Villous Adenoma of the Prostate Coexisting with Ductal Adenocarcinoma: Clinical Features, Diagnosis, and Treatment Strategies

Villous Adenoma of the Prostate Coexisting with Ductal Adenocarcinoma: Clinical Features, Diagnosis, and Treatment Strategies | 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 Case Report Villous Adenoma of the Prostate Coexisting with Ductal Adenocarcinoma: Clinical Features, Diagnosis, and Treatment Strategies Han Yang, Xinbao Yin, Zongliang Zhang, Kai Zhao, Yulian Zhang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6319176/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 In the realm of urological oncology, the coexistence of primary prostatic villous adenoma (PVA) and prostatic ductal adenocarcinoma (PDA) is an extremely rare occurrence, presenting a significant diagnostic and therapeutic conundrum. This case report is of particular interest as it details a unique instance of this dual diagnosis, which is novel due to the scarcity of such cases in the existing literature and the complex molecular characteristics associated with it. The patient was a 79-year-old male with a decade-long history of worsening urinary difficulties. Initially misdiagnosed as benign prostatic hyperplasia based on a normal serum prostate-specific antigen (PSA) level, he underwent transurethral resection of the prostate. This procedure revealed a villous mass, leading to a diagnosis of PVA. Further investigation through radical prostatectomy uncovered coexisting PDA with a high Gleason score, indicating aggressive malignancy. The patient received surgical treatment and showed uneventful recovery with no recurrence within one year of follow-up. Conclusion: This case emphasizes the importance of comprehensive diagnostic approaches in patients with refractory urinary symptoms, as relying solely on traditional markers like PSA can be misleading. It also highlights the need for further research to better understand the relationship between these two rare tumors, develop more accurate diagnostic methods, and establish optimal treatment strategies for such complex cases. Villous adenoma Prostatic ductal adenocarcinoma Androgen receptor Pathology Immunohistochemistry Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Primary prostatic villous adenoma (PVA) was an extremely rare benign tumor, typically occurring in the bladder and urethra, with cases in the prostate being even less common[ 1 , 2 ]. Epidemiological data indicated that the incidence of PVA in the urinary system was very low, primarily affecting middle-aged and elderly men[ 3 ]. Despite its benign nature and relatively favorable prognosis for patients, the rarity of this tumor posed significant challenges for clinical diagnosis and treatment[ 4 ]. Prostatic ductal adenocarcinoma (PDA) was a rare and highly aggressive subtype of prostate cancer (PCa), with serum prostate-specific antigen (PSA) levels that could be normal or only slightly elevated[ 5 ], potentially leading to missed diagnoses in patients relying on PSA levels for screening[ 6 ]. This study aimed to provide a detailed analysis of a rare case of PVA combined with PDA, exploring its clinical manifestations, diagnostic process, and treatment strategies. Case Presentation A 79-year-old male patient presented with a decade-long history of progressively worsening urinary difficulty, initially manifesting as frequent urination without associated urgency, dysuria, or gross hematuria; he reported approximately five episodes of nocturia, which significantly impacted his quality of life. Despite prior medication treatment at a local hospital, his symptoms showed no substantial improvement. Laboratory evaluation revealed a serum PSA level of 3.76 ng/ml, leading to an initial clinical diagnosis of benign prostatic hyperplasia (BPH). Given the patient’s advanced age and the persistence of symptoms, detailed discussions were conducted with the patient and his family, culminating in informed consent for transurethral resection of the prostate (TURP) on May 11, 2023, as a therapeutic and diagnostic intervention. During the endoscopic procedure, direct visualization via resectoscope revealed a distinctive cauliflower-like mass measuring approximately 2.5×2 cm on the right lateral aspect of the seminal colliculus (Fig. 1 A), juxtaposed with marked hyperplasia and protrusion of both prostatic lateral lobes that narrowed the urethral lumen to a slit-like configuration (Fig. 1 B). The median lobe protruded into the bladder, elevating the bladder neck and occupying approximately two visual fields, while the bladder mucosa exhibited obstructive changes characterized by trabeculation and small diverticular chambers, without evidence of neoplastic lesions. The resection was performed using normal saline irrigation, following a systematic approach: the median lobe was first excised to decompress the bladder outflow, followed by leveling of the bladder neck and sequential removal of the lateral lobes and apical tissue, with circumferential layer-by-layer resection down to the prostatic capsule, using the seminal colliculus as a landmark. A notable finding occurred during resection of the right posterolateral region (7–9 o’clock position relative