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Introduction Materials and Methods Results Discussion Borderline ovarian tumours (BOT) are a common epithelial ovarian tumours. Typically diagnosed at an early stage with a good prognosis, many BOT are treated conservatively. Recurrence is common. This update to our last audit in 1997 represents one of the largest audits of BOT to date.All patients with BOT managed at ‘the hospital’ from 1984 to 2021 were included. Expert pathology review was available.There were 549 cases included. The recurrence rate was 5% (n = 29/549) with 1.4% (n = 8/549) undergoing malignant transformation. Three of the eight women who recurred as cancer died from their disease. Frozen section was predictive of histologic diagnosis in 92% (n = 55/60) of serous tumours (SBOT), but only 62% (n = 54/87) of mucinous tumours (MBOT). In MBOT where the appendix appeared normal intra‐operatively, it was histologically benign in all cases (n = 63). In SBOT, the recurrence rate was 5/23 (22%), 12/52 (23%), 1/29 (3%) and 3% (P = <0.01) for unilateral cystectomy, unilateral oophorectomy ± cystectomy, bilateral oophorectomy, and bilateral oophorectomy with hysterectomy, respectively, as index procedure. In MBOT this correlated to 2/20 (10%), 3/93 (3%), 0 and 1/58 (2%), respectively.This study describes important information correlating first surgical procedure and fertility‐sparing surgery to recurrence and malignant transformation. For all BOT subtypes, fertility‐preserving surgery increased the risk of recurrence and hysterectomy was not superior to removal of both ovaries. In MBOT, frozen section is of limited utility and the macroscopically normal appendix is very unlikely to be anything but benign, if MBOT is the true histologic diagnosis. [ABSTRACT FROM AUTHOR]

Borderline ovarian tumours (BOTs) show intriguing characteristics distinguishing them from other ovarian tumours. The aim of the systematic review was to analyse the spectrum of molecular changes found in BOTs and discuss their significance in the context of the overall therapeutic approach. The systematic review included articles published between 2000 and 2023 in the databases: PubMed, EMBASE, and Cochrane. After a detailed analysis of the available publications, we qualified for the systematic review: 28 publications on proto-oncogenes: BRAF, KRAS, NRAS, ERBB2, and PIK3CA, 20 publications on tumour suppressor genes: BRCA1/2, ARID1A, CHEK2, PTEN, 4 on adhesion molecules: CADM1, 8 on proteins: B-catenin, claudin-1, and 5 on glycoproteins: E-Cadherin. In addition, in the further part of the systematic review, we included eight publications on microsatellite instability and three describing loss of heterozygosity in BOT. Molecular changes found in BOTs can vary on a case-by-case basis, identifying carcinogenic mutations through molecular analysis and developing targeted therapies represent significant advancements in the diagnosis and treatment of ovarian malignancies. Molecular studies have contributed significantly to our understanding of BOT pathogenesis, but substantial research is still required to elucidate the relationship between ovarian neoplasms and extraneous disease, identify accurate prognostic indicators, and develop targeted therapeutic approaches.

Borderline ovarian tumours (BOTs) are characterized by the presence of cellular proliferation and nuclear atypia without stromal invasion. Compared to malignant ovarian tumours, BOTs have better prognoses. The most important treatment of BOT is surgery. Considering the good prognosis of BOT, fertility-sparing surgery (FSS) can be considered for young women who desire to preserve fertility. Our study evaluated the pregnancy rate in patients with childbearing desire, the efficacy and risk of recurrence of women affected by BOTs who have undergone FSS. Patients characteristics have been restrospectively retrieved for diagnosis made from June 2000 to December 2017 from San Raffaele Hospital and Policlinico Cagliari. Patients underwent FSS for BOT were interviewed about child wishing and pregnancy outcomes. 85 patients were recruited for the study. Median age at diagnosis was 33 years. Unilateral salpingo-oophorectomy was performed in 33 patients (38%), unilateral cystectomy in 40 (47%) and 12 underwent both procedures (14%). 40 women (50%) tried to conceive after surgery. The pregnancy rate was 73% and live birth rate was 67%. Childbearing desire and age at diagnosis were significantly associated with the pregnancy rate. Conservative surgical treatment seems to be a reasonable therapeutic option for women with BOTs who wish to preserve fertility. Our results suggest that the obstetric outcomes after FSS are promising. Maternal desire and the age of diagnosis are the most important factors affecting PR after surgery. Fertility counselling should be an integral part of the clinical management of women with BOT. [ABSTRACT FROM AUTHOR]

