Serous Borderline Ovarian Tumors Research Articles

Expression of p-Akt in ovarian serous carcinoma and its association with proliferation and apoptosis

The aim of the present study was to determine the expression of p-Akt in ovarian serous carcinoma (OSC) and its association with proliferation and apoptosis. Paraffin-embedded tissues of patients aged between 35 and 64 years old without history of radiotherapy, chemotherapy and hormone therapy prior to surgery were collected. In total, samples included 12 ovarian serous cystadenomas (OSAs), 18 ovarian serous borderline tumors (OS-BTs) and 46 OSCs. Of the 46 OSC samples, 16 were well-differentiated, 20 were moderately differentiated and 10 were poorly differentiated, while 22 developed lymphatic metastases and 24 were metastasis-free. An additional 10 paraffin-embedded normal ovarian tissues (NOTs) were used as controls. Streptavidin-peroxidase immunohistochemistry assays were used to investigate the expression of p-Akt and cyclin D1 in the collected samples. Compared with NOT, p-Akt expression in the OS-BT and OSC groups, as well as cyclin D1 expression in the OSA and OSC groups, was significantly elevated (P<0.05). Compared with the OSA group, p-Akt expression in the OSC group was significantly elevated (P<0.01) and reversely associated with tumor differentiation (P<0.01), whereas cyclin D1 expression showed no correlation with tumor differentiation (P>0.05). The expression of p-Akt, caspase-3 and cyclin D1 was positively associated with lymphatic metastasis (r=0.334; P=0.023). The expression of p-Akt gradually increased with carcinoma development and was associated with differentiation and metastasis of OSC, revealing that the activation of the PI3K/Akt signaling pathway is involved in the development of OSC. Furthermore, the expression of cyclin D1 gradually increased in the NOT, OSA, OS-BT and OSC groups and was associated with tumor metastasis.

Overcoming Platinum Resistance in Preclinical Models of Ovarian Cancer Using the Neddylation Inhibitor MLN4924

The nearly ubiquitous development of chemoresistant disease remains a major obstacle against improving outcomes for patients with ovarian cancer. In this investigation, we evaluated the preclinical activity of MLN4924, an investigational inhibitor of the NEDD8-activating enzyme, in ovarian cancer cells. Efficacy of MLN4924 both alone and in combination with platinum was assessed. Overall, single-agent MLN4924 exhibited moderate activity in ovarian cancer cell lines. However, the combination of MLN4924 with cisplatin or carboplatin produced synergistic effects in SKOV3 and ES2 cells, as well as in primary ovarian cancer cell lines established from high-grade serous, clear cell, and serous borderline ovarian tumors. The efficacy of cisplatin plus MLN4924 was also evident in several in vitro models of platinum-resistant ovarian cancer. Mechanistically, the combination of cisplatin and MLN4924 was not associated with DNA re-replication, altered platinum-DNA adduct formation, abrogation of FANCD2 monoubiquitination, or CHK1 phosphorylation. An siRNA screen was used to investigate the contribution of each member of the cullin RING ligase (CRL) family of E3 ubiquitin ligases, the best-characterized downstream mediators of MLN4924's biologic effects. Cisplatin-induced cytotoxicity was augmented by depletion of CUL3, and antagonized by siCUL1 in both ES2 and SKOV3 ovarian cancer cells. This investigation identifies inhibition of neddylation as a novel mechanism for overcoming platinum resistance in vitro, and provides a strong rationale for clinical investigations of platinum and MLN4924 combinations in ovarian cancer.