to the seminal colliculus): despite repeated attempts, the cauliflower-like lesion demonstrated a seemingly endless proliferation of pinkish villous tissue that re-emerged with each pass of the resectoscope (Figs. 1 C–F), precluding complete endoscopic resection under microscopic guidance. Postoperative histopathological examination of the resected tissue confirmed the diagnosis of PVA (Fig. 2 ), prompting further clinical discussion regarding the risk of underlying malignancy given the lesion’s aggressive endoscopic appearance. After comprehensive counseling about the findings and treatment options, the patient elected to undergo radical prostatectomy, which was successfully performed via laparoscopic approach on November 20, 2023. Final pathological analysis revealed the presence of PDA (Fig. 3 A), characterized by a Gleason score of 4 + 5 = 9 with intratumoral necrosis, indicating a high-grade malignant phenotype. Immunohistochemical staining showed strong positive expression for androgen receptor (AR) (++-+++ in approximately 80% of tumor cells) and Ki-67 (positivity in approximately 40% of cells, reflecting moderate proliferative activity) (Figs. 3 B–C), while markers for other epithelial lineages and prostate-specific antigens were negative: CK7, CK20 (focal positivity), CDX-2, villin, SATB2, PSA, and GATA3 (Figs. 4 A–G). The patient exhibited uneventful postoperatie recovery, with restoration of normal urinary continence and voiding dynamics. A one-year follow-up assessment, including imaging and serum PSA monitoring, demonstrated no evidence of tumor recurrence, underscoring the importance of integrating endoscopic findings with histopathological correlation in managing complex prostatic lesions. Discussion Primary PVA, an exceedingly rare benign neoplasm within the urinary system, demonstrates an elusive clinical profile, as evidenced by scarce case reports and even rarer documentation of its coexistence with PCa[ 7 , 8 ]. In this case, a 79-year-old male patient was diagnosed with PVA combined with PDA, which posed challenges for clinical diagnosis and treatment. Clinically, PVA typically manifests with nonspecific lower urinary tract symptoms (LUTS)—such as urinary hesitancy, frequency, and nocturia—that closely mimic BPH[ 9 , 10 ], as evident in this patient’s decade-long history of progressive urinary difficulty unresponsive to medical therapy. The intraoperative discovery of a cauliflower-like villous mass during transurethral resection, rather than preoperative suspicion, ultimately instigated the pathological workup, highlighting the necessity of maintaining a high index of suspicion for atypical lesions in patients with recalcitrant LUTS, particularly when standard treatments fail to alleviate symptoms. Pathologically, PVA’s histological features can overlap with malignant counterparts, complicating differential diagnosis and necessitating meticulous immunohistochemical profiling[ 11 , 12 ]. In this case, final pathology revealed coexisting PDA—a rare, aggressive PCa subtype—with a Gleason score of 9, indicative of high-grade malignancy. Notably, the patient’s preoperative serum PSA level was within the normal range (3.76 ng/mL), and tumor tissue exhibited absent PSA expression on immunohistochemistry, a characteristic that distinguishes PDA from conventional acinar adenocarcinoma and underscores the unreliability of PSA as a sole diagnostic marker for rare PCa variants[ 13 , 14 ]. This finding reinforces the clinical imperative to integrate multimodal diagnostics—including multiparametric MRI, targeted biopsies, and histopathological analysis—especially in high-risk populations or cases with discordant clinical-pathological features[ 15 ]. The negative PSA expression in immunohistochemical testing suggested that the tumor cells did not express PSA, which was more common in atypical PCa and some highly aggressive cancers. Since PSA could not serve as a follow-up indicator for such patients, imaging studies and other biomarkers were needed to monitor disease progression and treatment efficacy post-treatment[ 16 ]. The paradoxical absence of PSA alongside strong androgen receptor (AR) positivity (80% tumor cell staining) and elevated Ki-67 proliferation index (40%) in this case suggests a unique molecular phenotype reliant on androgen signaling despite PSA loss, a biological discrepancy that warrants further exploration of AR pathway dysregulation and potential therapeutic vulnerabilities[ 14 ]. Due to the paucity of large-scale clinical data and evidence-based guidelines, the optimal management of PVA coexisting with PCa remains undefined, with surgical resection currently serving as the primary intervention[ 17 ]. In this case, the patient underwent laparoscopic radical prostatectomy achieved favorable short-term outcomes, with no recurrence observed over 12 months. However, due to its inherent metastatic potential, the aggressive biology of PDA required long - term surveillance. It remained uncertain whether PVA had the potential for malignant transformation or if there were common pathogenic factors leading to the coexistence of the two tumors. Some studies also reported that when PVA coexisted with adenocarcinoma, even with surgical