Case 10 - Epithelioid Angiomyolipoma

Slide 19 - Epithelioid cells of variable size, low magnification Slide 20 - Large ganglion cell-like and multinucleate giant cells, high magnification Click on thumbnail images of slide for an enlarged view Gross Features: Angiomyolipoma a complex neoplasm typically composed of thick-walled blood vessels, smooth muscle, and fat, the relative proportions of which vary widely When fat predominates, angiomyolipoma is yellow and has a greasy appearance. When smooth muscle and blood vessels predominate, angiomyolipoma is pink or tan. Hemorrhage and degeneration may give a friable and mottled appearance.   Angiomyolipoma Extending into Vena Cava 21 cases, all but one female 7 with tuberous sclerosis Mean age 44, range 16-75 Mean follow up 33 months (n=14) range 1-122 All alive and well Sporadic angiomyolipomas are single and tend to be larger than 4 cm in diameter since the fat density on CT scan facilitates the radiologic diagnosis and it is recommended that asymptomatic ones be removed only when they exceed 4 cm (rupture and hemorrhage are uncommon in smaller ones). In tuberous sclerosis, there usually are multiple angiomyolipomas (indeed multiple angiomyolipomas suffice for the diagnosis of tuberous sclerosis). Angiomyolipomas tend to be well-circumscribed but confluence of multiple angiomyolipomas in tuberous sclerosis can cause an appearance of infiltration. Rarely, angiomyolipoma extends into the renal vein or vena cava. Microscopic Features: The microscopic diagnosis of angiomyolipoma usually is straightforward because of the typical mixture of spindle-shaped smooth muscle cells, fat, and thick-walled blood vessels. Nuclear pleomorphism and mitotic activity are occasional present. The smooth muscle of angiomyolipoma frequently consists of both spindle and epithelioid cells but it is rare for epithelioid smooth muscle to predominate.   Diagnostic Problems with Epithelioid Angiomyolipoma Epithelioid cells mimicking renal cell carcinoma Predominance of spindle cells mimicking leiomyoma Nuclear atypia and high cellularity mimicking leiomyosarcoma Confluent angiomyolipomas mimicking an infiltrative process Collision between angiomyolipoma and renal cell carcinoma 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. At first examination, tumors in this category have some features which suggest carcinoma: polygonal cells with abundant eosinophilic cytoplasm growing in sheets with areas of necrosis, mitotic activity, and nuclear pleomorphism. Differential Diagnosis: 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.