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Chapter

Challenging Issues in Hepatic


Adenoma
Mirela Patricia Sîrbu Boeți, Beatrice Tivadar,
Ioana G. Lupescu, Vlad Herlea, Mirela Boroș, Dana Tomescu
and Vladislav Brașoveanu

Abstract

Hepatic adenoma is known as a benign lesion encountered mainly in female


patients and classically linked to the administration of oral contraceptives. In the
last decade, the risk factors for its occurrence have changed and so did the sex
ratio. The histopathological classification of hepatic adenomas was found to be
related with certain genetic mutations that determine the risk for malignancy. The
diagnosis of hepatic tumor is correlated with clinical and imaging data in an effort
not only to rule out other tumors but also to distinguish the subtype of adenoma,
which is very important for the management of the patient. The ultimate diagnosis
is established by pathologists by routine histopathological and specific immunohis-
tochemical staining. There are two major issues that pathologists need to recognize:
the presence of β-catenin gene mutation and/or malignant degeneration. The best
imaging examination is considered to be MRI. However, along with MRI, ultra-
sound and computer tomography have proved themselves to be effective not only in
evaluating the number, size, localization, and complications of hepatic adenomas,
but also in identifying their subtype. A detailed presentation of characteristics of
all groups of hepatic adenoma is provided. The means of management of hepatic
adenomas are documented and decisional algorithm is explained, based on certain
criteria.

Keywords: hepatic adenoma, hepatocellular adenoma, liver adenoma, adenomatosis,


hepatectomy, laparoscopic hepatectomy, liver transplantation, liver imaging

1. Introduction

Hepatic adenoma (HA) is a rare, benign tumor of epithelial origin (2% of all
liver tumors [1]) that develops usually in healthy liver [2] and is known to occur
mainly in young female patients, having been linked to the prolonged use of oral
contraceptives [3]. In Europe and North America, it has an incidence of 3/100,000/
year [4]. Even though multiple hepatic adenomas have been described in the litera-
ture, this is a rare occurrence, most of the adenomas being solitary (70–80%), and
thus, often asymptomatic unless they become complicated (voluminous adenomas
causing upper quadrant pain and/or rupture of the tumor with hemoperitoneum
and malignant transformation) [5]. Hepatocellular adenoma is a term sometimes
used instead of hepatic adenoma, being correct in contradiction to liver adenoma

1
Liver Disease and Surgery

or liver cell adenoma, which are less desirable because these two can also include
the bile duct adenoma [6]. Even though the prognosis of this type of tumor is
not well established, it is important to differentiate it from other hepatic tumors
since the hepatic adenoma has a particular therapeutic management. Differential
diagnosis however can be challenging, but can be achieved preoperatively by imag-
ing techniques. Positive diagnosis is a histopathological one and is often obtained
postoperatively [7].

2. Epidemiology

The incidence of HA has increased in recent years, but at the same time, imaging
techniques have improved, and therefore, this higher incidence might be explained
by the better diagnostic techniques nowadays available. Also, in recent years, it
seems to be a change in epidemiology, as more cases of HA in male patients are
described, particularly in Europe and Asia. This may be caused by an increased inci-
dence of obesity, another recognized risk factor of HA. Moreover, in recent years,
more and more cases of malignant transformation of HA have been reported, and
this also might be a result of improved histopathological diagnosis.
Although the link between HA and use or oral contraceptive in women of child-
bearing age is maintained, recent studies have shown other emerging important risk
factors such as metabolic syndrome [8].

3. Risk factors

The most important risk factor seems to be the use of oral contraceptives.
Hepatic adenoma used to be exceptionally rare before the age of oral contraceptives,
but after these became popular as a contraceptive solution, more and more cases
of HA were reported. In women who were long-time users of oral contraceptives,
the incidence was 1 in 30–40,000, whereas in women who have never used oral
contraceptives, the incidence was 1 in 1 million, which proves a strong link between
these two. Hepatic adenomas in women with prolonged use of oral contraceptives
tend to be more numerous, more voluminous, and with a higher risk of spontaneous
rupture and bleeding [9–12].
Another important risk factor that became even more important than other
known risk factors, such as glycogen storage diseases and diabetes mellitus type 2
alone, is the metabolic syndrome. Obesity is more and more prevalent in the general
population, and thus, it became a more important risk factor in this pathology.
Weight loss should be considered as the first therapeutic option in the management
of HA in obese patients [13]. A recent study has proved that bariatric-induced
weight loss results in significant regression of HA in severely obese women, which
emphasizes the role of overweight in HA pathophysiology [14]. Even more so,
patients with metabolic syndrome and hepatic adenomas seem to be associated
with a higher rate of malignization [8]. The association between oral contraceptive
use and metabolic syndrome on one hand and HA on the other tends to prove an
important hormonal sensitivity of the tumor (obesity is associated with higher
estrogen levels), and this is supported by the fact that adenomas may stop their evo-
lution or even regress as a result of oral contraceptive cessation [15]. In spite of this,
immunohistological studies failed to prove the direct effect of these hormones via
steroid receptors in normal and adenomatous hepatic tissue, and so the mechanism
by which high estrogen levels may cause an adenomatous transformation is still
incompletely understood [16]. As a hyperestrogenic state, pregnancy has also been

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Challenging Issues in Hepatic Adenoma
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incriminated as a risk factor, and there have been many reports of ruptured HAs in
pregnant patients with a very high mortality for both mother and child [16–19].
Apart from estrogen, use of anabolic androgens has also been linked to a higher
incidence in HAs, which is being proved not only in body builders but also in
patients treated with steroids for Fanconi syndrome, aplastic anemia, etc. Cessation
of steroid use has also been linked to regression in size of HAs [15].
Hepatic adenoma has also been linked to glycogen storage disease and hepato-
cyte nuclear factor 1A maturity onset diabetes of the young (HNF1A MODY). The
incidence is 51% in patients with type I glycogen storage disease and 25% in those
with type III glycogen storage disease (GSD) [8]. Hepatic adenoma in GSD occurs
before the age of 20 years, is more common in males, and is typically multiple.
Dietary therapy and correction of insulin, glucose, and glucagon levels have been
proved to lead to regression of adenomas [15]. The mechanism by which GSD is
involved in the development of HA is also unknown.
Finally, there seems to be a genetic predisposition, and nowadays, HAs are
believed to result from specific genetic mutations involving TCF1 (transcription
factor 1 gene), IL6ST (interleukin 6 signal transducer gene), and CTNNB1
(β catenin-1 gene) [20].

