A Rare Case of Fibrolamellar Hepatocellular Carcinoma in a Young Adult: A Case Report and Literature Review

Patient History: A 25-year-old female with no significant past medical history, family history of cancer, or history of alcohol, tobacco, or drug use presented to the emergency department with a two-week history of progressive right upper quadrant abdominal pain. The pain was described as dull, aching, and non-radiating, and it was not associated with nausea, vomiting, diarrhea, or fever. The patient had noticed a recent decrease in her appetite and a 5-pound weight loss over the past month.

Physical Examination: On physical examination, the patient was afebrile, with a blood pressure of 120/70 mmHg, a heart rate of 80 beats per minute, and a respiratory rate of 18 breaths per minute. She appeared well-nourished but slightly pale. The abdominal examination revealed tenderness in the right upper quadrant, with a palpable mass approximately 8 cm in diameter. The mass was firm, non-tender, and fixed. There was no evidence of jaundice, ascites, or hepatosplenomegaly. The remainder of the physical examination was unremarkable.

Laboratory Investigations: Initial laboratory tests showed a normal complete blood count, except for a mild anemia with a hemoglobin level of 11 g/dL. The liver function tests were abnormal, with an elevated aspartate aminotransferase (AST) of 120 U/L (normal range: 10-40 U/L), an elevated alanine aminotransferase (ALT) of 150 U/L (normal range: 7-56 U/L), and a slightly elevated alkaline phosphatase (ALP) of 200 U/L (normal range: 45-115 U/L). The total bilirubin, direct bilirubin, and albumin levels were within normal limits. The serum alpha-fetoprotein (AFP) level, a tumor marker commonly associated with HCC, was normal at 5 ng/mL (normal range: < 20 ng/mL).

Imaging Studies: A contrast-enhanced computed tomography (CT) scan of the abdomen and pelvis was performed, which revealed a large, well-defined, heterogeneous mass measuring approximately 10 cm in diameter in the right hepatic lobe. The mass showed arterial enhancement with washout in the portal venous and delayed phases, consistent with a hypervascular liver tumor (Figure 1). There was no evidence of intrahepatic or extrahepatic metastases, portal vein thrombosis, or ascites.

[Insert Figure 1 here: Contrast-enhanced CT scan showing a large, well-defined, heterogeneous mass in the right hepatic lobe with arterial enhancement (arrow) and washout in the portal venous and delayed phases.]

Subsequently, a magnetic resonance imaging (MRI) scan of the liver was obtained for further characterization of the mass. The MRI demonstrated a T1-weighted hypointense mass with areas of hyperintensity, consistent with hemorrhage or necrosis. On T2-weighted images, the mass was hyperintense, and it showed enhancement on gadoxetic acid-enhanced images, with a characteristic "fibrous capsule" appearance (Figure 2). The MRI findings were highly suggestive of FL-HCC.

[Insert Figure 2 here: MRI scan showing a T1-weighted hypointense mass with areas of hyperintensity (arrow) on T1-weighted image (A), hyperintense mass on T2-weighted image (B), and enhancement with a characteristic "fibrous capsule" appearance on gadoxetic acid-enhanced image (C).]

Histopathological Examination: Based on the imaging findings, a percutaneous liver biopsy was performed under ultrasound guidance. The histological examination of the biopsy specimen revealed neoplastic hepatocytes with abundant eosinophilic cytoplasm and prominent nucleoli, arranged in nests and trabeculae, and separated by dense collagenous stroma (Figure 3). Immunohistochemical staining showed positive expression of hepatocyte-specific antigen (HepPar-1), cytokeratin 7 (CK7), and epithelial membrane antigen (EMA), and negative expression of AFP, CD34, and desmin. These findings were consistent with the diagnosis of FL-HCC.

[Insert Figure 3 here: Histopathological examination of the liver biopsy specimen showing neoplastic hepatocytes with abundant eosinophilic cytoplasm and prominent nucleoli (arrow) arranged in nests and trabeculae, separated by dense collagenous stroma (Hematoxylin and Eosin stain, original magnification x200).]

Treatment and Follow-up: The patient was referred to the hepatobiliary surgery department for further management. Given the size and location of the tumor, a right hepatectomy was planned. The patient underwent a successful right hepatectomy, and the surgical specimen confirmed the diagnosis of FL-HCC with negative surgical margins.

Postoperatively, the patient had an uneventful recovery and was discharged home on the fifth postoperative day. She was followed up regularly with physical examinations, laboratory tests, and imaging studies. At the six-month follow-up, there was no evidence of recurrence or metastasis. The patient's liver function tests had returned to normal, and she reported feeling well.

