Retrospective Study on the Incidence of Benign, Premalignant, and Malignant Gynecologic Disorders in Patients with Adenomyosis: Analysis of 5648 Specimens

Retrospective Study on the Incidence of Benign, Premalignant, and Malignant Gynecologic Disorders in Patients with Adenomyosis: Analysis of 5648 Specimens | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Retrospective Study on the Incidence of Benign, Premalignant, and Malignant Gynecologic Disorders in Patients with Adenomyosis: Analysis of 5648 Specimens Yunlei Cao, Cenyu Li, Ding Ding This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4448561/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Adenomyosis is an estrogen-dependent disease and ranks among the most common gynecological benign conditions in women of childbearing age. Adenomyosis has been reported to coincide with endometrial hyperplasia, polyps, and even endometrial cancer. This study aims to investigate the incidence of benign, premalignant, and malignant gynecological diseases in women undergoing gynecological surgery for adenomyosis. A retrospective review of medical records collected from January 2021 to May 2023 for surgeries performed at the Obstetrics and Gynecology Hospital affiliated with Fudan University was conducted. Pathology reports of 5648 cases of adenomyosis were studied. The incidence of benign, premalignant, and malignant gynecological pathologies in women with adenomyosis who underwent gynecological surgery were analyzed. The mean age of women with adenomyosis was 49.0 ± 9.0 years. Adenomyosis without other gynecological pathologies was detected in 16.7% of specimens of 5648 patients, while coexistence with one or more gynecological pathologies was present in 82.3% of cases. Additionally, coexistence with two or more gynecological diseases (benign or malignant) was present in 1806 of 5648 patients (31.9%). The most common comorbidities were uterine leiomyoma (57.1%), followed by endometrial cancer (11.8%) and endometriosis (10.7%). Furthermore, we found that women with adenomyosis, leiomyoma, endometriosis, endometrial polyps, or atypical hyperplasia were younger (p < 0.05) compared with adenomyotic patients with malignant tumors. Adenomyosis is a common benign, progressive disease that has garnered increasing attention in recent years. Some studies have suggested a potential association of adenomyosis with several gynecological diseases. Our study shows a high prevalence of endometrial cancer in patients with adenomyosis compared to the general population. Health sciences/Diseases/Reproductive disorders Biological sciences/Cancer adenomyosis benign premalignant malignant gynecological diseases endometrial cancer Introduction Adenomyosis is an estrogen-dependent disease and ranks among the most common gynecological benign conditions in women of childbearing age ( 1 ). It is characterized by the ectopic growth of endometrial epithelium and stroma into the muscle layer of the uterus, leading to diffuse or focal enlargement of the uterus ( 2 – 4 ). This entity was first described by Carl von Rokitansky in 1860 as "cystosarcoma adenoids uterinum" ( 5 ), the frequency of adenomyosis has been reported to range from 10–70%, with a higher prevalence observed in women aged 40 to 55 years ( 6 ). Vercellini et al. speculated that adenomyosis could be present in 30–60% of hysterectomy specimens ( 7 ). Additionally, literature indicates its coexistence with endometriosis and uterine fibroids. Although distinct diseases, 35–55% of women diagnosed with fibroids exhibit clinical features common to adenomyosis, such as irregular vaginal bleeding, menstrual cycle-related pain, and chronic pelvic pain. Moreover, adenomyosis has been reported to coincide with endometrial hyperplasia, polyps, and even endometrial cancer ( 8 – 11 ). Risk factors associated with adenomyosis include being in one’s mid-forties, experiencing multiple births, smoking habits, and elevated levels of hormones such as follicle-stimulating hormone (FSH) and prolactin. Prior cesarean section and uterine surgery are also significant risks, potentially damaging the junctional zone ( 5 ). This study aims to investigate the incidence of benign, premalignant, and malignant gynecological diseases in women undergoing gynecological surgery for adenomyosis. Materials and Methods We conducted a retrospective review of medical records from patients who underwent gynecological surgery at the Obstetrics and Gynecology Hospital affiliated with Fudan University between January 2021 and May 2023. Exclusion criteria included histological evidence of non-adenomyosis. A final retrospective examination was conducted on 5648 patients with histologically confirmed adenomyosis. Recorded data encompassed age, surgical method, and presence of other benign, premalignant, and malignant gynecological diseases. Pathological features of gynecological diseases were classified according to FIGO criteria. The protocol for this study was approved by the Ethics Committee of the Obstetrics and Gynecology Hospital affiliated with Fudan University. Statistical Analysis Statistical analysis was performed using SPSS version 6.0 software. The number and percentage of patients were presented for qualitative variables, while median and range were used for continuous variables. T-tests and Chi-square tests were employed to compare the means of various characteristics. In cases where the data did not adhere to normal distribution, the Mann-Whitney U test was conducted. Results are reported as mean ± standard deviation (SD). A p-value of < 0.05 was considered statistically significant. Results In this study, we included patients diagnosed with adenomyosis based on histopathological findings from uterine-sparing and non-uterine-sparing specimens. A total of 5648 women with adenomyosis were diagnosed with or without other gynecological pathology. Isolated adenomyosis was found in 942 cases (16.7%), and 82.3% (4647/5648) of patients with adenomyosis had at least one gynecological disease (Table 1 ). While coexistence with two or more gynecological pathology was found in 1806 cases (31.9%). Table 1 Coexistence of adenomyosis with more than one gynecological pathologies. Gynecological pathologies No (%) Total number of cases with coexisted pathology 4647/5648(82.3%) Coexistence with leiomyomas and endometriosis 356(6.3%) Coexistence with leiomyomas and benign ovarian cyst 249(4.4%) Coexistence with leiomyomas and borderline ovarian tumer 23(0.4%) Coexistence with leiomyomas and ovarian cancer 99(1.8%) Coexistence with leiomyomas and endometrial polyps 254(4.5%) Coexistence with leiomyomas and endometrial hyperplasia 106(1.9%) Coexistence with leiomyomas and atypical hyperplasia 114(2.0%) Coexistence with leiomyomas and endometrial cancer 344(6.1%) Coexistence with leiomyomas and uterine sarcoma 22(0.4%) Coexistence with leiomyomas and cervical intraepithelial neoplaisa 210 (3.7%) Coexistence with leiomyomas and cervical cancer 207(3.7%) This table describes the incidence of more than one gynecological pathologies in 5648 women with adenomyosis. No: number of cases, %: percentage. The mean age of patients at the time of surgery was 49.0 ± 9.0 years. The main surgical indications were abnormal vaginal bleeding, pelvic