Metastasis of nasopharyngeal carcinoma to the brain: a case report and literature review

Metastasis of nasopharyngeal carcinoma to the brain: a case report and literature review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Metastasis of nasopharyngeal carcinoma to the brain: a case report and literature review Junwei Sun, Jianhua Li, Mingyu Wang, Zhisheng Kan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1577540/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: Nasopharyngeal carcinoma (NPC) is one of the most common tumors in the head and neck. Brain metastasis from NPC is extremely rare and few case reports describe it in detail. Case presentation: We presented the experience of a 51-year-old patient with NPC that progressed to brain metastases and was surgically removed. The primary lesion of NPC was located in his left pharynx, while the metastatic mass appeared in the right temporal lobe, and it caused significant space-occupying effects. Surgical resection was performed and histopathology after surgery confirmed that the mass was a non-keratinizing undifferentiated carcinoma. Conclusions: Clinicians should pay continuous attention to the occurrence of NPC brain metastasis. More studies should focus on the epidemiological characteristics, the mechanisms of metastasis, advanced diagnostic methods, and better treatment strategies for NPC brain metastases. nasopharyngeal carcinoma brain metastases temporal lobe surgery case report Figures Figure 1 Figure 2 Background Nasopharyngeal carcinoma (NPC) is a kind of cervical cancer that is epithelial, radiation-sensitive, and has a poor prognosis with a five-year overall survival rate of less than 30% [ 1 ]. Radiation therapy, with or without platinum-based chemotherapy, is the first-line treatment for NPC [ 2 , 3 ]. NPC is endemic in Southeast Asia and North Africa, particularly in southern China, where the incidence rate can reach 30 to 80 cases per 100,000 persons [ 4 ]. Non-keratinizing carcinoma is the most common histological type and is commonly associated with EBV, pickled foods, and genetics [ 5 ]. The main causes of treatment failure are local recurrence and distant metastasis; The incidence of distant metastasis can reach 17%-53%, and 52% of patients with metastases develop within the first year after radiotherapy [ 6 – 9 ]. Bone, lung, liver, and retroperitoneal lymph nodes are common sites of distant metastases [ 10 , 11 ]. Cisplatin-based chemotherapy is currently the first-line treatment for NPC distant metastases [ 12 ]. True brain metastases are extremely rare [ 7 – 10 , 13 – 17 ], although the locally advanced tumor may invade the brain directly, such as destroying the skull and invading the cavernous sinus. The occurrence of brain metastases from NPC should not be ignored and strategies for identifying them include routine brain imaging examinations and keeping cautious about suspicious symptoms. The mechanism of brain metastasis has not been fully elucidated, and the hematogenous route or cerebral spinal fluid (CSF) spread may be essential in it [ 10 ]. Brain metastases can be partially destroyed by radiotherapy and chemotherapy, and they also can be removed surgically if necessary [ 7 , 9 , 10 , 15 , 16 ]. In this study, we report the case of a man who underwent successful surgery for a right temporal lobe metastasis from NPC in our institution. In addition, we review the literature on cases of brain metastases from NPC to discover more about this uncommon occurrence. Case Presentation A 51-year-old man from Guangxi, China, was diagnosed with NPC in October 2020. Electronic nasopharyngoscopy was used to obtain pathological tissue, and the histologic type was identified to be undifferentiated nonkeratinizing carcinoma. Brain Magnetic Resonance Imaging (MRI) showed that the tumor size was about 3.9× 3.3× 3.2cm, which had invaded the skull base, left cavernous sinus, and left internal carotid artery. The tumor had also metastasized to multiple lymph nodes in the left retropharyngeal and bilateral necks. The patient also underwent Positron emission tomography and computer tomography (PET/CT) and no other metastatic lesions were found. The stage of the tumor was determined to be stage IVA (T4N2M0, according to the eighth edition of AJCC TNM). From December 2020 to February 2021, the patient received five cycles of induction chemotherapy with the regimen TPF (paclitaxel liposome + cisplatin + 5-FU). Following that, the patient received concurrent chemoradiotherapy (radiotherapy with VMAT technology, total dose of 69.96 Gy in 33 fractions; concurrent chemotherapy with cisplatin 100mg/m2, every three weeks). In April 2021, the full course of treatment was completed and according to Response Assessment in Neuro-Oncology (RANO) criteria, the post-treatment response was rated as a partial response. In July 2021, a new small nodular enhancing lesion appeared in the right temporal lobe in a routine MRI examination after treatment. The size was around 0.6 × 0.5 cm. There was no evidence of a relationship between the nasopharynx and the lesion and close follow-up continued. After three months, MRI showed that the maximum section of the mass had reached 3.7×3.5cm, which was cystic with the cyst wall was isointense on T1-weighted imaging (T1WI), hyperintense on T2-weighted imaging (T2WI) and contrast-enhanced T1WI showed enhancement of the cyst wall. The right lateral and third ventricles were compressed and shifted to the left, while the midline was relocated to the left by 1.6 cm. Within the enhanced area of the lesion, high flow perfusion was on Perfusion-Weighted Imaging (PWI), and magnetic resonance spectroscopy (MRS) showed an almost disappeared NAA peak and decreased Cr and Cho peak (Fig. 1). At the moment, the patient was still free of any symptoms. To eliminate the risk of acute brain herniation caused possibly by the shift of the midline and to identify the pathology of