A Case of Acinic Cell Carcinoma Metastasizing to the Heart

A Case of Acinic Cell Carcinoma Metastasizing to the Heart | 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 A Case of Acinic Cell Carcinoma Metastasizing to the Heart Aniqa Nuzhat Chowdhury, Shayna DeSando, Fatima Zahra Aly This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6531041/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract We present the case of a patient with acinic cell carcinoma of the parotid gland who was found to have metastasis to the left atrium of the heart. The pathologic findings and prior reports of metastasis of acinic cell carcinoma are discussed in this article. Grading of acinic cell carcinoma and utility of immunohistochemical study using NOR-1 is discussed. Acinic cell carcinoma salivary gland neoplasm metastasis to heart NOR-1 Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Acinic cell carcinoma of the salivary glands is a low-grade malignant cancer. Acinic cell carcinoma accounts for 17% of primary malignant salivary gland tumors 1 and 1–6% of all epithelial salivary gland neoplasms 2 . The primary cause of treatment failure and death in patients with salivary gland carcinoma is distant metastasis 3 . In general, distant metastasis occurs in approximately 20% of salivary gland cancer cases 4 . Acinic cell carcinoma has a 12–16% incidence of distant metastasis, with the lungs being the most common site 5 , 6 . Metastasis of salivary gland carcinoma to the heart is rare, with only seven cases reported in the literature. This case report presents the first published case of metastasis of acinic cell carcinoma of the parotid gland to the left atrium. Case Report A 56-year-old female was found to have a mass in the parotid gland and subsequently underwent parotidectomy and radical neck dissection in 2015. Histopathology showed multifocal acinic cell carcinoma without lymphovascular or perineural invasion and with close margins of less than 0.1 cm in multiple areas of the right carotid bed. Following parotidectomy, the patient underwent adjuvant radiation therapy to the right carotid bed (30 fractions over 6 weeks). Three years later, the patient was found to have multiple lung nodules, and biopsy revealed metastatic acinic cell carcinoma with a BRAF mutation. She received 5 fractions of stereotactic body radiotherapy (SBRT) to the dominant left lung nodule. Subsequent imaging showed a gradual increase in the size of her multiple lung nodules; however, despite the clinical progression of her disease, the patient did not undergo any additional treatment or follow-up until May 2023 (4 years after initial SBRT), when she began experiencing dyspnea on exertion and weight loss. A computed tomography (CT) scan showed further increases in mediastinal adenopathy and lung metastasis. Due to the worsening disease burden, the patient commenced treatment with a combined BRAF/MET inhibitor (dabrafenib and trametinib). Approximately 2 weeks after beginning this regimen, a CT scan showed findings concerning for either a thrombus in the left atrium and pulmonary veins or progression of her metastatic disease. The patient was treated for thromboembolic disease with anticoagulation. A subsequent cardiac magnetic resonance imaging (MRI) 7 months after beginning treatment with the BRAF/MET inhibitor revealed a 4 cm mass arising from the right pulmonary veins and entering the left atrium, with impingement of the mitral valve. The mass was excised, and the histology was most consistent with metastatic acinic cell carcinoma. One week after the removal of the tumor from the left atrium, a pontomedullary intracerebral hemorrhage was discovered. The patient underwent suboccipital craniotomy for removal, and pathologic evaluation was consistent with metastatic acinic cell carcinoma. Review of the original parotid gland tumor showed two foci of acinic cell carcinoma (2.8 cm and 1.9 cm in size) with extensive tumor necrosis. The tumor showed large, polyhedral acinar cells with basophilic cytoplasm, prominent nucleoli, and nuclear pleomorphism, morphologically consistent with acinic cell carcinoma (Fig. 1 ). Margins were negative for carcinoma; however, the distance from the closest margin was less than 0.1 cm at multiple foci. Lymphovascular and perineural invasion were not identified. Subsequent pathology from the left atrium mass showed an epithelial neoplasm with polyhedral acinar cells, basophilic cytoplasm, eccentric nuclei, and prominent nucleoli (Fig. 2 ). The cells from the tumor in the left atrium were less pleomorphic than those from the original parotid gland tumor. Immunohistochemical studies were performed, demonstrating DOG1, MOC31, and Claudin4 positivity; GATA3 was negative. Periodic Acid-Schiff with diastase (PASD) stain was positive (Fig. 3 ). Nuclear expression of NOR-1, which is a specific and sensitive marker for acinic cell carcinoma of the salivary gland 7 , showed strong nuclear staining (Fig. 3 ), confirming the metastasis is acinic cell carcinoma. Additionally, histology from the tumor in the 4th ventricle of the brain was also consistent with metastatic acinic cell carcinoma, with a similar histomorphology to the mass in the heart. Discussion Acinic cell carcinoma is a relatively rare malignant salivary gland neoplasm 8 . Cases of metastasis of acinic cell carcinoma have been reported to the lungs, cervical lymph nodes, and to the orbit. However, as per the authors’ literature review, this is the first case study of metastatic acinic cell carcinoma to the heart. Although acinic cell carcinoma is considered a low-grade salivary gland neoplasm, it is known to locally recur and metastasize. Case reports of acinic cell carcinoma with distant metastasis have identified lymph node involvement, perineural