Serous Borderline Ovarian Tumors Research Articles

Diagnostic extended usefulness of RMI: comparison of four risk of malignancy index in preoperative differentiation of borderline ovarian tumors and benign ovarian tumors

BackgroundThis study aimed to examine the performance of the four risk of malignancy index (RMI) in discriminating borderline ovarian tumors (BOTs) and benign ovarian masses in daily clinical practice.MethodsA total of 162 women with BOTs and 379 women with benign ovarian tumors diagnosed at the Second Affiliated Hospital of Harbin Medical University from January 2012 to December 2016 were enrolled in this retrospective study. Also, we classified these patients into serous borderline ovarian tumor (SBOT) and mucinous borderline ovarian tumor (MBOT) subgroup. Preoperative ultrasound findings, cancer antigen 125 (CA125) and menopausal status were reviewed. The area under the curve (AUC) of receiver operator characteristic curves (ROC) and performance indices of RMI I, RMI II, RMI III and RMI IV were calculated and compared for discrimination between benign ovarian tumors and BOTs.ResultsRMI I had the highest AUC (0.825, 95% CI: 0.790–0.856) among the four RMIs in BOTs group. Similar results were found in SBOT (0.839, 95% CI: 0.804–0.871) and MBOT (0.791, 95% CI: 0.749–0.829) subgroups. RMI I had the highest specificity among the BOTs group (87.6, 95% CI: 83.9–90.7%), SBOT (87.6, 95% CI: 83.9–90.7%) and MBOT group (87.6, 95% CI: 83.9–90.7%). RMI II scored the highest overall in terms of sensitivity among the BOTs group (69.75, 95% CI: 62.1–76.7%), SBOT (74.34, 95% CI: 65.3–82.1%) and MBOT (59.18, 95% CI: 44.2–73.0%) group.ConclusionCompared to other RMIs, RMI I was the best-performed method for differentiation of BOTs from benign ovarian tumors. At the same time, RMI I also performed best in the discrimination SBOT from benign ovarian tumors.

Outcomes of fertility-sparing surgery for stage II and III serous borderline ovarian tumors.

ObjectiveThis study was performed to assess the feasibility of conservative treatment for stage II or III serous borderline ovarian tumors (BOTs).MethodsTwenty-one patients were treated conservatively for advanced serous BOTs from 2006 to 2017. Two patients were lost to follow-up. The patients’ clinical status, surgical results, fertility results, and oncological outcomes were collected.ResultsThe patients’ median age at surgery was 28 years (range, 22–37 years). The median follow-up interval was 74 months (range, 16–214 months). Among the 19 patients who were followed up, 8 had stage II tumors and 11 had stage III tumors. Sixteen patients had noninvasive peritoneal implants. Two patients developed tumor metastasis to the fallopian tubes and one developed metastasis to the pelvic lymph nodes and omentum. The total recurrence rate was 26.3%. Seventeen (89.5%) patients were nulliparous. Four of 10 patients who wished to preserve their fertility obtained natural pregnancy. No patients died of their disease.ConclusionsThis study supports the efficacy of conservative treatment for advanced BOTs with respect to its favorable fertility result. The overall prognosis is not changed by conservative treatment.

New sonographic marker of borderline ovarian tumor: microcystic pattern of papillae and solid components.

