Erdheim–Chester Disease Mimicking Wilms Tumor in a Child: A Diagnostic Challenge

Erdheim–Chester Disease Mimicking Wilms Tumor in a Child: A Diagnostic Challenge | 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 Erdheim–Chester Disease Mimicking Wilms Tumor in a Child: A Diagnostic Challenge Svitozar Khalak, Andrii Nakonechnyi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8562480/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Mar, 2026 Read the published version in BMC Pediatrics → Version 1 posted 15 You are reading this latest preprint version Abstract Background Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocytosis driven by activating mutations of the MAPK signaling pathway, most commonly BRAF V600E. Pediatric cases are exceedingly rare and often present with atypical, multisystem manifestations, resulting in significant diagnostic delay. Renal and retroperitoneal involvement may mimic primary renal malignancies, particularly Wilms tumor. Case presentation We report a case of Erdheim–Chester disease in Ukraine, Lviv. A male child who initially presented at the age of two years with central diabetes insipidus and progressive urinary tract infections. Over two years, the patient developed bilateral obstructive uropathy, retroperitoneal and paravertebral masses, and multifocal central nervous system and orbital involvement. Recurrent urinary tract infections and progressive hydronephrosis necessitated multiple surgical interventions. Initial histopathological findings were inconclusive and suggested alternative diagnoses, including ganglioneuroma and reactive histiocytic proliferation. Due to discordance between clinical, radiological, and histological findings, extended immunohistochemical and molecular analyses were performed. Detection of a pathogenic BRAF V600E mutation confirmed the diagnosis of Erdheim–Chester disease. Lifelong targeted therapy with the BRAF inhibitor dabrafenib was initiated, resulting in clinical stabilization. Conclusions This case highlights the diagnostic complexity of Erdheim–Chester disease in children and emphasizes the importance of considering histiocytic disorders in the differential diagnosis of renal and retroperitoneal masses. Multisystem involvement, atypical imaging findings, and molecular testing are key elements for accurate diagnosis and appropriate management, particularly in cases mimicking Wilms tumor. Erdheim-Chester disease pediatric histiocytosis Wilms tumor differential diagnosis BRAF mutation obstructive uropathy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Introduction Erdheim–Chester disease is a rare form of non-Langerhans cell histiocytosis characterized by tissue infiltration with lipid-laden histiocytes and chronic inflammatory fibrosis. Although traditionally considered an inflammatory disorder, ECD is now recognized as a clonal neoplastic disease driven by activating mutations in the MAPK pathway, most commonly BRAF V600E . The disease predominantly affects adults between the fifth and seventh decades of life, while pediatric cases are exceedingly uncommon. Clinical presentation is highly heterogeneous and depends on the organs involved, most frequently the skeleton, central nervous system, cardiovascular system, lungs, retroperitoneum, and kidneys. Renal involvement typically results from perirenal and retroperitoneal soft-tissue infiltration, leading to ureteral compression and hydronephrosis. In children, such manifestations may closely resemble primary renal or retroperitoneal tumors, particularly Wilms tumor, which remains the most common malignant renal neoplasm in pediatric patients. Distinguishing between these entities is critical, as their management and prognosis differ substantially. We present a pediatric case of Erdheim–Chester disease with predominant urinary tract involvement that initially mimicked a renal tumor, illustrating the diagnostic challenges and the pivotal role of molecular testing. Case Presentation A male child with unremarkable prenatal, perinatal, and family history first presented in 2020 at the age of two years in Clinical Center of Children's Healthcare, Lviv, Ukraine with pronounced polydipsia and polyuria. Endocrinological evaluation confirmed central diabetes insipidus (CDI). Initial ultrasonography of the urinary tract revealed right-sided megaureter and left-sided hydronephrosis. The etiology of these findings remained unclear, and the patient did not receive specific treatment for approximately 8 months due to the mother declining the subsequent examinations and proposed treatment. In June 2021, due to the above-mentioned complaints and worsening manifestations of CDI, the patient presented for a repeat evaluation. Further diagnostic evaluation using computer tomography (CT) identified a paravertebral mass at the Th4–Th6 level in addition to persistent renal abnormalities (Figure 1). FIGURE 1 CT scan of paravertebral mass at the Th4–Th6 level and left renal abnormalities In July 2021, at the age of 3 years, thoracoscopic resection of the paravertebral lesion was performed. Immunohistochemical examination indicated a ganglioneuroma. The patient was discharged with diagnoses of CDI, suspected neurofibromatosis type 2 (based on clinical features only), right-sided megaureter, left-sided hydronephrosis grade II, speech and language developmental delay (SLDD). Treatment with desmopressin resulted in resolution of polyuria and polydipsia. Follow-up ultrasonography in January 2022 demonstrated persistent signs of left-sided hydronephrosis and right-sided megaureter. The patient was subsequently lost to follow-up for seven months for unknown reasons. In July 2022, at the age of four years, he was admitted to the