Surgery for borderline tumor of the ovary

The five-year survival for women with Stage I borderline tumors is about 95% to 97%, but because of late recurrence the 10-year survival is only 70% to 95%. The five-year survival for Stage II-III patients is 65% to 87%. A more correct staging procedure, classification of true serous implants, and agreement on how the presence of gelatinous ascites in mucinous tumors contributes to cancer stage might change the distribution of stage and survival data by stage for women with borderline tumors in the future. Independent prognostic factors for patients with borderline tumors without residual tumor after primary surgery are: DNA ploidy, morphometry, International Federation of Gynecology and Obstetrics (FIGO) stage, histologic type, and age. Different types of surgery and chemotherapy were not independent prognostic factors. Questions which should be addressed include the following: 1) Have patients with borderline tumors been over treated in general, and how should these patients be treated? 2) In which group of patients is fertility-sparing surgery advisable? 3) Do patients with borderline tumors benefit from adjuvant treatment? And 4) How is the high-risk patient defined?     

Influence of histological subtypes on the risk of an invasive recurrence in a large series of stage I borderline ovarian tumor including 191 conservative treatments

BackgroundThe overall prognosis of stage I borderline ovarian tumors (BOT) is excellent but a small percentage of patients die to their disease. The prognostic factors for such a rare event are still not clearly defined. The aim of this study was to determine these factors for recurrence per se and recurrence in the form of invasive carcinoma in a large series of stage I tumors.MethodsA retrospective review of patients with BOT. Three inclusion criteria were defined: (i) a centralized histological review; (ii) macroscopic stage I tumors; (iii) exclusion of metastatic disease to the ovaries.ResultsFrom 2000 to 2010, 254 patients fulfilled inclusion criteria [140 had mucinous BOT (MBOT) and 114 a serous BOT (SBOT)], and 191 had undergone conservative management. After a median follow-up of 45 months, 43 patients had developed recurrences (31 borderline and 12 invasive).The risks of recurrences were statistically increased after conservative treatment, particularly after a cystectomy, in patients with stage IB and among patients with incompletely staged tumors. In the subgroup of conservatively treated patients (representing 75% of our population), the risks of recurrences were statistically increased in patients affected by a SBOT, in patients who had undergone a cystectomy, in patients with stage IB disease and in patients with a micropapillary pattern (MPP). MBOT and the presence of a MPP were identified as prognostic factors for invasive disease.ConclusionsIn the present series of BOT with the largest number of patients treated conservatively to date, the presence of a MPP and the mucinous subtype were associated with a higher rate of progression to carcinoma after conservative management. These important results suggest that MBOT belong to a ‘high-risk’ group likely to develop an invasive recurrence after fertility-sparing surgery in stage I BOT.     

Contemporary treatment of borderline ovarian tumors

In conclusion, the prognosis for women with stage I borderline tumors is excellent. Surgery alone is the recommended treatment. For young patients, fertility-sparing surgery is optimal, with a small percentage eventually developing tumor in the contralateral ovary. For patients with advanced stage borderline tumors, 10-30% will relapse and approximately 10% will die of tumor. This risk is clearly higher for those with invasive peritoneal implants. Several controversies exist, including the classification of advanced stage serous borderline tumors and the issue of postoperative treatment. Future studies involving larger series and molecular biomarkers will hopefully elucidate the biologic behavior and optimal therapy for this interesting group of tumors.     

Borderline ovarian tumour: pathological diagnostic dilemma and risk factors for invasive or lethal recurrence

By comparison with ovarian carcinomas, borderline ovarian tumours are characterised clinically by superior overall survival, even in women with peritoneal spread. In this Review, we aimed to clarify the histological and clinical factors potentially defining a high-risk group in whom disease is likely to evolve to invasive disease. Invasive peritoneal implants (in serous borderline ovarian tumours) and residual disease after surgery were the two factors clearly identified. Other factors are controversial owing to increased risk of invasive recurrence: micropapillary patterns in serous borderline ovarian tumour, intraepithelial carcinoma in mucinous lesions, stromal microinvasion in serous lesions, and use of cystectomy in mucinous borderline ovarian tumours. The pathologist has a pivotal role in assessment of the borderline nature of ovarian tumours and in identification of high-risk criteria, most of which are histological. But, reproducibility of the histological interpretation of some of these potential criteria--eg, classification of peritoneal implants (particularly in desmoplastic subtype), stromal microinvasion, micropapillary patterns, and intraepithelial carcinoma in mucinous borderline ovarian tumours--remains unclear, and should be investigated.     