the lesion, the patient underwent right temporal lobe mass resection, and NPC brain metastases were diagnosed according to postoperative pathological analysis (Fig. 2). The pathological type was identified as non-keratinizing undifferentiated carcinoma and the immunohistochemical results were as follows: NUT (-), P6 (-), P40 (2+), P63 (2+), Ki-67 (80%+), CD117 (-), EBER (+). In addition, we perform a lumbar puncture to collect CSF and the cytology reveal no tumor cells in his CSF. MRI one month after surgery showed no residual tumor in the surgical area, and the right ventricle and third ventricle displacement had partially recovered. The patient was regularly re-examined for cranial MRI after discharge and no recurrence has been observed to date. This study was conducted under an agreement approved by the Ethics Committee of the Cancer Hospital of the Chinese Academy of Medical Sciences Shenzhen Hospital. The patient's written informed consent was acquired. We reported this case following CARE reporting guidelines [ 18 ]. Discussion The failure of NPC treatment is frequently attributed to local recurrence and distant metastases [ 19 ]. Bone, lung, and liver are the most organs of NPC distant metastasis, while true brain metastasis (not the tumor breaking through the skull and invading the brain directly) is uncommon [ 10 , 11 , 20 ]. Khor et al. reported that among 99 patients with NPC metastases, 3 of them were brain metastases (3.3%), and Geng et al. reported that the incidence of brain metastasis in NPC patients was 0.3% in their institution [ 13 , 20 ]. We present the case of a patient with locally advanced NPC who developed brain metastases after completing concurrent chemoradiotherapy. The primary tumor invaded his cavernous sinus on the left side directly, but brain metastases appeared in the right temporal lobe several months later. To understand more about this rare occurrence, we searched through PubMed for relevant literature. Some reporters have described NPC brain metastases earlier, but these cases lacked specific clinical information [ 20 – 22 ]. We summarize the case reports of NPC brain metastasis with more detailed information in Table 1 . Case reports of spinal cord metastases and direct brain invasion were excluded. Men are more likely to develop NPC than women, as is NPC brain metastases. From the diagnosis of nasopharyngeal carcinoma to the discovery of brain metastasis, the length of time varies greatly, with the longest reaching 53 months [ 7 ]. The symptoms of NPC brain metastases are similar to those of other intracranial space-occupying lesions, making their diagnosis more difficult. The most common pathological subtype of brain metastases, according to WHO (2003) classification of NPC, is non-keratinizing undifferentiated carcinoma, and it is also the most common subtype found in other metastatic organs [ 23 ]. Ngan et al. pointed out that the occipital lobe is the most common area for NPC brain metastases [ 15 ]. However, our study has shown that the frontal lobe is also a common area. To our knowledge, primary tumor types are highly correlated with the spatial distribution of brain metastases, for example, brain metastases from pulmonary and gastrointestinal tumors favored the infratentorial area, while brain metastases from skin cancer and sarcoma chose the supratentorial space [ 24 ]. In addition, NPC metastases to the dura and the skull have also been reported [ 9 , 13 ]. More cases will help us to draw a reliable conclusion on which area of the brain NPC favors. In general, imaging plays an important role in the diagnosis of brain metastases, but it is not easy to distinguish the specific tumor type. On MRI, most NPC brain metastases present as a T1-enhancing mass with surrounding edema, which is typical of brain metastases. In particular, the MRI characteristic of NPC metastases in the dura may greatly mimic those of meningiomas [ 9 ]. Unfortunately, functional MRI of NPC brain metastases has not been described in past studies. In our case, hyperperfusion was shown on PWI, and MRS revealed the disappearance of the NAA peak and a decrease in the Cr and Cho peaks. With the development of imageology, we have been able to identify metastases from details in MRI by some algorithm [ 25 , 26 ]. We are optimistic that a sufficient number of images from MRI will enable us to diagnose NPC brain metastases timely and precisely in the future. The treatment of NPC brain metastases is a huge challenge and there is no standard treatment to date. To choose the appropriate treatment option, the degree of invasiveness, the presence of multiple metastases, Karnofsky Performance Status (KPS) score, and lifespan should all be taken into account. Chemotherapy and radiotherapy are the most common treatment strategies. and targeted therapy and immunotherapy were also tried [ 13 ]. Despite the use of various local and systemic therapies, these patients still have a poor prognosis. Surgery is more recommended in metastasis to the brain rather than other common metastatic organs. Surgical removal of the mass can effectively minimize the risk of brain herniation due to the tumor mass effect. In our study, the brain midline of the patient has been displaced by more than 1 cm and excision of the tumor is unavoidable to lower the intracranial pressure. Table 1 Summary of Previous Reports of Brain Metastasis from Nasopharyngeal Author and Year Age gender Time * Histology Site in the brain Treatment Geng et al. 2021 66 Man 8 months a Basaloid squamous cell carcinoma Multiple lesions CHEMO + IMT + targeted therapy Park et al. 2019 49 Woman 53 months a Unknown Frontal lobe RT 44 Man 23 months b Unknown Cerebellum Surgery + RT Su et al. 2019 43 Man 3 years a Non-keratinizing undifferentiated carcinoma Occipital lobe and frontal bone CHEMO + RT Shen et al. 2017 47 Woman 16 months c Non-keratinizing undifferentiated carcinoma Frontal lobe CHEMO + RT 47 