For certain thyroid lesions, the shift is on

The diagnostic criteria for those categories may or may not change, says Dr. Ohori, who was not involved in the study. But there have been recent pilot studies looking at the influence of NIFTP diagnosis on the rate of malignant outcome. “As you would imagine, there is a drop in each of the diagnostic categories,” he says, with the “suspicious” diagnostic category showing the biggest decline—just over 40 percent.

Notes Dr. Ohori: “Each institution has a somewhat different threshold as to what they call NIFTP in surgical pathology, and where they draw the line for each diagnostic category in cytology.” Given such variations, “I would advocate each institution do its homework, if you will, in calculating out the risk of malignancy, based on the change in this categorization,” by doing the cyto-histo correlation for each of the Bethesda categories.

“I know that is a lot of work,” acknowledges Dr. Ohori, who adds that he and his colleagues were in the midst of doing this themselves. But the need is clear, he says. “It’s a matter of communicating the risk of a particular nodule to a clinician and patient. And in my opinion, nothing is better than your own personal data.”

Every change includes growing pains, Dr. Carty says. “When you remove the word ‘cancer,’ you reassure the patient and you reduce the health care cost burden. But you complicate the cytology reporting.”

There are also adjustments to be made on the clinical end, she says. The American Thyroid Association (she’s a board member) is responding to the JAMA Oncology study with a letter that will include concrete suggestions for implementing NIFTP. “This is groundbreaking,” she says. “But just like any enzyme, it requires some activation energy to get working.”

For the group Dr. Nikiforov assembled, the work continued right up until the meeting was adjourned. Once the group reviewed the clinical outcomes and refined the diagnostic criteria, one crucial task remained: What should they call these less-threatening lesions?

Enter MGH’s Dr. Maytal. “I have to give him credit for doing a lot to convince people,” says Dr. Nikiforov, who asked the psychiatrist to talk about the impact of the word “cancer.” “When patients hear that word, it’s a huge, huge change in how you see life, and this is a very, very big stress. And yet we know these tumors are indolent.”

Are psychiatrists typically part of the mix?

“I can tell you, this was not a usual meeting,” Dr. Nikiforov says. Conferences involving a pathological reclassification typically include only pathologists, he says. In this case, including a thyroid surgeon and two endocrinologists raised the level of discussion. So, he says, did the patient advocate. “She said, ‘Look, I am not a physician—I cannot tell you how to name this tumor. But you need to know that what you do is important for us,’” Dr. Nikiforov says. “I can tell you, it was very important for all of us in the room to hear that.”

Dr. LiVolsi called Dr. Maytal’s talk “absolutely amazing.” She recalls being particularly struck by one example. If a patient is told he has congestive heart failure and has a 50 percent risk of dying within five years without a transplant, he is likely to by buoyed by the idea he can be treated and will accept the diagnosis. Ditto for a patient who’s told he has chronic renal failure—he will accept the need for dialysis, understand he might be put on a transplant list, and, again, accept the diagnosis.

“But if you tell a patient they have basal cell carcinoma of the earlobe . . . ,” Dr. LiVolsi says.

Regardless of prognosis, says Dr. Giordano, “‘Carcinoma’ gives the message you’re a cancer patient. So FCIS, like DCIS, sent the wrong message.” It’s an idea he says he’s struggled with for years in his own practice. When he makes a cancer diagnosis but doesn’t think the entity will behave like a true cancer, he includes in his path report a comment to the effect that the likelihood of a clinically significant cancer occurring is exceptionally low, the implication being to refrain from drastic treatment.

Listening to Dr. Maytal speak about the impact on patients, Dr. Giordano says, was powerful. “As pathologists, we’re sort of removed from that. And it drove home the point that what we do is profoundly significant for people. ‘I’ve got a NIFTP in my thyroid’ doesn’t carry the same connotation as, ‘I have thyroid cancer.’”

Dr. Maytal’s clinical work involves caring for patients along the cancer spectrum, from diagnosis to end of life, through remission or relapse. “I think quite a bit about what the diagnosis means to people, and how they make sense of it.” Not surprisingly, he sees conversations, and creating the opportunity for conversations, as crucial.

Once people hear the word “cancer” in their diagnosis, Dr. Maytal says, “they’re down that rabbit hole. The word destroys space for inquiry, no matter how well a clinician explains the word and why it may not be worrisome.” Patients simply stop listening when they hear it. On the other hand, “If I say you have a noninvasive follicular thyroid neoplasm with papillary-like nuclear features, you’re probably going to say, ‘What is that?’ And then you and your doctor can actually have a conversation.” These talks require more time, and physicians will have to answer more questions, he says. But it avoids trapping patients in the metaphor of cancer.

Naming these lesions would fluster even the slickest marketer. Neither encapsulated follicular variant of papillary thyroid cancer nor EFVPTC rolls off the tongue. Even as pathologists recognized, informally, that a new name might be useful, their efforts fell short. “A raft of names have been applied,” Dr. LiVolsi says. Follicular tumor of uncertain malignant potential? Follicular tumor borderline type?

