Benign and Malignant Iris Tumors

What is Benign and Malignant Iris Tumors?

Tumors that form in the iris of the eye are not as common as similar tumors that grow in the ciliary body of the eye. These tumors can be either benign (non-cancerous) or malignant (cancerous). Benign iris tumors are less likely to spread to other parts of the body, so they tend to have a better outcome than malignant ones. However, even non-cancerous tumors can harm vision.

Benign iris tumors can take one of two shapes: they’re either cystic (filled with fluid) or solid. Cystic tumors generally stay the same size and act in ways that doctors can predict. Solid tumors, on the other hand, can be a variety of different types, both melanocytic (related to the pigment cells in our skin and eyes) and nonmelanocytic. Melanoma, a type of cancer that starts in these pigment cells, is the most common malignant iris tumor and has a high risk of spreading to other parts of the body.

This review looks at a number of iris tumors, considering their cause, how they appear to the naked eye, how they’re evaluated, what they look like under a microscope, how they’re treated, and what chance there is of recovery. Each type of tumor – whether it’s melanomas, adenocarcinomas, tumors that have spread from another part of the body, or benign growths – is dealt with individually for the best results.

The types of iris tumors that this article talks about are:
Malignant tumors (cancerous):

• Tumors that have spread to the iris from another part of the body
• Iris melanoma
• Adenocarcinoma of the iris pigment epithelium (a type of cancer that begins in the pigment-producing cells in the iris)

Benign tumors (non-cancerous):

• Iris cysts
• Iris nevus (a mole or birthmark in the eye)
• Adenoma of the iris pigment epithelium (a non-cancerous tumor that starts in the pigment cells in the iris)
• Iris leiomyoma (a tumor that begins in the smooth muscle cells in the iris)
• Iridic nodules (small lumps in the iris)
• Vascular tumors of the iris (tumors that start in the blood vessels of the iris)

What Causes Benign and Malignant Iris Tumors?

Cancerous Lesions

Some cancers from the breast or lung can spread to the iris, the colored part of the eye. These account for 37% and 27% of iris cancer cases, respectively. Other common places for these cancers to come from include the kidney (8%), the gastrointestinal tract (8%), and the prostate (2%).

Iris melanoma, a type of cancer that starts in the iris, usually forms from what we call spindle cells. There’s a gene known as BAP1 that can prevent tumors, but if it’s not working well, it can lead to iris melanoma. Most iris melanomas (over 75%) start in the bottom half of the iris. While we’re still not certain if UV light leads to iris melanoma, studies show that people with lighter-colored irises, exposure to UV light, and uveal melanoma might be at higher risk. This type of cancer is 30% more common in men and is most frequently seen in non-Hispanic White people in the US. In Europe, it happens more often in northern locations.

Iris epithelium adenoma and adenocarcinoma, two types of cancer in the iris, come from a different origin than melanomatous proliferations, another type of cancer.

Non-Cancerous Lesions

Iris cysts, which are small, sac-like structures that can form in the iris, can be primary (they form on their own) or secondary (they form due to other factors like injury, infection, parasitic infection, or medical procedures). Distinguishing cysts from other changes in the iris can be difficult because there are many potential causes.

Iris nevus, a melanocytic-origin lesion that develops in the iris, can transform into malignant melanoma, a type of cancer. In fact, studies have shown that about 8% of iris nevi turn into melanoma within 15 years.

Iris leiomyoma, a very rare type of neoplasm in the eye, was often misdiagnosed in the past. However, with improved diagnostic abilities, many of these cases are now correctly identified as either spindle cell nevi or low-grade melanomas.

There are certain nodules that can appear on the iris. These include Brushfield and Wolffilin spots, once thought to be markers for Down syndrome. Today, their precise role is unclear. Lisch nodules, which often appear on the iris in patients above 6 years old who have neurofibromatosis type 1, a genetic disorder, are considered a key indicator of this condition.

Inflammatory iris nodules can indicate systemic conditions like Vogt-Koyanagi-Harada syndrome, sarcoidosis, multiple sclerosis, or Fuchs heterochromic iridocyclitis. Certain types of bacteria may also be associated with the formation of these nodules. Nodules can also appear due to certain medications or conditions like juvenile xanthogranuloma.

Vascular tumors, tumors in the blood or lymph vessels, may infrequently appear in the iris and are usually related to systemic diseases such as hereditary hemorrhagic telangiectasia. In rare instances, they can be isolated blood vessel malformations in the iris.

Risk Factors and Frequency for Benign and Malignant Iris Tumors

Malignant lesions are harmful growths that can occur in the eyes. There are several types of these harmful growths:

• Metastases to the Iris, which are usually the most common eye malignancy but make up only 2% of all iris tumors and 8% of all metastases to the eye.
• Iris melanoma, which forms 3% to 10% of uveal melanomas making the iris the least common area for this kind of melanoma to occur. But, melanoma is the most common type of iris growth, making up about 68% of all iris tumors. They don’t prefer any particular eye side or gender, especially in people under 65; however, it is more common in men over 65.
• Iris pigment epithelium adenocarcinoma, an extremely rare growth of the pigment epithelium, with about one case reported each year in the United States.

