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. 2021 Jun 10;2021:6615284. doi: 10.1155/2021/6615284

Presumed Retinal Metastasis from Lung Adenocarcinoma: A Case Report and Literature Review

Gökçen Özcan 1, Ahmet Kaan Gündüz 1,✉, Ibadulla Mirzayev 1, Ayhan Sağlik 2
PMCID: PMC8270721  PMID: 34306783

Abstract

A 63-year-old Caucasian man with metastatic lung adenocarcinoma undergoing chemotherapy and external radiotherapy was referred for routine eye examination. Although he was asymptomatic, ocular examination revealed a relatively well-circumscribed whitish retinal lesion measuring 0.5 × 0.5 × 0.5 mm located along the inferotemporal vascular arcade in the right eye. Optical coherence tomography (OCT) showed a hyperreflective dome-shaped lesion occupying the inner retinal layers with few hyperreflective dots overlying the retina in the posterior vitreous consistent with tumor cells. Fluorescein angiography revealed early hyperfluorescence and late staining without leakage at the lesion site. A diagnosis of presumed retinal metastasis from lung adenocarcinoma was made. At 2 months follow-up after completion of chemotherapy, the retinal lesion was found to have regressed completely leaving minor irregularities in the inner retinal layers on OCT. To date, there have been only 41 cases of carcinoma metastasis to the retina reported in the literature including the current case. Despite its rarity, retinal metastasis should be considered in the differential diagnosis of a white-yellow retinal mass with/without overlying vitreous cells especially in patients with a history of systemic cancer.

1. Introduction

Metastatic tumors of the uveal tract are the most common intraocular malignancies, whereas retinal metastases are rare compared to uveal metastases [1]. The choroid is the most common site of uveal metastasis. The choroid receives 85% of the ocular blood flow compared to the retina which receives only 5%, thereby explaining the rarity of retinal metastasis [2]. Carcinomas metastasize to the choroid more often compared to sarcomas and melanomas. However, melanomas tend to metastasize to the retina more frequently than carcinomas [3]. Tumor cells are periodically shed to the circulation from the primary site. Expression of specific adhesion molecules on extravasated metastatic cells allows the proliferation of these cells on the metastatic host sites [4]. Several previously published papers reviewed vitreous and retinal metastasis from cutaneous melanomas [5, 6]. We hereby present a case of retinal metastasis from lung carcinoma and review the literature on carcinoma metastasis to the retina.

2. Case Report

A 63-year-old Caucasian man diagnosed with metastatic lung adenocarcinoma 5 months ago and receiving systemic chemotherapy and external radiotherapy to the right hip underwent routine eye examination. He had no history of known ocular disease and intervention and was asymptomatic. Best corrected visual acuities were 20/32 in the right eye and 20/20 in the left eye. Intraocular pressures were 15 mmHg and 17 mmHg in the right and left eyes, respectively. Anterior segment examination showed both eyes had moderate nuclear sclerosis. Fundus examination of the right eye revealed a relatively well-circumscribed whitish retinal lesion measuring 0.5 × 0.5 × 0.5 mm located along the inferotemporal vascular arcade. There was no apparent vitreous and choroidal involvement. The left eye had normal funduscopic findings with blunted foveal reflex. Spectral domain optical coherence tomography (SD-OCT) of the right eye showed a hyperreflective dome-shaped lesion occupying the inner retinal layers with few hyperreflective dots overlying the retina consistent with tumor cells in the posterior vitreous. The outer retina was compressed by tumor and partial choroidal shadowing was observed without clinical or imaging evidence for choroidal involvement. The lesion was hypofluorescent on fundus autofluorescence (FAF) imaging. Fluorescein angiography (FA) revealed early hyperfluorescence of the lesion, late staining, and no leakage. The tumor was flat and nonmeasurable on B-mode ultrasonography. Brain magnetic resonance imaging revealed normal findings. Based on the clinical and imaging features, a diagnosis of presumed lung carcinoma metastasis to the retina was made. At a follow-up examination 2 months later after completion of systemic chemotherapy, the visual acuity in the right eye was 20/60 due to the worsening of the cataract. Fundus examination revealed that the retinal lesion in the right eye had regressed completely. There were only focal irregularities in the inner retinal layers on SD-OCT (Figure 1). The patient passed away 6 months after the diagnosis of retinal metastasis.

Figure 1.