pain, and benign or malignant gynecological pathology of the reproductive system. Patients who underwent hysterectomy (50.0 ± 9.0) were older than those who underwent non-hysterectomy (40.0 ± 7.0) (p = 0.002). Uterine leiomyoma accounted for 57.1% (3227/5648), followed by endometrial cancer (11.8%), endometriosis (10.7%), cervical cancer (9.8%), cervical intraepithelial neoplasia (8.3%), benign ovarian cyst (7.7%), endometrial polyps (7.6%), endometrial atypical hyperplasia (4.1%), ovarian cancer (3.9%), and endometrial hyperplasia (3.4%) (Table 2 ). Table 2 Coexistence of benign or premalignant gynecological pathologies and adenomyosis. Benign or premalignant gynecological pathologies No (%) Coexistence with leiomyomas 3227(57.1%) Coexistence with endometriosis 605(10.7%) Coexistence with endometrial polyps 432(7.6%) Coexistence with endometrial simple and complex hyperplasia 191(3.4%) Coexistence with atypical hyperplasia 234(4.1%) Coexistence with benign ovarian cyst 432(7.7%) Coexistence with borderline ovarian tumer 57(1.0%) Coexistence with cervical intraepithelial neoplaisa ( CIN) 469(8.3%) This table describes the frequency of benign and premalignant gynecological pathologies in 5648 women with adenomyosis. No: number of cases, %: percentage. The coexistence of adenomyosis and gynecological benign or premalignancies was shown in Table 2 . Among them, 8.3% (469/5648) were cervical intraepithelial neoplasia (CIN) and 1.0% (57/5648) were borderline ovarian tumors. Table 3 shows the coexistence of adenomyosis and gynecological malignancies. Of these, 0.7%(42/5648) were uterine sarcoma and 3.9%(219/5648) were ovarian cancer. Table 3 Coexistence of gynecological malignancy pathologies and adenomyosis. Gynecological malignancy pathologies No (%) Coexistence with endometrial cancer 667(11.8%) Coexistence with cervical cancer 546(9.7%) Coexistence with uterine sarcoma 42(0.7%) Coexistence with ovarian cancer 219(3.9%) This table describes the frequency of gynecological malignancy pathologies in women with adenomyosis. No: number of cases, %: percentage. At the same time, abnormal ectopic endometrium were observed in 50 patients with adenomyosis, including 30 cases of atypical hyperplasia, 3 cases of ectopic glandular carcinoma, and 17 cases of atypical polypoid adenomyoma(APA) (Table 4 ). Table 4 Ectopic endometrial pathologies of adenomyosis. Ectopic endometrium pathologies No (%) Normal ectopic endometrium 5598(99.0%) Ectopic endometrium dysplasia 30(0.53%) Ectopic endometrium carcinoma 3(0.05%) APA (atypical polypoid adenomyoma) 17(0.3%) This table describes the frequency of abnormal ectopic endometrial pathologies in 5648 women with adenomyosis. No: number of cases, %: percentage. In addition, we observed that endometrial and ovarian cancers were prominent in postmenopausal women. In contrast, benign lesions were more prevalent in younger women (p < 0.05). Discussion Literature reports have associated adenomyosis with various gynecological diseases, and our study confirms a significantly higher prevalence of endometrial cancer in patients with adenomyosis. Adenomyosis, characterized by the chronic invasion of endometrial glands and stroma into the myometrium, leads to uterine enlargement, tissue hyperplasia, and hypertrophy ( 12 ). The pathogenesis of adenomyosis remain unknown. Recent studies have implicated various inflammatory molecules, sex steroid hormone receptors, extracellular matrix enzymes, growth factors, and neuro-angiogenic factors in the pathogenesis of adenomyosis ( 3 ). Additionally, genetic alterations in signaling pathways have been identified as contributing factors. Previous research has suggested that the occurrence of gynecological diseases may be influenced by factors such as inflammation, diet, genetics, and the environment ( 13 ). In recent years, increasing attention has been directed towards investigating the common pathogenesis and causality linking adenomyosis with other gynecological benign and malignant diseases. Adenomyosis and Hormone-Dependent Diseases Variations in the expression levels of estrogen receptor (ER) and progesterone receptor (PR) have been observed in patients with adenomyosis and leiomyoma ( 14 ), while elevated levels of metalloproteinases (MMPs) such as MMP-2 and MMP-9, along with certain specific cytokines, are significantly heightened in patients with adenomyosis, leiomyoma, and endometrial polyps ( 15 ). Polymorphisms in the estrogen receptor-alpha (ERα) gene have also been linked to endometriosis, adenomyosis, and leiomyoma ( 16 ). Furthermore, polymorphisms in MMP-1, MMP-7, and peroxisome proliferator-activated receptor γ (PPARγ) genes have been identified as risk factors for adenomyosis and endometriosis, albeit not for leiomyoma ( 17 ). A recent study utilizing next-generation sequencing (NGS) has revealed an association between the presence of KRAS mutations and the co-occurrence of adenomyosis and endometriosis ( 18 ). Polymorphisms in fibroblast growth factor (FGF-1 and − 2), pivotal angiogenic factors, may also contribute to the initiation of angiogenesis in endometriosis and adenomyosis ( 19 ). In summary, several common genetic risk factors are implicated in the coexistence of adenomyosis with other gynecological diseases, although it is evident that disease-specific genes also exert influence. A considerable body of previous research has indicated a comorbidity relationship between adenomyosis and both benign and malignant gynecological tumors ( 8 – 11 , 20 ). Findings from a large retrospective study on hysterectomized women demonstrated that patients with leiomyoma and adenomyosis were more likely to present with similar complaints( 21 ). The common occurrence is a high estrogen environment in these diseases ( 22 ). Considering the epidemiological standards outlined in the current literature regarding gynecological benign diseases in the general population, we did not observe high incidences of these conditions in patients with adenomyosis. For instance, up to 70% of women are known to develop leiomyomas by the time of menopause ( 23 ). The prevalence of endometrial polyps varies from 7.8% to nearly 35% depending on the geographic area and study population ( 24 ). Additionally, abnormal uterine bleeding and endometrial hyperplasia have been reported in 10% of premenopausal women and 6% of postmenopausal women at some point in their lives ( 25 ). For nearly a century, except for endometriomas, and adenomyosis were considered to be the same entity ( 3 , 22 ). Although they can coexist in patients, adenomyosis and endometriosis are considered two distinct diseases from a causative perspective, as they have specific causative pathways and clinical symptoms. In the general population, 10–15% of women of reproductive age are affected by endometriosis ( 26 ). In our study, we identified 605 patients with adenomyosis combined with endometriosis (10.7%). Thus, based on our data, we did not observe an increased risk of leiomyoma, endometriosis, endometrial hyperplasia, and atypical hyperplasia in women with adenomyosis compared to the general population. Recent studies have suggested that adenomyosis increases the risk of endometrial cancer and thyroid cancer, while endometrial cancer and ovarian cancer