Endometrial stromal sarcoma in a 20-year-old woman

Abstract

Endometrial stromal sarcoma (ESS) is an uncommon and challenging condition comprising 10% of all uterine sarcomas and found in women 42–58 years of age. ESS is difficult to diagnose in young women as it masquerades as a leiomyoma. We report this tumour in a 20-year-old woman presenting with heavy and prolonged menses and urinary retention. She was not sexually active and did not give consent for pelvic examination. A preoperative diagnosis of a submucous leiomyoma with an adnexal mass was made. At laparotomy, the leiomyoma was found to be wedged between the cervix and the vagina, and was removed vaginally. A 5–6 cm retroperitoneal mass was adherent to the right pelvic wall, which was also removed. Histopathology of both specimens revealed ESS. The final diagnosis according to the International Federation of Gynaecology and Obstetrics classification was stage IV ESS. After oncology consult, she was referred for chemotherapy. She is now on follow-up.

Background

Uterine sarcomas are uncommon malignant tumours with an incidence of 1–2 per 100 000 women. According to 2014 WHO classification, this condition has four categories: endometrial stromal nodule, low-grade endometrial stromal sarcoma (ESS), high-grade ESS and undifferentiated uterine sarcoma. Greater cytological atypia is associated with an increase in relapse rate. Pelvic irradiation, unopposed oestrogen exposure, tamoxifen and polycystic ovarian syndrome can be the causative factors.¹ Ninety per cent of women present with abnormal uterine bleeding and 70% with uterine enlargement. Ultrasound imaging can be confusing as these tumours are usually mistaken as leiomyoma, adenomyosis or intrauterine polyps.² The disease is a common presentation among postmenopausal women, and for these women the treatment of choice is total abdominal hysterectomy and bilateral salpingo-oophorectomy. However, in young women only total abdominal hysterectomy may be acceptable. Postoperatively hormonal treatment in the form of progesterone, gonadotropin-releasing hormone (GnRH) analogues and aromatase inhibitors may be effective.³ In case of recurrence, radiotherapy may be effective.⁴

Case presentation

A 20-year-old woman presented in outpatient with complaints of prolonged, heavy menstrual bleeding and dysmenorrhoea for 1 year and urinary retention for 1 month. The patient looked pale. Abdominal examination revealed a 16-week-pregnancy-sized, non-tender, firm mass with regular margins and restricted mobility, arising from the pelvis. She was not sexually active and refused a pelvic examination. On ultrasound examination, the uterus was enlarged, and the endometrial cavity, cervix and upper vagina were distended with a mass. There was a heterogeneous lesion in the right adnexa. Laparotomy was performed, and histopathology of the resected specimens revealed low-grade ESS.

Further to this, a total abdominal hysterectomy was planned but could not be performed as postoperative investigations confirmed stage IV irresectable disease with liver metastasis. The patient was referred for chemotherapy.

Investigations

The patient’s haemoglobin was 64 g/L. Abdominopelvic ultrasound confirmed a large uterus measuring 15×6.3×7.8 cm, with an elongated, heterogeneous, well-defined lesion of 11×6 cm arising from the uterine fundus, filling the endometrial cavity and distending the cervical canal and upper vagina. The right adnexa had a heterogeneous cystic lesion of 6.3×4.7 cm with internal echoes. There were bilateral hydronephrosis and hydroureter. Abdomen and pelvis MRI carried out a few months ago showed enlarged uterus with apparently 11.6×6.1×7.2 cm (craniocaudal × anteroposterior × transverse), T1-weighted hypointense, T2-weighted hyperintense lesion along the anterior wall of the uterus and the cervix. It had internal haemorrhage and necrosis. The lesion caused significant compression of the urinary bladder and rectum. The fat plane between the urinary bladder and the lesion was intact. There was no significant pelvic lymphadenopathy. Both kidneys showed dilatation of the pelvicalyceal system with prominent ureters. MRI features were suggestive of leiomyoma. Other laboratory tests showed the following: blood urea nitrogen (BUN) 20.3 mg/dL; serum creatinine 2.3 mg/dL; alpha-fetoprotein <2.0; cancer antigen-125 (CA-125) 53.5 IU; carcinoembryonic antigen (CEA) 1.47 ng/mL; and ml.β-human chorionic gonadotrophin (hCG) <2.30 mIU.

