Giant Olfactory Cleft Schwannoma Arising from the Nasal Septum: A Case Report with Immunohistochemical Insights

Giant Olfactory Cleft Schwannoma Arising from the Nasal Septum: A Case Report with Immunohistochemical Insights | 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 Giant Olfactory Cleft Schwannoma Arising from the Nasal Septum: A Case Report with Immunohistochemical Insights Daili Mou, Jing Li, Xiaoquan He, Yan Xie, Feifei Chen, Luyun Jiang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7752469/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Olfactory cleft schwannomas arising from the nasal septum are exceedingly rare, with fewer than 50 cases documented globally. Preoperative differentiation from other sinonasal spindle cell tumors remains challenging due to overlapping clinical and imaging features. Methods Here, we report a case of A 43-year-old woman presented with a 2-month history of progressive left nasal obstruction and intermittent epistaxis. Nasal endoscopy revealed a 3.5 × 2.8 cm smooth-surfaced mass originating from the posterior nasal septum within the left olfactory cleft. Computed tomography (CT) demonstrated a nodular lesion with local septal cartilage compression. Endoscopic cryo-plasma resection under general anesthesia achieved complete tumor removal while preserving septal integrity. Histopathology confirmed a benign schwannoma characterized by spindle cells arranged in Antoni A/B patterns, strong diffuse S-100 (++++) and CD34 (++++) positivity, and low proliferative activity (Ki67: 3%). Margins were tumor-free on intraoperative frozen section. No recurrence was observed at 6-month follow-up. Conclusion This case underscores the diagnostic utility of immunohistochemistry (S-100, CD34) in distinguishing schwannomas from neurofibromas, hemangiomas, and other sinonasal tumors. Endoscopic cryo-plasma excision offers a minimally invasive approach for septal schwannomas, ensuring complete resection with reduced morbidity. Long-term surveillance remains essential given the rarity of recurrence. schwannoma nasal septum diagnosis and differential diagnosis rare tumor immunohistochemical Figures Figure 1 Figure 2 Figure 3 Introduction Schwannomas are benign tumors formed by the nerve sheaths of peripheral nerves. They originate mainly from Schwann cells, which are neuroglia in the peripheral nervous system(1–7). The most common site for this tumor is the head and neck region, with an incidence of 25-45%(4,6–9).However, this tumor is rare in the nasal cavity and paranasal sinuses, with an incidence of approximately 4%(1,6,8,10).In addition, it is very rare in the nasal septum(1,3,4,7), where it usually involves the posterior part of the nasal septum and most likely originates from the nasopalatine branch of the trigeminal nerve(4).In general, there is no difference in the incidence of this tumor between males and females, and it can develop at any age，Strong positivity of S-100 protein by immunoassay is a distinctive histopathologic manifestation(4,8) Case Report A 43-year-old female patient had a 2-month history of left-sided nasal congestion, intermittent left-sided rhinorrhea, occasional morning postnasal drip, no sneezing or runny nose, no headache, no olfactory loss, no sneezing or asthma, and normal vision. Nasal endoscopy showed a left olfactory cleft tumor: tough texture, smooth surface, visible capillaries, originating from the nasal septum and compressing the ipsilateral middle turbinate (Figure 1A). Computed tomography scan showed localized slight thickening of bilateral sieve sinus mucosa, nodular shadowing of the left upper nasal tract, and polyps? Scattered punctate and focal hyperdense shadows were seen within the polyps, and the mass was locally attached to the mucosa of the middle and lower posterior part of the nasal septum, with the cartilage of the nasal septum slightly compressed and deflected to the right (Figure 2). Subsequently, the patient underwent nasal endoscopic nasal tumor resection under general anesthesia（ Video 1） . The tumor was resected by cryoablation using a monopolar low-temperature plasma tip to avoid perforation of the nasal septum caused by tumor resection. During the operation, it was seen that the surface of the mass was smooth, and it was widely adhered to the mucosa of the middle and lower and posterior lower segments of the nasal septum, and the bone was partially exposed. Meanwhile, a safe margin of 1 cm at the base of the tumor was excised to ensure complete resection of the tumor. And the tumor and tumor margin tissue were sent together for intraoperative frozen pathology. Intraoperative