{"paper_id":"d1c04f4b-c739-45ae-9e00-0663b76905e5","body_text":"Case Report\nJ Gynecol Oncol Vol. 20, No. 2:122-125, June 2009  DOI:10.3802/jgo.2009.20.2.122\n122\nA case of multiple metastatic low-grade endometrial stromal \nsarcoma arising from an ovarian endometriotic lesion\nJoo Yeon Kim1, Seong Yeon Hong1, Hyun Jung Sung2, Hoon Kyu Oh2, Suk Bong Koh1\nDepartments of 1Obstetrics and Gynecology, 2Pathology, School of Medicine, Catholic University of Daegu, Daegu, Korea\nThe development of endometrial stromal sarcomas (ESSs) in foci of endometriosis is extremely rare, and few cases \nhave been reported in the literature to date, particularly with regard to multiple extrauterine ESS. Here we report a \ncase of endometrial stromal sarcoma with multiple metastasis that arose from an ovarian endometriotic lesion. The \nliterature is also briefly reviewed.\nKey Words: Endometrial stromal sarcomas, Endometriosis, Ovary\nReceived October 16, 2008, Revised January 9, 2009,\nAccepted February 13, 2009\nAddress reprint requests to Suk Bong Koh\nDepartment of Obstetrics and Gynecology, Catholic University of \nDaegu School of Medicine, 3056-6, Daemyung 4-dong, Nam-gu, \nDaegu 705-718, Korea \nTel: 82-53-650-4074, Fax: 82-53-650-4078\nE-mail: sbko@cu.ac.kr\nINTRODUCTION\n  Uterine sarcomas are rare tumors that are characterized by \nrapid progression and a poor prognosis. Histologically, they \nare classified as leiomyosarcomas, endometrial stromal sarco-\nmas (ESSs) and mixed mesodermal tumors. ESSs are rare ne-\noplasms that comprise approximately 0.2% of all uterine ma-\nlignancies and about 10-15% of all uterine sarcomas.\n1 In par-\nticular, the development of ESS in endometriotic lesions is \nvery rarely reported. Such extrauterine ESSs can develop in \nthe ovary, fallopian tube, pelvic cavity, colon and retroperito-\nneum.\n2  Since ovarian ESS is so rare, very little is known about \nits pathogenesis.\n  However, at least in some cases, it may be a metastatic tumor \nthat originates from a uterine tumor, perhaps years after a \nhysterectomy was performed to remove the primary tumor.  \n  Here we describe a case of low-grade ESS with multiple \nmetastasis that arose from an ovarian endometriotic lesion af-\nter hysterectomy.\nCASE REPORT\n  A 50-year-old gravida 4, para 3, abortion 1 woman presented \nwith lower back pain that had lasted for 1 month. In April \n2000, the patient underwent total abdominal hysterectomy \ndue to uterine myoma in our hospital. The uterus was sent for \npathohistological analysis. Histologically, the myoma ap-\npeared to be an adenomyomtous polyp. In September 2008, \nthe patient returned to our hospital due to back pains. Com-\nputed tomography (CT) showed a necrotic solid mass meas-\nuring 7 cm in diameter in the left adnexa, a para-aortic solid \nmass lesion, and left renal vein and inferior vena cava throm-\nbosis, which was suggestive of nodal metastasis, probably pel-\nvic nodal metastasis (Fig. 1). We performed a ultrasound - \nguided biopsy of the para-aortic solid mass. Histological anal-\nysis revealed a spindle cell tumor with malignant features, in-\ncluding high cellularity and abnormal mitotic figures. The da-\nta from the tumor marker studies are as follows: cancer anti-\ngen (CA)-125, 118.4 IU/ml; CA 19-9, 38.7 IU/ml; carcinoem-\nbryonic antigen (CEA), 1.8 ng/ml; alpha-foetoprotein (AFP), \n1.6 ng/ml. The complete blood cell count data are as follows: \nhemoglobin, 12.6 g/dl; white blood cell count, 8,900/mm\n3; \nplatelet count, 273,000/mm3. Other examinations, including \nurinalysis, liver function tests and renal function tests, re-\nvealed