Carol L. Shields
BASICS
DESCRIPTION
• Intraocular metastasis – most common tumor of the eye
• Most common site of involvement is choroid (63%)
• Other sites – iris, ciliary body (6%), vitreous, retina, optic disc, eyelid, and orbit (32%)
• 25% of patients have no known history of cancer. Primary site remains unknown in 10%
• Most common primary site – breasts in women and lungs in men
EPIDEMIOLOGY
Prevalence
• Increasing incidence paralleling improving cancer survival rates
• True incidence unknown in view of poor detection because of advanced cancer stage and asymptomatic nature of disease
• Postmortem incidence 10%
• Estimated prevalence of uveal metastasis – 2.3–9.2% of all patients with systemic cancer
• Estimated prevalence of orbital metastasis – 2–4.7% of all patients with systemic cancer
RISK FACTORS
• Risk factor for uveal metastasis – presence of metastatic disease in 2 or more organs
• 70–90% of patients have metastatic lesion elsewhere at time of ocular diagnosis
• Median time from diagnosis of primary cancer to ocular metastasis – 12–55 months, depending on the primary cancer site
PATHOPHYSIOLOGY
Choroid has a rich vascular supply and is recognized as the tissue with the highest metastatic efficiency index (measure of metastatic deposits in relation to blood flow).
COMMONLY ASSOCIATED CONDITIONS
• Primary cancer sites that promote ocular metastasis (pooled from multiple studies)
– Breast cancer– 40–47%
– Lung cancer– 14–30%
– GI cancer– 4%
– Prostate cancer– 1–4%
– Melanoma – 5%
– Kidney cancer– 2–4%
DIAGNOSIS
HISTORY
• Most cases are asymptomatic
• Blurred vision is the most common presentation
• Other features
– Uveal metastasis – pain, scotoma, redness, and photophobia
– Orbital metastasis – diplopia, proptosis, pain, ptosis, and visible mass
PHYSICAL EXAM
• Choroidal metastasis
– Bilaterality in 20–50%
– Multifocal lesions 30%
– Commonly affects posterior choroid, especially macula
– Usually cream colored lesions
– Orange color in metastasis from bronchial carcinoid, renal cell carcinoma, and thyroid cancer.
– Gray–brown color in melanoma metastasis
– Extensive subretinal fluid in active lesions
– “Leopard skin appearance” – due to clumps of brown pigment
• Iris metastasis
– Yellow to white single or multiple nodules
– Other likely features – iridocyclitis, hyphema, and glaucoma
• Ciliary body metastasis
– Solitary sessile or dome shaped
– Other features – cataract, iridocyclitis, and hyphema
• Retinal metastasis
– Resemble occlusive vasculitis
– Vitreous seeding may be present
• Vitreous metastasis
– Tumor infiltration of vitreous resembling lymphoma
• Optic nerve metastasis
– Occurs as juxtapapillary spread from choroidal metastasis or isolated optic nerve involvement
– Unilateral optic nerve elevation
– Significant visual loss observed
• Orbit metastasis
– Mass effect causing proptosis, globe displacement, pain, chemosis, and eyelid swelling
– Soft tissue infiltration – ptosis, restricted extraocular movement
– Enophthalmos in scirrhous carcinoma (commonly breast and stomach metastasis)
– Carcinoid – frequently, orbital metastasis is the first sign.
– Primary small intestinal carcinoids typically metastasizes to orbit and bronchial carcinoid metastasizes to choroid
– Pediatric population – metastasis are rare but the most likely primary sites are– neuroblastoma, Wilms tumor, Ewing’s sarcoma, rhabdomyosarcoma
• Eyelid metastasis
– Varied presentation – solitary or multiple nodules or diffuse lid infiltration
DIAGNOSTIC TESTS & INTERPRETATION
Initial approach
• Diagnosis primarily clinical
• CNS imaging of paramount importance because of coexistent brain metastasis
Imaging
• Uveal metastasis
– Fluorescein angiography – early hypofluorescence and late leakage
– Ultrasound –
A-scan – moderate to high internal reflectivity
B-scan – Acoustic solidity
Rarely mushroom shaped configuration noted
Ultrasound biomicroscopy useful for ciliary body metastasis
• Orbital metastasis
– CT and MRI primary diagnostic tests – MRI provides better soft tissue resolution. CT appropriate for imaging bony lesions (e.g., Prostatic metastasis)
Diagnostic Procedures/Other
• Definitive diagnosis – fine needle aspiration biopsy or open biopsy
• Immunohistochemistry beneficial in select cases to diagnose primary cell type
Pathological Findings
• Orbital tissue metastasis rate – bone–fat-muscle ratio – 2:2:1
• Diagnosis of ocular metastasis consistent with Stage IV cancer
• Work up with oncologist required for restaging tumor and investigating for other sites of metastasis
DIFFERENTIAL DIAGNOSIS
• Choroidal metastasis
– Melanoma/nevus
– Hemangioma
– Osteoma
– Lymphoma
– Inflammatory diseases
• Iris metastasis
– Amelanotic melanoma/nevus
– Granulomas
• Orbit/Eyelid metastasis
– Benign and malignant orbital/eyelid tumors
TREATMENT
Uveal Metastasis
• External beam radiotherapy (Grade B treatment recommendation)
– Dose – 20–50 Gy
– Response – 63–83%
– Visual improvement – 27–89%
– Complications – ocular surface changes, cataract, and radiation retinopathy
• Systemic chemotherapy/Hormonal therapy
– Success based on type of primary tumor
– Useful in breast/lung cancer
• Plaque radiotherapy
– High dose targeted radiation dosage
– Useful for solitary choroidal metastasis
– Beneficial for recurrent tumor following external beam radiation
• Proton beam therapy
– Shorter duration of therapy
– More precise tissue targeting due to minimal scatter
• Local therapy
– Transpupillary thermotherapy, laser photocoagulation, photodynamic therapy
– Can be used as adjuvant treatment to radiation
– Isolated reports of successful treatment with intravitreal bevacizumab – role unknown
• Enucleation
– Indicated for blind painful eye due to glaucomatous damage
Orbit Metastasis
• Treatment considerations dependent on systemic features and life expectancy.
