Serous Borderline Tumors Research Articles

Malignant ovarian tumors (MOTs) and borderline ovarian tumors (BOTs) differ in treatment strategies and prognosis. However, accurate preoperative diagnosis remains challenging, and improving diagnostic accuracy is crucial. We developed and validated a system using artificial intelligence (AI) to integrate machine learning (ML) models based on blood test data and deep learning (DL) models based on magnetic resonance imaging (MRI) findings to distinguish between MOT and BOT. We analyzed 78 patients with malignant serous ovarian tumors and 31 with borderline serous ovarian tumors treated at our institution. A classification model was developed using ML for blood test data, and a DL model was constructed using MRI data. By integrating these models, we developed three fusion models as multimodal diagnostic AI and compared them with standalone models. The performance was evaluated using precision, recall, and accuracy. The classification model using Light Gradient Boosting Machine achieved an accuracy of 0.825, and the DL model using Visual Geometry Group 16-layer network achieved an accuracy of 0.722 for discriminating BOT from MOT. The intermediate, late, and dense fusion models achieved accuracies of 0.809, 0.776, and 0.825, respectively. Integrating multimodal information such as blood test and imaging data may enhance learning efficiency and improve diagnostic accuracy.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-21128-w.

The RAS-MEK-ERK pathway in low-grade serous ovarian cancer.

BackgroundFertility-sparing surgery (FSS) is commonly performed in patients with borderline ovarian tumors (BOT) due to their favorable prognosis. However, the long-term prognosis and pregnancy outcomes for these patients remain uncertain. This study aims to assess the feasibility of ovarian cystectomy (OC) and evaluate both oncologic and reproductive outcomes in BOT patients.MethodsA retrospective analysis of oncologic and reproductive outcomes was conducted on BOT patients who underwent OC at our department between July 1, 2007, and April 30, 2024, using univariate and multivariate analyses and survival curves.ResultsAmong 85 patients in the study, 12 experienced recurrence post-ovarian cystectomy. High-risk indicators included ultrasound findings, CA-125 levels, extent of surgery, and histological type. Of the 45 who attempted pregnancy, 38 conceived successfully, though no specific factors significantly influenced pregnancy outcomes. Among patients with micropapillary serous borderline ovarian tumors (MP-sBOT), 8 did not receive chemotherapy, while 6 did. Recurrence (2/8 vs. 1/6, p = 0.707) and fertility outcomes (1/8 vs. 2/6, p = 0.347) were not significantly different between those who received adjuvant chemotherapy and those who did not.ConclusionsOC is the preferred fertility-preserving treatment for BOT patients, with laparoscopic ovarian cystectomy recommended for most young, reproductive-aged patients. Early conception and close monitoring are advised for those with bilateral or high-risk tumors, though more research is needed on managing pregnancy-associated BOT.

BackgroundTubo-ovarian carcinoma, a leading cause of gynaecological-related mortality, holds substantial biological and clinical heterogeneity. Despite advancements in drug development, predicting therapeutic efficacy remains challenging, partly due to the limited availability of in vitro models that accurately replicate tumour behaviour. We present a concise overview of the intrahospital workflow for establishing patient-derived organoids and analyse the morphological and immunophenotypical features of high-grade serous carcinoma (HGSC), serous borderline tumour (SBT)/low-grade serous carcinoma (LGSC), and normal fallopian tube (FT) organoids.ResultsSamples were collected from patients undergoing surgery or paracentesis. Tissue underwent mechanical and enzymatical digestion. Resulting cell suspensions were resuspended in an extracellular matrix substitute for subsequent culture. Despite the low efficacy in establishing HGSC organoids (n = 1/7, 14%; 96 days, 11 passages), we successfully established two organoid lines of SBT/LGSC (n = 2/2, 100%; 65 days, 7 passages; 134 days, 16 passages) and normal FT (n = 2/2, 100%; 73 days, 10 passages; 58 days, 8 passages). HGSC organoids exhibited limited growth and mostly irregular structures, while preserving the p53 immunostaining pattern of the original tumour. SBT/LGSC and FT organoids maintained features of architectural complexity and faithfully recapitulated the original immunoprofile.ConclusionsThis study highlights the need for a multidisciplinary collaboration in both clinical and research settings to establish patient-derived organoids. It emphasises the pivotal contribution of pathologists in meticulous sampling and organoid characterisation. The integration of diverse expertise is essential for maximising the potential of organoids as preclinical tools, advancing our understanding of tubo-ovarian carcinoma, and ultimately improving patient outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13048-025-01766-4.

