1 Benign Liver Lesions

Transcription

1
Benign Liver Lesions
RONALD S. CHAMBERLAIN, MD, MPA
DOUGLAS DECORATO, MD
WILLIAM R. JARNAGIN, MD
Benign liver lesions are often found serendipitously
on evaluation of unrelated conditions whereas some
patients with known hepatic malignancies will have
coexistent benign hepatic lesions. Symptoms related
to these lesions will bring them to attention in some
patients; in rare cases, the first manifestation will be
a catastrophic event such as spontaneous rupture and
hemorrhage. In most instances, 83 percent of liver
lesions identified serendipitously are benign.1–2 In
nearly all of these instances, the surgeon will be
called upon to make decisions regarding further
work-up and therapeutic options. The appropriate
treatment of benign liver lesions requires a thorough
knowledge of their natural history and mature clinical judgment.
Benign liver lesions may be solid or cystic and
may arise from hepatocellular or biliary epithelial
cells or mesenchymal cells. A number of miscellaneous disorders that may masquerade as liver tumors
have also been described (Table 1–1). The relative frequency of different types of hepatic tumors is difficult
to determine, but more than 50 percent of incidentally
discovered hepatic lesions are hemangiomas or focal
nodular hyperplasias (FNH) (Table 1–2), and simple
cysts account for another large proportion. Several
other benign liver tumors have been described, but
nearly all are extraordinarily uncommon and are
unlikely to be encountered in general practice.
While patients with symptoms directly attributable to a benign hepatobiliary tumor should be considered for resection, the majority are asymptomatic,
and resection or other interventions are seldom warranted. However, certain benign tumors are associated
with life-threatening complications (eg, hemorrhage)
or malignant transformation and should be resected
even in the absence of symptoms. Establishing a firm
diagnosis relies heavily on the radiographic appearance of these lesions, which in turn requires highquality imaging studies and experienced radiologists.
Advances in imaging technology have greatly
improved the clinician’s ability to differentiate among
the various benign lesions, but diagnostic uncertainty
remains a persistent problem. Indeed, a common indication for resecting “benign” liver tumors is the
inability to exclude a malignancy or to exclude a
Table 1–1. BENIGN LIVER TUMORS
Cell of Origin
Epithelial
Hepatocellular
Cholangiocellular
Other
Mesenchymal
Endothelial
Tumor
Focal nodular hyperplasia
Hepatocellular adenoma
Regenerative nodule
Biliary adenoma
Biliary cystadenoma
Simple cyst
Epitheliod leiomyoma
Hemangioma
Hemangioendothelioma (adult,
infantile)
Mesothelial
Solitary fibrous tumor (benign
mesothelioma, or fibroma)
Adipocyte
Lipoma
Myelolipoma
Angiomyolipoma
Other
Tumor
Pseudotumor
Biliary hamartoma
Focal fatty infiltration
Adrenal neoplasm
Inflammatory pseudotumor
1
2
HEPATOBILIARY CANCER
Table 1–2. DIAGNOSTIC FREQUENCY
OF INCIDENTAL LIVER TUMORS
Tumor
Relative Frequency (%)
Hemangioma
Focal nodular hyperplasia
Metastatic tumor
Hepatocellular adenoma
Focal fatty infiltration
Hepatocellular carcinoma
Extrahepatic process
(abscess, adrenal tumor)
Other benign hepatic process
52
11
11
8
8
6
3
1
Reprinted with permission from Little JM. Benign tumors of the liver. In:
Terblanche J, editor. Hepatobiliary malignancies: its multidisciplinary management. London: Edward Arnold; 1994. p. 235–49.
benign lesion that should be resected (eg, liver cell
adenoma). In our experience with over 155 patients
with benign hepatic tumors, inability to exclude
malignancy was the indication for resection in 46 percent of patients (Table 1–3).3 Risk of malignant transformation or rupture and a tumor that has ruptured are
less common indications for surgical intervention.
Patients with newly diagnosed hepatic lesions
should be approached systematically and all information reviewed critically to avoid premature and
erroneous diagnoses. A careful history may provide
some useful information, such as information about
the patient’s previous or current use of oral contraceptives. In patients with symptoms possibly related
to the tumor, specific details are important since
such symptoms may be arising from a coexistent
condition, such as peptic ulcer disease or cholecystitis, and may be entirely unrelated to the liver
lesion. Physical examination is typically unrevealing
unless the tumor is quite large; in this setting, pain
or abdominal discomfort is often present. Laboratory tests, including liver function tests, are gener-
ally normal in patients with asymptomatic liver
tumors and are therefore usually not helpful for
establishing the diagnosis. Serum tumor markers
such as α-fetoprotein (AFP), carcinoembryonic
antigen (CEA), and CA-19-9 are almost never elevated in benign liver tumors. Any previous computed tomography (CT) scans should be obtained for
comparison since benign tumors frequently evolve
over many years.
Radiologic studies are critical in evaluating
benign hepatic processes and often provide a precise
diagnosis based on the characteristic appearance of
the lesion. In most situations, multiple studies providing complementary data are required (Table
1–4). Ultrasonography (US) is the most common
initial study and effectively differentiates cystic and
solid lesions. Contrast-enhanced CT with precontrast images, arterial dominant-phase images, and
delayed imaging (a so-called triple-phase CT scan)
may provide precise diagnostic information while
also determining the location and extent of the
lesion. Magnetic resonance imaging (MRI) may be
the most useful imaging modality for differentiating
between benign and malignant tumors and also for
distinguishing among the various types of benign
solid tumors. Although angiography was previously
a common imaging technique, it has generally been
replaced by noninvasive imaging modalities.
Angiography occasionally may be useful for distinguishing hepatic adenoma from FNH, which is an
important distinction since treatment recommendations are different. In our experience, the majority of
benign hepatobiliary lesions can be diagnosed accurately without invasive studies. Strategies for evaluating patients with incidentally discovered hepatic
lesions are described in detail in Chapter 2.
Table 1–3. EXPERIENCE IN MANAGING PATIENTS WITH BENIGN LIVER TUMORS BETWEEN 1992 AND 1999*
Diagnosis
Hemangioma
FNH
Adenoma
Cystadenoma
Total
Patients
Mean Age
97
42
12
4
155
52
38
34
45
47
Resected (%)
39
18
8
3
68
(40)
(43)
(67)
(75)
(44)
? Malignant (%)†
13
11
6
1
31
(13)
(25)
(50)
(25)
(46)
Symptoms (%)†
48
18
8
2
36
(49)
(44)
(67)
(50)
(53)
*Experience at Memorial Sloan-Kettering Cancer Center.
†
The percentage of the total number submitted to resection.
FNH = focal nodular hyperplasia.
Reprinted with permission from Charny CK, Jarnagin WR, Schwartz LH, et al. Benign liver tumors: radiologic and surgical management. Br J Surg 2000.