Man 3 years a Non-keratinizing undifferentiated carcinoma Frontal lobe Surgery + CHEMO + RT Kuo et al. 2014 37 Woman 7 months a Non-keratinizing differentiated carcinoma Frontotemporal lobe and dura Surgery + RT + CHEMO Kaidar et al. 2012 54 Man Unknown Poorly differentiated carcinoma Occipital lobe RT Ozyar et al. 2004 41 Man 45 months c Undifferentiated carcinoma Temporal lobe Surgery + RT Ngan et al. 2002 33 Man Unknown Undifferentiated carcinoma Occipital lobe CHEMO Liaw et al. 1994 69 Man Concurrence Non- keratinizing squamous cell carcinoma Occipital lobe CHEMO + RT * : Time refers to the interval from the diagnosis of NPC (a), surgery (b), radiotherapy (c) to the discovery of brain metastases. CHEMO: chemotherapy IMT: immunotherapy RT: radiotherapy Why are brain metastases from NPC so rare? The "seed and soil theory" states that tumor metastasis is dependent on the molecular and genetic features of tumor cells, as well as the systemic and brain microenvironment [ 15 , 24 ]. Su et al. suggested that tumor cells enter veins through regional lymph nodes, and the single direction valve in veins prevents reverse flow, resulting in a low incidence of NPC brain metastases [ 8 ]. Another viewpoint is that patients did not live long enough for brain metastases to develop [ 14 ]. Although hematogenous metastasis is recognized by most people, some researchers have also proposed the possibility of cerebrospinal fluid metastasis, especially in patients with spinal cord metastasis, and a possible mechanism was the destruction of the blood-brain barrier following the invasion of venous sinuses [ 15 , 27 ]. For the patient in our study, it is difficult to determine which metastatic pattern was involved. The negative results of his cerebrospinal fluid cytology could not completely exclude the metastasis through cerebrospinal fluid. Conclusion Brain metastases of NPC are very rare and have an extremely poor prognosis. We report the experience of a patient with non-keratinizing undifferentiated carcinoma that progressed to brain metastases and was surgically removed. The possible transfer pathway of the NPC brain is by hematogenous dissemination or cerebrospinal fluid. Palliative radiotherapy and chemotherapy are difficult to achieve satisfactory results, and targeted therapy and immunotherapy have also been tried. Surgery can save the lives of some patients with NPC brain metastases. Clinicians should keep continuous attention to the risk of metastases after the initial treatment of NPC and remain vigilant for rare manifestations. Further studies are needed to focus on the epidemiological characteristics, the mechanisms of metastasis, advanced diagnostic methods, and better treatment strategies for NPC brain metastases. Abbreviations NPC: nasopharyngeal carcinoma; CSF: cerebral spinal fluid; MRI: Magnetic Resonance Imaging; PET/CT: Positron emission tomography and computer tomography; RANO: Response Assessment in Neuro-Oncology; T1WI: T1-weighted imaging; T2WI: T2-weighted imaging; PWI: Perfusion-Weighted Imaging; MRS: magnetic resonance spectroscopy. Declarations Ethics approval and consent to participate The study has been approved by the Ethics Committee of the Cancer Hospital of the Chinese Academy of Medical Sciences Shenzhen Hospital. Informed consent was assigned in Chinese format. Consent for publication Written informed consent was obtained from the patient for publication of this case report and accompanying images. Availability of data and materials The authors confirm the data and materials are available. Competing interests The authors declare that they have no competing interests. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors' contributions Junwei Sun: drafting of the manuscript; disease treatment. Jianhua Li, Mingyu Wang: acquisition of data; analysis and interpretation of pathology. Zhisheng Kan: reading and approving the final manuscript. Acknowledgments The authors thank Jian Guan, MD, from the Department of Pathology, the Chinese Academy of Medical Sciences Shenzhen Hospital, for the provision of pathological images. References Liu F, Xiao J, Xu G et al. (2013) Fractionated stereotactic radiotherapy for 136 patients with locally residual nasopharyngeal carcinoma. Radiat Oncol 8:157. https://doi.org/10.1186/1748-717X-8-157 Pfister DG, Spencer S, Adelstein D et al. (2020) Head and Neck Cancers, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 18:873–898. https://doi.org/10.6004/jnccn.2020.0031 Razak ARA, Siu LL, Liu F-F et al. (2010) Nasopharyngeal carcinoma: the next challenges. Eur J Cancer 46:1967–1978. https://doi.org/10.1016/j.ejca.2010.04.004 Chen Y-P, Chan ATC, Le Q-T et al. (2019) Nasopharyngeal carcinoma. The Lancet 394:64–80. https://doi.org/10.1016/S0140-6736(19)30956-0 Guo X, Johnson RC, Deng H et al. (2009) Evaluation of nonviral risk factors for nasopharyngeal carcinoma in a high-risk population of Southern China. Int J Cancer 124:2942–2947. https://doi.org/10.1002/ijc.24293 Huang C-L, Guo R, Li J-Y et al. (2020) Nasopharyngeal carcinoma treated with intensity-modulated radiotherapy: clinical outcomes and patterns of failure among subsets of 8th AJCC stage IVa. Eur Radiol 30:816–822. https://doi.org/10.1007/s00330-019-06500-5 Park S-H, Yoon S-Y, Park K-S et al. (2019) Brain Metastasis from Nasopharyngeal Carcinoma Treated with Stereotactic Radiosurgery. World Neurosurg 126:160–163. https://doi.org/10.1016/j.wneu.2019.03.029 Su Z, Cao X, Zou G (2019) Brain and frontal-bone metastasis from nasopharyngeal carcinoma: Case report and literature review. Head Neck 41:E153-E158. https://doi.org/10.1002/hed.25859 Kuo C-L, Ho DM-T, Ho C-Y (2014) Dural metastasis of nasopharyngeal carcinoma: rare, but worth considering. Singapore Med J 55:e82-4. https://doi.org/10.11622/smedj.2013214 Shen C, Ying H, Lu X et al. (2017) Nasopharyngeal carcinoma with central nervous system metastases: Two case reports and a review of the