A case of masquerade syndrome caused by metastatic iris tumor diagnosed by a high CEA level in the aqueous humor and iris biopsy

A case of masquerade syndrome caused by metastatic iris tumor diagnosed by a high CEA level in the aqueous humor and iris biopsy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A case of masquerade syndrome caused by metastatic iris tumor diagnosed by a high CEA level in the aqueous humor and iris biopsy Shun Konno, Sayaka Yuzawa, Reiko Kinouchi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4835056/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Sep, 2024 Read the published version in Diagnostic Pathology → Version 1 posted 8 You are reading this latest preprint version Abstract Background With the advent of targeted therapies, the survival prognosis for metastatic tumors has extended, and it has become necessary to diagnose and consider treatment that takes into account QOL for metastatic tumors of the eye. The reports of checking tumor marker in the aqueous humor for diagnosis of metastatic intraocular tumors are few. Here, we report a case of masquerade syndrome with secondary glaucoma in which a high carcinoembryonic antigen (CEA) level in the aqueous humor could assist diagnosis, and continuing targeted therapy and trabeculectomy were effective. Case presentation A 73-year-old man was referred to us for iritis and high intraocular pressure (IOP) with severe eye pain in the left eye. He had Stage IVB lung adenocarcinoma treated with a molecularly targeted drug, Osimertinib. His best corrected visual acuity was 0.15, and IOP was 52 mmHg in the left eye. Anterior chamber cells (+), numerous small nodules in the iris, and small masses in the inferior angle were observed. In the aqueous humor, the CEA level was higher than in the blood. Napsin A and Thyroid Transcription Factor-1 (TTF-1) positive cells showed in the resected tissue at iridectomy performed during trabeculectomy. The pathological diagnosis of metastatic iris tumor of the lung adenocarcinoma was made, and we injected bevacizumab intravitreally once and continued Osimertinib. His IOP lowered to 8-10 mmHg, and the iris masses disappeared. He lost vision by metastasis to the left optic nerve after termination of Osimertinib one and a half years later. The metastasis shrank after restarting the drug. He passed away from an exacerbation of his primary lung cancer two years and nine months after the first visit. Although he lost vision in his left eye, the metastatic tumor in his left eye and optic nerve had disappeared, and his quality of life was maintained without any pain in his eye. Conclusions Checking tumor markers in the aqueous humor can aid in diagnosis, and aggressive treatment of metastatic iris tumors must help maintain patients’ QOL. case report CEA in the aqueous humor masquerade syndrome iris tumor trabeculectomy molecular targeted therapy Figures Figure 1 Figure 2 Figure 3 Background Since intraocular masquerade syndrome of neoplastic origin resembles iritis, differential diagnosis between them is crucial for ophthalmologists. Metastatic ocular tumors are relatively rare among all ocular tumors,[1, 2] and iris metastasis was reported to account for 8% of all metastatic uveal tumors.[3] Moreover, a limited amount of iris tissue can be obtained by biopsy, and methods helpful for auxiliary diagnosis of iris malignancy are needed. On the other hand, recent advances in cancer treatment, such as molecular targeted therapies, have improved the prognosis of patients with malignancy, and that can increase the need for diagnosis and treatment of metastatic ocular tumors to maintain quality of life (QOL). There are few reports detailing tumor markers checked in the aqueous humor for auxiliary diagnosis of metastatic intraocular tumors. We present a case of intraocular masquerade syndrome who had severe eye pain caused by high ocular pressure and a tumor marker, carcinoembryonic antigen (CEA) level in the aqueous humor and pathology of the resected iris tissue of iridectomy during trabeculectomy led the diagnosis. Case presentation A 73-year-old man had had blurred vision in the left eye for a month, and he was diagnosed with iritis and secondary glaucoma by a local clinic. He referred to us for high intraocular pressure (IOP) with severe eye pain in the left eye. He