Diagnostic Challenges of Dural-Based Lesions: Clinical, Radiologic, and Pathologic Differentiation of Meningioma, IgG4-RHP, and RDD

Diagnostic Challenges of Dural-Based Lesions: Clinical, Radiologic, and Pathologic Differentiation of Meningioma, IgG4-RHP, and RDD | 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 Research Article Diagnostic Challenges of Dural-Based Lesions: Clinical, Radiologic, and Pathologic Differentiation of Meningioma, IgG4-RHP, and RDD Tao Zeng, Jie Bai, Xinru Xiao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9421179/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background IgG4-related hypertrophic pachymeningitis (IgG4-RHP) is a rare fibroinflammatory manifestation of IgG4-related disease (IgG4-RD) that produces localized or diffuse dural thickening and frequently mimics meningioma on clinical and radiologic evaluation. Coexistence of IgG4-RD with Rosai–Dorfman–Destombes disease (RDD) has not been well characterized. Methods We retrospectively reviewed seven patients referred with a presumptive diagnosis of meningioma. Postoperative histopathology and laboratory data were used to establish definitive diagnoses. Results Four patients were diagnosed with isolated IgG4-RHP and three patients had concomitant IgG4-RD and RDD. All seven were initially suspected to have meningioma based on outpatient assessment and imaging; definitive diagnosis required serological testing and histopathological confirmation. We summarize distinguishing clinical, imaging, laboratory, and pathological features that aid differentiation from meningioma, including patterns of dural involvement, skull-base predilection, infiltrative behavior with disproportionate vasogenic edema, absence of typical meningioma signs (hyperostosis, calcification, clear dural tail), CSF and serum IgG4/IgG4Loc considerations, and characteristic histology for IgG4-RHP (IgG4 + plasma-cell–rich infiltrate, storiform fibrosis, obliterative phlebitis) versus RDD (S100+/CD68 + histiocytes with emperipolesis). Conclusions Awareness of these distinguishing features and the potential for IgG4-RD/RDD coexistence can facilitate earlier, targeted diagnostic workup and appropriate management, avoiding misdiagnosis and suboptimal treatment. IgG4-RHP Meningioma RDD Figures Figure 1 Figure 2 Introduction IgG4-RD is an uncommon chronic fibroinflammatory condition that can involve virtually any organ. One of its principal intracranial manifestations is IgG4-RHP, which produces focal or diffuse dural thickening and represents a rare but important cause of fibroinflammatory meningeal disease. Diagnosis of IgG4-RHP is challenging because its radiological appearance is often atypical: lesions may present as tumor-like, dural-based masses that closely mimic meningiomas on MRI, leading to frequent misdiagnosis and treatment delay [ 1 , 2 ]. Although the disease is characterized by tissue infiltration with IgG4-positive plasma cells and, in many cases, elevated serum IgG4, serology may be noncontributory in CNS-restricted disease. RDD is a histiocytic disorder that primarily affects lymph nodes but can rarely involve extranodal sites, including the calvarium, dura, orbit, paranasal sinuses, brain parenchyma, and spine. Neurologic involvement is uncommon but, when present, RDD lesions may produce organ enlargement or mass-like hardening that is easily confused with IgG4-RD and meningioma [ 3 ]. Because clinical and imaging features overlap considerably among meningioma, IgG4-RHP, and intracranial RDD, histopathological examination is often required for definitive diagnosis. Although IgG4-RD and RDD have traditionally been regarded as distinct entities [ 4 ], we identified coexisting IgG4-RD and RDD in three of our patients. Previous reports have described IgG4-RHP and RDD separately [ 5 , 6 ], but to our knowledge coexistence and a direct comparative analysis have not been reported. In this study, we compare clinical, radiologic, laboratory, and pathological features across seven cases to improve recognition of these mimickers and to inform appropriate diagnostic and therapeutic strategies. Materials and methods We collected data on patients with IgG4-RHP and IgG4-RD combined with RDD who were hospitalized in the Department of Neurosurgery at Xuanwu Hospital, Capital Medical University, from August 1, 2020, to August 1, 2025, and investigated their clinical symptoms, laboratory tests, imaging, and pathological features. There were 3 males and 4 females, with an average age of 48 years. All patients were diagnosed based on clinical symptoms, signs, and auxiliary examination results, in accordance with the diagnostic criteria proposed by Deshpande in 2012.[ 7 ] This study was approved by the Medical Research Ethics Committee of Xuanwu Hospital (303-01-007-0720) and conducted in accordance with the Declaration of Helsinki (2013 revision). Due to the retrospective nature of the study, the requirement for informed consent was waived. Results Patient demographics and clinical characteristics The demographic and clinical characteristics of the four patients diagnosed with IgG4-RHP are summarized in Table 1 . The mean age at disease onset was 46 years (range, 45–48 years). Headache was the most common presenting symptom and was observed in all four patients. Cranial nerve involvement was identified in three patients, affecting the hypoglossal nerve, optic nerve, and facial nerve, respectively. Detailed clinical manifestations are presented in Table 1 . The demographic and clinical data of the three patients with IgG4-RD coexisting with RDD are summarized in Table 2 . The mean age at onset was 50 years (range, 44–59 years). Two patients exhibited cranial nerve dysfunction, involving the auditory, optic, and trigeminal nerves, while one patient presented with gait ataxia. The specific clinical features are detailed in Table 2 . Neuroimaging findings Magnetic resonance imaging (MRI) revealed tumor-like dural-based lesions in all seven patients. Lesions were irregular in shape and demonstrated homogeneous or heterogeneous enhancement following gadolinium administration. Patient 1: Axial (Fig. 1 A) and sagittal (Fig. 1 B) contrast-enhanced T1-weighted images demonstrate an irregular, dural-based mass centered at the clivus with heterogeneous enhancement and inferior extension to the medulla oblongata. The lesion abuts and mildly compresses the ventral brainstem; margins are partially indistinct, suggesting dural adherence. The patient underwent subtotal resection in 2020 followed by postoperative corticosteroid therapy and maintained sustained clinical improvement at 5-year follow-up. Patient 2: T2-weighted image (Fig. 1 C) shows extensive left temporal lobe vasogenic