Eye Cancer

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What is Eye Cancer?

Eye cancer is a general term used to describe many types of tumors that occur in various parts of the eye. It occurs when cells in or around the eye change and grow uncontrollably, forming a mass called a tumor. A tumor may be benign (noncancerous) or malignant (cancerous, meaning cells can spread to other parts of the body). Cancer that forms in the eyeball is called an intraocular malignancy.

       

Medical doctors who specialize in the diseases and function of the eye are called ophthalmologists (or “eye MDs”). These doctors can diagnose and treat intraocular melanoma. Optometrists are another type of eye doctor. They prescribe eyeglasses and contact lenses. They are not medical doctors and are not trained to treat intraocular cancer.

Parts of the eye

The eye is the organ that collects light and sends messages to the brain to form a picture. The three main parts of the eye are:

Eyeball

Orbit (eye socket)

Adnexal (accessory) structures (such as the eyelid and tear glands)

The outer part of the eye is made up of the sclera, retina, and uvea. The sclera is the outer wall of the eyeball. The retina is a thin-layered structure that lines the eyeball and sends information from the eye to the brain. The uvea nourishes the eye. Both the retina and the uvea contain blood vessels. The uvea consists of the following:

Iris: The colored part of the eye that controls the amount of light entering the eye

Ciliary body: Muscular tissue that produces the watery fluid in the eye and helps the eye focus

Choroid: The layer of tissue underneath the retina that contains connective tissue and melanocytes and nourishes the inside of the eye; the choroid is the most common site for a tumor.

Types of intraocular cancer

The most common intraocular cancer in adults is uveal metastases, which is cancer that has spread to the uvea from another place in the body; this is called secondary cancer. This article is about primary intraocular cancer, meaning that the tumor started in the eye, not somewhere else in the body.

Melanoma is the most common type of primary intraocular cancer in adults. It begins when pigmented (colored) cells in the eye called melanocytes grow uncontrollably. Intraocular melanoma is also called uveal melanoma.

Other, less common types of an intraocular tumor include:

Intraocular lymphoma is lymphoma that begins in the eyeball. This condition is rare and can be difficult for doctors to diagnose. Many doctors consider intraocular lymphoma to be a type of central nervous system lymphoma. Most intraocular lymphomas are non-Hodgkin lymphoma.

Retinoblastoma is a rare form of childhood eye cancer.

Hemangioma is a benign vascular tumor of the choroid and retina.

Other, rare cancers of the eye include the following:

Conjunctival melanoma is a tumor of the conjunctiva (a membrane that lines the eyelid and eyeball). If it is not treated, it can spread to the lymph nodes (tiny, bean-shaped organs located throughout the body that fight disease). A conjunctival melanoma tends to recur (come back after treatment) on the eye's surface and looks like dark spots on the eye. Doctors often perform a biopsy (removal of a sample of the tissue for examination under a microscope) on a spot that appears to be conjunctival melanoma.

Eyelid carcinoma (basal or squamous cell) is a variation of skin cancer. This tumor may be surgically removed and is usually not dangerous if it is treated early.

Lacrimal gland tumor is a benign or malignant tumor of the glands that produce tears.

Symptoms & Signs

People with intraocular melanoma often have no symptoms. Many times, an ophthalmologist finds the melanoma during a regular eye examination. The most common symptom is painless loss of vision.

People with eye cancer may experience the following symptoms or signs. Sometimes people with eye cancer do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not cancer. If you are concerned about a symptom or sign on this list, please talk with your doctor.

Having trouble seeing

Losing part of the field of vision

Seeing flashes of light

Seeing spots, squiggly lines, or floating objects (floaters)

Having a dark spot on the iris. Unlike choroidal and ciliary body melanoma, iris melanoma can sometimes be seen because it looks like dark spots on the eye.

Your doctor will ask you questions about the symptoms you are experiencing to help find out the cause of the problem, called a diagnosis. This may include how long you've been experiencing the symptom(s) and how often.