measures taken, the risk of disease recurrence or distant metastasis would increase. Considering the similarities of these tumors to colorectal tumors, fluoropyrimidines such as capecitabine or 5 - fluorouracil might have applicability, and further exploration was necessary[ 3 , 18 ]. The application of molecular biology techniques might reveal potential gene mutations and abnormalities in signaling pathways[ 19 ]. Given the limitations of traditional histological and immunohistochemical diagnoses, the search for specific molecular markers would help improve the accuracy of differential diagnoses. Additionally, establishing a systematic follow-up mechanism to focus on long-term prognosis and identify key factors influencing outcomes would provide a basis for clinical decision-making. Conclusions In conclusion, we present a rare case of successfully treated coexistence of PVA and PDA, which is characterized by diagnostic complexity resulting from paradoxical immunohistochemical features (PSA-negative/strong AR-positive) and aggressive histology (Gleason score 9). Although the surgical treatment achieved favorable outcomes, the optimal treatment strategy and long - term prognosis for such rare tumor composites require further investigation to provide evidence - based clinical guidelines for future management. Declarations Acknowledgements Not applicable. Authors' contributions Han Yang, Ke Wang, and Xinbao Yin were jointly responsible for research design and the initial drafting of the paper. Zongliang Zhang and Kai Zhao assisted in clinical data collection and case follow-up. Yulian Zhang provided clinical resources and participated in data verification. Guanqun Zhu and Xuechuan Yan were responsible for data statistical analysis and revision of the paper’s figures and tables. All authors reviewed the manuscript. Funding This research was funded by the Qingdao Science and Technology Benefit People Demonstration Special Project (NO: 24-1-8-smjk-4-nsh) and the Beijing Dadi Medical Charity Foundation (NO: DDYL-KY-20240327 and DDYL-KY-20240328). Ethical approval and consent to participate All procedures performed in the study were in line with the 1964 Helsinki Declaration and its subsequent amendments or comparable ethical standards. The study was approved by the Ethics Committee of Qingdao University Affiliated Hospital (NO: QYFY WZLL 29511). Informed consent for publication was obtained from the patient. Data availability All data generated or analysed during this study are included in this published article. The data presented in this study are available in article. Consent for publication The patient provided written informed consent for the publication of their personal details, clinical information, and identifiable images. Ethical guidelines were followed to ensure patients fully understood the purpose and implications of data/image inclusion. Competing interests The authors declare that they have no competing interests. References Algaba, F., X. Matias-Guiu, F. Badia, et al., Villous adenoma of the prostatic urethra[J]. Eur Urol, 1988. 14 (3): p. 255-7. Ho, S.Y., N. Rosli, and L.Y. Lim, Villous adenoma of the prostatic urethra[J]. J Postgrad Med, 2022. 68 (2): p. 106-108. Corsi, A.J., T.P. Bradley, and S.D. Geetha, Treatment of Villous Adenoma With Underlying Adenocarcinoma of the Prostatic Urethra Using Combined Chemoradiation: A Case Report[J]. Cureus, 2024. 16 (7): p. e64841. Qin, L.F., Y. Liang, X.M. Xing, et al., Villous adenoma coexistent with focal well-differentiated adenocarcinoma of female urethral orifice: A case report and review of literature[J]. World J Clin Cases, 2019. 7 (7): p. 891-897. Morgan, T.M., C.J. Welty, F. Vakar-Lopez, et al., Ductal adenocarcinoma of the prostate: increased mortality risk and decreased serum prostate specific antigen[J]. J Urol, 2010. 184 (6): p. 2303-7. Seipel, A.H., B. Delahunt, H. Samaratunga, et al., Ductal adenocarcinoma of the prostate: histogenesis, biology and clinicopathological features[J]. Pathology, 2016. 48 (5): p. 398-405. Yin, W., X.L. Mo, Z.H. Wen, et al., [Villous adenoma of the urinary tract: a clinicopathological study][J]. Zhonghua Bing Li Xue Za Zhi, 2013. 42 (7): p. 438-41. Shang, Y., C. Guo, and D. Zhang, Modified enhanced recovery after surgery protocols are beneficial for postoperative recovery for patients undergoing emergency surgery for obstructive colorectal cancer: A propensity score matching analysis[J]. Medicine (Baltimore), 2018. 97 (39): p. e12348. Sung, M.T., J.W. Lin, and W.J. Chen, Villous adenomas of the urinary tract: report of two cases[J]. Chang Gung Med J, 2000. 23 (5): p. 291-5. Melicow, M.M., Tumors of the urinary bladder: a clinico-pathological analysis of over 2500 specimens and biopsies[J]. J Urol, 1955. 74 (4): p. 498-521. McKenney, J.K., Mesenchymal tumors of the prostate[J]. Mod Pathol, 2018. 31 (S1): p. S133-142. Cheng, C.J., K.C. Chen, W.Y. Chen, et al., Ductal adenocarcinoma of the prostate with endometrioid features in a 69-year-old man[J]. J Formos Med Assoc, 2001. 100 (10): p. 707-11. Liu, T., Y. Wang, R. Zhou, et al., The update of prostatic ductal adenocarcinoma[J]. Chin J Cancer Res, 2016. 