Uncommon Presentation of Follicular Thyroid Carcinoma with Scalp and Intracranial Extension - Case report

Uncommon Presentation of Follicular Thyroid Carcinoma with Scalp and Intracranial Extension - Case report | 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 Uncommon Presentation of Follicular Thyroid Carcinoma with Scalp and Intracranial Extension - Case report Danushka PGN, Jayasinghe MR, Jeyaratnam Y, Aththanayaka AMDK This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7378655/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Background Follicular variant of papillary thyroid carcinoma (FV-PTC) is a distinct subtype of thyroid cancer with intermediate clinical behavior between classical papillary and follicular carcinomas. While generally associated with favorable prognosis, FV-PTC can rarely present with distant metastases, including to the skull and scalp, posing diagnostic and therapeutic challenges. Case Description We report a 51-year-old woman initially diagnosed with primary hypothyroidism and a thyroid goitre, later confirmed as FV-PTC after total thyroidectomy. Three years postoperatively, she developed a painless scalp lump. Magentic resonance imaging (MRI) revealed a large heterogeneously enhancing mass involving bilateral frontal skull bones with bone erosion and extension into scalp tissues, compressing adjacent brain structures without parenchymal invasion. Surgical excision of the scalp mass confirmed metastatic follicular thyroid carcinoma. The patient was managed with levothyroxine replacement and calcium supplementation after receiving radioiodine ablation therapy. Conclusion This case highlights the importance of recognizing late solitary skull and scalp metastases in FV-PTC, which can lead to bone erosion and potential involvement of the brain parenchyma. The complementary use of MRI and computed tomography (CT) is vital for thorough assessment of both soft tissue and bony invasion. Given the risk of intracranial extension, management often requires a neurosurgical approach combined with reconstructive surgery to achieve effective tumor resection and restore structural integrity. Long-term surveillance and multidisciplinary treatment strategies remain essential to optimize outcomes in these complex and atypical metastatic presentations. Follicular variant papillary thyroid carcinoma Scalp metastasis RAI-refractory thyroid cancer Figures Figure 1 Figure 2 Figure 3 Introduction FV-PTC is a distinct subtype of papillary thyroid carcinoma with follicular architecture but typical papillary nuclear features. Over time, diagnostic criteria have evolved to recognize FV-PTC as a unique clinical entity among thyroid cancers ( 1 , 2 ). Clinically, FV-PTC generally follows a more indolent course compared to classical PTC but demonstrates a relatively higher propensity for distant metastases, especially in bone and skull, though such metastases are rare. These metastatic lesions often indicate advanced disease and increased morbidity ( 3 ). The pattern of metastasis in FV-PTC tends to resemble follicular thyroid carcinoma, favoring hematogenous spread with potential for late presentations years after initial treatment ( 4 , 5 ). Diagnosis of FV-PTC involves cytological, histopathological, and molecular analyses. RAS mutations are common in encapsulated or well-circumscribed tumors like NIFTP, while invasive FV-PTC often harbors BRAF mutations. However, these mutations are not definitive predictors of clinical behavior, which is influenced by other factors ( 6 ). Although the overall prognosis is generally favorable, the presence of aggressive features or the occurrence of delayed distant metastases can pose significant challenges to treatment. Radioactive iodine (RAI) therapy is key in managing differentiated thyroid cancers like FV-PTC for remnant ablation and metastasis treatment. Recent studies show lower RAI doses can effectively ablate low- to intermediate-risk FV-PTC, matching success rates of higher doses ( 7 ). However, a subset of patients develops RAI-refractory disease, in which thyroid cancer cells lose their ability to uptake iodine, limiting the efficacy of this therapy and complicating management ( 7 , 8 ). This case report describes an unusual presentation of FV-PTC with delayed solitary metastasis to the skull and scalp, highlighting important considerations regarding diagnosis, imaging, and management. Awareness of the potential for late metastatic spread and RAI-refractoriness emphasizes the need for long-term follow-up and a multidisciplinary approach in managing FV-PTC patients ( 7 , 8 ). Case presentation A 51 year old woman first presented in 2016 with complaints of progressive weight gain, constipation, and shortness of breath. The shortness of breath was not associated with any features suggestive of cardiac or respiratory causes, and there were no symptoms such as orthopnea, paroxysmal nocturnal dyspnea, chest pain, wheezing, or cough and had an anterior neck lump. She appeared clinically hypothyroid. There was no cervical lymphadenopathy, and no signs of tracheal compression or voice changes. Laboratory investigations at that time showed a TSH level of 18.5 µIU/mL (normal range: 0.4–4.0 µIU/mL), suggestive of primary hypothyroidism. She was referred for imaging, and a neck ultrasound was performed, which revealed a solid hypoechoic nodule measuring 2.8 × 2.5 cm in