literature. Medicine (Baltimore) 96:e9175. https://doi.org/10.1097/MD.0000000000009175 Ahmad A, Stefani S (1986) Distant metastases of nasopharyngeal carcinoma: a study of 256 male patients. J Surg Oncol 33:194–197. https://doi.org/10.1002/jso.2930330310 Li X-Y, Chen Q-Y, Sun X-S et al. (2019) Ten-year outcomes of survival and toxicity for a phase III randomised trial of concurrent chemoradiotherapy versus radiotherapy alone in stage II nasopharyngeal carcinoma. Eur J Cancer 110:24–31. https://doi.org/10.1016/j.ejca.2018.10.020 Geng X, Hao F, Han G et al. (2021) Dural and Multiple Brain Metastases From Basaloid Nasopharyngeal Carcinoma: Case Report and Literature Review. Front Oncol 11:665652. https://doi.org/10.3389/fonc.2021.665652 Kaidar-Person O, Kuten J, Atrash F et al. (2012) Brain metastasis of nasopharyngeal carcinoma: a case report and literature review. Case Rep Med 2012:405917. https://doi.org/10.1155/2012/405917 Ngan RKC, Yiu HHY, Cheng HKM et al. (2002) Central nervous system metastasis from nasopharyngeal carcinoma: a report of two patients and a review of the literature. Cancer 94:398–405. https://doi.org/10.1002/cncr.10179 2004 Enis …zyar1 Nasopharyngeal carcinoma with brain metastasis: A case report Gagnier JJ, Kienle G, Altman DG et al. (2013) The CARE Guidelines: Consensus-based Clinical Case Reporting Guideline Development. Glob Adv Health Med 2:38–43. https://doi.org/10.7453/gahmj.2013.008 Sun X-S, Liu S-L, Luo M-J et al. (2019) The Association Between the Development of Radiation Therapy, Image Technology, and Chemotherapy, and the Survival of Patients With Nasopharyngeal Carcinoma: A Cohort Study From 1990 to 2012. Int J Radiat Oncol Biol Phys 105:581–590. https://doi.org/10.1016/j.ijrobp.2019.06.2549 Khor TH, Tan BC, Chua EJ et al. (1978) Distant metastases in nasopharyngeal carcinoma. Clinical Radiology 29:27–30. https://doi.org/10.1016/S0009-9260(78)80160-3 Ho JH (1978) An epidemiologic and clinical study of nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 4:182–198 Bydder GM, Steiner RE, Young IR et al. (1982) Clinical NMR imaging of the brain: 140 cases. AJR Am J Roentgenol 139:215–236. https://doi.org/10.2214/ajr.139.2.215 Wang H-Y, Chang Y-L, To K-F et al. (2016) A new prognostic histopathologic classification of nasopharyngeal carcinoma. Chin J Cancer 35:41. https://doi.org/10.1186/s40880-016-0103-5 Schroeder T, Bittrich P, Kuhne JF et al. (2020) Mapping distribution of brain metastases: does the primary tumor matter? J Neurooncol 147:229–235. https://doi.org/10.1007/s11060-020-03419-6 Cho SJ, Sunwoo L, Baik SH et al. (2021) Brain metastasis detection using machine learning: a systematic review and meta-analysis. Neuro Oncol 23:214–225. https://doi.org/10.1093/neuonc/noaa232 Grøvik E, Yi D, Iv M et al. (2020) Deep learning enables automatic detection and segmentation of brain metastases on multisequence MRI. J Magn Reson Imaging 51:175–182. https://doi.org/10.1002/jmri.26766 Cvitkovic E, Bachouchi M, Boussen H et al. (1993) Leukemoid reaction, bone marrow invasion, fever of unknown origin, and metastatic pattern in the natural history of advanced undifferentiated carcinoma of nasopharyngeal type: a review of 255 consecutive cases. J Clin Oncol 11:2434–2442. https://doi.org/10.1200/JCO.1993.11.12.2434 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-1577540","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":100323542,"identity":"c0d9fdf7-f465-4212-82d4-29bf0bc07537","order_by":0,"name":"Junwei Sun","email":"","orcid":"","institution":"National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital \u0026 Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Junwei","middleName":"","lastName":"Sun","suffix":""},{"id":100323543,"identity":"3a0932a8-a704-479f-ac27-640db25a3eb0","order_by":1,"name":"Jianhua Li","email":"","orcid":"","institution":"National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital \u0026 Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Jianhua","middleName":"","lastName":"Li","suffix":""},{"id":100323544,"identity":"8294b489-2268-43f4-802a-f707ddeefd7a","order_by":2,"name":"Mingyu Wang","email":"","orcid":"","institution":"National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital \u0026 Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Mingyu","middleName":"","lastName":"Wang","suffix":""},{"id":100323545,"identity":"9fe9082f-9d1f-400c-bbc7-5216a4283a79","order_by":3,"name":"Zhisheng Kan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYBACCQYehgOMDUAWe2Pjww+kaeE53GwsQawWBrAWifQ2AR5itEj2nz148OcOmzz5yIdtQAPs5HQbCGiRZjiXcJj3TFqx4e3EtgcFDMnGZgcIaJFj7DE4zNh2OHHj7MR2AwmGA4nbCGph5jE4+LPtf+LGmQfbJHiI0SLNxmNwgLftQOJ8CUYitUj28Bgc5m1LTtzAkwgMZAMi/CJx/ozxx59tdonz248/fPihwk6OoBY4MACrNCBWOQjIN5CiehSMglEwCkYUAAD2ZEYVNshrfgAAAABJRU5ErkJggg==","orcid":"","institution":"National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital \u0026 Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":true,"prefix":"","firstName":"Zhisheng","middleName":"","lastName":"Kan","suffix":""}],"badges":[],"createdAt":"2022-04-20 15:59:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1577540/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1577540/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":20667830,"identity":"b8460b4f-a6ef-4ea1-8f37-9e54995556f1","added_by":"auto","created_at":"2022-04-22 16:57:15","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":97736,"visible":true,"origin":"","legend":"\u003cp\u003eBrain\u003cstrong\u003e \u003c/strong\u003eMRI of the patient before surgery. Contrast-enhanced T1WI shows a well-enhanced tumor, 3.7×3.5cm in size, in (A) axial, (B) sagittal, and (C) coronal views. T2WI (D) showed a high signal intensity of the tumor with surrounding cerebral edema. Cerebral Blood Flow (CBV, a parameter of PWI) (E) showed high flow perfusion of the tumor. MRS (F) showed an almost disappeared NAA peak and decreased Cr peak and Cho peak.