A Rare Case of Multifocal Xanthogranulomatous Disease Involving the Entire Urinary Tract: Diagnosis and Management Challenges

A Rare Case of Multifocal Xanthogranulomatous Disease Involving the Entire Urinary Tract: Diagnosis and Management Challenges | 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 A Rare Case of Multifocal Xanthogranulomatous Disease Involving the Entire Urinary Tract: Diagnosis and Management Challenges Zhongwei Zhang, Yuwan Zhao, Zhuo Li This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7133075/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 Background: Xanthogranuloma is a granulomatous lesion caused by a bacterial infection, usually found in the lungs, skin, and digestive system. Xanthogranulomas in the urinary system are relatively rare, and cases of total urinary tract involvement are even rarer. Case presentation: This report presents a case of total urinary xanthogranuloma in a 67-year-old woman with long-term hypertension and diabetes, presenting with multiple urinary tract infections and renal failure, who was initially misdiagnosed as metastatic malignancy by PET-CT imaging. The final diagnosis was a total urinary xanthogranuloma. Conclusions: This paper reviews the diagnostic process, treatment methods, and prognosis of this patient, and discusses the underlying pathophysiological mechanisms between diabetes-related immunosuppression and disease progression. To provide a reference for the clinical diagnosis and treatment of similar diseases in the future. Xanthogranulomatous inflammation Diabetic immunocompromise Pan-urological disease Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Xanthogranulomatous inflammation (XGI) is a rare chronic granulomatous disorder characterized by lipid-laden macrophage infiltration, typically occurring as a localized process in organs such as the kidney (xanthogranulomatous pyelonephritis, XGP) or gallbladder[ 1 ]. While unilateral renal XGP is well-documented, multifocal involvement beyond a single organ is exceedingly uncommon[ 2 ], and pan-urological XGI—affecting the kidneys, ureters, bladder, and adjacent structures—represents an exceptional entity with fewer than 10 cases reported worldwide[ 3 ]. Diagnostic challenges arise from its radiological mimicry of malignancy, particularly on FDG-PET/CT, where hypermetabolic lesions may falsely suggest metastatic urothelial carcinom[ 4 ]. This discordance underscores the critical role of histopathological confirmation[ 5 ]. Additionally, immunocompromised states, such as uncontrolled diabetes, are recognized risk factors due to impaired bacterial clearance and dysregulated macrophage responses[ 6 ], yet the precise immunometabolic mechanisms driving systemic XGI remain poorly understood. We present a novel case of diffuse XGI involving the entire urinary tract and retroperitoneal nodes in a diabetic patient, initially misdiagnosed as metastatic cancer by PET/CT. This case aims to augment the sparse literature on pan-urological XGI and refine diagnostic strategies for this masquerading entity. Case Presentation A 67-year-old female with poorly controlled diabetes (HbA1c 9.2%) and an 8-year history of hypertension presented to our hospital in February 2023 with left hydronephrosis. The patient underwent transurethral resection of the left ureteral orifice with electrocautery of the bladder mucosa. Histopathological examination revealed xanthogranulomatous inflammation at the left ureteral orifice (Fig. 1 ), with immunohistochemical staining showing: CK(-), CD68(+), Ki67(10%), S-100(-), CD1a(-), CD163(-), CD3(+) (T cells), CD20(+) (B cells), and ALK(5A4)(-). In situ hybridization (EBER Probe) and special stains (PAS, GMS) were negative. The patient was discharged after her stable condition. On September 23, 2024, the patient was readmitted to Nanfang Hospital with elevated serum creatinine persisting for one month. Laboratory tests showed renal dysfunction (creatinine 229 µmol/L, urea 13.6 mmol/L, eGFR 18.43 mL/min). Cystoscopy revealed multiple masses in the trigone, left wall, right wall, and posterior wall of the bladder. Transurethral resection of bladder lesions was performed on September 24, followed by epirubicin bladder perfusion. Renal function progressively deteriorated (creatinine 453 µmol/L, eGFR 12.25 mL/min by