the left thyroid lobe, with irregular margins, microcalcifications, and increased vascularity, raising suspicion for malignancy. The thyroid capsule was intact, and no cervical lymphadenopathy was seen. The findings were consistent with a TI-RADS 5 lesion. In view of the clinical suspicion and imaging findings, she underwent a total thyroidectomy. Histopathology confirmed a diagnosis of follicular variant of papillary carcinoma of thyroid without evidence of vascular invasion or extrathyroidal extension. Postoperatively, she was commenced on levothyroxine 200 mcg daily for hormone replacement and calcium 50 mg TDS. After the radioiodine ablation therapy, she continued regular follow-up at the clinic. In 2019, she noted a small, painless lump on the left side of her scalp, which remained stable for four years during which she continued her regular medication and did not seek any other treatments. Approximately one year ago, the lump rapidly enlarged. Although she presented to the hospital, no additional treatments were provided. She subsequently underwent a course of radioiodine ablation therapy; however, the treatment was ineffective in controlling the lesion. She was referred to the neurosurgical clinic for further management of the scalp lump. Given the history of follicular thyroid carcinoma, a contrast-enhanced MRI brain was performed to evaluate the lesion and assess for intracranial extension. MRI showed a large (10 × 8.3 × 10 cm), heterogeneously enhancing solid mass involving the bilateral frontal lobes. The lesion was isointense to grey matter on T1- and T2/FLAIR images, with areas of high signal and central diffusion restriction. Blooming low-signal foci indicated internal hemorrhage or calcification. The mass compressed both frontal lobes and caused thickening and irregularity of the adjacent dura but did not invade brain parenchyma. The superior sagittal sinus was compressed without thrombosis. The mass extended through the calvarium into the left scalp at two sites. No other skull lesions were present. After the comprehensive MDT (Multi-disciplinary team) discussion, she underwent surgical excision of the scalp mass in 2024. Histological analysis confirmed that the lesion was a metastatic deposit of follicular thyroid carcinoma, consistent with late solitary skull/scalp metastasis from her primary thyroid malignancy. Then again she underwent a course of radioactive iodine therapy. Discussion The metastatic lesion in this patient caused erosion of the calvarium and extended into the scalp, which is a relatively rare but recognized manifestation of thyroid carcinoma metastasis. Bone involvement, particularly skull metastasis, indicates hematogenous spread and suggests a more aggressive disease course despite the generally favorable prognosis of FV-PTC( 1 ). The erosion of the bone and extension into soft tissues highlight the tumor’s locally invasive potential and the need for thorough imaging and surgical planning. Compared to other reported cases, our patient’s presentation is unique due to the large bilateral frontal bone involvement with extracranial scalp extension and the absence of neurological symptoms, highlighting the importance of high clinical suspicion and comprehensive imaging in patients with a history of FTC presenting with new scalp lesions ( 8 , 9 ). In addition to the painless scalp lump that developed as a late manifestation of metastatic FV-PTC, other presenting symptoms of thyroid carcinoma metastasis to the scalp and skull may include localized swelling, tenderness, and, in cases with intracranial extension or compression of adjacent brain structures, neurological symptoms such as headaches, seizures, focal neurological deficits, cranial nerve palsies, or cognitive disturbances( 8 ). A major clinical issue highlighted here is the diagnosis and management of RAI-refractory disease. Despite undergoing RAI therapy post-thyroidectomy, the patient developed a large metastatic scalp lesion demonstrating resistance to RAI ablation, a scenario increasingly observed in FV-PTC and follicular thyroid carcinoma ( 7 ). RAI-refractory metastases pose a therapeutic dilemma, as these lesions do not respond to standard systemic therapy, limiting treatment options and worsening prognosis. Early identification of RAI resistance is therefore critical to guide alternative therapeutic strategies, including surgery, external beam radiotherapy, or novel systemic agents ( 7 , 8 ). Optimal management of such metastatic lesions begins with thorough preoperative evaluation. Imaging with MRI provides superior assessment of soft tissue involvement, dural thickening, and potential brain parenchymal invasion, while CT complements by better delineating bony destruction ( 10 , 11 ). In this patient, the large mass with extension through the calvarium warranted careful surgical planning involving a multidisciplinary team including endocrinology, neurosurgery, and reconstructive surgery. Ideally, before proceeding to surgery, whole-body iodine scans or fluorodeoxyglucose positron emission tomography (FDG-PET) could have helped to detect additional metastatic sites and evaluate the metabolic activity of lesions, further informing prognosis and treatment planning ( 12 ). Surgical resection remains the mainstay for isolated skull and scalp metastases causing mass effect, cosmetic deformity, or neurological symptoms, and allows