Endometrial stromal sarcoma of the sigmoid colon: a case report and literature review

Endometrial stromal sarcoma (ESS) is a rare mesenchymal tumor of the uterus that accounts for 7–25% of uterine sarcomas and < 1% of uterine tumors. Previously reported sites include the ovary, bowel wall, abdomen, peritoneum, pelvis, and vagina; however, ESS in the extrauterine area is rare. We report a rare case of endometrial stromal sarcoma that developed in the sigmoid colon along the gonadal vasculature, which was difficult to distinguish from colon cancer. A large polyp was found in the sigmoid colon of a 74-year-old woman during a routine medical examination and was diagnosed as tubular adenoma. On colonoscopy 7 months later, the tumor had grown and blocked the lumen, causing stenosis. She was referred to our hospital for surgery. Although detailed examination at our hospital did not yield a definitive diagnosis, bowel obstruction was considered likely and we performed laparoscopic low anterior resection under a preoperative diagnosis of sigmoid colon cancer. The tumor protruded into the sigmoid colon from the stump of the ovarian arteries and veins outside the intestinal tract. As the left ovarian artery and vein were involved in the tumor, we extracted them as a lump. The tumor was diagnosed as low-grade ESS (LG-ESS). She had a history of hysterectomy and left salpingo-oophorectomy for uterine myoma 25 years ago, and radiation therapy was performed after surgery for an unknown reason. The postoperative course was uneventful, and follow-up was continued at the request of the patient. We report a rare case of ESS infiltrating the sigmoid colon, which was probably a lesion derived from endometriosis of the ovarian arteriovenous stump remaining after surgery 25 years ago.

Endometrial stromal sarcoma, Sigmoid colon, Extrauterine, Case report

Endometrial stromal sarcoma (ESS) is a rare mesenchymal tumor of the uterus [1], which accounts for 7–25% of uterine sarcomas and < 1% of uterine tumors [1, 2]. ESS is most frequently observed in premenopausal women, affecting those aged 40–55 years. Although it can develop in older women, it is commonly associated with endometriosis [2–4]. Previously reported sites include the ovary, bowel wall, abdomen, peritoneum, pelvis, and vagina [5]; however, ESS in the extrauterine area is rare. We report a rare case of endometrial stromal sarcoma developing in the sigmoid colon along the gonadal vasculature. Case report A polyp in the sigmoid colon was found in an asymptomatic 74-year-old woman during a routine medical examination and was diagnosed as tubular adenoma. On colonoscopy 7 months later, the tumor had grown in size, blocking the lumen and causing stenosis. She was referred to our hospital for surgery. Her vital signs were normal. On physical examination, her abdomen was soft and she had no abdominal symptoms. She had a history of hysterectomy and left salpingo-oophorectomy for uterine myoma 25 years ago, and radiation therapy was performed after surgery. As the hospital where the patient had surgery 25 years ago has since closed and the records were unattainable, we unable to ascertain the reason for the radiation therapy. She had no history of being diagnosed with endometriosis. Laboratory findings were unremarkable, with no increases in tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9. Colonoscopy revealed a movable elevated lesion similar to a submucosal tumor obstructing the lumen at the sigmoid colon (20 cm from the anal verge) with no epithelial change, and colon cancer was suspected (Fig. 1a). It was diagnosed as necrotic tissue by biopsy. Contrast-enhanced computed tomography (CT) demonstrated a mass protruding into the lumen, and sigmoid colon cancer was suspected (Fig. 1b). In addition, a nodule with a length of approximately 2 cm was observed on the cranial side of the tumor and a contrast effect similar to that of a tumor was noted in the colon with possible continuity (Fig. 1c). Lymph node enlargement was not detected. Although detailed examination at our hospital did not yield a definitive diagnosis, as bowel obstruction was considered likely, we performed laparoscopic sigmoid colon resection under a preoperative diagnosis of sigmoid colon cancer (Fig. 1d). The left ovarian artery and vein were involved in the tumor even though left ovariectomy was previously performed, and we extracted them as a lump. The patient was discharged on postoperative day 14 with no postoperative complications. On pathological findings, the tumor growth and infiltration were continuously observed from the area submitted as the left ovarian arteriovenous, and it protruded like a polyp into the sigmoid colon (Fig. 2a, b). On histopathological examination, the tumor was composed of oval and spindle cells, and formed slit-like gaps (Fig. 2c). We observed tumor cells with a relatively uniform morphology of round and oval proliferations. Although the cell density was high, mitotic fugures was inconspicuous, and the coagulative necrosis image was unclear. No findings of endometriosis could be detected on the specimen. Lymph node metastasis was not found. The tumor cells were slightly positive for CD10 and strongly positive for estrogen receptor (ER), but negative for vimentin, AE1/AE3, CD34, D2-40, desmin, synaptophysin, inhibin, calretinin, WT-1, GATA3, TTF-1, and PAX8 on immunostaining (Fig. 2d). The tumor was finally diagnosed as low-grade ESS. There was a possibility that the stump of the ovarian artery and vein was positive, so we recommended additional excision including left salpingo-oophorectomy, and performed follow-up at the patient's request. The patient was alive 7 months after resection.

