Borderline tumour recurrence: how quickly does the tumour grow?

This abstract describes a case of the growth of a serous borderline tumour recurrence and cyst to papillary projection ratio with associated ultrasound images. The aetiology, presentation and management of such cases are explored and compared to the literature.

Nongestational ovarian choriocarcinoma with bilateral teratoma: A rare case report and literature review.

INTRODUCTION: Trophoblastic neoplasms are often associated with pregnancy, and nongestational trophoblastic neoplasms are extremely rare. Nongestational ovarian choriocarcinoma (NGCO) is a highly aggressive germ cell-derived tumor frequently presenting with early hematogenous metastasis. PATIENT CONCERNS: Herein, we report a case of a 28-year-old unmarried woman with regular menstruation who experienced vaginal bleeding 1 week after her last menstrual cycle. Doppler ultrasound revealed bilateral adnexal masses and elevated serum human chorionic gonadotropin (hCG) levels. The patient was initially misdiagnosed as presenting an ectopic pregnancy. DIAGNOSIS: The final pathology confirmed an International Federation of Gynecology and Obstetrics stage IA NGCO with bilateral mature teratoma of the ovary. This is an extraordinary instance of ovarian choriocarcinoma which emerged without any prior gestation, and the patient's lack of a history of pregnancy made the diagnosis ignored. INTERVENTIONS: After initial surgery and 1 cycle of bleomycin, etoposide, and cisplatin (BEP) chemotherapy, a laparoscopic fertility-preserving comprehensive staging surgery was performed. Two cycles of chemotherapy with BEP were administered as supplemental therapy postsurgery, and leuprorelin was administered to protect ovarian function. OUTCOMES: Menstruation resumed 4 months after chemotherapy completion, and tumor indicators were within the normal range. No signs of recurrence were observed at the 36-month follow-up. CONCLUSION: NGCO should be considered if a female patient exhibits irregular vaginal bleeding and masses in the adnexal area. The present case and our literature review also highlighted that fertility-sparing surgery and multidrug chemotherapy are effective methods for treating NGCO.

Perioperative management of a patient with unexpectedly detected early-stage ovarian mucinous carcinoma combined with progressive bulbar paralysis: a case report and literature review.

BACKGROUND: Giant ovarian cysts (GOCs)complicated with progressive bulbar paralysis (PBP) are very rare, and no such literature about these cases have been reported. Through the diagnosis and treatment of this case, the perioperative related treatment of such patients was analyzed in detail, and early-stage ovarian mucinous carcinoma was unexpectedly found during the treatment, which provided reference for clinical diagnosis and treatment of this kind of diseases. CASE PRESENTATION: In this article, we reported a 38-year-old female patient. The patient was diagnosed with PBP 2 years ago. Examination revealed a large fluid-dominated cystic solid mass in the pelvis measuring approximately 28.6×14.2×8.0 cm. Carbohydrate antigen19-9(CA19-9) 29.20 IU/mL and no other significant abnormalities were observed. The patient eventually underwent transabdominal right adnexal resection under regional anesthesia, epidural block. Postoperative pathology showed mucinous carcinoma in some areas of the right ovary. The patient was staged as stage IA, and surveillance was chosen. With postoperative follow-up 1 month later, her CA19-9 decreased to 14.50 IU/ml. CONCLUSIONS: GOCs combined with PBP patients require a multi-disciplinary treatment. Preoperative evaluation of the patient's PBP progression, selection of the surgical approach in relation to the patient's fertility requirements, the nature of the ovarian cyst and systemic condition are required. Early mucinous ovarian cancer accidentally discovered after operation and needs individualized treatment according to the guidelines and the patient's situation. The patient's dysphagia and respiratory function should be closely monitored during the perioperative period. In addition, moral support from the family is also very important.

Mature cystic teratoma with co-existent mucinous cystadenocarcinoma: describing a diagnostic challenge-a case report.