To describe and evaluate the utility of a new sonographic microcystic pattern, which is typical of borderline ovarian tumor (BOT) papillary projections, solid component(s) and/or septa, as a new ultrasound marker that is capable of distinguishing BOT from other adnexal masses, and to present/obtain histologic confirmation. In this retrospective study, we identified women with a histologic diagnosis of BOT following surgical resection who had undergone preoperative transvaginal ultrasound (TVS) examination. All images were reviewed for presence or absence of thin-walled, fluid-filled cluster(s) of 1-3-mm cystic formations, associated with solid component(s), papillary projections and/or septa. From the same cases, histopathologic slides of each BOT were examined for presence of any of these microcystic features which had been identified on TVS. To confirm that the microcystic TVS pattern is unique to BOTs, we also selected randomly from our ultrasound and surgical database 20 cases of epithelial ovarian cancer and 20 cases of benign cystadenoma, for review by the same pathologists. To confirm the novelty of our findings, we searched PubMed for literature published in the English language between 2010 and 2018 to determine whether the association between microcystic tissue pattern and BOT has been described previously. Included in the final analysis were 62 patients (67 ovaries) with preoperative TVS and surgically confirmed BOT on pathologic examination. The mean patient age at surgery was 39.8 years. The mean BOT size at TVS was 60.7 mm. Of the 67 BOTs, 47 (70.1%) were serous, 15 (22.4%) were mucinous and five (7.5%) were seromucinous. We observed on TVS a microcystic pattern in the papillary projections, solid component(s) and/or septa in 60 (89.6%) of the 67 BOTs, including 46 (97.9%) of the 47 serous BOTs, 11 (73.3%) of the 15 mucinous BOTs and three (60.0%) of the five seromucinous BOTs. On microscopic evaluation, 60 (89.6%) of the 67 samples had characteristic 1-3-mm fluid-filled cysts similar to those seen on TVS. In seven cases there was a discrepancy between sonographic and histologic observation of a microcystic pattern. The 20 cystadenomas were mostly unilocular and/or multilocular and largely avascular. None of them or the 20 epithelial ovarian malignancies displayed microcystic characteristics, either on TVS or at histology. On review of 23 published articles in the English medical literature, containing 163 sonographic images of BOT, we found that, while all images contained it, there was no description of the microcystic tissue pattern. We report herein a novel sonographic marker of BOT, a 'microcystic pattern' of BOT papillary projections, solid component(s) and/or septa. This was seen in the majority of both serous and mucinous BOT cases. Importantly, based on comparison of sonographic images and histopathology of benign entities and malignancies, the microcystic appearance seems to be unique to BOTs. No similar description has been published previously. Utilization of this new marker should help to identify BOT correctly, discriminating it from ovarian cancer and benign ovarian pathology, and should ensure appropriate clinical and surgical management. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

PARAGON: A Phase II study of anastrozole in patients with estrogen receptor-positive recurrent/metastatic low-grade ovarian cancers and serous borderline ovarian tumors

ObjectiveTreatment options are limited for patients with recurrent/metastatic low-grade ovarian cancers (LGOCs) and serous borderline ovarian tumors (SBOTs) as response rates to chemotherapy are low. A subset of patients appears to derive clinical benefit from antiestrogens, but most studies have been retrospective and clinical benefit rates (CBR) remain uncertain. The primary aim of PARAGON was to prospectively investigate the CBR of anastrozole, an aromatase inhibitor, in patients with estrogen receptor (ER) and/or progesterone receptor (PR) positive LGOC and SBOT. MethodsPost-menopausal women with ER-positive and/or PR-positive recurrent/metastatic LGOCs and SBOTs and evaluable disease by RECIST v1.1 or GCIG CA125 criteria were treated with anastrozole 1 mg daily until progression or unacceptable toxicity. ResultsThirty-six patients were enrolled. Clinical benefit at 3 months (primary endpoint) was observed in 23 patients (64%, 95% CI 48%–78%) and was similar at 6 months (61%, 95% CI 43%–75%). The median duration of clinical benefit was 9.5 months (95% CI 8.3–25.8). Best study response was partial response by RECIST in 5 patients (14%), stable disease in 18 patients (50%) with progressive disease in 13 patients (36%). Median PFS was 11.1 months (95% CI 3.2–11.9). Anastrozole was well-tolerated. Patients with evidence of clinical benefit at 3 months reported less pain, fatigue, and improved physical and role functioning as early as 1 month of commencing treatment. ConclusionsAnastrozole was associated with a CBR of 61% of patients with recurrent ER-positive and/or PR-positive LGOC or SBOT for at least 6 months with acceptable toxicity.

Risk of ovarian cancer in women treated with ovarian stimulating drugs for infertility.

