Hepatocellular Adenoma

Subtype

Prevalence

Clinical

Genotype

Histological appearance

Immunohistochemistry

MRI features

Comments

HNF1α-inactivated

15–18

Biallelic inactivation of TCF1

Steatosis

↓LFABP

Homogeneous fat distribution

β-Catenin activated

35–50

β-Catenin activation

↑Nuclear β-catenin ↓Glutamine synthetase

Increased risk of malignant transformation

Inflammatory

25–35

Predominantly in female patients and frequently associated with alcohol use and obesity

Wild-type TCF1 and β-catenin IL6ST gene mutation

Inflammatory infiltrates, sinusoidal dilatation/telangiectasia, dystrophic vessels, ductular reactions

↑SAA, ↑CRP

Hyperintense signal on T2W images, strong arterial enhancement, persistent enhancement on delayed phase

1/6 cases also have β-catenin mutation

Unclassified

Wild-type TCF1 and β-catenin

Diagnosis of exclusion

HNF1α hepatocyte nuclear factor 1 alpha, TCF1 transcription factor 1, LFABP liver fatty acid binding protein, SAA serum amyloid A protein, CRP C-reactive protein, MRI magnetic resonance imaging, T2W T2-weighted images

13.3 Clinical Presentation

Patients may be completely asymptomatic, and the diagnosis may only be made as an incidental finding by imaging studies, e.g., during the course of investigation of abnormal liver function tests, liver mass on ultrasound, or research for metastasis in patients with a history of cancer.

The clinical presentation is either with a palpable mass lesion or its complications including chronic or acute upper abdominal pain as a result of intratumoral hemorrhage, necrosis, or hepatomegaly and hemorrhagic shock.

The diagnosis may be suspected from MRI characteristics (with typical arterial-type hypervascularized attenuation pattern), but diagnostic biopsy should be considered to confirm the diagnosis of HA.

HA mostly presents as solitary nodule, but two or more tumors may be found; if more than ten nodules are detected, hepatic adenomatosis must be considered. Tumor size is variable with a range of 1–30 cm (usually 8–15 cm). In reports from Southeast Asia and North America, the rate of solitary lesions is 80 and 65.2 %, respectively; in European reports, more than half of patients with HA have multiple lesions: the reason for this difference is unclear [5].

13.4 Evolution

HA is of clinical importance because its tendency is to bleed and to rupture spontaneously, with catastrophic consequences and intraperitoneal bleeding. There is no conclusive evidence to prove a correlation of the size of HA and rupture; some authors report an increased risk of rupture in tumors more than 6.5 cm in size [17]. A report, analyzing the evolution of HAs and their risk of rupture, found that the mean diameter of the lesions in China, Europe, and North America were 10.8, 12.4, and 14 cm, respectively [5]. There are two types of hemorrhage which are mostly observed in HA: hemorrhage inside the HA nodule, usually admixed with necrotic changes, and spontaneous hemorrhagic rupture which can cause subcapsular hematoma and possible hemoperitoneum. In reported series, the incidence of bleeding is around 20–25 % of cases (see Table 13.2), and it is more frequent in HA with sinusoidal dilatation and congestion.

Table 13.2

Published series with more than 15 cases and completed data

Study	Year	HA (n)	Mean diameter (cm)	HCC transformation (%)	Hemorrhage (%)	Resected
Edmondson et al. [18]	1976	42	–	0	69	41
Kerlin et al. [19]	1983	23	9	8.6	69.5	17
Mathieu et al. [20]	1986	27	7.5	0	40.7	27
Leese et al. [21]	1988	18	13	0	50	17
Iwatsuki et al. [22]	1990	25	12	0	16	25
Arrivé et al. [23]	1994	29	5.4	10.3	51.7	21
Pertschy et al. [24]	1994	30	–	0	0	29
Chung et al. [25]	1995	16	5.4	0	75	15
Nagorney [26]	1995	24	9	4.1	16.6	19
De Carlis et al. [27]	1997	19	7.9	10.5	26.3	19
Ott and Hohenberger [28]	1998	23	–	–	17.4	23
Closset et al. [29]	2000	16	8.1	6.2	43.7	16
Ichikawa et al. [30]	2000	24	–	8.3	41.6	13
Reddy et al. [31]	2001	25	5.9	4	12	25
Terkivatan et al. [32]	2001	33	–	0	36.3	19
Decotte et al. [33]	2003	17	–	0	0	17
Toso et al. [34]	2005	23	–	8.7	43.4	23
Erdogan et al. [35]	2006	22	7.2	0	100	22
Van der Windt et al. [36]	2006	48	–	0	27	16
Chaib et al. [37]	2007	28	8	0	10.7	28
Koffron et al. [38]	2007	47	–	0	–	47
Reddy et al. [39]	2007	25	8.5	0	–	25
Buell et al. [40]	2008	25	–	0	–	25
Cho et al. [41]	2008	41	–	4.8	29.2	41
Petri et al. [42]	2008	22	7.7	0	–	22
Bioulac-Sage et al. [16]	2009	128	7	3.6	17.9	128
Deneve et al. [43]	2009	124	–	4	25	119
Dokmak et al. [44]	2009	91	–	9.8	24.1	91
Mounajjed and Wu [45]	2011	35	–	0	20	35
Bunchorntavakul et al. [46]	2011	60	–	0	11.6	25
De Angelis et al. [47]	2014	62	7.2	–	11.8	62

Further, malignant transformation of HAs to HCC has been described by several groups and occurs in 5–9 % of cases ([29, 48], see Table 13.2). The issue of when HA develops into malignancy and which factors influence malignant degeneration are still being investigated. In some reports [5] a total of 5.6 % showed HCC foci within an adenoma upon final pathology; the mean size of the tumor with HCC was larger than the mean tumor diameter in benign HA (11.2 cm vs 7.8 cm). The risk of malignancy is particularly higher for β-catenin mutation HA, which are most frequently associated with glycogenosis type I, androgenic hormone intake, and familial adenomatous polyposis.

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