Melanoma

Adding the novel immune checkpoint inhibitor relatlimab to the more established nivolumab (Opdivo) significantly extended the progression-free survival (PFS) of patients with previously untreated advanced melanoma in comparison with nivolumab alone in the phase 3 RELATIVITY-047 trial.

Both drugs are from Bristol-Myers Squibb, which funded the study.

“Our findings demonstrate that relatlimab plus nivolumab is a potential novel treatment option for this patient population,” said lead researcher Evan J. Lipson, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Relatlimab has a different mechanism of action from currently available immune checkpoint inhibitors, such as nivolumab and similar agents, which act as inhibitors of the programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1). In contrast, relatlimab acts as an antibody that targets lymphocyte-activation gene 3 (LAG-3), which inhibits T cells and thus helps cancer cells evade immune attack.

“This is the first phase 3 study to validate inhibition of the LAG-3 immune checkpoint as a therapeutic strategy for patients with cancer, and it establishes the LAG-3 pathway as the third immune checkpoint pathway in history, after CLTA-4 and PD-1, for which blockade appears to have clinical benefit,” Dr. Lipson said at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology (ASCO), where this study will be presented (abstract 9503).

Commenting for ASCO, Julie R. Gralow, MD, chief medical officer and executive vice president, agreed that “these results provide validation of the LAG-3 immune checkpoint as a therapeutic target ... and they also support combination treatment with immunotherapies that act on different parts of the immune system.”

When Dr. Lipson was asked whether he would recommend the combination of relatlimab plus nivolumab as a first-line treatment for this patient population, he said that “for many patients,” the first-line treatment choice is made on a “case-by-case” basis.

“We are fortunate in melanoma that we have an ever-expanding list of seemingly effective options, and I think we’ll find at some point this will be added to that list,” he said. “Whether this is the first-line choice for any given patient really depends on a lot of factors,” he added.

Dr. Gralow added a note of caution. “The combination was clearly more toxic, and so I think there will be a lot of discussion” as to when it would be used and for which patients, she said.

In the absence of head-to-head comparisons, “I’m not sure that we have one answer” as to which treatment to choose, she added. With the ever-increasing number of options available in melanoma, the individual treatment choice is “getting more complicated,” she said.
 

Study details

The global RELATIVITY-047 study was conducted in 714 patients with previously untreated unresectable or metastatic melanoma. The participants were randomly assigned to receive either relatlimab plus nivolumab or nivolumab alone.

Dr. Lipson explained that the treatments were given as a fixed-dosed combination, meaning the preparation of relatlimab and nivolumab was given in the “same medication phial and administered as a single intravenous infusion in order to reduce preparation and infusion times and minimize the risk of administration errors.”

PFS, as determined on blinded independent central review, was significantly longer with the combination therapy than with nivolumab alone, at a median of 10.12 months vs. 4.63 months (hazard ratio, 0.75; P = .0055).

At 12 months, the PFS rate among patients given relatlimab plus nivolumab was 47.7%, versus 36.0% among those given nivolumab alone.

“This significant improvement meant that the study met its primary endpoint,” Dr. Lipson said, adding that the PFS benefit “appeared relatively early in the course of therapy.” The curves separated at 12 weeks, and benefit was “sustained” over the course of follow-up.

He added that the performance of nivolumab alone was “in the range” of that seen in previous studies, although he underlined that cross-trial comparison is difficult, given the differences in study design.

“In general, treatment-related adverse events” associated with the combination therapy were “manageable and reflected the safety profile that we typically see with immune checkpoint inhibitors,” he noted.

The results showed that 40.3% of patients who received the combination therapy experienced a grade 3-4 adverse event, compared with 33.4% of those given nivolumab alone. Grade 3-4 treatment-related adverse events leading to discontinuation occurred in 8.5% and 3.1% of patients, respectively.

Three treatment-related deaths occurred in the relatlimab and nivolumab arm. Two such deaths occurred in the nivolumab-alone group.

The study was funded by Bristol Myers Squibb. Dr. Lipson has relationships with Array BioPharma, Bristol Myers Squibb, EMD Serono, Genentech, Macrogenics, Merck, Millennium, Novartis, Sanofi/Regeneron, and Sysmex (inst). Dr. Gralow has relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

A version of this article first appeared on Medscape.com.

Adding the novel immune checkpoint inhibitor relatlimab to the more established nivolumab (Opdivo) significantly extended the progression-free survival (PFS) of patients with previously untreated advanced melanoma in comparison with nivolumab alone in the phase 3 RELATIVITY-047 trial.

Both drugs are from Bristol-Myers Squibb, which funded the study.

“Our findings demonstrate that relatlimab plus nivolumab is a potential novel treatment option for this patient population,” said lead researcher Evan J. Lipson, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Relatlimab has a different mechanism of action from currently available immune checkpoint inhibitors, such as nivolumab and similar agents, which act as inhibitors of the programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1). In contrast, relatlimab acts as an antibody that targets lymphocyte-activation gene 3 (LAG-3), which inhibits T cells and thus helps cancer cells evade immune attack.

“This is the first phase 3 study to validate inhibition of the LAG-3 immune checkpoint as a therapeutic strategy for patients with cancer, and it establishes the LAG-3 pathway as the third immune checkpoint pathway in history, after CLTA-4 and PD-1, for which blockade appears to have clinical benefit,” Dr. Lipson said at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology (ASCO), where this study will be presented (abstract 9503).

Commenting for ASCO, Julie R. Gralow, MD, chief medical officer and executive vice president, agreed that “these results provide validation of the LAG-3 immune checkpoint as a therapeutic target ... and they also support combination treatment with immunotherapies that act on different parts of the immune system.”

When Dr. Lipson was asked whether he would recommend the combination of relatlimab plus nivolumab as a first-line treatment for this patient population, he said that “for many patients,” the first-line treatment choice is made on a “case-by-case” basis.

“We are fortunate in melanoma that we have an ever-expanding list of seemingly effective options, and I think we’ll find at some point this will be added to that list,” he said. “Whether this is the first-line choice for any given patient really depends on a lot of factors,” he added.

Dr. Gralow added a note of caution. “The combination was clearly more toxic, and so I think there will be a lot of discussion” as to when it would be used and for which patients, she said.

In the absence of head-to-head comparisons, “I’m not sure that we have one answer” as to which treatment to choose, she added. With the ever-increasing number of options available in melanoma, the individual treatment choice is “getting more complicated,” she said.
 

Study details

The global RELATIVITY-047 study was conducted in 714 patients with previously untreated unresectable or metastatic melanoma. The participants were randomly assigned to receive either relatlimab plus nivolumab or nivolumab alone.

Dr. Lipson explained that the treatments were given as a fixed-dosed combination, meaning the preparation of relatlimab and nivolumab was given in the “same medication phial and administered as a single intravenous infusion in order to reduce preparation and infusion times and minimize the risk of administration errors.”

PFS, as determined on blinded independent central review, was significantly longer with the combination therapy than with nivolumab alone, at a median of 10.12 months vs. 4.63 months (hazard ratio, 0.75; P = .0055).

At 12 months, the PFS rate among patients given relatlimab plus nivolumab was 47.7%, versus 36.0% among those given nivolumab alone.

“This significant improvement meant that the study met its primary endpoint,” Dr. Lipson said, adding that the PFS benefit “appeared relatively early in the course of therapy.” The curves separated at 12 weeks, and benefit was “sustained” over the course of follow-up.

He added that the performance of nivolumab alone was “in the range” of that seen in previous studies, although he underlined that cross-trial comparison is difficult, given the differences in study design.

“In general, treatment-related adverse events” associated with the combination therapy were “manageable and reflected the safety profile that we typically see with immune checkpoint inhibitors,” he noted.

The results showed that 40.3% of patients who received the combination therapy experienced a grade 3-4 adverse event, compared with 33.4% of those given nivolumab alone. Grade 3-4 treatment-related adverse events leading to discontinuation occurred in 8.5% and 3.1% of patients, respectively.

Three treatment-related deaths occurred in the relatlimab and nivolumab arm. Two such deaths occurred in the nivolumab-alone group.

The study was funded by Bristol Myers Squibb. Dr. Lipson has relationships with Array BioPharma, Bristol Myers Squibb, EMD Serono, Genentech, Macrogenics, Merck, Millennium, Novartis, Sanofi/Regeneron, and Sysmex (inst). Dr. Gralow has relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

A version of this article first appeared on Medscape.com.

Adding the novel immune checkpoint inhibitor relatlimab to the more established nivolumab (Opdivo) significantly extended the progression-free survival (PFS) of patients with previously untreated advanced melanoma in comparison with nivolumab alone in the phase 3 RELATIVITY-047 trial.

Both drugs are from Bristol-Myers Squibb, which funded the study.

“Our findings demonstrate that relatlimab plus nivolumab is a potential novel treatment option for this patient population,” said lead researcher Evan J. Lipson, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Relatlimab has a different mechanism of action from currently available immune checkpoint inhibitors, such as nivolumab and similar agents, which act as inhibitors of the programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1). In contrast, relatlimab acts as an antibody that targets lymphocyte-activation gene 3 (LAG-3), which inhibits T cells and thus helps cancer cells evade immune attack.

“This is the first phase 3 study to validate inhibition of the LAG-3 immune checkpoint as a therapeutic strategy for patients with cancer, and it establishes the LAG-3 pathway as the third immune checkpoint pathway in history, after CLTA-4 and PD-1, for which blockade appears to have clinical benefit,” Dr. Lipson said at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology (ASCO), where this study will be presented (abstract 9503).

Commenting for ASCO, Julie R. Gralow, MD, chief medical officer and executive vice president, agreed that “these results provide validation of the LAG-3 immune checkpoint as a therapeutic target ... and they also support combination treatment with immunotherapies that act on different parts of the immune system.”

When Dr. Lipson was asked whether he would recommend the combination of relatlimab plus nivolumab as a first-line treatment for this patient population, he said that “for many patients,” the first-line treatment choice is made on a “case-by-case” basis.

“We are fortunate in melanoma that we have an ever-expanding list of seemingly effective options, and I think we’ll find at some point this will be added to that list,” he said. “Whether this is the first-line choice for any given patient really depends on a lot of factors,” he added.

Dr. Gralow added a note of caution. “The combination was clearly more toxic, and so I think there will be a lot of discussion” as to when it would be used and for which patients, she said.

In the absence of head-to-head comparisons, “I’m not sure that we have one answer” as to which treatment to choose, she added. With the ever-increasing number of options available in melanoma, the individual treatment choice is “getting more complicated,” she said.
 

Study details

The global RELATIVITY-047 study was conducted in 714 patients with previously untreated unresectable or metastatic melanoma. The participants were randomly assigned to receive either relatlimab plus nivolumab or nivolumab alone.

Dr. Lipson explained that the treatments were given as a fixed-dosed combination, meaning the preparation of relatlimab and nivolumab was given in the “same medication phial and administered as a single intravenous infusion in order to reduce preparation and infusion times and minimize the risk of administration errors.”

PFS, as determined on blinded independent central review, was significantly longer with the combination therapy than with nivolumab alone, at a median of 10.12 months vs. 4.63 months (hazard ratio, 0.75; P = .0055).

At 12 months, the PFS rate among patients given relatlimab plus nivolumab was 47.7%, versus 36.0% among those given nivolumab alone.

“This significant improvement meant that the study met its primary endpoint,” Dr. Lipson said, adding that the PFS benefit “appeared relatively early in the course of therapy.” The curves separated at 12 weeks, and benefit was “sustained” over the course of follow-up.

He added that the performance of nivolumab alone was “in the range” of that seen in previous studies, although he underlined that cross-trial comparison is difficult, given the differences in study design.

“In general, treatment-related adverse events” associated with the combination therapy were “manageable and reflected the safety profile that we typically see with immune checkpoint inhibitors,” he noted.

The results showed that 40.3% of patients who received the combination therapy experienced a grade 3-4 adverse event, compared with 33.4% of those given nivolumab alone. Grade 3-4 treatment-related adverse events leading to discontinuation occurred in 8.5% and 3.1% of patients, respectively.

Three treatment-related deaths occurred in the relatlimab and nivolumab arm. Two such deaths occurred in the nivolumab-alone group.

The study was funded by Bristol Myers Squibb. Dr. Lipson has relationships with Array BioPharma, Bristol Myers Squibb, EMD Serono, Genentech, Macrogenics, Merck, Millennium, Novartis, Sanofi/Regeneron, and Sysmex (inst). Dr. Gralow has relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

A version of this article first appeared on Medscape.com.

A majority of Mohs surgeons have adopted telemedicine during the COVID-19 pandemic, a new survey finds, but only half expressed interest in making it a permanent part of their practices.

A variety of factors combine to make it “very difficult for surgeons to make long-term plans for implementing telemedicine in their practices,” said Mario Maruthur, MD, who presented the findings at the annual meeting of the American College of Mohs Surgery. “Telemedicine likely has a role in Mohs practices, particularly with postop follow-up visits. However, postpandemic reimbursement and regulatory issues need to be formally laid out before Mohs surgeons are able to incorporate it into their permanent work flow.”

Dr. Maruthur, a Mohs surgery and dermatologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York, and colleagues sent a survey to ACMS members in September and October 2020. “We saw first-hand in our surgical practice that telemedicine quickly became an important tool when the pandemic surged in the spring of 2020,” he said. Considering that surgical practices are highly dependent on in-person visits, the impetus for this study was to assess to what degree Mohs practices from across the spectrum, including academic and private practices, embraced telemedicine during the pandemic, and “what these surgical practices used telemedicine for, how it was received by their patients, which telemedicine platforms were most often utilized, and lastly, what are their plans if any for incorporating telemedicine into their surgical practices after the pandemic subsides.”

The researchers received responses from 115 surgeons representing all regions of the country (40% Northeast, 21% South, 21% Midwest, and 18% West). Half practiced in urban areas (37%) and large cities (13%), and 40% were in an academic setting versus 36% in a single-specialty private practice.

More than 70% of the respondents said their case load fell by at least 75% during the initial surge of the pandemic; 80% turned to telemedicine, compared with just 23% who relied on the technology prior to the pandemic. The most commonly used telemedicine technologies were FaceTime, Zoom, Doximity, and Epic.

Mohs surgeons reported most commonly using telemedicine for postsurgery management (77% of the total 115 responses). “Telemedicine is a great fit for this category of visits as they allow the surgeon to view the surgical site and answer any questions they patient may have,” Dr. Maruthur said. “If the surgeon does suspect a postop infection or other concern based on a patient’s signs or symptoms, they can easily schedule the patient for an in-person assessment. We suspect that postop follow-up visits may be the best candidate for long-term use of telemedicine in Mohs surgery practices.”

Surgeons also reported using telemedicine for “spot checks” (61%) and surgical consultations (59%).

However, Dr. Maruther noted that preoperative assessments and spot checks can be difficult to perform using telemedicine. “The quality of the video image is not always great, patients can have a difficult time pointing the camera at the right spot and at the right distance. Even appreciating the actual size of the lesion are all difficult over a video encounter. And there is a lot of information gleaned from in-person physical examination, such as whether the lesion is fixed to a deeper structure and whether there are any nearby scars or other suspicious lesions.”

Nearly three-quarters of the surgeons using the technology said most or all patients were receptive to telemedicine.

However, the surgeons reported multiple barriers to the use of telemedicine: Limitations when compared with physical exams (88%), fitting it into the work flow (58%), patient response and training (57%), reimbursement concerns (50%), implementation of the technology (37%), regulations such as HIPAA (24%), training of staff (17%), and licensing (8%).

In an interview, Sumaira Z. Aasi, MD, director of Mohs and dermatologic surgery, Stanford University, agreed that there are many obstacles to routine use of telemedicine by Mohs surgeons. “As surgeons, we rely on the physical and tactile exam to get a sense of the size and extent of the cancer and characteristics such as the laxity of the surrounding tissue whether the tumor is fixed,” she said. “It is very difficult to access this on a telemedicine visit.”

In addition, she said, “many of our patients are in the elderly population, and some may not be comfortable using this technology. Also, it’s not a work flow that we are comfortable or familiar with. And I think that the technology has to improve to allow for better resolution of images as we ‘examine’ patients through a telemedicine visit.”

She added that “another con is there is a reliance on having the patient point out lesions of concern. Many cancers are picked by a careful in-person examination by a qualified physician/dermatologist/Mohs surgeon when the lesion is quite small or subtle and not even noticed by the patient themselves. This approach invariably leads to earlier biopsies and earlier treatments that can prevent morbidity and save health care money.”

On the other hand, she said, telemedicine “may save patients some time and money in terms of the effort and cost of transportation to come in for simpler postoperative medical visits that are often short in their very nature, such as postop check-ups.”

Most of the surgeons surveyed (69%) said telemedicine probably or definitely deserves a place in the practice Mohs surgery, but only 50% said they’d like to or would definitely pursue giving telemedicine a role in their practices once the pandemic is over.

“At the start of the pandemic, many regulations in areas such as HIPAA were eased, and reimbursements were increased, which allowed telemedicine to be quickly adopted,” Dr. Maruther said. “The government and payers have yet to decide which regulations and reimbursements will be in place after the pandemic. That makes it very difficult for surgeons to make long-term plans for implementing telemedicine in their practices.”

Dr. Aasi predicted that telemedicine will become more appealing to patients and physicians as it its technology and usability improves. More familiarity with its use will also be helpful, she said, and surgeons will be more receptive as it’s incorporated into efficient daily work flow.

The study was funded in part by the National Institutes of Health.

A majority of Mohs surgeons have adopted telemedicine during the COVID-19 pandemic, a new survey finds, but only half expressed interest in making it a permanent part of their practices.

A variety of factors combine to make it “very difficult for surgeons to make long-term plans for implementing telemedicine in their practices,” said Mario Maruthur, MD, who presented the findings at the annual meeting of the American College of Mohs Surgery. “Telemedicine likely has a role in Mohs practices, particularly with postop follow-up visits. However, postpandemic reimbursement and regulatory issues need to be formally laid out before Mohs surgeons are able to incorporate it into their permanent work flow.”

Dr. Maruthur, a Mohs surgery and dermatologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York, and colleagues sent a survey to ACMS members in September and October 2020. “We saw first-hand in our surgical practice that telemedicine quickly became an important tool when the pandemic surged in the spring of 2020,” he said. Considering that surgical practices are highly dependent on in-person visits, the impetus for this study was to assess to what degree Mohs practices from across the spectrum, including academic and private practices, embraced telemedicine during the pandemic, and “what these surgical practices used telemedicine for, how it was received by their patients, which telemedicine platforms were most often utilized, and lastly, what are their plans if any for incorporating telemedicine into their surgical practices after the pandemic subsides.”

The researchers received responses from 115 surgeons representing all regions of the country (40% Northeast, 21% South, 21% Midwest, and 18% West). Half practiced in urban areas (37%) and large cities (13%), and 40% were in an academic setting versus 36% in a single-specialty private practice.

More than 70% of the respondents said their case load fell by at least 75% during the initial surge of the pandemic; 80% turned to telemedicine, compared with just 23% who relied on the technology prior to the pandemic. The most commonly used telemedicine technologies were FaceTime, Zoom, Doximity, and Epic.

