A High-Grade Undifferentiated Endometrial Stromal Sarcoma Presenting as Inversion of the Uterus: A Rare Case

Case Report A High‑Grade Undifferentiated Endometrial Stromal Sarcoma Presenting as Inversion of the Uterus: A Rare Case Departments of Obstetrics and Gynaecology, 1 Pathology and 2Radiology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong, Meghalaya, India Submitted: 04‑May‑2019 Revised: 02‑Nov‑2019 Accepted: 03‑Mar‑2020 Published: 04‑May‑2020 Abstract Nalini Sharma, Jaya Mishra1, Anusmita Saha, Aranab Kalita2 Endometrial stromal sarcoma (ESS) is a rare malignant tumor that constitutes about 0.2% of all uterine malignancies and 10% of uterine sarcomas. ESS is generally misdiagnosed as leiomyoma or endometrial polyp and typically discovered on histopathological examination postoperatively because of its rarity. Endometrial stromal tumors are composed of cells resembling normal endometrial stroma in its proliferative phase. The histologic diagnosis of the high grade is made if there is a high‑grade sarcoma with a high mitotic index and nuclear anaplasia. The mean age of presentation of high‑grade endometrial sarcoma is about 61 years with the most common presenting complaint is menorrhagia. The median overall survival for high‑grade endometrial sarcoma is 53 months with optimal cytoreduction. A 49‑year‑old woman P2 L2 presented with nonspecific complaint of discharge and spotting per vaginum. In the present case, the provisional diagnosis by clinical findings as well as imaging was in favor of the inversion of submucous fibroid. Preoperative histopathological examination and immunohistochemistry confirmed the diagnosis of high‑grade undifferentiated ESS. Haultain’s operation followed by total abdominal hysterectomy and bilateral salpingo‑oophorectomy was performed. The patient was referred to another center for radiotherapy. From there, she was lost to follow‑up. Rarity of endometrial stromal tumor limits the clinician view to diagnose it preoperatively. We were fortunate to have preoperative histopathological diagnosis of ESS. Furthermore, as ESS is rare and undifferentiated stromal sarcoma is even rarer, literature is lacking on its optimal management. Hence, it is important for all clinicians to keep the high degree of suspicion for ESS while working up any case of abnormal uterine bleeding. Keywords: Low‑grade endometrial stromal sarcoma, undifferentiated endometrial stromal sarcoma, uterine inversion, uterine sarcoma Introduction S arcoma is a rarely encountered malignancy of the uterus. The site of origin may be connective tissue, smooth muscle, or endometrial stroma.[1] Endometrial stromal sarcoma (ESS) is a rare malignant tumor that constitutes about 0.2% of all uterine malignancies and 10% of uterine sarcomas.[1] The annual incidence of ESS is 1–2/million women.[2] Past exposure to pelvic radiation, exposure to tamoxifen, unopposed estrogen, and polycystic ovary syndrome are implicated in the pathogenesis of ESS. Access this article online Quick Response Code: Chromosomal aberrations are found linked with ESS, deletion on chromosome 7p being the most common finding (55.6%).[2] On the basis of mitotic activity, vascular invasion and observed differences in prognosis endometrial stromal tumors are divided into the following three types: Address for correspondence: Dr. Nalini Sharma, Department of Obstetrics and Gynecology, B 1 D, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong ‑ 793 018, Meghalaya, India. E‑mail: [email protected] This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. Website: www.jmidlifehealth.org For reprints contact: [email protected] DOI: 10.4103/jmh.JMH_75_19 40 How to cite this article: Sharma N, Mishra J, Saha A, Kalita A. A high-grade undifferentiated endometrial stromal sarcoma presenting as inversion of the uterus: A rare case. J Mid-life Health 2020;11:40-4. © 2020 Journal of Mid-life Health | Published by Wolters Kluwer - Medknow Sharma, et al.: A High‑Grade undifferentiated endometrial stromal sarcoma 1. Endometrial stromal nodule 2. ESS 3. High grade or undifferentiated stromal sarcoma.