Intraocular Metastasis from an Anal Squamous Cell Carcinoma: A Case Report

Intraocular Metastasis from an Anal Squamous Cell Carcinoma: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Intraocular Metastasis from an Anal Squamous Cell Carcinoma: A Case Report Sameeha Sajid, Muhammad Daud Abdullah, Ammar Yousif This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7071980/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: Anal cancer is a relatively less common gastrointestinal cancer, with common sites of metastasis being para-aortic nodes, liver, lungs, and skin. Intraocular metastasis from anal squamous cell carcinoma is an extremely rare occurrence with no reported cases so far. Case Description: We present a case of a 70-year-old male with a past medical history of metastatic anal squamous cell carcinoma who presented to the oncology clinic with complaints of sudden onset complete vision loss in his right eye. Patient was then referred to a retina specialist and was found to have a posterior choroidal tumor that raised concerns of a primary uveal melanoma vs metastatic spread from his known primary cancer. He underwent right eye enucleation and prosthesis placement with pathology confirming metastatic carcinoma consistent with anal carcinoma. Conclusion: This case presents the rare phenomenon of intraorbital metastasis from a primary anal squamous cell carcinoma. Per our literature review, this is the only reported case of such an occurrence, which adds to the clinical complexity of this case in terms of timely diagnosis, effective treatment modalities and prognosis. Intraocular metastasis metastatic anal squamous cell carcinoma Intraocular squamous cell carcinoma case report Highlight box Key findings Anal squamous cell carcinoma, although rarely but can lead to intraorbital metastasis What is known and what is new? Intraocular metastasis from a primary anal squamous cell carcinoma is an extremely rare phenomenon, without any published cases per our literature review. Prognosis of intraocular metastatic disease regardless of site of primary tumor generally remains poor and treatment is mostly aimed at improving quality of life. What is the implication, and what should change now? This is the first reported case of anal squamous cell carcinoma with metastasis to the orbit. Physicians should maintain a high level of suspicion for intraorbital metastasis in patients with history of anal squamous cell carcinoma presenting with acute onset visual symptoms. 1. Introduction Intraocular metastasis from distant sites is a relatively uncommon phenomenon, accounting for around 2% of cases ( 1 ). Out of these, most common primary tumors to metastasize to the eye include cancer of the breast, lung, and gastrointestinal tract ( 2 ). Gastrointestinal (GI) cancers represent more than a quarter of all cancers worldwide ( 3 ). In 2021, the incidence rate from GI cancers increased to 5.26 million, and accounted for 3.70 million deaths ( 4 ). The greatest burden was noted to be from colorectal cancer, followed by gastric, esophageal, pancreatic, liver and biliary tract cancer ( 4 ). On the other hand, anal cancers are relatively scarce, accounting for only 0.3% cases ( 3 ), and ocular metastasis from an anal primary is an even more rare phenomenon. To our knowledge, we present the first reported case of advanced anal squamous cell carcinoma with intraocular metastasis (in accordance with the CARE reporting checklist). 2. Case Presentation A 70-year-old male with a past medical history of hypertension, hyperlipidemia, atrial fibrillation and metastatic anal squamous cell carcinoma presented to the oncology clinic with complaints of sudden onset complete vision loss in his right eye. The patient was diagnosed with squamous cell anal cancer after he presented with complaints of progressively worsening bloody diarrhea, shortness of breath on exertion and lightheadedness for the past 6 months. Labs at the time were remarkable for microcytic anemia with a hemoglobin level of 8.3 g/dl. Esophagogastroduodenoscopy and colonoscopy was done which showed an anal mass, with pathology reporting moderately differentiated invasive squamous cell carcinoma. PET scan at the time revealed a 6 cm hypermetabolic active anorectal mass with a metastatic lymph node located at the left common iliac lymph node chain, as well as a nonspecific 3 mm left lower lobe lung nodule. He was started on concurrent chemoradiation with 5-fluorouracil and Mitomycin, and received the treatment for about three months. Follow-up PET scan showed disease progression, with markedly increased size of the anorectal mass but with resolution of pathologic lymphadenopathy, however, also revealed a new 10 mm hypermetabolic foci in the right lobe of the liver and increasing left lower lobe pulmonary nodule now measuring 4 mm. MRI of the abdomen showed two right hepatic masses with the largest measuring up to 25 mm. Patient