Müllerian Adenosarcoma Arising From Rectal Endometriosis

Mullerian adenosarcoma; Endometriosis; Rectal neoplasms; Adenosarcoma

A Müllerian adenosarcoma was first reported in 1974 by Clement and Scully to describe an unusual variant of a Müllerian mixed tu- mor of the uterus [1, 2]. It is characterized by a mixture of a be- nign glandular epithelium and a malignant sarcomatous stroma, which are regarded as intermediate features between a benign ad- enofibroma and a carcinosarcoma. It occurs mainly in the uterus of postmenopausal women and also in young adults and in extra- uterine locations. An extrauterine Müllerian adenosarcoma is rare and is thought to arise in ectopic foci of endometriosis. The most common site of an extrauterine Müllerian adenosarcoma is the ovary, but other reported locations are the vagina, fallopian tube, peritoneal sites such as the pouch of Douglas, intestinal serosa, and liver [3, 4]. We present a case of primary extrauterine Müllerian adenosarcoma arising from endometriosis of the rectum. CASE REPORT A 36-year-old female visited Daegu Catholic University Medical Center complaining of having had a loose stool for several months. She complained of dysmenorrhea, deep dyspareunia, and mild intermittent hematochezia. A Cesarean section had been performed 10 years earlier due to a narrow pelvis. Except these, she had no significant medical history or family history. Rectal examination revealed a 3-cm-sized, fixed, round, lobulated, firm mass at the anterior side of the rectum, about 8 cm from the anal verge. Laboratory studies were unremarkable. Colonoscopy (Fig. 1) showed that a polypoid mass accounted for one-third of the diameter of the rectum, and biopsy revealed it to be a hyper- plastic polyp. Computed tomography (Fig. 2A) showed a 2.7-cm- sized mass at the anterior side of the rectum, and magnetic reso- nance imaging (Fig. 2B) showed intermediate high signal inten- sity on the T2-weighted image. Based on the patient’s wish and clinical pictures, we advised a local excision. Because of the high-lying tumor and its fixation to surrounding tissue, the patient underwent a transanal incisional biopsy. Frozen biopsy revealed inflammation with an ulcer, and permanent bi- Received: May 25, 2014 • Accepted: July 23, 2014 Correspondence to: Daedong Kim, M.D. Department of Surgery, Daegu Catholic University Medical Center, Catholic University of Daegu School of Medicine, 33 Duryugongwon-ro 17-gil, Nam-gu, Daegu 705-718, Korea Tel: +82-53-650-4061, Fax: +82-53-624-7185 E-mail: [email protected] © 2014 The Korean Society of Coloproctology This is an open-access article distributed under the terms of the Creative Commons Attribution Non- Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non- commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Annals of Coloproctology www.coloproctol.org 233 Volume 30, Number 5, 2014 Ann Coloproctol 2014;30(5):232-236 opsy revealed an inflammatory myofibroblastic tumor. A subse- quent laparoscopic low anterior resection was performed to excise the tumor completely and to rule out a possible malignancy. In- traoperative findings showed that left fallopian tube was twisted and had adhesed to the lateral pelvic wall and that the uterus was thick, edematous and severely attached to the rectum. The final slides showed a biphasic appearance of epithelial and stromal components. The excised rectum was a 11.5-cm-sized segment, and a 1:1 mounted H&E stained section (Fig. 3) shows a 2.5 × 2-cm intramural nodular mass (arrow) with a polypoid mu- cosal protrusion (arrowhead). Multiple intramural and serosal endometriotic foci (circles) are also present. The histologic find- ings suggested a diagnosis of an adenosarcoma (Fig. 4). To iden- tify the characteristics of the adenosarcoma, we performed im- munohistochemistry on the endometriosis and the mural mass (Fig. 5). The postoperative clinical course of the patient was uneventful, and the patient did not undergo any cycle of chemotherapy or ra- diotherapy. We followed this patient for 5 years without any evi- dence of recurrence.