Ovarian epithelial tumors of borderline malignancy. A clinical and pathologic study of 109 cases

One hundred nine cases of ovarian tumors of low malignant potential (borderline tumors) diagnosed at Stanford University Medical Center from 1958 to 1982 were reviewed. The patients ranged in age from 10 to 79 years (mean, 40.5 years). The histologic types and corresponding stages of these neoplasms were 73 serous (Stage IA: 35 patients; Stage IB+C: 16 patients; stage II: 8 patients; Stage III: 14 patients), 30 mucinous (Stage IA: 27 patients; Stage IB+C: 3 patients), and 6 mixed seromucinous (all Stage IA). Borderline endometrioid, clear cell, and Brenner tumors were excluded. Follow-up information from 3 to 27 years from the time of initial diagnosis (mean, 7.6 years; median, 7.1 years) revealed that 89 patients are alive without further evidence of neoplasm, and three patients died of unrelated disease without recurrent tumor. Seventeen patients have developed persistent or recurrent neoplasms in the contralateral ovary (six patients) and/or elsewhere within the peritoneal cavity (15 patients) at 5 to 226 months (mean, 61 months) after the initial excision. All of the second neoplasms were borderline serous or seromucinous tumors histologically identical to the original tumor; none of the borderline mucinous tumors recurred. Patients who initially had Stage III borderline serous tumors developed persistent or recurrent neoplasms more commonly (64%) than did patients with lower stage tumors (12%). No correlation was found between the development of a subsequent serous neoplasm and patient age, the primary tumor size, or any single histologic feature. Following treatment of the subsequent neoplasms, 13 patients are free of neoplasm, one patient is alive with tumor, one patient has died of intercurrent disease with tumor, and two patients have died with widespread abdominal tumor 53 and 232 months after their initial diagnosis. These findings confirm the excellent prognosis for patients with borderline serous tumors, despite involvement of the peritoneal cavity and the development of recrudescent tumor, although long-term follow-up is indicated. Mucinous borderline tumors, as defined by published criteria, almost invariably present as localized (low-stage) tumors and, in our experience, do not recur when confined to the ovary.     

Paratubal serous borderline tumor

Although paratubal cysts are well-characterized incidental findings, paratubal serous borderline tumors are very rare, with only one case report in the literature. We describe here a 27-year-old, nulliparous, married woman with a paratubal serous borderline tumor. The patient presented with a huge pelvic mass accompanied by flank pain and underwent paratubal cystectomy and fertility-sparing surgical staging procedures. Thirteen months after surgery, she delivered a healthy baby at term. She is well, without evidence of disease, 20 months after surgery. Because paratubal serous borderline tumors are very rare, their optimal management must be extrapolated from their ovarian counterparts.     

Borderline ovarian tumors

Borderline ovarian tumors account for approximately 15% of all epithelial ovarian tumors. In the early 1970s, borderline tumors were categorized as either serous or mucinous with overall survival rates of 75–90%. Since then, it has been recognized that the two categories are heterogonous. There are now many different groups following the recognition of serous tumors with microinvasion, non‐invasive and invasive peritoneal implants and a micropapillary pattern, and of mucinous tumors with microinvasion, intraepithelial carcinoma and pseudomyxoma peritoneal implants, in addition to further delineation of endometrial, clear cell and transitional cell tumors with atypical proliferation. This review outlines the most recent information regarding the epidemiology, pathology and clinical management of borderline tumors. Surgical management to excise all visible tumors remains the cornerstone of therapy. Because borderline ovarian tumors often occur in reproductive‐age women, fertility is an important issue. Conservative surgery is a safe in carefully selected patients. Effective non‐surgical therapies are yet to be identified.     

Paratubal borderline tumor incidentally found during cesarean section: Case report and review of literature

Diagnosis of a gynecologic malignancy during cesarean section is quite rare. We report a case of a 39-year-old, nulliparous woman who underwent elective cesarean section during which a paratubal cyst was noticed and removed. The pathology revealed serous borderline tumor. Subsequent staging laparotomy was done 23 days after cesarean section. She was diagnosed with stage IC paratubal serous borderline tumor and underwent no further therapy. For the time being 15 months have passed from the staging laparotomy and she is currently free of disease recurrence. This case presented the importance of the evaluation of adnexa during cesarean section together with a short review of the literature on the rare paratubal borderline tumors and the role of fertility-sparing, conservative surgery in their management.     

