Case Report of Refractory advanced thyroid Oncocytic carcinoma

Case Report of Refractory advanced thyroid Oncocytic carcinoma | 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 Case Report of Refractory advanced thyroid Oncocytic carcinoma Mengsong Liu, Zhenying Cai, Jianyong Zhang, Ming Cai This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9014044/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background: Thyroid Oncocytic carcinoma (OCA), a rare differentiated thyroid carcinoma subtype, accounts for approximately 3 - 7% of cases. This malignancy is high aggressive, frequently metastasizing, and poorly responsive to radioactive iodine therapy. Standardized treatment protocols are currently lacking because its rarity. Method: We report a 67-year-old female with a >9 cm thyroid tumor, lung/bone metastases. and a history of 7-year nodules and hoarseness. Histopathology confirmed OCA with vascular invasion. Due to inoperability and financial constraints, we administered lenvatinib (16 mg/d) and sorafenib (0.4 g BID). Results: Imaging showed disease control, enabling > 1-year survival. Tyrosine kinase inhibitors (sorafenib and Lenvatinib) effectively control advanced OCA progression. Conclusion: This case underscores OCA’s aggressive and highlights targeted therapy as a viable option for metastatic/recrudescent disease, prolonging survival where surgery is not feasible. This adds to limited literature on advanced OCA management. advanced thyroid oncocytic carcinoma Lenvatinib Sorafenib Case report Figures Figure 1 Figure 2 Introduction Thyroid cancer as one of the most common malignant tumor of the endocrine system 1 . Its global incidence has risen over recent decades, and it now constitutes about 3% of all cancer diagnoses worldwide 2 . Thyroid oncocytic carcinoma (OCA), historically termed "Hürthle cell" carcinoma, is a rare subtype that accounts for 3% to 7% of differentiated thyroid follicular carcinomas 3 . The 2022 fifth edition of the World Health Organization (WHO) Classification of Endocrine Tumors formally recognized thyroid oncocytic carcinoma as a distinct pathological entity 4 . This malignancy originates from oncocytic follicular cells, defined by containing over 75% oncocytic cells, and is characterized by abundant granular eosinophilic cytoplasm rich in mitochondria, large round nuclei, and prominent nucleoli 5 . OCA demonstrates greater aggressiveness, a higher risk of recurrence and metastasis, and a consequently poorer prognosis than other differentiated thyroid cancers 6 . Prognostic factors include age, tumor size, TNM stage, and gender 7 . The disease is marked by high aggressiveness, frequent metastasis, and poor responsiveness to radioactive iodine therapy 8 – 10 . No standardized treatment protocols exist, largely due to its rarity. Tumor extension and recurrence are strongly linked to poor prognosis and increased mortality, while therapeutic options for recurrent disease remain limited 11 . We report an extremely rare case of a giant thyroid tumor in a 67-year-old female, detailing her treatment with sorafenib and lenvatinib and her subsequent follow-up. Case presentation A 67-year-old woman presented with large bilateral neck masses. She had undergone thyroid surgery at another hospital in 2012, with satisfactory postoperative recovery. In 2017, bilateral thyroid nodules were identified, accompanied by a three-year history of hoarseness. A tender thyroid mass was palpable in the suprasternal notch. Ultrasound examination on March 19, 2024, revealed a large, solid, heterogeneously hypoechoic mass in the left thyroid lobe extending into the suprasternal notch, measuring approximately 9.3*5.7*9.5 cm with indistinct borders and abundant internal blood flow. A solid nodule in the right lobe, measuring approximately 3.2*1.8*2.4 cm, was irregularly shaped, heterogeneously hypoechoic, and also demonstrated internal vascularity. Bilateral level IV cervical lymph nodes were identified, the largest measuring approximately 1.0*0.8 cm, exhibiting a hypoechoic, heterogeneous appearance with visible blood flow. Due to the lesion's marked vascularity and the absence of a safe needle path, ultrasound-guided fine-needle aspiration was not performed. Fiberoptic nasopharyngoscopy revealed vocal cord paralysis. Contrast-enhanced CT of the neck and chest demonstrated multiple masses in the left parapharyngeal space, anterior cervical space, and anterior mediastinum. The largest mass, located in the anterior mediastinum (Fig. 1 A), measured 7.0*12.8 cm in maximum cross-section with an apical-basal diameter of approximately 11.4 cm, exhibiting an irregular shape and poorly defined margins. It showed marked heterogeneous enhancement with non-enhancing patchy hypodense areas (Fig. 1 B). The arterial phase revealed multiple thickened, tortuous vessels traversing the lesions, some supplied by the left subclavian artery and others draining into the internal jugular vein. Lytic destructive changes were present in the bilateral first ribs and sternum (Fig. 1 C). Several lesions were indistinct from the thyroid gland and surrounded the trachea, causing slight compression and displacement. The left thyroid lobe was poorly visualized. Multiple low-density nodules were noted in the right lobe, the largest measuring 2.2*1.8 cm. Multiple small, homogenously enhancing lymph nodes were visible bilaterally in the neck. Multiple variably sized nodular opacities were observed in both lungs (Fig. 1 