[In press]
3
Table 1–4. RADIOGRAPHIC IMAGING OF COMMON BENIGN LIVER TUMORS
Imaging Modality
Tumor
US
CT
MRI
Tc-99m RBC Scan
Tc-99m SC Scan
Hemangioma
Hyperechoic
Well demarcated
Increased
vascular flow
Central venous
pooling
Delayed central
filling
Very sensitive
Isodense on noncontrast
scan
Contrast-enhanced scan
shows delayed nodular
enhancement from the
periphery of the lesion
Very sensitive
Isodense on T1
Highly specific
Very sensitive
Not indicated
Hyperdense on T2
Gadolinium-enhanced
scan has similar
findings to contrast
CT
Blood pooling of
radionucleotide
Nonspecific
?Hyperechoic
Isodense on
noncontrast CT
May be well demarcated
on contrast CT, with
central scar—often
isodense
Isodense on T1
and T2
Early hyperdense
appearance after
gadolinium
Not indicated
Nonspecific
Hyperechoic
Nonspecific
Hyperechoic
Nonspecific
Focal nodular
hyperplasia
Hepatic
adenoma
Nonspecific
?Hyperechoic
Increased blood
flow on duplex
scanning
Takes up Tc-99 SC
Contains bile ducts and
Kupffer’s cells
Nonspecific
Generally does not take
up Tc-99 SC because
of lack of bile ducts
and Kupffer’s cells
Nonspecific
CT = computed tomography; MRI = magnetic resonance imaging; T1 = T1-weighted MRI; T2 = T2-weighted MRI; Tc-99m RBC = technetium-99m-labeled red
blood cell; Tc-99m SC = technetium-99m sulfur colloid; US = ultrasonography.
SOLID TUMORS
Hemangiomas
Hemangiomas, the most common benign solid
tumors of the liver (see Table 1–2),4–6 occur in two
variants, capillary and cavernous. Capillary hemangiomas are far more common but are clinically
insignificant. They tend to be small hypervascular
lesions (< 2 cm) encountered at the time of laparotomy and may be the source of considerable diagnostic uncertainty. Establishing the diagnosis and
excluding a malignancy are all that is required.
Cavernous hemangiomas are more relevant clinically because of the potential for complications and
associated symptoms.4,7,8 Cavernous hemangiomas
may vary in size from less than 1 cm to 30 to 40 cm
or more (“giant hemangiomas”)9 (Fig. 1–1). The size
of the lesion appears to correlate with symptoms, and
it is the large pedunculated tumors that are most commonly symptomatic and that are encountered at operation.4,7,10 These tumors are usually sharply demarcated from surrounding liver tissue and may be partly
necrotic or fibrotic (Fig. 1–2). In some instances,
infarct of the hemangioma may cause fibrosis or calcification, making it difficult to distinguish from
other benign or malignant tumors. The acute nature of
some symptoms related to hemangiomas may not be
related to increase in size but rather to thrombosis and
infarction of part of the tumor.
The incidence of cavernous hemangiomas has
been documented to be as high as 7 percent in one
autopsy series,5 and these tumors occur more commonly in adults than in children.4 Their etiology is
unclear, but cavernous hemangiomas appear to represent progressive growth of congenital lesions. The
incidence has been reported as between 1.3 to 6
times higher in women than in men,4,7,8 prompting
some researchers to suggest that sex hormones are
somehow involved in stimulating growth and producing symptoms. However, sex hormones have not
been etiologically linked to the development of
hemangioma, and autopsy series have reported a
nearly equal sex incidence.10
Pathology
Hemangiomas are typically well demarcated and
distinct from the surrounding hepatic parenchyma.
The sharp interface between the tumor and the normal liver parenchyma permits surgical enucleation
in most cases. However, not all of these tumors can
4
be enucleated, and it is the histologic features of the
tumor-liver interface that defines how easily a
parenchymal-sparing technique may be utilized. In
our experience, over half of these lesions were
amenable to enucleation while the remainder
required formal hepatic resection.3
Histologically, four variants of the interface
between the hemangioma and normal liver have
been described. A fibrolamellar interface, characterized by a capsule-like fibrous ring of variable thickness, is most common. In this situation, blood vessels either traverse the fibrous lamella or parallel the
A
B
Figure 1–1. Intraoperative views of a giant hemangioma during enucleation. A, Intraoperative view
of a giant hemangioma involving the left liver. The tumor is held upward to reveal the porta hepatis.
A loop (blue) has been passed around the left hepatic artery, and the gallbladder is visible between
the tumor and the normal-appearing right liver. B, A different view, showing the full extent of the tumor.
periphery of the hemangioma. The normal hepatic
parenchyma may be atrophic, and a plane between
the hemangioma and the normal liver tissue can be
well defined. A second variant, the “interdigiting”
pattern, is marked by the lack of a fibrous lamella
surrounding the hemangioma, the lamella being
replaced by an ill-defined plane between the normal
liver tissue and the vascular channels of the hemangioma. This tumor can be quite hazardous to remove
5
without a formal resection. Unfortunately, the presence of this variant is usually only manifest after an
initial attempt at enucleation results in unanticipated
bleeding. The other two histologic variants of the
hemangioma-liver interface are a compression interface, in which the periphery of the tumor is well
demarcated in the absence of a fibrous lamella and
in which the surrounding liver parenchyma demonstrates marked atrophy, and an irregular or spongy
A
B
Figure 1–2. Cavernous hemangioma. A, The gross appearance of a cavernous hemangioma on cut
section. B, A sponge-like architecture with venous lakes is the characteristic histologic appearance.
6
interface characterized by an ill-defined margin. The
latter variant may appear to be intercalated into the
surrounding liver parenchyma at various points,
making enucleation difficult. Despite the invasive
appearance of this histologic variant, hemangiomas
are not premalignant lesions.
Generally, the histologic diagnosis of a cavernous hemangioma is straightforward (see Fig.
1–2). Rarely, an atypical hemangioma may be mistaken for other liver conditions including peliosis
hepatis, hemorrhagic telangiectasia (Osler-WeberRendu disease), hemangioendothelioma, and other
malignant vascular tumors. Appropriate correlation
with the patient’s age, sex, medication history, and
clinical condition normally resolves such diagnostic
dilemmas. Although the diagnosis of cavernous
hemangioma can be made on histologic review, a
percutaneous biopsy should be avoided as this may
result in uncontrollable hemorrhage. Symptomatic,
large, or indeterminate lesions should be managed
surgically.
Clinical Presentation and Evaluation
The true incidence of symptoms caused by hemangiomas is unclear but is probably lower than that
reported in most surgical series as the presence of
symptoms is a major indication for resection. In our
experience, approximately half of patients presented
with symptoms.3 Thus, many patients are asymptomatic, and the tumors are discovered incidentally
when a radiologic investigation or laparotomy is performed for other indications. According to literature
reports, the majority of hemangiomas that come to
medical attention are found in young women (mean
age of 45 years).
The most commonly reported symptoms associated with hemangioma are abdominal pain, increasing abdominal girth, early satiety, nausea, vomiting,
and/or prolonged fever. Rare presentations have
been reported, including obstructive jaundice, biliary colic, torsion of a pedunculated lesion, gastric
obstruction, pulmonary embolism, and spontaneous
rupture with intraperitoneal hemorrhage.4,7,8 Severe
thrombocytopenia and the development of a consumptive coagulopathy have also been associated
with cavernous hemangioma of the liver. Although
the term Kasabach-Merritt syndrome was initially
used to describe thrombocytopenia and afibrinogenemia associated with hemangiomas of the skin and
spleen in infants, this term is now often used to
describe similar coagulopathies in children and
adults (rare) with hemangiomas of the liver.11
Symptoms from hepatic hemangioma are generally attributed to rapid expansion of the tumor or to
thrombosis and infarction that result in stretching or
inflammation of Glisson’s capsule. A very large
hemangioma may occasionally present as a palpable
nontender mass in the right upper quadrant; more
often, physical examination reveals only a vague
upper abdominal tenderness with no mass. It may be
possible to detect a bruit over the liver if the hemangioma is large, but this is not pathognomonic. In rare
cases, a hemangioma may rupture, resulting in a
hemoperitoneum and shock requiring emergency
treatment.4,12,13 In many cases, the symptom complex associated with hemangioma is nonspecific,
and a diagnostic investigation is begun.