had stage IVB lung adenocarcinoma with multiple metastases including bone, and had a targeted drug, osimertinib, for two months. The drug was effective in stabilizing his systemic condition. While his best corrected visual acuity (BCVA) was 1.2 and IOP was 16 mmHg in the right eye, his BCVA was 0.15, and IOP was 52 mmHg in the left eye. A slit lamp examination showed anterior chamber cells (+) and numerous small nodules in the iris (Fig. 1 ). A gonioscopy examination showed small masses and peripheral anterior synechia on the inferior angle (Fig. 2 ). Since we suspected secondary glaucoma caused by a metastatic iris tumor, we performed a trabeculotomy and iris biopsy in the left eye to lower the IOP and to make a pathological diagnosis. The pathological examination result was negative for malignancy. The intraocular pressure temporarily decreased to 10 to 13mmHg but rose again to 30mmHg one month after surgery. During this period, we received information that his primary lung cancer was a lung adenocarcinoma of TTF-1 positive and a tumor marker CEA level was high from an internist treating lung cancer. We performed a trabeculectomy with anterior aqueous humor sampling and pathological examination using iris tissue obtained at iridectomy. The CEA level in the aqueous humor was 75.6 ng/mL, higher than 17.3 ng/mL in the blood. Napsin and TTF-1 positive cells were observed in the iris tissue (Fig. 3 ), and the pathological diagnosis was metastasis of the lung adenocarcinoma. The surgery resulted in a decrease in IOP. We injected Bevacizumab intravitreally once and continued the targeted drug osimertinib. The anterior chamber became clear, the iris tumor shrank, and the iris nodules disappeared. Since then, his IOP has been controlled to 8mmHg-10mmHg, and his eye pain has disappeared. One and half years later, Osimertinib was terminated due to the systemic condition maintained stable, and metastases were observed at the left optic nerve. Although the optic nerve metastases shrank with the resumption of osimertinib, the BCVA decreased to no light perception. He died two years and nine months after the first visit because of an exacerbation of his primary lung cancer. Although he lost vision in his left eye, the metastatic tumor in his left eye and optic nerve had disappeared, and his QOL was maintained without any pain in his eye. Discussion We presented a case of painful secondary glaucoma caused by masquerade syndrome. High CEA level in the aqueous humor and pathological examination of iridectomy tissue during trabeculectomy led to the diagnosis of metastatic iris tumor from lung adenocarcinoma. His severe pain in the eye disappeared by controlling intraocular pressure with trabeculectomy. Anterior cells and iris nodules disappeared with a vitreous injection of molecularly targeted drug and continued targeted therapy systemically. There were reports of detecting tumor markers in the aqueous humor.[4, 5, 6] High levels of Interleukin10 in the aqueous humor are known to occur in primary vitreoretinal lymphoma, and higher Interleukin10 level than Interleukin6 levels has diagnostic value.[7, 8] On the other hand, there are few reports of metastatic ocular tumors with CEA measurements of aqueous humor.[9] In the current case, we obtained information on the tumor marker in the blood that showed high levels in the primary tumor and compared that with the values in the aqueous humor. The aqueous humor CEA level was four times higher than the serum CEA level. Since limited tissue can be obtained from an eye by biopsy, it causes the result of false negatives. Thus, if a tumor marker that shows a high level in the primary tumor is known, it must be informative to check the tumor marker in the aqueous humor for auxiliary diagnosis of metastatic intraocular tumors. The effectiveness of intravitreal bevacizumab injection for glaucoma secondary to metastatic iris tumor was reported,[9] and we performed a single intravitreal injection in the present case. The iris metastatic tumor remained in remission after only one injection of bevacizumab, suggesting that the intravitreal injection contributed to the regression of the iris tumor and that the systemic administration of the molecular-targeted drug contributed to the maintenance of remission after the filtration surgery. In other words, the molecularly targeted drug possibly showed efficacy in the eye by the drug transferred to the anterior chamber after the filtration surgery. Surgical treatments were reported to be performed rarely in metastatic iris tumors. In a clinical study of 104 cases, management of iris metastasis included systemic chemotherapy (n = 18, 22%), external beam radiotherapy (n = 34, 41%), plaque radiotherapy (n = 20, 24%), surgical excision (n = 4, 5%), enucleation (n = 3, 4%), or observation (n = 4, 5%).