BACKGROUND: Mature cystic teratoma co-existing with a mucinous cystadenocarcinoma is a rare tumor that few cases have been reported until now. In these cases, either a benign teratoma is malignantly transformed into adenocarcinoma or a collision tumor is formed between a mature cystic teratoma and a mucinous tumor, which is either primarily originated from epithelial-stromal surface of the ovary, or secondary to a primary gastrointestinal tract tumor. The significance of individualizing the two tumors has a remarkable effect on further therapeutic management. CASE PRESENTATION: In this case, a mature cystic teratoma is co-existed with a mucinous cystadenocarcinoma in the same ovary in a 33-year-old Iranian female. Computed Tomography (CT) Scan with additional contrast of the left ovarian mass suggested a teratoma, whereas examination of resected ovarian mass reported an adenocarcinoma with a cystic teratoma. A dermoid cyst with another multi-septate cystic lesion including mucoid material was revealed in the gross examination of the surgical specimen. Histopathological examination revealed a mature cystic teratoma in association with a well-differentiated mucinous cystadenocarcinoma. The latter showed a CK7-/CK20 + immune profile. Due to the lack of clinical, radiological, and biochemical discoveries attributed to a primary lower gastrointestinal tract tumor, the immune profile proposed the chance of adenocarcinomatous transformation of a benign teratoma. CONCLUSIONS: This case shows the significance of large sampling, precise recording of the gross aspects, histopathological examination, immunohistochemical analysis, and the help of radiological and clinical results to correctly diagnose uncommon tumors.

Human Epidermal Growth Factor Receptor 2 Overexpression/Amplification in Primary Ovarian Endometrioid Carcinoma.

Human epidermal growth factor receptor 2 (HER2) expression has become increasingly helpful in predicting responses to anti-HER2 agents in gynecological cancers. This study retrospectively analyzed HER2 expression in 48 primary ovarian endometrioid carcinomas. HER2 immunohistochemistry was performed using the Ventana platform (Clone 4B5 monoclonal predilute) following the manufacturer's protocol. HER2 expression was equivocal (score 2+) by image analysis in 2 cases (4.17%) based on the breast cancer criteria. Fluorescence in situ hybridization was negative for HER2 amplification in one case (International Federation of Gynecology and Obstetrics, grade 1) and positive in the other (International Federation of Gynecology and Obstetrics, grade 3). Our findings contribute to the growing evidence that HER2 is overexpressed in a small proportion of ovarian endometrioid carcinoma, and thus may serve as a potential therapeutic target in selected cases.

Exceptional lymph node recurrence of an unusual ovarian tumor 16 years later: a case report.

BACKGROUND: Sex cord-stromal tumors with annular tubules are a rare tumor accounting for less than 1% of all ovarian malignancies. However, they are characterized by very late recurrence, which can be as late as 30 years after diagnosis and treatment. CASE PRESENTATION: A 16-year-old female Caucasian patient was treated in our department for a stage IA ovarian sex cord-stromal tumors with annular tubules. She underwent a left salpingo-oophorectomy and ipsilateral pelvic node biopsy with no adjuvant treatment. She was seen for amenorrhea after being lost to follow up for 16 years. The diagnosis of recurrence was made by radiology and the elevation of serum inhibin B level. The patient underwent resection of the tumor, left segmental colectomy, and paraaortic lymphadenectomy because the mass was massively adherent to the left mesocolon. Histology confirmed the diagnosis with no metastatic lymph nodes. No adjuvant therapy was indicated. The patient was lost to follow-up again for 4 years and re-presented for amenorrhea. Serum inhibin B level was high. A second recurrence was suggested, and the patient underwent a laparoscopic surgery. We performed left pelvic and paraaortic lymphadenectomy, and 3 months after surgery the patient was pregnant. CONCLUSION: Sex cord-stromal tumors with annular tubules is a slow-growing ovarian tumor with a high potential for recurrence and metastasis. Surgery is the mainstay of treatment. Due to the rarity of these tumors, they are often unsuspected and thus incompletely staged before primary surgery; the diagnosis is made by histological examination. The prognosis of these patients is unknown, and they require long-term follow-up.

Diagnosing and staging epithelial ovarian cancer by serum glycoproteomic profiling.

