How to cite this article:Nicolas D, Ben G Arno T, Glenn d W, Bart B. Early Transfusion vs. Malignant Degeneration of a Giant Hepatic Adenoma during 002 Pregnancy. Adv Res Gastroentero Hepatol. 2019; 12(4): 555843. DOI: 10.19080/ARGH.2019.12.555843.
Abbrevations: OC: Oral Contraceptive; EASL: European Association for the Study of the Liver; BMI: Body Mass Index; HCA Hepatocellular Adenoma; NGS: Next Generation Sequencing; NSE: Non-Standard Exception; BeLIAC: Belgian Liver & Intestine Advisory Committee; ICU: Intensive Care Unit; FFP: Fresh Frozen Plasma
Hepatocellular adenomas are rare, benign, hormonally inactive liver tumors composed of well-circumscribed nodules that contain sheets of hepatocytes with a vacuolated cytoplasm. Most diagnosed tumors are discovered incidentally because of modern imaging. Hepatocellular adenomas are usually asymptomatic, but symptoms such as pain, dyspepsia and abdominal mass are described as the result of tumor bulk or hemorrhage. They are commonly found in people with elevated systemic levels of estrogen. Malignant transformation is rare. We report the case of a giant hepatocellular adenoma in a 30-year-old female who acutely presented with abdominal pain three days after uncomplicated vaginal delivery. The resected tumor measured 36 x 21 x 11 centimeters
A 30-year-old pregnant woman presented to the emergency department with preterm premature rupture of the membranes at 35 weeks and 5 days gestational age. Shortly thereafter, she developed spontaneous contractions leading to an uncomplicated vaginal delivery. Three days postpartum, she experienced complaints of a generally swollen and tender abdomen accompanied by a stabbing pain in the right upper quadrant, prompting readmission to the emergency department. Urgent abdominal computed tomography scanning revealed an extremely enlarged right liver lobe with multiple heterogeneous hypodense nodules together with intrahepatic bleeding components, clustering into one sizable mass. Diagnosis of a giant hepatocellular adenoma
with contained intrahepatic hemorrhage was made. Subsequently, regarding further diagnostic work-up, magnetic resonance
imaging was conducted confirming a voluminous hepatocellular
adenoma with focal internal hemorrhages, comprising a volume
of no less than 3856 cubic centimeters (Figure 1, panel A). Remarkably,
prenatal ultrasounds did not withhold any abnormalities.
Apart from one event two weeks before going into labor, the
patient was completely asymptomatic. She experienced vague
abdominal pain with nausea and vomiting, common symptoms
during pregnancy and therefore believed to be pregnancy-related.
Liver function tests during the first trimester of pregnancy
were normal, afterwards no liver function tests were taken.
Given the sheer extent of the lesion, the bleeding diathesis,
and the abdominal discomfort, an open right hemi hepatectomy
was performed via Mercedes incision (Figure 1, panel B). An
anterior approach was used with minimal mobilization of the
right liver. After careful dissection of the liver hilum, the right
portal vein was ligated, followed by the right hepatic artery. To
further minimize intraoperative bleeding, an intermittent Pringle
maneuver was applied at the time of liver transection which
consisted of cross-clamping the hepatoduodenal ligament for
15 minutes and releasing the clamp for 5 minutes until the liver
transection was completed. The inferior vena cava was not clamped
but porto-venous extracorporeal bypass was stand-by. Total
procedure time was 5 hours. Intraoperative blood loss was 10
liters of which 4 liters was recovered using a Cell Saver® with
leukocyte depletion filter. An additional 6 units of packed cells,
9 units of fresh frozen plasma (FFP) and 2 units of platelet concentrate
were given. Postoperative stay in the intensive care unit
(ICU) was characterized by transient right-sided heart decompensation
and pleural effusion after extensive fluid resuscitation,
which was managed by the administration of diuretics. After
5 days, she was transferred to the ward and further recovery was
uneventful. She was discharged 11 days after surgery.
Liver transplantation was considered, however when liver
adenomas are requested for listing via the Belgian Liver & Intestine
Advisory Committee (BeLIAC) they only receive a Non-Standard
Exception (NSE) in Belgium. If the indication was approved,
the patient would receive a MELD score of 22 points that increased
3 points every 90 days, giving her a long waiting time. In
addition, the liver adenoma was respectable
The resected tissue specimen was examined anatomopathological.
