Fibrolamellar hepatocellular carcinoma

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.

Epidemiology

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.

Clinical presentation

Presentation is non-specific, with constitutional symptoms and occasionally gynecomastia due to elevated estrone levels ¹. Hepatomegaly is usually evident as these masses are typically large.

Pathology

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. 

Markers

Fibrolamellar hepatocellular carcinomas often do not produce alpha-fetoprotein (AFP) ⁵.

Radiographic features

Ultrasound

• variable sonographic appearance

• contrast-enhanced ultrasound ⁶

  • arterial phase:

    • heterogeneous enhancement

  • portal venous phase:

    • decreased echogenicity relative to background liver ("washout")

CT

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.

MRI

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

Nuclear medicine

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.

Differential diagnosis

General imaging differential considerations include:

• hepatocellular carcinoma (HCC)

  • different demographics: underlying liver disease

  • less likely to have calcification or central scar

  • elevated AFP

• focal nodular hyperplasia (FNH)

  • 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 fibrolamellar hepatocellular carcinoma

• hepatic adenoma

  • uptake of Tc-99m sulfur colloid in up to 25% of cases ³

• hepatic metastasis

• large liver hemangioma

  • peripheral pooling, delayed central filling-in with contrast

  • may also have central scar if large

Mnemonic

A mnemonic to help remember the features of fibrolamellar hepatocellular carcinoma is PSYCH.