Information for this Review was obtained by a Search of Medline and references from relevant articles using the search terms: “sarcoma”, “endometrial stromal”, “leiomyosarcoma”, “uterine”, “ultrasonography”, “hormonal”, “magnetic resonance imaging”, “computed tomography”, “neoplasm”, “genetics”, “imaging”, “surgery”, “chemotherapy”, “molecular signature”, and “targeted therapy”. The search strategy was not limited by date and no language restrictions were applied.
ReviewClinical management of uterine sarcomas
Introduction
Mesenchymal tumours other than uterine fibroids are uncommon because sarcomas of the uterus constitute only 3% of uterine malignancies.1 Uterine sarcomas encompass leiomyosarcoma (figure 1), carcinosarcoma, and endometrial stromal sarcoma (ESS) according to traditional classification systems. Tumour biology of carcinosarcomas points toward an epithelial origin, as shown by in-vitro data, immunohistochemical studies, and molecular comparison between the epithelial and mesenchymal component.2 The focus in this Review will be on the most common pure mesenchymal tumours: uterine leiomyosarcoma and ESS. ESS was formerly classified as low-grade ESS. Tumours previously termed high-grade ESS are currently called poorly differentiated or undifferentiated uterine sarcoma. Although there is no universal staging system for uterine sarcomas, the International Federation of Gynecology and Obstetrics (FIGO) surgical staging system for endometrial cancer is used.
No imaging modality can offer a reliable preoperative diagnosis. CT is unable to differentiate between different types of uterine pathology. However, ultrasonography and MRI are able to offer a much more detailed analysis of pathology.3 Thus, uterine sarcomas are uncommon and the preoperative diagnosis is problematic. Preoperative referrals are rare. Many women have surgery for presumed benign conditions (eg, uterine leiomyoma) and snap frozen tissues are not preserved. As a result, the collection of satisfactory tumour samples and the undertaking of prospective trials are challenging. Only a few series are reported and results from studies with level 1 evidence are non-existent.
The purpose of this Review is to provide information on the pathology, preoperative diagnosis, and standard treatment of uterine leiomyosarcoma and ESS. Knowledge of tumour biology forms the basis for delineating targeted treatment modalities that are currently used, under investigation, or avoidable.
Section snippets
Histopathology
Most uterine leiomyosarcomas are sufficiently differentiated, at least focally, to allow recognition of their smooth-muscle nature. They are obviously malignant on microscopic examination. The diagnostic strategy should include a search for the mitotic index, presence of atypia, and coagulative tumour-cell necrosis.4 Uterine leiomyosarcomas need to be distinguished from mitotically active or atypical leiomyomas and uterine smooth-muscle neoplasms with low malignant potential. Coagulative
Histopathology
Endometrial stromal neoplasms are exclusively composed of cells resembling the endometrial stroma in its proliferative phase. The stromal nodule is the benign variant; it has well circumscribed borders and is rare.57, 58 ESS represents the entity with infiltrating borders and behaves like a low-grade sarcoma, with the potential for recurrence and metastasis.59 Microscopic findings that unequivocally correspond to ESS include a uniform population of endometrial stromal-type cells invading the
Undifferentiated sarcoma
Undifferentiated uterine sarcoma is a poorly defined group. These tumours do not show evidence of gene-specific fusions, suggesting that they arise by a different pathogenetic mechanism compared with ESS. Immunohistochemical data are also sparse, including only a few cases per article published. On the basis of these data, it seems that undifferentiated sarcomas are positive for PDGFR-α,34 androgen receptor,38 and WT1.51 Of note, one of four samples were positive for ERBB2.39
Gastrointestinal stromal tumours
Gastrointestinal
Conclusion
Uterine sarcomas are uncommon and preoperative diagnosis is frequently unknown. As a result, centralisation, large series, and randomised trials are problematic. Hysterectomy is the cornerstone of treatment for early stage uterine leiomyosarcoma and ESS. There is no proven benefit from any adjuvant treatment (ie, radiotherapy, chemotherapy, or hormonal targeted) for both entities. Hormone receptors are the most important targets for primarily advanced or recurrent ESS, as for a subset of
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