Correct diagnosis of patients with fibrolamellar carcinoma: A Dutch nationwide study

Aims Fibrolamellar carcinoma (FLC) is a rare primary liver cancer. Adequate diagnosis is essential for appropriate treatment. The current study evaluates the diagnosis of fibrolamellar carcinoma in a Dutch cohort.Methods and results Adult patients diagnosed with FLC between 1990 and 2020, with pathology slides and clinical data available, were included. Two expert hepatopathologists revised all slides, including CD68 and CK7 stainings. In total, 54 adult patients diagnosed with FLC were included. Biopsies were available for 31 patients (57%) and resection or transplantation specimens in 23 patients (43%). Upon expert review, in nine patients (17%), the diagnosis of FLC was unequivocally confirmed. Four additional lesions harboured characteristics of both FLC and conventional hepatocellular carcinoma (HCC). Three patients exhibited histomorphological features suggestive of FLC, yet with negative CD68 staining. In the remaining 38 patients, the diagnosis was revised to intrahepatic cholangiocarcinoma (iCCA, n = 7, 13%), combined HCC/iCCA (n = 5, 9.3%) and conventional HCC (n = 26, 48%, of which 11 were steatohepatitic and 10 scirrhous subtypes).Conclusions The presence of extensive fibrosis in both iCCA and conventional HCC may result in misdiagnosis of FLC, in particular for the steatohepatitic and scirrhous variants of HCC. Misdiagnosis has important treatment consequences, as evidence supporting the efficacy of systemic treatments for FLC remains limited and extensive resection is the only curative option. Our Dutch historical cohort underlines the challenging diagnosis of FLC and emphasizes the critical role of expert review in accurate diagnosis.