frozen biopsy showed that the mass was a spindle cell lesion with mild cellular anisotropy, and there was no tumor tissue growth growth at the margin of the tumor incision. The histopathologic diagnosis was schwannoma with active multifocal cell growth. Under the microscope, 1. the nuclei of the cells were purple, mostly spindle-shaped or ovoid; 2. the cytoplasm of the cells was light pink, rich, with less clear boundaries, and there was a tendency for the cells to merge with each other; 3. proliferation of collagen fibers was seen in the interstitium of the cells; and 4. the cells were arranged in bundles or fenestrations (Fig. 3A and Fig. 3B). Immunohistochemical staining: Ki67 (+ about 3%), Vim (++++), CD34 (++++), S-100 (++++), EMA (-), SMA (-), WT-1 (-), Des (-), Act (-), MyoD1 (-), Myogenin (-), CD68 (-). Six months after surgery, the patient had no recurrence of symptoms or tumor (Figure 1B). Discussion Peripheral nerve tumors are classified into two types: schwannomas and neurofibromas, which may or may not undergo malignant transformation. Schwannomas are solitary, slow-growing tumors with a low risk of malignant progression. In contrast, neurofibromas are often multifocal and carry a high risk of sarcomatous transformation(4,11). In the head and neck region, schwannomas account for 25%-45% of neural tumors, with approximately 4% of these cases occurring in the nasal cavity and paranasal sinuses.(1,3,4,8–10). Nasal septal schwannomas may originate from the sympathetic nerves innervating nasal septal blood vessels, parasympathetic nerves controlling mucous glands, or sensory nerves including the anterosuperior nasociliary nerve (branch of the trigeminal nerve V1) and posteroinferior nasopalatine nerve (branch of the trigeminal nerve V2)(4). Although occasionally associated with neurofibromatosis type II (NF2)and presenting with multifocal bilateral lesions, most schwannomas are solitary and rarely malignant(12). The average age of onset is approximately 40 years, with the ethmoid sinus being the most frequently involved among paranasal sinuses(9). Clinical manifestations include hypoesthesia or paraesthesia from nerve compression, along with nonspecific symptoms such as epistaxis, nasal obstruction, and facial pain(10,13). Imaging characteristics on CT and MRI typically reveal heterogeneously enhancing mass lesions. These studies are crucial for determining the tumor origin, sinonasal extension, and orbital or intracranial involvement(7). Schwannomas present as well-defined encapsulated cysts connected to neural tissue, appearing as soft-tissue density expandable masses in sinonasal regions. Unlike squamous cell carcinoma or sarcoma, they may resemble anterior nasal polyps and typically cause bone thinning or displacement rather than destruction(12,14). Histopathologically, schwannomas exhibit classic microscopic features classified as Antoni type A (densely arranged spindle cells with nuclear palisading, showing nuclear clefts and Verocay bodies) and Antoni type B (loosely arranged spindle cells in a myxoid matrix)(9). Immunohistochemically, S-100 protein – particularly its neural tissue-specific S-100B subtype – serves as a key diagnostic marker. Over 95% of schwannomas demonstrate strong S-100 positivity due to preserved Schwann cell characteristics(12). As this condition is clinically uncommon and often misdiagnosed, differential diagnosis should include: Neurofibroma: Typically multifocal with high sarcomatous risk. CT shows well-defined oval or fusiform soft-tissue masses (30-50 HU) with variable calcification and mild-moderate enhancement. While strong diffuse S-100 positivity favors schwannoma, focal S-100 with CD34 positivity suggests neurofibroma. Notably, NF2-associated tumors may show strong S-100 expression(15). Hemangioma: Subtypes include capillary (pediatric, nasal septum predilection) and cavernous (elderly). CT demonstrates muscle-isodense masses with possible phleboliths and intense homogeneous enhancement. Immunoprofile: CD31/CD34+, S-100-(16). Lymphoma: Primarily non-Hodgkin's (NK/T-cell type). Imaging reveals homogeneous nasal soft-tissue masses with mild-moderate enhancement and characteristic "moth-eaten" bone destruction showing post-treatment calcification. EBER in situ hybridization positivity is typical. Short-course chemotherapy is recommended(17). Inverted Papilloma: Most common sinonasal benign tumor. CT shows muscle-isodense lesions with calcification/residual bone and focal hyperostosis at tumor origin. MRI exhibits characteristic "cerebriform" pattern. Surgical en bloc resection with involved mucoperiosteum is