Simultaneous medullary thyroid carcinoma and primary non-small cell lung cancer: case report and literature review

Simultaneous medullary thyroid carcinoma and primary non-small cell lung cancer: case report and literature review | 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 Simultaneous medullary thyroid carcinoma and primary non-small cell lung cancer: case report and literature review Zhang Jianyong, Zheng Yu, An Xiaoxiao, Peng Yunsong This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5927634/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor, accounting for 1–2% of all thyroid cancers. MTC originates from the C cells or parafollicular cells, which produce and release two critical hormones called calcitonin (CT) and carcinoembryonic antigen (CEA), both serving as key tumor markers. Elevated basal serum calcitonin is critical for diagnosing lateral neck lymph node metastasis, with levels exceeding 500 pg/mL indicating distant metastasis. Persistently elevated postoperative calcitonin levels are associated with poorer prognosis. Surgical intervention remains the only curative treatment for MTC, though local metastasis is present in 50% of cases, and distant metastasis in 10–15%, commonly affecting the lungs, liver, and bones. When pulmonary nodules are detected in MTC patients, distinguishing whether they are metastatic is crucial. Here, we present a rare case of MTC accompanied by primary non-small cell lung cancer. A 55-year-old male patient presenting with cough and sputum was diagnosed with lung nodule measuring approximately 1.8 *1.5 cm and thyroid nodules via computed tomography (CT) examination. The right thyroid nodule was diagnosed as MTC based on fine needle aspiration (FNA) and calcitonin. In addition, pulmonary nodule was evaluated as the potential for malignant tumor and lung metastasis originating from MTC by thoracic surgeons and oncologists. Due to the difficulty of percutaneous biopsy, a thoracoscopic segmentectomy was performed. Intraoperative frozen section analysis revealed that the pulmonary nodules were non-small cell lung cancer, ruling out metastasis from MTC. Subsequently, the patient underwent a radical surgery for thyroid carcinoma, and follow-up showed no recurrence based on ultrasound and lab tests. We also review clinical findings from similar cases and discuss possible treatment strategies. Medullary thyroid carcinoma lung cancer surgery simultaneous cancer Figures Figure 1 Figure 2 Introduction Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from parafollicular cells that produce calcitonin, accounting for 1–2% of all thyroid cancers 1 . Of these cases, 75% occur sporadically, while the remaining 25% are associated with multiple endocrine neoplasia (MEN) type 2, a hereditary condition 2 , 3 . Sporadic MTC is often diagnosed at an advanced stage due to its presentation as a solitary thyroid nodule with few symptoms 2 . The diagnosis of sporadic MTC primarily relies on fine-needle aspiration (FNA) biopsy and immunohistochemical analysis 2 , 3 . However, the preoperative diagnosis of medullary thyroid carcinoma (MTC) is challenging due to its presentation as a solitary thyroid nodule and its relatively rare incidence. Complete surgical resection remains the only curative treatment for locoregional MTC, with the bone, lung, and liver being the most common sites of distant metastases 4 , 5 . Consequently, early diagnosis and detection of MTC are crucial for improving prognosis. Management of recurrent or metastatic MTC includes surgical resection, external beam radiation therapy (EBRT), and targeted local or systemic therapies. However, the treatment approach for patients with metastatic MTC is debated, as many display indolent disease over time 2 , 6 . Recent advances in molecular biology have enhanced our understanding of the genetic and epigenetic alterations driving MTC. Calcitonin and carcinoembryonic antigen (CEA), both secreted by C-cells, serve as key tumor markers for MTC. While calcitonin holds diagnostic significance, both basal and stimulated levels are utilized for follow-up and predicting disease progression 4 , 7 . Niederle et al. showed that basal serum calcitonin levels above 85 pg/mL in females and 100 pg/mL in males have 100% sensitivity for diagnosing lateral neck lymph node metastasis 8 . However, calcium-stimulated calcitonin levels did not enhance the accuracy of preoperative diagnosis. Notably, basal serum calcitonin levels are correlated with disease extent. Machens et al. demonstrated that thresholds of 20, 50, 200, and 500 pg/mL as indicative of metastasis in different neck regions and the upper mediastinum, respectively 7 . MTC’s high rate of central and distant metastases contributes to cancer-related mortality. Central and lateral cervical lymph node metastases occur in 11–14% of T1 patients and 86–93% of T4 patients 4 . Additionally, approximately 70% of sporadic MTC patients with palpable thyroid nodules already have cervical lymph node metastases, and 10% have distant metastases 9 , 10 . Common sites for hematogenous metastasis include the liver, bone, and