{"paper_id":"e2959b48-350a-491e-94de-ff0addf5e54f","body_text":"pISSN 2287-9714   eISSN 2287-9722\nwww.coloproctol.org\nAnnals of\nColoproctology\nwww.coloproctol.org232\nMüllerian Adenosarcoma Arising From Rectal Endometriosis\nChunseok Y ang, Hoon Kyu Oh1, Daedong Kim\nDepartment of Surgery, Catholic University of School of Medicine, Daegu; 1Department of Surgery, Daegu Catholic University Medical \nCenter, Daegu, Korea\nCase Report\nAnn Coloproctol 2014;30(5):232-236\nhttp://dx.doi.org/10.3393/ac.2014.30.5.232\nA Müllerian adenosarcoma is an extremely rare tumor characterized by a stromal component of usually low-grade malig-\nnancy and by a benign glandular epithelial component. A Müllerian adenosarcoma occurs mainly in the uterus, but also \nin extrauterine locations. Extrauterine Müllerian adenosarcomas are thought to arise from endometriotic deposits. A \n36-year-old female presented to Daegu Catholic University Medical Center with a symptom of loose stool for several \nmonths. The imaging studies revealed a rectal mass, so she underwent a laparoscopic low anterior resection. Although ex-\ntemporary pathology revealed an inflammatory myofibroblastic tumor, the final histologic diagnosis was a Müllerian ade-\nnosarcoma arising from rectal endometriosis. To our knowledge, except a concomitant rectal villotubular adenoma, cases \nof Müllerian adenosarcomas arising the rectal wall are rare. An adenosarcoma arising from endometriosis should be con-\nsidered in the differential diagnosis of a pelvic mass, even one appearing in rectal wall, because ectopic endometrial tissue \nexists everywhere.\nKeywords: Mullerian adenosarcoma; Endometriosis; Rectal neoplasms; Adenosarcoma\nINTRODUCTION\nA Müllerian adenosarcoma was first reported in 1974 by Clement \nand Scully to describe an unusual variant of a Müllerian mixed tu-\nmor of the uterus [1, 2]. It is characterized by a mixture of a be-\nnign glandular epithelium and a malignant sarcomatous stroma, \nwhich are regarded as intermediate features between a benign ad-\nenofibroma and a carcinosarcoma. It occurs mainly in the uterus \nof postmenopausal women and also in young adults and in extra-\nuterine locations.\nAn extrauterine Müllerian adenosarcoma is rare and is thought \nto arise in ectopic foci of endometriosis. The most common site \nof an extrauterine Müllerian adenosarcoma is the ovary, but other \nreported locations are the vagina, fallopian tube, peritoneal sites \nsuch as the pouch of Douglas, intestinal serosa, and liver [3, 4]. \nWe present a case of primary extrauterine Müllerian adenosarcoma \narising from endometriosis of the rectum.\nCASE REPORT\nA 36-year-old female visited Daegu Catholic University Medical \nCenter complaining of having had a loose stool for several \nmonths. She complained of dysmenorrhea, deep dyspareunia, \nand mild intermittent hematochezia. A Cesarean section had been \nperformed 10 years earlier due to a narrow pelvis. Except these, \nshe had no significant medical history or family history.\nRectal examination revealed a 3-cm-sized, fixed, round, lobulated, \nfirm mass at the anterior side of the rectum, about 8 cm from the \nanal verge. Laboratory studies were unremarkable. Colonoscopy \n(Fig. 1) showed that a polypoid mass accounted for one-third of \nthe diameter of the rectum, and biopsy revealed it to be a hyper-\nplastic polyp. Computed tomography (Fig. 2A) showed a 2.7-cm-\nsized mass at the anterior side of the rectum, and magnetic reso-\nnance imaging (Fig. 2B) showed intermediate high signal inten-\nsity on the T2-weighted image. Based on the patient’s wish and \nclinical pictures, we advised a local excision.\nBecause of the high-lying tumor and its fixation to surrounding \ntissue, the patient underwent a transanal incisional biopsy. Frozen \nbiopsy revealed inflammation with an ulcer, and permanent bi-\nReceived: May 25, 2014   •   Accepted: July 23, 2014\nCorrespondence to: Daedong Kim, M.D.\nDepartment of Surgery, Daegu Catholic University Medical Center, Catholic \nUniversity of Daegu School of Medicine, 33 Duryugongwon-ro 17-gil, \nNam-gu, Daegu 705-718, Korea\nTel: +82-53-650-4061, Fax: +82-53-624-7185\nE-mail: ddkim@cu.ac.kr\n© 2014 The Korean Society of Coloproctology\nThis is an open-access article distributed under the terms of the Creative Commons Attribution Non-\nCommercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-\ncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.