High-grade Endometrial Stromal Sarcoma With BCOR Gene Alterations is Recommended as an Independent Subtype of Endometrial Carcinoma: A Case Report

Background:The uterine leiomyosarcoma combined high-grade endometrial stromal sarcoma (HGESS) with BCOR gene alterations is exceedingly rare. The subtype of YWHAE-FAM22 HGESS is shown in the current World Health Organization classication, but not HGESS with BCOR alterations. Case presentation: We reported such a case in which HGESS with BCOR gene alterations and leiomyosarcoma coexist in a patient. And, most impressively, HGESS with BCOR gene alterations caused ovarian and pelvic metastases, although its volume was less than 1% of leiomyosarcoma. Conclusions: Given the more aggressive of HGESS with BCOR gene alterations, we suggest that it is classied as an independent subtype of HGESS, and when it coexists with other types of tumors, the HGESS with BCOR gene alterations needs to be noted in the pathological report even if it accounts for less than 1% of the tumour mass.

Conclusions: Given the more aggressive of HGESS with BCOR gene alterations, we suggest that it is classi ed as an independent subtype of HGESS, and when it coexists with other types of tumors, the HGESS with BCOR gene alterations needs to be noted in the pathological report even if it accounts for less than 1% of the tumour mass.

Case Presentation
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, especially when the volume of ESS accounts for less than 1% of the tumour mass but causes ovarian and pelvic metastases. We reported such a case and con rmed that the existence of BOCR gene alterations in HGESS.

Patient Information
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. She has no previous medical history, unusual psychosocial history and relevant family history.

Clinical ndings
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 were not detected in leiomyosarcoma (FIGURE 3). Therefore, less than 1% of the tumour cells were diagnosed as HGESS with BCOR gene alterations, a newly described subtype of HGESS (4). More interestingly, the metastases on the left ovary and pelvis showed the same histological morphology and immunophenotype as the HGESS.

Therapeutic intervention and follow-up
The patient was treated with combination chemotherapy with docetaxel and gemcitabine followed by doxorubicin. No regeneration or metastasis was observed within 6 months after surgery. The long-term effect is still under review.

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, there were signi cant differences in the morphology and mitotic activity of the two kinds of tumor cells, and there was no intersections between them, which have been proved by the results of H&E staining and mmunohistochemistry. In addition, uorescence in situ hybridization revealed that the genetic changes of them were different: BCOR gene alterations were only detected in HGESS, and neither the BCOR gene alterations nor the YWHAE gene alterations were detected in leiomyosarcoma. Of course, ESS can be accompanied by smooth muscle differentiation. It should been 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 lowgraded (6). But it is inconsistent, the both of two kinds of tumor cells were malignant and poorly differentiated in this case. Based on, we considered that HGESS and leiomyosarcoma were coexisting in this patient. The volume 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.
The HGESS in the current World Health Organization classi cation is limited to tumors characterized by high-grade round cell morphology and harboring t(10;17)(q22;p13) resulting in YWHAE-NUTM2 fusion (7), A recent study have described a rare subtype of ESS with high grade features and BCOR alterations, caused by either a gene fusion between BCOR and ZC3H7B or a mutually exclusive somatic internal tandem duplication of exon 15 of BCOR (8). In the only few cases reported in the literature to date, it has been proposed that it is more aggressive as another morphological variant of HGESS (4). The present case had been con rmed the existence of BOCR gene alterations.
However, some questions about this case remain: According to the principle of superiority, HGESS, which accounts for less than 1% of mass volume, may be easily neglected in a pathological diagnosis. In this case, the HGESS metastasized to the left ovary and pelvis, naturally, seems to be the key factor determining the patient's clinical prognosis. Does this nding indicate that HGESS with BCOR gene alterations metastasizes earlier than leiomyosarcoma (7)? Should the HGESS 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
Given the high aggressive of HGESS with BCOR gene alterations, we suggest that it be classi ed as an independent subtype of HGESS. Further, we recommend that when both HGESS with BOCR gene alterations and other malignant tumors such as leiomyosarcoma are coexistent in a patient, the HGESS with BOCR gene alterations needs to be noted in the pathological report even if it accounts for less than 1% of the tumour mass.

Patient cinsent for publication
It is attached to the submission.

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