This is an updated version of the original Cochrane Review published in the Cochrane Library in 2013 (Issue 8) on the risk of ovarian cancer in women using infertility drugs when compared to the general population or to infertile women not treated. The link between fertility drugs and ovarian cancer remains controversial. To evaluate the risk of invasive ovarian cancer and borderline ovarian tumours in women treated with ovarian stimulating drugs for subfertility. The original review included published and unpublished observational studies from 1990 to February 2013. For this update, we extended the searches from February 2013 to November 2018; we evaluated the quality of the included studies and judged the certainty of evidence by using the GRADE approach. We have reported the results in a Summary of findings table to present effect sizes across all outcome types. In the original review and in this update, we searched for randomised controlled trials (RCTs) and non-randomised studies and case series including more than 30 participants. At least two review authors independently conducted eligibility and 'Risk of bias' assessments and extracted data. We grouped studies based on the fertility drug used for two outcomes: borderline ovarian tumours and invasive ovarian cancer. We conducted no meta-analyses due to expected methodological and clinical heterogeneity. We included 13 case-control and 24 cohort studies (an additional nine new cohort and two case-control studies), which included a total of 4,684,724 women.Two cohort studies reported an increased incidence of invasive ovarian cancer in exposed subfertile women compared with unexposed women. One reported a standardised incidence ratio (SIR) of 1.19 (95% confidence interval (CI) 0.54 to 2.25) based on 17 cancer cases. The other cohort study reported a hazard ratio (HR) of 1.93 (95% CI 1.18 to 3.18), and this risk was increased in women remaining nulligravid after using clomiphene citrate (HR 2.49, 95% CI 1.30 to 4.78) versus multiparous women (HR 1.52, 95% CI 0.67 to 3.42) (very low-certainty evidence). The slight increase in ovarian cancer risk among women having between one and three cycles of in vitro fertilisation (IVF) was reported, but this was not clinically significant (P = 0.18). There was no increase in risk of invasive ovarian cancer after use of infertility drugs in women with the BRCA mutation according to one cohort and one case-control study. The certainty of evidence as assessed using GRADE was very low.For borderline ovarian tumours, one cohort study reported increased risk in exposed women with an SIR of 3.61 (95% CI 1.45 to 7.44), and this risk was greater after treatment with clomiphene citrate (SIR 7.47, 95% CI 1.54 to 21.83) based on 12 cases. In another cohort study, the risk of a borderline ovarian tumour was increased, with an HR of 4.23 (95% CI 1.25 to 14.33), for subfertile women treated with IVF compared with a non-IVF-treated group with more than one year of follow-up. A large cohort reported increased risk of borderline ovarian tumours, with HR of 2.46 (95% CI 1.20 to 5.04), and this was based on 17 cases. A significant increase in serous borderline ovarian tumours was reported in one cohort study after the use of progesterone for more than four cycles (risk ratio (RR) 2.63, 95% CI 1.04 to 6.64). A case-control study reported increased risk after clomiphene citrate was taken, with an SIR of 2.5 (95% CI 1.3 to 4.5) based on 11 cases, and another reported an increase especially after human menopausal gonadotrophin was taken (odds ratio (OR) 9.38, 95% CI 1.66 to 52.08). Another study estimated an increased risk of borderline ovarian tumour, but this estimation was based on four cases with no control reporting use of fertility drugs. The certainty of evidence as assessed using GRADE was very low.However, although some studies suggested a slight increase in risks of ovarian cancer and borderline ovarian tumour, none provided moderate- or high-certainty evidence, as summarised in the GRADE tables. Since the last version of this review, only a few new relevant studies have provided additional findings with supporting evidence to suggest that infertility drugs may increase the risk of ovarian cancer slightly in subfertile women treated with infertility drugs when compared to the general population or to subfertile women not treated. The risk is slightly higher in nulliparous than in multiparous women treated with infertility drugs, and for borderline ovarian tumours. However, few studies have been conducted, the number of cancers is very small, and information on the dose or type of fertility drugs used is insufficient.

Fertility preservation, contraception and menopause hormone therapy in women treated for rare ovarian tumours: guidelines from the French national network dedicated to rare gynaecological cancers

IntroductionRare ovarian tumours include complex borderline ovarian tumours, sex-cord tumours, germ cell tumours and rare epithelial tumours. Indications and modalities of fertility preservation (FP), infertility management, contraindications for hormonal contraception or menopause hormone therapy are frequent issues in clinical practice. A panel of experts from the French national network dedicated to rare gynaecological cancers, and experts in reproductive medicine and gynaecology have built guidelines on FP, contraception and menopause hormone therapy in women treated for ovarian rare tumours. Material and methodsA panel of 35 experts from different specialties contributed to the preparation of the guidelines, following the DELPHI method (formal consensus method). Statements were drafted after a systematic literature review and then rated through two successive rounds. ResultsThirty-five recommendations were identified, concerning indications for FP, contraindications for ovarian stimulation, contraceptive options and menopause hormone therapy for each tumour type. DiscussionOverall, caution has been recommended in the case of potentially hormone-sensitive tumours such as sex-cord tumours, serous and endometrioid low-grade adenocarcinomas, as well as for high-risk serous borderline ovarian tumours. ConclusionIn the context of a scarce literature, a formal consensus method allowed the elaboration of guidelines, which will help clinicians in the management of these patients.