If cancer is diagnosed, relieving symptoms and side effects remains an important part of cancer care and treatment. This may also be called symptom management, palliative care, or supportive care. Be sure to talk with your health care team about symptoms you experience, including any new symptoms or a change in symptoms.

Risk Factors

A risk factor is anything that increases a person's chance of developing cancer. Although risk factors often influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop the disease, while others with no known risk factors do. However, knowing your risk factors and talking about them with your doctor may help you make more informed lifestyle and health care choices.

The following factors can raise a person's risk of developing eye cancer:

Age. People over age 50 are most likely to be diagnosed with primary intraocular melanoma. In fact, the average age of diagnosis is 55. It is rare in children and people over age 70.

Race. Primary intraocular melanoma is more common in white people and less common in black people.

Gender. Intraocular melanoma affects about equal numbers of men and women.

Individual history. People with the following medical conditions have a higher risk of developing primary intraocular melanoma:

Ocular or oculodermal melanocytosis (pigmentation of the eye or skin around the eye; it is also called nevus of Ota)

Nevi, or spots like moles in the eye

Dysplastic nevus syndrome (a condition marked by multiple flat moles that are irregular in shape or color)

Family history. Intraocular melanoma doesn't generally run in families, although a couple of rare cases have been reported.

Other factors. Some studies have suggested that sunlight or certain chemicals may be a risk factor for intraocular melanoma, but the data are not conclusive about this association.

People with a combination of these risk factors may benefit from seeing an ophthalmologist for a yearly examination and protecting their eyes from ultraviolet (UV) radiation with sunglasses. Anyone who finds unusual moles or other skin growths around the eye or elsewhere on the body should see a dermatologist (a doctor specializing in skin diseases), especially if there is a family history of melanoma.

Diagnosis

Doctors use many tests to diagnose cancer and find out if it has metastasized (spread). Some tests may also determine which treatments may be the most effective. For most types of cancer, a biopsy is the only way to make a definitive diagnosis of cancer. However, for eye melanoma, a diagnosis can often be made without a biopsy. The doctor may also suggest other tests that will help make a diagnosis. Imaging tests may be used to find out whether the cancer has metastasized. Your doctor may consider these factors when choosing a diagnostic test:

Age and medical condition

Type of cancer suspected

Severity of symptoms

Previous test results

In addition to a physical examination, the following tests may be used to diagnose eye cancer:

Eye examination. Most cases of melanoma are found during a regular eye examination. The doctor will examine the eye with a lighted instrument called an ophthalmoscope and a slit lamp (a microscope with a light attached to it).

Ultrasound. An ultrasound uses sound waves to create a picture of the eye.

Fluorescein angiography. This procedure takes a picture of the blood vessels in the eye. A fluorescent dye (called fluorescein) is injected into the patient's arm. The dye moves through the body and into the blood vessels in the back of the eye. The doctor then takes several, quick pictures of the eye. Fluorescein angiography may be used to rule out eye problems other than cancer. Indocyanine green angiography is a similar test that uses a different dye, called indocyanine green.

Fine needle biopsy. This procedure removes tumor cells from the eye with a needle. This allows the doctor to look at the cells under a microscope. Because doctors can correctly diagnose more than 95% of intraocular melanoma without a biopsy, this procedure is not needed for most people. Furthermore, patients who receive radiation treatment  will not be able to have a biopsy in the future.

Cytogenetics and gene expression profiling. Your doctor may recommend one of these tests to help gather more information about your prognosis (chance of recovery) and treatment options. Cytogenetics or gene expression profiling tests are done using a tissue sample removed during either a biopsy or surgery. (Or, in some situations, on an older tissue sample that was previously removed and preserved.)

Cytogenetics is the analysis of a cell's chromosomes (strands of DNA), including the number, size, shape, and arrangement of the chromosomes. Gene expression profiling is a test that identifies specific genes, proteins, and other factors unique to the tumor. Results of these tests may affect your treatment options. Talk with your doctor about the risks and benefits of having one of these tests and what the results could mean for your care.

