{"paper_id":"595744b8-a0f2-485c-92e0-13886976efa1","body_text":"INTRODUCTION\nEndometriosis is defined as the presence of endometrial\ntissue outside the uterus. The most common sites affected\nare the ovaries, uterine ligaments, recto- and vesico-vaginal\nseptae, pelvic peritoneum, cervix, labia and vagina. Malig-\nnant transformation of endometriosis may occur in up to\n1% of women, with the most common site being the ovary\n(1). The risk of ovarian cancer increases among patients with\na long history of ovarian endometrioma (2), and the malig-\nnant transformation of endometriosis may be affected by the\nhormonal changes associated with menopause (3, 4) Endo-\nmetriosis is present in 10% to 15% of patients with ovarian\ncancer, with the most common extra-ovarian site of neoplas-\ntic transformation being the rectovaginal septum (5). Forty\npatients with endometriosis-associated intestinal tumors have\nbeen reported (6-7), but malignant transformation of endo-\nmetriosis in the uterine cervix is exceedingly rare. \nIn this report, we describe a woman with endometrioid\nadenocarcinoma arising from endometriosis of the uterine\ncervix. In addition, we review the literature on this condition,\nand discuss the prognostic factors and the most appropriate\ntherapeutic approaches.\nCASE REPORT\nA 48-yr-old woman complaining of severe dysmenorrhea\nwas referred for investigation of a pelvic mass. She was oth-\nerwise well, was not taking hormone medication, and had a\nbody mass index of 24.4 kg/m\n2. A cervical smear revealed\nbenign cellular changes. Magnetic resonance imaging showed\nan image typical of an endometrial cyst of the uterine cervix,\nwith high intensity in T1W1 and T2W1, a smooth surface,\nand shading. Adenomyosis was observed in the body of the\nuterus, but there was no evidence of enlarged lymph nodes\nor ascites (Fig. 1). Her serum concentration of CA125 was\n359 U/mL (normal <35 U/mL). At the time of laparotomy,\nshe had an enlarged uterus (12×7×6 cm\n3), which weighed\n231 g, and her uterine cervix was enlarged to the size of an\negg, with multiple round masses. Severe adhesion was observed,\nwith endometrial tissue in the posterior wall of the uterus and\nthe peritoneum and total posterior cul-de-sac obliteration. The\nleft ovary was adherent to the posterior surface of the uterus,\nwith a dark brownish cyst typical of an endometrial cyst. Total\nabdominal hysterectomy and bilateral salpingo-oophorecto-\nmy with adhesiolysis were performed, and the specimens were\nsubmitted for frozen section analysis. The extra-ovarian lesi-\nons were electrically cauterized. Pathologic examination of\nthe frozen sections suggested an adenocarcinoma arising from\nendometriosis in the cervical wall. \n767\nHan Moie Park\n1\n, Sang Soo Lee\n1\n,\nDae Woon Eom\n2\n, Gil Hyun Kang\n2\n,\nSang Wook Yi\n1\n, and Woo Seok Sohn\n1\nDepartments of Obstetrics and Gynecology1 and\nPathology2, Gangneung Asan Hospital, University of\nUlsan, Gangneung, Korea\nAddress for correspondence\nWoo Seok Sohn, M.D.\nDivision of Gynecologic Oncology, Department of\nObstetrics and Gynecology, University of Ulsan,\nGangneung Asan Hospital, 415 Bangdong-ri,\nSacheon-myeon, Gangneung, 210-711, Korea\nTel : +82.33-610-3293, Fax : +82.33-641-3300\nE-mail : silabus@hanmail.net\nJ Korean Med Sci 2009; 24: 767-71\nISSN 1011-8934\nDOI: 10.3346/jkms.2009.24.4.767\nCopyright \n� The Korean Academy\nof Medical Sciences\nEndometrioid Adenocarcinoma Arising from Endometriosis of the\nUterine Cervix: A Case Report\nEndometrioid adenocarcinoma arising from endometriosis of the uterine cervix is\nrare in premenopausal woman. We describe here a patient with this condition and\nreview the clinical and pathological features of these tumors. A 48-yr-old woman\ncomplaining of severe dysmenorrhea was referred for investigation of a pelvic mass.