Tumors of the liver and billiary tract

Teja Koswara, dr., Sp.PA

Dept. Anatomical Pathology
Benign Tumors and Tumor-Like Lesions of the
liver
• Hepatic Adenoma *
• Focal nodular hyperplasia *
• Nodular regenerative hyperplasia
• Haemangioma
• Cystic disease
 Malignant tumors of the liver
• Hepatocellular carcinoma (HCC)
• Cholangiocarcinoma
• Hepatoblastoma
• Metastatic tumors
 Hepatic adenoma
• The increased prevalence of patients with liver cell adenoma
is due to the widespread use of estrogen-based oral
contraceptives

• Some large adenomas have been reported to disappear after

discontinuation of oral contraceptive use

• A few adenomas are encountered in men, and they have

occasionally been reported in association with the use of
anabolic steroids.
 Hepatic adenoma
• Macroscopic : The tumor is encapsulated and paler
than the surrounding parenchyma.

• Microscopic :
– The tumor is circumscribed by a fibrous capsule
– Neoplastic hepatocytes resemble their normal
counterparts, except that they are not arranged in
a lobular architecture.
– Portal tracts and central venules are absent.
Hepatic adenoma
 Hepatic adenoma
• In about one third of patients the tumors bleed into the
peritoneal cavity and require treatment as a surgical
emergency

• About 10% of liver cell adenomas progress to liver cancer.

• Pregnancy often stimulates rapid growth in liver adenomas

with risk of potentially fatal spontaneous rupture.

• Surgical excision is usually done for solitary liver adenomas.

 Focal nodular hyperplasia
• Nodular lesion resembles cirrhosis
• Has no malignant potential
• Generally it does not grow in size, spread or
bleed, and in most people it does not produce
any symptoms.
• More common in young and middle age women
• Varies from 5 to 15 cm in diameter
 Focal nodular hyperplasia
• Macroscopic :
The cut surface exhibits a characteristic central
scar from which fibrous septa radiate.

• Microscopic:
Hepatocytic nodules are circumscribed by fibrous
septa which contain numerous bile ducts and
mononuclear inflammatory cells.
Within the nodules, lobular architecture is absent
 Hepatocellular carcinoma (HCC)
• Hepatocellular carcinoma is the 5th most common malignancy
worldwide & the 3rd cause of cancer related death
• Etiology :
• Hepatitis B
– Increase risk 100 -200 fold
– 90% of HCC are positive for HBs Ag
• Hepatitis C
• Cirrhosis
- 70% of HCC arise on top of cirrhosis
• Toxins (alcohol, aflatoxins)
• Autoimmune hepatitis
 HCC : Pathogenesis
• Most (>80%) cases of HCC associated with HBV infection occur in patients with
cirrhosis,.
– The genome of HBV is integrated into the host DNA of liver cells.
– The X gene of HBV encodes a viral protein (HBxAg) that inactivates tumor suppressor
proteins.

• HCC in patients with hepatitis C occurs almost exclusively in the setting of

cirrhosis

• Aflatoxin can bind covalently with cellular DNA and cause a mutation in p53.

• The cell of origin of HCC has been the subject of considerable debate. It seems
that the tumors may arise from both mature hepatocytes and progenitor cells
(known as oval cells).
 HCC : Pathogenesis
• Cell death, hepatocyte replication, and inflammation, seen in
all forms of chronic hepatitis are believed to be main
contributors to DNA damage.
• Poor regulation of hepatocyte replication can occur by
– Point mutations or overexpression of specific cellular genes (such as
β-catenin),
– Mutations or loss of heterozygosity of tumor suppressor genes (such
as p53),
• Defects in DNA repair, particularly those in repair systems for
double-stranded DNA breaks, perpetuate DNA damage and
may cause chromosome defects.
 HCC : Signs & symptoms
• HCC usually presents as a painful and enlarging mass in the liver.

• The prognosis is dismal, patients can die of malignant cachexia,

rupture of the tumor with bleeding into the peritoneal cavity
• Other nonspecific symptoms :
– Abdominal pain
– Fever
– Anorexia, weight loss
– Jaundice
• Physical findings
– Abdominal mass
– Ascites
 HCC: Diagnosis
• Clinical presentation
• Elevated AFP
• USG
• CT scan
• MRI
• Biopsy
 AFP (Alfa feto protein)
– Tumor marker for HCC
– Values more than 100 ng/ml are highly suggestive
of HCC
– Elevation seen in more than 70% of patients
 HCC: Metastases
• Rest of the liver
• Portal vein
• Lymph nodes
• Lung
• Bone
• Brain
 HCC: labs
• Labs of liver cirrhosis
• AFP (Alfa feto protein)
– Is an HCC tumor marker
– Values more than 100ng/ml are highly suggestive
of HCC
– Elevation seen in more than 70% of patients
 HCC: Diagnosis
• Clinical presentation
• Elevated AFP
• USG
• CT scan
• MRI
• Biopsy
Hepatocellular carcinoma
• Macroscopic :
– Nodular
– Massive
– Diffuse
– Pedunculated

All patterns of HCC have a strong propensity

for invasion of vascular channels.
 Hepatocellular carcinoma

Microscopic :