[2,3] Here, we report the undifferentiated ESS. rare case of high‑grade Case Report A 49‑year‑old woman, P2 L2, presented to the gynae outpatient department with complaints of discharge and spotting per vaginum for the past 3 months. Her previous menstrual cycles were regular. Her personal and family history was not significant. There was no history of radiation, tamoxifen, or estrogen use. She was a known case of hypertension. On general examination, pallor was present, and blood pressure was 150/90 mmHg. There was no tachycardia, clubbing, cyanosis, or lymphadenopathy. On systemic examination, cardiorespiratory and neurological systems were normal. On per abdominal examination, there was no organomegaly or lump. On per speculum examination, a cauliflower‑like growth of about 6 cm × 8 cm was present completely filling the vagina [Figure 1]. Growth was friable and bled on touch. On pervaginal examination, same growth was felt, and the whole mass was of 10 weeks size and fornices were free. Due to friability, few fragments from the mass were separated and the same sent for histopathological examination. The clinical impression was of advanced‑stage cancer cervix. Except for her Hb which was 7.9% g, other blood investigations were within the normal limits. Her ultrasonography reported a large 5.9 cm × 3.4 cm × 6.3 cm heterogeneous mass in the vaginal canal with inferiorly displaced uterine fundus and body with the impression of large prolapsed submucosal fibroid with resultant inversion of uterus or a large cervical growth. Her contrast‑enhanced computed tomography of the abdomen reported the inversion of the uterus and occupying the vaginal canal [Figure 2]. The hypodense lesion was noted surrounding the inverted uterus with a thickness measuring 3.5 cm. The final impression was submucosal fibroid with uterine inversion. Histopathological examination reported the possibility of ESS with a heterologous element or leiomyosarcoma with a heterologous element. On immunohistochemistry, it was CD10‑positive weakly [Figure 3], and tumor cells were negative for desmin, and thus the diagnosis of high‑grade ESS with smooth muscle differentiation and heterologous element was made [Figure 4]. The case was discussed in the institute’s multidisciplinary therapy board and was planned for surgery. Preoperatively, two units of packed red cell were transfused. On opening the abdomen, uterine fundus was not visualized. A vas‑like appearance was seen [Figure 5] with both the ovaries, tubes, and round ligaments entering into the crater. Debulking was done vaginally, and Haultain’s operation was performed. The uterus was then reposited followed by hysterectomy and bilateral salpingo‑oophorectomy. Postoperative period was uneventful. Her final histopathological report was high‑grade endometrial stromal sarcoma with more than 10 mitosis/10 high‑power field and extensive hemorrhage and necrosis with more than 50% of myometrial invasion with estrogen and progesterone receptor positivity. In view of high‑grade undifferentiated sarcoma, the patient was referred for radiotherapy postoperatively. Discussion ESS is generally misdiagnosed with leiomyoma or endometrial polyp and typically discovered on b a Figure 1: On per speculum examination, cauliflower‑like growth was seen c Figure 2: (a) Sagittal T2‑weighted magnetic resonance imaging shows T2 hyperintense mass (M) in the pelvis causing inversion of the uterus (U) seen as “V‑shape” fundus; (b) axial T2‑weighted magnetic resonance imaging shows inverted uterus (U) with “Bull’s eye” configuration; (c) axial T2‑weighted magnetic resonance imaging at a lower level shows the mass (M) Journal of Mid-life Health ¦ Volume 11 ¦ Issue 1 ¦ January-March 2020 41 Sharma, et al.: A High‑Grade undifferentiated endometrial stromal sarcoma mean age is 42–58 years.[2] Nearly 10%–25% affected women are premenopausal.[2] High‑grade ESS are seen in the older age group, with a median age of 61 years at presentation and are usually aggressive.[6] Endometrial stromal tumors are composed of cells resembling normal endometrial stroma in its proliferative phase. Figure 3: ×10 is showing sprinkling positivity of CD10, consistent with high‑grade stromal sarcoma Figure 4: It showing frank areas of endometrial stromal tumor with foci of heterologous cartilaginous formation Figure 5: Intraoperatively, vas‑like appearance was seen histopathological examination postoperatively because of its rarity.