histopathological confirmation ( 8 , 13 ). However, Cranial metastases that erode bone and involve dura or brain require neurosurgical expertise for safe excision and reconstruction to maintain cranial integrity and prevent complications like herniation or infection. Reconstruction may use autologous or synthetic grafts. Managing advanced metastatic thyroid carcinoma involves balancing aggressive local control with preserving neurological function and quality of life. Given that FV-PTC can exhibit varied molecular alterations and clinical behaviors, individualized long-term follow-up with regular imaging and thyroglobulin monitoring is crucial to detect recurring or metastatic disease early ( 6 , 7 ). When recurrence or metastasis is identified, a multimodal approach incorporating surgery, appropriate use of RAI (if residual iodine responsiveness exists), and consideration of external beam radiotherapy or systemic therapies for RAI-refractory disease is recommended ( 7 , 8 ). Compared to other reported cases, our patient’s presentation is unique due to the large bilateral frontal bone involvement with extracranial scalp extension and the absence of neurological symptoms, highlighting the importance of high clinical suspicion and comprehensive imaging in patients with a history of FTC presenting with new scalp lesions ( 9 , 13 ) Conclusion This rare case of FV-PTC with scalp metastasis and intracranial extension highlights the need for careful evaluation of new scalp lesions in such patients. MRI is crucial for determining tumor extent and guiding treatment. Due to potential aggressive progression despite standard therapy, multidisciplinary care and personalized treatment are essential. Long-term follow-up is important to detect and manage unusual metastases early. Abbreviations FV - PTC - Follicular variant of papillary thyroid carcinoma MRI - Magnetic Resonance Imaging CT - Computed tomography RAI - Radio active iodine MDT - Multi-disciplinary team FTC - Follicular thyroid carcinoma Declarations Ethical approval Ethical review was not sought for this case report as it describes a retrospective analysis of clinical data obtained during routine patient care, without any additional interventions. Patient confidentiality and anonymity have been maintained throughout. According to institutional policies and applicable regulations, formal ethics committee approval is not required for single case reports. Consent to participate /publication Written informed consent for publication of clinical information and images was obtained from the patient prior to submission. Participation in the case report did not involve any additional interventions beyond routine clinical care. Therefore, specific informed consent to participate was not separately required. Ethical review and approval were waived/not applicable as this is a retrospective single case report conducted in accordance with institutional policies. Availability of data and materials Not applicable Competing interests All authors declare that there are no competing interests. Funding This research did not receive any specific grant from funding agencies in the public,commercial,or not-for-profit sectors. Authors’ contributions Authors Responsibilities and Contributions 1 PGN Danushka Design the study, data entering and analysis, manuscript writing 2 MR Jayasinghe Design the study, data entering and analysis, manuscript writing 3 Y Jeyaratnam Design the study, data entering and analysis, manuscript writing 4 Aththanayaka AMDK Design the study, data entering and analysis, manuscript writing A cknowledgements Not applicable References Yu X-M, Schneider DF, Leverson G, Chen H, Sippel RS. Follicular variant of papillary thyroid carcinoma is a unique clinical entity: a population-based study of 10,740 cases. Thyroid. 2013;23(10):1263-8. Cipriani NA, Nagar S, Kaplan SP, White MG, Antic T, Sadow PM, et al. Follicular thyroid carcinoma: how have histologic diagnoses changed in the last half-century and what are the prognostic implications? Thyroid. 2015;25(11):1209-16. Machens A, Lorenz K, Weber F, Dralle H. Risk patterns of distant metastases in follicular, papillary and medullary thyroid cancer. Hormone and Metabolic Research. 2022;54(01):7-11. Parameswaran R, Shulin Hu J, Min En N, Tan W, Yuan N. Patterns of metastasis in follicular thyroid carcinoma and the difference between early and delayed presentation. The Annals of The Royal College of Surgeons of England. 2017;99(2):151-4. Matta-Coelho C, Simões-Pereira J, Vilar H, Leite V. Bone metastases from thyroid carcinoma of follicular origin: a single institutional experience. European Thyroid Journal. 2019;8(2):96-101. Mehrzad R, Nishino M, Nucera C, Dias-Santagata D, Hennessey JV, Hasselgren P-O. Invasive follicular variant of papillary thyroid cancer harboring the NRAS mutation Q61K and presenting with bone metastasis—a case report. International journal of surgery case reports. 2017;38:180-4. Stegenga MT, van Velsen EF, Oudijk L, Verburg FA, van Ginhoven TM, Peeters RP, et al. Clinical and Histopathological Risk Factors for Radioactive Iodine–Refractory Follicular and Oncocytic Thyroid Carcinoma. The Journal of Clinical Endocrinology & Metabolism. 2024;109(12):e2334-e41. Suga Y, Wondafrash M, Abebe MW, Eshetu H. Multidisciplinary Management of Skull Metastatic Follicular Thyroid Cancer in a Resource-Limited Setting. JCEM Case Reports. 