lung, with lung metastases being the most frequent (52.2%) and bone metastases the most adverse 4 , 5 . We present a case of primary medullary thyroid carcinoma with non-small cell lung cancer, initially suspected as lung metastasis. Case description A 55-year-old male patient presented with cough and sputum was diagnosed with a 1.8*1.5 cm lung nodule and thyroid nodules via computed tomography (CT) examination over a six-day period. A subsequent thyroid ultrasound examination identified a 3.5*2.9 cm right thyroid nodule. Additionally, enhanced CT imaging revealed significant enlargement and calcification of the right thyroid gland (Shown in Fig. 1 ). Ultrasound-guided fine-needle aspiration detected malignant tumor cells, and immunocytochemistry showed positivity for calcitonin, carcinoembryonic antigen (CEA), CD56, chromogranin A (CgA), synaptophysin (Syn), and Ki-67. Furthermore, our findings indicated that serum calcitonin levels exceeded 2000 pg/mL, with CEA at 305 ng/mL. Notably, the patient, a non-smoker with no history of alcohol consumption, had no vocal cord paralysis on laryngoscopy. Preoperative thyroid function was normal, with standard levels of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH), and normal thyroid peroxidase and thyroglobulin antibodies. Prior to the surgical intervention, thoracic surgeons and oncologists evaluated the potential for malignancy in the pulmonary nodules and the likelihood of lung metastasis from thyroid cancer. Due to the infeasibility of percutaneous pulmonary puncture cytology, a thoracoscopic segmentectomy was conducted to biopsy the pulmonary nodules. Intraoperative frozen section analysis confirmed non-small cell lung cancer, ruling out metastatic thyroid cancer. Subsequently, the patient underwent a thoracic lymph node dissection encompassing levels II, IV, VII, IX, X, and XI, followed by a bilateral total thyroidectomy and bilateral neck lymph node (Ⅱ, Ⅲ, Ⅳ, Ⅵ) dissection. Postoperative pathological examination identified the pulmonary nodules as invasive lung squamous cell carcinoma, positive for P40 and P63, with 40% Ki67 expression. No malignancy was detected in the thoracic lymph nodes, though one cervical lymph node metastasis from MTC was detected among fifty examined. Three months post-surgery, serum levels of calcitonin and carcinoembryonic antigen (CEA), which serve as tumor markers for medullary thyroid carcinoma, returned to normal (Shown in Fig. 2 ). Discussion MTC is an uncommon and aggressive tumor that typically spreads to lymph nodes and, less frequently, to bones and lungs through lymphovascular pathways. Half of the patients present with local metastasis at diagnosis, while 10–15% have distant metastasis 5 , 11 . Surgery constitutes the only curative intervention for MTC, as MTC cells neither concentrate radioactive iodine nor respond to the modulation of thyroid-stimulating hormone (TSH) levels 5 , 12 . Complete surgical resection of the thyroid mass and locoregional metastasis remains the only curative approach for locoregional MTC. The initial standard treatment protocol for MTC involves a total thyroidectomy accompanied by neck lymph node dissection. Total thyroidectomy and bilateral central neck dissection (ND) are recommended for bilateral thyroid involvement or tumors ≥ 1 cm 2 , 3 . Nonetheless, the necessity of lateral neck dissection for patients without LN metastasis on preoperative US remains debated. Ipsilateral neck dissection (ND) is often based on intraoperative findings of central LN involvement. In localized disease, total thyroidectomy, central LN dissection, and lateral neck dissection (levels II–V) are advised 6 , 13 . According to the guidelines set forth by the American Thyroid Association (ATA) and the European Society for Medical Oncology (ESMO), contralateral ND should be considered if the basal serum calcitonin level exceeds 200 pg/mL and ipsilateral LN involvement is confirmed, despite negative contralateral findings on preoperative imaging 6 , 9 , 12 . In locally advanced or metastatic MTC, total thyroidectomy with lymph node dissection is recommended to preserve speech, swallowing, and parathyroid functions. Postoperative management is contingent upon the levels of serum calcitonin and CEA to identify any residual disease 2 , 13 . Total thyroidectomy with lymph node dissection is recommended to preserve speech, swallowing, and parathyroid function Current guidelines suggest measuring serum calcitonin and CEA levels three months post-surgery 2 , 6 , 13 , 14 MTC has a 10-year survival rate of 72%, which decreases to 52% at 20 years 15 , 16 . Patients with normal postoperative calcitonin levels have a 5-year survival rate of 98.9% and 10-year survival of 97.7%, while those with elevated levels have reduced survival rates of 80.2% and 70.3% 4,17 , respectively. The presence of distant metastasis in MTC significantly worsens the prognosis, with 10–15% of patients presenting with metastasis at the time of diagnosis 5 . The 10-year survival rate of only 40% in cases involving distant metastasis 1 , 18 , 19 . A previous study indicated that