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

Published on Jan 6, 2021in Histopathology5.087
· DOI :10.1111/HIS.14330
Kemal Deniz20
Estimated H-index: 20
(Erciyes University),
Sarah E. Umetsu21
Estimated H-index: 21
(UCSF: University of California, San Francisco)
+ 17 AuthorsGülen Akyol19
Estimated H-index: 19
(Gazi University)
AIMS Hepatocellular adenoma is an uncommon liver neoplasm and the studies of HCA subtypes have been primarily limited to France, United States and Japan. We aimed to describe the clinicopathologic features of hepatocellular adenoma 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 classify according to the current WHO 2019 classification. Glutamine synthetase, Liver-fatty acid binding protein, C-reactive protein, β-catenin and reticulin stains were performed. Of the 59 cases, 48 (81%) were diagnosed as hepatocellular adenoma. We identified 24 (50%) HNF1α-inactivated adenomas, 5 (10%) inflammatory adenomas, 15 (32%) β-catenin activated adenomas, 3 (6%) β-catenin activated inflammatory adenomas and 1 (2%) unclassified adenoma. Hepatocellular adenoma patients were predominantly female (F:M=5:1) with a median age of 34 and a median tumor diameter of 6 cm. In the β-catenin activated adenoma group nine cases (19%) showed cytoarchitectural atypia which also were referred to as atypical hepatocellular neoplasms. Three cases (6%) displayed focal areas supportive of transition to hepatocellular carcinoma in the β-catenin activated adenoma group. The original diagnosis of hepatocellular adenoma was changed to well-differentiated hepatocellular carcinoma in 9 cases and to focal nodular hyperplasia in 2 cases. CONCLUSION The major adenoma subtype is HNF1α-inactivated adenoma in our series. We found a low incidence of inflammatory type hepatocellular adenoma. Our data also showed β-catenin activated hepatocellular neoplasms including cases with atypical histology constitutes a relatively high portion of the cases. These findings are in contrast to most other studies of hepatocellular adenoma subtypes.
#1Margaux Sala (University of Bordeaux)H-Index: 5
#2Delphine Gonzales (French Institute of Health and Medical Research)H-Index: 6
Last. Amedeo Sciarra (UNIL: University of Lausanne)H-Index: 9
view all 36 authors...
Until recently, 10% of hepatocellular adenomas (HCAs) remained unclassified (UHCA). Among the UHCAs, the sonic hedgehog HCA (shHCA) was defined by focal deletions that fuse the promoter of Inhibin beta E chain with GLI1. Prostaglandin D2 synthase was proposed as immunomarker. In parallel, our previous work using proteomic analysis showed that most UHCAs constitute a homogeneous subtype associated with overexpression of argininosuccinate synthase (ASS1). To clarify the use of ASS1 in the HCA clas...
#1Juan Putra (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 13
#2Linda D. Ferrell (UCSF: University of California, San Francisco)H-Index: 82
Last. Paulette Bioulac-Sage (French Institute of Health and Medical Research)H-Index: 78
view all 9 authors...
The molecular classification of hepatocellular adenomas highlights a distinctive genotype-phenotype correlation. Malignant transformation is an exceptionally rare complication of hepatocyte nuclear factor 1α (HNF1A)-inactivated hepatocellular adenomas. This subtype is characterized by loss of liver fatty acid binding protein immunoexpression. In this study, we characterized the histopathologic spectrum of 13 liver fatty acid binding protein-deficient hepatocellular adenoma cases showing malignan...
#1Nancy M. Joseph (UCSF: University of California, San Francisco)H-Index: 30
#2Sarah E. Umetsu (UCSF: University of California, San Francisco)H-Index: 21
Last. Sanjay Kakar (UCSF: University of California, San Francisco)H-Index: 53
view all 5 authors...
Well-differentiated hepatocellular neoplasms are currently classified in the World Health Organization scheme as hepatocellular adenoma or hepatocellular carcinoma. There is no recognized diagnostic category for atypical cases with borderline features, and we have designated these as atypical hepatocellular neoplasms. Diffuse glutamine synthetase staining is used as a surrogate marker to detect β-catenin activation, a well-recognized high risk feature in hepatocellular tumors. This study examine...