hospital with diagnosis of recurrent febrile urinary tract infections, repeatedly caused by Klebsiella pneumoniae . Contrast-enhanced ultrasonography (SonoVue) revealed a 25 × 17 × 15 mm soft-tissue mass compressing the left ureter with moderate contrast enhancement. Computer tomography demonstrated left-sided hydronephrosis grade III, right-sided obstructive non-refluxing megaureter grade IV, and multiple retroperitoneal soft-tissue proliferations initially interpreted as possible manifestations of neurofibromatosis (Figures 2, 3A, 3B). Given the imaging appearance and progressive obstructive uropathy, a Wilms tumor was also considered in the differential diagnosis. FIGURE 2 Left-sided hydronephrosis grade III, right-sided obstructive non-refluxing megaureter grade IV To achieve renal decompression, a decision was made to proceed with ureteral 4.7 Fr × 12 cm stenting. Cystoscopy intervention included unsuccessful left-sided JJ stenting due to significant resistance in the upper ureter, while right-sided stenting was successful (Figure 4). A left percutaneous nephrostomy was subsequently placed, resulting in adequate urinary drainage Given the presence of SLDD and the patient’s medical history, a brain MRI was obtained. Brain MRI was performed on July 11, 2022, revealed multiple intraventricular, intra- and parasellar nodular lesions, involvement along venous sinuses, bilateral orbital and retrobulbar infiltration, and lesions within the pterygopalatine fossae (Figure 5). FIGURE 5 Brain MRI (July 11, 2022) Given the multisystem involvement, extensive molecular genetic testing (“INVITAE” laboratory, 27 July 2022) was performed to exclude neurofibromatosis and tuberous sclerosis; sequencing and deletion/duplication analysis of 2,782 genes yielded negative results. Due to progressive worsening of hydronephrosis and deterioration of clinical and laboratory parameters, in September 2022, the patient underwent an upper midline laparotomy, which revealed multiple xanthomatous infiltrative lesions involving the ureters and renal hilum. Maximal surgical debulking was performed, resulting in restoration of urinary flow (Figure 6). Postoperative histopathology (No. 22SP074829, CSD Laboratory) demonstrated xanthogranulomatous pyelonephritis with involvement of both ureters. FIGURE 6 Upper midline laparotomy. Restoration of urinary patency Due to the discrepancy between the clinical picture and conventional histology, extended immunohistochemical analysis for histiocytic disorders was initiated. The results of immunohistochemical analysis bloc 22SP074829 А1 were as follows: CD1a (DAKO, clone O10) showed a negative reaction in histiocytes; CD68 (DAKO, clone KP1) demonstrated a positive reaction in histiocytes; CD14 (Cell Marque, clone EPR3653) was positive in histiocytes; factor XIIIa (Cell Marque, clone EP3372) showed a negative reaction in the lesional cells; BRAF (v22) was negative in the lesional cells. Findings were inconclusive, and differentiation between Erdheim–Chester disease and reactive histiocytic proliferation remained uncertain; therefore, a decision was made to proceed with molecular analysis. Subsequent molecular testing №22MOL004617 from CSD Laboratory identified a pathogenic BRAF V600E mutation on October 2022 at the age of 4 years and 5 months. Based on the combined clinical, radiological, histological, and molecular findings, a diagnosis of Erdheim–Chester disease was established. In November 2022, lifelong targeted therapy with the BRAF inhibitor dabrafenib was initiated at a dose of 5.25 mg/kg/day, administered in two divided doses, under pediatric oncologist supervision. The treatment outcomes were positive, with a significant reduction of lesions in the brain and retroperitoneal space. Urinary tract patency was fully restored, and the patient remains under close clinical follow-up for 3 years (Figures 7, 8). Discussion This case highlights the diagnostic complexity of Erdheim–Chester disease (ECD) in children, where early manifestations may be subtle, fragmented across specialties, and easily misattributed to more common pediatric entities. CDI as seen at disease onset in our patient, is a recognized early feature of ECD and may precede systemic disease by months to years, particularly when the hypothalamic–pituitary axis is involved. Pediatric ECD case reports repeatedly emphasize CDI/polydipsia–polyuria as an initial clue that should trigger targeted neuroimaging and consideration of histiocytic disorders rather than isolated endocrine disease [1]. The principal diagnostic dilemma in our patient was the combination of progressive obstructive uropathy, retroperitoneal and peri-ureteral soft-tissue masses, and imaging findings mimicking a Wilms tumor. Wilms tumor is the most common renal malignancy in early childhood and may present with hydronephrosis or urinary tract compression; however, it typically manifests as a unilateral intrarenal mass rather than diffuse retroperitoneal or peri-ureteral infiltration. In contrast, our patient demonstrated bilateral urinary tract involvement, multifocal retroperitoneal lesions, central nervous system infiltration, and endocrinological manifestations, which are not characteristic of Wilms tumor. These atypical features ultimately argued against Wilms tumor and prompted further histopathological, immunohistochemical, and molecular investigations. In ECD, renal compromise is typically not due to a primary intrarenal neoplasm but rather to infiltrative peri-renal and retroperitoneal soft-tissue proliferation that may encase the kidneys/ureters (“hairy kidney” spectrum) and cause extrinsic obstruction with hydronephrosis and recurrent urinary infections. Urological involvement—ureteral