Mohs surgeons reported most commonly using telemedicine for postsurgery management (77% of the total 115 responses). “Telemedicine is a great fit for this category of visits as they allow the surgeon to view the surgical site and answer any questions they patient may have,” Dr. Maruthur said. “If the surgeon does suspect a postop infection or other concern based on a patient’s signs or symptoms, they can easily schedule the patient for an in-person assessment. We suspect that postop follow-up visits may be the best candidate for long-term use of telemedicine in Mohs surgery practices.”

Surgeons also reported using telemedicine for “spot checks” (61%) and surgical consultations (59%).

However, Dr. Maruther noted that preoperative assessments and spot checks can be difficult to perform using telemedicine. “The quality of the video image is not always great, patients can have a difficult time pointing the camera at the right spot and at the right distance. Even appreciating the actual size of the lesion are all difficult over a video encounter. And there is a lot of information gleaned from in-person physical examination, such as whether the lesion is fixed to a deeper structure and whether there are any nearby scars or other suspicious lesions.”

Nearly three-quarters of the surgeons using the technology said most or all patients were receptive to telemedicine.

However, the surgeons reported multiple barriers to the use of telemedicine: Limitations when compared with physical exams (88%), fitting it into the work flow (58%), patient response and training (57%), reimbursement concerns (50%), implementation of the technology (37%), regulations such as HIPAA (24%), training of staff (17%), and licensing (8%).

In an interview, Sumaira Z. Aasi, MD, director of Mohs and dermatologic surgery, Stanford University, agreed that there are many obstacles to routine use of telemedicine by Mohs surgeons. “As surgeons, we rely on the physical and tactile exam to get a sense of the size and extent of the cancer and characteristics such as the laxity of the surrounding tissue whether the tumor is fixed,” she said. “It is very difficult to access this on a telemedicine visit.”

In addition, she said, “many of our patients are in the elderly population, and some may not be comfortable using this technology. Also, it’s not a work flow that we are comfortable or familiar with. And I think that the technology has to improve to allow for better resolution of images as we ‘examine’ patients through a telemedicine visit.”

She added that “another con is there is a reliance on having the patient point out lesions of concern. Many cancers are picked by a careful in-person examination by a qualified physician/dermatologist/Mohs surgeon when the lesion is quite small or subtle and not even noticed by the patient themselves. This approach invariably leads to earlier biopsies and earlier treatments that can prevent morbidity and save health care money.”

On the other hand, she said, telemedicine “may save patients some time and money in terms of the effort and cost of transportation to come in for simpler postoperative medical visits that are often short in their very nature, such as postop check-ups.”

Most of the surgeons surveyed (69%) said telemedicine probably or definitely deserves a place in the practice Mohs surgery, but only 50% said they’d like to or would definitely pursue giving telemedicine a role in their practices once the pandemic is over.

“At the start of the pandemic, many regulations in areas such as HIPAA were eased, and reimbursements were increased, which allowed telemedicine to be quickly adopted,” Dr. Maruther said. “The government and payers have yet to decide which regulations and reimbursements will be in place after the pandemic. That makes it very difficult for surgeons to make long-term plans for implementing telemedicine in their practices.”

Dr. Aasi predicted that telemedicine will become more appealing to patients and physicians as it its technology and usability improves. More familiarity with its use will also be helpful, she said, and surgeons will be more receptive as it’s incorporated into efficient daily work flow.

The study was funded in part by the National Institutes of Health.

A majority of Mohs surgeons have adopted telemedicine during the COVID-19 pandemic, a new survey finds, but only half expressed interest in making it a permanent part of their practices.

A variety of factors combine to make it “very difficult for surgeons to make long-term plans for implementing telemedicine in their practices,” said Mario Maruthur, MD, who presented the findings at the annual meeting of the American College of Mohs Surgery. “Telemedicine likely has a role in Mohs practices, particularly with postop follow-up visits. However, postpandemic reimbursement and regulatory issues need to be formally laid out before Mohs surgeons are able to incorporate it into their permanent work flow.”

Dr. Maruthur, a Mohs surgery and dermatologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York, and colleagues sent a survey to ACMS members in September and October 2020. “We saw first-hand in our surgical practice that telemedicine quickly became an important tool when the pandemic surged in the spring of 2020,” he said. Considering that surgical practices are highly dependent on in-person visits, the impetus for this study was to assess to what degree Mohs practices from across the spectrum, including academic and private practices, embraced telemedicine during the pandemic, and “what these surgical practices used telemedicine for, how it was received by their patients, which telemedicine platforms were most often utilized, and lastly, what are their plans if any for incorporating telemedicine into their surgical practices after the pandemic subsides.”

The researchers received responses from 115 surgeons representing all regions of the country (40% Northeast, 21% South, 21% Midwest, and 18% West). Half practiced in urban areas (37%) and large cities (13%), and 40% were in an academic setting versus 36% in a single-specialty private practice.

More than 70% of the respondents said their case load fell by at least 75% during the initial surge of the pandemic; 80% turned to telemedicine, compared with just 23% who relied on the technology prior to the pandemic. The most commonly used telemedicine technologies were FaceTime, Zoom, Doximity, and Epic.

Mohs surgeons reported most commonly using telemedicine for postsurgery management (77% of the total 115 responses). “Telemedicine is a great fit for this category of visits as they allow the surgeon to view the surgical site and answer any questions they patient may have,” Dr. Maruthur said. “If the surgeon does suspect a postop infection or other concern based on a patient’s signs or symptoms, they can easily schedule the patient for an in-person assessment. We suspect that postop follow-up visits may be the best candidate for long-term use of telemedicine in Mohs surgery practices.”

Surgeons also reported using telemedicine for “spot checks” (61%) and surgical consultations (59%).

However, Dr. Maruther noted that preoperative assessments and spot checks can be difficult to perform using telemedicine. “The quality of the video image is not always great, patients can have a difficult time pointing the camera at the right spot and at the right distance. Even appreciating the actual size of the lesion are all difficult over a video encounter. And there is a lot of information gleaned from in-person physical examination, such as whether the lesion is fixed to a deeper structure and whether there are any nearby scars or other suspicious lesions.”

Nearly three-quarters of the surgeons using the technology said most or all patients were receptive to telemedicine.

However, the surgeons reported multiple barriers to the use of telemedicine: Limitations when compared with physical exams (88%), fitting it into the work flow (58%), patient response and training (57%), reimbursement concerns (50%), implementation of the technology (37%), regulations such as HIPAA (24%), training of staff (17%), and licensing (8%).

In an interview, Sumaira Z. Aasi, MD, director of Mohs and dermatologic surgery, Stanford University, agreed that there are many obstacles to routine use of telemedicine by Mohs surgeons. “As surgeons, we rely on the physical and tactile exam to get a sense of the size and extent of the cancer and characteristics such as the laxity of the surrounding tissue whether the tumor is fixed,” she said. “It is very difficult to access this on a telemedicine visit.”

In addition, she said, “many of our patients are in the elderly population, and some may not be comfortable using this technology. Also, it’s not a work flow that we are comfortable or familiar with. And I think that the technology has to improve to allow for better resolution of images as we ‘examine’ patients through a telemedicine visit.”

She added that “another con is there is a reliance on having the patient point out lesions of concern. Many cancers are picked by a careful in-person examination by a qualified physician/dermatologist/Mohs surgeon when the lesion is quite small or subtle and not even noticed by the patient themselves. This approach invariably leads to earlier biopsies and earlier treatments that can prevent morbidity and save health care money.”

On the other hand, she said, telemedicine “may save patients some time and money in terms of the effort and cost of transportation to come in for simpler postoperative medical visits that are often short in their very nature, such as postop check-ups.”

Most of the surgeons surveyed (69%) said telemedicine probably or definitely deserves a place in the practice Mohs surgery, but only 50% said they’d like to or would definitely pursue giving telemedicine a role in their practices once the pandemic is over.

“At the start of the pandemic, many regulations in areas such as HIPAA were eased, and reimbursements were increased, which allowed telemedicine to be quickly adopted,” Dr. Maruther said. “The government and payers have yet to decide which regulations and reimbursements will be in place after the pandemic. That makes it very difficult for surgeons to make long-term plans for implementing telemedicine in their practices.”

Dr. Aasi predicted that telemedicine will become more appealing to patients and physicians as it its technology and usability improves. More familiarity with its use will also be helpful, she said, and surgeons will be more receptive as it’s incorporated into efficient daily work flow.

The study was funded in part by the National Institutes of Health.

You’ve successfully resected a skin cancer lesion, leaving clear margins. Now what?

That’s the question the authors of an evidence-based guideline on reconstruction after skin cancer resection set out to answer.

The guideline – a joint effort of the American Society of Plastic Surgeons, American Society for Dermatologic Surgery, American Academy of Dermatology, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology – Head and Neck Surgery Foundation, American College of Mohs Surgery, American Society for Mohs Surgery, and American Society of Ophthalmic Plastic and Reconstructive Surgery – was published online in the Journal of the American Academy of Dermatology.

From the outset, the panel members realized that to keep the guideline manageable they had to limit recommendations to the practice of reconstruction defined as “cutaneous closure that requires a flap, graft, or tissue rearrangement.”

Other wound closure methods, such as secondary intention healing; simple closures; and complex closures that do not involve flaps, grafts, muscle, or bone, were not covered in the recommendations.

As with similar guidelines, the developers selected seven clinical questions to be addressed, and attempted to find consensus through literature searches, appraisal of the evidence, grading of recommendations, peer review, and public comment.

“We had a very heterogeneous set of things that we were trying to comment on, so we had to keep things somewhat generic,” lead author Andrew Chen, MD, chief of the division of plastic surgery, at the University of Connecticut Health Center, Farmington, said in an interview.

“Skin cancer and reconstruction affect different body areas and areas of different sizes. When we were creating the guidelines, we had to tailor the questions we could ask based on things that would make sense to answer, because obviously we couldn’t ask a question such as: ‘What’s better, a skin graft or a flap?’ Well, there are some things you can’t put a skin graft on – it won’t last, so we couldn’t ask that kind of question,” Dr. Chen said.

Curtis Cetrulo, MD, a plastic and reconstructive surgeon at Massachusetts General Hospital, Boston, who was not involved in the guideline process, said in an interview that the broad recommendations are in keeping with his practice and experience. He also acknowledged, however, the difficulty in creating a guideline that covers the complexity and heterogeneity of reconstructive surgery.

“These are generally good recommendations, but they’re recommendations only, with generally weak levels of evidence. What we really need are clinical trials that can give us definitive answers to some of these questions,” he said.

Recommendations
 

The seven key recommendations, based on the clinical questions raised, are summarized below:

• Delayed (asynchronous) reconstruction is acceptable. Although the quality of the evidence is low and the recommendations are listed as an option, the guideline authors said that depending on the situation, reconstruction can be performed either immediately after resection or delayed by days, weeks, “or even months.”
• Systemic antibiotics should not be routinely prescribed in the interim between resection and reconstruction in adults. Here too, the evidence is low and the recommendation strength is weak, but in “the absence of data showing convincing benefits, systemic antibiotic therapy does not appear necessary or desirable in most cases when there is an interval between cancer resection and reconstruction,” the work group wrote.
• Clinicians may administer perioperative systemic antibiotics in a facility-based setting for adults undergoing reconstruction (3a), but antibiotics should not be routinely prescribed in an office-based setting (3b). The rationale for these recommendations, supported by a moderate level of evidence, is that the risk of surgical-site infection is generally higher in facilities, compared with an office-based setting. Patients who undergo reconstruction in hospitals or surgical centers are more likely to have complex reconstructions or have risks that may make them suitable candidates for antibiotics, but patients in office-based setting may often be spared from the additional costs, side effects, and possible drug interactions from antibiotic use. “There is no evidence in either setting that long-term antibiotic prophylaxis provides infection risk reduction, compared with short-term prophylaxis,” the guideline working group wrote.
• Continue anticoagulant, antithrombotic, and antiplatelet medications for adult patients undergoing reconstruction after skin cancer resection in the office-based setting (4a), and in the facility-based setting should coordinate with the physician managing anticoagulation before modifying the medication prior to surgery (4b). Evidence quality and recommendation strength are both moderate.
• The guideline authors recommend against routine prescription of narcotics as first-line treatment for pain in adults undergoing skin reconstruction (5a), favoring instead acetaminophen and NSAIDs as first-line therapy (5b). Evidence quality and recommendation strength are both moderate.
• In the absence of standardized protocols for the management of pain medications, oral antibiotics, and/or anticoagulants in the perioperative period, clinicians should discuss possible approaches with adult patients. “Educating patients about their perioperative treatment through discussion of treatment strategies may help alleviate anxiety, improve communication, increase patient satisfaction, and maximize patient compliance with the postoperative orders,” the guideline authors wrote.
• The authors suggest that adult patients may be offered follow-up assessments to discuss functional and cosmetic outcomes. “The return of the patient for follow-up visits is an excellent opportunity to better understand and measure these outcomes, improve patient-physician communication, and foster quality improvement. Postoperative follow-up can lead to increased communication between the patient and physician, thereby empowering patients to comment on satisfaction and other important outcomes measures,” they wrote.

What’s next

The guideline developers acknowledged that data are limited regarding reconstructive surgery following skin cancer resection, and that higher-quality studies would help to improve future guidelines. Dr. Chen said that greater use of prospective surgical databases and more systematic collection of patient-reported outcomes could inform further efforts.

The guideline development process was supported by the various groups represented. Dr. Chen and Dr. Cetrulo reported no relevant disclosures.

You’ve successfully resected a skin cancer lesion, leaving clear margins. Now what?

That’s the question the authors of an evidence-based guideline on reconstruction after skin cancer resection set out to answer.

The guideline – a joint effort of the American Society of Plastic Surgeons, American Society for Dermatologic Surgery, American Academy of Dermatology, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology – Head and Neck Surgery Foundation, American College of Mohs Surgery, American Society for Mohs Surgery, and American Society of Ophthalmic Plastic and Reconstructive Surgery – was published online in the Journal of the American Academy of Dermatology.

From the outset, the panel members realized that to keep the guideline manageable they had to limit recommendations to the practice of reconstruction defined as “cutaneous closure that requires a flap, graft, or tissue rearrangement.”

Other wound closure methods, such as secondary intention healing; simple closures; and complex closures that do not involve flaps, grafts, muscle, or bone, were not covered in the recommendations.

As with similar guidelines, the developers selected seven clinical questions to be addressed, and attempted to find consensus through literature searches, appraisal of the evidence, grading of recommendations, peer review, and public comment.

“We had a very heterogeneous set of things that we were trying to comment on, so we had to keep things somewhat generic,” lead author Andrew Chen, MD, chief of the division of plastic surgery, at the University of Connecticut Health Center, Farmington, said in an interview.

“Skin cancer and reconstruction affect different body areas and areas of different sizes. When we were creating the guidelines, we had to tailor the questions we could ask based on things that would make sense to answer, because obviously we couldn’t ask a question such as: ‘What’s better, a skin graft or a flap?’ Well, there are some things you can’t put a skin graft on – it won’t last, so we couldn’t ask that kind of question,” Dr. Chen said.

Curtis Cetrulo, MD, a plastic and reconstructive surgeon at Massachusetts General Hospital, Boston, who was not involved in the guideline process, said in an interview that the broad recommendations are in keeping with his practice and experience. He also acknowledged, however, the difficulty in creating a guideline that covers the complexity and heterogeneity of reconstructive surgery.

“These are generally good recommendations, but they’re recommendations only, with generally weak levels of evidence. What we really need are clinical trials that can give us definitive answers to some of these questions,” he said.

Recommendations
 

The seven key recommendations, based on the clinical questions raised, are summarized below:

• Delayed (asynchronous) reconstruction is acceptable. Although the quality of the evidence is low and the recommendations are listed as an option, the guideline authors said that depending on the situation, reconstruction can be performed either immediately after resection or delayed by days, weeks, “or even months.”
• Systemic antibiotics should not be routinely prescribed in the interim between resection and reconstruction in adults. Here too, the evidence is low and the recommendation strength is weak, but in “the absence of data showing convincing benefits, systemic antibiotic therapy does not appear necessary or desirable in most cases when there is an interval between cancer resection and reconstruction,” the work group wrote.
• Clinicians may administer perioperative systemic antibiotics in a facility-based setting for adults undergoing reconstruction (3a), but antibiotics should not be routinely prescribed in an office-based setting (3b). The rationale for these recommendations, supported by a moderate level of evidence, is that the risk of surgical-site infection is generally higher in facilities, compared with an office-based setting. Patients who undergo reconstruction in hospitals or surgical centers are more likely to have complex reconstructions or have risks that may make them suitable candidates for antibiotics, but patients in office-based setting may often be spared from the additional costs, side effects, and possible drug interactions from antibiotic use. “There is no evidence in either setting that long-term antibiotic prophylaxis provides infection risk reduction, compared with short-term prophylaxis,” the guideline working group wrote.
• Continue anticoagulant, antithrombotic, and antiplatelet medications for adult patients undergoing reconstruction after skin cancer resection in the office-based setting (4a), and in the facility-based setting should coordinate with the physician managing anticoagulation before modifying the medication prior to surgery (4b). Evidence quality and recommendation strength are both moderate.
• The guideline authors recommend against routine prescription of narcotics as first-line treatment for pain in adults undergoing skin reconstruction (5a), favoring instead acetaminophen and NSAIDs as first-line therapy (5b). Evidence quality and recommendation strength are both moderate.
• In the absence of standardized protocols for the management of pain medications, oral antibiotics, and/or anticoagulants in the perioperative period, clinicians should discuss possible approaches with adult patients. “Educating patients about their perioperative treatment through discussion of treatment strategies may help alleviate anxiety, improve communication, increase patient satisfaction, and maximize patient compliance with the postoperative orders,” the guideline authors wrote.
• The authors suggest that adult patients may be offered follow-up assessments to discuss functional and cosmetic outcomes. “The return of the patient for follow-up visits is an excellent opportunity to better understand and measure these outcomes, improve patient-physician communication, and foster quality improvement. Postoperative follow-up can lead to increased communication between the patient and physician, thereby empowering patients to comment on satisfaction and other important outcomes measures,” they wrote.

What’s next

The guideline developers acknowledged that data are limited regarding reconstructive surgery following skin cancer resection, and that higher-quality studies would help to improve future guidelines. Dr. Chen said that greater use of prospective surgical databases and more systematic collection of patient-reported outcomes could inform further efforts.

The guideline development process was supported by the various groups represented. Dr. Chen and Dr. Cetrulo reported no relevant disclosures.

You’ve successfully resected a skin cancer lesion, leaving clear margins. Now what?

That’s the question the authors of an evidence-based guideline on reconstruction after skin cancer resection set out to answer.

The guideline – a joint effort of the American Society of Plastic Surgeons, American Society for Dermatologic Surgery, American Academy of Dermatology, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology – Head and Neck Surgery Foundation, American College of Mohs Surgery, American Society for Mohs Surgery, and American Society of Ophthalmic Plastic and Reconstructive Surgery – was published online in the Journal of the American Academy of Dermatology.

From the outset, the panel members realized that to keep the guideline manageable they had to limit recommendations to the practice of reconstruction defined as “cutaneous closure that requires a flap, graft, or tissue rearrangement.”

Other wound closure methods, such as secondary intention healing; simple closures; and complex closures that do not involve flaps, grafts, muscle, or bone, were not covered in the recommendations.

As with similar guidelines, the developers selected seven clinical questions to be addressed, and attempted to find consensus through literature searches, appraisal of the evidence, grading of recommendations, peer review, and public comment.