invasion, and lymphovascular invasion as prognostic predictors that aid in choosing a treatment plan 2 . Lymph node metastasis, one of the major prognostic indicators in acinic cell carcinoma, has a reported 10% incidence, despite it being considered to be a low-grade salivary gland malignancy 9 . Currently, there is no specific histologic grading system for acinic cell carcinoma. High-grade transformation of acinic cell carcinoma was first described by Stanley et al. in 1988. It was defined as “areas of dedifferentiated high-grade adenocarcinoma or undifferentiated carcinoma” with associated areas of low-grade acinic cell carcinoma 10 . This and subsequent studies found that increased adverse outcomes are associated with so-called high-grade acinic cell carcinoma 11 . However, the definition of high-grade acinic cell carcinoma has not been consistent 11 . Xu et al. proposed a grading system that includes 4 histologic features: tumor necrosis, mitotic index, fibrosis at invasive front, and tumor borders 11 . Using this grading system, high-grade acinic cell carcinomas carried a worse prognosis when compared with low-grade and intermediate-grade acinic cell carcinomas. This study also identified tumor size, older age, infiltrative border, lymphovascular invasion, nuclear anaplasia, necrosis, and advanced pT and pN stages as independent factors for adverse prognosis 11 . While there is no formal grading system for acinic cell carcinoma in the current AJCC Cancer Staging System and WHO classification of salivary glands, there is the inclusion of the presence or absence of high-grade transformation, which is defined as marked cytologic atypia, histologically distinct areas, atypical mitoses, increased mitotic activity, and tumor necrosis 12 . In this case, the primary parotid gland tumor possessed high-grade features in the form of significant tumor necrosis, although it possessed a relatively low mitotic rate of 2/2 mm 2 . Thus, histologic grading of the parotid gland tumor may have predicted an adverse prognosis. Khan et al. conducted a study utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database to identify risk factors that affect survival in patients with acinic cell carcinoma 12 . This study graded tumors as well-differentiated, moderately differentiated, poorly differentiated, and undifferentiated. The study found that the variable with the highest hazard ratio for death compared to the other variables is high tumor grade, as defined by the criteria for high-grade transformation in the current AJCC Cancer Staging System 12 . Thus, this study highlights the significant negative impact of histologic grade on prognosis for patients with acinic cell carcinoma. Poorly differentiated and high-grade variants of acinic cell carcinoma are known to have increased rates of recurrence and metastasis, usually via hematogenous spread 9 . These high-grade and poorly differentiated variants have a reported recurrence rate of about 35% with a trend for late recurrence, going up to 30 years after initial presentation 13 . Spencer et al. detail a case of a woman who experienced multiple recurrences of acinic cell carcinoma with lung and intracranial metastasis over 32 years 14 . A retrospective study with 2362 cases of acinic cell carcinoma of the parotid gland showed factors associated with poor prognosis, including advanced tumor stage, regional metastases, high histologic grade, tumors greater than 3 cm, and age over 70 years old 15 . Studies have identified molecular alterations with potential for prognostic implications. The genes most commonly altered in acinic cell carcinoma of the salivary gland are CDKN2A, PTEN, and TP53. Dogan et al. showed a statistically significant worse prognosis in those patients with CDKN2A/B alterations, with associated higher-grade morphology and increased risk of distant metastasis. Haller et al. demonstrated that over 90% of acinic cell carcinoma cases contain translocation t(4;9) (q13; q31), resulting in the upregulation of nuclear receptor subfamily 4 group member 3 (NRA4A3) 7 , 16 . This transcription factor can be detected using an antibody to neuron-derived orphan receptor 1 (NOR-1), which showed strong nuclear staining in our case. However, currently there are no available therapies targeting this molecular alteration. In our case, the patient’s metastatic acinic cell carcinoma was found to harbor a BRAF mutation, which occurs in approximately 4–5% of all acinic cell carcinomas. This molecular alteration offers the opportunity to use a BRAF inhibitor for treatment; however, the prognostic or therapeutic value of BRAF mutations has not been established in acinic cell carcinoma 17 . The 10-year survival of acinic cell carcinoma drops from 99.15% (local disease only) to 31.52% with distant metastasis 18 . Thus, distant metastasis of acinic cell carcinoma is a significant poor prognostic factor for this disease. Due to the rarity of metastatic salivary gland cancers, there are no large clinical trials to determine the optimal treatment. Vidyadhara et al. detail a case of simultaneous metastasis of acinic cell carcinoma to the lymph nodes, lungs, and spine, and suggest the importance of postoperative radiotherapy if there is incomplete resection of the primary tumor 8 . A study of 301 patients undergoing excision of major salivary glands for cancer at Memorial Sloan-Kettering between 1985 and 2009 showed 20% of salivary gland carcinomas had distant metastasis with most being to the lung (49%) or bone (40%) 4 . In this study, 16% of acinic cell carcinomas developed distant metastasis. The heart’s unique lymphatic organization protects it from metastasis. Still, metastatic disease is more common than primary tumors of the heart 19 . Metastases are the most common neoplasms