Benign or non-harmful lesions can also occur in the eyes:

• Iris cysts, though they are rare among all eye tumors. However, they are relatively common among iris lesions, making up 21% of all recorded iris tumors.
• Iris nevus, these flat, pigmented lesions are rarely seen in children but appear in almost 50% of adults. They can be singular or multifold.
• Iris pigment epithelium adenoma, accounts for less than 1% of iris tumors. It’s rare and that makes it hard to link it to age and gender; though the suggested median age for diagnosis is 60 years.
• Iris leiomyoma, are extremely rare and usually more commonly seen in younger individuals and females.
• Iridic nodules, between 10%-63% of the population have them, the percentage depends on the type of examination method used. Lisch nodules are usually bilateral and multifocal, but other types of nodules are very rare and lack substantial data.
• Vascular tumors of the iris, with the most common being racemose hemangiomas making up 65% of iris vascular tumors. The rest is made up of cavernous hemangiomas, varix, microhemangiomatosis, arteriovenous malformation, and pediatric capillary hemangiomas. These tumors are more common in middle-aged and older adults and usually show no gender preference.

Signs and Symptoms of Benign and Malignant Iris Tumors

People with iris tumors often notice a change in color or a spot on the part of their eye known as the iris. It’s not common, but some people might have blurry vision or pain. It’s important to share your full medical history with your healthcare provider, including any recent travels, accidents, or foreign objects that have entered the eye.

Here are some common types of iris tumors:

Malignant Lesions

• Metastases to the iris: These are spots on the iris that have spread from a tumor somewhere else in the body. They usually look colorless and can lead to problems like increased pressure inside the eye.
• Iris melanoma: The most noticeable sign is a large, dark, or colorless spot. There are two types – circumscribed (90% of cases) and diffuse (10%). Circumscribed melanomas are flat or rounded and yellow or brown, while diffuse melanomas increase eye pressure and lack focal thickening and color changes.
• Iris pigment epithelium adenocarcinoma: These tumors cause very dark, possibly lumpy masses. Most people don’t experience symptoms; however, loss of vision might occur.

Benign Lesions

• Iris cysts: These are dark structures that transmit light and usually appear on one side. They can detach and become free-floating in the eye but this is rare.
• Iris nevus: These are typically smaller than melanomas with a diameter of less than 3mm and 1mm thick. They usually present as flat, pigmented spots and are often accompanied by changes in the stroma, uvea and pupil.
• Iris pigment epithelium adenoma: These usually appear as a dark grey lesions at the periphery of the iris and they could have multiple nodules. These can lead to forward displacement, thinning, and erosion of the iris stroma.
• Iris leiomyoma: These are typically solitary, slow-growing, well-defined, nodular lesions that may be nonpigmented or lightly pigmented.
• Iridic nodules: These nodules are often lighter in color than others and are usually accompanied by cells in the anterior chamber or vitreous; a washout of the protein in the eye or a fibrin clot formation is common. They are associated with various systemic diseases and skin lesions.
• Vascular tumors of the iris: These often present with spontaneous bleeding into the anterior chamber of the eye and subsequent blurred vision. Similar vascular anomalies on other parts of the body may suggest a systemic disorder.

Testing for Benign and Malignant Iris Tumors

For patients with iris tumors, a detailed eye examination is essential. This can include the use of a specialized microscope called a slit lamp and measurement of the pressure within the eye, as some iris tumors can increase the risk of glaucoma, an eye disease leading to vision loss. Another diagnostic test, gonioscopy, may be conducted too. Special techniques like transillumination help in identifying the type of the eye lesion. Other diagnostic tools that provide detailed images of the eye include B-scan and ultrasound biomicroscopy.

Malignant Lesions

If the cancer has spread to the iris and doctors don’t know the primary location of the cancer, they can take a small sample of cells from the edge of the eye’s colored part (the limbus) to examine under a microscope. An imaging test called a B-scan can reveal a dense mass typical of these cancers.

If the patient has iris melanoma, which is a type of cancer, techniques involving light can be used to see if the shadow of the cancer extends into certain areas of the eye. Frequent photographs of the eye may be taken to monitor how the cancer changes over time. If the melanoma is small, it might be seen clearly with a special imaging technique. Bigger melanomas often need additional imaging tests like B-scan or ultrasound. Another diagnostic test, which involves injecting dye into blood vessels, can be especially useful for examining these cancers.