are at a higher risk in patients with endometriosis ( 20 , 22 ). Although the association between the pathogenesis of adenomyosis and endometrial cancer remains unclear, endometrial cancer complicated with adenomyosis has been reported to have a better prognosis due to hormonal imbalance ( 9 , 22 ). Conversely, in a large preliminary study, the authors did not find significant differences in the epidemiological profiles between patients with endometrial cancer combined with adenomyosis and those with isolated endometrial cancer ( 27 ). Additionally, Raffone et al. recently assessed the prevalence of adenomyosis in patients with endometrial cancer and found no difference in the prevalence of adenomyosis in endometrial cancer cases compared to other gynecological diseases requiring surgical treatment ( 28 ). Koshiyama et al. reported that 4 out of 564 women with adenomyosis developed adenocarcinoma ( 29 ). In a retrospective study based on 647 patients with adenomyosis, Matalliotakis reported that endometrial cancer accounted for 3.6% of patients with adenomyosis ( 6 ). In the present study, we confirmed that endometrial cancer was present in 11.8% of patients with adenomyosis. However, the National Cancer Institute mentions that about 3.1% of women will be diagnosed with uterine cancer at some point in their lifetime ( 30 ). Therefore, based on the above studies, we speculate that women with adenomyosis have an increased risk of endometrial cancer compared to patients without adenomyosis. Further studies are needed to confirm our findings and investigate the molecular mechanisms responsible for this phenomenon. Although adenomyosis may serve as a genetic precursor to certain cancers, the precise molecular mechanisms underlying this malignant transformation remain elusive. Adenomyosis and type 1 endometrial cancer are both influenced by the effects of sex steroids, and the gene expression profile of this condition is linked to cancer, cell death, and cell cycle networks ( 31 ). Additionally, mRNA levels of phosphatase and tensin homolog (PTEN) are reduced in adenomyosis. Notably, PTEN is considered a tumor suppressor gene and is mutated in numerous cancers ( 32 ). The association between PTEN and endometrial cancer has been well established ( 33 ), and mutations in KRAS and BCL2 genes further bolster the potential link between adenomyosis and endometrial cancer ( 31 ). Adenomyosis and Non-Hormone Dependent Diseases Regarding ovarian cancer, findings from a large case-control study have confirmed that adenomyosis significantly increases the risk of ovarian cancer ( 34 ). However, contrasting results have been reported in another study, suggesting that adenomyosis does not elevate the risk of ovarian cancer ( 20 ). According to the National Cancer Institute, approximately 3.1% of women will be diagnosed with uterine cancer at some point in their lifetime, less than 2% will develop ovarian cancer, and 0.6% will be diagnosed with cervical cancer ( 30 ). Matalliotakis reported that ovarian cancer accounted for 1.4% of patients with adenomyosis, followed by cervical cancer (0.8%) ( 8 ). A recent study suggests that both adenomyosis and endometriosis may increase the risk of endometrial cancer, while endometriosis alone may elevate the risk of ovarian cancer, but neither condition appears to affect the risk of cervical cancer ( 20 ). To date, there have been limited studies investigating the association between adenomyosis and the risk of cervical cancer. In our study, we observed that cervical cancer was present in 9.7% of patients with adenomyosis, followed by cervical intraepithelial neoplasia (CIN) (8.3%) and ovarian cancer (3.9%). Based on these findings, we cannot definitively conclude that adenomyosis increases the risk of cervical cancer. The observed discrepancy may largely be attributed to the availability of HPV vaccines in developed countries. Endometriosis is known to increase the risk of ovarian cancer, and our study did not exclude the occurrence of ovarian cancer in patients with coexisting adenomyosis and endometriosis, thereby contributing to the slightly higher observed risk of ovarian cancer. Adenomyosis with Abnormal Ectopic Endometrial Pathology Interestingly, literature reports suggest that the growth, invasion, and angiogenesis patterns observed in adenomyosis may serve as precursors to cancerous transformation ( 35 ). Notably, malignant transformation of adenomyosis is more prevalent in postmenopausal and older women, as well as in individuals with preexisting benign gynecological conditions ( 9 ). Malignant changes in adenomyosis account for approximately 6.8% of cases of endometrial cancer ( 36 ). Moreover, the transformation of endometrial epithelium into cancer cells may contribute to the malignant transformation of adenomyosis, leading to tumorigenesis ( 9 ). Recent research has shed light on the impact of adenomyosis on the aggressiveness of endometrial cancer. While adenomyosis has not been established as an independent prognostic factor for endometrial tumors, cases of endometrial cancer combined with adenomyosis tend to have better prognoses ( 37 ). A study in 2022 further confirmed increased survival rates among women with endometrial cancer and histologically proven endometriosis or adenomyosis ( 38 ). This improved prognosis may be attributed to various factors, including younger age at diagnosis, earlier disease stages, more favorable histological subtypes, lower tumor grades, higher rates of surgery, and lower rates of chemotherapy. However, a large preliminary study did not find significant differences in the epidemiological, clinicopathological, and prognostic characteristics between patients with endometrial cancer combined with adenomyosis and those with isolated endometrial cancer ( 27 ). Moreover, recent systematic reviews and meta-analyses have demonstrated that adenomyosis and endometrial cancer are two distinct pathologies ( 28 ). Additionally, due to de novo malignant transformation of adenomyosis foci and simultaneous malignant transformation of eutopic endometrium and adenomyosis, studies suggest that the presence of adenomyosis may play a significant role in determining the prognosis of adenocarcinoma ( 22 ). Atypical Polypoid Adenomyoma (APA), also known as atypical polypoid adenoma-uterine fibroma, is a rare uterine lesion initially described by Mazur in 1981 ( 39 ). It serves as an indicator or precursor of endometrial adenocarcinoma or may coexist with endometrial adenocarcinoma ( 40 , 41 ). Literature data indicate that APA is an endometrial tumor with low malignant potential and low incidence, more commonly affecting patients of childbearing age ( 42 ). Among 237 patients included in eleven retrospective studies, 85.5% were premenopausal, and 62.9% were nulliparous. Atypical polypoid adenomyoma with atypical hyperplasia accounted for 5.5%, while endometrial cancer was observed in 5.9% of cases. The overall risk of recurrence and progression to cancer was reported to be 28.9% and 16.6%, respectively ( 43 ). Numerous studies have linked the pathogenesis of APA with estrogen-related factors, obesity, diabetes, long-term estrogen stimulation, and hormone replacement therapy (HRT) ( 42 ). Due to the rarity of APA, there