4. Pathology

HAs present as solitary lesions in most cases (70–80%), although multiple


adenomas can exist of variable sizes. HAs usually occur in the right hepatic lobe.
Macroscopically, HAs present as a smooth, tan-colored lesion, well demarcated
from the normal hepatic tissue in spite of not having a capsule, often with areas
of hemorrhage and necrosis (Figure 1). Large blood vessels that surround it are
the source of hemorrhage in a complicated adenoma. The lack of a fibrous capsule
means that the bleeding can extend into the liver parenchyma unrestricted.
Microscopically, adenomas are made of adenoma cells, which are typi-
cally larger than normal hepatocytes and contain glycogen and lipid inclusions
(Figures 2 and 3). The nuclei are small and regular and mitoses are infrequent.
The normal architecture of hepatic tissue is severely disrupted, with no portal
tracts of bile ducts, while adenoma cells are disposed in trabeculae interspersed
with arteries and thin-walled blood vessels and sinusoids. The absence of bile
ducts is a notable feature that helps in the differential diagnosis of HA with non-
neoplastic liver tissue and focal nodular hyperplasia. Kupffer cells may only rarely
be present in HA.

Figure 1.
Resected specimen after mesohepatectomy for a large IHA.

3
Liver Disease and Surgery

Figure 2.
Normal liver (left) and hepatocellular adenoma (right), HE ×40.

Figure 3.
Hepatocellular adenoma—benign hepatocytes (large, clear, and pale due to accumulation of glycogen)
arranged in plates, cords, and sheets, HE ×200.

Similarities with a well differentiated hepatocellular carcinoma (Edmonson I)


makes the differential diagnosis a challenging one.
Based on an extensively characterized clinical, morphological, phenotypical,
and genotypical profile, four distinct subtypes of HA have been identified [3, 21]:

1. Hepatocyte nuclear factor-1 (HNF-1)—mutated HAs (H-HA)

2. β-Catenin-mutated hepatic adenomas (β-HA)

3. Inflammatory hepatic adenomas (which harbor mutations involving the


interleukin-6 signal transducer) (IHA)

4. Unclassified hepatic adenomas (U-HA).

Inflammatory and HNF1-mutated hepatic adenomas are the most frequent


subtypes (80%).
The first group (H-HA) comprises 35–40% of all patients and almost exclusively
includes women. It is related to the presence of transcription factor 1 gene muta-
tions that inactivate hepatocyte nuclear factor 1α (HNF-1α). The nonfunctioning
HNF-1α protein promotes lipogenesis and hepatocellular proliferation. Moreover,
abnormal HNF-1α protein determines silencing of liver fatty acid-binding protein
FABP1. FABP1 is a gene positively regulated by HNF-1α and expressed in normal

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Challenging Issues in Hepatic Adenoma
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liver tissue, but in H-HA its downregulation results in impaired fatty acid traf-
ficking in hepatocytes, which causes intracellular fat deposition [22]. H-HA is
sometimes associated with maturity-onset diabetes of the young (MODY), type 3,
and familial hepatic adenomatosis. Half of these patients have multiple HAs. More
than 90% have a history of oral contraceptive use. The tumors are characterized
by marked steatosis (Figures 4–7), a very low risk of complications, and a low
risk of malignant transformation. On immunohistochemistry staining, H-HA is
LFABP (liver fatty acid binding protein) negative, which is in contrast with normal
expression in the surrounding nontumoral liver [21]. The sharp contrast between
tumor and adjacent parenchyma in terms of steatosis and LFABP expression enables
delineation of tumor borders which are often irregular and lobulated with often
small HA foci in vicinity.
The second group comprises 10–15% of all patients, includes mainly men, and
is characterized by the presence of mutations that activate β-catenin and cellular
abnormalities. β-Catenin is encoded by catenin β 1 gene (CTNNB1) on chromo-
some 3p21 and represents an important downstream effector of the Wnt/β-catenin
pathway. This pathway is important in liver embryogenesis, cell adhesion, growth,
zonation, and regeneration [22]. An activating β-catenin mutation is also associated
with specific conditions such as glycogen storage disorders or androgen administra-
tion. The phenotype is represented by cellular atypia with high nuclear-cytoplasmic
ratio, nuclear atypia, and pseudoglandular growth pattern. It is identified by
immunohistochemistry due to a strong expression of glutamine synthetase with or
without aberrant cytoplasmic and nuclear expression of β-catenin. β-HA has the
highest risk of malignant transformation than other HA subtypes, and it is very
difficult to be distinguished from the well-differentiated hepatocellular carcinoma
(HCC). Some risk factors are related to β-HA, such as male hormone administra-
tion, glycogenosis, and familial polyposis.
The third group (IHA) includes 50% of all patients and is most common in
overweight women who suffer from metabolic syndrome or have had prolonged
estrogen exposure. Patients with IHA demonstrate both serum and lesional indi-
cators of an active inflammatory response. IHA is characterized histological by
inflammation, marked sinusoidal dilatation or congestion, numerous thick-walled
arteries, and ductular reaction (Figures 8 and 9). This subgroup was previously
named ‘telangiectatic focal nodular hyperplasia.’ The extent of congestion, peliosis,
and hemorrhage is different from case to case. Steatosis may be present in IHA but
is not as extensive as in H-HA. In case of multiple tumors, the amount of steatosis

Figure 4.
Hepatocellular adenoma—HNF1 alpha mutated subtype—steatosis within the tumor, HE ×200.

5
Liver Disease and Surgery

Figure 5.
Hepatocellular adenoma—HNF1 alpha mutated subtype—steatosis and pseudoglandular formations,
HE ×200.

Figure 6.
Hepatocellular adenoma—HNF1 alpha mutated subtype—pseudoglandular formations and steatosis within
the tumor, HE ×200.

Figure 7.
Hepatocellular adenoma—steatosis within the tumor, HE ×200.

varies among the tumors in the same patient. Immunohistochemically, it is distinc-


tive by a strong expression of inflammation-associated proteins such as serum
amyloid A and C-reactive protein at mRNA and protein levels. The genetics of this

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Figure 8.
Hepatocellular adenoma—inflammatory subtype, HE ×200.