This study was conducted to determine the demographic and clinicopathologic characteristics and evaluate the prognostic value of various factors, such as the extensiveness of surgery, related to the tumour itself and the clinical features in the recurrence of borderline ovarian tumours (BOT). We retrospectively evaluated the data of 103 patients with a borderline ovarian tumours treated at our institution between the years 2000 and 2012. The median age was 37 (16-79) years and the majority of the patients were premenopausal (76.7%). During the follow-up, 16 recurrences were observed (15.5%). The multivariate analysis showed that the micropapillary architecture and fertility sparing surgery were the only significant independent predictors for the development of a recurrence amongst all of the demographic and clinicopathological features. In our study group, we identified that the micropapillary architecture itself and the fertility sparing surgery had a significant impact on the development of a BOT recurrence. The patients who possess these features should be followed up more closely for a long time period. Impact statement What is already known on this subject? A borderline ovarian tumour is known as a recurrent disease. The recurrence rate varies between 5 and 20%. It is well known in the literature that patients treated by an oophorectomy have a relatively lower risk of development of a recurrence compared to the patients treated by cystectomy. What do the results of this study add? Although some of the clinicopathological features are shown to be risk factors for the development of a recurrence in many studies, some of the pathological-clinical and the demographic features have not been described as yet, or have been considered to be equivocal regarding the development of a recurrence. In this study, we investigate all possible demographic, pathological, and clinical factors associated with a recurrence. Not only the well-known pathological characteristics but also the new pathological parameters and clinical approaches have been investigated. For instance, microinvasion architecture and lymphadenectomy speculated in the literature as the risk factors for the development of a recurrence, have not been identified as risk factors in our study. On the other hand, our statistical analyses have revealed that micropapillary architecture should be described as a risk factor for the development of a recurrence. What are the implications of these findings for clinical practice and/or further research? We hope our study becomes influential in the literature on the field of a micropapillary architecture and the development of a recurrence. The patients carrying this feature have to be followed up very closely and carefully. Furthermore, our findings have indicated no significant relation between the performing of a lymphadenectomy and the rate of a recurrence. This result might be encouraging for the gynaecological surgeons to refrain from a lymphadenectomy for the borderline ovarian tumours. [ABSTRACT FROM AUTHOR]

Background and objectives: ultrasound is considered to be the primary tool for preoperative assessment of ovarian masses; however, the discrimination of borderline ovarian tumours (BOTs) is challenging, and depends highly on the experience of the sonographer. The Assessment of Different NEoplasias in the adneXa (ADNEX) model is considered to be a valuable diagnostic tool for preoperative assessment of ovarian masses; however, its performance for BOTs has not been widely studied, due to the low prevalence of these tumours. The aim of this study was to evaluate the performance of ADNEX model for preoperative diagnosis of BOTs. Methods: retrospective analysis of preoperative ultrasound datasets of patients diagnosed with BOTs on the final histology after performed surgery was done at a tertiary oncogynaecology centre during the period of 2012–2018. Results: 85 patients were included in the study. The performance of ADNEX model based on absolute risk (AR) improved with the selection of a more inclusive cut-off value, varying from 47 (60.3%) correctly classified cases of BOTs, with the selected cut-off of 20%, up to 67 (85.9%) correctly classified cases of BOTs with the cut-off value of 3%. When relative risk (RR) was used to classify the tumours, 59 (75.6%) cases were identified correctly. Forty (70.2%) cases of serous and 16 (72.7%) cases of mucinous BOTs were identified when AR with a 10% cut-off value was applied, compared to 44 (77.2%) and 15 (68.2%) cases of serous and mucinous BOTs, correctly classified by RR. The addition of Ca125 improved the performance of ADNEX model for all BOTs in general, and for different subtypes of BOTs. However, the differences were insignificant. Conclusions: The International Ovarian Tumour Analysis (IOTA) ADNEX model performs well in discriminating BOTs from other ovarian tumours irrespective of the subtype. The calculation based on RR or AR with the cut-off value of at least 10% should be used when evaluating for BOTs.

Objective: To develop a risk scoring system (RSS) for predicting recurrence in women with borderline ovarian tumours (BOTs).Design: Cohort study of women with BOTs.Setting: French multicentre tertiary care centres.Population: A cohort of 360 women with BOTs who received primary surgical treatment between January 2000 and December 2013.Methods: Clinical and pathological factors affecting recurrence in women with BOTs.Main Outcome Measure: The development of a model for the prediction of recurrence in women with BOTs.Results: Overall the recurrence rate was 20.0% (72/360). Recurrence was associated with five variables: age < 45 years; preoperative serum tumour marker CA125 > 150 IU/mL; a serous histological subtype; International Federation of Gynecology and Obstetrics (FIGO) stage other than IA; and ovarian surgery other than bilateral salpingo-oophorectomy (BSO; i.e. cystectomy and unilateral salpingo-oophorectomy). These variables were included in the RSS and assigned scores ranging from 0 to 6. The discrimination of the RSS was 0.82 (95% confidence interval, 95% CI 0.79-0.85). A total score of 8 points corresponded to the optimal threshold of the RSS, with a rate of recurrence of 11.8% (35/297) and 58.7% (37/63) for women at low risk (<8 points) and women at high risk (≥8 points), respectively. The diagnostic accuracy was 85.0%.Conclusions: This study shows that the risk of BOT recurrence can be accurately predicted so that women at high risk can benefit from adapted surgical treatment.Tweetable Abstract: Our RSS permitted women with BOTs at low risk to be distinguished from women with BOTs at high risk of recurrence. [ABSTRACT FROM AUTHOR]