have been no retrospective studies with large sample sizes, and the exact pathogenesis of APA remains unclear. In our study, among the 5648 patients with adenomyosis, we observed 30 cases with ectopic endometrial hyperplasia, 3 cases with ectopic endometrial carcinoma, and 17 cases with APA. As the number of cases of these conditions increases in the future, further studies are warranted to explore the molecular mechanisms underlying their pathogenesis. The limitations of this study are partly attributable to its retrospective nature. Since we did not exclude cases where ovarian cancer, adenomyosis, and endometriosis coexisted, there may be a bias in the reported incidence of ovarian cancer among patients with adenomyosis. The large sample size and histopathology-based analysis are the outstanding strengths of the study. This rigorous approach enhances the reliability of our findings and strengthens the validity of the associations observed. Conclusions In summary, the present retrospective study supported the increased incidence of endometrial cancer in patients with adenomyosis. However, the incidence of other gynecological diseases is not elevated in patients with adenomyosis compared to the general population. Further research is necessary to investigate this speculation. Declarations Funding Statement There is no funding for the project. Conflict of Interest Disclosure The authors declare that they have no conflicts of interest and have nothing further to disclose. Ethical Approval The Ethics committee of Obstetrics and Gynecology Hospital Affiliated to Fudan University approved the protocol. This article does not contain any animal studies conducted by any of the authors. Informed Consent Informed consent was obtained from all individuals involved in the study. Data Availability Statement The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. Author Contribution Statement Yunlei Cao (First Author): Data curation, Formal analysis, Methodology, Writing-original draft Cenyu Li: Data curation Ding Ding (Corresponding Author): Resources, Supervision, Writing-review & editing References J. Chikumi, T. Oishi, T. 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Kanda, Y. Ojima, T. Kizaki, N. Ohara, Coexistence of endometrioid adenocarcinoma in atypical polypoid adenomyoma, Kobe J Med Sci 60(3) (2014) E74-7. L. Javed, N. Ashraf, M. Sabqat, A. Zareen, Atypical Polypoid Adenomyoma (APAM), J Coll Physicians Surg Pak 30(6) (2021) 719-721. M.I. Mitranovici, I.E. Oala, I. Petre, et al, Atypical Polypoid Adenomyoma of the Vagina: Follow Up and Subsequent Evolution: A Case Report and Update, Diagnostics (Basel) 12(2) (2022). A. Raffone, A. Travaglino, G. Saccone, et al, Management of women with atypical polypoid adenomyoma of the uterus: A quantitative systematic review, Acta Obstet Gynecol Scand 98(7) (2019) 842-855. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4448561","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":311693521,"identity":"fb579970-475e-4c47-bcb3-07a35f37c98d","order_by":0,"name":"Yunlei Cao","email":"","orcid":"","institution":"Obstetrics and Gynecology Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Yunlei","middleName":"","lastName":"Cao","suffix":""},{"id":311693522,"identity":"d791d72d-97fa-4224-ad28-6759e8c5325e","order_by":1,"name":"Cenyu Li","email":"","orcid":"","institution":"Shanghai Jiao Tong University","correspondingAuthor":false,"prefix":"","firstName":"Cenyu","middleName":"","lastName":"Li","suffix":""},{"id":311693523,"identity":"2fddc346-fe40-4c86-a420-037748034e68","order_by":2,"name":"Ding Ding","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCElEQVRIiWNgGAWjYDCCw0DMYwBhH/hgYCPHxt5+gGgtjAdnVKQZ8/GcScCvBWQiD4TJfJjnzOHEeRIOBnh18B3nPfziTcEdu/kRuQcO8LalpbdJMCQw/KjYhlOL5GG+NMs5Bs+SN97ISzgg2WaT2ybdeICx58xtnFoMDvOYGfMYHE42nJFjcMCwLS23TeZAAjNjG7FaEtsOp7NJJBgQ0mL8GKjFTl4CqOXAmcMJBLVIAm1hnGNwOMGA543BwYaKNMM2YCAfxOcXvvNnjD+8+XPYXr49x/jzHwMbefn29oMPflTg1gIEbBJAInHDhQSE0AF86oGA+QOQsJfvJ6RuFIyCUTAKRiwAAHGVYn+ks3aJAAAAAElFTkSuQmCC","orcid":"","institution":"Obstetrics and Gynecology Hospital of Fudan University","correspondingAuthor":true,"prefix":"","firstName":"Ding","middleName":"","lastName":"Ding","suffix":""}],"badges":[],"createdAt":"2024-05-20 10:43:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4448561/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4448561/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58925222,"identity":"6f6ace14-f1c8-4b65-8787-ded347167330","added_by":"auto","created_at":"2024-06-24 08:05:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":444755,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4448561/v1/8abdb98d-a17d-477d-9304-9d34feff9b8f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Retrospective Study on the Incidence of Benign, Premalignant, and Malignant Gynecologic Disorders in Patients with Adenomyosis: Analysis of 5648 Specimens","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAdenomyosis is an estrogen-dependent disease and ranks among the most common gynecological benign conditions in women of childbearing age (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). It is characterized by the ectopic growth of endometrial epithelium and stroma into the muscle layer of the uterus, leading to diffuse or focal enlargement of the uterus (\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). This entity was first described by Carl von Rokitansky in 1860 as \"cystosarcoma adenoids uterinum\" (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e), the frequency of adenomyosis has been reported to range from 10\u0026ndash;70%, with a higher prevalence observed in women aged 40 to 55 years (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Vercellini et al. speculated that adenomyosis could be present in 30\u0026ndash;60% of hysterectomy specimens (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Additionally, literature indicates its coexistence with endometriosis and uterine fibroids. Although distinct diseases, 35\u0026ndash;55% of women diagnosed with fibroids exhibit clinical features common to adenomyosis, such as irregular vaginal bleeding, menstrual cycle-related pain, and chronic pelvic pain. Moreover, adenomyosis has been reported to coincide with endometrial hyperplasia, polyps, and even endometrial cancer (\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRisk factors associated with adenomyosis include being in one\u0026rsquo;s mid-forties, experiencing multiple births, smoking habits, and elevated levels of hormones such as follicle-stimulating hormone (FSH) and prolactin. Prior cesarean section and uterine surgery are also significant risks, potentially damaging the junctional zone (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). This study aims to investigate the incidence of benign, premalignant, and malignant gynecological diseases in women undergoing gynecological surgery for adenomyosis.