edema with mass effect and compression of the lateral ventricle. Contrast-enhanced T1-weighted image (Fig. 1 D) reveals a dural-based enhancing lesion with apparent infiltration of adjacent temporal lobe parenchyma and an ill-defined tumor–brain interface. A diagnostic partial dural resection was performed in 2025, followed by corticosteroid treatment; the patient demonstrated favorable recovery at 8 months postoperatively. Patient 3: Sagittal and axial contrast-enhanced T1-weighted images (Fig. 1 E, F) depict an irregularly enhancing clival mass extending superiorly into the optic canal and inferiorly beyond the level of the medulla into the upper cervical spinal canal, forming a continuous dural-based lesion with close apposition to neurovascular foramina. The patient underwent subtotal resection in 2025 and postoperative corticosteroid therapy, with good clinical recovery at 6 months. Patient 4: Axial and sagittal contrast-enhanced T1-weighted images (Fig. 2 G, H) demonstrate an irregularly enhancing clival/dural lesion with inferior extension to the medulla oblongata and intimate contact with the ventral brainstem. The patient underwent endoscopic endonasal subtotal resection in 2020 and received postoperative corticosteroids; clinical status remained stable over 5 years of follow-up. Patient 5: Axial (Fig. 2 A) and coronal (Fig. 2 B) contrast-enhanced T1-weighted images demonstrate an irregularly enhancing dural-based mass centered at the clivus with extension into and frank invasion of the cavernous sinus on the affected side. The lesion exhibits heterogeneous enhancement and contact with adjacent neurovascular structures. The patient underwent gross total resection via craniotomy in 2022 followed by corticosteroid therapy and remained in good clinical condition at > 3-year follow-up. Patient 6: Axial (Fig. 2 C) and coronal (Fig. 2 D) contrast-enhanced T1-weighted images show an irregularly enhancing left temporal lobe mass with a dural base and well-demarcated margins. The lesion produced local mass effect without extensive perilesional edema. Complete microsurgical resection was performed in 2022; no adjuvant therapy was given and the patient demonstrated favorable neurologic recovery at 3-year follow-up. Patient 7: Axial (Fig. 2 E) and coronal (Fig. 2 F) contrast-enhanced T1-weighted images depict an irregularly enhancing petroclival lesion on the right, with inferior–medial extension into the adjacent right temporal lobe parenchyma. Enhancement is heterogeneous and the tumor abuts the petroclival neurovascular corridor. Gross total resection was achieved in 2022 without postoperative adjuvant therapy; the patient remained neurologically stable at 3-year follow-up. Overall, all seven patients exhibited dural-based, tumor-like lesions with either homogeneous or heterogeneous enhancement; several cases showed surrounding vasogenic edema or apparent parenchymal infiltration and proximity to critical neurovascular structures, findings that influenced surgical approach and perioperative management. Discussion In this series of seven cases, we highlight the diagnostic challenges posed by three dural-based entities—meningioma, IgG4-RHP, and RDD—that frequently mimic one another clinically and radiographically. All patients were initially presumed to harbor meningiomas on outpatient evaluation, but definitive postoperative histopathology refuted that diagnosis. This discordance underscores the critical need for accurate preoperative differentiation to inform surgical planning and perioperative management. Clinical presentations of IgG4-RHP and intracranial RDD are largely attributable to mass effect: dural-based lesions mechanically compress neural and vascular structures, producing focal deficits (e.g., cranial neuropathies, sensory disturbances) and, when diffuse, non-localizing symptoms such as headache and seizures[ 5 , 8 ]. These manifestations overlap substantially with meningioma, limiting the discriminatory utility of clinical assessment alone. Likewise, serum IgG4 concentration is of limited value for purely intracranial disease because levels may be normal in CNS-restricted IgG4-RHP; elevated serum IgG4 more commonly reflects systemic involvement[ 5 ]. In contrast, cerebrospinal fluid (CSF) assays can provide greater specificity: the presence of IgG4 oligoclonal bands and an elevated IgG4 local synthesis index (IgG4Loc > 0.47) have been reported as sensitive and specific markers to distinguish IgG4-RHP from RDD and should be considered when clinical suspicion exists[ 8 ]. Neuroimaging remains essential but is not definitive. Both IgG4-RHP and RDD present as extra-axial, dural-based enhancing lesions that can closely resemble meningiomas. Nevertheless, several imaging features may favor an inflammatory process: longitudinal, plaque-like or nodular dural spread beyond a single broad-based attachment; preferential involvement of skull-base structures (clivus, petroclival region, cavernous sinus, tentorium); encasement rather than simple displacement of cranial nerves; infiltrative parenchymal invasion with disproportionately extensive vasogenic edema; and the relative absence of meningioma-associated signs such as hyperostosis, calcification, or a robust dural-tail. Specific signs described in IgG4-RHP—linear dural thickening, focal raised masses, frequent leptomeningeal extension and the “double-track/Mercedes-Benz” sign within the falx or tentorium—can further orient the diagnosis[ 6 ]. RDD more often presents as a solitary, uniformly enhancing dural mass with a higher propensity for infratentorial/parenchymal involvement, which may aid differentiation when present[ 10 , 11 ]. Pathology remains the diagnostic gold standard. IgG4-RHP is characterized by dense lymphoplasmacytic infiltrates enriched in IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis; diagnostic thresholds commonly cited include an IgG4/IgG ratio > 40% and > 10 IgG4-positive plasma cells per high-power field[ 7 , 12 ]. RDD is defined by proliferation of S100- and OCT2-positive histiocytes demonstrating emperipolesis[ 13 ]. In our cohort, cases of IgG4-RD coexisting with RDD displayed classical RDD histopathologic features (S100+, CD68+, CD38+, emperipolesis/hemorrhage) that were absent in IgG4-RHP–only cases, supporting the notion that mixed histology can occur and has implications for management. Therapeutic strategies diverge substantially between these entities. First-line therapy for IgG4-RHP is immunosuppression—initial high-dose corticosteroids with tapering and steroid-sparing maintenance agents (e.g., azathioprine, mycophenolate)[ 9 , 14 ]; rituximab is effective for refractory or systemic disease[ 15 ]. In our series, all