\n\nAnnals of\nColoproctology\nwww.coloproctol.org 233\nVolume 30, Number 5, 2014\nAnn Coloproctol 2014;30(5):232-236\nopsy revealed an inflammatory myofibroblastic tumor. A subse-\nquent laparoscopic low anterior resection was performed to excise \nthe tumor completely and to rule out a possible malignancy. In-\ntraoperative findings showed that left fallopian tube was twisted \nand had adhesed to the lateral pelvic wall and that the uterus was \nthick, edematous and severely attached to the rectum. \nThe final slides showed a biphasic appearance of epithelial and \nstromal components. The excised rectum was a 11.5-cm-sized \nsegment, and a 1:1 mounted H&E stained section (Fig. 3) shows a \n2.5 × 2-cm intramural nodular mass (arrow) with a polypoid mu-\ncosal protrusion (arrowhead). Multiple intramural and serosal \nendometriotic foci (circles) are also present. The histologic find-\nings suggested a diagnosis of an adenosarcoma (Fig. 4). To iden-\ntify the characteristics of the adenosarcoma, we performed im-\nmunohistochemistry on the endometriosis and the mural mass \n(Fig. 5).\nThe postoperative clinical course of the patient was uneventful, \nand the patient did not undergo any cycle of chemotherapy or ra-\ndiotherapy. We followed this patient for 5 years without any evi-\ndence of recurrence.\nDISCUSSION\nA Müllerian adenosarcoma is an uncommon mixed epithelial-\nmesenchymal tumor of low-grade malignancy that affects the fe-\nmale genital tract [2]. Usually, postmenopausal women have a \nhigher risk for a uterine Müllerian adenosarcoma compared with \nyounger women, and its median age at diagnosis is 58 years [5]. \nHowever, extrauterine Müllerian adenosarcomas occur in younger \nwomen (mean age, 44 years) and are more aggressive than uterine \ntumors. Probably because the extrauterine location allows free ac-\ncess to the peritoneal cavity, the spread of an extrauterine Mülle-\nrian adenosarcoma may not be retarded by the thick myometrial \nwall. Therefore, for a uterine Müllerian adenosarcoma, surgery \nalone is often curative, and a recurrent tumor occurs in approxi-\nmately 25% of the cases. In contrast, an extrauterine Müllerian \nadenosarcoma recurs in over 50% of the patients and is associated \nwith a mortality rate of approximately 35% [6].\nThe pathogenesis of the extrauterine Müllerian adenosarcoma is \nunclear. However, the association between exogenous hormonal \ntherapy and the development of malignancy in endometriosis is \nwell known, and the possibility of a neoplastic transformation of \nendometriotic foci has been suggested by several studies [7, 8]. A \nlarge review by Stern of endometriosis-associated neoplasms re-\nFig. 1. A polypoid mass accounting for one-third of the diameter of \nthe rectum was seen during the colonoscopy. \nFig. 2. (A) Abdominal computed tomographic scan showing a 2.7-cm-sized mass (arrow) in the anterior wall of the rectum. (B) Magnetic res-\nonance imaging scan showing a 2.7-cm-sized mass (arrow) in the anterior wall of the rectum and intermediate high signal intensity on the T2-\nweighted image.\nA B\n\nAnnals of\nColoproctology\nwww.coloproctol.org234\nMüllerian Adenosarcoma Arising From Rectal Endometriosis \nChunseok Yang, et. al.\nFig. 3. The excised colon (A) and 1:1 mounted H&E-stained section (B) show an intramural nodular mass (arrow) with a polypoid mucosal \nprotrusion (arrowhead). Multiple intramural and serosal endometriotic foci (circles) are also present.\nA B\nFig. 4. (A) The intramural nodular mass shows a characteristic biphasic appearance of this neoplasm with a polypoid projection into the glan-\ndular space, a typical low power appearance of a phyllodes tumor of the breast (H&E, ×40). (B) The mucosal polypoid protrusion of the tumor \nalso show biphasic components (H&E, ×100). (C) The high-power view of the intramural mass shows a single layer, bland-looking epithelial \nlining and cellular stroma (H&E, ×100). (D) The stromal cells are spindle-like and plump in shape with a fascicular growth pattern and have \nenlarged nuclei with mild cytologic atypia. A few abnormal mitotic figures are noted. Many inflammatory cells, including lymphocytes, \nplasma cells and eosinophils, and infiltration are frequently noted throughout the tumor (H&E, ×400).