BACKGROUND: There is a need for diagnostic tests for screening, triaging and staging of epithelial ovarian cancer (EOC). Glycoproteomics of blood samples has shown promise for biomarker discovery. METHODS: We applied glycoproteomics to serum of people with EOC or benign pelvic masses and healthy controls. A total of 653 analytes were quantified and assessed in multivariable models, which were tested in an independent cohort. Additionally, we analyzed glycosylation patterns in serum markers and in tissues. RESULTS: We identified a biomarker panel that distinguished benign lesions from EOC with sensitivity and specificity of 83.5% and 90.1% in the training set, and of 86.7 and 86.7% in the test set, respectively. ROC analysis demonstrated strong performance across a range of cutoffs. Fucosylated multi-antennary glycopeptide markers were higher in late-stage than in early-stage EOC. A comparable pattern was found in late-stage EOC tissues. CONCLUSIONS: Blood glycopeptide biomarkers have the potential to distinguish benign from malignant pelvic masses, and early- from late-stage EOC. Glycosylation of circulating and tumor tissue proteins may be related. This study supports the hypothesis that blood glycoproteomic profiling can be used for EOC diagnosis and staging and it warrants further clinical evaluation.

Granulosa cell tumor of the ovary: a series of 6 cases.

Granulosa cell tumor (GCT) is a rare ovarian malignancy that represents only 2-3% of all cases. There are two subtypes of GCT: juvenile/JGCT (5% of cases) and adult/AGCT (95% of cases). This study aimed to describe a series of 6 GCT cases. The 6 study patients were managed from June 2011 to November 2022 in a private oncology clinic located in Teresina (PI), Brazil. At diagnosis, the mean patient age was 47 years, and symptoms in 5 patients (83%) were pelvic pain and/or increased abdominal volume. The majority of the patients (N=4/67%) had no comorbidities or findings related to GCT on physical examination. The mean tumor size was 11 cm. Five (83%) tumors were stage Ia and one tumor (17%) was stage III. Regarding tumor subtype, 5 (83%) were AGCT and 1 (17%) was JGCT. Surgical treatment consisted of unilateral salpingo-ophorectomy in 2 patients (33%), total hysterectomy and bilateral salpingo-ophorectomy in 3 patients (50%), and cytoreduction (suboptimal) in 1 patient (17%). After a mean follow-up period of 62.7 months, 5 patients (83%) are still alive and free of disease. One (17%) died from disease progression after 126 months. In the current study, disease-free overall survival was 83%, in a mean follow-up period of 62.7 months.

The evaluation of miR-1181 and miR-4314 as serum microRNA biomarkers for epithelial ovarian cancer diagnosis and prognosis.

AIM: Epithelial ovarian cancer (EOC) is the most ominous tumor of gynecological cancers due to its poor early detection rate and unfavorable prognosis. To date, there is no reliable screening method for the diagnosis of ovarian cancer at an early stage. MiRNAs are small non-coding RNA molecules, and their main function is to regulate gene expression. The present study compared the serum miR-1181 and miR-4314 levels in patients with EOC and healthy controls to measure the diagnostic and prognostic value as candidate biomarkers. MATERIALS AND METHODS: We collected serum samples from a total of 135 participants (69 patients with EOC and 66 healthy controls). Relative expressions of miR-1181 and miR-4314 were measured by quantitative real-time polymerase chain reaction assay (qPCR). RESULTS: The present study revealed that both serum miR-1181 and miR-4314 levels in patients with EOC were significantly increased compared to healthy controls for each marker. In addition, there was a significant relationship between miR-1181 and miR-4314 overexpressions and the stage and prognosis of the disease. Finally, patients with high expression levels of miR-1181 and miR-4314 had significantly shorter survival rates than those with low expression levels. CONCLUSION: The current study proposed that serum miR-1181 and miR-4314 could discriminate the EOC patients from healthy controls. In addition, both miR-1181 and miR-4314 may be predictive biomarkers for ovarian cancer prognosis. Further studies are needed to confirm the findings of the present study.

A Study on the Retrospective Reinterpretation of BRCA1 and BRCA2 Variants.

