DISCUSSION
Epithelioid angiomyolipoma is an uncommon variant of angiomyolipoma
where the epithelioid smooth muscle cells predominate and is classified
as a perivascular epithelioid cell tumor [4]. Epithelioid
angiomyolipoma occurs most commonly in the kidneys and rarely involves
the liver. More than 200 cases of hepatic angiomyolipomas have been
reported in the English language literature so far. The age at diagnosis
ranges from 10 to 80 years. Cases in children are rare [5]. Our
patient was 37 years old. In contrast to renal angiomyolipomas, which
are associated with tuberous sclerosis in up to 20% of patients,
hepatic angiomyolipomas are associated with tuberous sclerosis in only
6% of patients, with a female predominance [6,7]. Our patient had
no past medical history of tuberous sclerosis. Most patients with
hepatic angiomyolipomas are asymptomatic, and their tumors are found
incidentally during routine health check-ups [1,5,6]. In a small
proportion of cases, patients may have mass compression effects
including epigastric intermittent pain, nausea, and dyspepsia
[1,5-7]. Our patient presented with a five-month history of weight
loss, anorexia, abdominal distention and discomfort. There are no
helpful laboratory tests for this disease. The liver function is normal,
tumor and hepatitis markers are negative as it was the case in our
patient. The imaging appearance of hepatic epithelioid angiomyolipoma is
variable since the relative proportion of tissue components varies
widely. Imaging studies are not necessarily adding diagnostic value,
especially in tumors with minimal fat component [8]. In our patient,
the imaging findings were not suggestive of hepatic angiomyolipoma since
the adipocytic component was inconspicuous. Contrast enhancement on
arterial phase and hypoattenuation/hypointensity on portal phase were a
common finding on imaging for epithelioid angiomyolipoma of the liver
[9]. Even with the advances of nuclear medicine technologies, in the
presence of hemorrhage and associated inflammatory response, hepatic
angiomyolipomas may present with increased fluorodeoxyglucose uptake on
imaging studies [10]. Macroscopically, hepatic angiomyolipomas with
significant fat content tend to be soft and yellow, whereas tumors with
predominantly smooth muscle content tend to be firm, with a tan-white
cut surface. Necrosis and hemorrhage may occur. Cystic appearance with
hemorrhagic areas is rare which added to the diagnostic difficulty in
our case [1,11]. Histologically, hepatic angiomyolipomas resemble
their counterpart in the kidney. They contain a variable amount of fat,
vessels, and smooth muscle cells [1,6,7,11]. Four types of smooth
muscle cell can be found histologically within angiomyolipomas including
spindle, intermediate, epithelioid and pleomorphic cells [6]. The
percentage of epithelioid cells that is required to make a diagnosis of
epithelioid angiomyolipoma was not defined in the published studies. A
study by Aydin et al. proposed that using 10% of epithelioid component
as the cut-off value was preferred [11]. In our patient, 100% of
the tumor cells were epithelioid. The vascular component is typically
made of thick-walled hyalinized arterial or venous-like vessels with
abnormally thickened hyperplastic elastic fibers as it was the case in
our patient [1,6]. Foam cells with fine lipid droplets and brown
melanin granules can be seen. In our case, brown melanin granules were
focally found within the tumor. Depending on the proportions of the
three tissue elements in angiomyolipoma, it can be classified into 10
types; mixed (conventional), myomatous, lipomatous, angiomatous,
myoangiomatous, angiomyomatous, myolipomatous, lipomyomatous,
lipoangiomatous, and angiolipomatous [1]. These subtypes have no
clinical or prognostic significance. Awareness of these types will be
useful in understanding and interpreting a wide range of imaging
findings for hepatic angiomyolipomas. In our patient, the tumor is
classified as a mixed epithelioid angiomyolipoma with a minor adipocytic
component. Hepatic angiomyolipoma often contains hematopoietic elements,
including megakaryocytes as well as erythroid and myeloid precursors. In
our case, there were extensive foci of extra-medullary hematopoiesis.
The pathognomonic feature of angiomyolipoma is the positivity of smooth
muscle cells for human melanoma black-45 (HMB-45) along with the
positivity for muscle markers. The expression of melanocytic and muscle
markers places this tumor in the category of PEComas. CD117 (c-kit) and
tyrosinase are also positive in angiomyolipomas [12,13]. In our
patient, HMB45, MelanA, Smooth Muscle Actin and Desmin showed diffuse
strong positive staining. However, the tumor cells showed negative
staining for anti-hepatocyte, and CD34.
The main differential diagnosis of epithelioid angiomyolipoma is
hepatocellular carcinoma or hepatocellular adenoma [1,14]. Many
features of hepatic angiomyolipoma can lead to a misdiagnosis of
hepatocellular carcinoma, such as polygonal cells in a trabecular
arrangement, nuclear pleomorphism, eosinophilic globules, and tumor
necrosis. However, hepatocellular carcinomas usually express HepPar 1
and do not express smooth muscle or melanoma antigens [1,14]. In our
case, the diagnosis of hepatocellular carcinoma was suggested on fine
needle biopsy because of the epitheliod morphology of tumor cells which
were arranged in a trabecular pattern. Tumors with a predominant fat
component may be mistaken for focal fatty change or hepatocellular
adenoma. The combination of spindle and epithelioid cells and positivity
for HMB-45 may mimic metastatic malignant melanoma [1,14].
Furthermore, when epithelioid smooth muscle cells with clear cytoplasm
arranged in a solid or alveolar pattern are encountered, the possibility
of metastatic renal cell carcinoma must be excluded.
Previous studies suggested that hepatic epithelioid angiomyolipoma can
be managed by conservative treatment with follow-up [15]. Surgical
intervention may be needed in selected patients with symptomatic masses
to alleviate effects on neighboring organs [16]. Hepatic epithelioid
angiomyolipoma is regarded as a tumor of uncertain behavior; cases of
epithelioid angiomyolipoma with local recurrence and multiple metastases
have been reported [16].
In conclusion, hepatic epithelioid angiomyolipomas can lead to
considerable diagnostic problems clinically, radiologically, and
pathologically because of their diverse morphology. Diagnostic confusion
arises when the fat cell component is inconspicuous and the smooth
muscle component assumes an unusual morphologic phenotype. The
diagnostic difficulty escalates in a fine needle aspiration setting. The
striking feature in our case was the unusual macroscopic appearance of
the tumor which was cystic with hemorrhage as well as the prominence of
extramedullary hematopoiesis. Positive HMB-45 immunostaining of the
myoid cells is a major diagnostic feature. The possibility of
angiomyolipoma should be considered whenever unfamiliar hepatic tumors
are encountered.