“We had a very heterogeneous set of things that we were trying to comment on, so we had to keep things somewhat generic,” lead author Andrew Chen, MD, chief of the division of plastic surgery, at the University of Connecticut Health Center, Farmington, said in an interview.

“Skin cancer and reconstruction affect different body areas and areas of different sizes. When we were creating the guidelines, we had to tailor the questions we could ask based on things that would make sense to answer, because obviously we couldn’t ask a question such as: ‘What’s better, a skin graft or a flap?’ Well, there are some things you can’t put a skin graft on – it won’t last, so we couldn’t ask that kind of question,” Dr. Chen said.

Curtis Cetrulo, MD, a plastic and reconstructive surgeon at Massachusetts General Hospital, Boston, who was not involved in the guideline process, said in an interview that the broad recommendations are in keeping with his practice and experience. He also acknowledged, however, the difficulty in creating a guideline that covers the complexity and heterogeneity of reconstructive surgery.

“These are generally good recommendations, but they’re recommendations only, with generally weak levels of evidence. What we really need are clinical trials that can give us definitive answers to some of these questions,” he said.

Recommendations
 

The seven key recommendations, based on the clinical questions raised, are summarized below:

• Delayed (asynchronous) reconstruction is acceptable. Although the quality of the evidence is low and the recommendations are listed as an option, the guideline authors said that depending on the situation, reconstruction can be performed either immediately after resection or delayed by days, weeks, “or even months.”
• Systemic antibiotics should not be routinely prescribed in the interim between resection and reconstruction in adults. Here too, the evidence is low and the recommendation strength is weak, but in “the absence of data showing convincing benefits, systemic antibiotic therapy does not appear necessary or desirable in most cases when there is an interval between cancer resection and reconstruction,” the work group wrote.
• Clinicians may administer perioperative systemic antibiotics in a facility-based setting for adults undergoing reconstruction (3a), but antibiotics should not be routinely prescribed in an office-based setting (3b). The rationale for these recommendations, supported by a moderate level of evidence, is that the risk of surgical-site infection is generally higher in facilities, compared with an office-based setting. Patients who undergo reconstruction in hospitals or surgical centers are more likely to have complex reconstructions or have risks that may make them suitable candidates for antibiotics, but patients in office-based setting may often be spared from the additional costs, side effects, and possible drug interactions from antibiotic use. “There is no evidence in either setting that long-term antibiotic prophylaxis provides infection risk reduction, compared with short-term prophylaxis,” the guideline working group wrote.
• Continue anticoagulant, antithrombotic, and antiplatelet medications for adult patients undergoing reconstruction after skin cancer resection in the office-based setting (4a), and in the facility-based setting should coordinate with the physician managing anticoagulation before modifying the medication prior to surgery (4b). Evidence quality and recommendation strength are both moderate.
• The guideline authors recommend against routine prescription of narcotics as first-line treatment for pain in adults undergoing skin reconstruction (5a), favoring instead acetaminophen and NSAIDs as first-line therapy (5b). Evidence quality and recommendation strength are both moderate.
• In the absence of standardized protocols for the management of pain medications, oral antibiotics, and/or anticoagulants in the perioperative period, clinicians should discuss possible approaches with adult patients. “Educating patients about their perioperative treatment through discussion of treatment strategies may help alleviate anxiety, improve communication, increase patient satisfaction, and maximize patient compliance with the postoperative orders,” the guideline authors wrote.
• The authors suggest that adult patients may be offered follow-up assessments to discuss functional and cosmetic outcomes. “The return of the patient for follow-up visits is an excellent opportunity to better understand and measure these outcomes, improve patient-physician communication, and foster quality improvement. Postoperative follow-up can lead to increased communication between the patient and physician, thereby empowering patients to comment on satisfaction and other important outcomes measures,” they wrote.

What’s next

The guideline developers acknowledged that data are limited regarding reconstructive surgery following skin cancer resection, and that higher-quality studies would help to improve future guidelines. Dr. Chen said that greater use of prospective surgical databases and more systematic collection of patient-reported outcomes could inform further efforts.

The guideline development process was supported by the various groups represented. Dr. Chen and Dr. Cetrulo reported no relevant disclosures.

Desmoplastic melanoma (DMM) is a rare variant of melanoma that presents major challenges to both clinicians and pathologists.¹ Clinically, the lesions may appear as subtle bland papules, nodules, or plaques. They can be easily mistaken for benign growths, leading to a delayed diagnosis. Consequently, most DMMs at the time of diagnosis tend to be thick, with a mean Breslow depth ranging from 2.0 to 6.5 mm.² Histopathologic evaluation has its difficulties. At scanning magnification, these tumors may show low cellularity, mimicking a benign proliferation. It is well recognized that S-100 and other tumor markers lack specificity for DMM, which can be positive in a range of neural tumors and other cell types.² In some amelanotic tumors, DMM becomes virtually indistinguishable from benign peripheral sheath tumors such as neurofribroma.³

Desmoplastic melanoma is exceedingly uncommon in the United States, with an estimated annual incidence rate of 2.0 cases per million.² Typical locations of presentation include sun-exposed skin, with the head and neck regions representing more than half of reported cases.² Desmoplastic melanoma largely is a disease of fair-skinned patients, with 95.5% of cases in the United States occurring in white non-Hispanic individuals. Advancing age, male gender, and head and neck location are associated with an increased risk for DMM-specific death.² It is important that new or changing lesions in the correct cohort and location are biopsied promptly. We present this case to highlight the ongoing challenges of diagnosing DMM both clinically and histologically and to review the salient features of this often benign-appearing tumor.

Case Report

A 51-year-old White man with a history of prostate cancer, a personal and family history of melanoma, and benign neurofibromas presented with a 6-mm, pink, well-demarcated, soft papule on the left lateral neck (Figure 1). The lesion had been stable for many years but began growing more rapidly 1 to 2 years prior to presentation. The lesion was asymptomatic, and he denied changes in color or texture. There also was no bleeding or ulceration. A review of systems was unremarkable. A shave biopsy of the lesion revealed a nodular spindle cell tumor in the dermis resembling a neurofibroma on low power (Figure 2). However, overlying the tumor was a confluent proliferation positive for MART-1 and S-100, which was consistent with a diagnosis of melanoma in situ (Figure 3). Higher-power evaluation of the dermal proliferation showed both bland and hyperchromatic spindled and epithelioid cells (Figure 4), with rare mitotic figures highlighted by PHH3, an uncommon finding in neurofibromas (Figure 5). The dermal spindle cells were positive for S-100 and p75 and negative for Melan-A. Epithelial membrane antigen highlighted a faint sheath surrounding the dermal component. Ki-67 revealed a mildly increased proliferative index in the dermal component. The diagnosis of DMM was made after outside dermatopathology consultation was in agreement. However, the possibility of a melanoma in situ growing in association with an underlying neurofibroma remained a diagnostic consideration histologically. The lesion was widely excised.

Comment

Differential for DMM
Early DMMs may not show sufficient cytologic atypia to permit obvious distinction from neurofibromas, which becomes problematic when encountering a spindle cell proliferation within severely sun-damaged skin, or even more so when an intraepidermal population of melanocytes is situated above a dermal population of slender, spindled, S-100–positive cells, as seen in our patient.⁴ For these challenging scenarios, Yeh and McCalmont⁴ have proposed evaluating for a CD34 “fingerprint” pattern. This pattern typically is widespread in neurofibroma but absent or limited in DMM, and it is a useful adjunct in the differential diagnosis when conventional immunohistochemistry has little contribution.

There are several case reports in the literature of DMM mimicking other benign or malignant proliferations. In 2012, Jou et al⁵ described a case of a 62-year-old White man who presented with an oral nodule consistent with fibrous inflammatory hyperplasia clinically. Incisional biopsy later confirmed the diagnosis of amelanotic DMM.⁵ Similar case reports have been described in which the diagnosis of DMM was later found to resemble a sarcoma and malignant peripheral nerve sheath tumor.^6,7

Diagnosis of DMM
The prototypical DMM is an asymmetrical and deeply infiltrative spindle cell lesion in severely sun-damaged skin. By definition, the individual melanocytes are separated by connective tissue components, giving the tumor a paucicellular appearance.¹ Although the low cellularity can give a deceptively bland scanning aspect, on high-power examination there usually are identifiable atypical spindled cells with enlarged, elongated, and hyperchromatic nuclei. S-100 typically is diffusely positive in DMM, though occasional cases show more limited staining.⁸ Other commonly used and more specific markers of melanocytic differentiation, including HMB45 and Melan-A, typically are negative in the paucicellular spindle cell components.⁹ Desmoplastic melanoma can be further categorized by the degree of fibrosis within a particular tumor. If fibrosis is prominent throughout the entire tumor, it is named pure DMM. On the other hand, fibrosis may only represent a portion of an otherwise nondesmoplastic melanoma, which is known as combined DMM.¹⁰

Conclusion

We present this case to highlight the ongoing challenges of diagnosing DMM both clinically and histologically. Although a bland-appearing lesion, key clinical features prompting a biopsy in our patient included recent growth of the lesion, a personal history of melanoma, the patient’s fair skin type, a history of heavy sun exposure, and the location of the lesion. According to Busam,¹¹ an associated melanoma in situ component is identified in 80% to 85% of DMM cases. Detection of a melanoma in situ component associated with a malignant spindle cell tumor can help establish the diagnosis of DMM. In the absence of melanoma in situ, a strong diffuse immunoreactivity for S-100 and lack of epithelial markers support the diagnosis.¹¹ After review of the literature, our case likely represents DMM as opposed to a melanoma in situ developing within a neurofibroma.

Desmoplastic melanoma (DMM) is a rare variant of melanoma that presents major challenges to both clinicians and pathologists.¹ Clinically, the lesions may appear as subtle bland papules, nodules, or plaques. They can be easily mistaken for benign growths, leading to a delayed diagnosis. Consequently, most DMMs at the time of diagnosis tend to be thick, with a mean Breslow depth ranging from 2.0 to 6.5 mm.² Histopathologic evaluation has its difficulties. At scanning magnification, these tumors may show low cellularity, mimicking a benign proliferation. It is well recognized that S-100 and other tumor markers lack specificity for DMM, which can be positive in a range of neural tumors and other cell types.² In some amelanotic tumors, DMM becomes virtually indistinguishable from benign peripheral sheath tumors such as neurofribroma.³

Desmoplastic melanoma is exceedingly uncommon in the United States, with an estimated annual incidence rate of 2.0 cases per million.² Typical locations of presentation include sun-exposed skin, with the head and neck regions representing more than half of reported cases.² Desmoplastic melanoma largely is a disease of fair-skinned patients, with 95.5% of cases in the United States occurring in white non-Hispanic individuals. Advancing age, male gender, and head and neck location are associated with an increased risk for DMM-specific death.² It is important that new or changing lesions in the correct cohort and location are biopsied promptly. We present this case to highlight the ongoing challenges of diagnosing DMM both clinically and histologically and to review the salient features of this often benign-appearing tumor.

Case Report

A 51-year-old White man with a history of prostate cancer, a personal and family history of melanoma, and benign neurofibromas presented with a 6-mm, pink, well-demarcated, soft papule on the left lateral neck (Figure 1). The lesion had been stable for many years but began growing more rapidly 1 to 2 years prior to presentation. The lesion was asymptomatic, and he denied changes in color or texture. There also was no bleeding or ulceration. A review of systems was unremarkable. A shave biopsy of the lesion revealed a nodular spindle cell tumor in the dermis resembling a neurofibroma on low power (Figure 2). However, overlying the tumor was a confluent proliferation positive for MART-1 and S-100, which was consistent with a diagnosis of melanoma in situ (Figure 3). Higher-power evaluation of the dermal proliferation showed both bland and hyperchromatic spindled and epithelioid cells (Figure 4), with rare mitotic figures highlighted by PHH3, an uncommon finding in neurofibromas (Figure 5). The dermal spindle cells were positive for S-100 and p75 and negative for Melan-A. Epithelial membrane antigen highlighted a faint sheath surrounding the dermal component. Ki-67 revealed a mildly increased proliferative index in the dermal component. The diagnosis of DMM was made after outside dermatopathology consultation was in agreement. However, the possibility of a melanoma in situ growing in association with an underlying neurofibroma remained a diagnostic consideration histologically. The lesion was widely excised.

Comment

Differential for DMM
Early DMMs may not show sufficient cytologic atypia to permit obvious distinction from neurofibromas, which becomes problematic when encountering a spindle cell proliferation within severely sun-damaged skin, or even more so when an intraepidermal population of melanocytes is situated above a dermal population of slender, spindled, S-100–positive cells, as seen in our patient.⁴ For these challenging scenarios, Yeh and McCalmont⁴ have proposed evaluating for a CD34 “fingerprint” pattern. This pattern typically is widespread in neurofibroma but absent or limited in DMM, and it is a useful adjunct in the differential diagnosis when conventional immunohistochemistry has little contribution.

There are several case reports in the literature of DMM mimicking other benign or malignant proliferations. In 2012, Jou et al⁵ described a case of a 62-year-old White man who presented with an oral nodule consistent with fibrous inflammatory hyperplasia clinically. Incisional biopsy later confirmed the diagnosis of amelanotic DMM.⁵ Similar case reports have been described in which the diagnosis of DMM was later found to resemble a sarcoma and malignant peripheral nerve sheath tumor.^6,7

Diagnosis of DMM
The prototypical DMM is an asymmetrical and deeply infiltrative spindle cell lesion in severely sun-damaged skin. By definition, the individual melanocytes are separated by connective tissue components, giving the tumor a paucicellular appearance.¹ Although the low cellularity can give a deceptively bland scanning aspect, on high-power examination there usually are identifiable atypical spindled cells with enlarged, elongated, and hyperchromatic nuclei. S-100 typically is diffusely positive in DMM, though occasional cases show more limited staining.⁸ Other commonly used and more specific markers of melanocytic differentiation, including HMB45 and Melan-A, typically are negative in the paucicellular spindle cell components.⁹ Desmoplastic melanoma can be further categorized by the degree of fibrosis within a particular tumor. If fibrosis is prominent throughout the entire tumor, it is named pure DMM. On the other hand, fibrosis may only represent a portion of an otherwise nondesmoplastic melanoma, which is known as combined DMM.¹⁰

Conclusion

We present this case to highlight the ongoing challenges of diagnosing DMM both clinically and histologically. Although a bland-appearing lesion, key clinical features prompting a biopsy in our patient included recent growth of the lesion, a personal history of melanoma, the patient’s fair skin type, a history of heavy sun exposure, and the location of the lesion. According to Busam,¹¹ an associated melanoma in situ component is identified in 80% to 85% of DMM cases. Detection of a melanoma in situ component associated with a malignant spindle cell tumor can help establish the diagnosis of DMM. In the absence of melanoma in situ, a strong diffuse immunoreactivity for S-100 and lack of epithelial markers support the diagnosis.¹¹ After review of the literature, our case likely represents DMM as opposed to a melanoma in situ developing within a neurofibroma.

Desmoplastic melanoma (DMM) is a rare variant of melanoma that presents major challenges to both clinicians and pathologists.¹ Clinically, the lesions may appear as subtle bland papules, nodules, or plaques. They can be easily mistaken for benign growths, leading to a delayed diagnosis. Consequently, most DMMs at the time of diagnosis tend to be thick, with a mean Breslow depth ranging from 2.0 to 6.5 mm.² Histopathologic evaluation has its difficulties. At scanning magnification, these tumors may show low cellularity, mimicking a benign proliferation. It is well recognized that S-100 and other tumor markers lack specificity for DMM, which can be positive in a range of neural tumors and other cell types.² In some amelanotic tumors, DMM becomes virtually indistinguishable from benign peripheral sheath tumors such as neurofribroma.³

Desmoplastic melanoma is exceedingly uncommon in the United States, with an estimated annual incidence rate of 2.0 cases per million.² Typical locations of presentation include sun-exposed skin, with the head and neck regions representing more than half of reported cases.² Desmoplastic melanoma largely is a disease of fair-skinned patients, with 95.5% of cases in the United States occurring in white non-Hispanic individuals. Advancing age, male gender, and head and neck location are associated with an increased risk for DMM-specific death.² It is important that new or changing lesions in the correct cohort and location are biopsied promptly. We present this case to highlight the ongoing challenges of diagnosing DMM both clinically and histologically and to review the salient features of this often benign-appearing tumor.

Case Report

A 51-year-old White man with a history of prostate cancer, a personal and family history of melanoma, and benign neurofibromas presented with a 6-mm, pink, well-demarcated, soft papule on the left lateral neck (Figure 1). The lesion had been stable for many years but began growing more rapidly 1 to 2 years prior to presentation. The lesion was asymptomatic, and he denied changes in color or texture. There also was no bleeding or ulceration. A review of systems was unremarkable. A shave biopsy of the lesion revealed a nodular spindle cell tumor in the dermis resembling a neurofibroma on low power (Figure 2). However, overlying the tumor was a confluent proliferation positive for MART-1 and S-100, which was consistent with a diagnosis of melanoma in situ (Figure 3). Higher-power evaluation of the dermal proliferation showed both bland and hyperchromatic spindled and epithelioid cells (Figure 4), with rare mitotic figures highlighted by PHH3, an uncommon finding in neurofibromas (Figure 5). The dermal spindle cells were positive for S-100 and p75 and negative for Melan-A. Epithelial membrane antigen highlighted a faint sheath surrounding the dermal component. Ki-67 revealed a mildly increased proliferative index in the dermal component. The diagnosis of DMM was made after outside dermatopathology consultation was in agreement. However, the possibility of a melanoma in situ growing in association with an underlying neurofibroma remained a diagnostic consideration histologically. The lesion was widely excised.

Comment

Differential for DMM
Early DMMs may not show sufficient cytologic atypia to permit obvious distinction from neurofibromas, which becomes problematic when encountering a spindle cell proliferation within severely sun-damaged skin, or even more so when an intraepidermal population of melanocytes is situated above a dermal population of slender, spindled, S-100–positive cells, as seen in our patient.⁴ For these challenging scenarios, Yeh and McCalmont⁴ have proposed evaluating for a CD34 “fingerprint” pattern. This pattern typically is widespread in neurofibroma but absent or limited in DMM, and it is a useful adjunct in the differential diagnosis when conventional immunohistochemistry has little contribution.

There are several case reports in the literature of DMM mimicking other benign or malignant proliferations. In 2012, Jou et al⁵ described a case of a 62-year-old White man who presented with an oral nodule consistent with fibrous inflammatory hyperplasia clinically. Incisional biopsy later confirmed the diagnosis of amelanotic DMM.⁵ Similar case reports have been described in which the diagnosis of DMM was later found to resemble a sarcoma and malignant peripheral nerve sheath tumor.^6,7

Diagnosis of DMM
The prototypical DMM is an asymmetrical and deeply infiltrative spindle cell lesion in severely sun-damaged skin. By definition, the individual melanocytes are separated by connective tissue components, giving the tumor a paucicellular appearance.¹ Although the low cellularity can give a deceptively bland scanning aspect, on high-power examination there usually are identifiable atypical spindled cells with enlarged, elongated, and hyperchromatic nuclei. S-100 typically is diffusely positive in DMM, though occasional cases show more limited staining.⁸ Other commonly used and more specific markers of melanocytic differentiation, including HMB45 and Melan-A, typically are negative in the paucicellular spindle cell components.⁹ Desmoplastic melanoma can be further categorized by the degree of fibrosis within a particular tumor. If fibrosis is prominent throughout the entire tumor, it is named pure DMM. On the other hand, fibrosis may only represent a portion of an otherwise nondesmoplastic melanoma, which is known as combined DMM.¹⁰

Conclusion

We present this case to highlight the ongoing challenges of diagnosing DMM both clinically and histologically. Although a bland-appearing lesion, key clinical features prompting a biopsy in our patient included recent growth of the lesion, a personal history of melanoma, the patient’s fair skin type, a history of heavy sun exposure, and the location of the lesion. According to Busam,¹¹ an associated melanoma in situ component is identified in 80% to 85% of DMM cases. Detection of a melanoma in situ component associated with a malignant spindle cell tumor can help establish the diagnosis of DMM. In the absence of melanoma in situ, a strong diffuse immunoreactivity for S-100 and lack of epithelial markers support the diagnosis.¹¹ After review of the literature, our case likely represents DMM as opposed to a melanoma in situ developing within a neurofibroma.