Figure 9.
Hepatocellular adenoma—inflammatory subtype, HE ×40, with sinusoidal dilatation and hemorrhage within
the tumor.

group is related to activation of the JAK/STAT pathway underlined by mutations


in different genes. In 60%, there are somatic gain-of-function mutations of the
interleukin-6 signal transducer gene (IL6ST), which is located at chromosome 5q11
and encodes for glycoprotein 130. Gain-of-function mutations in glycoprotein 130
activate JAK–STAT-3 without interleukin-6 binding. The other 40% show overex-
pression of wild-type glycoprotein 130, which activates STAT-3 through an uniden-
tified mechanism. Marked peliosis is probably caused by suppression of albumin
gene, insulin-like growth factor gene IGF1, and/or transthyretin gene. Mutations of
β-catenin may coexist in 10% of IHA (β-IHA). These patients may have signs and
symptoms of systemic inflammatory syndrome, manifested as fever, leukocytosis,
and elevated serum levels of CRP. Abnormal results of liver function tests may
occur, with elevation of alkaline phosphatase and γ-glutamyl transferase. Systemic
AA amyloidosis is a rare complication of HA which causes nephrotic syndrome with
deteriorating renal function. Resection of the tumor is followed by improvement in
renal function and a marked decrease of the serum concentrations of acute phase
proteins [23].
The last group that is unclassified (UHA) accounts for 5–10% of adenomas. For this
group, the genotype is unknown and the phenotype and immunohistochemistry—
unspecific. In this group is also included HA that cannot be classified due to near-total
necrosis or hemorrhage [21].
The first important thing for the pathologist is to correctly identify the
β-catenin-activated HA and to decide when immunostaining is needed. Morphology

7
Liver Disease and Surgery

and additional immunohistochemical markers can discriminate between different


types of HA in more than 90% of cases [24]. Identification of beta-catenin positive
adenomas has important implications in the decision for surveillance and treat-
ment of these patients. Even if very specific, nuclear β-catenin immunostaining is
of low sensitivity in accurate detection of β-HA and β-IHA due to uneven staining
distribution or focal nuclear staining. Therefore, additional molecular biology is
required. It is recommended to perform glutamine synthetase (GS) staining on
every single HA, because GS is one of the target genes in case of β-catenin activa-
tion, and it is usually diffusely and strongly expressed in β-catenin-activated
HA. GS staining can also be patchy or diffuse but less intense and still be an indica-
tion of β-catenin-activating mutations, but in this case, a molecular analysis must
be performed to confirm it.
The second important thing for the pathologist is to correctly recognize foci
of HCC inside HA. The problem is to avoid overdiagnosis in case of mild or focal
cellular atypia. Some HAs may look worrisome due to the presence of architectural
distortion, thicker liver cell plates, extensive pseudogland formation, and decreased
reticulin framework together with increased CD34 staining (Figure 10). These
are called “atypical HA,” “borderline lesions,” and, recently, “well-differentiated
hepatocellular neoplasms of uncertain malignant potential.” Reticulin staining
(Figure 11) is the most powerful tool to identify foci of definite malignant trans-
formation, especially in association with architectural distortion, cellular atypia,
and increased CD34 staining. Glypican 3 is also very useful when it is positive
(Figure 12), but its negativity does not rule out malignancy [25]. In most cases of
HA and occasionally in HCC, the CD34 staining intensity is variable in different
areas and virtually all HCCs have homogenous CD34-positive staining intensity and
density [26]. Total loss of reticulin network and diffuse increased CD34 expres-
sion, possible presence of glypican 3, and increased MIB1 staining are indications
for HCC foci. HSP70 can be also useful. There is no specific phenotype of HCC
developed from HA, but some observed that these HCC are often pigmented or
cholestatic.
The pathologist needs enough samples, some of them at the junction with the
nontumoral liver. For immunohistochemical results, it is mandatory to have a
biopsy of the nontumoral liver for comparison.
Interestingly, certain magnetic resonance imaging (MRI) features seem to
correlate with the histologic subtypes, suggesting that it may be possible to classify
them by MRI [7]. HNF1-inactivated HA and inflammatory HA can particularly be
diagnosed by radiologists with considerable accuracy.

Figure 10.
Hepatocellular adenoma—CD34 immunohistochemical stain for endothelial cells, few sinusoids are seen in the
tumor, ×200.

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Figure 11.
Hepatocellular adenoma—reticulin stain—left normal liver and right hepatocellular adenoma—there is no
loss of reticulin network, Gomori ×200.

Figure 12.
Hepatocellular adenoma—HNF1 alpha mutated subtype—mild lipofuscin deposits revealed by glypican 3
immunohistochemical stain, ×200.

4.1 Adenomatosis

Adenomatosis is a distinct clinical entity and was first described in 1985 [27] and
since then has been defined by the presence of more than 10 adenomas, involving
both hepatic lobes, in the absence of glycogen storage diseases, prolonged use of
steroids, or resolution with steroid cessation [28]. It is estimated that adenomatosis
affects both men and women, and, unlike HA, is correlated with a higher risk of
impaired liver function, manifested as an increase in serum alkaline phosphatase
and GGT levels [27] and also with a higher risk of bleeding. Instead, the malignant
degeneration does not correlate with the number of lesions. There are two dif-
ferent patterns of adenomatosis: (1) the massive pattern, which is defined by the
existence of larger lesions, up to 10 cm, that often result in gross hepatomegaly with
deformed contour of the liver and (2) the multifocal pattern, which is character-
ized by smaller lesions, with diameter less than 4 cm, that rarely deform the liver,
but has a tendency to progress fast and become symptomatic [29]. The etiology of
hepatic adenomatosis is suspected to be linked to congenital or acquired abnor-
malities of hepatic vasculature. In a study of 15 patients with adenomatosis, 5 had
abnormalities in hepatic vasculature: congenital absence of portal vein, portal
venous thrombosis with cavernous modification, and intrahepatic portosystemic
shunts [1, 30].

9
Liver Disease and Surgery

The conditions that predispose to adenomatosis and evolution of the disease


are poorly understood, since the medical literature reports only information in
regard to individual cases or small case series, but some similarities with the HA
are evident: the tendency toward hemorrhage (especially in adenomas larger than
4 cm) and the risk of malignant transformation. Adenomas in hepatic adenomatosis
may be of inflammatory, hepatocyte nuclear factor 1 alpha mutated, or beta-catenin
mutated subtype.

