Multiple Focal Nodular Hyperplasia of the Liver in - Department of ...

594 Kim et al.
Journal of
Gastrointestinal Surgery
that surround hyperplastic parenchymal nodules. The
central scar contains an anomalous feeding artery. 7,8
The hepatocytes in the lesion are normal, and bile
duct proliferation is usually prominent. 9,10 It is usually
a stable lesion that does not enlarge over long periods
of time. Rarely, it is complicated by growth, rupture,
portal hypertension, hemorrhage, or necrosis. 11
In this patient, the history and CT images mandated
consideration of FNH, FHC, and hepatic adenoma in
the differential diagnosis. As compared to FNH, on CT
imaging, adenomas tend to be larger, more heterogeneous,
may have hemorrhage, and lack a central scar.
They generally have less arterial enhancement and
may contain fat. Fibrolamellar hepatocellular carcinoma
tends to be large, have calcification, and be heterogeneous.
It is also prone to hemorrhage and to
have areas of necrosis. The lesions in this patient were
large, heterogeneous, had little enhancement, and
lacked a scar. Thus, on the basis of imaging characteristics,
the lesions in this patient were more consistent
with adenoma or fibrolamellar hepatocellular carcinoma.
As such, definitive biopsy was indicated.
Histologically, adenoma and FHC can have similar
characteristics to FNH. Adenoma is often composed
of sheets of normal-appearing hepatocytes without
features of malignancy. There are few or no portal
tracts or central veins, and bile ducts are absent. 12,13
These features distinguish adenoma from FNH.
FHC may similarly be composed of sheets of hepatocytes.
However, these cells are distinctively plump
and deeply eosinophilic. Pale or hyaline bodies in the
cytoplasm, prominent nucleoli, and rare mitoses are
characteristic of FHC. 14
The pathogenesis of FNH is unclear, but two predominant
theories exist. FNH may be a response to
a preexisting vascular abnormality. 8,15 The artery associated
with the central scar is larger than normal
and causes hyperperfusion in this region and/or arterialization
of sinusoids, with resulting hyperplasia of
the surrounding parenchyma. Growth of surrounding
hepatocytes stops when the sinusoids are compressed
and vascular resistance increases with slowing of the
blood flow. 8 The second theory relates to the use of
oral contraceptives. In contrast to adenoma, the
origin of FNH has not been definitively linked to
estrogen, but based on isolated reports, it is still
thought that estrogen may act as a growth factor
and can increase the size and vascularity of the
nodules. 8,16–18 Therefore, in any patient with FNH,
the use of oral contraceptives should be strongly
discouraged.
Another important finding among patients with
multiple FNH is an identified association with other
vascular malformations and/or neoplasia. 19 The most
frequent associations include arterial dysplasia, portal
vein atresia, berry aneurysm of the brain, and pulmonary
arterial hypertension. 16,19–21 There are additional
associations with meningioma, astrocytoma,
liver hemangioma, and Klippel-Trenaunay and von
Recklinghausen syndromes. 16,19,20,22 As such, patients
with multiple FNH are advised to undergo CT or
MRI of the brain to detect treatable aneurysmal lesions.
Despite such associated pathologic conditions,
multiple FNH appears to have a good prognosis. Once
the diagnosis of multiple FNH was secured, our patient
underwent MRI of the brain. This revealed no
evidence of vascular malformations.
Our patient’s presentation highlights the difficulty
in making the diagnosis of multiple FNH. The historical
attributes of youth, postpartum status, female sex,
and particularly oral contraceptive use raise suspicion
for adenoma. The physical examination finding of a
mass in her right upper quadrant was nondiagnostic
but is, nevertheless, a most common feature of multiple
FNH. 6,16,19,23 Radiographic evaluation by CT exhibited
features more consistent with fibrolamellar
hepatocellular carcinoma or adenoma, as opposed to
FNH. MRI, which we often use to clarify equivocal
CT findings, was not used in this case. Because the
features of this lesion gave us sufficient cause to suspect
malignancy, we did not think that further imaging
of any kind would be sufficiently definitive to
Table 1. Clinicopathologic distinction between focal nodular hyperplasia, hepatic adenoma, and fibrolamellar
hepatocellular carcinoma
Typical features FNH HA FHC
Physical examination Asymptomatic, RUQ pain Asymptomatic, RUQ pain Asymptomatic, RUQ pain
CT examination Central scar, feeding artery Lesional hemorrhage, Calcifications, central scar
hematoma, necrosis
Histologic findings Central fibrous scar, sheets Sheets of hepatocytes, Sheets of hepatocytes,
of hepatocytes, bile duct eosinophilic inclusions, abundant fibrous stroma,
proliferation absence of bile ducts prominent nucleoli, mitoses
FNH focal nodular hyperplasia; HA hepatic adenoma; FHC fibrolamellar hepatocellular carcinoma; RUQ right upper quadrant;
CT computed tomography.