Q&A: Identifying, treating rare mucosal melanoma

Mucosal melanoma — or melanoma in the mucous membranes — differs from cutaneous melanoma in its genesis, its treatment and its severity.

Sometimes called a “hidden cancer,” mucosal melanoma is often more deadly than cutaneous melanoma. It is difficult to diagnose and often not found until the later stages, making treatment and survival more difficult.

Healio spoke to Brian Gastman, MD, surgical director of the melanoma and high risk skin cancer program at the Cleveland Clinic, regarding mucosal melanoma and how physicians can be better equipped to diagnose and treat this rare form of cancer.

Healio: What is mucosal melanoma and why can it be difficult to diagnose?

Gastman: Mucosal melanoma under a microscope looks just like a skin melanoma. The difference is the location and some of the genetics. From a location standpoint, we tend to hear about it in the rectal and vaginal/vulva areas, and then in the sinonasal and oral cavities. There is also conjunctival melanoma, which in a way is also mucosal because the conjunctiva around your eye is mucosa, but because it's so related to the sun it genetically starts to act a little bit more like skin melanoma. Because of these locations, they're harder to find and they present later.

Basically, the main area is the eyelid, but also the nasal and oral locations are the classic head and neck ones. Then you go down to the vagina and rectum, and technically an uncircumcised male who gets melanoma in the foreskin is also considered mucosal melanoma. That has to do with the location and how that skin looks under the microscope.

Patients often have symptoms before they know they have melanoma, such as a bleeding nose, vagina or rectum, or even weight loss. They may even have metastatic disease when it's discovered.

Healio: What are the normal treatment options for mucosal melanoma?

Gastman: Well, like all melanoma, they are usually surgical if possible. I always tell my patients surgery is the most likely way of curing any melanoma. Unfortunately, sometimes these patients present either in an inoperable fashion because there's already metastasis in other locations or, many times, you just can't get a true negative margin, such as in the sinuses. For those patients, especially in the sinonasal area, there has been a lot of data in using specialty radiation such as proton beam radiation, but the numbers are so small that it's hard to know how effective it is long-term.

Ultimately, we still use similar therapies as we do to cutaneous melanoma, which is really our immunotherapy.

A lot of excitement in melanoma has been around immunotherapy, but the overall data so far in mucosal melanoma is that immunotherapy does work, but not as well as it does in regular melanoma. Regular skin melanoma is caused by the sun’s radiation hitting the skin and causing mutations. So, when the melanoma arises in the skin, they have a lot of mutations. Mucosal does not have the number of mutations that a genus melanoma has because it's not arising from the sun. We think it could be genetically related, but also could be caused by some type of chronic inflammation. Again, they're rare, but as a result, any cancer that's harder for the body to differentiate from the normal cell will make the immune system less likely to be effective.

There are some known mutations in mucosal, but they're not that easy. They haven't been shown to be very great targeting. The one exception would be that mucosal melanoma probably has the most new blood vessels of all the melanomas. We call that neoangiogenesis. And there is a drug called [vascular endothelial growth factor (VEGF)] that blocks that neoangiogenesis and, in combination with immunotherapy, has been found to be effective. The numbers are small, but it was very intriguing, and a lot of physicians have taken notice of that kind of data and have since have been developing new clinical trials to try to see whether VEGF drugs are effective.

Healio: How does early diagnosis affect patient outcomes?

Gastman: Like I said earlier, surgery is the mainstay of therapy and has the most likeliness of curability. The earlier or more localized the disease is, the more likely you can get a good negative margin of normal tissue around it and the more likely it hasn't gone to lymph nodes or beyond. So, I think early diagnosis is the main thing. If you catch it early it puts you at an earlier stage and those stages are based on risk stratification and lower risk of death.

Healio: What should patients be looking for in terms of rare cancers?

Gastman: There are some systemic findings that are common in anybody with cancer, especially with some of the cancers once it gets into your blood system, such as weight loss, skin color changes, or blood coming from orifices such as your oral cavity, your nose, your rectum. Those are things that we are concerned about. Other than that, it could be very innocuous. You could have headaches and vision changes and those are unfortunately common with noncancer diagnoses.

I do think that someone with a history of skin melanoma should be more concerned about melanoma in funny places, such as mucosal melanoma. But it is still a rare entity. Ultimately, the only way to know is if you biopsy it. Sometimes it does have that dark melanin look to it, but even then, we see melanocytic lesions in mucosa that are not even cancer.

Healio: What should clinicians be looking for and how should they be advising their patients regarding mucosal melanoma and other rare cancers?

Gastman: First of all, clinicians need to know that this entity exists. And for someone who is already going to a dermatologist, I think this concept of head to toe and everywhere the sun doesn't shine kind of skin mucosa evaluation is key. That's why someone with a history of melanoma, will usually get an oral cavity exam. But a dermatologist is not going to go all the way up into someone's cervix. So, I think if you're worried that you're bleeding from an orifice, you should definitely see somebody and a PCP should know who would be best. Ultimately your subspecialist sees things that are rare to most doctors but not rare to them.

Healio: What new research is underway regarding mucosal melanoma and its treatment?

Gastman: Well, the big one is the use of these VEGF inhibitors. There are other targeted therapies that are out there that are being studied in mucosal melanoma, too. One of the areas that I know is being looked into is when patients have had surgery and are at high risk of recurrence even though we don't see any cancer right now — trying to find the best therapies at that point to try to prevent these patients from becoming recurrent or even from becoming stage 4 and inoperable.