underwent a CT guided biopsy of the liver mass which was consistent with metastatic, poorly differentiated squamous cell carcinoma. In light of progressive disease, the patient was started on carboplatin/paclitaxel. After four cycles of the regimen, CT imaging showed excellent response to treatment with no evidence of anorectal malignancy, decreased size of the two hepatic lesions, and significant decrease in size versus complete resolution of pulmonary metastasis, but with a new 10 mm adrenal lesion concerning malignancy. Three months later, MRI of the abdomen also showed an interval decrease in hepatic metastatic disease, and colonoscopy at the time revealed no dysplasia or malignancy. However, two months later repeat CT imaging showed disease relapse with evidence of numerous bilateral pulmonary nodules/masses, right inferior hepatic lobe hepatic metastases with one appearing to significantly enlarged, increase in size of right adrenal nodule, Hyperdense right superior pole renal lesion and left-sided retroperitoneal lymphadenopathy. In light of disease relapse, systemic therapy was switched to single agent immunotherapy with Pembrolizumab. Shortly after, about a month later, almost two years since initial diagnosis of anal cancer the patient presented to the clinic with acute loss of vision in his right eye. He was seen by a retina specialist and was found to have a posterior choroidal tumor that raised concerns of a primary uveal melanoma vs metastatic spread from his known primary cancer. Patient underwent right eye enucleation and prosthesis placement with pathology confirming metastatic carcinoma consistent with anal carcinoma. Post-operation MRI brain and orbit showed no evidence of disease. However, CT chest, abdomen and pelvis revealed worsening disease when compared to 3 months ago with interval progression of disease in the chest with pulmonary and chest wall metastasis, stable hepatic lesions and new necrotic mass interposed between the rectum and seminal vesicles. A long discussion was held with patient and his family regarding the relatively poor prognosis the disease process and switching to either a different chemotherapy regimen versus transition to palliative or comfort care. After much consideration the patient elected for comfort care, and passed away. 3. Discussion Anal cancer is a relatively rare cancer accounting for only 2% of all gastrointestinal tract malignancies ( 8 ). However, in recent years, anal cancer is found to have a relatively rapid increase in incidence, in many populations such as the Americas, Northern and Western Europe, and Australia, with anal squamous cell carcinoma being the most prevalent subtype ( 9 , 10 ). Known risk factors for the disease include HPV infection, especially HPV 16, HIV infection, men who have sex with men (MSM), women with HPV-related gynecological cancer or precancerous lesions, individuals with a solid organ transplant or autoimmune disorders, female sex, old age and smoking ( 8 , 10 ). Common sites of metastasis from anal cancer include para-aortic nodes, liver, lungs, and skin ( 11 ). However, this case highlights the rare phenomenon of intraorbital metastasis from an anal primary. Intraocular metastasis is mostly seen in the uvea, and rarely involves the retina ( 5 ). The most common site of uveal metastasis includes the choroid (88%), followed by the iris (9%) and lastly the ciliary body (2%) ( 2 ). The pathophysiology of metastasis of anal cancer to the uvea, can most likely be explained by hematogenous spread, due to absence of lymphatic system in the eye ( 6 ). In this case, the patient was found to have a posterior choroidal tumor, which can be explained by the rich blood supply of the uveal tract ( 5 ) and in particular to the perimacular choroid ( 6 ). The presence of metastatic disease to the liver and lung before the diagnosis of intraorbital metastasis further supports the mechanism of spread through dissemination in blood. Most common presenting symptoms include visual disturbances and vision loss, as experienced by our patient. In a literature review by Khawaja et al. where eight previously published cases of colorectal cancer with metastasis to the orbit were studied, all patients were found to experience visual disturbance as the presenting symptom ( 7 ). This can be explained by macular or peripapillary retinal involvement ( 5 ) or due to extensive accumulation leading to retinal detachment ( 6 ). Treatment is mainly aimed at improving quality of life. Systemic treatment options for intraorbital metastasis include systemic chemotherapy, and immunotherapy ( 5 ). Radiation treatment modalities include external beam radiation therapy (EBRT), proton beam radiotherapy (PBT), brachytherapy, and stereotactic radiotherapy ( 5 ). In addition, patients have also shown good response with intravitreal selective vascular endothelial growth factor (VEGF)-A inhibitor, in particular with