Case Report Metastatic Intraocular Tumor Due to Colorectal Adenocarcinoma: Case Report and Literature Review Deivy Cruzado-Sanchez1, MD; Luis A. Saavedra-Mejia2, MD; Walter A. Tellez2, MD Grissnery Maquera-Torres3, MD; Solon Serpa-Frias1, MD 1Ophthalmic Oncology Service, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru 2Sociedad Científica de Estudiantes de Medicina Villarrealinos, Universidad Nacional Federico Villarreal, Lima, Peru 3Pathology Service, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru ORCID: Deivy Cruzado-Sanchez: https://orcid.org/0000-0003-0826-8928 Abstract Purpose: To describe the clinical and histopathological findings of a case of intraocular metastasis due to colorectal adenocarcinoma and to carry out a literature review. Case Report: A 64-year-old man with a history of tumor resection due to infiltrating colorectal adenocarcinoma three years previously sought ophthalmological care because of severe ocular pain without response to medical treatment and progressive vision loss in the left eye. On ultrasonographic examination, there was a heterogeneous intraocular choroidal tumor, which occupied approximately 40% of the vitreous cavity, as well as peritumoral serous retinal detachment. The patient underwent left eyeball enucleation. The histopathological diagnosis was metastatic tubular adenocarcinoma involving the retina and choroid that partially infiltrated the sclera and the proximal optic nerve. Conclusion: The present case highlights a rare pathological entity associated with variable therapeutic schemes and survival times and poor prognosis in patients with metastatic intraocular tumors due to colorectal adenocarcinoma. Keywords: Colorectal Neoplasms; Eye Neoplasms; Neoplasm Metastasis J Ophthalmic Vis Res 2020; 15 (4): 565–570 INTRODUCTION Colon cancer is the second cause of death associated with cancer in developed countries, Correspondence to: Deivy Cruzado-Sanchez, MD. 2520 Angamos Avenue, Ophthalmic Oncology Service, Instituto Nacional de Enfermedades Neoplásicas, 15038 Lima, Peru. E-mail: dcruzados@gmail.com Received: 24-02-2019 Accepted: 13-01-2020 Access this article online Website: https://knepublishing.com/index.php/JOVR DOI: 10.18502/jovr.v15i4.7794 representing 9% of all cancer estimated deaths;[1] while in developing countries like Peru, it is the fifth cause of death, accounting for 6 deaths per 100,000 inhabitants.[2] The most frequent sites of metastasis are liver (77%), peritoneum (25%), and lungs (22%), while intraocular involvement is infrequent and rarely reported.[3–5] This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. How to cite this article: Cruzado-Sánchez D, Saavedra-Mejía LA, Tellez WA, Maquera-Torres G, Serpa-Frias S. Metastatic Intraocular Tumor Due to Colorectal Adenocarcinoma: Case Report and Literature Review. J Ophthalmic Vis Res 2020;15:565–570. © 2020 JOURNAL OF OPHTHALMIC AND VISION RESEARCH | PUBLISHED BY KNOWLEDGE E 565 http://crossmark.crossref.org/dialog/?doi=10.18502/jovr.v15i4.7794&domain=pdf&date_stamp=2019-07-17 https://knepublishing.com/index.php/JOVR Ocular Metastasis from Colorectal Adenocarcinoma; Cruzado-Sánchez et al The aim of this report is to describe the clinical and histopathological findings of a case of intraocular metastasis from colorectal adenocarcinoma and to carry out a literature review. CASE REPORT The patient was a 64-year-old man with six months of severe and progressive vision loss in the left eye associated with severe ocular pain. He had a history of resection of a moderately differentiated colorectal adenocarcinoma with muscle layer involvement, invasive borders, and involvement in 3 of the 25 regional lymph nodes (T3N1M0) three years ago. He refused complementary treatment with chemotherapy at that time (Figures 1A1 and 1A2). The ophthalmological examination showed a visual acuity (VA) of 20/20 in the right eye and no light perception in the left eye. Intraocular pressure was 16 mmHg in the right eye and 50 mmHg in the left eye. Biomicroscopic examination showed moderate conjunctival hyperemia, mydriatic and unreactive pupil, moderate corneal edema, and moderate crystalline opacity in the left eye and unremarkable findings in the right eye. Funduscopy revealed extensive whitish tumor mass with multiple hemorrhagic foci on its surface, moderate vitreous opacity and retinal detachment in the left eye. On ultrasonographic examination, there was a heterogeneous intraocular choroidal tumor, which occupied approximately 40% of the vitreous cavity, as well as peritumoral serous retinal detachment (Figure 2). Computed tomography