Lacrimal Gland Malignancies

What is Lacrimal Gland Malignancies?

Tumors located in the lacrimal gland fossa, which is the small depression in the bone that holds the lacrimal gland, make up about 10% of all tumor samples taken from the orbit (the bony socket that contains the eye). There are many reasons why these tumors can form, including infections, inflammation, or cancerous growth. Some of these tumors are benign, or non-cancerous, while others can be malignant, or cancerous. This article will primarily discuss the cancerous tumors in the lacrimal gland, which we’ll refer to as lacrimal gland carcinomas.

The lacrimal gland fossa is located in the front upper outer corner of the eye socket. Tumors in this region usually push the eyeball down and slightly inward. However, if the tumor grows towards the back of the eye socket, it can also push the eye forward, a condition known as proptosis.

Cancerous tumors generally grow faster than non-cancerous ones. On average, it takes less than six months from the time symptoms first appear to when a cancerous tumor is diagnosed. In contrast, it might take 1 to 2 years to diagnose a benign tumor.

It’s vital to identify malignant lacrimal gland tumors quickly and early because they often have a poor outlook. Early detection is key to reducing harm and improving a patient’s chances of survival.

What Causes Lacrimal Gland Malignancies?

Tumors of the tear gland, or lacrimal gland, closely resemble tumors of the saliva gland, owing to their shared developmental origins. Tumors can be classified depending on the type of cell they originate from, typically being either epithelial (skin or tissue) or non-epithelial.

Almost half of the epithelial tumors in the tear gland are malicious or cancerous. However, this can change depending on the factors like from where the patients are referred, their geographical location, and the demographic makeup of the patient.

The most common type of malicious epithelial tumor is known as Adenoid cystic carcinoma (ACC), accounting for 66% of these cases. This typically causes symptoms like the movement of the eyeball, protruding eyes and drooping eyelids. Pain and numbness in the forehead or temple area are more specific symptoms because ACC is known for affecting the nerves around the eye.

The second most common type of malicious epithelial tumor, Carcinoma ex pleomorphic adenoma (CEPA), can develop from a benign tumor called a pleomorphic adenoma which were previously biopsied or removed. This change can take place even years after the original tumor has been treated. Its malicious form can take any form of an epithelial cell but is most commonly adenocarcinoma not-otherwise-specified or mucoepidermoid carcinoma.

Other common types include Mucoepidermoid carcinoma, a common salivary gland tumor but uncommon in the tear gland, and Adenocarcinoma NOS, a primary adenocarcinoma of the tear gland without the features of other listed types. Other epithelial tumors include ductal carcinoma, acinic cell carcinoma, myoepithelial carcinoma, and more.

The lymph nodes near the tear gland are most commonly affected by Non-Hodgkin’s B cell lymphomas. The most typical subtype of these lymphomas is extranodal marginal zone lymphoma (EMZL, MALT lymphoma), contributing to 40% of the tear gland lymphomas. This may be related to conditions that cause inflammation like reactive (benign) lymphoid hyperplasia, Sjogren syndrome, and gastric H. pylori infection.

Tumors known as malignant mesenchymal grow from the layer of cells that forms bones and muscles and are very rare in the tear gland, while the presence of blood vessels is more common. Lastly, the spread of cancer to the tear gland from other parts of the body is extremely rare since there are no lymph nodes in the tear gland. The few cases that have been reported suggest the breast as the most common primary location.

Risk Factors and Frequency for Lacrimal Gland Malignancies

Lacrimal gland carcinomas, or cancers, don’t usually favor one gender over the other, but there are some exceptions. For instance, adenocarcinoma NOS and ductal carcinoma are slightly more common in males, while MEC and lymphoma are slightly more common in females.

• These cancerous lesions can appear at any age, although they are most commonly found in older adults, typically those in their 60s or later.
• An exception is adenoid cystic carcinoma, which is usually diagnosed at around the age of 40.
• There’s no link between these tumors and race or geographical location. However, this could be because these types of cancers are quite rare in general.

Signs and Symptoms of Lacrimal Gland Malignancies

When diagnosing eye conditions, doctors collect basic details such as age, gender, ethnicity, and race. They also need to know if a patient has had any illnesses, autoimmune diseases, cancers, treatments lowering their immunity, or prior surgeries or injuries. This can help identify potential causes of the issue.

