Liver & Biliary Tumors Beyond HCC
Which liver masses to leave alone, which bleed, and which kill
Metastases: the most common liver malignancy
Sources. In the United States, metastases far outnumber every primary liver cancer. Colorectal carcinoma, arriving through the portal vein, is the leading source, followed by pancreas, stomach, lung, breast, melanoma, and neuroendocrine tumors. The liver typically holds multiple nodules, often umbilicated at the capsule where their centers have necrosed, with hepatomegaly and a raised ALP. Limited colorectal liver metastases can be resected with curative intent, an exception to the usual rule for metastatic disease.
Benign liver lesions
| Feature | Cavernous hemangioma | Focal nodular hyperplasia | Hepatic adenoma |
|---|---|---|---|
| Frequency | Most common benign tumor | Second most common | Less common |
| Patient | Any adult; usually incidental | Young to middle-aged women | Women on OCPs; men on anabolic steroids; glycogen storage disease I |
| Pathology | Blood-filled channels lined by flat endothelium, fibrous septa | Polyclonal hepatocyte nodules around a central stellate scar with thick-walled arteries and ductules | Monoclonal sheets of hepatocytes without portal tracts or bile ducts |
| Risk | Bleeds if biopsied | None; rarely bleeds | Rupture; β-catenin subtype can become HCC |
| Management | Observe; never biopsy | Observe | Stop hormones; resect if >5 cm, in men, or β-catenin activated |
Cavernous hemangioma. Most are small and found incidentally. Imaging shows peripheral nodular enhancement with centripetal fill-in on CT or MRI, and the lesion is hyperechoic on ultrasound. Because it is essentially a sponge of blood, a needle can cause hemorrhage (by contrast, needle-tract seeding is the worry with HCC, and anaphylaxis with a hydatid cyst).
Focal nodular hyperplasia. FNH is a hyperplastic response to an anomalous artery, not a true neoplasm and not hormone-induced. It contains Kupffer cells and ductules, so it takes up sulfur colloid and hepatobiliary contrast agents, which adenomas usually do not. It needs no treatment.
Hepatic adenoma. This benign hepatocyte neoplasm is linked to oral contraceptives in women of reproductive age, anabolic steroids in men, and glycogen storage disease type I. Large (>5 cm) or subcapsular tumors can rupture into the peritoneum, especially in pregnancy. Subtype sets the risk: HNF1A-inactivated adenomas are steatotic and lowest risk, inflammatory adenomas tend to bleed, and β-catenin–activated adenomas, more common in men and with anabolic steroids or glycogen storage disease, carry the highest risk of becoming HCC.
Malignant primary tumors other than HCC
Angiosarcoma. A highly aggressive malignant endothelial tumor that appears decades after exposure to vinyl chloride (PVC manufacturing), arsenic (pesticides, contaminated water), or Thorotrast, a radioactive thorium dioxide contrast agent used until the 1950s that also caused cholangiocarcinoma and HCC. Tumor cells express CD31, CD34, ERG, and von Willebrand factor.
Hepatoblastoma. The most common primary liver malignancy of early childhood, usually before age 3, with a very high AFP and fetal or embryonal hepatocyte-like cells, sometimes mixed with osteoid. It is linked to Beckwith-Wiedemann syndrome (11p15 imprinting defects, IGF2 excess) and FAP (APC loss activating Wnt/β-catenin), and very low birth weight raises risk. Children with Beckwith-Wiedemann syndrome are screened with serial AFP for hepatoblastoma and with ultrasound for Wilms tumor. Cisplatin-based chemotherapy plus resection cures most patients.
A central scar in a young adult's liver mass is usually FNH, but fibrolamellar carcinoma, an HCC variant of young adults without cirrhosis and with a normal AFP, also has one.
Biliary tract cancers
Cholangiocarcinoma. A desmoplastic, mucin-secreting adenocarcinoma of bile duct epithelium that can be intrahepatic, perihilar, or distal; it stains for CK7. Chronic ductal injury underlies it: primary sclerosing cholangitis (often with ulcerative colitis), the liver flukes Clonorchis sinensis and Opisthorchis viverrini acquired from raw freshwater fish in East and Southeast Asia, choledochal cysts, hepatolithiasis, chronic hepatitis B or C, and cirrhosis. Other parasites leave different marks: Schistosoma causes periportal fibrosis, and Echinococcus forms hydatid cysts.
Klatskin tumor. The perihilar tumor at the confluence of the right and left hepatic ducts is the most common site. It causes painless obstructive jaundice with pruritus, pale stools, dark urine, and weight loss. Bile is trapped above the tumor, so intrahepatic ducts dilate while the gallbladder and common bile duct stay collapsed. A distal bile duct tumor, like pancreatic head cancer, instead produces the Courvoisier sign: painless jaundice with a palpable, nontender gallbladder. CA 19-9 is often elevated but is nonspecific, rising also in pancreatic cancer and cholangitis.
Gallbladder adenocarcinoma. It grows from chronically inflamed mucosa: gallstones are present in most cases, and other risks are a calcified porcelain gallbladder, polyps ≥1 cm, an anomalous pancreaticobiliary junction, and chronic Salmonella Typhi carriage. Older women and Native Americans are most affected. It presents late with RUQ pain, weight loss, or jaundice, or is discovered incidentally at cholecystectomy, and invades the liver directly. A porcelain gallbladder has traditionally prompted prophylactic cholecystectomy, whereas cholesterolosis and adenomyomatosis are benign.