There are a total of ten cases of both MODY 3 and HCA phenotypes reported in the literature to date; incomplete penetrance for HCA was observed, and all the patients with HCA developed diabetes.
Scientific research over the period of three decades has reported it as an important player in various liver malignancies such as hepatocellular cancers (HCCs), hepatocellular adenoma (HA), and a more specific HNF-1α-inactivated human hepatocellular adenoma (H-HCAs).
HCAs have been divided into four subtypes based on molecular and pathological features: hepatocyte nuclear factor 1α-mutated HCA, inflammatory HCA, β-catenin-mutated HCA, and unclassified HCA.
Potential predictors included age, body mass index, and HCA diameter at diagnosis (T0), HCA-subtype (hepatocyte nuclear factor 1α inactivated HCA, inflammatory-HCA, unclassified HCA) and "T0-T1 regression-over-time" (percentage of regression between T0 and first follow-up (T1) divided by weeks between T0 and T1).
After initial diagnostic and aetiologic uncertainty HNF1A germline mutation c.815G>A (p.Arg272His) was confirmed 8 years later.No HCA-related complications occurred.
Liver fatty acid-binding protein, serum amyloid A, C-reactive protein, prostaglandin D2 synthetase, GS, and β-catenin can be used either on biopsy or surgical specimen to classify hepatocellular adenoma into hepatocyte nuclear factor (HNF-1α) inactivated (steatotic), inflammatory, with dysregulation of sonic hedgehog and prostaglandin pathways, β-catenin mutated, and unclassified.
A molecular classification has divided HCA in several subgroups linked with risk factors, clinical behaviour, histological features and imaging: HNF1A inactivated HCA, Inflammatory HCA, CTNNB1 mutated HCA in exon 3, CTNNB1 mutated in exon 7 and 8 HCA, sonic hedgehog HCA and unclassified HCA.
HAs presented as a heterogeneous group, with loss of PTEN observed in the inflammatory and HNF1A-mutated subtype and relatively intact PTEN expression in HA with nuclear β-catenin overexpression.
The expression in HA was variable and differed between molecular subtypes of this neoplasm: inflammatory and HNF1A mutation-associated type are characterized by overexpression of c-MET to an extent comparable with poorly-differentiated HCC, whereas Wnt/β-catenin dysfunction-associated type lacks overexpression, and the amount of c-MET protein accumulated in its cells is similar to the levels in non-neoplastic tissue and well- to moderately-differentiated HCC.
Four subtypes of hepatocellular adenomas (HCA) are recognized: hepatocyte-nuclear-factor-1α mutated (H-HCA), β-catenin-mutated type with upregulation of glutamine synthetase (b-HCA), inflammatory type (IHCA) with serum-amyloid-A overexpression, and unclassified type.
Hepatocellular adenomas (HCAs) are heterogeneous group of benign tumors; three pathomolecular subtypes have been identified so far: hepatocyte nuclear factor 1 α-inactivated HCA (H-HCA) (35-40%), inflammatory HCA (I-HCA) (>50%), β-catenin activated HCA (10%).
HCAs are categorized into four subtypes on the basis of genetic and pathological features: hepatocyte nuclear factor 1α-mutated HCA, β-catenin-mutated HCA, inflammatory HCA, and unclassified HCA.
The HCA cases were further subclassified into hepatocyte nuclear factor 1α inactivated (29%), inflammatory (32%), inflammatory with β-catenin activation (3%), noninflammatory β-catenin activated (0%), and unclassified (36%).
Key features include metabolic alterations (induced by defects in HNF1A), oncogene-induced inflammation (activation of JAK-STAT signaling in inflammatory adenomas), and an association between activation of Wnt/β-catenin signaling and progression of HCAs in hepatocellular carcinomas.
The histological features of these tumors were similar to those of focal nodular hyperplasia (FNH) with a central scar and HCA; however, these tumors were diagnosed as HNF-1α-inactivated HCA by immunohistochemistry according to the criteria of the current World Health Organization (WHO) classification.
In contrast, no HNF1A inactivation was observed, showing a different molecular subtype distribution in GSD-associated HCA from that observed in sporadic HCA (p = 0.0008).