EP203: Decoding Overdiagnosis: A Deep Dive with Dr. Wolfie Weyers

In Conversation with Dr. Wolfgang Weyers: The Complexities of Dermatopathology Diagnosis

In this episode of The Girl Doc Survival Guide, Christine welcomes Dr. Wolfgang Weyers, a highly respected dermatopathologist and author, to discuss his experience and perspectives on medical diagnosis. Dr. Weyers shares a personal anecdote about his influential mentor, Dr. Bernie Ackerman, and dives into a critical discussion on overdiagnosis, the importance of specific diagnosis in dermatopathology, problems caused by partial samples, and the criteria for diagnosing melanoma. He emphasizes the importance of experience, proper training, and the need to biopsy adequately developed lesions. The conversation also touches on the complexity of biological classification and the role of behavior and molecular studies in understanding diseases. 

00:00 Introduction to Dr. Wolfgang Weyers

00:46 Personal Anecdotes and Influences

02:05 Discussion on Overdiagnosis

05:04 Criteria for Melanoma Diagnosis

08:34 Challenges in Diagnosis and Solutions

16:48 Final Thoughts and Conclusion

Transcript

Christine Ko: [00:00:00] Welcome back to The Girl Doc Survival Guide. Today I am very excited to be with Dr. Wolfgang Weyers. Dr. Wolfgang Weyers MD is among the most respected dermatopathologist in Europe, not only by virtue of his skills as a dermatologist and a histopathologist, but for his literary contributions to medicine. He was also a sports broadcaster in Germany for football for more than 20 years. Currently he works in Freiburg, Germany as a dermatopathologist. In addition to that, he has written multiple books, two that are in English, one's called The Abuse of Man, and the other, Medicine in Nazi Germany. He is also the author of other books in German that are in verse.

Welcome to Wolfie. 

Wolfie Weyers: Hello. Hello. 

Christine Ko: Can you first share a personal anecdote so people can get to know you a little bit? 

Wolfie Weyers: Personal anecdote. Let's stick in the medical arena. I was very strongly [00:01:00] influenced by Bernie Ackerman, who was, when I was still an assistant, of course, already quite famous. We met at a meeting in Giessen where some not very good lectures were given by a variety of people, and then we were standing around and nothing had been arranged for this very evening. The other evenings, yes. And what are we to do? We said, We can go to a pub somewhere. And so Bernie and I headed off and had a beer together. And another one, and then we met two more colleagues. But from that time on, the next day, I was sitting with him. And then on his way back, I took him to the airport, and he said, Come on and visit me in New York City. As you may know, at that point, the fellowship with Bernie was expensive. Yeah. So it was for free. And I told him, I love my vacation, so I am not sure whether I wanna do that. It turned out that I spent much time then in New York City, and he became a very close [00:02:00] friend. He was my best man at the wedding. He is the godfather of my son.

Christine Ko: Oh wow. That's amazing. It's nice that you brought Dr. Ackerman up because it's a nice segue into my first question that's more medically related and not a personal anecdote. One of the articles that I recently read of yours, and a major reason why I wanted to talk to you on this podcast, is for the American Journal of Dermatopathology that was titled, "The Specific Diagnosis: Pretension or Illusion". And that fascinated me because I have been more recently thinking about overdiagnosis, which is an epidemiologic phenomenon. Not that we are wrong at the microscope, but that patient wouldn't ever be harmed or have symptoms by what we diagnose. The diagnosis actually ends up causing them more harm with what happens to them due to that diagnosis. But overcalling is where I'm wrong. Everyone else would agree that [00:03:00] I'm wrong. I made an error. And so then if I overcall something cancer, that patient does get, say treatment and have maybe some, related symptoms from getting that cancer treated. But that diagnosis was wrong. And so if it had been shown to those a hundred other people who knew and agree that it's not a cancer, those problems would've never happened for the patient 'cause the patient would've never gotten that diagnosis. 

