There was a news story the other day about a groundbreaking study at Shanghai Ruijin Hospital that proved that benign thyroid nodules do not become thyroid cancer! Many readers in the background asked me what was going on.
I think:
- This is a great study. It has valuable ideas and conclusions that will likely allow many people to avoid overtreatment in the future.
- This is a small study. It’s too early to say that “100% of benign thyroid nodules will not turn into thyroid cancer”. I think it’s reasonable to say that most benign thyroid nodules don’t become cancerous in the context of other data.
Either way, this is excellent translational medicine research from China, and kudos to Academician Ning Guang and Director Wang Weiqing’s team at the Department of Endocrinology at Ruijin Hospital!
(Image from Station Cool Helo)
(a)
What problem is this study trying to solve?
The overtreatment of thyroid nodules!
We often talk about early diagnosis, early detection, and early treatment.
This is for conditions that are at risk of malignancy. For example, some polyps inside the colorectum have the potential to become malignant and are precursors to colorectal cancer, so during a physical exam, removal is usually recommended if a polyp is found by colonoscopy, an operation that has led to a significant reduction in colorectal cancer mortality in the United States.
But thyroid cancer is a little different.
As thyroid B-ultrasound resolution gets better, more thyroid nodules are being diagnosed and more are being treated.
But for a long time, the scientific community has suspected that benign thyroid nodules are not the precursor to thyroid cancer. Many people who did not need treatment at all underwent surgery, radiation, and chemotherapy, causing a triple whammy of mental, physical, and monetary damage.
An important piece of evidence is that while the number of patients with benign thyroid nodules has recently skyrocketed N-fold in many countries, the number of patients dying from thyroid cancer has not changed much. This indirectly suggests that the vast majority of thyroid nodules do not get worse and affect a person’s life expectancy.
But this idea has been lacking direct evidence, so it hasn’t changed clinical practice.
This study from Ruijin Hospital is direct evidence that shows that benign thyroid nodules and thyroid cancer are completely different at the genetic level.
(ii)
What direct evidence is provided?
By sequencing the genes of dozens of benign thyroid nodules and malignant thyroid cancers, scientists found that while they both have mutations, the two have completely different types of major mutations!
Many benign nodules have mutations like ZNF148, SPOP, and EZH2, but thyroid cancer has no such mutations at all; instead, malignant tumors have more BRAF mutations, which are absent in benign nodules.
This is direct evidence, at least in the samples in this study, that malignant thyroid cancer never develops from benign nodules.
Because the process of tumor progression is an accumulation of mutations, if the malignant tumor came from a benign node, it must have retained important mutations in the node. For example, in the figure below, if the node has mutations A, B, and C, then the malignant tumor that comes from it must also have A, B, and C.
But now the result is the following.
The only explanation is that the malignant tumor actually had another source and the benign nodule was wrongly accused.
Another important piece of information is that ZNF148, SPOP, and EZH2 are three mutations that can be used as “benign markers. If a node is found to have one of these three mutations, it has a very high probability of being benign. There is no need for aggressive treatment; active surveillance is the best option.
In contrast, if a BRAF mutation is found, it is almost certainly a malignant thyroid cancer. Of course, there is no need to panic, and the cure rate is still very high as long as you are actively working with scientific treatment.
The pineapple ends with a little fable.
(3)
Yiyangfinger of the Bear
It has always been thought that if a bear child steals something, he will definitely grow up to be a terrorist, so it was decided to nip in the bud by taking all the kids who steal and feeding them to the sharks.
Many parents actually don’t want their bear kids to feed the sharks because not only does it cause huge psychological trauma, but they also have to pay the shark feeders. But there’s nothing you can do about it, because everyone says that in case the kid grows up to be a real terrorist, you can’t eat it yourself.
At one point, the shark feeding industry was booming.
More worryingly, the number of kids caught stealing in China has grown exponentially in recent years, and people feel that society is getting more and more dangerous.
But some people feel something is not quite right:
- Many bear kids are being caught purely because the surveillance apparatus is getting more advanced. Now even kids who steal erasers from the same table are being caught and fed to sharks.
- A great deal of data proves that the vast majority of kids who steal grow up harmless. It’s purely a matter of momentary curiosity and mental immaturity, and they may become science writers later.
So many people are calling for the idea that bear children should not all be fed to sharks indiscriminately.
But every time this issue is raised, there are people who object on the grounds that:
- How do you know that terrorists don’t start out as petty thieves?
- Even if only 1% of bear children become terrorists, how do you know which ones? It’s better to kill a thousand than to let one go!
That means the terrorists didn’t come from the thieving bear child!
Because once martial arts are learned, they are not forgotten. If the terrorists came from thieves, then they must still know the One Yang Finger, or even evolve into the Six Veins of Divine Sword!
Since now it turns out that they don’t know this martial art at all, but are veteran players of Toad Kung Fu. This means that the bear children are from the Southern Emperor’s school, and the terrorists are mainly from the Western Poison’s school.
Truly, so many children who stole pencils from next door over the years have been mistakenly fed to sharks!
Also, while we can’t be completely sure that 100% of bear kids won’t turn out to be terrorists, we do know that if a child is found to know one yang finger, then we know that the likelihood of them becoming a terrorist later on is extremely low and they shouldn’t be dragged off to feed the sharks.
YiYangFinger is a “bear safety indicator.”
Since the terrorists are of the Western poisonous Ouyang Feng school, we should be on the lookout not for bear kids who steal, but for bear kids who poison their table!
I hope you’ve read this.
(Image from Station Cool Helo)
(iv)
What to do next?
This study is undoubtedly a good early attempt. But there’s a lot more that needs to be done to change clinical practice and prevent overtreatment.
- Most importantly, the results need to be validated on a large scale. This trial used only a few dozen patients from one hospital, and it was kind of a pilot effort. More hospitals and more data are needed.
- More “safety markers” need to be found. Only about 26% of benign thyroid nodules carry the 3 “safety mutations” ZNF148, SPOP, and EZH2, so how do you determine the remaining 74%? If a child with a finger is safe, is a child with a dog fighting stick or a finger snapping power safe?
- Everyone with a thyroid nodule wants to know exactly whether it’s benign and doesn’t need to be treated, or if it’s worsening and needs to be treated early.
- Breast nodules and lung nodules both have very similar problems. It is important to find their “safety markers” through genetic testing.
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Still, China has very good medical resources, and if scientists use them well, they can do outstanding work.