma: Treatment.
Liver transplantation often necessary due to multifocality.
Recurrence in 40% of cases.
Epithelioid hemangioendothelioma: Gross pathology.
Central scar.
Epithelioid hemangioendothelioma: Histopathology (3).
Poorly defined vascular channels lined by atypical epithelioid tumor cells.
Sparing of sinusoids.
Myxoid or sclerotic stroma.
Epithelioid hemangioendothelioma: Possibly helpful cytologic feature.
Intracytoplasmic vacuoles.
Intraductal papillary neoplasm of the bile duct: Prognosis.
Frequently complicated by recurrence.
Epithelioid hemangioendothelioma: Immunohistochemistry (3).
+: Vascular markers, (occasionally) LMW-CK.
-: Villin.
Epithelioid hemangioendothelioma: Electron microscopy.
Weibel-Palade bodies.
Synchronous extrahepatic epithelioid hemangioendothelioma:
A. Incidence.
B. Organs (4).
A. Occurs in 30% of cases.
B. Spleen, lymph nodes, lungs, bones.
Angiosarcoma: Epidemiology (2).
Sixth and seventh decades; males.
Angiosarcoma: Chemical risk factors (4).
Thorium dioxide.
Vinyl chloride.
Arsenic.
Anabolic steroids.
Angiosarcoma: Growth patterns (4).
Growth along sinusoids.
Cavernous structures lined by pseudopapillae.
Solid nests.
Individual malignant cells.
Angiosarcoma: Immunohistochemistry (2).
Vascular markers may be relatively weak.
Keratin may be positive in epithelioid variant.
Mesenchymal hamartoma: Epidemiology (2).
First 2 years of life; mostly in males.
Mesenchymal hamartoma: Associations (3).
Polycystic disease.
Congenital hepatic fibrosis.
Bile-duct hamartoma.
Mesenchymal hamartoma: Gross pathology (3).
Solitary, smooth, spherical.
Fluctuant and made up of solid and cystic areas.
Can be very large (>1 kg).
Mesenchymal hamartoma: Appearance on low power.
Resembles fibroadenoma.
Mesenchymal hamartoma: Histopathology (5).
Loose, edematous, myxoid stroma containing
− Fluid-filled cysts.
− Dilated lymphatics and blood vessels.
− Disorganized bile ducts.
− Scattered hepatocellular nodules.
Mesenchymal hamartoma: Possible additional histopathologic finding.
Extramedullary hematopoiesis.
Mesenchymal hamartoma: Putative origin.
Connective tissue of portal tracts.
Angiosarcoma: Mutation.
Point mutations in K-Ras-2 (in cases associated with vinyl chloride).
Embryonal sarcoma: Laboratory finding.
Normal AFP.
Embryonal sarcoma: Epidemiology.
Prepubertal children, especially at ages 5-10.
Embryonal sarcoma: Cytologic feature.
Intracytoplasmic eosinophilic globules that are positive for PAS-D and α₁-antitrypsin.
Embryonal sarcoma: Histopathology (3).
Mesenchymal only, albeit with benign entrapped bile ducts.
Phenotypically diverse malignant cells.
Extensive necrosis.
Embryonal sarcoma: Prognosis.
Poor.
Embryonal sarcoma: Gross pathology (3).
Large, solid and cystic, fibrous pseudocapsule.