Differential diagnosis

Submucosal leiomyoma (fibroid polyp).

Treatment

At laparotomy, the uterus was found enlarged along with a distended cervix and vagina. The incision in the anterior wall of the uterus revealed a 15×10 cm mass that appeared to be a leiomyoma extending into the vagina assuming an hourglass shape. Following resection of its attachment to the uterine wall, it was found impacted in the vaginal canal and had to be removed vaginally. It was soft and necrotic with a yellowish hue (figure 1). Another spherical retroperitoneal mass around 6 cm in size was found adherent to the right pelvic wall and was removed with the assistance of a general surgeon (figure 2). This was semisolid with central necrosis. Both the specimens were sent for histopathology.

Figure 1.

Specimen of resected endometrial fibroid polyp yellowish in colour and necrotic with degenerative changes.

Figure 2.

(A) Retroperitoneal semisolid, spherical mass yellowish in colour and necrotic. (B) Retroperitoneal semisolid, spherical, 8×8 cm mass.

Outcome and follow-up

Histological examination of the two samples revealed similar morphology of a malignant neoplasm arranged in nests and islands infiltrating into the myometrium. The individual tumour cells were monotono ovoid-to-spindle-shaped with minimal cytoplasm and prominent nucleoli. Immunostain results showed the following: CD10 (cluster of differentiation), focal positive; cyclin-D1, positive; cytokeratin, negative; smooth muscle actin, negative; inhibin, negative; calretinin, negative; DOG-1 (discovered on gastrointestinal stromal tumour protein), negative; and CD117, negative. The tumour was negative for oestrogen and progesterone receptors. Histological and immunostain examinations favoured low-grade ESS.

Follow-up CT scan of the chest was normal, but CT scan of the abdomen and pelvis 4 weeks following surgery showed a 16×14 cm, large, heterogeneous mass inseparable from the uterus. Fat planes with the anterior pelvic wall were lost. Fat planes posteriorly with the rectum were also lost. Laterally the lesion was inseparable from the caecum and the descending and ascending colon. Bilaterally ureters were compressed and entrapped by the lesion, resulting in hydroureteronephrosis. Multiple para-aortic lymph nodes were enlarged. The tumour had metastasised into liver segments VII and IV-B. In view of such rapid progression, the patient was referred for chemotherapy. She is receiving doxorubicin and cyclophosphamide. Follow-up is planned.

Discussion

In the case under discussion, the initial diagnosis was leiomyoma and a haemorrhagic cyst. Intraoperatively an impacted necrotic mass with yellowish hue was found along with a solid-looking retroperitoneal mass. Although the histopathology report showed a low-grade stromal sarcoma, the tumour was aggressive, and within a month it progressed to stage IV disease.

The tumour often affects postmenopausal women, but in the literature there is increasing evidence of this tumour also occurring in younger age group, as seen in our patient who is 20 years of age. Dong et al ⁵ reported stage III high-grade ESS in a 19-year-old woman. Other reports show the occurrence of this tumour in women 28, 29 and 39 years of age.^{6 7} Amant et al have reported this tumour in a 28-year-old Caucasian woman during pregnancy.^{6 8} It may involve the fallopian tubes, vagina and adjacent structures. Distant metastasis to other organs may also occur.^{9 10}In the index case, none of the risk factors was present.