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e We conducted a retrospective review of medical records from patients who underwent gynecological surgery at the Obstetrics and Gynecology Hospital affiliated with Fudan University between January 2021 and May 2023. Exclusion criteria included histological evidence of non-adenomyosis. A final retrospective examination was conducted on 5648 patients with histologically confirmed adenomyosis. Recorded data encompassed age, surgical method, and presence of other benign, premalignant, and malignant gynecological diseases. Pathological features of gynecological diseases were classified according to FIGO criteria.\u003c/p\u003e \u003cp\u003e The protocol for this study was approved by the Ethics Committee of the Obstetrics and Gynecology Hospital affiliated with Fudan University.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using SPSS version 6.0 software. The number and percentage of patients were presented for qualitative variables, while median and range were used for continuous variables. T-tests and Chi-square tests were employed to compare the means of various characteristics. In cases where the data did not adhere to normal distribution, the Mann-Whitney U test was conducted. Results are reported as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). A p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eIn this study, we included patients diagnosed with adenomyosis based on histopathological findings from uterine-sparing and non-uterine-sparing specimens. A total of 5648 women with adenomyosis were diagnosed with or without other gynecological pathology. Isolated adenomyosis was found in 942 cases (16.7%), and 82.3% (4647/5648) of patients with adenomyosis had at least one gynecological disease (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). While coexistence with two or more gynecological pathology was found in 1806 cases (31.9%).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCoexistence of adenomyosis with more than one gynecological pathologies.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGynecological pathologies\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal number of cases with coexisted pathology\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4647/5648(82.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with leiomyomas and endometriosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e356(6.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with leiomyomas and benign ovarian cyst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e249(4.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with leiomyomas and borderline ovarian tumer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23(0.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with leiomyomas and ovarian cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e99(1.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with leiomyomas and endometrial polyps\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e254(4.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with leiomyomas and endometrial hyperplasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e106(1.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with leiomyomas and atypical hyperplasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e114(2.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with leiomyomas and endometrial cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e344(6.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with leiomyomas and uterine sarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22(0.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with leiomyomas and cervical intraepithelial neoplaisa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e210 (3.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with leiomyomas and cervical cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e207(3.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eThis table describes the incidence of more than one gynecological pathologies in 5648 women with adenomyosis. No: number of cases, %: percentage.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe mean age of patients at the time of surgery was 49.0\u0026thinsp;\u0026plusmn;\u0026thinsp;9.0 years. The main surgical indications were abnormal vaginal bleeding, pelvic pain, and benign or malignant gynecological pathology of the reproductive system. Patients who underwent hysterectomy (50.0\u0026thinsp;\u0026plusmn;\u0026thinsp;9.0) were older than those who underwent non-hysterectomy (40.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0) (p\u0026thinsp;=\u0026thinsp;0.002). Uterine leiomyoma accounted for 57.1% (3227/5648), followed by endometrial cancer (11.8%), endometriosis (10.7%), cervical cancer (9.8%), cervical intraepithelial neoplasia (8.3%), benign ovarian cyst (7.7%), endometrial polyps (7.6%), endometrial atypical hyperplasia (4.1%), ovarian cancer (3.9%), and endometrial hyperplasia (3.4%) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCoexistence of benign or premalignant gynecological pathologies and adenomyosis.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBenign or premalignant gynecological pathologies\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with leiomyomas\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3227(57.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with endometriosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e605(10.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with endometrial polyps\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e432(7.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with endometrial simple and complex hyperplasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e191(3.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with atypical hyperplasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e234(4.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with benign ovarian cyst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e432(7.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with borderline ovarian tumer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e57(1.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with cervical intraepithelial neoplaisa ( CIN)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e469(8.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eThis table describes the frequency of benign and premalignant gynecological pathologies in 5648 women with adenomyosis. No: number of cases, %: percentage.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe coexistence of adenomyosis and gynecological benign or premalignancies was shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Among them, 8.3% (469/5648) were cervical intraepithelial neoplasia (CIN) and 1.0% (57/5648) were borderline ovarian tumors.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the coexistence of adenomyosis and gynecological malignancies. Of these, 0.7%(42/5648) were uterine sarcoma and 3.9%(219/5648) were ovarian cancer.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCoexistence of gynecological malignancy pathologies and adenomyosis.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGynecological malignancy pathologies\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with endometrial cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e667(11.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with cervical cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e546(9.