The major differential diagnostic problem presented by atypical polypoid adenomyofibroma (atypical polypoid adenomyoma) (APA), which usually affects young women, is the exclusion of well-differentiated endometrial carcinoma invading the myometrium. This distinction, however, is of great clinical importance from the standpoint of treatment because reproductive conservation is feasible for patients with APA. Recently, CD10, known to be a marker of endometrial stromal cells, was reported to be also expressed in cells immediately surrounding the neoplastic glands invading the myometrium [Am J Surg Pathol 27 (2003) 786-789; Mod Pathol 16(1) (2003) 22-27]. However, CD10 expression in the myofibromatous component of APA has not been previously examined in the literature. We therefore decided to examine whether the CD10-immunostaining pattern in APA is different from that in myoinvasive carcinoma. Furthermore, we also attempted to obtain any histopathologic findings that may offer some insight regarding the histogenesis of APA. Seven cases of APA were immunostained for CD10 using curettage or polypectomy specimens, in addition to hysterectomy specimens in 1 case. Areas with more fibrotic rather than muscular stroma were focally observed in 4 cases. The pattern of staining was compared with hysterectomy specimens taken from 19 cases in which well- to moderately differentiated endometrioid adenocarcinoma had deeply invaded the myometrium (outer two thirds of the myometrium) but was not associated with adenomyosis. In 6 of 7 cases of APA, CD10 was never expressed in the myofibromatous stromal components. In 1 case of APA, the fascicles of fibrotic and muscular mesenchymal cells in the interglandular areas were focally and weakly positive for CD10. All 19 myoinvasive carcinomas expressed CD10 to some extent in cells immediately surrounding the neoplastic myoinvasive glands (fringe-like staining pattern). The proportion of the myoinvasive nests immediately surrounded by CD10-positive mesenchymal cells was as follows: mean, 74%; median, 80%; minimum, 5%; maximum, 100%. The fringe-like CD10-staining pattern was not observed in APA. Furthermore, we identified a gradual transformation from preexisting endometrial stromal cells (CD10 positive) into the typical myofibromatous stromal component (CD10 negative) of APA in 1 case. In conclusion, this study demonstrated differences in the CD10 immunoreactivity or immunostaining pattern between the stromal components of APA and myoinvasive endometrial carcinoma. This difference should lead to a more accurate diagnosis of APA (pseudo-myoinvasive lesion). Furthermore, the histogenesis of APA may perhaps be explained by "myofibromatous metaplasia" of the endometrial stromal cells.