Synchronous Oral Heterotopic Gastrointestinal Cyst and Oral Squamous Cell Carcinoma: First Case Report

Synchronous Oral Heterotopic Gastrointestinal Cyst and Oral Squamous Cell Carcinoma: First Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Synchronous Oral Heterotopic Gastrointestinal Cyst and Oral Squamous Cell Carcinoma: First Case Report Caroline Alfaia Silva, Túlio Silva Rosa, Lidiane de Paula Ribeiro, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5313009/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background. Synchronous lesions in the oral cavity are uncommon and present diagnostic challenges, particularly when a benign lesion coexists with a malignancy. Heterotopic gastrointestinal cyst of the oral cavity (HGIC), typically seen in pediatric patients, contains ectopic gastrointestinal tissue and is rarely found in adults. This report describes a case of a HGIC in an adult patient concomitant with oral squamous cell carcinoma (OSCC), which is believed to be the first report of this unique entity. Methods and results. A 62-year-old man presented with an ulcerated lesion on the right floor of the mouth. An incisional biopsy was performed, and the pathology revealed that it was an HGIC with a pathological cavity lined by tall columnar epithelial cells with basally displaced nuclei and apical microvilli (brush border), synchronous with an SCC exhibiting a proliferation of epidermoid cells with moderate cellular atypia, pleomorphism, and nuclear hyperchromatism. The patient is currently undergoing regular follow-up, with further evaluations planned to monitor local disease control and prevent potential complications. Conclusion. Early and accurate identification of coexisting lesions may be crucial for effective clinical management and a broader understanding of the pathogenesis of these conditions. Cysts Heterotopia Intestines Oral Cavity Squamous Cell Carcinoma Figures Figure 1 BACKGROUND Simultaneous lesions, also known as synchronous lesions, are characterized by the occurrence of two or more lesions in different anatomical sites simultaneously. 1 When these lesions are diagnosed within a six-month interval, they are classified as metachronous, provided that recurrences or metastases are excluded. 2,3 Although relatively common in the head and neck region, concomitant lesions encompass a wide range of diagnoses, from benign conditions such as hyperplasia to malignancies. 4,5 Among head and neck malignancies, oral cancer stands out due to its high prevalence and significant contribution to global mortality. 6 Oral squamous cell carcinoma (OSCC) often presents in conjunction with other simultaneous lesions, both benign and malignant, which can complicate diagnosis and clinical management. 7 Metachronous lesions associated with OSCC are more frequent than synchronous ones, but both scenarios pose considerable diagnostic challenges. 8–13 Heterotopic gastrointestinal cyst of the oral cavity is a rare and benign condition, characterized by the presence of ectopic gastrointestinal tissue in an unusual location, 14–16 . Although typically diagnosed in childhood, this condition can also occur in adults. 17,18 The etiology of this cyst is poorly understood, but the most accepted hypothesis suggests that during embryonic development, endodermal cells may migrate to an abnormal location 19,20 . Clinically, the cyst may be asymptomatic, but in cases of significant growth, it may interfere with feeding and oral function. 19 Among the most affected anatomical regions, the tongue, the floor of the mouth. 19,21 This case report describes a rare and unprecedented combination of oral heterotopic gastrointestinal cyst associated with concomitant OSCC, with no previous reports in the literature. Therefore, this is the first report of this condition. CASE PRESENTATION A 62-year-old Caucasian male presented with the chief complaint of discomfort in the floor of the mouth. Intraoral clinical examination revealed a crater-like ulcerated lesion, approximately 2 cm in diameter, with raised and indurated borders. The lesion had an 8-month history. The patient had a significant history of smoking for 36 years and regular alcohol consumption. During extraoral clinical examination, submandibular lymphadenopathy was identified on the right side. An incisional biopsy was performed, and histopathological analysis revealed two distinct lesions. The first, a heterotopic gastrointestinal cyst, was characterized by oral mucosa lined by stratified squamous parakeratinized epithelium, with acanthosis and hydropic degeneration. In the deeper specimen, a pathological cavity lined by tall columnar epithelial cells with basally displaced nuclei and apical microvilli (brush borders) was