Malignant transformation of liver fatty acid binding protein-deficient hepatocellular adenomas: histopathologic spectrum of a rare phenomenon

Putra, Juan; Ferrell, Linda D.; Gouw, Annette S.H.; Paradis, Valérie; Rishi, Arvind; Sempoux, Christine; Balabaud, Charles; Thung, Swan N.; Bioulac‐Sage, Paulette

doi:10.1038/s41379-019-0374-x

Cited by 28 publications

(24 citation statements)

References 48 publications

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“…In this population of 40 MT-HCA patients, the main subtypes were IHCA (50%) and β-catenin subtype (30%), including 8 patients with a CTNNB1 exon 3 and 1 J o u r n a l P r e -p r o o f patient with a CTNNB1 exon 7 mutation, which is consistent with previous findings (5). Only 1 patient had the H-HCA subtype, which confirms the extremely low risk of malignant transformation in this subtype despite their higher incidence (18).…”

Section: <H1>discussionsupporting

confidence: 88%

Long-term outcomes following resection of hepatocellular adenomas with small foci of malignant transformation or malignant adenomas

et al. 2021

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Section: <H1>discussionsupporting

confidence: 88%

Long-term outcomes following resection of hepatocellular adenomas with small foci of malignant transformation or malignant adenomas

et al. 2021

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“…Although the frequency of malignant change is high in B‐HCA, cases of H‐HCA and IHCA with HCC transformation have been observed 21 . Malignant transformation in H‐HCA was reported in a recent article, predominantly in female patients, and this may be related to a different pathway of hepatocarcinogenesis 22 . In the literature, simultaneous HNF1A mutation and diffuse heterogeneous GS expression with a T41 mutation in CTNNB1 were reported in two AHNs 23 .…”

Section: Discussionmentioning

confidence: 99%

Hepatocellular adenomas in the Turkish population: reclassification according to updated World Health Organization criteria

et al. 2021

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Aims Hepatocellular adenoma (HCA) is an uncommon liver neoplasm, and studies of HCA subtypes have been primarily limited to France, the USA, and Japan. The aim of this study was to describe the clinicopathological features of HCA subtypes in Turkey. Methods and results The resection specimens of 59 cases diagnosed as ‘hepatocellular adenoma’ collected from 15 institutions were reviewed to confirm the diagnosis and to classify them according to the current World Health Organization 2019 classification. Immunostaining for glutamine synthetase, liver fatty acid‐binding protein, C‐reactive protein, β‐catenin and reticulin was performed. Of the 59 cases, 48 (81%) were diagnosed as HCA. We identified 24 (50%) hepatocyte nuclear factor 1α (HNF1α)‐inactivated HCAs, five (10%) inflammatory HCAs, 15 (32%) β‐catenin‐activated HCAs, three (6%) β‐catenin‐activated inflammatory HCAs, and one (2%) unclassified HCA. HCA patients were predominantly female (female/male ratio of 5:1); they had a median age of 34 years and a median tumour diameter of 60 mm. In the β‐catenin‐activated HCA group, nine cases (19%) showed cytoarchitectural atypia, and were also referred to as atypical hepatocellular neoplasms. In the β‐catenin‐activated HCA group, three cases (6%) showed focal areas supportive of transition to HCA. The original diagnosis of HCA was changed to well‐differentiated hepatocellular carcinoma in nine cases and to focal nodular hyperplasia in two cases. Conclusion In our series, the major HCA subtype was HNF1α‐inactivated HCA. We found a low incidence of inflammatory‐type HCA. Our data also showed that β‐catenin‐activated hepatocellular neoplasms, including cases with atypical histology, constituted a relatively high proportion of the cases. These findings are in contrast to those of most other studies of HCA subtypes.

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“…Malignant transformation has recently been reported in the H‐HCA subtype, with a greater frequency in women with multiple lesions 40 . It should be noted that the mean size of the H‐HCA with malignant transformation was 8.9 cm, suggesting that tumor size probably plays a role in malignant progression 40 …”

Section: Malignant Transformation Of Hepatocellular Adenoma Into Hccmentioning

confidence: 94%

“…In contrast to the molecular steps described in HCC that develop on cirrhosis, the CTNNB1 exon 3 mutation is the earliest genetic alteration, while mutations in the TERT promotor seem to be involved in the final transitional step from HCA to HCC 39 . Malignant transformation has recently been reported in the H‐HCA subtype, with a greater frequency in women with multiple lesions 40 . It should be noted that the mean size of the H‐HCA with malignant transformation was 8.9 cm, suggesting that tumor size probably plays a role in malignant progression 40 …”

Section: Malignant Transformation Of Hepatocellular Adenoma Into Hccmentioning

confidence: 98%

Hepatocellular Carcinomas: Towards a pathomolecular approach

Paradis

2021

Liver International

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Molecular analysis of primary liver malignancies has provided a refinement of the pathological diagnosis of this entity and the identification of an increasing number of tumor subtypes of hepatocellular proliferation, either malignant (hepatocellular carcinomas) or benign (hepatocellular adenomas). Besides the diagnosis, a combined pathomolecular approach can also provide further insights into patient prognosis, and help select patients who can benefit from targeted therapies. Hepatocellular carcinomas define a heterogeneous group of malignant hepatocellular proliferation at various levels: macroscopic, histological and molecular. While most carcinomas occur in patients with chronic liver diseases and advanced fibrosis in the background liver, some arise from the malignant transformation of a pre‐existing hepatocellular adenoma. TERT promoter mutations are the most frequent genomic alterations observed in the process of malignancy, and they occur early in the process of liver carcinogenesis. Overall, a more active biopsy strategy should be considered a key step in the management of patients with HCC.

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Malignant transformation of liver fatty acid binding protein-deficient hepatocellular adenomas: histopathologic spectrum of a rare phenomenon

Cited by 28 publications

References 48 publications

Long-term outcomes following resection of hepatocellular adenomas with small foci of malignant transformation or malignant adenomas

Long-term outcomes following resection of hepatocellular adenomas with small foci of malignant transformation or malignant adenomas

Hepatocellular adenomas in the Turkish population: reclassification according to updated World Health Organization criteria

Hepatocellular Carcinomas: Towards a pathomolecular approach

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