28 (1): p. 50-7. Sha, J., J. Bo, J. Pan, et al., Ductal adenocarcinoma of the prostate: immunohistochemical findings and clinical significance[J]. Onco Targets Ther, 2013. 6 : p. 1501-6. Amin, A., Prostate Ductal Adenocarcinoma[J]. Appl Immunohistochem Mol Morphol, 2018. 26 (7): p. 514-521. Humphrey, P.A., Histopathology of Prostate Cancer[J]. Cold Spring Harb Perspect Med, 2017. 7 (10). Mottet, N., R.C.N. van den Bergh, E. Briers, et al., EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent[J]. Eur Urol, 2021. 79 (2): p. 243-262. Cheng, L., R. Montironi, and D.G. Bostwick, Villous adenoma of the urinary tract: a report of 23 cases, including 8 with coexistent adenocarcinoma[J]. Am J Surg Pathol, 1999. 23 (7): p. 764-71. Kench, J.G., M.B. Amin, D.M. Berney, et al., WHO Classification of Tumours fifth edition: evolving issues in the classification, diagnosis, and prognostication of prostate cancer[J]. Histopathology, 2022. 81 (4): p. 447-458. Additional Declarations No competing interests reported. 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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-6319176","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":456633543,"identity":"1d6098af-b2f8-4dc0-8724-aa0bca192d38","order_by":0,"name":"Han Yang","email":"","orcid":"","institution":"The Affiliated Hospital of Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Han","middleName":"","lastName":"Yang","suffix":""},{"id":456633544,"identity":"8bc10042-df59-4129-97ba-2af459e47f1c","order_by":1,"name":"Xinbao Yin","email":"","orcid":"","institution":"The Affiliated Hospital of Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Xinbao","middleName":"","lastName":"Yin","suffix":""},{"id":456633545,"identity":"8e355c88-b7bf-4ec4-b569-1e0835f70ece","order_by":2,"name":"Zongliang Zhang","email":"","orcid":"","institution":"The Affiliated Hospital of Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Zongliang","middleName":"","lastName":"Zhang","suffix":""},{"id":456633546,"identity":"0744f4d7-286b-40bf-a2b5-02ea853acdbc","order_by":3,"name":"Kai Zhao","email":"","orcid":"","institution":"The Affiliated Hospital of Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Kai","middleName":"","lastName":"Zhao","suffix":""},{"id":456633547,"identity":"311f6344-60ef-4ca1-95a0-802fb8db7bfc","order_by":4,"name":"Yulian Zhang","email":"","orcid":"","institution":"The Affiliated Hospital of Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Yulian","middleName":"","lastName":"Zhang","suffix":""},{"id":456633548,"identity":"ff63ac81-8025-4399-9402-f19a8fdfbc4d","order_by":5,"name":"Guanqun Zhu","email":"","orcid":"","institution":"The Affiliated Hospital of Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Guanqun","middleName":"","lastName":"Zhu","suffix":""},{"id":456633549,"identity":"8bd96cbe-9d97-46a4-baa0-5ec5fed91e05","order_by":6,"name":"Xuechuan Yan","email":"","orcid":"","institution":"The Affiliated Hospital of Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Xuechuan","middleName":"","lastName":"Yan","suffix":""},{"id":456633550,"identity":"8e2586b9-aee2-4500-94f0-f6df85948fab","order_by":7,"name":"Ke Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyUlEQVRIiWNgGAWjYJACxgYGGwaGA0AWDwla0kjXcpgELQbHzx5+OaPivGzfjQTGB2/bGOTNCWo5k5dmueHMbeOZNxKYDee2MRjubCCgxexAjpnhw7bbiRtuJLBJ87YxJBgcIKTl/Bugln/nQFrYfxOn5UaO8cONDQfAtjATpcX+xhszxhnHko1nnnnYLDnnnIThBkJaJPtzjD/21NjJ9h1PPvjhTZmNPEFbgIBNggEcN0DEwCBBWD0QMH+AaBkFo2AUjIJRgAMAABUqSh38U95VAAAAAElFTkSuQmCC","orcid":"","institution":"The Affiliated Hospital of Qingdao University","correspondingAuthor":true,"prefix":"","firstName":"Ke","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2025-03-27 09:38:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6319176/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6319176/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":83025429,"identity":"3ded859b-af9d-44b2-9a3d-a0f089d44fee","added_by":"auto","created_at":"2025-05-19 08:22:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":283478,"visible":true,"origin":"","legend":"\u003cp\u003eIntraoperative findings during transurethral resection of the prostate.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6319176/v1/1c893ef0e42e15408bf22d8c.png"},{"id":83025431,"identity":"1e7dbd66-c9f9-46f8-9c8d-948e0daf2ec6","added_by":"auto","created_at":"2025-05-19 08:22:52","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":195206,"visible":true,"origin":"","legend":"\u003cp\u003ePostoperative pathology of the villous adenoma.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6319176/v1/9ced3d5aec1447f57c672fef.png"},{"id":83025434,"identity":"cba06d18-77ab-4635-9a62-c5885ca91159","added_by":"auto","created_at":"2025-05-19 08:22:52","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":427676,"visible":true,"origin":"","legend":"\u003cp\u003ePostoperative pathological findings of prostatic ductal adenocarcinoma. (A) Hematoxylin and eosin (H\u0026amp;E) staining showing the histological features of prostatic ductal adenocarcinoma, with a high Gleason score of 4+5=9, accompanied by necrosis. (B) Immunohistochemical staining for androgen receptor (AR), demonstrating strong positive expression (approximately 80%) in the tumor cells. (C) Immunohistochemical staining for Ki-67, indicating a high proliferation index (approximately 40%). The left panel shows a low-power view (200 µm scale), and the right panel shows a high-power view (100 µm scale).