\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1577540/v1/2fc12cd17e299ff131c50003.jpg"},{"id":20667829,"identity":"792c8678-9f77-44c0-b5f5-03551b184291","added_by":"auto","created_at":"2022-04-22 16:57:15","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":123672,"visible":true,"origin":"","legend":"\u003cp\u003ePathological\u0026nbsp;image of the surgical specimen (Hematoxylin and eosin stain, ×40). The left side of the image shows non-keratinizing undifferentiated carcinoma and the upper right side of the image shows normal brain tissue.\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1577540/v1/6088755031e985f28ea1f01d.jpg"},{"id":20667832,"identity":"21b8ca96-83a8-4d10-9812-f7b34e53c964","added_by":"auto","created_at":"2022-04-22 16:57:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":368178,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1577540/v1/1d119b65-ed33-4d41-9cd1-6c6c2f26deb1.pdf"},{"id":20667831,"identity":"25f33e4c-ebf2-457c-9483-28f7406f6dfe","added_by":"auto","created_at":"2022-04-22 16:57:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":368178,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1577540/v1/d89761b6-0c86-469c-95e9-79dae6886e36.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Metastasis of nasopharyngeal carcinoma to the brain: a case report and literature review","fulltext":[{"header":"Background","content":"\u003cp\u003eNasopharyngeal carcinoma (NPC) is a kind of cervical cancer that is epithelial, radiation-sensitive, and has a poor prognosis with a five-year overall survival rate of less than 30% [\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e]. Radiation therapy, with or without platinum-based chemotherapy, is the first-line treatment for NPC [\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]. NPC is endemic in Southeast Asia and North Africa, particularly in southern China, where the incidence rate can reach 30 to 80 cases per 100,000 persons [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]. Non-keratinizing carcinoma is the most common histological type and is commonly associated with EBV, pickled foods, and genetics [\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e]. The main causes of treatment failure are local recurrence and distant metastasis; The incidence of distant metastasis can reach 17%-53%, and 52% of patients with metastases develop within the first year after radiotherapy [\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]. Bone, lung, liver, and retroperitoneal lymph nodes are common sites of distant metastases [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]. Cisplatin-based chemotherapy is currently the first-line treatment for NPC distant metastases [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e]. True brain metastases are extremely rare [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e], although the locally advanced tumor may invade the brain directly, such as destroying the skull and invading the cavernous sinus. The occurrence of brain metastases from NPC should not be ignored and strategies for identifying them include routine brain imaging examinations and keeping cautious about suspicious symptoms. The mechanism of brain metastasis has not been fully elucidated, and the hematogenous route or cerebral spinal fluid (CSF) spread may be essential in it [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]. Brain metastases can be partially destroyed by radiotherapy and chemotherapy, and they also can be removed surgically if necessary [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e]. In this study, we report the case of a man who underwent successful surgery for a right temporal lobe metastasis from NPC in our institution. In addition, we review the literature on cases of brain metastases from NPC to discover more about this uncommon occurrence.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 51-year-old man from Guangxi, China, was diagnosed with NPC in October 2020. Electronic nasopharyngoscopy was used to obtain pathological tissue, and the histologic type was identified to be undifferentiated nonkeratinizing carcinoma. Brain Magnetic Resonance Imaging (MRI) showed that the tumor size was about 3.9\u0026times; 3.3\u0026times; 3.2cm, which had invaded the skull base, left cavernous sinus, and left internal carotid artery. The tumor had also metastasized to multiple lymph nodes in the left retropharyngeal and bilateral necks. The patient also underwent Positron emission tomography and computer tomography (PET/CT) and no other metastatic lesions were found. The stage of the tumor was determined to be stage IVA (T4N2M0, according to the eighth edition of AJCC TNM). From December 2020 to February 2021, the patient received five cycles of induction chemotherapy with the regimen TPF (paclitaxel liposome\u0026thinsp;+\u0026thinsp;cisplatin\u0026thinsp;+\u0026thinsp;5-FU). Following that, the patient received concurrent chemoradiotherapy (radiotherapy with VMAT technology, total dose of 69.96 Gy in 33 fractions; concurrent chemotherapy with cisplatin 100mg/m2, every three weeks). In April 2021, the full course of treatment was completed and according to Response Assessment in Neuro-Oncology (RANO) criteria, the post-treatment response was rated as a partial response.\u003c/p\u003e\n\u003cp\u003eIn July 2021, a new small nodular enhancing lesion appeared in the right temporal lobe in a routine MRI examination after treatment. The size was around 0.6 \u0026times; 0.5 cm. There was no evidence of a relationship between the nasopharynx and the lesion and close follow-up continued. After three months, MRI showed that the maximum section of the mass had reached 3.7\u0026times;3.5cm, which was cystic with the cyst wall was isointense on T1-weighted imaging (T1WI), hyperintense on T2-weighted imaging (T2WI) and contrast-enhanced T1WI showed enhancement of the cyst wall. The right lateral and third ventricles were compressed and shifted to the left, while the midline was relocated to the left by 1.6 cm. Within the enhanced area of the lesion, high flow perfusion was on Perfusion-Weighted Imaging (PWI), and magnetic resonance spectroscopy (MRS) showed an almost disappeared NAA peak and decreased Cr and Cho peak (Fig.