Introduction: Uterine mesenchymal tumors are derived from endometrial stroma, smooth muscle cells, or blood vessels. One subtype, Endometrial Stromal Sarcoma (ESS), is a rare malignant tumor that comprises approximately 1% of gynecological malignancies and less than 10% of all uterine malignancies (1). The World Health Organization classifies ESS into four subtypes: endometrial stromal nodule (ENS), low grade ESS (LG-ESS), high grade ESS (HG-ESS), and undifferentiated uterine sarcoma (UUS) due to cell morphology and mitotic counts (2). In a Surveillance, Epidemiology, and End Results (SEER) analysis of endometrial stromal sarcoma, the five-year disease-free survival was 91.4% (ENS), 95.4% (LG-ESS), and 42.1% (HG-ESS and UUS) for the respective subtypes (1). Late recurrences have been identified in LG-ESS in up to 60% of patients (3). Typical clinical presentations of ESS include the following: abnormal uterine bleeding, pelvic pressure, enlarged uterus, and abdominal distention. Diagnosis is made based upon pathology evaluation. Standard initial treatment for ESS includes a hysterectomy and bilateral salpingo-oophorectomy. There is currently no consensus on adjuvant therapy.

Case Presentation: A 22-year-old G0 female reported to the Emergency Department of an outside facility due to worsening lower pelvic pain. Out of precaution for the risk of ovarian torsion, the patient was taken for a robotic-assisted diagnostic laparoscopy with directed uterine biopsies as well as hysteroscopy with directed biopsies. During the procedure, the uterus was markedly enlarged and a fundal complex mass was subsequently incised and biopsied. Hysteroscopy was performed and revealed normal-appearing endometrium. Endometrial curettage was benign. Postoperatively, an MRI showed an 8.8 x 8 x 8.3cm intrauterine abnormality with 4mm capsule, multiple thin septations of uncertain etiology, and bladder distention. The patient was transferred to a higher-level acuity center for further evaluation and management due to ongoing post-operative pain and urinary retention.

Upon arrival, the patient reported her pain as an 8 out of 10 scale and described the character of the pain as “cramping.” The patient notably had not had a bowel movement in the past 7 days but did report passing flatus. The patient tolerated oral intake without nausea and vomiting. The patient’s vital signs were within normal limits. On physical examination, her abdomen was soft, tender without rebound or guarding and the port incisions were clean, dry, and intact. Her pelvic exam revealed normal external genitalia. The patient could not tolerate a bimanual exam, and the speculum exam was deferred as the patient was not sexually active. A small amount of vaginal bleeding was noted. A foley catheter was placed for urinary retention and adequate urine output was recorded subsequently. The foley was discontinued 24 hours later and the patient could void spontaneously without issues. The patient was discharged from the hospital 48 hours after admission due to adequate pain control with a plan for follow up after final pathology returned.

Pathology resulted as ENS vs. LG-ESS with the following characteristics: CD 10 positive, ER/PR positive, SMA negative, no mitosis or necrosis identified. The patient was notified of these results and consented to exploratory laparotomy with resection of the endometrial mass via hysterotomy. During the procedure, the mass was noted as “fleshy and soft, mostly avascular and necrotic with yellow/tan discoloration with what appeared to be adipose tissue vs thecal tissue within it.” The mass was completely resected, though fragmented. The mass was described by the surgeon as an “intracavitary lesion with some areas having clear planes and in other places the mass appeared to be clearly infiltrating the myometrium.” The gynecological oncology team then counseled the patient on treatment options of hysterectomy versus wedge resection of the myometrium given high risk of recurrence balanced with desire for future fertility. The patient chose to proceed with an attempt at a wedge resection.

A second laparotomy was performed 4 weeks later with fundal wedge resection performed. Final pathology of the anterior uterine wedge confirmed multiple clusters of atypical endometrial stroma in the myometrium with focal lymphovascular invasion (LVI) and negative margins were not achieved. Thus, concluding a low-grade mesenchymal neoplasm with JAZF1 gene rearrangement detected by FISH, consistent with a LG-ESS. It was recommended the patient undergo a total laparoscopic hysterectomy (TLH).

Robotic-assisted TLH was completed without complication. After surgery, pathology reported persistent LG-ESS with 8mm invasion into the myometrium (total myometrium thickness 13mm) with lymphovascular invasion in addition to negative margins, negative biopsies, and no other signs of cancer metastasis. Given the high risk of recurrence with invasion of uterus and LVI as well as history of prior surgery with mass fragmentation, the patient was offered a GnRH agonist hormonal blockage with norethindrone add back therapy for a duration of two years to block endogenous estrogen. She has tolerated this treatment course well with minor side effects such as hot flashes during the course of her treatment. The patient is now two years disease free.

Final Working Diagnosis: Low grade Endometrial Stromal Sarcoma

Management/outcome/Follow-up: The patient is currently well managed on a GnRH agonist hormonal blockage with norethindrone add back therapy for a duration of two years to block endogenous estrogen administration. The patient continues to be without evidence of recurrence at this time and will continue to seek follow up with the gynecologist-oncologist every six months for the next three years.

References and Resources

1. Chan, J., Kawar, N., Shin, J. et al. Endometrial stromal sarcoma: a population-based analysis. Br J Cancer 99, 1210–1215 (2008).
2. Conklin CJ, Longacre TA. Endometrial Stromal Tumors. Advances In Anatomic Pathology. 2014; 21 (6): 383-393.
3. Tse KY, Crawford R, Ngan HY. Staging of uterine sarcomas. Best Pract Res Clin Obstet Gynaecol 2011; 25:7.