Nuclear localization of phosphorylated ERK1 and ERK2 as markers for the progression of ovarian cancer

We examined the possibility that the localization of phosphorylated ERK1 and ERK2 (pERK1/2) can serve as a marker for the development of benign and borderline tumors as well as carcinoma of the ovary by an immunohistochemical method on ovarian paraffin sections, obtained from women aged 41-83 years. In normal tissue, 28.3% of nuclei were labeled, mainly confined to the epithelial cells at the surface of the ovary. In benign serous tumors, the label rose to 55.0%, while the intensity of the staining was weak. In contrast, in borderline serous tumors and in ovarian serous carcinoma (stage II) 52.1% and 70.3% of nuclei, respectively, were labeled with a high intensity. In mucinous benign tumors, the number of labeled nuclei was as in the control, but in addition, 49.4% of the cells demonstrated high concentration of pERK1/2 in aggregated form that was evident in the cytoplasm of the cells. In the mucinous and endometrioid ovarian carcinomas (stage II) very intensive labeling was found in 60% and 77.3% of cells, respectively. It is, therefore, suggested that since nuclear pERK1/2 can be mitogenic, it can serve as a reliable marker for the progression of ovarian cancer. Interestingly, the intense labeling of pERK1/2 was mainly confined to the peripheral areas of ovarian endometrioid carcinoma (stage II). In addition, all tumor cells in this class of cancer were positively stained with mutated p53. It seems, therefore, that immunohistochemical staining of normal and ovarian tumor cells with anti-pERK1/2 is a reliable marker for early detection of the cancer, which may assist in the early diagnosis and prognosis of this lethal disease.     

Ovarian tumors of low malignant potential (borderline tumors): immune morphology and current status

CA 125, CA 19-9 and CEA were demonstrated in tissue samples of 30 ovarian borderline tumors by immunohistochemistry. Of the 21 serous and 9 mucinous borderline tumors, 23 were in stage I and 7 stage III. None of the patients died of disease. All mucinous borderline tumors were CA 125 negative, 89% CA 19-9 positive and 44% CEA positive. 62% of the serous borderline tumors were CA 125 positive, 52% CA 19-9 and 19% CEA positive. Tumors of low malignant potential responded to CA 19-9 like invasive carcinomas. The incidence of positive responses to CA 125 ands CEA fell between that of benign and malignant tumors. The marker pattern did not correlate with tumor stage and cytological grading. The biological behavior of ovarian borderline tumors ranges between that of benign tumors and invasive carcinomas and cannot be classified as definitely belonging to either group. It is plausible that they are primarily of the borderline type, and not benign tumors that undergo malignant degeneration.     

Synchronous ovarian and endometrial malignancies

Synchronous ovarian primaries are infrequently found in patients with endometrial cancer. Although numerous investigators have examined the characteristics of these women, most include patients with tumors of similar histology, which may simply represent ovarian metastases. To overcome this problem, we present here patients found to have tumors of dissimilar histology. Of 499 patients with endometrial cancer undergoing primary surgery between 1980 and 1997, 18 (3.6%) were found to have endometrial and ovarian primaries of dissimilar histology. The median age was 64.2 years. Most had stage I, grades I and II, minimally invasive endometrial adenocarcinomas and stage IA mucinous or serous ovarian cystadenocarcinomas. Most ovarian tumors were either borderline or grades I and II. The 5-year actuarial disease-free (DFS) and cause-specific survivals of the entire group were 81.2% and 89.5%, respectively. Those with both stage I ovarian and endometrial primaries had a trend to a better DFS (100 versus 68.6%, p = 0.07) than did women with higher stage disease. Our data demonstrate that synchronous ovarian primaries of dissimilar histology are infrequently found in women undergoing surgery for endometrial cancer. These women seek treatment at a relatively advanced age, and have early-stage, low grade disease in both sites. Their outcome is favorable, particularly those with stage I disease in both sites.     

