2021-04 / January 25
Contributors: Christopher Metter, Rajal Shah

A male in his 50s with a history of multiple bilateral renal masses, the largest of which was a left sided 14.5 cm mass, and multiple pulmonary nodules. The patient underwent a left radical nephrectomy. Sections from the main tumor and background kidney are shown.


1. What is the correct diagnosis?

a. Clear cell renal cell carcinoma

b. FH deficient renal cell carcinoma

c. Epithelioid angiomyolipoma

d. Translocation renal cell carcinoma

1. Epithelioid angiomyolipoma

Epithelioid angiomyolipomas (eAML) are a rare variant of angiomyolipoma (AML) and has also been referred to as perivascular epithelioid cell tumor (PECOMA), accounting for up to 5% of all AMLs. Epithelioid cells are the defining feature of eAML, with the 2016 WHO classification requiring at least 80% of the tumor to be epithelioid in order to render the diagnosis. Epithelioid cells are enlarged, polygonal cells with eosinophilic or clear cytoplasm, atypical nuclei, and prominent nucleoli (Picture 1 and 4). Two patterns of eAMLs have been described, the “carcinoma-like” pattern and the so-called “epithelioid and plump spindled cells with diffuse growth” pattern. The “carcinoma-like” pattern manifests with a cohesive heterogeneous population of tumor cells arranged in compartmentalized sheets with intervening vasculature rich septa. When compared to the “carcinoma-like” pattern, the “epithelioid and plump spindled cells with diffuse growth” pattern is populated by a smaller in size and more monotonous collection of epithelioid and spindled cells arranged in tightly packed sheets. By immunohistochemistry, the tumors are immuno-reactive for melanocytic markers (e.g. HMB45, Melan A, and microphthalmia transcription factor) (Picture 2), cathepsin K (Picture 3), and smooth muscle markers.

Like classical angiomyolipoma, eAML has been described in patients both with and without evidence of tuberous sclerosis and in the TSC2/PKD1 contiguous gene syndrome. The examination of the background kidney provides important clues regarding this association. The presence of tumorlets (microscopic angiomyolipomas) (Picture 5), suggests an association with tuberous sclerosis in this patient.

It is important to recognize eAML because they, in contrast to classical AML, can demonstrate some malignant potential. Some have suggested that certain histologic features can predict the malignant potential of eAMLS, such as: tumor size >7 cm, presence of tuberous sclerosis syndrome, presence of the “carcinoma-like” pattern, invasion into perinephric fat or renal vein, necrosis, high mitotic count (>2/10hpf), older age at presentation, and the presence of severely atypical cells. Others, more recently, have suggested that these features do not correlate with malignant potential and that the previous findings may have been related to the type of cases/population the previous studies had incorporated into their cohort.

1. He, Wenlei, et al. “Epithelioid Angiomyolipoma of the Kidney: Pathological Features and Clinical Outcome in a Series of Consecutively Resected Tumors.” Modern Pathology, vol. 26, no. 10, Oct. 2013, pp. 1355–64. (Crossref), doi:10.1038/modpathol.2013.72.

2. Nese, Nalan. “Pure Epithelioid PEComas (So-Called Epithelioid Angiomyolipoma) of the Kidney: A Clinicopathologic Study of 41 Cases: Detailed Assessment of Morphology and Risk Stratification.” Am J Surg Pathology, vol. 35, no. 2, Feb. 2011, pp. 161–76.

3. WHO Classification of Tumours of the Urinary System and Male Genital Organs. 4th ed., 2016.

Christopher Metter, MD

Rajal B. Shah, MD


Angiomyolipoma, Epithelioid angiomyolipoma, Tuberous sclerosis complex