Although hemangiomas may grow to huge proportions (see Fig. 1–1), they typically do not compromise normal liver function, and unless an acute
complication such as thrombosis or intraparenchymal hemorrhage has occurred, all serologic tests are
generally normal. The initial radiologic evaluation of
a suspected hemangioma is often dictated by the clinical presentation. In many situations, hemangiomas
are discovered incidentally on a study performed for
other reasons, and the degree of diagnostic certainty
provided by this study may obviate the need for additional testing. If a patient presents with dull nonspecific right-upper-quadrant complaints, ultrasonography (US) is typically the first study performed. The
quality of the US study, unlike that of most other
imaging modalities, depends on the operator rather
than on the technology. Hemangiomas appear on US
imaging as hyperechoic masses clearly demarcated
from the surrounding liver; the addition of duplex US
can provide further information on peripheral blood
flow and central pooling of venous blood. In spite of
the skill of many ultrasonographers, US imaging
cannot definitively exclude other diagnostic possibilities, and a CT scan is often the next study requested.
Hemangiomas are hypodense on noncontrast abdominal CT scans and have a characteristic pattern of
irregular peripheral nodular enhancement after the
initial injection of contrast material. Delayed CT
scanning (several minutes after contrast injection)
demonstrates central filling of the hypodense lesion;
the filling persists for some time and is felt to be
diagnostic14,15 (Fig. 1–3). High-quality dynamic CT
may provide a conclusive diagnosis in many cases.
However, MRI is considered to be the most sensitive
and the most specific diagnostic study. A T2weighted image demonstrates a characteristic hyperintense pattern (Fig. 1–4). The administration of
gadolinium demonstrates similar peripheral nodular
enhancement with delayed central filling as was
described with CT (Fig. 1–5). Although the cost of
MRI was previously prohibitive, it has considerably
decreased, and in our opinion, MRI with gadolinium
is the preferred study for the evaluation of most
hepatic lesions.
Scintigraphy with technetium-99m-labeled red
blood cells (Tc-99m RBC scan) has historically
been considered the gold standard for diagnostic
evaluation of hemangiomas14,16 (Fig. 1–6). However,
advances in diagnostic axial imaging techniques
such as MRI and CT, combined with the additional
staging information these studies offer with regard
to assessing the remainder of the abdomen, have led
to less reliance on red blood cell (RBC) scintigra-
7
phy. In our opinion, RBC scintigraphy can be misleading, and we do not use it routinely.
Selective hepatic angiography demonstrates a
characteristic neovascularity to these lesions that is
often described as “corkscrewing.” Rapid filling of the
central portion of hemangiomas from the neovascular
periphery yields a “cotton wool” appearance to these
lesions (Fig. 1–7). Despite the use of angiography in
characterizing hemangiomas, the diagnostic yield of
less invasive studies is much greater, and arteriography is seldom warranted. At many institutions, MRI is
not readily available or is otherwise prohibitive; in this
situation, dynamic CT may be a good substitute.17
Given the risk of low but nonetheless significant
bleeding, fine-needle aspiration (FNA) should be
avoided if hemangioma remains a diagnostic possibility, in which case an MRI should be performed. As
discussed elsewhere, MRI may in fact be sufficient to
provide a conclusive diagnosis and thus obviate the
need for a biopsy. While needle biopsy may be necessary in a few patients when imaging studies are inconclusive, it should be used sparingly. Furthermore, it
must be stressed that over-reliance on negative or
inconclusive FNA results, particularly if malignancy
cannot be excluded, is ill-advised.14–18 As a rule, a
biopsy is unnecessary unless a histologic diagnosis
will alter planned therapy.
Figure 1–3. Hemangioma. Computed tomography
image of the liver after contrast administration demonstrates a mass with peripheral nodular enhancement
(arrow). This pattern of enhancement is diagnostic of
a hemangioma.
8
Treatment
In nearly all cases of asymptomatic hemangiomas,
observation is the most appropriate treatment. To
date, there has been no documented case in which a
hemangioma has spontaneously ruptured while being
observed. Trastek and colleagues observed 36
patients with cavernous hemangiomas for up to 15
years (mean, 5.5 years).15 One adult patient was
treated with external beam radiation and showed
marked reduction in the size of the lesion. The other
33 patients were observed, with no other treatment.
There were no spontaneous ruptures and—most
important—no changes in symptoms over the course
of the follow-up. In 4 patients, the size of the hemangioma increased; in 3 patients, the size decreased.
Foster observed 44 patients with hemangiomas for a
period ranging from 2 months to 12 years. There
were no reports of rupture, death, or changes in clinical symptoms in their series.16 In the absence of clinical symptoms, careful observation is the recommendation of most experienced liver surgeons.
In symptomatic patients, some form of treatment
is frequently required. Patients with disabling pain,
pressure symptoms, or acute symptoms related to
hemangioma should undergo resection.19,20 In general, the likelihood of symptoms increases with
tumor size. In our series, tumors in symptomatic
patients had a mean size of 10 ± 8 cm versus
6.8 ± 5.8 cm for tumors in asymptomatic patients
Figure 1–4. Hemangioma seen on magnetic
resonance imaging (MRI) of the liver, demonstrating a mass in hepatic segment III. The mass
is hyperintense on T2-weighted images (arrow).
This mass maintained increased signal on the
heavily T2-weighted images and demonstrated
peripheral nodular enhancement (see Fig. 1–5)
consistent with a hemangioma.
(p = .03), and patients with tumors ≥ 10 cm were
much more likely to report symptoms.3 It must be
emphasized, however, that vague symptoms or
symptoms inconsistent with the lesion should be
thoroughly investigated to exclude other causes.
Resection is also indicated when there is diagnostic uncertainty or the possibility of a malignancy. On
the other hand, resection solely to avoid the risk of
rupture and intra-abdominal hemorrhage is not indicated even for large hemangiomas. Although Shumacker reported that the estimated lifetime risk of
rupture for a hemangioma is 19.7 percent, this is
inconsistent with other published reports.19 Henson
and colleagues observed 35 patients with hepatic
hemangiomata for 10 years and reported no ruptures,10 and Trastek and colleagues reported no spontaneous hemorrhage among 49 patients with hepatic
hemangiomas observed for a mean of 5.5 years.15 A
review of the literature reveals only 21 cases of spontaneous rupture reported since 1898. Although cautious observation seems the most appropriate initial
therapy for most patients, this does not equate to a
recommendation in favor of therapeutic nihilism in
the management of all hepatic hemangiomas.
Patients with large hemangiomas should be carefully
observed, and if a change in size or symptoms occurs
either abruptly or over time, reconsideration of surgical resection is appropriate.
The location of the hemangioma often dictates
the operative approach, and full assessment of the
tumor’s extent is critical. While most lesions are
amenable to enucleation, a formal anatomic resection may be the safest approach in some cases. Large
central lesions that abut the portal vein, hepatic outflow tract, or inferior vena cava over a long distance
may pose a prohibitive surgical risk even in experienced hands. In these situations, alternative therapeutic modalities might be considered. Although
radiotherapy has been used successfully to treat
symptoms and induce involution of hemangioma in
some situations, the rarity of this occurrence makes
the results difficult to interpret. On the whole, data
justifying the use of radiotherapy for hemangioma
are scant. However, radiotherapy seems a reasonable
9
alternative approach to the treatment of symptomatic
hemangioma if surgical therapy is not possible.21
Resection for hemangioma should be approached
as would any other hepatic resection. The surgeon
should have extensive knowledge of the anatomy and
vascular supply of the liver and should be prepared to
perform a major resection if necessary. Wide exposure and full mobilization of the liver are required.