bevacizumab ( 5 , 6 , 12 , 13 ). Lastly, enucleation may be considered for patients with eye pain and complete loss of vision ( 5 ). Our patient underwent eye enucleation, followed by initiation of systemic Pembrolizumab. Pembrolizumab has shown good response with choroidal metastasis in metastatic uveal melanoma and non-small cell lung cancer ( 14 , 15 ). However, overall prognosis is variable, depending on the extent of systemic/extraocular disease burden, and patient’s performance status at the time of diagnosis of intraocular metastasis but generally remains poor. In a case series of 96 patients indicated a median survival time between diagnosis of choroidal metastasis and death of only six months ( 16 ). Similarly, our patient passed away after about three months from the initial diagnosis of intra-ocular metastasis, further underscoring the poor prognosis associated with the disease process. 4. Conclusion In conclusion, anal cancer is one of the less common GI cancers, and intraorbital metastasis from an anal squamous cell carcinoma is an even rarer phenomenon, with no available cases reported per our literature review. This case aims to highlight the consideration of intraocular metastasis for any patient with a known history of anal cancer presenting with acute onset visual symptoms. However, given the scarcity of such cases, further research to study the pathogenesis, effective treatment modalities and prognostic factors is warranted to guide therapy in these patients. Declarations Acknowledgments: This article has not been submitted to other publications and/or presented at a conference or meeting. Footnote The authors have completed the CARE checklist. Funding: "This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities." Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form. The authors have no conflicts of interest to declare. Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal. Contributions: (I) Conception and design: Ammar Yousif, MD and Sameeha Sajid, MD (II) Administrative support: Ammar Yousif, MD (III) Provision of study materials or patients: Ammar Yousif, MD (IV) Collection and assembly of data: Sameeha Sajid, MD and Muhammad Daud Abdullah, MD (V) Data analysis and interpretation: Sameeha Sajid, MD (VI) Manuscript writing: All authors (VII) Final approval of manuscript: All authors Consent Statement: A written consent was obtained by the patient’s wife/POA to publish this case report. References Ohtsuka K, Hashimoto M, Suzuki Y (2005) A Review of 244 Orbital Tumors in Japanese Patients During a 21-Year Period: Origins and Locations. Jpn J Ophthalmol 49(1):49–55 Shields CL, Shields JA, Gross NE et al (1997) Survey of 520 Eyes with Uveal Metastases. Ophthalmology 104(8):1265–1276 Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. Cancer J Clin 71(3):209–249 Danpanichkul P, Suparan K, Tothanarungroj D, Dejvajara K, Rakwong, Pang Y et al Epidemiology of gastrointestinal cancers: a systematic analysis from the Global Burden of Disease Study 2021. Gut [Internet]. 2024;gutjnl-333227. Available from: https://pubmed.ncbi.nlm.nih.gov/39242191/ Konstantinidis L, Damato B (2017) Intraocular Metastases — A Review. Asia-Pacific Journal of Ophthalmology. ;6(2):208–214. Available from: https://journals.lww.com/apjoo/Fulltext/2017/03000/Intraocular_Metastases_A_Review.12.aspx Cohen VML (2012) Ocular metastases. Eye 27(2):137–141 Khawaja MR, Minturn JT, Spittler AJ et al (2015) Ocular metastasis of colorectal cancer: An uncommon presentation of a common malignancy. Hematol Oncol Stem Cell Ther 8(4):176–180 Gondal TA, Chaudhary N, Bajwa H, Rauf A, Le D, Ahmed S (2023) Anal Cancer: The Past, Present and Future. Current Oncology [Internet]. ;30(3):3232–50. Available from: https://www.mdpi.com/1718-7729/30/3/246 Islami F, Ferlay J, Lortet-Tieulent J et al (2016) International trends in anal cancer incidence rates. Int J Epidemiol. ;dyw276 Albuquerque A, Nathan M, Cappello C (2021) Mário Dinis-Ribeiro. Anal cancer and precancerous lesions: a call for improvement. Lancet Gastroenterol Hepatol 6(4):327–334 Glynne-Jones R, Meadows HM, Lopes A et al (2020) Impact of compliance to chemoradiation on long-term outcomes in squamous cell carcinoma of the anus: results of a post hoc analysis from the randomised phase III ACT II trial. Ann Oncol 31(10):1376–1385 Augustine H, Munro M, Adatia F et al (2014) Treatment of ocular metastasis with anti-VEGF: A literature review and case report. Can J Ophthalmol 49(5):458–463 Fenicia V, Abdolrahimzadeh S, Mannino G et al (2014) Intravitreal bevacizumab in the successful management of choroidal metastases secondary to lung and breast cancer unresponsive to systemic therapy: a case series. Eye 28(7):888–891 Rossi E, Pagliara M, Orteschi D et al (2019) Pembrolizumab as first-line treatment for metastatic uveal melanoma. Cancer Immunol Immunother 68(7):1179–1185 Li X, Liang Y, Wang J et al (2021) Pembrolizumab for choroidal metastases from non-small cell lung cancer: a case report and literature review. Hum Vaccines Immunotherapeutics 17(8):2626–2629 Konstantinidis L, Rospond-Kubiak I, Zeolite I et al (2013) Management of patients with uveal metastases at the Liverpool Ocular Oncology Centre. Br J Ophthalmol 98(1):92–98 Additional Declarations The authors declare no competing interests. 