2024;2(6):luae080. Kalode S, Bhake A. The cytodiagnosis of metastasis of follicular thyroid carcinoma in the scalp: an unusual case report. The Pan African Medical Journal. 2025;50:63. Schellinger PD, Meinck HM, Thron A. Diagnostic accuracy of MRI compared to CCT in patients with brain metastases. Journal of neuro-oncology. 1999;44:275-81. Arora V, Sidhu BS, Singh K. Comparison of computed tomography and magnetic resonance imaging in evaluation of skull lesions. Egyptian Journal of Radiology and Nuclear Medicine. 2022;53(1):67. Boktor RR, Lee ST, Berlangieri SU, Scott AM. Impact of 18F-FDG PET/CT on treatment of patients with differentiated thyroid carcinoma, negative 131I whole body scan and elevated serum thyroglobulin. Asia Oceania Journal of Nuclear Medicine and Biology. 2022;10(1):20. Kumar M, Singh A, Mishra S. Scalp metastasis from follicular thyroid carcinoma diagnosed by fine needle aspiration cytology: A case series. Thyroid Research and Practice. 2016;13(2):80-2. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 04 Sep, 2025 Reviews received at journal 03 Sep, 2025 Reviews received at journal 24 Aug, 2025 Reviews received at journal 24 Aug, 2025 Reviewers agreed at journal 23 Aug, 2025 Reviewers agreed at journal 22 Aug, 2025 Reviewers agreed at journal 21 Aug, 2025 Reviewers agreed at journal 18 Aug, 2025 Reviewers invited by journal 18 Aug, 2025 Editor assigned by journal 18 Aug, 2025 Submission checks completed at journal 18 Aug, 2025 First submitted to journal 15 Aug, 2025 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. 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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-7378655","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":504875813,"identity":"405a4960-ddf0-4a23-b550-642b083301dc","order_by":0,"name":"Danushka PGN","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyElEQVRIiWNgGAWjYDCCAyDCgIGHH0QnFBCvxYBHsgGkxYBoLUBrDKDWEQZ8x88eky4o+CNjfH514ocHBgzy/GIH8GuRPJOXJj0D6DCzG283SwAdZjhzdgJ+LQYHcsykecBazm4AaUkwuE1Iy/k3EC3GM85u/kGclhtQWwz4e7cRZ4vkjTfG1jMMjHkkbvBus0gwkCDsF77zOYa3C/7I2fP3n91880eFjTy/NAEtIMAMJiXAKiUIK0do4T9AnOpRMApGwSgYeQAA/XQ/4WjMTbcAAAAASUVORK5CYII=","orcid":"","institution":"National Hospital Sri Lanka","correspondingAuthor":true,"prefix":"","firstName":"Danushka","middleName":"","lastName":"PGN","suffix":""},{"id":504875814,"identity":"eea4235e-5591-4420-b27d-59e4b80c713b","order_by":1,"name":"Jayasinghe MR","email":"","orcid":"","institution":"University Hospitals Plymouth NHS Trust","correspondingAuthor":false,"prefix":"","firstName":"Jayasinghe","middleName":"","lastName":"MR","suffix":""},{"id":504875818,"identity":"2b65b5af-52e6-4a1e-a9d1-2ea893df2d33","order_by":2,"name":"Jeyaratnam Y","email":"","orcid":"","institution":"University of Colombo","correspondingAuthor":false,"prefix":"","firstName":"Jeyaratnam","middleName":"","lastName":"Y","suffix":""},{"id":504875820,"identity":"77fb4500-6274-4eae-ad25-fdd997f65bad","order_by":3,"name":"Aththanayaka AMDK","email":"","orcid":"","institution":"National Hospital Sri Lanka","correspondingAuthor":false,"prefix":"","firstName":"Aththanayaka","middleName":"","lastName":"AMDK","suffix":""}],"badges":[],"createdAt":"2025-08-15 05:53:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7378655/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7378655/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90122223,"identity":"948a518f-c241-4c40-9d99-848a0cbcd01b","added_by":"auto","created_at":"2025-08-28 17:57:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":127323,"visible":true,"origin":"","legend":"\u003cp\u003eClinical image demonstrating a large, well-defined scalp swelling over the frontal region\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7378655/v1/4205aa69b48eb96c279c6884.png"},{"id":90122950,"identity":"f805b78b-243c-4122-808c-711641457b46","added_by":"auto","created_at":"2025-08-28 18:13:19","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":153020,"visible":true,"origin":"","legend":"\u003cp\u003eContrast-enhanced MRI brain showing a large frontal bone mass compressing the underlying frontal lobes\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7378655/v1/b6b4808378865b5573d8e2d9.png"},{"id":90122225,"identity":"e7d0da70-e49c-46e0-b87d-7469280c56d6","added_by":"auto","created_at":"2025-08-28 17:57:19","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":132068,"visible":true,"origin":"","legend":"\u003cp\u003eThe bone defect was reconstructed with a 3d printed PEEK cranioplasty\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7378655/v1/d77dd417efd1ace602822934.png"},{"id":90122951,"identity":"2591182e-866b-4faf-83ac-4a3a1d80dacd","added_by":"auto","created_at":"2025-08-28 18:13:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":802621,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7378655/v1/e0d45eeb-bb39-4883-87aa-a85ac7457f33.