obstruction, hydronephrosis, and renal insufficiency—has been systematically described as part of ECD’s retroperitoneal phenotype [2]. By contrast, Wilms tumor (WT) typically presents in children as a unilateral intrarenal mass, commonly with abdominal distension/palpable mass and sometimes hematuria or hypertension. Imaging guidelines emphasize characterization of the primary renal mass, vascular involvement, and metastatic assessment (lungs), with management pathways that may proceed without pre-treatment biopsy in many protocols—creating a real risk of “treating as WT” when a non-WT condition masquerades as a renal tumor [3]. Practical differentiators: ECD vs Wilms tumor Several features in our case argued against WT and favored ECD: Multisystem pattern: Multifocal intracranial (intraventricular and parasellar) and orbital/retrobulbar lesions are highly atypical for newly diagnosed WT but are well-described in ECD [4]. Bilateral urinary tract involvement: The coexistence of bilateral obstructive pathology (megaureter/hydronephrosis) and multifocal retroperitoneal infiltrates is more consistent with an infiltrative systemic disorder than a solitary embryonal renal tumor [5]. Absence of a discrete intrarenal tumor: WT usually forms a definable intrarenal mass; ECD more often produces peri-renal/retroperitoneal encasement and ureteral compression [6]. Pathology discordance: Initial histology may be misleading in rare histiocytoses, particularly if sampling is limited or fibrosis is prominent—necessitating clinicoradiologic correlation and deeper testing. This challenge is explicitly addressed in consensus recommendations [7]. Multiple publications document that ECD can present as a renal mass-like process or with striking renal/retroperitoneal involvement that prompts tumor work-up and sometimes major surgery before the correct diagnosis is established. A renal mass presentation with biopsy-confirmed ECD and emphasis on the “hairy kidney” sign was reported (adult), illustrating how ECD can mimic neoplastic renal disease on imaging and clinically [8]. Similarly, classic descriptions of urologic ECD manifestations include ureteral obstruction and hydronephrosis, reinforcing that urinary tract disease may dominate the course and drive surgical/endourological interventions [5]. In pediatric ECD reports, diagnostic delay is commonly attributed to non-specific early symptoms and fragmented specialist pathways. For example, pediatric cases with CDI followed by central nervous system (CNS) manifestations underscore the need for early recognition of a unifying systemic diagnosis [1]. This case also illustrates that immunohistochemistry (IHC) may not be sufficient to conclusively separate ECD from reactive histiocytic proliferations when tissue is fibrotic or limited. Contemporary ECD guidance positions molecular testing for MAPK pathway alterations (including BRAF ) as an essential diagnostic pillar—both for confirmation and for immediate therapeutic implications [7]. Clinical takeaway: in a child with suspected renal tumor/obstructive uropathy, the combination of CDI, multifocal CNS/orbital findings, bilateral urinary tract involvement, and peri-renal/retroperitoneal infiltrative masses should trigger early consideration of ECD (and related histiocytoses) and prompt multidisciplinary review plus molecular testing before committing to WT-directed therapy. Abbreviations ECD Erdheim–Chester disease WT Wilms tumor BRAF B-rapidly accelerated fibrosarcoma protein MAPK Mitogen-activated protein kinase CDI Central diabetes insipidus CT Computer tomography SLDD Speech and language developmental delay MRI Magnetic resonance imaging CNS Central nervous system IHC Immunohistochemistry Declarations Ethics approval The study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Ethics Committee of Danylo Halytsky Lviv National Medical University, Lviv, Ukraine (protocol No. 12, December 16, 2024). Informed consent to participate Written informed consent was obtained from the patient’s legal guardians for publication of this case report and accompanying images. Funding This research received no external funding. Data Availability Statement The raw data supporting the conclusions of this article will be made available by the authors on request. Author Contributions Conceptualization, S.K.; investigation, S.K. and A.N.; resources, S.K.; writing—original draft preparation S.K.; writing—review and editing A.N; supervision, A.N.; funding acquisition, - . All authors have read and agreed to the published version of the manuscript. Conflicts of Interest: The authors declare no conflicts of interest. Acknowledgements The authors would like to thank the patient and his family for their cooperation. Clinical trial number Not applicable. References Ma Y, Guo X, Wan Z, Liu H, Gao J. Paediatric Erdheim-Chester Disease in the Lateral Ventricle: A Case Report and Review of the Literature. Front Oncol. 2022;12:835076. 10.3389/fonc.2022.835076 . PMID: 35494046; PMCID: PMC9046972. Daniel A, Yelfimov DJ, Lightner MK, Tollefson. Urologic Manifestations of Erdheim-Chester Disease, Urology, Volume 84, Issue 1, 2014, Pages 218–221, ISSN 0090-4295. https://doi.org/10.1016/j.urology.2013.10.023 Smith V, Wahba A, Chintagumpala M, Mahajan P. A review of Wilms tumor. Pediatr Rev. 2025;46(4):206–12. https://doi.org/10.1542/pir.2024-006444 . Ma Y, Guo X, Wan Z, Liu H, Gao J. Paediatric Erdheim-Chester Disease in the Lateral Ventricle: A Case Report and Review of the Literature. Front Oncol. 2022;12:835076. 10.3389/fonc.2022.835076 . PMID: 35494046; PMCID: PMC9046972. Yelfimov DA, Lightner DJ, Tollefson MK. Urologic manifestations of Erdheim-Chester Disease. Urology. 