Frontiers in Oncology

Case Report: Primary solid pseudopapillary neoplasm of the ovary with “cholesteroma-like” denaturation

Solid pseudopapillary neoplasms (SPNs) primarily arise in the pancreas and are uncommon in the ovaries. Here, we present a case of ovarian-origin SPN. Alongside the typical solid and pseudopapillary structures, “cholesteroma-like” denaturation areas and tissue degeneration regions are also observed. Immunohistochemistry analysis demonstrates positive results for β-catenin (nucleus), CD99 (dot-like), CD56, and vimentin. Imaging studies rule out pancreatic or other origins. This study aims to enhance comprehension, diagnosis, and differential diagnosis of primary ovarian SPN among pathologists and clinicians, as well as to investigate the origin and management of primary solid pseudopapillary tumors in the ovary.

Spatial and temporal trend analysis of the burden of endocrine-related cancers among women of reproductive age in the Asia-Pacific region from 1990 to 2021: results based on the GBD study

Background Endocrine-related cancers pose an escalating challenge for reproductive-age women in the Asia-Pacific region, characterized by persistent socioeconomic disparities. Methods Using data from the Global Burden of Disease Study 2021, we analyzed the incidence, mortality, and DALYs of breast, ovarian, and thyroid cancers across 15 countries (1990–2021). Trends were quantified using EAPC, and mortality trajectories through 2050 were projected using GAM. Results Breast cancer exhibited a polarized pattern: mortality steadily declined in High-SDI nations but surged in Low-SDI regions. Thyroid cancer revealed a dichotomy of screening-driven overdiagnosis in High-SDI settings versus high lethality in Low-SDI areas. Ovarian cancer maintained the poorest prognosis in resource-limited settings. Crucially, primary risk drivers are shifting from traditional behavioral factors to metabolic factors. Conclusion With disparities projected to widen by 2050, stratified interventions are urgent. We recommend screening de-escalation for High-SDI nations and resource-adapted measures for Low-to-Middle SDI nations to bridge the growing equity gap. reproductive-age women.

Case Report: An incidentally discovered HPV-associated endocervical adenocarcinoma presenting as pseudomyxoma peritonei

This case report describes a 48-year-old woman with occult HPV-associated endocervical adenocarcinoma (Silva pattern B) presenting as bilateral ovarian metastases and pseudomyxoma peritonei–like gelatinous ascites, despite normal cervical morphology and resolved HPV type 45 infection. Initial misdiagnosis as primary ovarian mucinous carcinoma was revised based on histopathology and immunohistochemistry (diffuse p16 positivity, ER-negative and PR-negative, Ki-67 index of 95%), confirming metastatic endocervical adenocarcinoma. The absence of appendiceal lesions excluded true PMP, attributing ascites to tumor mucin secretion. This case highlights the diagnostic challenges of occult cervical adenocarcinoma mimicking PMP and underscores the critical role of immunohistochemical profiling (p16, PAX8, WT1) to differentiate metastatic from primary ovarian tumors. The study emphasizes a multidisciplinary approach for accurate classification of mucinous neoplasms and raises awareness of rare metastatic pathways, such as transtubal dissemination, in HPV-associated cervical adenocarcinoma.

Uterine tumors resembling ovarian sex cord tumors: rare case report and literature review

Uterine tumors resembling ovarian sex-cord tumors (UTROSCT) are rare mesenchymal neoplasms with low malignant potential and polyphenotypic immunoprofiles. A 38-year-old nullipara presented with menorrhagia; trans-vaginal ultrasound revealed a 26-mm, richly vascular submucosal mass. Complete hysteroscopic excision was achieved without residual disease. Microscopy showed anastomosing cords, hollow tubules and bland spindled cells (0–1 mitosis/10 HPF). Immunohistochemistry demonstrated diffuse AE1/3, CD56, WT-1 and synaptophysin positivity, while inhibin-α, calretinin and ER/PR were negative; desmin highlighted entrapped myometrium. Ki-67 index was ~5%. Break-apart FISH and next-generation sequencing (141-gene solid-tumor panel) disclosed no pathogenic fusions involving ESR1, GREB1, NCOA2/3 or NR4A3, nor mutations in TP53, BRCA1/2 or mismatch-repair genes, consistent with the fusion-negative UTROSCT subset (~30–45% of cases). At 20 months the patient is disease-free with regular menses and intact fertility. We review diagnostic clues, differential diagnoses, molecular taxonomy and fertility-sparing strategies, underscoring the value of comprehensive genomic profiling for accurate classification and prognostication of this uncommon uterine tumor.

Case report: High grade serous fallopian tube carcinoma with rare NRG1 gene fusion presenting as widespread peritoneal carcinomatosis

The discovery of gene fusions involving Neuregulin-1 (NRG1) within solid tumors has important therapeutic implications, as they are being actively explored as targets for emerging ERBB/ERBB2/ERBB3-directed anti-cancer agents. NRG1 fusions are very uncommon across all tumor types and are infrequently documented in the medical literature. We report a female patient presenting with widespread peritoneal carcinomatosis diagnosed as high grade serous fallopian tube carcinoma, which harbored a previously undescribed MYH10::NRG1 fusion. Moreover, we queried the whole transcriptome sequencing results of neoplasms analyzed by a commercial laboratory (Caris Life Sciences) to determine the overall incidence of NRG1 fusions in carcinomas of the ovary, fallopian tube, and peritoneum (0.18%). Twenty-five additional tumors were found to demonstrate NRG1 fusions, including 20 new genes partners that had not been previously identified in gynecologic carcinomas. Overall, NRG1 fusion events are rare in ovarian, fallopian tube, and primary peritoneal carcinomas, but they may carry diagnostic significance in the context of borderline/low grade serous tumors, which demonstrated exclusively CLU::NRG1 fusions, and could have important predictive implications for response to ERBB/ERBB2/ERBB3-directed therapies.