5. Signs and symptoms

Most commonly, HA goes unnoticed due to its lack of signs and symptoms,
but when it does become symptomatic, it is either due to its increase in volume,
tumor necrosis, or complications such as life-threatening intra-abdominal bleed-
ing due to spontaneous rupture of the highly vascularized tumor. Sudden, severe
pain with hypotension in a patient with HA indicates rupture into the perito-
neum, an event associated with a mortality of up to 20 percent if not identified
and/or treated accordingly [9, 31, 32]. The risk of bleeding is difficult to estimate
overall, but it is quite high in patients with symptomatic HAs (25–64%). Tumor
size that exceeds 35 mm has been associated with an increased risk of bleeding
[33]. The risk of bleeding depends on the localization of the tumor. Exophytic
lesions (protruding from liver) had the highest risk of bleeding (67%), followed
by subcapsular ones (19%) and at last intrahepatic HA (11%). Lesions in seg-
ments II and III had more bleeds than those in the right liver (34% versus 19%).
The visualization on imaging of peripheral or central arteries represents a risk
of bleeding comparative with no visible vascularization in the lesion [33]. Also
a long history of contraceptive use and recent hormonal use are risk factors for
bleeding from HA. Young age seems to be associated with an increased incidence
of HA rupture, independent of hormonal treatment duration, suggesting a
need for careful surveillance or prophylactic treatment in this population [34].
Bleeding is graded as intratumoral (grade I), intrahepatic (grade II), or extra-
hepatic (grade III) and represents a potentially life-threatening complication in
patients with HAs.
Hepatic adenomas are diagnosed when they cause epigastric or upper quadrant
pain or during an imaging study done for unrelated ailments, and less commonly
when an abdominal mass is palpated on clinical examination. When HA is suffi-
ciently large and compresses bile ducts, jaundice may become another sign.

6. Diagnosis and differential diagnosis

There are no specific serologic markers or laboratory findings for HA, but cer-
tain findings can lead the diagnosis away from an adenoma and toward a liver cell
carcinoma in case of an increased serum alpha-fetoprotein, or toward a metastasis
in the case of increased serum tumor markers for digestive tract tumors [35].
The definite diagnosis in this pathology is naturally a histological one; however,
obtaining it preoperatively means making a biopsy from a fragile and highly vas-
cular tissue, with significant risk of bleeding. Having to deal with a benign lesion,
and given the fact that the amount of tissue obtained is rarely enough or suitable
for a diagnosis, this risk is not justified. Thus, the diagnosis of this tumor is based
on analyzing a combination of epidemiologic and clinical data and imaging stud-
ies, but often the confirmation of the diagnosis is done by the pathologist, after the
hepatic resection.

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DOI: http://dx.doi.org/10.5772/intechopen.87993

Usually a HA is suspected in a young adult with a singular and asymptomatic


hepatic lesion, but a thorough differential diagnosis should be made and often this
proves to be difficult. The differential diagnosis between adenomas and focal nodu-
lar hyperplasia is usually challenging, but can be done, most of the times, based on
imaging characteristics.

6.1 Imaging in liver adenomas

Imaging in adenomas includes mostly ultrasound, contrast-enhanced ultra-


sound (CEUS), multislice computer tomography (MSCT), and magnetic resonance
imaging (MRI) (Figure 13).

6.1.1 Ultrasound

The most accessible, cost-friendly, and probably responsible for most discover-
ies of asymptomatic HA is the ultrasound, even though it cannot distinguish it from
other liver tumors. On gray scale ultrasound, HA is seen as a well-defined solid,
echogenic mass, but sometimes as complex hyper/hypoechoic, heterogeneous mass
with anechoic areas due to fat, hemorrhage, necrosis, and calcifications; a capsule
may also be seen [36]. Color Doppler US can aid in the distinction from FNH in the
absence of a central arterial signal, FNH having characteristic intratumoral and
peritumoral vessels [37, 38]. Contrast-enhanced ultrasound with sulfur hexafluo-
ride microbubbles (SonoVue or Lumason) greatly improves diagnosis as compared
to US without contrast.

6.1.2 Computer tomography

One of the most accurate imaging tools in diagnosing a HA is contrast enhanced


computed tomography (CECT), on which it appears as a well demarcated tumor,
with characteristic peripheral enhancement during the early phase with subsequent
centripetal flow during the portal venous phase. A heterogeneous consistency is
usually a sign of necrosis, hemorrhage, or fibrosis [5].
Multiphasic computed tomography (CT) has a detection rate of 100% for
adenomas, which is however different per type of examination: nonenhanced 86%,
hepatic arterial-dominant phase (HAP) 100%, portal venous-dominant phase
(PVP) 82%, and delayed 88%. Tumor margins are well defined by a low-attenuation
pseudocapsule in 86% of adenomas and the surface appears smooth, without
lobulated contour, in 95%. Tumor fat and calcifications are uncommon (7%, respec-
tively 5%). Other than areas of fat, hemorrhage, or necrosis, the adenomas show
homogenous enhancement, especially on PVP and delayed-phase scans [39].

Figure 13.
HA located in segment VII as shown by imaging on NECT (A), CECT—arterial phase (B), portal venous phase
(C), parenchymal phase (D), MRI T1w (E), and T2w (F). Atoll sign characterized by a hyper intense band in
the periphery and isodensity in the center of the lesion with respect of the surrounding liver is relevant on CT in
portal venous phase (C). A hyperintense rim in T2 wi is described in inflammatory adenoma (arrow in F).

11
Liver Disease and Surgery

MSCT technique: nonenhanced CT and enhanced triphasic CT: in arterial


(30–35 s after the bolus tracker detection), portal venous (60–80 s after contrast
medium injection), and equilibrium/late phases (after 3–5 min). 1.5 ml/kg of
nonionic iodinated contrast material is injected into an antecubital vein with a rate
of 3 ml/s using a power injector.
CT findings are depending on HA subtype. On nonenhanced CT (NECT), hem-
orrhage within tumor is seen on as hyperdense foci, intratumoral lipid as hypodense
foci (negative density), and focal coarse calcifications are rarely seen (Figure 14).
On contrast-enhanced (CECT), encapsulation is present in ~20% of HAs, best seen
on the late phase (Figure 14). Hypervascularity is most intense and persistent in
inflammatory subtype of HA (Figure 15).
CT is most useful in distinguishing a HA from other liver tumors or lesions: (1)
focal nodular hyperplasia which has a characteristic central star-shaped hypodense
scar, (2) hemangiomas with their peripheral enhancement on arterial phase and
progressive centripetal fill-in pattern, (3) liver cell carcinoma which has a par-
ticular wash-in, wash-out pattern, and (4) singular liver metastases with no fat or
hemorrhage.

6.1.3 Magnetic resonance imaging (MRI)

6.1.3.1 MRI technique

Unenhanced conventional sequences: T2w is useful in detection of focal liver


lesions. T2* is important in the evaluation of iron content and chemical shift artifact
sequences; T1 in/out of phase is important to delineate steatosis or intralesional lipo-
matous content; ssFSE short TE/long TE makes differentiation between cysts and
solid mass; and diffusion is the most sensitive sequence for liver lesion detection.
Contrast enhanced T1: multiphase dynamic 3D acquisitions without and with
intravenous injection of 0.1 ml/kgbw of extracellular or liver-specific contrast para-
magnetic agents (Gd-EOB-DTPA) in arterial phase (AP): detection of hypervascular
lesions, portal venous phase (PVP), late phase (LP), and hepatobiliary phase (HBP).
Imaging key features in HAs are: hypervascularity, fat content, hemorrhage,
and encapsulation. MRI shows some elements better than CT (lipid and hemor-
rhage). HA shows no substantial uptake or retention in contrast enhanced MRI with
Gadoxetate (Primovist). MRI features for adenomas are distinct from FNH. T1WI:
mass with heterogeneous signal intensity; increased signal intensity (due to fat or
recent hemorrhage); decreased signal intensity (necrosis, calcification, old hemor-
rhage) T1 + C: heterogeneous, hypervascular liver mass with foci of fat or hemor-
rhage in a young woman.