Unlike a malignant lesion, a hemangioma need not
be resected with a margin of normal tissue around the
tumor. Enucleation is therefore the most appropriate
treatment for most hemangiomas since it will remove
essentially no functional parenchyma. Ligation and
division of the principal hepatic arterial inflow
Figure 1–5. Hemangioma seen on magnetic
resonance imaging (MRI). A, T1-weighted
images of the same patient studied in Fig. 1–4
demonstrate the mass (arrow) to be hypointense
with respect to hepatic parenchyma. B, Images
after gadolinium enhancement demonstrate
peripheral nodular enhancement (arrow) (as
also seen on computed tomography images),
characteristic of a hemangioma.
A
B
10
parenchyma. As the dissection proceeds, pedicle and
hepatic venous branches extending from the tumor to
the liver parenchyma will be encountered and should
be controlled with clips or ties.
The effectiveness of hepatic artery ligation or
embolization as primary treatment for hemangioma
has been described anecdotally; however, the benefit
of either procedure is likely transient.22,23 On the
other hand, these approaches play a pivotal role in
temporarily controlling hemorrhage from a hemangioma that has ruptured spontaneously and thus
allow stabilization and definitive surgical treatment.
Special Issues: Hemangioma in Children
Figure 1–6. Tagged red blood cell (RBC) scintiscan of a
cavernous hemangioma of the liver, 2 minutes (top) and 45
minutes (bottom) after injection of radionuclide-tagged
RBCs. Note the early lack of filling of the hemangioma and
the late pooling of the tagged RBCs within the lesion.
should be done early in the operation, especially for
very large tumors, as this procedure may result in
significant tumor decompression and may facilitate
resection. Enucleation is performed by defining the
plane between the tumor and hepatic parenchyma.
The majority of hemangiomas requiring resection are
contained within a tough fibrous capsule that can be
grasped firmly with a clamp, which can be used for
retraction. Careful dissection within the proper plane
allows the tumor to be separated from the normal
In general, hepatic hemangiomas of infancy and
childhood are different from those seen in
adults.24–27 The lesion is typically large, and symptoms are rarely subtle. The vast venous lakes within
the lesion can function as tremendous siphons for a
large proportion of the total cardiac output, leading
to congestive heart failure and death. In children
who develop high-output cardiac failure, the initial
treatment usually consists of digitalis, diuretics,
oxygen, corticosteroids, and ligation of the hepatic
artery.2,25,27 Radiation treatment is often employed
and may result in improved cardiac performance.21,26 The risk of spontaneous rupture of a
hepatic hemangioma in infancy is much greater
than that of such tumors in adults.25 Similarly,
Kasabach-Merritt syndrome, associated with lifethreatening thrombocytopenia and afibrinogenemia, occurs much more frequently in infants than in
adults and is a common cause of morbidity and
mortality. The treatment of hemangioma in infants
and children (in contrast to that in adults) often
requires a lifesaving operation, and such cases
should be referred immediately to an experienced
tertiary pediatric center.
Focal Nodular Hyperplasia
Focal nodular hyperplasia (FNH), the second most
common benign tumor of the liver, was initially
described by Edmundson in 1958.28 Like hepatic
adenoma, FNH is most often found in women of
reproductive age. It is usually asymptomatic and is
often discovered incidentally during a radiologic
investigation for other reasons. In rare instances,
FNH may present as a palpable abdominal mass on
physical examination. Although FNH was rarely
seen prior to the 1960s, its incidence has increased
markedly in the last three decades. The rise in the
number of cases has occurred concurrently with the
introduction and widespread use of both US and CT
in clinical practice. Whether the increased reporting
of FNH represents a true change in incidence or
merely reflects the proficiency of scanning in identifying these lesions is not clear, but the latter is
probably the case.
Klatskin and Vana and colleagues each reported
collective series of FNH; both studies suggested an
etiologic relationship between oral contraceptive pill
(OCP) usage and the development of both FNH and
hepatic adenoma.29,30 However, the numerous
reports of FNH before the 1960s and the high frequency of FNH in the absence of OCP use suggest
that there is probably no cause-and-effect relation-
11
ship. The potential effect of pregnancy on FNH
remains poorly understood. In one provocative
report, Scott and colleagues described a 36-year-old
woman who had used OCPs for 11 years prior to
developing FNH,31 which regressed after cessation
of the medication but subsequently increased in size
during a later pregnancy. Other than such anecdotal
reports, there are no firm data linking pregnancy and
changes in the size or symptoms of FNH, and meaningful conclusions are therefore not possible. Unlike
hepatic adenoma, FNH carries little risk of spontaneous rupture and no risk of malignant transformation,32 which underscores the importance of distinguishing these lesions.
Pathology
Macroscopically, FNH is a pale firm lesion distinct
from the surrounding liver (Fig. 1–8). Histologically,
FNH is sharply demarcated from the normal liver
but lacks a true capsule. The architecture of the
Figure 1–7. Hemangioma seen by catheter
angiography; a conventional angiogram of the
hepatic artery of a patient with a large hepatic
mass. The mass demonstrates peripheral puddling of contrast material (arrows), characteristic
of a hemangioma. (Image courtesy of Dr. George
Getrajdman)
12
lesion suggests a regenerative rather than a neoplastic process; as such, the lesion can be difficult to distinguish histopathologically from cirrhosis with
regenerating nodules. This difficulty can be readily
overcome by informing the pathologist of the diagnostic imaging findings and providing a sample of
normal-appearing liver tissue away from the mass.
Unlike in hepatic adenoma, bile duct hyperplasia
and Kupffer’s cells are prominent in FNH. This feature is the basis for using labeled sulfur colloid scans
to distinguish FNH from other lesions as Kupffer’s
cells will take up the radiolabel while tumors with a
paucity of Kupffer’s cells (such as adenoma) will
not. Radiographically, FNH is described as having a
“central scar.” The central portion of an FNH is
composed of fibrous septae containing a round cell
infiltrate and prominent thick-walled blood vessels,32,33 which may give the appearance of a scar on
imaging studies. This finding, however, is by no
means constant or pathognomonic.
A
B
Figure 1–8. Focal nodular hyperplasia (FNH). A, On cross section, this FNH appears as a yellowtan lesion sharply demarcated from the normal liver in the absence of a true capsule. B, The gross
and microscopic architecture of these lesions suggests a regenerative rather than a neoplastic
process. Bile duct hyperplasia and Kupffer’s cells are prominent.
Clinical Presentation and Evaluation
Focal nodular hyperplasia usually presents as a solitary hepatic mass but may be multiple in up to 20
percent of patients33,34 and may occur in association
with other benign tumors of the liver, such as
hemangioma.35,36 The lesion is typically small and
intraoperatively appears as firm nodules, pale red to
brown, with prominent blood vessels on the surface.
Larger lesions can be particularly difficult to distinguish from well-differentiated hepatocellular carcinoma (HCC). Tumors of FNH are frequently asymptomatic, and spontaneous rupture is extremely rare.
