Answer: Epithelioid angiomyolipoma with atypia

Histology: The tumor is composed of two cell types. Areas of the tumor are composed of fascicles of spindle cells with ovoid nuclei and lightly eosinophilic cytoplasm (image 2). Other cells are epithelioid with abundant eosinophilic cytoplasm, atypical vesicular nuclei and prominent nucleoli with focal huge multinucleated giant cells with ‘strap-like’ appearance (image 3). Some of the neoplastic multinucleated giant cells had nuclei arranged peripherally in a ring-like fashion tracing the cell contour. The entire tumor had the above morphology. Mitotic figures were scant but an atypical mitotic figure was identified (image 4). The lesion lacked necrosis.

Discussion: Renal angiomyolipoma (AML) is a mesenchymal neoplasm composed of a variable proportion of adipose tissue, spindle and epithelioid smooth muscle-like cells and abnormal thick-walled blood vessels. There is a rare form of AML with malignant potential, composed partially or entirely of atypical large epithelioid cells with abundant cytoplasm, vesicular nuclei and prominent nucleoli. We denote AMLs with epithelioid morphology as “epithelioid AMLs” which are then divided into epithelioid AMLs without and with atypia, the latter category associated in the literature with malignant potential.

In a recent series of 40 cases of atypical epithelioid AMLs, we developed a predictive model that includes:

1) nuclear atypia in 70% or more of the epithelioid cells;
2) mitotic count at least 2 per 10 hpf; 3) presence of atypical mitotic figures; and
3) necrosis. Using the presence of at least 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 our series.

The current case had 2 of these features, such that we stated in our report that the lesion had some worrisome features for malignancy yet not enough features to diagnose a malignant AML. Nonetheless, follow-up of the patient is warranted for the possibility of aggressive behavior.

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 (not present in this case);
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 configuration; and
4) immunohistochemical reactivity for melanocytic markers (HMB-45 and/or Melan-A) and negativity for epithelial markers, which was the immunoprofile in this case.