no abnormalities. Esophagoduodenoscopy revealed re-\nflux esophagitis and gastropathy. Colonoscopy detected hem-\norrhoids and a 0.2 cm diameter polyp 50 cm from the anal \nverge. Histologically, the tumor appeared to be a tubular \nadenoma. On the basis of these findings, we performed an ex-\nploratory laparotomy followed by a tumor debulking pro-\ncedure. The surgical procedure consisted of a bilateral sal-\npingoophorectomy, an appendectomy, an omentum biopsy, a \nposterior cul-de-sac area biopsy and cytology. In the left ad-\nnexa, a 6×5 cm-sized mass was detected. It was composed of \na solid and a cystic portion. It adhered to the posterior cul-de- \nsac and was accidentally ruptured during the operation. In the \nright adnexa, multiple small nodules approximately 1cm in \n\nOvarian endometrial stromal sarcoma \n123\nFig. 1. Computed tomography showing a necrotic solid mass meas-\nurin g 7  cm  in  d iam eter o n  th e left ad n e xa (B ), a h ug e pa ra -ao rtic \nsolid mass lesion, and left renal vein and inferior vena cava throm-\nbosis, which is suggestive of nodal metastasis (A, C). (A, B) axial \nimage, (C) coronal image.\nFig. 2. Gross findings of the left ovary. The cut surface shows a dif-\nfuse dark reddish hemorrhagic lesion containing a solid focal yel-\nlowish lesion.\nFig. 3. Microscopic findings of the \nleft ovary. The sections of the left \novary exhibit perivascular whorling \nproliferation of plump and spindle \ncells with a scanty cytoplasm and \nindistinct cell borders (A, hema-\ntoxylin-eosin, ×200; B, hematox-\nylin-eosin, ×400). Immunohisto-\nchemical staining analyses revealed \nthat the neoplastic cells were im-\nmunoreactive to CD10 (C, ×400)\nand ER (D, ×400).\ndiameter were detected. In addition, the right adnexa had ad-\nhered to the omentum. A hard nodule about 2-3 cm in diame-\nter was detected at the right infundibulopelvic ligament. The \npara-aortic lymph node was enlarged to a size of 10×8×5 cm \nand had invaded the aorta, inferior vena cava and common \niliac vessels. Consequently, it was not possible to perform an \nen bloc excision of the para-aortic mass. The rectum con-\ntained numerous nodules up to 0.5 cm in diameter. The ap-\npendix, liver surface and diaphragm were normal.\n  Grossly, the left ovary measured 8.0×6.5×4.0 cm in size and \nweighed 83 gm. The external surface was pale pink to whitish \nand smooth. Upon sectioning, the cut surface showed a dif-\nfuse dark reddish hemorrhagic lesion containing a focal yel-\nlowish solid lesion (Fig. 2). The right ovary had a smooth sur-\nface and a unilocular cyst with hemorrhaging. The cul-de-sac \nmass measured 1.3×0.5 cm in size. The omentum exhibited \nmultiple small nodules.\n  Microscopically, the left ovary exhibited perivascular whorl-\ning proliferation of plump spindle cells with scanty cytoplasm \nand indistinct cell borders. There were many irregular small \n\nJ Gynecol Oncol Vol. 20, No. 2:122-125, 2009 Joo Yeon Kim, et al.\n124\nTable 1.  Result of immunohistochemical examination \nAb Endometrial stromal sarcoma\nCD 10 +\nVimentin +\nKi-67 +\nER 3+\nPR 3+\nSMA −\nCD10: cluster of differentiation 10, ER: estrogen receptor, PR: pro-\ngesterone receptor, SMA: smooth muscle actin\nTable 2.Microscopic features of ovarian endometrioid stromal sar-\ncoma\nDiffuse growth pattern\nExtraovarian intravascular growth\nSmall round or oval cells with scanty cytoplasm\nPericellular reticulum\nFibromatous component\nAssociated endometriosis\nvessels around the tumor cells and hemorrhage was con-\nspicuous (Fig. 3B). Benign endometrial glands and sparse \nstroma were observed at the