the bone, liver, and lungs are particularly susceptible to metastasis, with approximately half of metastatic cases involving multiple sites 20 . Surgical resection of the primary tumor may provide survival benefits for individuals with metastatic medullary thyroid carcinoma (MTC) 20 . Due to this significant metastatic heterogeneity, the optimal management strategies for patients with metastatic MTC remain a subject of debate 20 . Notably, the lungs represent the one of most frequent site of metastasis. High-resolution lung CT scans detect a substantial number of pulmonary nodules, with around 1.6 million nodules incidentally found annually in the United States 21 . In cases where MTC is accompanied by pulmonary nodules, distinguishing between primary lung cancer and metastatic disease is critical 21 . For cases with concurrent primary non-small cell lung cancer (NSCLC) and MTC, radical surgery is necessary, yet preoperative differentiation remains a significant challenge. Previous research has demonstrated that serum calcitonin levels exceeding 500 pg/mL are indicative of distant metastasis 8 , and this serves as a key diagnostic criterion in the preoperative assessment of pulmonary nodules in MTC. In this particular case, although serum calcitonin levels were elevated beyond 2000 pg/mL, the pulmonary nodules were identified as primary NSCLC, challenging the conclusions of earlier studies. This discrepancy highlights the urgent need for more refined diagnostic protocols to accurately distinguish the origin of pulmonary nodules in patients with MTC. A large-scale follow-up study is necessary to determine optimal treatment strategies for MTC and co-occurring pulmonary nodules. Conclusions Surgery constitutes the only curative option for MTC. For patients with MTC confined to the neck and cervical lymph nodes, radical surgical intervention is recommended. However, when MTC is accompanied by pulmonary nodules, the focus must shift to accurately determining the origin of the pulmonary malignancy. Developing more precise diagnostic protocols in these cases is essential for guiding appropriate treatment strategies. Declarations Data availability statement Data supporting the findings of this study are available upon reasonable request by the corresponding author. All clinical data were collected from the clinical data repository of Guizhou Provincial People's Hospital. Ethics statement An informed consent was obtained from a legally authorized representative(s) for the publication of anonymized patient information. This study was approved by the Ethics Committee of Guizhou Provincial People's Hospital and complies with the Declaration of Helsinki. Conflict of Interest Disclosures: None. Funding National Natural Science Foundation of China (No. 82060390, 82460590). Additional Contributions We thank the patient for granting permission to publish this information. Author contributions All authors reviewed and approved the final manuscript. ZJ, ZY, AX, and PY were responsible for the surgical management of the patient. ZJ, AX and ZY wrote the original draft of the manuscript. ZJ, ZY, and PY were edited the final manuscript. References Noone AM, Cronin KA, Altekruse SF, et al. Cancer Incidence and Survival Trends by Subtype Using Data from the Surveillance Epidemiology and End Results Program, 1992–2013. Cancer Epidemiol Biomarkers Prev. 2017;26(4):632–41. Kim M, Kim BH. Current Guidelines for Management of Medullary Thyroid Carcinoma. Endocrinol Metab (Seoul). 2021;36(3):514–24. Wells SA Jr., Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567–610. Pelizzo MR, Mazza EI, Mian C, Merante Boschin I. Medullary thyroid carcinoma. Expert Rev Anticancer Ther. 2023;23(9):943–57. Park H, Yang H, Heo J, Kim TH, Kim SW, Chung JH. Long-Term Outcomes and Causes of Death among Medullary Thyroid Carcinoma Patients with Distant Metastases. Cancers (Basel). 2021;13:18. Filetti S, Durante C, Hartl D, et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-updagger. Ann Oncol. 2019;30(12):1856–83. Machens A, Dralle H. Biomarker-based risk stratification for previously untreated medullary thyroid cancer. J Clin Endocrinol Metab. 2010;95(6):2655–63. Niederle MB, Scheuba C, Riss P, Selberherr A, Koperek O, Niederle B. Early Diagnosis of Medullary Thyroid Cancer: Are Calcitonin Stimulation Tests Still Indicated in the Era of Highly Sensitive Calcitonin Immunoassays? Thyroid. 2020;30(7):974–84. Raue F, Frank-Raue K. Epidemiology and Clinical Presentation of Medullary Thyroid Carcinoma. Recent Results Cancer Res. 2015;204:61–90. Moley JF. Medullary thyroid carcinoma: management of lymph node metastases. J Natl Compr Canc Netw. 2010;8(5):549–56. Roy M, Chen H, Sippel RS. Current understanding and management of medullary thyroid cancer. Oncologist. 2013;18(10):1093–100. Rendl G, Manzl M, Hitzl W, Sungler P, Pirich C. Long-term prognosis of medullary thyroid carcinoma. Clin Endocrinol (Oxf). 2008;69(3):497–505. Haddad RI, Bischoff L, Ball D, et al. Thyroid Carcinoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022;20(8):925–51. Stepanas AV, Samaan NA, Hill CS Jr., Hickey RC. Medullary thyroid carcinoma: importance of serial serum calcitonin measurement. Cancer. 