• External beam radiotherapy – primary treatment modality
– Advantages – decrease tumor size, reduce proptosis, preserve vision
– Dose – 20–40 Gy over 2–4 weeks
– Complications – Cataract, Radiation retinopathy
– Concurrent intracranial irradiation required for brain metastases
• Systemic chemotherapy – reserved for chemosensitive tumors like small cell lung cancer
• Hormonal therapy – Breast/prostate metastasis
• Orbital surgery – debulking reserved to reduce ocular pain, proptosis, and diplopia
• Exenteration – for disfiguring orbital mass
EyelID Metastasis
• Dependent on tumor size, location, extent, and systemic features.
• Excisional biopsy – Small solitary lesion
• External beam radiotherapy – for multiple/recurrent lesions
• Systemic chemotherapy/immunotherapy – for extensive systemic metastasis
• Palliative care – for terminal metastasis
• Topical Imiquimod – for cutaneous melanoma metastasis
ADDITIONAL TREATMENT
General Measures
Treatment of primary tumor and other metastatic foci
Additional Therapies
• Palliative care
• Pain management
COMPLEMENTARY & ALTERNATIVE THERAPIES
• In 3–5% of patients the primary site remains unknown after workup
• Following evaluation of all sites of metastasis, therapeutic chemotherapy trial can be attempted
• 85% of these patients die within 1 year
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
• Multidisciplinary coordinated care required
• Close monitoring for detection of systemic metastatic foci
• Close ophthalmic follow-up for detection of new metastasis, especially in the fellow eye
PATIENT EDUCATION
• Counsel regarding warning eye signs in patients with advanced cancers
• After diagnosis of ocular metastasis – careful monitoring is required to detect new metastasis in both eyes
PROGNOSIS
• Median life expectancy – 6–9 months
• Prognosis dependent on type of tumor and extent of metastasis
• Favorable prognosis – Breast cancer and carcinoid metastasis
ADDITIONAL READING
• Ahmad SM, Esmaeli B. Metastatic tumors of the orbit and ocular adnexa. Curr Opin Ophthalmol 2007;18:405–413.
• Bianciotto C, Demirci H, Shields CL, et al. Metastatic tumors to the eyelid: Report of 20 cases and review of the literature. Arch Ophthalmol 2009;127:999–1005.
• Kanthan GL, Jayamohan J, Yip D, et al. Management of metastatic carcinoma of the uveal tract: An evidence-based analysis. Clin Experiment Ophthalmol 2007;35:553–565.
• Shields JA, Shields CL, Kiratli H, et al. Metastatic tumors to the iris in 40 patients. Am J Ophthalmol 1995;119:422–430.
• Shields CL, Shields JA, Gross NE, et al. Survey of 520 eyes with uveal metastases. Ophthalmology 1997;104:1265–1276.
• Shields JA, Shields CL. Metastatic tumors to the uvea, retina, and optic disc. In: Shields JA, Shields CL, eds. Eyelid, Conjunctival, and Orbital Tumors. A Textbook and Atlas, 2nd ed. Philadelphia, PA: Lippincott, Williams & Wilkins, 2007;727–745, 168–173.
• Shields JA, Shields CL. Metastatic tumors to the uvea, retina, and optic disc. In: Shields JA, Shields CL, eds. Intraocular Tumors. A Textbook and Atlas, 2nd ed. Philadelphia, PA: Lippincott, Williams & Wilkins, 2007;198–227.
• Shields CL, Shields JA. Metastatic cancer to the eye and adnexa. In Tasman WS, Jaeger E, eds, Duane’s Clinical Ophthalmology Vol. 5, Chapter 34, Philadelphia, PA: Lippincott Williams & Wilkins, 2010.
See Also (Topic, Algorithm, Electronic Media Element)
• www.malignantmelanomainfo.com
CODES
ICD9
• 198.4 Secondary malignant neoplasm of other parts of nervous system
• 198.2 Secondary malignant neoplasm of skin
CLINICAL PEARLS
• Increasing incidence of ocular metastasis
• High index of suspicion required for diagnosis
• Early diagnosis and appropriate therapy improves prognosis and visual morbidity.
• Ocular metastasis is the first presentation of malignancy in around 30%.
• Choroid is the most common site of metastasis.
• External beam radiotherapy is the treatment of choice in most patients.
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