Laparoscopic resection of a giant post-mesenteric ovarian seromucinous cystadenoma: a case report and review

BackgroundOvarian seromucinous tumors represent a rare subclass of ovarian neoplasms. While the majority of these tumors are benign, the potential for malignant transformation persists and should be considered. To enhance patient outcome and mitigate the risk, early detection and timely intervention are paramount. In cases involving large or complex ovarian masses, open surgery is often the preferred approach, as it provides superior access for comprehensive tumor resection and enables immediate histopathological evaluation. Nevertheless, with advancements in laparoscopic techniques, single-port laparoscopic surgery has emerged as a viable alternative for patients. This approach not only demonstrates comparable effectiveness but also offers the benefits of expedited recovery and reduced scarring.Case reportA 65-year-old female presented with a seven-month history of abdominal distension, a sensation of fullness beneath the xiphoid, left-sided discomfort, and intermittent morning cramping. Laboratory findings revealed a mild elevation in CA-125 to 46 U/mL, and CT imaging suggested a diagnosis of an ovarian cystadenoma or possibly a retroperitoneal mass. Preoperative assessment was challenging due to the tumor’s irregular morphology, substantial size, and its adhesions to surrounding pelvic and abdominal structures, making it difficult to precisely determine its origin. In light of these complexities, a single-port laparoscopic approach was chosen to minimize trauma, allow for more precise handling of the tumor, and reduce the risk of cystic fluid leakage or inadvertent dissemination of the tumor. Postoperative pathological examination confirmed the lesion to be a seromucinous ovarian cystadenoma.ConclusionThis case exemplifies the imperative for a multidisciplinary approach in the diagnosis and treatment of ovarian seromucinous tumors, emphasizing the advantages of minimally invasive surgical techniques. Given the rarity of such tumors, it is essential that ongoing research into the pathogenesis, classification, and treatment strategies be prioritized to enhance patient outcomes.

Research progress in endometriosis-associated ovarian cancer

Endometriosis-associated ovarian cancer (EAOC) is a unique subtype of ovarian malignant tumor originating from endometriosis (EMS) malignant transformation, which has gradually become one of the hot topics in clinical and basic research in recent years. According to clinicopathological and epidemiological findings, precancerous lesions of ovarian clear cell carcinoma (OCCC) and ovarian endometrioid carcinoma (OEC) are considered as EMS. Given the large number of patients with endometriosis and its long time window for malignant transformation, sufficient attention should be paid to EAOC. At present, the pathogenesis of EAOC has not been clarified, no reliable biomarkers have been found in the diagnosis, and there is still a lack of basis and targets for stratified management and precise treatment in the treatment. At the same time, due to the long medical history of patients, the fast growth rate of cancer cells, and the possibility of eliminating the earliest endometriosis-associated ovarian cancer, it is difficult to find the corresponding histological evidence. As a result, few patients are finally diagnosed with EAOC, which increases the difficulty of in-depth study of EAOC. This article reviews the epidemiology, pathogenesis, risk factors, clinical diagnosis, new treatment strategies and prognosis of endometriosis-associated ovarian cancer, and prospects the future direction of basic research and clinical transformation, in order to achieve stratified management and personalized treatment of ovarian cancer patients.

BRCA-associated hereditary male cancers: can gender affect the prevalence and spectrum of germline pathogenic variants?

IntroductionAlthough hereditary male neoplasms are quite rare, individuals harbouring germline BRCA1/2 pathogenic variants (PVs) may have a risk of developing tumours associated with Hereditary Breast and Ovarian Cancer (HBOC) syndrome, including male breast (MBC), prostate (PCa) and pancreatic (PC) cancers, and melanoma. Women and men showed a comparable genetic architecture of cancer susceptibility, but there are some gender-specific features. Since little is known about cancer genetic susceptibility in male population, our study was aimed at investigating the frequency of BRCA1/2 PVs in men with HBOC syndrome-associated tumors, in order to understand whether differences in gender may reflect in the prevalence and spectrum of germline alterations.Patients and methodsWe retrospectively collected and analysed clinical information of 352 HBOC-associated male cancer patients genetically tested for germline BRCA1/2 PVs by Next-Generation Sequencing analysis, enrolled, from February 2018 to January 2024, at the “Regional Center for the prevention, diagnosis and treatment of rare and heredo-familial tumors of adults” of the University-Hospital Policlinico “P. Giaccone” of Palermo (Italy).ResultsOur investigation revealed that 7.4% of patients was carrier of a germline BRCA PV, with an almost total prevalence of BRCA2 alterations. In particular, 65.4% of BRCA-positive patients developed MBC, 19.2% had PC, 11.6% developed PCa, and only 3.8% had melanoma. Specifically, MBC individuals showed a BRCA-associated genetic predisposition in 17% of cases, whereas patients with PCa or PC exhibited a lower frequency of BRCA2 PVs, taking into account the current national criteria for access to germline genetic testing.DiscussionOur study showed a high heterogeneity in prevalence of germline BRCA2 PVs among men which could reflect a potential gender-specific genetic heterogeneity. Therefore, BRCA-associated male tumours could be due to BRCA2 PVs different from those usually detected in women. In the event that it is demonstrated, in future, that male cancers are genetically distinct entities from those female this could improve personalized risk evaluation and guide therapeutic choices for patients of both sexes, in order to obtain a gender equality in cancer care.

Effects of joint screening for prostate, lung, colorectal, and ovarian cancer – results from a controlled trial

