{"paper_id":"3e059c0c-41f4-4f7c-a59d-79d9edee9594","body_text":"Synchronous primary neoplasms (SPN) of the female reproductive tract represent a rare situation with a \nspecial clinical interest. It is an idiomorphous phenomenon with unknown pathogenesis and etiology. It occurs \nin 10% of all women with ovarian cancer and 5% of all women with endometrial cancer \n[ 1 ]. A first effort to delineate a set of pathologic criteria to \ndistinguish the metastatic disease from synchronous primary tumors was made by Ulbright and Roth \n[ 2 ], in 1985. Nowadays, a similar but more extensive list of \nclinicopathologic features created by Scully et al. [ 3 ] is used \nto differentiate between endometrial cancer with metastasis to the ovary, ovarian cancer with metastasis to \nthe endometrium, and independent primary cancers ( Table 1 ).\nEndometrioid tumors of the ovary and endometrium, Independent primary tumors.\n[ 3 ]\nIn our institution, gynecologic pathologists use these criteria to determine whether the tumors of the \nendometrium and ovary represent a metastatic disease or independent primary tumors. The most common hypothesis \nabout pathogenesis is that embryologically, similar tissues may develop synchronous neoplasms, when subjected \nto hormonal influences or to carcinogens. Primary malignancies of the ovary and endometrium have been investigated \nin many trials. In addition, endometriosis may be the precursor of clear cell or endometrioid ovarian cancer.\nThe pathological and epidemiological evidence demonstrates a strong association with ovarian cancer as well. \nEstrogen receptors may be responsible for the development of multiple primary malignancies in predisposed \ntissue. Actually, the presence of endometriosis is associated with an increased risk of synchronous primary \nneoplasms mainly in ovary and endometrium. In our study, we present the frequency and types of synchronous cancers \nof female genital tract that appear in women surgically treated for endometriosis.\n\nIn the present study, we investigated the prevalence of SPN in cases with endometriotic ovarian cysts \nthat underwent surgery at ‘Lito’ Maternity hospital of Athens and at Anticancer Institute of \nBucharest. In our analysis, a total number of 811 women have been included, after clinical and ultrasound \ndiagnosis of ovarian endometriomas (transvaginal ultrasound). All the patients underwent surgery and some of \nthem underwent hysterectomy. The review period was from the year 2000 to 2008. The medical records and pathology \nwere reviewed to confirm the diagnosis and stage of tumors. Stage was assigned according to the FIGO \ncriteria. Pathology specimens of SPN were reviewed to confirm original pathologic type and grade. The tumor \ngrades for ovarian and endometrial cancer were assigned as it follows: grade Ⅰ (well differentiated), \ngrade Ⅱ (moderately differentiated), grade Ⅲ (poorly differentiated).\n\nDuring the reported period of time, 811 patients underwent surgery for the excision of ovarian \nendometriosis (severe endometriosis). The mean age of the women was 40.9 years old (19–68 years old). In \n380 (46.8%) cases the mass was located at the left adnexal, in 294 (36.2%) in the right and in \n137 (17%) women in both ovaries. Diameter of masses ranged from 2–15 cm, the median diameter being \nof 4.95 cm.\nBased on the pathologic reports, nine women with synchronous cancers of the genital tract were identified. \nAfter reviewing, though, the pathological sections 4 out of 9 patients were identified as metastatic cases. So, \nfive (0.62%) patients were identified as having synchronous primary neoplasms. The mean age of the five \nwomen was of 54.2 years old. Three patients were nulliparous. All of our patients had a \ngrade–Ⅰ endometrioid carcinoma of the uterus, while stage was Ⅰa in 3 and Ⅰb in 2. \nThe myometrium was invaded less than 1/3 in 4 cases and less than 2/3 in all cases. In the case where \ncarcinoma invaded more than 1/3 of the myometrium, simple atypical hyperplasia of the endometrium was \nalso identified. Similarly, 4 out of 5 ovarian cancers were endometrioid, while one was serous cystadenosarcoma. \nAll of the ovarian malignancies were grade Ⅰ (three of them were staged with ࡰb and Ⅱ \nas Ⅰa). In two cases, ovarian malignancy was positive for HER–2/neu. The median diameter of the \novarian neoplasias was of 4.3cm, compared to 4.5cm that was the median diameter of all endometrioid cysts. When \nthe larger ovarian malignant cyst in each patient was accounted, the median diameter was calculated as having \n5.8cm. In two cases, ovarian malignancy was detected only to the right ovary, while to the rest it was \nbilateral. What is interesting is that in 2 out of 3 cases of bilateral ovarian malignancies the larger cyst was \nin the right ovary ( Table 2 ).