What are the characteristics and treatment options for Fibrolamellar Carcinoma (FLC) liver cancer, particularly in younger individuals without underlying liver disease?

Fibrolamellar Carcinoma: A Rare Hepatocellular Carcinoma Variant

Surgical resection remains the mainstay of treatment for fibrolamellar carcinoma (FLC), as it is the only potentially curative option for this rare liver cancer that predominantly affects young adults without underlying liver disease. 1, 2

Key Clinical Characteristics

FLC is a distinct variant of hepatocellular carcinoma with unique features that differentiate it from conventional HCC:

• Occurs in young patients (median age 27 years) without cirrhosis or chronic liver disease 1, 3
• Accounts for only 1-9% of all hepatocellular carcinomas 4
• Not associated with hepatitis B, hepatitis C, or other typical HCC risk factors 5, 4, 3
• Alpha-fetoprotein (AFP) is typically normal or minimally elevated - only 7% of patients have AFP >200 ng/mL 3
• Characterized by a unique DNAJB1-PRKACA fusion transcript at the molecular level 4, 6

Clinical Presentation

Patients typically present late with symptomatic disease:

• Vague abdominal pain, nausea, malaise, and weight loss are common presenting symptoms 4
• Tumors are usually large and symptomatic at diagnosis due to the absence of underlying liver disease surveillance 1
• Median tumor size at resection is approximately 9 cm 3

Diagnostic Approach

The diagnosis requires integration of clinical, imaging, and histologic findings:

• Imaging (CT or MRI) shows a large solitary liver mass in a non-cirrhotic liver 5
• Histology reveals large polygonal cells with oncocytic cytoplasm separated by dense parallel bands of collagen 5
• Immunohistochemistry panel including cytokeratin 7, CD68, and HepPar-1 helps distinguish FLC from conventional HCC and cholangiocarcinoma 5
• AFP levels are typically normal, unlike conventional HCC 4, 3

Treatment Strategy

Primary Treatment: Surgical Resection

Surgical resection is the first-line treatment and offers the best chance for long-term survival:

• Five-year overall survival after complete resection is 76% 3
• Resection is less likely to produce liver failure compared to HCC in cirrhotic patients, since FLC arises in non-cirrhotic liver 1
• Up to 70% of patients can be offered curative treatment options despite often presenting at advanced stages 4
• Perioperative mortality is minimal in experienced centers 3

Liver Transplantation

Transplantation can be considered but has limitations:

• Five-year survival after liver transplantation ranges from 28-49% 1
• Tumor recurrence is relatively common after transplantation 1
• Resection remains the mainstay of therapy, particularly where donor organ shortages exist 1

Management of Unresectable Disease

For patients who cannot undergo resection:

• Median survival for unresectable FLC is only 12 months, with no patients surviving beyond 5 years 3
• FLC is relatively insensitive to chemotherapy compared to conventional HCC 1
• Multimodality treatments including chemoembolization and hepatic artery embolization can be considered in advanced cases 5, 4

Critical Prognostic Factors

Lymph node metastasis is the only significant negative prognostic factor identified 3

Additional prognostic considerations:

• Vascular invasion occurs in approximately 36% of resected cases 3
• Lymph node metastases are present in 50% of resected patients 3
• Tumor resectability strongly correlates with prognosis 5

Surveillance After Resection

Aggressive long-term surveillance is essential due to the indolent tumor biology and high recurrence rates:

• Five-year recurrence-free survival is only 18% despite good overall survival 3
• Late recurrences are common - 78% of patients with >5 years follow-up developed recurrences 3
• Repeat resections for recurrence should be strongly considered, as 61% of patients undergo second operations for recurrent disease 3
• Perform AFP and liver imaging every 3-6 months for at least 2 years, then continue surveillance given the high late recurrence rate 7, 3

Important Clinical Pitfalls

• Do not exclude FLC from consideration based on normal AFP levels - this is characteristic of the disease 4, 3
• Do not assume better prognosis means less aggressive surveillance - the recurrence rate is extremely high despite good initial survival 3
• Do not dismiss surgical options for recurrent disease - repeat resections offer meaningful benefit in the absence of effective systemic therapies 3
• FLC has a slower doubling time than conventional HCC, but this does not translate to better recurrence-free survival 1, 3