[10] Previous reviews have also suggested that minimally invasive glaucoma surgery (MIGS) can be considered to manage secondary glaucoma in the absence of iris or ciliary body involvement and for eyes with treated and regressed posterior ocular malignancies.[11] However, there is concern that the malignant cells spread out by filtration surgery in the eye with masquerade syndrome. The current case suggests that when the systemic molecularly targeted drug is effective outside the eye, the iris tumor can be suppressed, and the risk of spreading outside is low after filtration surgery. Although the visual function of the affected eye could not be maintained in the current case, the QOL maintained fine until his death without any pain in his eye. Since survival can be extended with targeted therapy, considering the treatment of metastatic iris tumors may be crucial to maintain patients’ QOL. Strength of the current case report is pathologically confirmed case and observation period of more than two and half years and limitation is a case report. We reported a masquerade syndrome caused by a metastatic iris tumor complicated with secondary glaucoma, which could be diagnosed by the CEA level of the aqueous humor and iris pathology. Obtaining information about tumor markers that are elevated in the primary tumor and comparing their concentrations in the blood and in the aqueous humor can aid in diagnosing of metastatic intraocular tumors. A trabeculectomy was effective in controlling the IOP and iris tumor together with systemic targeted therapy. Aggressive treatment for metastatic iris tumors may contribute to maintaining patients’ QOL. Abbreviations BCVA: best corrected visual acuity CEA: carcinoembryonic antigen HA: Hematoxylin and eosin staining IOP: intraocular pressure QOL: quality of life TTF-1: Thyroid Transcription Factor-1 Declarations Ethics approval and consent to participate This article does not contain any studies with human participants or animals. Consent for publication Written informed consent for publication of this case and accompanying images was obtained from the patient prior to his death. Competing interests The authors declare no competing interests. Funding No funding or grant support was received. Authors' contributions Analyzed and interpreted the patient data: SK. RK. Treatment: RK. Pathological diagnosis: SY. Manuscript drafting: SK, RK. Manuscript revision: RK. All authors reviewed and approved the final manuscript. Availability of data and materials The data used in this case report is available from the corresponding author on reasonable request. References Wong M, Frank JH, Shields CL (2022) Non-small cell lung cancer with iris metastasis controlled with osimertinib and monthly intravitreal bevacizumab. Am J Ophthalmol Case Rep 25:101269 Shields CL, Shields JA, Gross NE et al. (1997) Survey of 520 eyes with uveal metastases. Ophthalmology 104:1265-1276 Shields CL, Welch RJ, Malik K et al. (2018) Uveal Metastasis: Clinical Features and Survival Outcome of 2214 Tumors in 1111 Patients Based on Primary Tumor Origin. Middle East Afr J Ophthalmol 25:81-90 Ghiam BK, Xu L, Berry JL (2019) Aqueous Humor Markers in Retinoblastoma, a Review. Transl Vis Sci Technol 8:13 Dias PL, Shanmuganathan SS, Rajaratnam M (1971) Lactic dehydrogenase activity of aqueous humour in retinoblastoma. Br J Ophthalmol 55:130-132 Zonis S, Bartal A, Navon D et al. (1979) Carcinoembryonic antigen in aqueous humor of patients with primary malignant choroidal melanoma. Ann Ophthalmol 11:1345-1347 Cassoux N, Giron A, Bodaghi B et al. (2007) IL-10 measurement in aqueous humor for screening patients with suspicion of primary intraocular lymphoma. Invest Ophthalmol Vis Sci 48:3253-3259 Kuo DE, Wei MM, Knickelbein JE et al. (2020) Logistic Regression Classification of Primary Vitreoretinal