of the heart with an incidence between 1.5–20% among autopsies of cancer patients 20 , 21 . Tumor spreads to the heart via direct spread, bloodstream, lymphatics, and intracavitary migration through the pulmonary veins. Some tumors have displayed higher rates of metastasis to the heart, such as melanoma and mediastinal primary tumors 19 . Metastasis of salivary gland carcinomas to the heart is particularly rare. A few cases of metastatic epithelial-myoepithelial carcinoma of the parotid gland to the heart have been reported 22 . Buchanan et al. describe a case of women with metastasis of epithelial myoepithelial carcinoma of the parotid gland to the right heart, which was identified by transthoracic echocardiography 22 . Kishida et al. describe a case of metastatic mucoepidermoid carcinoma to the heart 23 . Foglietta et al. present a case of polymorphous adenocarcinoma of the minor salivary glands with metastasis to the right ventricle 20 . Table 1 provides a summary of prior literature describing salivary gland carcinoma metastasis to the heart. Table 1 Summary of prior literature on salivary gland carcinoma metastasis to the heart. Study Primary Type of Carcinoma Description of Case Buchanan et al. (2022) 22 Epithelial-myoepithelial carcinoma of the parotid gland 59 y.o. female with metastasis to the right ventricle with reduction of right ventricular systolic function. Kishida et al. (2022) 23 Mucoepidermoid carcinoma of the parotid gland 30 y.o. male with cardiac tamponade secondary metastasis to the pericardium of inferior heart. Foglietta et al. (2021) 20 Polymorphous adenocarcinoma of the minor salivary glands 70 y.o. female with metastasis to the right ventricle. Demirozu et al. (2012) 24 Adenocarcinoma of the parotid gland 51 y.o. male with metastasis to the right ventricular wall and ventricular septum. Barbetakis et al. (2003) 25 Adenocarcinoma of the parotid gland 61 y.o. female with cardiac tamponade secondary to metastasis to the pericardium. Sulkes et al. (1982) 26 Adenocarcinoma of the parotid gland 46 y.o. female with pericardial effusion secondary to metastasis to the pericardium. Becker et al. (1975) 27 Mucoepidermoid carcinoma of the parotid gland 39 y.o. female with pericardial effusions secondary to metastasis to the pericardium. To our knowledge, this case report is the only published account of a case of acinic cell carcinoma metastasis to the heart. Due to the significant prognostic significance of distant metastasis in salivary gland carcinomas, this is a unique case of a patient that presented with metastasis to the heart 8 years after initial diagnosis. Because of the rarity of these cases, it is important to highlight the disease course in cases of salivary gland carcinoma with distant metastasis. In conclusion, acinic cell carcinoma is a low-grade carcinoma of the salivary gland, with the distinct ability to metastasize to distant sites, including the heart. Declarations Disclosures: None Acknowledgements We are grateful to Dr Ronald Ghassan MD (Memorial Sloan-Kettering, USA) for his advice during the preparation of the manuscript and for the NOR-1 immunohistochemical stain. Funding: This study was not supported by any funding. Conflict of Interest: The authors declare that they have no conflict of interest. Ethical Approval: For this type of study formal consent is not required. This study was approved by the Institutional Review Board. Consent to Participate: This study has obtained IRB approval from Atrium Health Wake Forest Baptist hospital and the need for informed consent was waived. Consent for Publication: Consent for publication was obtained for every individual person’s data included in the study. Availability of Data and Materials: This study is a case study. Code Availability: No software application or custom code has been used in the preparation of this case study. References Al-Zaher N, Obeid A, Al-Salam S, Al-Kayyali B. Acinic cell carcinoma of the salivary glands: A literature review. Hematol Oncol Stem Cell Ther. 2009;2:259–64. Ali SA, et al. Predictors of distant metastasis in acinic cell carcinoma of the parotid gland. WJCO. 2020;11:11–9. Mimica X, et al. Distant metastasis of salivary gland cancer: Incidence, management, and outcomes. Cancer. 2020;126:2153–62. Ali S, et al. Distant Metastases in Patients with Carcinoma of the Major Salivary Glands. Ann Surg Oncol. 2015;22:4014–9. Kademani D, Bagheri SC. Oral Cancer. Clin Rev Oral Maxillofacial Surg. 2008;Elsevier243–62. 10.1016/B978-0-323-04574-2.50015-6 . Grasl S, et al. Nodal Metastases in Acinic Cell Carcinoma of the Parotid Gland. JCM. 2019;8:1315. Nguyen L, et al. NOR-1 distinguishes acinic cell carcinoma from its mimics on fine-needle aspiration biopsy specimens. Hum Pathol. 2020;102:1–6. Vidyadhara S, Shetty AP, Rajasekaran S. Widespread metastases from acinic cell carcinoma of parotid gland. Singap Med J. 2007;48:e13–15. Khelfa Y, et al. Relapsed Acinic Cell Carcinoma of the Parotid Gland With Diffuse Distant Metastasis: Case Report With Literature Review. J Investig Med High Impact Case Rep. 2016;4:232470961667474. Stanley RJ, Weiland LH, Olsen KD, Pearson BW. Dedifferentiated Acinic Cell (Acinous) Carcinoma of the Parotid Gland. Otolaryngol --head neck surg. 1988;98:155–61. Xu B, et al. Head and Neck Acinic Cell Carcinoma: A New Grading System Proposal and Diagnostic Utility of NR4A3 Immunohistochemistry. Am J Surg Pathol. 2022;46:933–41. Khan J, et al. Acinic Cell Carcinoma in the 21st Century: A Population-Based Study from the SEER Database and Review of Recent Molecular Genetic Advances. Cancers. 2023;15:3373. Mirzaian E, Asgarikarchekani S, Abdoli AA. Rare Case of Brain Metastasis from dedifferentiated Acinic Cell Carcinoma of Parotid Gland and Review of the Literature. Iran J Pathol. 