BackgroundAlthough screening is widely used to reduce cancer burden, untargeted cancers are frequently missed after single cancer screening. Joint cancer screening is presumed as a more effective strategy to reduce overall cancer burden.MethodsGender-specific screening effects on PLCO cancer incidence, PLCO cancer mortality, all-neoplasms mortality and all-cause mortality were evaluated, and meta-analyses based on gender-specific screening effects were conducted to achieve the pooled effects. The cut-off value of time-dependent receiver-operating-characteristic curve of 10-year combined PLCO cancer risk was used to reclassify participants into low- and high-risk subgroups. Further analyses were conducted to investigate screening effects stratified by risk groups and screening compliance.ResultsAfter a median follow-up of 10.48 years for incidence and 16.85 years for mortality, a total of 5,506 PLCO cancer cases, 1,845 PLCO cancer deaths, 3,970 all-neoplasms deaths, and 14,221 all-cause deaths were documented in the screening arm, while 6,261, 2,417, 5,091, and 18,516 outcome-specific events in the control arm. Joint cancer screening did not significantly reduce PLCO cancer incidence, but significantly reduced male-specific PLCO cancer mortality (hazard ratio and 95% confidence intervals [HR(95%CIs)]: 0.88(0.82, 0.95)) and pooled mortality [0.89(0.84, 0.95)]. More importantly, joint cancer screening significantly reduced both gender-specific all-neoplasm mortality [0.91(0.86, 0.96) for males, 0.91(0.85, 0.98) for females, and 0.91(0.87, 0.95) for meta-analyses] and all-cause mortality [0.90(0.88, 0.93) for male, 0.88(0.85, 0.92) for female, and 0.89(0.87, 0.91) for meta-analyses]. Further analyses showed decreased risks of all-neoplasm mortality was observed with good compliance [0.72(0.67, 0.77) for male and 0.72(0.65, 0.80) for female] and increased risks with poor compliance [1.61(1.40, 1.85) for male and 1.30(1.13, 1.40) for female].ConclusionJoint cancer screening could be recommended as a potentially strategy to reduce the overall cancer burden. More compliance, more benefits. However, organizing a joint cancer screening not only requires more ingenious design, but also needs more attentions to the potential harms.Trial registrationNCT00002540 (Prostate), NCT01696968 (Lung), NCT01696981 (Colorectal), NCT01696994 (Ovarian).

High-grade serous papillary ovarian carcinoma combined with nonkeratinizing squamous cell carcinoma of the cervix: a case report

Multiple primary malignant neoplasms are a rare gynecologic malignancy; particularly, cases originating from the heterologous organs, such as the ovary and cervix. Here, we report a case of two primary malignant neoplasms in a patient who had undergone laparoscopic radical hysterectomy + bilateral salpingo-oophorectomy + pelvic lymph node dissection + para-aortic lymphadenectomy + appendectomy + omentectomy + metastasectomy under general anesthesia. The patient experienced complete remission after six courses of postoperative chemotherapy with a standard Taxol and Carboplatin regimen. Genetic testing was performed to detect BRCA2 mutations, and poly (ADP-ribose) polymerase (PARP) inhibitors were used for maintenance therapy.

Pre-malignant conditions diagnosed following a positive cancer signal from a multi-cancer early detection test

Blood-based tests for multi-cancer early detection (MCED) are being developed to facilitate the detection of various cancer types. The Detecting cancers Earlier Through Elective mutation-based blood Collection and Testing study (DETECT-A) study evaluated an MCED test in 9,911 women, age 65-75, without personal history of cancer. In a post-hoc analysis, we report on the detection of precancerous neoplasms consequent to MCED testing and follow-up. Participants with positive baseline and confirmatory MCED testing underwent 2-deoxy-2[fluorine-18] fluoro-D-glucose positron emission tomography-computed tomography (PET-CT) and diagnostic evaluation as indicated by PET-CT results. We reviewed the electronic health records of participants with a precancerous neoplasm and summarized their clinical course. MCED results were positive in 134 participants. Clinically significant pre-malignant conditions were identified in three of these participants: A 71-year-old with an ovarian mucinous cystadenoma, a 67-year-old with an appendiceal mucinous neoplasm, and a 70-year-old with colon adenomas displaying high-grade dysplasia. All three participants underwent surgical treatment and remain alive and cancer-free as of last follow up. The diagnostic evaluation of a positive MCED test may occasionally reveal clinically significant pre-cancerous conditions amenable to interventions. The frequency of such findings and their clinical impact warrants further study.

Case Report: Postmenopausal hyperandrogenism misled by adrenal incidentaloma: a rare case of androgen-secreting ovarian adult granulosa cell tumor and clinical implications

Background Ovarian adult-type granulosa cell tumors (AGCTs) are rare sex cord-stromal neoplasms, accounting for 95% of ovarian granulosa cell tumors (GCTs) but only 10% of which secrete androgens. For postmenopausal women, hyperandrogenism is commonly attributed to conditions like polycystic ovary syndrome (PCOS), while androgen-secreting AGCTs are extremely rare, often leading to diagnostic challenges—especially when accompanied by adrenal incidentalomas that may divert clinical attention. Case presentation This study presents a case of a 57-year-old postmenopausal Chinese woman (menopause at 48) with 5 years of progressive hyperandrogenic symptoms (facial/perianal/leg hirsutism, vertex/frontal alopecia, deepened voice, clitoral hypertrophy). Initial evaluation revealed a left adrenal nodule and elevated testosterone; however, pelvic ultrasound (limited by bowel gas) showed no obvious abnormalities in the ovaries. Further tests at the First Affiliated Hospital of China Medical University confirmed markedly elevated serum testosterone (37.00 nmol/L, ref: 0.69-1.49 nmol/L) and free testosterone (300.90 pmol/L, ref: 0.77-33.03 pmol/L), suppressed LH/FSH, low AMH (0.01 ng/mL), and a 2.6×2.0 cm enhancing nodule in the right adnexa on pelvic MRI. Notably, adrenal-derived androgens were within normal ranges in this case, ruling out adrenal origin of hyperandrogenism. She underwent laparoscopic total hysterectomy + bilateral salpingo-oophorectomy; permanent pathological examination (with immunohistochemistry: Vimentin+, α-inhibin+, Calretinin+, Ki67+ ~2%) confirmed FIGO Stage IA AGCT (frozen section initially suggested benign tissue). Postoperatively, her androgen levels normalized, hirsutism/oily skin/acne improved, blood pressure decreased, though voice deepening persisted. Discussion This case underscores critical clinical lessons: Postmenopausal women with severe hyperandrogenism require comprehensive adrenal and pelvic evaluation (prioritizing MRI over ultrasound due to higher sensitivity for small tumors) even with adrenal findings. Comprehensive hormonal profiling (testosterone, adrenal androgens, gonadotropins, AMH) aids in distinguishing tumorous from non-tumorous causes, and permanent pathology is essential to avoid misdiagnosis from frozen sections. Surgical resection (bilateral salpingo-oophorectomy for postmenopausal patients) is effective for AGCT management, and long-term follow-up is crucial given the risk of late recurrence. Additionally, AGCT diagnosis is feasible in institutions without inhibin B/genetic testing via integrated clinical, hormonal, and imaging data. This case aims to raise awareness of rare androgen-secreting AGCTs to reduce diagnostic delays and improve management.

