Malignant Transformation of Endometriosis: A Rare Case of Extrauterine Endometrial Stromal Sarcoma

Abstract

Endometrial stromal sarcoma (ESS) is an extremely uncommon uterine malignancy, and commonly arises from preexisting endometriosis. On rare occasions, ESS arises from extrauterine tissues and is known as extra-uterine ESS. This case report focuses on a 31-year-old woman who presented with chronic pelvic pain secondary to extensive deep-infiltrating endometriosis. Pelvic ultrasound revealed the presence of bilateral endometriomas with extensive endometriosis infiltrating segments of bowel and ureter. This was confirmed on laparoscopic exploration. Consequently, a series of surgical procedures were performed for excision of endometriosis, which included left nephroureterectomy, bowel resection with defunctioning loop ileostomy, subtotal hysterectomy, and bilateral salpingo-oophorectomy. Histological examination identified estrogen and progesterone receptor positive low-grade ESS alongside endometriosis in the omentum, large bowel, and ovaries. The disease was primarily extrauterine, with no involvement of the uterus. Following debulking surgery, the patient was commenced on adjuvant hormonal therapy to suppress the disease. This rare case highlights that existing chronic endometriotic lesions have the potential to transform into malignancy, and clinicians must be aware of this. Clinical manifestation and radiological features of ESS are the same as endometriosis and diagnosis is based on histopathological evaluation.

INTRODUCTION

Endometrial stromal sarcoma (ESS) is an uncommon malignancy, accounting for approximately 0.2% of all uterine malignancies and 10% to 15% of all uterine sarcomas.[1] On rare occasions, ESS arises from extrauterine tissues and is known as extra-uterine endometrial stromal sarcoma (EESS).[2] Ovaries and fallopian tubes have been reported to be the most common sites of EESS, comprising nearly 50% of the cases.[3] EESS presumably arises from preexisting endometriosis; however, on histological examination, not all EESS show associated endometriosis.[1,2] Malignant transformation of endometriosis into EESS is known to occur in only 0.1% to 0.7% cases of endometriosis.[4] EESS is typically confirmed through postoperative histopathological evaluation. ESS has both high-grade and low-grade variants. Low-grade ESS has an annual occurrence of 2 cases per million women worldwide.[5] A systematic analysis published in 2022 analysed 151 cases of EESS. Most women were above the age of 40 years. Only 10 women had ESS involving both the gastrointestinal and the gynecological system.[3]

This is a rare case of a 31-year-old woman who presented with chronic pelvic pain secondary to extensive, deep-infiltrating endometriosis. Nearly 2 years after the initial presentation, she developed low-grade ESS in her ovary, omentum and large bowel. This case is noteworthy due to the patient’s young age at presentation, the rarity of the disease and involvement of both gynecological and gastrointestinal systems. The case highlights the multidisciplinary team (MDT) approach required in the management of such complex cases.

CASE REPORT

A 31-year-old woman with previous one vaginal birth presented to our gynecological emergency unit with severe lower abdominal pain. She had a long-standing history of severe dysmenorrhea, which had progressed to chronic pelvic pain over the past year. A preliminary ultrasound of the pelvis performed in the emergency unit revealed bilateral endometriomas.

Following counseling, she was commenced on GnRH analogs with addback hormone replacement therapy. Detailed ultrasound imaging performed by a radiology specialist 3 months later, revealed an immobile uterus with characteristic retroflexion at the fundus, tethering of multiple bowel loops to the torus, bilateral endometriomas adhered to pelvic sidewalls, extensive deposits of endometriosis over bowel and appendix and left-sided hydronephrosis possibly secondary to endometriosis involving the distal left ureter [Figure 1].

Figure 1.

Ultrasound scan of pelvis showing (a) Right endometrioma adhered to right pelvic side wall and a loop of bowel inferiorly, (b) Endometrioma in left ovary adhered to left pelvic side wall, (c) Bowel loops tethered at the torus

A month later, a laparoscopy for surgical planning was performed. On laparoscopy, bilateral endometriomas were noted along with the presence of endometriotic tissue infiltrating segments of bowel and omentum. In addition, there was evidence of a large endometriotic nodule on the left pelvic brim, likely causing left ureteric obstruction and left-sided hydronephrosis. Right ureteric stenting was performed; however, a stent could not be passed through the left ureter due to obstruction caused by endometriosis.

A follow-up dimercaptosuccinic acid scan for the kidney function was performed, which confirmed the left kidney to be nonfunctional [Figure 2].

Figure 2.