September 29), prompting percutaneous bilateral nephrostomy[ 7 ]. PET-CT on September 30 demonstrated hypermetabolic lesions in the bladder, bilateral ureters, renal pelvis, cervix, and lymph nodes (SUVmax 8.2; Fig. 2 ), initially suggestive of urothelial malignancy. However, histopathological findings on October 10 confirmed chronic inflammation with xanthogranuloma formation (Fig. 3 ). Immunohistochemistry showed: CK(+), CD68(+), Ki-67(15%), with negative staining for CK20 and BRAF-V600E. Special stains for fungi were negative. The patient was treated with piperacillin-tazobactam and discharged in stable condition. The patient was readmitted on January 3, 2025 with fever and left flank pain 3 months post-nephrostomy. Laboratory tests revealed urinary tract infection (WBC 54,000/µL, pyuria 2+/HPF), anemia (Hb 51 g/L), and elevated inflammatory markers (CRP 153 mg/L, PCT 30.2 ng/mL). CT urography (January 6) showed left renal abscess, diffuse ureteral wall thickening, and retroperitoneal lymphadenopathy (Fig. 4 ). Following abscess drainage on January 9 and meropenem therapy, infection parameters improved (WBC 11.5×10^9/L, PCT 0.217 ng/mL by January 24), though anemia persisted (Hb 66 g/L post-transfusion). Discussion This case of pan-urological xanthogranulomatous inflammation (XGI) underscores several critical challenges in diagnosing and managing this rare entity. The diffuse involvement of the urinary tract—spanning bilateral kidneys, ureters, bladder, cervix, and retroperitoneal lymph nodes—represents an exceptionally rare manifestation of XGI, typically confined to a single organ (e.g., xanthogranulomatous pyelonephritis). The clinical and radiological mimicry of metastatic malignancy, coupled with histopathological ambiguity, highlights the need for a multidisciplinary diagnostic approach and raises questions about the pathophysiology of systemic XGI. 1. Radiological-Pathological Discordance: Malignancy Mimicry The initial PET-CT findings met PERCIST criteria for malignancy[ 7 ], with hypermetabolic lesions (SUVmax 8.7 in the bladder, 7.8 in retroperitoneal nodes) and an anatomical distribution suggestive of urothelial carcinoma with metastatic spread. However, repeated histopathological examinations consistently demonstrated chronic inflammation with xanthogranuloma formation, devoid of malignant cells or microbial pathogens[ 8 ]. This discrepancy may be attributed to the following mechanisms: A .Para-inflammatory lymphatic activation: Chronic granulomatous inflammation can induce reactive lymph node hyperplasia with increased glucose metabolism[ 9 ], mimicking metastatic spread. Similar phenomena have been reported in IgG4-related diseases and sarcoidosis. B. Macrophage-driven FDG avidity**: Lipid-laden CD68+/Lys + macrophages, the hallmark of XGI, exhibit upregulated glycolytic activity, contributing to false-positive PET findings[ 10 ]. C. Tumor-like angiogenesis**: Progressive tissue destruction and reparative neovascularization in chronic inflammation may enhance radiotracer uptake, as seen in this patient’s bladder and ureteral lesions[ 11 ] This case emphasizes the necessity of histopathological confirmation for PET-positive lesions, even when clinical and imaging features strongly suggest malignancy. 2. Immunometabolic Dysregulation: Role of Diabetes The patient’s poorly controlled diabetes (HbA1c 9.2%) likely played a pivotal role in disease progression. Hyperglycemia induces advanced glycation end-product (AGE) accumulation, which impairs macrophage phagocytic function and promotes a pro-inflammatory cytokine[ 12 ] milieu (e.g., IL-1β, TNF-α). This creates a self-perpetuating cycle: Impaired bacterial clearance → Persistent antigenic stimulation → Foamy macrophage aggregation→Sustained inflammation → Tissue necrosis and granuloma formation[ 13 ]. Notably, the abrupt discontinuation of antidiabetic medications 1 month prior to the final admission coincided with rapid clinical deterioration[ 14 ] (procalcitonin surge from 0.2 to 56.7 ng/mL), suggesting that metabolic control may modulate disease activity. Experimental models indicate that AGE-RAGE signaling inhibition reduces xanthogranulomatous inflammation[ 15 ], proposing a potential therapeutic target. Conclusion Holurinary xantholigranuloma is a rare disease with challenging diagnosis and