\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6319176/v1/5823a9b0a8ee7b0453044842.png"},{"id":83025432,"identity":"caeaead3-c82c-490b-b8c6-d8a1ab3f3727","added_by":"auto","created_at":"2025-05-19 08:22:52","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":241302,"visible":true,"origin":"","legend":"\u003cp\u003eImmunohistochemical staining results for various markers in prostatic ductal adenocarcinoma. (A) CK7 expression was negative. (B) CK20 showed focal positivity. (C) CDX-2 expression was negative. (D) villin expression was negative. (E) SATB2 expression was negative. (F) PSA expression was negative. (G) GATA3 expression was negative.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6319176/v1/13f120d3d243bef89e009a48.png"},{"id":99686920,"identity":"a1428f73-deac-4991-825f-31729720e303","added_by":"auto","created_at":"2026-01-07 09:40:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1538982,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6319176/v1/68cc454e-ecb3-4430-9b3c-61c358528b2f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Villous Adenoma of the Prostate Coexisting with Ductal Adenocarcinoma: Clinical Features, Diagnosis, and Treatment Strategies","fulltext":[{"header":"Background","content":"\u003cp\u003ePrimary prostatic villous adenoma (PVA) was an extremely rare benign tumor, typically occurring in the bladder and urethra, with cases in the prostate being even less common[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Epidemiological data indicated that the incidence of PVA in the urinary system was very low, primarily affecting middle-aged and elderly men[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Despite its benign nature and relatively favorable prognosis for patients, the rarity of this tumor posed significant challenges for clinical diagnosis and treatment[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Prostatic ductal adenocarcinoma (PDA) was a rare and highly aggressive subtype of prostate cancer (PCa), with serum prostate-specific antigen (PSA) levels that could be normal or only slightly elevated[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], potentially leading to missed diagnoses in patients relying on PSA levels for screening[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. This study aimed to provide a detailed analysis of a rare case of PVA combined with PDA, exploring its clinical manifestations, diagnostic process, and treatment strategies.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 79-year-old male patient presented with a decade-long history of progressively worsening urinary difficulty, initially manifesting as frequent urination without associated urgency, dysuria, or gross hematuria; he reported approximately five episodes of nocturia, which significantly impacted his quality of life. Despite prior medication treatment at a local hospital, his symptoms showed no substantial improvement. Laboratory evaluation revealed a serum PSA level of 3.76 ng/ml, leading to an initial clinical diagnosis of benign prostatic hyperplasia (BPH). Given the patient\u0026rsquo;s advanced age and the persistence of symptoms, detailed discussions were conducted with the patient and his family, culminating in informed consent for transurethral resection of the prostate (TURP) on May 11, 2023, as a therapeutic and diagnostic intervention.\u003c/p\u003e \u003cp\u003eDuring the endoscopic procedure, direct visualization via resectoscope revealed a distinctive cauliflower-like mass measuring approximately 2.5\u0026times;2 cm on the right lateral aspect of the seminal colliculus (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA), juxtaposed with marked hyperplasia and protrusion of both prostatic lateral lobes that narrowed the urethral lumen to a slit-like configuration (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). The median lobe protruded into the bladder, elevating the bladder neck and occupying approximately two visual fields, while the bladder mucosa exhibited obstructive changes characterized by trabeculation and small diverticular chambers, without evidence of neoplastic lesions. The resection was performed using normal saline irrigation, following a systematic approach: the median lobe was first excised to decompress the bladder outflow, followed by leveling of the bladder neck and sequential removal of the lateral lobes and apical tissue, with circumferential layer-by-layer resection down to the prostatic capsule, using the seminal colliculus as a landmark. A notable finding occurred during resection of the right posterolateral region (7\u0026ndash;9 o\u0026rsquo;clock position relative to the seminal colliculus): despite repeated attempts, the cauliflower-like lesion demonstrated a seemingly endless proliferation of pinkish villous tissue that re-emerged with each pass of the resectoscope (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC\u0026ndash;F), precluding complete endoscopic resection under microscopic guidance.