In our experience, less than half of patients with
FNH were symptomatic,3 and (like hemangiomas)
the likelihood of symptoms increases with tumor
size. Furthermore, there were no cases of spontaneous hemorrhage in patients who were observed.
By contrast, Mays and Christopherson reported a 9.2
percent incidence of rupture in a series of 98 patients
with FNH; however, this percentage is extraordinarily high compared to other large series in which no
spontaneous ruptures were reported.35–38
Making a definitive diagnosis of FNH can be
difficult. The lesion is visible by US but exhibits no
characteristic features. Technetium-99m-labeled
sulfur colloid scintigraphy may be helpful in
demonstrating the presence of Kuppfer’s cells
within a hepatic tumor; however, a positive result is
not specific enough to make the diagnosis conclu-
13
sively. CT may demonstrate a well-demarcated
enhancing lesion with enhancement of the central
scar during the portal venous phase (Fig. 1–9).
Magnetic resonance imaging may be more sensitive
than CT, but the characteristic MRI features of FNH
are subtle and require high-quality imaging studies
and an experienced radiologist. Precontrast images
may reveal a lesion that is hypointense or even
isointense with respect to the surrounding liver tissue on T1-weighted images. Features on T2weighted images are also subtle, with the lesion
being isointense to mildly hyperintense with respect
to the liver. Focal nodular hyperplasia usually
enhances early and appears hyperintense on the
immediate postgadolinium images and becomes
gradually isointense on the delayed sequences. Like
CT, contrast MRI images may demonstrate a central
scar, but this finding is less reliable than the overall
appearance of the lesion on pre- and postcontrast
sequences (Fig. 1–10). The use of reticuloendothelial agents (such as Ferridex), which are taken up
selectively by Kupffer’s cells, can increase the
specificity of both CT and MRI; however, the
results are not specific to FNH. Angiography typically demonstrates a hypervascular mass with
enlarged peripheral vessels and a single central
feeding artery (Fig. 1–11). This so-called wheelspoke appearance with the vessels radiating out
from the center of the tumor may help distinguish
FNH from hepatic adenoma (see below).
Figure 1–9. Focal nodular hyperplasia. Noncontrast computed tomography image of the
liver demonstrates a mass (straight arrows) similar in attenuation to the surrounding hepatic
parenchyma. Note that there is an area of low
attenuation centrally consistent with a central
scar (curved arrow).
14
Treatment
As with all benign hepatic tumors, symptoms and
the clinician’s inability to exclude malignancy are
the most common reasons for resection of FNH.
Inability to exclude malignancy is particularly common with FNH and was the reason for operation in
61 percent of those with FNH who were submitted
to resection in our series.3 In many cases, diagnostic
uncertainty prompts a percutaneous needle biopsy.
The results of these biopsies are seldom diagnostic
and are often misleading. One should therefore use
caution when making treatment recommendations
based on biopsy results alone. If the lesion is defin-
Figure 1–10. Magnetic resonance imaging
(MRI) of focal nodular hyperplasia. A, T1weighted image demonstrates a mass (arrows)
that is isointense to hepatic parenchyma. B, T2weighted image of the liver demonstrates a mass
(arrows) that is isointense to hepatic parenchyma.
A
B
itively shown to be an FNH at the time of operation,
enucleation of the tumor is sufficient treatment.
More often, a firm histologic diagnosis is not available before operation and cannot be reliably
obtained on frozen-section histologic study. In such
cases, a formal resection with a rim of normal tissue
is required in the unfortunate event that the final
pathology demonstrates a malignant lesion. When
the diagnosis of FNH can be made confidently by
imaging criteria, particularly if the tumor is small
and centrally located, a trial of close observation
with repeat imaging every 3 to 4 months is rational.
Any change in size, number, or symptoms of the
lesion(s) should prompt reconsideration of surgical
resection. Even in the absence of strong evidentiary
data, discontinuation of OCP use in all patients with
resected or unresected FNH seems prudent.
Hepatic Adenomas
Hepatic adenomas are generally solitary lesions but
may be multiple in up to 30 percent of cases.35 As with
FNH, the incidence of hepatic adenoma has increased
since the late 1960s. Baum and colleagues were the
first to suggest a cause-and-effect link between the
development of a hepatic adenoma and OCP use,
although the effects of exogenous estrogen on hepatic
parenchyma had been previously reported.37 After
starting OCP, 40 percent of women will develop hepatocellular dysfunction, manifested by increased retention of bromsulphothalein; rare patients will develop
cholestatic jaundice.35,38–40 Alterations in hepatocyte
architecture and trafficking have also been documented in association with OCP usage and pregnancy,
and these changes appear to be related to dose and to
duration of treatment. Klatskin and colleagues suggested that alterations in hepatic vasculature occur following OCP administration and may be the primary
15
mechanism through which the effects of OCP on the
liver are mediated.41 A persuasive body of information
now exists in support of an etiologic link between
OCP use and the development of hepatic adenoma,40–43 which supports the initial observation by
Baum and colleagues. The risk of developing hepatic
adenoma appears commensurate with the duration of
OCP use and with age of over 30 years. Ninety percent of patients who develop hepatic adenoma have
used OCPs, and the incidence of hepatic adenoma
among those who have used OCP for more than 2
years is 3 to 4 per 100,000. The risk of developing a
hepatic adenoma while taking OCP may be related to
the amount of estrogen in the OCP preparation. If this
is true, then the recent trend of marketing low-estrogen OCP should affect the future incidence of hepatic
adenoma. Regression of hepatic adenoma once OCP
has been stopped is well documented; however, this is
not a universal occurrence as tumor growth despite
the stopping of medication has been reported.44–45
There is no convincing evidence linking pregnancy to the development of hepatic adenoma, but
pregnancy may increase the incidence of associated
complications. Rooks and colleagues documented
Figure 1–11. Angiogram of focal nodular
hyperplasia (FNH). Catheter angiogram of the
hepatic artery demonstrates a hypervascular
mass with a wheel-spoke pattern (arrows) of vessels characteristic of FNH. (Image courtesy of
Dr. Karen Brown)
16
ruptures of hepatic adenomas in 5 of 6 women who
either were currently pregnant or had recently given
birth.43 This rate of rupture is alarmingly high in
comparison to a rupture rate of less than 30 percent
reported for nonpregnant women with hepatic adenomas.35 In addition to estrogens, several other hormones used as therapies, including androgens,
clomiphene, danazol, and human growth hormone,
have been linked to the development of hepatic adenoma and other benign liver tumors.46–51 Additional
reports of an increased incidence of hepatic adenoma in patients with type I glycogen storage disease, galactosemia, Klinefelter’s syndrome, and
Turner’s syndrome has led to significant speculation
as to whether hepatic adenoma may be the result of
an inborn genetic error in carbohydrate metabolism.
Hepatic adenomas are capable of malignant
transformation, but this appears to be an uncommon
occurrence. Several authors have reported cases of
hepatocellular carcinoma (HCC) arising adjacent
to or within pre-existing hepatic adenomas.33,52–55
Similarly, Rooks and colleagues reported a patient
who developed HCC in the same area where a
hepatic adenoma had been removed 5 years earlier.43 By contrast, Tao and colleagues, after careful
review of the histologic differences between adenomatous and dysplastic liver lesions, suggested
that malignant transformation may not occur.54,55
However, given the difficulty inherent in differentiating between these entities, and given the significant anecdotal evidence in the literature, all
hepatic adenomas should be considered to potentially harbor dysplastic changes or frank cancer until
pathologic review of the entire tumor (and not a
limited biopsy) proves otherwise.