preformed for metastasis work-up demonstrated tumoral lesions in the lungs. He was diagnosed as a secondary non- controlled glaucoma due to probable metastatic choroidal tumor. He received maximum antihypertensive ocular treatment in the left eye with poor response and persistence of pain. Due to the evidence of a blind, painful eye with a large intraocular tumor, left eyeball enucleation was performed with patient’s informed consent. The histopathological diagnosis was metastatic tubular adenocarcinoma involving the retina and choroid, partially infiltrating the sclera and the proximal optic nerve. Immunohistochemical study was positive to CDX2; some tumor cells expressed CK20 focally, and the tumor was negative for CK7. All these findings were consistent with a primary colorectal adenocarcinoma as the source of metastasis (Figures 1B1–1B5). Medical oncology team assessed the patient. Treatment with chemotherapy and palliative radiotherapy was indicated, but he refused it and just accepted palliative pain therapy. He died six months after the enucleation. DISCUSSION Metastasis of colorectal carcinoma to the eye is infrequent,[3] and it is associated with advanced stages of the disease with an unfavorable prognosis and poor survival.[6] We performed a literature review through a systematic search in PubMed and Google Scholar using an appropriate search strategy for each database (supplementary material 1) and reviewed the references of the reports included in the systematic search to increase the chances of identifying all reported cases of intraocular metastasis due to colorectal adenocarcinoma. We included 23 case reports and 1 case series (Table 1), accounting for 25 cases, for which 19 patients presented with metastasis only to the choroid,[4–23] three with metastasis only to the retina,[24–26] one with metastasis to the retina and choroid,[27] one with metastasis to the sclera, retina, and optic nerve,[28] and one with metastasis to the choroid and optic nerve.[29] The average age was 55.2 years (ranging from 30 to 80 years), and 15 patients were men. Regarding the source of the primary neoplasia, 12 were derived from the colon, 12 from the rectum, and 1 was colorectal. However, most of the papers did not report the TNM staging. The average time of detection of intraocular metastasis after the diagnosis of the primary colorectal neoplasm was 24.7 months (ranging from immediately up to 96 months); only in five cases was the diagnosis of intraocular metastasis made at the same time as the primary colorectal neoplasm diagnosis.[8, 10, 13, 18, 24] In addition to intraocular metastasis, an involvement of other organs have also been found, such as liver, lung, skin, bone, brain, and cerebellum (Table 1). In the current case, intraocular metastasis was detected 36 months after the diagnosis of the primary tumor. In the cases reported in the literature (Table 1), the most frequent reason for ophthalmological consultation was some type of vision dysfunction 566 JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 15, ISSUE 4, OCTOBER-DECEMBER 2020 Ocular Metastasis from Colorectal Adenocarcinoma; Cruzado-Sánchez et al Figure 1. Primary neoplasms from A1 to A3. (A1) Colonic macroscopy of a single tumor above the junction of the rectum and sigmoid. (A2) Tubular adenocarcinoma moderately differentiated in the submucosal layer of colon pT3N1b. Intraocular metastasis from B1 to B5. (B1) Eyeball with exophytic tumor. H&E staining. (B2) Metastasis of tubular adenocarcinoma in the retina. (B3) Metastasis of tubular adenocarcinoma in the optic nerve. (B4) Positive nuclear staining for CDX2. (B5) Positive focal expression of CK20. Figure 2. (A) Ocular ultrasound demonstrating a heterogeneous intraocular choroidal tumor associated with retinal detachment. (B) Enucleated surgical tissue from the eye with a whitish tumor mass with signs of hemorrhage. JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 15, ISSUE 4, OCTOBER-DECEMBER 2020 567 Ocular Metastasis from Colorectal Adenocarcinoma; Cruzado-Sánchez et al Table 1. Characteristics of previous intraocular metastasis cases due to colorectal adenocarcinoma reported in the literature Author Year of publication Sex Age Colorectal cancer Intraocular metastasis Other sites of metastasis Survival time (months) Primary lesion TNM or stage Intraocular site Time to diagnosis (months) Symptom Treatment Kennedy[24] 1958 M 51 Rectosigmoid NS Retina S Blurred vision Enucleation None 9 Howard[27]∗ 1968 M 63 Colon NS Retina, choroid 36 Visual disturbance Enucleation Orbit 16 Cole[7]∗ 1985 F 48 Rectum