Renal angiomyolipoma - Further immunophenotypic characterization of an expanding morphologic spectrum

Background - Renal angiomyolipoma is a benign tumor histologically characte rized by proliferation of spindle cells, epithelioid cells, and adipocytic cells in concert with many thick-walled blood vessels. To add further diagn ostic confusion, an epithelioid cell-predominant variant of renal angiomyol ipoma has recently been described. HMB-45 immunoreactivity correlates with ultrastructural striated organelles that closely resemble premelanosomes, a lthough no evidence of melanogenesis has been documented in this tumor. Objective - To further characterize the immunophenotypic and ultrastructura l profile of renal angiomyolipoma based on phenotypic cell type (epithelioi d, spindle, and adipocytic cell). Design - Formalin-fixed, paraffin-embedded tissues from 27 renal angiomyoli pomas and 8 venal cell carcinomas were immunostained with monoclonal antibo dies to the melanoma-associated antigens HMB-45, HMB-50, NKI/C3 (CD63), and tyrosinase; the smooth muscle-related antigens calponin and muscle-specifi c actin (HHF-35); S100; and cytokeratin (CK). All renal angiomyolipomas wer e also immunostained with a polyclonal antibody to renin. Ultrastructural e xamination was performed on 9 selected cases. Results - All renal angiomyolipomas stained positive for HMB-45, HMB-50, NK I/C3, muscle-specific actin (HHF-35), and calponin. Overall, HMB-45, HMB-50 , and NKI/C3 preferentially stained the epithelioid cells. Tyrosinase stain ing was present in 50% of the renal angiomyolipomas with adequate tissue fo r staining (12 of 24 cases); positive staining and intensity paralleled HMB -45, HMB-50, and NKI/C3. Muscle-specific actin (HHF-35) and calponin prefer entially stained the spindle cells. The adipocytic cells stained positive f or both melanoma-associated antigene and smooth muscle antigens. Epithelioi d cells, spindle cells, and adipocytic cells were CK, S100, and renin negat ive. Ultrastructural findings paralleled immunohistochemical staining patte rns. Premelanosome-like organelles and electron dense granules were more re adily detected in the epithelioid cells within the tumor, whereas ultrastru ctural characteristics of smooth muscle cells were more easily found in the spindle cells. All renal cell carcinomas stained positive for CK, NKI/C3 s taining was variable, and all were negative for HMB-45, HMB-50, smooth musc le actin (HHF-35), and calponin. Conclusion - In renal angiomyolipoma, the epithelioid and spindle cells hav e preferential staining patterns for melanoma-associated antigens versus sm ooth muscle antigens, respectively. Positivity in renal angiomyolipoma for HMB-50, NKI/C3, and tyrosinase, in addition to HMB-45, provides evidence fo r the presence of different melanoma-associated gene products. Immunophenot ypic overlap of: the 3 histologically distinct renal angiomyolipoma cell po pulations suggests a common cell line, supporting a unitarian concept for r enal angiomyolipoma. Ultrastructural characteristics of the 3 venal angiomy olipoma cell phenotypes parallel the immunophenotype, giving further suppor t to a common cell line. Our study lends further credence to the perivascul ar epithelioid cell concept as proposed by Bonetti and colleagues.