BACKGROUND: Hereditary breast/ovarian cancer is associated with BRCA gene mutations. As large volumes of clinical data on BRCA variants are continuously updated, their clinical interpretation may change, leading to their reclassification. This study analyzed the class and proportion of the changed clinical interpretations of BRCA variants to validate the need for periodic reviews of these variants. METHODS: This retrospective study reinterpreted previously reported BRCA1 and BRCA2 exon variants according to the 2015 American College of Medical Genetics and Genomics guidelines and the clinical significance of the recent public genomic database. Reanalyzed results were obtained for patients tested for BRCA genetic mutation for 10 years and 4 months. RESULTS: We included data from 4,058 patients, with 595 having at least one pathogenic variant (P), likely pathogenic variant (LP), or variant of uncertain significance (VUS) at a detection rate of 14.66%. The numbers of exon and intron variants were 562 (87.81%) and 78 (12.19%), respectively. BRCA1 exhibited a significantly higher P/LP detection rate of 6.96% compared to that of BRCA2 at 6.89% (p < 0.001). Conversely, BRCA2 demonstrated a significantly higher VUS rate of 10.38% compared to that of BRCA1 at 5.08% (p < 0.001). Among BRCA1 mutations, substitutions were the most prevalent in P/LP and VUS. Among BRCA2 mutations, deletions were most prevalent in P/LP, and substitutions were most prevalent in VUS. Among the 131 patients with P/LP in BRCA1 exons, the clinical interpretation was reclassified in two cases (1.53%), one VUS and one benign/likely benign (B/LB), and 48 cases (48.00%) with VUS were reclassified; one to P/LP and 47 to B/LB. Among the 138 patients with P/LP in BRCA2 exons, the clinical interpretation was reclassified in six (4.35%), five to VUS, and one to B/LB, and all 74 with VUS were reclassified to B/LB. CONCLUSIONS: We determined the class and proportion of reclassified BRCA variants. In conclusion, reviews are required to provide clinical guidance, such as determining treatment direction and preventive measures in the future.

Diagnostic value of ultrasonography in identifying unilateral ovarian luteoma in a dog.

Background: Diagnosing ovarian tumors in dogs can be challenging since the clinical symptoms are often generic. The present case report underscores a rare case in which a suspected unilateral ovarian tumor in a dog was initially identified using ultrasonography and subsequently confirmed to be a luteoma through postoperative histopathology. Case Description: An 8-year and 6-month-old female Maltese dog presented with a 10-day history of vulvovaginal bleeding, hematuria, and decreased appetite. Physical examination revealed only vaginal bleeding, with no other abnormalities. Laboratory examinations showed no abnormalities, while abdominal radiography revealed the presence of cystic calculi as the sole abnormality. Abdominal ultrasound revealed an enlarged right ovary with regular contour and echogenicity, featuring unusual cystic components surrounding the right ovarian parenchyma. Furthermore, irregular thickening with multiple cystic lesions was observed in the endometrial wall of the bilateral uterine horns, indicative of cystic endometrial hyperplasia. Ultrasonographic findings suggested unilateral right ovarian disease. During ovariohysterectomy, the right ovary was slightly larger than the left ovary and adhered to the surrounding mesenteric fat layer and right pancreatic parenchyma. Histopathological examination confirmed the diagnosis of luteoma in the right ovary. Three days after surgery, the patient's clinical signs exhibited complete improvement, with the return of normal appetite. Conclusion: This case report highlights a rare diagnosis of unilateral ovarian luteoma based on mild ultrasonographic abnormalities, which was ultimately confirmed on histopathological examination.

Stretchable Photonic Crystal-Assisted Glycoprotein Identification for Ovarian Cancer Diagnosis.

Photonic crystals with specific wavelengths can realize surface-enhanced excitation and emission intensities of fluorophores and enhance the fluorescence signals of fluorescent molecules. Herein, stretchable photonic crystals with good mechanochromic properties provide continuously adjustable forbidden wavelengths by stretching to change the lattice spacing, with reflectance peaks blue-shifted up to 110 nm to match indicators of different wavelengths and produce differentiated optical enhancement effects. Glycoproteins are significantly identified as clinical markers. However, the wide participation of glycoproteins in various life processes poses enormous complexity and critical challenges for rapid, facile, high-throughput, and accurate clinical analysis or health assessment. In this work, we proposed a stretchable photonic crystal-assisted glycoprotein identification approach for early ovarian cancer diagnosis. Stretchable photonic crystals can provide rich optical information to efficiently identify glycoproteins in complex matrices. A double-indicator fluorescence sensor was designed to respond to the protein trunk and oligosaccharide segment of glycoproteins separately for improved recognition accuracy. Seven typical glycoproteins could be discriminated from proteins, saccharides, or mixture interferents. Clinical ovarian cancer samples for early, intermediate, and advanced ovarian cancer and healthy subjects were verified with 100% accuracy. This strategy of stretchable photonic crystal-assisted glycoprotein identification provides an effective method for accurate, rapid ovarian cancer diagnosis and timely clinical treatment.

