Salivary Gland Cancer: As Rare As It Is Diverse

It wasn’t the first time Sharon Haber found a lump in her neck. She’d had them twice before – the last one 10 years prior. Both times, they were benign. Still, she knew she had to get it checked out.

Haber’s primary care doctor in Encino, California, agreed that the small lump in her neck, under her left ear, most likely was nothing. But he ordered a CT scan, just in case. When the scan came back, the doctor still believed the lump was benign. Out of an abundance of caution, he sent her to a head and neck specialist for a second look. The specialist biopsied the lump, which he also expected to be benign.

“A couple of days later, when I got the call that I have cancer, that was probably the scariest moment of my life,” Haber says. The 69-year-old retired marriage and family counselor now has been cancer free for more than six years.

Haber had three lesions on her parotid gland — one of the three major salivary glands and the most common one on which tumors can form. The majority of growths that develop on this gland are benign. In fact, salivary gland cancers are extremely rare. In the U.S., they make up less than 1% of all cancers diagnosed each year.

“And that’s cases spread throughout the U.S., so, of course, a lot of people haven’t even heard of it,” says Dr. Maie St. John, chair of head and neck surgery at Ronald Reagan UCLA Medical Center in Los Angeles.

There are dozens of types of salivary gland cancers — nearly as many as there are types of cells that compose the salivary glands. Most of the time, these can be treated with single modality surgery, depending on the anatomic location, and patients can have a very good outcome. Doctors usually recommend radiation after surgery to ensure no cancer cells are left behind and to lower the risk of recurrence. But for some people surgery is not possible or doesn’t completely remove the cancer. In some cases, the cancer returns. Clinical trials underway are exploring the roles that chemotherapy and targeted drugs can play in treating this rare disease.

WHAT IS SALIVARY GLAND CANCER?

Cancerous tumors can arise in the three major salivary glands or any of the thousands of minor glands that line the mouth and extend into the nose and pharynx, the cavity that connects the nose and mouth to the esophagus.

The three pairs of major salivary glands are the parotid, sublingual and submandibular glands. The parotid, the largest of these glands, occupies the side of the face between the ear and the back molars. It extends to the height of the upper and lower jaws. The sublingual gland sits in the floor of the mouth under the tongue. The submandibular is located under the lower jaw.

Doctors grade cancers from low to high based on how abnormal the cells look under a microscope. Low-grade cancer cells look the most like normal cells and tend to be slower growing and less aggressive. These cancers are usually easier to treat and have better long-term survival rates. High-grade cancers, on the other hand, look very different from normal cells and grow and spread faster than lower grade cases.

Salivary gland cancers are as diverse as they are rare.

“There are many differences in salivary gland cancers,” says Dr. Ashok Shaha, the Jatin P. Shah Chair in Head and Neck Surgery and Oncology at Memorial Sloan Kettering Cancer Center in New York. “The greatest variation in human cancers is probably in salivary gland tumors. And the more we look into the basic differentiation of these cells, the more different names for them keep coming up.”

Mucoepidermoid carcinomas are the most common salivary gland cancers. They most often arise in the parotid gland but can appear in the other major glands, as well. These are usually low-grade cancers, but intermediate- and high-grade cases do occur.

Adenoid cystic carcinomas are slow growing, low- grade cancers, but they spread along nerves. “Even if you go in and remove everything you can see and feel, there still could be a few cells that run along the nerve. Those cells spread by using the nerve like a little highway, and this would predispose patients to recurrence,” St. John says. This type of cancer can recur many years after the initial treatment.

Adenocarcinoma is a general term to describe cancers of the gland cells. Salivary adenocarcinoma describes numerous subtypes of both low- and high-grade cancers, some of them quite rare.

WHAT ARE THE SYMPTOMS?

A common symptom of salivary gland cancers, particularly those that arise in the parotid gland, is a lump in the side of the face or neck like Haber had.

“Something I hear from my male patients is ‘I was shaving, and I felt this lump,’” says Dr. Theodoros Teknos, president and scientific director of the UH Seidman Cancer Center and a head and neck oncologist at University Hospitals Cleveland Medical Center.

A painless lump could be an early sign of cancer. As the disease progresses, depending on the location of the tumor, it can cause earaches, trouble swallowing or difficulty opening the mouth.

Numbness and pain can develop in the face, as well. It’s not a sudden paralysis such as Bell’s palsy. The gradual numbness may start with one lip, then include another, and eventually spread to other parts of the mouth or face.

Mark Fetterman, a 59-year-old construction foreman in Olmstead Falls, Ohio, started having pain and numbness on one side of his face in 2016. A neurologist told him he had trigeminal neuropathy. This disorder affects the trigeminal nerve, which controls facial sensation and movement. Imaging tests didn’t find any cause for the condition. The doctor prescribed medications, but over the next two years, the pain and numbness became worse. In 2018, Fetterman found a lump in the roof of his mouth. A biopsy found that it was salivary duct carcinoma, a rare, high-grade adenocarcinoma.

