Clinical and pathologic factors associated with survival in young adult patients with fibrolamellar hepatocarcinoma

Abstract

Background: Fibrolamellar Carcinoma (FLC), a subtype of hepatocellular carcinoma (HCC), is a rare primary hepatic malignancy. Several aspects of the clinic features and epidemiology of FLC remain unclear because most of the literature on FLC consists of case reports and small cases series with limited information on factors that affect survival.

Methods: We did a retrospective analysis of the clinical and histological characteristics of FLC. We also determined the rate of cellular proliferation in biopsies of these tumors. We assessed whether these variables were associated with survival.

Results: We found 15 patients with FLC out of 174 patients with HCC (8.6%). Between patients with these neoplasms, we found statistically significant survival, age at onset, level of alpha fetoprotein, and an earlier stage of the disease. The 1, 3 and 5 year survival in patients with FLC was of 66, 40 and 26% respectively. The factors associated with a higher survival in patients with FLC were age more than 23 years, feasibility of surgical resection, free surgical borders, absence of thrombosis or invasion to hepatic vessels and the absence of alterations in liver enzymes. The size of the tumor, gender, cellular proliferation and atypia did not affect the prognosis.

Conclusion: We concluded that FLC patients diagnosed before 23 years of age have worse prognosis than those diagnosed after age 23. Other factors associated with worse prognosis in this study are: lack of surgical treatment, presence of positive surgical margins, vascular invasion, and altered hepatic enzymes.

Figure 1

Survival analysis of patients with HCC (n = 159) compared with FLC (n = 15) p = 0.007.

Figure 2

Fibrolamellar Hepatocarcinoma (400#215;), hematoxylin-eosin with big polygonal cells, and abundant eosinophil granular cytoplasm (A). Masson trichromic (100×) with cordons of hepatocytes separated with dense collagen septum (B). Immunohistochemistry for PCNA that shows high index of cellular proliferation of the nucleus (C)

Figure 3

Global survival of patients with FLC at 6, 12, 24, 36 and 60 months was 66, 66, 53, 40 and 26% (median survival of 30 ± 6 months).

Figure 4

Survival analysis of prognostic factors of patients with FLC. Age = 23 years (n = 7, median survival of 8 ± 2 months) compared to age > 23 years (n = 8, median survival of 65 ± 19 months), p = 0.0132.

Figure 5

Survival analysis of prognostic factors of patients with FLC. Patients who underwent surgical treatment (n = 10, median survival of 60 ± 10 months) vs patients with medical treatment only (n = 5, median survival of 5 ± 2 months), p = 0.0011.

Figure 6

Survival analysis of prognostic factors of patients with FLC. Patients who underwent surgical treatment with positive (n = 5, median survival of 20 ± 5 months) and negative (n = 5, median survival of 65 ± 4 months) surgical borders, p= 0.06.

Figure 7

Survival analysis of prognostic factors of patients with FLC. Patients with (n = 9, median survival of 5 ± 2 months) and without (n = 6, median survival of 60 ± 10 months) vascular invasion, p = 0.006.

Figure 8

Survival analysis of prognostic factors of patients with FLC. Patients with (n = 10, median survival of 26 ± 11 months) and without (n = 5, median survival of 65 ± 21 months) altered liver enzymes, p = 0.04.