Abstract A13: Molecular profiling of low grade serous ovarian tumors

Abstract Borderline ovarian tumors fill an unusual niche between completely benign tumors and frank malignancies. These tumors tend to follow a relatively benign clinical course; however, they can recur as low grade serous carcinoma. Tumor features such as invasive implants and micropapillary growth pattern have been proposed to separate serous borderline tumors (SBTs) with invasive-like behaviour from SBTs with benign behaviour. It is currently unknown whether these features are associated with specific molecular events and whether molecular profiling of borderline tumors could offer a significant improvement of predicting likelihood of recurrence and progression. This study aimed to perform genome-wide high-resolution molecular analysis of a large cohort of serous borderline ovarian tumors (n=57), employing copy number analysis and mutation screening, and compared these to a cohort of low grade serous carcinomas (n=19). Clinical features such as tumor stage and laterality were found to correlate with the identity of the underlying oncogenic driver mutation, as were the presence or absence of genomic copy number aberrations and the presence of specific copy number aberrations in the SBT cohort. Comparison of genomic aberrations in SBTs to low grade serous carcinomas (LGSCs) identified loss of heterozygosity events that were very significantly enriched in carcinomas. In conclusion, we have identified correlations between the specific oncogenic mutation a tumor carries and tumor characteristics such as level of genomic aberration and spread beyond the ovary. These findings are consistent with previous reports that specific oncogenic mutations may have a better prognosis in low grade serous tumors. Identifiable correlations between molecular events and tumor characteristics suggest it will be possible to use patient-specific tumor characteristics to better define a suitable level of treatment and follow-up. This is an important consideration as although patients have a very good short term prognosis, over an extended period recurrence and progression of SBTs to LGSCs is not insignificant and later stage LGSCs are relatively chemoresistant. Citation Format: Sally M. Hunter, Kylie L. Gorringe, Michael S. Anglesio, Raghwa Sharma, Yoke-Eng Chiew, Phillip Moss, Andrew Stephens, C Blake Gilks, Group Australian Ovarian Cancer Study, David Hunstman, Anna deFazio, Ian Campbell. Molecular profiling of low grade serous ovarian tumors. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A13.

Fertility sparing treatment of recurrent stage I serous borderline ovarian tumours

Here we report the outcomes of 26 patients who relapsed following conservative surgical treatment of stage I serous borderline ovarian tumours treated initially with fertility-sparing surgery. All recurrences were diagnosed by systematic ultrasonography during follow-up. Eleven patients relapsed at least twice after such management. Twenty-one pregnancies were observed in 13 patients. Eleven of these patients became pregnant after the treatment of their first recurrence. All patients had a borderline ovarian tumour and/or non-invasive peritoneal implants at the time of the first recurrence but two of them had invasive ovarian and peritoneal disease at the time of the second or third recurrence (one of them died of disease). Fertility-preserving surgery remains a valuable alternative (if technically feasible), in young patients with recurrent SBOT, in the form of a non-invasive ovarian lesion, who wish to start a pregnancy. However, it should be associated with meticulous follow-up because the risk of progression to carcinoma exists, albeit small.

Recurrence of borderline ovarian tumour after fertility treatment

Background Borderline ovarian tumours account for 10–20% of all epithelial ovarian tumours. As one-third of these tumours are seen in women less than 40 years of age, fertility remains a major concern in their management. Conservative surgery has been advocated in these cases. Fertility treatment has been successfully used in some of these cases with good results. However, the risk of tumour recurrence cannot be ignored. Case report A young nulliparous woman had fertility sparing surgery (bilateral salpingo-oophorectomy and omentectomy) for serous borderline ovarian tumours with noninvasive implants (stage IIIc). After 10 years of uneventful follow-up, she decided to undergo an in-vitro fertilization with donor oocytes. She received unopposed oestrogen stimulation for 12 days to prime the endometrium and developed ascites. Subsequent investigations revealed tumour recurrence in the form of low-grade serous adenocarcinoma. The carcinoma proved resistant to chemotherapy and pursued an aggressive course culminating in death within 6 months of diagnosis. Conclusion Borderline ovarian tumours can recur in an aggressive manner even after a prolonged follow-up. Large clinical trials with longer follow-up are needed to evaluate the safety of controlled ovarian hyperstimulation after conservative surgery for borderline ovarian tumours.

Abstract 3380: Overcoming platinum resistance in ovarian cancer using the novel compound MLN4924.