Guidelines on Skin Cancer Surgeries During the COVID-19 Pandemic

At the start of the COVID-19 pandemic, the Centers for Disease Control and Prevention issued recommendations to decrease the spread of SARS-CoV-2 and optimize the use of personal protective equipment (PPE) for frontline workers.¹ In the field of dermatologic surgery, the American College of Mohs Surgery, the National Comprehensive Cancer Network, the American Society for Dermatologic Surgery, and the American Academy of Dermatology made recommendations to postpone nonessential and nonurgent procedures.^2-4 The initial guidelines of the American College of Mohs Surgery advised cancellation of all elective surgeries and deferred treatment of most cases of basal cell carcinoma for as long as 3 months; low-risk squamous cell carcinoma (SCC) and melanoma in situ treatment was deferred for as long as 2 or 3 months.³ Additional recommendations were made to reserve inpatient visits for suspicious lesions and high-risk cancers, postpone other nonessential and nonurgent appointments, and utilize telemedicine whenever possible.⁵

These recommendations led to great uncertainty and stress for patients and providers. Although numerous important variables, such as patient risk factors, severity of disease, availability of PPE and staff, and patient-to-provider transmission were considered when creating these guidelines, the patient’s experience likely was not a contributing factor.

COVID-19 Transmission During Mohs Surgery

There have been concerns that surgeons performing Mohs micrographic surgery (MMS) might be at an increased risk for COVID-19, given their close contact with high-risk sites (ie, nose, mouth) and cautery-generated aerosols; most of the estimated transmission risk associated with MMS has been based on head and neck surgery experience and publications.^6-8 Tee and colleagues⁹ recently published their institution’s MMS COVID-19 preventive measures, which, to their knowledge, have prevented all intraoperative transmission of SARS-CoV-2, even in disease-positive patients. Currently, evidence is lacking to support a high risk for SARS-CoV-2 transmission during MMS when proper PPE and personal hygiene measures as well as strict infection control protocols—presurgical COVID-19 testing in high-risk cases, COVID-19 screening optimization, visitor restrictions, and appropriate disinfection between patients—are in place.

The Impact of Postponing Treatment on Patients

Although studies have focused on the effects of the COVID-19 pandemic on physicians practicing MMS,¹⁰ little is known about the effects of delays in skin cancer treatment on patients. A survey conducted in the United Kingdom investigating the patient’s perspective found that patients expressed worry and concern about the possibility that their MMS would be postponed and greatly appreciated continuation of treatment during the pandemic.¹¹

Other medical specialties have reported their patient experiences during the pandemic. In a study examining patient perception of postponed surgical treatment of pelvic floor disorders due to COVID-19, nearly half of survey respondents were unhappy with the delay in receiving care. Furthermore, patients who reported being unhappy were more likely to report feelings of isolation and anxiety because their surgery was postponed.¹² In another study involving patients with lung cancer, 9.1% (N=15) of patients postponed their treatment during the COVID-19 pandemic because of pandemic-related anxiety.¹³

With the goal of improving care at our institution, we conducted a brief institutional review board–approved survey to evaluate how postponing MMS treatment due to the COVID-19 pandemic affected patients. All MMS patients undergoing surgery in June 2020 and July 2020 (N=99) were asked to complete our voluntary and anonymous 23-question survey in person during their procedure. We obtained 88 responses (response rate, 89%). Twenty percent of surveyed patients (n=18) reported that their MMS had been postponed; 78% of those whose MMS was postponed (n=14) indicated some level of anxiety during the waiting period. It was unclear which patients had their treatment postponed based on national guidelines and which ones elected to postpone surgery.

Tips for Health Care Providers

Patient-provider communication highlighting specific skin cancer risk and the risk vs benefit of postponing treatment might reduce anxiety and stress during the waiting period.¹⁴ A study found that COVID-19 posed a bigger threat than most noninvasive skin cancers; therefore, the authors of that study concluded that treatment for most skin cancers could be safely postponed.¹⁵ Specifically, those authors recommended prioritizing treatment for Merkel cell carcinoma, invasive SCC, and melanoma with positive margins or macroscopic residual disease. They proposed that all other skin cancers, including basal cell carcinoma, SCC in situ, and melanoma with negative margins and no macroscopic residual disease, could be safely delayed for as long as 3 months.¹⁵

For patients with multiple risk factors for COVID-19–related morbidity or mortality, delaying skin cancer treatment likely has less risk than contracting the virus.¹⁵ This information should be communicated with patients. Investigation of specific patient concerns is warranted, and case-by-case evaluation of patients’ risk factors and skin cancer risk should be considered.

Based on the current, though limited, literature, delaying medical treatment can have a negative impact on the patient experience. Furthermore, proper precautions have been shown to limit intraoperative transmission of SARS-CoV-2 during MMS, but research is lacking. Practitioners should utilize shared decision-making and evaluate a given patient’s risk factors and concerns when deciding whether to postpone treatment. We encourage other institutions to evaluate the effects that delaying MMS has had on their patients, as further studies would improve understanding of patients’ experiences during a pandemic and potentially influence future dermatology guidelines.

Guidelines on Skin Cancer Surgeries During the COVID-19 Pandemic

At the start of the COVID-19 pandemic, the Centers for Disease Control and Prevention issued recommendations to decrease the spread of SARS-CoV-2 and optimize the use of personal protective equipment (PPE) for frontline workers.¹ In the field of dermatologic surgery, the American College of Mohs Surgery, the National Comprehensive Cancer Network, the American Society for Dermatologic Surgery, and the American Academy of Dermatology made recommendations to postpone nonessential and nonurgent procedures.^2-4 The initial guidelines of the American College of Mohs Surgery advised cancellation of all elective surgeries and deferred treatment of most cases of basal cell carcinoma for as long as 3 months; low-risk squamous cell carcinoma (SCC) and melanoma in situ treatment was deferred for as long as 2 or 3 months.³ Additional recommendations were made to reserve inpatient visits for suspicious lesions and high-risk cancers, postpone other nonessential and nonurgent appointments, and utilize telemedicine whenever possible.⁵

These recommendations led to great uncertainty and stress for patients and providers. Although numerous important variables, such as patient risk factors, severity of disease, availability of PPE and staff, and patient-to-provider transmission were considered when creating these guidelines, the patient’s experience likely was not a contributing factor.

COVID-19 Transmission During Mohs Surgery

There have been concerns that surgeons performing Mohs micrographic surgery (MMS) might be at an increased risk for COVID-19, given their close contact with high-risk sites (ie, nose, mouth) and cautery-generated aerosols; most of the estimated transmission risk associated with MMS has been based on head and neck surgery experience and publications.^6-8 Tee and colleagues⁹ recently published their institution’s MMS COVID-19 preventive measures, which, to their knowledge, have prevented all intraoperative transmission of SARS-CoV-2, even in disease-positive patients. Currently, evidence is lacking to support a high risk for SARS-CoV-2 transmission during MMS when proper PPE and personal hygiene measures as well as strict infection control protocols—presurgical COVID-19 testing in high-risk cases, COVID-19 screening optimization, visitor restrictions, and appropriate disinfection between patients—are in place.

The Impact of Postponing Treatment on Patients

Although studies have focused on the effects of the COVID-19 pandemic on physicians practicing MMS,¹⁰ little is known about the effects of delays in skin cancer treatment on patients. A survey conducted in the United Kingdom investigating the patient’s perspective found that patients expressed worry and concern about the possibility that their MMS would be postponed and greatly appreciated continuation of treatment during the pandemic.¹¹

Other medical specialties have reported their patient experiences during the pandemic. In a study examining patient perception of postponed surgical treatment of pelvic floor disorders due to COVID-19, nearly half of survey respondents were unhappy with the delay in receiving care. Furthermore, patients who reported being unhappy were more likely to report feelings of isolation and anxiety because their surgery was postponed.¹² In another study involving patients with lung cancer, 9.1% (N=15) of patients postponed their treatment during the COVID-19 pandemic because of pandemic-related anxiety.¹³

With the goal of improving care at our institution, we conducted a brief institutional review board–approved survey to evaluate how postponing MMS treatment due to the COVID-19 pandemic affected patients. All MMS patients undergoing surgery in June 2020 and July 2020 (N=99) were asked to complete our voluntary and anonymous 23-question survey in person during their procedure. We obtained 88 responses (response rate, 89%). Twenty percent of surveyed patients (n=18) reported that their MMS had been postponed; 78% of those whose MMS was postponed (n=14) indicated some level of anxiety during the waiting period. It was unclear which patients had their treatment postponed based on national guidelines and which ones elected to postpone surgery.

Tips for Health Care Providers

Patient-provider communication highlighting specific skin cancer risk and the risk vs benefit of postponing treatment might reduce anxiety and stress during the waiting period.¹⁴ A study found that COVID-19 posed a bigger threat than most noninvasive skin cancers; therefore, the authors of that study concluded that treatment for most skin cancers could be safely postponed.¹⁵ Specifically, those authors recommended prioritizing treatment for Merkel cell carcinoma, invasive SCC, and melanoma with positive margins or macroscopic residual disease. They proposed that all other skin cancers, including basal cell carcinoma, SCC in situ, and melanoma with negative margins and no macroscopic residual disease, could be safely delayed for as long as 3 months.¹⁵

For patients with multiple risk factors for COVID-19–related morbidity or mortality, delaying skin cancer treatment likely has less risk than contracting the virus.¹⁵ This information should be communicated with patients. Investigation of specific patient concerns is warranted, and case-by-case evaluation of patients’ risk factors and skin cancer risk should be considered.

Based on the current, though limited, literature, delaying medical treatment can have a negative impact on the patient experience. Furthermore, proper precautions have been shown to limit intraoperative transmission of SARS-CoV-2 during MMS, but research is lacking. Practitioners should utilize shared decision-making and evaluate a given patient’s risk factors and concerns when deciding whether to postpone treatment. We encourage other institutions to evaluate the effects that delaying MMS has had on their patients, as further studies would improve understanding of patients’ experiences during a pandemic and potentially influence future dermatology guidelines.

Guidelines on Skin Cancer Surgeries During the COVID-19 Pandemic

At the start of the COVID-19 pandemic, the Centers for Disease Control and Prevention issued recommendations to decrease the spread of SARS-CoV-2 and optimize the use of personal protective equipment (PPE) for frontline workers.¹ In the field of dermatologic surgery, the American College of Mohs Surgery, the National Comprehensive Cancer Network, the American Society for Dermatologic Surgery, and the American Academy of Dermatology made recommendations to postpone nonessential and nonurgent procedures.^2-4 The initial guidelines of the American College of Mohs Surgery advised cancellation of all elective surgeries and deferred treatment of most cases of basal cell carcinoma for as long as 3 months; low-risk squamous cell carcinoma (SCC) and melanoma in situ treatment was deferred for as long as 2 or 3 months.³ Additional recommendations were made to reserve inpatient visits for suspicious lesions and high-risk cancers, postpone other nonessential and nonurgent appointments, and utilize telemedicine whenever possible.⁵

These recommendations led to great uncertainty and stress for patients and providers. Although numerous important variables, such as patient risk factors, severity of disease, availability of PPE and staff, and patient-to-provider transmission were considered when creating these guidelines, the patient’s experience likely was not a contributing factor.

COVID-19 Transmission During Mohs Surgery

There have been concerns that surgeons performing Mohs micrographic surgery (MMS) might be at an increased risk for COVID-19, given their close contact with high-risk sites (ie, nose, mouth) and cautery-generated aerosols; most of the estimated transmission risk associated with MMS has been based on head and neck surgery experience and publications.^6-8 Tee and colleagues⁹ recently published their institution’s MMS COVID-19 preventive measures, which, to their knowledge, have prevented all intraoperative transmission of SARS-CoV-2, even in disease-positive patients. Currently, evidence is lacking to support a high risk for SARS-CoV-2 transmission during MMS when proper PPE and personal hygiene measures as well as strict infection control protocols—presurgical COVID-19 testing in high-risk cases, COVID-19 screening optimization, visitor restrictions, and appropriate disinfection between patients—are in place.

The Impact of Postponing Treatment on Patients

Although studies have focused on the effects of the COVID-19 pandemic on physicians practicing MMS,¹⁰ little is known about the effects of delays in skin cancer treatment on patients. A survey conducted in the United Kingdom investigating the patient’s perspective found that patients expressed worry and concern about the possibility that their MMS would be postponed and greatly appreciated continuation of treatment during the pandemic.¹¹

Other medical specialties have reported their patient experiences during the pandemic. In a study examining patient perception of postponed surgical treatment of pelvic floor disorders due to COVID-19, nearly half of survey respondents were unhappy with the delay in receiving care. Furthermore, patients who reported being unhappy were more likely to report feelings of isolation and anxiety because their surgery was postponed.¹² In another study involving patients with lung cancer, 9.1% (N=15) of patients postponed their treatment during the COVID-19 pandemic because of pandemic-related anxiety.¹³

With the goal of improving care at our institution, we conducted a brief institutional review board–approved survey to evaluate how postponing MMS treatment due to the COVID-19 pandemic affected patients. All MMS patients undergoing surgery in June 2020 and July 2020 (N=99) were asked to complete our voluntary and anonymous 23-question survey in person during their procedure. We obtained 88 responses (response rate, 89%). Twenty percent of surveyed patients (n=18) reported that their MMS had been postponed; 78% of those whose MMS was postponed (n=14) indicated some level of anxiety during the waiting period. It was unclear which patients had their treatment postponed based on national guidelines and which ones elected to postpone surgery.

Tips for Health Care Providers

Patient-provider communication highlighting specific skin cancer risk and the risk vs benefit of postponing treatment might reduce anxiety and stress during the waiting period.¹⁴ A study found that COVID-19 posed a bigger threat than most noninvasive skin cancers; therefore, the authors of that study concluded that treatment for most skin cancers could be safely postponed.¹⁵ Specifically, those authors recommended prioritizing treatment for Merkel cell carcinoma, invasive SCC, and melanoma with positive margins or macroscopic residual disease. They proposed that all other skin cancers, including basal cell carcinoma, SCC in situ, and melanoma with negative margins and no macroscopic residual disease, could be safely delayed for as long as 3 months.¹⁵

For patients with multiple risk factors for COVID-19–related morbidity or mortality, delaying skin cancer treatment likely has less risk than contracting the virus.¹⁵ This information should be communicated with patients. Investigation of specific patient concerns is warranted, and case-by-case evaluation of patients’ risk factors and skin cancer risk should be considered.

Based on the current, though limited, literature, delaying medical treatment can have a negative impact on the patient experience. Furthermore, proper precautions have been shown to limit intraoperative transmission of SARS-CoV-2 during MMS, but research is lacking. Practitioners should utilize shared decision-making and evaluate a given patient’s risk factors and concerns when deciding whether to postpone treatment. We encourage other institutions to evaluate the effects that delaying MMS has had on their patients, as further studies would improve understanding of patients’ experiences during a pandemic and potentially influence future dermatology guidelines.

The obesity epidemic in the United States may be slowing improvements in cancer mortality, according to a new analysis of over 50 million cancer and heart disease deaths.

“By integrating 20 years of cancer mortality data, we demonstrated that trends in obesity-associated cancer mortality showed signs of recent deceleration, consistent with recent findings for heart disease mortality,” Christy L. Avery, PhD, and associates wrote in JAMA Network Open.

Improvements in mortality related to heart disease slowed after 2011, a phenomenon that has been associated with rising obesity rates. The age-adjusted mortality rate (AAMR) declined at an average of 3.8 deaths per 100,000 persons from 1999 to 2011 but only 0.7 deaths per 100,000 from 2011 to 2018, based on data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER).

To understand trends in cancer mortality and their possible connection with obesity, data for 1999-2018 from the WONDER database were divided into obesity-associated and non–obesity-associated categories and compared with heart disease mortality, they explained. The database included more than 50 million deaths that matched inclusion criteria.

The analysis showed there was difference between obesity-associated and non–obesity-associated cancers that was obscured when all cancer deaths were considered together. The average annual change in AAMR for obesity-associated cancers slowed from –1.19 deaths per 100,000 in 1999-2011 to –0.83 in 2011-2018, Dr. Avery and associates reported.

For non–obesity-associated cancers, the annual change in AAMR increased from –1.62 per 100,000 for 1999-2011 to –2.29 for 2011-2018, following the trend for all cancers: –1.48 per 100,000 during 1999-2011 and –1.77 in 2011-2018, they said.

“The largest mortality decreases were observed for melanoma of the skin and lung cancer, two cancers not associated with obesity. For obesity-associated cancers, stable or increasing mortality rates have been observed for liver and pancreatic cancer among both men and women as well as for uterine cancer among women,” the investigators wrote.

Demographically, however, the slowing improvement in mortality for obesity-associated cancers did not follow the trend for heart disease. The deceleration for cancer was more pronounced for women and for non-Hispanic Whites and not seen at all in non-Hispanic Asian/Pacific Islander individuals. “For heart disease, evidence of a deceleration was consistent across sex, race, and ethnicity,” they said.

There are “longstanding disparities in obesity” among various populations in the United States, and the recent trend of obesity occurring earlier in life may be having an effect. “Whether the findings of decelerating mortality rates potentially signal a changing profile of cancer and heart disease mortality as the consequences of the obesity epidemic are realized remains to be seen,” they concluded.

The investigators reported receiving grants from the National Institutes of Health during the conduct of the study, but no other disclosures were reported.

[email protected]

The obesity epidemic in the United States may be slowing improvements in cancer mortality, according to a new analysis of over 50 million cancer and heart disease deaths.

“By integrating 20 years of cancer mortality data, we demonstrated that trends in obesity-associated cancer mortality showed signs of recent deceleration, consistent with recent findings for heart disease mortality,” Christy L. Avery, PhD, and associates wrote in JAMA Network Open.

Improvements in mortality related to heart disease slowed after 2011, a phenomenon that has been associated with rising obesity rates. The age-adjusted mortality rate (AAMR) declined at an average of 3.8 deaths per 100,000 persons from 1999 to 2011 but only 0.7 deaths per 100,000 from 2011 to 2018, based on data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER).

To understand trends in cancer mortality and their possible connection with obesity, data for 1999-2018 from the WONDER database were divided into obesity-associated and non–obesity-associated categories and compared with heart disease mortality, they explained. The database included more than 50 million deaths that matched inclusion criteria.

The analysis showed there was difference between obesity-associated and non–obesity-associated cancers that was obscured when all cancer deaths were considered together. The average annual change in AAMR for obesity-associated cancers slowed from –1.19 deaths per 100,000 in 1999-2011 to –0.83 in 2011-2018, Dr. Avery and associates reported.