Overarching view of trends and disparities in malignant neoplasm of the ovary between 1999-2023: a comprehensive CDC WONDER database study

Background Ovarian cancer contributes significantly to the morbidity and mortality rates for women worldwide. As observed with other types of cancer, health disparities disproportionately affect ovarian cancer incidence rates and outcomes, especially in African American and older women. However, the trends in ovarian cancer mortality rates up until 2023 with regard to various demographic identifiers have not been fully elucidated, which this study aims to rectify. Methods Mortality trends due to malignant neoplasms of the ovary in individuals 25 and older in the US from 1999 to 2023 were analyzed using the Centers for Disease Control Wide Ranging Online Data for Epidemiological Research (CDC WONDER) database. Trends in age-adjusted mortality rate (AAMR) were analyzed on the basis of race, 10-year age-group, region and urban/rural designation. Results Between 1999 and 2023, the AAMR related to malignant neoplasms of the ovary fell from 14.62 in 1999 to 9.52 in 2023. All races analyzed saw a decrease in overall mortality related to malignant neoplasms of the ovary, with the largest decrease being observed in White patients (AAPC: -1.78). Regionally, the Northeast (AAPC: -1.95), Midwest (AAPC: -1.99), South (AAPC: -1.72), and West (AAPC: -1.73) regions of the United States (US) all saw reduced ovarian neoplasm mortality rates. Similarly, rates also decreased in urban (AAPC: -1.83) and rural (AAPC: -1.75) localities, as well as in each ten-year age category analyzed, with the largest decrease seen in the 55–64 years old category (AAPC: -2.15). States such as Delaware, South Carolina, and Idaho experienced some of the largest decreases in AAMR, whereas the District of Columbia saw an increase in AAMR during this period. Conclusions Over the last twenty-years, mortality rates for malignant neoplasms of the ovary have declined, with the largest decreases being seen in White patients, those residing in the Midwest, urban locality, and women between 55–64 years olds. While mortality rates have declined, health disparities still continue to negatively affect ovarian cancer outcomes, and more research is needed to improve accessibility, availability, and affordability of care for patients.

Artificial intelligence based on ultrasound for initial diagnosis of malignant ovarian cancer: a systematic review and meta-analysis

Purpose This meta-analysis aimed to evaluate the diagnostic performance of artificial intelligence (AI) in ultrasound imaging for the initial diagnosis of malignant ovarian cancer, comparing its performance to that of sonographers. Methods A systematic literature search was conducted in PubMed, Web of Science, Embase, and the Cochrane Library up to February 2025. Inclusion criteria targeted studies employing AI algorithms to analyze ultrasound images in patients with suspected ovarian cancer, using pathology as the reference standard. Bivariate random-effects models were utilized to aggregate sensitivity, specificity, and area under the curve (AUC). The methodological quality of the included studies was assessed using a modified version of the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Results Eighteen studies encompassing a total of 22,697 total patients/images/lesions were analyzed. AI demonstrated a sensitivity of 0.95 (95% CI: 0.88-0.98) and specificity of 0.95 (95% CI: 0.89-0.98) in internal validation sets, yielding an AUC of 0.98. In external validation, sensitivity was 0.78 (95% CI: 0.56-0.91) and specificity was 0.88 (95% CI: 0.76-0.95), with an AUC of 0.91. In comparison, sonographers exhibited a sensitivity of 0.83 (95% CI: 0.62-0.94), specificity of 0.84 (95% CI: 0.79-0.88), and an AUC of 0.87. These results indicate that ultrasound-based AI significantly outperforms sonographer diagnostics. Meta-regression analysis indicated that the heterogeneity was primarily attributed to the analysis method (image-based vs. patient-based, specificity P = 0.01). Conclusions AI based on ultrasound diagnosis demonstrates excellent performance for malignant ovarian cancer detection, with potentially superior performance compared to sonographers. Despite high heterogeneity across studies and the observed publication bias, these results indicate the potential for AI integration into clinical practice. Further studies with external, multicenter prospective head-to-head design are still needed.

Similarities and differences in gene expression profiles of BRCA1 methylated and mutated epithelial ovarian cancers

IntroductionBRCA1 methylated (BRCA1met) epithelial ovarian cancer (EOC) is a recently defined and not well-investigated subset of neoplasms. To date, no studies have focused on the transcriptional profiles of BRCA1met cases, and, as a matter of fact, we still do not know if this subset of EOCs is similar, and to what extent, to BRCA1 mutated (BRCA1mut) cases.MethodsWe compared a group of 17 BRCA1met cases against 10 BRCA1mut cases using a subset of carefully selected 17 BRCAwt EOCs as a control group.ResultsFirst, BRCA1met cases showed a downregulation of the relative transcript, while this association was not observed for BRCA1mut EOCs. The BRCA1met group exhibited a general upregulation of homologous recombination (HR)-related genes, as well as BRCA1mut. Overall, BRCA1met had a different gene expression profile, characterized by diffuse downregulation, whereas BRCA1mut showed a general upregulation (p < 0.0001). Both BRCA1-defective groups showed a slightly activated immune response mediated by interferon (IFN) gamma pathways.DiscussionIn conclusion, even if the expression profile of many genes related to DNA damage and repair system is shared between BRCA1mut and BRCA1met EOCs supporting that BRCA1met EOCs may benefit from PARPi therapies, our data demonstrate that BRCA1mut and BRCA1met EOCs show different expression profiles, suggesting a different mechanism of carcinogenesis that can be reflected in different responses to therapies and disease recovery.