Lymphoma versus Uveitis by Interleukin 6 and Interleukin 10 Levels. Ophthalmology 127:956-962 Daxecker F, Zirm M (1980) [Diagnostic value of determining carcino-embryonic antigens in the aqueous humor (author's transl)]. Klin Monbl Augenheilkd 177:768-771 Shields CL, Kaliki S, Crabtree GS et al. (2015) Iris metastasis from systemic cancer in 104 patients: the 2014 Jerry A. Shields Lecture. Cornea 34:42-48 Camp DA, Yadav P, Dalvin LA et al. (2019) Glaucoma secondary to intraocular tumors: mechanisms and management. Curr Opin Ophthalmol 30:71-81 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 27 Sep, 2024 Read the published version in Diagnostic Pathology → Version 1 posted Editorial decision: Revision requested 29 Aug, 2024 Reviews received at journal 18 Aug, 2024 Reviewers agreed at journal 11 Aug, 2024 Reviewers agreed at journal 08 Aug, 2024 Reviewers invited by journal 05 Aug, 2024 Editor assigned by journal 31 Jul, 2024 Submission checks completed at journal 31 Jul, 2024 First submitted to journal 31 Jul, 2024 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-4835056","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":342306552,"identity":"def1afa6-9a46-47e8-aede-4fbd0ff06501","order_by":0,"name":"Shun Konno","email":"","orcid":"","institution":"Asahikawa Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shun","middleName":"","lastName":"Konno","suffix":""},{"id":342306553,"identity":"97b6f495-2720-48f0-a3c4-2afafe53af9c","order_by":1,"name":"Sayaka Yuzawa","email":"","orcid":"","institution":"Asahikawa Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sayaka","middleName":"","lastName":"Yuzawa","suffix":""},{"id":342306554,"identity":"915bdf1b-086c-4b4a-9e61-3f99f19f0a48","order_by":2,"name":"Reiko Kinouchi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCUlEQVRIiWNgGAWjYDACHsYGBoYKIEOCsRkmZgAimPFrOUOaFiBmbANpQSgywOsu857DbQ8+zrOz55/d3Gzws82OQbe9eQPDjxoGdnMcWmTONrYbztyWnDjjzsHmxN62ZAazM8cKGHuOMTBbNmDXIsHP2CbNu405geFGYvMBIKN+240cAwbeBgZmgwP4tMypt5cHajn4d1s9g9n9NwaMf/Fp4W0Eamk4zLgBqCWZd9thBrMbPAbMeG3hOdgmOePY8cSNQC3Gsv+OA/2SVnBY5pgEbr/wpD+T+FBTbS93I/2x5Jsz1Qxmxw9vfPimxiYZV4hhB0AnSSTjjx1swI50LaNgFIyCUTBMAQCa41lJiIzvWwAAAABJRU5ErkJggg==","orcid":"","institution":"Asahikawa Medical University","correspondingAuthor":true,"prefix":"","firstName":"Reiko","middleName":"","lastName":"Kinouchi","suffix":""}],"badges":[],"createdAt":"2024-07-31 11:23:49","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4835056/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4835056/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13000-024-01553-7","type":"published","date":"2024-09-27T15:56:58+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":64006402,"identity":"f56783a6-8274-4bb6-8a38-c7d9cdbca86b","added_by":"auto","created_at":"2024-09-04 21:50:27","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":32991,"visible":true,"origin":"","legend":"\u003cp\u003eSlit-lamp photograph of the left eye showing small nodules.\u003c/p\u003e\n\u003cp\u003eArrows point to the iris nodules. Iris nodules were observed scattered on the iris surface.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4835056/v1/be2c2aaa4e434f5efe647ab2.jpg"},{"id":64007323,"identity":"d6bf474e-6bd1-4079-828b-dae4473a92db","added_by":"auto","created_at":"2024-09-04 21:58:27","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":25799,"visible":true,"origin":"","legend":"\u003cp\u003eSmall masses located at the inferior angle.\u003c/p\u003e\n\u003cp\u003eArrows indicate the small masses located in the inferior angle of the left eye observed with a Gonioscope.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4835056/v1/f610ba13b6b08838117ae9b3.jpg"},{"id":64006404,"identity":"19d82e24-8ea1-4868-9c37-703352b637b6","added_by":"auto","created_at":"2024-09-04 21:50:27","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":146808,"visible":true,"origin":"","legend":"\u003cp\u003ePathological picture of the iris tissue taken at the peripheral iridectomy during the trabeculectomy.\u003c/p\u003e\n\u003cp\u003eA, B: Hematoxylin and eosin staining (HA) showing different magnification. C: Immunostaining for Thyroid Transcription Factor-1 (TTF-1). Positive cells stain brown. D: Immunostaining for Napsin A. Brown-stained positive cells are observed on the surface of the iris. TTF-1 and Napsin A are markers for lung adenocarcinoma.