Hepatocellular Carcinoma

Question 1

Aetiology of hepato-cellular carcinoma

Answer 1

~ malignant tumour from hepatocytes
~ multifactorial, multi step Disease
~ males: females of 2.4:1

Aetiology :
1.Major risk factors
~ chronic HBV/HCV - liver cell necrosis- genome of HBV is incorporated into host DNA of liver cells
~ alcoholic cirrhosis
~ aflatoxin B1- aspergillus flavus- contaminates peanuts and grains- bind with cellular DNA of hepatocytes- mutation of TP 53
~ non-alcoholic steato hepatitis
~ metabolic syndrome, obesity, diabetes mellitus

2. Minor risk factors
   ~ hereditary Hemochromatosis
   ~ Wilson’s disease
   ~ alpha-1 antitrypsin deficiency
   ~ glycogen storage disease
   ~ oral contraceptives
   ~ cigarette smoking

Question 2

Pathogenesis of HCC

Answer 2

Genetic alterations
~ Mutation in tumour DNA repair genes - repeated cycles of liver cell death, regeneration and repair
~ activation of oncogene: POINT MUTATIONS of KRAS, over expression of TGF alpha, beta catenin
~ in activation of tumour suppressor gene: integration of HBV genome into host hepatocyte

Epigenetic alterations
~ c-MYC amplification
~ Activation of telomerase

Question 3

Precursor lesions of HCC

Answer 3

1. Hepato-Cellular adenoma
2. Cellular dysplasia in chronic liver disease
   ~ small cell change: High NC ratio, nuclear hyperchromasia, pleomorphism
   ~ large cells change: larger liver cells, multiple, pleomorphic nuclei with normal NC ratio
3. Dysplastic Nodules
   ~ low-grade: do not have cytological or architectural atypia
   ~ high grade: cytological+ architectural changes

Question 4

Morphology of HCC

Answer 4

Gross:
~ enlarged liver, areas of haemorrhage and necrosis
~ light brown, yellow, gray
~ Production of bile: greenish brown discolouration
1. Uni focal: large, circumscribed, single Mass
2. Multifocal: multiple nodules of variable size.
3. Diffusely infiltrative: large part of liver infiltrated by homogenous, indistinct tumour nodules

Micro:
1. Well-Differentiated :
~bile production by tumour cells
~ tumour cells recognisable as hepatocytes
* trabecular pattern: several layers, polygonal, abundant granular cytoplasm, nuclei large hyperchromatic, prominent nucleoli
* Acinar pseudo glandular (adenoid): arranged around the lumen, resemble glands

2. Moderately differentiated:
   * solid variety: small tumour cells
   * Scirrhous variety: narrow bundles/fibrous stroma
   * Clear cell variety: clear glycogen cytoplasm
3. Poorly or undifferentiated:
   ~ Pleomorphic, variation, in size and shape
   ~ bizarre looking, anaplastic giant cells
   ~ Globular hyaline structures: alpha-fetoprotein, alpha-1 antitrypsin
   ~ Mallory’s hyaline seen

Question 5

Spread and clinical features of HCC

Answer 5

Spread:
1. Local: Liver- satellite nodules, intrahepatic metastasis
2. Lymphatic: perihilar, peripancreatic, paraaortic nodes
3. Blood: long snake like tumour masses invade portal vein > invade IVC > lungs

Clinical features :
~ upper abdominal pain, malaise, fatigue, weight loss
~ liver :enlarged, irregular, nodular

Laboratory findings :
~ alpha-fetoprotein : High
~ alpha L fucosidase: raised
~does- alpha carboxy prothrombin: raised

Cause of death :
~Cachexia
~ Esophageal variceal bleeding
~ liver failure, hepatic coma
~ rupture of tumour- fatal haemorrhage

Question 6

Fibrolamellar HCC

Answer 6

~ uncommon variant of HCC
~ young patients without cirrhosis

Gross: single, large, hard, scirrhous, well circumscribed tumour+ central stellate fibrous scar

Micro: large, polygonal cells, deeply eosinophilic cytoplasm, prominent nucleoli
~ Nests/ cords / dense collagen fibres

Good prognosis