Spatial proteo-transcriptomic profiling reveals the molecular landscape of borderline ovarian tumors and their invasive progression.

Epithelial ovarian cancer (EOC) is the most frequent histological subtype of ovarian cancer, accounting for 95% of ovarian cancer. Radiologists are familiar with the imaging appearances of high-grade serous ovarian cancer (HGSOC) that accounts for about 70% of EOC. Low grade serous ovarian cancer (LGSOC) represents 2-5% of ovarian carcinomas and 5-10% of serous ovarian carcinoma. Historically, it was thought that LGSOC and HGSOC were a continuum. It is now clear that these are two completely separate entities. They have different molecular biology and clinical course. As a result of the low prevalence of LGSOC, there is limited data on its imaging findings. In this paper, we illustrate the pathology, molecular biology and treatment options of LGSOC. We present imaging appearances of LGSOC of primary tumor and metastasis in a cohort of 33 patients with pathologically-proven LGSOC. We also elucidate the differences between LGSOC and HGSOC. Since LGSOC often arise from serous borderline ovarian tumors (SBOT), we describe the imaging appearances of SBOT and highlight the differences between these two entities.

Abstract Background: Dickkopf-related protein 3 (DKK3) is regarded as a tumor suppressor in cancer tissue. DKK3 gene effect has an important role in the prognosis of ovarian cancer with the possibility to discover new line treatment in ovarian cancer. Many cancers of the uterus, cervix, colon, rectum, and pancreas show an association between decreased DKK3 protein and poor outcomes in these cancers. Objective: The study aims to evaluate the immunoreactive scores of DKK3 in all serous epithelial ovarian tumors (serous cystadenoma, serous borderline tumor, and invasive serous adenocarcinoma). Materials and Methods: A cross-sectional research was evaluated by immunohistochemistry, and involved 47 cases of ovarian serous tumor. DKK3 immunoreactive scoring resulted from multiplying the positive cells (mean percentage) by the staining intensity of the ovarian tissue. Therefore, the DKK3 expression score involves a 0 (undetected), 1+ (weakly positive), 2+ (moderately positive), and 3+ (intensely positive). Results: Of 47 patients, 12 (25.5%) had benign serous cystadenoma, 14 had (29.8%) serous borderline tumor, and 21 (44.7) had invasive serous adenocarcinoma. DKK3 immunoreactive score was significantly high in different types of ovarian tumors. Tumor ovarian locations were highly significant, in which unilateral tumor ovarian locations were mostly presented in serous borderline tumors 92.9% (13 of 14), whereas bilateral locations of ovarian tumors were more in invasive serous adenocarcinoma 71.4% (15 of 21). There is a significant positive correlation between the immunoreactive DKK3 score and ovarian neoplasms in benign serous cystadenoma, as well as a positive correlation between immunoreactive DKK3 score and the location of ovarian neoplasms in both serous borderline tumor and invasive serous adenocarcinoma. Conclusion: Serous ovarian tumors have a significant decrease in DKK3 protein expression, especially in serous borderline tumors and invasive serous adenocarcinoma. The DKK3 protein expression is affected by age groups, site location of tumor, and not affected by tumor size.

The aim of the study is to describe the subpopulations of CD4+, CD8+ T-lymphocytes of the greater omentum in serous borderline ovarian tumor. Materials and Methods. The immunohistochemical method was used to analyze the markers of CD4, CD8 T-lymphocytes in the greater omentum in 30 patients. In a research study, inclusion criteria were: the serous borderline ovarian tumor (with and without implants), surgeries for borderline ovarian tumor with omentectomy, age 20-45 years old. At the same time, severe concomitant diseases served as an exclusion criterion. The authors conducted morphometric assessment and analyzed images. STATISTICA 10 (StatSoft) program was used for statistical processing of the results. Results: Evaluation of CD4 and CD8 expression levels in the greater omentum demonstrated that it was higher in serous borderline tumor without implants compared to tumor with implants. Conclusion. The greater omentum is involved in immune reactions due to the T-lymphocyte population.

