Gynaecological PathologyEndometrial stromal sarcomas and related neoplasms: new developments and diagnostic considerations
Introduction
With the exclusion of carcinosarcomas, that are now considered an epithelial malignancy, endometrial stromal sarcomas (ESS) account for 7–25% of all uterine mesenchymal tumours and less than 1% of all malignancies arising in the uterus.1, 2, 3, 4 The incidence of uterine sarcomas is 1.5–1.7/100,000 females, with a slight increase over time.3, 4, 5, 6 ESS is the second most common type of uterine mesenchymal neoplasm after leiomyosarcoma.3, 5
In the most recent 2014 World Health Organization (WHO) classification of gynecological malignancies, endometrial stromal tumours (EST) are divided into four categories: (1) endometrial stromal nodule (ESN), (2) low-grade endometrial stromal sarcoma (LGESS), (3) high-grade endometrial stromal sarcoma (HGESS), and (4) undifferentiated uterine sarcoma (UUS). To avoid confusion in this review, the abbreviations LGESS and HGESS will only be used in reference to the 2014 WHO definition of these tumours.
Section snippets
The history and evolution of endometrial stromal sarcoma classification
Classification of uterine sarcomas has evolved considerably over the last half century, driven by several landmark studies that have improved our understanding of these rare neoplasms (Fig. 1). The first popularised classification scheme for uterine sarcomas was put forth in 1959 by W. B. Ober who adopted the philosophy of F. A. Zenker from almost a century prior. Ober proposed nomenclature based on histogenesis, thereby dividing uterine sarcomas into homologous types (bearing mesenchymal
Endometrial stromal nodule
This tumour is morphologically indistinguishable from LGESS, except by the absence of myometrial infiltration and lymphovascular invasion.
Clinical presentation
LGESS typically affects young and perimenopausal women of ages ranging from 18 to 83 (mean 46) years.33 Vaginal bleeding and pelvic pain are common symptoms.33, 38 Rarely, an association with tamoxifen or oestrogen use and pelvic radiation has been reported.43, 44 Obesity, diabetes, and younger age at menarche have also been associated with an increased risk of developing LGESS.45
Although LGESS is most commonly encountered in the uterus, it can occasionally occur at extrauterine sites,
HGESS WITH t(10;17) YWHAE-NUTM2A/B
Currently, the 2014 WHO classification formally recognises HGESS as ‘a malignant tumour of endometrial stromal derivation with high-grade, round-cell morphology sometimes associated with a low-grade spindle cell component that is most commonly fibromyxoid … High-grade endometrial stromal sarcoma typically harbours the YWHAE-FAM22 gene fusion … ’.38
Clinical presentation
Patients range in age from 28 to 67 (mean 50) years and often present with abnormal vaginal bleeding. There has been a single report of HGESS
Undifferentiated uterine sarcoma
This category of tumours lacks morphological resemblance to proliferative-phase endometrial stroma and exhibits high-grade cytological features. The term UES was replaced by UUS in the recent WHO classification to acknowledge that not all UES arise from the endometrium. As this is a diagnosis of exclusion, it is essential to rule out other types of uterine sarcoma in the differential diagnosis.
Conclusion
Studies investigating the molecular underpinnings of EST have allowed us to make great strides in understanding EST pathogenesis and refining tumour classification. The approach to EST classification has shifted from a purely morphology-based scheme to a paradigm which amalgamates molecular genetic findings. In the past 5 years, two new types of high-grade endometrial stromal sarcoma have been uncovered, characterised by underlying YWHAE-NUTM2 and ZC3H7B-BCOR fusions, and each with its own
Conflicts of interest and sources of funding
The authors state that there are no conflicts of interest to disclose.
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