Borderline ovarian tumours (BOT) may occur in young women and have an excellent survival rate. Therefore, there is the obligation to put emphasis on fertility preservation in affected women. On the other hand, it has also been underlined that the disease should be managed with caution because these tumours can relapse and, albeit rare, malignant transformation can also occur. Unfortunately, evidence on fertility preservation in women with BOT is scanty. In this opinion paper, we tried to draw some clinical indications based on the few available studies on the clinical management of BOT and their possible relation with controlled ovarian hyper-stimulation (COH). We ultimately came to the following conclusions: (1) Fertility counselling should become an integral part of the clinical management of women with BOT. Conservative management without pre-surgical counselling may expose women without reasonable chances of future conceptions to undue risks. (2) Despite some epidemiological concerns on the possible relation between COH and BOT, the conservative surgical treatment should be associated to oocyte cryopreservation considering the high risk of recurrence of the disease. (3) Letrozole during COH should be considered to temper the theoretical risk of increased recurrences. (4) Pregnancy should not be delayed in women at low-moderate risk of recurrences. Fertility preservation may be avoided in these women provided that they start active pregnancy seeking early. (5) Albeit experimental, oocytes retrieval from affected ovaries removed at the time of surgery can be considered. Conversely, ovarian cortex cryopreservation is not justified given the possible risks of malignant reseeding. [ABSTRACT FROM AUTHOR]

Study Question: Can a nomogram be used to predict the individual probability of live birth (LB) in women with borderline ovarian tumours (BOTs) receiving primary fertility-sparing surgery?Summary Answer: A nomogram built according to the woman's age, histological subtype (serous versus mucinous), type of ovarian surgical treatment and FIGO stage can accurately predict the probability of LB in women with BOT.What Is Known Already: Current prediction models determine the probability of pregnancy after medically assisted reproduction (MAR) and form the basis of patient counselling to guide the decision as to whether to consider in vitro fertilization but do not take into account prediction of the LB rate.Study Design, Size, Duration: This was a retrospective multi-centre study including 187 women with fertility-sparing surgery for BOT diagnosed between January 1980 and December 2013.Participants/materials, Setting, Methods: A multivariate logistic regression analysis of selected factors and a nomogram to predict the subsequent LB rate was constructed. A bootstrapping technique was used for internal validation.Main Results and the Role Of Chance: Fifty-one women had LB (27.3%). Taking into account multiple pregnancies, the overall LB rate was 40.1% (75/187). Federation International of Gynaecology and Obstetric (FIGO) stage, age at diagnosis, histological subtype and surgery type were included in the nomogram. The predictive model had an AUC of 0.742 (95% CI, 0.644-0.825) and 0.72 (95% CI, 0.621-0.805) before and after the 200 repetitions of bootstrap sample corrections, respectively, and showed a good calibration.Limitations, Reasons For Caution: The retrospective nature of the study cannot exclude all biases. Our nomogram is based on simple criteria, but did not take into account the evaluation of ovarian reserve. It demonstrates a fair relevance, but requires external validation before routine use.Wider Implications Of the Findings: Clinicians are increasingly interested in such tools to support the patient in making an informed decision about treatment options. This nomogram contributes to the decision-making by defining simple risk factors of poor LB probability that can help identify good candidates for MAR.Study Funding/competing Interests: No external funding was used for this study. There are no conflicts of interest to declare.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Borderline ovarian tumours (BOTs) are characterised histologically by a low degree of cellular proliferation and nuclear atypia in the absence of infiltrative growth or stromal invasion. Surgical treatment has been a crucial component of BOT therapy. Surgical decisions are established intraoperatively via the frozen section. We evaluated the accuracy of frozen section diagnosis. The rate of correct diagnosis, underdiagnosis and overdiagnosis of BOTs with frozen sections was 78%, 17% and 5%, respectively. The sensitivity and positive predictive values for the diagnosis of BOTs with frozen sections were 82.3% and 93.3%, respectively. The positive likelihood ratio was 0.82 (95% CI: 0.85–0.96). The histological classification of BOTs had a significant effect on the accuracy of diagnosis (p = 0.001). Frozen section diagnosis is not suitable to be considered as the gold standard for a definitive diagnosis. Clinicians should be aware that using frozen sections is insufficient for the accurate staging of BOTs. [ABSTRACT FROM PUBLISHER]

Background Recent reports have stirred the debate regarding the optimal conservative treatment for both serous and mucinous borderline ovarian tumour (BOT). The aim of this study is to examine the optimal oncological approach of conservative surgery in unilateral BOT (cystectomy (C) versus unilateral salpingo-oophorectomy (USO)) and in bilateral BOT (bilateral C (BC) versus USO + contralateral C (CC)), as well as fertility outcomes. Materials and methods The PubMed database and Cochrane Library were searched using the search terms (((Borderline) OR (low malignant potential)) AND (ovarian)) AND ((tumour) OR (cancer)) AND (((fertility sparing) OR (conservative)) AND surgery). Results We analysed 39 studies that included 5105 women (2624 patients with serous-, 2120 patients with mucinous- and the remaining with other types of BOT), 2752 of which underwent conservative surgery (817 underwent C, 89 BC, 1686 USO and 118 USO + CC). Eight studies included only stage I patients, in 14 studies more than 90% of patients were stage I and five studies included only late-stage patients. Seven studies included only patients with serous borderline ovarian tumour (sBOT) and two only mucinous borderline ovarian tumour (mBOT). A total of 296 patients with non-invasive-, 76 patients with invasive- and 50 patients with unspecified implants were pooled. Of the patients undergoing C, BC, USO and USO + CC the pooled recurrence estimates were respectively 25.3%, 25.6%, 12.5% and 26.1%. In meta-analysis, USO was significantly favored over C with an OR for recurrence reduction = 2200, 95% CI = 0.793–2.841 and p < 0.0001. The pooled recurrence estimate as invasive ovarian cancer was 15.4% and the pooled 95% CI was 0.120–0.196. The cumulative pregnancy rate was 55.7% with 45.4% for USO and 40.3.0% for C. Conclusion Cystectomy in unilateral serous BOT is significantly associated with a higher recurrence rate, albeit no impact on survival can be demonstrated. Whether this is related to the duration of follow-up, remains to be proven. Nonetheless, recent data seem to suggest that USO is advisable in the case of mucinous BOT. On the contrary, a more conservative approach (BC) should be definitively favored in bilateral BOT, which is almost always serous, because no significant difference is seen in terms of recurrence rate when compared to USO + CC. [ABSTRACT FROM AUTHOR]