2014;84(1):218–21. https://doi.org/10.1016/j.urology.2013.10.023 . Merai H, Collas D, Bhagat A, Mandalia U. Erdheim-Chester Disease: A Case Report and Review of the Literature. J Clin Imaging Sci. 2020;10:37. Goyal G, Heaney ML, Collin M, Cohen-Aubart F, Vaglio A, Durham BH, Hershkovitz-Rokah O, Girschikofsky M, Jacobsen ED, Toyama K, Goodman AM, Hendrie P, Cao X, Estrada-Veras JI, Shpilberg O, Abdo A, Kurokawa M, Dagna L, McClain KL, Diamond EL. Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis, and treatment in the molecular era. Blood. 2020;135(22):1929–45. https://doi.org/10.1182/blood.2019003507 . Abu Rass HB, Abuawad M, Abueideh Y, Malhis EL. Erdheim-Chester Disease with Renal Mass Presentation: Report of the First Case From Palestine and a Review of the Literature. Am J Case Rep. 2023;24:e941912. PMID: 37974387; PMCID: PMC10665577. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 12 Mar, 2026 Read the published version in BMC Pediatrics → Version 1 posted Editorial decision: Revision requested 27 Jan, 2026 Reviews received at journal 26 Jan, 2026 Reviewers agreed at journal 26 Jan, 2026 Reviewers agreed at journal 26 Jan, 2026 Reviewers agreed at journal 24 Jan, 2026 Reviewers agreed at journal 24 Jan, 2026 Reviews received at journal 22 Jan, 2026 Reviewers agreed at journal 22 Jan, 2026 Reviewers agreed at journal 22 Jan, 2026 Reviewers agreed at journal 21 Jan, 2026 Reviewers invited by journal 21 Jan, 2026 Editor invited by journal 13 Jan, 2026 Editor assigned by journal 12 Jan, 2026 Submission checks completed at journal 12 Jan, 2026 First submitted to journal 09 Jan, 2026 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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1","display":"","copyAsset":false,"role":"figure","size":59375,"visible":true,"origin":"","legend":"\u003cp\u003eCT scan of paravertebral mass at the Th4–Th6 level and left renal abnormalities\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8562480/v1/6b645dfe8c998fd66e31d466.jpg"},{"id":101205130,"identity":"dcfa516f-d8ca-4f3d-ad50-8c2a5bfa00d1","added_by":"auto","created_at":"2026-01-27 09:47:21","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":50904,"visible":true,"origin":"","legend":"\u003cp\u003eLeft-sided hydronephrosis grade III, right-sided obstructive non-refluxing megaureter grade IV\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8562480/v1/d72fe21e3ef792fade90bd56.jpg"},{"id":101205427,"identity":"39d741fc-fe73-4ace-8aac-759c40318f9e","added_by":"auto","created_at":"2026-01-27 09:49:22","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":97465,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8562480/v1/84e109b01645dc5cb166b9a1.jpg"},{"id":101205422,"identity":"87d4126a-b489-43de-ab7c-39132e7b0cf6","added_by":"auto","created_at":"2026-01-27 09:49:21","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":103626,"visible":true,"origin":"","legend":"\u003cp\u003eCystoscopic ureteral JJ stent placement\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8562480/v1/0fb35b1f72f9fdb9872f85cc.jpg"},{"id":101067649,"identity":"75e83a11-bf21-4a30-9257-c0c118110de9","added_by":"auto","created_at":"2026-01-25 07:13:58","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":45479,"visible":true,"origin":"","legend":"\u003cp\u003eBrain MRI (July 11, 2022)\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8562480/v1/5822bf6a638935e5cba341c7.jpg"},{"id":101205612,"identity":"e1c870da-095d-417d-961b-1f79b62212ed","added_by":"auto","created_at":"2026-01-27 09:49:55","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":103983,"visible":true,"origin":"","legend":"\u003cp\u003eUpper midline laparotomy. Restoration of urinary patency\u003c/p\u003e","description":"","filename":"6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8562480/v1/4ea4ff8dd57547fc5ad21833.jpg"},{"id":101067653,"identity":"98ff23b2-ff3b-460d-b548-4d458dae6c48","added_by":"auto","created_at":"2026-01-25 07:13:58","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":30134,"visible":true,"origin":"","legend":"\u003cp\u003eCT scan after dabrafenib therapy follow-up\u003c/p\u003e","description":"","filename":"7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8562480/v1/b6a3bc7e5076c8682f887dc6.jpg"},{"id":101067662,"identity":"11d0a991-1d0d-42c5-aaec-da98cda8894e","added_by":"auto","created_at":"2026-01-25 07:13:58","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":72562,"visible":true,"origin":"","legend":"\u003cp\u003eBrain MRI after dabrafenib therapy follow-up\u003c/p\u003e","description":"","filename":"8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8562480/v1/19394034dcefeb7f16575785.jpg"},{"id":104739397,"identity":"63d9dbd1-4075-4b71-8c43-a16cc4f41539","added_by":"auto","created_at":"2026-03-16 16:05:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":943527,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8562480/v1/b79a0170-92e3-4f63-ab18-f097fe6753a2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Erdheim–Chester Disease Mimicking Wilms Tumor in a Child: A Diagnostic Challenge","fulltext":[{"header":"Introduction","content":"\u003cp\u003eErdheim–Chester disease is a rare form of non-Langerhans cell histiocytosis characterized by tissue infiltration with lipid-laden histiocytes and chronic inflammatory fibrosis. Although traditionally considered an inflammatory disorder, ECD is now recognized as a clonal neoplastic disease driven by activating mutations in the MAPK pathway, most commonly \u003cem\u003eBRAF V600E\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003eThe disease predominantly affects adults between the fifth and seventh decades of life, while pediatric cases are exceedingly uncommon. Clinical presentation is highly heterogeneous and depends on the organs involved, most frequently the skeleton, central nervous system, cardiovascular system, lungs, retroperitoneum, and kidneys. Renal involvement typically results from perirenal and retroperitoneal soft-tissue infiltration, leading to ureteral compression and hydronephrosis.