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-7071980","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":482211507,"identity":"d2d6144f-4953-49b5-b9e7-3fbb9bf18f4c","order_by":0,"name":"Sameeha Sajid","email":"data:image/png;base64,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","orcid":"https://orcid.org/0009-0000-2416-987X","institution":"Department of Internal Medicine, HCA Healthcare; MountainView Hospital, Las Vegas, NV, USA","correspondingAuthor":true,"prefix":"","firstName":"Sameeha","middleName":"","lastName":"Sajid","suffix":""},{"id":482211508,"identity":"c6fef15d-f772-4f2b-88e3-e409e360a984","order_by":1,"name":"Muhammad Daud Abdullah","email":"","orcid":"","institution":"Department of Internal Medicine, HCA Healthcare; MountainView Hospital, Las Vegas, NV, USA","correspondingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"Daud","lastName":"Abdullah","suffix":""},{"id":482211509,"identity":"0630b3f3-a525-46df-b502-3f74c6644f65","order_by":2,"name":"Ammar Yousif","email":"","orcid":"","institution":"Comprehensive Cancer Centers, Las Vegas, NV, USA","correspondingAuthor":false,"prefix":"","firstName":"Ammar","middleName":"","lastName":"Yousif","suffix":""}],"badges":[],"createdAt":"2025-07-08 07:40:33","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7071980/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7071980/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":86264607,"identity":"33512eb0-0fe1-4e26-a140-1f495a570975","added_by":"auto","created_at":"2025-07-08 15:25:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":347096,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7071980/v1/b38ed371-ed14-4e75-b69e-ad8f48e474ce.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eIntraocular Metastasis from an Anal Squamous Cell Carcinoma: A Case Report\u003c/p\u003e","fulltext":[{"header":"Highlight box ","content":"\u003cp\u003e\u003cstrong\u003eKey findings\u003c/strong\u003e\u003c/p\u003e\n\u003cul start=\"50\"\u003e\n \u003cli\u003eAnal squamous cell carcinoma, although rarely but can lead to intraorbital metastasis\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is known and what is new?\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cul start=\"50\"\u003e\n \u003cli\u003eIntraocular metastasis from a primary anal squamous cell carcinoma is an extremely rare phenomenon, without any published cases per our literature review.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePrognosis of intraocular metastatic disease regardless of site of primary tumor generally remains poor and treatment is mostly aimed at improving quality of life.\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is the implication, and what should change now?\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cul start=\"50\"\u003e\n \u003cli\u003eThis is the first reported case of anal squamous cell carcinoma with metastasis to the orbit.\u003c/li\u003e\n \u003cli\u003ePhysicians should maintain a high level of suspicion for intraorbital metastasis in patients with history of anal squamous cell carcinoma presenting with acute onset visual symptoms.\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"1. Introduction","content":"\u003cp\u003eIntraocular metastasis from distant sites is a relatively uncommon phenomenon, accounting for around 2% of cases (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Out of these, most common primary tumors to metastasize to the eye include cancer of the breast, lung, and gastrointestinal tract (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eGastrointestinal (GI) cancers represent more than a quarter of all cancers worldwide (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In 2021, the incidence rate from GI cancers increased to 5.26\u0026nbsp;million, and accounted for 3.70\u0026nbsp;million deaths (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The greatest burden was noted to be from colorectal cancer, followed by gastric, esophageal, pancreatic, liver and biliary tract cancer (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). On the other hand, anal cancers are relatively scarce, accounting for only 0.3% cases (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), and ocular metastasis from an anal primary is an even more rare phenomenon. To our knowledge, we present the first reported case of advanced anal squamous cell carcinoma with intraocular metastasis (in accordance with the CARE reporting checklist).