Tests for metastases and risk of metastases. A tumor that starts in the eye can spread through the blood to other parts of the body, most commonly the liver. The doctor may see if the tumor has spread to the liver by testing the levels of liver enzymes in the person's blood or through a computed tomography (CT or CAT) scanor an ultrasound of the liver. A CT scan creates a three-dimensional picture of the inside of the body with an x-ray machine. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities or tumors. Sometimes, a contrast medium (special dye) is injected into a patient's vein to provide better detail. The doctor may also order a positron emission tomography (PET) scan. A PET scan is a way to create pictures of organs and tissues inside the body. A small amount of a radioactive substance is injected into a patient's body. This substance is absorbed mainly by organs and tissues that use the most energy. Because cancer tends to use energy actively, it absorbs more of the radioactive substance. A scanner then detects this substance to produce images of the inside of the body. The doctor may also recommend a chest x-ray to check if the cancer has spread to the lung.

After these diagnostic tests are done, your doctor will review all of the results with you. If the diagnosis is cancer, these results also help the doctor describe the cancer; this is called staging.

Stages and Grades

Staging is a way of describing where the cancer is located, if or where it has spread, and whether it is affecting the functions of other organs in the body. Doctors use diagnostic tests to determine the cancer's stage, so staging may not be complete until all the tests are finished. Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient's prognosis. There are different stage descriptions for different types of cancer.

One tool that doctors use to describe the stage is the TNM system. This system judges three factors: the tumor itself, the lymph nodes around the tumor, and if the tumor has spread to other parts of the body. The results are combined to determine the stage of cancer for each person. The stage provides a common way of describing the cancer, so doctors can work together to plan the best treatments.

In addition to staging, doctors may use other information to help figure out prognosis and the risk of the cancer spreading. These findings may also be included on the pathology report and include:

Alterations to the cancer cell's chromosomes ; for example, one copy of chromosome three, called monosomy 3, can indicate a higher risk of the cancer spreading

Gene expression profiles ; these tests classify a tumor into class I (at lower risk for metastasis) and class II (at higher risk for metastasis)

Other characteristics of the cancer cells, such as the grade (see below for more details)

TNM is an abbreviation for tumor (T), node (N), and metastasis (M). Doctors look at these three factors to determine the stage of cancer:

How large is the primary tumor, and where is it located? (T, tumor)

Has the tumor spread to the lymph nodes? (N, node)

Has the cancer spread to other parts of the body? (M, metastasis)

Some ophthalmologists may not use the TNM system to stage an intraocular tumor. However, they still consider the size of the tumor and how it is affecting a person's vision when deciding on a treatment plan.

Specific information about the TNM system is listed below. In eye cancer, T for an iris melanoma is described differently than T for choroidal and ciliary body melanomas. N and M are described the same for iris, choroidal, and ciliary body melanomas.

Tumor. Using the TNM system, the “T” plus a letter and/or number (0 to 4) is used to describe the size and location of the tumor. Some stages are also divided into smaller groups that help describe the tumor in even more detail. The following classifications are the same for any type of intraocular melanoma:

TX: The primary tumor cannot be evaluated.

T0: There is no tumor in the eye.

Iris melanoma

An iris tumor is classified as T1, T2, T3, or T4. Some stages are divided into smaller groups that help describe the tumor in even more detail.

T1: The tumor is limited to the iris.

T1a: The tumor is in one quadrant (one-fourth) or less of the iris.

T1b: The tumor is in more than one quadrant of the iris.

T1c: The tumor is only in the iris, but there is melanomalytic glaucoma. This means that a buildup of certain cells in the eye blocks the flow of fluid in the eye, causing pressure.

T2: The tumor has joined or grown into the ciliary body and/or choroid.