2022;17:97–103. Spencer ML, Neto G, Fuller A, G. N., Luna MA. Intracranial Extension of Acinic Cell Carcinoma of the Parotid Gland. Arch Pathol Lab Med. 2005;129:780–2. Scherl C, et al. Outcomes and prognostic factors for parotid acinic cell Carcinoma: A National Cancer Database study of 2362 cases. Oral Oncol. 2018;82:53–60. Krishnan V, et al. NOR-1 (NR4A3) immunostaining on cytologic preparations for the preoperative diagnosis of acinic cell carcinoma of the salivary gland. J Am Soc Cytopathol. 2022;11:352–8. Dogan S, et al. Loss of CDKN2A/B is a Molecular Marker of High-grade Histology and is Associated with Aggressive Behavior in Acinic Cell Carcinoma. Mod Pathol. 2023;36:100150. Patel NR, et al. Demographic trends and disease-specific survival in salivary acinic cell carcinoma: An analysis of 1129 cases. Laryngoscope. 2014;124:172–8. Nova-Camacho LM, et al. Cardiac Metastasis From Solid Cancers: A 35-Year Single-Center Autopsy Study. Arch Pathol Lab Med. 2023;147:177–84. A Rare Case. of a Minor Salivary Gland Carcinoma with a Voluminous Cardiac Metastasis. Ann med clin Oncol. 2021. 10.29011/AMCO-128.000128 . Burazor I, et al. Metastatic cardiac tumors: from clinical presentation through diagnosis to treatment. BMC Cancer. 2018;18:202. Buchanan L, et al. Metastatic Carcinoma to the Right Heart: The Complementary Utility of Contrast-Enhanced Echocardiography and Cardiac Positron Emission Tomography/Computed Tomography. CASE (Phila). 2022;6:3–7. Kishida T, et al. Pericardial metastasis of parotid mucoepidermoid carcinoma diagnosed by pericardial biopsy. Auris Nasus Larynx. 2022;49:727–32. Demirozu ZT, Ho JK, Sarwar AB, Delgado RM, Frazier OH. Adenocarcinoma of the parotid gland metastatic to the ventricular septum and right ventricular wall. Tex Heart Inst J. 2012;39:258–60. Barbetakis NG, Vassiliadis M, Krikeli M, Antoniadis T, Tsilikas C. Cardiac Tamponade Secondary to Metastasis from Adenocarcinoma of the Parotid Gland. World J Surg Oncol. 2003;1:20. Sulkes A, Weshler Z, Dolberg L, Biran S. Isolated pericardial metastasis of parotid tumor origin. Head Neck Surg. 1982;4:344–8. Becker SN, Reza MJ, Greenberg SH, Stein JJ. Pericardial effusion secondary to mucoepidermoid carcinoma of the parotid gland. A report of an unusual case. Cancer. 1975;36:1080–5. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 05 May, 2025 Reviews received at journal 05 May, 2025 Reviews received at journal 01 May, 2025 Reviewers agreed at journal 01 May, 2025 Reviewers agreed at journal 30 Apr, 2025 Reviewers invited by journal 29 Apr, 2025 Editor assigned by journal 26 Apr, 2025 Submission checks completed at journal 25 Apr, 2025 First submitted to journal 25 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6531041","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":450783828,"identity":"7fcd902f-c32b-4f5b-9544-26e63f5af916","order_by":0,"name":"Aniqa Nuzhat Chowdhury","email":"","orcid":"","institution":"Wake Forest Baptist Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Aniqa","middleName":"Nuzhat","lastName":"Chowdhury","suffix":""},{"id":450783830,"identity":"22b1ea4a-8c58-4151-b519-0b130c96a3ee","order_by":1,"name":"Shayna DeSando","email":"","orcid":"","institution":"Wake Forest Baptist Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Shayna","middleName":"","lastName":"DeSando","suffix":""},{"id":450783833,"identity":"d5d96f11-d137-45a4-b0c9-e3ba650b7d06","order_by":2,"name":"Fatima Zahra Aly","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYBAC9gbmBoYPDAwGDBJA3gOGA0AyAb8WngOMDYwzYFoSEojUwsxDmhb2g23Stm12xvzSzQc/JP64w8DPnmOAXwtPYpt0bluymeScY8kSCQnPGCR73uDXYs8A0rKN2cbgRo4BUMthBhADvy38D9ukLbfV29jfyP/8A6TFnqAWCaAtjNsOmxlI5LBBbJEgqOVhs2Xvv+PGEjfSzCwS0g7zSJx5VkDAYckHb/w4U23YPyP58Y0PNofl+NuTN+DVAgQsEihmEFIOAswfiFE1CkbBKBgFIxgAADE9Sb//aKABAAAAAElFTkSuQmCC","orcid":"","institution":"Wake Forest Baptist Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Fatima","middleName":"Zahra","lastName":"Aly","suffix":""}],"badges":[],"createdAt":"2025-04-25 18:23:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6531041/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6531041/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82159963,"identity":"398d5ba5-8649-4e62-a930-4b89d74ceca5","added_by":"auto","created_at":"2025-05-07 08:28:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":482524,"visible":true,"origin":"","legend":"\u003cp\u003eA) Cardiac MRI showing tumor indicated by red arrow arising from the pulmonary veins and into the left atrium. B) Brain MRI showing pontomedullary hemorrhage as indicated by red arrows.\u003c/p\u003e","description":"","filename":"Figure115.png","url":"https://assets-eu.researchsquare.com/files/rs-6531041/v1/1a2c65b4650cb5f5296f245a.png"},{"id":82160638,"identity":"f992bd0b-33f8-492c-93dc-d193c4550843","added_by":"auto","created_at":"2025-05-07 08:36:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":292349,"visible":true,"origin":"","legend":"\u003cp\u003eHistology images of original parotid gland tumor: A) Low power magnification, B) High power magnification.\u003c/p\u003e","description":"","filename":"OnlineFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6531041/v1/13bf623b95cc03f56e00b253.png"},{"id":82159964,"identity":"84868480-e92a-4462-a876-ea7a5c5ec46b","added_by":"auto","created_at":"2025-05-07 08:28:53","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":496622,"visible":true,"origin":"","legend":"\u003cp\u003eHistology images of tumor from left atrium: A) Low power magnification, B) High power magnification.