\u003c/p\u003e"},{"header":"2. Case Presentation","content":"\u003cp\u003eA 70-year-old male with a past medical history of hypertension, hyperlipidemia, atrial fibrillation and metastatic anal squamous cell carcinoma presented to the oncology clinic with complaints of sudden onset complete vision loss in his right eye.\u003c/p\u003e\u003cp\u003eThe patient was diagnosed with squamous cell anal cancer after he presented with complaints of progressively worsening bloody diarrhea, shortness of breath on exertion and lightheadedness for the past 6 months. Labs at the time were remarkable for microcytic anemia with a hemoglobin level of 8.3 g/dl. Esophagogastroduodenoscopy and colonoscopy was done which showed an anal mass, with pathology reporting moderately differentiated invasive squamous cell carcinoma. PET scan at the time revealed a 6 cm hypermetabolic active anorectal mass with a metastatic lymph node located at the left common iliac lymph node chain, as well as a nonspecific 3 mm left lower lobe lung nodule. He was started on concurrent chemoradiation with 5-fluorouracil and Mitomycin, and received the treatment for about three months. Follow-up PET scan showed disease progression, with markedly increased size of the anorectal mass but with resolution of pathologic lymphadenopathy, however, also revealed a new 10 mm hypermetabolic foci in the right lobe of the liver and increasing left lower lobe pulmonary nodule now measuring 4 mm. MRI of the abdomen showed two right hepatic masses with the largest measuring up to 25 mm. Patient underwent a CT guided biopsy of the liver mass which was consistent with metastatic, poorly differentiated squamous cell carcinoma. In light of progressive disease, the patient was started on carboplatin/paclitaxel. After four cycles of the regimen, CT imaging showed excellent response to treatment with no evidence of anorectal malignancy, decreased size of the two hepatic lesions, and significant decrease in size versus complete resolution of pulmonary metastasis, but with a new 10 mm adrenal lesion concerning malignancy. Three months later, MRI of the abdomen also showed an interval decrease in hepatic metastatic disease, and colonoscopy at the time revealed no dysplasia or malignancy.\u003c/p\u003e\u003cp\u003eHowever, two months later repeat CT imaging showed disease relapse with evidence of numerous bilateral pulmonary nodules/masses, right inferior hepatic lobe hepatic metastases with one appearing to significantly enlarged, increase in size of right adrenal nodule, Hyperdense right superior pole renal lesion and left-sided retroperitoneal lymphadenopathy. In light of disease relapse, systemic therapy was switched to single agent immunotherapy with Pembrolizumab.\u003c/p\u003e\u003cp\u003eShortly after, about a month later, almost two years since initial diagnosis of anal cancer the patient presented to the clinic with acute loss of vision in his right eye. He was seen by a retina specialist and was found to have a posterior choroidal tumor that raised concerns of a primary uveal melanoma vs metastatic spread from his known primary cancer. Patient underwent right eye enucleation and prosthesis placement with pathology confirming metastatic carcinoma consistent with anal carcinoma. Post-operation MRI brain and orbit showed no evidence of disease. However, CT chest, abdomen and pelvis revealed worsening disease when compared to 3 months ago with interval progression of disease in the chest with pulmonary and chest wall metastasis, stable hepatic lesions and new necrotic mass interposed between the rectum and seminal vesicles. A long discussion was held with patient and his family regarding the relatively poor prognosis the disease process and switching to either a different chemotherapy regimen versus transition to palliative or comfort care. After much consideration the patient elected for comfort care, and passed away.\u003c/p\u003e"},{"header":"3. Discussion","content":"\u003cp\u003eAnal cancer is a relatively rare cancer accounting for only 2% of all gastrointestinal tract malignancies (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). However, in recent years, anal cancer is found to have a relatively rapid increase in incidence, in many populations such as the Americas, Northern and Western Europe, and Australia, with anal squamous cell carcinoma being the most prevalent subtype (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Known risk factors for the disease include HPV infection, especially HPV 16, HIV infection, men who have sex with men (MSM), women with HPV-related gynecological cancer or precancerous lesions, individuals with a solid organ transplant or autoimmune disorders, female sex, old age and smoking (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Common sites of metastasis from anal cancer include para-aortic nodes, liver, lungs, and skin (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). However, this case highlights the rare phenomenon of intraorbital metastasis from an anal primary.