Abstract Hepatocellular adenomas (HCA) are rare benign hepatocellular tumors occurring mainly in women taking oral contraceptives with 2 major complications: severe bleeding and malignant transformation that can be avoided if nodules exceeding 5 cm are resected. This simple attitude has been challenged in the recent years with HCA in men, in young adolescent, in aged persons, and complications in hepatocellular adenomas below 5 cm. The discovery of specific mutations leading to specific phenotyp...
#1Won-Tak Choi (UCSF: University of California, San Francisco)H-Index: 16
#2Sanjay KakarH-Index: 53
: The distinction of hepatocellular adenoma from well-differentiated hepatocellular carcinoma (HCC) can be difficult in some cases, especially on biopsy specimens. These borderline cases often occur in men or older patients and may have β-catenin activation or focal atypical morphologic features (such as small cell change, prominent pseudoacinar formation, cytologic atypia, focally thick plates, and/or focal reticulin loss) that are insufficient for an unequivocal diagnosis of HCC. The term "aty...
#1Paulette Bioulac-Sage (University of Bordeaux)H-Index: 78
#2Christine Sempoux (UNIL: University of Lausanne)H-Index: 65
Last. Charles Balabaud (University of Bordeaux)H-Index: 66
view all 3 authors...
Hepatocellular adenomas (HCAs) are rare benign tumors. This single entity has been split into 3 subtypes corresponding to specific mutations: HNF1α-inactivated HCA; inflammatory HCA related to different mutations, all leading to activation of STAT3 pathway; and β-catenin–activated HCA related to CTNNB1 mutations. The risk of malignant transformation depends on the level of β-catenin activation, reported mainly for exon 3, including S45. It is possible using specific immunohistochemical markers t...
#1Jean-Charles Nault (French Institute of Health and Medical Research)H-Index: 44
#2Gabrielle Couchy (French Institute of Health and Medical Research)H-Index: 30
Last. Jeanne RamosH-Index: 27
view all 56 authors...
Background & Aims Hepatocellular adenomas (HCAs) are benign liver tumors that can be assigned to molecular subtypes based on inactivating mutations in hepatocyte nuclear factor 1A, activating mutations in β-catenin, or activation of inflammatory signaling pathways. We aimed to update the classification system for HCA and associate the subtypes with disease risk factors and complications. Methods We analyzed expression levels of 20 genes and sequenced exon regions of 8 genes ( HNF1A, IL6ST, CTNNB...
#1Sandra Rebouissou (French Institute of Health and Medical Research)H-Index: 30
#2Andrea Franconi (French Institute of Health and Medical Research)H-Index: 6
Last. Jessica Zucman-RossiH-Index: 88
view all 12 authors...
CTNNB1 mutations activating s-catenin are frequent somatic events in hepatocellular carcinoma (HCC) and adenoma (HCA), particularly associated with a risk of malignant transformation. We aimed to understand the relationship between CTNNB1 mutation types, tumor phenotype, and level of s-catenin activation in the malignant transformation. To this purpose, CTNNB1 mutation spectrum was analyzed in 220 HCAs, 373 HCCs, and 17 borderline HCA/HCC lesions. s-catenin activation level was assessed in tumor...
#1Gillian Hale (UCSF: University of California, San Francisco)H-Index: 10
#2Xinxin Liu (YZU: Yangzhou University)H-Index: 2
Last. Sanjay Kakar (UCSF: University of California, San Francisco)H-Index: 53
view all 11 authors...
The current clinical practice is based on the assumption of strong correlation between diffuse glutamine synthetase expression and β-catenin activation in hepatocellular adenoma and hepatocellular carcinoma. This high correlation is based on limited data and may represent an oversimplification as glutamine synthetase staining patterns show wide variability in clinical practice. Standardized criteria for interpreting diverse glutamine synthetase patterns, and the association between each pattern ...
#1Soo-Jin Cho (UCSF: University of California, San Francisco)H-Index: 11
#2Linda D. Ferrell (UCSF: University of California, San Francisco)H-Index: 82
Last. Ryan M. Gill (UCSF: University of California, San Francisco)H-Index: 21
view all 3 authors...
Loss of expression of liver fatty acid binding protein (LFABP) by immunohistochemistry has been shown to be characteristic of a subset of hepatocellular adenomas (HCAs) in which HNF1A is inactivated. Transformation to hepatocellular carcinoma is thought to be a very rare phenomenon in the HNF1A-inactivated variant of HCA. However, we recently observed 2 cases at our institution, 1 definite hepatocellular carcinoma and 1 possible hepatocellular carcinoma, with loss of LFABP staining, raising the ...
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