Sensitive circulating tumor DNA-based residual disease detection in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is one of the leading causes of cancer-related death in women worldwide, and is characterized by a high rate of recurrence after surgery and chemotherapy. We sought to implement a circulating tumor DNA (ctDNA)-based blood test for more accurate post-operative surveillance of this disease. We analyzed 264 plasma samples collected between June 2016 and September 2021 from 63 EOC patients using tumor-guided plasma cell-free DNA analysis to detect residual disease after treatment. Assay specificity was verified using cross-patient analysis of 1,195 control samples. ctDNA was detected in 51 of 55 (93%) samples at diagnosis, and 18 of 18 (100%) samples at progression. Positive ctDNA in the last on-treatment sample was associated with rapid progression (median 1.02 versus 3.38 yr, HR = 5.63, P < 0.001) and reduced overall survival (median 2.31 versus NR yr, HR = 8.22, P < 0.001) in patients with high-grade serous cancer. In the case of 12 patients, ctDNA assays detected progression earlier than standard surveillance, with a median lead time of 5.9 mo. To approach the physical limits of ctDNA detection, five patients were analyzed using ultra-sensitive assays interrogating 479-1,856 tumor mutations, capable of tracking ctDNA fractions down to 0.0004%. Our results demonstrate that ctDNA assays achieve high sensitivity and specificity in detecting post-operative residual disease in EOC.

Laparoscopic transabdominal-sacrococcygeal approach for resection of Altman type III sacrococcygeal teratoma in adult women: A case report.

INTRODUCTION: Adult sacrococcygeal teratoma (SCT) is a rare disease that is not easily detected or easily missed, and its treatment is based on surgery, including transabdominal, transsacral, or a combination of both, but there are no clear guidelines for diagnosis and treatment. We share a case of Altman type III SCT in order to provide more reference protocols for the diagnosis and treatment of adult SCT, and more importantly to increase our understanding of different types of SCT cases in adults. PATIENT CONCERNS: Our patient was a 31-year-old adult woman who underwent complete surgical resection of a cystic mature teratoma of the right ovary 8 years ago and is currently 13 months postpartum without menstruation, usually with a feeling of anal bulge, with symptoms such as constipation. DIAGNOSIS: We diagnosed SCT by vaginal ultrasonography, computed tomography and magnetic resonance imaging (MRI); benign tumors were considered in the results of serum tumor markers. INTERVENTIONS: We chose the surgical approach of laparoscopic transabdominal-sacrococcygeal approach to completely remove the patient SCT and coccyx. OUTCOMES: The location of SCT is concealed and the clinical symptoms are not obvious. Vaginal ultrasonography, CT and MRI can not only improve the diagnostic rate of SCT, but also understand the size and mass of SCT, providing an exact basis for clinicians to select the laparoscopic transabdominal-sacrococcygeal approach. CONCLUSION: Our sharing increases the reports of rare cases of teratoma with the same histological findings in different organ tissues of the same patient at different times, whether this occurs incidentally requires more case reports and further basic research; in addition, the laparoscopic transabdominal-sacrococcygeal approach is a safe and effective surgical approach for the treatment of Altman type III SCT in adults; finally, this case reminds us that SCT may not affect pregnancy and pregnancy outcomes and provides a reference for the selection of interventions for SCT with pregnancy.

High-Grade Serous Ovarian Cancer during Pregnancy: From Diagnosis to Treatment.