treatment. This case suggests two key lessons: 1. PET-CT hypermetabolism does not rule out inflammatory disease.2. When imaging examination indicates malignancy, repeated histopathological examination must be performed to confirm the diagnosis. Clinicians should improve the awareness of the disease, combine the clinical manifestations, imaging examination and pathological examination, make clear the diagnosis as soon as possible, and make an individualized treatment plan according to the specific condition of the patient. For diabetic patients with pan-urological lesions showing PET hypermetabolism,we recommend: (1) Tissue biopsy prior to anticancer therapy[ 5 , 8 ] (2) Strict glycemic controlas adjuvant anti-inflammatory strategy[ 14 ].As the disease is rare, the understanding of the disease needs to be improved, and it is necessary to conduct more case reports and studies to improve the level of diagnosis and treatment. Declarations Availability of data and materials The data used to support the findings of this case report are included within the article. Further inquiries can be directed to the corresponding author. Ethical approval and consent to participate Our institution does not require ethical approval for the reporting of individual cases. So, ethical approval is not applicable in this case. Patient gave his full consent for publication and written informed consent was obtained from the patient for anonymized information to be published in this article. Consent to Publish declaration Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the editor of this journal. Conflict of Interest Statement The authors have no conflicts of interest to declare. Funding Sources This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Corresponding author Correspondence to Zhuo Li Email: [email protected] Author Contributions Zhongwei Zhang conceptualized and designed the work including data acquisition and drafting of the manuscript.Yuwan Zhaotook part in the drafting of the manuscript. Zhuo Li took part in manuscript revision.All authors have read and agreed to the published version of the manuscript. Acknowledgements Not applicable. Clinical Trial Registration declaration Not applicable Authors and Affiliations Zhongwei Zhang,Laboratory of Urology, Affiliated Hospital of Guangdong Medical University, 57 Renmin Street South, Zhanjiang, Guangdong 524001, China. Email: [email protected] D.rYuwan Zhao, Laboratory of Urology, Affiliated Hospital of Guangdong Medical University, 57 Renmin Street South, Zhanjiang, Guangdong 524001, China. Email: [email protected] D.r Zhuo Li, Laboratory of Urology, Affiliated Hospital of Guangdong Medical University, 57 Renmin Street South, Zhanjiang, Guangdong 524001, China. Email: [email protected] References Craig WD, Wagner BJ, Travis MD. Pyelonephritis: radiologic-pathologic review. Radiographics. 2008;28(1):255–77. Korkes F, Favoretto RL, Bróglio M, et al. Xanthogranulomatous pyelonephritis: clinical experience with 41 cases. Urology. 2009;71(2):178–80. Sharma D, Javali TD, Mahajan A, et al. Pan-urothelial xanthogranulomatous inflammation: a case report of an aggressive mimic of malignancy. Urol Case Rep. 2020;33:101389. Ozülker T, Ozülker F. Incidental detection of xanthogranulomatous pyelonephritis on FDG PET/CT. Clin Nucl Med. 2010;35(10):808–10. Tufano A, Costa D, Stizzo M, et al. Xanthogranulomatous pyelonephritis mimicking renal malignancy: the role of renal biopsy. Eur Urol Focus. 2019;5(5):722–4. Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia: Elsevier Saunders; 2014. pp. 71–80. Wahl RL, Jacene H, Kasamon Y, et al. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50(Suppl 1):S122–50. Kato T, Komiyama I, Maehata Y, et al. Xanthogranulomatous cystitis mimicking bladder cancer: a case report and review of literature. BMC Urol. 2018;18(1):110. Zhang J, Sun H, Liu W, et al. CT and MRI findings of xanthogranulomatous pyelonephritis: a pictorial review. Eur Radiol. 2020;30(2):1094–103. Glaudemans AW, de Vries EF, Galli F, et al. The use of ¹⁸F-FDG-PET/CT for diagnosis and treatment monitoring of inflammatory and infectious diseases. Semin Nucl Med. 2013;43(5):331–40. Jamar F, Buscombe J, Chiti A, et al. EANM/SNMMI guideline for 18F-FDG use in inflammation and infection. J Nucl Med. 2013;54(4):647–58. Goldin A, Beckman JA, Schmidt AM, et al. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006;114(6):597–605. Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860–7. Dreger NM, et al. Hyperglycemia and Urinary Tract Infections: A Review. Curr Diab Rep. 2023;23(1):1–9. Yan SF, Ramasamy R, Schmidt AM. The receptor for advanced glycation endproducts (RAGE) and cardiovascular disease. Expert Rev Mol Med. 2009;11:e9. 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7133075","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":502935030,"identity":"f0204c72-4f7d-4094-b836-3b55afe0ad1a","order_by":0,"name":"Zhongwei Zhang","email":"","orcid":"","institution":"Affiliated Hospital of Guangdong Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhongwei","middleName":"","lastName":"Zhang","suffix":""},{"id":502935035,"identity":"c5334363-ecc0-44eb-aaaf-a214688b91cc","order_by":1,"name":"Yuwan Zhao","email":"","orcid":"","institution":"Affiliated Hospital of Guangdong Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yuwan","middleName":"","lastName":"Zhao","suffix":""},{"id":502935036,"identity":"934beed8-4ff1-4c06-a221-a8fd5f6587cd","order_by":2,"name":"Zhuo Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAr0lEQVRIiWNgGAWjYDACCQgpx8befoAkLRbGfDxnEkjSUpE4T8LBgDgd8rN7DB/+qJFIb5NgSGD4UbGNsBbGOWeMjXmOSeS2STceYOw5c5uwFmaJHDNpBjagFpkDCcyMbURoYQNqkfzxTyKdTSLBgDgtPEAtErxtEgnEa5GQSCs25u2TMGwDBvJBovwiPyN548Mf3+rk5dvbDz74UUGEFhRwgET1o2AUjIJRMApwAQAXvDP3JSeYHwAAAABJRU5ErkJggg==","orcid":"","institution":"Affiliated Hospital of Guangdong Medical University","correspondingAuthor":true,"prefix":"","firstName":"Zhuo","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2025-07-15 17:38:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7133075/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7133075/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89562890,"identity":"f9fe44d6-1534-4ba7-96eb-2cb948a4710c","added_by":"auto","created_at":"2025-08-21 10:26:45","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":827683,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathology of the left ureteral orifice(a) Hematoxylin and eosin (H\u0026amp;E) staining (×100) shows mucosal erosion with dense infiltration of lipid-laden macrophages(b)CD68 immunohistochemistry (IHC) (×400) confirms abundant foamy histiocytes, characteristic of xanthogranulomatous inflammation.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7133075/v1/1015b267ad14456cdf2e67e4.jpeg"},{"id":89562887,"identity":"9dee57ce-a2e4-4e4e-9660-eba9a66a8b9d","added_by":"auto","created_at":"2025-08-21 10:26:45","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":134061,"visible":true,"origin":"","legend":"\u003cp\u003ePET-CT findings during disease progression (September 2024)\u003c/p\u003e\n\u003cp\u003ea:Bilateral renal pelvis soft-tissue filling with hypermetabolism (SUVmax 8.7)\u003c/p\u003e\n\u003cp\u003eb:Renal cortical hypermetabolism with fascial thickening, suggesting pyelitis.\u003c/p\u003e\n\u003cp\u003eB:Focal hypermetabolic thickening of left ureter\u003c/p\u003e\n\u003cp\u003ed:Hypermetabolic lesion at right distal ureter\u003c/p\u003e\n\u003cp\u003ee:Heterogeneous bladder wall thickening with hypermetabolism\u003c/p\u003e\n\u003cp\u003ef: Nodular hypermetabolic lesions in cervix\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7133075/v1/e9899d87790f72cfe1d65b8b.jpeg"},{"id":89562892,"identity":"dd12109b-782a-4c1b-904a-36f51fd8d7e6","added_by":"auto","created_at":"2025-08-21 10:26:45","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":828355,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eHistopathology of bladder lesions (October 2024).\u003c/em\u003eH\u0026amp;E staining (×200) reveals chronic inflammation with xanthogranuloma formation. Inset: Immunohistochemistry shows CK (epithelial+, brown), CD68 (histiocyte+, red), and Ki-67 (proliferation index 15%, purple). Negative stains: CK20, BRAF-V600E, and fungal markers (PAS/GMS).\u003cem\u003ePathological exclusion of malignancy and infection, confirming diffuse xanthogranulomatous inflammation.