T2a: The tumor has joined or grown into the ciliary body and/or choroid with melanomalytic glaucoma.

T3: The tumor has joined or grown into the ciliary body and/or choroid and extends to the sclera (outer wall of the eyeball).

T3a: The tumor has joined or grown into the ciliary body and/or choroid and extends to the sclera in association with melanomalytic glaucoma.

T4: The tumor has spread to the outside of the eyeball, the optic nerve, or to the eye socket. This is called extraocular extension.

T4a: The tumor has spread is less than 5 millimeters (mm) outside of the eye.

T4b: The tumor has spread more than 5 mm outside of the eye.

Ciliary body and choroid melanoma

A tumor in the ciliary body and choroid is also classified as T1, T2, T3, or T4 based on the size of the tumor, which is measured in optic disc diameters or millimeters (mm). The tumor is measured for both width and height (also called thickness). A tumor is given a classification according to the table below, based on its width and height.

Your doctors may use and refer to this classification, called a category, even more than the stage. This is because the size and thickness of the tumor (the T) is most important for finding out a patient's prognosis.

Size Category Classification Table for Ciliary Body and Choroid Melanoma

Thickness (mm)	Category
Thicker than 15 mm					4	4	4
12.1 to 15.0				3	3	4	4
9.1 to 12.0		3	3	3	3	3	4
6.1 to 9.0	2	2	2	2	3	3	4
3.1 to 6.0	1	1	1	2	2	3	4
Less than 3.0	1	1	1	1	2	2	4
Largest basal diameter (mm)	Less than 3.0 mm	3.1 to 6.0 mm	6.1 to 9.0 mm	9.1 to 12.0 mm	12.1 to 15.0 mm	15.1 to 18.0 mm	Larger than 18.0 mm

T1: The tumor is size category 1.

T1a: The tumor is size category 1 and does not involve the ciliary body or other parts of the eye.

T1b: The tumor is a category 1 and involves the ciliary body.

T1c: The tumor is size category 1 that does not involve the ciliary body. But, there is a very small area (5 mm or less in diameter) of visible spread beyond the eyeball (called extraocular spread).

T1d: Thetumor is a size category 1 that involves the ciliary body with extraocular spread less than 5 mm.

T2: The tumor is size category 2.

T2a: The tumor is size category 2 and does not involve the ciliary body or other parts of the eye.

T2b: The tumor is size category 2 and involves the ciliary body.

T2c: The tumor is size category 2 that does not involve the ciliary body. But, there is a very small area (5 mm or less in diameter) of visible spread beyond the eyeball.

T2d: The tumor is size category 2 that involves the ciliary body with extraocular spread less than 5 mm.

T3: The tumor is size category 3.

T3a: The tumor is size category 3 and does not involve the ciliary body or other parts of the eye.

T3b: The tumor is size category 3 and involves the ciliary body.

T3c: The tumor is size category 3 that does not involve the ciliary body. But, there is a very small area (5 mm or less in diameter) of visible spread beyond the eyeball.

T3d: The tumor is size category 3 that involves the ciliary body with extraocular spread less than 5 mm.

T4: The tumor is size category 4.

T4a: The tumor is size category 4 and does not involve the ciliary body or other parts of the eye.

T4b: The tumor is size category 4 and involves the ciliary body.

T4c: The tumor is size category 4 that does not involve the ciliary body. But, there is a very small area (5 mm or less in diameter) of visible spread beyond the eyeball.

T4d: The tumor is size category 4 that involves the ciliary body with extraocular spread less than 5 mm.

T4e: The tumor is any size category with extraocular spread of more than 5 mm in diameter.

Node. The “N” in the TNM staging system stands for lymph nodes, the tiny, bean-shaped organs that help fight infection. Lymph nodes near the eye are called regional lymph nodes. Lymph nodes in other parts of the body are called distant lymph nodes. N is described the same for melanomas of the iris, ciliary body, and choroid.

NX: The regional lymph nodes cannot be evaluated.

