Low Grade Extrauterine Endometrial Stromal Sarcoma Arising from Peritoneum Endometriosis: A Case Report and Literature Review

Endometriosis, a condition characterized by endometrial glands and stroma outside the uterus, was initially described by Rokitansky in 1860 ( 1). It affects approximately 6% to 10% of women of reproductive age, which translates to around 190 million women worldwide, and is associated with significant healthcare costs ( 2, 3). While endometriosis primarily affects pelvic organs, it can also be found in extra pelvic organs and tissues ( 4). However, extra-pelvic endometriosis is relatively rare, accounting for less than 12% of reported cases ( 5). Although most cases of endometriosis are benign, a small percentage (0.5% to 1%) can develop into malignancy ( 6). Dr. Sampson first described the transformation of endometriosis into malignancy in 1925. Malignant tumors originating from endometriosis are typically endometrioid adenocarcinoma and clear cell types, with extremely rare cases of endometrial stromal sarcoma (ESS) ( 7, 8). Endometrial stromal sarcoma is a rare form of uterine sarcoma, comprising approximately 0.2% of all uterine malignancies and 10% to 15% of all uterine sarcomas ( 9). It arises from the invasive proliferation of cells resembling stromal cells of the normal proliferative endometrium, primarily in the uterine corpus but can also originate from extrauterine sites ( 9). The majority of extrauterine ESS cases result from the malignant transformation of endometriosis, which occurs in only 0.1% to 0.7% of cases ( 10). Endometrial stromal sarcoma is often misdiagnosed as benign conditions, such as leiomyoma, and is typically confirmed through post-operative histopathological evaluation ( 11). The exact pathogenesis of ESS is still not fully understood but identified risk factors include past exposure to pelvic radiation therapy, long-term tamoxifen use, and unopposed estrogen use ( 12). The World Health Organization (WHO) categorizes ESS into low- and high-grade forms, as well as nodular and undifferentiated variants, providing a comprehensive classification system for this neoplasm ( 13). Different subtypes of endometrial sarcoma have distinct therapeutic and prognostic characteristics. High-grade and undifferentiated endometrial sarcoma, referred to as high-grade ESS, is known for its aggressive behavior and has a 5-year survival rate of only 33%. On the other hand, low-grade endometrial stromal sarcoma (LG-ESS) behaves more indolently and is associated with a 5-year survival rate of 91% ( 14, 15). Low-grade endometrial stromal sarcoma is a rare form of cancer that originates from the mesenchymal cells in the endometrium. It accounts for only 0.2% of all gynecological malignancies and has an annual occurrence of 2 cases per million women worldwide. Several risk factors have been associated with LG-ESS, including obesity, diabetes mellitus, and prolonged exposure to hormones such as early onset of menstruation, late menopause, and hormonal treatments. Among these risk factors, it has been found that prolonged use of tamoxifen or pelvic radiation therapy are the most significant contributors to the development of LG-ESS ( 16, 17). Typically, the clinical manifestation of this condition involves the presence of non-specific symptoms, including chronic vaginal bleeding, pelvic pain, and dysmenorrhea ( 18). Low-grade endometrial stromal sarcoma is typically found in the uterus but can also occur in extrauterine sites, known as LG-EESS. The incidence of LG-EESS is even rarer and not well-documented. LG-EESS is believed to stem from ectopic endometrial stroma, which may account for its close association with endometriosis. A review of literature published between 1970 and 2016 on PubMed identified 76 cases of extrauterine endometrial stromal sarcoma (EESS) originating from endometriosis. The most commonly involved sites were the ovary (44.3%), pelvic organs outside the uterus and ovaries (15.2%), sigmoid rectum (7.6%), and small intestine (7.6%) ( 19). Extrauterine endometrial stromal sarcoma arising in the peritoneum is a rare occurrence, and as a result, only a few studies have reported such cases ( 20, 21). In previous reports, the age of the patients was over 42 years old and usually in menopause. Furthermore, previous reports have not described the radiological features of the disease in a precise manner. This case report presents a 35-year-old female who initially presented with pelvic pain and was diagnosed with disseminated peritoneal endometriosis on multiple occasions. Five years after the initial diagnosis, the patient developed LG-EESS. This case is noteworthy due to the patient's young age at diagnosis and the rarity of the disease. To the best of our knowledge, there are only a few reports that describe the radiological features of an LG-EESS originating from the peritoneum, particularly in the context of deep infiltrating endometriosis without involvement of the endometrial cavity.