\u003c/p\u003e\n\u003cp\u003eIn children, such manifestations may closely resemble primary renal or retroperitoneal tumors, particularly Wilms tumor, which remains the most common malignant renal neoplasm in pediatric patients. Distinguishing between these entities is critical, as their management and prognosis differ substantially. We present a pediatric case of Erdheim–Chester disease with predominant urinary tract involvement that initially mimicked a renal tumor, illustrating the diagnostic challenges and the pivotal role of molecular testing.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA male child with unremarkable prenatal, perinatal, and family history first presented in 2020 at the age of two years in\u0026nbsp;Clinical Center of Children\u0026apos;s Healthcare, Lviv, Ukraine\u0026nbsp;with pronounced polydipsia and polyuria. Endocrinological evaluation confirmed central diabetes insipidus (CDI). Initial ultrasonography of the urinary tract revealed right-sided megaureter and left-sided hydronephrosis. The etiology of these findings remained unclear, and the patient did not receive specific treatment for approximately 8 months due to the mother declining the subsequent examinations and proposed treatment.\u003c/p\u003e\n\u003cp\u003eIn June 2021, due to the above-mentioned complaints and worsening manifestations of \u0026nbsp;CDI, the patient presented for a repeat evaluation. Further diagnostic evaluation using computer tomography (CT) identified a paravertebral mass at the Th4\u0026ndash;Th6 level in addition to persistent renal abnormalities (Figure 1).\u003c/p\u003e\n\u003cp\u003eFIGURE 1 CT scan of paravertebral mass at the Th4\u0026ndash;Th6 level and left renal abnormalities\u003c/p\u003e\n\u003cp\u003eIn July 2021, at the age of 3 years, thoracoscopic resection of the paravertebral lesion was performed. Immunohistochemical examination indicated a ganglioneuroma.\u003c/p\u003e\n\u003cp\u003eThe patient was discharged with diagnoses of CDI, suspected neurofibromatosis type 2 (based on clinical features only), right-sided megaureter, left-sided hydronephrosis grade II, speech and language developmental delay (SLDD). Treatment with desmopressin resulted in resolution of polyuria and polydipsia.\u003c/p\u003e\n\u003cp\u003eFollow-up ultrasonography in January 2022 demonstrated persistent signs of left-sided hydronephrosis and right-sided megaureter.\u003c/p\u003e\n\u003cp\u003eThe patient was subsequently lost to follow-up for seven months for unknown reasons.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn July 2022, at the age of four years, he was admitted to the hospital with diagnosis of recurrent febrile urinary tract infections, repeatedly caused by \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003eContrast-enhanced\u0026nbsp;ultrasonography (SonoVue) revealed a 25 \u0026times; 17 \u0026times; 15 mm soft-tissue mass compressing the left ureter with moderate contrast enhancement. Computer tomography demonstrated left-sided hydronephrosis grade III, right-sided obstructive non-refluxing megaureter grade IV, and multiple retroperitoneal soft-tissue proliferations initially interpreted as possible manifestations of neurofibromatosis (Figures 2, 3A, 3B). Given the imaging appearance and progressive obstructive uropathy, a Wilms tumor was also considered in the differential diagnosis.\u003c/p\u003e\n\u003cp\u003eFIGURE 2 Left-sided hydronephrosis grade III, right-sided obstructive non-refluxing megaureter grade IV\u003c/p\u003e\n\u003cp\u003eTo achieve renal decompression, a decision was made to proceed with ureteral 4.7 Fr \u0026times; 12 cm stenting. Cystoscopy intervention included unsuccessful left-sided JJ stenting due to significant resistance in the upper ureter, while right-sided stenting was successful (Figure 4). A left percutaneous nephrostomy was subsequently placed, resulting in adequate urinary drainage\u003c/p\u003e\n\u003cp\u003eGiven the presence of SLDD and the patient\u0026rsquo;s medical history, a brain MRI was obtained.\u003c/p\u003e\n\u003cp\u003eBrain MRI was performed on July 11, 2022, revealed multiple intraventricular, intra- and parasellar nodular lesions, involvement along venous sinuses, bilateral orbital and retrobulbar infiltration, and lesions within the pterygopalatine fossae (Figure 5).\u003c/p\u003e\n\u003cp\u003eFIGURE 5 Brain MRI (July 11, 2022)\u003c/p\u003e\n\u003cp\u003eGiven the multisystem involvement, extensive molecular genetic testing (\u0026ldquo;INVITAE\u0026rdquo; laboratory, 27 July 2022) was performed to exclude neurofibromatosis and tuberous sclerosis; sequencing and deletion/duplication analysis of 2,782 genes yielded negative results.\u003c/p\u003e\n\u003cp\u003eDue to progressive worsening of hydronephrosis and deterioration of clinical and laboratory parameters, in September 2022, the patient underwent an upper midline laparotomy, which revealed multiple xanthomatous infiltrative lesions involving the ureters and renal hilum. Maximal surgical debulking was performed, resulting in restoration of urinary flow (Figure 6). Postoperative histopathology (No. 22SP074829, CSD Laboratory) demonstrated xanthogranulomatous pyelonephritis with involvement of both ureters.\u003c/p\u003e\n\u003cp\u003eFIGURE 6 Upper midline laparotomy. Restoration of urinary patency\u003c/p\u003e\n\u003cp\u003eDue to the discrepancy between the clinical picture and conventional histology, extended immunohistochemical analysis for histiocytic disorders was initiated.