Case of the Week

2021-34/ August 23

Contributors: Leila Ali, Reza Alaghehbandan

A man in his mid-30s presented with a 17 cm left kidney mass and underwent radical nephrectomy. Imaging had shown a solid heterogeneous mass with calcifications.

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Quiz

1. What is the correct diagnosis?

a. Clear cell renal cell carcinoma

b. MiT family translocation associated renal cell carcinoma

c. Epithelioid angiomyolipoma

d. Epithelioid angiosarcoma

e. Malignant melanoma

The tumor grossly showed a heterogeneous, solid dark brown mass with large areas of necrosis. Histologic sections show an infiltrative and epithelioid renal tumor composed of large and polygonal cells with dense eosinophilic as well as clear cytoplasm. The neoplastic cells have marked nuclear atypia with prominent nucleoli arranged in cohesive nests, alveoli and sheets. The tumor also exhibits focal spindle cells arranged in diffuse and densely packed sheets. Mitotic figures including atypical mitoses are noted in more than 2-3 per HPF. Furthermore, the tumor shows extensive hemorrhage and necrosis with focal ganglion cell-like appearance morphology. The neoplastic cells are positive for Melan-A and HMB45, while negative for MNF116, AE1/3, PAX8, and CK7. Overall, the features are consistent with epithelioid angiomyolipoma (AML).

Epithelioid AML is a rare variant of AML with predominant epithelioid histology (at least 80-95% epithelioid cells). It can occur sporadically or in patients with tuberous sclerosis and in the TSC2/PKD1 contiguous gene syndrome. These tumors are potentially malignant and can recur and metastasize.

Epithelioid AML typically displays two morphological appearances: “carcinoma-like” and “epithelioid and plump spindle cells in diffuse growth”. A few cases of classic AML with a sarcomatous overgrowth and aggressive clinical course have also been reported, displaying leiomyosarcoma or liposarcoma component. There are a few studies that have proposed prognostic criteria for epithelioid AML. In 2011 Nese et al. proposed the following as prognostic adverse features in epithelioid AMLs: presence of tuberous sclerosis and/or concurrent AML, tumour size (>7 cm), carcinoma-like morphologic pattern, invasion of perinephric fat and/ or renal vein and presence of necrosis. The authors developed a risk-stratified model as follows: low (0–1 parameter), intermediate (2–3 parameters), and high risk (4 or more parameters), corresponding to 15%, 64%, and 100% risk for disease progression in each of the categories, respectively.

As for the differential diagnosis, epithelioid AML is the most challenging and important variant to be recognized from clear cell renal cell carcinoma, given the therapeutic implications. This can become more difficult particularly when clear cell renal cell carcinoma is associated with sarcomatoid features. In such cases, generous sampling along with immunohisotchemical examination would be most helpful. Cathepsin K, HMB45 and Melan-A are positive in epithelioid AML. It should be noted that this immunophenotype overlaps with MiT family translocation renal cell carcinoma, in which case a negative PAX8 would be most useful.

1. Caliò A, Brunelli M, Segala D, Zamboni G, Bonetti F, Pea M, Martignoni G. Angiomyolipoma of the kidney: from simple hamartoma to complex tumour. Pathology. 2021 Jan;53(1):129-140.

2. Nese N, Martignoni G, Fletcher CD, Gupta R, Pan CC, Kim H, Ro JY, Hwang IS, Sato K, Bonetti F, Pea M, Amin MB, Hes O, Svec A, Kida M, Vankalakunti M, Berel D, Rogatko A, Gown AM, Amin MB. 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 Pathol. 2011 Feb;35(2):161-76.

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The Genitourinary Pathology Society (GUPS) was formed with the vision of advancing the care of patients with urologic diseases through enhancements of best practices, research, and education in the subspecialty of Urological Pathology.

GUPS is an official Companion Society of the United States and Canadian Academy of Pathology (USCAP).

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