Comparison of Angiomyofibroblastoma and Aggressive Angiomyxoma in Both Sexes: Four Cases Composed of Bimodal CD34 and Factor XIIIa Positive Dendritic Cell Subsets

Aggressive angiomyxoma (AA) is a distinctive, locally aggressive, fibromyxoid tumor of the pelvic and genital soft tissues. AA is of unknown histogenesis but the cytologically bland spindled tumor cells, which surround characteristic variegated blood vessels, show fibroblastic or myofibroblastic features. AA may be related to angiomyofibroblastoma (AMF), another cytologically bland fibromyxoid genital spindle cell tumor with variable myoid differentiation that does not, as a rule, recur. Recently, CD34+ primitive fibroblasts and factor XIIIa+ dendritic histiocytes have been found in varying combination in many fibrovascular, fibrohistiocytic, and myxoid soft tissue tumors. Both cells belong to the microvascular unit, a tissue responsible for stromal repair and remodeling and angiogenesis. To determine if these ubiquitous stromal cells participate in the histogenesis of AA and AMF, we examined two scrotal tumors, one AA with multiple recurrences and one AMF, for the presence of CD34+ and FXIIIa+ dendritic cell subsets. For comparison, a vaginal AMF and a pararectal AA in a woman were included. We also studied actins and desmin to detect myofibroblastic differentiation, and, through double labeling studies, assessed hormone receptors and the cell cycle marker Ki 67 in the different cell subsets. The AA showed unusual cytologic atypia and was initially diagnosed as liposarcoma. It massively recurred four times over 12 years, the first time after seven years. The histologic appearance was fairly constant over the years. The scrotal AMF was a circumscribed 6 cm mass in a 37 year old man. In both cases, most tumor cells were wavy and fibrillar, spindled, stellate, or polygonal fibroblast-like CD34+ dendritic cells. Depending on the area examined, a 20-50% subset of dendritic cells showed both nuclear and cytoplasmic staining for FXIIIa. Actin+ cells were rare but vessels had actin+ myopericytes, although a small focus of the initial male AA was desmin positive. The recurring AA expressed androgen receptors and had Ki 67 index of 10-20% in "hot spots" of the primary and up to 30% in recurrent tumors. The scrotal AMF widely expressed androgen and progesterone receptors with focal estrogen receptor positivity and the Ki 67 index was 10%. Both CD34+ fibroblasts and FXIIIa+ histiocytes were present in the Ki 67+ cycling fraction in both the male AA and AMF and both cell types expressed androgen receptors. The female pararectal AA had more focal CD34 reactivity, particularly in perivascular fibroblasts and these cells were admixed with small FXIIIa+ cells. The vaginal AMF was strongly desmin+ and variably to weakly CD34+ with 20% FXIIIa+ dendritic cells and Ki 67 index of 2%. The vaginal AMF strongly expressed estrogen, progesterone, and androgen receptors. In conclusion our data suggest that at least some AA and AMF are myxoid fibrohistiocytic tumors composed of CD34+ fibroblasts and FXIIIa+ dendritic histiocytes. In our tumors, neoplastic CD34+ dendritic fibroblasts showed predominantly myxo-collagenous differentiation with prominent myofibroblastic differentiation in only one desmin+ vaginal AMF. Our results support the notion that AMF and AA are part of a morphologic and histogenetic continuum of myxofibrous and myoid tumors that may arise due to interactions between microvascular CD34+ fibroblasts and FXIIIa+ histiocytes. CD34 and FXIIIa reactivity may be underappreciated in these tumors and is more important when considered histogenetically and biologically rather than in classifying individual neoplasms. Hormonal stimulation of proliferating pelvico-gential microvascular dendritic cells appears to play a role in the morphogenesis of both tumors.