Orientation notes for study. After this note you should be able to name each liver tumour, link it to its risk factor and tumour marker, say which one you must never biopsy, and choose the right investigation and treatment.
Overview
The commonest tumour in the liver is a metastasis, not a primary. Among primary tumours, benign lesions (haemangioma, focal nodular hyperplasia, adenoma) are usually found by chance, and hepatocellular carcinoma (HCC) is the commonest primary malignancy, almost always on a background of chronic liver disease.
Benign tumours
| Tumour | Who and why | Key features | What matters |
|---|---|---|---|
| Cavernous haemangioma | Any age, women more | Commonest benign liver tumour; vascular channels; incidental on ultrasound or CT | Do not biopsy (risk of haemorrhage); usually needs no treatment |
| Focal nodular hyperplasia (FNH) | Young women | Central stellate scar; hyperplastic response to an arterial malformation; no link to the pill, no malignant potential, no rupture | Reassure; follow-up only |
| Hepatocellular adenoma | Young women on oral contraceptives; anabolic steroids, glycogen storage disease | Benign hepatocytes without portal tracts; can rupture and bleed into the abdomen; rarely turns malignant | Stop the pill (it may regress); resect large (over 5 cm), symptomatic or bleeding lesions |
Adenoma versus FNH: adenoma has a bleeding risk and is linked to the pill; FNH has a central scar and neither.
Primary malignant tumours
Hepatocellular carcinoma (HCC)
- Epidemiology: commonest primary liver cancer; male to female about 3-8 : 1; very common in sub-Saharan Africa and East Asia.
- Risk factors: chronic hepatitis B (about 200-fold risk, and HBV can cause HCC even without cirrhosis), hepatitis C, cirrhosis of any cause, alcohol, aflatoxin B1 (contaminated maize and groundnuts; the p53 codon 249 mutation), NAFLD/NASH, haemochromatosis.
- Pathogenesis: repeated injury and regeneration, viral DNA integration and aflatoxin-induced mutations cause dysplastic nodules, then carcinoma. Vascular invasion (portal vein) is common.
- Presentation: weight loss, right upper quadrant pain or mass, decompensation of known cirrhosis (new ascites, jaundice, encephalopathy), paraneoplastic features (hypoglycaemia, polycythaemia, hypercalcaemia), rupture with haemoperitoneum.
- Diagnosis:
- Alpha-fetoprotein (AFP) raised; above 1000 ng/mL is highly suggestive (it can be normal in some HCCs and raised in other conditions).
- Multiphase CT or MRI: arterial-phase enhancement with venous-phase washout is diagnostic in a cirrhotic liver, so biopsy is often not needed.
- Biopsy when imaging is not typical, with the small risk of seeding.
- Surveillance: ultrasound with or without AFP every 6 months in cirrhosis and in chronic hepatitis B carriers at risk.
- Treatment (by stage, e.g. BCLC): resection or liver transplantation for early disease; ablation (radiofrequency, microwave) for small tumours; TACE (transarterial chemoembolisation) for intermediate disease; systemic therapy (sorafenib, or atezolizumab with bevacizumab) for advanced disease. Prognosis is poor without treatment, often 6 to 12 months, and depends as much on the underlying liver function (Child-Pugh) as on the tumour.
- Fibrolamellar variant: young adults, no cirrhosis, normal AFP, large tumour with a central scar and lamellar fibrosis, better prognosis.
- Prevention: hepatitis B vaccination, treating hepatitis B and C, reducing alcohol, safe storage of grain.
Cholangiocarcinoma
- Origin: bile duct epithelium (intrahepatic, perihilar Klatskin tumour at the confluence of the hepatic ducts, or distal).
- Risk factors: primary sclerosing cholangitis, liver flukes (***Opisthorchis viverrini* and Clonorchis sinensis), choledochal cysts, hepatolithiasis, Thorotrast. Not linked to hepatitis B or C**, which is the key contrast with HCC.
- Features: painless obstructive jaundice, itching, weight loss, a palpable gallbladder (Courvoisier sign when distal); AFP normal, CA 19-9 raised.
- Treatment: surgery when resectable; biliary drainage or stenting and chemotherapy (gemcitabine-based) when not; prognosis poor.
Angiosarcoma
- A rare vascular sarcoma of the liver linked to vinyl chloride (PVC workers), arsenic and Thorotrast. Aggressive, with bleeding.
Hepatoblastoma
- The commonest primary liver tumour of young children (usually under 3 years): raised AFP, linked to Beckwith-Wiedemann syndrome and familial adenomatous polyposis. Responds well to surgery and chemotherapy.
Secondary (metastatic) tumours
- The commonest malignant tumours of the liver overall. The liver receives the portal blood from the gut and is a filter for all blood.
- Common primaries: colorectal (by far the commonest, through the portal vein), then lung and breast; also stomach, pancreas, melanoma, neuroendocrine tumours.
- Features: multiple nodules, hepatomegaly, raised ALP and GGT with near-normal bilirubin; weight loss; the liver is knobbly. AFP is normal. Treatment depends on the primary; a solitary colorectal metastasis may be resected.