[4,5] It affects a younger age group, and the 42 Although menorrhagia is present in 90% of cases, 70% of patients present with uterine enlargement, pelvic pain, and dysmenorrhea. However, many patients can be asymptomatic.[1,2,7] In spite of presenting with typical symptoms and signs, it is rarely suspected as the first diagnosis and more common causes of abnormal uterine bleeding (AUB) such as leiomyoma, endometrial polyps, or submucous fibroid are considered as the etiology. Although endometrial curettage is the frequently used diagnostic modality for AUB, it is not sensitive for ESS, particularly when the lesion is entirely rooted in the myometrium. Furthermore, because of similarity between ESS and normal endometrial tissue curettage fragments, the diagnosis of ESS can be missed.[2] Ultrasound, especially, transvaginal can be helpful in diagnosing uterine leiomyoma, adenomyosis, or endometrial polyps but unpredictable in diagnosing ESS. Transvaginal Doppler can play a role in diagnosing ESS in which ESS has a low‑impedance flow and hence delineates it from the rest of uterine tissue. Magnetic resonance imaging scan can also diagnose it by the presence of low‑intensity bands within the area of myometrial invasion due to worm‑like permeations of tumor.[2] This can help in the preoperative diagnosis of ESS. Undifferentiated endometrial sarcoma (UES) may present as heterogeneous signal intensity voluminous polypoidal mass with more frequent myometrial involvement which can be demarcated or diffusely infiltrative on T1‑ and T2‑weighted images.[8] UES frequently has hemorrhage and necrosis and shows vascular and lymphatic invasion. While often indolent in behavior, ESS is malignant and can spread to the vagina, Fallopian tubes, ovaries, bladder, and ureters. Distant metastasis to the lung, heart, and other sites has also been reported.[9,10] High‑grade undifferentiated tumor tends to be larger, more polypoidal as presented in the index case (Stage IB). Due to the large growth, the uterus got inverted. High‑grade undifferentiated tumor displaces the myometrium more destructively, leading to prominent hemorrhage and necrosis.[11] At times, it is very difficult to differentiate ESS from cellular leiomyoma. In these cases, immunohistochemistry is particularly helpful to get the final diagnosis. The immunohistochemical markers such Journal of Mid-life Health ¦ Volume 11 ¦ Issue 1 ¦ January-March 2020 Sharma, et al.: A High‑Grade undifferentiated endometrial stromal sarcoma as h‑caldesmon and CD 10 may solve the diagnostic problem as CD 10 staining is positive in ESS but not in leiomyosarcoma. We performed CD‑10 staining to establish the diagnosis. Survival in patients with undifferentiated ESS appears to be related to the extent of residual disease after initial surgery and would suggest the necessity for aggressive cytoreduction as a main modality of the treatment.[2] Limited clinical data suggest that patients presenting at higher stage have a worse prognosis as compared to published outcomes in low‑grade ESS. Moreover, in the same study, the mean age of presentation was 54 years, and they were predominantly based in endomyometrium and demonstrated tongue‑like projections.[12] The treatment includes debulking followed by total hysterectomy with salpingo‑oophorectomy).[13] surgery bilateral Postoperative radiotherapy or progesterone is an effective adjuvant treatment providing high local control rates in uterine sarcomas. Hormone therapy with medroxyprogesterone, tamoxifen, gonadotropin‑releasing hormone analogs, and aromatase inhibitors are suggested for low‑grade ESS Stage 3‑4 and for recurrent disease.[14,15] In contrast, high‑grade undifferentiated tumors are not responsive to progestin therapy, and the poor therapeutic result suggests that radiation therapy, chemotherapy, or both should be used in combination to the surgery.[16] Our patient was referred for radiotherapy postoperatively. One of the retrospective studies reported that adjuvant radiotherapy and chemotherapy appear to improve overall survival.