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePostoperative histopathological examination of the resected tissue confirmed the diagnosis of PVA (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), prompting further clinical discussion regarding the risk of underlying malignancy given the lesion\u0026rsquo;s aggressive endoscopic appearance. After comprehensive counseling about the findings and treatment options, the patient elected to undergo radical prostatectomy, which was successfully performed via laparoscopic approach on November 20, 2023. Final pathological analysis revealed the presence of PDA (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA), characterized by a Gleason score of 4\u0026thinsp;+\u0026thinsp;5\u0026thinsp;=\u0026thinsp;9 with intratumoral necrosis, indicating a high-grade malignant phenotype. Immunohistochemical staining showed strong positive expression for androgen receptor (AR) (++-+++ in approximately 80% of tumor cells) and Ki-67 (positivity in approximately 40% of cells, reflecting moderate proliferative activity) (Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB\u0026ndash;C), while markers for other epithelial lineages and prostate-specific antigens were negative: CK7, CK20 (focal positivity), CDX-2, villin, SATB2, PSA, and GATA3 (Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA\u0026ndash;G).\u003c/p\u003e \u003cp\u003eThe patient exhibited uneventful postoperatie recovery, with restoration of normal urinary continence and voiding dynamics. A one-year follow-up assessment, including imaging and serum PSA monitoring, demonstrated no evidence of tumor recurrence, underscoring the importance of integrating endoscopic findings with histopathological correlation in managing complex prostatic lesions.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePrimary PVA, an exceedingly rare benign neoplasm within the urinary system, demonstrates an elusive clinical profile, as evidenced by scarce case reports and even rarer documentation of its coexistence with PCa[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In this case, a 79-year-old male patient was diagnosed with PVA combined with PDA, which posed challenges for clinical diagnosis and treatment. Clinically, PVA typically manifests with nonspecific lower urinary tract symptoms (LUTS)\u0026mdash;such as urinary hesitancy, frequency, and nocturia\u0026mdash;that closely mimic BPH[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], as evident in this patient\u0026rsquo;s decade-long history of progressive urinary difficulty unresponsive to medical therapy. The intraoperative discovery of a cauliflower-like villous mass during transurethral resection, rather than preoperative suspicion, ultimately instigated the pathological workup, highlighting the necessity of maintaining a high index of suspicion for atypical lesions in patients with recalcitrant LUTS, particularly when standard treatments fail to alleviate symptoms.\u003c/p\u003e \u003cp\u003ePathologically, PVA\u0026rsquo;s histological features can overlap with malignant counterparts, complicating differential diagnosis and necessitating meticulous immunohistochemical profiling[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In this case, final pathology revealed coexisting PDA\u0026mdash;a rare, aggressive PCa subtype\u0026mdash;with a Gleason score of 9, indicative of high-grade malignancy. Notably, the patient\u0026rsquo;s preoperative serum PSA level was within the normal range (3.76 ng/mL), and tumor tissue exhibited absent PSA expression on immunohistochemistry, a characteristic that distinguishes PDA from conventional acinar adenocarcinoma and underscores the unreliability of PSA as a sole diagnostic marker for rare PCa variants[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. This finding reinforces the clinical imperative to integrate multimodal diagnostics\u0026mdash;including multiparametric MRI, targeted biopsies, and histopathological analysis\u0026mdash;especially in high-risk populations or cases with discordant clinical-pathological features[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The negative PSA expression in immunohistochemical testing suggested that the tumor cells did not express PSA, which was more common in atypical PCa and some highly aggressive cancers. Since PSA could not serve as a follow-up indicator for such patients, imaging studies and other biomarkers were needed to monitor disease progression and treatment efficacy post-treatment[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The paradoxical absence of PSA alongside strong androgen receptor (AR) positivity (80% tumor cell staining) and elevated Ki-67 proliferation index (40%) in this case suggests a unique molecular phenotype reliant on androgen signaling despite PSA loss, a biological discrepancy that warrants further exploration of AR pathway dysregulation and potential therapeutic vulnerabilities[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDue to the paucity of large-scale clinical data and evidence-based guidelines, the optimal management of PVA coexisting with PCa remains undefined, with surgical resection currently serving as the primary intervention[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In