1979;43(3):825–37. Girelli ME, Nacamulli D, Pelizzo MR, et al. Medullary thyroid carcinoma: clinical features and long-term follow-up of seventy-eight patients treated between 1969 and 1986. Thyroid. 1998;8(6):517–23. Kebebew E, Greenspan FS, Clark OH, Woeber KA, Grunwell J. Extent of disease and practice patterns for medullary thyroid cancer. J Am Coll Surg. 2005;200(6):890–6. Modigliani E, Cohen R, Campos JM, et al. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d'etude des tumeurs a calcitonine. Clin Endocrinol (Oxf). 1998;48(3):265–73. Cupisti K, Wolf A, Raffel A, et al. Long-term clinical and biochemical follow-up in medullary thyroid carcinoma: a single institution's experience over 20 years. Ann Surg. 2007;246(5):815–21. Roman S, Lin R, Sosa JA. Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1252 cases. Cancer. 2006;107(9):2134–42. Liu CQ, Shen CK, Du YX, et al. Survival Outcome and Optimal Candidates of Primary Tumor Resection for Patients With Metastatic Medullary Thyroid Cancer. J Clin Endocrinol Metab. 2024;109(11):2979–85. Paez R, Kammer MN, Tanner NT, et al. Update on Biomarkers for the Stratification of Indeterminate Pulmonary Nodules. Chest. 2023;164(4):1028–41. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 02 May, 2025 Reviews received at journal 21 Apr, 2025 Reviewers agreed at journal 21 Apr, 2025 Reviewers invited by journal 17 Apr, 2025 Submission checks completed at journal 16 Apr, 2025 First submitted to journal 02 Apr, 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. 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-5927634","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":444226549,"identity":"928807d2-9a0c-4090-a97b-c5ba8f6d7dca","order_by":0,"name":"Zhang Jianyong","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYDACCRDBwyDHz97Y+OADKVqMJXsONxvOIF4LA0PihhvpbdIcxOiQn9387OEXmcOJDTcfNkgzMNjJ6TYQ0MI455i5sQzPYePG2YkNxgUMycZmBwhoYZZIMJOW4Dks2yyd2JA8g+FA4jZCWtgk0r+BtDC2SR5sOMxDjBYeiRwzyQ88hxV7JBgbm4nSIiGRUybNwJNuLMGT2Mw4w4AIv8jPSN8m+bPHWs7++PHnPz5U2MkR1AICzLw9zVCmARHKQYDxx486IpWOglEwCkbBiAQACqtCQwC8QCgAAAAASUVORK5CYII=","orcid":"","institution":"Guizhou Provincial People's Hospital","correspondingAuthor":true,"prefix":"","firstName":"Zhang","middleName":"","lastName":"Jianyong","suffix":""},{"id":444226550,"identity":"9bc5d0a2-ae9d-45dd-a8e6-8904effdfa18","order_by":1,"name":"Zheng Yu","email":"","orcid":"","institution":"The Affiliated Hospital of Guizhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zheng","middleName":"","lastName":"Yu","suffix":""},{"id":444226551,"identity":"5aff7a7c-1a5b-4fe7-a49c-7a9b939100f6","order_by":2,"name":"An Xiaoxiao","email":"","orcid":"","institution":"Guizhou Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"An","middleName":"","lastName":"Xiaoxiao","suffix":""},{"id":444226552,"identity":"a3f6baae-8541-4877-bae1-267eaaae4393","order_by":3,"name":"Peng Yunsong","email":"","orcid":"","institution":"Guizhou Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Peng","middleName":"","lastName":"Yunsong","suffix":""}],"badges":[],"createdAt":"2025-01-30 04:53:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5927634/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5927634/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":81002732,"identity":"3bc7b35d-e886-4e7a-8a2a-dd344db5820f","added_by":"auto","created_at":"2025-04-21 06:36:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":4797239,"visible":true,"origin":"","legend":"\u003cp\u003ePreoperative imaging images.\u003c/p\u003e\n\u003cp\u003eA. Ultrasound examination detected the right thyroid gland measuring approximately 3.5 cm.\u003c/p\u003e\n\u003cp\u003eB. Computed tomography imaging demonstrates a large thyroid tumor.\u003c/p\u003e\n\u003cp\u003eC. Axial section of computed tomography imagingdemonstrates a high-density mass in the right thyroid.\u003c/p\u003e\n\u003cp\u003eD. Computed tomography imaging demonstrates pulmonary nodules.\u003c/p\u003e","description":"","filename":"FIG14.png","url":"https://assets-eu.researchsquare.com/files/rs-5927634/v1/272c6dee801e279125e3ab8c.png"},{"id":81002724,"identity":"ac0bcab1-9d63-4055-a297-d59493231d6d","added_by":"auto","created_at":"2025-04-21 06:36:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":418847,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in tumor markers. A. The serum levels of calcitonin (CT). B. The serum levels of carcinoembryonic antigen (CEA).\u003c/p\u003e","description":"","filename":"FIG25.png","url":"https://assets-eu.researchsquare.com/files/rs-5927634/v1/42cc8195286c8091c0e6b326.png"},{"id":81004145,"identity":"f09ba05f-4ef1-42eb-90a1-570fe87ea407","added_by":"auto","created_at":"2025-04-21 06:44:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5282131,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5927634/v1/df0faa78-d88f-469c-a865-b192a6da6351.