1. Nodules & Tumors Nodular Hyperplasia non-cirrhotic liver nodules
types:
Focal nodular hyperplasia
spontaneous mass lesion; female preponderance
Morphology:
central stellate scar with large arterial vessels exhibiting fibromuscular hyperplasia  (+) narrowed lumen
Intense lymphocytic infiltration
bile duct proliferation

2. Focal Nodular Hyperplasia: Subcapsular solid mass with central scar, composed  of the normal components of liver lobule

3. Central portion of nodular hyperplasia showing the interphase between the fibrous scar and the hepatocytic nodules.

4. Nodules & Tumors Nodular Hyperplasia Nodular regenerative hyperplasia
(+) development of portal HPN
Associated with conditions affecting intrahepatic blood flow  renal transplant, BM transplant, vasculitic conditions
Morphology: plump hepatocytes surrounded by atrophic cells; no fibrosis

5. Nodular Regenerative Hyperplasia: non-cirrhotic non-neoplastic nodular transformation of the liver parenchyma.

6. Nodules & Tumors
Benign Neoplasms
Cavernous hemangioma
Most common; blood vessel tumor
Soft nodules < 2 cm diameter immediately beneath the capsule
Clinical significance: mistaken for metastatic tumors  blind percutaneous biopsies not done

7. Cavernous Hemangioma
Hemangioma
Normal liver

8. Nodules & Tumors Benign Neoplasms Liver cell adenomas
Cell of origin: hepatocytes
Young women on oral contraceptives  regress on discontinuance of use
Clinical significance:
Present as intrahepatic mass  mistaken for HCC
If subcapsular  (+) rupture  intraperitoneal hemorrhage
May harbor HCC – rare
Morphology: cords of hepatocytes with clear cytoplasm (w/ glycogen), absent portal tracts & prominent arterial vessels and draining veins

9. At the upper right is a well-circumscribed neoplasm that is arising in liver. This is an hepatic adenoma.
The hepatic adenoma is composed of cells that closely resemble normal hepatocytes with disorganized hepatocyte cords and does not contain a normal lobular architecture.
Adenoma
Normal liver

10. Nodules & Tumors
Malignant Tumors
Primary tumors uncommon  often involved in metastatic spread
Hepatoblastoma
rare; most common liver tumor of young children
fatal if not resected
(+) activation of Wnt/β-catenin signaling pathway  stabilize mutations of β-catenin

11. Hepatoblastoma
Hepatoblastoma found to be invading the inferior vena cava at the time of surgical exploration.

13. Nodules & Tumors
Malignant Tumors
Angiosarcoma
rare; malignant endothelial neoplasm
associated with exposure to vinyl chloride, arsenic or Thorotrast
highly aggressive, metastatic, fatal

14. Angiosarcoma: Section of liver, showing multiple hemorrhagic tumor deposits.

15. Nodules & Tumors Cholangiocarcinoma
malignancy of intrahepatic biliary tract
risk factors:
Primary sclerosing cholangitis
Congenital fibropolycystic diseases of biliary system
Previous exposure to Thorotrast
Chronic liver fluke infection (O. sinensis)
Morphology: resemble sclerosing adenocarcinoma  well-defined glandular & tubular structures separated by dense collagenous stroma

16. Intrahepatic cholangiocarcinomas are classified as either peripheral or hilar. The hilar variety are located in the hepatic hilum region and appear as discrete masses.

17. Peripheral cholangiocarcinoma is the most common and develops in the interlobular ducts of the liver, where the interlobular bile duct branches within the portal triads. They may be a single or multiple masses.

18. Nodules & Tumors Hepatocellular Carcinoma
male preponderance; 20 – 40 y/o
Risk factors:
Viral infection – chronic HBV & HCV infection  no cirrhosis
Chronic alcoholism – (+) cirrhosis
Food contaminants – aflatoxin from Aspergillus flavus  bind covalently with cellular DNA  (+) p53 mutation
>85% occur in countries with high rates of chronic HBV and HCV infections

19. Hepatocellular Carcinoma
Morphology:
Gross
Unifocal large mass
Multifocal
Diffusely infiltrative

20. Hepatocellular Carcinoma
Morphology:
Microscopic:
Well differentiated  trabecular pattern or acinar, pseudoglandular pattern
Poorly differentiated  pleiomorphic with anaplastic giant cells
bile

21. upper abdominal pain or fullness malaise, fatigue, weight loss
Hepatocellular Carcinoma
Clinical features:
upper abdominal pain or fullness
malaise, fatigue, weight loss
hepatomegaly with irregularity or nodularity
Laboratory:
increased tumor markers – serum AFP and serum CEA  not conclusive  false (+) in non-neoplastic conditions (e.g. cirrhosis, chronic hepatitis, massive liver necrosis, fetal neural defects such as anencephaly)

22. Take a home message
In the setting of a cirrhotic patient with a hepatic mass lesion larger than 2 cm in diameter and suggestive features of hepatocellular carcinoma, an AFP level higher than 200 ng/mL is considered diagnostic for hepatocellular carcinoma.
Hepatocellular carcinoma can be diagnosed with confidence in patients with a serum AFP level higher than 200 ng/mL and a mass in the liver.