Is high-grade endometrial stromal sarcoma the key to disease prognosis in cases of coexisting leiomyosarcoma? A case report

Background: The uterine leiomyosarcoma combined high-grade endometrial stromal sarcoma (ESS) is quite rare. Case presentation: We reported such a case in which high-grade ESS with BCOR gene alterations and leiomyosarcoma coexist in a patient. And, most impressively, high-grade ESS with BCOR gene alterations caused ovarian and pelvic metastases, although its volume was less than 1% of leiomyosarcoma. Conclusions: We suggested that when both high-grade ESS BCOR gene alterations and leiomyosarcoma are present in a patient, the high-grade ESS needs to be noted in the pathological report even if it accounts for less than 1% of the tumour mass.


Background
Uterine leiomyosarcoma and endometrial stromal sarcoma (ESS) are both malignant mesenchymal tumours originating from the primitive paramedian duct. Among them, uterine leiomyosarcoma is the most universal malignant mesenchymal tumor, accounting for 1% of uterine malignant tumor [1]. ESS accounts for 0.2% of malignant uterine tumors [2]. The coexistence of these two kinds of malignant tumours in one patient is extremely rare.

Clinical history and findings
A 46-year-old female patient who had a history of abdominal pain for more than 4 months, with aggravated pain for half a month, went to the hospital.
Admission examination: A palpable mass of approximately 20 cm in diameter was found on palpation of the abdomen. The mass was hard, with poor movement, a poor boundary and no tenderness. Total abdominal enhanced computed tomography (CT) showed multiple solid intrapelvic masses with accessory blood supply (FIGURE 1). The patient underwent bilateral resection of pelvic metastases, pelvic adhesions and intestinal adhesions under general anaesthesia.

Pathological findings
A 17 cm×13 cm×19 cm solid mass was under the serous membrane of the anterior uterine wall. There was no polyp or mass in the uterine cavity. The Currently, based on different molecular characteristics, two subtypes of high-grade ESS have been identified: YWHAE-FAM22 gene fusion and BCOR gene alteration [3]. Furthermore, alterations in the YWHAE and BCOR genes (GSP YWHAE and GSP BCOR, Guangzhou LBP Medicine Science and Technology Co., LTD., China) were detected by fluorescence in situ hybridization, which identified BCOR gene alterations but not YWHAE gene alterations. However, the genetic alterations of BCOR or YWHAE were not detected in leiomyosarcoma (FIGURE 4). Therefore, less than 1% of the tumour cells were diagnosed as high-grade ESS with BCOR gene alterations, a newly described subtype of high-grade ESS [4]. More interestingly, the metastases on the left ovary and pelvis showed the same histological morphology and immunophenotype as the high-grade ESS.

Discussion
The presence of both leiomyosarcoma and ESS with ovarian and pelvic metastases in a patient is extremely rare. Immunohistochemistry is a very useful adjunct method to identify ESS and leiomyosarcoma, which has helped in the present case as well. As far as this case was concerned, although only one mass was seen, we were more inclined to be two primary tumors, which involves several reasons. Firstly, the two tumors were completely separated, and there was no intersections and transition between them, which could be proved by the results of immunohistochemistry. Of course, ESS can be accompanied by smooth muscle differentiation. It have been are diagnosed as mixed endometrial stromal-smooth muscle tumors (MSST) when a minimum of 30% of the minor component is present in an otherwise typical stromal neoplasm or leiomyoma [5]. In other words, the mixed tumors are those tumors in which each of the two components comprises at least 30% of the area of the whole tumor [4]. Obviously, this case was not. In addition, it was reported that the MSST was benign or low-graded [6,7]. But it is inconsistent, depending on the both of two cells in this case are were malignant and poorly differentiated.
In addition, fluorescence in situ hybridization revealed that the genetic changes of the two tumors were different: BCOR gene alterations were only detected in high-grade endometrial stromal sarcoma, and neither the BCOR gene alterations nor the YWHAE gene alterations were detected in leiomyosarcoma. Based on, we considered that high-grade ESS and leiomyosarcoma were coexisting in this patient. The size of leiomyosarcoma was so large that the uterine structure was deformed and the mass formed by ESS was compressed. As a result, only one mass was observed.
Furthermore, high-grade ESS in the current World Health Organization classification is limited to tumors characterized by high-grade round cell morphology and harboring t(10;17)(q22;p13) resulting in YWHAE-NUTM2 fusion [8], A recent study have described another genetic alteration of ESS, harboring t(X;22)(p11.4;q13.2) resulting in ZC3H7B-BCOR fusion. It has been proposed as another morphologic variant of high-grade ESS [9]. The present case had been confirmed the existence of BOCR gene alterations. It has been reported that the clinical biological behavior of ESS with BOCR gene alterations is more aggressive [9].
However, some questions about this case remain: According to the principle of superiority, high-grade ESS, which accounts for less than 1% of tumour volume, may be easily neglected in a pathological diagnosis. in this case, the high-grade ESS metastasized to the left ovary and pelvis, naturally, seems to be the key factor determining the patient's clinical prognosis. Does this finding indicate that high-grade ESS with BCOR gene alterations metastasizes earlier than leiomyosarcoma [10]? Should the high-grade ESS drive the disease prognosis when both two tumours are present? At present, limited case reports cannot answer these questions. More similar case reports are needed to enrich the existing sparse knowledge of these rare tumors.

Conclusions
we suggest that when both high-grade ESS with BOCR gene alterations and leiomyosarcoma are coexistent in a patient, the high-grade ESS with BOCR gene alterations needs to be noted in the pathological report even if it accounts for less than 1% of the tumour mass.

Consent for publication
Written informed consent for publication was obtained from patient in the present study.

Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests.

Funding
The present study was supported by the Initiation fund of Medical PhD. in the Affiliated Hospital of Southwest Medical University (No.:18110) and Undergraduate Training Programs for Innovation and Entrepreneurship of the Sichuan Provincial (No.: S201910711080).

Authors' contributions
Feng Ling and SiBei Ruan performed immunohistochemical staining and molecular experiments. XiaoMing Xiong contributed to morphological observation. Na Li was responsible for clinical data collection. DongMei Zhao performed radiographic observation. CuiWei Zhang participated in and supervised the whole progression, wrote the manuscript and provided funding support. All authors read and approved the final manuscript.