Doctors will ask about eye symptoms like blurry or double vision, changes in how the eye or face looks, pain, discomfort in bright light, pain when moving the eye, swollen or red eyelids, discharge, tenderness, tearing, or dryness. Sometimes, old photos are used to notice subtle changes in the eye or eyelid.

Then the eye is examined thoroughly by an eye professional. This exam checks:

• Visual acuity: how clear the vision is
• Pupillary light reflex: how well the pupil responds to light
• Signs of optic neuropathy: more complex tests for nerve damage
• Ocular motility: how well the eye can move
• Globe malposition: whether the eyeball is displaced
• Exophthalmometry: whether the eye is bulging out

A doctor may also touch the area around the eye and the lacrimal gland (which produces tears) to check for masses, and test how well you feel touch on the face to evaluate for nerve damage. They will look at signs of inflammation in the eyelid, the outer eye, and the inside of the eye. This can give hints about what might be causing the problem.

Testing for Lacrimal Gland Malignancies

Examining an individual solely based on physical signs and symptoms may not always be enough to tell whether a tumor is benign (non-cancerous) or malignant (cancerous). Sometimes, signs like a fast-growing tumor hint towards a more serious or malignant condition. For example, if a tumor was growing slowly at first but then started growing rapidly, this could mean that a benign tumor known as a pleomorphic adenoma has turned into a cancerous tumor. Also, the tumor’s presentation, such as whether it causes pain or not, can hint at what type of tumor it might be, given that the most commonly found malignant tumor, adenoid cystic carcinoma, can invade the nerves causing pain.

To confirm and better understand a possible tumor near the eye (an orbital lesion), imaging tests are often recommended. These can help determine several properties of the tumor – whether it is solid or filled with fluid (cystic), has clearly marked borders or not (well-defined vs. infiltrative), contains or lacks calcified areas, has areas of fat or fluid, causes changes in the bone surrounding it (modelling or destruction), and lights up under contrast dye (contrast enhancement). A sign where the tumor extends towards the back of the eye socket (a ‘wedge sign’) hints at the severity of the disease and indicates the need for a biopsy (a test where a sample of the tumor is removed for examination).

A type of scan called a computed tomography (CT) scan is a quick, easily available, and relatively affordable method that is especially good at examining the structure of the tear gland area. It is usually the first go-to technique for diagnosing tear gland tumors, particularly if a benign tumor is suspected. It allows doctors to identify the presence and size of a mass and see its effects on the surrounding structures like the bones, muscles around the eye, and the eyeball itself. Administering contrast dye can be helpful to check for tumors that may light up under the dye. CT scans are also great at showing calcifications, which can help differentiate between various types of tumors.

Another type of scan, the magnetic resonance imaging (MRI), although more expensive, harder to get, and takes longer, provides a more detailed view of the soft tissues in the body. This makes it particularly useful for getting a detailed picture of the tumor. MRI might even distinguish benign from malignant tumors. While it doesn’t visualize bones well, it is better at assessing tumor involvement of the nerves around the eye, which is especially important for certain types of tumors like adenoid cystic carcinoma. Due to these reasons, MRI might be a better choice when a malignant tumor is suspected. In many cases, both CT and MRI scans may be required to make management decisions.

Treatment Options for Lacrimal Gland Malignancies

Treating cancerous tumors in the lacrimal gland (which helps produce tears) can be tricky due to them being rare and usually having a poor prognosis. The main goals of treatment are to control the local tumor and prevent it from recurring locally or spreading to other parts of the body.

If your doctor suspects cancer, the first step is usually to get a formal diagnosis by taking a tissue sample of the tumor, a process called a biopsy. Once the diagnosis is confirmed, the treatment can vary depending on how advanced and aggressive the tumor is. Traditionally, most carcinomas of the lacrimal gland would be treated by removing all or part of the orbit (the bony socket that contains the eye), sometimes followed by high dose radiation treatment after the surgery.

For a specific type of lacrimal gland cancer known as adenoid cystic carcinoma, treatment options have been developing, but there’s not a universally agreed approach. Treatments can involve a combination of removing the tumor, radiation therapy, and removing the orbit. There’s a growing trend towards eye-preserving surgery to avoid the negative impacts of removing the orbit, like cosmetic and psychological issues, and studies have shown similar survival rates with this approach.