“Noninvasive follicular tumor” worked for many, but it also describes follicular adenoma, which doesn’t have nuclear features. Hence the addition of the phrase “papillary-like nuclei.” Asks Dr. LiVolsi: “Do we like the term? Not really.” She says it sounds “stilted and a little strange.” But, like a cast-iron skillet, it’s useful, if not elegant. “It serves the purpose.”

Dr. Seethala says many have told him the name is awkward (bringing to mind the old saw that a camel is a horse planned by a committee). “I can’t disagree,” he says. “Luckily, the acronym is nice.” When you can’t say cancer or carcinoma, he says, “your options change quite a bit. How do you describe these nuclei if you’re not going to call this papillary carcinoma?”

As he considers the name, Dr. Giordano’s sympathies lie with his cytopathologist colleagues. Because they can’t assess invasion on FNA, they have to focus on nuclear features. Say they make a diagnosis of suspicious for papillary alterations based on nuclear alterations, which are recognized as papillary carcinoma, Dr. Giordano says. At surgery, “If we call it a noninvasive follicular thyroid neoplasm, we’re not closing that loop. We’re leaving cytologists out to dry.” Adding the phrase “with papillary-like features” ties things together and renders a diagnosis consistent with what cytopathologists see. “But as a consequence, the name got really long.” NIFTP, by comparison, seems positively elegant.

But even the acronym has sent people stumbling. Says one observer, “We’re not really sure how to pronounce it.” Some call it nift-P. Others recite the letters, N-I-F-T-P, and some are suggesting that despite its spelling, “Nifty” might be appropriate. Dr. Ohori is fond of using “Nift shift” to describe the transition.

Some question whether the name needed to change at all.

“I think the nomenclature change is a bad thing,” Boston University’s Dr. Doherty says. The impact on treatment is nil, he says, since these patients have been seen, and treated, as low risk for years.

He’s not insensitive to the impact of the words “cancer” and “carcinoma.” They might be important from a personal point of view, he says. Likewise, not being labeled with a cancer diagnosis might make it easier to obtain, say, life insurance. And for a patient needing a kidney transplant, for example, a diagnosis of a benign neoplasm doesn’t have the same implication as a malignant neoplasm. But even in that latter scenario, says Dr. Doherty, the fix is relatively simple. “It has involved someone with molecular knowledge writing a letter saying there’s no risk of recurrence.” It’s an extra step, not a prohibitive problem, in other words.

Given the choice, Dr. Carty says she prefers “carcinoma in situ.”

Are her patients okay with the word “carcinoma”? It depends, she says, on who they it hear it from. “What I really dread is when someone has shared the pathology report with the patient before I do.”

“When my patients hear the words ‘thyroid cancer,’ they’re unsettled until I talk to them,” she says. “I immediately explain to them that most forms of thyroid cancer have a wonderful prognosis, and the odds are excellent they’re going to live to be 99 and die of something else.”

Dr. Doherty agrees. In his experience, it’s the clinicians’ job to recognize how the word “cancer” might affect patients. “We have to manage their expectations of what the diagnosis means, whether it’s cancer or not.” While the psychological implications are real, and important, he says, “It’s not as simple as saying, ‘This isn’t cancer; this is cancer.’ We need a deeper conversation with our patients.”

While the study has generally garnered high praise, more work needs to be done.

The study looked at and validated the nuclear features in isolation. Now “it would be good to validate that across different practice patterns,” Dr. Seethala says. It works among experts and specialists, but what about those who practice in a more general setting? And though the study addressed nuclear features in a methodical fashion, it would be nice to do the same for the other inclusion/exclusion criteria as well, he says. The group decided on the latter by consensus, so they’re not as well vetted.

The follow-up is impressive, Dr. Seethala says, but thyroid cancer itself is somewhat indolent. “So is 13 years enough? Possibly not. Some people talk about much longer follow-up.”

Most agree that the variant papillary lesions are diagnostically challenging. “Pathologists have had trouble with these lesions for a long time,” Dr. Doherty says. “In fact, we all know we can send the same slides to different pathologists and get different results. Whether they’re encapsulated or not, some pathologists will call most of them benign; some pathologists will call most of them cancer. And that has more to do with individual bias and criteria than the biology of the lesion.”

Ideally, he adds, “We would like to see a more definitive way to make a consistent diagnosis on the part of the pathologist,” perhaps through different criteria for light microscopy or more definitive molecular characterization. But even if this category can be tidied up, so to speak, “That might make the other categories adjacent to this one more fuzzy,” he says with a rueful laugh.
It would also be good to look at NIFTP prospectively, on a population-level scale, Dr. Seethala says. “That’s where its role in terms of being reported in the registry becomes important. It’s better to know that there’s a half a percent recurrence for these tumors based on thousands of cases, rather than hundreds.”

As he continues to talk about additional studies he would like to see, including scoring schemes for oncocytic lesions and multifocal, small tumors, Dr. Seethala suddenly stops. He applauds the multidisciplinary, systematic approach to reclassification, but contrary to what optimists might think, he says, the NIFTP entity “doesn’t solve all the thyroid problems we have, even pertaining to these indolent entities.” Rather, he says, “It’s a shift in the right direction.”

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Karen Titus is CAP TODAY contributing editor and co-managing editor.