Serous borderline tumors of the testis and paratestis are rare, and experience with these neoplasms is limited. We report a series of 19 tumors, emphasizing their morphologic spectrum and clinical behavior. Eighteen tumors (95%) had conventional serous borderline tumor morphology identical to ovarian serous borderline tumors, and 1 case (5%) had a pattern resembling the epithelial subtype of noninvasive implants of serous borderline tumor. A component of micropapillary serous borderline tumor was present in 6 tumors (31%), including 1 that was exclusively micropapillary. Five tumors (26%) had associated autoimplants. Microinvasion was identified in 4 tumors (21%). One tumor had associated low-grade serous carcinoma, and 1 tumor had associated high-grade serous carcinoma. Immunohistochemical stains demonstrated diffuse expression of PAX8 in 12 of 12 (100%) cases. Estrogen receptor was diffusely positive in 11 of 12 (92%) cases and progesterone receptor was positive in 8 of 9 (89%) cases. D2-40 was negative in 7 of 9 (78%) cases and calretinin was negative in 11 of 11 cases (100%). Clinical follow-up data were available in 9 patients (47%) with pure serous borderline tumors, of which 4 had micropapillary features (44%), 3 had microinvasion (33%), and 2 had autoimplants (22%). None of these 9 patients experienced adverse outcomes related to serous borderline tumor over the follow-up period (mean: 94mo, median: 85mo, range: 17 to 204mo). Serous borderline tumors of the testis and paratestis are identical morphologically to their ovarian counterparts and can be associated with similar histologic phenomena (microinvasion, autoimplants, and micropapillary features). Although they can develop associated serous carcinoma, we conclude that serous borderline tumors of the testis and paratestis (when pure) appear to show indolent behavior.

Background/Objectives: According to recent reports, the BRAFV600E mutation in serous borderline tumors (SBTs) plays a protective role against progression to low-grade serous carcinoma through oncogene-induced senescence. One consequence of this is the appearance of eosinophilic cells (ECs). The aim of the current study was to determine the interobserver reproducibility of ECs and their predictive significance for the detection of the BRAFV600E mutation in SBTs. Methods: The study was conducted using 63 cases of ovarian SBTs. Three gynecological pathologists, blinded to each tumor’s mutation status, assessed the presence of ECs. Immunohistochemical staining with p16 and Ki-67 was performed to validate ECs. Mutational analysis was carried out using targeted NGS. Results: Genetic analysis revealed 30 BRAF-mutated, 1 NRAS-mutated, and 9 KRAS-mutated SBTs. ECs were identified by the majority of pathologists (two or three) in 78% of the BRAFV600E-mutated and 11% of the wild-type tumors with other mutations (p < 0.0001). The interobserver reproducibility of the presence of ECs was substantial (κ = 0.66). ECs validated with p16/Ki-67 were identified in 92.6% of the BRAFV600E-mutated and in 13.8% of the wild-type tumors with other mutations (p < 0.0001). For the ECs identified by the majority of pathologists, the sensitivity and specificity when predicting the BRAFV600E mutation were 77.8% and 88.9%, respectively. For the ECs validated with p16/Ki-67, the sensitivity and specificity when predicting the BRAFV600E mutation were 95.3% and 90.5%, respectively. Conclusions: Overall, these results suggest that ECs in SBTs have potential association with the BRAFV600E mutation.

Isolated nodal involvement in early-stage ovarian serous borderline tumor.

ObjectivesTo evaluate the effectiveness of habitat-based radiomics in differentiating early-stage serous borderline ovarian tumors (SBOTs) from serous malignant ovarian tumors (SMOTs), thereby enhancing diagnostic precision and treatment strategies.MethodsWe conducted a retrospective analysis of 210 patients with histopathologically confirmed SBOTs (n=95) and SMOTs (n=115) between December 2017 and February 2021. Multi-detector computed tomography images were obtained and analyzed using habitat-based radiomics, which segments tumors into distinct microenvironments based on Hounsfield Unit values. Clinical characteristics and imaging features were assessed, and predictive models were developed using logistic regression. Model performance was evaluated through receiver operating characteristic analysis, calibration curves, and decision curve analysis (DCA).ResultsThe habitat-based models, the Habitat2 and the combined model, demonstrated high area under the curve values of 0.960 and 0.957 in the training set, with similar performance observed in the validation set. Solid components of tumors were identified as key differentiators, with only one radiomics feature from cystic regions retained in the final model. DCA indicated that habitat-based models provided significant clinical utility.ConclusionsHabitat-based radiomics model was developed and validated for accurately preoperative differentiation between SBOTs and SMOTs, emphasizing the importance of solid tumor regions for accurate diagnosis.

