Endometrial Stromal Sarcoma: A Masked Foe

Author Information

Shilotri M*,  Panchbudhe S**,  Satia MN***, Gupte P****.
(* Second Year Resident, ** Assistant Professor, *** Professor, Department of Obstetrics and Gynecology; **** Assistant Professor, Department of Pathology, Seth G S Medical College and KEM Hospital, Mumbai, India.)

Abstract

Endometrial stromal sarcomas (ESS) are rare, malignant uterine tumors composed of cells that morphologically resemble endometrial stromal cells of the non-neoplastic proliferative phase endometrium.It is difficult to diagnose these tumors clinically and on imaging. They are usually diagnosed on histopathological examination after undertaking a hysterectomy or curettage for a presumed benign pathology. We present a case with a clinical impression of a leiomyoma with its histopathological examination revealing an ESS.

Introduction

ESS accounts for approximately 10% of all uterine sarcomas and 0.2% of all uterine malignancies.[1] We report a case of a 30 year old Para 3 that presented with abnormal uterine bleeding (AUB) with uterine enlargement with a clinical impression of uterine fibroid. In view of her age, she was posted for myomectomy SOS hysterectomy for the same. However, due to excessive intra-operative bleeding, a hysterectomy was undertaken. The histopathological examination revealed a low grade endometrial stromal sarcoma (LGESS).

Case Report

A 30 year old with previous three normal vaginal deliveries, presented with menorrhagia with severe anemia. She complained of regular but prolonged, painful and excessive menstruation since one year. Her past menstrual cycles were regular, painless and with moderate flow. On general examination, she was markedly pale and had a corroborative pulse of 100 beats per minute, with the other vital parameters being normal. Systemic examination revealed no abnormality. On per abdominal and per vaginal examination, the uterus was 18 weeks size and bilateral fornices were free. Ultrasonography of the pelvis and abdomen revealed a 14 x 9 x 7.5 cm intramural, posterior uterine wall fibroid with cystic degeneration and an endometrial thickness of 8 mm. No other abnormality was detected. Her hemoglobin was 3.6 g/dl for which 3 packed red cell units were transfused and two doses of injection Iron sucrose 200 mg IV were given and her hemoglobin was built up to 9.4 g/dl. The patient was subsequently posted for myomectomy with the patient’s consent for SOS total abdominal hysterectomy under general anesthesia. Intraoperatively a 12x10x8 cm posterior wall uterine fibroid with cystic changes was identified, extending into the right broad ligament, pushing the right round ligament anteriorly. The plane of cleavage was distorted and the myometrium was thinned out. The mass was degenerated with about 20-30 ml of fluid which was drained from it. In view of persistent, excessive bleeding from the myoma bed, its broad ligament extension and the right uterine artery, the decision to perform a total abdominal hysterectomy was taken and the specimen was sent for histopathological examination. Both ovaries were preserved in view of the young age of the patient. The patient tolerated the procedure well.
Grossly, the cut section of the mass appeared fleshy, tan colored with areas of hemorrhage and necrosis and irregular, infiltrating borders. There was suspicion of vascular invasion near the serosa. Cervix was uninvolved. On microscopy, myometrium showed a tumor composed of uniform oval to spindle shaped cells of endometrial stromal type with minimal atypia and pleomorphism. Mitoses were infrequent (3-4/10 high power fields) with a rich network of delicate, small arterioles resembling spiral arterioles interspersed between the tumor cells. The tumor was infiltrating the surrounding myometrium but the serosa was intact. Vascular emboli were seen. A diagnosis of LGESS with vascular invasion was made. The patient was referred to a specialized cancer institute for further management. On histopathological re-evaluation at the cancer institute, the mitotic count was found to be 2-3/10 hpf. Focal vascular invasion was seen. On immunohistochemistry, the tumor was diffusely positive for Cyclin D1 while negative for CD 10. The test for estrogen receptors (ER) was moderately positive and focally strong and progesterone receptors (PR) was strongly positive in 70% of tumor cells. Post-operative CT scan of the abdomen and pelvis revealed no lymphadenopathy and metastasis. She was hence advised to undergo a bilateral salpingo-oophorectomy. We undertook a bilateral salpingo-oophorectomy about a month after the primary surgery. The left ovary had a cystic lesion of 3x3 cm. The right ovary appeared normal. On histopathology, both ovaries had no evidence of atypical or malignant cells. The patient was hence asked to follow up every 6 months at the specialized cancer institute.


