Genomic analysis of focal nodular hyperplasia with associated hepatocellular carcinoma unveils its malignant potential: a case report

Abstract

Background Focal nodular hyperplasia (FNH) is typically considered a benign tumor of the liver without malignant potential. The co-occurrence of FNH and hepatocellular carcinoma (HCC) has been reported in rare cases. In this study we sought to investigate the clonal relationship between these lesions in a patient with FNH-HCC co-occurrence. Methods A 74-year-old female patient underwent liver tumor resection. The resected nodule was subjected to histologic analyses using hematoxylin and eosin stain and immunohistochemistry. DNA extracted from microdissected FNH and HCC regions was subjected to whole exome sequencing. Clonality analysis were performed using PyClone. Results Histologic analysis reveals that the nodule consists of an FNH and two adjoining HCC components with distinct histopathological features. Immunophenotypic characterization and genomic analyses suggest that the FNH is clonally related to the HCC components, and is composed of multiple clones at diagnosis, that are likely to have progressed to HCC through clonal selection and/or the acquisition of additional genetic events. Conclusion To the best of our knowledge, our work is the first study showing a clonal relationship between FNH and HCC. We show that FNH may possess the capability to undergo malignant transformation and to progress to HCC in very rare cases.

Benign to Malignant Hepatic Lesion Transformation in Abernethy Malformation

“…5,10 Immunophenotypic analyses have identified identical genes between HCA and HCC, evidence that erroneous genetic alterations in HCA could lead to HCC. 11 Our case features the presentation and progression of tumors in adults with CEPS and highlights that HCA, FNH, and HCC can coincide despite AFP being normal. We make a case for serial diagnostic imaging to monitor enlarging or atypical hepatic lesions in patients with CEPS who have FNH and HCA.…”

“…5,10 Immunophenotypic analyses have identified identical genes between HCA and HCC, evidence that erroneous genetic alterations in HCA could lead to HCC. 11…”

The Role of Chronic Liver Diseases in the Emergence and Recurrence of Hepatocellular Carcinoma: An Omics Perspective

“…In line with these observations, the TERT promoter is frequently mutated in premalignant cirrhotic nodules early during hepatocarcinogenesis (23). Recently, hotspot mutations in the TERT promoter were found to be altered in a focal nodular hyperplasia lesion and clonally related HCC lesions (41). In contrast to other studies, Kim et al found that TERT promoter mutations were only detectable in HCC, yet not in the cirrhotic nodules (24).…”

Pedunculated Focal Nodular Hyperplasia: When in Doubt, Should We Cut It Out?

“…It is worth mentioning that the co-occurrence of FNH and hepatocellular adenomas or carcinomas has been described in the literature [ 70 , 71 , 72 , 73 , 74 ]. Despite FNH being a rare condition, Langrehr et al [ 71 ] suggested that a high index of suspicion and awareness should be maintained for rapidly growing FNH lesions, considering there are a few patients with hepatocellular carcinomas associated with FNH.…”

“…Despite FNH being a rare condition, Langrehr et al [ 71 ] suggested that a high index of suspicion and awareness should be maintained for rapidly growing FNH lesions, considering there are a few patients with hepatocellular carcinomas associated with FNH. Furthermore, Ercan et al [ 72 ] studied a patient with hepatocellular carcinoma and FNH coexistence, revealing a clonal relationship between them and indicating the malignant potential of FNH. Interestingly, several authors have supported that certain subtypes of FNH are associated with the potential for malignant transformation [ 75 , 76 ].…”