For non–obesity-associated cancers, the annual change in AAMR increased from –1.62 per 100,000 for 1999-2011 to –2.29 for 2011-2018, following the trend for all cancers: –1.48 per 100,000 during 1999-2011 and –1.77 in 2011-2018, they said.

“The largest mortality decreases were observed for melanoma of the skin and lung cancer, two cancers not associated with obesity. For obesity-associated cancers, stable or increasing mortality rates have been observed for liver and pancreatic cancer among both men and women as well as for uterine cancer among women,” the investigators wrote.

Demographically, however, the slowing improvement in mortality for obesity-associated cancers did not follow the trend for heart disease. The deceleration for cancer was more pronounced for women and for non-Hispanic Whites and not seen at all in non-Hispanic Asian/Pacific Islander individuals. “For heart disease, evidence of a deceleration was consistent across sex, race, and ethnicity,” they said.

There are “longstanding disparities in obesity” among various populations in the United States, and the recent trend of obesity occurring earlier in life may be having an effect. “Whether the findings of decelerating mortality rates potentially signal a changing profile of cancer and heart disease mortality as the consequences of the obesity epidemic are realized remains to be seen,” they concluded.

The investigators reported receiving grants from the National Institutes of Health during the conduct of the study, but no other disclosures were reported.

[email protected]

The obesity epidemic in the United States may be slowing improvements in cancer mortality, according to a new analysis of over 50 million cancer and heart disease deaths.

“By integrating 20 years of cancer mortality data, we demonstrated that trends in obesity-associated cancer mortality showed signs of recent deceleration, consistent with recent findings for heart disease mortality,” Christy L. Avery, PhD, and associates wrote in JAMA Network Open.

Improvements in mortality related to heart disease slowed after 2011, a phenomenon that has been associated with rising obesity rates. The age-adjusted mortality rate (AAMR) declined at an average of 3.8 deaths per 100,000 persons from 1999 to 2011 but only 0.7 deaths per 100,000 from 2011 to 2018, based on data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER).

To understand trends in cancer mortality and their possible connection with obesity, data for 1999-2018 from the WONDER database were divided into obesity-associated and non–obesity-associated categories and compared with heart disease mortality, they explained. The database included more than 50 million deaths that matched inclusion criteria.

The analysis showed there was difference between obesity-associated and non–obesity-associated cancers that was obscured when all cancer deaths were considered together. The average annual change in AAMR for obesity-associated cancers slowed from –1.19 deaths per 100,000 in 1999-2011 to –0.83 in 2011-2018, Dr. Avery and associates reported.

For non–obesity-associated cancers, the annual change in AAMR increased from –1.62 per 100,000 for 1999-2011 to –2.29 for 2011-2018, following the trend for all cancers: –1.48 per 100,000 during 1999-2011 and –1.77 in 2011-2018, they said.

“The largest mortality decreases were observed for melanoma of the skin and lung cancer, two cancers not associated with obesity. For obesity-associated cancers, stable or increasing mortality rates have been observed for liver and pancreatic cancer among both men and women as well as for uterine cancer among women,” the investigators wrote.

Demographically, however, the slowing improvement in mortality for obesity-associated cancers did not follow the trend for heart disease. The deceleration for cancer was more pronounced for women and for non-Hispanic Whites and not seen at all in non-Hispanic Asian/Pacific Islander individuals. “For heart disease, evidence of a deceleration was consistent across sex, race, and ethnicity,” they said.

There are “longstanding disparities in obesity” among various populations in the United States, and the recent trend of obesity occurring earlier in life may be having an effect. “Whether the findings of decelerating mortality rates potentially signal a changing profile of cancer and heart disease mortality as the consequences of the obesity epidemic are realized remains to be seen,” they concluded.

The investigators reported receiving grants from the National Institutes of Health during the conduct of the study, but no other disclosures were reported.

[email protected]

According to National Institutes of Health estimates, more than 90,000 new cases of melanoma were diagnosed in 2018.¹ Overall 5-year survival for patients with melanoma exceeds 90%, but individual survival estimates are highly dependent on stage at diagnosis, and survival decreases markedly with metastasis. Therefore, early and accurate diagnosis is critical.

Diagnosis of melanocytic neoplasms usually is performed by dermatopathologists through microscopic examination of stained tissue biopsy sections, a technically simple and effective method that enables a definitive diagnosis of benign nevus or malignant melanoma to be made in most cases. However, approximately 15% of all biopsied melanocytic lesions will exhibit some degree of histopathologic ambiguity,^2-4 meaning that some of their microscopic features will be characteristic of a benign nevus while others will suggest the possibility of malignant melanoma. Diagnostic interpretations often vary in these cases, even among experts, and a definitive diagnosis of benign or malignant may be difficult to achieve by microscopy alone.^2-4 Because of the marked reduction in survival once a melanoma has metastasized, these diagnostically ambiguous lesions often are treated as possible malignant melanomas with complete surgical excision (or re-excision). However, some experts suggest that many histopathologically ambiguous melanocytic neoplasms are, in fact, benign,⁵ a notion supported by epidemiologic evidence.^6,7 Therefore, excision of many ambiguous melanocytic neoplasms might be avoided if definitive diagnosis could be achieved.

A gene expression signature was developed and validated for use as an adjunct to traditional methods of differentiating malignant melanocytic neoplasms from their benign counterparts.^8-11 This test quantifies the RNA transcripts produced by 14 genes known to be overexpressed in malignant melanomas by comparison to benign nevi. These values are then combined algorithmically with measurements of 9 reference genes to produce an objective numerical score that is classified as benign, malignant, or indeterminate. When used by board-certified dermatopathologists and dermatologists confronting ambiguous melanocytic lesions, the test produces substantial increases in definitive diagnoses and prompts changes in treatment recommendations.^12,13 However, the long-term consequences of foregoing surgical excision of melanocytic neoplasms that are diagnostically ambiguous but classified as benign by this test have not yet been formally assessed. In the current study, prospectively tested patients whose ambiguous melanocytic neoplasms were classified as benign by the gene expression signature were followed for up to 4.5 years to evaluate the long-term safety of treatment decisions aligned with benign test results.

Methods

Study Population
As part of a prior study,¹² US-based dermatopathologists submitted tissue sections from biopsied melanocytic neoplasms determined to be diagnostically ambiguous by histopathology for analysis with the gene expression signature (Myriad Genetics, Inc). Diagnostically ambiguous lesions were those lesions that were described as ambiguous, uncertain, equivocal, indeterminate, or other synonymous terms by the submitting dermatopathologist and therefore lacked a confident diagnosis of benign or malignant prior to testing. Patients initially were tested between May 2014 and August 2014, with samples submitted through a prospective clinical experience study designed to assess the impact of the test on diagnosis and treatment decisions. This study was performed under an institutional review board waiver of consent (Quorum #33403/1).

Patients were eligible for inclusion in the current study if their biopsy specimens (1) had an uncertain preliminary diagnosis according to the submitting dermatopathologist (pretest diagnosis of indeterminate); (2) received a negative (benign) score from the gene expression test; (3) were treated as benign by the dermatologist(s) involved in follow-up care; and (4) were submitted by a single site (St. Joseph Medical Center, Houston, Texas). Although a single dermatopathology site was used for this study, multiple dermatologists were involved in the final treatment of these patients. Patients with benign scores who received additional intervention were excluded, as they may have a lower rate of adverse events (ie, metastasis) than those who did not receive intervention and would therefore skew the analysis population. A total of 25 patients from the prior study met these inclusion criteria. The previously collected¹² pretest and posttest de-identified data were compiled from the commercial laboratory databases, and the patients were followed from the time of testing via medical record review performed by the dermatology providers at participating sites. Clinical follow-up data were collected using study-specific case report forms (CRFs) that captured the following: (1) the dates and results of clinical follow-up visits; (2) the type(s) of treatment and interventions (if any) performed at those visits; (3) the specific indication for any intervention performed; (4) any evidence of persistent, locally recurrent, and/or distant melanocytic neoplasia (whether definitively attributable to the tested lesion or not); and (5) death from any cause. The CRF assigned interventions to 1 of 5 categories: excision, excision with sentinel lymph node biopsy, referral to dermatologic or other surgeon, examination only (without surgical intervention), and other. Selection of other required a free-text description of the treatment and indications. Pertinent information not otherwise captured by the CRF also was recordable as free text.

Gene Expression Testing
Gene expression testing was carried out at the time of specimen submission in the prior study¹² as described previously.¹⁴ Briefly, formalin-fixed, paraffin-embedded, unstained tissue sections and/or tissue blocks were submitted for testing along with a single hematoxylin and eosin–stained slide used to identify and designate the representative portion(s) of the lesion to be tested. These areas were macrodissected from unstained tissue sections and pooled for RNA extraction. Expression of 14 biomarker genes and 9 reference genes was measured via quantitative reverse transcription–polymerase chain reaction, performed in triplicate for each individual gene. The assay score was generated through application of a weighted algorithm to the expression values generated through quantitative reverse transcription–polymerase chain reaction. Scores were plotted on a scale ranging from −16.7 to 11.1, with scores from 0.0 to 11.1 classified as malignant, scores from −16.7 to −2.1 as benign, and scores from −2.1 to −0.1 as indeterminate.

Statistical Analysis
Demographic and other baseline characteristics of the patient population were summarized. Follow-up time was calculated as the interval between the date a patient’s gene expression test result was first issued to the provider and the date of the patient’s last recorded visit during the study period. All patient dermatology office visits within the designated follow-up period were documented, with a nonstandard number of visits and follow-up time across all study patients. Statistical analyses were conducted using SAS software (SAS Institute Inc), R software version 3.5.0 (R Foundation for Statistical Computing), and IBM SPSS Statistics software (IBM SPSS Statistics for Windows, Version 25).

Results

Patient Sample
A total of 25 ambiguous melanocytic neoplasms from 25 patients met the study inclusion criteria of a benign gene expression result with subsequent treatment as a benign neoplasm during follow-up. The patient sample statistics are summarized in Table 1. Most patients were younger than 65 years, with an average age at the time of biopsy of 48.4 years. All 25 neoplasms produced negative (benign) gene expression signature scores, all were diagnosed as benign nevi posttest by the submitting dermatopathologist, and all patients were initially treated in accordance with the benign diagnosis by the dermatologist(s) involved in clinical follow-up care. Prior to testing with the gene expression signature, most of these histopathologically indeterminate lesions received differential diagnoses, the most common of which were dysplastic nevus (84%), melanoma arising from a nevus (72%), and superficial spreading melanoma (64%; eTable). After testing with the gene expression signature and receiving a benign score, most lesions received a single differential diagnosis of dysplastic nevus (88%).

Follow-up and Survival
Clinical follow-up time ranged from 0.6 to 53.3 months, with a mean duration (SD) of 38.5 (16.6) months, and patients attended an average of 4 postbiopsy dermatology appointments (mean [SD], 4.6 [3.6]). According to the participating dermatology care providers, none of the 25 patients developed any indication during follow-up that the diagnosis of benign nevus was inaccurate. No patient had evidence of locally recurrent or metastatic melanoma, and none died during the study period.

Treatment/Interventions
The treatment recorded in the CRF was examination only for 21 of 25 patients, excision for 3, and other for 1 (Table 2). Because the explanation for the selection of other in this case described an excision performed at the same anatomic location as the biopsy, this treatment also was considered an excision for purposes of the study analyses. The 3 excisions all occurred at the first postbiopsy dermatology encounter. Across all follow-up visits, no additional surgical interventions occurred (Table 2).

The third excision (case 3) involved a 32-year-old woman with a pigmented lesion on the abdomen (Table 3; Figure, E and F). The clinical description was irregular-appearing black papule, nevus with atypia, and the histopathologic differential diagnosis again included dysplastic nevus, superficial spreading melanoma, and melanoma arising within a preexisting nevus. The gene expression signature result was benign (score, −7.2), and the final diagnosis issued within the accompanying pathology report was nevus with moderate junctional dysplasia. Despite the benign diagnosis, excision was performed 89 days after test result availability, with apparent residual pigmentation as the specified indication. As with the other 2 cases, the treating dermatologist confirmed that neither clinical features nor follow-up events suggested malignancy.

Comment

This study followed a cohort of 25 patients with histopathologically ambiguous melanocytic neoplasms that were classified as benign by a diagnostic gene expression test with the intent of determining the outcomes of patients whose treatment aligned with their benign test result. All patients initially were managed according to their test result. During an average posttest clinical follow-up time of more than 3 years (38.5 months), the 25 biopsied lesions, most of which received a differential diagnosis of dysplastic nevus, were regarded as benign nevi by their dermatologists, and the vast majority (88%) received no further surgical intervention. Three patients underwent subsequent excision of the biopsied lesion, with patient or physician preference as the indication in each instance. None of the 25 patients developed evidence of local recurrence, metastasis, or other findings that prompted doubt of the benign diagnosis. The absence of adverse events during clinical follow-up, particularly given that most lesions were not subjected to further intervention, supports use of the gene expression test as a safe and effective adjunct to the diagnosis and treatment of ambiguous melanocytic neoplasms by dermatologists and dermatopathologists.

Ambiguous melanocytic neoplasms evaluated without the aid of molecular adjuncts often result in equivocal or less-than-definitive diagnoses, and further surgical intervention is commonly undertaken to mitigate against the possibility of a missed melanoma.¹³ In this study, treatment that was aligned with the benign test result allowed most patients to avoid further surgical intervention, which suggests that adjunctive use of the gene signature can contribute to reductions in the physical and economic burdens imposed by unnecessary surgical interventions.^15,16 Moreover, any means of increasing accurate and definitive diagnoses may produce an immediate impact on health outcomes by reducing the anxiety that uncertainty often provokes in patients and health care providers alike.

Study Limitations
This study must be interpreted within the context of its limitations. Obtaining meaningful patient outcome data is a common challenge in health care research due to the requisite length of follow-up and sometimes the lack of definitive evidence of adverse events. This is particularly difficult for melanocytic neoplasms because of an apparent inclination for patients with benign diagnoses to abandon follow-up and an increasing tendency for even minimal diagnostic uncertainty to prompt complete excision. Additionally, the only definitive clinical outcome for melanocytic neoplasms is distant metastasis, which (fortunately for patients) is relatively rare. Not surprisingly, studies documenting clinical outcomes of patients with ambiguous melanocytic neoplasms tested prospectively with diagnostic adjuncts are scarce, and this study’s sample size and clinical follow-up compare favorably with the few that exist.^17,18 Although most melanomas declare themselves through recurrence or metastasis within several years of initial biopsy,^1,19 some are clinically dormant for as long as 10 years after initial detection.^20,21 This may be particularly true for the small or early-stage lesions that now comprise the majority of biopsied neoplasms, and such events would go undetected by this study and many others. It also must be recognized that uneventful follow-up, regardless of duration, cannot prove that a biopsied melanocytic neoplasm was benign. Although only 5 patients had a follow-up time of less than 2 years (the time frame in which most recurrence or metastasis will occur), it cannot be definitively proven that a minimum of 2 years recurrence- or metastasis-free survival indicates a benign lesion. Many early-stage malignant melanomas are eradicated by complete excision or even by the initial biopsy if margins are uninvolved.

Because these limitations are intrinsic to melanocytic neoplasms and current management strategies, they pertain to all investigations seeking insights into biological potential through clinical outcomes. Similarly, all current diagnostic tools and procedures have the potential for sampling error, including histopathology. The rarity of adverse outcomes (recurrence and metastasis) in patients with benign test results within this cohort indicates that false-negative results are uncommon, which is further evidenced by a similar rarity of adverse events in prior studies of the gene expression signature.^8-10,22 A particular strength of this study is that most of the ambiguous melanocytic neoplasms followed did not undergo excision after the initial biopsy, an increasingly uncommon situation that may increase their likelihood to be informative.

It must be emphasized that the gene expression test, similar to other diagnostic adjuncts, is neither a replacement for histopathologic interpretation nor a substitute for judgment. As with all tests, it can produce false-positive and false-negative results. Therefore, it should always be interpreted within the constellation of the many other data points that must be considered when making a distinction between benign nevus and malignant melanoma, including but not limited to patient age, family and personal history of melanoma, anatomic location, clinical features, and histopathologic findings. As is the case for many diseases, careful consideration of all relevant input is necessary to minimize the risk of misdiagnosis that might occur should any single data point prove inaccurate, including the results of adjunctive molecular tests.

Conclusion

Ancillary methods are emerging as useful tools for the diagnostic evaluation of melanocytic neoplasms that cannot be assigned definitive diagnoses using traditional techniques alone. This study suggests that patients with ambiguous melanocytic neoplasms may benefit from diagnoses and treatment decisions aligned with the results of a gene expression test, and that for those with a benign result, simple observation may be a safe alternative to surgical excision. This expands upon prior observations of the test’s influence on diagnoses and treatment decisions and supports its role as part of dermatopathologists’ and dermatologists’ decision-making process for histopathologically ambiguous melanocytic lesions.

According to National Institutes of Health estimates, more than 90,000 new cases of melanoma were diagnosed in 2018.¹ Overall 5-year survival for patients with melanoma exceeds 90%, but individual survival estimates are highly dependent on stage at diagnosis, and survival decreases markedly with metastasis. Therefore, early and accurate diagnosis is critical.

Diagnosis of melanocytic neoplasms usually is performed by dermatopathologists through microscopic examination of stained tissue biopsy sections, a technically simple and effective method that enables a definitive diagnosis of benign nevus or malignant melanoma to be made in most cases. However, approximately 15% of all biopsied melanocytic lesions will exhibit some degree of histopathologic ambiguity,^2-4 meaning that some of their microscopic features will be characteristic of a benign nevus while others will suggest the possibility of malignant melanoma. Diagnostic interpretations often vary in these cases, even among experts, and a definitive diagnosis of benign or malignant may be difficult to achieve by microscopy alone.^2-4 Because of the marked reduction in survival once a melanoma has metastasized, these diagnostically ambiguous lesions often are treated as possible malignant melanomas with complete surgical excision (or re-excision). However, some experts suggest that many histopathologically ambiguous melanocytic neoplasms are, in fact, benign,⁵ a notion supported by epidemiologic evidence.^6,7 Therefore, excision of many ambiguous melanocytic neoplasms might be avoided if definitive diagnosis could be achieved.

A gene expression signature was developed and validated for use as an adjunct to traditional methods of differentiating malignant melanocytic neoplasms from their benign counterparts.^8-11 This test quantifies the RNA transcripts produced by 14 genes known to be overexpressed in malignant melanomas by comparison to benign nevi. These values are then combined algorithmically with measurements of 9 reference genes to produce an objective numerical score that is classified as benign, malignant, or indeterminate. When used by board-certified dermatopathologists and dermatologists confronting ambiguous melanocytic lesions, the test produces substantial increases in definitive diagnoses and prompts changes in treatment recommendations.^12,13 However, the long-term consequences of foregoing surgical excision of melanocytic neoplasms that are diagnostically ambiguous but classified as benign by this test have not yet been formally assessed. In the current study, prospectively tested patients whose ambiguous melanocytic neoplasms were classified as benign by the gene expression signature were followed for up to 4.5 years to evaluate the long-term safety of treatment decisions aligned with benign test results.