critical(18). Endoscopic endonasal surgery represents the preferred treatment for sinonasal schwannomas due to clear visualization, shortened hospitalization, and absence of external scarring(9,10,13). Postoperative surveillance for recurrence, adhesions, secondary sinusitis, and residual lesions is essential. Tumors involving skull base may require staged resection(4). Thus, schwannomas originating from the nasal septum are rare, and their preoperative differentiation from other tumors is difficult; histological and immunohistochemical tests (strong positivity of S-100 protein) are required for final diagnosis, but they should be used as one of the differential diagnoses in patients with unilateral nasal masses. Nasal endoscopic cryo-plasma excision of intranasal masses is the ideal treatment. Abbreviations Act Actin CD34 Cluster of Differentiation 34 CD68 Cluster of Differentiation 68 CT Computed Tomography Des Desmin EBER Epstein-Barr Virus-encoded small RNA EMA Epithelial Membrane Antigen HU Hounsfield Units Ki-67 Ki-67 Antigen MRI Magnetic Resonance Imaging MyoD1 Myogenic Differentiation 1 NF2 Neurofibromatosis Type 2 S100 S100 Calcium-Binding Protein B SMA Smooth Muscle Actin Vim Vimentin WT-1 Wilms Tumor Protein 1 Declarations Funding：No funding was received for this manuscript. Conflict of Interest: The authors have no conflict of interest. Originality Statement:This manuscript is original, has not been published elsewhere, and is not under concurrent consideration by another journal. A preliminary abstract of this case was presented at a local clinical conference; however, the comprehensive dataset, immunohistochemical analysis, and 6-month follow-up presented herein are entirely novel and unpublished. Ethics Statement: Approval of the research protocol by an Institutional Reviewer Board: N/A Patient Consent Statement:Written informed consent was obtained from the patient for publication of this case report, including all clinical details, imaging, and histopathological findings. Registry and the Registration No. of the study/trial: N/A Animal Studies: N/A. Figure/Table/Copyright Statement:N/A Author’s Contribution All authors (Daili Mou, Jing Li, Xiaoquan He, Yan Xie, Feifei Chen, and Luyun Jiang) have contributed significantly to this work. Dr. Luyun Jiang supervised the clinical management, manuscript preparation, and revisions. Dr. Daili Mou and Dr. Jing Li performed the endoscopic resection and clinical data acquisition. Dr. Xiaoquan He conducted the histopathological and immunohistochemical analyses. Dr. Yan Xie and Feifei Chen contributed to radiological interpretation and longitudinal follow-up. All authors have critically reviewed the final manuscript and approve its submission. References Alrasheed W, Almomen A, Alkhatib A (2019) A rare case of nasal septal schwannoma: Case report and literature review. Int J Surg Case Rep 55:149–151 Aslan G, Cinar F, Cabuk FK Schwannoma of the submandibular gland: a case report Cadd B, Offiah C, Alusi G (2014) A surprising cause of unilateral nasal obstruction and epistaxis: nasal septal schwannoma. J Surg Case Rep 2014(3):rju023–rju023 Min HJ, Kim KS (2017) Differential Diagnosis Between Nasal Septal Schwannoma and Nasal Septal Neurofibroma. J Craniofac Surg 28(7):1780–1783 Kolberg M, Høland M, Agesen TH, Brekke HR, Liestøl K, Hall KS et al (2013) Survival meta-analyses for > 1800 malignant peripheral schwannoma patients with and without neurofibromatosis type 1. Neuro Oncol 15(2):135–147 Mitra B, Debnath S, Paul B, Pal M, Banerjee TJ, Saha TN (2012) Schwannoma of nasal septum: A rare case report with literature review. Egypt J Ear Nose Throat Allied Sci 13(3):121–125 Park EH, Lee SS, Byun SW (2008) A schwannoma in the nasal septum. Eur Arch Otorhinolaryngol 265(8):983–985 Rathnakara SH Endoscopic Management of Ethmoidal Schwannoma: A Case Report Roy R, Patel B, Gahlot GPS (2022) An Extensive Unilateral Nasal Mass: Septal Schwannoma—Case Report. Indian J Otolaryngol Head Neck Surg 74(S2):1540–1543 Valsamidis K, Koutsampasopoulou I, Titelis K (2017) Nasal septal schwannoma: An extremely rare tumor. Acta Otorrinolaringologica (English Edition) 68(2):127–128 Berlucchi M, Piazza C, Blanzuoli L, Battaglia G, Nicolai P (2000) Schwannoma of the nasal septum: a case report with review of the literature. Eur Arch Otorhinolaryngol 257(7):402–405 Coy S, Rashid R, Stemmer-Rachamimov A, Santagata S (2020) An update on the CNS manifestations of neurofibromatosis type 2. Acta Neuropathol 139(4):643–665 Skouras A, Skouras G, Diab A, Asimakopoulou FA, Dimitriadi K, Divritsioti M (2011) Schwannoma of the nasal tip: diagnosis and