identified. These features resembled duodenal mucosecretory epithelium, including goblet cells and tubular structures like Brunner’s glands (Fig. 1 D-L). The second lesion was diagnosed as OSCC. The examination revealed a proliferation of oral keratinocytes with moderate cellular atypia, displaying pleomorphism and nuclear hyperchromatism. Significant abortive keratinization and occasional mitotic figures were also noted. The lesion presented with islands, trabeculae, and solid cords of tumor epithelial cells, characteristic of OSCC (Fig. 1 B-C). Based on the histopathological diagnosis, the simultaneous occurrence of a heterotopic gastrointestinal cyst and a well-differentiated OSCC was confirmed. Subsequent clinical management involved multidisciplinary discussions to plan the appropriate surgical approach and follow-up, given the rare and challenging nature of this simultaneous lesion presentation. The patient is currently under regular follow-up, and additional exams will be conducted to monitor local disease control and prevent potential complications. DISCUSSION This case report of a 62-year-old male, with a significant history of smoking and alcohol consumption, presenting with simultaneous oral heterotopic gastrointestinal cyst and OSCC, highlights the diagnostic complexity and the importance of careful management of these rare and concomitant conditions. The presence of a heterotopic gastrointestinal cyst in the oral cavity is extremely rare, particularly in adult patients. 22,23 Most documented cases occur in pediatric patients, making this case even more unique. 24,25 The identification of a heterotopic cyst alongside a malignant neoplasm, such as OSCC, may present a diagnostic challenge, as both lesions may coexist and potentially influence each other in terms of clinical presentation and progression. This case underscores the need for detailed histopathological evaluation of unusual oral lesions, especially in patients with high-risk factors, such as smoking and alcohol consumption, which are known to increase the incidence of OSCC. 26 The coexistence of a heterotopic gastrointestinal cyst, which typically does not present malignancy, with a OSCC raises questions about possible interactions between these lesions, though the existing literature is limited in this regard. Compared to previous studies, which report the isolated presence of heterotopic cysts or OSCC, this case highlights a combination that may be underdiagnosed due to the rarity of the heterotopic condition and the clinical predominance of the carcinoma. 27 Precise differential diagnosis and consideration of multiple hypotheses are crucial to avoid diagnostic errors and plan appropriate treatment. The treatment approach would be significantly different if the case involved only the heterotopic gastrointestinal cyst, as a benign lesion would generally require a less aggressive intervention. However, the coexistence of a malignant lesion such as OSCC drastically alters the management plan, demanding a more comprehensive treatment strategy that typically includes surgery, radiotherapy, or chemotherapy. Therefore, the synchronous occurrence of both lesions also impacts the prognosis—while a benign lesion associated with a cyst usually leads to a favorable outcome, the presence of a malignant tumor significantly worsens the prognosis, making the clinical scenario much more complex. Limitations of this study include the fact that it is a single case report, and especially the first case of the mutual manifestation of two lesions, mainly benign and malignant. Furthermore, long-term monitoring of this patient will be crucial to determine clinical behavior, prognosis and to verify whether there are different characteristics resulting from the coexistence of lesions. Future research may benefit from cohort studies investigating the coexistence of benign and malignant lesions in the oral cavity to better understand the clinical implications and prognosis of these patients. CONCLUSIONS This case highlights the rare and unique coexistence of a synchronous oral heterotopic gastrointestinal cyst and squamous cell carcinoma, underscoring the importance of considering the possibility of a concomitant lesion when formulating the primary diagnosis. The combination of these conditions presents significant diagnostic challenges, particularly in patients with risk factors such as smoking and alcohol consumption. Performing biopsy followed by histopathological analysis is crucial for accurate diagnosis and appropriate treatment. Declarations DATA AVAILABILITY No datasets were generated or analysed during the current study. CODE AVAILABILITY Not applicable. FUNDING This study was not supported by any funding. Acknowledgements AUTHOR