D); the largest, located in the anterior segment of the right upper lobe, measured approximately 0.8 cm in diameter and demonstrated enhancement. A few cord-like opacities with indistinct margins were seen in the middle and lower lobes of the right lung and in the left lung. The thoracic spine was deformed to the right. The C3, C6, and C7 vertebral bodies were flattened, with osteolytic destruction at C3 and C4. Laboratory tests revealed elevated thyroid peroxidase antibodies (92.90 IU/mL; normal: 0–34 IU/mL) and thyroglobulin (> 500.00 ng/mL; normal: 3.5–77 ng/mL), while thyroid function and calcitonin levels were normal. Other hematological parameters showed no significant abnormalities. Physical examination revealed a 5 cm scar on the anterior neck. Multiple neck masses were palpable, including a 10*6 cm, non-tender, firm, and poorly mobile mass on the left neck without skin changes. A separate anterior neck mass, approximately 10*12 cm, was markedly tender, highly vascular, firm, and poorly mobile, with no associated erythema, ulceration, or warmth. A right neck mass, approximately 3*3 cm, was non-tender, firm, and poorly mobile. The trachea was deviated to the left. Treatment and subsequent follow-up situation Intraoperative biopsy pathology confirmed eosinophilic thyroid carcinoma with focal necrosis, invasion into surrounding fibrous and adipose tissue, and intravascular tumor thrombi. Given the tumor size, metastatic status, and the patient's financial constraints, based on clinical judgment, we initiated a combination therapy regimen of lenvatinib mesylate (16 mg daily) and sorafenib tosylate (0.4 mg twice daily in 30-day cycles) in April 2024. A non-contrast neck CT scan with 3D reconstruction on May 20, 2025, revealed multiple masses in the left parapharyngeal space, anterior cervical space, and anterior mediastinum. The largest mass, situated in the left neck, measured 9.5*7.2 cm in cross-section with an approximate vertical diameter of 10.2 cm. This mass was irregular with poorly defined borders and contained multiple patchy areas of slightly increased density. Bilateral osteolytic destruction was present in the first ribs and sternum. The lesions demonstrated indistinct borders with the thyroid gland and esophagus, encircling and compressing the trachea and esophagus to cause displacement. Local skin discontinuity was evident. The left thyroid lobe was poorly visualized, whereas the right lobe showed heterogeneous density with low-density areas. Multiple lymph nodes were present bilaterally, the largest with a short-axis diameter of approximately 1.1 cm. Lytic lesions were observed in T7, the C2-4 vertebrae and their appendages, and the C3 vertebral body was compressed and flattened. Discussion Thyroid oncocytic carcinoma (OCA) is a rare malignant tumor derived from thyroid follicular cells, characterized by abundant eosinophilic granules within the cytoplasm. This tumor exhibits high invasiveness and a significant risk of recurrence, posing substantial challenges for clinical management. Diagnosis primarily relies on fine-needle aspiration cytology (FNA), though its accuracy is limited by the morphological diversity of Hürthle cells 12 . Integrating molecular marker analysis with imaging studies can enhance diagnostic reliability. The treatment approach for OCA generally aligns with that of other differentiated thyroid cancers 6 , 13 , 14 . Given its distinct biological behavior, particularly regarding metastasis and recurrence, management requires a more individualized strategy 15 . Surgical resection constitutes the primary treatment for OCA 16 – 18 . Research indicates that for tumors exceeding 4 cm in diameter or presenting with lymph node metastasis, total thyroidectomy is recommended to achieve maximal tumor removal and mitigate recurrence risk 17 . The aggressive and metastatic potential of OCA makes early surgical intervention especially critical. In this case, however, the patient presented at a stage where radical surgery was no longer feasible. Radioactive iodine therapy (RAI) is a standard adjuvant treatment for thyroid cancer, particularly following surgery for residual disease or distant metastases 19 – 21 . While effective for many thyroid cancer subtypes, RAI demonstrates lower uptake and diminished therapeutic efficacy in patients with OCA 22 . This poor response likely stems from the distinct biological characteristics of OCA. Consequently, although RAI remains a consideration for postoperative residual lesions, its clinical benefit is typically inferior to that observed in other thyroid cancer types. In this case, the absence of radical surgery precluded the administration of RAI. Targeted therapies are increasingly important for treating OCA, particularly in advanced or recurrent disease. Multi-kinase inhibitors like sorafenib and lenvatinib have been used in this setting 23 . These agents inhibit multiple signaling pathways involved in tumor proliferation and metastasis, which can extend progression-free survival 24 . The tyrosine kinase inhibitors sorafenib and lenvatinib, both oral multi-kinase inhibitors targeting VEGFR, remain the only approved pharmacological treatments for advanced thyroid oncocytic carcinoma 17 , 25 . Immunotherapy directed at the PD-1/PD-L1 axis has also shown promise, demonstrating tumor growth suppression in preclinical studies and clinical trials for aggressive thyroid cancers 26 , 27 . The patient presented with a seven-year history, a tumor