Renal Neoplasia: Diagnostic Problems and Recently Recognized Entities
Case 11 -
John N Eble, M.D.
Holger Moch, M.D.
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.
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.
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
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.
- 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
- 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,