Malignant Transformation of Hepatic Adenoma in Glycogen Storage Disease Type-1a: Report of an Exceptional Case Diagnosed on Surveillance Imaging

Abstract

Hepatocellular adenoma is a heterogeneous group of benign neoplasms arising from hepatocellular cells and can be subclassified into four major groups based on genotypic and phenotypic characteristics. These four subtypes are hepatocyte nuclear factor (HNF) 1α-inactivated, β-catenin-activated, inflammatory, and unclassified adenomas. Immunohistochemistry studies have demonstrated that since β-catenin-activated adenomas have a higher risk of malignant transformation, the identification of the subtype of adenoma remains crucial in patient management. However, malignant transformation of hepatic adenoma without β-catenin overexpression can be seen in 30-65% cases. We report a case of malignant transformation of hepatic adenoma without overexpression of β-catenin in a 31-year-old man with a known glycogen storage disease (GSD) Type-1a, which was diagnosed on surveillance magnetic resonance imaging (MRI). The MRI showed a mild interval increase in one lesion with relative stability of the other adenomas. The lesion was presumed to be suspicious for a hepatocellular carcinoma (HCC) and was confirmed on pathology.

Keywords: glycogen storage disease; hepatic adenoma; hepatocellular carcinoma; malignant transformation; β-catenin mutation.

Figure 1

31-year-old man with known glycogen storage disease Type-1a undergoing surveillance imaging. Dynamic multiphase contrast-enhanced MRI obtained in May 2014. (a) Pre-contrast T1W axial image shows two hepatic lesions in segments 4 (double arrows) and 8 (single arrow). (b) T1W axial image (arterial phase) shows variable heterogeneity foci of both of the lesions and arterial enhancement. (c) T1W axial image (venous phase) shows persistent enhancement of hepatic lesions. (d) T1W axial image (delayed or equilibrium phase) shows subtle washout in both of the lesions; posterior lesion also shows peripheral rim enhancement (double arrows).

Figure 2

31-year-old man with known glycogen storage disease Type-1a undergoing surveillance imaging diagnosed with hepatic adenoma. (a) T1W opposed-phase axial image shows diffuse loss of intensity of hepatic parenchyma (asterisk), which suggests the presence of diffuse hepatic steatosis. Two hepatic lesions in segments 4 and 8 are relatively hyperintense on the background of steatosis and lack microscopic fat. (b) T1W in-phase axial image shows two hepatic lesions in segments 4 (double arrows) and 8 (single arrow). (c) Fat-suppressed T2W axial image demonstrates isointense to slightly increased intensity of the above-described hepatic lesions (see the corresponding arrows), with an eccentric, ill-defined, T2-hyperintense possible scar.

Figure 3

31-year-old man with known glycogen storage disease Type-1a undergoing surveillance imaging. Dynamic multiphase contrast-enhanced MRI obtained in Nov 2014 with gadolinium-EOB-DTPA. (a) Pre-contrast fat-suppressed T1W axial image shows two hepatic lesions in segments 4 (double arrows) and 8 (single arrow). The anterior lesion (single arrow) shows interval decrease in size, whereas the posterior lesion is slightly increased in size compared to MR dated May 2014 [Figure 2]. (b) Fat-suppressed T1W axial image (arterial phase) shows arterial enhancement of both hepatic lesions. (c) Fat-suppressed T1W axial image (venous phase) shows persistent enhancement of hepatic lesions; however, the anterior lesion (single arrow) appears fainter. (d) Fat-suppressed T1W axial image (delayed or equilibrium phase) shows remarkable washout in the posterior lesion (double arrows) with well-evident peripheral rim enhancement. (e and f) Fat-suppressed T1W axial image (hepatobiliary phases at 10 and 20 min, respectively) shows peripheral retention of the contrast in the anterior lesion (image f, star), which can be seen with inflammatory adenomas. The posterior lesion gradually becomes hypointense to the liver parenchyma and shows no uptake of contrast.

Figure 4

31-year-old man with known glycogen storage disease Type-1a undergoing surveillance imaging. Index images of two hepatic lesions with an interval of 6 months. (a) Fat-suppressed T1W fat post-contrast image acquired in Nov 2014. (b) Fat-suppressed T1W fat post-contrast image obtained in May 2014. The anterior lesion (single arrow) shows interval decrease in size on follow-up imaging, whereas the posterior lesion (double arrows) is slightly increased in size.

Figure 5

31-year-old man with known glycogen storage disease Type-1a. Post-biopsy histopathology of suspicious lesion seen on imaging. There is lack of portal tracts in all fragments. (a) In low-power magnification (hematoxylin and eosin stain), there is moderate steatosis (thin arrows) with many ballooned cells (thick arrow), some containing Mallory–Denk bodies (blue arrow). (b) In low-power magnification (hematoxylin and eosin stain), there are increased unpaired arteries (arrows). (c) In low-power magnification, there is focal Glypican-3 staining of the tumor cells. (d) In higher magnification, a reticulin stain shows focal loss of the reticulin framework (arrow).