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Uncommon Presentation of Follicular Thyroid Carcinoma with Scalp and Intracranial Extension - Case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFV-PTC is a distinct subtype of papillary thyroid carcinoma with follicular architecture but typical papillary nuclear features. Over time, diagnostic criteria have evolved to recognize FV-PTC as a unique clinical entity among thyroid cancers (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eClinically, FV-PTC generally follows a more indolent course compared to classical PTC but demonstrates a relatively higher propensity for distant metastases, especially in bone and skull, though such metastases are rare. These metastatic lesions often indicate advanced disease and increased morbidity (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The pattern of metastasis in FV-PTC tends to resemble follicular thyroid carcinoma, favoring hematogenous spread with potential for late presentations years after initial treatment (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDiagnosis of FV-PTC involves cytological, histopathological, and molecular analyses. RAS mutations are common in encapsulated or well-circumscribed tumors like NIFTP, while invasive FV-PTC often harbors BRAF mutations. However, these mutations are not definitive predictors of clinical behavior, which is influenced by other factors (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Although the overall prognosis is generally favorable, the presence of aggressive features or the occurrence of delayed distant metastases can pose significant challenges to treatment.\u003c/p\u003e\u003cp\u003eRadioactive iodine (RAI) therapy is key in managing differentiated thyroid cancers like FV-PTC for remnant ablation and metastasis treatment. Recent studies show lower RAI doses can effectively ablate low- to intermediate-risk FV-PTC, matching success rates of higher doses (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). However, a subset of patients develops RAI-refractory disease, in which thyroid cancer cells lose their ability to uptake iodine, limiting the efficacy of this therapy and complicating management (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThis case report describes an unusual presentation of FV-PTC with delayed solitary metastasis to the skull and scalp, highlighting important considerations regarding diagnosis, imaging, and management. Awareness of the potential for late metastatic spread and RAI-refractoriness emphasizes the need for long-term follow-up and a multidisciplinary approach in managing FV-PTC patients (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 51 year old woman first presented in 2016 with complaints of progressive weight gain, constipation, and shortness of breath. The shortness of breath was not associated with any features suggestive of cardiac or respiratory causes, and there were no symptoms such as orthopnea, paroxysmal nocturnal dyspnea, chest pain, wheezing, or cough and had an anterior neck lump. She appeared clinically hypothyroid. There was no cervical lymphadenopathy, and no signs of tracheal compression or voice changes.\u003c/p\u003e\u003cp\u003eLaboratory investigations at that time showed a TSH level of 18.5 \u0026micro;IU/mL (normal range: 0.4\u0026ndash;4.0 \u0026micro;IU/mL), suggestive of primary hypothyroidism. She was referred for imaging, and a neck ultrasound was performed, which revealed a solid hypoechoic nodule measuring 2.8 \u0026times; 2.5 cm in the left thyroid lobe, with irregular margins, microcalcifications, and increased vascularity, raising suspicion for malignancy. The thyroid capsule was intact, and no cervical lymphadenopathy was seen. The findings were consistent with a TI-RADS 5 lesion.\u003c/p\u003e\u003cp\u003eIn view of the clinical suspicion and imaging findings, she underwent a total thyroidectomy. Histopathology confirmed a diagnosis of follicular variant of papillary carcinoma of thyroid without evidence of vascular invasion or extrathyroidal extension. Postoperatively, she was commenced on levothyroxine 200 mcg daily for hormone replacement and calcium 50 mg TDS. After the radioiodine ablation therapy, she continued regular follow-up at the clinic.\u003c/p\u003e\u003cp\u003eIn 2019, she noted a small, painless lump on the left side of her scalp, which remained stable for four years during which she continued her regular medication and did not seek any other treatments. Approximately one year ago, the lump rapidly enlarged. Although she presented to the hospital, no additional treatments were provided. She subsequently underwent a course of radioiodine ablation therapy; however, the treatment was ineffective in controlling the lesion. She was referred to the neurosurgical clinic for further management of the scalp lump.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eGiven the history of follicular thyroid carcinoma, a contrast-enhanced MRI brain was performed to evaluate the lesion and assess for intracranial extension.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eMRI showed a large (10 \u0026times; 8.3 \u0026times; 10 cm), heterogeneously enhancing solid mass involving the bilateral frontal lobes. The lesion was isointense to grey matter on T1- and T2/FLAIR images, with areas of high signal and central diffusion restriction. Blooming low-signal foci indicated internal hemorrhage or calcification. The mass compressed both frontal lobes and caused thickening and irregularity of the adjacent dura but did not invade brain parenchyma. The superior sagittal sinus was compressed without thrombosis. The mass extended through the calvarium into the left scalp at two sites. No other skull lesions were present.