A Müllerian adenosarcoma is an uncommon mixed epithelial- mesenchymal tumor of low-grade malignancy that affects the fe- male genital tract [2]. Usually, postmenopausal women have a higher risk for a uterine Müllerian adenosarcoma compared with younger women, and its median age at diagnosis is 58 years [5]. However, extrauterine Müllerian adenosarcomas occur in younger women (mean age, 44 years) and are more aggressive than uterine tumors. Probably because the extrauterine location allows free ac- cess to the peritoneal cavity, the spread of an extrauterine Mülle- rian adenosarcoma may not be retarded by the thick myometrial wall. Therefore, for a uterine Müllerian adenosarcoma, surgery alone is often curative, and a recurrent tumor occurs in approxi- mately 25% of the cases. In contrast, an extrauterine Müllerian adenosarcoma recurs in over 50% of the patients and is associated with a mortality rate of approximately 35% [6]. The pathogenesis of the extrauterine Müllerian adenosarcoma is unclear. However, the association between exogenous hormonal therapy and the development of malignancy in endometriosis is well known, and the possibility of a neoplastic transformation of endometriotic foci has been suggested by several studies [7, 8]. A large review by Stern of endometriosis-associated neoplasms re- Fig. 1. A polypoid mass accounting for one-third of the diameter of the rectum was seen during the colonoscopy. Fig. 2. (A) Abdominal computed tomographic scan showing a 2.7-cm-sized mass (arrow) in the anterior wall of the rectum. (B) Magnetic res- onance 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- weighted image. A B Annals of Coloproctology www.coloproctol.org234 Müllerian Adenosarcoma Arising From Rectal Endometriosis Chunseok Yang, et. al. Fig. 3. The excised colon (A) and 1:1 mounted H&E-stained section (B) show an intramural nodular mass (arrow) with a polypoid mucosal protrusion (arrowhead). Multiple intramural and serosal endometriotic foci (circles) are also present. A B Fig. 4. (A) The intramural nodular mass shows a characteristic biphasic appearance of this neoplasm with a polypoid projection into the glan- dular space, a typical low power appearance of a phyllodes tumor of the breast (H&E, ×40). (B) The mucosal polypoid protrusion of the tumor also show biphasic components (H&E, ×100). (C) The high-power view of the intramural mass shows a single layer, bland-looking epithelial lining and cellular stroma (H&E, ×100). (D) The stromal cells are spindle-like and plump in shape with a fascicular growth pattern and have enlarged nuclei with mild cytologic atypia. A few abnormal mitotic figures are noted. Many inflammatory cells, including lymphocytes, plasma cells and eosinophils, and infiltration are frequently noted throughout the tumor (H&E, ×400). A C B D Annals of Coloproctology www.coloproctol.org 235 Volume 30, Number 5, 2014 Ann Coloproctol 2014;30(5):232-236 Fig. 5. (A) The endometriotic foci of the wall show tubular endometrial glands with cuffs of endometrial stromal cells (H&E, ×100). (B) The endometrial glandular epithelial cells and stromal cells show positive immunoreaction to estrogen receptor (ER) (×200). (C) The periglandular endometrial stromal cells show CD10 immunoreactivity (×100). (D) The epithelial cell and stromal cells of the intramural mass (H&E, ×100) shows (E) ER immunoreactivity (×200), but not (F) CD10 (×100). (G) The tumor stromal cells (H&E, ×200) have strong reactions to (H) smooth-muscle actin (×200), but not to (I) desmin (×100). A D G B E H C F I vealed that an adenosarcoma was the second most common ma- lignancy after a clear cell carcinoma to arise in the setting of extra- ovarian endometriosis [7]. Although most tumors associated with endometriosis are of epithelial origin, rare cases of stromal neo- plasms, including an adenosarcoma, have been reported and rep- resent 20.8% of the cases arising in endometriosis from extrago- nadal sites [9]. This case meets Sampson’s criteria for malignant transformation of endometriosis, which include the following: the foci of endometriosis were found in close proximity to the malig- nancy, the histological appearance was compatible with an endo- metrial origin, and no other possible primary tumor was seen [10]. First, confirming a histological diagnosis of an adenosarcoma is important. A Müllerian adenosarcoma arising from