We reported a case of ESS that was difficult to distinguish from colon cancer clinically. According to the current World Health Organization classification, uterine sarcomas are distinguished from malignant mesenchymal tumors and malignant mixed epithelial-mesenchymal tumors, and classified into the following entities: leiomyosarcoma, LG-ESS, high-grade endometrial stromal sarcoma (HG-ESS), undifferentiated uterine sarcoma (UUS), and others [6]. ESS only accounts for 7–25% of uterine sarcomas, < 1% of uterine tumors [1, 2], and around 0.2% of all uterine malignancies [7]. The annual incidence is 0.19 per 100,000 women, and a gradual increase has been observed [8]. Previously reported sites include the ovary, bowel wall, abdomen, peritoneum, pelvis, and vagina [5]. Currently, ESS is classified into LG-ESS, HG-ESS, and UUS. ESS and UUS are distinguished based on morphological, immunohistochemical, and molecular-pathological criteria [9]. Similar to other uterine sarcomas, LG-ESS is also rare [10]. ESS is frequently noted in premenopausal women, especially those aged 40–55 years, although it can develop in older women [2–4]. Obesity, diabetes mellitus, and early menarche are associated with an increased risk of LG-ESS [11]. There have been rare cases of tumors developing after radiotherapy [12]. These tumors are often found due to abnormal vaginal bleeding, and may also accompany uterine enlargement and associated symptoms such as lower abdominal pain [6]. The preoperative diagnosis of ESS is difficult because imaging procedures, such as ultrasound, CT, and magnetic resonance imaging, cannot display specific characteristics of ESS [13]. The primary treatment for LG-ESS is surgery with total hysterectomy (without morcellation) and bilateral salpingo-oophorectomy [9]. We identified 15 previous cases of extrauterine ESS in the colorectum (Table 1). ESS has been reported to be associated with endometriosis [14]. The most common sites were the sigmoid colon and rectum because these areas have the highest incidence of endometriosis and anatomic proximity to the ovary [15]. A preoperative diagnosis is often difficult because of development at unexpected sites. Gastrointestinal stromal tumor (GIST) is a differential diagnosis and immunohistological diagnosis is effective. In general, ESS is immunohistochemically positive for CD10, ER, and progesterone receptor (PR), but negative for c-kit. In contrast, GIST is positive for c-kit, but negative for CD10, ER, and PR. If a patient has a history of ESS, suspecting recurrence of ESS, biopsy, and immunostaining may be useful for diagnosis. The risk of recurrence in LG-ESS is 10–20%, and late recurrences after more than 10–30 years are characteristic [16]. Even in patients with negative lymph node status, recurrence rates of up to 30% within 2 years were reported [17]. Increased expression of steroid receptors and aromatases in LG-ESS was reported; however, the benefits of gestagens, gonadotropin-releasing hormone analogues, and aromatase inhibitors are unclear because the data are limited due to the small number of patients [18, 19]. Postoperative radiotherapy in patients with ESS improves locoregional control, but long-term side effects of pelvic irradiation need to be considered carefully [9]. Surgery, radiotherapy, and systemic therapy are regarded as potential treatment options for patients with recurrences and metastases of uterine sarcomas [20]. Surgical resection is associated with an increased rate of cure and prolonged survival [21, 22]. Treatment using monoclonal antibodies or tyrosine kinase inhibitors may be feasible due to the expression of epidermal growth factor receptor in 70% of ESS [23]. Table 1. | References | Age | Lesion of colorectum | Primary/recurrence/synchronous | Foci of endometriosis | Past treatment | Years from past treatment | Treatment | Clinical course | |---|---|---|---|---|---|---|---|---| | Baiocchi et al. [24] | 38 | A/C, T/C, terminal ileum | Recurrence | Ovary | Ovarian systectomy, TAH, BSO | NA | Resection of ileum and colon | NED | | Baiocchi et al. [24] | 50 | T/C SDJ | Recurrence | Ovary | TAH, RSO | NA | Hormone therapy after LSO and omentectomy | NED | | Yantiss et al. [25] | 63 | Rectum | Primary | Rectum | None | None | Radiation after colorectal resection | Recurrent, 3 years | | Bosincu et al. [26] | 42 | Rectum | Synchronous | Adventitial rectal layer | None | None | Chemotherapy after TAH, BSO, omentectomy and colorectal resection | NED, 20 months | | Moura et al. [27] | 61 | Rectum S/C | Primary | Rectum, S/C, posterior wall of right broad ligament | None | None | Resection of colon | NED, 30 months | | Cho et al. [28] | 48 | S/C | Recurrence | Left ovary | TAH, BSO | 3 | Sigmoidectomy | NED, 4 months | | Kovac et al. [29] | 46 | Rectum S/C | Recurrence | Rectum, S/C | TAH, RSO | None | Oophorectomy, tumorectomy, omentectomy, resection of colon | NED, 11 months | | Asada et al. [30] | 49 | S/C | Recurrence | Uterus | TAH | 3 | Hormone therapy after resection | NED, 4 months | | Chen et al. [31] | 42 | S/C | Primary | S/C | None | None | Sigmoidectomy, ATH + BSO | NED, 1 years | | Li et al. [32] | 41 | Caecum | Recurrence | Uterus | RHC | 18 | Hormone therapy after resection | NED, 2 years | | Ayuso et al. [33] | 80 | S/C | Recurrence | Uterus | ATH + BSO | 37 | Hormone therapy after resection | NED, 4 years | | Bakker et al. [34] | 78 | Rectum | Recurrence | Uterus, retroperitoneal cyst | ATH + BSO/excision of a retroperitoneal cyst | 26/17 | Hartmann’s resection with a partial cystectomy | NA | | Son et al. [15] | 52 | S/C | Primary | Not identified | None | None | Colectomy, TAH and BSO | NED, 4 months | | Chowdri et al. [35] | 52 | Caecum | Recurrence | Uterus, ovary | Radiation after ATH, BSO | 10 | Hormone therapy after partial caecectomy, appendectomy, and omental biopsy | NED, more than 1 year | | Ann et al. [36] | 42 | S/C | Synchronous | S/C, ovary | None | None | Hormone therapy after anterior resection, TAH and BSO | ESS endometrial stromal sarcoma, A/C ascending colon, T/C transverse colon, S/C sigmoid colon, SDJ junction of descending and sigmoid colon, TAH total abdominal hysterectomy, BSO bilateral salpingo-oophorectomy, RHC right hemicolectomy, NA not available, NED no evidence of recurrence ESS is associated with endometriosis. In a previous report, ESS was considered to be an indolent tumor arising from endometriosis [14]. In our case, as there was a malignant lesion derived from endometriosis (or ESS with malignant lesion although it may not be ESS) 25 years ago, RT was performed, and was diagnosed as a lesion derived from endometriosis. At the patient’s request, the lesion of endometriosis was not detected, but its existence was suspected in consideration of her past history of treatment.

We report a rare case of ESS infiltrating the sigmoid colon, which was probably a lesion derived from endometriosis of the ovarian arteriovenous stump remaining after surgery 25 years ago.

We thank Dr. Daniel Mrozek: President of Medical English Service for editing a draft of this manuscript. Abbreviations - ESS Endometrial stromal sarcoma - LG-ESS Low-grade endometrial stromal sarcoma - CEA Carcinoembryonic antigen - ER Estrogen receptor - UUS Undifferentiated uterine sarcoma - GIST Gastrointestinal stromal tumor - PR Progesterone receptor Author contributions TT described and designed the article. KM edited the article. NM supervised editing of the manuscript. The other co-authors collected the data and discussed the content of the manuscript. All authors read and approved the final manuscript. Funding There is no funding. Data availability All data generated or analyzed during this study are included in this published article. Declarations Conflict of interest The authors declare no potential conflicts of interest. Ethics approval and consent to participate Written informed consent was received from the patient for publication of this case report and any accompanying images. Consent for publication Written informed consent was received from the patient for publication of this case report and any accompanying images. Footnotes Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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