INFORMATION Authors and Affiliations Post-Graduate Program in Dentistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil. Caroline Alfaia Silva Túlio Silva Rosa Lidiane de Paula Ribeiro Assistant Professor at the University of Southern Santa Catarina, Florianópolis, Santa Catarina, Brazil. Angélica Reinheimer Department of Pathology, Health Sciences Center, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil. Elena Riet Correa Rivero Filipe Modolo Rogério de Oliveira Gondak Ricardo Luiz Cavalcanti de Albuquerque Júnior ETHICAL APPROVAL All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Consent to Participate Informed consent was obtained from all individual participants included in the study. Consent for Publication Consent for publication was obtained for every individual person’s data included in the study. Competing Interests The authors declare no competing interests. References Amer M. Multiple neoplasms, single primaries, and patient survival. Cancer Manag Res . Published online March 2014:119. doi:10.2147/CMAR.S57378 Panosetti E, Luboinski B, Mamelle G, Richard JM. Multiple Synchronous and Metachronous Cancers of the Upper Aerodigestive Tract: A Nine-Yeah Study. The Laryngoscope . 1989;99(12):1267-1273. Zhang Q, Li Y, Gao N, Huang Y, Li LJ. Synchronous multicentric osteosarcoma involving mandible and maxillas. Int J Oral Maxillofac Surg . 2011;40(4):446-449. Kaushal DrS, Shah DrS, Goswami DrH, Patel DrS. FNAC of neoplastic lesions of head and neck. Int J Clin Diagn Pathol . 2022;5(4):36-41. Perez-Ordonez B. Special tumours of the head and neck. Curr Diagn Pathol . 2003;9(6):366-383. Warnakulasuriya S. Causes of oral cancer – an appraisal of controversies. Br Dent J . 2009;207(10):471-475. Slaughter DP, Southwick HW, Smejkal W. “Field cancerization” in oral stratified squamous epithelium. Clinical implications of multicentric origin. Cancer . 1953;6(5):963-968. Morris LGT, Sikora AG, Hayes RB, Patel SG, Ganly I. Anatomic sites at elevated risk of second primary cancer after an index head and neck cancer. Cancer Causes Control . 2011;22(5):671-679. Sturgis EM, Miller RH. Second Primary Malignancies in the Head and Neck Cancer Patient. Ann Otol Rhinol Laryngol . 1995;104(12):946-954. Jones AS, Morar P, Phillips DE, Field JK, Husband D, Helliwell TR. Second primary tumors in patients with head and neck squamous cell carcinoma. Cancer . 1995;75(6):1343-1353. Haughey BH, Arfken CL, Gates GA, Harvey J. Meta-Analysis of Second Malignant Tumors in Head and Neck Cancer: The Case for an Endoscopic Screening Protocol. Ann Otol Rhinol Laryngol . 1992;101(2):105-112. Maiorano E, Lo Muzio L, Favia G, Piattelli A. Warthin’s tumour: a study of 78 cases with emphasis on bilaterality, multifocality and association with other malignancies. Oral Oncol . 2002;38(1):35-40. Sarode G, Mahindre S, Mehta V, et al. A Rare Synchronous Existence of Warthin’s Tumour and Oral Cancer: A systematic review. Sultan Qaboos Univ Med J . Published online March 21, 2024. Kwon MJ, Kim DH, Park HR, et al. Heterotopic Intestinal Cyst of the Submandibular Gland: A Case Study. Korean J Pathol . 2013;47:279-283. Sáenz MAM. Respiratory distress associated with heterotopic gastrointestinal cysts of the oral cavity: A case report. Ann Med Surg . Published online 2016. Şimşek-Kaya G, Özbudak İH, Kader D. Coexisting sublingual dermoid cyst and heterotopic gastrointestinal cyst: Case report. J Clin Exp Dent . 2018;10 (2):e196-e199. Erdem E, Tüz HH, Günhan Ö. Gastric mucosal choristoma of the tongue and floor of the mouth. J Oral Maxillofac Surg . 2001;59(2):210-212. doi:10.1053/joms.2001.20497 Martins F, Hiraki KR, Mimura MÂ, et al. Heterotopic gastrointestinal mucosa in the oral cavity of adults. Oral Surg Oral Med Oral Pathol Oral Radiol . 2013;115(6):e51-e54. doi:10.1016/j.oooo.2012.12.010 Bains GK, Pilkington R, Stafford J, Bhatia S. A case report of oral heterotopic gastrointestinal cysts (HGIC) and review of the literature. Oral Surg . 2020;15:71-80. Kieran M. S, Robson CD, Nosé V, Rahbar R. Foregut Duplication Cysts in the Head and Neck. Arch Otolaryngol - Head Neck Surg . 2010;136(8):778-782. doi:doi:10.1001/archoto.2010.127 Drennen KC, Myers EN. Heterotopic Gastrointestinal Mucosa of the Oral Cavity. Otolaryngol Neck Surg . 1998;118(1):99-101. doi:10.1016/S0194-5998(98)70382-1 Saleh E, Mansouri M, Nolan PJ, Kelsch R, Shifteh K. Heterotopic gastrointestinal cyst within the submandibular space in an adult: A case report and review of the literature. Radiol Case Rep . 2022;17(9):2972-2978. Ohbayashi Y, Miyake M, Nagahata S. Gastrointestinal Cyst of the Tongue: A Possible Duplication Cyst of Foregut Origin. J Oral Maxillofac Surg . 