T4a Choroid 23 Blurred vision RT, CT Lung 4 Tano[8]∗ 1989 M 30 Rectum NS Choroid S Blurred vision Enucleation Bone, skin 4 Endo[9]∗ 1997 F 49 Rectum NS Choroid 84 Flashes Enucleation Liver, lung 3 Ward[10] 2000 F 52 Colon NS Choroid S Vision loss None Intraabdominal 1 Nakamura[11] 2002 M 79 Colon IIIb Choroid 18 Blurred vision CT Lung NS Fujiwara[12]∗ 2004 M 53 Rectum NS Choroid 30 Vision loss RT, CT Liver, lung, bone 1 Linares[13] 2004 M 47 Rectum NS Choroid S Blurred vision RT, CT Liver, lung 9 Apte[25] 2005 M 39 Colon NS Retina 3 Visual disturbance RT, CT Liver, lung 7 Hisham[28] 2006 F 32 Rectum NS Sclera, retina, optic nerve 10 Ocular pain RT Spine, breast, orbit 0.5 Kuo[14] 2008 F 65 Colon NS Choroid 20 Vision loss Intravitreous Bev Brain 5 Sashiyama[15] 2010 M 49 Rectum NS Choroid 15 Vision loss CT Lung, bone 11 Lin[16] 2010 M 43 Colon NS Choroid 96 Vision loss CT, intravitreous Bev Bone 4 Neale[17] 2010 M 43 Rectum T2N0M0 Choroid 18 Blurred vision NS Lung, pelvis, brain NS Miyake[18]∗ 2012 M 74 Rectum NS Choroid S Vision loss CT Liver, lung 8 Tei[19] 2014 M 60 Rectum T1 Choroid 30 Floaters RT Lung 27 Maudgil[20] 2015 F 57 Colon NS Choroid 18 Vision loss Intravitreous Bev NS NS 2015 M 80 Colon NS Choroid 6 Vision loss Intravitreous Bev Liver NS Kawhaja[4] 2015 F 60 Rectum T3N1M0 Choroid 42 Flashes RT, CT, systemic Bev Lung 31 Huo[21] 2015 F 51 Colon T3N1M0 Choroid 27 Ocular redness, foreign body sensation RT Lung, bone 2.5 Nookala[26] 2016 M 56 Colon T3N0Mx Retina 25 Vision loss and ocular pression sensation RT Liver, lung NS Boss[22] 2016 F 68 Rectum T3N0Mx Choroid 96 Floaters and flashes intravitreous Bev Lung, cerebellum NS Ha[23] 2016 F 78 Colon T3N0M0 Choroid 6 Visual disturbance CT Lung, skin 8 Walker[29] 2017 M 54 Colon T1N0M0 Choroid, optic nerve 16 Vision loss RT, systemic Bev, CT, photodynamic therapy Lung 24 Present case 2018 M 64 Rectosigmoid T3N1M0 Choroid , retina, optic nerve, sclera 36 Ocular pain and vision loss Enucleation Lung 6 *The data from these articles were extracted secondarily from other articles that cited them because it was not possible to access to the full-text article. M, male; F, female; NS, not specified; RT, radiotherapy; CT, chemotherapy; Bev, bevacizumab; S, simultaneous 568 JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 15, ISSUE 4, OCTOBER-DECEMBER 2020 Ocular Metastasis from Colorectal Adenocarcinoma; Cruzado-Sánchez et al Supplementary Material 1. Literature review through a systematic search of PubMed and Google Scholar Date Results PubMed (”neoplasm metastasis”[MeSH Terms] OR ”metastasis”[Title/Abstract] OR ”metastases”[Title/Abstract] OR ”ocular metastasis”[Title/Abstract] OR ”intraocular metastasis”[Title/Abstract]) AND (”choroid”[MeSH Terms] OR ”choroid”[Title/Abstract] OR ”retina”[MeSH Terms] OR ”retina”[Title/Abstract]) AND (”case reports”[Publication Type] OR ”case study”[Title/Abstract] OR ”case report”[Title/Abstract]) October 2018 593 Google Scholar (”neoplasm metastasis” OR ”metastasis” OR ”metastases” OR ”ocular metastasis” OR ”intraocular metastasis”) AND (”choroid” OR ”retina”) AND (“colorectal cancer” OR “colon cancer” OR “colonic neoplasm” OR “colonic cancer”) October 2018 17200 (decreased VA, blurred vision, floaters or flashes), whereas in the present case, the patient had severe ocular pain related to uncontrolled secondary glaucoma in addition to vision loss, similar to a case reported in Malaysia.[28] Four cases of eyeball enucleation have been reported in the literature.[8, 9, 24, 27] Currently, enucleation is considered a reserved therapeutic option for intraocular malignant tumors in advanced stages with extensive ocular involvement and severe pain due to secondary glaucoma.[30, 31] In the present case, enucleation was performed because of the extensive ocular involvement, absent visual function, secondary uncontrollable glaucoma, and the refusal of the patient to submit to other therapeutic proposals. The survival time ranged from 14 days to 31 months after the diagnosis of intraocular metastasis in previously published reports (Table 1). In the present case, the patient’s survival time was six months. In previous cases treated with enucleation,[8, 9, 24, 27] the survival time ranged from 3 to 16 months, while longer survival times were reported in patients treated with radiotherapy, chemotherapy, and systemic bevacizumab treatment (24 and 31 months). In the present case, the immunohistochemical assessment of the intraocular tumor was positive for CDX2, focally positive for CK20, and negative for CK7. 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