periphery of the tumor (Fig. 3A). \nMitotic figures 4-5 per 10 high power field (HPF) were ob-\nserved. The right ovary exhibited pure ESS nodules with lym-\nphovascular invasion. However, there were no endometriotic \nfoci in the right ovary. The cul-de-sac mass exhibited ESS with \nendometrial glands. The omentum exhibited metastatic ESS. \nImmunohistochemical staining revealed that the neoplastic \ncells were immunoreactive to antibodies specific for cluster of \ndifferentiation 10 (CD10) (Fig. 3C), Vimentin, Ki-67, estro-\ngen receptor (ER) (Fig. 3D), progesterone receptor (PR) \n(Table 1).\n  To treat this ESS, which had arisen from the ovarian endo-\nmetriotic lesion and exhibited multiple metastasis, chemo-\nradiation therapy was planned. The patient is currently under-\ngoing a course of chemoradiation therapy and hormonal ther-\napy with progestins. Thus, the para-aortic area was irradiated \nwith 5,040 cGY, and 60 mg/m\n2 cisplatin plus 4,000 mg/m2 \nifosfamide is now being administered a total of 6 cycles, at \nthree week intervals. In December 2008, the radiation therapy \nwas completed and the patient had received her fifth che-\nmotherapy. A follow-up CT showed interval improvement of \nthe nodal metastasis in the pelvic and para-aortic spaces. \nMoreover, the venous thrombosis of the inferior vena cava \nand the left renal vein was no longer apparent.\nDISCUSSION \n  The development of ESS in foci of endometriosis is ex-\ntremely rare and differentiating such tumors from other tu-\nmors, such as myogenic, vascular, hemopoietic or epithelial \norigin tumors, may be difficult.\n3 The etiology of ESS is \nunknown. However, there are some reports that suggest that \nESS is an endometriosis-associated de novo tumor derived \nfrom submesothelial pluripotential mullerian cells.\n4 Ovarian \nsex cord stromal tumors with a predominant spindle cell com-\nponent, Sertoli-Leydig cell tumors and primary mesenchymal \ntumors such as gastrointestinal stromal tumors (GISTs) are \nalso important differential diagnostic considerations.\n3,5,6 \nMalignant transformation is an infrequent complication of \nendometriosis.\n  Of the extrauterine ESSs, the ovary is the primary site in 76% \nof cases, while extragonadal sites accounts for the remaining \n24%.\n5 The microscopic differential diagnosis of ovarian ESS \nincludes three major categories of neoplasms: namely, other \npure sarcomas; malignant mesodermal mixed tumors, partic-\nularly mesodermal adenosarcoma; and sex cord-stromal \ntumors. The major diagnostic features that are helpful in iden-\ntifying the endometrioid stromal nature of an ovarian tumor \nare listed in Table 2. The possible origins of ESS of the ovary \nare endometriosis of the usual type and pure stromal endome-\ntriosis (foci of gland-free endometrial stroma in the ovary).\n7,8 \nSimilar neoplasms have arisen in association with endome-\ntriosis in various other locations.\n9 It is also possible that some \nESSs of the ovary arise directly from ovarian stromal cells that \nhave undergone neometaplasia into endometrial stromal-type \ncells. In this case, the left ovary showed gradual progression of \nusual endometriotic foci to low grade ESS (Fig. 3A) with mul-\ntiple metastatic nodules in the right ovary, cul-de-sac and \nomentum.\n  ESS has traditionally been divided into two categories, \nnamely, low-grade and high-grade stromal sarcoma. In most \nstudies, ESS comprises less than 20% of uterine sarcomas and \nmost are low-grade stromal sarcomas (LGSSs).