Borderline ovarian tumours are low malignant potential tumours. They represent 10–15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. [ABSTRACT FROM AUTHOR]

STUDY QUESTION: Do fertility drugs increase the risk for borderline ovarian tumours, overall and according to histological subtype? SUMMARY ANSWER: The use of any fertility drug did not increase the overall risk for borderline ovarian tumours, but an increased risk for serousborderline ovarian tumours was observed after the use of progesterone. WHAT IS KNOWN ALREADY: Many epidemiological studies have addressed the connection between fertility drugs use and risk for ovarian cancer; most have found no strong association. Fewer studies have assessed the association between use of fertility drugs and risk for borderline ovarian tumours, and the results are inconsistent. STUDY DESIGN, SIZE, DURATION: A retrospective case-cohort study was designed with data from a cohort of 96 545 Danish women with fertility problems referred to all Danish fertility clinics in the period 1963-2006. All women were followed for first occurrence of a borderline ovarian tumour from the initial date of infertility evaluation until a date of migration, date of death or 31 December 2006, whichever occurred first. The median length of follow-up was 11.3 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Included in the analyses were 142 women with borderline ovarian tumours (cases) and 1328 randomly selected sub-cohort members identified in the cohort during the follow-up through 2006. Cases were identified by linkage to the Danish Cancer Register and the Danish Register of Pathology by use of personal identification numbers. To obtain information on use of fertility drugs, hospital files and medical records of infertility-associated visits to all Danish fertility clinics were collected and supplemented with information from the Danish IVF register. We used case-cohort techniques to calculate rate ratios (RRs) and corresponding 95% confidence intervals (CIs) for borderline ovarian tumours, overall and according to histological subtype, associated with the use of any fertility drug or five specific groups of fertility drugs: clomiphene citrate, gonadotrophins (human menopausal gonadotrophins and follicle-stimulating hormone), gonadotrophin-releasing hormone analogues, human chorionic gonadotrophins and progesterone. MAIN RESULTS AND THE ROLE OF CHANCE: Analyses within the cohort showed that the overall risk for borderline ovarian tumours was not associated with the use of any fertility drug (RR 1.00; 95% CI 0.67-1.51) or of gonadotrophins (RR 1.32; 95% CI 0.81-2.14), clomiphene citrate (RR 0.96; 95% CI 0.64-1.44), human chorionic gonadotrophins (RR 0.91; 95% CI 0.61-1.36) or gonadotrophin-releasing hormone analogues (RR 1.10; 95% CI 0.66-1.81). Furthermore, no associations were observed between the risk for borderline ovarian tumours and these groups of fertility drugs according to the number of cycles of use, length of follow-up or parity. In contrast, use of progesterone increased the risk for borderline ovarian tumours, particularly serous tumours, for which statistically significantly increased risks were observed with any use of progesterone (RR 1.82; 95% CI 1.03-3.24), among women treated with ≥4 cycles of progesterone (RR 2.63; 95% CI 1.04-6.64) and for all women followed up for ≥4 years after their first treatment with progesterone. LIMITATIONS, REASONS FOR CAUTION: Although we tried to minimize the effects of the underlying infertility, the severity of infertility might have affected our risk estimates, as women with more severe fertility problems may receive more treatment. The results from the subgroup analyses, e.g. the findings of an elevated risk for borderline ovarian tumours associated with increased time since first use of progesterone and with increased number of treatment cycles, should be interpreted with caution as these analyses are based on a limited number of women with borderline ovarian tumours. WIDER IMPLICATIONS OF THE FINDINGS: Although this study, which is the largest to date, provides reassuring evidence that there is no strong link between the use of fertility drugs and risk for borderline ovarian tumours, the novel observation of an increased risk for serous tumours after use of progesterone should be investigated in large epidemiological studies. The results of the present study provide valuable knowledge for clinicians and other health care personnel involved in the diagnosis and treatment of fertility problems. STUDY FUNDING/COMPETING INTERESTS: No conflict of interest was reported. S.M.B. was supported by a research scholarship from the Danish Cancer Society. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To compare the risk of borderline ovarian tumours in women having in vitro fertilization (IVF) with women diagnosed with infertility but not having IVF. Methods: This was a whole-population cohort study of women aged 20–44years seeking hospital infertility treatment or investigation in Western Australia in 1982–2002. Using Cox regression, we examined the effects of IVF treatment and potential confounders on the rate of borderline ovarian tumours. Potential confounders included parity, age, calendar year, socio-economic status, infertility diagnoses including pelvic inflammatory disorders and endometriosis and surgical procedures including hysterectomy and tubal ligation. Results: Women undergoing IVF had an increased rate of borderline ovarian tumours with a hazard ratio (HR) of 2.46 (95% confidence interval [CI] 1.20–5.04). Unlike invasive epithelial ovarian cancer, neither birth (HR 0.89; 95% CI 0.43–1.88) nor hysterectomy (1.02; 0.24–4.37) nor sterilization (1.48; 0.63–3.48) appeared protective and the rate was not increased in women with a diagnosis of endometriosis (HR 0.31; 95% CI 0.04–2.29). Conclusions: Women undergoing IVF treatment are at increased risk of being diagnosed with borderline ovarian tumours. Risk factors for borderline ovarian tumours appear different from those for invasive ovarian cancer. [Copyright &y& Elsevier]