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with uterine sarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e42(0.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence with ovarian cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e219(3.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eThis table describes the frequency of gynecological malignancy pathologies in women with adenomyosis. No: number of cases, %: percentage.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAt the same time, abnormal ectopic endometrium were observed in 50 patients with adenomyosis, including 30 cases of atypical hyperplasia, 3 cases of ectopic glandular carcinoma, and 17 cases of atypical polypoid adenomyoma(APA) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEctopic endometrial pathologies of adenomyosis.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEctopic endometrium pathologies\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal ectopic endometrium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5598(99.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEctopic endometrium dysplasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30(0.53%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEctopic endometrium carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3(0.05%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPA (atypical polypoid adenomyoma)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17(0.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eThis table describes the frequency of abnormal ectopic endometrial pathologies in 5648 women with adenomyosis. No: number of cases, %: percentage.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn addition, we observed that endometrial and ovarian cancers were prominent in postmenopausal women. In contrast, benign lesions were more prevalent in younger women (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eLiterature reports have associated adenomyosis with various gynecological diseases, and our study confirms a significantly higher prevalence of endometrial cancer in patients with adenomyosis. Adenomyosis, characterized by the chronic invasion of endometrial glands and stroma into the myometrium, leads to uterine enlargement, tissue hyperplasia, and hypertrophy (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). The pathogenesis of adenomyosis remain unknown. Recent studies have implicated various inflammatory molecules, sex steroid hormone receptors, extracellular matrix enzymes, growth factors, and neuro-angiogenic factors in the pathogenesis of adenomyosis (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Additionally, genetic alterations in signaling pathways have been identified as contributing factors. Previous research has suggested that the occurrence of gynecological diseases may be influenced by factors such as inflammation, diet, genetics, and the environment (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). In recent years, increasing attention has been directed towards investigating the common pathogenesis and causality linking adenomyosis with other gynecological benign and malignant diseases.\u003c/p\u003e\n\u003ch3\u003eAdenomyosis and Hormone-Dependent Diseases\u003c/h3\u003e\n\u003cp\u003eVariations in the expression levels of estrogen receptor (ER) and progesterone receptor (PR) have been observed in patients with adenomyosis and leiomyoma (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e), while elevated levels of metalloproteinases (MMPs) such as MMP-2 and MMP-9, along with certain specific cytokines, are significantly heightened in patients with adenomyosis, leiomyoma, and endometrial polyps (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Polymorphisms in the estrogen receptor-alpha (ERα) gene have also been linked to endometriosis, adenomyosis, and leiomyoma (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Furthermore, polymorphisms in MMP-1, MMP-7, and peroxisome proliferator-activated receptor γ (PPARγ) genes have been identified as risk factors for adenomyosis and endometriosis, albeit not for leiomyoma (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). A recent study utilizing next-generation sequencing (NGS) has revealed an association between the presence of KRAS mutations and the co-occurrence of adenomyosis and endometriosis (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Polymorphisms in fibroblast growth factor (FGF-1 and \u0026minus;\u0026thinsp;2), pivotal angiogenic factors, may also contribute to the initiation of angiogenesis in endometriosis and adenomyosis (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). In summary, several common genetic risk factors are implicated in the coexistence of adenomyosis with other gynecological diseases, although it is evident that disease-specific genes also exert influence.\u003c/p\u003e \u003cp\u003eA considerable body of previous research has indicated a comorbidity relationship between adenomyosis and both benign and malignant gynecological tumors (\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Findings from a large retrospective study on hysterectomized women demonstrated that patients with leiomyoma and adenomyosis were more likely to present with similar complaints(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). The common occurrence is a high estrogen environment in these diseases (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Considering the epidemiological standards outlined in the current literature regarding gynecological benign diseases in the general population, we did not observe high incidences of these conditions in patients with adenomyosis. For instance, up to 70% of women are known to develop leiomyomas by the time of menopause (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). The prevalence of endometrial polyps varies from 7.8% to nearly 35% depending on the geographic area and study population (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Additionally, abnormal uterine bleeding and endometrial hyperplasia have been reported in 10% of premenopausal women and 6% of postmenopausal women at some point in their lives (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). For nearly a century, except for endometriomas, and adenomyosis were considered to be the same entity (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Although they can coexist in patients, adenomyosis and endometriosis are considered two distinct diseases from a causative perspective, as they have specific causative pathways and clinical symptoms. In the general population, 10\u0026ndash;15% of women of reproductive age are affected by endometriosis (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). In our study, we identified 605 patients with adenomyosis combined with endometriosis (10.7%). Thus, based on our data, we did not observe an increased risk of leiomyoma, endometriosis, endometrial hyperplasia, and atypical hyperplasia in women with adenomyosis compared to the general population.