patients with isolated IgG4-RHP received corticosteroid therapy after pathologic confirmation and experienced favorable outcomes. By contrast, solitary intracranial RDD is frequently managed successfully with complete surgical resection[ 16 ]; in our three patients with IgG4-RD coexisting with RDD, two achieved durable good outcomes after gross total resection without adjuvant therapy, while one improved following corticosteroid treatment. For multifocal or unresectable disease, systemic therapies targeting cytokines (e.g., anti–IL-6) or molecular pathways (e.g., MAPK inhibitors) are emerging options[ 17 , 18 ]. Meningiomas, conversely, are treated primarily with maximal safe resection with or without radiotherapy. Thus, distinguishing inflammatory from neoplastic dural lesions preoperatively directly influences the extent of resection sought, the decision to pursue biopsy versus aggressive resection, and the need for immunomodulatory therapy. Practical implications from our series are fourfold: (1) maintain a high index of suspicion for IgG4-RHP or RDD in atypical dural-based lesions—particularly those with extensive or skull-base involvement, infiltrative features, disproportionate edema, or absent classic meningioma imaging signs; (2) integrate CSF IgG4 testing when serum studies are unrevealing and clinical suspicion persists; (3) pursue targeted biopsy for histopathological confirmation before committing to radical resections when imaging and clinical data suggest an inflammatory etiology; and (4) tailor postoperative management to histopathology, reserving immunosuppression for IgG4-RHP and considering extent of resection as primary therapy for isolated RDD. Limitations of this study include its small sample size and retrospective design, which preclude definitive recommendations on optimal management for IgG4-RD coexisting with RDD. Nonetheless, our findings emphasize that combined interpretation of advanced imaging, CSF biomarkers, and histopathology is essential to distinguish these entities and to guide appropriate, disease-specific therapy. Conclusion IgG4-RHP, RDD, and meningioma are frequently indistinguishable on clinical and radiological grounds, with important therapeutic implications. Definitive diagnosis therefore relies on histopathological confirmation, supplemented by integration of clinical presentation, neuroimaging characteristics, and targeted laboratory testing (including CSF IgG4 assays when appropriate). In this series we report the coexistence of IgG4-RD and RDD—which, to our knowledge, has not been previously described—and note that the clinical and pathological phenotype in these mixed cases closely resembled RDD. Recognition of this overlap is important for diagnostic accuracy and subsequent management. We hope these observations will raise clinical awareness and aid clinicians in selecting appropriate diagnostic pathways and tailored treatments for atypical dural-based lesions. Declarations Funding This work was funded by the National Natural Science Foundation of China(No. 82573350 to X.Xiao.) Ethics declarations Ethics approval and consent to participate This retrospective study was conducted in accordance with the principles outlined in the Declaration of Helsinki and its subsequent revisions, and received approval from the Medical Research Ethics Committee of Xuanwu Hospital(303-01-007-0720). The requirement for informed consent to participate was officially waived by the the Medical Research Ethics Committee of Xuanwu Hospital due to the retrospective nature of the study and the use of anonymized clinical data. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests Data availability The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Authors' contributions Xinru Xiao did study design, performed the surgeries, supervised clinical data collection, and supervised the manuscript; Tao Zeng did data curation and statistical analysis, selected images and prepared figures/tables, and finished the manuscript; Jie Bai did histopathologic slide analysis and immunohistochemistry, prepared pathology images, and conducted literature review and discussion writing. All authors read and approved the final manuscript. Acknowledgements Not applicable References Kuroda N, Inenaga C, Arai Y, Otsuki Y, Tanaka T. Intracranial multiple pseudotumor due to immunoglobulin G4-related disease without other lesions: case report and literature review. World Neurosurg 2019. 2019;132:69–74. Tanji H, Okada H, Igari R, Yamaguchi Y, Sato H, Takahashi Y, Koyama S, Arawaka S, Wada M, Kawanami T, Wakabayashi K, Kato T. (2016) Inflammatory pseudotumor of the brain parenchyma with IgG4 hypergammaglobulinemia. Intern Med.2016; 55:1911–1916. Cooper SL, Jenrette JM. Rosai–Dorfman disease: management of CNS and systemic involvement. Clin Adv Hematol Oncol. 2012;10(3):199–202. Luke YC, Chen,Graham W, Slack,Mollie. N Carruthers Lancet. 2021;398:1213–4. Lucy XL, Della-Torre E, Stone JH, Clark SW. (2014) IgG4-related hypertrophic pachymeningitis: clinical features, diagnostic criteria, and treatment. JAMA Neurol. 2014; 71:785–793. Li WW. Zhang Orphanet J Rare Dis. 2020;15:285. Li;Shangzhu Zhang;Linyi Peng;Min Shen;Shuoning Song;Wei Zhang;Xinxin Cao;Ruie Feng;Wen. Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181. Della-Torre E, Passerini G, Furlan R, et al. Cerebrospinal fluid analysis in immunoglobulin G4-related hypertrophic pachymeningitis. J Rheumatol. 2013;40(11):1927–9. Della Torre E, Bozzolo EP, Passerini G, Doglioni C, Sabbadini MG. IgG4-related pach–ymeningitis:evidence of intrathecal IgG4 on cerebrospinal fluid analysis. Ann Intern Med. 2012;156(5):401–3. Morandi X, Godey B, Riffaud L, Heresbach N, Brassier G. Isolated Rosai-Dorfman disease of the fourth ventricle. Case illustration. J Neurosurg. 2000;92(5):890. Antuña Ramos A, Alvarez Vega MA, Alles JV, Antuña Garcia MJ. Meil ´an Mart´ınez A.Multiple involvement of the central nervous system in Rosai-Dorfman disease. Pediatr Neurol. 2012;46(1):54–6. Lindstrom KM, Cousar JB, Lopes MB. IgG4-related meningeal disease: clinico-pathological features and proposal for diagnostic criteria. Acta Neuropathol. 2010;120(6):765–76. Aishwarya Ravindran G, Goyal RS, Karen L. Rech Am J Surg Pathol. 2021;45:35–44. Xiao X, Fu D, Feng L. (2020) Hypertrophic pachymeningitis in a southern Chinese population: a retrospective study. Front Neurol. 2020; 11:565088. Khosroshahi A, Carruthers MN, Deshpande V, Unizony S, Bloch DB, Stone JH. Rituximab for the treatment of IgG4-related disease: lessons from 10 consecutive patients. Med (Baltim). 