The article discusses the study that looked into the clinical reproductive outcome and the rate of recurrence of the low malignant ovarian tumors in adolescent girls following a surgical laparoscopy in Germany. It states that the borderline ovarian tumor (BOT) lesions in teenagers were determined through ultrasound investigations. It implies that BOTs have negative effect on fertility, pregnancy outcome, and survival in the young patients.

Abstract: Since borderline ovarian tumours came into light in the early 1970s, they continued to present a challenge to doctors and patients equally. The majority of affected women present with an early stage disease, and they are usually 10–15 years younger than those with ovarian cancer. Most ovarian borderline tumours are either serous or mucinous. In general, borderline ovarian tumours have a very good prognosis; however, this is much dependant on the histological subtype, disease stage and the presence or absence of invasive implants. The micropapillary serous pattern is often associated with invasive implants and unfavourable outcome; this emphasises the importance of adequate surgical staging as a prognostic indicator. Mucinous borderline ovarian tumours demonstrate an overwhelmingly benign course. It is now established that cases of pseudomyxoma peritonei are all related to gastrointestinal primary either occult or obvious. So far, no pre-operative test can identify ovarian cyst as borderline with a high degree of certainty. Therefore, maintaining a high index of suspicion, arrangement for frozen section and thorough examination of the abdominal cavity are indispensable, as well as adequate counselling. Conservative surgery in younger patients with stage I disease is a reasonable option; fertility outcome is favourable, however, there is a relatively higher risk of recurrence. This option can even be considered in advanced stages but without invasive implants; fortunately most recurrences can be salvaged surgically. It is now well established that patients with treated stage I disease do not required any adjuvant chemotherapy in view of the excellent long term survival of nearly 100%. Prospective trials are needed for those with advanced stage especially in the presence of invasive implants before a conclusion can be reached. Regular follow up is necessary for early detection and successful management of recurrences, particularly in those who were inadequately staged, managed conservatively or demonstrate high risk histological features. [Copyright &y& Elsevier]

Recently it was estimated that about one-third of postmenopausal British women aged 50-64 years currently uses hormone replacement therapy (HRT) for treatment of climacteric symptoms and for other medical reasons. To reduce an excess risk of endometrial cancer induced by oestrogens, modern HRT regimens contain either sequential or continuous progestogens. The protective effect of parity and oral contraceptive use observed in the majority of epidemiological studies on epithelial ovarian cancer (EOC) suggest that hormonal factors are likely to operate in ovarian carcinogenesis. However, the studies where HRT was examined in relation to the risk of EOC have reported conflicting results. The objective of this epidemiological review is to evaluate the risk of EOC in relation to the use of HRT, with particular focus on the few studies where oestrogens and progestogens in HRT were assessed separately. Further, the findings regarding HRT and EOC risk will be discussed in the context of available aetiological hypotheses. Finally, any clinical implications are commented upon. [ABSTRACT FROM AUTHOR]

Aims:To determine the diagnostic and prognostic value of the immunohistochemical analysis of CD44 variants in benign borderline and malignant tumours of the ovary. Methods and results:The reactivity of tumour cells with three monoclonal antibodies, respectively, directed to all CD44 variants, CD44-v3 isoform and CD44-v6 isoform, was assessed by using an indirect immunoperoxidase technique applied to formalin-fixed, paraffin-embedded samples of 36 cases of borderline, as compared to 20 cases of benign tumours and 20 cases of carcinomas. CD44 variants were detected in 97% of borderline tumours, as compared to 60% of benign tumours and 100% of carcinomas. CD44-v3 was detected in 25% of borderline tumours, as compared to 0% of benign tumours (P = 0.003) and 55% of carcinomas (P = 0.065). The expression of CD44-v6 was detected in 28% of borderline tumours, as compared to 20% of benign tumours and 30% of carcinomas. In borderline tumours, as in carcinomas, CD44-v6, but not CD44-v3, expression was correlated with an increased proliferative index and with a higher incidence of p53 expression. Conclusion:Borderline tumours of the ovary present frequent quantitative and qualitative alterations in the pattern of expression of CD44 proteins. However, these alterations are unlikely to represent useful diagnostic or prognostic markers. [ABSTRACT FROM AUTHOR]