Figure 1

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(a) Whitish perivascular retinal lesion measuring approximately 0.5 x 0.5 x 0.5 mm located along the inferotemporal arcade in the right eye. (b) The lesion is hyporeflective on infrared imaging. (c) The lesion shows hypoautofluorescence on fundus autofluorescence imaging. (d) Spectral domain optical coherence tomography (SD-OCT) imaging shows the hyperreflective dome-shaped lesion replacing inner retinal structures, causing disorganization and compression of the outer retina. Multiple hyperreflective dots are observed overlying the retina consistent with tumor cells in the posterior vitreous (arrowhead). Ellipsoid zone cannot be observed clearly because of partial posterior shadowing by the tumor, but the retinal pigment epithelium is intact. (e) At 2 months follow-up examination after completion of chemotherapy, the retinal lesion regressed completely leaving only focal irregularities in the inner retinal layers on SD-OCT.

3. Discussion

Cutaneous melanoma is the most common metastatic retinal tumor. Tang et al. reviewed 42 cases of tumor metastasis to the retina published in the English literature from 1935 to 2017 and noted that the most common primary sites for metastatic tumors to the retina were cutaneous melanoma followed by lung carcinoma and gastrointestinal carcinoma [7]. Ramaesh et al. reported 39 melanoma metastases to the vitreous and retina in his literature review in 1998 [6]. Our search of the literature showed that there were at least 60 cases of melanoma metastasis to the vitreous and retina reported so far and the total number of reported carcinoma metastasis to the retina was 40. Of the 41 cases with carcinoma metastasis to the retina including our case, 15 (36.6%) cases had lung carcinoma, 13 (31.7%) cases had gastrointestinal carcinoma including 1 case of pancreatic carcinoma and 1 case of hepatocholangiocarcinoma, 6 (14.6%) had breast carcinoma, 3 (7.3%) had adenocarcinoma with unknown primary site, 2 (4.9%) had genitourinary tract carcinoma, 1 (2.4%) had uterine carcinoma, and 1 (2.4%) had nasopharyngeal carcinoma. The mean age of all reported cases was 56.1 (range 15-75, SD ± 11.9) years. Twenty-five out of 41 (61.0%) patients were males, and the remaining 16 (39.0%) were females.

Retinal metastases are usually unilateral and solitary; however, bilateral and multifocal involvement have also been reported [8–10]. At the time of diagnosis of retinal metastasis, the majority of patients have metastasis at other sites as well (Table 1). Alternatively, ocular involvement may be the first finding of metastatic disease, and these patients must be carefully evaluated for the presence of systemic metastases at other sites.

Table 1.

Review of cases with metastatic retinal cancer reported in the literature.

