Hepatic Angiomyolipoma

Archives of Pathology & Laboratory Medicine, Oct 2008 by Petrolla, Amber A, Xin, Wei

Hepatic angiomyolipoma is a rare, benign, hepatic mesenchymal neoplasm found in both males and females, and most commonly in adult females. Angiomyolipoma occurs most commonly in the kidneys. The liver represents the second most frequent site of involvement. Hepatic angiomyolipomas are composed of varying amounts of smooth muscle cells, adipose tissue, and vessels. The smooth muscle cell component is the most specific to the diagnosis. The smooth muscle cells can have varying morphologies and are positive for homatropine methylbromide-45 but are negative for hepatocyte paraffin 1 and S100 protein. The definitive diagnostic study remains the histologic examination of the surgically resected lesion coupled with immunohistochemical stains. The differential diagnosis includes hepatocellular carcinoma, hepatic adenoma, leiomyoma, hepatoblastoma, melanoma, and gastrointestinal stromal tumor. The immunohistochemical staining pattern differentiates this lesion from other malignant and benign liver lesions. If the diagnosis of hepatic angiomyolipoma has been made, it can be followed conservatively or surgically resected.

(Arch Pathol Lab Med. 2008;132:1679-1682)

Hepatic angiomyolipoma (AML) is a rare, benign, hepatic mesenchymal neoplasm, first described in 1976 by Ishak.1,2 To date, approximately 200 hepatic AMLs have been reported.3 The tumor consists of 3 components: smooth muscle cells (SMCs), adipose tissue, and vessels. These components can vary greatly within the lesion. This heterogeneity makes the preoperative diagnosis by imaging, needle biopsy, and other techniques difficult.

It is possible to misdiagnose hepatic AML as a number of entities, both benign and malignant. Commonly confused entities include lipoma, hepatocellular adenoma and carcinoma, sarcoma, or other metastatic neoplasms. Hepatic AML has been reported in patients from many ethnicities, including whites, Asians (Chinese and Japanese), and blacks.1,4,5 Hepatic AML has not been proven, at this time, to be associated with any virus or genetic abnormality. When tested or reported, none or only a very small proportion (8%) of the patients from studied cases were positive for hepatitis viral markers or had abnormal liver function tests.6,7 Uncommonly, there have been lesions in patients with tuberous sclerosis reported (6%-10%); however, that association is far more common in renal AML (20%-40%).1,8,9 Most patients with hepatic AML do not have tuberous sclerosis. There is no proven association between hepatic and renal AML.1,2 Although hepatic AML can be confused with many entities, the diagnosis can be made reliably and definitively on histologic examination along with immunohistochemical analysis, specifically with homatropine methylbromide-45 (HMB-45).

ETIOLOGY

Although the exact etiology of hepatic AML has yet to be definitively proven, a number of proposals have been made. One of the major components of hepatic AML is the SMC; a defining and consistent feature of hepatic AML is SMC positivity for the immunohistochemical stain HMB-45. HMB-45 is an antibody that reacts with an oncofetal premelanosome-associated glycoprotein 2, found in neoplastic (but not normal) melanocytes, as well as other cells bearing those structures.1,10 Perivascular epithelioid cell (PEC) is a term proposed to describe the SMCs found in hepatic AML, which are always positive for HMB-45, and has been postulated as the underlying neoplasticmesenchymal cell.1,9-11 These cells share some common features with melanocytes, neuroendocrine, and muscle cells.11 PECs are also found in pulmonary lymphangiomyomatosis and clear cell ("sugar") tumors of the lung. PECs are HMB-45 positive in these lesions as well. Therefore, it has been proposed that these tumors and hepatic AMLs belong to a family referred to as PEComas, but that theory has not yet been solidified.1,5-7,9,11,12 A possible origin from neural crest cells has been postulated as well.9

CLINICAL PRESENTATION

Hepatic AML can be found in both males and females, with a female preponderance, and is found in adult patients ranging from 26 to 86 years of age.1,2,4-9,11-13 Most patients with hepatic AML are asymptomatic, and the lesions are found incidentally on imaging for other medical issues or at autopsies. Large lesions may cause symptoms related to mass effect.1,7 Other reported symptoms include abdominal discomfort and mild fever.1,4,11 Acute tumor rupture, although uncommon, has been reported.1,6

Angiomyolipoma occurs most commonly in the kidneys. Hepatic AMLs represent the second most common site of involvement. Rare occurrences at many other sites have been reported, including the uterus, retroperitoneum, mediastinum, renal capsule, the nasopharyngeal cavity, the buccal mucosa, the hard palate, penis, vagina, fallopian tube, abdominal wall, skin, stomach, and spinal cord.5,11,12 Invasive growth has been reported as exceedingly rare, and these lesions do not show malignant potential and most do not metastasize. To date, 2 metastatic lesions have been reported-to the omentum and lung.14,15