Bilateral ovarian metastases from gastric signet-ring cell carcinoma in an 18-year-old: a case report and narrative review

Background/objectives Krukenberg tumors (KTs) are rare metastatic ovarian neoplasms, most frequently secondary to gastric adenocarcinomas, and typically occur in women aged 30–60 years. Their presentation in adolescents is exceedingly uncommon and often leads to diagnostic delays due to nonspecific symptoms and low clinical suspicion. Case presentation We describe the case of an 18-year-old female presenting with progressive abdominal pain and bilateral adnexal masses. Imaging suggested advanced ovarian pathology, and surgical exploration with histopathological evaluation confirmed metastatic signet-ring cell carcinoma. Upper gastrointestinal endoscopy subsequently identified a poorly differentiated gastric adenocarcinoma, establishing the diagnosis of KT. Methods To place this case in context, a narrative literature review was performed using PubMed, Google Scholar, and ScienceDirect. English-language case reports and case series describing KTs in patients aged ≤20 years were selected. Fifteen studies were analyzed regarding clinical presentation, histopathological features, diagnostic approach, and patient outcomes. Results The majority of reported cases demonstrated bilateral ovarian involvement, vague abdominal symptoms, and gastric origin. Diagnostic delays were frequent, and prognosis remained poor despite multimodal treatment strategies. Conclusions This case highlights the importance of considering metastatic gastrointestinal malignancies in the differential diagnosis of ovarian tumors in adolescents and emphasizes the value of early endoscopic assessment. By combining a rare adolescent case with a focused literature review, this work provides one of the few comprehensive syntheses of KTs in patients under 20 years, offering a unique contribution to improving clinical awareness and guiding future diagnostic strategies.

Case Report: Synchronous primary high-grade appendiceal mucinous neoplasm and ovarian borderline mucinous cystadenoma: a rare case and diagnostic challenges

Background Appendiceal mucinous neoplasms (AMNs), particularly high-grade (HAMN) variants, are rare and pose significant diagnostic challenges. Their presentation can mimic other abdominal pathologies, and the occurrence of synchronous primary mucinous tumors of the appendix and ovary is an exceptionally rare phenomenon that is poorly described in the literature. Case presentation We report a case of a 59-year-old woman who presented with right lower quadrant pain and a palpable mass. Preoperative imaging identified a large, complex cystic mass suspicious for an ovarian primary. Tumor markers (CA19-9, CA125, CA15-3) were elevated. Colonoscopy revealed mucous discharge from the appendiceal orifice, shifting diagnostic suspicion. Exploratory laparotomy revealed a large appendiceal mass with cellular peritoneal mucinous deposits and involvement of the right adnexa. The patient underwent right hemicolectomy and bilateral salpingo-oophorectomy. Histopathological and immunohistochemical analysis confirmed a synchronous primary HAMN (CK20+, Villin+, CK7-) of the appendix and a primary borderline mucinous cystadenoma (CK7+, PAX-8+, CK20-) of the left ovary. Conclusion This case underscores the diagnostic difficulty in distinguishing synchronous primary mucinous neoplasms from metastatic disease. A multidisciplinary approach, meticulous histopathological examination, and adjunctive immunohistochemistry are critical for accurate diagnosis and appropriate surgical management. This rare coexistence suggests the possibility of shared oncogenic pathways, warranting further investigation. Long-term surveillance is essential for these patients.

Case Report: Successful natural conception and delivery in a primary cancer survivor involving the reproductive, respiratory, and endocrine systems auth

Background Natural conception in patients with multiple primary neoplasms (MPNs) is exceedingly rare, particularly those involving metachronous triple cancers of the reproductive, respiratory, and endocrine systems. This article reports the case of a young female patient who suffered from three primary neoplasms successively covering the three major systems of the ovary, lung, and thyroid, and achieved successful natural conception and delivery through comprehensive management by a multi-disciplinary team (MDT). This case provides a valuable reference for the diagnosis and treatment of similar patients. Case Description A 28-year-old married female underwent right ovary-preserving radical surgery for bilateral borderline serous ovarian tumors (Stage IIIB) in February 2021. She received six cycles of postoperative leuprorelin therapy. She was diagnosed with microinvasive adenocarcinoma of the left lung (Stage IA1, ERBB2 p.A775_G776insYVMA mutation) in May 2021 and underwent thoracoscopic wedge resection. The patient underwent radical surgery for papillary thyroid microcarcinoma (pT1aN0M0) in October 2022. She presented to the hospital with fertility concerns in March 2023. An MDT comprising specialists in gynecology, genetics, thoracic surgery, breast and thyroid surgery, obstetrics, and reproductive medicine held a consultation to evaluate the patient’s condition. The assessment concluded that all three neoplasms were in complete remission and that pregnancy did not increase the risk of tumor recurrence. Auxiliary examination revealed an anti-Müllerian hormone level of 1.40 ng/mL (only the right ovary remained intact). Hysteroscopy confirmed the diagnosis of chronic endometritis and endometrial polyps. The polyp was resected, and the patient received a 14-day course of anti-infective therapy with metronidazole and levofloxacin, after which she was guided by natural conception. She achieved a natural pregnancy in August 2023. The MDT provided dynamic monitoring throughout the pregnancy until April 2024, when she vaginally delivered a healthy female infant weighing 3090 grams at 39 weeks and 2 days of gestation. Postpartum follow-up revealed no signs of recurrence or significant abnormalities in the offspring. Conclusion This is the first case of successful natural conception and delivery in a patient with metachronous MPNs involving the reproductive, respiratory, and endocrine systems. It establishes an MDT management pathway encompassing “determination of oncologic remission status, intervention for reversible fertility-compromising factors, and cross-trimester monitoring.” This confirms that natural pregnancy is safe and feasible for patients in cancer remission, with multi-disciplinary collaboration and rigorous monitoring. The absence of postpartum neoplasm recurrence and abnormalities in offspring provides a practical paradigm for fertility management in patients with MPNs.

