Immunohistochemical study of microphthalmia transcription factor and tyrosinase in angiomyolipoma of the kidney, renal cell carcinoma, and renal and retroperitoneal sarcomas - Comparative evaluation with traditional diagnostic markers

Angiomyolipoma has a unique immunophenotype with co-expression of muscle-sp ecific actin and melanocytic markers such as HMB-45 and Melan-A. The most r ecently developed melanocytic markers, microphthalmia transcription factor and tyrosinase, have not been studied in the diagnosis of angiomyolipoma. W e tested 29 renal angiomyolipomas (21 classic histology, 4 epithelioid vari ants, 2 lipomatous variants, and 2 leiomyomatous variants) with an immunohi stochemical panel, including microphthalmia transcription factor, tyrosinas e, HMB-45, Melan-A, and muscle-specific actin. Results were compared with 1 5 renal cell carcinomas (9 conventional types, 6 with sarcomatoid change), 2 leiomyosarcomas, 5 liposarcomas, and 1 unclassified high-grade sarcoma. M icrophthalmia transcription factor expression was seen in 22 of 29 angiomyo lipomas, one renal cell carcinoma, and one well-differentiated liposarcoma (that is, 2 of 23 non-angiomyolipomas; sensitivity 75%, specificity 91%). T yrosinase expression was seen in 4 of 29 angiomyolipomas and 0 of 23 non-an giomyolipomas (sensitivity 14%, specificity 100%). HMB-45 was positive in 2 4 of 29 angiomyolipomas and 0 of 23 non-angiomyolipomas (sensitivity 83%, s pecificity 100%). Melan-A was expressed by 25 of 29 angiomyolipomas and 0 o f 23 non-angiomyolipomas (sensitivity 86%, specificity 100%). Muscle-specif ic actin was expressed by 29 of 29 angiomyolipomas and 2 of 23 non-angiomyo lipomas (both leiomyosarcomas; sensitivity 100%, specificity 91% [100% excl uding leiomyosarcomas]). Microphthalmia transcription factor showed the mos t widespread staining in angiomyolipoma (50% of cases staining more than ha lf of the tumor cells) followed by Melan-A (24% of cases staining more than 50%). Only three cases showed positivity for all four melanocytic markers, while in one case each only microphthalmia transcription factor and Melan- A were positive. We conclude that microphthalmia transcription factor, but not tyrosinase immunostaining, has a sensitivity and specificity that rival s those of the established markers, HMB-45 and Melan-A, in the diagnosis of angiomyolipoma. Our data supports the use of a panel in difficult cases th at includes antibodies to microphthalmia transcription factor, either Melan -A or HMB-45, and muscle-specific actin to provide the best mix of high sen sitivity, high specificity, nuclear and cytoplasmic immunolocalization, and widespread staining of cells within a given tumor.