13. Prevention of Recurrent Mucinous Borderline Ovarian Tumor with Aromatase Inhibitor

Aromatase inhibitors (AIs) have been utilized for a number of estrogen-modulated conditions, including hormone-sensitive breast cancer, endometriosis and ovulation induction. Some borderline ovarian tumors (BOT) are estrogen-receptor positive, and case reports suggest the use of AIs in the prevention of recurrent serous BOT. We present a case of progression from mucinous cystadenoma to mucinous BOT after two prior cystectomies in whom an AI was used and the patient is now 2 years without recurrent disease.

Expression of zinc finger transcription factors (ZNF143 and ZNF281) in serous borderline ovarian tumors and low-grade ovarian cancers

Low-grade ovarian cancers represent up to 8% of all epithelial ovarian carcinomas (EOCs). Recent studies demonstrated that epithelial-mesenchymal transition (EMT) is crucial for the progression of EOCs. EMT plays a key role in cancer invasion, metastasis formation and chemotherapy resistance. An array of novel EMT transcription factors from the zinc finger protein family have been described recently, among them zinc finger protein 143 (ZNF143) and zinc finger protein 281 (ZNF281). The study included tissue specimens from 42 patients. Based on histopathological examination of surgical specimens, eight lesions were classified as serous borderline ovarian tumors (sBOTs) and 34 as low-grade EOCs. The proportions of the ovarian tumors that tested positively for ZNF143 and ZNF281 were 90 and 57%, respectively. No statistically significant differences were found in the expressions of ZNF143 and ZNF281 transcription factors in SBOTs and low-grade EOCs. Considering the expression patterns for ZNF143 and ZNF281 identified in this study, both sBOTs and low-grade EOCs might undergo a dynamic epithelial-mesenchymal interconversion. The lack of statistically significant differences in the expressions of the zinc finger proteins in sBOTs and low-grade serous EOCs might constitute an evidence for common origin of these two tumor types.

Tubal Origin of "Ovarian" Low-Grade Serous Carcinoma: A Gene Expression Profile Study.

Objective Ovarian low-grade serous carcinomas are thought to evolve in a stepwise fashion from ovarian epithelial inclusions, serous cystadenomas, and serous borderline tumors. Our previous study with clinicopathological approach showed that the majority ovarian epithelial inclusions are derived from the fallopian tubal epithelia rather than from ovarian surface epithelia. This study was designed to gain further insight into the cellular origin of ovarian low-grade serous carcinomas by differential gene expression profiling studies. Methods Gene expression profiles were studied in 43 samples including 11 ovarian low-grade serous carcinomas, 7 serous borderline tumors, 6 serous cystadenomas, 6 ovarian epithelial inclusions, 7 fallopian tubal epithelia, and 6 ovarian surface epithelia. Comprehensive analyses with hierarchical clustering, Rank-sum analysis and Pearson correlation tests were performed. Final validation was done on selected genes and corresponding proteins. Results The gene expression profiles distinguished ovarian low-grade serous carcinomas from ovarian surface epithelia, but not from fallopian tubal epithelia cells. Hierarchical clustering analysis showed ovarian serous tumors and ovarian epithelial inclusions were clustered closely in a branch, but separated from ovarian surface epithelia. The results were further validated by selected proteins of OVGP1, WT-1, and FOM3, which were highly expressed in the samples of the fallopian tube, ovarian epithelial inclusions, and ovarian serous tumors, but not in ovarian surface epithelia. The reverse was true for the protein expression patterns of ARX and FNC1. Conclusions This study provides evidence in a molecular level that ovarian low-grade serous carcinomas likely originate from the fallopian tube rather than from ovarian surface epithelia. Similar gene expression profiles among fallopian tube, ovarian epithelial inclusions, and serous tumors further support that ovarian low-grade serous carcinomas develop in a stepwise fashion. Such findings may have a significant implication for “ovarian” cancer-prevention strategies.

Assessing the landscape of ovarian serous borderline tumors.

To compare distinct clinicopathological features between atypical proliferative serous tumors and non-invasive low-grade ovarian serous carcinomas. Our study group comprised 203 cases of serous borderline tumors sub-classified as atypical proliferative serous tumors or as non-invasive low-grade serous carcinomas. All pathological features related to borderline tumors were re-evaluated by two gynecological pathologists. Data concerning recurrences and survival were retrieved from the medical records of the patients. When comparing atypical proliferative serous tumors to non-invasive low-grade serous carcinomas, the latter were statistically related to advanced stage at diagnosis, bilateral disease, exophytic pattern of growth, microinvasive carcinoma, and the presence of invasive implants. In univariate analysis, recurrences were statistically related to the exophytic pattern of growth, to microinvasion, and to the presence of implants (both invasive and non-invasive). Nevertheless, in multivariate analysis, only microinvasion and the presence of invasive implants were related to recurrence. Women who eventually succumbed to the disease were only those with invasive implants. Their ovarian tumor was either a non-invasive low-grade serous carcinoma or an atypical proliferative serous tumor with 'minimal' micropapillary pattern. Neither lymph node involvement nor endosalpingiosis seemed to influence the course of the disease. The results of our study underline the increased possibility of non-invasive low-grade serous carcinomas to be related with features indicative of aggressive behavior as opposed to atypical proliferative serous tumors. Nevertheless, irrespective of tumor histology, the presence of invasive implants and microinvasion were the only independent prognostications of recurrence.