Real-world data-based assessment of therapy-related myeloid neoplasms after poly(ADP-ribose) polymerase inhibitor treatment in ovarian cancer

Background Poly(ADP-ribose) polymerase inhibitors (PARPi) have significantly improved outcomes in ovarian cancer. However, therapy-related myeloid neoplasms (t-MNs) have emerged as rare but serious late complications. Although an increased incidence of t-MNs has been reported following PARPi exposure, clinical predictors remain poorly understood. Methods This retrospective study analyzed 181 patients with ovarian cancer treated with PARPi at two Japanese institutions. Clinical characteristics and routine hematologic parameters were compared between patients with and without t-MNs. Hematological values were assessed at initial diagnosis, PARPi initiation, 4 weeks after initiation, and at nadir within 12 weeks. Relative changes from initial diagnosis and from PARPi initiation to nadir were also evaluated. Results t-MNs developed in 6 (3.3%) patients. All patients in the t-MN group had received multiple platinum-containing regimens, and in five of the six cases, t-MN was diagnosed more than 5 years after initial diagnosis. No definitive clinical predictors were identified, although the t-MN group tended to have higher body mass index. Median white blood cell (WBC), hemoglobin, and platelet counts, as well as their relative changes from initial diagnosis or PARPi initiation to nadir, did not differ significantly between the groups. However, the t-MN group exhibited a larger reduction in WBC count from PARPi initiation to nadir, not statistically significant. Conclusions This real-world study highlights the importance of survivorship care in the era of improved outcomes for ovarian cancer. Continued long-term hematologic monitoring, along with the collection of more cases, is essential to elucidate risk factors for t-MNs in patients receiving PARPi therapy.

Bilateral serous surface papillary borderline ovarian tumor with non-invasive implantation: a case report

Introduction Serous surface papillary borderline ovarian tumors (SSPBOTs), a clinically distinct variant of serous borderline ovarian tumors (SBOTs), are frequently misdiagnosed as malignant tumors during preoperative diagnostic assessments. Presentation of case This case report describes a 22-year-old female patient who presented with abdominal pain. Gynecological examination revealed a painless 11-cm diameter mass on the right posterior side of the uterine body. Ultrasonography demonstrated a solid mass in the right ovary (O-RADS 5, highly indicative of malignant germ cell tumor). It also revealed a unilocular cystic mass in the left ovary (O-RADS 2, with benign characteristics). During the operation, a cauliflower-like mass was observed on one side of the surface of the right ovary. On the left ovary, a cystic mass was found, with multiple small cauliflower-like masses scattered on its surface. Additionally, pelvic cavity examination revealed millet-sized lesions and fibrinous exudate. The pathological diagnosis confirmed the presence of bilateral serous borderline tumors with multiple non-invasive implants. Treatment involved the excision of bilateral ovarian masses and the resection of secondary lesions. No evidence of recurrence was observed during the one-year follow-up. Discussion SSPBOTs are a distinct subtype of serous borderline ovarian tumors that predominantly affecting women of reproductive age and often involve bilateral ovaries. Ultrasound findings mostly show solid hypoechoic masses growing on the surface of the ovary. These masses surround normal ovarian tissue and exhibit a visible “microcystic sign” within. Punctate strong echoes or coarse calcified spots may also be observed. Color Doppler ultrasound demonstrates abundant intratumoral vascularity with a ‘firework-like’ perfusion pattern. Insufficient understanding of this disease can easily lead to misdiagnosis as a germ cell tumor. Although CA-125 levels may be elevated, the marker lacks diagnostic specificity. Given the tumor’s indolent growth pattern and low recurrence rate, fertility-sparing surgery is feasible for patients desiring reproductive preservation. Conclusion This report systematically summarizes the ultrasonographic characteristics of SSPBOTs, aiming to enhance diagnostic accuracy and provide evidence-based support for fertility preservation strategies in young patients.

Genomic landscape of pediatric germ cell tumors reveals oncogenic mutations and copy number alterations

Introduction Germ cell tumors (GCTs) are rare neoplasms affecting approximately 3.5% of all pediatric patients, with diverse histological subtypes. Despite their clinical and biological heterogeneity, pediatric GCTs generally exhibit a low mutational burden. Compared to adult GCTs, however, the molecular characterization of pediatric cases remains limited, hindering the development of targeted therapeutic strategies. Therefore, we aimed to elucidate the genomic landscape of pediatric GCT patients via whole exome sequencing (WES). Methods WES was performed in 16 pediatric GCTs and respective matched normal samples, including ten ovarian, five testicular, and one mediastinal tumor. The somatic alterations found were described and compared with the clinicopathological characteristics, as well as related to molecular databases. Results The somatic mutations found resemble those observed in adult GCTs and recent pediatric GCTs studies. Genes with predicted oncogenic variants were found in seven samples (43.75%) out of 16 and included KIT (12.5%), KRAS (6.25%), MTOR (12.5%), PIK3CA (6.25%), AKT2 (6.25%), LARP4B (6.25%), and ACSL6 (6.25%). Copy number alterations were identified on chromosomes 4, 7, 8, 10, 12, 21, and 22, with amplification of CDKN1B , KRAS , CCND2 , ETV6 , and KDM5A genes, and deletions of KIT and PTEN genes. Clinically significant mutations ( KIT : Asp816Val, Ala829Pro; and KRAS : Gln61Leu) suggest potential therapeutic targets for GCT, while MTOR , PIK3CA , and AKT2 emerge as candidates for targeted therapy. Discussion These findings provide insights into the genomic alterations of pediatric GCTs and emphasize the potential for targeted therapies.

Urinary bladder paraganglioma presenting with abdominal pain and elevated cardiac enzymes: a case report of atypical manifestations and diagnostic challenges

Urinary bladder paraganglioma (UBPGL) is a very rare neuroendocrine tumor, accounting for 0.05% of all bladder neoplasms. Classic symptoms include paroxysmal hypertension, palpitations, and sweating triggered by micturition. However, atypical presentations may complicate the diagnosis. This report describes the case of a 35-year-old woman who presented with persistent lower abdominal pain and isolated elevation of cardiac enzymes. Imaging revealed a pelvic mass initially suspected to be adnexal pathology. Emergency laparoscopy identified a retroperitoneal mass adjacent to the bladder and an endometriotic ovarian cyst. Postoperative pathology confirmed UBPGL, with immunohistochemistry positive for neuroendocrine markers (CD56, chromogranin-A, synaptophysin). Elevated cardiac enzymes and a prolonged QTc interval were observed preoperatively, likely secondary to catecholamine-induced myocardial injury, although biochemical confirmation was not available. The patient recovered uneventfully after resection of the tumor. This case highlights the potential for UBPGL to have atypical cardiovascular manifestations, including isolated elevation of cardiac enzymes without classic hypertensive crises. Such findings may reflect catecholamine-driven cardiomyocyte stress, emphasizing the need for heightened suspicion in cases that present with unexplained abdominal pain and cardiac abnormalities. Diagnostic challenges arise from overlapping symptoms with gynecologic emergencies and the rarity of preoperative biochemical testing in acute settings. UBPGL should be considered in patients with a pelvic mass accompanied by unexplained cardiac abnormalities. Early resection remains curative, but multidisciplinary evaluation, including biochemical screening for catecholamine excess, is critical to mitigate the cardiovascular risk. Long-term surveillance is warranted in view of the potential for metastasis. This case underscores the importance of including rare neuroendocrine tumors in the differential diagnoses for atypical abdominal presentations.