N0 (N plus zero): There is no regional lymph node metastasis.

N1: There is regional lymph node metastasis.

Distant metastasis. The “M” in the TNM system indicates whether the cancer has spread from the eye to other parts of the body. M is described the same for iris, ciliary body, and choroidal melanomas.

MX: Distant metastasis cannot be evaluated.

M0 (M plus zero): There is no distant metastasis.

M1: There is metastasis to other parts of the body.

M1a: There is metastasis to other parts of the body and the largest metastasis is 3 centimeters (cm) or less in diameter.

M1b: There is metastasis to other parts of the body and the largest metastasis is between 3.1 cm and 8 cm in diameter.

M1c: There is metastasis to other parts of the body and the largest metastasis is larger than 8 cm in diameter.

Cancer stage grouping

Doctors assign the stage of the cancer by combining the T, N, and M classifications.

Stage I: The tumor is size category 1 and does not involve the ciliary body or other parts of the eye, nor has it spread to the regional lymph nodes or to other areas of the body (T1a, N0, M0).

Stage IIA: The tumor is either a size category 1 that may or may not involve the ciliary body, with or without extraocular extension, or it is a size category 2 that does not involve the ciliary body. There is no spread to the regional lymph nodes or to other areas of the body (T1b, T1c, T1d, or T2a; N0, M0).

Stage IIB: The tumor is either a size category 2 that involves the ciliary body but has not spread beyond the eyeball, or it is a size category 3 that has not spread to the ciliary body or eyeball. It has not spread to the regional lymph nodes or to other areas of the body (T2b or T3a; N0, M0).

Stage IIIA: Stage IIIA describes any one of these conditions:

A tumor of size category 2 with extraocular spread to a diameter of 5 mm or less, with or without ciliary body involvement that has not spread to the lymph nodes or to other parts of the body (T2c or T2d, N0, M0)

A tumor of size category 3 that may or may not involve the ciliary body, with or without extraocular spread to a diameter of 5 mm or less, but hasn't spread to the lymph nodes or to other parts of the body (T3b or T3c, N0, M0)

A tumor of size category 4 that does not involve the ciliary body and has not spread to the lymph nodes or to other parts of the body (T4a, N0. M0)

Stage IIIB: Stage IIIB describes any one of these conditions:

The tumor is a size category 3 with ciliary body involvement and extraocular spread that has not spread to the lymph nodes or to other parts of the body (T3d, N0, M0).

The tumor is a size category 4 with or without ciliary body involvement that may or may have spread outside the eyeball. It has not spread to the regional lymph nodes or to other areas of the body (T4b or T4c, N0, M0).

Stage IIIC: The tumor is a size category 4 that involves the ciliary body and has spread outside the eyeball. However, it has not spread to the regional lymph nodes or to other areas of the body (T4d or T4e; N0, M0).

Stage IV: This stage describes a tumor of any size that has spread to the lymph nodes and/or to other parts of the body outside of the eye (any T, N1, M0; or, any T, any N, M1).

Recurrent: Recurrent cancer is cancer that has come back after treatment. It may return in the eye or in another part of the body. If there is a recurrence, the cancer may need to be staged again (called re-staging) using the system above.

Histopathology and grading

After a biopsy or when the tumor is surgically removed, doctors may look at the types of cells that are in the tumor; this is called histopathology. Three types of histopathology patterns may be present in the tumor:

Spindle cell melanoma (the cells are longer and tapered at the ends)

Epithelioid melanoma (the cells are oval-shaped)

Mixed cell melanoma (both spindle and epithelioid)

Generally, a tumor made up of spindle cells has a better prognosis than a tumor made up of epithelioid cells. The tumor is given a grade (G) to describe the composition of its cells. A lower grade generally indicates a better prognosis than a higher grade.

GX: The grade cannot be evaluated.

G1: A spindle cell melanoma

G2: A mixed cell melanoma

G3: An epithelioid melanoma

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