Hepatocellular Carcinoma

Risk Factors

Cirrhosis:  80% of HCC

Hepatitis B (Chronic Hepatitis B carriers have a 100-fold relative risk of developing HCC compared with non-carriers)

Hepatitis C (related to development of cirrhosis; arrest of progression of disease to cirrhosis ultimately will prevent HCC development)

Aflatoxin B1 (three-fold increased risk, correlates with mutation on codon 249 of p53 tumour suppressor gene)

Alcohol

Surveillance and Diagnosis

Surveillance is recommended in the setting of:

Established cirrhosis

Chronic Hep B

Liver nodules (<2cm)
Surveillance should consist of ultrasonography and alpha-feto protein every six months. The following schema for management of nodules has been proposed:

<1cm – close follow-up (reliable diagnosis of HCC difficult)

1-2cm – pathological diagnosis required (but not always definitive; esp with FNA, 30-40% false negative rate

>2cm, diagnosis established by the finding of a nodule larger than 2cm with arterial hypervascularization on two imaging techniques, or by one imaging technique associated with an alpha-fetoprotein concentration higher than 400 ug/L.

Natural History and Prognosis

Very Early HCC or “carcinoma in situ”

-    A well-differentiated HCC that contains bile ducts and portal veins, has ill-defined nodular appearance, and has not invaded any structure.

-    5-year survival 89%-93% with resection; 71% with percutaneous treatment

-    Need to be differentiated from high-grade dysplastic nodules; no current consensus agreement on the histological criteria to be applied

Early HCC

-    One tumour <5cm or multiple tumours (2-3) < 3cm

-    5 year survival rates 50-70%

-    Natural history unclear as almost all individuals are treated

Intermediate HCC

-    Asymptomatic, no invasive pattern

-    1,2, & 3 year survival 80%, 65%, and 50% with no treatment

Advanced HCC

-    Symptomatic and/or invasive pattern

-    1,2, & 3 year survival 29%, 16%, and 8% with no treatment

Endstage HCC

-    Terminal cancer-related symptoms or Childs ‘C’ liver disease

-    Less than 6 months life expectancy, no survival benefit to treatment

Macroscopy

-Most HCCs associated with liver cirrhosis present as an expansile tumour with a fibrous capsule and intratumoral septa; those without cirrhosis tend to be massive and non-encapsulated.  May have varying degrees of infiltrative growth, tumour thrombi in portal veins, and intrahepatic metastases.

-Occasionally may be pedunculated – usually female patients with tumours arising in accessory lobes of the liver – these have excellent prognosis with resection.

Histopathology

-Consist of tumour cells that resemble hepatocytes.  Stroma composed of sinusoid-like blood spaces lined by a single layer of endothelial cells, IHC positive for CD34 and factor VIII.
Architectural variants:

Trabecular (plate-like)

Pseudoglandular and acinar

Compact

Scirrhous
Cytological variants:

Pleomorphic cell

Clear cell

Sarcomatous change

Fatty change

Bile production

Mallory hyaline bodies

Globular hyaline bodies

Pale bodies

Ground glass inclusions

Treatment
Curative:

a.    Resection

b.    Transplantation

c.    Percutaneous ablation

Palliative:

d.    Embolization/Chemoembolization (probably the only palliative treatment that’s actually beneficial!)

e.    Arterial/systemic chemotherapy

f.    Internal radiation with 131I lipidiol

g.    Hormonal compounds (tamoxifen)

h.    Immunotherapy
Sources:
WHO, Pathology & Genetics:  Tumours of the Digestive System.
Llovet JM, Burroughs A, Bruix J.  Hepatocellular carcinoma.  The Lancet: 362 (9399):1907-1917.