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe results of immunohistochemical analysis\u0026nbsp;bloc 22SP074829 А1\u0026nbsp;were as follows: CD1a (DAKO, clone O10) showed a negative reaction in histiocytes; CD68 (DAKO, clone KP1) demonstrated a positive reaction in histiocytes; CD14 (Cell Marque, clone EPR3653) was positive in histiocytes; factor XIIIa (Cell Marque, clone EP3372) showed a negative reaction in the lesional cells; BRAF (v22) was negative in the lesional cells.\u003c/p\u003e\n\u003cp\u003eFindings were inconclusive, and differentiation between Erdheim\u0026ndash;Chester disease and reactive histiocytic proliferation remained uncertain; therefore, a decision was made to proceed with molecular analysis.\u003c/p\u003e\n\u003cp\u003eSubsequent molecular testing №22MOL004617 from CSD Laboratory identified a pathogenic \u003cem\u003eBRAF\u003c/em\u003e V600E mutation on October 2022 at the age of 4 years and 5 months.\u003c/p\u003e\n\u003cp\u003eBased on the combined clinical, radiological, histological, and molecular findings, a diagnosis of Erdheim\u0026ndash;Chester disease was established. In November 2022, lifelong targeted therapy with the BRAF inhibitor dabrafenib was initiated at a dose of 5.25 mg/kg/day, administered in two divided doses, under pediatric oncologist supervision.\u003c/p\u003e\n\u003cp\u003eThe treatment outcomes were positive, with a significant reduction of lesions in the brain and retroperitoneal space. Urinary tract patency was fully restored, and the patient remains under close clinical follow-up for 3 years (Figures 7, 8).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case highlights the diagnostic complexity of Erdheim–Chester disease (ECD) in children, where early manifestations may be subtle, fragmented across specialties, and easily misattributed to more common pediatric entities. CDI as seen at disease onset in our patient, is a recognized early feature of ECD and may precede systemic disease by months to years, particularly when the hypothalamic–pituitary axis is involved. Pediatric ECD case reports repeatedly emphasize CDI/polydipsia–polyuria as an initial clue that should trigger targeted neuroimaging and consideration of histiocytic disorders rather than isolated endocrine disease [1].\u003c/p\u003e\n\u003cp\u003eThe principal diagnostic dilemma in our patient was the combination of progressive obstructive uropathy, retroperitoneal and peri-ureteral soft-tissue masses, and imaging findings mimicking a Wilms tumor.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWilms tumor is the most common renal malignancy in early childhood and may present with hydronephrosis or urinary tract compression; however, it typically manifests as a unilateral intrarenal mass rather than diffuse retroperitoneal or peri-ureteral infiltration. In contrast, our patient demonstrated bilateral urinary tract involvement, multifocal retroperitoneal lesions, central nervous system infiltration, and endocrinological manifestations, which are not characteristic of Wilms tumor. These atypical features ultimately argued against Wilms tumor and prompted further histopathological, immunohistochemical, and molecular investigations.\u003c/p\u003e\n\u003cp\u003eIn ECD, renal compromise is typically not due to a primary intrarenal neoplasm but rather to infiltrative peri-renal and retroperitoneal soft-tissue proliferation that may encase the kidneys/ureters (“hairy kidney” spectrum) and cause extrinsic obstruction with hydronephrosis and recurrent urinary infections. Urological involvement—ureteral obstruction, hydronephrosis, and renal insufficiency—has been systematically described as part of ECD’s retroperitoneal phenotype [2].\u003c/p\u003e\n\u003cp\u003eBy contrast, Wilms tumor (WT) typically presents in children as a unilateral intrarenal mass, commonly with abdominal distension/palpable mass and sometimes hematuria or hypertension. Imaging guidelines emphasize characterization of the primary renal mass, vascular involvement, and metastatic assessment (lungs), with management pathways that may proceed without pre-treatment biopsy in many protocols—creating a real risk of “treating as WT” when a non-WT condition masquerades as a renal tumor [3].\u003c/p\u003e\n\u003cp\u003ePractical differentiators: ECD vs Wilms tumor\u003c/p\u003e\n\u003cp\u003eSeveral features in our case argued against WT and favored ECD:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eMultisystem pattern: Multifocal intracranial (intraventricular and parasellar) and orbital/retrobulbar lesions are highly atypical for newly diagnosed WT but are well-described in ECD [4].\u003c/li\u003e\n \u003cli\u003eBilateral urinary tract involvement: The coexistence of bilateral obstructive pathology (megaureter/hydronephrosis) and multifocal retroperitoneal infiltrates is more consistent with an infiltrative systemic disorder than a solitary embryonal renal tumor [5].\u003c/li\u003e\n \u003cli\u003eAbsence of a discrete intrarenal tumor: WT usually forms a definable intrarenal mass; ECD more often produces peri-renal/retroperitoneal encasement and ureteral compression [6].\u003c/li\u003e\n \u003cli\u003ePathology discordance: Initial histology may be misleading in rare histiocytoses, particularly if sampling is limited or fibrosis is prominent—necessitating clinicoradiologic correlation and deeper testing. This challenge is explicitly addressed in consensus recommendations [7].