exceeding 9 cm in maximum diameter, and locally advanced symptoms including hoarseness and tracheal compression, indicating a high tumor burden and advanced disease stage. Given the patient's age and financial constraints, and in full respect of the patient's and family's wishes, genetic testing was not performed. Empirical therapy was initiated with lenvatinib mesylate (16 mg daily) and sorafenib tosylate (0.4 mg twice daily on a 30-day cycle). Despite subsequent distant metastasis and recurrence, this combination therapy sustained survival for over one year. This experience suggests that for patients who are not surgical candidates, targeted therapies such as these can be considered to achieve meaningful therapeutic effect and prolong survival. In summary, this case illustrates the clinical activity of sorafenib and lenvatinib in a patient with advanced, multifocal metastatic thyroid oncocytic carcinoma. Declarations Ethics approval The studies involving humans were approved by Ethics Committee of Guizhou Provincial People’s Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. Consent to publish Written informed consent for participation in this study was provided by the participants’ legal guardians/next of kin. Authorship contribution statement Liu Mengsongand Cai Zhenying: analyzed the date, was responsible for collecting the relevant literature, and wrote the original the manuscript. Zhang Jianyong and Cai Ming: contributed to funding acquisition, project administration, designed the study and revised this manuscript. All authors have read and approved the final manuscript, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data. Funding The authors declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China under Grand 82502837 (ZJ), QiankeheLC-2026-001 (JZ) and the health research project of Guizhou Province gzwkj2025-302 (JZ). Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments We thank the patient for granting permission to publish this information. Fig. 2 are created by BioRender.com. Data Availability Statement The raw data supporting the conclusions of this article will be made available by the corresponding author, without undue reservation. Clinical trial number Not applicable. References Wan Y, Li G, Cui G, Duan S, Chang S. Reprogramming of thyroid cancer metabolism: from mechanism to therapeutic strategy. Mol Cancer. 2025;24(1):74–103. Trigo JM, Capdevila J, Grande E, Grau J, Lianes P. Thyroid cancer: SEOM clinical guidelines. Clin Transl Oncol. 2014;16(12):1035–42. Li W, Xia S, Aronova A, et al. CHL1 expression differentiates hürthle cell carcinoma from benign hürthle cell nodules. J Surg Oncol. 2018;118(6):1042–9. Rossi ED, Baloch Z. The impact of the 2022 WHO classification of thyroid neoplasms on everyday practice of cytopathology. Endocr Pathol. 2023;34(1):23–33. Tallini G, Carcangiu ML, Rosai J. Oncocytic neoplasms of the thyroid gland. Acta Pathol Jpn. 1992;42(5):305–15. Ahmadi S, Stang M, Jiang X, Sosa JA. Hürthle cell carcinoma: current perspectives. OncoTargets Ther 2016;Volume 9:6873–84. Kushchayeva Y, Duh Q-Y, Kebebew E, Clark OH. Prognostic indications for hürthle cell cancer. World J Surg. 2004;28(12):1266–70. Ding L, Jiang Y, Yang W. Approach the invasive potential with hurthle cell tumors of thyroid. Pathol Oncol Res. 2019;25(2):697–701. Wenter V, Albert NL, Unterrainer M, et al. Clinical impact of follicular oncocytic (hürthle cell) carcinoma in comparison with corresponding classical follicular thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2021;48(2):449–60. Yutan E, Clark O. Hürthle cell carcinoma. Curr Treat Options Oncol. 2001;2(4):331–5. Wenter V, Albert NL, Unterrainer M, et al. Clinical impact of follicular oncocytic (hürthle cell) carcinoma in comparison with corresponding classical follicular thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2021;48(2):449–60. Ringel MD, Sosa JA, Baloch Z, et al. 2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer. Thyroid®. 2025;35(8):841–985. McFadden DG, Sadow PM. Genetics, diagnosis, and management of hürthle cell thyroid neoplasms. Front Endocrinol. 2021;12:696386. Khafif A, Khafif RA, Attie JN. Hürthle cell carcinoma: a malignancy of low-grade potential. Head Neck. 1999;21(6):506–11. Bischoff LA, Ganly I, Fugazzola L, et al. Molecular alterations and comprehensive clinical management of oncocytic thyroid carcinoma: a review and multidisciplinary 2023 update. JAMA Otolaryngol Neck Surg. 2024;150(3):265–73. Coca-Pelaz A, Rodrigo JP, Shah JP, et al. Hürthle Cell Carcinoma of the Thyroid Gland: Systematic Review and Meta-analysis. Adv Ther. 2021;38(10):5144–64. Cabanillas ME, McFadden DG, Durante C. Thyroid cancer Lancet. 2016;388(10061):2783–95. Sloan DA, Vasconez HC, Weeks JA. Mediastinal dissection and reconstruction for recurrent hürthle cell carcinoma of the thyroid. Head Neck. 1994;16(1):64–71. Jillard CL, Youngwirth L, Scheri RP, Roman S, Sosa JA. Radioactive iodine treatment is associated with improved survival for patients with hürthle cell carcinoma. Thyroid. 2016;26(7):959–64. Zhang K, Wang X, Wei T, Li Z, Zhu J, Chen Y-W. Radioactive iodine therapy improves overall survival outcome in oncocytic carcinoma of the thyroid by reducing death risks from noncancer causes: a competing risk analysis of 4641 patients. Head Neck. 2024;46(10):2550–68. Albalawi IA, Mirghani HO. Radioactive iodine timing in differentiated thyroid carcinoma: a meta-analysis. Teikyo Med J 2021;44(05). Wang X, Zheng X, Zhu J, Li Z, Wei T. Radioactive iodine therapy does not improve cancer-specific survival in hürthle cell carcinoma of the thyroid. J Clin Endocrinol Metab. 