A rat model of serous borderline ovarian tumors induced by 7,12-dimethylbenz[a]anthracene.

Serous borderline ovarian tumors (SBOTs) behave between benign cystadenomas and carcinomas, and the effective detection and clinical management of SBOTs remain clinical challenges. Because it is difficult to isolate and enrich borderline tumor cells, a borderline animal model is in need. 7,12-dimethylbenz[a]anthracene (DMBA) is capable of inducing the initiation, promotion, and progression of serous ovarian tumors. This study aims to investigate the proper dosage and induction time of DMBA for rat models of SBOTs, and explore their morphological features demonstrated by magnetic resonance (MR) imaging and molecular genetic characteristics. Rats were randomly divided into six groups (1 mg/70 D, 2 mg/70 D, 3 mg/70 D, 2 mg/50 D, 2 mg/90 D, and 2 mg/110 D). The 3 mg/70 D group induced the most SBOTs (50.0%, 12/24). The micropapillary projections were shown on MR imaging, which was the characteristic of SBOTs. The Cyclin D1 characterizing an early pathogenetic event strongly expressed in induced serous benign tumors (SBTs). The immunoreactivity staining scores of P53 expression significantly increased from SBTs, SBOTs to serous ovarian carcinomas (SCAs), which elucidate that P53 might be a promising biomarker to grade serous ovarian tumors. Based on morphological and molecular genetic similarities, this rodent SBOT model was suitable for investigating the pathogenesis of serous ovarian tumors and developing an early detection strategy.

RETROSPECTIVE ANALYSIS OF BORDERLINE OVARIAN TUMORS: OUTCOMES AT A SINGLE CENTER.

SUMMARYWe wanted to discuss our experiences in the approach to borderline ovarian tumors, which constitute a group different from epithelial ovarian tumors with respect to their biological structure in line with retrospective information gathered from our cases. A total of 25 patients operated on for the indication of adnexal masses diagnosed as borderline ovarian tumors based on frozen section results were included in our study. Patient age, tumor diameter, tumor markers and surgeries performed were discussed in the light of the literature. Statistical analyses were performed using the SPSS software. The patient mean age was 43.84±11.34 years. The mass was localized in the right (n=13), left (n=11) or both (n=1) adnexal regions. The mean tumor diameter was 12.9±5.84 cm. Histopathologic examination established the diagnosis of serous borderline (n=14 patients) and mucinous borderline (n=11) ovarian tumors. Although the results of our study are consistent with current literature data, a greater number of current studies should be performed on borderline ovarian tumors, which are defined as a class of tumors different from epithelial ovarian tumors.

A study detection of the ROS1 gene fusion by FISH and ROS1 protein expression by IHC methods in patients with ovarian malignant or borderline serous tumors

ObjectiveROS1 is an orphan receptor protein tyrosine kinase which is supposed to undergo genetic rearrangement in carcinogenesis. In the current study, we aimed to investigate the frequency and clinicopathologic features associated with ROS1 gene fusion and ROS1 protein expression in patients with ovarian serous carcinoma or serous borderline tumors. Materials and methodsTissue samples of 102 patients with high or low grade serous carcinoma and borderline serous tumors were selected randomly from the archives of Department of Gyneco-pathology, and analyzed for ROS1 gene expression. (Fluorescence in situ hybridization (FISH) method was used to assess ROS1 gene rearrangement, while ROS1 protein expression was analyzed using immunohistochemistry. ResultsThe study consisted of 94 cases of high-grade serous carcinoma (92.1%), 2 cases of low-grade serous carcinoma (%2) and 6 cases of serous borderline tumor (5.9%). ROS1 gene rearrangement analysis revealed that 4 patients (3.9%) were FISH-positive; whereas the immunohistochemical analysis yielded only 1 patient (0.9%) exhibiting faint positive expression of ROS1 protein. Given the low incidences of ROS1 gene rearrangement and protein expression, their relationships with clinicopathologic parameters could not be statistically analyzed. ConclusionAlthough rare, patients with ovarian serous carcinoma or serous borderline tumor may exhibit ROS1 gene rearrangement and ROS1 protein expression. Further large-scale studies are necessary to explore the clinicopathologic significance of ROS1 gene expression in ovarian serous carcinoma.

