Extrauterine Undifferentiated Uterine Sarcoma Arising from Bladder Endometriosis in a Postmenopausal Woman: A Case Report

Endometriosis (EMS) is a rare condition in postmenopausal women. The incidence of transition from EMS to malignancy is as low as 1%, with endometrial stromal tumors (ESTs) occurring at an even lower incidence of 0.7%. Undifferentiated uterine sarcomas (UUSs) are a subtype of ESTs that account for 25% of all ESTs. Extrauterine UUSs are exceptionally rare, with only a few reported cases in the literature. We present the case of a woman who underwent surgery for deep infiltrating EMS and was later diagnosed with UUS, which originated from the bladder after surgical menopause.

Endometriosis (EMS), an estrogen-dependent disease, primarily occurs in women of reproductive age; postmenopausal women only account for approximately 2.5% of all cases [1]. The overall incidence of malignant transformation in cases of EMS is low (approximately 0.7%–1%), especially in postmenopausal women [2]. EMS malignant transformation primarily occurs within the ovaries, with only 20%–25% of cases occurring outside the ovaries. Extrauterine endometrial stromal tumors (ESTs) further have an exceptionally low occurrence, accounting for approximately 0.7% among the overall malignant transformation cases in postmenopausal women [3]. In this report, we have described a case of an undifferentiated uterine sarcoma (UUS), a subtype of ESTs, in a postmenopausal woman with a history of a previous deep infiltrating endometriosis (DIE) surgery and recurrence in the bladder. CASE REPORT A 53-year-old woman was referred to our hospital in September 2022, with a pelvic mass progressively increasing in size and protruding through the skin (Fig. 1). In 2015, she underwent an exploratory laparotomy at another hospital, including total abdominal hysterectomy, bilateral salpingo-oophorectomy, partial bladder cystectomy, left ureter reimplantation, and sigmoid colon resection, leading to surgical menopause. Pathological findings confirmed DIE involving the bladder, sigmoid colon, and peritoneum. She had received gonadotropin-releasing hormone agonists after the surgery. Fig. 1 Protruding pelvic mass. In May 2021, during her hospital visit for hematuria, abdominopelvic computed tomography (CT) revealed a 10-cm mass in the urinary bladder. Recurred EMS was suspected, and vesical artery embolization was performed accordingly, with no resolution. After being referred to our hospital for the protruding mass, the mass was sampled and subjected to an office-based biopsy. The pathological findings revealed fibrotic tissue with chronic inflammation. Additional work-up was performed with positron emission tomography (PET)-CT, magnetic resonance imaging (MRI), and cystoscopy to determine the possibility of malignancy. The pelvic mass (21 cm in size) showed an increased fluorodeoxyglucose uptake on PET-CT. MRI findings raised the suspicion of a sarcoma originating from the bladder (Fig. 2). During cystoscopy, the mass was observed to be inside the bladder. Fig. 2 Magnetic resonance image showing findings indicative of a sarcoma originating from the bladder. A malignancy was suspected from the results of PET-CT and MRI. Thus, the patient underwent a cytoreduction surgery for tumor removal. Surgical findings revealed a 20 × 13-cm mass protruding outside the abdominal cavity and beyond the skin. It adhered to the bladder and small bowel. Thus, a pelvic mass excision, radical cystectomy with ureterocutaneostomy, transureteroureterostomy, ileocecectomy, and segmental resection of the small intestine were performed. Histopathological findings confirmed the diagnosis of a UUS, stage IV, originating from the bladder EMS (Fig. 3). Fig. 3 Histological staining of the pelvic mass. (A) Hematoxylin and eosin (H&E), (magnification, ×40). (B) H&E (magnification, ×100). (C) Low cyclin-D expression. The low expression of cyclin-D helps distinguish UUS and HG-ESS. HG-ESS shows strong and diffuse positivity (> 70% tumor cell nuclei) for cyclin-D. (D) Estrogen receptor positivity. ER expression is positive in endometrial glands in endometriosis. (E) Progesterone receptor positivity. PR expression is positive in endometrial glands in endometriosis. (F) Paired box gene 8 positivity. PAX-8 expression is positive in endometrial glands in endometriosis. UUS: undifferentiated uterine sarcoma, HG-ESS: high-grade endometrial stromal sarcomas, ER: estrogen receptor, PR: progesterone receptor. The patient was scheduled for postoperative adjuvant chemotherapy (POAC) but experienced repeated bowel perforations after the cytoreductive surgery. Thus, pan-peritonitis was managed conservatively. After a second operation for repair of bowel perforation, the patient had recovered and was discharged with plans for POAC. However, she expired because of the deterioration of her general condition at another hospital in March 2023, just 6 months after her initial visit to our hospital in September 2022.

ESTs are extremely rare among uterine mesenchymal tumors, with an approximate incidence of 0.3 cases per 100,000 individuals [4]. Histologically, these tumors resemble the stroma of a functioning endometrium [5]. UUSs, a subtype of ESTs, predominantly occur in postmenopausal women; they account for approximately 5% of all sarcomas, represent a very rare condition, and comprise 25% of all EST cases [6]. Cases of UUSs originating from EMS have rarely been reported in the medical literature [7]. An advanced International Federation of Gynecology and Obstetrics (FIGO) stage and complete tumor resection can impact a patient’s survival [8, 9]. Because the stage at diagnosis significantly impacts a patient’s prognosis, a prompt diagnosis through pathological confirmation is very important [10]. In the present case, the patient was diagnosed with a stage IV tumor and exhibited a poor prognosis. The likelihood of a malignant transformation of EMS, although low, exists in postmenopausal women, as seen in our case. The size of an endometrioma and postmenopausal status have been reported as risk factors for the development of malignancy from EMS [11]. As mentioned above, a prompt diagnosis can improve the prognosis; thus, postmenopausal women with EMS must be investigated for malignancy. It is also well known that extra-pelvic EMS, which invades the organs outside the uterus and ovaries, is very rare [12]. To date, only few cases of UUSs have been reported in women with extra-pelvic EMS [13, 14]. The present case is the first case of an UUS that originated from a recurrent EMS lesion in the bladder. Our case highlights the importance of a prompt diagnosis of malignancy in postmenopausal women with EMS and its impact on the disease course. There is one limitation to the diagnostic process in this study. High-grade endometrial stromal sarcomas (HG-ESSs) may show histological features like those of UUSs. According to the 2020 World Health Organization classification [3], to confirm the diagnosis of a UUS and exclude HG-ESSs, next-generation sequencing should be performed to determine the presence of the t(10;17)(q23;p13) translocation and BCOR gene abnormalities. However, next-generation sequencing was not performed in the present case. It may not be possible to rule out HG-ESSs completely. Despite this, we believe that our reports hold considerable importance in the literature, given the absence of reported cases of HG-ESSs and UUSs following EMS recurrence in the bladder among postmenopausal women. We have presented the diagnosis and prognosis of a UUS that originated from recurrent EMS in the bladder of a postmenopausal woman. FUNDING:This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2022R1F1A1074121). CONFLICT OF INTEREST:No potential conflict of interest relevant to this article was reported.

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