treatment. Aesthetic Plast Surg 35(4):657–661 Kim YS, Kim HJ, Kim C-H, Kim J (2013) CT and MR Imaging Findings of Sinonasal Schwannoma: A Review of 12 Cases. AJNR Am J Neuroradiol 34(3):628–633 Trimeche O, Hajji E, Missaoui A, Ben Amor B, Bayar I, Abid S et al (2025) Portraying the full picture of NeurofibromatosisNoonan syndrome: a systematic review of literature. J Med Genet 62(2):109–116 Bellinato F, Marocchi M, Pecoraro L, Zaffanello M, Del Giglio M, Girolomoni G et al (2024) Diagnosis and Treatment of Infantile Hemangioma from the Primary Care Paediatricians to the Specialist: A Narrative Review. Children 11(11):1397 Qi S, Yahalom J, Hsu M, Monica Chelius, Lunning M, Moskowitz A et al (2016) Encouraging experience in the treatment of nasal type extranodal NK/T-cell lymphoma in a non-Asian population. Leuk Lymphoma 57(11):2575–2583 Upadhya IB, Rao K (2022) Sinonasal Inverted Papilloma: A Narrative Review. Indian J Otolaryngol Head Neck Surg 74(S2):1017–1022 Additional Declarations No competing interests reported. Supplementary Files Video1.mp4 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7752469","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":524262043,"identity":"9c978b12-9200-4c69-9093-6ce28d47448d","order_by":0,"name":"Daili Mou","email":"","orcid":"","institution":"Affiliated Hospital of Chengdu University of Traditional Chinese Medicine ，Chengdu","correspondingAuthor":false,"prefix":"","firstName":"Daili","middleName":"","lastName":"Mou","suffix":""},{"id":524262044,"identity":"68ab065b-c317-4a9f-b0a0-a26f7bdae05d","order_by":1,"name":"Jing Li","email":"","orcid":"","institution":"Affiliated Hospital of 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neoplasm.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7752469/v1/7d2ad49f04ea3ac1e63b9904.png"},{"id":93024417,"identity":"c0cda3d5-32a4-44e5-aa89-3b37553ef758","added_by":"auto","created_at":"2025-10-08 09:16:46","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":277199,"visible":true,"origin":"","legend":"\u003cp\u003eCT examination of the paranasal sinuses showed a nodular shadow (3.5×2.8 cm )of the left upper nasal tract with scattered dots and focal hyperdense shadows, and the mass was locally connected to the mucosa of the middle and lower part of the nasal septum.The mass was partially connected to the mucosa of the middle and lower posterior nasal septum, and the cartilage of the nasal septum was slightly compressed with a right deviation(red arrow).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7752469/v1/a450e2e738d77e198f0a5c19.png"},{"id":93024421,"identity":"53f54577-a864-45ee-91d4-4bbec6b347af","added_by":"auto","created_at":"2025-10-08 09:16:46","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":528160,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e3A, \u003c/strong\u003eHematoxylin-eosin (original magnification*20),\u003cstrong\u003e 3B\u003c/strong\u003e, Hematoxylin-eosin (original magnification *40)microscopy can be seen: 1. cell nucleus is purple, most of them are pike or oval; 2. cytoplasm is light pink, more abundant, the border is not too clear, the cells show a tendency to fuse with each other; 3 inter-cellular cytoplasm can be seen in the collagen fibers hyperplasia; 4. the cells show a fascicular or fenestrated arrangement.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7752469/v1/dc12678c4b5d241d7430b03a.png"},{"id":94989388,"identity":"b5b09c18-d636-44e7-a1b3-e2ed07c23a15","added_by":"auto","created_at":"2025-11-03 07:12:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1811272,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7752469/v1/9464f3c7-9dce-4cce-a249-e31caa8f8a7c.pdf"},{"id":93024430,"identity":"466f10a9-5777-4f87-90c0-a9e77f0afa0d","added_by":"auto","created_at":"2025-10-08 09:16:48","extension":"mp4","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":47550885,"visible":true,"origin":"","legend":"","description":"","filename":"Video1.mp4","url":"https://assets-eu.researchsquare.com/files/rs-7752469/v1/964edf903ea9b871baef66bf.mp4"}],"financialInterests":"No competing interests reported.","formattedTitle":"Giant Olfactory Cleft Schwannoma Arising from the Nasal Septum: A Case Report with Immunohistochemical Insights","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSchwannomas are benign tumors formed by the nerve sheaths of peripheral nerves. They originate mainly from Schwann cells, which are neuroglia in the peripheral nervous system(1\u0026ndash;7). The most common site for this tumor is the head and neck region, with an incidence of 25-45%(4,6\u0026ndash;9).However, this tumor is rare in the nasal