\nHistopathological analysis of the 5 patients with synchronous primary carcinomas of the endometrium \nand ovary. EN: Endometrioid, CS: Serum cystedenosarcoma, R: Right, B: Bilateral. *Simple atypical \nhyperplasia was also identified\n\nThe synchronous occurrence of endometrial and ovarian cancer is well known but still poses a diagnostic dilemma. \nA still existing diagnostic dilemma is the synchronous occurrence of malignancies of the female genital tract. \nIn cases of different histologic types, the dilemma of which cancer is primary and which is metastatic remains. \nOn the other hand, if the histologic types are different it is easy to identify the coexistence of the two \nprimary cancers. Although immunohistochemical and DNA flow cytometric studies have been used to distinguish \nbetween neoplasms of similar histology, the differential diagnosis still lies primarily on \nconventional clinicopathologic criteria. It is important to separate women with two primary cancers from those \nwith metastases, since prognosis is significantly better for the first group.\nThe most frequently documented synchronous malignancies are those of the ovary and endometrium. It is well \nknown the fact that the simultaneous malignancies are predominantly of low stage and this finding was confirmed \nby our study as well. Earlier studies suggested that women diagnosed with synchronous primary cancers have a \nbetter overall prognosis than if their disease was classified as single organ disease with metastasis \n[ 4 – 6 ]. A study undergone by \nthe Gynecologic Oncology Group (GOG) on 74 patients with synchronous cancers of the genital tract, reported \na 5–year survival of 86% and a 10– year survival of 80% \n[ 1 ]. Few studies, however, focused on risk factors in these patients.\nSeveral hypotheses have been proposed regarding the simultaneous involvement of the endometrium and ovary. \nThe most popular hypothesis concerning the pathogenesis of this extremely rare condition is that estrogen \nreceptors may be responsible for the development of multiple primary malignancies in predisposed tissues. \nAnother hypothesis is that an ‘extended’ or secondary mullerian system exists, so that the \nsimilarity of the female's upper genital tracts undergoing common metaplastic diseases could be \nexplained. Endometriosis seems to be a precursor of a clear cell or endometrioid ovarian cancer. The \nhistopathology and epidemiological evidence demonstrates a strong association between endometriosis and \novarian cancer.\nThis is one of the few studies that, instead of focusing on women with synchronous neoplasms of the genital \ntract and identifying the percentage of endometriosis on them, goes the other way round; in a population \nwith moderate and severe endometriosis we identified the prevalence of synchronous cancers. In our cohort, median \nage at diagnosis was of 54 years old in women with synchronous primary cancers of the endometrium and ovary. \nIn contrast, women who develop endometrial or ovarian cancer alone are predominantly postmenopausal and in the \nsixth or seventh decade of life. Previous studies have also reported a younger median age in patients \nwith synchronous primary endometrial and ovarian cancers. Eifel et al. [ 4\n ] (n=29), in particular, found a younger than expected median age of 41 years old in women \nwith endometrioid/endometrioid cancers, while GOG (n=74) reported a median age of 49 years old \n[ 1 ]. Herrinton et al. [ 7 ] reported \nthat 39% of patients were under the age of 50 at the time of diagnosis in a case–control study \n(n=56). Finally, in studies examining young women with endometrial cancer (age less than 45 \nyears), 10–29% of these young women were found with synchronous ovarian cancers \n[ 8 , 9 ].\nOur study indicates that women with synchronous primary cancers of the endometrium and ovary have \ndistinct clinical characteristics including younger age, premenopausal status, and nulliparity. This suggests that \na hormonal ‘field effect’ may account for the development of these simultaneous endometrioid \ncancers, supporting the theory of estrogen receptors. Eifel et al. [ 4 ] \nalso suggested that the response of the uterine corpus, fallopian tubes, and ovarian epithelium as a morphologic \nunit could explain the development of synchronous endometrioid tumors in different components of the \nmullerian system. Future studies are needed to further evaluate the role of estrogen in these \nsynchronous endometrioid cancers of the endometrium and ovary.","source_license":"public-domain-us","license_restricted":false}