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7133075/v1/3c5f6d927151fcc19e563a70.jpeg"},{"id":89562894,"identity":"d7c0b1bc-cc3f-426b-bc34-d1a31d7bc31c","added_by":"auto","created_at":"2025-08-21 10:26:45","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":54773,"visible":true,"origin":"","legend":"\u003cp\u003eCT urography during renal abscess progression (January 2025)\u003c/p\u003e\n\u003cp\u003e(a) Axial contrast-enhanced CT: Heterogeneous bladder wall thickening with nodular enhancement (arrows) and involvement of the anterior uterine wall (b)and(c)Coronal reconstruction: Left renal enlargement with multiple non-enhancing hypodense areas indicating abscesses, loss of pelvicalyceal architecture, and retroperitoneal lymphadenopathy.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7133075/v1/23c37dd5c02ebce0a2ffaa16.jpeg"},{"id":107524425,"identity":"a7127b82-9273-440e-94c6-d72381079b0a","added_by":"auto","created_at":"2026-04-22 09:28:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3083458,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7133075/v1/8247243f-1402-4772-a47c-2b057cf819e2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Rare Case of Multifocal Xanthogranulomatous Disease Involving the Entire Urinary Tract: Diagnosis and Management Challenges","fulltext":[{"header":"Background","content":"\u003cp\u003eXanthogranulomatous inflammation (XGI) is a rare chronic granulomatous disorder characterized by lipid-laden macrophage infiltration, typically occurring as a localized process in organs such as the kidney (xanthogranulomatous pyelonephritis, XGP) or gallbladder[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. While unilateral renal XGP is well-documented, multifocal involvement beyond a single organ is exceedingly uncommon[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], and pan-urological XGI—affecting the kidneys, ureters, bladder, and adjacent structures—represents an exceptional entity with fewer than 10 cases reported worldwide[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDiagnostic challenges arise from its radiological mimicry of malignancy, particularly on FDG-PET/CT, where hypermetabolic lesions may falsely suggest metastatic urothelial carcinom[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. This discordance underscores the critical role of histopathological confirmation[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Additionally, immunocompromised states, such as uncontrolled diabetes, are recognized risk factors due to impaired bacterial clearance and dysregulated macrophage responses[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], yet the precise immunometabolic mechanisms driving systemic XGI remain poorly understood.\u003c/p\u003e\u003cp\u003eWe present a novel case of diffuse XGI involving the entire urinary tract and retroperitoneal nodes in a diabetic patient, initially misdiagnosed as metastatic cancer by PET/CT. This case aims to augment the sparse literature on pan-urological XGI and refine diagnostic strategies for this masquerading entity.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 67-year-old female with poorly controlled diabetes (HbA1c 9.2%) and an 8-year history of hypertension presented to our hospital in February 2023 with left hydronephrosis. The patient underwent transurethral resection of the left ureteral orifice with electrocautery of the bladder mucosa. Histopathological examination revealed xanthogranulomatous inflammation at the left ureteral orifice (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e), with immunohistochemical staining showing: CK(-), CD68(+), Ki67(10%), S-100(-), CD1a(-), CD163(-), CD3(+) (T cells), CD20(+) (B cells), and ALK(5A4)(-). In situ hybridization (EBER Probe) and special stains (PAS, GMS) were negative. The patient was discharged after her stable condition.\u003c/p\u003e\n\u003cp\u003eOn September 23, 2024, the patient was readmitted to Nanfang Hospital with elevated serum creatinine persisting for one month. Laboratory tests showed renal dysfunction (creatinine 229 \u0026micro;mol/L, urea 13.6 mmol/L, eGFR 18.43 mL/min). Cystoscopy revealed multiple masses in the trigone, left wall, right wall, and posterior wall of the bladder. Transurethral resection of bladder lesions was performed on September 24, followed by epirubicin bladder perfusion. Renal function progressively deteriorated (creatinine 453 \u0026micro;mol/L, eGFR 12.25 mL/min by September 29), prompting percutaneous bilateral nephrostomy[\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003ePET-CT