\u003c/p\u003e \u003cp\u003eRecent studies have suggested that adenomyosis increases the risk of endometrial cancer and thyroid cancer, while endometrial cancer and ovarian cancer are at a higher risk in patients with endometriosis (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Although the association between the pathogenesis of adenomyosis and endometrial cancer remains unclear, endometrial cancer complicated with adenomyosis has been reported to have a better prognosis due to hormonal imbalance (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Conversely, in a large preliminary study, the authors did not find significant differences in the epidemiological profiles between patients with endometrial cancer combined with adenomyosis and those with isolated endometrial cancer (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Additionally, Raffone et al. recently assessed the prevalence of adenomyosis in patients with endometrial cancer and found no difference in the prevalence of adenomyosis in endometrial cancer cases compared to other gynecological diseases requiring surgical treatment (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Koshiyama et al. reported that 4 out of 564 women with adenomyosis developed adenocarcinoma (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). In a retrospective study based on 647 patients with adenomyosis, Matalliotakis reported that endometrial cancer accounted for 3.6% of patients with adenomyosis (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In the present study, we confirmed that endometrial cancer was present in 11.8% of patients with adenomyosis. However, the National Cancer Institute mentions that about 3.1% of women will be diagnosed with uterine cancer at some point in their lifetime (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Therefore, based on the above studies, we speculate that women with adenomyosis have an increased risk of endometrial cancer compared to patients without adenomyosis. Further studies are needed to confirm our findings and investigate the molecular mechanisms responsible for this phenomenon.\u003c/p\u003e \u003cp\u003eAlthough adenomyosis may serve as a genetic precursor to certain cancers, the precise molecular mechanisms underlying this malignant transformation remain elusive. Adenomyosis and type 1 endometrial cancer are both influenced by the effects of sex steroids, and the gene expression profile of this condition is linked to cancer, cell death, and cell cycle networks (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Additionally, mRNA levels of phosphatase and tensin homolog (PTEN) are reduced in adenomyosis. Notably, PTEN is considered a tumor suppressor gene and is mutated in numerous cancers (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). The association between PTEN and endometrial cancer has been well established (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), and mutations in KRAS and BCL2 genes further bolster the potential link between adenomyosis and endometrial cancer (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eAdenomyosis and Non-Hormone Dependent Diseases\u003c/h3\u003e\n\u003cp\u003eRegarding ovarian cancer, findings from a large case-control study have confirmed that adenomyosis significantly increases the risk of ovarian cancer (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). However, contrasting results have been reported in another study, suggesting that adenomyosis does not elevate the risk of ovarian cancer (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). According to the National Cancer Institute, approximately 3.1% of women will be diagnosed with uterine cancer at some point in their lifetime, less than 2% will develop ovarian cancer, and 0.6% will be diagnosed with cervical cancer (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Matalliotakis reported that ovarian cancer accounted for 1.4% of patients with adenomyosis, followed by cervical cancer (0.8%) (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). A recent study suggests that both adenomyosis and endometriosis may increase the risk of endometrial cancer, while endometriosis alone may elevate the risk of ovarian cancer, but neither condition appears to affect the risk of cervical cancer (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). To date, there have been limited studies investigating the association between adenomyosis and the risk of cervical cancer. In our study, we observed that cervical cancer was present in 9.7% of patients with adenomyosis, followed by cervical intraepithelial neoplasia (CIN) (8.3%) and ovarian cancer (3.9%). Based on these findings, we cannot definitively conclude that adenomyosis increases the risk of cervical cancer. The observed discrepancy may largely be attributed to the availability of HPV vaccines in developed countries. Endometriosis is known to increase the risk of ovarian cancer, and our study did not exclude the occurrence of ovarian cancer in patients with coexisting adenomyosis and endometriosis, thereby contributing to the slightly higher observed risk of ovarian cancer.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eAdenomyosis with Abnormal Ectopic Endometrial Pathology\u003c/h2\u003e \u003cp\u003eInterestingly, literature reports suggest that the growth, invasion, and angiogenesis patterns observed in adenomyosis may serve as precursors to cancerous transformation (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). Notably, malignant transformation of adenomyosis is more prevalent in postmenopausal and older women, as well as in individuals with preexisting benign gynecological conditions (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Malignant changes in adenomyosis account for approximately 6.8% of cases of endometrial cancer (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). Moreover, the transformation of endometrial epithelium into cancer cells may contribute to the malignant transformation of adenomyosis, leading to tumorigenesis (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Recent research has shed light on the impact of adenomyosis on the aggressiveness of endometrial cancer. While adenomyosis has not been established as an independent prognostic factor for endometrial tumors, cases of endometrial cancer combined with adenomyosis tend to have better prognoses (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). A study in 2022 further confirmed increased survival rates among women with endometrial cancer and histologically proven endometriosis or adenomyosis (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). This improved prognosis may be attributed to various factors, including younger age at diagnosis, earlier disease stages, more favorable histological subtypes, lower tumor grades, higher rates of surgery, and lower rates of chemotherapy. However, a large preliminary study did not find significant differences in the epidemiological, clinicopathological, and prognostic characteristics between patients with endometrial cancer combined with adenomyosis and those with isolated endometrial cancer (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Moreover, recent systematic reviews and meta-analyses have demonstrated that adenomyosis and endometrial cancer are two distinct pathologies (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Additionally, due to de novo malignant transformation of adenomyosis foci and simultaneous malignant transformation of eutopic endometrium