\u003c/p\u003e\u003cp\u003eAfter the comprehensive MDT (Multi-disciplinary team) discussion, she underwent surgical excision of the scalp mass in 2024. Histological analysis confirmed that the lesion was a metastatic deposit of follicular thyroid carcinoma, consistent with late solitary skull/scalp metastasis from her primary thyroid malignancy. Then again she underwent a course of radioactive iodine therapy.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe metastatic lesion in this patient caused erosion of the calvarium and extended into the scalp, which is a relatively rare but recognized manifestation of thyroid carcinoma metastasis. Bone involvement, particularly skull metastasis, indicates hematogenous spread and suggests a more aggressive disease course despite the generally favorable prognosis of FV-PTC(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The erosion of the bone and extension into soft tissues highlight the tumor\u0026rsquo;s locally invasive potential and the need for thorough imaging and surgical planning.\u003c/p\u003e\u003cp\u003eCompared to other reported cases, our patient\u0026rsquo;s presentation is unique due to the large bilateral frontal bone involvement with extracranial scalp extension and the absence of neurological symptoms, highlighting the importance of high clinical suspicion and comprehensive imaging in patients with a history of FTC presenting with new scalp lesions (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). In addition to the painless scalp lump that developed as a late manifestation of metastatic FV-PTC, other presenting symptoms of thyroid carcinoma metastasis to the scalp and skull may include localized swelling, tenderness, and, in cases with intracranial extension or compression of adjacent brain structures, neurological symptoms such as headaches, seizures, focal neurological deficits, cranial nerve palsies, or cognitive disturbances(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eA major clinical issue highlighted here is the diagnosis and management of RAI-refractory disease. Despite undergoing RAI therapy post-thyroidectomy, the patient developed a large metastatic scalp lesion demonstrating resistance to RAI ablation, a scenario increasingly observed in FV-PTC and follicular thyroid carcinoma (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). RAI-refractory metastases pose a therapeutic dilemma, as these lesions do not respond to standard systemic therapy, limiting treatment options and worsening prognosis. Early identification of RAI resistance is therefore critical to guide alternative therapeutic strategies, including surgery, external beam radiotherapy, or novel systemic agents (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eOptimal management of such metastatic lesions begins with thorough preoperative evaluation. Imaging with MRI provides superior assessment of soft tissue involvement, dural thickening, and potential brain parenchymal invasion, while CT complements by better delineating bony destruction (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). In this patient, the large mass with extension through the calvarium warranted careful surgical planning involving a multidisciplinary team including endocrinology, neurosurgery, and reconstructive surgery. Ideally, before proceeding to surgery, whole-body iodine scans or fluorodeoxyglucose positron emission tomography (FDG-PET) could have helped to detect additional metastatic sites and evaluate the metabolic activity of lesions, further informing prognosis and treatment planning (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eSurgical resection remains the mainstay for isolated skull and scalp metastases causing mass effect, cosmetic deformity, or neurological symptoms, and allows histopathological confirmation (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). However, Cranial metastases that erode bone and involve dura or brain require neurosurgical expertise for safe excision and reconstruction to maintain cranial integrity and prevent complications like herniation or infection. Reconstruction may use autologous or synthetic grafts. Managing advanced metastatic thyroid carcinoma involves balancing aggressive local control with preserving neurological function and quality of life.\u003c/p\u003e\u003cp\u003eGiven that FV-PTC can exhibit varied molecular alterations and clinical behaviors, individualized long-term follow-up with regular imaging and thyroglobulin monitoring is crucial to detect recurring or metastatic disease early (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). When recurrence or metastasis is identified, a multimodal approach incorporating surgery, appropriate use of RAI (if residual iodine responsiveness exists), and consideration of external beam radiotherapy or systemic therapies for RAI-refractory disease is recommended (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eCompared to other reported cases, our patient\u0026rsquo;s presentation is unique due to the large bilateral frontal bone involvement with extracranial scalp extension and the absence of neurological symptoms, highlighting the importance of high clinical suspicion and comprehensive imaging in patients with a history of FTC presenting with new scalp lesions (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis rare case of FV-PTC with scalp metastasis and intracranial extension highlights the need for careful evaluation of new scalp lesions in such patients. MRI is crucial for determining tumor extent and guiding treatment. Due to potential aggressive progression despite standard therapy, multidisciplinary care and personalized treatment are essential. Long-term follow-up is important to detect and manage unusual metastases early.