1997;55:626-628. Schrotenboer J, Heider A, Smith E, Aronovich S. Foregut duplication cyst of the floor of mouth in a neonate: case report. Br J Oral Maxillofac Surg . 2016;54(9):1019-1021. Lee AD, Harada K, Tanaka S, et al. Large lingual heterotopic gastrointestinal cyst in a newborn: A case report. World J Clin Cases . 2020;8(17):3808-3813. Eloranta R, Vilén ST, Keinänen A, et al. Oral squamous cell carcinoma: Effect of tobacco and alcohol on cancer location. Tob Induc Dis . 2024;22(June):1-9. Alnour A, Sahlol E, Wehbi E, Achour H, Abdo A. Heterotopic gastrointestinal cyst in the mandible of a young adult: A rare case-report from Syria. Ann Med Surg . 2022;80. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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-5313009","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":370120873,"identity":"508284fe-ee7d-4b52-bf4d-130d76a0ce2f","order_by":0,"name":"Caroline Alfaia Silva","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3UlEQVRIiWNgGAWjYLCCBxDKEETz8BGlJQFCGRuAtLCRosVMAkQS1MLffvbhgwQGO3sG9uZtlV9z7GTYGJgfPrqBR4vEmXRjgwSG5MQGnmNlt2W3JQMdxmZsnINHiwFDGptEAgNzAoNEjtltyW3MQC08bNJ4tfA/A2mptwdpKZbcVk+EFgmwLYcZG4BaGD9uO0xYi8SNZ8wGCQbHE9t4jhVLM247zsPGTMAv/P1pjA8+VFTb87M3b/z4cxuY8fAxPi1Q50Gig5kHxGEmqBwJMP4gRfUoGAWjYBSMGAAAxIA6WnvEoIQAAAAASUVORK5CYII=","orcid":"","institution":"Federal University of Santa Catarina","correspondingAuthor":true,"prefix":"","firstName":"Caroline","middleName":"Alfaia","lastName":"Silva","suffix":""},{"id":370120874,"identity":"e724339b-c8ac-4eb6-aa7a-91e26bff45df","order_by":1,"name":"Túlio Silva Rosa","email":"","orcid":"","institution":"Federal University of Santa Catarina","correspondingAuthor":false,"prefix":"","firstName":"Túlio","middleName":"Silva","lastName":"Rosa","suffix":""},{"id":370120876,"identity":"6695fc61-b0d1-4422-8d4a-181e97c5e608","order_by":2,"name":"Lidiane de Paula Ribeiro","email":"","orcid":"","institution":"Federal University of Santa Catarina","correspondingAuthor":false,"prefix":"","firstName":"Lidiane","middleName":"de Paula","lastName":"Ribeiro","suffix":""},{"id":370120878,"identity":"1b1eff38-5701-4f4f-867e-d520f7e2c167","order_by":3,"name":"Angélica Reinheimer","email":"","orcid":"","institution":"University of Southern Santa Catarina","correspondingAuthor":false,"prefix":"","firstName":"Angélica","middleName":"","lastName":"Reinheimer","suffix":""},{"id":370120879,"identity":"2aa06e91-5f1b-42e9-912e-8c07f400569a","order_by":4,"name":"Elena Riet Correa Rivero","email":"","orcid":"","institution":"Federal University of Santa Catarina","correspondingAuthor":false,"prefix":"","firstName":"Elena","middleName":"Riet Correa","lastName":"Rivero","suffix":""},{"id":370120880,"identity":"e9b10d89-f5b8-4e05-8039-460cda985571","order_by":5,"name":"Filipe Modolo","email":"","orcid":"","institution":"Federal University of Santa Catarina","correspondingAuthor":false,"prefix":"","firstName":"Filipe","middleName":"","lastName":"Modolo","suffix":""},{"id":370120881,"identity":"079ab896-726d-42e7-85c1-8b621721f6f4","order_by":6,"name":"Rogério Oliveira Gondak","email":"","orcid":"","institution":"Federal University of Santa Catarina","correspondingAuthor":false,"prefix":"","firstName":"Rogério","middleName":"Oliveira","lastName":"Gondak","suffix":""},{"id":370120882,"identity":"674f17aa-72a9-455f-a926-d82871d796ef","order_by":7,"name":"Ricardo Luiz Cavalcanti Albuquerque-Júnior","email":"","orcid":"","institution":"Federal University of Santa Catarina","correspondingAuthor":false,"prefix":"","firstName":"Ricardo","middleName":"Luiz Cavalcanti","lastName":"Albuquerque-Júnior","suffix":""}],"badges":[],"createdAt":"2024-10-22 15:23:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5313009/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5313009/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":67471287,"identity":"d3bd49be-c549-483d-a954-3896813043ef","added_by":"auto","created_at":"2024-10-25 11:36:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1801746,"visible":true,"origin":"","legend":"\u003cp\u003eClinical and histopathological images. A - Ulcerated lesion located on the floor of the mouth. B - Histopathological aspect of the squamous cell carcinoma component (H\u0026amp;E). D-L - Pathological cavity lined by tall columnar epithelial cells with basally displaced nuclei and apical microvilli forming a brush border, along with goblet cells and tubular structures resembling Brunner's glands (H\u0026amp;E; PAS).\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5313009/v1/bf6ef76d011d7e618babed69.png"},{"id":68093098,"identity":"f505f5f5-1718-497c-bc03-54f1e0fc8d86","added_by":"auto","created_at":"2024-11-02 19:31:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2183666,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5313009/v1/91cdc9a9-68d0-49d1-8253-d73495b8fd19.