2022;107(11):3144–51. Kim M, Jin M, Jeon MJ, et al. Lenvatinib compared with sorafenib as a first-line treatment for radioactive iodine-refractory, progressive, differentiated thyroid carcinoma: real-world outcomes in a multicenter retrospective cohort study. Thyroid. 2023;33(1):91–9. Wilson L, Huang W, Chen L, Ting J, Cao V. Cost effectiveness of lenvatinib, sorafenib and placebo in treatment of radioiodine-refractory differentiated thyroid cancer. Thyroid. 2017;27(8):1043–52. Kreissl MC, Janssen MJR, Nagarajah J. Current treatment strategies in metastasized differentiated thyroid cancer. J Nucl Med. 2019;60(1):9–15. Doerfler WR, Nikitski AV, Morariu EM, et al. Molecular alterations in hürthle cell nodules and preoperative cancer risk. Endocr Relat Cancer. 2021;28(5):301–9. He H, Xu T, Li P, Jia G, Li X, Song Q. Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Positive Patient With Refractory Metastatic Thyroid Hürthle Cell Carcinoma: A Case Report and Literature Review. Front Oncol. 2021;11:782646. Additional Declarations No competing interests reported. Supplementary Files CAREchecklistEnglish2013.pdf Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 30 Mar, 2026 Reviews received at journal 28 Mar, 2026 Reviews received at journal 25 Mar, 2026 Reviewers agreed at journal 20 Mar, 2026 Reviewers agreed at journal 18 Mar, 2026 Reviewers agreed at journal 18 Mar, 2026 Reviewers invited by journal 18 Mar, 2026 Editor invited by journal 18 Mar, 2026 Editor assigned by journal 14 Mar, 2026 Submission checks completed at journal 12 Mar, 2026 First submitted to journal 12 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9014044","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":609527860,"identity":"ba705b0f-6636-4bc5-9717-29f1d4fe25a0","order_by":0,"name":"Mengsong Liu","email":"","orcid":"","institution":"Guiyang Medical University","correspondingAuthor":false,"prefix":"","firstName":"Mengsong","middleName":"","lastName":"Liu","suffix":""},{"id":609527869,"identity":"d90de263-b6ab-4366-a249-9216271b1230","order_by":1,"name":"Zhenying Cai","email":"","orcid":"","institution":"Guiyang Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhenying","middleName":"","lastName":"Cai","suffix":""},{"id":609527873,"identity":"ecabb60c-e9fe-44f6-ba7d-8b6c12ad58ca","order_by":2,"name":"Jianyong Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYDACCRDBwyDHz97Y+OADKVqMJXsONxvOIF4LA0PihhvpbdIcxOiQn9387OEXmcOJDTcfNkgzMNjJ6TYQ0MI455i5sQzPYePG2YkNxgUMycZmBwhoYZZIMJOW4Dks2yyd2JA8g+FA4jZCWtgk0r+BtDC2SR5sOMxDjBYeiRwzyQ88hxV7JBgbm4nSIiGRUybNwJNuLMGT2Mw4w4AIv8jPSN8m+bPHWs7++PHnPz5U2MkR1AICzLw9zVCmARHKQYDxx486IpWOglEwCkbBiAQACqtCQwC8QCgAAAAASUVORK5CYII=","orcid":"","institution":"Chongqing Cancer Hospital","correspondingAuthor":true,"prefix":"","firstName":"Jianyong","middleName":"","lastName":"Zhang","suffix":""},{"id":609527875,"identity":"9129554d-4862-412a-977d-dff512aa26c2","order_by":3,"name":"Ming Cai","email":"","orcid":"","institution":"Chongqing Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ming","middleName":"","lastName":"Cai","suffix":""}],"badges":[],"createdAt":"2026-03-02 22:23:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9014044/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9014044/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105198314,"identity":"7f6807c6-0095-4c62-bfb2-7ceb74e30e86","added_by":"auto","created_at":"2026-03-23 10:42:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2333568,"visible":true,"origin":"","legend":"\u003cp\u003eA The largest mass located in the anterior mediastinum. B. Enhanced CT of the mass. C. Bilateral first ribs and sternum show signs of dissolution and destructive changes. D. Multiple nodular shadows of varying sizes are visible in both lungs.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-9014044/v1/d651c82124de2434e8064166.png"},{"id":105198238,"identity":"b6a9993a-d71c-4cab-9ee6-a56f2263a253","added_by":"auto","created_at":"2026-03-23 10:42:44","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":198811,"visible":true,"origin":"","legend":"\u003cp\u003eDiagnostic and Treatment Flowchart, Created with BioRender.com\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9014044/v1/6dfc4fe30de02490f1c635a8.jpg"},{"id":105198339,"identity":"ad032489-6dc4-40c8-bf9e-81f362f0d909","added_by":"auto","created_at":"2026-03-23 10:43:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3154345,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9014044/v1/0120ffd7-d6b4-4916-a5ef-b7f06a489dcc.pdf"},{"id":105198239,"identity":"3c36dde6-bffe-46bc-a424-0cf31bc04d1d","added_by":"auto","created_at":"2026-03-23 10:42:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":832719,"visible":true,"origin":"","legend":"","description":"","filename":"CAREchecklistEnglish2013.