Around 90% of women present with abnormal uterine bleeding, 70% with enlarged uterus, pelvic pain or dysmenorrhoea, and 30%–50% with metastases outside the uterus. In 25% of patients, it can be an incidental finding.¹¹ ESS has a high degree of resemblance with normal endometrium, which poses great diagnostic difficulty. None of the imaging techniques has a high degree of diagnostic accuracy. The definitive diagnostic modality is histopathology coupled with immunohistochemistry of the hysterectomy specimen. Ultrasound finding may mislead to adenomyosis and uterine leiomyoma. MRI, however, can be used as preoperative diagnostic tool with some accuracy. On MRI the characteristic features are worm-like permeation of the cancerous cell in the myometrium and adjacent organs.^{12 13} CD10 can be helpful in distinguishing this tumour from uterine leiomyoma. However, in preoperative diagnosis, literature review has not demonstrated any utility of CD10. Mostly these tumours are oestrogen-positive and progesterone-positive.^{14 15}

In the index case, symptoms were mimicking that of uterine leiomyoma. The same preoperative diagnostic difficulty has been mentioned in the literature as well. None of the imaging techniques in our case helped in making the diagnosis. The tumour receptor status was also negative.

The management depends on the stage of the disease. As it occurs more commonly in postmenopausal women, surgery includes total abdominal hysterectomy with bilateral salpingo-oophorectomy. In young women with stage I disease, ovarian conservation can be considered.¹⁶ Prognosis depends on the stage of the disease. Extrauterine extension found at the time of surgery is an adverse prognostic factor, as was demonstrated in our patient. Other poor prognostic factors include older age (more than 50 years), black race, lymph node involvement and immunohistochemical indicators.¹⁷ In the literature, nodal metastasis, negative CD10, and lack of oestrogen and progesterone receptors are independent prognostic factors for poor survival, as was seen in this case.^{18 19}

The main prognostic factor for survival is nodal metastasis. There is higher chance of lymph node involvement in ESS. With nodal metastasis, there is a poor chance of survival (35.3%), while survival rate is around 80% in the absence of nodal metastasis.^{20 21}

The stage of ESS is determined according to the International Federation of Gynaecology and Obstetrics (FIGO) staging of uterine sarcoma.²² For early-stage disease, hormone therapy in the form of medroxyprogesterone, GnRH analogues and aromatase inhibitors is suggested. For advanced disease, hormone therapy and/or radiotherapy can be used, while for recurrent disease surgical re-excision combined with radiotherapy, hormone therapy or chemotherapy may be used.^{23 24}

According to FIGO stage I ESS, the 5-year survival rate is 54%–100%, for stage II it is 30%, and for advanced disease (stages III and IV) the survival is only 11%. In our case, at the time of surgery, a diagnosis of stage III was made. At postoperative CT scan, it was designated as a stage IV disease.

In our patient surgery was initially performed to remove the intrauterine mass along with resection of the adnexal mass. This was followed by chemotherapy due to the advanced stage of the disease.

A thorough review of published cases was done and a brief summary of these cases is presented for review (table 1).

Table 1.