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Synchronous Oral Heterotopic Gastrointestinal Cyst and Oral Squamous Cell Carcinoma: First Case Report","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eSimultaneous lesions, also known as synchronous lesions, are characterized by the occurrence of two or more lesions in different anatomical sites simultaneously.\u003csup\u003e1\u003c/sup\u003e When these lesions are diagnosed within a six-month interval, they are classified as metachronous, provided that recurrences or metastases are excluded.\u003csup\u003e2,3\u003c/sup\u003e Although relatively common in the head and neck region, concomitant lesions encompass a wide range of diagnoses, from benign conditions such as hyperplasia to malignancies.\u003csup\u003e4,5\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAmong head and neck malignancies, oral cancer stands out due to its high prevalence and significant contribution to global mortality.\u003csup\u003e6\u003c/sup\u003e Oral squamous cell carcinoma (OSCC) often presents in conjunction with other simultaneous lesions, both benign and malignant, which can complicate diagnosis and clinical management.\u003csup\u003e7\u003c/sup\u003e Metachronous lesions associated with OSCC are more frequent than synchronous ones, but both scenarios pose considerable diagnostic challenges.\u003csup\u003e8\u0026ndash;13\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eHeterotopic gastrointestinal cyst of the oral cavity is a rare and benign condition, characterized by the presence of ectopic gastrointestinal tissue in an unusual location,\u003csup\u003e14\u0026ndash;16\u003c/sup\u003e. Although typically diagnosed in childhood, this condition can also occur in adults.\u003csup\u003e17,18\u003c/sup\u003e The etiology of this cyst is poorly understood, but the most accepted hypothesis suggests that during embryonic development, endodermal cells may migrate to an abnormal location\u003csup\u003e19,20\u003c/sup\u003e. Clinically, the cyst may be asymptomatic, but in cases of significant growth, it may interfere with feeding and oral function.\u003csup\u003e19\u003c/sup\u003e Among the most affected anatomical regions, the tongue, the floor of the mouth.\u003csup\u003e19,21\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThis case report describes a rare and unprecedented combination of oral heterotopic gastrointestinal cyst associated with concomitant OSCC, with no previous reports in the literature. Therefore, this is the first report of this condition.\u003c/p\u003e"},{"header":"CASE PRESENTATION","content":"\u003cp\u003eA 62-year-old Caucasian male presented with the chief complaint of discomfort in the floor of the mouth. Intraoral clinical examination revealed a crater-like ulcerated lesion, approximately 2 cm in diameter, with raised and indurated borders. The lesion had an 8-month history. The patient had a significant history of smoking for 36 years and regular alcohol consumption. During extraoral clinical examination, submandibular lymphadenopathy was identified on the right side.\u003c/p\u003e \u003cp\u003eAn incisional biopsy was performed, and histopathological analysis revealed two distinct lesions. The first, a heterotopic gastrointestinal cyst, was characterized by oral mucosa lined by stratified squamous parakeratinized epithelium, with acanthosis and hydropic degeneration. In the deeper specimen, a pathological cavity lined by tall columnar epithelial cells with basally displaced nuclei and apical microvilli (brush borders) was identified. These features resembled duodenal mucosecretory epithelium, including goblet cells and tubular structures like Brunner’s glands (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD-L). The second lesion was diagnosed as OSCC. The examination revealed a proliferation of oral keratinocytes with moderate cellular atypia, displaying pleomorphism and nuclear hyperchromatism. Significant abortive keratinization and occasional mitotic figures were also noted. The lesion presented with islands, trabeculae, and solid cords of tumor epithelial cells, characteristic of OSCC (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB-C).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBased on the histopathological diagnosis, the simultaneous occurrence of a heterotopic gastrointestinal cyst and a well-differentiated OSCC was confirmed. Subsequent clinical management involved multidisciplinary discussions to plan the appropriate surgical approach and follow-up, given the rare and challenging nature of this simultaneous lesion presentation. The patient is currently under regular follow-up, and additional exams will be conducted to monitor local disease control and prevent potential complications.