Methods

Study Population
As part of a prior study,¹² US-based dermatopathologists submitted tissue sections from biopsied melanocytic neoplasms determined to be diagnostically ambiguous by histopathology for analysis with the gene expression signature (Myriad Genetics, Inc). Diagnostically ambiguous lesions were those lesions that were described as ambiguous, uncertain, equivocal, indeterminate, or other synonymous terms by the submitting dermatopathologist and therefore lacked a confident diagnosis of benign or malignant prior to testing. Patients initially were tested between May 2014 and August 2014, with samples submitted through a prospective clinical experience study designed to assess the impact of the test on diagnosis and treatment decisions. This study was performed under an institutional review board waiver of consent (Quorum #33403/1).

Patients were eligible for inclusion in the current study if their biopsy specimens (1) had an uncertain preliminary diagnosis according to the submitting dermatopathologist (pretest diagnosis of indeterminate); (2) received a negative (benign) score from the gene expression test; (3) were treated as benign by the dermatologist(s) involved in follow-up care; and (4) were submitted by a single site (St. Joseph Medical Center, Houston, Texas). Although a single dermatopathology site was used for this study, multiple dermatologists were involved in the final treatment of these patients. Patients with benign scores who received additional intervention were excluded, as they may have a lower rate of adverse events (ie, metastasis) than those who did not receive intervention and would therefore skew the analysis population. A total of 25 patients from the prior study met these inclusion criteria. The previously collected¹² pretest and posttest de-identified data were compiled from the commercial laboratory databases, and the patients were followed from the time of testing via medical record review performed by the dermatology providers at participating sites. Clinical follow-up data were collected using study-specific case report forms (CRFs) that captured the following: (1) the dates and results of clinical follow-up visits; (2) the type(s) of treatment and interventions (if any) performed at those visits; (3) the specific indication for any intervention performed; (4) any evidence of persistent, locally recurrent, and/or distant melanocytic neoplasia (whether definitively attributable to the tested lesion or not); and (5) death from any cause. The CRF assigned interventions to 1 of 5 categories: excision, excision with sentinel lymph node biopsy, referral to dermatologic or other surgeon, examination only (without surgical intervention), and other. Selection of other required a free-text description of the treatment and indications. Pertinent information not otherwise captured by the CRF also was recordable as free text.

Gene Expression Testing
Gene expression testing was carried out at the time of specimen submission in the prior study¹² as described previously.¹⁴ Briefly, formalin-fixed, paraffin-embedded, unstained tissue sections and/or tissue blocks were submitted for testing along with a single hematoxylin and eosin–stained slide used to identify and designate the representative portion(s) of the lesion to be tested. These areas were macrodissected from unstained tissue sections and pooled for RNA extraction. Expression of 14 biomarker genes and 9 reference genes was measured via quantitative reverse transcription–polymerase chain reaction, performed in triplicate for each individual gene. The assay score was generated through application of a weighted algorithm to the expression values generated through quantitative reverse transcription–polymerase chain reaction. Scores were plotted on a scale ranging from −16.7 to 11.1, with scores from 0.0 to 11.1 classified as malignant, scores from −16.7 to −2.1 as benign, and scores from −2.1 to −0.1 as indeterminate.

Statistical Analysis
Demographic and other baseline characteristics of the patient population were summarized. Follow-up time was calculated as the interval between the date a patient’s gene expression test result was first issued to the provider and the date of the patient’s last recorded visit during the study period. All patient dermatology office visits within the designated follow-up period were documented, with a nonstandard number of visits and follow-up time across all study patients. Statistical analyses were conducted using SAS software (SAS Institute Inc), R software version 3.5.0 (R Foundation for Statistical Computing), and IBM SPSS Statistics software (IBM SPSS Statistics for Windows, Version 25).

Results

Patient Sample
A total of 25 ambiguous melanocytic neoplasms from 25 patients met the study inclusion criteria of a benign gene expression result with subsequent treatment as a benign neoplasm during follow-up. The patient sample statistics are summarized in Table 1. Most patients were younger than 65 years, with an average age at the time of biopsy of 48.4 years. All 25 neoplasms produced negative (benign) gene expression signature scores, all were diagnosed as benign nevi posttest by the submitting dermatopathologist, and all patients were initially treated in accordance with the benign diagnosis by the dermatologist(s) involved in clinical follow-up care. Prior to testing with the gene expression signature, most of these histopathologically indeterminate lesions received differential diagnoses, the most common of which were dysplastic nevus (84%), melanoma arising from a nevus (72%), and superficial spreading melanoma (64%; eTable). After testing with the gene expression signature and receiving a benign score, most lesions received a single differential diagnosis of dysplastic nevus (88%).

Follow-up and Survival
Clinical follow-up time ranged from 0.6 to 53.3 months, with a mean duration (SD) of 38.5 (16.6) months, and patients attended an average of 4 postbiopsy dermatology appointments (mean [SD], 4.6 [3.6]). According to the participating dermatology care providers, none of the 25 patients developed any indication during follow-up that the diagnosis of benign nevus was inaccurate. No patient had evidence of locally recurrent or metastatic melanoma, and none died during the study period.

Treatment/Interventions
The treatment recorded in the CRF was examination only for 21 of 25 patients, excision for 3, and other for 1 (Table 2). Because the explanation for the selection of other in this case described an excision performed at the same anatomic location as the biopsy, this treatment also was considered an excision for purposes of the study analyses. The 3 excisions all occurred at the first postbiopsy dermatology encounter. Across all follow-up visits, no additional surgical interventions occurred (Table 2).

The third excision (case 3) involved a 32-year-old woman with a pigmented lesion on the abdomen (Table 3; Figure, E and F). The clinical description was irregular-appearing black papule, nevus with atypia, and the histopathologic differential diagnosis again included dysplastic nevus, superficial spreading melanoma, and melanoma arising within a preexisting nevus. The gene expression signature result was benign (score, −7.2), and the final diagnosis issued within the accompanying pathology report was nevus with moderate junctional dysplasia. Despite the benign diagnosis, excision was performed 89 days after test result availability, with apparent residual pigmentation as the specified indication. As with the other 2 cases, the treating dermatologist confirmed that neither clinical features nor follow-up events suggested malignancy.

Comment

This study followed a cohort of 25 patients with histopathologically ambiguous melanocytic neoplasms that were classified as benign by a diagnostic gene expression test with the intent of determining the outcomes of patients whose treatment aligned with their benign test result. All patients initially were managed according to their test result. During an average posttest clinical follow-up time of more than 3 years (38.5 months), the 25 biopsied lesions, most of which received a differential diagnosis of dysplastic nevus, were regarded as benign nevi by their dermatologists, and the vast majority (88%) received no further surgical intervention. Three patients underwent subsequent excision of the biopsied lesion, with patient or physician preference as the indication in each instance. None of the 25 patients developed evidence of local recurrence, metastasis, or other findings that prompted doubt of the benign diagnosis. The absence of adverse events during clinical follow-up, particularly given that most lesions were not subjected to further intervention, supports use of the gene expression test as a safe and effective adjunct to the diagnosis and treatment of ambiguous melanocytic neoplasms by dermatologists and dermatopathologists.

Ambiguous melanocytic neoplasms evaluated without the aid of molecular adjuncts often result in equivocal or less-than-definitive diagnoses, and further surgical intervention is commonly undertaken to mitigate against the possibility of a missed melanoma.¹³ In this study, treatment that was aligned with the benign test result allowed most patients to avoid further surgical intervention, which suggests that adjunctive use of the gene signature can contribute to reductions in the physical and economic burdens imposed by unnecessary surgical interventions.^15,16 Moreover, any means of increasing accurate and definitive diagnoses may produce an immediate impact on health outcomes by reducing the anxiety that uncertainty often provokes in patients and health care providers alike.

Study Limitations
This study must be interpreted within the context of its limitations. Obtaining meaningful patient outcome data is a common challenge in health care research due to the requisite length of follow-up and sometimes the lack of definitive evidence of adverse events. This is particularly difficult for melanocytic neoplasms because of an apparent inclination for patients with benign diagnoses to abandon follow-up and an increasing tendency for even minimal diagnostic uncertainty to prompt complete excision. Additionally, the only definitive clinical outcome for melanocytic neoplasms is distant metastasis, which (fortunately for patients) is relatively rare. Not surprisingly, studies documenting clinical outcomes of patients with ambiguous melanocytic neoplasms tested prospectively with diagnostic adjuncts are scarce, and this study’s sample size and clinical follow-up compare favorably with the few that exist.^17,18 Although most melanomas declare themselves through recurrence or metastasis within several years of initial biopsy,^1,19 some are clinically dormant for as long as 10 years after initial detection.^20,21 This may be particularly true for the small or early-stage lesions that now comprise the majority of biopsied neoplasms, and such events would go undetected by this study and many others. It also must be recognized that uneventful follow-up, regardless of duration, cannot prove that a biopsied melanocytic neoplasm was benign. Although only 5 patients had a follow-up time of less than 2 years (the time frame in which most recurrence or metastasis will occur), it cannot be definitively proven that a minimum of 2 years recurrence- or metastasis-free survival indicates a benign lesion. Many early-stage malignant melanomas are eradicated by complete excision or even by the initial biopsy if margins are uninvolved.

Because these limitations are intrinsic to melanocytic neoplasms and current management strategies, they pertain to all investigations seeking insights into biological potential through clinical outcomes. Similarly, all current diagnostic tools and procedures have the potential for sampling error, including histopathology. The rarity of adverse outcomes (recurrence and metastasis) in patients with benign test results within this cohort indicates that false-negative results are uncommon, which is further evidenced by a similar rarity of adverse events in prior studies of the gene expression signature.^8-10,22 A particular strength of this study is that most of the ambiguous melanocytic neoplasms followed did not undergo excision after the initial biopsy, an increasingly uncommon situation that may increase their likelihood to be informative.

It must be emphasized that the gene expression test, similar to other diagnostic adjuncts, is neither a replacement for histopathologic interpretation nor a substitute for judgment. As with all tests, it can produce false-positive and false-negative results. Therefore, it should always be interpreted within the constellation of the many other data points that must be considered when making a distinction between benign nevus and malignant melanoma, including but not limited to patient age, family and personal history of melanoma, anatomic location, clinical features, and histopathologic findings. As is the case for many diseases, careful consideration of all relevant input is necessary to minimize the risk of misdiagnosis that might occur should any single data point prove inaccurate, including the results of adjunctive molecular tests.

Conclusion

Ancillary methods are emerging as useful tools for the diagnostic evaluation of melanocytic neoplasms that cannot be assigned definitive diagnoses using traditional techniques alone. This study suggests that patients with ambiguous melanocytic neoplasms may benefit from diagnoses and treatment decisions aligned with the results of a gene expression test, and that for those with a benign result, simple observation may be a safe alternative to surgical excision. This expands upon prior observations of the test’s influence on diagnoses and treatment decisions and supports its role as part of dermatopathologists’ and dermatologists’ decision-making process for histopathologically ambiguous melanocytic lesions.

According to National Institutes of Health estimates, more than 90,000 new cases of melanoma were diagnosed in 2018.¹ Overall 5-year survival for patients with melanoma exceeds 90%, but individual survival estimates are highly dependent on stage at diagnosis, and survival decreases markedly with metastasis. Therefore, early and accurate diagnosis is critical.

Diagnosis of melanocytic neoplasms usually is performed by dermatopathologists through microscopic examination of stained tissue biopsy sections, a technically simple and effective method that enables a definitive diagnosis of benign nevus or malignant melanoma to be made in most cases. However, approximately 15% of all biopsied melanocytic lesions will exhibit some degree of histopathologic ambiguity,^2-4 meaning that some of their microscopic features will be characteristic of a benign nevus while others will suggest the possibility of malignant melanoma. Diagnostic interpretations often vary in these cases, even among experts, and a definitive diagnosis of benign or malignant may be difficult to achieve by microscopy alone.^2-4 Because of the marked reduction in survival once a melanoma has metastasized, these diagnostically ambiguous lesions often are treated as possible malignant melanomas with complete surgical excision (or re-excision). However, some experts suggest that many histopathologically ambiguous melanocytic neoplasms are, in fact, benign,⁵ a notion supported by epidemiologic evidence.^6,7 Therefore, excision of many ambiguous melanocytic neoplasms might be avoided if definitive diagnosis could be achieved.

A gene expression signature was developed and validated for use as an adjunct to traditional methods of differentiating malignant melanocytic neoplasms from their benign counterparts.^8-11 This test quantifies the RNA transcripts produced by 14 genes known to be overexpressed in malignant melanomas by comparison to benign nevi. These values are then combined algorithmically with measurements of 9 reference genes to produce an objective numerical score that is classified as benign, malignant, or indeterminate. When used by board-certified dermatopathologists and dermatologists confronting ambiguous melanocytic lesions, the test produces substantial increases in definitive diagnoses and prompts changes in treatment recommendations.^12,13 However, the long-term consequences of foregoing surgical excision of melanocytic neoplasms that are diagnostically ambiguous but classified as benign by this test have not yet been formally assessed. In the current study, prospectively tested patients whose ambiguous melanocytic neoplasms were classified as benign by the gene expression signature were followed for up to 4.5 years to evaluate the long-term safety of treatment decisions aligned with benign test results.

Methods

Study Population
As part of a prior study,¹² US-based dermatopathologists submitted tissue sections from biopsied melanocytic neoplasms determined to be diagnostically ambiguous by histopathology for analysis with the gene expression signature (Myriad Genetics, Inc). Diagnostically ambiguous lesions were those lesions that were described as ambiguous, uncertain, equivocal, indeterminate, or other synonymous terms by the submitting dermatopathologist and therefore lacked a confident diagnosis of benign or malignant prior to testing. Patients initially were tested between May 2014 and August 2014, with samples submitted through a prospective clinical experience study designed to assess the impact of the test on diagnosis and treatment decisions. This study was performed under an institutional review board waiver of consent (Quorum #33403/1).

Patients were eligible for inclusion in the current study if their biopsy specimens (1) had an uncertain preliminary diagnosis according to the submitting dermatopathologist (pretest diagnosis of indeterminate); (2) received a negative (benign) score from the gene expression test; (3) were treated as benign by the dermatologist(s) involved in follow-up care; and (4) were submitted by a single site (St. Joseph Medical Center, Houston, Texas). Although a single dermatopathology site was used for this study, multiple dermatologists were involved in the final treatment of these patients. Patients with benign scores who received additional intervention were excluded, as they may have a lower rate of adverse events (ie, metastasis) than those who did not receive intervention and would therefore skew the analysis population. A total of 25 patients from the prior study met these inclusion criteria. The previously collected¹² pretest and posttest de-identified data were compiled from the commercial laboratory databases, and the patients were followed from the time of testing via medical record review performed by the dermatology providers at participating sites. Clinical follow-up data were collected using study-specific case report forms (CRFs) that captured the following: (1) the dates and results of clinical follow-up visits; (2) the type(s) of treatment and interventions (if any) performed at those visits; (3) the specific indication for any intervention performed; (4) any evidence of persistent, locally recurrent, and/or distant melanocytic neoplasia (whether definitively attributable to the tested lesion or not); and (5) death from any cause. The CRF assigned interventions to 1 of 5 categories: excision, excision with sentinel lymph node biopsy, referral to dermatologic or other surgeon, examination only (without surgical intervention), and other. Selection of other required a free-text description of the treatment and indications. Pertinent information not otherwise captured by the CRF also was recordable as free text.

Gene Expression Testing
Gene expression testing was carried out at the time of specimen submission in the prior study¹² as described previously.¹⁴ Briefly, formalin-fixed, paraffin-embedded, unstained tissue sections and/or tissue blocks were submitted for testing along with a single hematoxylin and eosin–stained slide used to identify and designate the representative portion(s) of the lesion to be tested. These areas were macrodissected from unstained tissue sections and pooled for RNA extraction. Expression of 14 biomarker genes and 9 reference genes was measured via quantitative reverse transcription–polymerase chain reaction, performed in triplicate for each individual gene. The assay score was generated through application of a weighted algorithm to the expression values generated through quantitative reverse transcription–polymerase chain reaction. Scores were plotted on a scale ranging from −16.7 to 11.1, with scores from 0.0 to 11.1 classified as malignant, scores from −16.7 to −2.1 as benign, and scores from −2.1 to −0.1 as indeterminate.

Statistical Analysis
Demographic and other baseline characteristics of the patient population were summarized. Follow-up time was calculated as the interval between the date a patient’s gene expression test result was first issued to the provider and the date of the patient’s last recorded visit during the study period. All patient dermatology office visits within the designated follow-up period were documented, with a nonstandard number of visits and follow-up time across all study patients. Statistical analyses were conducted using SAS software (SAS Institute Inc), R software version 3.5.0 (R Foundation for Statistical Computing), and IBM SPSS Statistics software (IBM SPSS Statistics for Windows, Version 25).

Results

Patient Sample
A total of 25 ambiguous melanocytic neoplasms from 25 patients met the study inclusion criteria of a benign gene expression result with subsequent treatment as a benign neoplasm during follow-up. The patient sample statistics are summarized in Table 1. Most patients were younger than 65 years, with an average age at the time of biopsy of 48.4 years. All 25 neoplasms produced negative (benign) gene expression signature scores, all were diagnosed as benign nevi posttest by the submitting dermatopathologist, and all patients were initially treated in accordance with the benign diagnosis by the dermatologist(s) involved in clinical follow-up care. Prior to testing with the gene expression signature, most of these histopathologically indeterminate lesions received differential diagnoses, the most common of which were dysplastic nevus (84%), melanoma arising from a nevus (72%), and superficial spreading melanoma (64%; eTable). After testing with the gene expression signature and receiving a benign score, most lesions received a single differential diagnosis of dysplastic nevus (88%).

Follow-up and Survival
Clinical follow-up time ranged from 0.6 to 53.3 months, with a mean duration (SD) of 38.5 (16.6) months, and patients attended an average of 4 postbiopsy dermatology appointments (mean [SD], 4.6 [3.6]). According to the participating dermatology care providers, none of the 25 patients developed any indication during follow-up that the diagnosis of benign nevus was inaccurate. No patient had evidence of locally recurrent or metastatic melanoma, and none died during the study period.

Treatment/Interventions
The treatment recorded in the CRF was examination only for 21 of 25 patients, excision for 3, and other for 1 (Table 2). Because the explanation for the selection of other in this case described an excision performed at the same anatomic location as the biopsy, this treatment also was considered an excision for purposes of the study analyses. The 3 excisions all occurred at the first postbiopsy dermatology encounter. Across all follow-up visits, no additional surgical interventions occurred (Table 2).

The third excision (case 3) involved a 32-year-old woman with a pigmented lesion on the abdomen (Table 3; Figure, E and F). The clinical description was irregular-appearing black papule, nevus with atypia, and the histopathologic differential diagnosis again included dysplastic nevus, superficial spreading melanoma, and melanoma arising within a preexisting nevus. The gene expression signature result was benign (score, −7.2), and the final diagnosis issued within the accompanying pathology report was nevus with moderate junctional dysplasia. Despite the benign diagnosis, excision was performed 89 days after test result availability, with apparent residual pigmentation as the specified indication. As with the other 2 cases, the treating dermatologist confirmed that neither clinical features nor follow-up events suggested malignancy.