BACKGROUND: Due to the rarity of ovarian cancer diagnosed during pregnancy, the literature on the treatment of subtypes of epithelial ovarian cancer in pregnancy is sparse. The aim of our review was to analyze cases of high-grade serous ovarian cancer in pregnancy. METHODS: The PubMed and Scopus databases were searched for relevant articles published in English between January 2000 and December 2023. The references of all the relevant reviews found were also checked to avoid omitting eligible studies. Information on the all retrieved cases was extracted and reviewed in detail. The most important detail was the subtype of high-grade serous ovarian cancer, which was referred to as serous adenocarcinoma (grade 2 or grade 3) in older cases. RESULTS: We found eleven cases with relevant details of high-grade serous ovarian cancer diagnosed in pregnancy. Despite the small number of cases we found, our study demonstrated the importance of an accurate initial vaginal ultrasound at the first examination in pregnancy and the safety of diagnostic surgery and chemotherapy in pregnancy. CONCLUSIONS: There have not been long-term follow-ups of patients' oncologic and obstetric outcomes. As patients should be comprehensively informed, more detailed case reports or series with longer follow-up periods are needed.

Spectrally separated dual-label upconversion luminescence lateral flow assay for cancer-specific STn-glycosylation in CA125 and CA15-3.

Multiplexed lateral flow assays (LFAs) offer efficient on-site testing by simultaneously detecting multiple biomarkers from a single sample, reducing costs. In cancer diagnostics, where biomarkers can lack specificity, multiparameter detection provides more information at the point-of-care. Our research focuses on epithelial ovarian cancer (EOC), where STn-glycosylated forms of CA125 and CA15-3 antigens can better discriminate cancer from benign conditions. We have developed a dual-label LFA that detects both CA125-STn and CA15-3-STn within a single anti-STn antibody test line. This utilizes spectral separation of green (540 nm) and blue (450 nm) emitting erbium (NaYF4:Yb3+, Er3+)- and thulium (NaYF4: Yb3+, Tm3+)-doped upconverting nanoparticle (UCNP) reporters conjugated with antibodies against the protein epitopes in CA125 or CA15-3. This technology allows the simultaneous detection of different antigen variants from a single test line. The developed proof-of-concept dual-label LFA was able to distinguish between the ascites fluid samples from diagnosed ovarian cancer patients (n = 10) and liver cirrhosis ascites fluid samples (n = 3) used as a negative control. The analytical sensitivity of CA125-STn for the dual-label LFA was 1.8 U/ml in buffer and 3.6 U/ml in ascites fluid matrix. Here we demonstrate a novel approach of spectrally separated measurement of STn-glycosylated forms of two different cancer-associated protein biomarkers by using UCNP reporter technology.

Serum anti-CFL1, anti-EZR, and anti-CYPA autoantibody as diagnostic markers in ovarian cancer.

The purpose of this study was to identify novel autoantibodies against tumor-associated antigens (TAAs) and explore a diagnostic panel for Ovarian cancer (OC). Enzyme-linked immunosorbent assay was used to detect the expression of five anti-TAA autoantibodies in the discovery (70 OC and 70 normal controls) and validation cohorts (128 OC and 128 normal controls). Machine learning methods were used to construct a diagnostic panel. Serum samples from 81 patients with benign ovarian disease were used to identify the specificity of anti-TAA autoantibodies for OC. In both the discovery and validation cohorts, the expression of anti-CFL1, anti-EZR, anti-CYPA, and anti-PFN1 was higher in patients with OC than that in normal controls. The area under the receiver operating characteristic curve, sensitivity, and specificity of the panel containing anti-CFL1, anti-EZR, and anti-CYPA were 0.762, 55.56%, and 81.31%. The panel identified 53.06%, 53.33%, and 51.11% of CA125 negative, HE4 negative and the Risk of Ovarian Malignancy Algorithm negative OC patients, respectively. The combination of the three anti-TAA autoantibodies can serve as a favorable diagnostic tool for OC and has the potential to be a complementary biomarker for CA125 and HE4 in the diagnosis of ovarian cancer.

Genomic alterations in ovarian endometriosis and subsequently diagnosed ovarian carcinoma.