on September 30 demonstrated hypermetabolic lesions in the bladder, bilateral ureters, renal pelvis, cervix, and lymph nodes (SUVmax 8.2; Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e), initially suggestive of urothelial malignancy. However, histopathological findings on October 10 confirmed chronic inflammation with xanthogranuloma formation (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Immunohistochemistry showed: CK(+), CD68(+), Ki-67(15%), with negative staining for CK20 and BRAF-V600E. Special stains for fungi were negative. The patient was treated with piperacillin-tazobactam and discharged in stable condition.\u003c/p\u003e\n\u003cp\u003eThe patient was readmitted on January 3, 2025 with fever and left flank pain 3 months post-nephrostomy. Laboratory tests revealed urinary tract infection (WBC 54,000/\u0026micro;L, pyuria 2+/HPF), anemia (Hb 51 g/L), and elevated inflammatory markers (CRP 153 mg/L, PCT 30.2 ng/mL). CT urography (January 6) showed left renal abscess, diffuse ureteral wall thickening, and retroperitoneal lymphadenopathy (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). Following abscess drainage on January 9 and meropenem therapy, infection parameters improved (WBC 11.5\u0026times;10^9/L, PCT 0.217 ng/mL by January 24), though anemia persisted (Hb 66 g/L post-transfusion).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case of pan-urological xanthogranulomatous inflammation (XGI) underscores several critical challenges in diagnosing and managing this rare entity. The diffuse involvement of the urinary tract\u0026mdash;spanning bilateral kidneys, ureters, bladder, cervix, and retroperitoneal lymph nodes\u0026mdash;represents an exceptionally rare manifestation of XGI, typically confined to a single organ (e.g., xanthogranulomatous pyelonephritis). The clinical and radiological mimicry of metastatic malignancy, coupled with histopathological ambiguity, highlights the need for a multidisciplinary diagnostic approach and raises questions about the pathophysiology of systemic XGI.\u003c/p\u003e\u003cp\u003e\u003cb\u003e1. Radiological-Pathological Discordance: Malignancy Mimicry\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe initial PET-CT findings met PERCIST criteria for malignancy[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], with hypermetabolic lesions (SUVmax 8.7 in the bladder, 7.8 in retroperitoneal nodes) and an anatomical distribution suggestive of urothelial carcinoma with metastatic spread. However, repeated histopathological examinations consistently demonstrated chronic inflammation with xanthogranuloma formation, devoid of malignant cells or microbial pathogens[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This discrepancy may be attributed to the following mechanisms:\u003c/p\u003e\u003cp\u003e\u003cb\u003eA\u003c/b\u003e.Para-inflammatory lymphatic activation: Chronic granulomatous inflammation can induce reactive lymph node hyperplasia with increased glucose metabolism[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], mimicking metastatic spread. Similar phenomena have been reported in IgG4-related diseases and sarcoidosis.\u003c/p\u003e\u003cp\u003e\u003cb\u003eB.\u003c/b\u003eMacrophage-driven FDG avidity**: Lipid-laden CD68+/Lys\u0026thinsp;+\u0026thinsp;macrophages, the hallmark of XGI, exhibit upregulated glycolytic activity, contributing to false-positive PET findings[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cb\u003eC.\u003c/b\u003eTumor-like angiogenesis**: Progressive tissue destruction and reparative neovascularization in chronic inflammation may enhance radiotracer uptake, as seen in this patient\u0026rsquo;s bladder and ureteral lesions[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThis case emphasizes the necessity of histopathological confirmation for PET-positive lesions, even when clinical and imaging features strongly suggest malignancy.