Use of immunohistochemical procedures in diagnosing angiosarcoma. Evaluation of 98 cases.
BACKGROUND
Differential diagnosis of angiosarcoma, predominantly showing a non- or poorly vasoformative proliferation from other types of sarcomas, poorly differentiated carcinomas, and amelanotic melanoma, is often problematic.


METHODS
The use of antibodies directed against Factor VIII-related antigen (FVIIIRA), Ulex europaeus lectin type 1 (UEA-1), CD31, and vascular endothelial growth factor (VEGF) in the diagnosis of angiosarcoma was examined in 98 cases of autopsy-proven angiosarcoma diagnosed during 1974-1990 in a survey of 178 Japanese hospitals. Reactivity of angiosarcoma cells for epithelial membrane antigen, cytokeratin, and melanoma cell antigen (HMB45) also was examined.


RESULTS
Histologic specimens were formed exclusively by vasoformative areas in 32 cases and combined vasoformative and varying extents of non- or poorly vasoformative areas in another 66 cases. In vasoformative areas, the proliferating cells showed a diffuse positive reaction in the cytoplasm and/or cell surface for anti-FVII-IRA in 82 (84%) of 98 cases, for anti-CD31 in 78 (80%), and for UEA-1 in 69 (70%). In non- or poorly vasoformative areas, the positivity rate for FVIIIRA, CD31, and UEA-1 was 29%, 62%, and 46%, respectively. A positive reaction was found for either one of three endothelial markers in the non- or poorly vasoformative areas of 57 cases (86%). Epithelial membrane antigen and anticytokeratin antibody were positive in 4 and 11 cases, respectively, in the vasoformative areas and in 3 and 14 cases, respectively, in non- or poorly vasoformative areas with a simultaneous positive reaction for either one of three endothelial cell markers. None of the proliferating cells showed a positive reactivity for HMB45. The positivity rates of the angiosarcoma cells for each marker were different according to the primary tumor sites. The angiosarcoma cells in non- or poorly vasoformative areas showed the lowest positivity rate for anti-FVIIIRA in the heart (9%) and for anti-CD31 in the extremities (17%) and the highest positivity rate for anticytokeratin in the trunk (60%). Ulex europaeus lectin type 1 had almost the same reactivity rate (30-56%) in every organ. Angiosarcoma cells in 13 (36%) of 36 biopsy specimens and 8 (14%) of 56 autopsy specimens were positive for the anti-VEGF antibody.


CONCLUSIONS
These findings suggest that the combined use of endothelial cell markers including FVIIIRA, UEA-1, and CD31 is useful in the diagnosis of angiosarcoma, especially in cases exclusively with a non- or poorly vasoformative pattern.
Ohsawa
M
M
Department of Pathology, Osaka University School of Medicine, Japan.
Naka
N
N
Tomita
Y
Y
Kawamori
D
D
Kanno
H
H
Aozasa
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000941:Antigens / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D016228:Endothelial Growth Factors / Q000032:analysis; D005169:Factor VIII / Q000032:analysis; D005260:Female; D006394:Hemangiosarcoma / Q000175:diagnosis*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D037102:Lectins / Q000032:analysis; D008222:Lymphokines / Q000032:analysis; D008297:Male; D008875:Middle Aged; D037121:Plant Lectins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000941:Antigens; D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D016228:Endothelial Growth Factors; D037102:Lectins; D008222:Lymphokines; D037121:Plant Lectins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C036850:Ulex europaeus lectins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005169:Factor VIII