Focal Nodular Hyperplasia and Hepatocellular Adenoma around the World Viewed through the Scope of the Immunopathological Classification

Abstract

Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are benign hepatocellular tumors. The risk of bleeding and malignant transformation of HCA are strong arguments to differentiate HCA from FNH. Despite great progress that has been made in the differential radiological diagnosis of the 2 types of nodules, liver biopsy is sometimes necessary to separate the 2 entities. Identification of HCA subtypes using immunohistochemical techniques, namely, HNF1A-inactivated HCA (35-40%), inflammatory HCA (IHCA), and beta-catenin-mutated inflammatory HCA (b-IHCA) (50-55%), beta-catenin-activated HCA (5-10%), and unclassified HCA (10%) has greatly improved the diagnostic accuracy of benign hepatocellular nodules. If HCA malignant transformation occurs in all HCA subgroups, the risk is by far the highest in the β -catenin-mutated subgroups (b-HCA, b-IHCA). In the coming decade the management of HCA will be more dependent on the identification of HCA subtypes, particularly for smaller nodules (<5 cm) in terms of imaging, follow-up, and resection.

Figure 1

Adapted from Bioulac-Sage et al., [1]. Algorithm for immunohistochemical (IHC) diagnosis of benign hepatocellular nodules: focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA). Glutamine synthetase (GS) is not always mandatory for the diagnosis of *FNH or **HCA in routine practice. IHC is mandatory for HCA subtyping: markers are presented in grey square with their results positive (+) or negative (−) in tumor (T) and nontumoral liver (NT). LFABP: liver fatty acid binding protein; CRP: C-reactive-protein. Final diagnosis of HCA subtypes is: HNF1a inactivated (H-HCA), inflammatory (IHCA), B-catenin activated (B-HCA), B-catenin activated inflammatory (B-IHCA), or unclassified (UHCA). ^a: GS negativity or positivity limited at the periphery and/or around some veins within HCA. ^b: serum amyloid A staining is usually less sensitive and specific than CRP. ^c: aberrant B-catenin nuclear staining. ^#: needs molecular biology confirmation. ^d: can be difficult to differentiate from FNH.

Figure 2

Practical guidelines for the identification of HCA subtypes (outside the emergency context).

Figure 3

Management of HCA subtypes <5 cm.

Box 1

Clinical and pathological information useful to manage the patient.

Box 2

Pathological record.

Box 3

Reasons to classify hepatocellular nodules using IHC methods.