\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eMultiple publications document that ECD can present as a renal mass-like process or with striking renal/retroperitoneal involvement that prompts tumor work-up and sometimes major surgery before the correct diagnosis is established. A renal mass presentation with biopsy-confirmed ECD and emphasis on the “hairy kidney” sign was reported (adult), illustrating how ECD can mimic neoplastic renal disease on imaging and clinically [8].\u003c/p\u003e\n\u003cp\u003eSimilarly, classic descriptions of urologic ECD manifestations include ureteral obstruction and hydronephrosis, reinforcing that urinary tract disease may dominate the course and drive surgical/endourological interventions [5].\u003c/p\u003e\n\u003cp\u003eIn pediatric ECD reports, diagnostic delay is commonly attributed to non-specific early symptoms and fragmented specialist pathways. For example, pediatric cases with CDI followed by central nervous system (CNS) manifestations underscore the need for early recognition of a unifying systemic diagnosis [1].\u003c/p\u003e\n\u003cp\u003eThis case also illustrates that immunohistochemistry (IHC) may not be sufficient to conclusively separate ECD from reactive histiocytic proliferations when tissue is fibrotic or limited. Contemporary ECD guidance positions molecular testing for MAPK pathway alterations (including \u003cem\u003eBRAF\u003c/em\u003e) as an essential diagnostic pillar—both for confirmation and for immediate therapeutic implications [7].\u003c/p\u003e\n\u003cp\u003eClinical takeaway: in a child with suspected renal tumor/obstructive uropathy, the combination of CDI, multifocal CNS/orbital findings, bilateral urinary tract involvement, and peri-renal/retroperitoneal infiltrative masses should trigger early consideration of ECD (and related histiocytoses) and prompt multidisciplinary review plus molecular testing before committing to WT-directed therapy.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eECD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eErdheim\u0026ndash;Chester disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWilms tumor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBRAF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eB-rapidly accelerated fibrosarcoma protein\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMAPK\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMitogen-activated protein kinase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCDI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCentral diabetes insipidus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComputer tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSLDD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSpeech and language developmental delay\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMagnetic resonance imaging\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCNS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCentral nervous system\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIHC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eImmunohistochemistry\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Ethics Committee of Danylo Halytsky Lviv National Medical University, Lviv, Ukraine (protocol No. 12, December 16, 2024).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient\u0026rsquo;s legal guardians for publication of this case report and accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe raw data supporting the conclusions of this article will be made available by the authors on request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization, S.K.; investigation, S.K. and A.N.; resources, S.K.; writing\u0026mdash;original draft preparation S.K.; writing\u0026mdash;review and editing A.N; supervision, A.N.; funding acquisition, - .\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e The authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e The authors would like to thank the patient and his family for their cooperation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e Not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMa Y, Guo X, Wan Z, Liu H, Gao J. Paediatric Erdheim-Chester Disease in the Lateral Ventricle: A Case Report and Review of the Literature. Front Oncol. 2022;12:835076. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fonc.2022.835076\u003c/span\u003e\u003cspan address=\"10.3389/fonc.2022.835076\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 35494046; PMCID: PMC9046972.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDaniel A, Yelfimov DJ, Lightner MK, Tollefson. Urologic Manifestations of Erdheim-Chester Disease, Urology, Volume 84, Issue 1, 2014, Pages 218\u0026ndash;221, ISSN 0090-4295. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.urology.2013.10.023\u003c/span\u003e\u003cspan address=\"10.1016/j.urology.2013.10.023\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmith V, Wahba A, Chintagumpala M, Mahajan P. A review of Wilms tumor. Pediatr Rev. 2025;46(4):206\u0026ndash;12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1542/pir.2024-006444\u003c/span\u003e\u003cspan address=\"10.1542/pir.2024-006444\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa Y, Guo X, Wan Z, Liu H, Gao J. Paediatric Erdheim-Chester Disease in the Lateral Ventricle: A Case Report and Review of the Literature. Front Oncol. 2022;12:835076. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fonc.2022.835076\u003c/span\u003e\u003cspan address=\"10.3389/fonc.2022.835076\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 35494046; PMCID: PMC9046972.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYelfimov DA, Lightner DJ, Tollefson MK. Urologic manifestations of Erdheim-Chester Disease. Urology. 