Recently, it has been recognized that some angiomyolipomas are composed mainly of epithelioid smooth muscle of epithelioid type, producing a histological picture distinctly different from the usual angiomyolipoma. These tumors are characterized by cells with abundant eosinophilic cytoplasm. Among primary renal epithelial tumors, the principal considerations are clear cell renal cell carcinoma with granular cytoplasm, the eosinophil variant of chromophobe renal cell carcinoma, and renal oncocytoma. Among mesenchymal tumors, benign fibrous histiocytoma is a consideration. 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 the differential 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. That smooth muscle cells of angiomyolipoma, especially those with epithelioid morphology, react with HMB-45 has been known since 1991. Recently, HMB-45 has been shown to react with leiomyomas arising from the renal capsule.