Summary of previously published cases

Article and journal	Authors	Cases (n)	Age (years)	Symptoms	Examination	Diagnostic tools	Treatment	Adjuvant treatment	Recurrence: yes/no	Disease-free survival	Death: yes/no	Overall survival	Follow-up
Low grade endometrial stromal sarcoma, Iran ian J ournal of Med ical Sci ences	Jain et al 8	1	39	Polymenorrhagia for 8 months, retention of urine for 2 days.	Speculum examination, a large, retort-shaped, shaggy mass about 3 inches in diameter was seen coming out through the os. On vaginal examination, the mass was felt as firm, globular and filling the vagina in its upper part. Cervical rim felt all around the pedicle was high up. Uterus was 8 weeks in size, soft and anteverted. Bilateral fornices were clear.	Pelvic ultrasound showed a cervical mass lesion with well-defined outline, 9×8×8 cm, with heterogeneous echo pattern and multiple hyperechoic lesions in it. Endometrial cavity was pushed anteriorly. Uterus was bulky, and bilateral adnexa were normal. Mild hydronephrotic changes were present in the left kidney. An impression of cervical leiomyoma was made. Cervical polypectomy with endometrial curettage.	Total abdominal hysterectomy with bilateral salpingo-oophorectomy.	Leuprolide acetate (3.75 mg) subcutaneously every 28 days for 6 months.	No.	3 months, mentioned in the article.	No.	Not mentioned.	Annual follow-up plan.
Conservative management of endometrial stromal sarcoma at stage III: a case report, Oncol ogy Lett ers	Dong et al 5	1	19	Acute hypogastralgia for 1 day.	Tenderness in lower abdomen. On rectal examination, enlarged uterus (pregnant uterus of ~3 months gestation in size).	B ultrasound examination demonstrated a heterogeneous echo (9.1×7.5 cm) in the anterior wall of the uterus. Frozen section of the resected mass.	Laparoscopy.	250 mg medroxyprogesterone acetate daily for 1 year.	No.	33 months.	No.	Not mentioned.	33 months.
The clinical and histologic spectrum of endometrial stromal neoplasms: a report of 41 cases, Int ernational J ournal of Gynecol ogical Pathol ogy	Fekete et al 4	9	18–79	Vaginal bleeding, pelvic pain, abdominal mass.							2 patients died within 8 months of diagnosis.
Endometrial stromal sarcoma in a 29-year-old patient. Case report and review of the literature, Eur opean J ournal of Gynaecol ogical Oncol ogy	Sofoudis et al 7	1	29	Surgical history of myomectomy.	Histopathology.	Total abdominal hysterectomy with bilateral salpingo-oophorectomy and elective pelvic lymphadenectomy.
High-grade endometrial stromal sarcoma presenting in a 28-year-old woman during pregnancy: a case report, J ournal of Med ical Case Reports	Amant et al 6	1	28	Pain in the right iliac fossa at gestational age of 15 weeks.	Ultrasound showed ovarian mass. Laparoscopy and microscopic examination of peritoneal lesion. MRI.	Hysterotomy/pregnancy termination.		Nil.	Yes.	Nil.	Died 6 weeks after surgery.	6 weeks.	6 weeks.
A case report of high-grade endometrial stromal sarcoma: a rare cause of abnormal uterine bleeding in a young woman, Case Reports in Obs tetrics and Gynecol ogy	Eamudomkarn et al 25	1	21	Excessive and prolonged bleeding for 4 months. A palpable mass in the lower abdomen, rapidly increasing in size.	Vaginal examination revealed a 3 cm exophytic mass at the posterior lip of the uterine cervix and a 14 cm, firm uterine mass.	Endometrial curettage (atypical round cell tumour). CT of abdominopelvic cavity. Biopsy of cervical mass.	Total abdominal hysterectomy with bilateral salpingo-oophorectomy.	Adriamycin (50 mg/m2) and isofosfamide (5 mg/m2). Pelvic irradiation.	Yes.	Nil.	Yes.	8 months.	8 months.
Successful pregnancy following conservative management of low-grade endometrial stromal sarcoma: a case report, Oncology Letters	Dong et al 26	1	23	Menorrhagia of 3 months and lower abdominal pain for 10 hours.	Pelvic examination revealed a regularly enlarged uterus, the size of 70 days’ pregnancy.	Hysteroscopic myomectomy.	Laparotomy.	Medroxyprogesterone acetate 250 mg daily for 1 year.	Nil.	1.5-year follow-up.	Nil.	Not mentioned.	1.5-year follow-up.

Patient’s perspective.

I was very worried before the operation as I am the sole breadwinner of my family. I had detailed counseling done. Now I’m advised further treatment and that makes me much worried about my future. The doctors have been supporting me in procuring medicines and getting assistance from various doctors.

Learning points.

• Endometrial stromal sarcoma is an uncommon uterine tumour, especially in young women.

• Clinical presentation is often like a uterine leiomyoma.

• A high degree of suspicion is mandatory in young women who present with abnormal and prolonged bleeding, multiple fibroids and anaemia.

• A preoperative CT scan/MRI is recommended in young women presenting with severe anaemia and multiple fibroids.

• If CT scan/MRI modalities are unavailable, an abdominopelvic ultrasound is mandatory with colour Doppler of large masses, which can then substantiate the need for CT scan or MRI.