Pathology
Hepatic adenomas are typically small (< 5 cm) solitary soft tumors that may or may not be encapsulated. The gross specimen appears pale yellow on
the cut surface and may have a variegated appearance secondary to internal hemorrhage. Microscopically, hepatic adenomas are composed of monotonous sheets of hepatocytes, often containing
considerable glycogen (Fig. 1–12). Unlike FNH,
portal triads and bile ducts are absent, and the exist-
ing blood vessels are thin-walled. Venous lakes (the
so-called peliosis hepatis) are common. Areas of
necrosis with “ghost cells” are characteristic of
many hepatic adenomas. However, there is little evidence of an inflammatory reaction, fibrosis, or
regeneration. Histologic differentiation of a hepatic
adenoma from a well-differentiated HCC or a fibrolamellar HCC can be very difficult.55,56 Distinguishing an adenoma from a fibrolamellar HCC may be
quite difficult also because both tumors occur most
commonly in females of reproductive age who have
no risk factors for chronic liver disease. In some
series, small foci of HCCs were found in association
with up to 10 percent of hepatic adenomas.
Clinical Presentation and Diagnosis
Because adenoma and FNH are common in young
women and may have similar appearances on radiographic studies, they are often confused. Distinguishing these lesions is critical, however, because
the recommended treatment for each is often different. There are often differences in presentation,
which may be helpful, but these are generally not
specific enough to be diagnostic. While the majority
of FNHs are small and asymptomatic, hepatic adenomas tend to be large and symptomatic. In our
series, two-thirds of patients with adenomas
reported symptoms, compared with less than half of
those with FNHs.3 Up to one-third of all patients
with hepatic adenoma initially present with an acute
rupture and intraperitoneal bleeding30,33,38,39,43
although the true incidence of this catastrophic complication is unclear. Additional complaints can
include abdominal pain, pressure, and nonspecific
gastrointestinal symptoms. Results of liver function
tests are usually normal or only mildly abnormal.
Tumor markers such as carcinoembryonic antigen
(CEA) and α-fetoprotein are not elevated.
Distinguishing hepatic adenoma from FNH or
well-differentiated HCC radiographically remains a
difficult problem. The findings on US are of a tumor
with mixed echogenicity and an overall heterogeneous appearance—generally nonspecific. Computed tomography can yield a wide spectrum of disparate findings but typically demonstrates a
hypodense lesion on noncontrast imaging, with a
variegated appearance following contrast administration. Although MRI findings may be similarly
nonspecific, we have increasingly used this modality to help distinguish adenoma from FNH. Adenomas are typically heterogenous but are usually
hyperintense in T1-weighted images and isointense
to mildly hyperintense on T2-weighted images.
Additionally, these masses tend to enhance early on
gadolinium-enhanced MRI (Fig. 1–13). In the past,
technetium-99m sulfur colloid scans have been used
to distinguish hepatic adenoma from FNH. Hepatic
adenomas usually contain fewer Kupffer’s cells than
FNH and will therefore not concentrate the radiola-
17
beled material and will appear as a cold nodule.
However, sulfur colloid scans lack sufficient specificity and sensitivity to be clinically useful. Angiography, once commonly used, may still have a role in
the occasional patient. Angiography of a hepatic
adenoma typically reveals a hypervascular lesion
with areas of necrosis and hemorrhage and tortuous
vessels penetrating the tumor from the periphery. By
contrast, the classic FNH angiogram demonstrates
multiple vessels radiating from a large central vessel
(the so-called central scar). Although imaging studies may provide evidence that is suggestive of the
diagnosis, diagnostic uncertainty is often the rule.
A
B
Figure 1–12. Hepatic adenoma. A, Hepatic adenomas grossly appear as soft, tan lesions. B, Microscopically, hepatic adenomas are composed of monotonous sheets of hepatocytes containing considerable glycogen. Portal triads and bile ducts are absent, and the existing blood vessels have thin walls.
Venous lakes and zones of necrotic ghost cells are characteristic.
18
A
B
Figure 1–13. Magnetic resonance imaging of a
hepatic adenoma. A, T1-weighted image demonstrates a mass (arrowheads) that is mildly heterogeneous with respect to hepatic parenchyma.
Note that there is a focus in the mass that is
hyperintense (arrow) from prior hemorrhage. B,
T2-weighted image demonstrates the mass
(arrow) to be mildly hyperintense compared to
hepatic parenchyma. C, Arterial dominant-phase
images through the mass demonstrate it to be
hypervascular (arrow) compared to background
parenchyma.
C
Treatment
Because of the significant risk of spontaneous hemorrhage and the low but apparently real risk of malignant transformation, all patients suspected of having
hepatic adenoma should be considered for resection.
Enucleation may be a reasonable operative approach,
especially if there is considerable doubt regarding the
diagnosis, but most presumed adenomas should be
approached as if they harbor an unsuspected malignancy. In this regard, surgical resection of these
tumors is advised, with an adequate margin of normal
tissue. Control of bleeding from a ruptured hepatic
adenoma may be achieved surgically or with hepatic
artery embolization. If surgical exploration is not feasible, angiographic embolization can be a temporary
lifesaving maneuver until transfer to a center with surgical capability is possible. Intraoperatively, hepatic
artery ligation can similarly be a lifesaving procedure
in the presence of ongoing hemorrhage.
All women diagnosed with hepatic adenoma
should be advised to stop OCP use for life. Recurrence of hepatic adenoma after resection or enucleation has not been a problem, provided that OCPs are
discontinued. Yearly follow-up with imaging is
advised for all patients and is mandatory in patients
with hepatic adenoma not causally linked to OCP use.
Although data are sparse, some reports suggest that
pregnancy increases the risk of spontaneous rupture.
Given the high mortality associated with this complication, women with untreated adenomas should be
advised to avoid becoming pregnant or to undergo
resection beforehand. Hepatic artery embolization,
radiofrequency ablation, or cryoablation may be useful in some settings. However, experience with these
nonoperative modalities has been insufficient for the
making of any firm recommendations regarding their
use as primary treatment for hepatic adenomas.
Other Liver Tumors5,6,35,42,55,56
Epithelial Tumors
(Biliary Hamartomas and Adenomas)
Bile duct adenomas and hamartomas are common
tumors. They are particularly noteworthy since they
may appear grossly and radiographically indistinguishable from metastatic lesions and are often mis-
19
takenly interpreted as such by the operating surgeon.
Clinically silent, these tumors are manifest only at
the time of operation or autopsy. Biliary hamartomas are small gray-white nodules scattered
throughout the liver.57 They are often multiple and
may be associated with liver cysts or other benign
hepatic pathology. Microscopically, they are composed of dilated mature bile ducts surrounded by
fibrous tissue. Bile duct adenomas are small white
masses that are usually solitary and subcapsular.
Their bile ducts are narrow with little or no lumen
and may be surrounded by fibrosis. Biliary hamartomas and adenomas are easily distinguished from
FNH on microscopic review due to their lack of
hyperplasia and cellular proliferation. When
encountered, biopsies on one or more lesions should
be performed to confirm the diagnosis and exclude
the possibility of malignancy.