cavity and paranasal sinuses, with an incidence of approximately 4%(1,6,8,10).In addition, it is very rare in the nasal septum(1,3,4,7), where it usually involves the posterior part of the nasal septum and most likely originates from the nasopalatine branch of the trigeminal nerve(4).In general, there is no difference in the incidence of this tumor between males and females, and it can develop at any age，Strong positivity of S-100 protein by immunoassay is a distinctive histopathologic manifestation(4,8)\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 43-year-old female patient had a 2-month history of left-sided nasal congestion, intermittent left-sided rhinorrhea, occasional morning postnasal drip, no sneezing or runny nose, no headache, no olfactory loss, no sneezing or asthma, and normal vision. Nasal endoscopy showed a left olfactory cleft tumor: tough texture, smooth surface, visible capillaries, originating from the nasal septum and compressing the ipsilateral middle turbinate (Figure 1A). Computed tomography scan showed localized slight thickening of bilateral sieve sinus mucosa, nodular shadowing of the left upper nasal tract, and polyps? Scattered punctate and focal hyperdense shadows were seen within the polyps, and the mass was locally attached to the mucosa of the middle and lower posterior part of the nasal septum, with the cartilage of the nasal septum slightly compressed and deflected to the right (Figure 2). Subsequently, the patient underwent nasal endoscopic nasal tumor resection under general anesthesia（\u003cstrong\u003eVideo 1）\u003c/strong\u003e. The tumor was resected by cryoablation using a monopolar low-temperature plasma tip to avoid perforation of the nasal septum caused by tumor resection. During the operation, it was seen that the surface of the mass was smooth, and it was widely adhered to the mucosa of the middle and lower and posterior lower segments of the nasal septum, and the bone was partially exposed. Meanwhile, a safe margin of 1 cm at the base of the tumor was excised to ensure complete resection of the tumor. And the tumor and tumor margin tissue were sent together for intraoperative frozen pathology. Intraoperative frozen biopsy showed that the mass was a spindle cell lesion with mild cellular anisotropy, and there was no tumor tissue growth growth at the margin of the tumor incision. The histopathologic diagnosis was schwannoma with active multifocal cell growth. Under the microscope, 1. the nuclei of the cells were purple, mostly spindle-shaped or ovoid; 2. the cytoplasm of the cells was light pink, rich, with less clear boundaries, and there was a tendency for the cells to merge with each other; 3. proliferation of collagen fibers was seen in the interstitium of the cells; and 4. the cells were arranged in bundles or fenestrations (Fig. 3A and Fig. 3B). Immunohistochemical staining:\u003cem\u003e\u0026nbsp;Ki67 (+ about 3%), Vim (++++), CD34 (++++), S-100 (++++), EMA (-), SMA (-), WT-1 (-), Des (-), Act (-), MyoD1 (-), Myogenin (-), CD68 (-).\u0026nbsp;\u003c/em\u003eSix months after surgery, the patient had no recurrence of symptoms or tumor (Figure 1B).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePeripheral nerve tumors are classified into two types: schwannomas and neurofibromas, which may or may not undergo malignant transformation. Schwannomas are solitary, slow-growing tumors with a low risk of malignant progression. In contrast, neurofibromas are often multifocal and carry a high risk of sarcomatous transformation(4,11).\u003c/p\u003e\n\u003cp\u003eIn the head and neck region, schwannomas account for 25%-45% of neural tumors, with approximately 4% of these cases occurring in the nasal cavity and paranasal sinuses.(1,3,4,8\u0026ndash;10). Nasal septal schwannomas may originate from the sympathetic nerves innervating nasal septal blood vessels, parasympathetic nerves controlling mucous glands, or sensory nerves including the anterosuperior nasociliary nerve (branch of the trigeminal nerve V1) and posteroinferior nasopalatine nerve (branch of the trigeminal nerve V2)(4). Although occasionally associated with neurofibromatosis type II (NF2)and presenting with multifocal bilateral lesions, most schwannomas are solitary and rarely malignant(12). The average age of onset is approximately 40 years, with the ethmoid sinus being the most frequently involved among paranasal sinuses(9). Clinical manifestations include hypoesthesia or paraesthesia from nerve compression, along with nonspecific symptoms such as epistaxis, nasal obstruction, and facial pain(10,13).