Abstract Purpose: The objective of this investigation was to evaluate the preclinical activity of MLN4924, an investigational inhibitor of the NEDD8-activating enzyme, against chemoresistant and chemosensitive ovarian cancer cells. ExperimentalDesign: Efficacy of MLN4924 both alone and in combination with cisplatin was assessed using short-term tetrazolium based and longer term focus formation assays. Mechanistic studies included cell cycle analysis, evaluation of DNA-platinum adduct formation (using an ELISA), and evaluation of DNA damage repair pathways. In addition, we employed an siRNA screen to assess the contribution of each member of the Cullin RING-Ligase (CRL) family of E3 ubiquitin ligases, the best characterized downstream mediators of MLN4924’s biological effects. Results: Single agent MLN4924 exhibited moderate activity in ovarian cancer cell lines. The combination of MLN4924 with cisplatin or carboplatin resulted in significant platinum sensitization in SKOV3 and ES2 cells, as well as, in several primary ovarian cancer cell lines established from high grade serous, clear cell, and serous borderline ovarian tumors. Furthermore, the platinum sensitizing effect of MLN4924 was also observed in several in vitro models of platinum resistant ovarian cancer (using both established and primary chemoresistant ovarian cancer cells). Mechanistically, we show that depletion of CUL3 and CUL5 augment, while knockdown of CUL1 and CUL4A antagonize cisplatin-induced cytotoxicity in ovarian cancer cells. The combination of cisplatin and MLN4924 was not associated with DNA re-replication, altered platinum-DNA adduct formation, or abrogation of FANCD2 monoubiquitination. Conclusions: Our investigation reveals a novel mechanism for overcoming platinum resistance in vitro, and provides a strong rationale for clinical investigations of platinum and MLN4924 combinations in ovarian cancer. This work also highlights that different CRL ubiquitination pathways can have distinct and opposing effects on platinum sensitivity and resistance in ovarian cancer cells. Citation Format: Amir A. Jazaeri, Etsuko Shibata, Jonghoon Park, Jennifer Bryant, Mark R. Conaway, Susan C. Modesitt, Peter G. Smith, Michael Milhollen, Allison J. Berger, Anindya Dutta. Overcoming platinum resistance in ovarian cancer using the novel compound MLN4924. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3380. doi:10.1158/1538-7445.AM2013-3380

Imaging in gynecological disease (8): ultrasound characteristics of recurrent borderline ovarian tumors

To describe the sonographic characteristics of borderline ovarian tumor (BOT) recurrence. From the databases of five ultrasound centers, we retrospectively identified 68 patients with histological diagnosis of recurrent BOT who had undergone preoperative ultrasound examination. All recurrences were detected during planned follow-up ultrasound examinations. Recurrent lesions were described using the terms and definitions of the International Ovarian Tumor Analysis (IOTA) group. Sixty-two patients had a serous BOT recurrence and six a mucinous BOT recurrence. All patients except one were premenopausal, 84% of them being < 40 years old. All but one patient were asymptomatic at diagnosis of the recurrence. Fertility-sparing surgery of the recurrent tumor was performed in 57/68 (84%) patients. The most frequent ultrasound feature of recurrent serous BOT was a unilocular solid cyst (49/62, 79%) and almost half of the recurrent serous BOTs (29/62, 47%) had multiple papillary projections. In 89% of the recurrent serous BOTs there was at least one papillation with irregular surface and in 73% there was at least one papillation vascularized at color Doppler examination. Recurrent mucinous BOTs appeared mainly as multilocular or multilocular solid cysts (5/6, 83%). Sonographic features of recurrent BOT resemble those described by others for different subtypes of primary BOT.

Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case–control studies

The majority of previous studies have observed an increased risk of mucinous ovarian tumors associated with cigarette smoking, but the association with other histological types is unclear. In a large pooled analysis, we examined the risk of epithelial ovarian cancer associated with multiple measures of cigarette smoking with a focus on characterizing risks according to tumor behavior and histology. We used data from 21 case-control studies of ovarian cancer (19,066 controls, 11,972 invasive and 2,752 borderline cases). Study-specific odds ratios (OR) and 95 % confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio using a random effects model. Current cigarette smoking increased the risk of invasive mucinous (OR = 1.31; 95 % CI: 1.03-1.65) and borderline mucinous ovarian tumors (OR = 1.83; 95 % CI: 1.39-2.41), while former smoking increased the risk of borderline serous ovarian tumors (OR = 1.30; 95 % CI: 1.12-1.50). For these histological types, consistent dose-response associations were observed. No convincing associations between smoking and risk of invasive serous and endometrioid ovarian cancer were observed, while our results provided some evidence of a decreased risk of invasive clear cell ovarian cancer. Our results revealed marked differences in the risk profiles of histological types of ovarian cancer with regard to cigarette smoking, although the magnitude of the observed associations was modest. Our findings, which may reflect different etiologies of the histological types, add to the fact that ovarian cancer is a heterogeneous disease.

DNA-Templated Silver Nanoclusters that Fluoresce upon Hybridization

DNA-templated silver nanoclusters (DNA/Ag NCs) are an emerging set of fluorophores that are smaller than semiconductor quantum dots and can have better photostability and brightness than commonly used organic dyes. Here we find the red fluorescence of DNA/Ag NCs can be enhanced 500-fold when placed in proximity to guanine-rich DNA sequences, termed enhancer sequences. On the basis of this new phenomenon, we have designed a DNA detection probe (NanoCluster Beacon, NCB) that “lights up” upon target binding. Since NCBs do not rely on Forster energy transfer for quenching, they can easily reach high (>100) signal-to-background ratios (S/B ratios) upon target binding. Here, in a separation-free assay, we demonstrate NCB detection of an influenza target with a S/B ratio of 175, a factor of 5 better than a conventional molecular beacon probe. In addition, we show the fluorescence emission color of a NCB can change substantially (a shift of 60-70 nm in the emission maximum) depending upon the alignment between the silver nanocluster and the DNA enhancer sequence. We have exploited this color shift to directly detect single nucleotide polymorphisms (SNPs). This SNP detection method has been validated on all single-nucleotide substitution scenarios in three synthetic DNA targets, in six disease-related SNP targets, and in two clinical samples taken from patients with ovarian serous borderline tumors. Since the observed fluorescence enhancement is caused by intrinsic nucleobases, our detection technique is simple, inexpensive, and compatible with commercial DNA synthesizers.

Survival of women with ovarian carcinomas and borderline tumors is not affected by estrogen and progesterone receptor status

ObjectiveTo examine the patterns of estrogen receptor (ER) and progesterone receptor (PR) expression in borderline ovarian tumors (BOTs) and ovarian carcinomas. We also assessed the disease-free survival (DFS) and overall survival (OS) in women with ovarian carcinoma, in relation to ER and/or PR expression.MethodsWe examined ER/PR expression in 38 BOTs and 172 ovarian carcinomas removed from patients treated at the State University of Campinas-UNICAMP (Brazil), from 1993 to 2008 and followed for up to 60 months using tissue microarray-based immunohistochemistry.ResultsTwenty-eight (73.7%) mucinous and 10 (26.3%) serous BOTs were included. Ovarian carcinomas consisted mainly of 79 (46.0%) serous, 44 (25.5%) mucinous, 17 (9.8%) endometrioid, 10 (5.8%) clear-cell types. There was no significant difference of the ER/PR expression between BOT and ovarian carcinoma (p=0.55 for ER alone, 0.90 for PR alone, and 0.12 for combined expression). The level of ER/PR expression in BOTs was significantly higher in serous than in mucinous tumors (p<0.01). In carcinomas, ER/PR was higher in serous tumors than in mucinous (p<0.01) and clear cell tumors (p=0.02), and higher in endometrioid tumors than in mucinous tumors (p<0.01). DFS was affected neither by the clinical characteristics nor by combined steroid receptor status. OS was found to be significantly worse (p<0.01) only in women with stages II-IV tumors and those with residual disease after surgery (p<0.01).ConclusionOverall, serous and endometrioid tumors were predominantly ER/PR positive, whereas mucinous and clear-cell tumors were preponderantly ER/PR negative. DFS and OS were not affected by ER/PR expression.