\u003c/p\u003e\n\u003cp\u003eThe black line in A indicates 100μm, and the black lines in B-D indicate 50μm.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4835056/v1/e44c932cb97fa653b13b8dd3.jpg"},{"id":65627072,"identity":"f21db3ef-3d91-440d-9383-b0b541c23941","added_by":"auto","created_at":"2024-09-30 16:11:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":441757,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4835056/v1/a333fde7-c19c-42a5-bb51-f6abcae98637.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A case of masquerade syndrome caused by metastatic iris tumor diagnosed by a high CEA level in the aqueous humor and iris biopsy","fulltext":[{"header":"Background","content":"\u003cp\u003eSince intraocular masquerade syndrome of neoplastic origin resembles iritis, differential diagnosis between them is crucial for ophthalmologists. Metastatic ocular tumors are relatively rare among all ocular tumors,[1, 2] and iris metastasis was reported to account for 8% of all metastatic uveal tumors.[3] Moreover, a limited amount of iris tissue can be obtained by biopsy, and methods helpful for auxiliary diagnosis of iris malignancy are needed. On the other hand, recent advances in cancer treatment, such as molecular targeted therapies, have improved the prognosis of patients with malignancy, and that can increase the need for diagnosis and treatment of metastatic ocular tumors to maintain quality of life (QOL). There are few reports detailing tumor markers checked in the aqueous humor for auxiliary diagnosis of metastatic intraocular tumors.\u003c/p\u003e \u003cp\u003eWe present a case of intraocular masquerade syndrome who had severe eye pain caused by high ocular pressure and a tumor marker, carcinoembryonic antigen (CEA) level in the aqueous humor and pathology of the resected iris tissue of iridectomy during trabeculectomy led the diagnosis.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 73-year-old man had had blurred vision in the left eye for a month, and he was diagnosed with iritis and secondary glaucoma by a local clinic. He referred to us for high intraocular pressure (IOP) with severe eye pain in the left eye. He had stage IVB lung adenocarcinoma with multiple metastases including bone, and had a targeted drug, osimertinib, for two months. The drug was effective in stabilizing his systemic condition. While his best corrected visual acuity (BCVA) was 1.2 and IOP was 16 mmHg in the right eye, his BCVA was 0.15, and IOP was 52 mmHg in the left eye. A slit lamp examination showed anterior chamber cells (+) and numerous small nodules in the iris (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). A gonioscopy examination showed small masses and peripheral anterior synechia on the inferior angle (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Since we suspected secondary glaucoma caused by a metastatic iris tumor, we performed a trabeculotomy and iris biopsy in the left eye to lower the IOP and to make a pathological diagnosis. The pathological examination result was negative for malignancy. The intraocular pressure temporarily decreased to 10 to 13mmHg but rose again to 30mmHg one month after surgery. During this period, we received information that his primary lung cancer was a lung adenocarcinoma of TTF-1 positive and a tumor marker CEA level was high from an internist treating lung cancer. We performed a trabeculectomy with anterior aqueous humor sampling and pathological examination using iris tissue obtained at iridectomy. The CEA level in the aqueous humor was 75.6 ng/mL, higher than 17.3 ng/mL in the blood. Napsin and TTF-1 positive cells were observed in the iris tissue (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), and the pathological diagnosis was metastasis of the lung adenocarcinoma. The surgery resulted in a decrease in IOP. We injected Bevacizumab intravitreally once and continued the targeted drug osimertinib. The anterior chamber became clear, the iris tumor shrank, and the iris nodules disappeared. Since then, his IOP has been controlled to 8mmHg-10mmHg, and his eye pain has disappeared. One and half years later, Osimertinib was terminated due to the systemic condition maintained stable, and metastases were observed at the left optic nerve. Although the optic nerve metastases shrank with the resumption of osimertinib, the BCVA decreased to no light perception. He died two years and nine months after the first visit because of an exacerbation of his primary lung cancer. Although he lost vision in his left eye, the metastatic tumor in his left eye and optic nerve had disappeared, and his QOL was maintained without any pain in his eye.