Comparing HCC and cholangiocarcinoma
| Feature | HCC | Cholangiocarcinoma |
|---|---|---|
| Hepatitis B or C | Yes | No |
| AFP | Raised | Normal |
| Other marker | AFP | CA 19-9 |
| Background | Cirrhosis, aflatoxin | PSC, liver flukes |
| Pattern | Hypervascular, invades the portal vein | Hypovascular, scirrhous, bile duct obstruction |
| Imaging | Arterial enhancement then washout | Delayed enhancement |
Differential diagnosis of a liver mass
| Finding | Think of |
|---|---|
| Incidental bright lesion on ultrasound, healthy liver | Haemangioma (do not biopsy) |
| Young woman on the pill, abdominal pain or collapse | Adenoma with bleeding |
| Cirrhosis plus a new mass and raised AFP | HCC |
| Multiple lesions with a known primary | Metastases |
| Fever, tender liver, travel or poor sanitation | Pyogenic or amoebic abscess |
| Jaundice with a hilar mass and normal AFP | Cholangiocarcinoma |
High-yield exam points
- Haemangioma: never biopsy (bleeding).
- FNH: central stellate scar, no pill link, no rupture. Adenoma: pill link, rupture risk.
- HBV carries about a 200-fold risk of HCC and can cause it without cirrhosis. Aflatoxin B1 and the p53 mutation are the other classic exam link.
- AFP above 1000 ng/mL points to HCC; arterial enhancement and washout make the diagnosis without biopsy in cirrhosis.
- Cholangiocarcinoma is not linked to hepatitis B or C; AFP normal; PSC and liver flukes.
- Angiosarcoma: vinyl chloride, arsenic, Thorotrast. Hepatoblastoma: child with raised AFP.
- Metastases are the commonest liver malignancy, usually from the colon.
Clinical case
A 52-year-old man with long-standing hepatitis B and known cirrhosis presents with weight loss, a new right upper quadrant mass and worsening ascites. AFP is 2,400 ng/mL. A multiphase CT shows a 7 cm hypervascular lesion in the right lobe with portal vein invasion.
- Diagnosis? Hepatocellular carcinoma on a background of hepatitis B cirrhosis; arterial enhancement with washout and a high AFP make biopsy unnecessary.
- Why is his outlook poor? Portal vein invasion, large size and decompensated cirrhosis (Child-Pugh B or C) limit resection, ablation and transplant.
- What could have been done earlier? Hepatitis B vaccination, antiviral treatment, and six-monthly ultrasound surveillance with AFP.
Practice questions
Question 1
A 28-year-old woman who has used oral contraceptives for six years collapses with sudden right upper quadrant pain and hypotension. CT shows a 9 cm liver lesion with intraperitoneal blood. What is the most likely lesion?
A. Cavernous haemangioma B. Focal nodular hyperplasia C. Hepatocellular adenoma D. Hepatoblastoma
Answer: C. Hepatocellular adenoma Explanation: Adenomas are linked to the pill and can rupture; FNH and haemangioma do not usually bleed.
Question 2
During an abdominal ultrasound for another reason, a bright, well-defined 3 cm liver lesion is found in a healthy woman. Which statement is correct?
A. It should be biopsied at once to exclude malignancy B. It is most likely a haemangioma and should not be biopsied C. It must be resected D. It is a metastasis until proven otherwise
Answer: B. It is most likely a haemangioma and should not be biopsied Explanation: Haemangioma is the commonest benign liver tumour and biopsy risks serious haemorrhage.
Question 3
Which of the following is the best distinguishing feature of cholangiocarcinoma compared with hepatocellular carcinoma?
A. Raised AFP B. Association with hepatitis B C. No association with hepatitis B or C and a normal AFP D. Arterial enhancement with washout on CT
Answer: C. No association with hepatitis B or C and a normal AFP Explanation: Cholangiocarcinoma arises from bile ducts, with PSC and liver flukes as risk factors, and AFP is normal.
Question 4
A man with cirrhosis from hepatitis B has a 4 cm liver nodule that shows arterial-phase enhancement and venous-phase washout on multiphase CT. AFP is 1,500 ng/mL. What is the next best step?
A. Percutaneous biopsy before any other step B. Treat as hepatocellular carcinoma and plan staging and management C. Repeat ultrasound in 12 months D. Start empiric antibiotics for abscess
Answer: B. Treat as hepatocellular carcinoma and plan staging and management Explanation: In a cirrhotic liver, typical imaging with a high AFP is diagnostic, so biopsy is not required.
Question 5
A factory worker exposed for many years to vinyl chloride develops a rapidly growing, haemorrhagic liver tumour. What is the most likely diagnosis?
A. Hepatoblastoma B. Angiosarcoma C. Fibrolamellar carcinoma D. Adenoma
Answer: B. Angiosarcoma Explanation: Vinyl chloride, arsenic and Thorotrast are the classic causes of hepatic angiosarcoma.
Question 6
Multiple nodules in the liver of a patient with weight loss and altered bowel habit, a normal AFP and a raised ALP most likely represent metastases from which primary?
A. Bladder B. Colorectal C. Prostate D. Thyroid
Answer: B. Colorectal Explanation: Colorectal cancer is the commonest source of liver metastases because the portal vein carries tumour cells directly to the liver.
Written for study from standard pathology and hepatology references. Check details against your lecture notes and the current guideline.