\nTotal abdominal hysterectomy and bilateral salpingo-oophorectomy were performed.\nHistological examination revealed an endometrioid adenocarcinoma directly adja-\ncent to the endometriosis at the uterine cervix, with a transition observed between\nendometriosis and endometrioid adenocarcinoma. The patient was diagnosed as\nhaving endometrioid adenocarcinoma arising from endometriosis of the uterine cervix\nand underwent postoperative chemotherapy. Gynecologists and pathologists should\nbe aware of the difficulties associated with a delay in diagnosis of endometrioid ad-\nenocarcinoma arising from endometriosis when the tumor presents as a benign\nlooking endometrioma. \nKey Words : Carcinoma, Endometrioid; Endometriosis; Cervix Uteri\nReceived : 29 November 2007\nAccepted : 17 March 2008\n\nOn gross examination, the cervical wall of the uterus con-\ntained a relatively well defined, cystic lesion filled with dark\nbrown fluid, measuring 3×2.2×2.2 cm. The dark brown\ncolored inner surface of the cyst showed multi-focal, papillary\ngrowing, solid and granular masses, measuring up to 0.8×\n0.8×0.5 cm (Fig. 2). Microscopically, these masses were com-\nposed of well differentiated endometrioid adenocarcinoma,\nwhich was directly adjacent to the epithelium of the endo-\nmetriotic cyst of the cervical wall. Transitional areas between\nthe glandular epithelium of the endometriosis and the endo-\nmetrioid adenocarcinoma cells were observed. There was no\ninvasion to the cervical stroma and no connection between\nthe overlying mucosal epithelium of the endo-ectocervix and\nthe epithelium of the endometriosis or the adenocarcinoma.\nA secretory phase endometrium measured 0.8 cm in thick-\nness. There was no evidence of a primary endometrial or en-\ndocervical adenocarcinoma in the endocervix or endometrium\n(Fig. 3). Multiple foci of endometriosis were present within\nthe posterior wall of the uterus and both ovaries. A serous\ncystadenoma was also present in the right ovary, measuring\n4.0 cm in greatest dimension.\nThe expression of estrogen and progesterone receptors, p53\nand c-erb B-2 was analyzed using paraffin immunohistochem-\nistry. The area of endometrioid adenocarcinoma was positive\nfor both estrogen and progesterone receptors. Weak expres-\nsion of p53 and c-erbB2 (10-20% of nuclear staining) was\nobserved in the carcinomatous area. The patient was diag-\nnosed as having an endometrioid adenocarcinoma arising from\nendometriosis of the uterine cervix. Following recovery from\nsurgery, she was treated with six courses of chemotherapy,\nconsisting of cyclophosphamide 600 mg/m\n2 and cisplatin 50\nmg/m2 every 4 weeks.\nAt the present time, she has been clinically free of disease\nfor 24 months since undergoing surgery.\nDISCUSSION\nEndometriosis of the cervix is generally regarded as a rare\nlesion, but its incidence has been as high as 2.4% in some\nseries (8). Previous trauma to the cervix may contribute to\nthis condition. For example, cervical endometriosis has been\nobserved in 43% of postconization hysterectomy specimens\nobtained from patients with cervical intraepithelial neopla-\nsia (CIN) recurrence and other conditions (not endometrio-\n768 H.M. Park, S.S. Lee, D.W. Eom, et al.\nFig. 1. MRI findings of the patient. On T1, T2W sagittal images (A, B), showing multiple round masses of variable size on the uterine cervix\n(arrows). Adenomyosis was observed in the body of the uterus, but no enlarged lymph nodes or ascites was observed.\nFig. 2.Cut surface of the cervical wall showing well defined hem-\norrhagic solid lesions (arrow).\nA B\n\nsis) (9). Therefore, the increasing incidence of invasive cervi-\ncal procedures may increase the incidence of endometriosis.