Areas with benign morphologic and immunohistochemical features are associated with some uterine leiomyosarcomas

The pathogenesis of uterine leiomyosarcomas (LMS) is poorly understood. It is unknown if these tumors arise de-novo or from pre-existing leiomyomata (LM) or atypical leiomyomata. In this study, we evaluated morphologic heterogeneity within uterine LMS to identify possible precursor lesions. We reviewed 11 cases of total hysterectomy in which the final diagnosis was LMS. All slides from the grossly recognized tumor were evaluated for the degree of atypia and mitotic counts within the leiomyosarcomas. The slides with the lowest and highest mitotic count were stained with monoclonal antibody to p53, MIB-1 and ER/PR. The number of cells stained was subjectively assessed to nearest 5%, with 1% for rare positive cells. Morphologically benign tumor areas were identified in 5 of the 11 tumors. These areas showed < 5 mitoses/10 HPF, with 1+ atypia in 4 cases and 1–2+ atypia in 1 case. No necrosis was seen by definition. Immunostains could be done in 4 of these 5 cases. These morphologically benign areas showed a p53 expression of 1% in each of the 4 cases, with low MIB-1 (5 to 15%) and high ER/PR expression (ER: 50–100%, PR: 10–100%). Morphologically malignant areas had 13 to 31 mitoses/10 HPF, 2+ to 3+ atypia, p53 expression of 70% to 100%, MIB-1 expression of 40% to 100%, ER expression of 1 to 100% and PR expression of 1 to 100%. The benign and malignant areas merged in all cases. Morphologic and immunohistochemical spectrum of changes from benign to malignant is seen in 50% of LMS. This raises the possibility of progression of some leiomyomata to LMS.