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Simultaneous medullary thyroid carcinoma and primary non-small cell lung cancer: case report and literature review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMedullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from parafollicular cells that produce calcitonin, accounting for 1\u0026ndash;2% of all thyroid cancers\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Of these cases, 75% occur sporadically, while the remaining 25% are associated with multiple endocrine neoplasia (MEN) type 2, a hereditary condition\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Sporadic MTC is often diagnosed at an advanced stage due to its presentation as a solitary thyroid nodule with few symptoms\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. The diagnosis of sporadic MTC primarily relies on fine-needle aspiration (FNA) biopsy and immunohistochemical analysis\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. However, the preoperative diagnosis of medullary thyroid carcinoma (MTC) is challenging due to its presentation as a solitary thyroid nodule and its relatively rare incidence. Complete surgical resection remains the only curative treatment for locoregional MTC, with the bone, lung, and liver being the most common sites of distant metastases\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Consequently, early diagnosis and detection of MTC are crucial for improving prognosis. Management of recurrent or metastatic MTC includes surgical resection, external beam radiation therapy (EBRT), and targeted local or systemic therapies. However, the treatment approach for patients with metastatic MTC is debated, as many display indolent disease over time\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Recent advances in molecular biology have enhanced our understanding of the genetic and epigenetic alterations driving MTC. Calcitonin and carcinoembryonic antigen (CEA), both secreted by C-cells, serve as key tumor markers for MTC. While calcitonin holds diagnostic significance, both basal and stimulated levels are utilized for follow-up and predicting disease progression\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Niederle et al. showed that basal serum calcitonin levels above 85 pg/mL in females and 100 pg/mL in males have 100% sensitivity for diagnosing lateral neck lymph node metastasis\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. However, calcium-stimulated calcitonin levels did not enhance the accuracy of preoperative diagnosis. Notably, basal serum calcitonin levels are correlated with disease extent. Machens et al. demonstrated that thresholds of 20, 50, 200, and 500 pg/mL as indicative of metastasis in different neck regions and the upper mediastinum, respectively\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. MTC\u0026rsquo;s high rate of central and distant metastases contributes to cancer-related mortality. Central and lateral cervical lymph node metastases occur in 11\u0026ndash;14% of T1 patients and 86\u0026ndash;93% of T4 patients\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Additionally, approximately 70% of sporadic MTC patients with palpable thyroid nodules already have cervical lymph node metastases, and 10% have distant metastases\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Common sites for hematogenous metastasis include the liver, bone, and lung, with lung metastases being the most frequent (52.2%) and bone metastases the most adverse\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. We present a case of primary medullary thyroid carcinoma with non-small cell lung cancer, initially suspected as lung metastasis.\u003c/p\u003e"},{"header":"Case description","content":"\u003cp\u003eA 55-year-old male patient presented with cough and sputum was diagnosed with a 1.8*1.5 cm lung nodule and thyroid nodules via computed tomography (CT) examination over a six-day period. A subsequent thyroid ultrasound examination identified a 3.5*2.9 cm right thyroid nodule. Additionally, enhanced CT imaging revealed significant enlargement and calcification of the right thyroid gland (Shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Ultrasound-guided fine-needle aspiration detected malignant tumor cells, and immunocytochemistry showed positivity for calcitonin, carcinoembryonic antigen (CEA), CD56, chromogranin A (CgA), synaptophysin (Syn), and Ki-67. Furthermore, our findings indicated that serum calcitonin levels exceeded 2000 pg/mL, with CEA at 305 ng/mL. Notably, the patient, a non-smoker with no history of alcohol consumption, had no vocal cord paralysis on laryngoscopy. Preoperative thyroid function was normal, with standard levels of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH), and normal thyroid peroxidase and thyroglobulin antibodies.