Wolfie Weyers: Let me interrupt because the way overdiagnosis is treated now is really very very illogical and harmful. The current definition of overdiagnosis? Basically a correct diagnosis is referred to as overdiagnosis only if it's at an early stage. A correct diagnosis is a correct diagnosis, and you have to give it. This has to do with specificity. A melanoma is a melanoma, and if it's in the early stage, and I can recognize it, I have [00:04:00] to refer to it as a melanoma at early stage. This is my duty. That's a specific diagnosis. To call it something different is harmful because it may not be treated the way it should be treated.

I had this experience, for example, you have a nevus, and you have overlooked at the edge in one section, a little melanoma. Because of being overlooked, it turned out to be a metastasizing melanoma. Everybody makes these mistakes. You can overlook something. Yeah. But if you see something and basically, you know what it is, you must make a specific diagnosis, and then you can say it's a very early stage. So you can modify it, but not to make this diagnosis, you are not doing your job as a pathologist. 

Christine Ko: I appreciate that perspective, and largely I agree with you about overdiiagnosis. I agree [00:05:00] with you that if it's a melanoma, we should call it a melanoma. The problem is, for me, I would love to hear your opinion on this, that when you think about criteria for a diagnosis, are there really set criteria that a hundred dermatopathologists would agree on that make something melanoma?

Wolfie Weyers: Okay, it matters how experienced you are and how you have been trained. Also what comes into it is a certain way of looking at things.

Criteria for diagnosis. How can they be developed? In the 1920s and the early 1930s, criteria for melanoma developed by examining the flat edges of a melanoma. What we see at the edges of a melanoma [00:06:00] is different from a nevus, and we see that those cells are not distributed regularly. We see nests that vary in size, shape and distance from one another. I think that the conclusion is justified that these are the early stages of melanoma. So there is a set of criteria that if they are fulfilled, I mean is basically a hundred percent. And really maybe people don't agree even if they see those lesions, this is possible. But then I think it's bad training.

If criteria are fulfilled, I actually think that really most people would agree on the diagnosis. Of course if there're conflicting criteria, judgment becomes more difficult. And of course we have always to ask ourselves, Are we overcalling a lesion? This is one problem. The other [00:07:00] problem, and I think it is more important is, Are we undercalling a lesion? Currently, quite understandably, there is a tendency to overcall lesions because you don't want to undercall them because if you call a melanoma a nevus, this might not be so good for the patient. And so this is a problem, but I think you have to distinguish between the definitions of overdiagnosis, the terrible definition given by epidemiologists, namely a correct diagnosis, just at an early stage when presumably it wouldn't harm patients. The real definition of overdiagnosis, which I think is correct, is a wrong diagnosis that says a lesion is more severe or disease is more severe than it really is.

So this is my definition. I think it makes much more [00:08:00] sense. And this is also the way the word overdiagnosis has been handled in the medical literature for decades before the epidemiologists came in. 

Christine Ko: Yes, absolutely. I fully agree with you. I agree with you that there are criteria. There are. textbooks, right? But then there are these studies where they take expert dermatopathologists who have had 20 plus years of experience, say, and show all of them the same slides, and they don't agree.

Wolfie Weyers: It depends, of course, on the lesions that you select. If you select a limited number of lesions that are difficult, then the discordance comes in. And why? Because the criteria are not yet telling enough. The thing is, how do we do it?

Basically, there're two methods of judging [00:09:00] any neoplasm. Either you do it from basically the the cause, mostly mutational, or behavior. Melanomas, they can have all kinds of mutations. It's not always the same. And still they looks the same or they do the same. Yeah. So, difficult. But basically this is an approach via cause. We have done it for decades, if not to say for centuries, not via cause, but we try to recognize them via behavior. For example, if you define malignant neoplasms as those who have the capacity, if left untreated, to kill through metastasis or destructive growth, then of course the most telling argument, in favor of malignancy, is death of the patient. And in fact, we can make the diagnosis of [00:10:00] melanoma reliably by looking at the behavior of this neoplasm.

