Exploring fibronodular hepatocellular carcinoma: a case series investigating histopathologic and clinical characteristics and its potential association with cirrhosis.

Ghandour, Fatme; Zein-Sabatto, Bassel; Lobo, Joao; Patel, Chirag; Dhall, Deepti; Manne, Upender; Al Diffalha, Sameer · Am J Clin Pathol · 2026

case_series · Level IV

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Abstract

Fibronodular hepatocellular carcinoma (FN-HCC) is a newly described variant of hepatocellular carcinoma (HCC), with only 29 cases reported. Histologically, it is divided into multiple smaller, well-defined tumor nodules by extensive fibrosis. Its differential diagnosis includes other HCC variants characterized by fibrous stroma, such as fibrolamellar hepatocellular carcinoma and scirrhous hepatocellular carcinoma. Fibronodular hyperplasia may also be considered in the differential diagnosis. We are reporting 7 cases to help better understand this entity. We retrospectively identified 7 cases of FN-HCC and analyzed the clinical and histologic features of each tumor, as well as disease progression and patient prognosis. The FN-HCC cases were diagnosed at a median age of 58 years (range, 40-75 years), with a male predilection (n = 6, 86%). Most patients were White (n = 6, 86%), and 1 was African American (n = 1, 14%). Tumors had a mean size of 3.15 cm (range, 1-9 cm) and were mainly located in the right lobe (n = 5, 71%). Background liver was cirrhotic in 6 cases (86%). Five patients were hepatitis C positive (71%). All tumors were surgically removed, with a free resection margin. Among 3 patients with evident vascular invasion, 1 had a positive lymph node. This patient had tumor metastasis 6 years later; otherwise, all patients were disease free on follow-up. Our cohort was concordant with published data showing a male predilection, hepatitis C association, and good prognosis when the disease is discovered before metastasis and is surgically excised with negative margins. However, it contradicts the published literature that associates FN-HCC with the absence of advanced fibrosis/cirrhosis.

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