Mesenchymal Tumors
Solitary Fibrous Tumor (Benign Mesothelioma,
Fibroma). Solitary fibrous tumors are rare mesenchymal tumors that can often be mistaken for
metastatic lesions because of their radiographic and
intraoperative appearance (Fig. 1–14). The clinical
course of these lesions appears to vary considerably,
with some behaving like benign tumors while others
are more aggressive. Moran and colleagues recently
reported on nine cases of primary solitary fibrous
tumors of the liver.57 The patients were seven women
and two men and were between the ages of 32 and
83 years (mean, 57.5 years). Most of the tumors
were large and symptomatic. Five tumors were palpable on physical examination. Grossly, the tumors
varied in size from 2 to > 20 cm in greatest dimension and were described as firm, white to gray, and
well to ill defined. Eight tumors were intraparenchymal lesions, two were necrotic, and one was attached
by a pedicle to the liver capsule. Most of the tumors
had a bland histologic appearance, with the classic
short storiform (so-called patternless) pattern and an
absence of cellular atypia, mitoses, and necrosis. In
two cases, however, there was marked cellular atypia
and mitotic figures varying from 2 to 4 mitoses per
10 high-power field (hpf) (Fig. 1–15). Immunohistochemically, all of the tumors showed a strong pos-
20
itive reaction against antibodies for CD34 and
vimentin. The diagnosis of either a benign or malignant solitary fibrous tumor is impossible without
definitive histologic review, and surgical resection is
indicated in all circumstances.
Lipoma (Myelolipoma or Angiomyolipoma). Fatty
tumors of the liver are extraordinarily rare. Several
reports of primary lipomas have appeared, but there
are no reports to date of a primary hepatic liposarcoma. Most benign fatty hepatic tumors have been
encountered at the time of autopsy, with rare reports
of operative resection of these tumors.5 Multiple
Figure 1–14. Imaging of a solitary fibrous
tumor. A, Computed tomography examination of
the liver demonstrates a large heterogeneous
mass (arrows). B, T2-weighted magnetic resonance image of the same patient demonstrates
the mass (arrows) to be heterogeneous with
respect to hepatic parenchyma.
A
B
variants, including myelolipoma, angiolipoma, and
angiomyolipoma, have been described.5,58 The term
“pseudolipoma” has been given to an extracapsular
fatty tumor with involutional changes. This lesion
probably results when a free-floating piece of fat
(eg, an appendix epiploica) becomes trapped
between the diaphragm and the surface of the liver.59
Definitive diagnosis requires resection to exclude
malignancy.
Mesenchymal Hamartoma. Mesenchymal hamartomas are extremely rare liver tumors that are seen
most commonly in infants less than 1 year of age.60
Unlike biliary hamartomas that are clinically
insignificant, mesenchymal hamartomas can reach
enormous size, resulting in significant impairment
of hepatic function. Microscopically, mesenchymal
hamartomas display a background of edematous
fibrous and myxoid mesenchyme with random
groupings of hepatic cells, bile ducts, blood vessels,
21
and cysts. The cystic component is generally the
most prominent feature, resulting in a honeycomb
appearance. Although benign, mesenchymal hamartomas can result in death due to mass effect and/or
hepatic insufficiency. Therefore, all mesenchymal
hamartomas should be completely excised if feasible. If complete resection is not possible or is pro-
A
B
Figure 1–15. A, Gross appearance of a resected solitary fibrous tumor. The
tumor measured 18 cm in diameter. B, Histopathologically, the tumor has a bland
appearance, with little or no cellular atypia and no necrosis.
22
hibitive for other reasons, surgical debulking may be
sufficient as there have been no reports of recurrence after an incomplete surgical resection.35
Myxoma. A primary hepatic myxoma is exceptional. To date, there are only three reports of such
lesions in the literature. Two hepatic myxomas were
resected from children, one of which proved to be
invasive. Both children remained free of disease at
the time of report.36 There has been only one
reported case of a hepatic myxoma in an adult; this
involved a 58-year-old man with a left-lobe myxoma
that ruptured. Definitive diagnosis was not made
until autopsy 4 months later.29
Teratoma. At least seven benign primary teratomas of the liver have been reported.61,62 Most
occur in children. Teratomas may be cystic and are
usually encapsulated and easily resected. Resection
is indicated to exclude malignancy. Secondary teratomas may be seen in the liver after systemic
chemotherapy to treat testicular cancer. Resection is
usually undertaken to remove residual disease that
may be malignant, and the diagnosis of teratoma is
made only after resection.
NONPARASITIC CYSTIC TUMORS
Cystic lesions of the liver and biliary tree are common, although many are not neoplasms in the true
sense. Cystic lesions are discussed apart from solid
benign tumors because such a finding within the
liver leads to a different group of diagnostic possibilities. A complete discussion of all cystic diseases
of the liver is beyond the scope of this section, which
will focus on the most common of these lesions.
Nonparasitic cystic lesions of the liver and intrahepatic biliary tree differ in many respects but share
some common features.63 First, these tumors appear
to result from congenital malformations of the intrahepatic biliary radicles and, as such, may be classified as epithelial in origin. Second, these lesions are
predominantly or entirely cystic in nature, which
distinguishes them from nearly all of the solid
benign tumors. Cystic lesions may be further subcategorized as simple or complex with respect to
their radiographic appearance, an important distinction that will dictate treatment recommendations
(see below). The finding of a complex cyst is potentially more ominous; in general, these lesions should
be resected, even in the absence of symptoms.
Simple Cyst
Simple hepatic cysts (also known as benign hepatic
cysts, congenital hepatic cysts, or unilocular cysts)
are round or ovoid cystic formations containing
serous fluid. The size of simple cysts ranges from a
few millimeters to 20 cm or more. Small cysts are
surrounded by normal hepatic parenchyma. Larger
cysts may cause atrophy of adjacent hepatic
parenchyma, and huge cysts may result in significant lobar atrophy with compensatory contralateral
hypertrophy. Simple cysts are considered to be congenital malformations resulting from an aberrant
bile duct that has lost its communication with the
biliary tree and that slowly but progressively accumulates fluid and dilates. Thus, simple cysts have no
communication with the biliary tree and are lined by
a single layer of uniform cuboidal or columnar
epithelium resembling biliary epithelium. In the
absence of spontaneous intracystic hemorrhage or
previous aspiration, the cyst fluid is clear and is similar in composition to the normal secretion of biliary
epithelial cells.
Approximately 50 percent of patients with nonparasitic cystic disease have a single cyst while the
remainder will have two or more.64 A small number
of patients will have multiple cysts, reminiscent of
the hepatic cysts seen in adult polycystic kidney disease. However, while some of these patients have
one or a few renal cysts, they must not be regarded
as having polycystic kidney disease.
In most cases, simple cysts are asymptomatic and
are discovered incidentally on evaluation of other
conditions. Such findings may cause considerable
consternation because they may be mistaken for evidence of metastatic disease, especially in patients
with a known malignancy elsewhere who are undergoing an evaluation for extent of disease. This is particularly true for small cysts that may be difficult to
characterize radiographically. Furthermore, distinguishing simple cysts from other cystic lesions,
specifically cystadenoma and hydatid disease, is
critical. The latter two conditions are treated with
resection in most cases, while asymptomatic simple
cysts require no specific therapy beyond serial follow-up examinations. Ultrasonography is a simple
and effective method for confirming the diagnosis
of simple hepatic cysts. The ultrasonographic
appearance is that of a circular or oval anechoic area,
well circumscribed and with sharp smooth borders
and a strong posterior wall echo, indicating a welldefined tissue-fluid interface65 (Fig. 1–16). Magnetic resonance imaging has also proven valuable in
diagnosing simple cysts, which appear very bright
on T2-weighted images (Fig. 1–17) Computed
tomography confirms the presence of one or several
round or oval thin-walled water-dense lesions without internal septations; it appears to be less useful
for evaluating smaller cysts.