\u003c/p\u003e "},{"header":"DISCUSSION","content":"\u003cp\u003eThis case report of a 62-year-old male, with a significant history of smoking and alcohol consumption, presenting with simultaneous oral heterotopic gastrointestinal cyst and OSCC, highlights the diagnostic complexity and the importance of careful management of these rare and concomitant conditions.\u003c/p\u003e\u003cp\u003eThe presence of a heterotopic gastrointestinal cyst in the oral cavity is extremely rare, particularly in adult patients.\u003csup\u003e22,23\u003c/sup\u003e Most documented cases occur in pediatric patients, making this case even more unique.\u003csup\u003e24,25\u003c/sup\u003e The identification of a heterotopic cyst alongside a malignant neoplasm, such as OSCC, may present a diagnostic challenge, as both lesions may coexist and potentially influence each other in terms of clinical presentation and progression.\u003c/p\u003e\u003cp\u003eThis case underscores the need for detailed histopathological evaluation of unusual oral lesions, especially in patients with high-risk factors, such as smoking and alcohol consumption, which are known to increase the incidence of OSCC.\u003csup\u003e26\u003c/sup\u003e The coexistence of a heterotopic gastrointestinal cyst, which typically does not present malignancy, with a OSCC raises questions about possible interactions between these lesions, though the existing literature is limited in this regard.\u003c/p\u003e\u003cp\u003eCompared to previous studies, which report the isolated presence of heterotopic cysts or OSCC, this case highlights a combination that may be underdiagnosed due to the rarity of the heterotopic condition and the clinical predominance of the carcinoma.\u003csup\u003e27\u003c/sup\u003e Precise differential diagnosis and consideration of multiple hypotheses are crucial to avoid diagnostic errors and plan appropriate treatment.\u003c/p\u003e\u003cp\u003eThe treatment approach would be significantly different if the case involved only the heterotopic gastrointestinal cyst, as a benign lesion would generally require a less aggressive intervention. However, the coexistence of a malignant lesion such as OSCC drastically alters the management plan, demanding a more comprehensive treatment strategy that typically includes surgery, radiotherapy, or chemotherapy. Therefore, the synchronous occurrence of both lesions also impacts the prognosis—while a benign lesion associated with a cyst usually leads to a favorable outcome, the presence of a malignant tumor significantly worsens the prognosis, making the clinical scenario much more complex.\u003c/p\u003e\u003cp\u003eLimitations of this study include the fact that it is a single case report, and especially the first case of the mutual manifestation of two lesions, mainly benign and malignant. Furthermore, long-term monitoring of this patient will be crucial to determine clinical behavior, prognosis and to verify whether there are different characteristics resulting from the coexistence of lesions. Future research may benefit from cohort studies investigating the coexistence of benign and malignant lesions in the oral cavity to better understand the clinical implications and prognosis of these patients.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eThis case highlights the rare and unique coexistence of a synchronous oral heterotopic gastrointestinal cyst and squamous cell carcinoma, underscoring the importance of considering the possibility of a concomitant lesion when formulating the primary diagnosis.\u003c/p\u003e \u003cp\u003eThe combination of these conditions presents significant diagnostic challenges, particularly in patients with risk factors such as smoking and alcohol consumption. Performing biopsy followed by histopathological analysis is crucial for accurate diagnosis and appropriate treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDATA AVAILABILITY\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eCODE AVAILABILITY\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eFUNDING\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was not supported by any funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAUTHOR INFORMATION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors and Affiliations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePost-Graduate Program in Dentistry, Federal University of Santa Catarina, Florian\u0026oacute;polis, Santa Catarina, Brazil.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCaroline Alfaia Silva\u003c/p\u003e\n\u003cp\u003eT\u0026uacute;lio Silva Rosa\u003c/p\u003e\n\u003cp\u003eLidiane de Paula Ribeiro\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssistant Professor at the University of Southern Santa Catarina, Florian\u0026oacute;polis, Santa Catarina, Brazil.