\n10 The mitotic \nactivity of LGSSs is low, namely, less than 10/10 HPF. \nHigh-grade stromal sarcomas (HGSSs), on the other hand, are \ntumors with mitotic activities that generally exceed 10/10 \nHPF, although some HGSSs can also have mitotic activities \nbelow 10/10 HPF.\n10 \n  Histological analyses of extrauterine extraovarian ESS reveal \ninfiltrative or tongue-like multinodular growth patterns. \nCytological atypia is minimal to mild, and mitotic figures are \ninfrequently seen, namely, up to 5 mitotic figures per 10 HPF. \nVascular and lymphatic invasion by the tumor is occasionally \npresent.\n11\n  Characteristic immunohistochemical features of ESS include \nreactivity to antibodies specific for Vimentin, ER and CD10, \nand nonreactivity to antibodies against CD117, smooth mus-\ncle actin (SMA) and cytokeratin (CK). A recent study has \nshown that among the cases of ESS that were examined, all \ncases were immunoreactive to anti-CD10 (5/5 cases) and an-\nti-progesterone receptor (10/10 cases) antibody, most re-\nacted with anti-estrogen receptor antibody (9/11 cases), 5/9 \nand 3/7 were focally positive for smooth muscle actin and des-\nmin, respectively, and all were negative for CD34 (0/7 cas-\n\nOvarian endometrial stromal sarcoma \n125\nes).11 While it is now widely accepted that diffuse CD10 im-\nmunoreactivity is a very useful positive predictive marker of \nESS, evaluating CD10 immunoreactivity alone is often not \nhelpful for differentiating ESS from its mimics. With regard to \nthe progesterone receptor, while ESSs show high sensitivity \nto antibodies against this antigen, this immunostain is less \nspecific for differentiating ESS from other mesenchymal \ntumors.  Therefore, a panel of immunohistochemical stains \nthat comprise CD10, estrogen receptor and CD34 may be \nmore helpful for diagnosing extrauterine extraovarian ESS.\n To the best of our knowledge, there is one previous report \nthat describes  ovarian ESSs, namely, that of Young et al.\n6, \nwho reviewed 23 cases of ESSs of the ovary. The patients' ages \nranged from 20 to 76 years (average, 54 years). The most com-\nmon presenting symptom was abdominal swelling or pain. In \n12 cases, the tumors were unilateral, while in 11 cases they in-\nvolved both ovaries. Four of the tumors were Stage I, nine \nwere Stage II, eight were Stage III and two were Stage IV be-\ncause of the presence of pulmonary metastases. In nine of the \ncases, there was a prior, synchronous or subsequent ESS of \nthe uterus. Nineteen tumors with HPF less than 10 MF/10 \nHPF were classified as low grade and the remaining four tu-\nmors with 12 to 30 MF/10 HPF were designated as high grade. \nOnly two of the 19 patients with low-grade tumors are known \nto have died of their disease, and nine of those whose tumor \nhad spread beyond the ovary at the time of presentation were \nalive one or more years postoperatively. However, three of the \nfour patients with high-grade tumors died of their disease \nwithin 4 years.\n  Surgery has always been described as the most effective \ntreatment for uterine sarcomas. Total abdominal hyster-\nectomy with bilateral salpingo-oophorectomy is considered to \nbe the standard treatment for early stage low-grade ESS.\n12 \nWhenever possible, complete tumor clearance should be \nattempted. The options of adjuvant therapy following surgery \ninclude radiotherapy, chemotherapy, hormonal therapy and \nobservation.\n12-14 The indications and the roles of adjuvant \ntherapies remain controversial. Low grade ESSs are mostly \nsteroid receptor-positive tumors, which means hormonal \ntherapy with progestins, aromatase inhibitors (third gen-\neration) and gonadotropin-releasing hormone (GnRH) ana-\nlogues is effective. Progesterone is considered to be a useful \nform of therapy for residual or recurring low grade ESS. LGSSs \nusually grow slowly and tend to recur many years after the ini-\ntial surgery. The pelvic cavity followed by the vagina and lung \nare the main sites of metastases.