2012;91(1):57–66. Arnao V, Riolo M, Savettieri G, Aridon P. Mercaptopurine treatment in an adult man with orbital and intracranial Rosai-Dorfman disease. Case Rep Neurol Med. 2016;2016:1030478. Sasaki K, Pemmaraju N, Westin JR, et al. A single case of Rosai-Dorfman disease marked by pathologic fractures, kidney failure, and liver cirrhosis treated with singleagent cladribine. Front Oncol. 2014;4:297. Simko SJ, Tran HD, Jones J, et al. Clofarabine salvage therapy in refractory multifocal histiocytic disorders, including Langerhans cell histiocytosis, juvenile xanthogranuloma and Rosai-Dorfman disease. Pediatr Blood Cancer. 2014;61(3):479–87. Tables Table 1 Summary of the demographic and clinical data of 4 cases of IgG4-RHP in the intracranial Case number Age(year) Main clinical manifestation Imaging manifestation CD38、CD3 CD20、CD138 CD68 1 45 Headache, deviation of the tongue to the right Slope tumor ＋ ＋ — 2 48 Headache，episodic spasms of the corners of the mouth A mass in the left temporal lobe ＋ ＋ ＋ 3 47 Headache, diplopia Slope tumor ＋ ＋ ＋ 4 46 Headache Slope tumor ＋ ＋ ＋ Table 2 Summary of the demographic and clinical data of 3 cases of IgG4-RD with RDD Case number Age(year) Main clinical manifestation Imaging manifestation CD68、S100、CD138、CD3 CD1a CD38、CD163 5 48 Difficulty pronouncing words, double vision, hearing loss Slope tumor ＋ — ＋ 6 44 Sudden fainting A mass in the left temporal lobe ＋ — — 7 59 Numbness on the right side of the face, hearing loss Petroclival tumor ＋ — ＋ Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 10 May, 2026 Reviewers agreed at journal 28 Apr, 2026 Reviewers invited by journal 26 Apr, 2026 Editor assigned by journal 24 Apr, 2026 Editor invited by journal 22 Apr, 2026 Submission checks completed at journal 21 Apr, 2026 First submitted to journal 21 Apr, 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. 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-9421179","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":630796907,"identity":"536d2f5c-5df8-494f-b2d4-fffd0f115f5f","order_by":0,"name":"Tao Zeng","email":"","orcid":"","institution":"Xuan Wu Hospital of the Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Tao","middleName":"","lastName":"Zeng","suffix":""},{"id":630796908,"identity":"394b1522-e4b3-4aaf-97f5-7246684702e6","order_by":1,"name":"Jie Bai","email":"","orcid":"","institution":"Xuan Wu Hospital of the Capital Medical 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03:38:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9421179/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9421179/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108629746,"identity":"e6ddf850-349c-4336-9eff-21ebf31d2b87","added_by":"auto","created_at":"2026-05-06 16:28:11","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":488105,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA, B \u003c/strong\u003ePatient 1, 30-year-old man: axial gadolinium (Gd)-enhanced fat-saturated T1-weighted MRI shows a tumour occupying the slope and the sagittal gadolinium (Gd)-enhanced fat-saturated T1-weighted MRI shows the tumor invading the medulla oblongata.\u003cstrong\u003e C,D \u003c/strong\u003ePatient 2, 48-year-old woman: T2-weighted axial images show extensive cerebral edema in the left temporal lobe and compression of the lateral ventricle. axial gadolinium (Gd)-enhanced fat-saturated T1-weighted MRI shows the tumor in the left temporal lobe infiltrating and invading the brain parenchyma. \u003cstrong\u003eE,F\u003c/strong\u003ePatient 3, 47-year-old woman: axial gadolinium (Gd)-enhanced fat-saturated T1-weighted MRI shows a tumor occupying the slope and the sagittal gadolinium (Gd)-enhanced fat-saturated T1-weighted MRI shows the tumor extending below the medulla oblongata. \u003cstrong\u003eG,H \u003c/strong\u003ePatient 4, 46-year-old man: axial gadolinium (Gd)-enhanced fat-saturated T1-weighted MRI shows a tumor occupying the slope and the sagittal gadolinium (Gd)-enhanced fat-saturated T1-weighted MRI shows the tumor extending to the medulla oblongata.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9421179/v1/21d06101e740763b08959fd2.jpeg"},{"id":108805984,"identity":"812a6021-3935-4410-be5b-f68d2f96c3da","added_by":"auto","created_at":"2026-05-08 15:27:22","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":409504,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA, B\u003c/strong\u003e Patient 5, 48-year-old woman: axial gadolinium (Gd)-enhanced fat-saturated T1-weighted MRI shows a Clival tumor which invading the cavernous sinus. \u003cstrong\u003eC,D\u003c/strong\u003e Patient 6, 44-year-old man: axial gadolinium (Gd)-enhanced fat-saturated T1-weighted MRI shows an irregularly enhanced mass in the left temporal lobe. \u003cstrong\u003eE,F\u003c/strong\u003e Patient 7, 59-year-old woman: axial gadolinium (Gd)-enhanced fat-saturated T1-weighted MRI shows an irregularly enhanced mass in the right paraclinoid region.The tumor has invaded the right temporal lobe.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9421179/v1/27b1f2aec06f85e15795e002.jpeg"},{"id":108809801,"identity":"f9e037cc-e487-4517-8a7e-76ebd243d371","added_by":"auto","created_at":"2026-05-08 15:55:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1095193,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9421179/v1/f29558d4-6d4c-4f87-a581-9a3b3bd7335c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Diagnostic Challenges of Dural-Based Lesions: Clinical, Radiologic, and Pathologic Differentiation of Meningioma, IgG4-RHP, and RDD","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIgG4-RD is an uncommon chronic fibroinflammatory condition that can involve virtually any organ. One of its principal intracranial manifestations is IgG4-RHP, which produces focal or diffuse dural thickening and represents a rare but important cause of fibroinflammatory meningeal disease. Diagnosis of IgG4-RHP is challenging because its radiological appearance is often atypical: lesions may present as tumor-like, dural-based masses that closely mimic meningiomas on MRI, leading to frequent misdiagnosis and treatment delay [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Although the disease is characterized by tissue infiltration with IgG4-positive plasma cells and, in many cases, elevated serum IgG4, serology may be noncontributory in CNS-restricted disease.\u003c/p\u003e \u003cp\u003eRDD is a histiocytic disorder that primarily affects lymph nodes but can rarely involve extranodal sites, including the calvarium, dura, orbit, paranasal sinuses, brain parenchyma, and spine. Neurologic involvement is uncommon but, when present, RDD lesions may produce organ enlargement or mass-like hardening that is easily confused with IgG4-RD and meningioma [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Because clinical and imaging features overlap considerably among meningioma, IgG4-RHP, and intracranial RDD, histopathological examination is often required for definitive diagnosis.