Macroscopic examination showed a fragment almost
completely comprised of a lobulated tumor mass, measuring 36
cm x 21 cm x 11 cm and weighing 4752 grams (Figure 1, panel
C). Cross section revealed lobules containing whitish-pink tissue
and hemorrhagic caverns. Microscopic examination showed
a sharply demarcated tumor without obvious capsulation. The
tumor itself had double cell-layered trabecular architecture with
isolated blood vessels and absence of accompanying bile ducts.
Nodules within the tumor showed trabecular architecture with
more than three cell layers and nuclear pleomorphism matching a well differentiated, grade 2 hepatocellular carcinoma (HCC)
originating from a hepatocellular adenoma, with no evidence
for blood vessel invasion. Molecular studies using Next Generation
Sequencing (NGS) revealed no mutations in BRAF, CTNNB1,
RET, TP53 or PIK3CA. There were no mutations found in β-catenin.
Surrounding liver parenchyma showed normal architecture
apart from reactive changes secondary to tumor mass effect.
Pathologic staging was pT3 G1, and complete resection was obtained.
Close follow-up was advised after multidisciplinary discussion.
Magnetic resonance imaging was planned one month
postoperatively together with alpha-fetoprotein testing. Based
on these results it will be decided whether or not to consider
A hepatocellular adenoma (HCA) is a rare benign liver tumor,
making up 2 percent of all liver neoplasms with an estimated incidence
of 3 per million per year in the general population. They
are predominantly found in young women in their reproductive
years, with an incidence of 3-4 per 100.000 women .
These types of adenomas usually vary in size between 1 and
30 cm diameter, HCAs exceeding a diameter of 30cm are extremely
Typically, patients with HCAs are asymptomatic. With increasing
size, they can cause symptoms of vague abdominal pain,
gastro-intestinal discomfort and in extreme cases, jaundice
because of mass effect. However, abdominal distension, vague
abdominal pain and gastro-intestinal discomfort are also very
common symptoms during pregnancy and can thus be attributed
to pregnancy, delaying diagnosis .
The most significant complications of hepatocellular adenomas
are spontaneous hemorrhage and malignant transformation
Risk factors for hemorrhage in liver adenomas are the presence
of more than ten lesions, a BMI (Body Mass Index) of more
than 25kg/m2, tumors located in segments II-III, an exophytic
localization in relation to the liver capsule, the presence of central
or peripheral arteries and lesion size greater than 35 mm
. Spontaneous rupture or spontaneous hemorrhage can be
Of all HCAs, approximately 4.2 percent will eventually transform
into malignant hepatocellular carcinoma .
Guidelines of the European Association for the Study of the
Liver (EASL) stated that resection is indicated for HCAs greater
than 5 cm, which do not regress by 6 months after conservative
measures or those continuing to grow . Very seldom does an
HCA smaller than 5 cm progress to an HCC.
Risk factors for malignant degeneration include a history
of anabolic androgen intake, male gender, increasing size of the adenoma, patients with type I or type III glycogen storage disease
and adenomas containing a β-catenin mutation . The
only risk factor present in our patient was increasing size of the
Oral contraceptive (OC) drug use could also play a potential
role in malignant degeneration; however, this is not yet clearly
established. OCs do stimulate the growth of HCAs and an increase
in adenoma size raises concern for malignant degeneration.
Given the influence of estrogens on tumor growth, all women
diagnosed with HCA should initially be treated conservatively
through cessation of oral contraceptives and weight reduction
Little is known about the behavior of HCAs during pregnancy.
The build-up of estrogen levels, the hyperdynamic circulation
and the increase in liver vascularization during pregnancy, especially
in the third trimester can lead to growth of the adenoma
. We hypothesize that this physiologic elevation of pregnancy
hormones contributed to the malignant degeneration of the
Although abdominal discomfort, nausea and vomiting are
frequent symptoms experienced during pregnancy, one should
always thoroughly investigate these complaints. Liver tumors
such as hepatocellular adenomas are rare but should be kept
in mind. Malignant transformation is even more infrequent. We
believe that increased endogenous levels of steroid hormones
during pregnancy can lead to rapid, hormone-induced growth
of hepatocellular adenomas, promoting rupture and effectuating