\u003c/p\u003e","description":"","filename":"OnlineFigure3.png","url":"https://assets-eu.researchsquare.com/files/rs-6531041/v1/4ab71d594773005f703976a6.png"},{"id":82159966,"identity":"c5396bc4-cc86-4679-8fd0-b53af6d21d9d","added_by":"auto","created_at":"2025-05-07 08:28:53","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":211933,"visible":true,"origin":"","legend":"\u003cp\u003eImmunohistochemistry images of tumor from left atrium showing positive DOG1 and NOR1 and focally positive Periodic Acid Schiff with diastase (PASD) staining: A) DOG1 20X, B) NOR1 20X, C) PASD 20X.\u003c/p\u003e","description":"","filename":"OnlineFigure4.png","url":"https://assets-eu.researchsquare.com/files/rs-6531041/v1/72327b29e2e5fc55f7da9ea9.png"},{"id":82159975,"identity":"ffdd7f99-a7b5-4fe2-bf7a-7949b4eaf182","added_by":"auto","created_at":"2025-05-07 08:28:53","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":519720,"visible":true,"origin":"","legend":"\u003cp\u003eHistology images of the tumor from 4th ventricle of the brain: A) Low power magnification, B) High power magnification.\u003c/p\u003e","description":"","filename":"OnlineFigure5.png","url":"https://assets-eu.researchsquare.com/files/rs-6531041/v1/618fe359260921e631167451.png"},{"id":82162958,"identity":"02883d2a-6a49-49bf-9e3d-3256ae835576","added_by":"auto","created_at":"2025-05-07 08:52:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2674648,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6531041/v1/43fe20bc-e036-44a4-8c57-10b31b75048d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Case of Acinic Cell Carcinoma Metastasizing to the Heart","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcinic cell carcinoma of the salivary glands is a low-grade malignant cancer. Acinic cell carcinoma accounts for 17% of primary malignant salivary gland tumors\u003csup\u003e1\u003c/sup\u003e and 1\u0026ndash;6% of all epithelial salivary gland neoplasms\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. The primary cause of treatment failure and death in patients with salivary gland carcinoma is distant metastasis\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. In general, distant metastasis occurs in approximately 20% of salivary gland cancer cases\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Acinic cell carcinoma has a 12\u0026ndash;16% incidence of distant metastasis, with the lungs being the most common site\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Metastasis of salivary gland carcinoma to the heart is rare, with only seven cases reported in the literature. This case report presents the first published case of metastasis of acinic cell carcinoma of the parotid gland to the left atrium.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 56-year-old female was found to have a mass in the parotid gland and subsequently underwent parotidectomy and radical neck dissection in 2015. Histopathology showed multifocal acinic cell carcinoma without lymphovascular or perineural invasion and with close margins of less than 0.1 cm in multiple areas of the right carotid bed. Following parotidectomy, the patient underwent adjuvant radiation therapy to the right carotid bed (30 fractions over 6 weeks).\u003c/p\u003e \u003cp\u003eThree years later, the patient was found to have multiple lung nodules, and biopsy revealed metastatic acinic cell carcinoma with a BRAF mutation. She received 5 fractions of stereotactic body radiotherapy (SBRT) to the dominant left lung nodule. Subsequent imaging showed a gradual increase in the size of her multiple lung nodules; however, despite the clinical progression of her disease, the patient did not undergo any additional treatment or follow-up until May 2023 (4 years after initial SBRT), when she began experiencing dyspnea on exertion and weight loss. A computed tomography (CT) scan showed further increases in mediastinal adenopathy and lung metastasis.\u003c/p\u003e \u003cp\u003eDue to the worsening disease burden, the patient commenced treatment with a combined BRAF/MET inhibitor (dabrafenib and trametinib). Approximately 2 weeks after beginning this regimen, a CT scan showed findings concerning for either a thrombus in the left atrium and pulmonary veins or progression of her metastatic disease. The patient was treated for thromboembolic disease with anticoagulation. A subsequent cardiac magnetic resonance imaging (MRI) 7 months after beginning treatment with the BRAF/MET inhibitor revealed a 4 cm mass arising from the right pulmonary veins and entering the left atrium, with impingement of the mitral valve. The mass was excised, and the histology was most consistent with metastatic acinic cell carcinoma.\u003c/p\u003e \u003cp\u003eOne week after the removal of the tumor from the left atrium, a pontomedullary intracerebral hemorrhage was discovered. The patient underwent suboccipital craniotomy for removal, and pathologic evaluation was consistent with metastatic acinic cell carcinoma.\u003c/p\u003e \u003cp\u003eReview of the original parotid gland tumor showed two foci of acinic cell carcinoma (2.8 cm and 1.9 cm in size) with extensive tumor necrosis. The tumor showed large, polyhedral acinar cells with basophilic cytoplasm, prominent nucleoli, and nuclear pleomorphism, morphologically consistent with acinic cell carcinoma (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Margins were negative for carcinoma; however, the distance from the closest margin was less than 0.1 cm at multiple foci. Lymphovascular and perineural invasion were not identified.\u003c/p\u003e \u003cp\u003eSubsequent pathology from the left atrium mass showed an epithelial neoplasm with polyhedral acinar cells, basophilic cytoplasm, eccentric nuclei, and prominent nucleoli (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The cells from the tumor in the left atrium were less pleomorphic than those from the original parotid gland tumor. Immunohistochemical studies were performed, demonstrating DOG1, MOC31, and Claudin4 positivity; GATA3 was negative. Periodic Acid-Schiff with diastase (PASD) stain was positive (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Nuclear expression of NOR-1, which is a specific and sensitive marker for acinic cell carcinoma of the salivary gland\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e, showed strong nuclear staining (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), confirming the metastasis is acinic cell carcinoma.