\u003c/p\u003e\u003cp\u003eIntraocular metastasis is mostly seen in the uvea, and rarely involves the retina (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The most common site of uveal metastasis includes the choroid (88%), followed by the iris (9%) and lastly the ciliary body (2%) (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The pathophysiology of metastasis of anal cancer to the uvea, can most likely be explained by hematogenous spread, due to absence of lymphatic system in the eye (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In this case, the patient was found to have a posterior choroidal tumor, which can be explained by the rich blood supply of the uveal tract (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) and in particular to the perimacular choroid (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The presence of metastatic disease to the liver and lung before the diagnosis of intraorbital metastasis further supports the mechanism of spread through dissemination in blood.\u003c/p\u003e\u003cp\u003eMost common presenting symptoms include visual disturbances and vision loss, as experienced by our patient. In a literature review by Khawaja et al. where eight previously published cases of colorectal cancer with metastasis to the orbit were studied, all patients were found to experience visual disturbance as the presenting symptom (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). This can be explained by macular or peripapillary retinal involvement (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) or due to extensive accumulation leading to retinal detachment (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eTreatment is mainly aimed at improving quality of life. Systemic treatment options for intraorbital metastasis include systemic chemotherapy, and immunotherapy (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Radiation treatment modalities include external beam radiation therapy (EBRT), proton beam radiotherapy (PBT), brachytherapy, and stereotactic radiotherapy (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). In addition, patients have also shown good response with intravitreal selective vascular endothelial growth factor (VEGF)-A inhibitor, in particular with bevacizumab (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Lastly, enucleation may be considered for patients with eye pain and complete loss of vision (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Our patient underwent eye enucleation, followed by initiation of systemic Pembrolizumab. Pembrolizumab has shown good response with choroidal metastasis in metastatic uveal melanoma and non-small cell lung cancer (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eHowever, overall prognosis is variable, depending on the extent of systemic/extraocular disease burden, and patient\u0026rsquo;s performance status at the time of diagnosis of intraocular metastasis but generally remains poor. In a case series of 96 patients indicated a median survival time between diagnosis of choroidal metastasis and death of only six months (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Similarly, our patient passed away after about three months from the initial diagnosis of intra-ocular metastasis, further underscoring the poor prognosis associated with the disease process.\u003c/p\u003e"},{"header":"4. Conclusion","content":"\u003cp\u003eIn conclusion, anal cancer is one of the less common GI cancers, and intraorbital metastasis from an anal squamous cell carcinoma is an even rarer phenomenon, with no available cases reported per our literature review. This case aims to highlight the consideration of intraocular metastasis for any patient with a known history of anal cancer presenting with acute onset visual symptoms. However, given the scarcity of such cases, further research to study the pathogenesis, effective treatment modalities and prognostic factors is warranted to guide therapy in these patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u0026nbsp;\u003c/strong\u003eThis article has not been submitted to other publications and/or presented at a conference or meeting.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFootnote\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have completed the CARE checklist.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding: \u003c/strong\u003e\u0026quot;This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.\u0026quot;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e \u003cem\u003eAll authors have completed the ICMJE uniform disclosure form. The authors have no conflicts of interest to declare.