Comment

This study followed a cohort of 25 patients with histopathologically ambiguous melanocytic neoplasms that were classified as benign by a diagnostic gene expression test with the intent of determining the outcomes of patients whose treatment aligned with their benign test result. All patients initially were managed according to their test result. During an average posttest clinical follow-up time of more than 3 years (38.5 months), the 25 biopsied lesions, most of which received a differential diagnosis of dysplastic nevus, were regarded as benign nevi by their dermatologists, and the vast majority (88%) received no further surgical intervention. Three patients underwent subsequent excision of the biopsied lesion, with patient or physician preference as the indication in each instance. None of the 25 patients developed evidence of local recurrence, metastasis, or other findings that prompted doubt of the benign diagnosis. The absence of adverse events during clinical follow-up, particularly given that most lesions were not subjected to further intervention, supports use of the gene expression test as a safe and effective adjunct to the diagnosis and treatment of ambiguous melanocytic neoplasms by dermatologists and dermatopathologists.

Ambiguous melanocytic neoplasms evaluated without the aid of molecular adjuncts often result in equivocal or less-than-definitive diagnoses, and further surgical intervention is commonly undertaken to mitigate against the possibility of a missed melanoma.¹³ In this study, treatment that was aligned with the benign test result allowed most patients to avoid further surgical intervention, which suggests that adjunctive use of the gene signature can contribute to reductions in the physical and economic burdens imposed by unnecessary surgical interventions.^15,16 Moreover, any means of increasing accurate and definitive diagnoses may produce an immediate impact on health outcomes by reducing the anxiety that uncertainty often provokes in patients and health care providers alike.

Study Limitations
This study must be interpreted within the context of its limitations. Obtaining meaningful patient outcome data is a common challenge in health care research due to the requisite length of follow-up and sometimes the lack of definitive evidence of adverse events. This is particularly difficult for melanocytic neoplasms because of an apparent inclination for patients with benign diagnoses to abandon follow-up and an increasing tendency for even minimal diagnostic uncertainty to prompt complete excision. Additionally, the only definitive clinical outcome for melanocytic neoplasms is distant metastasis, which (fortunately for patients) is relatively rare. Not surprisingly, studies documenting clinical outcomes of patients with ambiguous melanocytic neoplasms tested prospectively with diagnostic adjuncts are scarce, and this study’s sample size and clinical follow-up compare favorably with the few that exist.^17,18 Although most melanomas declare themselves through recurrence or metastasis within several years of initial biopsy,^1,19 some are clinically dormant for as long as 10 years after initial detection.^20,21 This may be particularly true for the small or early-stage lesions that now comprise the majority of biopsied neoplasms, and such events would go undetected by this study and many others. It also must be recognized that uneventful follow-up, regardless of duration, cannot prove that a biopsied melanocytic neoplasm was benign. Although only 5 patients had a follow-up time of less than 2 years (the time frame in which most recurrence or metastasis will occur), it cannot be definitively proven that a minimum of 2 years recurrence- or metastasis-free survival indicates a benign lesion. Many early-stage malignant melanomas are eradicated by complete excision or even by the initial biopsy if margins are uninvolved.

Because these limitations are intrinsic to melanocytic neoplasms and current management strategies, they pertain to all investigations seeking insights into biological potential through clinical outcomes. Similarly, all current diagnostic tools and procedures have the potential for sampling error, including histopathology. The rarity of adverse outcomes (recurrence and metastasis) in patients with benign test results within this cohort indicates that false-negative results are uncommon, which is further evidenced by a similar rarity of adverse events in prior studies of the gene expression signature.^8-10,22 A particular strength of this study is that most of the ambiguous melanocytic neoplasms followed did not undergo excision after the initial biopsy, an increasingly uncommon situation that may increase their likelihood to be informative.

It must be emphasized that the gene expression test, similar to other diagnostic adjuncts, is neither a replacement for histopathologic interpretation nor a substitute for judgment. As with all tests, it can produce false-positive and false-negative results. Therefore, it should always be interpreted within the constellation of the many other data points that must be considered when making a distinction between benign nevus and malignant melanoma, including but not limited to patient age, family and personal history of melanoma, anatomic location, clinical features, and histopathologic findings. As is the case for many diseases, careful consideration of all relevant input is necessary to minimize the risk of misdiagnosis that might occur should any single data point prove inaccurate, including the results of adjunctive molecular tests.

Conclusion

Ancillary methods are emerging as useful tools for the diagnostic evaluation of melanocytic neoplasms that cannot be assigned definitive diagnoses using traditional techniques alone. This study suggests that patients with ambiguous melanocytic neoplasms may benefit from diagnoses and treatment decisions aligned with the results of a gene expression test, and that for those with a benign result, simple observation may be a safe alternative to surgical excision. This expands upon prior observations of the test’s influence on diagnoses and treatment decisions and supports its role as part of dermatopathologists’ and dermatologists’ decision-making process for histopathologically ambiguous melanocytic lesions.

Intentional tanning—through sun exposure and tanning beds—is an easily avoidable contributor to skin cancer development and an important area for public education. Since the advent of social media, a correlation between social media use and increased indoor tanning behaviors has been reported.¹ In 2010, 11.3% of US adults aged 18 to 29 years reported using a tanning bed in the last 12 months.² The American Academy of Dermatology first published their “Position Statement on Indoor Tanning” in 1998, endorsing a ban on the sale of indoor tanning equipment for nonmedical purposes.³

Although there has been no outright ban on indoor tanning, regulations have been put in place in many states—including Texas, where (as of 2013) a person younger than 18 years must have written consent from their parent(s) to use a tanning bed. Despite efforts of organizations including the American Academy of Dermatology and the government to educate the public on skin cancer prevention and sun safety, the skin cancer rate has been steadily increasing over the last 20 years.

There is a constant campaign among dermatologists to educate their patients on how to reduce or avoid the risk for skin cancer, including the use of sunscreen and avoidance of tanning. Adolescents and young adults are an especially important demographic to reach and educate because increased UV light exposure during these years leads to a greatly increased risk for skin cancer later in life.⁴ Data on the overall prevalence of tanning and the demographics of participation in tanning activities are important to capture and can be used to efficiently target higher-risk populations.

In this study, we aimed to investigate the attitudes and behaviors of adolescents and young adults regarding sun protection and tanning. We also aimed to determine which avenues, including social media, would be most effective at educating about skin cancer awareness and sun protection to the higher-risk younger population.

Materials and Methods

We developed an institutional review board–approved protocol for the prospective collection of data from registered patients at the dermatology clinic of the Mays Cancer Center at the University of Texas Health at San Antonio. A paper survey containing 15 rating-scale questions was administered to 60 patients aged 13 to 27 years. Surveys were administered during intake, prior to the patients’ visit with a dermatologist; all visits were of a functional (not cosmetic) nature. Data collection spanned June to August 2018. Survey results were entered into Research Electronic Data Capture (REDCap) software for qualitative analysis.

Results

Sixty patients responded to the survey. The mean age of respondents was 19.5 years. No surveys were excluded from the data set. Table 1 provides baseline characteristics of respondents. Some respondents left questions unanswered, resulting in questions with fewer than 60 responses.

Among respondents to the survey, 70% (42/60) reported it is very important to protect their skin from sun exposure, and 30% (18/60) reported it is somewhat important. Regarding sunscreen use, 70% (42/60) indicated they use sunscreen only before outdoor activities, 12% (7/60) use sunscreen daily, and 17% (10/60) never use sunscreen. Of those who use sunscreen, 52% (28/54) do so to prevent skin damage and aging and 44% (24/54) to prevent skin cancer. Twenty-three percent (13/56) of respondents reported finding tanned skin attractive; 26% (14/55) reported wanting to be tan. Looking at race, 28% (10/36) of Whites, 25% (5/20) of Spanish/Hispanic/Latinos, and 22% (2/9) of Asians found tanned skin attractive; no Black respondents found tanned skin attractive.

Regarding tanning, 12% (7/57) reported using a tanning bed in their lifetime and 4% (2/57) in the last year; 34% (19/56) reported deliberately tanning outdoors; and 9% (5/56) reported using sunless or spray-on tanning. Dermatologists (75% [42/56]), primary care physicians (69.6% [39/56]), and parents (46.4% [26/56]) were perceived as more effective sources of skin care education; among media modalities, television (33.9% [19/56]), Instagram (30.4% [17/60]), and YouTube (23.2% [13/60]) were perceived as more effective sources of skin care education (Table 2).

Comment

Perceptions of Tanning
Almost one-quarter of respondents found tanned skin attractive, which might reflect a shift from prior generations. Compared to the 11% of respondents in the 2010 survey,² only 3.5% (2/57) of our respondents reported using a tanning bed in the last year, which could reflect the results of recent Texas legislation restricting the use of tanning beds by adolescents.

An alarming number of respondents reported going outdoors with the intention of tanning; although it appears that indoor tanning education has been successful, this finding shows that there is still a need for sun protection education because outdoor tanning is not a suitable alternative. A small number of respondents reported getting a sunless or spray-on tan, which is a risk-free alternative to indoor tanning.

Despite all respondents stating that protecting skin from the sun is important, most respondents surveyed do not use sunscreen daily. More respondents use sunscreen to prevent damage and aging than to prevent skin cancer. Young people might be more alarmed by the threat of early aging and losing their “youthful appearance” than by the possibility of developing skin cancer in the distant future. This discrepancy might indicate a lack of knowledge and be an important focus for future education efforts.

Perceptions of Trustworthiness of Education Sources
Our findings show dermatologists and primary care physicians are important educators on skin protection. Primary care physicians should remain vigilant to recognize at-risk patients who would benefit from skin protection education, especially those who do not see a dermatologist. Education of young people focusing on their concern over maintaining a youthful appearance instead of the possibility of developing skin cancer in the future might be more effective.

Although education provided by a physician is effective, using media—particularly social media—might be more efficient. Television, Instagram, and YouTube were listed by respondents as the 3 most preferred media outlets for skin health education, which shows important areas of focus for future advertising. Facebook was listed at a surprisingly low level, possibly showing the change in use of certain social media websites among this age group. According to the Pew Research Center, the most widely used social media apps among young adults aged 18 to 29 years are YouTube (91%), Facebook (63%), Instagram (67%), and Snapchat (62%). More than half of the same demographic visit Facebook (74%), Instagram (63%), Snapchat (61%), and YouTube (51%) daily.⁵ Although respondents to our survey were not specifically asked about the frequency of their use of social media and our data set includes patients younger than 18 years, we know that social media use has been increasing over the last decade among adolescents.¹ Therefore, we assume that more than one-half of respondents to our survey use their reported social media platforms daily.

Social media is an underused medium for skin cancer prevention education and can reach those who do not regularly see a dermatologist. Unlike printed pamphlets and posters, advertisements through social media can use metrics such as age, race, gender, and interests to target high-risk individuals.

Study Limitations
This was a single-site study of currently enrolled dermatology patients who might be more aware of skin protection than the general population because they are being treated by a dermatologist. Survey questions regarding demographics, required by our institution, could not effectively differentiate Hispanic and White patients. Respondents could have been subject to the Hawthorne effect—awareness that their behavior is being observed—when responding to the survey because it was administered in the office prior to being seen by a dermatologist.

Intentional tanning—through sun exposure and tanning beds—is an easily avoidable contributor to skin cancer development and an important area for public education. Since the advent of social media, a correlation between social media use and increased indoor tanning behaviors has been reported.¹ In 2010, 11.3% of US adults aged 18 to 29 years reported using a tanning bed in the last 12 months.² The American Academy of Dermatology first published their “Position Statement on Indoor Tanning” in 1998, endorsing a ban on the sale of indoor tanning equipment for nonmedical purposes.³

Although there has been no outright ban on indoor tanning, regulations have been put in place in many states—including Texas, where (as of 2013) a person younger than 18 years must have written consent from their parent(s) to use a tanning bed. Despite efforts of organizations including the American Academy of Dermatology and the government to educate the public on skin cancer prevention and sun safety, the skin cancer rate has been steadily increasing over the last 20 years.

There is a constant campaign among dermatologists to educate their patients on how to reduce or avoid the risk for skin cancer, including the use of sunscreen and avoidance of tanning. Adolescents and young adults are an especially important demographic to reach and educate because increased UV light exposure during these years leads to a greatly increased risk for skin cancer later in life.⁴ Data on the overall prevalence of tanning and the demographics of participation in tanning activities are important to capture and can be used to efficiently target higher-risk populations.

In this study, we aimed to investigate the attitudes and behaviors of adolescents and young adults regarding sun protection and tanning. We also aimed to determine which avenues, including social media, would be most effective at educating about skin cancer awareness and sun protection to the higher-risk younger population.

Materials and Methods

We developed an institutional review board–approved protocol for the prospective collection of data from registered patients at the dermatology clinic of the Mays Cancer Center at the University of Texas Health at San Antonio. A paper survey containing 15 rating-scale questions was administered to 60 patients aged 13 to 27 years. Surveys were administered during intake, prior to the patients’ visit with a dermatologist; all visits were of a functional (not cosmetic) nature. Data collection spanned June to August 2018. Survey results were entered into Research Electronic Data Capture (REDCap) software for qualitative analysis.

Results

Sixty patients responded to the survey. The mean age of respondents was 19.5 years. No surveys were excluded from the data set. Table 1 provides baseline characteristics of respondents. Some respondents left questions unanswered, resulting in questions with fewer than 60 responses.

Among respondents to the survey, 70% (42/60) reported it is very important to protect their skin from sun exposure, and 30% (18/60) reported it is somewhat important. Regarding sunscreen use, 70% (42/60) indicated they use sunscreen only before outdoor activities, 12% (7/60) use sunscreen daily, and 17% (10/60) never use sunscreen. Of those who use sunscreen, 52% (28/54) do so to prevent skin damage and aging and 44% (24/54) to prevent skin cancer. Twenty-three percent (13/56) of respondents reported finding tanned skin attractive; 26% (14/55) reported wanting to be tan. Looking at race, 28% (10/36) of Whites, 25% (5/20) of Spanish/Hispanic/Latinos, and 22% (2/9) of Asians found tanned skin attractive; no Black respondents found tanned skin attractive.

Regarding tanning, 12% (7/57) reported using a tanning bed in their lifetime and 4% (2/57) in the last year; 34% (19/56) reported deliberately tanning outdoors; and 9% (5/56) reported using sunless or spray-on tanning. Dermatologists (75% [42/56]), primary care physicians (69.6% [39/56]), and parents (46.4% [26/56]) were perceived as more effective sources of skin care education; among media modalities, television (33.9% [19/56]), Instagram (30.4% [17/60]), and YouTube (23.2% [13/60]) were perceived as more effective sources of skin care education (Table 2).

Comment

Perceptions of Tanning
Almost one-quarter of respondents found tanned skin attractive, which might reflect a shift from prior generations. Compared to the 11% of respondents in the 2010 survey,² only 3.5% (2/57) of our respondents reported using a tanning bed in the last year, which could reflect the results of recent Texas legislation restricting the use of tanning beds by adolescents.

An alarming number of respondents reported going outdoors with the intention of tanning; although it appears that indoor tanning education has been successful, this finding shows that there is still a need for sun protection education because outdoor tanning is not a suitable alternative. A small number of respondents reported getting a sunless or spray-on tan, which is a risk-free alternative to indoor tanning.

Despite all respondents stating that protecting skin from the sun is important, most respondents surveyed do not use sunscreen daily. More respondents use sunscreen to prevent damage and aging than to prevent skin cancer. Young people might be more alarmed by the threat of early aging and losing their “youthful appearance” than by the possibility of developing skin cancer in the distant future. This discrepancy might indicate a lack of knowledge and be an important focus for future education efforts.

Perceptions of Trustworthiness of Education Sources
Our findings show dermatologists and primary care physicians are important educators on skin protection. Primary care physicians should remain vigilant to recognize at-risk patients who would benefit from skin protection education, especially those who do not see a dermatologist. Education of young people focusing on their concern over maintaining a youthful appearance instead of the possibility of developing skin cancer in the future might be more effective.

Although education provided by a physician is effective, using media—particularly social media—might be more efficient. Television, Instagram, and YouTube were listed by respondents as the 3 most preferred media outlets for skin health education, which shows important areas of focus for future advertising. Facebook was listed at a surprisingly low level, possibly showing the change in use of certain social media websites among this age group. According to the Pew Research Center, the most widely used social media apps among young adults aged 18 to 29 years are YouTube (91%), Facebook (63%), Instagram (67%), and Snapchat (62%). More than half of the same demographic visit Facebook (74%), Instagram (63%), Snapchat (61%), and YouTube (51%) daily.⁵ Although respondents to our survey were not specifically asked about the frequency of their use of social media and our data set includes patients younger than 18 years, we know that social media use has been increasing over the last decade among adolescents.¹ Therefore, we assume that more than one-half of respondents to our survey use their reported social media platforms daily.

Social media is an underused medium for skin cancer prevention education and can reach those who do not regularly see a dermatologist. Unlike printed pamphlets and posters, advertisements through social media can use metrics such as age, race, gender, and interests to target high-risk individuals.

Study Limitations
This was a single-site study of currently enrolled dermatology patients who might be more aware of skin protection than the general population because they are being treated by a dermatologist. Survey questions regarding demographics, required by our institution, could not effectively differentiate Hispanic and White patients. Respondents could have been subject to the Hawthorne effect—awareness that their behavior is being observed—when responding to the survey because it was administered in the office prior to being seen by a dermatologist.

Intentional tanning—through sun exposure and tanning beds—is an easily avoidable contributor to skin cancer development and an important area for public education. Since the advent of social media, a correlation between social media use and increased indoor tanning behaviors has been reported.¹ In 2010, 11.3% of US adults aged 18 to 29 years reported using a tanning bed in the last 12 months.² The American Academy of Dermatology first published their “Position Statement on Indoor Tanning” in 1998, endorsing a ban on the sale of indoor tanning equipment for nonmedical purposes.³

Although there has been no outright ban on indoor tanning, regulations have been put in place in many states—including Texas, where (as of 2013) a person younger than 18 years must have written consent from their parent(s) to use a tanning bed. Despite efforts of organizations including the American Academy of Dermatology and the government to educate the public on skin cancer prevention and sun safety, the skin cancer rate has been steadily increasing over the last 20 years.

There is a constant campaign among dermatologists to educate their patients on how to reduce or avoid the risk for skin cancer, including the use of sunscreen and avoidance of tanning. Adolescents and young adults are an especially important demographic to reach and educate because increased UV light exposure during these years leads to a greatly increased risk for skin cancer later in life.⁴ Data on the overall prevalence of tanning and the demographics of participation in tanning activities are important to capture and can be used to efficiently target higher-risk populations.

In this study, we aimed to investigate the attitudes and behaviors of adolescents and young adults regarding sun protection and tanning. We also aimed to determine which avenues, including social media, would be most effective at educating about skin cancer awareness and sun protection to the higher-risk younger population.

Materials and Methods

We developed an institutional review board–approved protocol for the prospective collection of data from registered patients at the dermatology clinic of the Mays Cancer Center at the University of Texas Health at San Antonio. A paper survey containing 15 rating-scale questions was administered to 60 patients aged 13 to 27 years. Surveys were administered during intake, prior to the patients’ visit with a dermatologist; all visits were of a functional (not cosmetic) nature. Data collection spanned June to August 2018. Survey results were entered into Research Electronic Data Capture (REDCap) software for qualitative analysis.

Results

Sixty patients responded to the survey. The mean age of respondents was 19.5 years. No surveys were excluded from the data set. Table 1 provides baseline characteristics of respondents. Some respondents left questions unanswered, resulting in questions with fewer than 60 responses.

