β-Catenin Activated Hepatocellular Adenoma: A Report of Three Cases in Korea

Abstract

Hepatocellular adenoma (HCA) is an uncommon benign hepatic tumor, and the use of oral contraceptives is known to contribute to the development of HCA. Recently, a genotype and phenotype classification system for HCA was suggested, and malignant transformation to hepatocellular carcinoma (HCC) was shown to be strongly associated with activating mutations in β-catenin. Here, we report three cases of HCA in Korean patients: 7-cm, inflammatory and β-catenin-activated HCA with HCC transformation in a 46-year-old man; 13-cm, β-catenin-activated HCA with cytological atypia in a 23-year-old woman; and 10-cm, pigmented, inflammatory and β-catenin-activated HCA in a 36-year-old man. All cases exhibited the nuclear expression of β-catenin and diffuse cytoplasmic expression of glutamine synthetase upon immunohistochemical staining. All tumors were completely resected, and the patients were followed for 3 to 6 years with no evidence of local recurrence or metastasis.

Pigmented hepatocellular adenomas have a high risk of atypia and malignancy

“…10,15 The findings in this study demonstrate the immunophenotype in pigmented adenomas is heterogeneous. HNF-1α inactivation is the most common phenotype overall, and is the most common phenotype in the subgroups of hepatocellular adenomas without atypia and hepatocellular adenomas with atypia (hepatocellular neoplasm of uncertain malignant potential).…”

“…It is this latter category that is typically referred to as pigmented adenomas in the literature. [10][11][12][13][14][15][16] Because we noticed that pigmentation in hepatocellular neoplasms has a spectrum of intensity and distribution, and because of the lack of a clear delineation of what constitutes a 'heavily pigmented adenoma' in previous studies, we decided to include any lesion containing 'easily identifiable pigment' in this series, ie, lesions with pigment visible at 100 × magnification. Hence, the latter criterion was used in this study as a reproducible feature in all pigmented hepatocellular neoplasms.…”

“…10,15 Furthermore, the malignant potential of these lesions is still unclear; as some studies have suggested that these lesions are essentially benign, 12,13 whereas others have described atypia and malignant transformation. 10,15 Finally, although believed to be rare, the exact frequency of pigment deposition in hepatocellular adenomas is unknown.…”

“…For instance, although pigment deposition in hepatocellular adenomas has been reported in rare cases (often referred to as pigmented hepatocellular adenoma) [10][11][12][13][14][15] and even rarer instances of hepatocellular carcinoma, 16,17 the overall pathological features of pigmented hepatocellular neoplasms have not been well characterized. A total of eight cases of pigmented hepatocellular adenomas have been reported in the literature, [10][11][12][13][14][15] but the phenotype of only two cases has been characterized.…”

“…A total of eight cases of pigmented hepatocellular adenomas have been reported in the literature, [10][11][12][13][14][15] but the phenotype of only two cases has been characterized. 10,15 Furthermore, the malignant potential of these lesions is still unclear; as some studies have suggested that these lesions are essentially benign, 12,13 whereas others have described atypia and malignant transformation. 10,15 Finally, although believed to be rare, the exact frequency of pigment deposition in hepatocellular adenomas is unknown.…”