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Statement:\u003c/strong\u003e \u003cem\u003eThe authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(I) Conception and design: Ammar Yousif, MD and Sameeha Sajid, MD\u003c/p\u003e\n\u003cp\u003e(II) Administrative support: Ammar Yousif, MD\u003c/p\u003e\n\u003cp\u003e(III) Provision of study materials or patients: Ammar Yousif, MD\u003c/p\u003e\n\u003cp\u003e(IV) Collection and assembly of data: Sameeha Sajid, MD and Muhammad Daud Abdullah, MD\u003c/p\u003e\n\u003cp\u003e(V) Data analysis and interpretation: Sameeha Sajid, MD\u003c/p\u003e\n\u003cp\u003e(VI) Manuscript writing: All authors\u003c/p\u003e\n\u003cp\u003e(VII) Final approval of manuscript: All authors\u003c/p\u003e\u003cp\u003eConsent Statement: A written consent was obtained by the patient\u0026rsquo;s wife/POA to publish this case report.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOhtsuka K, Hashimoto M, Suzuki Y (2005) A Review of 244 Orbital Tumors in Japanese Patients During a 21-Year Period: Origins and Locations. Jpn J Ophthalmol 49(1):49\u0026ndash;55\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShields CL, Shields JA, Gross NE et al (1997) Survey of 520 Eyes with Uveal Metastases. Ophthalmology 104(8):1265\u0026ndash;1276\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. Cancer J Clin 71(3):209\u0026ndash;249\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDanpanichkul P, Suparan K, Tothanarungroj D, Dejvajara K, Rakwong, Pang Y et al Epidemiology of gastrointestinal cancers: a systematic analysis from the Global Burden of Disease Study 2021. Gut [Internet]. 2024;gutjnl-333227. 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Eye 27(2):137\u0026ndash;141\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKhawaja MR, Minturn JT, Spittler AJ et al (2015) Ocular metastasis of colorectal cancer: An uncommon presentation of a common malignancy. Hematol Oncol Stem Cell Ther 8(4):176\u0026ndash;180\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGondal TA, Chaudhary N, Bajwa H, Rauf A, Le D, Ahmed S (2023) Anal Cancer: The Past, Present and Future. Current Oncology [Internet]. ;30(3):3232\u0026ndash;50. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.mdpi.com/1718-7729/30/3/246\u003c/span\u003e\u003cspan address=\"https://www.mdpi.com/1718-7729/30/3/246\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIslami F, Ferlay J, Lortet-Tieulent J et al (2016) International trends in anal cancer incidence rates. 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Hum Vaccines Immunotherapeutics 17(8):2626\u0026ndash;2629\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKonstantinidis L, Rospond-Kubiak I, Zeolite I et al (2013) Management of patients with uveal metastases at the Liverpool Ocular Oncology Centre. Br J Ophthalmol 98(1):92\u0026ndash;98\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"HCA healthcare","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":"Intraocular metastasis, metastatic anal squamous cell carcinoma, Intraocular squamous cell carcinoma, case report","lastPublishedDoi":"10.21203/rs.3.rs-7071980/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7071980/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Anal cancer is a relatively less common gastrointestinal cancer, with common sites of metastasis being para-aortic nodes, liver, lungs, and skin. Intraocular metastasis from anal squamous cell carcinoma is an extremely rare occurrence with no reported cases so far.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Description:\u003c/strong\u003e We present a case of a 70-year-old male with a past medical history of metastatic anal squamous cell carcinoma who presented to the oncology clinic with complaints of sudden onset complete vision loss in his right eye. Patient was then referred to a retina specialist and was found to have a posterior choroidal tumor that raised concerns of a primary uveal melanoma vs metastatic spread from his known primary cancer. He underwent right eye enucleation and prosthesis placement with pathology confirming metastatic carcinoma consistent with anal carcinoma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e \u0026nbsp;This case presents the rare phenomenon of intraorbital metastasis from a primary anal squamous cell carcinoma. Per our literature review, this is the only reported case of such an occurrence, which adds to the clinical complexity of this case in terms of timely diagnosis, effective treatment modalities and prognosis.\u003c/p\u003e","manuscriptTitle":"Intraocular Metastasis from an Anal Squamous Cell Carcinoma: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-08 15:17:20","doi":"10.21203/rs.3.rs-7071980/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":"58f81b13-ac93-4e24-b305-7bcfc130e0d7","owner":[],"postedDate":"July 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-08T15:17:20+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-08 15:17:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7071980","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7071980","identity":"rs-7071980","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}