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePrior to the surgical intervention, thoracic surgeons and oncologists evaluated the potential for malignancy in the pulmonary nodules and the likelihood of lung metastasis from thyroid cancer. Due to the infeasibility of percutaneous pulmonary puncture cytology, a thoracoscopic segmentectomy was conducted to biopsy the pulmonary nodules. Intraoperative frozen section analysis confirmed non-small cell lung cancer, ruling out metastatic thyroid cancer. Subsequently, the patient underwent a thoracic lymph node dissection encompassing levels II, IV, VII, IX, X, and XI, followed by a bilateral total thyroidectomy and bilateral neck lymph node (Ⅱ, Ⅲ, Ⅳ, Ⅵ) dissection. Postoperative pathological examination identified the pulmonary nodules as invasive lung squamous cell carcinoma, positive for P40 and P63, with 40% Ki67 expression. No malignancy was detected in the thoracic lymph nodes, though one cervical lymph node metastasis from MTC was detected among fifty examined. Three months post-surgery, serum levels of calcitonin and carcinoembryonic antigen (CEA), which serve as tumor markers for medullary thyroid carcinoma, returned to normal (Shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eMTC is an uncommon and aggressive tumor that typically spreads to lymph nodes and, less frequently, to bones and lungs through lymphovascular pathways. Half of the patients present with local metastasis at diagnosis, while 10\u0026ndash;15% have distant metastasis\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Surgery constitutes the only curative intervention for MTC, as MTC cells neither concentrate radioactive iodine nor respond to the modulation of thyroid-stimulating hormone (TSH) levels\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Complete surgical resection of the thyroid mass and locoregional metastasis remains the only curative approach for locoregional MTC. The initial standard treatment protocol for MTC involves a total thyroidectomy accompanied by neck lymph node dissection. Total thyroidectomy and bilateral central neck dissection (ND) are recommended for bilateral thyroid involvement or tumors\u0026thinsp;\u0026ge;\u0026thinsp;1 cm\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Nonetheless, the necessity of lateral neck dissection for patients without LN metastasis on preoperative US remains debated. Ipsilateral neck dissection (ND) is often based on intraoperative findings of central LN involvement. In localized disease, total thyroidectomy, central LN dissection, and lateral neck dissection (levels II\u0026ndash;V) are advised\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. According to the guidelines set forth by the American Thyroid Association (ATA) and the European Society for Medical Oncology (ESMO), contralateral ND should be considered if the basal serum calcitonin level exceeds 200 pg/mL and ipsilateral LN involvement is confirmed, despite negative contralateral findings on preoperative imaging\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. In locally advanced or metastatic MTC, total thyroidectomy with lymph node dissection is recommended to preserve speech, swallowing, and parathyroid functions. Postoperative management is contingent upon the levels of serum calcitonin and CEA to identify any residual disease\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Total thyroidectomy with lymph node dissection is recommended to preserve speech, swallowing, and parathyroid function Current guidelines suggest measuring serum calcitonin and CEA levels three months post-surgery\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\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 MTC has a 10-year survival rate of 72%, which decreases to 52% at 20 years\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Patients with normal postoperative calcitonin levels have a 5-year survival rate of 98.9% and 10-year survival of 97.7%, while those with elevated levels have reduced survival rates of 80.2% and 70.3%\u003csup\u003e4,17\u003c/sup\u003e, respectively.\u003c/p\u003e \u003cp\u003eThe presence of distant metastasis in MTC significantly worsens the prognosis, with 10\u0026ndash;15% of patients presenting with metastasis at the time of diagnosis\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. The 10-year survival rate of only 40% in cases involving distant metastasis\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. A previous study indicated that the bone, liver, and lungs are particularly susceptible to metastasis, with approximately half of metastatic cases involving multiple sites\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Surgical resection of the primary tumor may provide survival benefits for individuals with metastatic medullary thyroid carcinoma (MTC)\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Due to this significant metastatic heterogeneity, the optimal management strategies for patients with metastatic MTC remain a subject of debate\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Notably, the lungs represent the one of most frequent site of metastasis. High-resolution lung CT scans detect a substantial number of pulmonary nodules, with around 1.6\u0026nbsp;million nodules incidentally found annually in the United States\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. In cases where MTC is accompanied by pulmonary nodules, distinguishing between primary lung cancer and metastatic disease is