\n  In conclusion, the behavior of ESSs of the ovary is similar to \nthat of their uterine counterparts, with the degree of mitotic \nactivity being of major prognostic significance. The prognosis \nof patients with low-grade tumors is considerably better than \nthat of patients with other pure ovarian sarcomas.\n15 This case \nillustrates the findings of low-grade ESS with multiple meta-\nstasis arising from an ovarian endometriotic lesion.\nREFERENCES\n1. Diesing D, Cordes T , Finas D, Loning M, Mayer K, Diedrich K, \net al. Endometrial stromal sarcomas: a retrospective analysis of \n11 patients. Anticancer Res 2006; 26(1B): 655-61.\n2. Yokosuka K, Kumagai M, Aiba S. Low-grade endometrial stro-\nmal sarcoma recurring after 9 years. South Med J 2002; 95: \n1196-200.\n3. Chang KL, Crabtree GS, Lim-Tan SK, Kempson RL, Hendrick-\nson MR. Primary extrauterine endometrial stromal neoplasms: \na clinicopathologic study of 20 cases and a review of the \nliterature. Int J Gynecol Pathol 1993; 12: 282-96. \n4. Baiocchi G, Kavanagh JJ, Wharton JT . Endometrioid stromal \nsarcomas arising from ovarian and extraovarian endometriosis: \nreport of two cases and review of the literature. Gynecol Oncol \n1990; 36: 147-51. \n5 . M o urra N , T iret E, P arc Y , d e Sa in t-M aur P , P a rc R, F lejo u JF . \nEndometrial stromal sarcoma of the rectosigmoid colon arising \nin extragonadal endometriosis and revealed by portal vein \nthrombosis. Arch Pathol Lab Med 2001; 125: 1088-90.\n6. Young RH, Prat J, Scully RE. Endometrioid stromal sarcomas of \nthe ovary: a clinicopathologic analysis of 23 cases. Cancer 1984; \n53: 1143-55.\n7. Hughesdon PE. The origin and development of benign stroma-\ntosis of the ovary. J Obstet Gynaecol Br Commonw 1972; 79: \n348-59. \n8. Hughesdon PE. The endometrial identity of benign stromatosis \nof the ovary and its relation to other forms of endometriosis. J \nPathol 1976; 119: 201-9.\n9. Mostoufizadeh M, Scully RE. Malignant tumors arising in en-\ndometriosis. Clin Obstet Gynecol 1980; 23: 951-63. \n1 0 . Z a l o u d e k  C ,  H e d r i c k s o n  M R .  M e s e n c h y m a l  t u m o r s  o f  t h e  \nuterus. In: Kurman RJ, editor.  Blaustein's pathology of the fe-\nmale genital tract. New York: Springer; 2002. p.586-90. \n11. Kim L, Choi SJ, Park IS, Han JY , Kim JM, Chu YC, et al. \nEndometrial stromal sarcoma of the small bowel. Ann Diagn \nPathol 2008; 12: 128-33.\n1 2 . Le u n e n  M , B r e u g e lm a n s  M , D e  S u t t e r P , B o u r g a in  C , A m y  JJ. \nLow-grade endometrial stromal sarcoma treated with the ar-\nomatase inhibitor letrozole. Gynecol Oncol 2004; 95: 769-71.\n13. Paillocher N, Lortholary A, Abadie-Lacourtoisie S, Morand C, \nVerriele V , Catala L, et al. Low-grade endometrial stromal sar-\ncoma: contribution of hormone therapy and etoposide. J \nGynecol Obstet Biol Reprod 2005; 34: 41-6. \n14. Burke C, Hickey K. Treatment of endometrial stromal sarcoma \nwith a gonadotropin-releasing hormone analogue. Obstet \nGynecol 2004; 104(5 Pt 2): 1182-4.\n15. Bodner K, Bodner-Adler B, Obermair A, Windbichler G, Petru \nE ,  M a y e r h o f e r  S ,  e t  a l .  P r o g n o s t i c  p a r a m e t e r s  i n  e n d o m e t r i a l  \nstromal sarcoma: a clinicopathologic study in 31 patients. \nGynecol Oncol 2001; 81: 160-5.","source_license":"CC0","license_restricted":false}