Figure 14.
NECT with large liver mass with central calcifications, small lipomatous inclusions, solid components and
necrosis (A), CECT—arterial phase (B), portal venous phase (C), and parenchymal phase (D).

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Figure 15.
CT evaluation: liver adenoma with central necrotic area and encapsulation (arrow).

6.1.3.2 MRI evaluation

Some MRI findings of HAs are similar to CT findings, but MRI is usually more
sensitive in detecting fat from hemorrhage. The appearance of HAs on MRI is highly
variable, especially in T1, but if contrast medium is used, then it may be better
characterized, showing early arterial enhancement and becoming nearly isointense
to liver on delayed images.
On T1-weighted images (T1wi), HA appears as a heterogeneous signal inten-
sity mass. The increased signal of HA is due to fat and recent hemorrhage, and the
decreased signal intensity is due to necrosis, calcification, or old hemorrhage. A
fibrous pseudocapsule may be seen in HA as a hypointense rim. In T2wi, the mass
appears heterogeneous; increased signal intensity corresponds to old hemorrhage
or necrosis, and the decreased signal intensity is due to the fat or recent hemor-
rhage. The peripheral rim (fibrous pseudocapsule) in HA appears hypointense
in liver parenchyma (Figure 16). After contrast injection (T1wi + C) in arte-
rial phase, adenomas are heterogeneous hypervascular masses (inflammatory
HA+++) and in delay phase a pseudocapsule, which is hyperintense comparative
to the normal liver, can be seen. After Gadoxetate-enhanced MR (Gd-EOB-
DTPA), in HA there is no substantial contrast uptake or retention on hepatobili-
ary phase [40].

Figure 16.
MRI evaluation: liver adenoma with central necrotic area and pseudocapsule hyperintense to the surrounding
liver (arrow).

13
Liver Disease and Surgery

MRI with hepatobiliary agents is an important tool not only in differential sub-
type definition but even in surveillance with early identification of complications
and discovery of some signs of HA malignant degeneration [41]. Lesion enlarge-
ment and heterogeneity of signal intensity and of contrast enhancement are signs
of malignant transformation [42].
Imaging recommendations: the best imaging tool is represented by Gadoxetate-
enhanced MRI including multiphase and hepato-biliary phase acquisition [43]. The
best sequence to evaluate fat into HA is T1wi with in and opposed TE.

6.1.3.3 Classification of HAs based on imaging examinations

MRI is the imaging modality of choice for characterization of HA subtypes


[22]. Inflammation, abnormal rich vascularization, peliotic areas, and abundant
fatty infiltration are pathologic findings differently present in the HA subtypes at
multiparametric MRI [41].
HNF1A-mutated adenoma (H-HA): on MRI, the diffuse and homogenous fat
deposition within HA-H determines a specific imaging pattern: on T1-weighted
Gradient-Echo MR, it is hyper- or isointense, with diffuse signal drop-off with
the use of chemical shift sequence (Figure 17). On T2-weight MR, images appears
isointense to slightly hyperintense. Gadolinium-enhanced T1-weighted MR images
show moderate enhancement in the arterial phase, with no persistent enhancement
in the portal venous and delayed phases. Generally, its size is less than 5 cm, and
there are minimal risks of bleeding and malignant transformation [22]. At multi-
detector CT, macroscopic fat deposits can be identified and establish the diagnosis
of H-HA. On CEUS, it has iso- to moderately increased vascularity, mixed filling in
the arterial phase after contrast and isoechoic appearance in the portal venous and
delayed phases.
β-catenin-mutated hepatic adenoma (β-HA): there are no distinctive patterns
established on MRI, multidetector CT, or CEUS, but they usually are hypervascular
with evidence of hemorrhage or necrosis within tumor. Besides the fact that has
the highest risk of malignant transformation (> 10%), it may mimic hepatocellular
carcinoma with strong enhancement during arterial phase and with portal venous
wash-out.
Inflammatory hepatic adenoma (IHA): includes those previously called “telan-
giectatic HA.” It has specific patterns on MRI due to less fat content, sinusoidal
dilation, peliotic areas, and abnormal vessels. On T1-weighted Gradient-Echo
MR images, it is depicted as isointense or mildly hyperintense, without signal
drop-off with the use of chemical sequence, and on T2-weighted MR images, it
becomes bright (diffusely hyperintense). On Gadolinium-enhanced T1-weighted
MR images, it shows intense enhancement during arterial phase that persists in

Figure 17.
HNF1A-mutated HA: diffuse lipid deposition within HA best seen using T1 with TE in and out of phase
(arrow).

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Figure 18.
Inflammatory liver adenoma: hyperintensity T2 wi and hypervascularity of the liver mass through the late AP,
and discreetly hyperintense in portal and late phase.

the portal venous and delayed phases (Figure 18). The atoll sign is specific for IHA
and may be due to sinusoidal dilatation. In up to 30% of cases, there is evidence of
hemorrhage, and a 10% likelihood of malignant degeneration is estimated. At mul-
tidetector CT, IHA is depicted as heterogeneously hyperattenuating mass in NECT
and in CECT shows enhancement features similar to those at MRI. At CEUS, it has
arterial vascularity with centripetal filling, a sustained enhanced rim and central
wash-out in the late venous phase.
Unclassified hepatic adenoma (U-HA) does not fit other profiles of HA subtypes.

6.1.3.4 Differential imaging diagnostic of adenomas

Hepatocellular carcinoma (HCC) may be hard to distinguish on imaging or


pathology. Biliary, vascular, nodal invasion and metastases of HCC typically occur
in older, cirrhotic men [42, 45]. Adenoma occurs in young, healthy women.
Fibrolamellar HCC is shown as a large, lobulated mass with scar and septa inside.
Vascular, biliary invasion and metastases are common.
Focal nodular hyperplasia (FNH) is depicted on MRI + C in arterial phase as
a homogeneously enhancing mass and in all other phases as an isodense mass
comparative to normal liver. In T2WI, a scar is typically seen as hyperintense. On
delayed phase MR, FNH uniformly retains Gadoxetate [44, 45]. Gadoxetic acid-
enhanced MRI can differentiate between HA and FNH with a high sensitivity and
specificity [46].
Hypervascular metastases are usually multiple. The primary tumor (i.e., thyroid,
breast, kidney, or endocrine) must be searched for. CT + C or MRI + C in arterial
phase shows heterogeneous enhancement. In portal and delayed phases, hypervas-
cular metastases may appear isodense, hypodense, or hypointense.

