A Rare Case of Low-Grade Endometrial Stromal Sarcoma: Diagnostic Insights and Therapeutic Considerations.

A 49-year-old perimenopausal patient with a history of diabetes managed with oral antidiabetic medication was admitted to the oncology hospital for evaluation of menometrorrhagia. On admission, clinical examination revealed a hemodynamically stable patient with good performance status (PS = 1) and no clinical signs of anemia. Vaginal examination identified a cervical mass protruding into the vaginal canal. Pelvic ultrasound revealed an endometrial thickening measuring 32 mm, along with a cystic image extending from the umbilicus, suggestive of a distended bladder. To further characterize the ultrasound findings, a pelvic MRI was performed, which demonstrated a large tumor process involving the genital tract and occupying the uterine, cervical, and vaginal lumens (Figure 1 ). The initial biopsy revealed a spindle-cell proliferation. A thoracic and abdominopelvic CT scan was performed, which showed no evidence of distant metastases. The patient underwent an enlarged colpohysterectomy, and histopathological examination, supplemented by immunohistochemistry (IHC), confirmed a diagnosis of LGESS measuring 9 cm in length. Surgical margins were negative, and there was no infiltration of the paracervical parameters (Figure 2 ). IHC demonstrated positive staining for anti-CD10, anti-desmin, anti-vimentin, anti-estrogen, and anti-progesterone antibodies (Figure 3 , Figure 4 ). The image shows a cellular proliferation arranged in sheets, predominantly composed of spindle-shaped cells. The nuclei appear enlarged with irregular contours, dense chromatin, and thickened nuclear membranes. Atypical mitotic figures are infrequent. After a discussion at a multidisciplinary consultation meeting, the patient was placed under surveillance. She has remained well-controlled, with a follow-up period of 45 months to date.

Low-grade endometrial stromal sarcoma (LGESS) is a rare mesenchymal tumor, accounting for 6-20% of all uterine sarcomas [ 1 ]. It primarily affects premenopausal women [ 2 ]. Diagnosis relies on histological evaluation, which must be interpreted with caution to distinguish it from other entities such as leiomyoma [ 3 ]. The standard treatment is surgical, with total hysterectomy being the mainstay of care [ 4 ]. The role of additional treatments - including lymph node dissection, radiotherapy, and medical therapies such as chemotherapy and hormone therapy - remains a subject of debate [ 4 ]. Compared to other types of endometrial sarcoma, low-grade stromal sarcoma is associated with a more favorable prognosis, with an overall five-year survival rate exceeding 90% [ 2 ].

The World Health Organization classifies endometrial stromal tumors into four histological types: endometrial stromal nodules, low-grade stromal sarcomas, high-grade stromal sarcomas, and undifferentiated sarcomas [ 5 ]. LGESS is a rare subtype, accounting for less than 1% of all endometrial cancers [ 1 ]. It most commonly affects premenopausal and perimenopausal women [ 2 ]. The uterine body and cervix are the primary sites of involvement, while the ovary is the most frequently reported extrauterine location [ 6 ]. LGESS typically follows an indolent clinical course, and distant metastases are rare [ 6 ]. Clinical symptoms, such as menometrorrhagia and pelvic pain, are nonspecific and overlap with those of other gynecological conditions, often leading to delayed diagnosis. LGESS presents a diagnostic challenge and is frequently misinterpreted as a benign lesion, such as uterine leiomyoma [ 3 ]. The differential diagnosis includes leiomyoma, adenomyosis, endometrial carcinoma, and other sarcomas [ 7 ]. Pelvic ultrasound is usually the first-line imaging modality and may reveal an irregular mass infiltrating the endometrium or myometrium, sometimes with necrotic, hemorrhagic, or cystic areas [ 8 ]. Pelvic MRI is particularly useful for evaluating uterine and ovarian lesions [ 9 ]. On MRI, LGESS may appear as a well-defined myometrial mass, an irregular lesion extending from the endometrium into the myometrium, or, less commonly, as a polypoid mass within the uterine cavity [ 10 ]. Definitive diagnosis is based on histopathological examination, which typically shows a proliferation of small, round neoplastic cells resembling proliferative-phase endometrial stromal cells [ 11 ]. Cytonuclear atypia is rare, and the proliferation index is generally low [ 11 ]. IHC usually demonstrates positivity for CD10, along with possible expression of hormone receptors, desmin, vimentin, and muscle-specific actin [ 12 ]. Molecular analysis frequently reveals the juxtaposed with another zinc finger gene 1 - suppressor of zeste 12 (JAZF1-SUZ12) fusion gene, which is the most common genetic alteration in LGESS [ 12 , 13 ]. The cornerstone of treatment is surgical resection, typically involving total hysterectomy with bilateral adnexectomy for stage I disease. Ovarian preservation may be considered in premenopausal women [ 2 ]. The role of adjuvant therapy, such as hormone therapy and radiotherapy, remains controversial and should be evaluated through multidisciplinary consultation, particularly for stage II-IVA disease and beyond. The benefit of these treatments in terms of survival has yet to be clearly established [ 14 ].

LGESS is a rare uterine malignancy with a slow-growing clinical course and the potential for late recurrence. Accurate diagnosis relies on a combination of morphological features, immunohistochemical profiling, and molecular identification of the JAZF1-SUZ12 fusion gene. Complete surgical resection remains the primary treatment, while long-term follow-up is essential due to the risk of delayed relapse. Further research into the molecular pathways involved in LGESS may help identify novel therapeutic targets and improve patient outcomes.