Case 11 -

Epithelioid Angiomyolipoma John N Eble, M.D. Holger Moch, M.D.

Case history: A 48 year-old man with diabetes and hepatitis C was found to have a renal mass by computerized tomography during evaluation of diverticulitis. Fine needle aspiration cytology was done and the diagnosis was "renal cell carcinoma." Left radical nephrectomy was performed. Macroscopic findings: An 8 cm, well-circumscribed solid mass protruded from the lower pole of the kidney. Its cut surface showed soft tan tissue with extensive hemorrhage. Diagnosis: Epithelioid angiomyolipoma Epithelioid angiomyolipomas have been mistaken for high grade renal cell carcinomas at frozen section, by fine needle aspiration cytology, and in permanent sections. While many angiomyolipomas contain epithelioid smooth muscle cells, "epithelioid angiomyolipoma" is given its name because its overall appearance so much suggests an epithelial tumor. The diagnosis is important because perhaps 50% cause the death of the patient through metastasis and local recurrence. Gross Pathology These tumors contain little or no fat so they are typically pink or gray. Hemorrhage is very common and often is extensive. Intercellular cohesion is poor so the tumors often have a friable texture. Microscopic Pathology Epithelioid angiomyolipoma usually is mainly composed of stubby spindle cells mixed with polygonal cells with eosinophilic cytoplasm. The combination of edema fluid and hemorrhage with poor intercellular cohesion leads to an appearance of incipient necrosis. Pools of hemorrhage can create cavities which are very convincingly similar to cysts filled with blood, heightening the illusion of epithelial differentiation. Of considerable diagnostic value are large cells with abundant amphophilic cytoplasm and eccentrically-located nuclei with prominent nucleoli. These cells look a bit like ganglion cells and their presence strongly suggests epithelioid angiomyolipoma. Multinucleated giant cells also are present in many tumors. Chronic and acute inflammatory infiltrates are common. Among primary renal epithelial tumors, the principal differential diagnostic considerations are sarcomatoid clear cell renal cell carcinoma, sarcomatoid urothelial carcinoma, clear cell renal cell carcinoma with granular cytoplasm, and the eosinophilic variant of chromophobe renal cell carcinoma. Clear cell renal cell carcinoma with granular cytoplasm differs from epithelioid angiomyolipoma in having the characteristic vascular pattern and alveolar, tubular, or microcystic architectural patterns, all of which are absent from epithelioid angiomyolipoma. Immunohistochemistry can be helpful in making the diagnosis. Epithelioid angiomyolipoma uniformly fails to react with antibodies to cytokeratins and epithelial membrane antigen, and reacts with antibodies to smooth muscle actin, and to a lesser extent, desmin. HMB45 and melanA often are positive, as is expected in angiomyolipoma. References Eble JN, Amin MB, et al: Epithelioid angiomyolipoma of the kidney, a report of five cases with a prominent and diagnostically confusing epithelioid smooth muscle component. Am J Surg Pathol 21:1123-1130, 1997 Martignoni G, Pea M, et al. Carcinoma-like monotypic epithelioid angiomyolipoma, in patients without evidence of tuberous sclerosis, a clinico-pathologic and genetic study. Am J Surg Pathol 22:663-672, 1998.