\u003c/p\u003e\u003cp\u003e\u003cb\u003e2. Immunometabolic Dysregulation: Role of Diabetes\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe patient\u0026rsquo;s poorly controlled diabetes (HbA1c 9.2%) likely played a pivotal role in disease progression. Hyperglycemia induces advanced glycation end-product (AGE) accumulation, which impairs macrophage phagocytic function and promotes a pro-inflammatory cytokine[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] milieu (e.g., IL-1β, TNF-α). This creates a self-perpetuating cycle:\u003c/p\u003e\u003cp\u003eImpaired bacterial clearance \u0026rarr; Persistent antigenic stimulation \u0026rarr; Foamy macrophage aggregation\u0026rarr;Sustained inflammation \u0026rarr; Tissue necrosis and granuloma formation[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eNotably, the abrupt discontinuation of antidiabetic medications 1 month prior to the final admission coincided with rapid clinical deterioration[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] (procalcitonin surge from 0.2 to 56.7 ng/mL), suggesting that metabolic control may modulate disease activity. Experimental models indicate that AGE-RAGE signaling inhibition reduces xanthogranulomatous inflammation[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], proposing a potential therapeutic target.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eHolurinary xantholigranuloma is a rare disease with challenging diagnosis and treatment. This case suggests two key lessons: 1. PET-CT hypermetabolism does not rule out inflammatory disease.2. When imaging examination indicates malignancy, repeated histopathological examination must be performed to confirm the diagnosis. Clinicians should improve the awareness of the disease, combine the clinical manifestations, imaging examination and pathological examination, make clear the diagnosis as soon as possible, and make an individualized treatment plan according to the specific condition of the patient. For diabetic patients with pan-urological lesions showing PET hypermetabolism,we recommend: (1) Tissue biopsy prior to anticancer therapy[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] (2) Strict glycemic controlas adjuvant anti-inflammatory strategy[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].As the disease is rare, the understanding of the disease needs to be improved, and it is necessary to conduct more case reports and studies to improve the level of diagnosis and treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data used to support the findings of this case report are included within the article. Further inquiries can be directed to the corresponding author.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur institution does not require ethical approval for the reporting of individual cases. So, ethical approval is not applicable in this case. Patient gave his full consent for publication and written informed consent was obtained from the patient for anonymized information to be published in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the editor of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Sources\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding author\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence to\u0026nbsp;Zhuo Li \u0026nbsp; Email: [email protected]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZhongwei Zhang conceptualized and designed the work including data acquisition and drafting of the manuscript.Yuwan Zhaotook part in the drafting of the manuscript. Zhuo Li took part in manuscript revision.All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Registration declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors and Affiliations\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZhongwei Zhang,Laboratory of Urology, Affiliated Hospital of Guangdong Medical University, 57 Renmin Street South, Zhanjiang, Guangdong 524001, China. Email: [email protected]\u003c/p\u003e\n\u003cp\u003eD.rYuwan Zhao, Laboratory of Urology, Affiliated Hospital of Guangdong Medical University, 57 Renmin Street South, Zhanjiang, Guangdong 524001, China. Email: [email protected]\u003c/p\u003e\n\u003cp\u003eD.r Zhuo Li, Laboratory of Urology, Affiliated Hospital of Guangdong Medical University, 57 Renmin Street South, Zhanjiang, Guangdong 524001, China. Email: [email protected]\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCraig WD, Wagner BJ, Travis MD. Pyelonephritis: radiologic-pathologic review. Radiographics. 2008;28(1):255\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKorkes F, Favoretto RL, Br\u0026oacute;glio M, et al. Xanthogranulomatous pyelonephritis: clinical experience with 41 cases. Urology. 