Morphologic and Molecular Findings in Myxoid Hepatic Adenomas

Abstract

Myxoid hepatic adenomas are a rare subtype of hepatic adenomas with distinctive deposition of extracellular myxoid material between the hepatic plates. A total of 9 cases were identified in 6 women and 3 men with an average of 59±12 years. The myxoid adenomas were single tumors in 5 cases and multiple in 4 cases. In 1 case with multiple adenomas, the myxoid adenoma arose in the background of GNAS-mutated hepatic adenomatosis. Myxoid hepatic adenomas had a high frequency of malignant transformation (N=5 cases). They were characterized at the molecular level by HNF1A inactivating mutations, leading to loss of LFABP protein expression. In addition, myxoid adenomas had recurrent mutations in genes within the protein kinase A (PKA) pathway or in genes that regulate the PKA pathway: GNAS, CDKN1B (encodes p27), and RNF123. In sum, myxoid adenomas are rare, occur in older-aged persons, have a high risk of malignant transformation, and are characterized by the combined inactivation of HNF1A and additional mutations that appear to cluster in the PKA pathway.

Figure 1.. The morphological findings in myxoid hepatic adenomas are distinctive.

Panel 1A. At low power, the adenoma on the right stands out clearly from the background liver located on the left. Panel 1B. The myxoid material separates the hepatic plates. Panel 1C. At high power, the myxoid material is loose and flocculent. Panel 1D. Within the myxoid adenomas, occasional hyalinized or fibrotic bands of acellular tissue were common. Panel 1E. Focal areas of congestion / hemorrhage could also be seen. Panel 1F. In case 8, the resection specimen contained 6 adenomas and all showed a myxoid morphology, including the smallest ones, as depicted in this image.

Figure 2.. GNAS mutated hepatic adenomas have a distinctive morphology, case 4.

Panel A. On gross examination, the GNAS mutated adenomas tended to have a subcapsular location (arrows). The larger tumor in the center is the myxoid adenoma. Panel B. At low power, the GNAS mutated adenoma is associated with puckering of the liver capsule. The background liver is separated from the adenoma by a black line. Panel C. A smooth muscle actin stain shows the GNAS mutated adenomas are well circumscribed. Panel D. The adenomas have mild lymphocytic inflammation and areas of intratumoral fibrosis that can resemble fibrolamellar carcinoma. Panel E. A higher power image shows cytology and intratumoral fibrosis reminiscent of fibrolamellar carcinoma. Panel F. Inflammation, ballooning, and Mallory hyaline are prominent. Panel G. An immunostain for CRP is strong and diffusely positive. Panel H. The myxoid adenoma on this case is shown.

Figure 3.. Malignant transformation of myxoid hepatic adenomas.

Panel A. The hepatocellular carcinoma component in case 3 stands out from the background adenoma. Panel B. On higher power, the carcinoma is moderately differentiated. Panel C. A well differentiated hepatocellular carcinoma was diagnosed in case 2 because of multifocal convincing reticulin loss.

Figure 4.. Immunostain and electron microscopy findings in myxoid hepatic adenomas.

Panel A. The myxoid adenoma shows loss of LFABP expression. The normal liver is present on the left and stains positive. Panel B. An immunostain for CD34 shows the myxoid material is not present within endothelial lined sinusoids. Panel C. A pCEA shows intact bile canaliculi. Panel D. The myxoid material shows loose fibrillary proteins by electron microscopy.