Jason Bok Lee, MD, is director of the Pigmented Lesion Clinic and a member of Thomas Jefferson University Hospital. His expertise and research interests are centered around skin cancer including melanoma, inflammatory skin disease, and dermatopathology. In an interview with The Dermatologist, Dr Lee discussed approaches to melanoma diagnosis prior to his session at AAD VMX, specifically highlighting the New England Journal of Medicine article “The Rapid Rise in Cutaneous Melanoma Diagnoses."

In the NEJM article,¹ it's noted that cutaneous melanoma is now the third most-commonly diagnosed cancer in the United States and that this rise may be in part due to a rise in diagnosis due to the frequency of skin exams. What would you say has attributed to this rise in examinations and how has the recent pandemic impacted any of these reported examinations as of yet?
In the 1970s and 1980s, there was a concerted effort by dermatologists wanting to diagnose the deadly form of melanoma early. You can just imagine the rewards of catching any cancers early, so that you don't encounter the morbidity and mortality of the cancer. This led to lots of public campaigns promoting the benefits of screening. Dermatologists, over the years, have done a good job promoting screening and melanoma awareness.

Now, everyone is aware that people who tend to showcase lots of moles, have fair skin, and easily sunburn should come in and get full body skin exams. That increased the frequency of skin exams and intense scrutiny over the years have resulted in a significant increase in biopsy rates of pigmented lesions that have led to the rise in the incidence of melanoma. Next, smaller and smaller pigmented lesions were biopsied with the aid of a dermatoscope, which can detect small changes. This has resulted in the skyrocketing incidence of in-situ melanomas and very thin melanomas. The low threshold to biopsy and the low threshold to diagnose melanomas by pathologists that reinforce the clinicians have led to what the article refers to as the cycle of overdiagnosis of melanoma. We may see a slight dip in the number of in-situ melanomas due to the less patients examined during the pandemic.

According to this article, “...the rise in melanoma diagnoses is restricted to the cutaneous form, whereas the incidence of non-cutaneous melanoma has remained stable.” Can you share and elaborate on the hypotheses surrounding the cause of this discordance, since currently this is unknown?
We don't know much about noncutaneous forms of melanomas, because there aren't very many. We know more about the ocular form of melanoma that is diagnosed by ophthalmologists, but these are rare. I, as a rule, send my high-risk patients to see an ophthalmologist to make sure that they don't have the ocular form.

Unlike the noncutaneous form of melanoma, skin is very accessible, allowing us to see what goes on easily, and the sun has been blamed for the rise in incidence of melanoma.

The article argues that the sun may account for a twofold increase in melanoma incidence but not the sixfold increase that they have noticed in the last 40 years. The authors think something else is going on, and the article asserts that it is the scrutiny and the overdiagnosis of melanoma that accounts for the overall significant rise in melanoma for the last 40 years.

This article also elaborates on the harmful effects of overdiagnoses such as resilience vulnerability, economic impact, and the physical effects from biopsies, among others. What should dermatologists implement within their practice to prevent overdiagnosis and to further extend their quality of care for patients who potentially do have melanoma?
Nobody wants to miss melanoma. It is the deadliest form of skin cancer, and there is a huge consequence—a huge downside—if you miss a melanoma that's deadly that results in a bad outcome. When you look at all the malpractice suits for dermatologists and pathologists, the highest payout is for those that have melanoma-involved and melanoma diagnosis that was delayed or missed. Dermatologists and dermatopathologists are acutely aware of this.

There is a heightened awareness of melanoma for many reasons. Over the years, smaller and smaller lesions have been biopsied, but it gets harder and harder to prognosticate and predict the biologic behavior of these small lesions. They may have microscopic features of melanoma, but we do not know if it will progress to behave aggressively.

What the epidemiologic data tells us is that the vast majority of the small, flat lesions that are, for example, less than 5 to 6 mm, do not progress even if they have a little bit of atypical features. Instead of reflexively biopsying them,  they can be monitored as they do in Europe and Australia. Once you biopsy them, they are subject to pathologists who are inclined to worry about any atypical features. There is also significant discordance among pathologists when it comes to thin and epidermal melanocytic lesions. Any atypical features will be a good chance of recommendation of aggressive management or overdiagnosis of melanoma. This has been the approach for a long time to make sure that we do not miss melanomas. If you get a melanoma in situ back as a diagnosis for small flat lesions that look mostly benign, you should, as a dermatologist, question that diagnosis and discuss it with your dermatopathologist. The dermatopathologist does not have the ability to predict the biologic behavior of small epidermal lesions. The histologic diagnosis of atypical nevi and melanoma in situ has been unhinged from the biologic behavior of these lesions.

A second thing you can do is to decrease the surveillance and removal dysplastic/Clark nevi. Over the years, because dysplastic/Clark nevi have a reputation of being bad moles, many of these lesions were biopsied and removed, but there are many studies out there now that you do not need go back and re-excise these because the association with melanoma is exceedingly low.

When they were first introduced, we thought they were precursor lesions, but they are no longer considered precursors. The patients who have many nevi may need to be monitored but not the nevi themselves.

In your December 2020 study,² it’s noted that Pagetoid Spitz nevus can be misdiagnosed as melanoma. How does this, and other misdiagnosed nonmelanoma disease states, highlight the diagnostic issues of melanoma? How does this relate with the recent findings presented in the NEJM article?
One of the frequent sites of melanoma in women is the thigh, and so is Pagetoid Spitz nevus, which was actually published more than 25 years ago. When you biopsy these lesions of the thigh, it frequently has histologic features that are associated with melanoma.