BRAFV600E mutations and immunohistochemical expression of VE1 protein in low-grade serous neoplasms of the ovary.

The most common BRAF mutation in ovarian low-grade serous neoplasms (LGSNs) involves substitution of valine by glutamic acid at position 600 (V600E). Small studies have demonstrated high specificity of immunohistochemistry with mutation-specific monoclonal antibody VE1. We sought to investigate the expression of VE1 protein in LGSNs and its correlation with BRAF mutation-associated histological features and BRAF mutation status. We reviewed pathology reports and available slides from ovarian serous borderline tumours (SBTs) and low-grade serous carcinomas (LGSCs) diagnosed between 2000 and 2012. VE1 immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections. Tumours with ≥50% positive cells were considered positive. Of 121 LGSNs, there were 73 SBTs, eight SBTs with micropapillary features (mpSBT) and 40 LGSCs (22 primary, 18 metastatic). VE1 was positive in 52% (38 of 73) of SBTs and 9% (two of 22) of primary LGSCs, and in none of the mpSBTs and metastatic LGSCs (P<0.0001). Of 76 tumours with known mutation status, 42 (55%) harboured mutations, including BRAFV600E (26, 34%), KRASG12D (eight, 11%), and KRASG12V (eight, 11%). BRAFV600E mutations were present in 48% (25 of 52) of SBTs and 5% (one of 22) of LGSCs (P<0.0001). VE1 was positive in 96% (25 of 26) of BRAFV600E -mutated tumours and correlated with BRAF mutation-associated histological features (P<0.0001). BRAFV600E mutations are significantly more common in SBTs than in LGSCs. Immunohistochemical expression of VE1 protein is associated strongly with BRAFV600E mutation and BRAF mutation-associated histological features. VE1 immunohistochemistry is a reliable method for the detection of BRAFV600E mutations.

Ovarian serous surface papillary borderline tumor: characteristic imaging features with clinicopathological correlation.

To retrospectively evaluate the clinical, pathological, and imaging features of ovarian serous surface papillary borderline tumors (SSPBTs). Imaging features were analyzed, including the tumor size, laterality, tumor spread and the presence of ascites. Morphological nature (encased normal ovary, characteristics on MRI) and contrast enhancement (increased flow on Doppler ultrasound) were also evaluated. Clinical and pathological features, such as tumor markers (CA 125), treatment methods, outcomes on follow-up, and surgical staging, were analyzed. 10 tumors in 5 patients were evaluated. Mean largest tumor diameter was 45 mm. All patients had bilateral involvement and ascites. 40% of all patients showed peritoneal implants. 20% of patients evaluated had lymph node metastasis. These patients showed grossly normal ovaries that were encased in or surrounded by irregular solid tumors. They had a mostly hyperintense papillary architecture with hypointense internal branching on T2weighted MR images (90%). Contrast enhancement and serum levels of CA 125 were elevated in all cases evaluated. All patients underwent radical surgery, and 80% of patients evaluated were of low stage. No recurrence occurred, during follow-up. SSPBT of the ovary, which has a good prognosis, should be considered as a diagnosis for patients who have bilateral enhancing irregular solid masses with papillary architecture and internal branching, and encasing normal-appearing ovaries. Advances in knowledge: Serous surface papillary borderline tumor of the ovary is unique and has characteristic features. Knowledge of this specific ovarian tumor and radiological suspicion can have important implications for the patient to facilitate management including fertility-preserving surgery.

Expression of selected epithelial-mesenchymal transition transcription factors in serous borderline ovarian tumors and type I ovarian cancers.