\nCervical smears taken from most patients with cervical endo-\nmetriosishave shown glandular cellularity (10, 11). In con-\ntrast, a cervical smear taken from our patient before explo-\nration showed normal features. There was no invasion to the\nstroma of the cervix, or to the mucosal layer of the endocervix\nor exocervix.\nNeoplastic transformation is a rare complication of endo-\nmetriosis, documented in 0.3-0.8% of patients with ovarian\nendometriosis (7). Of 147 women with pelvic endometrio-\nsis, only one had ovarian cancer arising from the endometrio-\nsis (0.7%) (12). The risk of cancer arising from pre-existing\nendometriosis has been estimated at 0.7% to 1.0% (1). Of\nneoplasms complicating endometriosis, 75% arise in the ov-\naries, with the majority (almost 70%) being of endometri-\noid type.\nMalignant ovarian tumors have been documented in wo-\nmen with endometriosis. Endometriosis-associated ovarian\ncancer (EAOC) usually occurs in younger women, has favor-\nable outcomes, and appears as either a low-grade tumor of\nendometrioid cell type or as a clear cell tumor. As the patho-\nlogic features of “atypical endometriosis” may constitute a\nprecancerous state, women with atypical endometriosis may\nbe at an increased risk of developing EAOC. Malignant ch-\nanges have also been diagnosed in extragonadal endometrio-\nsis. For example, a survey of 45 extragonadal malignancies\nassociated with endometriosis in 1977 found that 16 (36%)\nwere in the rectovaginal area, 5 (11%) in the colorectal area,\n4 (9%) each in the bladder and vagina, 3 (7%) in the pelvic\nligaments, and 2 (4%) each in the umbilicus, cervix, and fal-\nlopian tube (13). A more recent survey of 27 malignancies\nassociated with endometriosis found that 17 (62%) were in\nthe ovary, 3 (11%) in the vagina, 2 (7%) each in the fallopian\ntube or mesosalpinx, pelvic sidewall, and colon, and 1 (4%)\nin the parametrium (14); this report, however, did not include\ncervical malignancies associated with endometriosis. Malig-\nnanttransformation of extra-ovarian endometriosis is thought\nto account for approximately 25% of all malignant transfor-\nmations of endometriosis (1, 15).\nBecause of the rarity of malignant transformation of endo-\nmetriosis at extraovarian sites, including the cervix, it is dif-\nficult to design an optimal surgical procedure. When feasi-\nble, however, primary surgical treatment should consist of\ncomplete resection of all disease containing tissue. Gross le-\nsions in the pelvis should be surgically staged (1). Although\npostoperative treatment has not been clearly defined, 70%\nof these patients have been reported to receive chemothera-\npy or radiotherapy after first line surgery (1, 15). \nThe 5-yr survival rate for patients with estrogen-stimu-\nEndometrioid Adenocarcinoma from Uterine Cervix 769\nFig. 3.Histopathological findings. (A) Dilated endocervical glands\nin the cervix. There was no evidence of adenocarcinoma or con-\nnection with the endometriotic cyst (H&E, ×40). (B) Direct conti-\nnuity was observed from the endometriosis (left upper) to the endo-\nmetrioid adenocarcinoma (right side) in the cervix (H&E, ×100).\n(C) High-power view of endometrioid adenocarcinoma in the cervix\n(H&E, ×400).\nA\nC\nB\n\nlated endometriosis-associated neoplasms arising at all sites\nhas been reported to be 82% (1). Moreover, patients with\nendometrioid adenocarcinoma coexisting with endometrio-\nsis have a favorable prognosis (16).