6.2 Nuclear medicine studies

Most HAs have a decreased uptake of Gallium and colloid, early and retained
uptake of hepatobiliary agents, and no uptake on PET scanning.
If radiological studies cannot distinguish HA from HCC and FNH, a combination
of radionuclide imaging, including technetium (99mTc)-sulfur colloid sulfur-colloid,

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Liver Disease and Surgery

Ga, and technetium-99 pyridoxyl-5-methyltryptophan (PMT) uptake may help estab-


lish the correct diagnosis [47]. Most adenomas do not take up technetium Tc-99m
sulfur colloid so they appear as a “cold” spot in the parenchyma of the liver. This
examination is not particularly good in diagnosing an adenoma but in distinguish-
ing one from a FNH, which shows equal or greater uptake of the radiolabeled agent
compared with surrounding liver [48]. 99mTc-labeled DISIDA (dimethyliminoacetic
acid) liver scintigraphy has also been used by some authors for diagnosis of HA [47].
Positron emission tomography (PET) scanning with fluorine-18-fluorodeoxy-
glucose (18FDG) is useful in differentiating HAs from malignant tumors, because
malignant tumors show uptake of 18FDG but not benign tumors, with some excep-
tions like inflammation and abscess.
Although CEUS, CT, MRI, and nuclear studies help in characterization of
hepatic lesions as adenomas, the findings sometimes are nonspecific, and biopsy
and/or resection may still be necessary.

6.3 Detection of malignant transformation

The pathogenesis of malignant transformation of hepatocellular adenoma


is still poorly understood. Some light was recently shed on the mechanisms of
hepatocarcinogenesis, which suggest the importance of telomerase reverse tran-
scriptase (TERT) promoter mutations beside the early event of β-catenin mutation.
Apparently, only the β-catenin mutations that occur on exon 3 and not those on
exon 7–8 are involved in malignant transformation of HA [49]. It still remains
unclear if hepatocellular carcinoma emerges from hepatocellular adenoma or if the
lesions are coincident. Malignant transformation of hepatocellular adenoma has
been reported in 4% of women and 47% of men with HA [50]. The risk of malig-
nancy is very high for β-HA, which is most frequently associated with glycogenosis
type 1, androgenic hormone intake (many of these tumors expressing androgen
receptors in men), and familial polyposis. It is important to remind that no HA sub-
type is devoid of risk of malignant transformation. Men are predisposed to hepato-
cellular carcinoma regardless of etiology, and for this reason, surgical treatment is
strongly recommended for male patients diagnosed with HA. For women, an older
age (50 years or older) or a younger age (15 years or less) is a risk factor for malig-
nant degeneration that must be taken into account to refer these patients to surgeon
for resection or at least to a hepatologist for very close and careful surveillance.
At present, no clinical assessment can distinguish between HA and degenerated
HA, and no rules for surveillance of HA in both sexes are clearly defined according to
subtypes. The methods and the periodicity of following these patients are variable.
Radiological assessments could include CEUS, multidetector raw CT, and dynamic
MRI. CEUS allows more sensitive recognition and specific exclusion of malignancy
compared with CT and dynamic MRI and has the advantage that can be repeatedly
performed without the risk associated with allergic reactions or radiation exposure.
Moreover, MRI has the disadvantage that cannot be performed everywhere in the
world because the technical skills and expertise are very much geographically depen-
dent. Two main features must be taken into consideration at reassessment of these
patients with HA: the size of the tumor and, more important, the hemodynamic
changes that precede the tumor growth [50]. Malignant degenerations are considered
when the tumor was first iso-attenuated when compared with normal liver during the
nonenhanced and delayed phases and appeared homogenous in the early phase but,
at a later examination, it becomes enhanced in the early phase and hypo-attenuated in
the delayed phase. Also, the presence of a nodule within a nodule during the arte-
rial phase is known as a sign of malignancy. β-HA often has cytological atypia and
pseudoglandular pattern, and it is sometimes almost impossible to identify HCC.

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7. Management and current guidelines

The surgeons must be convinced that HA subtypes are important for the man-
agement of the patients. From now on, a diagnosis of HA cannot be conceived
without group classification. The number and location of HA play a great role
in management, but various clinical conditions such as age, sex, etiology, back-
ground liver, or comorbidities must be taken into consideration. Other aspects
also play a role in decision making, like where the patient lives, the degree of his/
her anxiety, and cost of surveillance. The management of patients with HA must
be planned by a complex team formed by surgeons, hepatologists, pathologists,
radiologists, gastroenterologist, molecular biologists, and geneticists.
There are no clear guidelines for the management of HA, because the treatment
depends on many factors such as HA size, number, localization, gender, age, pres-
ence of symptoms, and complications.
In young women treated with contraceptive pills, asymptomatic lesions under
5 cm in diameter should be kept under close observation with CT/CEUS repeated
every 6 months [51] and repeated alpha-feto-protein, all the while ceasing to use
contraceptive pills [52]. Any modification in imaging suggesting a malignant trans-
formation or an increase in the serum tumor marker should lead to liver resection.
There are some authors who advocate resection of adenomas of any size given their
risk of malignization and bleeding, if the resection can be performed with accept-
able risk. The facts that surgical excision guarantees a definitive diagnosis and
long-term cure favor the universal indication of surgery for HA [53].