Assessment of the argyrophilic nucleolar organizer region area/nucleus ratio in ovarian serous epithelial adenomas, borderline tumors and cancers

IntroductionThere is a need to assess the value of the novel potentially useful biomarkers in ovarian tumors. The aim of study was to assess the value of sAgNOR analysis in ovarian serous epithelial tumors.Material and methodsThe analysis was performed in ovaries from 113 patients treated operatively due to serous ovarian tumors (30 adenomas, 14 borderline tumors and 69 cancers). After silver staining of paraffin specimens from surgery, sAgNOR in tumor cells was analyzed. Additionally, the value of the argyrophilic nucleolar organizer region area/nucleus ratio (sAgNOR) in the prediction of disease-free survival (DFS) and overall survival (OS) in 52 patients with serous ovarian cancer with complete follow-ups in November 2009 was evaluated. Age, grading, radicality of surgery and FIGO staging were analyzed as additional factors.ResultssAgNOR in adenomas, borderline tumors and cancers was in the following ranges: (0.73 ±0.23) × 106, (0.81 ±0.18) × 106 and (0.96 ±0.33) × 106 [AgNOR/cm2] respectively. In cancers from G1 to G3 sAgNOR was (1.02 ±0.32) × 106 (G1), (0.98 ±0.37) × 106 (G2) and (0.82 ±0.24) × 106 (G3) [AgNOR/cm2] respectively. In univariate analysis, but not in multivariate analysis, staging negatively correlated with better DFS and OS. sAgNOR, age of patients, grading and radicality of surgery were not associated with DFS or OS in either univariate or multivariate analysis.ConclusionssAgNOR analysis is not sufficient to precisely characterize cellular kinetics in serous ovarian tumors, and the analysis of sAgNOR, mAgNOR and pAgNOR should be performed commonly. The prognostic significance of sAgNOR in patients with serous ovarian cancer was not proven.

Ovarian Serous Borderline Tumor Identified in Endometrial Biopsy: A Case Report

Endometrial biopsies are useful for evaluating endometrial disease, but the presence of non-endometrial, noncervical tissue is rare and is typically restricted to metastasis to the endometrial cavity. We report, for the first time, a case of an endometrial biopsy seeded with serous cells in a young patient with a known history of a serous borderline tumor of the ovary. Given the patient’s diagnosis of an ovarian serous borderline tumor, the most likely explanation for the presence of serous cells in her endometrial biopsy is transit via the fallopian tube into the endometrial cavity. The morphologic and IHC profile of the cells from the endometrial biopsy were consistent with that of the ovarian tumor counterpart. The impact of this finding on tumor prognosis cannot be determined, and follow-up should be observed.

Fertility and borderline ovarian tumor: a systematic review of conservative management, risk of recurrence and alternative options

The aim of this systematic review was to evaluate the fertility outcome after borderline ovarian tumor (BOT) management and the results of conservative management, risk of recurrence and alternative options. The search strategy was based on relevant terms concerning BOT using Medline and the Central Cochrane Library. Both early and advanced stages of serous and mucinous BOT were included, but not rare entities such as endometrioid, Brenner or clear-cell BOT because of their low incidence. We considered all articles-case reports, original studies, meta-analyses and reviews-in English and French. Overall, 230 articles were screened of which 120 were retained for review. Most pregnancies were spontaneous but some data were obtained from studies analyzing the contribution of assisted reproductive technology (ART). However, not all studies differentiated spontaneous pregnancy from those obtained after fertility treatment including ovulation induction, intrauterine insemination and IVF. Conservative management of early stage BOT resulted in a pooled estimate for spontaneous pregnancy rate of 54% with a low risk of lethal recurrence (pooled estimate: 0.5%). In patients with advanced stage BOT, the spontaneous pregnancy rates was lower (34% in the single series reporting pregnancy rate in this context) and the risk of lethal recurrence increased (pooled estimate: 2%). This systematic review underlines that fertility subsequent to treatment of BOT depends mainly on histology and initial staging to distinguish early from advanced stages. In patients with advanced stage BOT, several alternative options to conservative management are available to allow patients to conceive without compromising their prognosis.

