The vascular pattern of ESN, composed of typical arterioles, is not a prominent feature of cellular leiomyoma. The differential diagnosis includes cellular leiomyoma and LG-ESS. Areas of smooth muscle metaplasia may be present and these should not mislead to an incorrect diagnosis of myometrial invasion. Areas of coagulative necrosis and sex-cord-like differentiation may be identified, but, by definition, lympho-vascular invasion (LVIS) is not present. The mitotic rate is not high (less than 10 × 10 HPF). ( B) ESNs show a non-infiltrative margin. ( A) Neoplastic cells in Endometrial Stromal Nodules (ESN) and Low-Grade Endometrial Stromal Sarcomas (LG-ESS) resemble endometrial stromal cells in the proliferative phase. However, their endometrial stromal origin has not been established with certainty and our current knowledge fails to classify these tumours appropriately. Similarly, NTRK-sarcomas, discovered by molecular analysis, appear to fall into the HG-ESSs. Molecular analysis of ESTs has resulted in better characterisation of these tumours, this, in turn, has caused the decrease in the diagnosis of UUS, which, at present, is a heterogeneous group of tumours, as well as the diagnosis of exclusion. The last classification of the World Health Organization (WHO) in 2020 sub-categorised ESTs into four groups: Endometrial Stromal Nodule (ESN), Low-Grade Endometrial Stromal Sarcoma (LG-ESS), High-Grade Endometrial Stromal Sarcoma (HG-ESS), and Undifferentiated Uterine Sarcoma (UUS) ( Table 1). Since the fundamental description of ESTs by Norris and Taylor, the classification of ESSs has undergone several modifications. In 1982Evans showed that the prognosis of ESSs is determined by nuclear atypia/pleomorphism rather than by the mitotic rate. The authors stated that the “size of the primary tumor and presence of vein invasion showed a slight correlation with the patient’s prognosis but no correlation was found with increasing degrees of cellular atypism”. Patients with stromal sarcoma presented with 55% survival rate within five years. In view of the clinical outcome (100% survival rate within five years), stromal nodules were considered benign. They divided the lesions into two groups the first group with pushing margins was labelled as stromal nodules and the second group with infiltrating margins was defined as endolymphatic stromal myosis or stromal sarcoma according to the mitotic index: lesions with ≤ 10 mitoses per 10 HPF (high-power field) were classified as endolymphatic stromal myosis and neoplasms with ≥ 10 mitoses per 10 HPF were categorised as stromal sarcomas. In 1966 Norris and Taylor attempted to classify ESTs in their seminal manuscript. Morphologically, ESTs resemble endometrial stromal cells in the proliferative phase of the menstrual cycle. Īpproximately 50% of endometrial stromal sarcomas (ESSs) occur in premenopausal women and the majority is detected at stage I of the International Federation of Gynecology and Obstetrics (FIGO). ESTs constitute ∼10% of uterine mesenchymal tumours. In this review, we summarise the morphological, immunohistochemical and molecular features of ESTs with particular reference to the most recent molecular findings.Įndometrial stromal tumours (ESTs) are a rare, fascinating and complex subset of mesenchymal uterine neoplasms with heterogeneous morphological, immunohistochemical and genetic features. In the future, the morphological and immunohistochemical features correlated with molecular categorisation of ESTs, will become a robust means to plan therapeutic decisions, especially in recurrences and metastatic disease. With the advent of molecular techniques, the morphological classification of ESTs can be integrated with molecular findings in enhanced classification of these tumours. UUSs show high-grade morphological features with very aggressive clinical behavior. HG-ESSs are tumours of high malignant potential with more aggressive clinical outcome. LG-ESSs are tumours of low malignant potential, often with indolent clinical behaviour, with some cases presented with a late recurrence after hysterectomy. In the most recent classification by the WHO (2020), ESTs have been divided into four categories: Endometrial Stromal Nodules (ESNs), Low-Grade Endometrial Stromal Sarcomas (LG-ESSs), High-Grade Endometrial Stromal Sarcomas (HG-ESSs) and Undifferentiated Uterine Sarcomas (UUSs). In 1966 Norris and Taylor classified ESTs into benign and malignant categories according to the mitotic count. Endometrial stromal tumours (ESTs) are rare, intriguing uterine mesenchymal neoplasms with variegated histopathological, immunohistochemical and molecular characteristics.