critical\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. For cases with concurrent primary non-small cell lung cancer (NSCLC) and MTC, radical surgery is necessary, yet preoperative differentiation remains a significant challenge. Previous research has demonstrated that serum calcitonin levels exceeding 500 pg/mL are indicative of distant metastasis\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e, and this serves as a key diagnostic criterion in the preoperative assessment of pulmonary nodules in MTC. In this particular case, although serum calcitonin levels were elevated beyond 2000 pg/mL, the pulmonary nodules were identified as primary NSCLC, challenging the conclusions of earlier studies. This discrepancy highlights the urgent need for more refined diagnostic protocols to accurately distinguish the origin of pulmonary nodules in patients with MTC. A large-scale follow-up study is necessary to determine optimal treatment strategies for MTC and co-occurring pulmonary nodules.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eSurgery constitutes the only curative option for MTC. For patients with MTC confined to the neck and cervical lymph nodes, radical surgical intervention is recommended. However, when MTC is accompanied by pulmonary nodules, the focus must shift to accurately determining the origin of the pulmonary malignancy. Developing more precise diagnostic protocols in these cases is essential for guiding appropriate treatment strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData supporting the findings of this study are available upon reasonable request by the corresponding author. All clinical data were collected from the clinical data repository of Guizhou Provincial People\u0026apos;s Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAn informed consent was obtained from a legally authorized representative(s) for the publication of anonymized patient information. This study was approved by the Ethics Committee of Guizhou Provincial People\u0026apos;s Hospital and complies with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Disclosures:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNational Natural Science Foundation of China (No. 82060390, 82460590).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the patient for granting permission to publish this information.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors reviewed and approved the final manuscript. ZJ, ZY, AX, and PY were responsible for the surgical management of the patient. ZJ, AX and ZY wrote the original draft of the manuscript. ZJ, ZY, and PY were edited the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eNoone AM, Cronin KA, Altekruse SF, et al. Cancer Incidence and Survival Trends by Subtype Using Data from the Surveillance Epidemiology and End Results Program, 1992\u0026ndash;2013. Cancer Epidemiol Biomarkers Prev. 2017;26(4):632\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim M, Kim BH. Current Guidelines for Management of Medullary Thyroid Carcinoma. Endocrinol Metab (Seoul). 2021;36(3):514\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWells SA Jr., Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567\u0026ndash;610.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePelizzo MR, Mazza EI, Mian C, Merante Boschin I. Medullary thyroid carcinoma. Expert Rev Anticancer Ther. 2023;23(9):943\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark H, Yang H, Heo J, Kim TH, Kim SW, Chung JH. Long-Term Outcomes and Causes of Death among Medullary Thyroid Carcinoma Patients with Distant Metastases. Cancers (Basel). 2021;13:18.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFiletti S, Durante C, Hartl D, et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-updagger. Ann Oncol. 2019;30(12):1856\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMachens A, Dralle H. Biomarker-based risk stratification for previously untreated medullary thyroid cancer. J Clin Endocrinol Metab. 2010;95(6):2655\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNiederle MB, Scheuba C, Riss P, Selberherr A, Koperek O, Niederle B. Early Diagnosis of Medullary Thyroid Cancer: Are Calcitonin Stimulation Tests Still Indicated in the Era of Highly Sensitive Calcitonin Immunoassays? Thyroid. 2020;30(7):974\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRaue F, Frank-Raue K. Epidemiology and Clinical Presentation of Medullary Thyroid Carcinoma. Recent Results Cancer Res. 2015;204:61\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoley JF. Medullary thyroid carcinoma: management of lymph node metastases. J Natl Compr Canc Netw. 2010;8(5):549\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoy M, Chen H, Sippel RS. Current understanding and management of medullary thyroid cancer. Oncologist. 2013;18(10):1093\u0026ndash;100.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRendl G, Manzl M, Hitzl W, Sungler P, Pirich C. Long-term prognosis of medullary thyroid carcinoma. Clin Endocrinol (Oxf). 2008;69(3):497\u0026ndash;505.