Renal angiomyolipoma (AML) is hamartomas composed of blood vessels, smooth muscle and fatty tissue. In most cases, it is a tumor with benign behavior that may appear sporadically or be associated with tuberous sclerosis complex (TSC).1,2 Rare cases of clinically aggressive or malignant AML have been reported.3-8 These atypical variants of AML are histologically categorized as epithelioid AML. Here, we report a case of a 27-year-old man who had malignant epithelioid AML with highly aggressive clinical features.
A 27-year-old man with complaints of left flank dull pain and abdominal fullness for five days consulted our clinic in May, 2008. Physical examination found a large mass in the left upper abdomen and no evidence of TSC. Computer tomography (CT) scan showed multiple masses in both kidneys; the low-density area of the tumor indicated the presence of a fat component. Of special interest was a large heterogeneous mass (15.5 cm × 13.0 cm) that occupied the upper middle portion of the left kidney (Figure 1). There were no lesions in the liver. Magnetic resonance imaging (MRI) studies confirmed the CT findings. Chest X-ray examination showed no abnormalities.
We diagnosed this case as bilateral renal AML and a left nephrectomy was performed. The patient recovered uneventfully and was discharged 9 days later. Pathology analysis of the left kidney tumor showed an epithelioid AML consisting of blood vessels, smooth muscle and adipose tissue, which are all characteristics of AML. However, the predominant cell type was epithelioid cells. The epithelioid cells had pleomorphic and hyper-chromatic nuclei with densely eosinophilic cytoplasm (Figure 2). Immunohistochemical findings were positive for human melanosome-associated protein (HMB-45) and melanoma antigen recognized by T cells 1 (MART1).
Approximately three months later the patient presented with fever and left flank pain. MRI scan showed a large mass arising in the left retroperitoneum and multiple lesions in the liver. Chest X-ray examination showed left medium pleural effusion. We diagnosed malignant epithelioid AML with multiple liver metastases. We considered that the patient was not a surgical candidate because of the characteristic of the tumor and the metastases into the liver. Thus, he was treated with conservative therapy. The patient's general state of health gradually deteriorated, and he died approximately four months after suffering his initial clinical symptoms.
Renal AML has traditionally been considered as a clinically benign lesion due to its lack of recurrence or metastases; therefore, AML found in the kidney is generally managed conservatively. AML appears in two distinct settings, namely as part of the TSC and sporadically in individuals who otherwise have no clinical features of that entity.
Epithelioid AML is a recently recognized variant of AML that is characterized by the presence of polygonal cells with densely eosinophilic cytoplasm and varying degrees of nuclear atypia. These cells display positive immuno-reactivity for melanogenesis markers (HMB-45, MART1), and contain premelanosomes. Extensive intratumoral hemorrhage and necrosis are more common in this variant than in the classic histological type. No parameters have been developed for the correlation with prognosis, but patients with tumors showing necrosis, nuclear anaplasia, mitosis, and extrarenal dissemination have a poorer outcome. In the present case, there were typical elements of classic AML, and the tumor consisted predominantly of epithelioid cells with atypical nuclei and focal mitotic figures that stain strongly for HMB-45 and MART1.
Previous reports have suggested that epithelioid AML may be potentially malignant.3-8 However, there are very few patients with epithelioid AML that exhibit highly aggressive biologic characteristics. Yamamoto et al 9 reported one patient with epithelioid AML who died three months after presentation due to widespread metastasis. But that patient had multiple liver metastases when they made the original clinical diagnosis. In the present case, there were no signs of metastases before surgery, but postoperative life span was only four months. Therefore, we believe that our patient may had the most invasive epithelioid AML among reported cases.
In conclusion, epithelioid AML is a rare tumor of unpredictable behavior. We should keep in mind that some epithelioid AMLs are capable of highly aggressive clinical behavior.
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