Immunohistochemical staining of GLUT1 in benign, borderline, and malignant ovarian epithelia

BACKGROUND: Aberrant expression of the facilitative glucose transporter GLUT1 is found in a wide spectrum of epithelial malignancies. The authors describe an immunohistochemical study of GLUT1 expression in benign, borderline, and malignant ovarian epithelia. METHODS: One hundred forty one formalin-fixed, paraffin-embedded sections were immunostained with rabbit anti-GLUT1 using the streptavidin-biotin method. The samples were as follows: 3 endometriotic cysts, 9 serous cystadenomas, 15 mucinous cystadenomas, 17 noninvasive borderline implants, 3 invasive borderline implants, and 3 endosalpingiosis. In addition, 35 borderline tumors (26 serous, 7 mucinous, 2 seromucinous) and 56 adenocarcinomas (50 serous, 4 endometrioid, 2 mucinous) were stained. RESULTS: Benign serous and mucinous cystadenomas and endosalpingiosis were non-staining with GLUT1 antiserum. Twenty-eight of 35 borderline tumors (80%) stained positively, with weak to moderate (1-2+ out of 3) staining intensity and focal or patchy distribution. Seventeen noninvasive serous borderline implants were negatively stained; however, three invasive serous borderline implants were positively stained with GLUT1 antiserum. Fifty four of 56 ovarian carcinomas (96%) stained positively, with moderate to strong (2-3+ out of 3) intensity and multifocal distribution. CONCLUSIONS: GLUT1 is a consistent marker of ovarian epithelial malignancy. GLUT1 staining is absent in benign ovarian epithelial tumors, and shows progressively more staining in invasive tumors as compared to borderline tumors. Anti-GLUT1 antibody may be useful in distinguishing invasive from noninvasive serous borderline implants.     

Association of Reproductive Factors, Oral Contraceptive Use and Selected Lifestyle Factors with the Risk of Ovarian Borderline Tumors: A Danish Case-control Study

Objective The aim was to examine risk factors for ovarian borderline tumors overall, and according to histological subtype (serous vs. mucinous), in a large Danish population-based case-control study. Methods Ovarian borderline cases and controls were recruited from 1995 to 1999, and personal interviews were conducted. In all, 202 cases and 1,564 randomly selected controls were included. The analysis was performed using multiple logistic regression models. Results The risk of ovarian borderline disease decreased with increasing parity (OR=0.79 per birth, 95% CI: 0.63–0.98) and older age at first birth (OR=0.67 per 5 years, 95% CI: 0.53–0.84). Both a history of breastfeeding and use of oral contraceptives reduced the risk of borderline tumor, the effect being most pronounced for serous tumors. Increasing body mass index (BMI) was associated with elevated risk of serous borderline tumor (OR=1.05 per BMI unit; 95% CI: 1.00–1.10), whereas current smoking was a strong risk factor only for mucinous tumors (OR=2.10; 95% CI: 1.22–3.60). Finally, increasing consumption of milk (all types) was found to increase the risk of borderline disease (OR=1.04 per glass milk per week; 95% CI: 1.02–1.06), and increasing intake of total lactose also increased the risk significantly (OR=1.16 per 50 gram lactose per week; 95% CI: 1.06–1.26). Conclusion The risk profile of ovarian borderline tumors is similar to that of ovarian carcinomas, and we observed significant etiological differences between serous and mucinous borderline tumors.     

卵巢交界性浆液、粘液性肿瘤病理诊断新概念

本文总结近年有关卵巢交界性浆液、小数点 液性肿瘤文献论述病理诊断的新概念。分别为：（1）卵巢交界性肿瘤基本诊断标准;（2）卵巢交界性浆液性肿瘤概括Piura(1992),Russel(1994)、Silva(1996),Eichhorn(1999),Scully(1999)病理诊断标准;（3）卵巢交界性粘液肿瘤概括Piura(1992),Kuman(1996),Riopel(1999),Scully(1999)病理诊断标准。（4）腹膜假粘液瘤;（5）上皮内癌;（6）微浸润;（7）种植;（8）淋巴结转移;（9）多中心性;（10）命名;（11）预后。     

Alteration of BRCA-1 tumor suppressor gene expression in serous and mucinous ovarian neoplasms in the benign-borderline-malignant pathway