2014;84(1):218\u0026ndash;21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.urology.2013.10.023\u003c/span\u003e\u003cspan address=\"10.1016/j.urology.2013.10.023\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMerai H, Collas D, Bhagat A, Mandalia U. Erdheim-Chester Disease: A Case Report and Review of the Literature. J Clin Imaging Sci. 2020;10:37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoyal G, Heaney ML, Collin M, Cohen-Aubart F, Vaglio A, Durham BH, Hershkovitz-Rokah O, Girschikofsky M, Jacobsen ED, Toyama K, Goodman AM, Hendrie P, Cao X, Estrada-Veras JI, Shpilberg O, Abdo A, Kurokawa M, Dagna L, McClain KL, Diamond EL. Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis, and treatment in the molecular era. Blood. 2020;135(22):1929\u0026ndash;45. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1182/blood.2019003507\u003c/span\u003e\u003cspan address=\"10.1182/blood.2019003507\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbu Rass HB, Abuawad M, Abueideh Y, Malhis EL. Erdheim-Chester Disease with Renal Mass Presentation: Report of the First Case From Palestine and a Review of the Literature. Am J Case Rep. 2023;24:e941912. PMID: 37974387; PMCID: PMC10665577.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Erdheim-Chester disease, pediatric histiocytosis, Wilms tumor, differential diagnosis, BRAF mutation, obstructive uropathy","lastPublishedDoi":"10.21203/rs.3.rs-8562480/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8562480/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eErdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocytosis driven by activating mutations of the MAPK signaling pathway, most commonly \u003cem\u003eBRAF\u003c/em\u003e V600E. Pediatric cases are exceedingly rare and often present with atypical, multisystem manifestations, resulting in significant diagnostic delay. Renal and retroperitoneal involvement may mimic primary renal malignancies, particularly Wilms tumor.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe report a case of Erdheim–Chester disease in Ukraine, Lviv. A male child who initially presented at the age of two years with central diabetes insipidus and progressive urinary tract infections. Over two years, the patient developed bilateral obstructive uropathy, retroperitoneal and paravertebral masses, and multifocal central nervous system and orbital involvement. Recurrent urinary tract infections and progressive hydronephrosis necessitated multiple surgical interventions. Initial histopathological findings were inconclusive and suggested alternative diagnoses, including ganglioneuroma and reactive histiocytic proliferation. Due to discordance between clinical, radiological, and histological findings, extended immunohistochemical and molecular analyses were performed. Detection of a pathogenic \u003cem\u003eBRAF\u003c/em\u003e V600E mutation confirmed the diagnosis of Erdheim–Chester disease. Lifelong targeted therapy with the BRAF inhibitor dabrafenib was initiated, resulting in clinical stabilization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case highlights the diagnostic complexity of Erdheim–Chester disease in children and emphasizes the importance of considering histiocytic disorders in the differential diagnosis of renal and retroperitoneal masses. Multisystem involvement, atypical imaging findings, and molecular testing are key elements for accurate diagnosis and appropriate management, particularly in cases mimicking Wilms tumor.\u003c/p\u003e","manuscriptTitle":"Erdheim–Chester Disease Mimicking Wilms Tumor in a Child: A Diagnostic Challenge","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-25 07:13:53","doi":"10.21203/rs.3.rs-8562480/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-27T08:46:21+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-26T23:09:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"160684505351860752092879157331731616250","date":"2026-01-26T12:21:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"117552936835811492427593007227535728966","date":"2026-01-26T10:06:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"286790261200894180406233300376365753144","date":"2026-01-24T10:29:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"73868578421249684439141077790360587530","date":"2026-01-24T09:11:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-22T12:21:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"304022546186461353776123074974956818075","date":"2026-01-22T12:11:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"301654165187203622974094815375129627803","date":"2026-01-22T07:46:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"210721359017845383752439579521012808221","date":"2026-01-21T23:16:04+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-21T08:26:38+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-13T05:44:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-13T01:02:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-13T01:01:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2026-01-09T15:08:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"91e4dbf0-bef4-4985-8f88-6c0c031f93e4","owner":[],"postedDate":"January 25th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-16T16:02:24+00:00","versionOfRecord":{"articleIdentity":"rs-8562480","link":"https://doi.org/10.1186/s12887-026-06678-w","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2026-03-12 15:59:01","publishedOnDateReadable":"March 12th, 2026"},"versionCreatedAt":"2026-01-25 07:13:53","video":"","vorDoi":"10.1186/s12887-026-06678-w","vorDoiUrl":"https://doi.org/10.1186/s12887-026-06678-w","workflowStages":[]},"version":"v1","identity":"rs-8562480","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8562480","identity":"rs-8562480","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}