\u003c/p\u003e \u003cp\u003eAlthough IgG4-RD and RDD have traditionally been regarded as distinct entities [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], we identified coexisting IgG4-RD and RDD in three of our patients. Previous reports have described IgG4-RHP and RDD separately [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], but to our knowledge coexistence and a direct comparative analysis have not been reported. In this study, we compare clinical, radiologic, laboratory, and pathological features across seven cases to improve recognition of these mimickers and to inform appropriate diagnostic and therapeutic strategies.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eWe collected data on patients with IgG4-RHP and IgG4-RD combined with RDD who were hospitalized in the Department of Neurosurgery at Xuanwu Hospital, Capital Medical University, from August 1, 2020, to August 1, 2025, and investigated their clinical symptoms, laboratory tests, imaging, and pathological features. There were 3 males and 4 females, with an average age of 48 years. All patients were diagnosed based on clinical symptoms, signs, and auxiliary examination results, in accordance with the diagnostic criteria proposed by Deshpande in 2012.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] This study was approved by the Medical Research Ethics Committee of Xuanwu Hospital (303-01-007-0720) and conducted in accordance with the Declaration of Helsinki (2013 revision). Due to the retrospective nature of the study, the requirement for informed consent was waived.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003ePatient demographics and clinical characteristics\u003c/h2\u003e\n \u003cp\u003eThe demographic and clinical characteristics of the four patients diagnosed with IgG4-RHP are summarized in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean age at disease onset was 46 years (range, 45\u0026ndash;48 years). Headache was the most common presenting symptom and was observed in all four patients. Cranial nerve involvement was identified in three patients, affecting the hypoglossal nerve, optic nerve, and facial nerve, respectively. Detailed clinical manifestations are presented in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The demographic and clinical data of the three patients with IgG4-RD coexisting with RDD are summarized in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The mean age at onset was 50 years (range, 44\u0026ndash;59 years). Two patients exhibited cranial nerve dysfunction, involving the auditory, optic, and trigeminal nerves, while one patient presented with gait ataxia. The specific clinical features are detailed in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eNeuroimaging findings\u003c/h3\u003e\n\u003cp\u003eMagnetic resonance imaging (MRI) revealed tumor-like dural-based lesions in all seven patients. Lesions were irregular in shape and demonstrated homogeneous or heterogeneous enhancement following gadolinium administration. Patient 1: Axial (Fig. \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA) and sagittal (Fig. \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB) contrast-enhanced T1-weighted images demonstrate an irregular, dural-based mass centered at the clivus with heterogeneous enhancement and inferior extension to the medulla oblongata. The lesion abuts and mildly compresses the ventral brainstem; margins are partially indistinct, suggesting dural adherence. The patient underwent subtotal resection in 2020 followed by postoperative corticosteroid therapy and maintained sustained clinical improvement at 5-year follow-up. Patient 2: T2-weighted image (Fig. \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC) shows extensive left temporal lobe vasogenic edema with mass effect and compression of the lateral ventricle. Contrast-enhanced T1-weighted image (Fig. \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD) reveals a dural-based enhancing lesion with apparent infiltration of adjacent temporal lobe parenchyma and an ill-defined tumor\u0026ndash;brain interface. A diagnostic partial dural resection was performed in 2025, followed by corticosteroid treatment; the patient demonstrated favorable recovery at 8 months postoperatively. Patient 3: Sagittal and axial contrast-enhanced T1-weighted images (Fig. \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eE, F) depict an irregularly enhancing clival mass extending superiorly into the optic canal and inferiorly beyond the level of the medulla into the upper cervical spinal canal, forming a continuous dural-based lesion with close apposition to neurovascular foramina. The patient underwent subtotal resection in 2025 and postoperative corticosteroid therapy, with good clinical recovery at 6 months. Patient 4: Axial and sagittal contrast-enhanced T1-weighted images (Fig. \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eG, H) demonstrate an irregularly enhancing clival/dural lesion with inferior extension to the medulla oblongata and intimate contact with the ventral brainstem. The patient underwent endoscopic endonasal subtotal resection in 2020 and received postoperative corticosteroids; clinical status remained stable over 5 years of follow-up. Patient 5: Axial (Fig. \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA) and coronal (Fig. \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB) contrast-enhanced T1-weighted images demonstrate an irregularly enhancing dural-based mass centered at the clivus with extension into and frank invasion of the cavernous sinus on the affected side. The lesion exhibits heterogeneous enhancement and contact with adjacent neurovascular structures. The patient underwent gross total resection via craniotomy in 2022 followed by corticosteroid therapy and remained in good clinical condition at \u0026gt;\u0026thinsp;3-year follow-up. Patient 6: Axial (Fig. \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC) and coronal (Fig. \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD) contrast-enhanced T1-weighted images show an irregularly enhancing left temporal lobe mass with a dural base and well-demarcated margins. The lesion produced local mass effect without extensive perilesional edema. Complete microsurgical resection was performed in 2022; no adjuvant therapy was given and the patient demonstrated favorable neurologic recovery at 3-year follow-up. Patient 7: Axial (Fig. \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE) and coronal (Fig. \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eF) contrast-enhanced T1-weighted images depict an irregularly enhancing petroclival lesion on the right, with inferior\u0026ndash;medial extension into the adjacent right temporal lobe parenchyma. Enhancement is heterogeneous and the tumor abuts the petroclival neurovascular corridor. Gross total resection was achieved in 2022 without postoperative adjuvant therapy; the patient remained neurologically stable at 3-year follow-up.