and adenomyosis, studies suggest that the presence of adenomyosis may play a significant role in determining the prognosis of adenocarcinoma (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAtypical Polypoid Adenomyoma (APA), also known as atypical polypoid adenoma-uterine fibroma, is a rare uterine lesion initially described by Mazur in 1981 (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). It serves as an indicator or precursor of endometrial adenocarcinoma or may coexist with endometrial adenocarcinoma (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e). Literature data indicate that APA is an endometrial tumor with low malignant potential and low incidence, more commonly affecting patients of childbearing age (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). Among 237 patients included in eleven retrospective studies, 85.5% were premenopausal, and 62.9% were nulliparous. Atypical polypoid adenomyoma with atypical hyperplasia accounted for 5.5%, while endometrial cancer was observed in 5.9% of cases. The overall risk of recurrence and progression to cancer was reported to be 28.9% and 16.6%, respectively (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e). Numerous studies have linked the pathogenesis of APA with estrogen-related factors, obesity, diabetes, long-term estrogen stimulation, and hormone replacement therapy (HRT) (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). Due to the rarity of APA, there have been no retrospective studies with large sample sizes, and the exact pathogenesis of APA remains unclear. In our study, among the 5648 patients with adenomyosis, we observed 30 cases with ectopic endometrial hyperplasia, 3 cases with ectopic endometrial carcinoma, and 17 cases with APA. As the number of cases of these conditions increases in the future, further studies are warranted to explore the molecular mechanisms underlying their pathogenesis.\u003c/p\u003e \u003cp\u003eThe limitations of this study are partly attributable to its retrospective nature. Since we did not exclude cases where ovarian cancer, adenomyosis, and endometriosis coexisted, there may be a bias in the reported incidence of ovarian cancer among patients with adenomyosis. The large sample size and histopathology-based analysis are the outstanding strengths of the study. This rigorous approach enhances the reliability of our findings and strengthens the validity of the associations observed.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn summary, the present retrospective study supported the increased incidence of endometrial cancer in patients with adenomyosis. However, the incidence of other gynecological diseases is not elevated in patients with adenomyosis compared to the general population. Further research is necessary to investigate this speculation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere is no funding for the project.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Disclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest and have nothing further to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Ethics committee of Obstetrics and Gynecology Hospital Affiliated to Fudan University approved the protocol. This article does not contain any animal studies conducted by any of the authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individuals involved in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYunlei Cao (First Author):\u0026nbsp;\u003c/strong\u003eData curation, Formal analysis, Methodology, Writing-original draft\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCenyu Li:\u003c/strong\u003e Data curation\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDing Ding (Corresponding Author):\u003c/strong\u003e Resources, Supervision, Writing-review \u0026amp; editing\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJ. 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Saccone, et al, Management of women with atypical polypoid adenomyoma of the uterus: A quantitative systematic review, Acta Obstet Gynecol Scand 98(7) (2019) 842-855.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"adenomyosis, benign, premalignant, malignant gynecological diseases, endometrial cancer","lastPublishedDoi":"10.21203/rs.3.rs-4448561/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4448561/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAdenomyosis is an estrogen-dependent disease and ranks among the most common gynecological benign conditions in women of childbearing age. Adenomyosis has been reported to coincide with endometrial hyperplasia, polyps, and even endometrial cancer. This study aims to investigate the incidence of benign, premalignant, and malignant gynecological diseases in women undergoing gynecological surgery for adenomyosis. A retrospective review of medical records collected from January 2021 to May 2023 for surgeries performed at the Obstetrics and Gynecology Hospital affiliated with Fudan University was conducted. Pathology reports of 5648 cases of adenomyosis were studied. The incidence of benign, premalignant, and malignant gynecological pathologies in women with adenomyosis who underwent gynecological surgery were analyzed. The mean age of women with adenomyosis was 49.0\u0026thinsp;\u0026plusmn;\u0026thinsp;9.0 years. Adenomyosis without other gynecological pathologies was detected in 16.7% of specimens of 5648 patients, while coexistence with one or more gynecological pathologies was present in 82.3% of cases. Additionally, coexistence with two or more gynecological diseases (benign or malignant) was present in 1806 of 5648 patients (31.9%). The most common comorbidities were uterine leiomyoma (57.1%), followed by endometrial cancer (11.8%) and endometriosis (10.7%). Furthermore, we found that women with adenomyosis, leiomyoma, endometriosis, endometrial polyps, or atypical hyperplasia were younger (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) compared with adenomyotic patients with malignant tumors. Adenomyosis is a common benign, progressive disease that has garnered increasing attention in recent years. Some studies have suggested a potential association of adenomyosis with several gynecological diseases. Our study shows a high prevalence of endometrial cancer in patients with adenomyosis compared to the general population.\u003c/p\u003e","manuscriptTitle":"Retrospective Study on the Incidence of Benign, Premalignant, and Malignant Gynecologic Disorders in Patients with Adenomyosis: Analysis of 5648 Specimens","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-10 11:51:38","doi":"10.21203/rs.3.rs-4448561/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"eb1fd65c-0afa-4b0e-967d-4c24d756142b","owner":[],"postedDate":"June 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":32943495,"name":"Health sciences/Diseases/Reproductive disorders"},{"id":32943496,"name":"Biological sciences/Cancer"}],"tags":[],"updatedAt":"2024-07-05T11:32:15+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-10 11:51:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4448561","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4448561","identity":"rs-4448561","version":["v1"]},"buildId":"B-jG_2CBjPDmsCi4Wdhf-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}