Liver Tumours Flashcards
Focal nodular hyperplasia
- Common, benign, nonneoplastic mass forming lesion of the liver
- Widely accepted to be a hyperplastic and regenerative response of hepatocytes to local vascular abnormalities
- Benign, nonneoplastic hepatocellular mass lesion predominantly affecting women
- Majority are solitary and have a central scar on imaging and gross examination
- Often subcapsular
- Overall excellent prognosis
- No evidence for malignant transformation
Micro:
* Nodules of hepatocytes are formed by fibrous septa, which may coalesce into a central scar that characteristically contains abnormally thick walled vessels, which may demonstrate fibromuscular hyperplasia, myxomatous change or myointimal hyperplasia
* Fibrous septa also contain a bile ductular reaction and an inflammatory cell infiltrate
* Features of cholestasis, including feathery degeneration of hepatocytes and Mallory-Denk bodies, may be present
* Hepatocytes are cytologically bland and are arranged in plates 1 - 2 cells thick
IHC:
* Glutamine synthetase: strong, patchy, map-like pattern is highly specific
* Trichrome: fibrous bands surrounding nodules of hepatocytes
* HepPar1 and arginase1: benign hepatocyte nodules
* Reticulin: retained framework without loss or thickened cell plate
Nodular regenerative hyperplasia
- Nodular regenerative hyperplasia (NRH) is a nonspecific pattern of liver injury that causes formation of liver nodules separated by regions of atrophy in the absence of fibrous septa
- It is a cause of idiopathic noncirrhotic portal hypertension and can mimic cirrhosis both clinically and radiologically
- More prevalent in the elderly population but can be seen in children
- Associated with a variety of vascular diseases, rheumatologic diseases, hematological diseases and use of antineoplastic and immunosuppressive drugs
Micro:
* Vague, ill defined, diffuse parenchymal nodules without fibrous septa between the nodules
* Inflammation is absent
* 2 morphologically distinct populations: hypertrophied hepatocytes centrally with atrophic hepatocytes on the periphery
* Atrophic hepatocytes can show feathery degeneration of the cytoplasm
* Hypertrophic cells can compress terminal hepatic venules that can appear shrunken or even be undetectable
* Hypertrophic cells can show regenerative changes (variation in nuclear size, mitotic figures and frequent binucleation)
IHC:
* Reticulin stain will highlight the nodules and the reticulin network will be compressed in between the nodules
* Trichrome –> compressed central veins
Hepatocellular adenoma
- Benign neoplasm of hepatocellular origin arising in the noncirrhotic liver
6 main subtypes
* HNF1A inactivating mutated hepatocellular adenoma (HA-H, ~30%) –> steatosis
* Beta catenin activating mutated hepatocellular adenoma (HA-B, ~11%)
* Inflammatory hepatocellular adenoma (HA-I, ~33%) –> STAT3, IL6ST, GNAS, FRK, Jak-1 activating
* Beta catenin activated mutated inflammatory hepatocellular adenoma (HA-IB, ~14%) Highest risk of malignant transformation
* Sonic hedgehog (SHH) hepatocellular adenoma (HA-sh, ~10%)
* Hepatocellular adenoma, not otherwise specified (HA-U, < 2%)
Hepatocellular carcinoma
- Most common (> 80%) primary liver malignancy worldwide
- M:F = 3:1
- Elevated AFP
- Stepwise process (low grade dysplastic nodule → high grade dysplastic nodule → early hepatocellular carcinoma → progressed hepatocellular carcinoma) accompanied by accumulation of molecular alterations
Risk Factors:
* Cirrhosis
* HBV
* HCV
* Fatty liver disease, alcohol, obesity, diabetes
* Hemochromatosis
* Anabolic steroids
* Aflotoxins
* Hepatocystic adenoma, alpha1-antitrypsin deficiency, tyrosinemia
* Schistosomiasis
Micro:
Trabecular
* Cords greater that three cells thick
* Lined by flat endothelial cells
* Lacking Kupffer cells
Acinar:
* Central degeneration of otherwise solid trabeculae
* Eventually replaced by pseudoglandular spaces containing colloid-like material or bile
Solid:
* Results from compression artifact or scarring
* Least common of three patterns
- Bile production by tumour cells is pathognomonic
- Neoplastic cells are variable in size, although typically large and polygonal, with central vesicular nuclei and prominent nucleoli
Modified Edmondson-Steiner grading system (4 tiered system)
* Grade I: tumor cells are difficult to differentiate from hyperplastic liver cells
* Grade II: tumor cells resemble mature hepatocytes with slightly larger and more hyperchromatic nuclei; sharp and clear cut cell borders; frequent acini formation
* Grade III: tumor cells are larger and have more hyperchromatic nuclei with less acidophilic cytoplasms; trabecular distortion; numerous tumor giant cells
* Grade IV: tumor cells are intensely hyperchromatic, with scant and less granular cytoplasm; tumor cells appear less cohesive and can appear giant, spindled or short and plump; medullary growth pattern with loss of trabeculation; less acini
IHC:
* Arginase1: cytoplasmic or nuclear; useful in confirming hepatocellular differentiation; highly sensitive and specific, thus more useful than HepPar1 for poorly differentiated hepatocellular carcinoma
* HepPar1: cytoplasmic and granular; overall highly sensitive but 50% of poorly differentiated hepatocellular carcinoma lose expression
* Glypican 3: cytoplasmic; high sensitivity in poorly differentiated and scirrhous hepatocellular carcinoma but low sensitivity in well differentiated hepatocellular carcinoma (nonneoplastic liver is negative)
* AFP: cytoplasmic; highly specific but low sensitivity; frequently negative in well differentiated hepatocellular carcinoma
* Polyclonal CEA, villin and CD10 reveal a canalicular pattern; limited sensitivity in poorly differentiated hepatocellular carcinoma
* Albumin ISH: high sensitivity for primary liver carcinoma, although this can also be positive in other adenocarcinomas not of biliary origin
* Pancytokeratins (MNF116 or OSCAR) and CAM5.2 (CK8 / CK18) are positive
* Reticulin: highlights the thickened hepatocyte plates (> 3 cells thick)
Budd-Chiari syndrome
- Venous outflow obstruction caused by occlusion of hepatic outflow
- Either acute thrombotic occlusion (usually fatal) or subacute / chronic occlusion with hepatomegaly, ascites, abdominal pain
- Hepatic vein thrombosis can occur for a variety of reasons (contraceptives, steroids, myeloproliferative disorders, paroxysmal nocturnal hemoglobinuria, pregnancy, postpartum state, hepatocellular carcinoma with inferior vena cava occlusion), though 30% of cases are idiopathic
- Venous obliteration can lead to bridging fibrosis and eventually cirrhosis