\u0026nbsp;1). At the moment, the patient was still free of any symptoms. To eliminate the risk of acute brain herniation caused possibly by the shift of the midline and to identify the pathology of the lesion, the patient underwent right temporal lobe mass resection, and NPC brain metastases were diagnosed according to postoperative pathological analysis (Fig.\u0026nbsp;2). The pathological type was identified as non-keratinizing undifferentiated carcinoma and the immunohistochemical results were as follows: NUT (-), P6 (-), P40 (2+), P63 (2+), Ki-67 (80%+), CD117 (-), EBER (+). In addition, we perform a lumbar puncture to collect CSF and the cytology reveal no tumor cells in his CSF. MRI one month after surgery showed no residual tumor in the surgical area, and the right ventricle and third ventricle displacement had partially recovered. The patient was regularly re-examined for cranial MRI after discharge and no recurrence has been observed to date.\u003c/p\u003e\n\u003cp\u003eThis study was conducted under an agreement approved by the Ethics Committee of the Cancer Hospital of the Chinese Academy of Medical Sciences Shenzhen Hospital. The patient\u0026apos;s written informed consent was acquired. We reported this case following CARE reporting guidelines [\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe failure of NPC treatment is frequently attributed to local recurrence and distant metastases [\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]. Bone, lung, and liver are the most organs of NPC distant metastasis, while true brain metastasis (not the tumor breaking through the skull and invading the brain directly) is uncommon [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]. Khor et al. reported that among 99 patients with NPC metastases, 3 of them were brain metastases (3.3%), and Geng et al. reported that the incidence of brain metastasis in NPC patients was 0.3% in their institution [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]. We present the case of a patient with locally advanced NPC who developed brain metastases after completing concurrent chemoradiotherapy. The primary tumor invaded his cavernous sinus on the left side directly, but brain metastases appeared in the right temporal lobe several months later.\u003c/p\u003e\n\u003cp\u003eTo understand more about this rare occurrence, we searched through PubMed for relevant literature. Some reporters have described NPC brain metastases earlier, but these cases lacked specific clinical information [\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e]. We summarize the case reports of NPC brain metastasis with more detailed information in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Case reports of spinal cord metastases and direct brain invasion were excluded. Men are more likely to develop NPC than women, as is NPC brain metastases. From the diagnosis of nasopharyngeal carcinoma to the discovery of brain metastasis, the length of time varies greatly, with the longest reaching 53 months [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e]. The symptoms of NPC brain metastases are similar to those of other intracranial space-occupying lesions, making their diagnosis more difficult. The most common pathological subtype of brain metastases, according to WHO (2003) classification of NPC, is non-keratinizing undifferentiated carcinoma, and it is also the most common subtype found in other metastatic organs [\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]. Ngan et al. pointed out that the occipital lobe is the most common area for NPC brain metastases [\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, our study has shown that the frontal lobe is also a common area. To our knowledge, primary tumor types are highly correlated with the spatial distribution of brain metastases, for example, brain metastases from pulmonary and gastrointestinal tumors favored the infratentorial area, while brain metastases from skin cancer and sarcoma chose the supratentorial space [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]. In addition, NPC metastases to the dura and the skull have also been reported [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]. More cases will help us to draw a reliable conclusion on which area of the brain NPC favors. In general, imaging plays an important role in the diagnosis of brain metastases, but it is not easy to distinguish the specific tumor type. On MRI, most NPC brain metastases present as a T1-enhancing mass with surrounding edema, which is typical of brain metastases. In particular, the MRI characteristic of NPC metastases in the dura may greatly mimic those of meningiomas [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]. Unfortunately, functional MRI of NPC brain metastases has not been described in past studies. In our case, hyperperfusion was shown on PWI, and MRS revealed the disappearance of the NAA peak and a decrease in the Cr and Cho peaks. With the development of imageology, we have been able to identify metastases from details in MRI by some algorithm [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e]. We are optimistic that a sufficient number of images from MRI will enable us to diagnose NPC brain metastases timely and precisely in the future. The treatment of NPC brain metastases is a huge challenge and there is no standard treatment to date. To choose the appropriate treatment option, the degree of invasiveness, the presence of multiple metastases, Karnofsky Performance Status (KPS) score, and lifespan should all be taken into account. Chemotherapy and radiotherapy are the most common treatment strategies. and targeted therapy and immunotherapy were also tried [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]. Despite the use of various local and systemic therapies, these patients still have a poor prognosis. Surgery is more recommended in metastasis to the brain rather than other common metastatic organs. Surgical removal of the mass can effectively minimize the risk of brain herniation due to the tumor mass effect. In our study, the brain midline of the patient has been displaced by more than 1 cm and excision of the tumor is unavoidable to lower the intracranial pressure.