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe presented a case of painful secondary glaucoma caused by masquerade syndrome. High CEA level in the aqueous humor and pathological examination of iridectomy tissue during trabeculectomy led to the diagnosis of metastatic iris tumor from lung adenocarcinoma. His severe pain in the eye disappeared by controlling intraocular pressure with trabeculectomy. Anterior cells and iris nodules disappeared with a vitreous injection of molecularly targeted drug and continued targeted therapy systemically.\u003c/p\u003e \u003cp\u003eThere were reports of detecting tumor markers in the aqueous humor.[4, 5, 6] High levels of Interleukin10 in the aqueous humor are known to occur in primary vitreoretinal lymphoma, and higher Interleukin10 level than Interleukin6 levels has diagnostic value.[7, 8] On the other hand, there are few reports of metastatic ocular tumors with CEA measurements of aqueous humor.[9] In the current case, we obtained information on the tumor marker in the blood that showed high levels in the primary tumor and compared that with the values in the aqueous humor. The aqueous humor CEA level was four times higher than the serum CEA level. Since limited tissue can be obtained from an eye by biopsy, it causes the result of false negatives. Thus, if a tumor marker that shows a high level in the primary tumor is known, it must be informative to check the tumor marker in the aqueous humor for auxiliary diagnosis of metastatic intraocular tumors.\u003c/p\u003e \u003cp\u003eThe effectiveness of intravitreal bevacizumab injection for glaucoma secondary to metastatic iris tumor was reported,[9] and we performed a single intravitreal injection in the present case. The iris metastatic tumor remained in remission after only one injection of bevacizumab, suggesting that the intravitreal injection contributed to the regression of the iris tumor and that the systemic administration of the molecular-targeted drug contributed to the maintenance of remission after the filtration surgery. In other words, the molecularly targeted drug possibly showed efficacy in the eye by the drug transferred to the anterior chamber after the filtration surgery.\u003c/p\u003e \u003cp\u003eSurgical treatments were reported to be performed rarely in metastatic iris tumors. In a clinical study of 104 cases, management of iris metastasis included systemic chemotherapy (n\u0026thinsp;=\u0026thinsp;18, 22%), external beam radiotherapy (n\u0026thinsp;=\u0026thinsp;34, 41%), plaque radiotherapy (n\u0026thinsp;=\u0026thinsp;20, 24%), surgical excision (n\u0026thinsp;=\u0026thinsp;4, 5%), enucleation (n\u0026thinsp;=\u0026thinsp;3, 4%), or observation (n\u0026thinsp;=\u0026thinsp;4, 5%).[10] Previous reviews have also suggested that minimally invasive glaucoma surgery (MIGS) can be considered to manage secondary glaucoma in the absence of iris or ciliary body involvement and for eyes with treated and regressed posterior ocular malignancies.[11] However, there is concern that the malignant cells spread out by filtration surgery in the eye with masquerade syndrome. The current case suggests that when the systemic molecularly targeted drug is effective outside the eye, the iris tumor can be suppressed, and the risk of spreading outside is low after filtration surgery.\u003c/p\u003e \u003cp\u003eAlthough the visual function of the affected eye could not be maintained in the current case, the QOL maintained fine until his death without any pain in his eye. Since survival can be extended with targeted therapy, considering the treatment of metastatic iris tumors may be crucial to maintain patients\u0026rsquo; QOL. Strength of the current case report is pathologically confirmed case and observation period of more than two and half years and limitation is a case report.