\u003c/p\u003e\n\u003cp\u003eOverall, all seven patients exhibited dural-based, tumor-like lesions with either homogeneous or heterogeneous enhancement; several cases showed surrounding vasogenic edema or apparent parenchymal infiltration and proximity to critical neurovascular structures, findings that influenced surgical approach and perioperative management.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this series of seven cases, we highlight the diagnostic challenges posed by three dural-based entities\u0026mdash;meningioma, IgG4-RHP, and RDD\u0026mdash;that frequently mimic one another clinically and radiographically. All patients were initially presumed to harbor meningiomas on outpatient evaluation, but definitive postoperative histopathology refuted that diagnosis. This discordance underscores the critical need for accurate preoperative differentiation to inform surgical planning and perioperative management.\u003c/p\u003e \u003cp\u003eClinical presentations of IgG4-RHP and intracranial RDD are largely attributable to mass effect: dural-based lesions mechanically compress neural and vascular structures, producing focal deficits (e.g., cranial neuropathies, sensory disturbances) and, when diffuse, non-localizing symptoms such as headache and seizures[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. These manifestations overlap substantially with meningioma, limiting the discriminatory utility of clinical assessment alone. Likewise, serum IgG4 concentration is of limited value for purely intracranial disease because levels may be normal in CNS-restricted IgG4-RHP; elevated serum IgG4 more commonly reflects systemic involvement[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In contrast, cerebrospinal fluid (CSF) assays can provide greater specificity: the presence of IgG4 oligoclonal bands and an elevated IgG4 local synthesis index (IgG4Loc\u0026thinsp;\u0026gt;\u0026thinsp;0.47) have been reported as sensitive and specific markers to distinguish IgG4-RHP from RDD and should be considered when clinical suspicion exists[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNeuroimaging remains essential but is not definitive. Both IgG4-RHP and RDD present as extra-axial, dural-based enhancing lesions that can closely resemble meningiomas. Nevertheless, several imaging features may favor an inflammatory process: longitudinal, plaque-like or nodular dural spread beyond a single broad-based attachment; preferential involvement of skull-base structures (clivus, petroclival region, cavernous sinus, tentorium); encasement rather than simple displacement of cranial nerves; infiltrative parenchymal invasion with disproportionately extensive vasogenic edema; and the relative absence of meningioma-associated signs such as hyperostosis, calcification, or a robust dural-tail. Specific signs described in IgG4-RHP\u0026mdash;linear dural thickening, focal raised masses, frequent leptomeningeal extension and the \u0026ldquo;double-track/Mercedes-Benz\u0026rdquo; sign within the falx or tentorium\u0026mdash;can further orient the diagnosis[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. RDD more often presents as a solitary, uniformly enhancing dural mass with a higher propensity for infratentorial/parenchymal involvement, which may aid differentiation when present[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePathology remains the diagnostic gold standard. IgG4-RHP is characterized by dense lymphoplasmacytic infiltrates enriched in IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis; diagnostic thresholds commonly cited include an IgG4/IgG ratio\u0026thinsp;\u0026gt;\u0026thinsp;40% and \u0026gt;\u0026thinsp;10 IgG4-positive plasma cells per high-power field[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. RDD is defined by proliferation of S100- and OCT2-positive histiocytes demonstrating emperipolesis[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In our cohort, cases of IgG4-RD coexisting with RDD displayed classical RDD histopathologic features (S100+, CD68+, CD38+, emperipolesis/hemorrhage) that were absent in IgG4-RHP\u0026ndash;only cases, supporting the notion that mixed histology can occur and has implications for management.\u003c/p\u003e \u003cp\u003eTherapeutic strategies diverge substantially between these entities. First-line therapy for IgG4-RHP is immunosuppression\u0026mdash;initial high-dose corticosteroids with tapering and steroid-sparing maintenance agents (e.g., azathioprine, mycophenolate)[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]; rituximab is effective for refractory or systemic disease[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In our series, all patients with isolated IgG4-RHP received corticosteroid therapy after pathologic confirmation and experienced favorable outcomes. By contrast, solitary intracranial RDD is frequently managed successfully with complete surgical resection[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]; in our three patients with IgG4-RD coexisting with RDD, two achieved durable good outcomes after gross total resection without adjuvant therapy, while one improved following corticosteroid treatment. For multifocal or unresectable disease, systemic therapies targeting cytokines (e.g., anti\u0026ndash;IL-6) or molecular pathways (e.g., MAPK inhibitors) are emerging options[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Meningiomas, conversely, are treated primarily with maximal safe resection with or without radiotherapy. Thus, distinguishing inflammatory from neoplastic dural lesions preoperatively directly influences the extent of resection sought, the decision to pursue biopsy versus aggressive resection, and the need for immunomodulatory therapy.\u003c/p\u003e \u003cp\u003ePractical implications from our series are fourfold: (1) maintain a high index of suspicion for IgG4-RHP or RDD in atypical dural-based lesions\u0026mdash;particularly those with extensive or skull-base involvement, infiltrative features, disproportionate edema, or absent classic meningioma imaging signs; (2) integrate CSF IgG4 testing when serum studies are unrevealing and clinical suspicion persists; (3) pursue targeted biopsy for histopathological confirmation before committing to radical resections when imaging and clinical data suggest an inflammatory etiology; and (4) tailor postoperative management to histopathology, reserving immunosuppression for IgG4-RHP and considering extent of resection as primary therapy for isolated RDD.