Primary dedifferentiated liposarcoma of the ovary: expanding the surgical management spectrum with a different resection extent than existing reports – a case report and literature review

Background Dedifferentiated liposarcoma (DDLPS) is a relatively common type of liposarcoma, typically occurring in the retroperitoneum and limbs. It is rarely found in the female reproductive system, leading to the absence of a standard treatment protocol for primary ovarian dedifferentiated liposarcoma. This case presents a personal experience-based approach, as there is a lack of standard treatment guidelines, relying on treatment consensus for more common locations and decades of clinical experience. Case presentation This case report describes a 55-year-old woman who was admitted due to a gradually enlarging mass in the right lower abdomen, accompanied by bloating and abdominal pain. Physical examination revealed a palpable abdominal mass. Gynecological ultrasound showed a hyperechoic mass measuring 135*128*91mm in the pelvic-abdominal cavity. CT imaging suggested a large cystic and solid mixed liposarcoma originating from the ovary, with unclear delineation of the uterine fundus and slight compression of surrounding organs. Pelvic MRI revealed an irregular mass approximately 10.7cm×12.6cm×12.2cm, with slightly prolonged T1 and heterogeneous T2 signals, showing fat signal in the right fatty tissue, suggesting invasion of the uterine wall by liposarcoma. The patient then underwent open surgery, and postoperative pathology with immunohistochemistry confirmed dedifferentiated liposarcoma. FISH testing was positive for MDM2, confirming the diagnosis of ovarian-origin dedifferentiated liposarcoma. Although the patient refused chemotherapy, she has been followed up every three months, and the current follow-up shows no signs of tumor recurrence. Conclusion Ovarian dedifferentiated liposarcoma is an extremely rare condition, with surgery being the preferred treatment method. This report presents a rare case of ovarian dedifferentiated liposarcoma, providing a reference for clinical diagnosis and treatment. Through collaboration between gynecology, pathology, and imaging departments, the accuracy of the diagnosis and comprehensiveness of treatment were ensured. Long-term follow-up of the patient provided valuable insights into the recurrence and prognosis of the disease.

The efficacy and safety of ATR inhibitors in the treatment of solid tumors: a systematic review and meta-analysis

Ataxia telangiectasia and Rad3-related kinase (ATR) is a central regulator of the DNA damage response and a promising therapeutic target in tumors with genomic instability. This meta-analysis evaluated the efficacy and safety of ATR inhibitors in patients with solid tumors. A systematic search of PubMed, Embase, and major Chinese and international databases up to September 2025 identified ten clinical trials including 810 patients treated with ATR inhibitors as monotherapy or in combination. Outcomes assessed included objective response rate, disease control rate, progression-free survival, overall survival, and treatment-related adverse events. Pooled analyses showed no significant overall improvement in efficacy endpoints compared with standard therapies. However, subgroup analysis demonstrated marked benefit in non-small cell lung cancer, with significantly prolonged progression-free survival and overall survival, while efficacy in other tumor types was minimal. The overall risk of adverse events was comparable to control groups, although hematologic toxicities such as myelosuppression (pooled RR = 1.04) and neutropenia (pooled RR = 1.34) were common. These findings suggest that ATR inhibitors may be particularly effective in non-small cell lung cancer and selected ovarian cancer subgroups, but further biomarker-driven randomized trials are required to confirm their clinical value and optimize patient selection. Systematic Review Registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420251123612.

“Is the incidence of non-epithelial ovarian tumors on the rise? insights from a Tunisian tertiary center”

IntroductionNon-epithelial ovarian tumors (NEOTs), mainly germ cell and sex cord-stromal tumors, are rare entities that pose diagnostic and therapeutic challenges due to their heterogeneity and often nonspecific presentation. This study aimed to describe the epidemiological, clinical, pathological, and surgical characteristics of NEOTs managed at Charles Nicolle University Hospital, Tunis, over a five-year period.Materials and methodsWe conducted a retrospective descriptive study including 48 patients operated for NEOTs between January 2020 and December 2024. Clinical, radiological, surgical, and pathological data were analyzed.ResultsNEOTs represented 20.9% (48/229) of ovarian tumors. Median age at diagnosis was 35 years (IQR 28–51). Germ cell tumors accounted for 68.8% and sex cord-stromal tumors for 29.1%. Malignant tumors were rare (6.3%), all stage IA. Conservative surgery was performed in 56.2%, predominantly in germ cell tumors, while laparotomy was the main approach (87.5%). Compared with germ cell tumors, sex cord-stromal tumors occurred in older (median 51 vs. 30 years, p=0.003), more frequently postmenopausal patients (57.1% vs. 12.1%, p=0.003), and were more often >10 cm (61.5% vs. 25.8%, p=0.04). Postoperative complications occurred in 8.3%, and no recurrences were observed during follow-up.ConclusionNEOTs, though rare, accounted for a relatively high proportion of ovarian tumors in our series. They were predominantly benign and diagnosed at an early stage, with favorable outcomes. Conservative surgery should be prioritized in young women to preserve fertility. This study represents the first Tunisian series addressing all histological subtypes of NEOTs and provides a reference for future multicenter research.

