Fibrolamellar hepatocellular carcinoma
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Fibrolamellar hepatocellular carcinoma is a distinct histological variant of hepatocellular carcinoma characterized on microscopy by laminated fibrous layers between the tumor cells. It is important as it has different demographics and risk factors compared to "standard" hepatocellular carcinomas.
Typically these tumors occur in young adults (20 to 40 years of age) without gender predilection. Unlike hepatocellular carcinoma, they do not have an association with cirrhosis, alcoholism, or hepatitis B/C infection 2.
These tumors are well-differentiated and well-circumscribed, with a dense fibrotic background 2. The tumor cells are arranged in cords that are separated by sheet-like fibrous bands arranged in a parallel or lamellar distribution 4; hence the name, fibrolamellar.
Fibrolamellar hepatocellular carcinomas often do not produce alpha-fetoprotein (AFP) 5.
variable sonographic appearance
contrast-enhanced ultrasound 6
portal venous phase:
decreased echogenicity relative to background liver ("washout")
Fibrolamellar hepatocellular carcinomas typically are single large tumors with dense fibrotic bands forming a central scar (seen in ~75% of cases) 1, resembling focal nodular hyperplasia (FNH). Enhancement is usually arterial. The central scar typically shows persistent enhancement on delayed contrast-enhanced CT. A few small calcifications are seen in 35-65% of cases 1. Regional (hepatic hilum) nodal enlargement is seen in ~50% of cases.
The central scar, when present, is usually hypointense on all sequences. Occasionally it may be T2 hyperintense mimicking focal nodular hyperplasia 1. Fibrolamellar hepatocellular carcinomas do not contain fat, and thus do not lose signal on out-of-phase imaging 7.
T1: typically iso to hypointense to the liver
T2: hypo to slightly hyperintense
T1 C+ (Gd)
arterial phase: heterogeneous enhancement
portal venous / delayed phase: iso to hypointense
T1 C+ (Eovist/Primovist)
liver-specific contrast agent uptake has not been reported in the hepatobiliary phase 7
Technetium-99m sulfur colloid scans (taken up by Kupffer cells) are useful as these tumors will not accumulate the agent, whereas focal nodular hyperplasia does.
Treatment and prognosis
Even though fibrolamellar hepatocellular carcinoma is less aggressive than hepatocellular carcinoma, the stage at presentation tends to be advanced due to a lack of symptoms until it becomes sizable, and a lack of secretion of AFP 5.
Resection is the treatment of choice, with a resulting 5-year survival of 76%. This compares favourably to hepatocellular carcinoma which, even when resectable, has a 5-year survival of only 37-56% 1.
If unresectable, this tumor is universally fatal.
General imaging differential considerations include:
different demographics: underlying liver disease
less likely to have calcification or central scar
uptake of Tc-99m sulfur colloid usually present
scar is often hyperintense on T2
less heterogeneity and fewer calcifications than fibrolamellar hepatocellular carcinoma
will retain liver-specific contrast agent (e.g. Eovist); this has not been reported in hepatocellular carcinoma
uptake of Tc-99m sulfur colloid in up to 25% of cases 3
large liver hemangioma
peripheral pooling, delayed central filling-in with contrast
may also have central scar if large
A mnemonic to help remember the features of fibrolamellar hepatocellular carcinoma is PSYCH.