Recently, intra-arterial cytoreductive chemotherapy (IACC), a treatment where chemotherapy drugs are delivered directly to the arteries feeding the tumor, has been used successfully before surgery and radiation therapy. This can also be combined with eye-preserving surgery and follow-up radiation therapy. However, in some advanced cases, more extensive surgery may still be necessary even though it doesn’t stop the spread of cancer or improve survival rates.

The treatment for carcinoma ex pleomorphic adenoma, another type of lacrimal gland cancer, depends on how advanced the cancer is when it’s diagnosed. For a single, well-defined lump, removing it with surgery may be enough. For less defined tumors that have spread to surrounding tissues, the treatment is usually similar to what’s used for adenoid cystic carcinoma: removal of the tumor, possible removal of the orbit, and follow-up radiation therapy.

Adenocarcinoma NOS and other malignant lacrimal gland tumors are usually treated in the same way as adenoid cystic carcinoma, with the addition of radiation therapy. If only a microscopic tumor is detected after examining the tissue under a microscope, then radiation therapy alone may be a treatment option for any lacrimal gland cancer.

For lymphoma, a type of cancer that involves the immune system, that affects the orbit, treatment depends on whether the cancer has spread to other parts of the body. To make a diagnosis, your doctor will take a biopsy to identify the type of lymphoma and its genetic characteristics. They will then carry out tests to find out if it has spread elsewhere in the body, which may include imaging scans and a bone marrow biopsy. Unlike other types of lacrimal gland cancers, the main treatment for lymphoma is not surgery. If the lymphoma is confined to the orbit, radiation therapy is usually the first treatment. Chemotherapy is used if the cancer has spread to other parts of the body, and radiation therapy may also be used in some cases.

What else can Lacrimal Gland Malignancies be?

Apart from the cancerous growths, the lacrimal gland fossa (a part of the eye) can be affected by other types of problems too. These can be divided into two major categories: inflammation-based issues and non-cancerous growths. The most common problem leading to the enlargement of the lacrimal gland is due to inflammation. The key cause among these is dacryoadenitis, which can occur in one or both eyes and can be due to inflammation or an infection.

Specific inflammations are:

• Orbital pseudotumor (Idiopathic orbital inflammatory syndrome)
• IgG-4 related disease
• Sarcoidosis
• Granulomatosis with polyangiitis
• Dacryoadenitis
• Sjogren syndrome
• Thyroid eye disease

Next, let’s look at benign (non-cancerous) growths:

• Epithelial, which can include:
  • Pleomorphic adenoma
  • Dacryops (lacrimal gland cyst)
  • Oncocytoma
  • Myoepithelioma
  • Cystadenoma
  • Warthin tumor
• Lymphoproliferative, such as:
  • Reactive lymphoid hyperplasia (benign lymphoepithelial lesion)
• Mesenchymal growths, for example:
  • Capillary or cavernous hemangioma
  • Angiolymphoid hyperplasia with eosinophilia
  • Granular cell tumor
  • Fibrous histiocytoma
  • A solitary fibrous tumor (hemangiopericytoma)
  • Neurofibroma
  • Schwannoma

There may also be some lesions near the superolateral orbit (at the corner of the eye) that could be mistaken for lacrimal gland tumors. They might include:

• Epidermoid or dermoid cyst, often found at the frontozygomatic suture with a possible intraorbital component
• Prolapsed orbital fat, causing fullness of the lateral upper lid or a mass in the superotemporal fornix
• Dermatolipoma, typically seen under the superotemporal conjunctiva
• Prolapsed lacrimal gland, which gives the appearance that it has been displaced by a mass

Another condition that can lead to lacrimal gland enlargement is amyloidosis, a rare disorder where a substance called amyloid builds up in the orbicular part of the eye, including the lacrimal gland. It is usually a localized issue rather than being tied to systemic amyloidosis.

What to expect with Lacrimal Gland Malignancies

Adenoid cystic carcinoma is the most common unfortunate type of cancer in the lacrimal gland (a gland near the eye that produces tears), which doesn’t have a good prognosis. In other words, it has been named the “slow killer” as it can come back or spread to other parts of the body years after treatment, often causing death within ten years of diagnosis. Several factors affect how the disease progresses, including the size of the tumor, its histologic subtype (the way the cancer cells look under a microscope), whether the cancer has invaded the nerves around it, and the stage of cancer at diagnosis.