Epithelial ovarian neoplasms are a heterogeneous group including tumor subsets with distinct clinicopathologic and molecular features. Recent evidence from molecular and genomic studies suggests that whereas low-grade serous carcinomas and high-grade serous carcinomas likely develop on two separate pathways, the low-grade serous carcinomas and serous borderline ovarian tumors may represent various stages of the same developmental continuum. The transformation of borderline ovarian tumors into an invasive neoplasm is associated with an array of molecular changes, inter alia controlled by p53 and PI3K/Akt pathway, as well as with a decrease in E-cadherin expression. The latter implies that epithelial-mesenchymal transition is a critical determinant of borderline ovarian tumor invasiveness. The aim of this study was to analyze the expression of transcription factors involved in epithelial-mesenchymal transition: SNAIL, SLUG, TWIST 1, TWIST 2, ZEB 1, and ZEB 2 in borderline tumors and type I ovarian cancers. The study included tissue specimens from 42 patients with histopathologically verified ovarian masses. The expressions for SLUG, TWIST 1, ZEB1, and ZEB 2 were scored based on the nuclear staining, and the expressions of SNAIL and TWIST 2 based on the cytoplasmic and/or nuclear staining. The proportions of ovarian tumors with the immunoexpression of the epithelial-mesenchymal transition transcription factors were 85.7% for SNAIL, 100% for SLUG, 9.5% for TWIST 1, 95.2% for TWIST 2, 23.8% for ZEB 1, and 0% for ZEB 2. The expression patterns of SNAIL, SLUG, TWIST, and ZEB identified in this study suggest that both serous borderline ovarian tumors and type I ovarian cancers undergo dynamic epithelial-mesenchymal interconversions. Our findings obtained in the two groups of tumors which shared some etiopathogenic pathways imply that the expression of the epithelial-mesenchymal transition transcription factors may be activated at early stages of the epithelial-mesenchymal transition, and thus these molecules may play a pivotal role in the development of both serous borderline ovarian tumors and type I ovarian cancer.

Mucosal Proliferations in Completely Examined Fallopian Tubes Accompanying Ovarian Low-grade Serous Tumors: Neoplastic Precursor Lesions or Normal Variants of Benign Mucosa?

Malignant transformation of the fallopian tube mucosa, followed by exfoliation of malignant cells onto ovarian and/or peritoneal surfaces, has been implicated as the origin of most pelvic high-grade serous carcinoma. Whether a parallel pathway exists for pelvic low-grade serous tumors [ovarian serous borderline tumor (SBT) and low-grade serous carcinoma (LGSC)] remains to be fully elucidated. The literature is challenging to interpret due to variation in the diagnostic criteria and terminology for cytologically low-grade proliferations of the fallopian tube mucosa, as well as variation in fallopian tube specimen sampling. Recently, a candidate fallopian tube precursor to ovarian SBT, so-called papillary tubal hyperplasia, was described in advanced stage patients. The current study was designed to identify fallopian tube mucosal proliferations unique to patients with low-grade serous ovarian tumors (serous cystadenoma, SBT, LGSC) and to determine if they may represent precursors to the ovarian tumors. Fallopian tubes were thinly sliced and entirely examined microscopically, including all of the fimbriated and nonfimbriated portions of the tubes, from patients with ovarian serous cystadenoma (35), SBT (61), and LGSC (11) and from a control population of patients with ovarian mucinous cystadenoma (28), mature cystic teratoma (18) or uterine leiomyoma (14). The slides of the fallopian tubes were examined in randomized order, without knowledge of the clinical history or findings in the ovaries or other organs. Alterations of the mucosa of the fallopian tube were classified as type 1: nonpapillary proliferation of cytologically bland tubal epithelium exhibiting crowding, stratification, and/or tufting without papillary fibrovascular cores or as type 2: papillary alterations consisting of a fibrovascular core lined by a cytologically bland layer of tubal epithelium. A third abnormality, type 3, consisted of detached intraluminal papillae, buds, or nests of epithelium that cytologically resembled the epithelial component of SBT or LGSC. Mucosal proliferations were identified in subsets of all populations, including the control populations. Overall, type 1 proliferations were in 28% to 61% of all patients and type 2 alterations in 4% to 16%. There was no statistically significant difference in the incidence of type 1 or type 2 proliferations between the class of ovarian serous tumors (benign, SBT, LGSC), between early and advanced stage SBT, or between patients with any ovarian serous tumor and the control population of nonserous diagnoses. Type 3 alterations were only identified in patients with advanced stage SBT/LGSC and not in any early stage SBT or cystadenoma. These findings suggest that type 3 alterations floating in the fallopian tube lumen represent exfoliation of tumor cells from ovarian and/or peritoneal origin. Our study did not identify a mucosal-based proliferation of the fallopian tubes that was specific to ovarian low-grade serous tumors. Cytologically bland mucosal proliferations appear to be common in fallopian tubes from patients of all ages and unrelated to ovarian tumorigenesis. A consensus on diagnostic criteria and terminology for these types of proliferations is needed, as well as further study into their etiology, including possible association with hormonal environment.

Clinical Predictors of Recurrence and Prognostic Value of Lymph Node Involvement in the Serous Borderline Ovarian Tumor.