\u003c/p\u003e \u003cp\u003eAdditionally, histology from the tumor in the 4th ventricle of the brain was also consistent with metastatic acinic cell carcinoma, with a similar histomorphology to the mass in the heart.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAcinic cell carcinoma is a relatively rare malignant salivary gland neoplasm\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Cases of metastasis of acinic cell carcinoma have been reported to the lungs, cervical lymph nodes, and to the orbit. However, as per the authors\u0026rsquo; literature review, this is the first case study of metastatic acinic cell carcinoma to the heart.\u003c/p\u003e \u003cp\u003eAlthough acinic cell carcinoma is considered a low-grade salivary gland neoplasm, it is known to locally recur and metastasize. Case reports of acinic cell carcinoma with distant metastasis have identified lymph node involvement, perineural invasion, and lymphovascular invasion as prognostic predictors that aid in choosing a treatment plan\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Lymph node metastasis, one of the major prognostic indicators in acinic cell carcinoma, has a reported 10% incidence, despite it being considered to be a low-grade salivary gland malignancy\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCurrently, there is no specific histologic grading system for acinic cell carcinoma. High-grade transformation of acinic cell carcinoma was first described by Stanley et al. in 1988. It was defined as \u0026ldquo;areas of dedifferentiated high-grade adenocarcinoma or undifferentiated carcinoma\u0026rdquo; with associated areas of low-grade acinic cell carcinoma\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. This and subsequent studies found that increased adverse outcomes are associated with so-called high-grade acinic cell carcinoma\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. However, the definition of high-grade acinic cell carcinoma has not been consistent\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Xu \u003cem\u003eet al.\u003c/em\u003e proposed a grading system that includes 4 histologic features: tumor necrosis, mitotic index, fibrosis at invasive front, and tumor borders\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Using this grading system, high-grade acinic cell carcinomas carried a worse prognosis when compared with low-grade and intermediate-grade acinic cell carcinomas. This study also identified tumor size, older age, infiltrative border, lymphovascular invasion, nuclear anaplasia, necrosis, and advanced pT and pN stages as independent factors for adverse prognosis\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWhile there is no formal grading system for acinic cell carcinoma in the current AJCC Cancer Staging System and WHO classification of salivary glands, there is the inclusion of the presence or absence of high-grade transformation, which is defined as marked cytologic atypia, histologically distinct areas, atypical mitoses, increased mitotic activity, and tumor necrosis\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. In this case, the primary parotid gland tumor possessed high-grade features in the form of significant tumor necrosis, although it possessed a relatively low mitotic rate of 2/2 mm\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Thus, histologic grading of the parotid gland tumor may have predicted an adverse prognosis.\u003c/p\u003e \u003cp\u003eKhan et al. conducted a study utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database to identify risk factors that affect survival in patients with acinic cell carcinoma\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. This study graded tumors as well-differentiated, moderately differentiated, poorly differentiated, and undifferentiated. The study found that the variable with the highest hazard ratio for death compared to the other variables is high tumor grade, as defined by the criteria for high-grade transformation in the current AJCC Cancer Staging System\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Thus, this study highlights the significant negative impact of histologic grade on prognosis for patients with acinic cell carcinoma.\u003c/p\u003e \u003cp\u003ePoorly differentiated and high-grade variants of acinic cell carcinoma are known to have increased rates of recurrence and metastasis, usually via hematogenous spread\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. These high-grade and poorly differentiated variants have a reported recurrence rate of about 35% with a trend for late recurrence, going up to 30 years after initial presentation\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Spencer et al. detail a case of a woman who experienced multiple recurrences of acinic cell carcinoma with lung and intracranial metastasis over 32 years\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. A retrospective study with 2362 cases of acinic cell carcinoma of the parotid gland showed factors associated with poor prognosis, including advanced tumor stage, regional metastases, high histologic grade, tumors greater than 3 cm, and age over 70 years old\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eStudies have identified molecular alterations with potential for prognostic implications. The genes most commonly altered in acinic cell carcinoma of the salivary gland are CDKN2A, PTEN, and TP53. Dogan et al. showed a statistically significant worse prognosis in those patients with CDKN2A/B alterations, with associated higher-grade morphology and increased risk of distant metastasis. Haller et al. demonstrated that over 90% of acinic cell carcinoma cases contain translocation t(4;9) (q13; q31), resulting in the upregulation of nuclear receptor subfamily 4 group member 3 (NRA4A3)\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. This transcription factor can be detected using an antibody to neuron-derived orphan receptor 1 (NOR-1), which showed strong nuclear staining in our case. However, currently there are no available therapies targeting this molecular alteration.