Borderline ovarian tumours (BOT) often affect young females, in whom conservative treatment may be desired in order to preserve fertility. It is unknown whether in vitro fertilisation (IVF) increases the risk of recurrent disease. This case-series will focus on four patients diagnosed with BOT, who were initially treated conservatively and subsequently received IVF. Five recurrences occurred prior to IVF and three recurrences occurred after IVF in three individuals. After a mean follow-up of 104 months after initial conservative treatment and 43 months after IVF treatment, all four patients were alive and disease-free. [ABSTRACT FROM AUTHOR]

Background and objectives: ultrasound is considered to be the primary tool for preoperative assessment of ovarian masses; however, the discrimination of borderline ovarian tumours (BOTs) is challenging, and depends highly on the experience of the sonographer. The Assessment of Different NEoplasias in the adneXa (ADNEX) model is considered to be a valuable diagnostic tool for preoperative assessment of ovarian masses; however, its performance for BOTs has not been widely studied, due to the low prevalence of these tumours. The aim of this study was to evaluate the performance of ADNEX model for preoperative diagnosis of BOTs. Methods: retrospective analysis of preoperative ultrasound datasets of patients diagnosed with BOTs on the final histology after performed surgery was done at a tertiary oncogynaecology centre during the period of 2012-2018. Results: 85 patients were included in the study. The performance of ADNEX model based on absolute risk (AR) improved with the selection of a more inclusive cut-off value, varying from 47 (60.3%) correctly classified cases of BOTs, with the selected cut-off of 20%, up to 67 (85.9%) correctly classified cases of BOTs with the cut-off value of 3%. When relative risk (RR) was used to classify the tumours, 59 (75.6%) cases were identified correctly. Forty (70.2%) cases of serous and 16 (72.7%) cases of mucinous BOTs were identified when AR with a 10% cut-off value was applied, compared to 44 (77.2%) and 15 (68.2%) cases of serous and mucinous BOTs, correctly classified by RR. The addition of Ca125 improved the performance of ADNEX model for all BOTs in general, and for different subtypes of BOTs. However, the differences were insignificant. Conclusions: The International Ovarian Tumour Analysis (IOTA) ADNEX model performs well in discriminating BOTs from other ovarian tumours irrespective of the subtype. The calculation based on RR or AR with the cut-off value of at least 10% should be used when evaluating for BOTs.

Purpose: Ovarian tumours are the second most common cause of death from gynaecological cancer. There are three types of ovarian cancer based on histopathological examination: benign, borderline, and malignant. However, it is difficult to distinguish the borderline and malignant tumours. Several studies used the apparent diffusion coefficient value to distinguish the ovarian tumour types, with various results. This preliminary report focused more on the use of the minimal ADC (mADC) value on the solid component, to differentiate borderline and malignant ovarian tumours., Material and Methods: In 21 cases of borderline ovarian tumours, of which 11 were regarded as malignant and 10 were regarded as borderline following histopathological examination, the mADC value was measured by two different radiologists by using free-hand technique. The intraclass correlation coefficient (ICC) was used to measure the reliability and agreement between the two radiologists. Receiver-operating characteristic (ROC) curves were then calculated to determine the optimum cut-off point., Results: There were statistically significant ( p = 0.001) of the mADC value between the borderline and malignant tumours. The intraclass correlation coefficient value showed excellent reliability and agreement between the examiners. The ROC curve showed the optimum cut-off point at 0.628 × 10 -3 mm 2 /s ( p = 0.001), which yielded 100% sensitivity and 80% specificity., Conclusions: The use of free-hand technique to measure the mADC value on the solid component can be valuable in differentiating borderline and malignant ovarian epithelial tumours. This result may assist clinicians in considering further treatment approaches., Competing Interests: The authors report no conflict of interest., (Copyright © Polish Medical Society of Radiology 2020.)

Objectives: To evaluate the diagnostic value of serum biomarkers in the management strategy of borderline ovarian tumours (BOT) to make management recommendations., Methods: English and French review of literature from 1990 to 2019 based on publications from Pubmed, Medline, Cochrane, with keywords: borderline ovarian tumors, tumour markers, CA125, CA19 9, ACE, CA72 4, TAG72, HE4, ROMA, mucinous, serous, mucinous, endometrioid ovarian tumours, peritoneal implants, recurrence, overall survival, follow-up. Among 1000 references, 400 were selected and only 30 were screened for this work., Results: Literature review: there is low evidence in literature concerning the discriminating value of serum tumour biomarkers (CA125, CA19-9, CEA, CA72-4, HE4) and specific score between presumed benign ovarian tumour/BOT/ovarian cancer (LE4). Serum CA125 antigen is higher in case of serous borderline ovarian tumour (LE4), increase with the tumor height, the FIGO stage, notably in case of serous borderline ovarian tumor. However, a normal value rate of serum CA125 antigen does not rule out a BOT (LE4). The preoperative positivity rate of CA19 9 in case of TFO is relatively lower than that of CA125 and is higher in mucinous TFO. The preoperative rate of serum CA19 9 antigen increases with the tumour height and the FIGO stage (LE4) and are higher in case of mucinous BOT (LE4). Preoperative rates of serum HE4 are not different between histologic type of BOT. A high level of serum biomarkers (CA125) is a predictive factor of peritoneal implants (LE4) and an independent predictive factor of recurrence (CA125) (LE4)., Recommendations: no recommendation can be made about the use of serum tumour biomarkers (CA125, CA19-9, CEA, CA72-4, HE4) or specific score in order to distinguish benign ovarian tumor/borderline ovarian tumor/ovarian cancer in case of indeterminate mass. In case of suspicion of mucinous ovarian tumour on imaging, the systematic dosage of serum CA19-9 antigen can be proposed (grade C). In case of an ovarian indeterminate mass on imaging; dosage of serum HE4 and C125 is recommended. If preoperative dosage of serum tumor biomarkers is normal, their systematic dosage is not recommended in the follow-up of BOT (grade C). If preoperative dosage of CA125 is high, the systematic dosage of CA125 is recommended in the follow-up of BOT with no precisions about the rhythm and the duration of the follow-up (grade B)., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