Literature Review

Epidemiology: FL-HCC is a rare tumor, accounting for approximately 1-2% of all HCC cases [9]. It has a distinct age and gender distribution compared to conventional HCC. While conventional HCC typically affects older individuals with underlying liver disease, FL-HCC often presents in young adults, with a median age at diagnosis of 25-30 years [5]. There is no significant gender predilection, with a male-to-female ratio of approximately 1:1 [10].

The incidence of FL-HCC is relatively low worldwide, but it has been reported to be more common in certain regions, such as North America and Europe [11]. The reasons for this geographical variation are not well understood, but it may be related to differences in environmental factors, genetic background, or diagnostic practices.

Pathogenesis: The exact pathogenesis of FL-HCC remains unclear. Unlike conventional HCC, which is strongly associated with chronic liver injury and cirrhosis, FL-HCC is often found in patients without underlying liver disease. However, some studies have suggested that certain risk factors may be associated with the development of FL-HCC, including exposure to certain toxins, such as aflatoxin B1, and genetic syndromes, such as hereditary hemochromatosis and Li-Fraumeni syndrome [6].

Recent molecular studies have identified several genetic and epigenetic alterations in FL-HCC. These include mutations in genes such as CTNNB1, TP53, and ARID1A, as well as alterations in the expression of microRNAs and long non-coding RNAs [12]. However, the role of these molecular alterations in the pathogenesis of FL-HCC is still being investigated, and more research is needed to fully understand the underlying mechanisms.

Diagnosis: The diagnosis of FL-HCC can be challenging, as its clinical and imaging features may overlap with those of other liver tumors. The typical presentation of FL-HCC is a young adult with abdominal pain or a palpable abdominal mass. Laboratory tests may show abnormal liver function tests, but the serum AFP level is usually normal, which differentiates FL-HCC from conventional HCC, in which AFP is often elevated.

Imaging studies play a crucial role in the diagnosis of FL-HCC. Contrast-enhanced CT and MRI are the most commonly used imaging modalities, and they can provide important information about the size, location, and characteristics of the tumor. FL-HCC typically appears as a large, well-defined, heterogeneous mass with arterial enhancement and washout in the portal venous and delayed phases on CT and MRI. The presence of a "fibrous capsule" or central scar on imaging is also a characteristic feature of FL-HCC [13].

Histopathological examination of a biopsy specimen is required for a definitive diagnosis of FL-HCC. The histological features of FL-HCC include neoplastic hepatocytes with abundant eosinophilic cytoplasm and prominent nucleoli, arranged in nests or trabeculae, and separated by dense collagenous stroma. Immunohistochemical staining can help to confirm the diagnosis, with positive expression of HepPar-1, CK7, and EMA, and negative expression of AFP being characteristic of FL-HCC [4].

Treatment: The mainstay of treatment for FL-HCC is surgical resection, with curative intent. Complete resection of the tumor with negative surgical margins is associated with the best prognosis. However, due to the large size and location of the tumor at the time of diagnosis, only a small percentage of patients with FL-HCC are eligible for surgical resection [14].

In patients who are not candidates for surgical resection, other treatment options may be considered, including liver transplantation, ablation therapy, transarterial chemoembolization (TACE), and systemic chemotherapy. Liver transplantation may be an option for selected patients with FL-HCC, especially those with tumors that are not resectable but are confined to the liver [15]. Ablation therapy, such as radiofrequency ablation or microwave ablation, can be used to treat small FL-HCC tumors, especially in patients who are not suitable for surgery. TACE is a palliative treatment option that can be used to reduce the size of the tumor and relieve symptoms in patients with unresectable FL-HCC. Systemic chemotherapy has shown limited efficacy in the treatment of FL-HCC, and its role in the management of this disease is still being investigated [16].

Prognosis: The prognosis of FL-HCC is variable, and it depends on several factors, including the stage of the disease at the time of diagnosis, the treatment modality used, and the presence of underlying liver disease. In general, patients with FL-HCC who undergo complete surgical resection have a better prognosis compared to those who do not. The reported 5-year survival rates for patients with resected FL-HCC range from 30% to 70% [8].

However, some studies have suggested that FL-HCC may have a more aggressive biological behavior and a worse prognosis compared to conventional HCC, especially in patients with advanced disease or those with certain molecular alterations [17]. Additionally, the recurrence rate of FL-HCC after surgical resection is relatively high, and long-term follow-up is essential to detect and treat recurrence early.