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.