The incidence (rate/100,000) of BOT gradually increases with age from 15-19 years of age and peaks at nearly 4.5 cases/100,000 for the 55-59 year age group (NP3). In the presence of a benign ovarian mass, the standardized risk ratio of serous and mucinous BOT is 1.69, (95% CI 1.39-2.03) and 1.75, (95% CI 1.45-2.10), respectively (NP2). At diagnosis, a median age of diagnosis of OFA is 46 years, unilateral forms (79.7% of cases) are predominant compared to cancers (45.3%) (<0.001) and FIGO I stages represent nearly 63.7% of cases (NP3). The 5-year survival rates for FIGO I, II, III, IV stages are: 99.7% (95% CI: 96.2-100%), 99.6% (95% CI: 92.6-100%), 95.3% (95% CI: 91.8-97.4%), 77.1% (95% CI: 58.0-88.3%), respectively (NP3). Survivors at 5 years for serous and mucinous tumours are 99.7% (95% CI: 99.2-99.9%), 98.5% (95% CI: 96.9-99.3%), respectively (NP3). An epidemiological association exists between personal BOT risk and: (1) a familial history of BOT/certain cancers (pancreas, lung, bone, leukemia) (NP3), (2) a personal history of benign ovarian cyst (NP2), (3) a personal history of pelvic inflammatory disease (IGH), (4) the use of intrauterine device levonorgestrel (NP3), (5) the use of oral contraceptive pills (NP3), (6) multiparity (NP3), (7) hormone replacement therapy (NP3), (8) high consumption of coumestrol (NP4), (9) medical treatment of infertility with progesterone (NP3), (10) non-steroidal anti-inflammatory drug (NSAID). An epidemiological association exists between previous/actual tabacco consumption and the risk of mucinous ovarian BOT (NP2). Relative risk (RR) varies between 2.2 and 2.7, however the relationship is not necessarily a causal one. An epidemiological association exists between overweight/obesity and the risk of serous BOT (NP2). RR varies between 1.2 to 1.8. The high Vitamin D was inversely associated to the risk of serous BOT (NP4). The risk of mucinous BOT was lowered with paracetamol use (OR=0.77; 95% CI: 0.60-0.98) (NP3). However, the relationship between these factors and BOT is not necessarily a causal one and no screening modality can be proposed in the general population (gradeC)., (Copyright © 2020. Published by Elsevier Masson SAS.)

Objective: To determine the place of imaging, tumour markers, type of treatment and surgical route, follow-up, delivery mode, and re-staging in case of BOT during pregnancy, in order to provide guidelines., Method: A systematic bibliographical analysis on BOT during pregnancy was performed through a PUDMED search on articles published from 1990 to 2019 using keywords « borderline ovarian tumour and pregnancy »., Results: Pelvic ultrasound is the gold standard and first-line examination for the detection and characterization of adnexal masses during pregnancy (grade C). Pelvic MRI is recommended from 12 gestational weeks in case of indeterminate adnexal masses and should be concluded by a diagnostic score (grade C). Gadolinium injection should be minimized because of proven risk to the fetus and should be discussed on a case-by-case basis after patient information (grade C). In the absence of data in the literature, it is not possible to recommend the use of any tumour marker for the diagnosis of BOT during pregnancy. In case of a surgical treatment of BOT during pregnancy, there is insufficient evidence to recommend either a cystectomy or an oophorectomy. For BOT, the laparoscopic approach should be preferred during pregnancy if it is feasible (grade C). Surgical route and type of surgery should be chosen after taking into account the tumour size, the obstetrical term, and the subsequent desire for pregnancy, following discussion in a multidisciplinary meeting. In the absence of sufficient data in the literature, it is not possible to make any recommendation on the follow-up of a BOT suspected during pregnancy. There is not enough evidence in the literature to change obstetrical management for delivery in patients with BOT. In case of incomplete staging of a BOT treated during pregnancy, restaging can be discussed as for non-pregnant patients (grade C)., Conclusion: The diagnosis of BOT occurring during pregnancy remains rare despite systematic screening of adnexal masses in the first trimester of pregnancy and an increasing maternal age. There is limited data in the literature concerning the management of BOT during pregnancy. All decisions must be taken after discussion in a multidisciplinary meeting., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