\u003c/p\u003e \u003cp\u003eIn our case, the patient\u0026rsquo;s metastatic acinic cell carcinoma was found to harbor a BRAF mutation, which occurs in approximately 4\u0026ndash;5% of all acinic cell carcinomas. This molecular alteration offers the opportunity to use a BRAF inhibitor for treatment; however, the prognostic or therapeutic value of BRAF mutations has not been established in acinic cell carcinoma\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. The 10-year survival of acinic cell carcinoma drops from 99.15% (local disease only) to 31.52% with distant metastasis\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Thus, distant metastasis of acinic cell carcinoma is a significant poor prognostic factor for this disease.\u003c/p\u003e \u003cp\u003eDue to the rarity of metastatic salivary gland cancers, there are no large clinical trials to determine the optimal treatment. Vidyadhara et al. detail a case of simultaneous metastasis of acinic cell carcinoma to the lymph nodes, lungs, and spine, and suggest the importance of postoperative radiotherapy if there is incomplete resection of the primary tumor\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. A study of 301 patients undergoing excision of major salivary glands for cancer at Memorial Sloan-Kettering between 1985 and 2009 showed 20% of salivary gland carcinomas had distant metastasis with most being to the lung (49%) or bone (40%)\u003csup\u003e4\u003c/sup\u003e. In this study, 16% of acinic cell carcinomas developed distant metastasis.\u003c/p\u003e \u003cp\u003eThe heart\u0026rsquo;s unique lymphatic organization protects it from metastasis. Still, metastatic disease is more common than primary tumors of the heart\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Metastases are the most common neoplasms of the heart with an incidence between 1.5\u0026ndash;20% among autopsies of cancer patients\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Tumor spreads to the heart via direct spread, bloodstream, lymphatics, and intracavitary migration through the pulmonary veins. Some tumors have displayed higher rates of metastasis to the heart, such as melanoma and mediastinal primary tumors\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Metastasis of salivary gland carcinomas to the heart is particularly rare. A few cases of metastatic epithelial-myoepithelial carcinoma of the parotid gland to the heart have been reported\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Buchanan et al. describe a case of women with metastasis of epithelial myoepithelial carcinoma of the parotid gland to the right heart, which was identified by transthoracic echocardiography\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Kishida et al. describe a case of metastatic mucoepidermoid carcinoma to the heart\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. Foglietta et al. present a case of polymorphous adenocarcinoma of the minor salivary glands with metastasis to the right ventricle\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e provides a summary of prior literature describing salivary gland carcinoma metastasis to the heart.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of prior literature on salivary gland carcinoma metastasis to the heart.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrimary Type of Carcinoma\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDescription of Case\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBuchanan \u003cem\u003eet al.\u003c/em\u003e (2022)\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEpithelial-myoepithelial carcinoma of the parotid gland\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 y.o. female with metastasis to the right ventricle with reduction of right ventricular systolic function.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKishida \u003cem\u003eet al.\u003c/em\u003e (2022)\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMucoepidermoid carcinoma of the parotid gland\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 y.o. male with cardiac tamponade secondary metastasis to the pericardium of inferior heart.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFoglietta \u003cem\u003eet al.\u003c/em\u003e (2021)\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePolymorphous adenocarcinoma of the minor salivary glands\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70 y.o. female with metastasis to the right ventricle.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDemirozu \u003cem\u003eet al.\u003c/em\u003e (2012)\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdenocarcinoma of the parotid gland\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51 y.o. male with metastasis to the right ventricular wall and ventricular septum.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBarbetakis \u003cem\u003eet al.\u003c/em\u003e (2003)\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdenocarcinoma of the parotid gland\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 y.o. female with cardiac tamponade secondary to metastasis to the pericardium.