Uterine Sarcomas and Atypical Smooth-Muscle Tumors: Clinic, Diagnostics and Appropriate Surgical Therapy

Abstract

In Europe, the incidence of leiomyosarcomas (LMS), low-grade endometrial stromal sarcomas (LG-ESS), high-grade endometrial stromal sarcomas (HG-ESS), undifferentiated uterine sarcomas (UUS), adenosarcomas (AS), and atypical smooth muscle tumors (synonym: STUMP – smooth muscle tumor of uncertain malignant potential) is around 1.2 cases/100,000 women (LMSs and LG-ESSs: around 0.9/100,000). Median age at the time of initial diagnosis of an LMS, an HG-ESS, a UUS, and an AS is 53, 58, 63 and 56 years, respectively, and is thus beyond menopause, with the exception of STUMPs and LG-ESSs (46 and 44 years). STUMPs are pathogenetically similar to LMSs, can recur after organ-sparing surgery in particular, and can also metastasize as LMS. Two of the following criteria must be fulfilled for an LMS to be classified as such: tumor cell necroses, ≥10 mitoses/10 HPF, and significant diffuse or multifocal moderate-to-severe atypia. One factor is sufficient for a STUMP to be diagnosed as such. However, it is unavoidable that a lesion be classified as an LMS when multiple TCNs have been positively and securely identified. LG-ESSs consist of uniform tumor cells that are reminiscent of proliferative endometrial stroma. The cellular atypia are typically low-grade, tumor cell necroses are rather the exception, and the number of mitoses is usually low. They express estrogen and progesterone receptors almost without exception. HG-ESSs consist both of a cytological low-grade component and of more predominant high-grade sections with higher grades of atypia, ample tumor cell necroses, and usually a clearly elevated mitotic index. UUSs are characterized by high-grade atypia, numerous mitoses and tumor cell necroses, with no specific type of differentiation. ASs are comprised of a benign adenous epithelial component and a sarcomatous component. The latter, in turn, can be LG-ESS, HG-ESS, UUS, LMS or another high-grade sarcoma. LG-ESSs and ASs with an LG-ESS-component have a relatively good prognosis, while the prognosis is extremely poor for the other types. Prognosis is primarily dependent on size and spread of the tumor as well as on the surgical techniques applied. Damaging the tumor (morcellation, enucleation, clamping, cutting) results in a shorter progression free interval and poorer overall survival. According to current data, for LG-ESSs and ASs with an LG-ESS component, tumor injury (only) results in a shorter progression-free interval and has no impact on survival. Apparently, causing damage to the uterus is already enough to impact negatively on prognosis. The therapeutic method of choice for uterine sarcomas is thus total hysterectomy without injuring the uterus. All surgical procedures that imply damaging the uterus or the tumor are to be deemed inappropriate. This includes all forms and variants of supracervical hysterectomy. The fundamental problem lies in the fact that, due to the diagnostic difficulties (and the fact that diagnostics are often insufficient or inadequate), 51 resp. 68 % of LMSs and LG-ESSs are operated under the indication or assumption of an LM. Oophorectomy is not necessary when a sarcoma that is confined to the uterus (!) is subjected to adequate and appropriate (!) surgery. There is no indication for systematic lymphadenectomy, parametric resection, or omentectomy. Adjuvant measures are not yet established. Where there is a postoperative incidental diagnosis following uterus-preserving surgery, hysterectomy should be subsequently performed with due haste. Should such surgery not take place, for various reasons, it is currently recommended that patients undergo follow-up laparoscopy and R0-resection of potential tumor residuals or early recurrences within three to six months. Aftercare is organized in accordance with the gynecologic oncological criteria. In order to prevent inadequate surgical procedures being performed on the basis of an indicated diagnosis of leiomyoma, an easy-to-use diagnostics flowchart is provided, the flow of which is based on patient age as well as results and findings from clinical and sonographic examinations. According to current data, performing an enucleation, a supracervical hysterectomy, or any form of morcellation without prior knowledge of sonographic presentation must be regarded as erroneous.