We look through the microscope, we see melanocytes not where they're supposed to be, but in the upper regions or down epithelial structure of adnexa. We see very irregularly distributed melanocytes. We see nests that are irregular, one in this shape, another one in another. These are direct consequences of the behavior of the cells in the tissue. Now, the earlier you want to look at those consequences of behavior, the more difficult it gets. Why? Because cells need some time to grow in order that those architectural features become visible. If you take out a lesion when it's only two millimeters, what are you to [00:11:00] do? Of course, then our criteria cannot work in the same way. And of course, then there will be discordance. Same thing is if many criteria are missing, especially the very important ones, symmetry, circumscription because of incomplete excision. Then judgment becomes a guessing game. And how could there not be discordance among experts? So, how can this problem be resolved? Don't biopsy too early. Wait until a lesion is five or six millimeters in diameter. Of course you can deviate from the suggestion if there are real clinical arguments. Then it's a different story. But in general, wait until it's five or six millimeters in diameter.

And of course, there are also some influencing factors. For example, sunlight. UV irradiation. There have been studies by Tronnier, Smolle, Wolff. They put some UV light on a nevus, on a [00:12:00] harmless nevus. And half of the nevus was covered by a tape. One half was completely normal. And the other half: large melanocytes, solitary melanocytes predominating, melanocytes in all region of the epidermis in all at all levels of the epidermis. So we know that external factors can really cause many problems. And the conclusion is don't biopsy an irradiated or otherwise traumatized melanocytic lesion. Biopsy it in two weeks.

Christine Ko: Yeah. Okay. So just first off then, to answer the question that I had when I read the title of your article, "The Specific Diagnosis: Pretension or Illusion". It sounds like from our conversation right now that you're saying that absolutely there are specific diagnoses. We do have criteria for melanoma, but problems can be 1) [00:13:00] training, experience as number 2.

Number 3, partial samples where we can't see the whole thing or just processing problems; we can't see the whole thing. So there are reasons why sometimes we can't come to the right diagnosis. And one way to solve that is to make sure that we biopsy something that isn't super early. 

Wolfie Weyers: Yeah. This was now one example. One has to put down criteria and try to look for specificity of diagnosis. At the same time, of course, one has to keep an open mind whether or not the approach still holds. You have to have an open mind. Lamarck, in the 19th century, said, Any classification is artificial, and in nature there only individuals. If I'm transfers it to melanoma, for example, in truth every [00:14:00] melanoma is different. But at the same time, of course, those categories that we set up are more than just fictions. Just as a different species of animals are more than just fictions, the same is true for diseases. 

Christine Ko: Yes. For example, just taking species. There are factually different species. Human beings exist and are separate from chimpanzees. Even though 97% of our DNA or something like that is similar, the difference is real. It's not just, as you were saying earlier, an arbitrary difference. A human being is definitely different than a chimpanzee. Even I think a young child would say, Yes, that's true. But if we just went by DNA say, if we said, Oh, you have to have more than 99% difference to be a different species, then human beings and chimpanzees would be the same species, actually.

So the reasons by which we classify are arbitrary.

Wolfie Weyers: Yeah. The thing [00:15:00] is you have to include different vantages and the more different vantages you include, I think, the safer you are in your judgment. For example, but just because you just mentioned it, DNA, how similar chimpanzees and humans are. The thing is you cannot judge from these small levels such as DNA. DNA doesn't tell you what a cell does. If you look at an individual cell, it doesn't tell you anything about the tissue. If you look at the tissue, it doesn't tell you anything about the organ. If you look at the organ, it doesn't tell you anything about the living being as a whole and its behavior.

This is how biology is. So at a higher level of organization, things become so complex that you simply [00:16:00] cannot conclude from some DNA how something is going to behave. 

Christine Ko: I love how you put that.

Wolfie Weyers: It's worthwhile of course. It's very important that you study the molecular basis of disease. But the view on the patient. Where are the lesions? How are they distributed? Or histopathological. How are the cells distributed? This is behavior, how they behave. So you don't look at one aspect only, but of course behavior is a consequence of many different aspects going into it. Molecular aberrations, epigenetics, proteomics, whatever. They all go in it. So you have a broader view, maybe not so specific, but broader. 

Christine Ko: Yes. I love it. This has been absolutely fascinating and wonderful to talk to you and hear your perspectives on diagnosis, overdiagnosis, overcalling, discordance. Thank you [00:17:00] so much. Any final thoughts?

Wolfie Weyers: I hope that the situation in the US will become stable again. I hope it for you.

Christine Ko: Thank you very much. 

Wolfie Weyers: Alright.