\nTo classify a malignancy as arising from endometriosis,\nstrict histopathologic criteria need to be met (17). These in-\nclude the demonstration of cancer arising in the tissue and\nnot invading it from another source, and the presence of tis-\nsue resembling endometrial stroma surrounding the epithe-\nlial glands. Microscopic endometriosis contiguous with the\nmalignant tissue should also be demonstrated. Our patient\nmet all these diagnostic criteria. \nThe risk factors for malignant transformation in endome-\ntriosis are poorly defined. Estrogen can stimulate the growth\nof ectopic endometrial tissue. Thus, if any ovarian tissue re-\nmains following a hysterectomy, the disease is likely to recur\nin as many as 40% of women after 5 yr (6, 18). In addition,\nan association has been noted between unopposed estrogen\ntherapy and the development of endometrioid or clear cell\nepithelial ovarian tumors (19, 20). Of 21 women with extr-\naovarian cancers arising in endometriosis, 13 (62%) had re-\nceived hormone replacement therapy (HRT) (15). In contrast,\nonly 10% of other groups of patients, including those with\novarian cancer arising within the endometriosis, ovarian can-\ncer with adjacent endometriosis and ovarian cancer with inci-\ndental endometriosis, had received HRT, with the majority\nof the latter receiving unopposed estrogen. In addition, ta-\nmoxifen therapy has been associated with endometriosis and\nthe exacerbation of endometriotic foci in postmenopausal\nwomen (21), and obesity may affect tumor development (22).\nHowever, the body mass index of our patient was 24.4 kg/\nm\n2 and she had no previous history of estrogen or tamoxifen\nuse. Also, our patient was 48 yr old and was premenopausal.\nOf three women with malignant tumors arising in endom-\netriosis, 2 showed loss of ER and PR expression, suggesting\nthat these tumors lose hormonal responsiveness as a result of\nmalignant transformation (20). In contrast, the tumors in our\npatient showed consistent ER and PR expression, and she had\nno history of exposure to unopposed estrogen. These findings\nsuggest that the loss of hormonal responsiveness did not play\na part in the malignant transformation of endometriosis in\nour patient.\nThe increased association of HRT use with extraovarian\ncancer arising in endometriosis raises interesting questions\nthat should prompt further investigation. Patients with en-\ndometrial cysts of the pelvic organs associated with high lev-\nels of serum CA125 should be managed with special care,\neven premenopausal women with no history of hormone ther-\napy. Further work is required to determine whether the dif-\nferences translate into a causal relationship. In conclusion, we\npresent an extremely rare case of endometriosis-associated ad-\nenocarcinoma of the uterine cervix in a premenopausal woman.\nThe clinical behavior of these tumors is unpredictable and\nlong-term follow-up is essential in all patients. Additional\ncase reports and prospective studies are needed to determine\noptimal treatment options to improve patient prognosis. \nREFERENCES\n1. Heaps JM, Nieberg RK, Berek JS. Malignant neoplasms arising in\nendometriosis. Obstet Gynecol 1990; 75: 1023-8.\n2. Brinton LA, Gridley G, Persson I, Baron J, Bergqvist A. Cancer risk\nafter a hospital discharge diagnosis of endometriosis. Am J Obstet\nGynecol 1997; 176: 572-9. \n3. Bergqvist A, Rannevik G, Thorell J. Estrogen and progesterone cy-\ntosol receptor concentration in endometriotic tissue and intrauterine\nendometrium. Acta Obstet Gynecol Scand Suppl 1981; 101: 53-8.\n4. Gould SF, Shannon JM, Cunha GR. Nuclear estrogen binding sites\nin human endometriosis. Fertil Steril 1983; 39: 520-4.\n5. Mostoufizadeh M, Scully RE. Malignant tumors arising in endome-\ntriosis. Clin Obstet Gynecol 1980; 23: 951-63.\n6. Jones KD, Owen E, Berresford A, Sutton C. Endometrial adenocar-\ncinoma arising from endometriosis of the rectosigmoid colon. 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Int J Gynecol Cancer 2003; 13: 376-80.\nEndometrioid Adenocarcinoma from Uterine Cervix 771","source_license":"CC0","license_restricted":false}