\nA\nC\nB\nD\n\nAnnals of\nColoproctology\nwww.coloproctol.org 235\nVolume 30, Number 5, 2014\nAnn Coloproctol 2014;30(5):232-236\nFig. 5. (A) The endometriotic foci of the wall show tubular endometrial glands with cuffs of endometrial stromal cells (H&E, ×100). (B) The \nendometrial glandular epithelial cells and stromal cells show positive immunoreaction to estrogen receptor (ER) (×200). (C) The periglandular \nendometrial stromal cells show CD10 immunoreactivity (×100). (D) The epithelial cell and stromal cells of the intramural mass (H&E, ×100) \nshows (E) ER immunoreactivity (×200), but not (F) CD10 (×100). (G) The tumor stromal cells (H&E, ×200) have strong reactions to (H) \nsmooth-muscle actin (×200), but not to (I) desmin (×100).\nA\nD\nG\nB\nE\nH\nC\nF\nI\nvealed that an adenosarcoma was the second most common ma-\nlignancy after a clear cell carcinoma to arise in the setting of extra-\novarian endometriosis [7]. Although most tumors associated with \nendometriosis are of epithelial origin, rare cases of stromal neo-\nplasms, including an adenosarcoma, have been reported and rep-\nresent 20.8% of the cases arising in endometriosis from extrago-\nnadal sites [9]. This case meets Sampson’s criteria for malignant \ntransformation of endometriosis, which include the following: the \nfoci of endometriosis were found in close proximity to the malig-\nnancy, the histological appearance was compatible with an endo-\nmetrial origin, and no other possible primary tumor was seen [10].\nFirst, confirming a histological diagnosis of an adenosarcoma is \nimportant. A Müllerian adenosarcoma arising from endometrio-\nsis should be distinguished from uncommon benign lesions that \nare characterized by benign glands, like polypoid endometriosis, \nadenofibroma, and low-grade endometrial stromal sarcoma with \nglandular differentiation. The diagnosis could be determined us-\ning the criteria recommended by Clement and Scully [1]. They \nproposed that the diagnosis of an adenosarcoma be made when \none or more of the following criteria are present: (1) a stromal mi-\ntotic count of two or more mitotic figures per 10 high power field; \n(2) marked stromal cellular-like periglandular cuffs and intrag-\nlandular protrusion of cellular stroma; and (3) more than a mild \ndegree of nuclear atypia of the stromal cells.\nExtrauterine tumors are distinctively less common and are pri-\nmarily located in the pelvic peritoneum, retroperitoneum, broad \nand round ligaments, vesicouterine pouch, and rectouterine pouch. \nUntil today, only a few cases of an extrauterine Müllerian adeno-\nsarcoma arising from endometriosis of the intestine, especially the \nrectum, have been reported [4]. To our knowledge, this is an ex-\ntremely rare case of an adenosarcoma arising from endometriosis \nof the rectum except that a concomitant rectal adenoma and ade-\nnosarcoma was reported [11].\nThe infrequency of a Müllerian adenosarcoma makes establish-\n\nAnnals of\nColoproctology\nwww.coloproctol.org236\nMüllerian Adenosarcoma Arising From Rectal Endometriosis \nChunseok Yang, et. al.\ning well-defined therapeutic protocols difficult. However, radical \nsurgery remains a therapeutic mainstay. For the treatment of a \nuterine Müllerian adenosarcoma, a surgical approach similar to \nthat used for the corresponding disease stages of an endometrial \ncarcinoma is recommended, and a total abdominal hysterectomy \nwith a bilateral adnexectomy appears adequate for stage I patients. \nThe decision on giving postoperative chemotherapy may be based \non the extent of muscular invasion and sarcomatous growth. Ad-\njuvant chemotherapy is also considered for treating an extrauter-\nine Müllerian adenosarcoma, although its role is still debatable. \nAlthough previous reports are inadequate to confirm first-line \nchemotherapeutic regimens, a few case reports suggest that pa-\ntients