Anytime there are overlapping histologic features of melanoma in a lesion, pathologists tend to err on the side of caution. They do not want to miss a melanoma, and there is a good chance that these lesions are overdiagnosed as melanomas. These lesions have not shown to behave in an aggressive manner.

They just have to be aware of the clinical features, that these are small, usually less than five millimeters, flat lesions. Clinically, they look very benign, but histologically, they have what's called pagetoid spread on histology, which you see in some melanomas.

I think these lesions are significantly overcalled, and so communication between the pathologist and the clinician is critical for appropriate management of these lesions. Again, this is one place where they can minimize biopsy and avoid overdiagnosis.

There are multiple different sites in the body that have their peculiar architecture and cytology with some overlapping features of melanoma, resulting in being overcalled frequently. As I said, anytime there are overlapping features of melanoma in histology, there is a tendency to err on the side of the caution to minimize missing melanoma. I am no exception to this approach. I am just more cognizant of the issue.

Looking toward the future, what treatment and strategies can you foresee being implemented that could aid physicians in diagnosing and managing melanoma?
The NEJM article has broad, far-reaching recommendations that I do not think the dermatology community will adopt anytime soon. One of the strategies they recommend is no skin cancer screenings. The hope is to promote minimizing overdiagnosis.

We may not need population-based melanoma screening, but we should focus on the real high-risk populations such as patients who are immunocompromised or who have a significant first-degree family history of melanoma, and older White men with lower socioeconomic status. These are the groups of patients who come into our office when the melanoma is symptomatic, large, and bulky. There needs to be more effort to reach out to these higher-risk population groups who develop the aggressive form of melanomas.

The benefits of screening and earlier detection of skin cancers have been ingrained into the minds of dermatologists and dermatopathologists. It is going to be difficult to pivot to a different strategy, but more than 40 years epidemiology data tell us that there is significant overdiagnosis. We can no longer ignore the epidemiologic data.

For example, thyroid cancer is another cancer where the incidence and mortality data look identical to melanoma. In multiple countries, when they have looked into the why there has been an increase in thyroid cancer, it is because of overscrutiny of the cancer. Additionally, it is noted that screenings and diagnostic tool availability has increased, which has contributed to the overdiagnosis.

So, how do we change the way we do things? Again, we are so used to doing what we are doing that it is going to be difficult to change and pivot. One thing we can do is to better educate the public, particularly on the fact that not all melanomas are the same and most are now highly curable. Often patients come into my office thinking that they have a death sentence because of their melanoma diagnosis. But when I look at the report and it says melanoma in situ or stage 1A disease, I take the time to explain that the survival rate is nearly 100%. I suggest there should be more studies with a focus on figuring out which melanomas are the aggressive ones. Right now, when we have a diagnosis of melanoma in situ, it is assumed that each one will progress, and, if left alone, it will kill the patient eventually. The epidemiologic data do not support this progression model.

In the near future, the genetic and molecular basis of diagnosing melanomas may allow us to tease out which ones are more aggressive and which ones are not.

What pearls of wisdom would you like to share with your colleagues regarding melanoma?
The first thing is to acknowledge that there is a problem of overdiagnosis. I do not think most dermatologists think about it, and we all think we are doing something good for our patients. Again, from the epidemiologic point of view, it is easy to see the overdiagnosis. But at the patient level, when you look at an individual skin lesion, you do not know which will progress and which will not, so you biopsy it. The melanoma incidence and mortality data tell us that most will not progress. The high incidence and flat mortality is referred to as the epidemiologic signature of overdiagnosis. Looking at some strategies, for example, in European countries and Australia, which are more socialized medicine settings, they monitor many of the flat, melanocytic lesions. They do not aggressively biopsy them. This showcases that we need to switch to monitoring, which can help us realize these are not aggressive lesions. This approach is supported by the epidemiologic data. We thought dysplastic nevi were high-risk lesions that progress to melanoma, but we now know that they have no more risk than other nevi. We can be reassured that most of these small, atypical-looking lesions that are flat can be monitored. That is where we can start and, hopefully, start pivoting away from biopsying a lot of these where if the pathology is not 100% sure, there is a good chance overdiagnosis will result.

I would like to add that not all melanomas are the same. We should probably send a different message out to our patients and to the population that melanoma in situ has an 100% curable stage, and that they do not have the deadly form of the disease.

One of the tools that every dermatologist has now is a dermatoscope. In European countries and other parts of the world, it has been published that the use of a dermatoscope has resulted in fewer biopsies. Unfortunately, in the United States, financial incentive is not aligned to doing less, whereas in a socialized medicine setting, there is no financial incentive to do more on a patient. They use a dermatoscope and leverage the dermatoscope to decrease biopsies.

We can do that here as well. Particularly, as a dermatopathologist, I see lots of biopsies from volar skin from the palms and  soles. This is a situation where a dermatoscope can be really useful and improve the management of volar melanocytic lesions. We should leverage the dermatoscope to increase our diagnostic accuracy, which can allow us to perform less biopsies and increase our specificity in the diagnosis of melanoma. These are small steps that we can begin to take to close the gap on overdiagnosis of melanoma.

References
1. Welch HG, Mazer BL, Adamson AS. The rapid rise in cutaneous melanoma diagnoses. New Engl J Med.  2021;384(1):72-79. doi:10.1056/nejmsb2019760

2. Chung J, Yuan ZM, Lee JB. Clinical and histopathological features of pagetoid Spitz nevi of the thigh. J Cutan Pathol. 2020;47(12):1143-1149. doi:10.1111/cup.13854