Elsevier

Pathology

Volume 50, Issue 2, February 2018, Pages 162-177
Pathology

Gynaecological Pathology
Endometrial stromal sarcomas and related neoplasms: new developments and diagnostic considerations

https://doi.org/10.1016/j.pathol.2017.11.086Get rights and content

Summary

Our understanding of endometrial stromal sarcomas has evolved dramatically since their earliest descriptions from over a century ago. Initial studies focused on establishing the relationship between histological appearances of endometrial stromal sarcomas and their clinical outcomes. Studies performed in the last decade have uncovered several recurrent cytogenetic aberrations occurring in low- and high-grade endometrial stromal sarcomas. Low-grade endometrial stromal sarcomas bear close histopathological resemblance to proliferative-type endometrial stroma, and approximately half harbour t(7;17)(p15;q21) resulting in JAZF1-SUZ12 gene fusion. Less common JAZF1-PHF1, EPC1-PHF1, MEAF6-PHF1, and MBTD1-CXorf67 fusions have also been reported. The term ‘high-grade endometrial stromal sarcoma’ was recently re-introduced in the classification of endometrial stromal tumours after the discovery of t(10;17)(q22;p13) resulting in YWHAE-NUTM2A/B fusion and is associated with distinct morphological characteristics. This review highlights the evolution of endometrial stromal sarcoma classification schemes over time and describes the salient clinicopathological and molecular features of endometrial stromal nodule, low-grade endometrial stromal sarcoma, high-grade endometrial stromal sarcoma, and undifferentiated uterine sarcoma. It also describes the recent characterisation of endometrial stromal sarcoma with t(X;22)(p11;q13) resulting in ZC3H7B-BCOR fusion, a noteworthy entity due to its close histological resemblance to myxoid leiomyosarcoma. We also provide insights into common challenging scenarios encountered when assessing endometrial stromal lesions in daily surgical pathology practice.

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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