should be treated with liposomal doxorubicin [6, 12]. The \nregimen of this recommendation is well tolerated and is effective \nbased on excellent response, minimal toxicity, and convenient \ndosing schedule in recurrences and adjuvant therapy for extra-\nuterine forms. As the risk of developing recurrent disease was \nhigh, a cautionary radiation therapy was given to prevent the \nprobability of a local recurrence. Neoadjuvant or adjuvant pelvic \nirradiation with chemotherapy was studied in advanced stages, \nand acceptable outcomes have been reported [13]. In fact, this \ntherapeutic approach was chosen in consideration of the aggres-\nsive behavior of the tumor. \nThe most important negative prognostic factors are lesion loca-\ntion, the degree of myometrial invasion, and sarcomatous over-\ngrowth. In a uterine Müllerian adenosarcoma, the degree of myo-\nmetrial invasion, sarcomatous overgrowth, and the recurrence \nrate are strongly correlated to the differentiation grade and the \nmitotic index of the sarcomatous stromal component [14]. By \ncontrast, a favorable prognostic factor in adenosarcoma patients \nis the presence of endometriosis [7].\nThe case we present provides an association with endometriosis, \nsupporting the hypothesis that an extrauterine Müllerian adeno-\nsarcoma is transformed from endometriosis. Exogenous or en-\ndogenous estrogen may have some role in the transformation \nprocess whereas the effectiveness of combined estrogen-proges-\nterone hormone-replacement therapy is still to be determined. \nFurther, the titers of the tumor marker CA 125 were well corre-\nlated with the clinical course of endometriosis and might be a \npredictor for the sarcomatous overgrowth [15].\nIn conclusion, an extrauterine Müllerian adenosarcoma is rare, \nbut it should be considered in a patient with atypical clinical fea-\ntures or preoperative pathology, especially in a patient with a his-\ntory of endometriosis. Further research is needed to establish the \npathogenesis of an extrauterine adenosarcoma and the therapeu-\ntic guidelines. \nCONFLICT OF INTEREST\nNo potential conflict of interest relevant to this article was re-\nported.\nREFERENCES\n1. Clement PB, Scully RE. Müllerian adenosarcoma of the uterus. A \nclinicopathologic analysis of ten cases of a distinctive type of mül-\nlerian mixed tumor. Cancer 1974;34:1138-49.\n2. Clement PB, Scully RE. Mullerian adenosarcoma of the uterus: a \nclinicopathologic analysis of 100 cases with a review of the litera-\nture. Hum Pathol 1990;21:363-81. \n3. Eichhorn JH, Y oung RH, Clement PB, Scully RE. Mesodermal \n(müllerian) adenosarcoma of the ovary: a clinicopathologic analy-\nsis of 40 cases and a review of the literature. Am J Surg Pathol 2002; \n26:1243-58. \n4. Y antiss RK, Clement PB, Y oung RH. Neoplastic and pre-neoplas-\ntic changes in gastrointestinal endometriosis: a study of 17 cases. \nAm J Surg Pathol 2000;24:513-24. \n5. Xie YP , Y ao HX, Shen YM. Müllerian adenosarcoma of the uterus \nwith heterologous elements: two case reports and literature re -\nview. Arch Gynecol Obstet 2012;286:537-40. \n6. Huang GS, Arend RC, Sakaris A, Hebert TM, Goldberg GL. 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Extra-\nuterine müllerian adenosarcoma associated with endometriosis \nand rectal villotubular adenoma: report of a case and review of \nthe literature. Int J Gynecol Cancer 2005;15:361-5. \n12. del Carmen MG, Lovett D, Goodman A. A case of Müllerian ade-\nnosarcoma of the uterus treated with liposomal doxorubicin. Gy-\nnecol Oncol 2003;88:456-8.\n13. Carvalho FM, Carvalho JP , Motta EV , Souen J. Müllerian adeno-\nsarcoma of the uterus with sarcomatous overgrowth following \ntamoxifen treatment for breast cancer. Rev Hosp Clin Fac Med \nSao Paulo 2000;55:17-20. \n14. Verschraegen CF , Vasuratna A, Edwards C, Freedman R, Kudelka \nAP , Tornos C, et al. Clinicopathologic analysis of mullerian ade-\nnosarcoma: the M.D. Anderson Cancer Center experience. Oncol \nRep 1998;5:939-44. \n15. Inoue M, Fukuda H, Tanizawa O. Adenosarcomas originating \nfrom sites other than uterine endometrium. Int J Gynaecol Obstet \n1995;48:299-306.","source_license":"CC0","license_restricted":false}