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9014044/v1/d263d257393686713377e2c1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Case Report of Refractory advanced thyroid Oncocytic carcinoma","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThyroid cancer as one of the most common malignant tumor of the endocrine system\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Its global incidence has risen over recent decades, and it now constitutes about 3% of all cancer diagnoses worldwide\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Thyroid oncocytic carcinoma (OCA), historically termed \"H\u0026uuml;rthle cell\" carcinoma, is a rare subtype that accounts for 3% to 7% of differentiated thyroid follicular carcinomas\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. The 2022 fifth edition of the World Health Organization (WHO) Classification of Endocrine Tumors formally recognized thyroid oncocytic carcinoma as a distinct pathological entity\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. This malignancy originates from oncocytic follicular cells, defined by containing over 75% oncocytic cells, and is characterized by abundant granular eosinophilic cytoplasm rich in mitochondria, large round nuclei, and prominent nucleoli\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. OCA demonstrates greater aggressiveness, a higher risk of recurrence and metastasis, and a consequently poorer prognosis than other differentiated thyroid cancers\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Prognostic factors include age, tumor size, TNM stage, and gender\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. The disease is marked by high aggressiveness, frequent metastasis, and poor responsiveness to radioactive iodine therapy\u003csup\u003e\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. No standardized treatment protocols exist, largely due to its rarity. Tumor extension and recurrence are strongly linked to poor prognosis and increased mortality, while therapeutic options for recurrent disease remain limited\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. We report an extremely rare case of a giant thyroid tumor in a 67-year-old female, detailing her treatment with sorafenib and lenvatinib and her subsequent follow-up.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 67-year-old woman presented with large bilateral neck masses. She had undergone thyroid surgery at another hospital in 2012, with satisfactory postoperative recovery. In 2017, bilateral thyroid nodules were identified, accompanied by a three-year history of hoarseness. A tender thyroid mass was palpable in the suprasternal notch. Ultrasound examination on March 19, 2024, revealed a large, solid, heterogeneously hypoechoic mass in the left thyroid lobe extending into the suprasternal notch, measuring approximately 9.3*5.7*9.5 cm with indistinct borders and abundant internal blood flow. A solid nodule in the right lobe, measuring approximately 3.2*1.8*2.4 cm, was irregularly shaped, heterogeneously hypoechoic, and also demonstrated internal vascularity. Bilateral level IV cervical lymph nodes were identified, the largest measuring approximately 1.0*0.8 cm, exhibiting a hypoechoic, heterogeneous appearance with visible blood flow. Due to the lesion's marked vascularity and the absence of a safe needle path, ultrasound-guided fine-needle aspiration was not performed. Fiberoptic nasopharyngoscopy revealed vocal cord paralysis. Contrast-enhanced CT of the neck and chest demonstrated multiple masses in the left parapharyngeal space, anterior cervical space, and anterior mediastinum. The largest mass, located in the anterior mediastinum (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA), measured 7.0*12.8 cm in maximum cross-section with an apical-basal diameter of approximately 11.4 cm, exhibiting an irregular shape and poorly defined margins. It showed marked heterogeneous enhancement with non-enhancing patchy hypodense areas (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). The arterial phase revealed multiple thickened, tortuous vessels traversing the lesions, some supplied by the left subclavian artery and others draining into the internal jugular vein. Lytic destructive changes were present in the bilateral first ribs and sternum (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). Several lesions were indistinct from the thyroid gland and surrounded the trachea, causing slight compression and displacement. The left thyroid lobe was poorly visualized. Multiple low-density nodules were noted in the right lobe, the largest measuring 2.2*1.8 cm. Multiple small, homogenously enhancing lymph nodes were visible bilaterally in the neck. Multiple variably sized nodular opacities were observed in both lungs (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD); the largest, located in the anterior segment of the right upper lobe, measured approximately 0.8 cm in diameter and demonstrated enhancement. A few cord-like opacities with indistinct margins were seen in the middle and lower lobes of the right lung and in the left lung. The thoracic spine was deformed to the right. The C3, C6, and C7 vertebral bodies were flattened, with osteolytic destruction at C3 and C4. Laboratory tests revealed elevated thyroid peroxidase antibodies (92.90 IU/mL; normal: 0\u0026ndash;34 IU/mL) and thyroglobulin (\u0026gt;\u0026thinsp;500.00 ng/mL; normal: 3.5\u0026ndash;77 ng/mL), while thyroid function and calcitonin levels were normal. Other hematological parameters showed no significant abnormalities. Physical examination revealed a 5 cm scar on the anterior neck. Multiple neck masses were palpable, including a 10*6 cm, non-tender, firm, and poorly mobile mass on the left neck without skin changes. A separate anterior neck mass, approximately 10*12 cm, was markedly tender, highly vascular, firm, and poorly mobile, with no associated erythema, ulceration, or warmth. A right neck mass, approximately 3*3 cm, was non-tender, firm, and poorly mobile. The trachea was deviated to the left.