Intraocular metastasis from an anal squamous cell carcinoma: a case report

Introduction

Intraocular metastasis from distant sites is a relatively uncommon phenomenon. A review of 244 patients with orbital tumors conducted by Ohtsuka et al. showed that only 2% of the cases resulted from metastatic spread to the eye from a distant primary site, whereas the majority of the cases were due to a primary orbital tumor (1). The most common primary tumors that metastasize to the eye include cancers of the breast, lung, and gastrointestinal (GI) tract (2).

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 attributed to colorectal cancer, followed by gastric, esophageal, pancreatic, liver and biliary tract cancers (4). In contrast, anal cancers are relatively rare, accounting for only 0.3% cases (3), and ocular metastasis from an anal primary is an even rarer 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 (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-453/rc).

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. Laboratory tests at the time were remarkable for microcytic anemia with a hemoglobin level of 8.3 g/dL. An esophagogastroduodenoscopy and colonoscopy were performed, revealing an anal mass, with pathology reporting moderately differentiated invasive squamous cell carcinoma. A positron emission tomography (PET) scan at the time revealed a 6-cm hypermetabolic 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 approximately 3 months. Follow-up PET scan showed disease progression, with markedly increased anorectal mass but resolution of pathologic lymphadenopathy. However, it also revealed a new 10-mm hypermetabolic focus in the right lobe of the liver and an enlarging left lower lobe pulmonary nodule now measuring 4 mm. Magnetic resonance imaging (MRI) of the abdomen showed two right hepatic masses with the largest measuring up to 25 mm. The patient underwent a computed tomography (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 an 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 a new 10-mm adrenal lesion concerning for 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, 2 months later repeat CT imaging showed disease relapse with evidence of numerous bilateral pulmonary nodules/masses, right inferior hepatic lobe hepatic metastases, increased size of right adrenal nodule, a 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 1 month later and almost 2 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. The patient underwent right eye enucleation and prosthesis placement, with pathology confirming metastatic carcinoma consistent with anal carcinoma. Post-operation MRI of the brain and orbit showed no evidence of disease. However, CT of the chest, abdomen and pelvis revealed worsening disease when compared to 3 months prior, with interval progression of disease in the chest with pulmonary and chest wall metastasis, stable hepatic lesions and a 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 of the disease process and switching to either a different chemotherapy regimen versus transitioning to palliative or comfort care. After much consideration, the patient elected for comfort care and subsequently passed away.

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’s wife for the publication of this case report. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Anal cancer is a relatively rare malignancy, accounting for only 2% of all GI tract cancers (5). However, in recent years, the incidence of anal cancer has been increasing rapidly in many populations, including the Americas, Northern and Western Europe, and Australia, with anal squamous cell carcinoma being the most prevalent subtype (6,7). Known risk factors for the disease include human papillomavirus (HPV) infection, especially HPV 16, human immunodeficiency virus (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, older age and smoking (5,7). Common sites of metastasis from anal cancer include para-aortic nodes, liver, lungs, and skin (8). However, this case highlights the rare phenomenon of intraocular metastasis from an anal primary.

Intraocular metastasis is mostly seen in the uvea, and rarely involves the retina (9). The most common site of uveal metastasis is the choroid (88%), followed by the iris (9%) and finally the ciliary body (2%) (2). The pathophysiology of anal cancer metastasis to the uvea can most likely be attributed to hematogenous spread, due to the absence of lymphatic system in the eye (10). 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 (9) and particularly to the perimacular choroid (10). The presence of metastatic disease in the liver and lung before the diagnosis of intraocular metastasis further supports the mechanism of spread through dissemination in blood.

The 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 (11). This can be explained by macular or peripapillary retinal involvement (9) or due to extensive accumulation leading to retinal detachment (10).

Treatment is primarily aimed at improving quality of life. Systemic treatment options for intraocular metastasis include systemic chemotherapy, and immunotherapy (9). Radiation treatment modalities include external beam radiation therapy (EBRT), proton beam radiotherapy (PBT), brachytherapy, and stereotactic radiotherapy (9). In addition, patients have also shown favorable responses with intravitreal selective vascular endothelial growth factor (VEGF)-A inhibitors, in particular with bevacizumab (9,10,12,13). Lastly, enucleation may be considered for patients experiencing eye pain and complete vision loss (9). 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, and depends on the extent of systemic or extraocular disease burden, and the patient’s performance status at the time of diagnosis of intraocular metastasis. Nonetheless, the prognosis generally remains poor. A case series of 96 patients indicated a median survival time between diagnosis of choroidal metastasis and death of only 6 months (16). Similarly, our patient passed away after about 3 months from the initial diagnosis of intra-ocular metastasis, further underscoring the poor prognosis associated with this disease process.

Conclusions

In conclusion, anal cancer is one of the less common GI cancers, and intraocular metastasis from anal squamous cell carcinoma is an even rarer phenomenon, with no reported cases available per our literature review. This case aims to highlight the need to consider intraocular metastasis as a possible differential diagnosis in 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.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-453/rc

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-453/prf

Funding: This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare-affiliated entity.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-453/coif). All authors report funding from the HCA MountainView Hospital. S.S. and M.D.A. report the employment relationship with HCA Healthcare Sunrise Health Graduate Medical Education (GME) Consortium. A.Y. reports the employment relationship with Comprehensive Cancer Centers. The authors have no other 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. 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’s wife for the publication of this case report. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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