this case, the patient underwent laparoscopic radical prostatectomy achieved favorable short-term outcomes, with no recurrence observed over 12 months. However, due to its inherent metastatic potential, the aggressive biology of PDA required long - term surveillance. It remained uncertain whether PVA had the potential for malignant transformation or if there were common pathogenic factors leading to the coexistence of the two tumors. Some studies also reported that when PVA coexisted with adenocarcinoma, even with surgical measures taken, the risk of disease recurrence or distant metastasis would increase. Considering the similarities of these tumors to colorectal tumors, fluoropyrimidines such as capecitabine or 5 - fluorouracil might have applicability, and further exploration was necessary[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The application of molecular biology techniques might reveal potential gene mutations and abnormalities in signaling pathways[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Given the limitations of traditional histological and immunohistochemical diagnoses, the search for specific molecular markers would help improve the accuracy of differential diagnoses. Additionally, establishing a systematic follow-up mechanism to focus on long-term prognosis and identify key factors influencing outcomes would provide a basis for clinical decision-making.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, we present a rare case of successfully treated coexistence of PVA and PDA, which is characterized by diagnostic complexity resulting from paradoxical immunohistochemical features (PSA-negative/strong AR-positive) and aggressive histology (Gleason score 9). Although the surgical treatment achieved favorable outcomes, the optimal treatment strategy and long - term prognosis for such rare tumor composites require further investigation to provide evidence - based clinical guidelines for future management.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHan Yang, Ke Wang, and Xinbao Yin were jointly responsible for research design and the initial drafting of the paper. Zongliang Zhang and Kai Zhao assisted in clinical data collection and case follow-up. Yulian Zhang provided clinical resources and participated in data verification. Guanqun Zhu and Xuechuan Yan were responsible for data statistical analysis and revision of the paper\u0026rsquo;s figures and tables. All authors reviewed the manuscript.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was funded by the Qingdao Science and Technology Benefit People Demonstration Special Project (NO: 24-1-8-smjk-4-nsh) and the Beijing Dadi Medical Charity Foundation (NO: DDYL-KY-20240327 and DDYL-KY-20240328).\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in the study were in line with the 1964 Helsinki Declaration and its subsequent amendments or comparable ethical standards. The study was approved by the Ethics Committee of Qingdao University Affiliated Hospital (NO: QYFY WZLL 29511). Informed consent for publication was obtained from the patient.\u0026nbsp;\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article. The data presented in this study are available in article.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient provided written informed consent for the publication of their personal details, clinical information, and identifiable images. Ethical guidelines were followed to ensure patients fully understood the purpose and implications of data/image inclusion.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAlgaba, F., X. Matias-Guiu, F. Badia, et al., Villous adenoma of the prostatic urethra[J]. Eur Urol, 1988. \u003cstrong\u003e14\u003c/strong\u003e(3): p. 255-7.\u003c/li\u003e\n\u003cli\u003eHo, S.Y., N. Rosli, and L.Y. Lim, Villous adenoma of the prostatic urethra[J]. J Postgrad Med, 2022. \u003cstrong\u003e68\u003c/strong\u003e(2): p. 106-108.\u003c/li\u003e\n\u003cli\u003eCorsi, A.J., T.P. Bradley, and S.D. Geetha, Treatment of Villous Adenoma With Underlying Adenocarcinoma of the Prostatic Urethra Using Combined Chemoradiation: A Case Report[J]. Cureus, 2024. \u003cstrong\u003e16\u003c/strong\u003e(7): p. e64841.\u003c/li\u003e\n\u003cli\u003eQin, L.F., Y. Liang, X.M. Xing, et al., Villous adenoma coexistent with focal well-differentiated adenocarcinoma of female urethral orifice: A case report and review of literature[J]. World J Clin Cases, 2019. \u003cstrong\u003e7\u003c/strong\u003e(7): p. 891-897.\u003c/li\u003e\n\u003cli\u003eMorgan, T.M., C.J. Welty, F. Vakar-Lopez, et al., Ductal adenocarcinoma of the prostate: increased mortality risk and decreased serum prostate specific antigen[J]. J Urol, 2010. \u003cstrong\u003e184\u003c/strong\u003e(6): p. 2303-7.\u003c/li\u003e\n\u003cli\u003eSeipel, A.H., B. Delahunt, H. Samaratunga, et al., Ductal adenocarcinoma of the prostate: histogenesis, biology and clinicopathological features[J]. Pathology, 2016. \u003cstrong\u003e48\u003c/strong\u003e(5): p. 398-405.\u003c/li\u003e\n\u003cli\u003eYin, W., X.L. Mo, Z.H. Wen, et al., [Villous adenoma of the urinary tract: a clinicopathological study][J]. Zhonghua Bing Li Xue Za Zhi, 2013. \u003cstrong\u003e42\u003c/strong\u003e(7): p. 438-41.