Alteration of expression of the tumor suppressor gene BRCA-1 has been widely studied in breast and ovarian carcinoma. However, pattern of this alteration in the benign-borderline-carcinoma sequence in serous and mucinous ovarian neoplasms have not yet fully described. Tissue sections from 214 formalin-fixed paraffin-embedded ovarian specimens were stained immunohistochemically with BRCA-1 antibody. Specimens were 10 normal ovarian surface epithelium, 10 fallopian tube epithelium, 70 benign adenoma (50 serous and 20 mucinous), 28 borderline (13 serous and 15 mucinous), 78 carcinoma (58 serous and 20 mucinous), and 18 metastatic deposit (13 serous and 5 mucinous). Expression was evaluated into 0, +1, +2, and +3. Score +3 staining similar to normal tissues was considered normal and other scores were considered altered expression. Strong expression was seen in all normal epithelium specimens. Altered expression was seen in 34 serous neoplasms; 17 of 50 (34%) of benign cystadenomas, 6 of 13 (46%) of borderline tumors, 43 of 58 (74%) of primary carcinoma, and in 8 of 13 (62%) of metastatic carcinoma. This alteration was significantly associated with higher histopathologic grade (P = 0.049), presence of necrosis (P = 0.0001), and higher proliferation rate (P = 0.001). In mucinous neoplasms; altered BRCA-1 was detected in 25 specimens; 7 of 20 (41%) of benign cystadenomas, 5 of 15 (33%) of borderline neoplasms, 9 of 20 (45%) of primary carcinoma, and 4 of 5 (80%) of the metastatic deposits. This alteration was not associated with any of the clinicopathologic tumor characteristics. In conclusion, alteration of BRCA-1 expression is more frequent in serous than in mucinous carcinomas and is associated with tumors of higher grades and high proliferation rate.     

Evaluation of serum CA 125 level as a tumor marker in borderline tumors of the ovary

Serum CA 125 was evaluated as a tumor marker in 85 patients with borderline ovarian tumors. Serum CA 125 levels were elevated preoperatively in 18 of 20 (90%) samples (median 66, range 5-272 U ml-1). Preoperative serum CA 125 levels did not correlate to FIGO stage. Preoperative serum CA 125 levels were elevated in seven of nine (78%) with serous tumors (median 131, range 5-272 U ml-1) and in all 11 with mucinous tumors (median 62, range 41-157 U ml-1). There was no significant difference in the CA 125 levels between these two histologic types. Postoperative serum CA 125 levels, measured 3-6 weeks after primary laparotomy, were significantly lower than the preoperative ones (P < 0.001). No difference in the postoperative CA 125 levels was found between those with and those without residual disease after surgery. Postoperative serum CA 125 levels were elevated in eight of 60 (13%) without residual tumor. None of these had relapsed at the time of analysis (26-87 months after surgery). Serum CA 125 levels tended to correlate with disease evolution during chemotherapy. Two with disease remissions had falling levels, one with stable disease had falling level and one with disease progression had rising level. Serum CA 125 samples were obtained before second-look laparotomy in seven patients. Two with negative findings at second-look had normal levels. Of five with positive findings at laparotomy only two had elevated serum CA 125 levels. Disease relapse was associated with elevated serum CA 125 levels in only one of six patients.     

Plasma alpha-L-fucosidase activity and the risk of borderline epithelial ovarian tumors

The authors obtained venous blood samples from 106 female residents of western Washington in whom serous and mucinous borderline ovarian tumors had been diagnosed between 1980 and 1985 ("cases") and from a randomly selected telephone sample of 134 control women from the same counties. Mean activity in plasma of alpha-L-fucosidase was slightly higher in cases (334 units/ml) compared to controls (306 units/ml). The risk for a serous borderline tumor was virtually the same for women in all four quartiles of alpha-L-fucosidase activity. Women in the three lowest quartiles of activity were at 50-70% the risk of women in the highest quartile for the development of a mucinous tumor, but within these three quartiles there was no trend of decreasing risk with decreasing activity. These results suggest that for most women plasma alpha-L-fucosidase activity has little or no bearing on the risk of borderline ovarian tumors. Whether such an association exists in women genetically predisposed to these tumors could not be assessed.     