In most cases, simple cysts are readily distinguished from other hepatic lesions by routine imaging
studies. Occasionally, however, simple cysts may be
difficult to distinguish from cystadenomas or hydatid
disease. While hydatid cysts are usually complex and
contain multiple septations and calcification, these
features may be absent. Also, serologic tests for
ecchinococcal infestation are not always positive, and
23
the disease can be acquired in areas where it is not
endemic. Furthermore, simple cysts with intracystic
hemorrhage and clotting, which may occur spontaneously (Fig. 1–18) or after instrumentation (Fig.
1–19), may be radiographically indistinguishable
from hydatid disease or cystadenomas. When the distinction between hydatid disease and simple cysts
cannot be made on radiographic grounds, microscopic examination of the cyst fluid obtained by aspiration may be useful.66 Likewise, tumors suspected of
being cystadenomas should be treated as such rather
than risk inappropriate treatment for a lesion that may
be premalignant or that may already contain a focus
of malignancy (see below).
Most simple cysts are asymptomatic, even when
large, and therefore require no specific therapy. Serial imaging of these lesions may show no appreciable
enlargement over several years. A small number of
patients may experience rapid enlargement, which
may be associated with severe pain; intracystic hemorrhage may also result in sudden and severe pain.
Symptoms are much more likely to occur in women
over 50 years of age.64 The most effective therapy for
symptomatic simple cysts is wide fenestration of the
Figure 1–16. Ultrasonography of the liver, demonstrating a simple hepatic cyst (arrow).
The lesion is well circumscribed and is hypoechoic with increased through transmission.
This constellation of findings is characteristic of a simple cyst.
24
cyst wall performed at laparotomy or laparoscopy.
Percutaneous aspiration by itself is ineffective treatment; reaccumulation of cyst fluid is generally
rapid.67 However, aspiration combined with infusion
of alcohol is more effective in preventing recurrence
and may be an alternative to fenestration for patients
who cannot tolerate general anesthesia.68–71
Biliary Cystadenoma
Biliary cystadenoma, also known as hepatobiliary
cystadenoma, is an uncommon tumor that has a tenFigure 1–17. Magnetic resonance imaging of
a simple cyst. A, T2-weighted image demonstrates small well-circumscribed markedly hyperintense masses (arrow). B, Postcontrast images
fail to demonstrate enhancement within these
masses (arrow), consistent with simple cysts.
A
B
dency to recur if incompletely resected and that also
has potential for malignant transformation. It is therefore essential that cystadenoma not be mistaken for a
simple cyst and disregarded or (worse) subjected to
fenestration. Cystadenomas are generally solitary and
often large, ranging in size from 10 to 20 cm (Fig.
1–20). The pathogenesis is uncertain, although a congenital origin from an abnormal intrahepatic bile duct
is generally favored.72 These lesions are most commonly seen in women over 40 years of age.72
Patients with large tumors may experience
abdominal discomfort or pain, anorexia, or other
symptoms related to tumor compression of adjacent
organs. Smaller tumors often cause no symptoms
and may be discovered only on evaluation of elevated liver enzymes. The diagnosis is suggested on
the basis of imaging studies. Unlike simple cysts,
cystadenomas usually have irregular margins, with
multiple internal septations delimiting locules of
various sizes. Papillary growths arising from the
cyst wall and extending into the cyst lumen are also
common.73 Cystadenomas are sometimes difficult to
distinguish from hydatid cysts or (rarely) from a
cluster of contiguous simple cysts.
25
Cystadenomas tend to progress slowly. Complications such as cholestasis from bile duct compression,74
intracystic hemorrhage, rupture, or bacterial infection
that will bring otherwise asymptomatic lesions to
medical attention have been described. Malignant
transformation is the potential complication of greatest concern. Cystadenocarcinomas arise almost
exclusively within pre-existing cystadenomas. Malignancy may affect the entire epithelial lining; more
often, only part of the cyst is involved. The finding of
abundant and large papillary projections on imaging
studies suggests the presence of malignancy.75–77
Figure 1–18. Magnetic resonance imaging of
a hemorrhagic cyst. A, T1-weighted image
demonstrates a mass with a hyperintense rim
(arrows). B, T2-weighted image demonstrates
the mass to be hyperintense, with the rim being
hypointense (arrow), consistent with hemorrhage. The lesion failed to enhance after contrast
administration.
A
B
26
Because of the risk of malignant transformation,
all suspected cystadenomas must be excised completely. Enucleations or partial excisions expose the
patient to the risk of recurrent cystadenoma or late
development of cystadenocarcinoma and are therefore not appropriate.
CONCLUSION
The key to managing patients with benign liver
tumors is an accurate diagnosis and a knowledge of
the natural history of the untreated lesion. Although
radiologists have made great strides in identifying
Figure 1–19. Computed tomography scan of a
patient with multiple simple cysts. A, A large cyst
within the right lobe and dome of the liver, causing respiratory symptoms. This cyst was aspirated percutaneously to relieve symptoms.
Notice the thickened wall and the homogenous
nature of the cyst fluid, consistent with intracystic hemorrhage. B, Lower cuts, showing additional simple cysts. Notice the typical sharp borders, thin wall, and homogenous nature of the
cyst fluid in contrast to the previously instrumented cyst.
A
B
and characterizing the features of benign hepatic
tumors and although gastroenterologists have developed greater skill in diagnosing these lesions, the
final burden of responsibility for both diagnosis and
therapy rests with the surgeon. Increasing experience, improved techniques, and better support systems have made hepatic surgery a safe and effective
therapeutic modality. However, as we have learned
more about the prognoses of certain lesions (particularly hemangioma and FNH), a more conservative
attitude has evolved, particularly since improvements in noninvasive imaging now permit careful
follow-up by serial examinations. On the other hand,
27
A
B
C
Figure 1–20. Magnetic resonance imaging of
cystadenoma. A, T1-weighted image demonstrates a heterogeneous mass (arrow) with a
fluid-fluid level. The mass has components that
are both hypo- and hyperintense to hepatic
parenchyma. B, T2-weighted image demonstrates the mass (arrow) to be well circumscribed, with similar levels of differing intensity.
C, Postgadolinium images fail to demonstrate
enhancement within the mass.
28
while some benign tumors may be safely observed,
others require resection, and it is ultimately the surgeon’s responsibility to determine the most appropriate course of action. As discussed above, such
decisions are not always simple or straightforward
and often require significant experience and mature
clinical judgment.
An otherwise fit patient with a symptomatic
benign hepatic tumor should be considered for
resection, provided that the tumor can be removed
safely. It is imperative to ensure that the symptoms
are indeed related to the tumor and do not arise from
some other abdominal pathology. Preoperative needle biopsies may be dangerous, are often inaccurate,
and should not be performed as a matter of routine.
Needle biopsies should be considered only after the
diagnosis of hemangioma has been excluded and
then only in asymptomatic patients who are not candidates for resection, to exclude a malignancy if
warranted on the basis of imaging studies or if the
biopsy results will otherwise alter management.
However, it is important to remember that distinguishing certain lesions (particularly FNH and adenoma) on needle biopsy is often difficult, and one
should exercise caution when using biopsy results to
make clinical decisions.
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1 Benign Liver Lesions

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