HMGA2 Is a Useful Marker of Vulvovaginal Aggressive Angiomyxoma But May Be Positive in Other Mesenchymal Lesions at This Site
Robert Harkness, W. Glenn McCluggage
Abstract
Aggressive angiomyxoma (AA) is a rare mesenchymal neoplasm occurring almost exclusively in the vulvovaginal region and which has a wide differential diagnosis. It has previously been suggested that the nuclear transcription factor HMGA2 is a useful marker of AA, although the number of studies is limited. We investigated HMGA2 immunoreactivity in a large series (n=284) of vulvovaginal mesenchymal lesions. HMGA2 nuclear staining was classified as diffuse (≥50%), focal (<50%), or negative. Of 38 cases of AA, 26 (68%) were positive; 77% (n=20) of these exhibited diffuse staining. Of the 41 smooth muscle tumors, 18 (44%) were positive with 16 (89%) exhibiting diffuse staining. 80 fibroepithelial stromal polyps were included and 15 (19%) were positive (8 diffuse; 7 focal). Most of the fibroepithelial stromal polyps that exhibited diffuse HMGA2 immunoreactivity were large and edematous. Occasional cases of a variety of other lesions were positive, including 1 of 30 superficial myofibroblastomas and 1 of 16 angiomyofibroblastomas. Cellular angiofibromas (n=12) and superficial angiomyxomas (n=6) were always negative. Our results confirm that HMGA2 is a useful marker of AA but a significant minority of cases are negative. The marker also lacks specificity, since a high percentage of smooth muscle tumors are positive, although these typically do not bear a close morphologic resemblance to AA. A novel observation in our study is positive staining of some fibroepithelial stromal polyps, particularly when large and edematous; these are particularly likely to be confused morphologically with AA and positive staining with HMGA2 represents a significant diagnostic pitfall.