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cul start=\"50\"\u003e\n \u003cli\u003eFV - PTC - Follicular variant of papillary thyroid carcinoma\u003c/li\u003e\n \u003cli\u003eMRI - Magnetic Resonance Imaging\u003c/li\u003e\n \u003cli\u003eCT - Computed tomography\u003c/li\u003e\n \u003cli\u003eRAI - Radio active iodine\u003c/li\u003e\n \u003cli\u003eMDT - Multi-disciplinary team\u003c/li\u003e\n \u003cli\u003eFTC - Follicular thyroid carcinoma\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eapproval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical review was not sought for this case report as it describes a retrospective analysis of clinical data obtained during routine patient care, without any additional interventions. Patient confidentiality and anonymity have been maintained throughout. According to institutional policies and applicable regulations, formal ethics committee approval is not required for single case reports.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003cstrong\u003e/publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of clinical information and images was obtained from the patient prior to submission. Participation in the case report did not involve any additional interventions beyond routine clinical care. Therefore, specific informed consent to participate was not separately required. Ethical review and approval were waived/not applicable as this is a retrospective single case report conducted in accordance with institutional policies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that there are no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public,commercial,or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"601\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eResponsibilities and Contributions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e1 PGN Danushka\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eDesign the study, data entering and analysis, manuscript writing\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e2 MR Jayasinghe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eDesign the study, data entering and analysis, manuscript writing\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e3 Y Jeyaratnam\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eDesign the study, data entering and analysis, manuscript writing\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e4 Aththanayaka AMDK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eDesign the study, data entering and analysis, manuscript writing\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e\u003cstrong\u003ecknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eYu X-M, Schneider DF, Leverson G, Chen H, Sippel RS. Follicular variant of papillary thyroid carcinoma is a unique clinical entity: a population-based study of 10,740 cases. Thyroid. 2013;23(10):1263-8.\u003c/li\u003e\n \u003cli\u003eCipriani NA, Nagar S, Kaplan SP, White MG, Antic T, Sadow PM, et al. Follicular thyroid carcinoma: how have histologic diagnoses changed in the last half-century and what are the prognostic implications? Thyroid. 2015;25(11):1209-16.\u003c/li\u003e\n \u003cli\u003eMachens A, Lorenz K, Weber F, Dralle H. Risk patterns of distant metastases in follicular, papillary and medullary thyroid cancer. Hormone and Metabolic Research. 2022;54(01):7-11.\u003c/li\u003e\n \u003cli\u003eParameswaran R, Shulin Hu J, Min En N, Tan W, Yuan N. Patterns of metastasis in follicular thyroid carcinoma and the difference between early and delayed presentation. The Annals of The Royal College of Surgeons of England. 2017;99(2):151-4.\u003c/li\u003e\n \u003cli\u003eMatta-Coelho C, Simões-Pereira J, Vilar H, Leite V. Bone metastases from thyroid carcinoma of follicular origin: a single institutional experience. European Thyroid Journal. 2019;8(2):96-101.\u003c/li\u003e\n \u003cli\u003eMehrzad R, Nishino M, Nucera C, Dias-Santagata D, Hennessey JV, Hasselgren P-O. Invasive follicular variant of papillary thyroid cancer harboring the NRAS mutation Q61K and presenting with bone metastasis—a case report. International journal of surgery case reports. 2017;38:180-4.\u003c/li\u003e\n \u003cli\u003eStegenga MT, van Velsen EF, Oudijk L, Verburg FA, van Ginhoven TM, Peeters RP, et al. Clinical and Histopathological Risk Factors for Radioactive Iodine–Refractory Follicular and Oncocytic Thyroid Carcinoma. The Journal of Clinical Endocrinology \u0026amp; Metabolism. 2024;109(12):e2334-e41.\u003c/li\u003e\n \u003cli\u003eSuga Y, Wondafrash M, Abebe MW, Eshetu H. Multidisciplinary Management of Skull Metastatic Follicular Thyroid Cancer in a Resource-Limited Setting. JCEM Case Reports. 2024;2(6):luae080.\u003c/li\u003e\n \u003cli\u003eKalode S, Bhake A. The cytodiagnosis of metastasis of follicular thyroid carcinoma in the scalp: an unusual case report. The Pan African Medical Journal. 2025;50:63.\u003c/li\u003e\n \u003cli\u003eSchellinger PD, Meinck HM, Thron A. Diagnostic accuracy of MRI compared to CCT in patients with brain metastases. Journal of neuro-oncology. 1999;44:275-81.