2009;71(2):178\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSharma D, Javali TD, Mahajan A, et al. Pan-urothelial xanthogranulomatous inflammation: a case report of an aggressive mimic of malignancy. Urol Case Rep. 2020;33:101389.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOz\u0026uuml;lker T, Oz\u0026uuml;lker F. Incidental detection of xanthogranulomatous pyelonephritis on FDG PET/CT. Clin Nucl Med. 2010;35(10):808\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTufano A, Costa D, Stizzo M, et al. Xanthogranulomatous pyelonephritis mimicking renal malignancy: the role of renal biopsy. Eur Urol Focus. 2019;5(5):722\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia: Elsevier Saunders; 2014. pp. 71\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWahl RL, Jacene H, Kasamon Y, et al. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50(Suppl 1):S122\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKato T, Komiyama I, Maehata Y, et al. Xanthogranulomatous cystitis mimicking bladder cancer: a case report and review of literature. BMC Urol. 2018;18(1):110.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang J, Sun H, Liu W, et al. CT and MRI findings of xanthogranulomatous pyelonephritis: a pictorial review. Eur Radiol. 2020;30(2):1094\u0026ndash;103.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGlaudemans AW, de Vries EF, Galli F, et al. The use of \u0026sup1;⁸F-FDG-PET/CT for diagnosis and treatment monitoring of inflammatory and infectious diseases. Semin Nucl Med. 2013;43(5):331\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJamar F, Buscombe J, Chiti A, et al. EANM/SNMMI guideline for 18F-FDG use in inflammation and infection. J Nucl Med. 2013;54(4):647\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGoldin A, Beckman JA, Schmidt AM, et al. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006;114(6):597\u0026ndash;605.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDreger NM, et al. Hyperglycemia and Urinary Tract Infections: A Review. Curr Diab Rep. 2023;23(1):1\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYan SF, Ramasamy R, Schmidt AM. The receptor for advanced glycation endproducts (RAGE) and cardiovascular disease. Expert Rev Mol Med. 2009;11:e9.\u003c/span\u003e\u003c/li\u003e\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":"Xanthogranulomatous inflammation, Diabetic immunocompromise, Pan-urological disease","lastPublishedDoi":"10.21203/rs.3.rs-7133075/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7133075/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Xanthogranuloma is a granulomatous lesion caused by a bacterial infection, usually found in the lungs, skin, and digestive system. Xanthogranulomas in the urinary system are relatively rare, and cases of total urinary tract involvement are even rarer.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e This report presents a case of total urinary xanthogranuloma in a 67-year-old woman with long-term hypertension and diabetes, presenting with multiple urinary tract infections and renal failure, who was initially misdiagnosed as metastatic malignancy by PET-CT imaging. The final diagnosis was a total urinary xanthogranuloma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e This paper reviews the diagnostic process, treatment methods, and prognosis of this patient, and discusses the underlying pathophysiological mechanisms between diabetes-related immunosuppression and disease progression. To provide a reference for the clinical diagnosis and treatment of similar diseases in the future.\u003c/p\u003e","manuscriptTitle":"A Rare Case of Multifocal Xanthogranulomatous Disease Involving the Entire Urinary Tract: Diagnosis and Management Challenges","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-21 10:26:40","doi":"10.21203/rs.3.rs-7133075/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":"8f543b1c-9ac1-4f1a-b974-3c8d23f32d44","owner":[],"postedDate":"August 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-22T09:25:55+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-21 10:26:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7133075","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7133075","identity":"rs-7133075","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}