Figure 1: Tumor composed of oval to spindly cells with minimal cytoplasm intimately associated with prominent spiral arterioles, closely resembling proliferative endometrial stroma.


Figure 2: Prominent spiral arterioles.


Figure 3:Angiolymphatic invasion seen within myometrium.


Figure 4: Left ovary showing 3x3cm cyst.

Discussion

ESSs form about 10% of all uterine sarcomas and 0.2% of all uterine malignancies. According to the World Health Organization (WHO) classification (2003), the term endometrial stromal tumor is applied to neoplasms composed of cells that morphologically resemble endometrial stromal cells of the non-neoplastic proliferative phase endometrium. The WHO classifies endometrial stromal tumors as Endometrial Stromal Nodules (ESN), Low Grade Endometrial Stromal Sarcomas (LGESS), High Grade Endometrial Stromal Sarcomas (HGESS) and Undifferentiated Endometrial Sarcoma (UES).[2] The average age of diagnosis is 42 to 58 years.[3] They may present with abnormal uterine bleeding (63%), abdominal lump (6%), pelvic pain (11%) or pressure symptoms while 26% may be asymptomatic.[4] Usually, a preoperative diagnosis of uterine leiomyoma is made as imaging techniques are also often unable to diagnose ESS. Sometimes, the suspicion of an alternate diagnosis can arise when an irregular margin on ultrasonography prompts an MRI for investigation and reveals an infiltrating tumor.[5] Although ESSs are indolent in behavior, they can spread to the vagina, fallopian tubes, ovaries, bladder and ureters. Distant metastasis to the lung, heart and other sites have also been reported.[6] The 2009 FIGO staging of uterine sarcomas applies to ESS.
When there is a difficulty in differentiating between ESS and leiomyoma, immunoreactivity with antibodies to CD 10 and smooth muscle actin and desmin are used. ESSs are negative for actin while leiomyomas consistently demonstrate a positive reaction.[7] On the other hand, ESSs are positive for CD 10 while leiomyomas are negative.[8] Histologically higher grade and clinically more aggressive ESSs are positive for Cyclin D1 and may be negative for CD 10.[9] As seen in our case, Cyclin D1 positivity and CD 10 negativity may imply a more aggressive form of ESS. The microscopic picture of ESN and LGESS is similar and hence needs to be differentiated by closely examining the myometrium-tumor interface. This is possible only on obtaining hysterectomy specimens as against curettage samples. LGESS demonstrate infiltrative margins and worm-like cords of growth into the myometrium whereas the margins are well preserved in ESN.
The tumor is generally considered to be hormone sensitive and a hysterectomy with bilateral salpingo-oophorectomy is advised and hormone replacement therapy post surgery is not recommended.[10] Lymphadenectomy in a scenario of obviously enlarged lymph nodes is accepted, while systematic pelvic and para-aortic lymphadenectomy in clinically unaffected nodes as a routine practice is still debatable and not recommended by many authors as it does not affect survival rates.[11] Adjuvant chemotherapy has not been studied in randomized controlled setups, but there have been trials showing the use of progestin and aromatase inhibitors.[12,13] In one study, 75% of patients with stage 1 disease did not recur if treated with adjuvant medroxyprogesterone acetate compared with 29% similar stage patients who did not receive it.[14] More aggressive treatment using doxorubicin containing regimens have been employed for high grade tumors or recurrent ESS not responsive to hormonal therapy.[15]
Recurrence is known in 25% of patients in low grade tumors and the median time to recurrence is about 36 months.[16] Despite this knowledge, the treatment of these recurrences is still to be streamlined.
In conclusion, endometrial stromal tumors often mimic leiomyomas in presentation and imaging. Given their relatively lesser incidence, a high index of suspicion and on diagnosis, an individualized treatment strategy must be formulated. Finally, counseling the patient post-treatment, regarding a possible recurrence and vigilance for the same is advisable.

References
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Citation

Shilotri M,  Panchbudhe S,  Satia MN, Gupte P. Endometrial Stromal Sarcoma: A Masked Foe. JPGO 2015 Vol 2 No 8. Available from: http://www.jpgo.org/2015/08/endometrial-stromal-sarcoma-masked-foe.html