Fertility-sparing surgery for malignancies in women

Never before have women with newly diagnosed gynecologic malignancies had more options for preservation of fertility. Girls or women of childbearing age with several ovarian cancer subtypes have a high probability of unilateral ovarian involvement, and, thus, may be candidates for fertility-sparing surgery with preservation of a contralateral normal ovary and uterus. These subtypes include ovarian tumors of low malignant potential, malignant ovarian germ cell tumors, and ovarian sex cord-stromal tumors. For women with invasive epithelial ovarian cancer who have early-stage disease, fertility-sparing surgery may be an option. In some cases, fertility-sparing surgery may be followed by postoperative chemotherapy. For women with invasive cervical cancer, fertility-sparing surgery may be possible. Options include conization alone for stage IA1 or IA2 disease, radical trachelectomy with stage IA2 or IB disease, or ovarian transposition for women undergoing chemoradiation. Non-operative options, such as hormonal therapy, may be considered for women with early-stage, low-grade endometrial cancer. For all women of childbearing age with gynecologic malignancies, in vitro fertilization techniques or cryopreservation of ovarian tissue may be an option prior to definitive treatment.     

Molecular Characterization of 103 Ovarian Serous and Mucinous Tumors

The pathogenesis of ovarian carcinomas is heterogeneous, with even the same entities showing great variance. In our study we investigated the mutations of the BRAF, KRAS, and p53 genes in serous and mucinous borderline tumors and in low grade and high grade serous and mucinous tumors. The mutations of BRAF and KRAS genes have been shown in 60% of borderline and low grade (well differentiated) serous and mucinous tumors, but very rarely in high grade (moderately and poorly differentiated) carcinomas. However mutations of p53 are very common in high grade tumors and this indicates a "dualistic" model of ovarian tumorigenesis. A total of 80 serous tumors, including serous borderline, low grade and high grade tumors, and 23 mucinous tumors, including borderline and invasive tumors were analysed for BRAF and KRAS mutations using real time PCR method followed by melting point analysis. P53 mutation was investigated by immunohistochemistry. We assumed mutation of the p53 gene when 100% of tumor cells showed strong nuclear positivity. We observed differences in genetic alterations in the development of the low grade tumors and between low and high grade tumors too. In some bilateral or stage II-III cases we observed differences between the mutation status of the left and right ovarian tumors and between the primary tumor and its implants. In one case in a tumor with micropapillary pattern showing high grade nuclear atypia we could detect mutations in both KRAS and p53 genes. The majority of our mucinous ovarian tumor cases showed a KRAS mutation. We have not found mutations of the BRAF and p53 genes in these cases. We have found as have others, that there is a dualistic pathway of ovarian carcinogenesis. In the majority of cases, low grade epithelial tumors develop in a stepwise manner due to genetic alterations of the members of MAP-kinase pathway; however mutation of the p53 gene is the key event in the development of high grade tumors.     

Survival among women with borderline ovarian tumors and ovarian carcinoma: a population-based analysis

BACKGROUND: Serous and mucinous ovarian tumors of low malignant potential (LMP-S and LMP-M, respectively) are noninvasive tumors that portend excellent survival when confined to the ovary. Comparison of the survival for women with LMP tumors staged as distant with women who have carcinoma may have important implications for diagnostic terminology and clinical management. METHODS: The authors compared relative survival rates among patients diagnosed with ovarian tumors during the period 1988-1999 (with follow-up through 2000) by histologic type, disease stage, tumor grade (for carcinomas), and patient age, using data from the Surveillance, Epidemiology, and End Results Program. RESULTS: The overall relative survival rate at 10 years (+/- 1.96 standard errors) was 96.9% +/- 2.3% for women with LMP-S tumors, 30.4% +/- 1.7% for women with serous carcinoma (CA-S); 94.0% +/- 3.1% for women with LMP-M tumors, and 64.7% +/- 3.4% for women with mucinous carcinoma (CA-M). The survival rate at 10 years for women with distant-stage LMP-S tumors was 89.9% +/- 5.3%, compared with 96.1% +/- 8.6% for women with well differentiated, localized CA-S. The survival rate for women with distant-stage LMP-M tumors at 5 years was 85.5% +/- 9.0%, compared with 95.5% +/- 3.4% for women with well differentiated, localized CA-M (data for 10 years were limited). Mucinous ovarian neoplasms were associated with an excess of second malignancies of the digestive tract. CONCLUSIONS: Relative survival among women with distant-stage LMP tumors was not 100% and resembled the survival of women who had carcinoma exhibiting favorable prognostic features (localized stage). Future studies of women with high-stage LMP tumors are required to clarify the pathogenesis of extraovarian lesions and their implications for management and prognosis.