\u003c/p\u003e\n\u003cp\u003eImaging characteristics on CT and MRI typically reveal heterogeneously enhancing mass lesions. These studies are crucial for determining the tumor origin, sinonasal extension, and orbital or intracranial involvement(7). Schwannomas present as well-defined encapsulated cysts connected to neural tissue, appearing as soft-tissue density expandable masses in sinonasal regions. Unlike squamous cell carcinoma or sarcoma, they may resemble anterior nasal polyps and typically cause bone thinning or displacement rather than destruction(12,14).\u003c/p\u003e\n\u003cp\u003eHistopathologically, schwannomas exhibit classic microscopic features classified as Antoni type A (densely arranged spindle cells with nuclear palisading, showing nuclear clefts and Verocay bodies) and Antoni type B (loosely arranged spindle cells in a myxoid matrix)(9). Immunohistochemically, S-100 protein \u0026ndash; particularly its neural tissue-specific S-100B subtype \u0026ndash; serves as a key diagnostic marker. Over 95% of schwannomas demonstrate strong S-100 positivity due to preserved Schwann cell characteristics(12).\u003c/p\u003e\n\u003cp\u003eAs this condition is clinically uncommon and often misdiagnosed, differential diagnosis should include:\u003c/p\u003e\n\u003cp\u003eNeurofibroma: Typically multifocal with high sarcomatous risk. CT shows well-defined oval or fusiform soft-tissue masses (30-50 HU) with variable calcification and mild-moderate enhancement. While strong diffuse S-100 positivity favors schwannoma, focal S-100 with CD34 positivity suggests neurofibroma. Notably, NF2-associated tumors may show strong S-100 expression(15).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHemangioma: Subtypes include capillary (pediatric, nasal septum predilection) and cavernous (elderly). CT demonstrates muscle-isodense masses with possible phleboliths and intense homogeneous enhancement. Immunoprofile: CD31/CD34+, S-100-(16).\u003c/p\u003e\n\u003cp\u003eLymphoma: Primarily non-Hodgkin\u0026apos;s (NK/T-cell type). Imaging reveals homogeneous nasal soft-tissue masses with mild-moderate enhancement and characteristic \u0026quot;moth-eaten\u0026quot; bone destruction showing post-treatment calcification. EBER in situ hybridization positivity is typical. Short-course chemotherapy is recommended(17).\u003c/p\u003e\n\u003cp\u003eInverted Papilloma: Most common sinonasal benign tumor. CT shows muscle-isodense lesions with calcification/residual bone and focal hyperostosis at tumor origin. MRI exhibits characteristic \u0026quot;cerebriform\u0026quot; pattern. Surgical en bloc resection with involved mucoperiosteum is critical(18).\u003c/p\u003e\n\u003cp\u003eEndoscopic endonasal surgery represents the preferred treatment for sinonasal schwannomas due to clear visualization, shortened hospitalization, and absence of external scarring(9,10,13). Postoperative surveillance for recurrence, adhesions, secondary sinusitis, and residual lesions is essential. Tumors involving skull base may require staged resection(4).\u003c/p\u003e\n\u003cp\u003eThus, schwannomas originating from the nasal septum are rare, and their preoperative differentiation from other tumors is difficult; histological and immunohistochemical tests (strong positivity of S-100 protein) are required for final diagnosis, but they should be used as one of the differential diagnoses in patients with unilateral nasal masses. Nasal endoscopic cryo-plasma excision of intranasal masses is the ideal treatment.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAct\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eActin\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCD34\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCluster of Differentiation 34\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCD68\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCluster of Differentiation 68\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\u003eComputed Tomography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eDes\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eDesmin\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eEBER\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eEpstein-Barr Virus-encoded small RNA\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eEMA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eEpithelial Membrane Antigen\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHU\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eHounsfield Units\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eKi-67\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eKi-67 