\u003c/p\u003e \u003cp\u003eLimitations of this study include its small sample size and retrospective design, which preclude definitive recommendations on optimal management for IgG4-RD coexisting with RDD. Nonetheless, our findings emphasize that combined interpretation of advanced imaging, CSF biomarkers, and histopathology is essential to distinguish these entities and to guide appropriate, disease-specific therapy.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIgG4-RHP, RDD, and meningioma are frequently indistinguishable on clinical and radiological grounds, with important therapeutic implications. Definitive diagnosis therefore relies on histopathological confirmation, supplemented by integration of clinical presentation, neuroimaging characteristics, and targeted laboratory testing (including CSF IgG4 assays when appropriate). In this series we report the coexistence of IgG4-RD and RDD\u0026mdash;which, to our knowledge, has not been previously described\u0026mdash;and note that the clinical and pathological phenotype in these mixed cases closely resembled RDD. Recognition of this overlap is important for diagnostic accuracy and subsequent management. We hope these observations will raise clinical awareness and aid clinicians in selecting appropriate diagnostic pathways and tailored treatments for atypical dural-based lesions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was funded by the National Natural Science Foundation of China(No. 82573350 to X.Xiao.)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study was conducted in accordance with the principles outlined in the Declaration of Helsinki and its subsequent revisions, and received approval from the Medical Research Ethics Committee of Xuanwu Hospital(303-01-007-0720). The requirement for informed consent to participate was officially waived by the the Medical Research Ethics Committee of Xuanwu Hospital due to the retrospective nature of the study and the use of anonymized clinical data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Xinru Xiao did study design, performed the surgeries, supervised clinical data collection, and supervised the manuscript; Tao Zeng did data curation and statistical analysis, selected images and prepared figures/tables, and finished the manuscript; Jie Bai did histopathologic slide analysis and immunohistochemistry, prepared pathology images, and conducted literature review and discussion writing. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKuroda N, Inenaga C, Arai Y, Otsuki Y, Tanaka T. Intracranial multiple pseudotumor due to immunoglobulin G4-related disease without other lesions: case report and literature review. World Neurosurg 2019. 2019;132:69\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTanji H, Okada H, Igari R, Yamaguchi Y, Sato H, Takahashi Y, Koyama S, Arawaka S, Wada M, Kawanami T, Wakabayashi K, Kato T. (2016) Inflammatory pseudotumor of the brain parenchyma with IgG4 hypergammaglobulinemia. Intern Med.2016; 55:1911\u0026ndash;1916.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCooper SL, Jenrette JM. Rosai\u0026ndash;Dorfman disease: management of CNS and systemic involvement. Clin Adv Hematol Oncol. 2012;10(3):199\u0026ndash;202.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuke YC, Chen,Graham W, Slack,Mollie. N Carruthers Lancet. 2021;398:1213\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLucy XL, Della-Torre E, Stone JH, Clark SW. (2014) IgG4-related hypertrophic pachymeningitis: clinical features, diagnostic criteria, and treatment. JAMA Neurol. 2014; 71:785\u0026ndash;793.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi WW. Zhang Orphanet J Rare Dis. 2020;15:285. Li;Shangzhu Zhang;Linyi Peng;Min Shen;Shuoning Song;Wei Zhang;Xinxin Cao;Ruie Feng;Wen.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDella-Torre E, Passerini G, Furlan R, et al. Cerebrospinal fluid analysis in immunoglobulin G4-related hypertrophic pachymeningitis. J Rheumatol. 2013;40(11):1927\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDella Torre E, Bozzolo EP, Passerini G, Doglioni C, Sabbadini MG. IgG4-related pach\u0026ndash;ymeningitis:evidence of intrathecal IgG4 on cerebrospinal fluid analysis. Ann Intern Med. 2012;156(5):401\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorandi X, Godey B, Riffaud L, Heresbach N, Brassier G. Isolated Rosai-Dorfman disease of the fourth ventricle. Case illustration. J Neurosurg. 2000;92(5):890.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAntu\u0026ntilde;a Ramos A, Alvarez Vega MA, Alles JV, Antu\u0026ntilde;a Garcia MJ. Meil \u0026acute;an Mart\u0026acute;ınez A.Multiple involvement of the central nervous system in Rosai-Dorfman disease. Pediatr Neurol. 2012;46(1):54\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLindstrom KM, Cousar JB, Lopes MB. IgG4-related meningeal disease: clinico-pathological features and proposal for diagnostic criteria. Acta Neuropathol. 2010;120(6):765\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAishwarya Ravindran G, Goyal RS, Karen L. Rech Am J Surg Pathol. 2021;45:35\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXiao X, Fu D, Feng L. (2020) Hypertrophic pachymeningitis in a southern Chinese population: a retrospective study. Front Neurol. 2020; 11:565088.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhosroshahi A, Carruthers MN, Deshpande V, Unizony S, Bloch DB, Stone JH. Rituximab for the treatment of IgG4-related disease: lessons from 10 consecutive patients. Med (Baltim). 2012;91(1):57\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArnao V, Riolo M, Savettieri G, Aridon P. Mercaptopurine treatment in an adult man with orbital and intracranial Rosai-Dorfman disease. Case Rep Neurol Med. 2016;2016:1030478.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSasaki K, Pemmaraju N, Westin JR, et al. A single case of Rosai-Dorfman disease marked by pathologic fractures, kidney failure, and liver cirrhosis treated with singleagent cladribine. Front Oncol. 2014;4:297.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSimko SJ, Tran HD, Jones J, et al. Clofarabine salvage therapy in refractory multifocal histiocytic disorders, including Langerhans cell histiocytosis, juvenile xanthogranuloma and Rosai-Dorfman disease. Pediatr Blood Cancer. 