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eTreatment and subsequent follow-up situation\u003c/h2\u003e \u003cp\u003eIntraoperative biopsy pathology confirmed eosinophilic thyroid carcinoma with focal necrosis, invasion into surrounding fibrous and adipose tissue, and intravascular tumor thrombi. Given the tumor size, metastatic status, and the patient's financial constraints, based on clinical judgment, we initiated a combination therapy regimen of lenvatinib mesylate (16 mg daily) and sorafenib tosylate (0.4 mg twice daily in 30-day cycles) in April 2024. A non-contrast neck CT scan with 3D reconstruction on May 20, 2025, revealed multiple masses in the left parapharyngeal space, anterior cervical space, and anterior mediastinum. The largest mass, situated in the left neck, measured 9.5*7.2 cm in cross-section with an approximate vertical diameter of 10.2 cm. This mass was irregular with poorly defined borders and contained multiple patchy areas of slightly increased density. Bilateral osteolytic destruction was present in the first ribs and sternum. The lesions demonstrated indistinct borders with the thyroid gland and esophagus, encircling and compressing the trachea and esophagus to cause displacement. Local skin discontinuity was evident. The left thyroid lobe was poorly visualized, whereas the right lobe showed heterogeneous density with low-density areas. Multiple lymph nodes were present bilaterally, the largest with a short-axis diameter of approximately 1.1 cm. Lytic lesions were observed in T7, the C2-4 vertebrae and their appendages, and the C3 vertebral body was compressed and flattened.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThyroid oncocytic carcinoma (OCA) is a rare malignant tumor derived from thyroid follicular cells, characterized by abundant eosinophilic granules within the cytoplasm. This tumor exhibits high invasiveness and a significant risk of recurrence, posing substantial challenges for clinical management. Diagnosis primarily relies on fine-needle aspiration cytology (FNA), though its accuracy is limited by the morphological diversity of H\u0026uuml;rthle cells\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Integrating molecular marker analysis with imaging studies can enhance diagnostic reliability.\u003c/p\u003e \u003cp\u003eThe treatment approach for OCA generally aligns with that of other differentiated thyroid cancers\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Given its distinct biological behavior, particularly regarding metastasis and recurrence, management requires a more individualized strategy\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Surgical resection constitutes the primary treatment for OCA\u003csup\u003e\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Research indicates that for tumors exceeding 4 cm in diameter or presenting with lymph node metastasis, total thyroidectomy is recommended to achieve maximal tumor removal and mitigate recurrence risk\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. The aggressive and metastatic potential of OCA makes early surgical intervention especially critical. In this case, however, the patient presented at a stage where radical surgery was no longer feasible. Radioactive iodine therapy (RAI) is a standard adjuvant treatment for thyroid cancer, particularly following surgery for residual disease or distant metastases\u003csup\u003e\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. While effective for many thyroid cancer subtypes, RAI demonstrates lower uptake and diminished therapeutic efficacy in patients with OCA\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. This poor response likely stems from the distinct biological characteristics of OCA. Consequently, although RAI remains a consideration for postoperative residual lesions, its clinical benefit is typically inferior to that observed in other thyroid cancer types. In this case, the absence of radical surgery precluded the administration of RAI. Targeted therapies are increasingly important for treating OCA, particularly in advanced or recurrent disease. Multi-kinase inhibitors like sorafenib and lenvatinib have been used in this setting\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. These agents inhibit multiple signaling pathways involved in tumor proliferation and metastasis, which can extend progression-free survival\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. The tyrosine kinase inhibitors sorafenib and lenvatinib, both oral multi-kinase inhibitors targeting VEGFR, remain the only approved pharmacological treatments for advanced thyroid oncocytic carcinoma\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Immunotherapy directed at the PD-1/PD-L1 axis has also shown promise, demonstrating tumor growth suppression in preclinical studies and clinical trials for aggressive thyroid cancers\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe patient presented with a seven-year history, a tumor exceeding 9 cm in maximum diameter, and locally advanced symptoms including hoarseness and tracheal compression, indicating a high tumor burden and advanced disease stage. Given the patient's age and financial constraints, and in full respect of the patient's and family's wishes, genetic testing was not performed. Empirical therapy was initiated with lenvatinib mesylate (16 mg daily) and sorafenib tosylate (0.4 mg twice daily on a 30-day cycle). Despite subsequent distant metastasis and recurrence, this combination therapy sustained survival for over one year. This experience suggests that for patients who are not surgical candidates, targeted therapies such as these can be considered to achieve meaningful therapeutic effect and prolong survival.