Antigen\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\"\u003eMyoD1\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMyogenic Differentiation 1\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNF2\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNeurofibromatosis Type 2\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eS100\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eS100 Calcium-Binding Protein B\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSMA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSmooth Muscle Actin\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eVim\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eVimentin\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eWT-1\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eWilms Tumor Protein 1\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding：No funding was received for this manuscript.\u003c/p\u003e\n\u003cp\u003eConflict of Interest: The authors have no conflict of interest.\u003c/p\u003e\n\u003cp\u003eOriginality Statement:This manuscript is original, has not been published elsewhere, and is not under concurrent consideration by another journal. A preliminary abstract of this case was presented at a local clinical conference; however, the comprehensive dataset, immunohistochemical analysis, and 6-month follow-up presented herein are entirely novel and unpublished.\u003c/p\u003e\n\u003cp\u003eEthics Statement: \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eApproval of the research protocol by an Institutional Reviewer Board: N/A\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatient Consent Statement:Written informed consent was obtained from the patient for publication of this case report, including all clinical details, imaging, and histopathological findings.\u003c/p\u003e\n\u003cp\u003eRegistry and the Registration No. of the study/trial: N/A\u003c/p\u003e\n\u003cp\u003eAnimal Studies: N/A. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFigure/Table/Copyright Statement:N/A\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors (Daili Mou, Jing Li, Xiaoquan He, Yan Xie, Feifei Chen, and Luyun Jiang) have contributed significantly to this work. Dr. Luyun Jiang supervised the clinical management, manuscript preparation, and revisions. Dr. Daili Mou and Dr. Jing Li performed the endoscopic resection and clinical data acquisition. Dr. Xiaoquan He conducted the histopathological and immunohistochemical analyses. Dr. Yan Xie and Feifei Chen contributed to radiological interpretation and longitudinal follow-up. All authors have critically reviewed the final manuscript and approve its submission.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAlrasheed W, Almomen A, Alkhatib A (2019) A rare case of nasal septal schwannoma: Case report and literature review. Int J Surg Case Rep 55:149\u0026ndash;151\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAslan G, Cinar F, Cabuk FK Schwannoma of the submandibular gland: a case report\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCadd B, Offiah C, Alusi G (2014) A surprising cause of unilateral nasal obstruction and epistaxis: nasal septal schwannoma. J Surg Case Rep 2014(3):rju023\u0026ndash;rju023\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMin HJ, Kim KS (2017) Differential Diagnosis Between Nasal Septal Schwannoma and Nasal Septal Neurofibroma. J Craniofac Surg 28(7):1780\u0026ndash;1783\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKolberg M, H\u0026oslash;land M, Agesen TH, Brekke HR, Liest\u0026oslash;l K, Hall KS et al (2013) Survival meta-analyses for \u0026gt;\u0026thinsp;1800 malignant peripheral schwannoma patients with and without neurofibromatosis type 1. Neuro Oncol 15(2):135\u0026ndash;147\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMitra B, Debnath S, Paul B, Pal M, Banerjee TJ, Saha TN (2012) Schwannoma of nasal septum: A rare case report with literature review. Egypt J Ear Nose Throat Allied Sci 13(3):121\u0026ndash;125\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePark EH, Lee SS, Byun SW (2008) A schwannoma in the nasal septum. Eur Arch Otorhinolaryngol 265(8):983\u0026ndash;985\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRathnakara SH Endoscopic Management of Ethmoidal Schwannoma: A Case Report\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRoy R, Patel B, Gahlot GPS (2022) An Extensive Unilateral Nasal Mass: Septal Schwannoma\u0026mdash;Case Report. Indian J Otolaryngol Head Neck Surg 74(S2):1540\u0026ndash;1543\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eValsamidis K, Koutsampasopoulou I, Titelis K (2017) Nasal septal schwannoma: An