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.

Hepatocellular adenoma: what we know, what we do not know, and why it matters

“…Myxoid changes can be present to a variable extent, and many of these cases show HNF1A abnormalities (e.g. heterozygous and monoallelic) and concurrent variable abnormalities of other genes 61,62 …”

“…heterozygous and monoallelic) and concurrent variable abnormalities of other genes. 61,62 Loss of liver fatty acid-binding protein (LFABP) is the hallmark of H-HCA, but lack of LFABP in a hepatic focal lesion does not automatically lead to the diagnosis of H-HCA. Loss or diminished expression of LFABP can be seen in HCC without any association with HCA.…”

Pathologic Diagnosis of Well-differentiated Hepatocellular Lesions: A Practical Approach to Diagnosis With Particular Focus in Core Needle Biopsies and Utilization of Ancillary Techniques

“…This rare subtype of adenoma was recently described, characterized by the deposition of myxoid material between the hepatic plates. 41 These also have HNF1A-inactivating mutations and loss of LFABP protein expression. In addition to HNF1A inactivating mutations, these tumors have recurrent mutations in genes within the protein kinase A pathway or in genes that regulate the protein kinase A pathway, such as GNAS, CDKN1B, and RNF123.…”

Hepatocellular adenoma: Where are we now?

“…Myxoid HCAs are characterized by the deposition of myxoid materials between the hepatic cords within the tumor[ 41 - 44 ]. In addition to loss of L-FABP expression and/or HNF-1A mutation as documented in all myxoid HCAs, a recent study identified recurrent mutations in genes within the protein kinase A (PKA) pathway or in genes that regulate the PKA pathway, such as GNAS, CDKN1B (p27) and RNF123, in myxoid HCAs[ 44 ]. Myxoid HCAs are often seen in individuals with older age and carry a high risk of malignant transformation[ 3 , 44 ].…”

“…In addition to loss of L-FABP expression and/or HNF-1A mutation as documented in all myxoid HCAs, a recent study identified recurrent mutations in genes within the protein kinase A (PKA) pathway or in genes that regulate the PKA pathway, such as GNAS, CDKN1B (p27) and RNF123, in myxoid HCAs[ 44 ]. Myxoid HCAs are often seen in individuals with older age and carry a high risk of malignant transformation[ 3 , 44 ]. It is still controversial whether this is a rare variant of H-HCA with additional mutations or a distinct subtype of HCAs.…”