Author/year Sex Age Primary tumor Location Primary tumor known at eye diagnosis The onset of eye findings (mo) Diagnosis Other known systemic metastasis Ocular treatment Follow-up Clinical signs/pathologic findings
1 Arisawa, 1914 [12]
(cited by Kennedy et al., 1958 [20])		 M 30 Pancreatic carcinoma Diffuse Yes N/A Autopsy? N/A N/A N/A Vitreous seeds, optic disc involvement
2 Smoleroff and Agatston, 1934 [18]
(cited by Kennedy et al., 1958 [20])		 M 55 Esophageal adenocarcinoma Inferotemporal quadrant Yes N/A Autopsy Liver, lung, adrenal gland, spine N/A 1 mo, deceased White irregular mass arising from nerve fiber layer, retinal and subretinal but no choroidal involvement
3 Kennedy et al., 1958 [20] M 51 Rectosigmoid adenocarcinoma Macula No 0 Enucleation Brain Enucleation 9 mo, deceased Grayish white nodular lesion
4 Duke and Walsh, 1959 [16]
(cited by Tang et al., 2019 [7])		 F 60 Uterine adenocarcinoma Macula Yes N/A Enucleation Brain Enucleation 6 mo, deceased Vitreous seeds, elevated white mass
5 Koenig et al., 1960 [10] M 56 Undifferentiated bronchogenic carcinoma Temporal retina No 0 Enucleation N/A Enucleation 13 mo, deceased Granulomatous uveitis, vitreous floaters, white mass with neovascularization, retinal and subretinal exudation, choroidal seeding
6 Flindall and Fleming, 1967 [25] M 68 Unknown primary Anterior to equator No N/A Enucleation N/A Enucleation 24 mo, alive Vitreous seeds, veil-like retinal exudates inferiorly, optic disc involvement
7 Levy and de Venecia, 1970 [14] M 49 Oat cell carcinoma of lung Posterior pole Yes 10 Autopsy Widespread Observation 10 mo, deceased Gross ophthalmic examination was normal; histopathology revealed anaplastic cells filling the lumens of retinal vessels, nerve fiber layer, and isolated choroid involvement
8 Klein et al., 1977 [8] M 52 Squamous cell carcinoma of lung Temporal macula OD, ERD OS Yes N/A Autopsy Widespread Observation 2 mo, deceased White retinal infiltrate, retinal choroidal, and optic disc involvement
9 Young et al., 1979 [26] M 63 Lung adenocarcinoma Macula Yes 4 VAB and autopsy Brain, bone External radiotherapy 7 mo, deceased Perivascular white infiltrates around optic disc, white macular mass
10 Piro et al., 1982 [17] F 56 Breast carcinoma Vitreous opacities OU No 0 PPV and autopsy OD, autopsy OS No Observation 12 mo, deceased Uveitis, vitreous seeds, no retinal infiltration; histopathology showed solitary tumor cells in retina
11 Eagle, 1988 [27]
(cited by Srivastava and Bergstrom, 2013 [28])		 F 53 Unknown primary Macula No 0 VAB, retinal and choroidal biopsy Brain, lung N/A 5 mo, deceased Vitreous balls, white macular lesions with satellites, and vascular sheathing
12 Takagi et al., 1989 [19] M 45 Adenocarcinoma of lung Inferotemporal quadrant Yes 24 Enucleation Adrenal gland, rectum Enucleation 3 mo, deceased Vitreous seeds, white exudates along the retinal veins, optic disc involvement, tumor cell emboli in central retinal vein
13 Leys et al., 1990 [29] M 49 Oat cell carcinoma of lung Temporal macula Yes 0 Autopsy Brain, kidney, liver Observation 1 mo, deceased Vitreous seeds, ERD, partially obscured retinal arteriole
14 Striebel-Gerecke et al., 1992 [24]
(cited by Srivastava and Bergstrom, 2013 [28])		 F 47 Oat cell carcinoma of lung Inferonasal quadrant Yes N/A VAB, autopsy Brain, liver, adrenal gland N/A 2.5 mo, deceased White cone shape mass in vitreous, plaque like retinal infiltration
15 Tachinami et al., 1992 [30]
(cited by Srivastava and Bergstrom, 2013 [28])		 M 61 Rectal adenocarcinoma Superior macula Yes N/A Autopsy Brain, lymph nodes N/A 5 mo, deceased White retinal mass, ERD
16 Spraul et al., 1995 [31] F 74 Muir-Torre syndrome/adenocarcinoma of lung or breast Superotemporal quadrant Yes N/A Enucleation Lung Enucleation 10 mo, alive Yellow-white tumor, shallow ERD, adenocarcinoma cells involving the retina
17 Cangiarella et al., 1996 [32] F 51 Esophageal adenocarcinoma Unknown No 0 VAB Lymph nodes N/A 4 mo, alive Vitreous seeds, white retinal infiltrate, ERD
18 Hutchison et al., 2001 [33]
(cited by Srivastava and Bergstrom, 2013 [28])		 F 63 Colon adenocarcinoma Superotemporal macula Yes N/A N/A Lung N/A 3 mo, alive Pale elevated vascular lesion superotemporal to macula, ERD