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAng\u0026eacute;lica Reinheimer\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDepartment of Pathology, Health Sciences Center, Federal University of Santa Catarina, Florian\u0026oacute;polis, Santa Catarina, Brazil.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eElena Riet Correa Rivero\u003c/p\u003e\n\u003cp\u003eFilipe Modolo\u003c/p\u003e\n\u003cp\u003eRog\u0026eacute;rio de Oliveira Gondak\u003c/p\u003e\n\u003cp\u003eRicardo Luiz Cavalcanti de Albuquerque J\u0026uacute;nior\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eETHICAL APPROVAL\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent for publication was obtained for every individual person\u0026rsquo;s data included in the study.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAmer M. Multiple neoplasms, single primaries, and patient survival. \u003cem\u003eCancer Manag Res\u003c/em\u003e. Published online March 2014:119. doi:10.2147/CMAR.S57378\u003c/li\u003e\n\u003cli\u003ePanosetti E, Luboinski B, Mamelle G, Richard JM. Multiple Synchronous and Metachronous Cancers of the Upper Aerodigestive Tract: A Nine-Yeah Study. \u003cem\u003eThe Laryngoscope\u003c/em\u003e. 1989;99(12):1267-1273.\u003c/li\u003e\n\u003cli\u003eZhang Q, Li Y, Gao N, Huang Y, Li LJ. Synchronous multicentric osteosarcoma involving mandible and maxillas. \u003cem\u003eInt J Oral Maxillofac Surg\u003c/em\u003e. 2011;40(4):446-449.\u003c/li\u003e\n\u003cli\u003eKaushal DrS, Shah DrS, Goswami DrH, Patel DrS. FNAC of neoplastic lesions of head and neck. \u003cem\u003eInt J Clin Diagn Pathol\u003c/em\u003e. 2022;5(4):36-41.\u003c/li\u003e\n\u003cli\u003ePerez-Ordonez B. Special tumours of the head and neck. \u003cem\u003eCurr Diagn Pathol\u003c/em\u003e. 2003;9(6):366-383.\u003c/li\u003e\n\u003cli\u003eWarnakulasuriya S. Causes of oral cancer \u0026ndash; an appraisal of controversies. \u003cem\u003eBr Dent J\u003c/em\u003e. 2009;207(10):471-475.\u003c/li\u003e\n\u003cli\u003eSlaughter DP, Southwick HW, Smejkal W. \u0026ldquo;Field cancerization\u0026rdquo; in oral stratified squamous epithelium. Clinical implications of multicentric origin. \u003cem\u003eCancer\u003c/em\u003e. 1953;6(5):963-968.\u003c/li\u003e\n\u003cli\u003eMorris LGT, Sikora AG, Hayes RB, Patel SG, Ganly I. Anatomic sites at elevated risk of second primary cancer after an index head and neck cancer. \u003cem\u003eCancer Causes Control\u003c/em\u003e. 2011;22(5):671-679.\u003c/li\u003e\n\u003cli\u003eSturgis EM, Miller RH. Second Primary Malignancies in the Head and Neck Cancer Patient. \u003cem\u003eAnn Otol Rhinol Laryngol\u003c/em\u003e. 1995;104(12):946-954.\u003c/li\u003e\n\u003cli\u003eJones AS, Morar P, Phillips DE, Field JK, Husband D, Helliwell TR. Second primary tumors in patients with head and neck squamous cell carcinoma. \u003cem\u003eCancer\u003c/em\u003e. 1995;75(6):1343-1353.\u003c/li\u003e\n\u003cli\u003eHaughey BH, Arfken CL, Gates GA, Harvey J. Meta-Analysis of Second Malignant Tumors in Head and Neck Cancer: The Case for an Endoscopic Screening Protocol. \u003cem\u003eAnn Otol Rhinol Laryngol\u003c/em\u003e. 1992;101(2):105-112.\u003c/li\u003e\n\u003cli\u003eMaiorano E, Lo Muzio L, Favia G, Piattelli A. Warthin\u0026rsquo;s tumour: a study of 78 cases with emphasis on bilaterality, multifocality and association with other malignancies. \u003cem\u003eOral Oncol\u003c/em\u003e. 2002;38(1):35-40.\u003c/li\u003e\n\u003cli\u003eSarode G, Mahindre S, Mehta V, et al. A Rare Synchronous Existence of Warthin\u0026rsquo;s Tumour and Oral Cancer: A systematic review. \u003cem\u003eSultan Qaboos Univ Med J\u003c/em\u003e. Published online March 21, 2024.\u003c/li\u003e\n\u003cli\u003eKwon MJ, Kim DH, Park HR, et al. Heterotopic Intestinal Cyst of the Submandibular Gland: A Case Study. \u003cem\u003eKorean J Pathol\u003c/em\u003e. 2013;47:279-283.\u003c/li\u003e\n\u003cli\u003eS\u0026aacute;enz MAM. Respiratory distress associated with heterotopic gastrointestinal cysts of the oral cavity: A case report. \u003cem\u003eAnn Med Surg\u003c/em\u003e. Published online 2016.\u003c/li\u003e\n\u003cli\u003eŞimşek-Kaya G, \u0026Ouml;zbudak İH, Kader D. Coexisting sublingual dermoid cyst and heterotopic gastrointestinal cyst: Case report. \u003cem\u003eJ Clin Exp Dent\u003c/em\u003e. 2018;10 (2):e196-e199.