Answer: Epithelioid angiomyolipoma

Histology: Tumor consists of areas with epithelioid large cells with abundant dense eosinophilic cytoplasm and pleomorphic nuclei containing prominent nucleoli. In other areas of the tumor, the cells are somewhat smaller with slight spindling of the cytoplasm. Focally, the tumor has a nested appearance. The tumor appears to extend into perinephric adipose tissue and involve a vessel at the perimeter of the tumor.

Discussion: The recognition of epithelioid AML with atypia, albeit very rare in incidence, has altered the concept of AML as a completely benign neoplasm. In a recent meta-analytical study in which 69 well documented cases of epithelioid AML in the literature were reviewed, the malignancy rate was found to be 38%. We recently studied 40 cases of epithelioid AML with atypia; among the 34 patients in whom clinical follow-up was available, 9 (26%) showed evidence of recurrence and/or distant metastases and 4 died of the disease, and in two patients distant metastases were already documented at the initial presentation. Based on our study, we were able to demonstrate that the following adverse histological features were more commonly associated with malignancy: large epithelioid cell component, severe nuclear atypia, extent of nuclear atypia, mitotic count, presence of atypical mitotic figures, necrosis and presence of lymphovascular invasion. A predictive model that includes nuclear atypia in greater than or equal to 70% of the epithelioid cells, mitotic count greater than or equal to 2 per 10 hpf, presence of atypical mitotic figures, and necrosis was the most accurate in determining tumor behavior. Using the presence of greater than or equal to 3 of those four histologic features as a cut-off to predict an aggressive course we were able to accurately categorize 78% of malignant epithelioid AMLs and 100% of the benign epithelioid AMLs in this series.

Due to its diffuse growth pattern, epithelioid morphology and nuclear atypia, epithelioid AML with atypia is usually confused by pathologists with renal cell carcinoma (RCC), unclassified type. The following histological criteria are the most helpful in identifying epithelioid AML: 1)presence of admixed typical AML components including intratumoral fat and/or abnormal thick-walled blood vessels; 2) low mitotic rate that is discrepant with the degree of cellular atypia in contrast to RCC where mitoses are easily identified when the tumor shows a severe degree of nuclear atypia; 3) presence of multinucleated giant cells with peripheral nuclear distribution and ‘strap-like’ appearance or ‘ameboid’ configuration present in 55% of our cases; and 4) immunohistochemical reactivity for melanocytic markers (HMB-45 and/or Melan-A) and negativity for epithelial markers. Pitfalls with the immunohistochemistry are that epithelioid AML has rarely been reported to show focal positivity for pan-cytokeratin (CAM5.2), and t(6;11) translocation-related RCCs may have absent epithelial antigen expression and aberrant melanocytic expression, although their morphology does not resemble epithelioid AML.