extremely rare tumor. Acta Otorrinolaringologica (English Edition) 68(2):127\u0026ndash;128\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBerlucchi M, Piazza C, Blanzuoli L, Battaglia G, Nicolai P (2000) Schwannoma of the nasal septum: a case report with review of the literature. Eur Arch Otorhinolaryngol 257(7):402\u0026ndash;405\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCoy S, Rashid R, Stemmer-Rachamimov A, Santagata S (2020) An update on the CNS manifestations of neurofibromatosis type 2. Acta Neuropathol 139(4):643\u0026ndash;665\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSkouras A, Skouras G, Diab A, Asimakopoulou FA, Dimitriadi K, Divritsioti M (2011) Schwannoma of the nasal tip: diagnosis and treatment. Aesthetic Plast Surg 35(4):657\u0026ndash;661\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKim YS, Kim HJ, Kim C-H, Kim J (2013) CT and MR Imaging Findings of Sinonasal Schwannoma: A Review of 12 Cases. AJNR Am J Neuroradiol 34(3):628\u0026ndash;633\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTrimeche O, Hajji E, Missaoui A, Ben Amor B, Bayar I, Abid S et al (2025) Portraying the full picture of NeurofibromatosisNoonan syndrome: a systematic review of literature. J Med Genet 62(2):109\u0026ndash;116\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBellinato F, Marocchi M, Pecoraro L, Zaffanello M, Del Giglio M, Girolomoni G et al (2024) Diagnosis and Treatment of Infantile Hemangioma from the Primary Care Paediatricians to the Specialist: A Narrative Review. Children 11(11):1397\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eQi S, Yahalom J, Hsu M, Monica Chelius, Lunning M, Moskowitz A et al (2016) Encouraging experience in the treatment of nasal type extranodal NK/T-cell lymphoma in a non-Asian population. Leuk Lymphoma 57(11):2575\u0026ndash;2583\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eUpadhya IB, Rao K (2022) Sinonasal Inverted Papilloma: A Narrative Review. Indian J Otolaryngol Head Neck Surg 74(S2):1017\u0026ndash;1022\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"schwannoma, nasal septum, diagnosis and differential diagnosis, rare tumor, immunohistochemical","lastPublishedDoi":"10.21203/rs.3.rs-7752469/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7752469/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\u003eOlfactory cleft schwannomas arising from the nasal septum are exceedingly rare, with fewer than 50 cases documented globally. Preoperative differentiation from other sinonasal spindle cell tumors remains challenging due to overlapping clinical and imaging features.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHere, we report a case of A 43-year-old woman presented with a 2-month history of progressive left nasal obstruction and intermittent epistaxis. Nasal endoscopy revealed a 3.5 × 2.8 cm smooth-surfaced mass originating from the posterior nasal septum within the left olfactory cleft. Computed tomography (CT) demonstrated a nodular lesion with local septal cartilage compression. Endoscopic cryo-plasma resection under general anesthesia achieved complete tumor removal while preserving septal integrity.\u003c/p\u003e\n\u003cp\u003eHistopathology confirmed a benign schwannoma characterized by spindle cells arranged in Antoni A/B patterns, strong diffuse S-100 (++++) and CD34 (++++) positivity, and low proliferative activity (Ki67: 3%). Margins were tumor-free on intraoperative frozen section. No recurrence was observed at 6-month follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case underscores the diagnostic utility of immunohistochemistry (S-100, CD34) in distinguishing schwannomas from neurofibromas, hemangiomas, and other sinonasal tumors. Endoscopic cryo-plasma excision offers a minimally invasive approach for septal schwannomas, ensuring complete resection with reduced morbidity. Long-term surveillance remains essential given the rarity of recurrence.\u003c/p\u003e","manuscriptTitle":"Giant Olfactory Cleft Schwannoma Arising from the Nasal Septum: A Case Report with Immunohistochemical Insights","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-08 09:16:41","doi":"10.21203/rs.3.rs-7752469/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a29d8ff2-85d2-43ac-8d02-4f804c21c5f2","owner":[],"postedDate":"October 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-02T22:08:07+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-08 09:16:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7752469","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7752469","identity":"rs-7752469","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}