19 Gupta et al., 2002 [13] M 46 Oat cell carcinoma of lung Juxtapapillary No 0 Clinical Skin, lymph nodes Chemotherapy only 1 mo, deceased Pale elevated juxtapapillary lesion, necrosis, optic disc, retinal and choroidal involvement
20 Truong et al., 2002 [34] F 59 Breast carcinoma Temporal to fovea Yes 36 Clinical Brain, lung, liver External radiotherapy N/A White retinal and subretinal mass, ERD
21 Saornil et al., 2004 [35] M 70 Gastric adenocarcinoma Juxtapapillary Yes 192 Enucleation Mediastinal lymph node Enucleation 23 mo, deceased White retinal tumor, iris neovascularization (neovascular glaucoma), ERD
22 Apte et al., 2005 [23] M 39 Cecal adenocarcinoma Inferior macula Yes 3 PPV, excisional biopsy Liver, lung External radiotherapy 3 mo, alive Vitreous seeds, ERD
23 Rossi et al., 2005 [36] M 41 Non-small-cell lung carcinoma Superotemporal macula OU Yes 6 Clinical Bone, brain Chemotherapy only 3 mo, deceased White elevated retinal mass, ERD
24 Rundle and Rennie, 2006 [22] F 55 Breast carcinoma Temporal to fovea Yes 108 Clinical Lung Photodynamic therapy 2 mo, alive White retinal mass, SRF
25 Sirimaharaj et al., 2006 [37] F 60 Breast carcinoma Nasal midperipheral retina Yes 36 PPV Spine, lung, brain External radiotherapy 8 mo, deceased Vitreous cell clumps, white precipitates vascular sheathing
26 Alegret et al., 2009 [21] M 15 Nasopharyngeal carcinoma Inferotemporal arcade Yes 12 Clinical Lung Chemotherapy only N/A White nodular lesion
27 Kim et al., 2010 [38] F 64 Gastric adenocarcinoma Macula OU, vitreous OD Yes 24 PPV Lung, liver, peritoneal External radiotherapy 1 mo, alive Vitreous seeds, white nodular lesion
28 Coassin et al., 2011 [39] F 54 Small cell lung carcinoma Temporal macula N/a N/A PPV, retinal biopsy Brain N/A 7 mo, alive Vitreous seeds, white retinal infiltrates
29 Payne et al., 2012 [40] M 62 Small cell lung carcinoma Temporal macula N/a N/A VAB, retinal biopsy, PPV N/A External radiotherapy 10 mo, alive Vitreous haze, retinal whitening
30 Shields et al., 2014 [3] F 75 Breast carcinoma Inferotemporal quadrant Yes 103 N/A N/A Observation N/A Yellow retinal mass, irregular contour, intrinsic hemorrhage, SRF
31 Shields et al., 2014 [3] M 56 Esophageal adenocarcinoma N/A Yes 26 N/A N/A Observation 1 mo, deceased Retinal whitening, SRF
32 Shields et al., 2014 [3] F 58 Breast carcinoma N/A Yes 214 N/A N/A Observation 1 mo, deceased Retinal whitening, SRF
33 Shields et al., 2014 [3] F 64 Lung carcinoma Temporal macula Yes 20 Fine needle biopsy N/A Plaque radiotherapy 4 mo, deceased White retinal mass, vitreous seeds, intrinsic vascularity, vitreous hemorrhage
34 Taubenslag et al., 2015 [20] M 75 Non-small-cell lung carcinoma Superotemporal quadrant No 0 PPV, retinal biopsy No External radiotherapy 18 mo, alive Branch retinal vein occlusion, SRF, vitreous cells, presumed optic disc involvement
35 Praidou et al., 2017 [41] M 70 Hepatocholangio carcinoma Inferotemporal arcade Yes 11 PPV, retinal biopsy Liver Resection and chemotherapy 12 mo, alive Vitreous seeds, white retinal lesion, SRF
36 Essadi et al., 2017 [42] M 62 Clear cell renal carcinoma N/A Yes 28 Clinical Lung Chemotherapy only 4 mo, alive Large retinal mass, retinal hemorrhage
37 Whalen et al., 2018 [9] M 55 Bladder cancer Inferonasal quadrant Yes 48 PPV No External radiotherapy, enucleation 23 mo, alive Uveitis, pseudohypopyon, SRF, and satellite lesions
38 Mano et al., 2018 [43] M 69 Esophageal adenocarcinoma Macula and peripheral retina Yes N/A PPV Widespread Antiviral treatment 3 mo, deceased Vitreous seeds, white infiltrates simulating acute retinal necrosis
39 Ramtohul et al., 2019 [44] M 51 Colon adenocarcinoma Superior macula Yes N/A N/A N/A N/A 6 mo N/A Large vascularized retinal mass, retinal hemorrhage (initially), choroidal involvement (at 6 mo follow-up)
40 Jorge et al., 2020 [15] F 63 Lung carcinoma Juxtapapillary No 0 Clinical Liver Chemotherapy only 8 mo alive Yellow retinal lesion
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M: male; F: female; N/A: not available; SRF: subretinal fluid; ERD: exudative retinal detachment; VAB: vitreous aspiration biopsy; PPV: pars plana vitrectomy; OD: right eye; OS: left eye; OU: both eyes; mo: month.