\u003c/p\u003e \u003cp\u003eIn summary, this case illustrates the clinical activity of sorafenib and lenvatinib in a patient with advanced, multifocal metastatic thyroid oncocytic carcinoma.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe studies involving humans were approved by Ethics Committee of Guizhou Provincial People’s Hospital. The studies were conducted in accordance with the local legislation and institutional requirements.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for participation in this study was provided by the participants’ legal guardians/next of kin.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthorship contribution statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLiu Mengsongand Cai Zhenying:\u003c/strong\u003e analyzed the date, was responsible for collecting the relevant literature, and wrote the original the manuscript.\u0026nbsp;\u003cstrong\u003eZhang Jianyong and Cai Ming:\u003c/strong\u003e contributed to funding acquisition, project administration, designed the study and revised this manuscript. All authors have read and approved the final manuscript, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China under Grand 82502837 (ZJ), QiankeheLC-2026-001 (JZ) and the health research project of Guizhou Province gzwkj2025-302 (JZ).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the patient for granting permission to publish this information. Fig. 2 are created by BioRender.com.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe raw data supporting the conclusions of this article will be made available by the corresponding author, without undue reservation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWan Y, Li G, Cui G, Duan S, Chang S. Reprogramming of thyroid cancer metabolism: from mechanism to therapeutic strategy. Mol Cancer. 2025;24(1):74\u0026ndash;103.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTrigo JM, Capdevila J, Grande E, Grau J, Lianes P. Thyroid cancer: SEOM clinical guidelines. Clin Transl Oncol. 2014;16(12):1035\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi W, Xia S, Aronova A, et al. CHL1 expression differentiates h\u0026uuml;rthle cell carcinoma from benign h\u0026uuml;rthle cell nodules. J Surg Oncol. 2018;118(6):1042\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRossi ED, Baloch Z. The impact of the 2022 WHO classification of thyroid neoplasms on everyday practice of cytopathology. Endocr Pathol. 2023;34(1):23\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTallini G, Carcangiu ML, Rosai J. Oncocytic neoplasms of the thyroid gland. Acta Pathol Jpn. 1992;42(5):305\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhmadi S, Stang M, Jiang X, Sosa JA. H\u0026uuml;rthle cell carcinoma: current perspectives. OncoTargets Ther 2016;Volume 9:6873\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKushchayeva Y, Duh Q-Y, Kebebew E, Clark OH. Prognostic indications for h\u0026uuml;rthle cell cancer. World J Surg. 2004;28(12):1266\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDing L, Jiang Y, Yang W. Approach the invasive potential with hurthle cell tumors of thyroid. Pathol Oncol Res. 2019;25(2):697\u0026ndash;701.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWenter V, Albert NL, Unterrainer M, et al. Clinical impact of follicular oncocytic (h\u0026uuml;rthle cell) carcinoma in comparison with corresponding classical follicular thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2021;48(2):449\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYutan E, Clark O. H\u0026uuml;rthle cell carcinoma. Curr Treat Options Oncol. 2001;2(4):331\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWenter V, Albert NL, Unterrainer M, et al. Clinical impact of follicular oncocytic (h\u0026uuml;rthle cell) carcinoma in comparison with corresponding classical follicular thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2021;48(2):449\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRingel MD, Sosa JA, Baloch Z, et al. 2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer. Thyroid\u0026reg;. 2025;35(8):841\u0026ndash;985.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcFadden DG, Sadow PM. Genetics, diagnosis, and management of h\u0026uuml;rthle cell thyroid neoplasms. Front Endocrinol. 2021;12:696386.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhafif A, Khafif RA, Attie JN. H\u0026uuml;rthle cell carcinoma: a malignancy of low-grade potential. Head Neck. 1999;21(6):506\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBischoff LA, Ganly I, Fugazzola L, et al. Molecular alterations and comprehensive clinical management of oncocytic thyroid carcinoma: a review and multidisciplinary 2023 update. JAMA Otolaryngol Neck Surg. 2024;150(3):265\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCoca-Pelaz A, Rodrigo JP, Shah JP, et al. H\u0026uuml;rthle Cell Carcinoma of the Thyroid Gland: Systematic Review and Meta-analysis. Adv Ther. 2021;38(10):5144\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCabanillas ME, McFadden DG, Durante C. Thyroid cancer Lancet. 