7.1 Surgical resection

The indications for surgery in nonemergent cases are: HA > 5 cm, female patients
taking oral contraceptives with HA > 3 cm [47], HA with growing size, HA with
HCC or dysplastic foci, β-catenin-activated HA, imaging features of malignant
transformation, increased serum alpha fetoprotein, HA in males regardless of the
tumor size, HA in GSD, symptomatic patients, or when malignancy cannot be
excluded [54]. The type of resection depends mainly on number, size, histological
type, and localization of HA. The resection techniques vary from simple enucleation
to liver transplantation [55]. Liver resection for HA can be anatomic or nonanatomic.
Anatomic resections reported in the literature for HA refer to minor hepatectomies
that imply the removal of the tumor with one or two segments of the liver [56], but
also major hepatectomies like left and right hemihepatectomy, mesohepatectomy
[57], and left or right extended hepatectomy [26, 58]. Nonanatomical resections are
wedge resections [59]. Enucleation seems to be a choice for such benign tumor, but
is not advisable due to the risk of remnant tumor that can cause tumor recurrence or,
worse, malignant degeneration, especially for β-catenin HA. It was speculated that
the classical 1 cm oncological safety margin could be lowered to 0.5 cm for HA. The
safety margin at the edge of resection is mandatory, if any suspicion of HCC exists.
Surgery in elective cases is less than 1% and most tumors can be operated
laparoscopically, with significant advantages [59–61]. A better cosmetic result,
a shorter hospitalization (4 days) with early return to normal life, and a lower
incisional rate are the main advantages that laparoscopy has comparative with
open approach. However, laparoscopy should be performed only in specialized
centers with extensive experience in both hepatic and laparoscopic surgery.
The first non-anatomical laparoscopic liver resection for HA reported by Ferzli
et al. [62] in 1995 was followed one year later by the first anatomic laparoscopic
resection for HA performed by Azagra et al. [63]. Pure laparoscopic procedure
can be performed for HA with no mortality and reduced morbidity even in

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Liver Disease and Surgery

hemodynamic stable patients with ruptured HA [61]. Moreover, some surgeons


consider laparoscopic surgery the standard of care for the treatment of HA [59].
Hand-assisted or “hybrid” techniques are also optional approaches [64] and the
parietal incision is later used for specimen retrieval. In pure laparoscopic surgery,
the specimen is retrieved through a Pfannenstiel incision even when the tumor is
as large as 180 mm [61].
Pringle maneuver can be of great use to minimize the intraoperative blood loss and
it is used by surgeons both in laparotomy and laparoscopy. Some authors consider it
unnecessary for laparoscopic left lateral sectionectomy [60]. Instead, others perform
the maneuver for both atypical and anatomical resections. Laparoscopy is restricted
by the localization of HA involving segments VII and VIII. The half-Pringle maneuver
was associated for right posterior sectionectomy and resulted in less bleeding [65].
Total vascular exclusion of the liver is routinely recommended in high dorsal
resections for HA [66].
Intraoperative blood transfusion is rarely needed and generally is performed
in case of ruptured bleeding adenoma. Conversion of laparoscopy to laparotomy
should be considered just in case of too much bleeding and difficulties for the
anesthesiologist to stabilize the patient.
The high rates of mortality and morbidity previously reported after liver resec-
tion for bleeding HA are recently denied by new evidences [30]. Emergency resec-
tion of ruptured HA has a mortality rate of 5–10%, whereas elective surgery has
a mortality rate of less than 1% [67]. These results are explained nowadays by the
availability of improved hemostatic techniques, excellent anesthesia support, and
postoperative intensive care. In the past, in the presence of signs of hemorrhagic
shock, the mortality was as high as 20% for resection [68]. At present, the mortality
for such patients trends toward zero. Nonsurgical strategies such as arterial embo-
lization or gauze packing have been recommended in order to stabilize the patient
and delay resection to an elective setting. There are situations when intraperitoneal
bleeding from a ruptured adenoma is self-limited and a laparotomy is done just
for biopsy. A recent bleeding adenoma does not necessarily need resection. After
this acute bleeding, some of these tumors regress, others are stationary, and few
rebleed. Transarterial embolization (TAE) can not only stabilize the patient but
also obtain complete avoidance of surgical intervention. Sometimes, repeated
embolization is needed to achieve hemostasis. However, liver resection remains the
best means to achieve hemostasis and also to obtain a thorough histology.

7.2 Liver transplantation

Liver transplantation is an extraordinary choice in a few selected patients,


with multiple HAs, giant HAs [69], or recurrent adenomas that are not technically
resectable [70]. Those HAs considered unresectable are either in close proximity
to major vascular structures or the liver hilum or less than 20% of viable hepatic
parenchyma remains after resection. Liver transplantation for recurrent HA is a
more technically demanding procedure if compared to the cases with chronic liver
disease due to the presence of postoperative adhesions that must be divided before
reaching the liver and also due to difficulties in liver implantation when at least a
major hepatic vein and hepatic pedicle are absent after major hepatectomy [70].
Transplanted liver is generally harvested from a cadaveric donor but living liver
transplantation has also been reported [71]. Due to an expanding armamentarium
and experience in angiographically controlling bleeding from a ruptured HA, liver
transplantation as an ultimate life-rescue therapy remains exceptionally rare, being
reported for spontaneous intra-partum rupture of hepatocellular adenoma [72]
(Algorithm 1).

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Algorithm 1. Management in hepatic adenoma.

7.3 Management of liver adenomatosis

The management of cases with liver adenomatosis is cumbersome. All women


with adenomatosis must discontinue exogenous hormone therapy and should avoid
pregnancies. In the massive pattern of adenomatosis, if larger lesions comprise a
single lobe, a hemihepatectomy or more limited hepatic resection (Figure 19) could
be a wise choice. Laparoscopic left lateral sectionectomy can be a good approach for
those patients expecting a future liver transplantation [73] (Algorithm 2).

Algorithm 2. Management in liver adenomatosis.

Even the resection of only the complicated nodule (i.e., hemorrhagic liver
nodule) seems appropriate as the first step toward enlisting for liver trans-
plantation. Multiple resections are the preferable options in patients with liver

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Liver Disease and Surgery

Figure 19.
Upper left: massive liver adenomatosis that deforms the contour of the left lateral sector. Upper right: a left
lateral sectionectomy is planned and a cotton loop around hepatic pedicle is placed for Pringle maneuver.
Lower left: intraoperative aspect after left lateral sectionectomy. Lower right: sectioned surgical specimen with
evidence of the largest HA.

adenomatosis, unless technically impossible or unsafe. Radiofrequency ablation


or embolization in these patients was successful in some authors’ experience
[74]. Liver adenomatosis becomes an indication for liver transplantation if there
is evidence of malignant transformation or complications [75]. Observing these
changes is possible only if patients are carefully followed on a regular basis with
imaging. Liver transplantation should be considered as the last resort for patients
with adenomatosis. Patients with GSD should undergo transplantation earlier
than other patients with HA because the literature considers this underlying
disease as a risk factor for malignant transformation of adenomas [72]. Like
in transplantation for HCC, imaging diagnosis of vascular invasion should be
considered an absolute contraindication to transplantation. So all the efforts are
directed to early diagnose a malignant transformation of HA, and any suspicion
of malignancy has to be rapidly confirmed by biopsy. Discussion with the patients
with liver adenomatosis about liver transplantation must be initiated when a major
criterion or at least 3 minor criteria are identified. The only major criterion is the
histological proof of malignancy in at least one adenoma. The minor criteria are:
(1) more than 2 serious (life-threatening) hemorrhages, (2) more than 2 previous
hepatectomies, (3) β mutated or inflammatory adenomas, (4) underlying liver
disease (major steatosis and vascular abnormalities), and (5) age > 30 years [72]
(Figure 20).

