FIGO staging for uterine sarcomas

Abstract

Jaime Prat, MD Hospital de la Santa Creu i Sant Pau Barcelona, Spain Dr Jaime Prat received an MD from the University of Madrid and trained in anatomic pathology at The New York Hospital, Cornell Medical College, USA. After a postdoctoral fellowship in surgical pathology at Memorial Sloan-Kettering Cancer Center, he became a faculty member of the Harvard Medical School at the Massachusetts General Hospital. During this time, he was a Junior Faculty Clinical Fellow of the American Cancer Society. He is a diplomat of the American Board of Pathology in anatomic pathology, a fellow of the Royal College of Pathologists of Great Britain, and has been on faculty at the US and Canadian Academy of Pathology since 1977. Dr Prat has served as Chairman of the Department of Pathology at Hospital de la Santa Creu i Sant Pau and Professor of Pathology at Autonomous University of Barcelona since 1986. His research has focused on clincopathologic features and molecular genetics of gynecological malignancies; he is the author of over 250 publications and serves on several editorial boards. Dr Prat is a past President of the European Board of Pathology (1999–2004), and is President of the International Society of Gynecologic Pathologists (2007–2009). He is also a member of the World Health Organization Committee for Classification of Tumours of the Female Genital Tract (IARC, Lyon France). Uterine sarcomas are rare tumors that account for approximately 1% of female genital tract malignancies and 3%–7% of uterine cancers [1]. Although the aggressive nature of most cases is well recognized, their rarity and histopathologic diversity have contributed to the lack of consensus on risk factors for poor outcome and optimal treatment [2]. Until now, the 1988 International Federation of Gynecology and Obstetrics (FIGO) criteria for endometrial carcinoma have been used to assign stages for uterine sarcomas despite the different nature of both tumor categories. A new FIGO classification and staging has been specifically designed for uterine sarcomas in an attempt to reflect their different biologic behavior. Traditionally, uterine sarcomas have been classified histologically into carcinosarcomas (malignant mesodermal mixed tumors), accounting for 40% of cases; leiomyosarcomas (40%); endometrial stromal sarcomas (10%–15%); and undifferentiated sarcomas (5%–10%). Carcinosarcoma, also referred to as "malignant mixed mullerian tumor," is a biphasic neoplasm composed of distinctive and separate, but admixed, malignant-appearing epithelial and mesenchymal elements. Recently, carcinosarcoma has been reclassified as a dedifferentiated or metaplastic form of endometrial carcinoma. Despite this, and probably because it behaves more aggressively than the ordinary endometrial carcinoma, carcinosarcoma is still included in most retrospective studies of uterine sarcomas, as well as the 2003 World Health Organization (WHO) classification [3]. According to the WHO classification [3], uterine tumors exhibiting smooth muscle differentiation are diagnosed as leiomyosarcomas based on the presence of at least two of the following three features: moderate to severe nuclear atypia; mitotic index ≥ 10 mitotic figures (MFs) per 10 high-power-fields (HPFs); and/or tumor cell necrosis [3], [4]. Occasionally, the histologic features are insufficient to allow classification into benign or malignant categories and, in such cases, the designation "smooth muscle tumors of uncertain malignant potential" (STUMP) is recommended [3], [4]. The term endometrial stromal tumor is applied to neoplasms typically composed of cells that resemble endometrial stromal cells of the proliferative endometrium [3]. They are classified into noninvasive (stromal nodules) and invasive (low-grade endometrial stromal sarcomas). Endometrial stromal sarcomas exhibit only mild nuclear atypia and characteristically invade the myometrium and lymphovascular spaces. Tumor cell necrosis is rarely seen. The diagnosis of undifferentiated endometrial sarcoma is applied to cases that lack smooth muscle or endometrial stromal differentiation and exhibit myometrial invasion, severe nuclear pleomorphism, high mitotic activity, and/or tumor cell necrosis. The histologic appearance of this tumor is more like the mesenchymal elements of a carcinosarcoma than a typical endometrial stromal tumor [3]. The rare mullerian adenosarcoma is a mixed tumor of low malignant potential that shows an intimate admixture of benign glandular epithelium and low-grade sarcoma, usually of endometrial stromal type [5]. Typically, the stroma concentrates around the glands forming periglandular cuffs. The histologic picture is reminiscent of a phyllodes tumor of the breast. Well-differentiated tumors may exhibit only mild nuclear atypia and very few or no MFs in the stromal component. In such cases, the presence of hypercellular periglandular cuffs helps to distinguish adenosarcoma from its rarer benign counterpart, the adenofibrom