endometrio- sis should be distinguished from uncommon benign lesions that are characterized by benign glands, like polypoid endometriosis, adenofibroma, and low-grade endometrial stromal sarcoma with glandular differentiation. The diagnosis could be determined us- ing the criteria recommended by Clement and Scully [1]. They proposed that the diagnosis of an adenosarcoma be made when one or more of the following criteria are present: (1) a stromal mi- totic count of two or more mitotic figures per 10 high power field; (2) marked stromal cellular-like periglandular cuffs and intrag- landular protrusion of cellular stroma; and (3) more than a mild degree of nuclear atypia of the stromal cells. Extrauterine tumors are distinctively less common and are pri- marily located in the pelvic peritoneum, retroperitoneum, broad and round ligaments, vesicouterine pouch, and rectouterine pouch. Until today, only a few cases of an extrauterine Müllerian adeno- sarcoma arising from endometriosis of the intestine, especially the rectum, have been reported [4]. To our knowledge, this is an ex- tremely rare case of an adenosarcoma arising from endometriosis of the rectum except that a concomitant rectal adenoma and ade- nosarcoma was reported [11]. The infrequency of a Müllerian adenosarcoma makes establish- Annals of Coloproctology www.coloproctol.org236 Müllerian Adenosarcoma Arising From Rectal Endometriosis Chunseok Yang, et. al. ing well-defined therapeutic protocols difficult. However, radical surgery remains a therapeutic mainstay. For the treatment of a uterine Müllerian adenosarcoma, a surgical approach similar to that used for the corresponding disease stages of an endometrial carcinoma is recommended, and a total abdominal hysterectomy with a bilateral adnexectomy appears adequate for stage I patients. The decision on giving postoperative chemotherapy may be based on the extent of muscular invasion and sarcomatous growth. Ad- juvant chemotherapy is also considered for treating an extrauter- ine Müllerian adenosarcoma, although its role is still debatable. Although previous reports are inadequate to confirm first-line chemotherapeutic regimens, a few case reports suggest that pa- tients should be treated with liposomal doxorubicin [6, 12]. The regimen of this recommendation is well tolerated and is effective based on excellent response, minimal toxicity, and convenient dosing schedule in recurrences and adjuvant therapy for extra- uterine forms. As the risk of developing recurrent disease was high, a cautionary radiation therapy was given to prevent the probability of a local recurrence. Neoadjuvant or adjuvant pelvic irradiation with chemotherapy was studied in advanced stages, and acceptable outcomes have been reported [13]. In fact, this therapeutic approach was chosen in consideration of the aggres- sive behavior of the tumor. The most important negative prognostic factors are lesion loca- tion, the degree of myometrial invasion, and sarcomatous over- growth. In a uterine Müllerian adenosarcoma, the degree of myo- metrial invasion, sarcomatous overgrowth, and the recurrence rate are strongly correlated to the differentiation grade and the mitotic index of the sarcomatous stromal component [14]. By contrast, a favorable prognostic factor in adenosarcoma patients is the presence of endometriosis [7]. The case we present provides an association with endometriosis, supporting the hypothesis that an extrauterine Müllerian adeno- sarcoma is transformed from endometriosis. Exogenous or en- dogenous estrogen may have some role in the transformation process whereas the effectiveness of combined estrogen-proges- terone hormone-replacement therapy is still to be determined. Further, the titers of the tumor marker CA 125 were well corre- lated with the clinical course of endometriosis and might be a predictor for the sarcomatous overgrowth [15]. In conclusion, an extrauterine Müllerian adenosarcoma is rare, but it should be considered in a patient with atypical clinical fea- tures or preoperative pathology, especially in a patient with a his- tory of endometriosis. Further research is needed to establish the pathogenesis of an extrauterine adenosarcoma and the therapeu- tic guidelines. CONFLICT OF INTEREST No potential conflict of interest relevant to this article was re- ported.

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