\u003c/li\u003e\n\u003cli\u003eShang, Y., C. Guo, and D. Zhang, Modified enhanced recovery after surgery protocols are beneficial for postoperative recovery for patients undergoing emergency surgery for obstructive colorectal cancer: A propensity score matching analysis[J]. Medicine (Baltimore), 2018. \u003cstrong\u003e97\u003c/strong\u003e(39): p. e12348.\u003c/li\u003e\n\u003cli\u003eSung, M.T., J.W. Lin, and W.J. Chen, Villous adenomas of the urinary tract: report of two cases[J]. Chang Gung Med J, 2000. \u003cstrong\u003e23\u003c/strong\u003e(5): p. 291-5.\u003c/li\u003e\n\u003cli\u003eMelicow, M.M., Tumors of the urinary bladder: a clinico-pathological analysis of over 2500 specimens and biopsies[J]. J Urol, 1955. \u003cstrong\u003e74\u003c/strong\u003e(4): p. 498-521.\u003c/li\u003e\n\u003cli\u003eMcKenney, J.K., Mesenchymal tumors of the prostate[J]. Mod Pathol, 2018. \u003cstrong\u003e31\u003c/strong\u003e(S1): p. S133-142.\u003c/li\u003e\n\u003cli\u003eCheng, C.J., K.C. Chen, W.Y. Chen, et al., Ductal adenocarcinoma of the prostate with endometrioid features in a 69-year-old man[J]. J Formos Med Assoc, 2001. \u003cstrong\u003e100\u003c/strong\u003e(10): p. 707-11.\u003c/li\u003e\n\u003cli\u003eLiu, T., Y. Wang, R. Zhou, et al., The update of prostatic ductal adenocarcinoma[J]. Chin J Cancer Res, 2016. \u003cstrong\u003e28\u003c/strong\u003e(1): p. 50-7.\u003c/li\u003e\n\u003cli\u003eSha, J., J. Bo, J. Pan, et al., Ductal adenocarcinoma of the prostate: immunohistochemical findings and clinical significance[J]. Onco Targets Ther, 2013. \u003cstrong\u003e6\u003c/strong\u003e: p. 1501-6.\u003c/li\u003e\n\u003cli\u003eAmin, A., Prostate Ductal Adenocarcinoma[J]. Appl Immunohistochem Mol Morphol, 2018. \u003cstrong\u003e26\u003c/strong\u003e(7): p. 514-521.\u003c/li\u003e\n\u003cli\u003eHumphrey, P.A., Histopathology of Prostate Cancer[J]. Cold Spring Harb Perspect Med, 2017. \u003cstrong\u003e7\u003c/strong\u003e(10).\u003c/li\u003e\n\u003cli\u003eMottet, N., R.C.N. van den Bergh, E. Briers, et al., EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent[J]. Eur Urol, 2021. \u003cstrong\u003e79\u003c/strong\u003e(2): p. 243-262.\u003c/li\u003e\n\u003cli\u003eCheng, L., R. Montironi, and D.G. Bostwick, Villous adenoma of the urinary tract: a report of 23 cases, including 8 with coexistent adenocarcinoma[J]. Am J Surg Pathol, 1999. \u003cstrong\u003e23\u003c/strong\u003e(7): p. 764-71.\u003c/li\u003e\n\u003cli\u003eKench, J.G., M.B. Amin, D.M. Berney, et al., WHO Classification of Tumours fifth edition: evolving issues in the classification, diagnosis, and prognostication of prostate cancer[J]. Histopathology, 2022. \u003cstrong\u003e81\u003c/strong\u003e(4): p. 447-458.\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":"Villous adenoma, Prostatic ductal adenocarcinoma, Androgen receptor, Pathology, Immunohistochemistry","lastPublishedDoi":"10.21203/rs.3.rs-6319176/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6319176/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIn the realm of urological oncology, the coexistence of primary prostatic villous adenoma (PVA) and prostatic ductal adenocarcinoma (PDA) is an extremely rare occurrence, presenting a significant diagnostic and therapeutic conundrum. This case report is of particular interest as it details a unique instance of this dual diagnosis, which is novel due to the scarcity of such cases in the existing literature and the complex molecular characteristics associated with it. The patient was a 79-year-old male with a decade-long history of worsening urinary difficulties. Initially misdiagnosed as benign prostatic hyperplasia based on a normal serum prostate-specific antigen (PSA) level, he underwent transurethral resection of the prostate. This procedure revealed a villous mass, leading to a diagnosis of PVA. Further investigation through radical prostatectomy uncovered coexisting PDA with a high Gleason score, indicating aggressive malignancy. The patient received surgical treatment and showed uneventful recovery with no recurrence within one year of follow-up. Conclusion: This case emphasizes the importance of comprehensive diagnostic approaches in patients with refractory urinary symptoms, as relying solely on traditional markers like PSA can be misleading. It also highlights the need for further research to better understand the relationship between these two rare tumors, develop more accurate diagnostic methods, and establish optimal treatment strategies for such complex cases.\u003c/p\u003e","manuscriptTitle":"Villous Adenoma of the Prostate Coexisting with Ductal Adenocarcinoma: Clinical Features, Diagnosis, and Treatment Strategies","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-19 08:22:47","doi":"10.21203/rs.3.rs-6319176/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":"29476b32-f81a-45df-8996-3379b0888c24","owner":[],"postedDate":"May 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-07T09:40:09+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-19 08:22:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6319176","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6319176","identity":"rs-6319176","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}