[17] For high‑grade ESS cytotoxic agents such as doxorubicin and ifosfamide or gemcitabine with docetaxel and doxorubicin have been used before surgery for tumor shrinkage.[18] In another retrospective study, vaginal vault brachytherapy as part of a multimodal adjuvant treatment was associated with a high locoregional control rate and with acceptable side effects in localized high‑grade ESS.[19] Long‑term follow‑up is necessary in these tumors as local recurrence and distant metastasis can occur even after 20 years of initial diagnosis. It shall be once in 3 months for the 1st year and half yearly for the next 4 years, and thereafter, annual follow‑up is recommended.[2] We referred our patient to another center for radiotherapy, and from there, she was lost to follow‑up. She did not report to our center thereafter. Conclusion Rarity of endometrial stromal tumor limits the clinician view to diagnose it preoperatively. In the present case, even though provisional diagnosis by clinical findings as well as imaging was in favor of submucous fibroid, we were fortunate to have the preoperative histopathological diagnosis of ESS. Furthermore, as ESS is rare and undifferentiated stromal sarcoma is even rarer literature is lacking on its optimal management. Hence, it is important for all clinicians to keep a high degree of suspicion for ESS while working up any case of AUB. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/ her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. References 1. Jassal CD, Patnaik BL, Divya A, Prasad S. Low‑grade endometrial stromal sarcoma in young age: A clinicopathological report. J Obstet Gynaecol India 2012;62:73‑5. 2. Puliyath G, Nair MK. Endometrial stromal sarcoma: A review of the literature. Indian J Med Paediatr Oncol 2012;33:1‑6. 3. Dowdy SC, Mariani A, Lurian JR. Uterine cancer. Berek and Novak’s Gynecology. 15th ed. Philadelphia, USA: Wolters Kleuner India Pvt., Limited; 2011. 4. Flam F, Rådestad A. Endometrial stromal sarcoma diagnosed by operative hysteroscopy. Hum Reprod 1996;11:2797‑8. 5. Somoye G, Lawton H, Havenga S. Endometrial stromal sarcoma: Experience from a district hospital and literature review. Eur J Gynaecol Oncol 2009;30:664‑7. 6. Adiga CP, Gyanchandani M, Goolahally LN, Itagi RM, Kalenahalli KV. Endometrial stromal sarcoma: An aggressive uterine malignancy. J Radiol Case Rep 2016;10:35‑43. 7. 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Lewis N, Soslow RA, Delair DF, Park KJ, Murali R, Journal of Mid-life Health ¦ Volume 11 ¦ Issue 1 ¦ January-March 2020 43 Sharma, et al.: A High‑Grade undifferentiated endometrial stromal sarcoma Hollmann TJ, et al. ZC3H7B‑BCOR high‑grade endometrial stromal sarcomas: A report of 17 cases of a newly defined entity. Mod Pathol 2018;31:674‑84. 13. Hasiakos D, Papakonstantinou K, Kondi‑Paphiti A, Fotiou S. Low‑grade endometrial stromal sarcoma of the endocervix. Report of a case and review of the literature. Eur J Gynaecol Oncol 2007;28:483‑6. 14. Palomba S, Falbo A, Mocciaro R, Russo T, Zullo F. Laparoscopic treatment for endometrial cancer: A meta‑analysis of randomized controlled trials (RCTs). Gynecol Oncol 2009;112:415‑21. 15. Lindner T, Pink D, Kretzschmar A, Mrozek A, Thuss‑Patience PC, Reichardt P. Hormonal treatment of endometrial stromal sarcoma: A possible indication for aromatase inhibitors. J ClinOncol 2005;23:9057. 44 16. Dowdy CS, Mariani A, Lurain J. Uterine cancer. Novacs Gynecology. 5th ed. Philadelphia, USA: Lippincott William and Wilkins a Wolter Kluwer Business; 2012. p. 1286‑917. 17. Meurer M, Floquet A, Ray‑Coquard I, Bertucci F, Auriche M, Cordoba A, et al. Localized high grade endometrial stromal sarcoma and localized undifferentiated uterine sarcoma: A retrospective series of the French sarcoma group. Int J Gynecol Cancer 2019;29:691‑8. 18. Lange SS, Novetsky AP, Powell MA. Recent advances in the treatment of sarcomas in gynecology. Discov Med 2014;18:133‑40. 19. Annede P, Gouy S, Mazeron R, Bentivegna E, Maroun P, Petit C, et al. Optimizing Local Control in high‑grade uterine sarcoma: Adjuvant vaginal vault brachytherapy as part of a multimodal treatment. Oncologist 2017;22:182‑8. Journal of Mid-life Health ¦ Volume 11 ¦ Issue 1 ¦ January-March 2020