\u003c/li\u003e\n\u003cli\u003eErdem E, T\u0026uuml;z HH, G\u0026uuml;nhan \u0026Ouml;. Gastric mucosal choristoma of the tongue and floor of the mouth. \u003cem\u003eJ Oral Maxillofac Surg\u003c/em\u003e. 2001;59(2):210-212. doi:10.1053/joms.2001.20497\u003c/li\u003e\n\u003cli\u003eMartins F, Hiraki KR, Mimura M\u0026Acirc;, et al. Heterotopic gastrointestinal mucosa in the oral cavity of adults. \u003cem\u003eOral Surg Oral Med Oral Pathol Oral Radiol\u003c/em\u003e. 2013;115(6):e51-e54. doi:10.1016/j.oooo.2012.12.010\u003c/li\u003e\n\u003cli\u003eBains GK, Pilkington R, Stafford J, Bhatia S. A case report of oral heterotopic gastrointestinal cysts (HGIC) and review of the literature. \u003cem\u003eOral Surg\u003c/em\u003e. 2020;15:71-80.\u003c/li\u003e\n\u003cli\u003eKieran M. S, Robson CD, Nos\u0026eacute; V, Rahbar R. Foregut Duplication Cysts in the Head and Neck. \u003cem\u003eArch Otolaryngol - Head Neck Surg\u003c/em\u003e. 2010;136(8):778-782. doi:doi:10.1001/archoto.2010.127\u003c/li\u003e\n\u003cli\u003eDrennen KC, Myers EN. Heterotopic Gastrointestinal Mucosa of the Oral Cavity. \u003cem\u003eOtolaryngol Neck Surg\u003c/em\u003e. 1998;118(1):99-101. doi:10.1016/S0194-5998(98)70382-1\u003c/li\u003e\n\u003cli\u003eSaleh E, Mansouri M, Nolan PJ, Kelsch R, Shifteh K. Heterotopic gastrointestinal cyst within the submandibular space in an adult: A case report and review of the literature. \u003cem\u003eRadiol Case Rep\u003c/em\u003e. 2022;17(9):2972-2978.\u003c/li\u003e\n\u003cli\u003eOhbayashi Y, Miyake M, Nagahata S. Gastrointestinal Cyst of the Tongue: A Possible Duplication Cyst of Foregut Origin. \u003cem\u003eJ Oral Maxillofac Surg\u003c/em\u003e. 1997;55:626-628.\u003c/li\u003e\n\u003cli\u003eSchrotenboer J, Heider A, Smith E, Aronovich S. Foregut duplication cyst of the floor of mouth in a neonate: case report. \u003cem\u003eBr J Oral Maxillofac Surg\u003c/em\u003e. 2016;54(9):1019-1021.\u003c/li\u003e\n\u003cli\u003eLee AD, Harada K, Tanaka S, et al. Large lingual heterotopic gastrointestinal cyst in a newborn: A case report. \u003cem\u003eWorld J Clin Cases\u003c/em\u003e. 2020;8(17):3808-3813.\u003c/li\u003e\n\u003cli\u003eEloranta R, Vil\u0026eacute;n ST, Kein\u0026auml;nen A, et al. Oral squamous cell carcinoma: Effect of tobacco and alcohol on cancer location. \u003cem\u003eTob Induc Dis\u003c/em\u003e. 2024;22(June):1-9.\u003c/li\u003e\n\u003cli\u003eAlnour A, Sahlol E, Wehbi E, Achour H, Abdo A. Heterotopic gastrointestinal cyst in the mandible of a young adult: A rare case-report from Syria. \u003cem\u003eAnn Med Surg\u003c/em\u003e. 2022;80.\u003c/li\u003e\n\u003c/ol\u003e "}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Cysts, Heterotopia, Intestines, Oral Cavity, Squamous Cell Carcinoma","lastPublishedDoi":"10.21203/rs.3.rs-5313009/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5313009/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground.\u003c/h2\u003e \u003cp\u003eSynchronous lesions in the oral cavity are uncommon and present diagnostic challenges, particularly when a benign lesion coexists with a malignancy. Heterotopic gastrointestinal cyst of the oral cavity (HGIC), typically seen in pediatric patients, contains ectopic gastrointestinal tissue and is rarely found in adults. This report describes a case of a HGIC in an adult patient concomitant with oral squamous cell carcinoma (OSCC), which is believed to be the first report of this unique entity.\u003c/p\u003e\u003ch2\u003eMethods and results.\u003c/h2\u003e \u003cp\u003eA 62-year-old man presented with an ulcerated lesion on the right floor of the mouth. An incisional biopsy was performed, and the pathology revealed that it was an HGIC with a pathological cavity lined by tall columnar epithelial cells with basally displaced nuclei and apical microvilli (brush border), synchronous with an SCC exhibiting a proliferation of epidermoid cells with moderate cellular atypia, pleomorphism, and nuclear hyperchromatism. The patient is currently undergoing regular follow-up, with further evaluations planned to monitor local disease control and prevent potential complications.\u003c/p\u003e\u003ch2\u003eConclusion.\u003c/h2\u003e \u003cp\u003eEarly and accurate identification of coexisting lesions may be crucial for effective clinical management and a broader understanding of the pathogenesis of these conditions.\u003c/p\u003e","manuscriptTitle":"Synchronous Oral Heterotopic Gastrointestinal Cyst and Oral Squamous Cell Carcinoma: First Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-25 11:36:33","doi":"10.21203/rs.3.rs-5313009/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d76918da-d228-4ee5-85da-47022e684bb9","owner":[],"postedDate":"October 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-11-02T19:23:21+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-25 11:36:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5313009","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5313009","identity":"rs-5313009","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}