Dimercaptosuccinic acid scan showing only 7% uptake of radiotracer in left kidney suggestive of nonfunctional left kidney. Right kidney was functional with 92% radiotracer uptake

In view of extensive endometriosis involving bowel, kidneys and ureter, surgical management was planned jointly between endometriosis surgeons, urologists, and colo-rectal surgeons. Surgical management was performed in two stages. Initially, a laparoscopic left nephroureterectomy, incision and drainage of bilateral endometriomas and right ovarian cystectomy were performed. This was followed by another laparoscopy a couple of months later, which had to be converted to a midline laparotomy due to surgical complexities. This included major adhesiolysis, subtotal hysterectomy, bilateral salpingo-oopherectomy, partial omentectomy, excision of terminal ileum, cecum and appendix with anastomosis formation, excision of rectosigmoid with anastomosis formation and defunctioning loop ileostomy.

Histopathological examination following the initial laparoscopy was suggestive of endometriosis in the ovarian cyst and chronic pyelonephritis in the left kidney. The histology from the completion surgery identified characteristic spindle cells of low-grade extrauterine endometrial sarcoma in the ovaries, omentum and segment of large bowel, showing positivity for estrogen receptor (ER)/progesterone receptor (PR) [Figure 3]. The disease was found to be extrauterine, with no involvement of the uterus.

Figure 3.

H and E histology image (a) 20X Low power image showing an area of extra-uterine endometrial stromal sarcoma on the left along with diffuse endometriosis on the right side, (b) 200X High power image showing characteristic spindle cells of low-grade endometrial stromal sarcoma in the ovary

Due to the complexity of the case, it was discussed in sarcoma and colorectal MDT meetings. Strong ER/PR positivity highlighted the endocrine-dependent nature of the disease, making hormone therapy a viable option. Hence, following primary debulking surgery, the patient was commenced on adjuvant hormonal therapy with megestrol acetate (160 mg daily) to suppress the disease. Progesterone therapy was continued over a period of 1 year.

A computed tomography (CT) scan performed a year later showed recurrence of the disease involving the remnant of the distal left ureter with enlarged pelvic side wall lymph nodes. Hormonal profile was performed, which raised some suspicion of residual functioning ovarian tissue. Following discussion in the regional gynecology oncology MDT, she was commenced on GnRH analogs along with aromatase inhibitors to encourage disease suppression. She is under the care of medical oncology and will be followed up until disease regression.

DISCUSSION

In 1925, Sampson first described three criteria for diagnosis of malignancy arising in endometriosis: (1) histological evidence of close proximity of benign endometriosis to the malignant tumor, (2) no other primary site of malignancy should be identified, and (3) tumor histology should be compatible with origin from an endometriotic focus.[6] Our case met all of Sampson’s criteria (presence of multiple endometriotic foci in the periphery of the tumor, presence of tumor in ovary, omentum and segments of large bowel excluding any other source of primary origin, histopathological examination consistent with that of ESS arising from endometriosis).

The clinical manifestation of ESS involves the presence of symptoms similar to endometriosis and there are no clear radiological signs suggestive of ESS. Hence, histological analysis is crucial. Histological examination of primary ESS in extrauterine locations is challenging due to rarity of the condition and difficulty in distinguishing it from metastatic uterine ESS.[7]

The treatment of EESS closely follows that of uterine ESS, comprising different combinations of surgical management, hormone therapy, chemotherapy, and radiation therapy. However, the effectiveness of different treatment protocols for EESS remains under-researched.[3] Total hysterectomy and bilateral salpingo-oophorectomy are the first-line treatment of early-stage low-grade ESS. In advanced or recurrent low-grade ESS, surgical cytoreduction followed by hormonal treatment, or vice versa, are acceptable treatment.[8] Optimal cytoreductive surgery and adjuvant hormone therapy were the treatment offered to the patient in this case.

The systematic review on EESS by Deb et al. reported that tumor site and mode of treatment significantly affect the overall survival (OS) and progression-free survival (PFS) of these patients. Patients with generalized involvement of the abdomen (without specific organ system) showed statistically significant poor outcomes both in terms of OS and PFS. In terms of treatment, patients who received hormonal therapy with any other form of treatment did significantly better in terms of OS and PFS, compared to patients who did not receive any hormonal therapy.[3]

Low-grade forms of ESS have been reported to have a favourable prognosis with a 5-year survival rate of 91%. High-grade variants are more aggressive, with a reported 5-year survival rate of 33%.[5] Although low-grade ESS is known for a good prognosis and long-term survival, it still carries a risk of recurrence, even years after the initial diagnosis. A case series of 10 cases of primary low-grade ESS reported a recurrence rate of 30%, with the longest recurrence duration being 60 months.[9]

This case highlights that chronic endometriotic lesions can transform into ESS, and a clinician should be aware of this rare possibility of malignant transformation when medically treating long-standing cases of extensive endometriosis. There are no specific features suggestive of malignant transformation of endometriosis, but could include worsening of endometriosis symptoms, development of resistance to a previously responsive medical treatment or sudden increase in the size of the endometriotic lesions. This case emphasizes the importance of multidisciplinary approach in treating complex cases of endometriosis and its malignant transformation.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.