This study was aimed to evaluate the risk factors of recurrence and the value of nodal involvement in patients with serous borderline ovarian tumors (SBOT). Two hundred twenty-five patients who underwent surgery and were diagnosed with SBOT were retrospectively studied. Univariate and multivariate analyses were used to assess the risk factors for recurrence. Patients' clinical pathologic characteristics were compared between the patients who presented lymph node involvement and those who did not. The significant values of lymph condition influencing 5-year disease-free survival were also evaluated by statistical analysis. Both univariate and multivariate analyses showed that risk factors for recurrence were micropapillary (P = 0.021), fertility-preserving surgery (P = 0.014), and laparoscopic approach (P = 0.009). Of these 112 patients on whom lymphadenectomy was performed, 17 cases showed lymph node positive, whereas the remaining 95 patients did not. Significant differences in terms of lymph node numbers (P < 0.0001), invasive implant (P = 0.022), and International Federation of Gynecology and Obstetrics staging (P < 0.0001) were observed between the 2 groups of lymphatic node involved or not. Kaplan-Meier curves of 5-year disease-free survival revealed that there were no significant differences either between groups of lymphatic node involved or not (P = 0.778) and groups of removed nodes whether more than 10 or not (P = 0.549). Micropapillary, fertility-preserving, and laparoscopic approach were factors significantly affecting the recurrence of SBOT by both univariate and multivariate analysis. Lymph node metastasis did not seem to be correlated to a worse prognosis of SBOT.

MRI appearance of ovarian serous borderline tumors of the micropapillary type compared to that of typical ovarian serous borderline tumors: radiologic-pathologic correlation

BackgroundSerous borderline tumor (SBT) of the micropapillary type (SBT-MP) became one of the major pathological SBT diagnoses in addition to typical SBT, and was also defined as “non-invasive” low-gradeserous carcinoma according to the World Health Organization (WHO) classification in 2014. In this study, we investigated the MRI appearance of SBT-MP compared to that of typical SBT in order to identify specific imaging features of SBT-MP that correspond to pathological findings.MethodsMR images of 6 histologically proven ovarian SBT-MP in four patients and 14 typical SBT in ten patients were reviewed retrospectively. Images were evaluated for laterality, size and morphology of the lesion and the solid component (SC) and signal intensity (SI) of the SC. MRI findings were correlated with pathological findings.ResultsThe patients with SBT-MP (mean 26.3 years) were younger than those with typical SBT (mean 44.5 years). Postoperative staging in patients with SBT-MP was II in two and III in two cases, while staging for typical SBT was I in seven, II in one and III in two cases. The morphologic patterns of SBT-MP were a unilateral cystic mass with intracystic mural nodules (CwMN) (n = 2), bilateral solid papillary masses (SM), and bilateral SM with CwMN. The pattern of typical SBT was CwMN (n = 13) in all but one lesion (SM with CwMN). All SCs showed inhomogeneous slight hyperintensity on T2 weighted images (WI) and high SI on diffusion-WI (DWI) except for in one typical SBT. Although diffuse proliferation of the tumor cells in micropapillary projections with little stroma seemed to correspond to inhomogeneous slightly hyperintense foci in SC on T2WI and high SI on DWI, similar MR findings were observed in typical SBT in all lesions on T2WI and 11 of 12 lesions on DWI. In typical SBT, inhomogeneous slightly hyperintense foci in SC on T2WI and high SI on DWI corresponded to highly cellular foci with densely branched papillae.ConclusionPathological findings and clinical behavior of SBT-MP differed from those of typical SBT, but morphology and SI of SC on MRI were similar, with papillary projections demonstrating inhomogeneous slight hyperintensity on T2WI and high SI on DWI.

EGFR Immunoexpression in Malignant Serous and Mucinous Ovarian Tumors.

The epithelial growth factor receptor (EGFR) is involved in various stages of cancer growth such as tumor initiation, angiogenesis and metastasis, being an attractive target for oncogenic therapy. The present study aims to evaluate the EGFR expression in 54 cases of serous and mucinous ovarian borderline tumors and carcinomas. EGFR expression was present in more than half of the investigated tumors, more frequently in carcinomas than in borderline tumors, especially in the serous type. The highest values of the final staining score (FSS) were observed only in serous carcinomas in the advanced stages of the disease. As a result of frequent expression of EGFR in ovarian tumors, it is necessary to monitor EGFR inhibitors for ovarian cancer therapy, but probably after establishing more rigorous selection and stratification criteria for patients.