Both iris pigment epithelium adenoma and adenocarcinoma can be observed through a detailed eye examination. However, due to limited information on these tumors, ultrasound and biopsy should be performed for a more certain diagnosis.

Benign Lesions

For non-cancerous eye conditions like iris cysts, B-scan and ultrasound can be beneficial to understand the lesion better. Sometimes, a thin needle may be needed to confirm the diagnosis.

Iris nevus, another benign condition, can be examined using various imaging tests. Some tests provide less helpful information because light penetrates poorly through highly pigmented lesions. Needle biopsy can be used to understand the exact nature of these growths.

For iris leiomyoma, which are smooth muscle tumors, diagnosis involves advanced techniques like immunohistochemistry and electron microscopy. The tests help confirm diagnosis as these tumors often look like other ones. If there’s potential involvement of the eye’s drainage angle, it needs to be evaluated as it may lead to secondary glaucoma, a serious eye condition.

Nodules in the iris may require further evaluation if their cause isn’t clear after a thorough history taking and physical examination. Doctors might need to take a sample of fluid from the front part of the eye and send it for further analysis.

Vascular tumors of the iris, which involve blood vessels, can be evaluated using a special test known as angiography. It examines blood vessels in the iris. If doctors still can’t confirm the diagnosis, a biopsy may be performed.

Treatment Options for Benign and Malignant Iris Tumors

When cancer spreads to the iris in the eye, it’s often part of a broader disease that’s already being treated with either hormone therapy or chemotherapy. This isn’t typically life-threatening, nor the first sign of cancer. The main aim of treating these eye lesions is to protect the patient’s vision as far as possible. Treatments can often involve discussions with cancer specialists or eye cancer specialists for possible changes to medication or local radiation therapy.

When it comes to a form of cancer called iris melanoma, the choice of treatment depends heavily on the specifics like size and behavior of the lesion. Very small and clearly defined lesions can just be monitored over time through imaging and regular eye pressure tests. But more extensive or non-removable tumors may require proton beam therapy or plaque radiotherapy, treatments that could lead to loss of vision. For smaller, yet symptomatic, melanomas surgical removal could be an option. Removal of sections of the eye might be necessary if the cancer has affected certain parts of the eye. In worst-case scenarios, removal of the entire eye may be needed if tumors are large, keep coming back, or severely impact vision.

Treatment for another type of cancer, called Iris pigment epithelium adenocarcinoma, could involve chemotherapy, radiation, surgical removal, or even removal of the eye, based on tumor size and the amount it’s spread.

On the brighter side, benign or non-cancerous tumors called iris cysts are usually just closely watched if they don’t affect vision and don’t cause any symptoms. But if they start increasing in size or causing symptoms, non-invasive treatments such as laser therapy or aspiration are recommended. If these don’t work, then surgical removal could be the last resort.

Similarly, benign moles on the iris, known as iris nevi, need only careful monitoring. Depending on the size and suspicious features, they can be checked by an eye doctor and imaged at regular intervals.

Another benign tumor called Iris pigment epithelium adenoma may only require regular check-ups if it’s small and doesn’t cause symptoms. However, larger or symptom causing ones might require surgical removal.

Iris leiomyomas are also often slow-growing, and so, regular monitoring may suffice for small, symptomless lesions. More troublesome ones might require radiation therapy or surgery, while those actively growing or spreading might even need eye removal.

Treating a bump or nodule on the iris depends heavily on the cause behind it. Infections are typically dealt with organism-specific systemic antibiotics. An intraocular injection may be suggested if systemic treatments don’t work. Other nodules may respond to medicines that control systemic disease. Sometimes the offending medication needs to be stopped in case of drug-induced nodules. Further, routine monitoring is essential for patients because of the increased risk of cancer.

Vascular iris tumors are most often symptomless and just need to be watched. Regular imaging can help assess any changes or growth.

What else can Benign and Malignant Iris Tumors be?

When assessing a lesion on the colored part of your eye (the iris), doctors consider all possible tumors that can develop in this area. There are also other conditions that may resemble tumors:

• Inflammatory granuloma (an area of inflamed tissue)
• Epithelial ingrowth (skin cell growth)
• Congenital iris heterochromia (different eye colors present from birth)
• Fuchs heterochromic iridocyclitis (a rare eye condition causing vision issues and color variation)
• Iris nevus syndrome (a rare condition where moles grow on the iris)
• Pigment dispersion (spreading of the pigment from the iris into other eye areas)
• Hemosiderosis (accumulation of an iron-rich pigment that can damage organs)
• Pigmentary glaucoma (a type of glaucoma caused by pigment dispersion)
• Ocular siderosis (a condition in which iron particles are deposited in eye tissues)

What to expect with Benign and Malignant Iris Tumors

Cancerous Lesions

Cancer Spread to the Iris

In general, cancers that spread to the eye have a very grim outlook if left untreated. However, your overall odds and risk of death really depend on where the cancer started. Cases where the cancer spreads to the uvea (parts of the eye including the iris), the general survival rate is around 32% after 3 years, and 24% at 5 years. Some types of cancers, such as carcinoid tumors, have a better outlook when they spread to the iris – almost 92% of these patients may still be alive after 5 years. This is not the case for kidney and pancreatic cancers, which unfortunately have a 0% survival rate after 5 years.