STUDY QUESTION: Can the alleged association between ovarian endometriosis and ovarian carcinoma be substantiated by genetic analysis of endometriosis diagnosed prior to the onset of the carcinoma? SUMMARY ANSWER: The data suggest that ovarian carcinoma does not originate from ovarian endometriosis with a cancer-like genetic profile; however, a common precursor is probable. WHAT IS KNOWN ALREADY: Endometriosis has been implicated as a precursor of ovarian carcinoma based on epidemiologic studies and the discovery of common driver mutations in synchronous disease at the time of surgery. Endometrioid ovarian carcinoma and clear cell ovarian carcinoma are the most common endometriosis-associated ovarian carcinomas (EAOCs). STUDY DESIGN, SIZE, DURATION: The pathology biobanks of two university hospitals in Sweden were scrutinized to identify women with surgically removed endometrioma who subsequently developed ovarian carcinoma (1998-2016). Only 45 archival cases with EAOC and previous endometriosis were identified and after a careful pathology review, 25 cases were excluded due to reclassification into non-EAOC (n = 9) or because ovarian endometriosis could not be confirmed (n = 16). Further cases were excluded due to insufficient endometriosis tissue or poor DNA quality in either the endometriosis, carcinoma, or normal tissue (n = 9). Finally 11 cases had satisfactory DNA from all three locations and were eligible for further analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Epithelial cells were collected from formalin-fixed and paraffin-embedded (FFPE) sections by laser capture microdissection (endometrioma n = 11) or macrodissection (carcinoma n = 11) and DNA was extracted. Normal tissue from FFPE sections (n = 5) or blood samples collected at cancer diagnosis (n = 6) were used as the germline controls for each included patient. Whole-exome sequencing was performed (n = 33 samples). Somatic variants (single-nucleotide variants, indels, and copy number alterations) were characterized, and mutational signatures and kataegis were assessed. Microsatellite instability and mismatch repair status were confirmed with PCR and immunohistochemistry, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: The median age for endometriosis surgery was 42 years, and 54 years for the subsequent ovarian carcinoma diagnosis. The median time between the endometriosis and ovarian carcinoma was 10 (7-30) years. The data showed that all paired samples harbored one or more shared somatic mutations. Non-silent mutations in cancer-associated genes were frequent in endometriosis; however, the same mutations were never observed in subsequent carcinomas. The degree of clonal dominance, demonstrated by variant allele frequency, showed a positive correlation with the time to cancer diagnosis (Spearman's rho 0.853, P < 0.001). Mutations in genes associated with immune escape were the most conserved between paired samples, and regions harboring these genes were frequently affected by copy number alterations in both sample types. Mutational burdens and mutation signatures suggested faulty DNA repair mechanisms in all cases. LARGE SCALE DATA: Datasets are available in the supplementary tables. LIMITATIONS, REASONS FOR CAUTION: Even though we located several thousands of surgically removed endometriomas between 1998 and 2016, only 45 paired samples were identified and even fewer, 11 cases, were eligible for sequencing. The observed high level of intra- and inter-heterogeneity in both groups (endometrioma and carcinoma) argues for further studies of the alleged genetic association. WIDER IMPLICATIONS OF THE FINDINGS: The observation of shared somatic mutations in all paired samples supports a common cellular origin for ovarian endometriosis and ovarian carcinoma. However, contradicting previous conclusions, our data suggest that cancer-associated mutations in endometriosis years prior to the carcinoma were not directly associated with the malignant transformation. Rather, a resilient ovarian endometriosis may delay tumorigenesis. Furthermore, the data indicate that genetic alterations affecting the immune response are early and significant events. STUDY FUNDING/COMPETING INTEREST(S): The present work has been funded by the Sjöberg Foundation (2021-01145 to K.S.; 2022-01-11:4 to A.S.), Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (965552 to K.S.; 40615 to I.H.; 965065 to A.S.), Swedish Cancer Society (21-1848 to K.S.; 21-1684 to I.H.; 22-2080 to A.S.), BioCARE-A Strategic Research Area at Lund University (I.H. and S.W.-F.), Mrs Berta Kamprad's Cancer Foundation (FBKS-2019-28, I.H.), Cancer and Allergy Foundation (10381, I.H.), Region Västra Götaland (A.S.), Sweden's Innovation Agency (2020-04141, A.S.), Swedish Research Council (2021-01008, A.S.), Roche in collaboration with the Swedish Society of Gynecological Oncology (S.W.-F.), Assar Gabrielsson Foundation (FB19-86, C.M.), and the Lena Wäpplings Foundation (C.M.). A.S. declares stock ownership and is also a board member in Tulebovaasta, SiMSen Diagnostics, and Iscaff Pharma. A.S. has also received travel support from EMBL, Precision Medicine Forum, SLAS, and bioMCC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.