This text presents organizational and methodological aspects of the development of the French guidelines on the management of borderline ovarian tumours., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Borderline ovarian tumors are rare and can occur in young women. For these patients, a fertility sparing surgery should be discussed. Two predicting borderline ovarian tumor relapse risk models were developed in 2014 (Nomogram of Bendifallah) and 2017 (Score of Ouldamer). This study aimed to valid in an external population, these two scores using a multi-institutional BOT database., Methods: In this bicentric and retrospective study, all consecutive patients comprising the variable nomogram documented treated between January 2006 and December 2012 for BOT in centre hospitalier de Poissy-Saint-Germain and hôpital René-Huguenin were included. A ROC model was established for each predicting scores., Results: Sixty-five patients were included in the study. Twelve patients showed a recurrence (19%), three of them experienced an infiltrative cancer (5%). The median time of recurrence was 25 months (range: 8-115). The concordance index for the Nomogram of Bendifallah and the Score of Ouldamer were 0.88 (IC 95% [0.78-0.98]) and 0.87 (IC 95% [0.77-0.96]) respectively., Conclusion: This study from an independent population valids the Bendifallah nomogram and Ouldamer score for clinical use in predicting borderline ovarian recurrence., (Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Approximately 3000 American women are diagnosed with borderline ovarian tumours annually. Borderline tumours are similar to other types of adnexal masses. Prognostic factors include the International Federation of Gynecology and Obstetrics (FIGO) stage, presence of peritoneal implants, micropapillary pattern (for serous histology), microinvasion and intra-epithelial carcinoma (for mucinous histology). Approximately 65-70% of serous tumours and 90% of mucinous tumours are stage I, and 30% and 10%, respectively, are associated with extra-ovarian spread. Fertility-preservation counselling is recommended for young patients. Fertility-sparing surgery is feasible in a high proportion of women in the reproductive age group. Surgical staging generally includes resection of the primary borderline tumour, by either unilateral salpingo-oophorectomy or ovarian cystectomy, cytologic washings, omentectomy and peritoneal biopsies, and routine lymphadenectomy is not recommended. However, because the accuracy of frozen-section examination is lower than optimal, caution is recommended. Postoperative therapy is recommended only for those women with serous borderline tumours and invasive implants. Fortunately, relapse is uncommon., (Copyright © 2016. Published by Elsevier Ltd.)

The majority of borderline ovarian tumours (BOTs) behave in a benign fashion, but some may show aggressive behavior. The reason behind this has not been elucidated. The epidermal growth factor receptor (EGFR) is known to contribute to cell survival signals as well as metastatic potential of some tumours. EGFR expression and gene status have not been thoroughly investigated in BOTs as it has in ovarian carcinomas. In this study we explore protein expression as well as gene mutations and amplifications of EGFR in BOTs in comparison to a subset of other epithelial ovarian tumours. We studied 85 tumours, including 61 BOTs, 10 low grade serous carcinomas (LGSCs), 9 high grade serous carcinomas (HGSCs) and 5 benign epithelial tumours. EGFR protein expression was studied using immunohistochemistry. Mutations were investigated by Sanger sequencing exons 18-21 of the tyrosine kinase domain of EGFR. Cases with comparatively higher protein expression were examined for gene amplification by chromogenic in situ hybridization. We also studied the tumours for KRAS and BRAF mutations. Immunohistochemistry results revealed both cytoplasmic and nuclear EGFR expression with variable degrees between tumours. The level of nuclear localization was relatively higher in BOTs and LGSCs as compared to HGSCs or benign tumours. The degree of nuclear expression of BOTs showed no significant difference from that in LGSCs (mean ranks 36.48, 33.05, respectively, p=0.625), but was significantly higher than in HGSCs (mean ranks: 38.88, 12.61 respectively, p< 0.001) and benign tumours (mean ranks: 35.18, 13.00 respectively, p= 0.010). Cytoplasmic expression level was higher in LGSCs. No EGFR gene mutations or amplification were identified, yet different polymorphisms were detected. Five different types of point mutations in the KRAS gene and the V600E BRAF mutation were detected exclusively in BOTs and LGSCs. Our study reports for the first time nuclear localization of EGFR in BOTs. The nuclear localization similarities between BOTs and LGSCs and not HGSCs support the hypothesis suggesting evolution of LGSCs from BOTs. We also confirm that EGFR mutations and amplifications are not molecular events in the pathogenesis of BOTs.

Background: Fertility preservation techniques are a growing area of research as more women in the reproductive age group develop gynaecologic cancers. We report here a novel technique of fertility preservation used in the treatment of a patient with borderline ovarian tumour., Case: A 29-year-old woman with stage I borderline ovarian tumour was referred to our tertiary level hospital. She had a history of infertility and requested fertility preservation be considered in treatment decisions. We performed bilateral laparoscopic partial decortication of the ovaries, and the patient successfully conceived spontaneously following the procedure., Conclusion: Fertility-preserving surgery should be an option for young women with borderline ovarian tumours who wish to retain fertility. Removing abnormal ovarian tissue may restore fertility. The laparoscopic approach is safe and feasible for these patients.