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSummary of Previous Reports of Brain Metastasis from Nasopharyngeal\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAuthor and Year\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003egender\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTime *\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHistology\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSite in the brain\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTreatment\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGeng et al. 2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 months \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBasaloid squamous cell carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMultiple lesions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCHEMO\u0026thinsp;+\u0026thinsp;IMT\u0026thinsp;+\u0026thinsp;targeted therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003ePark et al. 2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWoman\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53 months \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFrontal lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRT\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23 months \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCerebellum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSurgery\u0026thinsp;+\u0026thinsp;RT\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSu et al. 2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 years \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon-keratinizing undifferentiated carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOccipital lobe and frontal bone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCHEMO\u0026thinsp;+\u0026thinsp;RT\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eShen et al. 2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWoman\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 months \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon-keratinizing undifferentiated carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFrontal lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCHEMO\u0026thinsp;+\u0026thinsp;RT\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 years \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon-keratinizing undifferentiated carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFrontal lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSurgery\u0026thinsp;+\u0026thinsp;CHEMO\u0026thinsp;+\u0026thinsp;RT\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKuo et al. 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWoman\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 months \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon-keratinizing differentiated carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFrontotemporal lobe and dura\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSurgery\u0026thinsp;+\u0026thinsp;RT\u0026thinsp;+\u0026thinsp;CHEMO\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKaidar et al. 2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePoorly differentiated carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOccipital lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRT\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOzyar et al. 2004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45 months \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUndifferentiated carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTemporal lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSurgery\u0026thinsp;+\u0026thinsp;RT\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNgan et al. 2002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUndifferentiated carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOccipital lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCHEMO\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLiaw et al. 1994\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConcurrence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon- keratinizing squamous cell carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOccipital lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCHEMO\u0026thinsp;+\u0026thinsp;RT\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003e\u003cstrong\u003e*\u003c/strong\u003e: Time refers to the interval from the diagnosis of NPC (a), surgery (b), radiotherapy (c) to the discovery of brain metastases.\u003c/p\u003e\n \u003cp\u003eCHEMO: chemotherapy\u003c/p\u003e\n \u003cp\u003eIMT: immunotherapy\u003c/p\u003e\n \u003cp\u003eRT: radiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003eWhy are brain metastases from NPC so rare? The \u0026quot;seed and soil theory\u0026quot; states that tumor metastasis is dependent on the molecular and genetic features of tumor cells, as well as the systemic and brain microenvironment [\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]. Su et al. suggested that tumor cells enter veins through regional lymph nodes, and the single direction valve in veins prevents reverse flow, resulting in a low incidence of NPC brain metastases [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]. Another viewpoint is that patients did not live long enough for brain metastases to develop [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. Although hematogenous metastasis is recognized by most people, some researchers have also proposed the possibility of cerebrospinal fluid metastasis, especially in patients with spinal cord metastasis, and a possible mechanism was the destruction of the blood-brain barrier following the invasion of venous sinuses [\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e]. For the patient in our study, it is difficult to determine which metastatic pattern was involved. The negative results of his cerebrospinal fluid cytology could not completely exclude the metastasis through cerebrospinal fluid.