Iris Melanoma

A study by Sabazade et al. found that 5-year death rates for iris melanoma (a form of skin cancer in the eye) were about 5%, increasing to 8% from 10 to 20 years after diagnosis. The specific type of iris melanoma and how big the tumor is can affect your prognosis. Spindle cell melanomas offer slightly better chances than more aggressive types of melanoma. Local spread of the cancer to the choroid (part of the eye’s wall) or the ciliary body (a part of the eye that produces aqueous humor) is usually indicative of a worse outcome. Widespread melanomas are more likely to spread to other parts and predict a worse outcome.

Iris Pigment Epithelium Adenocarcinoma

There have been no reports of iris pigment epithelium adenocarcinoma (a type of cancer originating from cells in the iris) spreading elsewhere in the body, but this could also be due to lack of studies. Early detection usually leads to better outcomes. This type of cancer can result from a malignant change in an iris pigment epithelium adenoma. Larger, invasive, and symptomatic tumors generally indicate a worse prognosis.

Non-Cancerous Lesions

Iris cysts

The outcome mainly depends on how invasive the cyst is. Iris cysts arising from the stroma (the supporting framework of an organ) generally have worse outcomes than those arising from pigment cells. Cysts resulting from a disease process usually have a worse outcome than primary cysts, especially if the cyst fills more than half of the front chamber of the eye.

Iris Nevus

Iris nevi or moles in the eye usually have good outcomes. Most of the times, these nevi remain stable and don’t turn into cancer.

Iris Pigment Epithelium Adenoma

These tumors generally have favorable outcomes, as long as they don’t transform into cancer. They need to be regularly monitored for recurrence or transformation.

Iris Leiomyoma

Iris leiomyomas (a type of benign smooth muscle tumor in the eye) generally have an excellent prognosis. However, consistent follow-ups are necessary to monitor for any complications or recurrence, which is rare.

Iridic Nodules

Early diagnosis and treatment of underlying diseases related to iridic nodules (small bumps on the iris), can greatly influence the outcome. Often, these nodules suggest a later stage of disease, making quick diagnosis and specific treatments vital.

Vascular Tumors of the Iris

Vascular tumors of the iris (tumors affecting the blood vessels of the iris) generally have pretty good outcomes. However, if the tumor is related to a systemic (bodywide) disease, the outlook might not be as good.

Possible Complications When Diagnosed with Benign and Malignant Iris Tumors

There are several types of malignant and benign eye diseases that can cause complications.

Malignant Lesions:

• Metastases to the iris: These can lead to a condition known as secondary open-angle glaucoma. This can cause high pressure in the eye, which should be managed, but doctors generally do not recommend surgeries to filter the fluid in the eye.
• Iris melanoma: Secondary glaucoma is a common complication of this disease. Doctors recommend avoiding the usual filtering surgery due to the risk of spreading the tumor.
• Iris pigment epithelium adenoma and adenocarcinoma: These tumors can sometimes cause the front part of the iris to move forward, thin out, and erode.

Benign Lesions:

• Iris cysts: These cysts can sometimes become dislodged and float in the front of the eye or in the jelly-like substance within the eye, although this is uncommon.
• Iris nevus: Most of the issues with iris nevi come from the lesion becoming malignant, or worsening vision. If these complications occur, doctors may need to intervene.
• Iris leiomyoma: These are typically not bothersome and do not need immediate intervention. However, if they start growing rapidly and begin to invade surrounding structures, doctors may need to remove the eye.
• Iridic nodules: According to one study, 34% of patients who underwent a certain type of biopsy experienced some bleeding in the eye. Although this is typically managed well, it is a possible complication of diagnostic procedures.
• Vascular tumors of the iris: The most common issue with this type of tumor is spontaneous bleeding in the front of the eye. This can generally be treated with topical medications. However, these tumors can complicate other eye surgeries, such as phacoemulsification. A 2022 study reported a case where the patient experienced mild bleeding during surgery, which was easily controlled by increasing pressure in the eye.

Preventing Benign and Malignant Iris Tumors

People with iris tumors need to understand the risks associated with their specific type of tumor, particularly the potential for it to become malignant or cancerous. They should closely follow their doctor’s check-up routine. As many iris tumors are associated with a high chance of glaucoma, which is a vision condition, it’s crucial for patients to promptly seek medical advice if they notice changes in their vision, experience sudden eye pain, or observe any changes in the appearance of their tumor.