Klippel-Trenaunay syndrome (KTS) is a rare overgrowth disorder characterized by capillary malformations, vascular anomalies, and limb length discrepancies. It is a congenital, mostly sporadic disorder with unknown pathogenesis, though recent studies have shown an association with somatic mosaic-activating mutations in the PIK3CA gene. The prognosis is variable, depending on the clinical presentation. Visceral involvement in KTS is rare, usually in the form of hemangiomas or venous malformations. Varied neoplastic pathologies have been reported in KTS; however, unlike other overgrowth syndromes, no clear association between KTS and malignancy has so far been elucidated. We report herein an account of a 2-yr-old female child with KTS who presented with abdominal distention and was diagnosed to have a serous borderline tumor (SBT) of bilateral fallopian tubes. Fallopian tube SBT is exceptionally rare and, to the best of our knowledge, has only been reported once previously in a premenarchal patient, who, incidentally, also had KTS. Bilateral fallopian tube involvement in a pediatric SBT has not been described hitherto.

TRPS1 expression in 451 tubo-ovarian tumours: a potential prognostic marker for high-grade serous carcinoma.

Tumor recurrence significantly impacts the quality of life and fertility of patients with serous borderline ovarian tumors (SBOT) and early-stage low-grade serous ovarian carcinoma (LGSOC). This study aims to characterize recurrence patterns, identify independent risk factors for recurrence, and develop a nomogram to predict recurrence-free survival (RFS). We conducted a retrospective case-control study to investigate recurrence in patients undergoing fertility-sparing surgery (FSS) and radical surgery (RS). Logistic regression and Cox regression were used to identify risk factors. Kaplan-Meier analysis was applied to evaluate RFS. A nomogram was developed based on identified variables to predict RFS. Tumor capsule disruption and micropapillary were associated with higher recurrence risk in the FSS group. Non-invasive implants were associated with higher recurrence risk in the RS group. The nomogram prediction model was developed based on identified risk factors. The area under the curve (AUC) for RFS predictions was 0.74 (95% CI: 0.62-0.85) at 3 years and 0.78 (95% CI: 0.67-0.89) at 5 years for the FSS group and 0.87 (95% CI: 0.76-0.98) at 3 years and 0.81 (95% CI: 0.65-0.97) at 5 years for the RS group. We identified the risk factors for recurrence of SBOT and early-stage LGSOC following FSS and RS procedures and developed a predictive model for forecasting RFS. This model provides valuable guidance for patients and clinicians in predicting recurrence risk for patients.

To define the diagnostic value of eosinophilic cells for the detection of BRAF-mutated serous borderline ovarian tumors. The study included 42 cases of serous borderline ovarian tumor, each of which was analyzed by 3 pathologists for the presence of eosinophilic cells. Genetic profiling using Sanger sequencing was performed to identify the BRAFV600E mutation. Comparisons between two groups were performed using the Mann-Whitney test, Fisher's exact test. Fleiss's kappa was used to assess the interobserver agreement. To assess the diagnostic value of eosinophilic cells, sensitivity and specificity were assessed. According to the results of a genetic study, the BRAFV600Emutation was found in 19 of 42 tumors. When analyzing interobserver agreement, the Fleiss's kappa values allowed us to determine the reliability of the test as sufficient (ϰ=0.7). The sensitivity and specificity for predicting BRAFV600Emutation for eosinophilic cells were 78.9% and 91.3%, respectively. Patients with the BRAFV600E mutation were significantly younger than patients without it. Thus, the average age of patients in the group with the BRAFV600E mutation was 33.6±15.6 years, while in the group of tumors without the mutation the average age of patients was 43.9±12.7 years (p=0.002). Non-invasive implants were less frequently found in tumors with the BRAFV600E mutation compared to tumors without the mutation: 11.76% (2/17) versus 33.3% (6/18), respectively, but these differences were not statistically significant (p=0.228). Eosinophilic cells in ovarian serous borderline tumors may sufficiently reflect the BRAFV600E mutation, thereby correlating with disease prognosis (low risk of progression to low-grade serous carcinoma).