- Well differentiated to poorly differentiated

- Arranged in cords, trabeculae or glandular patterns
- More than 2-3 cell-thick hepatocellular plates/cords, nuclear atypia,
and absence of portal tracts.
- In poorly diff tumor : Large multinucleate anaplastic tumor giant cells.
 HCC: Liver Transplantation
• Best available treatment
• Removes tumor and liver
• Only if single tumor less than 5cm or less than
3 tumors less than 3 cm each
• Recurrence rate is low
• Not widely available
 HCC: Resection
• Feasible for small tumors with preserved liver
function (no jaundice or portal HTN)
• Recurrence rate is high
 HCC: Local Ablation
• For non resectable tumors
• For patients with advanced liver cirrhosis
• Ablation : Alcohol (ethanol) injection
 HCC: Chemoembolization
• Inject chemotherapy selectively in hepatic
artery
• Then inject an embolic agent
• Only in patients with early cirrhosis
 HCC : Prognosis
• The overall prognosis of HCC is poor
• It is significantly better for individuals who have a single tumor
less than 2 cm in diameter and good liver function.
• The median survival is 7 months, with death from : Profound
cachexia, gastrointestinal or esophageal variceal bleeding, liver
failure with hepatic coma, or rupture of the tumor with fatal
hemorrhage
 Fibro-Lamellar carcinoma

• Variant of HCC that has a distinctive histologic appearance

• Arises in an apparently normal liver,
• Adolescents and young adults (20-40 years old).
• AFP usually not elevated
• The prognosis is considered more favorable than in most
cases of HCC.
• Histopathology :
Well-differentiated polygonal cells growing in nests or cords
and separated by parallel lamellae of dense collagen bundles
Fibrolamellar carcinoma
 Hepatoblastoma
• Usually discovered at birth or before the age of 3 years

• Clinical features :
– Enlargement of the abdomen, vomiting, and failure to thrive.
– Serum Alpha-fetoprotein level is almost invariably elevated,
– Some patients also exhibit congenital anomalies, including:
Cardiac and renal malformations, and macroglossia.
– Untreated hepatoblastomas are fatal but but liver
transplantation or surgical resection by partial hepatectomy
has been curative in many instances
 Hepatoblastoma
• Hepatoblastoma presents as a partially necrotic and hemorrhagic
circumscribed mass up to 25 cm in diameter.

• Microscopic :
– Tumor cells : Epithelial and mesenchymal.
– The epithelial component of hepatoblastoma includes cells resembling
embryonal and fetal cells.
• The embryonal cells are small and fusiform and are arranged in
ribbons or rosettes.
• The fetal cells more closely resemble hepatocytes, contain glycogen
and fat, and are arranged in trabeculae with intervening sinusoids.
– The mesenchymal elements include those often present in teratomas,
including connective tissue, cartilage, and osteoid
Hepatoblastoma
 Intrahepatic cholangiocarcinoma
• Intrahepatic cholangiocarcinoma originates anywhere in the
biliary tree, from the large intrahepatic bile ducts at the porta
hepatis to the smallest bile ductules at the periphery of the
hepatic lobule.

• Occurs predominantly in older persons of both sexes, with an

average age at presentation of 60 years.

• A combined form of HCC and peripheral cholangiocarcinoma has

been labeled “cholangiohepatocellular carcinoma“
 Intrahepatic cholangiocarcinoma
• Tumor cells are arranged in a ductular or glandular configuration

• Cholangiocarcinomas show less tendency to invade the portal

and hepatic veins than do HCCs.

• They metastasize to a wide range of extrahepatic sites and show

a greater predilection for the portal lymph nodes than do HCCs
 Cholangiocarcinoma

Tubular adenocarcinoma, well diff. Papillotubular adenocarcinoma, well diff.

 Metastatic tumors

• The most common site for blood born metastases

• The liver is involved in a third of all metastatic cancers
• Common primaries : colon, breast, lung, stomach,
pancreases, and melanoma
• The liver may show a single nodule or multiple nodules
• Clinical features :
– Weight loss is a common early finding in cases of metastatic
cancer in the liver.
– Portal hypertension with splenomegaly, ascites, jaundice or
hepatic failure .
 Carcinoma of gallbladder
• Most patients are in the 6th or 7th decades of life.
• 1-3% of all GI malignancy
• Gallbladder carcinomas have a strong female predominance
• Risk factor : Gallstones, anomaly of pancreaticobiliary junction
(reflux of pancreatic enzymes to bile duct)
• Histopathology :
– Adenocarcinoma (*)
– Signet ring cell carcinoma
– Adenosquamous carcinoma
– Squamous cell carcinoma
– Undifferentiated carcinoma
• Prognosis : Poor (5 years survival rate < 5%)
 Carcinoma of gall bladder

• The symptoms produced by carcinoma of the

gallbladder are similar to those encountered with
gallstone disease.
• By the time the tumor becomes symptomatic, it is
almost invariably incurable, 5-year survival rate
being less than 3%.
 Benign tumor of gallbladder (rare)
• Adenoma *
• Billiary cystadenoma
• Leiomyoma
• Neurofibroma
Very rare
 Extrahepatic cholangiocarcinoma
• Extrahepatic bile duct.
• Almost always adenocarcinoma
• The tumor is less common than gallbladder cancer.
• Female predominance of gallbladder cancer is not
evident.
• Gallstones are frequently found in those affected
• The prognosis is poor, but because symptoms arise
early in the course of the disease, the outcome is
somewhat better than that of gallbladder carcinoma.