Detection of the BRAF V600E mutation in serous ovarian tumors: a comparative analysis of immunohistochemistry with a mutation-specific monoclonal antibody and allele-specific PCR

Mutations of components of the mitogen-activated protein kinase pathway, mainly BRAF, are common in serous ovarian borderline tumors, whereas high-grade serous ovarian carcinomas rarely show this feature. With the advent of specific kinase inhibitors active against BRAF-mutated cancers, rapid and sensitive detection of the BRAF V600E, by far the most common mutation of this gene, is of great practical relevance. Currently, BRAF mutations are detected by DNA-based techniques. Recently, a monoclonal antibody (VE1) specific for the BRAF V600E protein suitable for archival tissues has been described. In this study, we compared detection of the V600E mutation in serous ovarian tumors by VE1 immunostaining and by allele-specific polymerase chain reaction. All 141 cases of high-grade serous ovarian cancer showed negative or rarely weak, diffuse background VE1 immunostaining, and BRAF wild type was confirmed by molecular analysis in all tested cases. In contrast, 1 (14%) of 7 low-grade serous carcinomas and 22 (71%) of 31 serous borderline tumors revealed moderate to strong VE1 positivity. Immunostaining was clearly evaluable in all cases with sufficient tumor cells, and only rare cases with narrow cytoplasm were difficult to interpret. The V600E mutation was confirmed by allele-specific polymerase chain reaction and sequencing in all VE1-positive cases. Two VE1-positive cases with low epithelial cell content required repeat microdissection to confirm the presence of the mutation. Immunohistochemistry with the VE1 antibody is a specific and sensitive tool for detection of the BRAF V600E mutation in serous ovarian tumors and may provide a practical screening test, especially in tumor samples with low epithelial content.

Is MRI a useful tool to distinguish between serous and mucinous borderline ovarian tumours?

To analyse the morphological magnetic resonance imaging (MRI) features of borderline ovarian tumours (BOT) and to evaluate whether MRI can be used to distinguish serous from mucinous subtypes. A retrospective study of 72 patients who underwent BOT resection was undertaken. MRI images were reviewed blindly by two radiologists to assess MRI features: size, tumour type, grouped and irregular thickened septa, number of septa, loculi of different signal intensity, vegetations, solid portion, signal intensity of vegetations, normal ovarian parenchyma, and pelvic ascites. Statistical analysis was performed using Mann-Whitney and Fisher's exact tests. Logistic regression analysis was used to assess the predictive value of the MRI findings for histological subtypes. At histology, there were 33 serous BOT (SBOT) and 39 mucinous BOT (MBOT). Predictive MRI criteria for SBOT were bilaterality, predominantly solid tumour, and the presence of vegetations, especially exophytic or with a high T2 signal (p<0.01), whereas predictive MRI criteria for MBOT were multilocularity, number of septa, loculi of different signal intensity, and grouped and irregular thickened septa (p<0.01). Using multivariate analysis, vegetations were independently associated with SBOT [odds ratio (OR)=29.5] and multilocularity with MBOT (OR=3.9). Vegetations and multilocularity are two independent MRI features that can help to distinguish between SBOT and MBOT.

Conservative Laparoscopic Staging and Restaging Procedures for Bilateral Serous Tumors of the Ovaries with a Micropapillary Pattern: Case Report

Fertility-sparing surgeries may be considered for selected young women with serous borderline ovarian tumors (SBOT). However, the prognostic significance of SBOT with micropapillary pattern (SBOT-MP) is still uncertain. Among the rare cases reported, laparoscopy is not mentioned as a treatment option. We report the case of a nuligravida 40-year-old patient with bilateral complex adnexal tumors. A laparoscopic left oophoroplasty and right adnexectomy were performed after diagnosis of a bilateral SBOT in an intraoperative frozen section.