Diagnosis and management of a rare bilateral ovarian mixed germ cell tumor: a case report

BackgroundMixed ovarian malignant germ cell tumors (MOGCTs) are rare neoplasms composed of two or more malignant germ cell components, representing less than 1% of all ovarian germ cell tumors. They primarily affect adolescents and young women, presenting a clinical challenge due to their histologic heterogeneity, potential for recurrence, and the need to balance oncologic safety with fertility preservation.Case presentationWe reported a 22-year-old woman diagnosed with a four-component MOGCT in the right ovary—comprising yolk sac tumor, immature teratoma, embryonal carcinoma, and dysgerminoma—along with a dysgerminoma component in the left ovary. Considering her age and fertility desire, fertility-sparing surgery was performed, followed by adjuvant BEP chemotherapy. At 12-month follow-up, the patient remained disease-free with regular menstruation and no signs of recurrence.ConclusionThis case highlights the feasibility of fertility-sparing treatment in patients with complex bilateral MOGCTs. Given the rarity and histological diversity of such tumors, individualized treatment planning, strict staging, and long-term surveillance are essential to optimize clinical outcomes and preserve reproductive potential.

Correction: Association between ERCC2 Lys751Gln, Asp312Asn, and Arg156Arg polymorphisms and gynecological cancer susceptibility: a meta-analysis

A rare case report of uterine carcinosarcoma with bilateral ovarian Brenner tumors

BackgroundUterine carcinosarcoma is a rare, highly aggressive malignancy characterized by both carcinomatous and sarcomatous components. Brenner tumors of the ovary are uncommon epithelial neoplasms, usually benign but occasionally coexisting with other pathologies. The co-occurrence of these two entities is extremely rare and poses diagnostic and therapeutic challenges.MethodsWe report a case of a 58-year-old female presenting with scant yellowish vaginal discharge. Imaging studies revealed an intrauterine mass. Histopathological analysis of curettage specimens confirmed endometrial malignancy. The patient underwent radical surgical resection followed by histopathological and immunohistochemical analysis.ResultsHistopathology confirmed uterine carcinosarcoma comprising high-grade endometrial adenocarcinoma and pleomorphic sarcoma with chondrosarcoma differentiation. Bilateral ovarian Brenner tumors were also identified. Given the aggressive nature of carcinosarcoma, the patient was referred for adjuvant therapy.ConclusionThis case highlights the importance of prompt pathological evaluation in atypical gynecologic presentations. Early diagnosis through histopathology and immunohistochemistry is crucial for managing rare and aggressive tumors such as uterine carcinosarcoma, particularly when coexisting with other uncommon neoplasms like Brenner tumors. Multidisciplinary care and individualized treatment plans are essential for optimizing outcomes.

Case Report: Hypercalcemic small-cell carcinoma of the ovary during pregnancy: diagnostic and therapeutic challenges

Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a rare, highly aggressive malignancy that predominantly affects young women. We report a 32-year-old pregnant woman diagnosed with SCCOHT during the first trimester of pregnancy. At 24 weeks, imaging revealed extensive peritoneal carcinomatosis. Following multidisciplinary evaluation, neoadjuvant chemotherapy was initiated, but the disease progressed. At 34 weeks, the patient underwent cesarean delivery followed by cytoreductive surgery. Despite achieving an initial complete resection, the disease recurred rapidly. The patient died shortly after completing adjuvant chemotherapy and initiating immunotherapy. This case highlights the diagnostic and therapeutic challenges of managing SCCOHT during pregnancy and the complex balance of maternal and fetal outcomes. Early diagnosis, coordinated multidisciplinary care, and timely intervention are critical, although the prognosis remains poor despite aggressive multimodal treatment.

Association between ERCC2 Lys751Gln, Asp312Asn, and Arg156Arg polymorphisms and gynecological cancer susceptibility: a meta-analysis

BackgroundGynecological tumors are diseases that pose serious threats to women’s health. Cervical, endometrial, and ovarian cancers are the most common gynecologic tumors. Excision repair cross-complementation group 2 (ERCC2) plays a critical role in nucleotide excision repair. Polymorphisms in ERCC2 can influence DNA damage repair mechanisms, potentially increasing susceptibility to tumors. However, several studies have investigated the association between ERCC2 polymorphisms and the risk of gynecological tumors, but the results have been inconsistent. Therefore, we performed this meta-analysis to estimate these associations more precisely.ObjectIn this paper, we summarized a larger sample for meta-analysis to explored the relationship between the polymorphisms of the ERCC2 Lys751Gln, Asp312Asn, and Arg156Arg and gynecological tumors.MethodsWe conducted a systematic search for relevant case-control studies in PubMed, the Cochrane Library, Embase, and the Web of Science databases, covering studies up to October 2024. The odds ratio (OR) and its 95% confidence interval (CI) were calculated using Stata 17 software.ResultsFinally, a total of 19 studies (9433 cases and 13144 controls) were included. 17 studies (3742 cases and 5591 controls) were conducted on the Lys751Gln polymorphism. Additionally, 9 studies(2,170 cases and 3,582 controls)were available for the Asp312Asn polymorphism, while 8 studies (3,521 cases and 3,971 controls)were included for the Arg156Arg polymorphism. Of these, 16 focused on ovarian cancer, 8 on cervical cancer, and 10 on endometrial cancer. The ERCC2 Lys751Gln polymorphism was found to increase the risk of gynecologic neoplasms(C vs A:OR 1.33, 95% CI 1.06-1.66;CC+CA vs AA:OR 1.33, 95% CI 1.11-1.59). Subgroup analysis by cancer type indicated an association of the Lys751Gln polymorphism with the development of ovarian cancer (CC+CA vs AA:OR 1.39, 95% CI 1.04-1.86), while no significant correlation was observed with cervical and endometrial cancers. Further subgroup analyses revealed that the Lys751Gln polymorphism increased the risk of gynecologic neoplasms in Caucasian and African populations, as well as in hospital-based studies. In contrast, the ERCC2 Asp312Asn polymorphism did not elevate the risk of gynecologic neoplasms, and the recessive gene variant was even protective against cervical cancer (AA vs GA+GG : OR 0.53, 95%CI 0.34-0.83, P=0.005). Additionally, this study did not find an association between the Arg156Arg polymorphism and susceptibility to gynecologic tumors.ConclusionThe ERCC2 Lys751Gln polymorphism is associated with an increased risk of gynecological tumors, particularly ovarian cancer. However, the Asp312Asn and Arg156Arg polymorphisms do not appear to elevate susceptibility to gynecological tumors. Even the recessive gene model of Asp312Asn polymorphism may have a protective effect on cervical cancer.