Renal angiomyolipoma: further immunophenotypic characterization of an expanding morphologic spectrum.
BACKGROUND
Renal angiomyolipoma is a benign tumor histologically characterized by proliferation of spindle cells, epithelioid cells, and adipocytic cells in concert with many thick-walled blood vessels. To add further diagnostic confusion, an epithelioid cell-predominant variant of renal angiomyolipoma has recently been described. HMB-45 immunoreactivity correlates with ultrastructural striated organelles that closely resemble premelanosomes, although no evidence of melanogenesis has been documented in this tumor.


OBJECTIVE
To further characterize the immunophenotypic and ultrastructural profile of renal angiomyolipoma based on phenotypic cell type (epithelioid, spindle, and adipocytic cell).


METHODS
Formalin-fixed, paraffin-embedded tissues from 27 renal angiomyolipomas and 8 renal cell carcinomas were immunostained with monoclonal antibodies to the melanoma-associated antigens HMB-45, HMB-50, NKI/C3 (CD63), and tyrosinase; the smooth muscle-related antigens calponin and muscle-specific actin (HHF-35); S100; and cytokeratin (CK). All renal angiomyolipomas were also immunostained with a polyclonal antibody to renin. Ultrastructural examination was performed on 9 selected cases.


RESULTS
All renal angiomyolipomas stained positive for HMB-45, HMB-50, NKI/C3, muscle-specific actin (HHF-35), and calponin. Overall, HMB-45, HMB-50, and NKI/C3 preferentially stained the epithelioid cells. Tyrosinase staining was present in 50% of the renal angiomyolipomas with adequate tissue for staining (12 of 24 cases); positive staining and intensity paralleled HMB-45, HMB-50, and NKI/C3. Muscle-specific actin (HHF-35) and calponin preferentially stained the spindle cells. The adipocytic cells stained positive for both melanoma-associated antigens and smooth muscle antigens. Epithelioid cells, spindle cells, and adipocytic cells were CK, S100, and renin negative. Ultrastructural findings paralleled immunohistochemical staining patterns. Premelanosome-like organelles and electron dense granules were more readily detected in the epithelioid cells within the tumor, whereas ultrastructural characteristics of smooth muscle cells were more easily found in the spindle cells. All renal cell carcinomas stained positive for CK, NKI/C3 staining was variable, and all were negative for HMB-45, HMB-50, smooth muscle actin (HHF-35), and calponin.


CONCLUSIONS
In renal angiomyolipoma, the epithelioid and spindle cells have preferential staining patterns for melanoma-associated antigens versus smooth muscle antigens, respectively. Positivity in renal angiomyolipoma for HMB-50, NKI/C3, and tyrosinase, in addition to HMB-45, provides evidence for the presence of different melanoma-associated gene products. Immunophenotypic overlap of the 3 histologically distinct renal angiomyolipoma cell populations suggests a common cell line, supporting a unitarian concept for renal angiomyolipoma. Ultrastructural characteristics of the 3 renal angiomyolipoma cell phenotypes parallel the immunophenotype, giving further support to a common cell line. Our study lends further credence to the perivascular epithelioid cell concept as proposed by Bonetti and colleagues.
Stone
C H
CH
Department of Pathology, Henry Ford Hospital, Detroit, MI 48202, USA. cstone3@hfhs.org
Lee
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Amin
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RJ
D000199:Actins / Q000378:metabolism; D017667:Adipocytes / Q000473:pathology; D000328:Adult; D000368:Aged; D018207:Angiomyolipoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm; D002135:Calcium-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007680:Kidney Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D058950:Melanoma-Specific Antigens; D020460:Melanosomes / Q000473:pathology; D008840:Microfilament Proteins; D008854:Microscopy, Electron; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009130:Muscle, Smooth / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D060149:Tetraspanin 30; D000096985:Calponins
D000199:Actins; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D002135:Calcium-Binding Proteins; D058950:Melanoma-Specific Antigens; D008840:Microfilament Proteins; D014442:Monophenol Monooxygenase; D009363:Neoplasm Proteins; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D000096985:Calponins; C554586:CD63 protein, human