Decreased vision, floaters, and ocular pain are the common presenting features in carcinoma metastasis to the retina. However, retinal metastasis can be asymptomatic as in our case. This underlines the necessity for patients with metastatic systemic cancer to have periodic eye examinations. Carcinoma metastasis to the retina most commonly presents as a focal, yellow-white, intraretinal mass with ill-defined borders. However, the tumor borders can sometimes be relatively well-circumscribed, as in our case. Overlying vitreous cells can be observed mimicking uveitis. Vitreous involvement may be seen as white-yellow cellular clumps or strands, sometimes hindering the view of the retina. Sometimes anterior chamber cells and a pseudohypopyon formed by tumor cells can also be observed [9, 10]. Glaucoma secondary to the obstruction of aqueous outflow by tumor cells in the trabecular meshwork may be observed.

Metastatic retinal melanoma usually presents with a brown lesion with ill-defined borders, but amelanotic melanoma metastasis with yellow color has also been described. Vitreous metastasis from cutaneous melanoma is characterized by pigmented cellular clumps. On the other hand, retinal carcinoma metastasis is characterized by ill-defined whitish retinal infiltration with overlying nonpigmented cellular aggregates [11].

In our literature review of metastatic retinal cancer (Table 1), vitreous involvement in addition to retinal metastasis was found in 17 (41.5%) cases. Optic disc and choroidal involvement together with retinal metastasis were reported in 5 (12.2%) cases [8, 10, 12–15]. Retinal involvement usually starts from the retinal nerve fiber and ganglion cell layers. The superficial vascular plexus located in the ganglion cell layer and supplied by the central retinal artery is the major source of metastatic tumors to the retina. As retinal metastasis grows, it replaces deeper retinal tissue. After full-thickness retinal involvement occurs, tumor cells may break through the retina pigment epithelium/Bruchs membrane and invade the choroid [10, 16]. Tumor cells may also penetrate the inner limiting membrane and spread into the vitreous cavity. Isolated carcinoma metastases to the vitreous have also been reported; however, histopathologic findings of enucleated eyes with isolated carcinoma metastases to the vitreous showed microscopic retinal involvement [5, 17].

Retinal metastases tend to be angiocentric and grow around the vessels as they are bloodborne [14, 18]. Histopathologic examination shows tumor emboli in the lumens of retinal vessels in the ganglion cell layer around retinal infiltrations [5, 14, 17, 19]. Retinal vascular occlusion has been reported leading to retinal nonperfusion and neovascularization [10, 20]. Complete disappearance of retinal metastatic lesion after chemotherapy as in our case is rare and has been reported only once before in a 15-year-old boy with nasopharyngeal carcinoma [21].

Diagnostic methods used in retinal metastatic tumors include OCT, OCT angiography, ultrasonography, FAF, FA, fine needle aspiration biopsy, pars plana vitrectomy, and chorioretinal biopsy. The differential diagnosis of carcinoma metastasis to the retina includes cotton wool spots, retinal astrocytic hamartoma, inflammatory retinitis, and primary vitreoretinal lymphoma. The former 2 lesions originate from the retinal nerve fiber layer, whereas carcinoma metastasis to the retina demonstrates multilayer involvement of the retina. Nonpigmented vitreous cells also pose a diagnostic challenge as they can resemble vitreoretinal lymphoma, amyloidosis, candida endophthalmitis, or intermediate uveitis. Cellular aggregates in the vitreous appearing as spherules or strands should always alert the clinicians to the possibility of metastatic cells.

Treatment options for carcinoma metastasis to the retina include observation, systemic chemotherapy, intravitreal chemotherapy, plaque radiotherapy, external radiotherapy, photodynamic therapy, surgical excision, and enucleation for a blind, painful eye [22–24]. The survival rate for patients with carcinoma metastasis to the retina is poor, and the mean survival for all reported cases with retinal metastasis was only 5.7 (range 1-23, SD ± 5.2) months (Table 1).

In summary, carcinoma metastasis to the retina is rare with only 41 cases being reported so far including the current case. The lung is the most common primary site for carcinoma metastasis to the retina followed by the gastrointestinal system. Retinal metastases are angiocentric, originate from the superficial vascular plexus, and are usually initially located in the inner retina. Vitreous involvement may also be seen. Patients generally have widespread metastasis at the time of diagnosis, and the life expectancy is poor. Treatment options are varied and should be tailored to the patients' needs.

4. Method of Literature Search

The literature search consisted of a systematic review of the literature using PubMed database till January 2021 using the following key words: “retinal metastasis” or “carcinoma metastasis to the retina” or “metastatic carcinoma to the retina”. The reference lists of the index publications identified through PubMed were also evaluated and relevant papers were retrieved. Chapters on metastatic tumors to the retina in major ophthalmology textbooks were reviewed. Articles written in non-English languages were also included. A total of 40 cases with carcinoma metastasis to the retina were found and reviewed for this study.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

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