Molecular oncology tumor board: Pathologist, oncologist dip into head and neck case

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“It has changed my conceptualization of what salivary duct carcinoma is,” he continued. “I don’t think it is a distinct, single entity. I am becoming more aware that salivary duct carcinoma is a genetic wastebasket,” full of tumors that have the known PI3 kinase pathway mutations and that never have fusions, “but also a source of these de-differentiated fusion-driven tumors. And they look identical and stain identically.”

Dr. Bishop now routinely performs ALK and pan-TRK IHC and sends out for RET FISH testing. “And if I had the ability to send all of these for sequencing I would, because it is worth looking for these things. I’ve learned a lot from cases like this.”

When fusions are identified, Dr. Khan said, those who work in drug development know there’s a subset for which a drug must be found. “And many times those drugs are already available and we just need to bring those two together.”

Dr. Khan likes Dr. Bishop’s use of the term “wastebasket” for salivary gland cancer, saying he made this very point to fellows with him in the clinic the day before. “I think pathologists understand this better than most oncologists do, which is when we say salivary gland cancer, you are really talking about a diverse group of very different diseases that are called salivary gland cancer just for convenience. And this applies more broadly toward head and neck cancer as well.”

Nasopharyngeal cancer differs completely from HPV-positive oropharyngeal cancer, Dr. Khan noted, and from hypopharyngeal squamous cell cancer. “All of them carry the same diagnosis of squamous cell cancer and have treatment similarities, but they have completely different oncogenesis, completely different outcomes, and are very different in terms of how we expect their treatments to evolve in the future.”

Dr. Bishop’s view of looking for TRK has changed in recent years, he said. “I would say it’s worth looking for even if it’s a small number.”

What is your number threshold? Dr. Khan asked, likening such a number to that used in the medical oncology world to treat. “At what point do you think it becomes worthwhile to chase down something that might impact the care of one percent, 10 percent, 0.1 percent of people?”

“If I believe in my diagnosis,” Dr. Bishop replied, “then I’m not going to chase down TRK fusions in every salivary gland cancer, regardless of histology. I think that’s wasteful and very low yield.” He cites adenoid cystic carcinoma as an example. “I’m not aware of any cases with TRK fusions in that group. Same for acinic cell carcinoma, mucoepidermoid carcinoma, et cetera.”

“Would a single case report of adenoid cystic carcinoma with whatever fusion be enough?” he asks himself. “I don’t know. Probably not, but it’s a question I should consider.” When it comes to high-grade salivary duct carcinoma, he said, “there’s enough out there, published and unpublished, and it’s kind of gaining steam.”

NTRK tumors have a “tremendous deep response” to drugs like larotrectinib and entrectinib, Dr. Khan said, “and if you find it and the patient gets the drug, the response is amazing.”

“If you win that golden ticket and have the TRK fusion identified,” he said of the patient, “you will have a great time as far as cancer treatment is concerned. You will leave my office thinking I really know what I’m doing, when what I am doing is piggybacking off of the pathologist’s thorough knowledge, and all of what we know about TRK fusions, and this great drug that seems to work really well.”

Dr. Bishop said he recently saw a child diagnosed with an intermediate grade of mucoepidermoid carcinoma. “On re-review it was a secretory carcinoma, which completely changed their approach”—they considered the use of targeted therapy upfront instead of radiation given that the patient was a child.

How does Dr. Bishop decide to opt for a full NGS panel versus a focused panel? Dr. Khan asked.

“When it’s diagnostic,” Dr. Bishop replied, “the focused approach is ideal. Usually you have it down to between two things and this answer will take you one way. It’s rare that you are completely lost and have no idea.” For the case he presented, “a broader NGS approach would be ideal, and that’s what was done.” NGS identifies more and thus will generally be preferred, he noted. “It’s just what you have the ability to do.” Were every salivary gland cancer sent for NGS, he “would love it,” he said. “The data would be great not only for treatment but also for research.”

Karen Lusky is a writer in Brentwood, Tenn.