The size of the tumor is an important factor: smaller tumors (less than 2.5 cm in diameter) tend to have a better prognosis. The type or subtype of the adenoid cystic carcinoma also matters, as cancer resembles Swiss cheese (cribriform pattern) possibly indicates a better prognosis, while the solid or ‘basaloid’ pattern may indicate a worse prognosis. The stage of the tumor, determined by the AJCC TNM system, can also predict patient outcomes, with worse outcomes for more advanced stages where cancer has spread more broadly.

When it comes to carcinoma ex pleomorphic adenoma, the behavior and identity of the part of the tumor that has spread beyond its original location are crucial factors. If the tumor is non-invasive or only minimally invasive, the prognosis is typically excellent. However, if it’s more aggressive, most patients unfortunately die within a few years due to the cancer spreading to the brain, lungs, chest, or bones.

Mucoepidermoid carcinoma has three types: low, intermediate, and high-grade tumors. The lower grades usually have a good prognosis – they are expected to do well, but the highest grade has a poor survival rate.

Ductal carcinoma is a harsh type of cancer which usually presents as an advanced local disease which is hard to treat. This has a high mortality rate of over 40%, and in more than half the cases, the cancer spreads to other parts of the body.

The prognosis for lymphoma (cancer that starts in cells that are part of the body’s immune system) largely depends on how much the cancer has spread in the body. For a type of lymphoma localized just to the orbit (eye area), called extranodal marginal zone lymphoma, the prognosis is usually very good, as it typically responds well to radiation therapy. However, another type called Diffuse large B-cell lymphoma has three subtypes, one of which (the ABC subtype) has the poorest prognosis.

Possible Complications When Diagnosed with Lacrimal Gland Malignancies

The problems associated with malignant tumors primarily stem from the treatments used to eliminate the tumor and prevent it from returning. If the tumors have a large size, they could apply pressure on the orbital structures in the eye such as the globe or optic nerve. Some malignant lesions can break through the orbital roof and reach the cranial vault, or in the case of adenoid cystic carcinoma, they can spread to reach the Central Nervous System (CNS) through perineural routes, potentially leading to serious neurological changes.

Getting a surgical biopsy or removing the tumor can have risks, and the complications are often tied to the surgery and the methods used. For surgeries involving the front or side of the orbit, common complications include bleeding in the orbit, postoperative infection in the orbit, damage to the external eye muscles, globe, or optic nerve, dryness due to decreased tear gland function, leakage of cerebral spinal fluid (CSF), or the tumor returning.

Radiation therapy also carries certain risks, including damage to the tissue surrounding the treatment area, skin inflammation, bone and soft tissue wasting, and effects on the eye such as retinopathy and dry eye disease. Chemotherapy can also lead to various side effects, with the most concerning being a weakened immune system and increased risk of infection. It’s essential to keep a close watch on the patient both short-term and long-term after the treatment to manage any complications and monitor for any return of the tumor.

Likely complications:

• Pressure on the orbital structures in the eye
• Potential access to the cranial vault or Central Nervous System (CNS)
• Possible neurological changes
• Orbital bleeding after surgery
• Postoperative infection in the orbit
• Possibility of damage to the external eye muscles, globe, or optic nerve
• Dryness from less function of tear glands
• Cerebral spinal fluid (CSF) leakage
• Return of the tumor
• Damage to surrounding tissue from radiation therapy
• Skin inflammation from radiation therapy
• Bone and soft tissue wasting
• Retinopathy and dry eye disease
• Weakened immune system from chemotherapy
• Increased risk of infection from chemotherapy

Preventing Lacrimal Gland Malignancies

Dealing with cancerous tumors in areas like the eye’s orbit can be quite complex. It’s critical to have a detailed conversation so that the patient fully understands the possible causes, treatments, side effects, and future outlook related to the disease and different treatment options. When discussing a potential cancer diagnosis, it’s really important to be compassionate and empathetic towards the patient and their situation. Sometimes, multiple conversations may be needed to ensure the patient can properly understand and make an informed decision about their treatment.

Every aspect of treatment, including potential risks, benefits, and other options, as well as the option not to treat, should be explained in depth. The emotional and mental impacts of the diagnoses and various treatments (like surgery, chemotherapy, radiation, and long-term monitoring for disease recurrence) can be quite significant, especially if complications occur. These concerns may need attention from several professionals such as a primary care doctor, oncologist, psychologist, or psychiatrist.