2014;61(3):479\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 \u0026nbsp;Summary of the demographic and clinical data of 4 cases of IgG4-RHP in the intracranial\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"586\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eCase number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eAge(year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003eMain clinical manifestation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117px;\"\u003e\n \u003cp\u003eImaging manifestation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eCD38、CD3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eCD20、CD138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003eCD68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003eHeadache, deviation of the tongue to the right\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117px;\"\u003e\n \u003cp\u003eSlope tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e＋\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e＋\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003eHeadache，episodic spasms of the corners of the mouth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117px;\"\u003e\n \u003cp\u003eA mass in the left temporal lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e＋\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e＋\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e＋\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003eHeadache, diplopia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117px;\"\u003e\n \u003cp\u003eSlope tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e＋\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e＋\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e＋\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003eHeadache\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117px;\"\u003e\n \u003cp\u003eSlope tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e＋\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e＋\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e＋\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 \u0026nbsp;Summary of the demographic and clinical data of 3 cases of IgG4-RD with RDD\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"570\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003eCase number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003eAge(year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eMain clinical manifestation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eImaging manifestation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eCD68、S100、CD138、CD3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eCD1a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003eCD38、CD163\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eDifficulty pronouncing words, double vision, hearing loss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eSlope tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e＋\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e＋\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eSudden fainting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eA mass in the left temporal lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e＋\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eNumbness on the right side of the face, hearing loss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003ePetroclival tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e＋\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e＋\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"IgG4-RHP, Meningioma, RDD","lastPublishedDoi":"10.21203/rs.3.rs-9421179/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9421179/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIgG4-related hypertrophic pachymeningitis (IgG4-RHP) is a rare fibroinflammatory manifestation of IgG4-related disease (IgG4-RD) that produces localized or diffuse dural thickening and frequently mimics meningioma on clinical and radiologic evaluation. Coexistence of IgG4-RD with Rosai\u0026ndash;Dorfman\u0026ndash;Destombes disease (RDD) has not been well characterized.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively reviewed seven patients referred with a presumptive diagnosis of meningioma. Postoperative histopathology and laboratory data were used to establish definitive diagnoses.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eFour patients were diagnosed with isolated IgG4-RHP and three patients had concomitant IgG4-RD and RDD. All seven were initially suspected to have meningioma based on outpatient assessment and imaging; definitive diagnosis required serological testing and histopathological confirmation. We summarize distinguishing clinical, imaging, laboratory, and pathological features that aid differentiation from meningioma, including patterns of dural involvement, skull-base predilection, infiltrative behavior with disproportionate vasogenic edema, absence of typical meningioma signs (hyperostosis, calcification, clear dural tail), CSF and serum IgG4/IgG4Loc considerations, and characteristic histology for IgG4-RHP (IgG4\u0026thinsp;+\u0026thinsp;plasma-cell\u0026ndash;rich infiltrate, storiform fibrosis, obliterative phlebitis) versus RDD (S100+/CD68\u0026thinsp;+\u0026thinsp;histiocytes with emperipolesis).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eAwareness of these distinguishing features and the potential for IgG4-RD/RDD coexistence can facilitate earlier, targeted diagnostic workup and appropriate management, avoiding misdiagnosis and suboptimal treatment.\u003c/p\u003e","manuscriptTitle":"Diagnostic Challenges of Dural-Based Lesions: Clinical, Radiologic, and Pathologic Differentiation of Meningioma, IgG4-RHP, and RDD","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-06 16:28:07","doi":"10.21203/rs.3.rs-9421179/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-10T18:12:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"261375897727866865684632320458741489461","date":"2026-04-28T06:19:26+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-27T03:51:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-24T07:38:41+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-22T07:24:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-21T16:58:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2026-04-21T16:03:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"823d1c83-4a6d-4e5d-86f8-5a886b9516eb","owner":[],"postedDate":"May 6th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-10T18:12:51+00:00","index":47,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-06T16:28:07+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-06 16:28:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9421179","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9421179","identity":"rs-9421179","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}