7.4 Alternative treatment of HA

Other options of treatment include: transarterial embolization or ablation and


radiofrequency ablation. TAE is considered as a safe and effective mini-invasive

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Figure 20.
Liver adenomatosis with a voluminous adenoma of the left liver in a 47-year-old male patient who had a liver
transplantation. A-C. CECT of the liver with adenomatosis. D. Total hepatectomy specimen with numerous
adenomas of various sizes, a voluminous adenoma in the left liver, and blood clots due to intratumoral
bleeding.

procedure to be used in both elective and emergency conditions. For small lesions,
TAE can achieve complete resolution and thus avoidance of liver surgery entirely.
TAE may be also used as means to shrink the tumors to a size that renders them
approachable for subsequent surgical resection [76]. TAE can reduce the size of
large adenomas, multiple adenomas, or adenomas that are in a surgical inacces-
sible localization alleviating the symptoms and reducing the risk of perioperative
bleeding. It has a low rate of complications (8%). These complications associated
with TAE include post-embolization syndrome, temporary renal failure, and cyst
formation [77]. One pyogenic abscess after TAE was also reported as a complication
after TAE for a large HA. No sufficient data exist until now to conclude that TAE
reduces the risk of hemorrhage or malignant transformation of residual HA, despite
reports of a reduction in tumor size.
Radiofrequency ablation has its shortcomings, such as the need of many ses-
sions in order to destruct the tumor completely, but it may be a very good option for
tumors that cannot be operated [78].
Medical treatment such as administration of the SRC inhibitor dasatinib or
JAK1/2 inhibitor ruxolitinib could be a new alternative in the future [79].

7.5 Management of pregnant patient

Pregnancy is no longer considered a contraindication in hepatocellular ade-


noma less than 5 cm. Given the fact that the HA behaves as a hormone-dependent
tumor that seems to grow or regress according to estrogen level increase or
decrease, respectively, it is advised that patients with adenomas who contemplate
pregnancy firstly resolve the liver tumor prior to remaining pregnant [80]. If HA
was diagnosed in a fertile but nonpregnant woman, and if the tumor is greater
than 5 cm or she has experienced adenoma-related complications, resection is
indicated before pregnancy. If HA is incidentally identified during pregnancy,
the best management varies from case to case. For the smaller lesions, a conserva-
tory approach is feasible on the condition of ultrasound follow-up every 6 weeks.

21
Liver Disease and Surgery

Adenomas greater than 5 cm that are discovered during pregnancy need individu-
alized approach. Surgery is recommended during second trimester to minimalize
the risks for both the mother and the fetus. Radiofrequency has been an option
performed during the first and second trimester [18]. Angioembolization poses
the radiation risk to the fetus early in pregnancy and must be avoided in the first
trimester.
Pregnancy induces not only an increased level of endogenous hormones
but also an increased liver vascularity that puts the patient at risk for adenoma
rupture especially in the third trimester [81]. However, a ruptured HA discovered
during pregnancy should be immediately resected by laparotomy or laparoscopy
[28, 82, 83].

7.6 Follow-up of the patients

The great majority of nonresected uncomplicated HA remains stable, in few


cases disappear, and in general do not grow. There is an observation that IHA may
disappear more rapidly.
The follow-up of the patients with H-HA and IHA with complete resection can
be stopped few years after surgery. In case of incomplete resection and with no
significant change in HA size during the first years, the follow-up must be contin-
ued but at longer intervals.
Instead, the patients with β-HA resected or RF ablated must be followed-up
very closely with AFP serum level check and repeated alternating imaging (US,
CEUS, CT, and MRI) in order to early diagnose a possible recurrence and, in a
much worse scenario, a possible malignancy with the same positioning in the
liver [84].

8. Conclusions

The incidence of hepatic adenoma has increased lately as a result of more


frequent imaging investigations performed for reasons not necessarily related
to the presence of this benign tumor. The classical profile of the patient with
adenoma has changed as a result of the emergence of new risk factors. As a result
of research into phenotype, genotype, and imaging and the correlations of these
results with clinical data, it is advisable that the diagnosis of hepatic adenoma
include the subgroup of classification, which indicates the appropriate manage-
ment of the case. The means of fitting the liver adenoma into the four subgroups
are primarily imagistic, of which MRI has an essential role. In the case of insuf-
ficient data for the correct and complete diagnosis of hepatic adenoma, tumor
biopsy is needed percutaneously or after tumor resection. Management of hepatic
adenoma may mean on the one hand careful monitoring to recognize one of the
two worrisome complications—hemorrhage and malignancy—and on the other
hand, the treatment of the tumor, which may be asymptomatic or symptomatic,
uncomplicated or complicated. In the elective cases, surgical resection remains the
gold standard with a clear tendency toward laparoscopic approach in specialized
centers, but in emergency cases caused by adenoma rupture, interventional arte-
riography has gained a net advantage over surgery. For rare cases of recurrent or
extremely bulky hepatic adenomas, for which surgery is not feasible, but also for
cases of liver adenomatosis on certain criteria, liver transplantation from cadav-
eric or living donor has become a reality. Careful monitoring of post-treatment
patients should be continued and adapted according to the therapeutic outcomes
and histopathology of the hepatic adenoma.

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DOI: http://dx.doi.org/10.5772/intechopen.87993

Thanks

We thank our mentor Prof. Dr. Irinel Popescu, MD, PhD, FACS, for giving us the
possibility to use data and iconography of patients that he operated on, in order to
complete writing this chapter.

Author details

Mirela Patricia Sîrbu Boeți1,2*, Beatrice Tivadar2, Ioana G. Lupescu1,3, Vlad Herlea4,5,
Mirela Boroș3, Dana Tomescu1,6 and Vladislav Brașoveanu2,5

1 ‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania

2 Department of General Surgery and Liver Transplantation, Fundeni Clinical


Institute, Bucharest, Romania

3 Radiology Medical Imaging and Interventional Radiology Department,


Fundeni Clinical Institute, Bucharest, Romania

4 Department of Anatomopathology, Fundeni Clinical Institute, Bucharest,


Romania

5 ‘Titu Maiorescu’ University of Medicine and Pharmacy, Bucharest, Romania

6 Department of Anesthesiology and Intensive Care, Fundeni Clinical Institute,


Bucharest, Romania

*Address all correspondence to: patriciaboeti@gmail.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms
of the Creative Commons Attribution License (http://creativecommons.org/licenses/
by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.

23
Liver Disease and Surgery

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