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eBrain metastases of NPC are very rare and have an extremely poor prognosis. We report the experience of a patient with non-keratinizing undifferentiated carcinoma that progressed to brain metastases and was surgically removed. The possible transfer pathway of the NPC brain is by hematogenous dissemination or cerebrospinal fluid. Palliative radiotherapy and chemotherapy are difficult to achieve satisfactory results, and targeted therapy and immunotherapy have also been tried. Surgery can save the lives of some patients with NPC brain metastases. Clinicians should keep continuous attention to the risk of metastases after the initial treatment of NPC and remain vigilant for rare manifestations. Further studies are needed to focus on the epidemiological characteristics, the mechanisms of metastasis, advanced diagnostic methods, and better treatment strategies for NPC brain metastases.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNPC: nasopharyngeal carcinoma; CSF: cerebral spinal fluid; MRI: Magnetic Resonance Imaging; PET/CT: Positron emission tomography and computer tomography; RANO: Response Assessment in Neuro-Oncology; T1WI: T1-weighted imaging; T2WI: T2-weighted imaging; PWI: Perfusion-Weighted Imaging; MRS: magnetic resonance spectroscopy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study has been approved by the Ethics Committee of the Cancer Hospital of the Chinese Academy of Medical Sciences Shenzhen Hospital. Informed consent was assigned in Chinese format.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors confirm the data and materials are available.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJunwei Sun: drafting of the manuscript; disease treatment.\u003c/p\u003e\n\u003cp\u003eJianhua Li, Mingyu Wang: acquisition of data; analysis and interpretation of pathology.\u003c/p\u003e\n\u003cp\u003eZhisheng Kan: reading and approving the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank Jian Guan, MD, from the Department of Pathology, the Chinese Academy of Medical Sciences Shenzhen Hospital, for the provision of pathological images.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eLiu F, Xiao J, Xu G et al. 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Neuro Oncol 23:214\u0026ndash;225. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/neuonc/noaa232\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eGr\u0026oslash;vik E, Yi D, Iv M et al. (2020) Deep learning enables automatic detection and segmentation of brain metastases on multisequence MRI. J Magn Reson Imaging 51:175\u0026ndash;182. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/jmri.26766\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eCvitkovic E, Bachouchi M, Boussen H et al. (1993) Leukemoid reaction, bone marrow invasion, fever of unknown origin, and metastatic pattern in the natural history of advanced undifferentiated carcinoma of nasopharyngeal type: a review of 255 consecutive cases. J Clin Oncol 11:2434\u0026ndash;2442. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1200/JCO.1993.11.12.2434\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\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":"nasopharyngeal carcinoma, brain metastases, temporal lobe, surgery, case report","lastPublishedDoi":"10.21203/rs.3.rs-1577540/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1577540/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eNasopharyngeal carcinoma (NPC) is one of the most common tumors in the head and neck. Brain metastasis from NPC is extremely rare and few case reports describe it in detail. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCase presentation: \u003c/strong\u003e\u003c/p\u003e\u003cp\u003eWe presented the experience of a 51-year-old patient with NPC that progressed to brain metastases and was surgically removed. The primary lesion of NPC was located in his left pharynx, while the metastatic mass appeared in the right temporal lobe, and it caused significant space-occupying effects. Surgical resection was performed and histopathology after surgery confirmed that the mass was a non-keratinizing undifferentiated carcinoma. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eClinicians should pay continuous attention to the occurrence of NPC brain metastasis. More studies should focus on the epidemiological characteristics, the mechanisms of metastasis, advanced diagnostic methods, and better treatment strategies for NPC brain metastases.\u003c/p\u003e","manuscriptTitle":"Metastasis of nasopharyngeal carcinoma to the brain: a case report and literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-04-22 16:57:13","doi":"10.21203/rs.3.rs-1577540/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":"fa955175-3994-4b21-8930-594e2a9b0412","owner":[],"postedDate":"April 22nd, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-04-22T16:57:14+00:00","versionOfRecord":[],"versionCreatedAt":"2022-04-22 16:57:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1577540","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1577540","identity":"rs-1577540","version":["v1"]},"buildId":"J0_U0BvcaRcwD8yVFaRlm","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}