\u003c/p\u003e \u003cp\u003eWe reported a masquerade syndrome caused by a metastatic iris tumor complicated with secondary glaucoma, which could be diagnosed by the CEA level of the aqueous humor and iris pathology. Obtaining information about tumor markers that are elevated in the primary tumor and comparing their concentrations in the blood and in the aqueous humor can aid in diagnosing of metastatic intraocular tumors. A trabeculectomy was effective in controlling the IOP and iris tumor together with systemic targeted therapy. Aggressive treatment for metastatic iris tumors may contribute to maintaining patients\u0026rsquo; QOL.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBCVA: best corrected visual acuity\u003c/p\u003e\u003cp\u003eCEA: carcinoembryonic antigen\u003c/p\u003e\u003cp\u003eHA: Hematoxylin and eosin staining\u003c/p\u003e\u003cp\u003eIOP: intraocular pressure\u003c/p\u003e\u003cp\u003eQOL: quality of life\u003c/p\u003e\u003cp\u003eTTF-1: Thyroid Transcription Factor-1\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis article does not contain any studies with human participants or animals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of this case and accompanying images was obtained from the patient prior to his death.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding or grant support was received.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnalyzed and interpreted the patient data: SK. RK. Treatment: RK. Pathological diagnosis: SY. Manuscript drafting: SK, RK. Manuscript revision: RK. All authors reviewed and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e \u003cp\u003eThe data used in this case report is available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWong M, Frank JH, Shields CL (2022) Non-small cell lung cancer with iris metastasis controlled with osimertinib and monthly intravitreal bevacizumab. Am J Ophthalmol Case Rep 25:101269\u003c/li\u003e\n\u003cli\u003eShields CL, Shields JA, Gross NE et al. (1997) Survey of 520 eyes with uveal metastases. Ophthalmology 104:1265-1276\u003c/li\u003e\n\u003cli\u003eShields CL, Welch RJ, Malik K et al. (2018) Uveal Metastasis: Clinical Features and Survival Outcome of 2214 Tumors in 1111 Patients Based on Primary Tumor Origin. Middle East Afr J Ophthalmol 25:81-90\u003c/li\u003e\n\u003cli\u003eGhiam BK, Xu L, Berry JL (2019) Aqueous Humor Markers in Retinoblastoma, a Review. Transl Vis Sci Technol 8:13\u003c/li\u003e\n\u003cli\u003eDias PL, Shanmuganathan SS, Rajaratnam M (1971) Lactic dehydrogenase activity of aqueous humour in retinoblastoma. Br J Ophthalmol 55:130-132\u003c/li\u003e\n\u003cli\u003eZonis S, Bartal A, Navon D et al. (1979) Carcinoembryonic antigen in aqueous humor of patients with primary malignant choroidal melanoma. Ann Ophthalmol 11:1345-1347\u003c/li\u003e\n\u003cli\u003eCassoux N, Giron A, Bodaghi B et al. (2007) IL-10 measurement in aqueous humor for screening patients with suspicion of primary intraocular lymphoma. Invest Ophthalmol Vis Sci 48:3253-3259\u003c/li\u003e\n\u003cli\u003eKuo DE, Wei MM, Knickelbein JE et al. (2020) Logistic Regression Classification of Primary Vitreoretinal Lymphoma versus Uveitis by Interleukin 6 and Interleukin 10 Levels. Ophthalmology 127:956-962\u003c/li\u003e\n\u003cli\u003eDaxecker F, Zirm M (1980) [Diagnostic value of determining carcino-embryonic antigens in the aqueous humor (author\u0026apos;s transl)]. Klin Monbl Augenheilkd 177:768-771\u003c/li\u003e\n\u003cli\u003eShields CL, Kaliki S, Crabtree GS et al. (2015) Iris metastasis from systemic cancer in 104 patients: the 2014 Jerry A. Shields Lecture. Cornea 34:42-48\u003c/li\u003e\n\u003cli\u003eCamp DA, Yadav P, Dalvin LA et al. (2019) Glaucoma secondary to intraocular tumors: mechanisms and management. Curr Opin Ophthalmol 30:71-81\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"diagnostic-pathology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dpat","sideBox":"Learn more about [Diagnostic Pathology](http://diagnosticpathology.biomedcentral.com)","snPcode":"13000","submissionUrl":"https://submission.nature.com/new-submission/13000/3","title":"Diagnostic Pathology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"case report, CEA in the aqueous humor, masquerade syndrome, iris tumor, trabeculectomy, molecular targeted therapy","lastPublishedDoi":"10.21203/rs.3.rs-4835056/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4835056/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground\u003c/p\u003e\n\u003cp\u003eWith the advent of targeted therapies, the survival prognosis for metastatic tumors has extended, and it has become necessary to diagnose and consider treatment that takes into account QOL for metastatic tumors of the eye. The reports of checking tumor marker in the aqueous humor for diagnosis of metastatic intraocular tumors are few. Here, we report a case of masquerade syndrome with secondary glaucoma in which a high carcinoembryonic antigen (CEA) level in the aqueous humor could assist diagnosis, and continuing targeted therapy and trabeculectomy were effective.