BackgroundMesonephric-like adenocarcinoma (MLA) is a rare and aggressive tumor found in the uterus and ovaries, characterized by unique morphological and immunophenotypic features similar to mesonephric carcinoma. It has been suggested that some tumors of MLA may originate from Müllerian-type lesions.Tumor PresentationA 54-year-old woman presented with abdominal discomfort and adnexal mass. Laboratory results revealed elevated carcinoembryonic antigen and CA-125 levels. Surgical findings showed ovarian MLA arising within a serous borderline tumor (SBT) with metastasis to lymph nodes, classified as FIGO stage IIIA2.Pathological FindingsThe SBT component exhibited typical papillary architecture, while the MLA component showed admixture of various architectural patterns, with intraluminal eosinophilic secretions. Immunohistochemistry revealed positivity for GATA3, TTF-1, and CD10, and negativity for ER and WT1. Molecular analysis identified a KRAS p.G12D mutation, typical of MLA, and a SMAD4 mutation.ConclusionThis tumor represents the ninth documented example of ovarian carcinoma with distinct components of MLA and low-grade serous neoplasm, SBT or low-grade serous carcinoma, providing valuable insights into the clinicopathological features and molecular characteristics of MLA, and contributing to the understanding of its origin and clinical behavior.

Fertility results and oncologic outcomes in patients with stage II and III serous borderline ovarian tumors.

Aim: As intrinsic resistance - often driven by concurrent genomic alterations in tumor suppressor genes or oncogenes - remains a major challenge in oncology, this work aimed to comprehensively analyze BRAF somatic alterations across cancer types and identify new potential therapeutic strategies to overcome drug resistance. Methods: We conducted an extensive analysis of genomics, transcriptomics, and clinical data retrieved from public repositories, including cBioPortal. Our comprehensive analysis examined BRAF alterations [point mutations, structural variants (SVs) and copy number alteration] in more than 217,000 tumor samples across 120 distinct tumor types from primary and metastatic sites in both adult and pediatric cohorts, focusing on mutual exclusivity and co-occurrence of mutations in other oncogenes or tumor suppressors. The work also explores the association of BRAF somatic alterations with survival, clinical and molecular features. Results: Analysis of mutation frequencies across cancer types revealed that BRAFV600E represents approximately 90% of all BRAF alterations. While melanoma and thyroid carcinoma show the highest prevalence of BRAF mutations, followed by colorectal and non-small cell lung cancer in terms of absolute number of patients harboring BRAF mutations worldwide, notably high mutation frequencies were identified in rare malignancies, including hairy-cell leukemia, ganglioglioma, and serous borderline ovarian tumors. The comprehensive analysis of genomic profiling data across these tumors uncovered distinct patterns of co-occurring and mutually exclusive alterations in oncogenes and tumor suppressor genes, illuminating resistance mechanisms and suggesting novel therapeutic combinations. Conclusion: Comprehensive genomic profiling is critical for optimizing targeted therapy and overcoming drug resistance in BRAF-mutated cancers. The identification of co-occurring alterations provides opportunities for rational combination therapies, emphasizing the importance of detailed mutation profiling in developing effective treatment strategies across diverse cancer types.

Background: The aim of this study was to evaluate the serous borderline ovarian tumours (BOTs), the recurrence rates, and the factors affecting recurrence. Methods: A total of 165 patients diagnosed with serous BOT between 2004 and 2019 were included. The patients were evaluated in respect of age, preoperative CA125 levels, FIGO stage, tumour size, stromal micro-invasion, the presence of non-invasive implants, surgical procedures, and lymphadenectomy performed, or all that affects disease-free survival. Results: Early-stage BOT (stage I-II) was determined in 149 (90.3%) patients. Conservative surgery was performed in 57 (34.5%) patients. The non-invasive implantation was detected in 19 (11.5%) patients, and micro-invasion was determined in 31 (18.8%) patients. The median follow-up was 120 months, and recurrence was observed in 8 (4.8%) patients. The 5-year disease-free survival rate was 95.2%, and the 10-year disease-free survival rate was also 95.2%. Univariate analysis showed that elevated preoperative CA125 levels and the presence of micro-invasion were associated with poor disease-free survival outcomes. In the multivariate analysis, the presence of micro-invasion was the only independent poor prognostic factor (HR: 8.944, 95%CI: 2.060-38.833; p:0.003). Conclusions: The micro-invasion was the main factor for recurrence in patients with serous BOT.