\u003c/li\u003e\n \u003cli\u003eArora V, Sidhu BS, Singh K. Comparison of computed tomography and magnetic resonance imaging in evaluation of skull lesions. Egyptian Journal of Radiology and Nuclear Medicine. 2022;53(1):67.\u003c/li\u003e\n \u003cli\u003eBoktor RR, Lee ST, Berlangieri SU, Scott AM. Impact of 18F-FDG PET/CT on treatment of patients with differentiated thyroid carcinoma, negative 131I whole body scan and elevated serum thyroglobulin. Asia Oceania Journal of Nuclear Medicine and Biology. 2022;10(1):20.\u003c/li\u003e\n \u003cli\u003eKumar M, Singh A, Mishra S. Scalp metastasis from follicular thyroid carcinoma diagnosed by fine needle aspiration cytology: A case series. Thyroid Research and Practice. 2016;13(2):80-2.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":false,"email":"[email protected]","identity":"surgical-and-experimental-pathology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"saep","sideBox":"Learn more about [Surgical and Experimental Pathology](http://surgexppathol.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/SAEP/default.aspx","title":"Surgical and Experimental Pathology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Follicular variant papillary thyroid carcinoma, Scalp metastasis, RAI-refractory thyroid cancer","lastPublishedDoi":"10.21203/rs.3.rs-7378655/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7378655/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\u003eFollicular variant of papillary thyroid carcinoma (FV-PTC) is a distinct subtype of thyroid cancer with intermediate clinical behavior between classical papillary and follicular carcinomas. While generally associated with favorable prognosis, FV-PTC can rarely present with distant metastases, including to the skull and scalp, posing diagnostic and therapeutic challenges.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Description\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe report a 51-year-old woman initially diagnosed with primary hypothyroidism and a thyroid goitre, later confirmed as FV-PTC after total thyroidectomy. Three years postoperatively, she developed a painless scalp lump. Magentic resonance imaging (MRI) revealed a large heterogeneously enhancing mass involving bilateral frontal skull bones with bone erosion and extension into scalp tissues, compressing adjacent brain structures without parenchymal invasion. Surgical excision of the scalp mass confirmed metastatic follicular thyroid carcinoma. The patient was managed with levothyroxine replacement and calcium supplementation after receiving radioiodine ablation therapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case highlights the importance of recognizing late solitary skull and scalp metastases in FV-PTC, which can lead to bone erosion and potential involvement of the brain parenchyma. The complementary use of MRI and computed tomography (CT) is vital for thorough assessment of both soft tissue and bony invasion. Given the risk of intracranial extension, management often requires a neurosurgical approach combined with reconstructive surgery to achieve effective tumor resection and restore structural integrity. Long-term surveillance and multidisciplinary treatment strategies remain essential to optimize outcomes in these complex and atypical metastatic presentations.\u003c/p\u003e","manuscriptTitle":"Uncommon Presentation of Follicular Thyroid Carcinoma with Scalp and Intracranial Extension - Case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-28 17:57:14","doi":"10.21203/rs.3.rs-7378655/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-04T10:34:59+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-03T07:59:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-24T18:16:22+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-24T09:01:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"200404962594713923083980605038334116711","date":"2025-08-23T11:26:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"101527169672020976103651327270761840028","date":"2025-08-22T14:14:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"113657518945020199629528204982285641276","date":"2025-08-22T01:46:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"288152050943144571701325464147893462696","date":"2025-08-19T00:11:11+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-18T22:30:51+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-18T05:13:23+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-18T05:12:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"Surgical and Experimental Pathology","date":"2025-08-15T05:51:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":false,"email":"[email protected]","identity":"surgical-and-experimental-pathology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"saep","sideBox":"Learn more about [Surgical and Experimental Pathology](http://surgexppathol.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/SAEP/default.aspx","title":"Surgical and Experimental Pathology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0f00a5b9-882d-4609-aa19-806ebd2bf433","owner":[],"postedDate":"August 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-30T13:39:13+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-28 17:57:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7378655","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7378655","identity":"rs-7378655","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}