\u003c/p\u003e\n\u003cp\u003eCase presentation\u003c/p\u003e\n\u003cp\u003eA 73-year-old man was referred to us for iritis and high intraocular pressure (IOP) with severe eye pain in the left eye. He had Stage IVB lung adenocarcinoma treated with a molecularly targeted drug, Osimertinib. His best corrected visual acuity was 0.15, and IOP was 52 mmHg in the left eye. Anterior chamber cells (+), numerous small nodules in the iris, and small masses in the inferior angle were observed. In the aqueous humor, the CEA level was higher than in the blood. Napsin A and Thyroid Transcription Factor-1 (TTF-1) positive cells showed in the resected tissue at iridectomy performed during trabeculectomy. The pathological diagnosis of metastatic iris tumor of the lung adenocarcinoma was made, and we injected bevacizumab intravitreally once and continued Osimertinib. His IOP lowered to 8-10 mmHg, and the iris masses disappeared. He lost vision by metastasis to the left optic nerve after termination of Osimertinib one and a half years later. The metastasis shrank after restarting the drug. He passed away from an exacerbation of his primary lung cancer two years and nine months after the first visit. Although he lost vision in his left eye, the metastatic tumor in his left eye and optic nerve had disappeared, and his quality of life was maintained without any pain in his eye.\u003c/p\u003e\n\u003cp\u003eConclusions\u003c/p\u003e\n\u003cp\u003eChecking tumor markers in the aqueous humor can aid in diagnosis, and aggressive treatment of metastatic iris tumors must help maintain patients’ QOL.\u003c/p\u003e","manuscriptTitle":"A case of masquerade syndrome caused by metastatic iris tumor diagnosed by a high CEA level in the aqueous humor and iris biopsy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-04 21:50:22","doi":"10.21203/rs.3.rs-4835056/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-08-29T23:25:40+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-18T08:52:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"238354015946202602229090693524612671620","date":"2024-08-11T18:56:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"281207567216999104492827037718839061768","date":"2024-08-08T08:18:35+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-06T03:55:22+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-01T03:40:40+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-01T02:37:14+00:00","index":"","fulltext":""},{"type":"submitted","content":"Diagnostic Pathology","date":"2024-07-31T11:22:30+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"diagnostic-pathology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dpat","sideBox":"Learn more about [Diagnostic Pathology](http://diagnosticpathology.biomedcentral.com)","snPcode":"13000","submissionUrl":"https://submission.nature.com/new-submission/13000/3","title":"Diagnostic Pathology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f304c88b-13c3-4aa8-8989-2865ed5af96c","owner":[],"postedDate":"September 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-09-30T15:59:31+00:00","versionOfRecord":{"articleIdentity":"rs-4835056","link":"https://doi.org/10.1186/s13000-024-01553-7","journal":{"identity":"diagnostic-pathology","isVorOnly":false,"title":"Diagnostic Pathology"},"publishedOn":"2024-09-27 15:56:58","publishedOnDateReadable":"September 27th, 2024"},"versionCreatedAt":"2024-09-04 21:50:22","video":"","vorDoi":"10.1186/s13000-024-01553-7","vorDoiUrl":"https://doi.org/10.1186/s13000-024-01553-7","workflowStages":[]},"version":"v1","identity":"rs-4835056","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4835056","identity":"rs-4835056","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}