“The [physician] said that the cancer was all along the trigeminal nerve going up to his brain, but not in his brain, and that it might have been this all along,” says Fetterman’s wife, Lori.

SURGERY & RADIATION

For almost everyone with salivary gland cancer, surgery is the first treatment. Depending on the tumor’s location and size, the surgeon may be able to remove the cancer completely. But, because tumors may be near the eyes, in the mouth or nose, near the brain, or in the face on crucial nerves or blood vessels, the surgery comes with risks of adverse effects. It can cause temporary or permanent loss of movement in the face. But surgeons make every effort to avoid this.

“We do parotid surgery with a nerve monitor so you can monitor and preserve the nerve,” St. John says. “We do not sacrifice the facial nerve unless the cancer is just wrapped around it and it has to be taken in order to clear the cancer. Otherwise, we dissect around it.”

Haber’s tumor was on her facial nerve. She knew going into it that surgery came with the risk of partial paralysis. “All I could think about was my grandkids,” she recalls.

“I didn’t want to look scary to them.” But after an 11-hour surgery performed by St. John, Haber says, “she not only got all the cancer, and took out all the lymph nodes around it, but she did not hit that nerve. She saved my face – and my life.”

Doctors often recommend following surgery with radiation therapy to address residual microscopic cancer cells. If a tumor is inoperable, radiation — sometimes in combination with chemotherapy — may be the main treatment.

SYSTEMIC TREATMENTS

Chemotherapy isn’t a first-line treatment for salivary gland cancers. “Salivary gland cancers are considered relatively chemo-resistant tumors,” says Shaha. “If a patient has a poor prognosis or if they have [had a recurrence], then we would add chemotherapy.”

Investigators are exploring through clinical trials whether chemotherapy, which is not typically used for salivary gland treatment, might improve outcomes when added to surgery and radiation.

In general, systemic treatments — medications that travel through the bloodstream as opposed to procedures that target the tumor directly — for salivary gland cancers are considered experimental. Patients with recurring or metastatic cancers may receive these treatments in clinical trials.

“In a salivary gland cancer that’s metastasized, we typically (gene) sequence the tumor, look at the muta- tions, and try to provide targeted therapies for the specific tumor,” Teknos says.

In salivary duct carcinomas, for example, the HER2 gene is often overactive. The gene’s hyperactivity can help the tumor grow and thrive. In HER2-positive tumors, the blockbuster breast cancer drug Herceptin (trastuzumab) blocks that gene’s activity and may slow or stop tumor growth.

Fetterman is still taking Herceptin. He receives an IV transfusion of the drug every three weeks. “On the last CT scan, the cancer was unchanged. It hadn’t grown or shrunk. So I will continue to take it, and they will just keep monitoring it,” he says.

People with this type of cancer also may be candidates for androgen receptor inhibitors, drugs commonly used to treat prostate cancer. Androgen receptors, which by some estimates, are present in up to 98% of salivary duct carcinomas, support the growth of tumors that thrive on androgen hormones. These drugs can block the receptors and deprive the tumor of the hormone. In a clinical trial, this treatment led to higher response rates than chemotherapy in metastatic or recurrent disease.

In other clinical trials, investigators are exploring other genetic targets in salivary gland tumors that might align with existing targeted drugs. In the phase 2 MyPathway trial (NCT02091141), researchers matched patients with targeted drugs based on the tumor’s genetic profile. Because salivary cancers are so rare, the trial included only 19 people. Twelve of them (63%) responded to the personalized treatments they received.

Numerous other trials are in progress. In cases of metastatic or recurring salivary gland cancers, clinical trials may be the only remaining treatment options.

FINDING CARE

Because salivary gland cancers are so rare, doctors recommend that patients find a hospital with a track record. “You don’t need to go to another state,” Shaha says, “but you need to go to a center where head and neck surgery is very common and there are recognized experts in salivary gland tumors.”

But it’s not just the surgeon that matters. Salivary gland cancers can affect facial appearance and function and psychological well-being. Treatment can require a team. Reconstructive surgeons help maintain or restore facial appearance. Physical and speech therapists work with patients to maintain function. Radiologists and medical oncologists collaborate on nonsurgical aspects of care. Mental health professionals provide support for coping with life changes brought about by the cancer.

“It is what we call a multidisciplinary team,” Shaha says. “You need a good surgeon. You need a good radiologist. You need a medical oncologist. You need a radiation therapist or radiation oncologist, and a good pathologist. If you have that team, that’s a real place where you want to be treated.”