Uveal Melanoma

Uveal Melanoma

Melanoma is a type of cancer that arises from melanocytes; a cell specialized in the production of melanin. This is a pigment that protects our cell’s DNA from the deleterious effects of sun radiation; in the eye, melanin is thought to aid light absorption. The most frequent melanoma in the body occurs in the skin (i.e. cutaneous melanoma). In the eye, melanoma appears in the uvea - most commonly in the choroid, followed by the ciliary body and then the iris.

Uveal melanoma is a tumour that grows and can invade the surrounding tissues. It sometimes spreads using the blood vessels to reach distant places like the liver. Up to 50% of UM patients develop such metastases, most often in the liver. Unfortunately uveal melanoma metastases remain very difficult and often impossible to treat.

Melanoma of the eye can also occur on the outermost layer of the eye, the conjunctiva, which lines the front part of the eye and the eyelid. This type of melanoma is very rare, and is called conjunctival melanoma. Despite affecting the same organ, uveal melanoma and conjunctival melanomas are very different in their nature.

Risks Factors

Uveal melanoma is a rare intraocular tumour. Nevertheless it is the most frequent eye cancer in the adult. It has an incidence rate of 5 cases per million individuals per year and is more common in the Nordic European countries. Since the early 1970s, the age-adjusted tumour incidence has remained stable. The incidence rates of this cancer vary in different countries. However some of the differences can be attributed to different inclusion criteria and methods of calculation.

We still do not know much about the risk factors leading to this disease. Uveal melanoma seems to be more common:

  • In Men than women, with a slightly higher male preponderance of 4.9 vs. 3.7 per million.
  • Between the ages of 50 and 70.
  • In individuals with white skin and light eyes (blue, grey, green colour);
  • In people with a lot moles (some of them can be inside the eye);

Several observational studies have tried to establish a link between uveal melanoma risk and sunlight exposure. To date, only weak associations or contradictory results have been found. There is no consistent evidence that UV light exposure or other environmental agents are risk factors for uveal melanoma. This is in contrast to skin melanoma and conjunctival melanoma, where UV light exposure is a definite risk for cancer development.

Eye cancer is rare. Many eye conditions can cause symptoms that are similar to the ones described here. Nonetheless one should always report them to a clinician, early diagnosis is very important for successful treatment.

Symptoms

Uveal melanoma is an intraocular tumour, which means that it will grow silently before any visible exterior change can be detected. The symptoms can start when there is a partial detachment of the retina. The signs and symptoms are common to all eye cancer types and include the following:

  • Sensation of flashing lights;
  • Seeing spots or flashes of light;
  • Poor or blurred vision in one eye;
  • Change in the appearance of the eye, for example:
    • A raised lump or spot on or near the iris;
    • Bulging of one eye;
    • A pale raised lump on the surface of the eye;
  • Partial or complete loss of sight;
  • Pain in or around the eye (rare with eye cancer).

Eye cancer can also cause

  • 'Blinkered' vision (loss of peripheral vision), one can see what is straight ahead clearly, but not the sides;
  • A change in the dark spot on the coloured part of the eye (the iris) that becomes larger with time;
  • Eye irritation, red eye or chronic inflammation of the conjunctiva (conjunctivitis).

Pain is a rare symptom unless the cancer has spread to the outside of the eye or has caused the pressure inside the eye (intraocular pressure) to become too high. In one third of cases the tumour is detected in a routine ophthalmologic evaluation, often with no symptoms reported by the patient.

A benign pigmented lesion in the eye such as a uveal naevus of a large size can be a risk factor and should be routinely checked.

Diagnosis

Close examination by an experienced clinician remains the most important diagnostic approach for uveal melanoma detection. It is very hard to distinguish a small uveal melanoma from a nevus. The routine examination of the latter is often important to observe if it is growing. Clinical findings that help to identify uveal melanoma are:

  • A lesion thickness of more than 2 mm.
  • Subretinal fluid.
  • Visual signs and symptoms (link).
  • An Orange Pigmented tumour surface.
  • A tumour margin touching the optic disc.