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSulkes \u003cem\u003eet al.\u003c/em\u003e (1982)\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdenocarcinoma of the parotid gland\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 y.o. female with pericardial effusion secondary to metastasis to the pericardium.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBecker \u003cem\u003eet al.\u003c/em\u003e (1975)\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMucoepidermoid carcinoma of the parotid gland\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 y.o. female with pericardial effusions secondary to metastasis to the pericardium.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTo our knowledge, this case report is the only published account of a case of acinic cell carcinoma metastasis to the heart. Due to the significant prognostic significance of distant metastasis in salivary gland carcinomas, this is a unique case of a patient that presented with metastasis to the heart 8 years after initial diagnosis. Because of the rarity of these cases, it is important to highlight the disease course in cases of salivary gland carcinoma with distant metastasis. In conclusion, acinic cell carcinoma is a low-grade carcinoma of the salivary gland, with the distinct ability to metastasize to distant sites, including the heart.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eDisclosures: None\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful to Dr Ronald Ghassan MD (Memorial Sloan-Kettering, USA) for his advice during the preparation of the manuscript and for the NOR-1 immunohistochemical stain.\u003c/p\u003e\n\u003cp\u003eFunding: This study was not supported by any funding.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConflict of Interest: The authors declare that they have no conflict of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEthical Approval: For this type of study formal consent is not required. This study was approved by the Institutional Review Board.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsent to Participate: This study has obtained IRB approval from Atrium Health Wake Forest Baptist hospital and the need for informed consent was waived.\u003c/p\u003e\n\u003cp\u003eConsent for Publication: Consent for publication was obtained for every individual person\u0026rsquo;s data included in the study.\u003c/p\u003e\n\u003cp\u003eAvailability of Data and Materials: This study is a case study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCode Availability: No software application or custom code has been used in the preparation of this case study. \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAl-Zaher N, Obeid A, Al-Salam S, Al-Kayyali B. Acinic cell carcinoma of the salivary glands: A literature review. Hematol Oncol Stem Cell Ther. 2009;2:259\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAli SA, et al. 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Cancer. 1975;36:1080\u0026ndash;5.\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":"head-and-neck-pathology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Head and Neck Pathology](https://www.springer.com/journal/12105)","snPcode":"12105","submissionUrl":"https://submission.springernature.com/new-submission/12105/3","title":"Head and Neck Pathology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Acinic cell carcinoma, salivary gland neoplasm, metastasis to heart, NOR-1","lastPublishedDoi":"10.21203/rs.3.rs-6531041/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6531041/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWe present the case of a patient with acinic cell carcinoma of the parotid gland who was found to have metastasis to the left atrium of the heart. The pathologic findings and prior reports of metastasis of acinic cell carcinoma are discussed in this article. Grading of acinic cell carcinoma and utility of immunohistochemical study using NOR-1 is discussed.\u003c/p\u003e","manuscriptTitle":"A Case of Acinic Cell Carcinoma Metastasizing to the Heart","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-07 08:28:48","doi":"10.21203/rs.3.rs-6531041/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-05T19:37:34+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-05T19:13:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-01T20:01:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"229041933082671000653131763627771008892","date":"2025-05-01T19:53:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"287505397195891923888186942635945820468","date":"2025-04-30T16:11:55+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-30T01:20:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-26T17:04:55+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-26T00:35:27+00:00","index":"","fulltext":""},{"type":"submitted","content":"Head and Neck Pathology","date":"2025-04-25T18:21:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"head-and-neck-pathology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Head and Neck Pathology](https://www.springer.com/journal/12105)","snPcode":"12105","submissionUrl":"https://submission.springernature.com/new-submission/12105/3","title":"Head and Neck Pathology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"c9c3f7ad-538d-47db-b06e-366700def479","owner":[],"postedDate":"May 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-05-29T17:23:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-07 08:28:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6531041","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6531041","identity":"rs-6531041","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}