Most retroperitoneal smooth muscle tumors are believed to be malignant, and leiomyomas are considered very rare. This study was undertaken to determine the clinicopathologic features and long-term follow-up of 56 tumors diagnosed as retroperitoneal leiomyomas (LM) or smooth muscle tumors with an uncertain malignant potential (SMTUMP) in an effort to correlate their behavior and clinicopathologic features. These tumors were compared with a series of 11 cases of retroperitoneal leiomyosarcomas (excluding gastrointestinal stromal tumors). Histologic slides and immunohistochemistry for SMA, desmin, S-100 protein, HMB45, CD34, C-KIT, estrogen (ER) and progesterone (PR) receptor proteins, and MIB-1 were analyzed. All tumors diagnosed as LM and all but one SMTUMP were well-differentiated smooth muscle tumors that lacked atypia and coagulative necrosis. There was \u3c1 mitosis per 50 high power field (HPF) in 38 tumors; no tumor had \u3e3 mitoses/50 HPF. Most tumors had a striking resemblance to uterine smooth muscle tumors with common hyaline change and trabecular patterns. There were 51 females and 5 males ranging in age from 25 to 79 years (mean 45 years, median 43 years). These tumors were typically large, with a mean size of 16.2 cm and weight of 1600 g. Immunohistochemically, all 35 tumors studied were positive for α-SMA, 30 of 35 tumors were positive for desmin, and all were negative for CD117, S100 protein, and HMB45 and all but one for CD34. Steroid receptors were commonly present: ER in 20 of 29 cases and PR in 26 of 31 cases in the tumors of female patients. MIB-1 score was \u3c2% in all of 28 cases. Long-term follow-up (mean 140 months) did not reveal metastases, but two patients had local recurrence; however, neither patient with recurrence demonstrated disease progression in follow-up. By contrast, all 11 leiomyosarcomas had at least mild atypia, and all were ER and PR negative, All cases had MIB-1-positive nuclei, but only four had \u3e10% nuclei positive. Four patients died of disease, four were alive with recurrence, and three had no evidence of disease. A group of benign leiomyomas can be identified among retroperitoneal smooth muscle tumors. Most of these tumors resemble uterine leiomyomas by histology and positive hormone receptors, and they seem to have a good long-term prognosis with a small potential for local recurrence