There are several tests important for the diagnosis of uveal melanoma such as:

  1. 1. An eye examination;
  2. 2. Ultrasound scan of the eye;
  3. 3. Angiogram or a fluorescein angiogram: this exam allows us to look at blood vessels using a type of dye. This will help physicians find out more about the nature of the tumour;
  4. 4. Fine needle aspiration biopsy: this is a rarely used exam because the above listed tests are usually accurate in the diagnosis but important for tumour staging and determining risk of metastasis upon genetic testing of the sample as below.
  5. 5. Testing genetic information in the cells: this is known as cytogenetic testing. It helps to provide the doctor information about the possibilities of the cancer coming back or spreading. At the moment the tumour genetics often don’t directly affect the treatment of the eye tumour, but this information is crucial to determine risk of recurrence of the disease in the future.
  6. 6. Other tests: include exams to evaluate general health.
  7. 7. Ultrasound or MRI scans of the liver: these exams are important since uveal melanoma has a risk of spreading to the liver. Which methods are best for these exams are still under debate, and may depend on details of the method and specialization of the physicians involved.

It is debated which exam and frequency should be taken, future research should help us establish the evidence for these guidelines.

If an ophthalmologist suspects uveal melanoma, an eye cancer specialist should be notified.

Patients may need to wait a while to get the results. Comprehensibly, this can be a very anxious period of time for most people. Access patient networks and other resources for organisations that can put patients and families in touch with support groups and provide further information.

Treatment

General Approach

Treatments for uveal cancer most often are surgery, radiation therapy, or both. When planning treatment a clinician will take into consideration the following aspects:

  • The size of the tumour and its location in the eye;
  • How far it has grown or spread – the stage of the tumour;
  • How much it is affecting sight;
  • The pathology report when available;
  • General health and fitness.

There are several concerns when treating uveal melanoma including the preservation of sight. As with many types of cancer, the earlier the diagnosis is made, the easier it is to cure or manage it.

If the tumour is large or already has stopped the patient from seeing, surgery may be needed to remove the eye. This surgery is called enucleation. Previously, treatment consisted only of this possibility. Nowadays, this has been superseded whenever possible by conservative eye-preserving therapies that include various forms of radiation therapy, laser treatment and local tumour resection.

Great concern must also be given to the prevention/treatment of spreading of the tumour to other parts of the body. A positive outcome with the initial treatment of the tumour is very important, however it does not mean the cancer has not spread. Uveal melanoma spreads through the blood vessels and there is no way of testing for this at the present time other than assessing risk with genetic examination of the primary (eye) tumour cells and checking for changes elsewhere in the body, namely the liver.

Managing Metastatic Uveal Melanoma

In a great number of patients with uveal melanoma, metastatic disease is not detected at diagnosis. Up to 50% of patients develop metastatic disease at any time from the initial UM diagnosis to several decades later. The liver may be the only metastatic site even though lung, bone and skin metastases can also form.

Surveillance/Follow up

Since there are controversial results about the different methods available for screening for the appearance of metastatic disease, patients should have an individual plan decided in collaboration with their clinicians. Patients should be informed about the benefits and limitations of a tumour biopsy at this point.

If the tumour is removed from the eye (surgical treatment) or if the patient has a biopsy taken, additional information can be obtained from the tumour tissue to assert:

  • The type of tumour cells present;
  • The cell cycle and division activity of the tumour cells;
  • The genetic profile of the tumour cells;

The importance of a tumour biopsy is the identification of a high-risk group allowing for determination of liver scan frequencies. The gathering of all clinical information with the auxiliary diagnostic scans and furthermore the genetic profile of the tumour (obtained through the biopsy tissue) is crucial for overall risk assessment. Patients should also be offered the decision as to how much information they would like to receive. As the decision whether to find out if they are at high risk of cancer spreading can be very difficult.

Patients that are considered high risk with respect to developing secondary tumours in the liver should be offered a follow up with a clinical review, scans with liver-specific imaging by a non-ionizing modality and a consultant for follow-up support. Continued CT scans of the liver should not be performed and blood tests alone are inadequate.

There is currently discussion on whether clear evidence exists to demonstrate if surveillance after treatment for uveal melanoma metastases is useful. However, it seems reasonable to perform cross-sectional imaging soon after a surgical or non-surgical liver procedure (4-6 weeks) to assess treatment response. Moreover it is recommended by the UK national guidelines (NICE accredited) that the same imaging modality is used for assessment and follow up; contrast-enhanced MRI with DWI is currently thought to be the optimal choice.

About this information

This information was compiled from several sources and applies to uveal melanoma or metastatic uveal melanoma. It does not apply to conjunctival eye melanoma or skin melanoma.