2016;388(10061):2783\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSloan DA, Vasconez HC, Weeks JA. Mediastinal dissection and reconstruction for recurrent h\u0026uuml;rthle cell carcinoma of the thyroid. Head Neck. 1994;16(1):64\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJillard CL, Youngwirth L, Scheri RP, Roman S, Sosa JA. Radioactive iodine treatment is associated with improved survival for patients with h\u0026uuml;rthle cell carcinoma. Thyroid. 2016;26(7):959\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang K, Wang X, Wei T, Li Z, Zhu J, Chen Y-W. Radioactive iodine therapy improves overall survival outcome in oncocytic carcinoma of the thyroid by reducing death risks from noncancer causes: a competing risk analysis of 4641 patients. Head Neck. 2024;46(10):2550\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlbalawi IA, Mirghani HO. Radioactive iodine timing in differentiated thyroid carcinoma: a meta-analysis. Teikyo Med J 2021;44(05).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang X, Zheng X, Zhu J, Li Z, Wei T. Radioactive iodine therapy does not improve cancer-specific survival in h\u0026uuml;rthle cell carcinoma of the thyroid. J Clin Endocrinol Metab. 2022;107(11):3144\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim M, Jin M, Jeon MJ, et al. Lenvatinib compared with sorafenib as a first-line treatment for radioactive iodine-refractory, progressive, differentiated thyroid carcinoma: real-world outcomes in a multicenter retrospective cohort study. Thyroid. 2023;33(1):91\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilson L, Huang W, Chen L, Ting J, Cao V. Cost effectiveness of lenvatinib, sorafenib and placebo in treatment of radioiodine-refractory differentiated thyroid cancer. Thyroid. 2017;27(8):1043\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKreissl MC, Janssen MJR, Nagarajah J. Current treatment strategies in metastasized differentiated thyroid cancer. J Nucl Med. 2019;60(1):9\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDoerfler WR, Nikitski AV, Morariu EM, et al. Molecular alterations in h\u0026uuml;rthle cell nodules and preoperative cancer risk. Endocr Relat Cancer. 2021;28(5):301\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHe H, Xu T, Li P, Jia G, Li X, Song Q. Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Positive Patient With Refractory Metastatic Thyroid H\u0026uuml;rthle Cell Carcinoma: A Case Report and Literature Review. Front Oncol. 2021;11:782646.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"advanced thyroid oncocytic carcinoma, Lenvatinib, Sorafenib, Case report","lastPublishedDoi":"10.21203/rs.3.rs-9014044/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9014044/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eThyroid Oncocytic carcinoma (OCA), a rare differentiated thyroid carcinoma subtype, accounts for approximately 3 - 7% of cases. This malignancy is high aggressive, frequently metastasizing, and poorly responsive to radioactive iodine therapy. Standardized treatment protocols are currently lacking because its rarity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod: \u003c/strong\u003eWe report a 67-year-old female with a \u0026gt;9 cm thyroid tumor, lung/bone metastases. and a history of 7-year nodules and hoarseness. Histopathology confirmed OCA with vascular invasion. Due to inoperability and financial constraints, we administered lenvatinib (16 mg/d) and sorafenib (0.4 g BID).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eImaging showed disease control, enabling \u0026gt; 1-year survival. Tyrosine kinase inhibitors (sorafenib and Lenvatinib) effectively control advanced OCA progression.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThis case underscores OCA’s aggressive and highlights targeted therapy\u003c/p\u003e\n\u003cp\u003eas a viable option for metastatic/recrudescent disease, prolonging survival where surgery is not feasible. This adds to limited literature on advanced OCA management.\u003c/p\u003e","manuscriptTitle":"Case Report of Refractory advanced thyroid Oncocytic carcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-23 10:39:02","doi":"10.21203/rs.3.rs-9014044/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-03-30T17:09:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-28T09:52:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-25T14:32:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"303824319684416145890798900617646053654","date":"2026-03-20T14:00:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"159339511640332962577316610506160776066","date":"2026-03-18T15:01:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"192041520175990239913904977197179128809","date":"2026-03-18T14:07:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-18T13:01:40+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-18T12:08:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-14T04:05:30+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-12T18:17:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Oncology","date":"2026-03-12T09:55:24+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bda465e3-677a-4fd7-930f-b8b8b2ded0fb","owner":[],"postedDate":"March 23rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-23T10:39:02+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-23 10:39:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9014044","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9014044","identity":"rs-9014044","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}