Doctors don’t regularly come across undiscovered bits of human anatomy, but a team of physicians recently reported a never-before-described set of salivary glands in patients’ necks. The first hint of this new gland emerged while Wouter Vogel, a radiation oncologist at the Netherlands Cancer Institute (NCI), was probing for damage to salivary glands after radiotherapy for cancer in the head, neck, or brain—injuries that can lead to issues such as problems with digestion, speech, and an increase in oral infections. While going through these scans, he found something usual.
Vogel was using a new technique for detecting cells in the salivary glands—PSMA PET/CT, a form of combined positron emission tomography (PET) and computed tomography (CT) that uses a radioactive tracer that binds to a prostate-specific membrane antigen (PSMA). This method is typically used to detect prostate cancer, but in a prior study, Vogel and his colleagues had found that it also labels salivary gland cells, where PSMA is also expressed. Humans have three major salivary glands and approximately 1,000 minor ones. “This scan is extremely sensitive for the salivary glands,” Vogel says. “So we can see more than ever before.”
What he saw was an unexpectedly high level of labeling in the upper section of the throat known as the nasopharynx, where only minor salivary glands are supposed to be found.
When Vogel first observed the unanticipated signal, he says he was confused—salivary gland cells were not thought to be abundant in this location. Immediately, he sought a second opinion from his colleague Matthijs Valstar, an oral and maxillofacial surgeon at the NCI. “You never believe something until you have some feedback from others,” Vogel tells The Scientist. “But we agreed that it really was an unexpected and significant signal that requires further investigation.”
I don’t think there is any doubt this is new salivary tissue that has been discovered.—Chris Nutting, Royal Marsden Hospital
To examine further, Vogel and Valstar assembled a team of more than a dozen researchers from NCI and three other medical centers in the Netherlands. Together, they went through the PSMA PET/CT scans of more than 100 patients with prostate or urethral gland cancer and found similar signals in the nasopharynx region in those individuals as well. This assessment also revealed that the glands existed as a pair and had an average length of four centimeters. The group then dissected two human cadavers to confirm that this was, indeed, salivary gland tissue. They dubbed these newly identified glands as “tubarial glands,” based on their location above the torus tubarius, the section of the nasopharynx just behind the pharynx. These findings appeared last week (October 16) in Radiotherapy & Oncology.
According to Vogel, there are likely two main reasons the tubarial glands haven’t been found before: researchers had not previously used PSMA PET/CT to look for salivary glands, and the newly discovered glands are located in a region that’s hard to access with standard surgical procedures. “With the other salivary glands, you can just feel them by either with your hand or see them during surgery,” Vogel explains. “The location we’re describing now, you can only see it with a nasal endoscopy.” Nasal endoscopy is a method in which a tube with a tiny camera and light are used to image the nose and sinuses. Based on the tubarial glands’ similarities to the volume and draining system of the sublingual gland—one of the three major salivary glands—the authors suggest that the new glands should be classified as a fourth major gland. However, they also note that some might disagree with this categorization, because the new glands share similarities with minor glands as well.
Because salivary glands are at risk of damage from radiotherapy, the team also set out to investigate whether radiotherapy exposure to the tubarial glands would affect patients. After examining data from a cohort of more than 700 head and neck cancer patients, they reported that the radiotherapy dose to the gland area was associated with dry mouth and swallowing difficulties after treatment.
Vincent Vander Poorten, an otorhinolaryngologist at University Hospital Leuven (UZ Leuven) in Belgium who was not involved in this study but has collaborated with the authors on other projects, says that while he agrees that the authors have found a new cluster of minor glands, whether the tubarial gland is truly a separate, major gland is somewhat controversial. “Of course, you could say that it’s just a cluster of minor salivary glands that are all over the place in the mucous membranes of the head and neck.”
“I don’t think there is any doubt this is new salivary tissue that has been discovered,” Chris Nutting, an oncologist at the Royal Marsden Hospital in the UK who was not involved in this study, tells The Scientist. “One of the areas that we are very keen on pursuing is trying to identify salivary tissue and avoiding it because it causes one of the main complications of radiotherapy.” The question is how much sparing this gland will actually improve patient outcomes, he adds. The authors conducted a retrospective study, which looks back at previously collected data, but Nutting says a prospective study, which enrolls participants and observes the outcomes of an exposure over time, will be important.
Vogel, too, notes that whether radiotherapy to spare the tubarial glands will actually make a difference in patient outcomes is an open question. “That is the reason that we cannot just implement this new finding into treatment today,” he adds. “We have to do prospective evaluations to see if it really helps patients. This is something that we envision [doing in] the coming years.”
M. Valstar et al., “The tubarial salivary glands: A potential new organ at risk for radiotherapy,” Radiotherapy & Oncology, doi:10.1016/j.radonc.2020.09.034, 2020.