977P - Prognostic Factors after Conservative Treatment of a Large Series of "Stage I" Serous Borderline Ovarian Tumors

ABSTRACT Objectives The aim of this study was to evaluate the prognostic factors of recurrence after conservative treatment of a large series of “apparent” stage I serous borderline ovarian tumors (SBOT). Methods A review of 119 patients treated conservatively between 2000 and 2010 with data on the follow-up. All pathological slides were reviewed by the same expert pathologist. Prognostic factors of recurrences were studied (age, histologic subtypes, surgical procedures used … ). Results Conservative procedures were: unilateral cystectomy/UC (n = 43; 36%); unilateral salpingo-oophorectomy/USO (n = 50; 42%); bilateral cystectomy (n = 11; 9%) and USO + CC (n = 15; 13%). Fourteen patients underwent complete peritoneal staging. Stages distributions were: IA (n = 80; 67%); IB (n = 18; 15%) & IC (n = 21; 18%). Twenty-six patients had bilateral tumors. Respectively 21 (18%) & 13 (11%) had stromal microinvasion and/or micropapillary pattern. With a median follow-up of 45 months, 40 (33%) patients recurred (in whom 10 had peritoneal recurrence under the form of non invasive implants during the 1st recurrence). Two of these 40 recurrent patients had evolution in the form of invasive recurrence (during the 2nd or 3rd recurrence): 1 in remaining ovary & 1 in the peritoneum. None patient died from disease. Only 2 prognostic factors of recurrence were identified in multivariate analysis: the young age of the patients ( Conclusions In this series (representing the largest series reported of conservative management of stage I SBOT), the risk of recurrence is not related to the histologic patterns of the tumor (micropapillary, stromal microinvasion) nor to the surgical procedures used (type of conservative approach, the use of staging surgery, the use of laparoscopic approach). The rate of invasive recurrence is very rare in stage I SBOT (2 cases in this series). Young age ( Disclosure All authors have declared no conflicts of interest.

Advanced stage micropapillary serous borderline ovarian tumor in a postmenopausal woman: a case report

Serous borderline ovarian tumors (SBOT) generally occur in young women, present at early stages and are associated with an excellent prognosis. However, there are rare subtypes of SBOT which may exhibit a more aggressive course. In contrast with other types of SBOT, the micropapillary variant SBOT (SBOT-MP) tends to present at advanced stages. Herein, we present a rare case of a SBOT-MP that occurred in a 66-year-old woman, who had tumoral involvement on bilateral ovaries, sigmoid serosa and a positive peritoneal cytology. The currently recommended treatment options for these cases are also discussed.

Low-grade Serous Neoplasms of the Ovary With Transformation to High-grade Carcinomas

Ovarian borderline tumors usually occur in young patients and are associated with good clinical outcomes. A proportion of these tumors, particularly those with micropapillary features, may progress to low-grade serous carcinomas. Evolution of low-grade serous neoplasms to high-grade carcinomas is rare and infrequently reported. In this case report, we describe 3 cases of serous borderline tumor that progressed to high-grade carcinoma. Patient ages were 22, 35, and 47 yr. Two patients were initially diagnosed with ovarian serous borderline tumor, and recurred in the pelvis 3 and 10 yr later with sarcomatoid carcinoma. The third patient presented with low-grade serous carcinoma arising in a micropapillary serous borderline tumor, and recurred with a carcinosarcoma 3 yr later. All 3 patients had an aggressive clinical course: 2 died of disease and 1 patient has disease progression on chemotherapy. Occasional low-grade serous tumors of the ovary may transform to high-grade carcinomas, which can occur many years after initial diagnosis. The presence of a high-grade component significantly worsens patient outcomes.

Invasive recurrence of serous borderline ovarian tumor as multifocal lymphadenopathy 25 years after initial diagnosis

► We present the case with the latest reported recurrence of low malignant potential ovarian tumor. ► Borderline ovarian tumors have the potential for delayed recurrence that is not always salvageable surgically. ► Optimization of surveillance strategies and lifelong follow up is required for these patients.