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaddad RI, Bischoff L, Ball D, et al. Thyroid Carcinoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022;20(8):925\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStepanas AV, Samaan NA, Hill CS Jr., Hickey RC. Medullary thyroid carcinoma: importance of serial serum calcitonin measurement. Cancer. 1979;43(3):825\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGirelli ME, Nacamulli D, Pelizzo MR, et al. Medullary thyroid carcinoma: clinical features and long-term follow-up of seventy-eight patients treated between 1969 and 1986. Thyroid. 1998;8(6):517\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKebebew E, Greenspan FS, Clark OH, Woeber KA, Grunwell J. Extent of disease and practice patterns for medullary thyroid cancer. J Am Coll Surg. 2005;200(6):890\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eModigliani E, Cohen R, Campos JM, et al. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d'etude des tumeurs a calcitonine. Clin Endocrinol (Oxf). 1998;48(3):265\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCupisti K, Wolf A, Raffel A, et al. Long-term clinical and biochemical follow-up in medullary thyroid carcinoma: a single institution's experience over 20 years. Ann Surg. 2007;246(5):815\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoman S, Lin R, Sosa JA. Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1252 cases. Cancer. 2006;107(9):2134\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu CQ, Shen CK, Du YX, et al. Survival Outcome and Optimal Candidates of Primary Tumor Resection for Patients With Metastatic Medullary Thyroid Cancer. J Clin Endocrinol Metab. 2024;109(11):2979\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePaez R, Kammer MN, Tanner NT, et al. Update on Biomarkers for the Stratification of Indeterminate Pulmonary Nodules. Chest. 2023;164(4):1028\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"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":"Medullary thyroid carcinoma, lung cancer, surgery, simultaneous cancer","lastPublishedDoi":"10.21203/rs.3.rs-5927634/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5927634/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMedullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor, accounting for 1\u0026ndash;2% of all thyroid cancers. MTC originates from the C cells or parafollicular cells, which produce and release two critical hormones called calcitonin (CT) and carcinoembryonic antigen (CEA), both serving as key tumor markers. Elevated basal serum calcitonin is critical for diagnosing lateral neck lymph node metastasis, with levels exceeding 500 pg/mL indicating distant metastasis. Persistently elevated postoperative calcitonin levels are associated with poorer prognosis. Surgical intervention remains the only curative treatment for MTC, though local metastasis is present in 50% of cases, and distant metastasis in 10\u0026ndash;15%, commonly affecting the lungs, liver, and bones. When pulmonary nodules are detected in MTC patients, distinguishing whether they are metastatic is crucial. Here, we present a rare case of MTC accompanied by primary non-small cell lung cancer. A 55-year-old male patient presenting with cough and sputum was diagnosed with lung nodule measuring approximately 1.8 *1.5 cm and thyroid nodules via computed tomography (CT) examination. The right thyroid nodule was diagnosed as MTC based on fine needle aspiration (FNA) and calcitonin. In addition, pulmonary nodule was evaluated as the potential for malignant tumor and lung metastasis originating from MTC by thoracic surgeons and oncologists. Due to the difficulty of percutaneous biopsy, a thoracoscopic segmentectomy was performed. Intraoperative frozen section analysis revealed that the pulmonary nodules were non-small cell lung cancer, ruling out metastasis from MTC. Subsequently, the patient underwent a radical surgery for thyroid carcinoma, and follow-up showed no recurrence based on ultrasound and lab tests. We also review clinical findings from similar cases and discuss possible treatment strategies.\u003c/p\u003e","manuscriptTitle":"Simultaneous medullary thyroid carcinoma and primary non-small cell lung cancer: case report and literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-21 06:36:37","doi":"10.21203/rs.3.rs-5927634/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-02T07:56:55+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-21T14:41:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"75579654826751209778049967044773638680","date":"2025-04-21T11:48:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-17T07:20:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-16T06:47:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Oncology","date":"2025-04-02T14:44:44+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":"April 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-06-27T11:08:05+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-21 06:36:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5927634","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5927634","identity":"rs-5927634","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}