Among respondents to the survey, 70% (42/60) reported it is very important to protect their skin from sun exposure, and 30% (18/60) reported it is somewhat important. Regarding sunscreen use, 70% (42/60) indicated they use sunscreen only before outdoor activities, 12% (7/60) use sunscreen daily, and 17% (10/60) never use sunscreen. Of those who use sunscreen, 52% (28/54) do so to prevent skin damage and aging and 44% (24/54) to prevent skin cancer. Twenty-three percent (13/56) of respondents reported finding tanned skin attractive; 26% (14/55) reported wanting to be tan. Looking at race, 28% (10/36) of Whites, 25% (5/20) of Spanish/Hispanic/Latinos, and 22% (2/9) of Asians found tanned skin attractive; no Black respondents found tanned skin attractive.

Regarding tanning, 12% (7/57) reported using a tanning bed in their lifetime and 4% (2/57) in the last year; 34% (19/56) reported deliberately tanning outdoors; and 9% (5/56) reported using sunless or spray-on tanning. Dermatologists (75% [42/56]), primary care physicians (69.6% [39/56]), and parents (46.4% [26/56]) were perceived as more effective sources of skin care education; among media modalities, television (33.9% [19/56]), Instagram (30.4% [17/60]), and YouTube (23.2% [13/60]) were perceived as more effective sources of skin care education (Table 2).

Comment

Perceptions of Tanning
Almost one-quarter of respondents found tanned skin attractive, which might reflect a shift from prior generations. Compared to the 11% of respondents in the 2010 survey,² only 3.5% (2/57) of our respondents reported using a tanning bed in the last year, which could reflect the results of recent Texas legislation restricting the use of tanning beds by adolescents.

An alarming number of respondents reported going outdoors with the intention of tanning; although it appears that indoor tanning education has been successful, this finding shows that there is still a need for sun protection education because outdoor tanning is not a suitable alternative. A small number of respondents reported getting a sunless or spray-on tan, which is a risk-free alternative to indoor tanning.

Despite all respondents stating that protecting skin from the sun is important, most respondents surveyed do not use sunscreen daily. More respondents use sunscreen to prevent damage and aging than to prevent skin cancer. Young people might be more alarmed by the threat of early aging and losing their “youthful appearance” than by the possibility of developing skin cancer in the distant future. This discrepancy might indicate a lack of knowledge and be an important focus for future education efforts.

Perceptions of Trustworthiness of Education Sources
Our findings show dermatologists and primary care physicians are important educators on skin protection. Primary care physicians should remain vigilant to recognize at-risk patients who would benefit from skin protection education, especially those who do not see a dermatologist. Education of young people focusing on their concern over maintaining a youthful appearance instead of the possibility of developing skin cancer in the future might be more effective.

Although education provided by a physician is effective, using media—particularly social media—might be more efficient. Television, Instagram, and YouTube were listed by respondents as the 3 most preferred media outlets for skin health education, which shows important areas of focus for future advertising. Facebook was listed at a surprisingly low level, possibly showing the change in use of certain social media websites among this age group. According to the Pew Research Center, the most widely used social media apps among young adults aged 18 to 29 years are YouTube (91%), Facebook (63%), Instagram (67%), and Snapchat (62%). More than half of the same demographic visit Facebook (74%), Instagram (63%), Snapchat (61%), and YouTube (51%) daily.⁵ Although respondents to our survey were not specifically asked about the frequency of their use of social media and our data set includes patients younger than 18 years, we know that social media use has been increasing over the last decade among adolescents.¹ Therefore, we assume that more than one-half of respondents to our survey use their reported social media platforms daily.

Social media is an underused medium for skin cancer prevention education and can reach those who do not regularly see a dermatologist. Unlike printed pamphlets and posters, advertisements through social media can use metrics such as age, race, gender, and interests to target high-risk individuals.

Study Limitations
This was a single-site study of currently enrolled dermatology patients who might be more aware of skin protection than the general population because they are being treated by a dermatologist. Survey questions regarding demographics, required by our institution, could not effectively differentiate Hispanic and White patients. Respondents could have been subject to the Hawthorne effect—awareness that their behavior is being observed—when responding to the survey because it was administered in the office prior to being seen by a dermatologist.

Mohs micrographic surgery (MMS) entails multiple time-consuming surgical and histological examinations for each patient. As surgical stages are performed and histological sections are processed, an efficient communication method among providers, medical assistants, histotechnologists, and patients is necessary to avoid delays. To address these and other communication issues, providers have focused on ways to increase clinic efficiency and improve patient-reported outcomes by utilizing new or repurposed communication technologies in their Mohs practice. 

Prior reports have highlighted the utility of hands-free headsets that allow real-time communication among staff members as a means of increasing clinic efficiency and decreasing patient wait times.^1-4 These systems may mediate a more rapid turnover between stages by mitigating the need for surgeons and support staff to assemble within a designated workspace.^1,3,4 However, there is no single or standardized communication method that best suits all surgical suites and MMS practices. Our study aimed to identify the current communication strategies employed by Mohs surgeons and thereby ascertain which method(s) portend(s) the highest benefit in average daily time savings and provider-perceived patient satisfaction.

Materials and Methods

Survey Instrument
A new 10-question electronic survey was published on the SurveyMonkey website, and a link to the survey was provided in a quarterly email that originated from the American College of Mohs Surgery and was distributed to all 1735 active members. Responses were obtained from January 2019 to February 2019.

Statistical Analysis
A statistical analysis was done to determine any significant associations among the providers’ responses. P<.05 was used to determine statistical significance. A Cochran-Armitage test for trend was used to identify significant associations between the number of rooms and the communication systems that were used. Thus, 7 total tests—1 for each device (whiteboard, light system, flag system, wired intercom, wireless intercom, walkie-talkie, or headset)—were conducted. The Cochran-Armitage test also was used to determine whether the probability of using the device was affected by the number of stations/surgical rooms that were attended by the Mohs surgeons. To determine whether the communication devices used were associated with higher patient satisfaction, a χ² test was conducted for each device (7 total tests), testing the categories of using that device (yes/no) and patient satisfaction (yes/no). A Fisher exact test of independence was used in any case where the proportion for the device and patient satisfaction was 25% or higher. To determine whether the communication method was associated with increased time savings, 7 total Cochran-Armitage tests were conducted, 1 for each device. A logistic regression model was used to determine whether there was a significant association between the number of stations and the likelihood of reporting patient satisfaction.

Results

Eighty-eight surgeons responded to the survey, with a response rate of 5% (88/1735). A total of 55 surgeons completed the survey in its entirety and were included in the data analysis. The most commonly used communication mediums were whiteboards (29/55 [53%]), followed by a flag system (16/55 [29%]) and a light system (13/55 [24%]). Most Mohs surgeons (52/55 [95%]) used the communication media to communicate with their staff only, and 76% (42/55) of Mohs surgeons believed that their communication media contributed to higher patient satisfaction. Overall, 58% (32/55) of Mohs surgeons stated that their communication media saved more than 15 minutes (on average) per day. The use of a whiteboard and/or flag system was reported as the least efficient method, with average daily time savings of 13 minutes. With the introduction of newer technology (wired or wireless intercoms, headsets, walkie-talkies, or internal messaging systems such as Skype) to the whiteboard and/or flag system, the time savings increased by 10 minutes per day. Nearly 25% (14/55) of surgeons utilized more than 1 communication system.

As the number of stations in an MMS suite increased, the probability of using a whiteboard to track the progress of the cases decreased. There were no statistically significant associations identified between the number of stations and the use of other communication devices (ie, flag system, light system, wireless intercom, wired intercom, walkie-talkie, headset). The stratified percentages of the amount of time savings for each communication modality are presented in the Figure (whiteboards and headsets were excluded because they did not increase time savings). The use of a light system was the only communication modality found to be statistically associated with an increase in provider-reported time savings (P=.0482; Figure). In addition, our analysis did not show an improvement in provider-reported patient satisfaction with any of the current systems used in MMS clinics.

Comment

The process of transmitting information among the medical team during MMS is a complex interplay involving the relay of crucial information, with many opportunities for the introduction of distraction and error. Despite numerous improvements in the efficiency of the preparation of histological specimens and implementation of various time-saving and tissue-saving surgical interventions, relatively little attention has been given to address the sometimes chaotic and challenging process of organizing results from each stage of multiple patients in an MMS surgical suite.⁵

As demonstrated by our survey, incorporation of a light-based system into an MMS clinic may improve workplace efficiency by decreasing the redundant use of support staff and allowing Mohs surgeons to transition from one station to the next seamlessly. Light-based communication systems provide an immediate notification for support staff via color-coded and/or numerically coded indicators on input switches located outside and inside the examination/surgery rooms. The switch indicators can be depressed with minimal disruption from station to station, thereby foregoing the need to interrupt an ongoing excision or closure to convey the status of the case. These systems may then permit enhanced clinic and workflow efficiency, which may help to shorten patient wait times.

Conclusion

Our study supports the use of light-based communication systems in MMS suites to improve efficiency in the clinic. Based on our analysis, light-based communication methods were significantly associated with improved time savings (P=.0482). Our study did not show an improvement in provider-reported satisfaction with any of the current systems used in MMS clinics. We hope that this information will help guide providers in implementing new communication techniques to improve clinic efficiency. 



Acknowledgments
The authors would like to thank Ms. Kathy Kyler (Oklahoma City, Oklahoma) for her assistance in preparing this manuscript. Support for Dr. Chen and Mr. Stubblefield was provided through National Institutes of Health, National Institute of General Medical Sciences [Grant 2U54GM104938-06, PI Judith James].

Mohs micrographic surgery (MMS) entails multiple time-consuming surgical and histological examinations for each patient. As surgical stages are performed and histological sections are processed, an efficient communication method among providers, medical assistants, histotechnologists, and patients is necessary to avoid delays. To address these and other communication issues, providers have focused on ways to increase clinic efficiency and improve patient-reported outcomes by utilizing new or repurposed communication technologies in their Mohs practice. 

Prior reports have highlighted the utility of hands-free headsets that allow real-time communication among staff members as a means of increasing clinic efficiency and decreasing patient wait times.^1-4 These systems may mediate a more rapid turnover between stages by mitigating the need for surgeons and support staff to assemble within a designated workspace.^1,3,4 However, there is no single or standardized communication method that best suits all surgical suites and MMS practices. Our study aimed to identify the current communication strategies employed by Mohs surgeons and thereby ascertain which method(s) portend(s) the highest benefit in average daily time savings and provider-perceived patient satisfaction.

Materials and Methods

Survey Instrument
A new 10-question electronic survey was published on the SurveyMonkey website, and a link to the survey was provided in a quarterly email that originated from the American College of Mohs Surgery and was distributed to all 1735 active members. Responses were obtained from January 2019 to February 2019.

Statistical Analysis
A statistical analysis was done to determine any significant associations among the providers’ responses. P<.05 was used to determine statistical significance. A Cochran-Armitage test for trend was used to identify significant associations between the number of rooms and the communication systems that were used. Thus, 7 total tests—1 for each device (whiteboard, light system, flag system, wired intercom, wireless intercom, walkie-talkie, or headset)—were conducted. The Cochran-Armitage test also was used to determine whether the probability of using the device was affected by the number of stations/surgical rooms that were attended by the Mohs surgeons. To determine whether the communication devices used were associated with higher patient satisfaction, a χ² test was conducted for each device (7 total tests), testing the categories of using that device (yes/no) and patient satisfaction (yes/no). A Fisher exact test of independence was used in any case where the proportion for the device and patient satisfaction was 25% or higher. To determine whether the communication method was associated with increased time savings, 7 total Cochran-Armitage tests were conducted, 1 for each device. A logistic regression model was used to determine whether there was a significant association between the number of stations and the likelihood of reporting patient satisfaction.

Results

Eighty-eight surgeons responded to the survey, with a response rate of 5% (88/1735). A total of 55 surgeons completed the survey in its entirety and were included in the data analysis. The most commonly used communication mediums were whiteboards (29/55 [53%]), followed by a flag system (16/55 [29%]) and a light system (13/55 [24%]). Most Mohs surgeons (52/55 [95%]) used the communication media to communicate with their staff only, and 76% (42/55) of Mohs surgeons believed that their communication media contributed to higher patient satisfaction. Overall, 58% (32/55) of Mohs surgeons stated that their communication media saved more than 15 minutes (on average) per day. The use of a whiteboard and/or flag system was reported as the least efficient method, with average daily time savings of 13 minutes. With the introduction of newer technology (wired or wireless intercoms, headsets, walkie-talkies, or internal messaging systems such as Skype) to the whiteboard and/or flag system, the time savings increased by 10 minutes per day. Nearly 25% (14/55) of surgeons utilized more than 1 communication system.

As the number of stations in an MMS suite increased, the probability of using a whiteboard to track the progress of the cases decreased. There were no statistically significant associations identified between the number of stations and the use of other communication devices (ie, flag system, light system, wireless intercom, wired intercom, walkie-talkie, headset). The stratified percentages of the amount of time savings for each communication modality are presented in the Figure (whiteboards and headsets were excluded because they did not increase time savings). The use of a light system was the only communication modality found to be statistically associated with an increase in provider-reported time savings (P=.0482; Figure). In addition, our analysis did not show an improvement in provider-reported patient satisfaction with any of the current systems used in MMS clinics.

Comment

The process of transmitting information among the medical team during MMS is a complex interplay involving the relay of crucial information, with many opportunities for the introduction of distraction and error. Despite numerous improvements in the efficiency of the preparation of histological specimens and implementation of various time-saving and tissue-saving surgical interventions, relatively little attention has been given to address the sometimes chaotic and challenging process of organizing results from each stage of multiple patients in an MMS surgical suite.⁵

As demonstrated by our survey, incorporation of a light-based system into an MMS clinic may improve workplace efficiency by decreasing the redundant use of support staff and allowing Mohs surgeons to transition from one station to the next seamlessly. Light-based communication systems provide an immediate notification for support staff via color-coded and/or numerically coded indicators on input switches located outside and inside the examination/surgery rooms. The switch indicators can be depressed with minimal disruption from station to station, thereby foregoing the need to interrupt an ongoing excision or closure to convey the status of the case. These systems may then permit enhanced clinic and workflow efficiency, which may help to shorten patient wait times.

Conclusion

Our study supports the use of light-based communication systems in MMS suites to improve efficiency in the clinic. Based on our analysis, light-based communication methods were significantly associated with improved time savings (P=.0482). Our study did not show an improvement in provider-reported satisfaction with any of the current systems used in MMS clinics. We hope that this information will help guide providers in implementing new communication techniques to improve clinic efficiency. 



Acknowledgments
The authors would like to thank Ms. Kathy Kyler (Oklahoma City, Oklahoma) for her assistance in preparing this manuscript. Support for Dr. Chen and Mr. Stubblefield was provided through National Institutes of Health, National Institute of General Medical Sciences [Grant 2U54GM104938-06, PI Judith James].

Mohs micrographic surgery (MMS) entails multiple time-consuming surgical and histological examinations for each patient. As surgical stages are performed and histological sections are processed, an efficient communication method among providers, medical assistants, histotechnologists, and patients is necessary to avoid delays. To address these and other communication issues, providers have focused on ways to increase clinic efficiency and improve patient-reported outcomes by utilizing new or repurposed communication technologies in their Mohs practice. 

Prior reports have highlighted the utility of hands-free headsets that allow real-time communication among staff members as a means of increasing clinic efficiency and decreasing patient wait times.^1-4 These systems may mediate a more rapid turnover between stages by mitigating the need for surgeons and support staff to assemble within a designated workspace.^1,3,4 However, there is no single or standardized communication method that best suits all surgical suites and MMS practices. Our study aimed to identify the current communication strategies employed by Mohs surgeons and thereby ascertain which method(s) portend(s) the highest benefit in average daily time savings and provider-perceived patient satisfaction.

Materials and Methods

Survey Instrument
A new 10-question electronic survey was published on the SurveyMonkey website, and a link to the survey was provided in a quarterly email that originated from the American College of Mohs Surgery and was distributed to all 1735 active members. Responses were obtained from January 2019 to February 2019.

Statistical Analysis
A statistical analysis was done to determine any significant associations among the providers’ responses. P<.05 was used to determine statistical significance. A Cochran-Armitage test for trend was used to identify significant associations between the number of rooms and the communication systems that were used. Thus, 7 total tests—1 for each device (whiteboard, light system, flag system, wired intercom, wireless intercom, walkie-talkie, or headset)—were conducted. The Cochran-Armitage test also was used to determine whether the probability of using the device was affected by the number of stations/surgical rooms that were attended by the Mohs surgeons. To determine whether the communication devices used were associated with higher patient satisfaction, a χ² test was conducted for each device (7 total tests), testing the categories of using that device (yes/no) and patient satisfaction (yes/no). A Fisher exact test of independence was used in any case where the proportion for the device and patient satisfaction was 25% or higher. To determine whether the communication method was associated with increased time savings, 7 total Cochran-Armitage tests were conducted, 1 for each device. A logistic regression model was used to determine whether there was a significant association between the number of stations and the likelihood of reporting patient satisfaction.

Results

Eighty-eight surgeons responded to the survey, with a response rate of 5% (88/1735). A total of 55 surgeons completed the survey in its entirety and were included in the data analysis. The most commonly used communication mediums were whiteboards (29/55 [53%]), followed by a flag system (16/55 [29%]) and a light system (13/55 [24%]). Most Mohs surgeons (52/55 [95%]) used the communication media to communicate with their staff only, and 76% (42/55) of Mohs surgeons believed that their communication media contributed to higher patient satisfaction. Overall, 58% (32/55) of Mohs surgeons stated that their communication media saved more than 15 minutes (on average) per day. The use of a whiteboard and/or flag system was reported as the least efficient method, with average daily time savings of 13 minutes. With the introduction of newer technology (wired or wireless intercoms, headsets, walkie-talkies, or internal messaging systems such as Skype) to the whiteboard and/or flag system, the time savings increased by 10 minutes per day. Nearly 25% (14/55) of surgeons utilized more than 1 communication system.

As the number of stations in an MMS suite increased, the probability of using a whiteboard to track the progress of the cases decreased. There were no statistically significant associations identified between the number of stations and the use of other communication devices (ie, flag system, light system, wireless intercom, wired intercom, walkie-talkie, headset). The stratified percentages of the amount of time savings for each communication modality are presented in the Figure (whiteboards and headsets were excluded because they did not increase time savings). The use of a light system was the only communication modality found to be statistically associated with an increase in provider-reported time savings (P=.0482; Figure). In addition, our analysis did not show an improvement in provider-reported patient satisfaction with any of the current systems used in MMS clinics.

Comment

The process of transmitting information among the medical team during MMS is a complex interplay involving the relay of crucial information, with many opportunities for the introduction of distraction and error. Despite numerous improvements in the efficiency of the preparation of histological specimens and implementation of various time-saving and tissue-saving surgical interventions, relatively little attention has been given to address the sometimes chaotic and challenging process of organizing results from each stage of multiple patients in an MMS surgical suite.⁵

As demonstrated by our survey, incorporation of a light-based system into an MMS clinic may improve workplace efficiency by decreasing the redundant use of support staff and allowing Mohs surgeons to transition from one station to the next seamlessly. Light-based communication systems provide an immediate notification for support staff via color-coded and/or numerically coded indicators on input switches located outside and inside the examination/surgery rooms. The switch indicators can be depressed with minimal disruption from station to station, thereby foregoing the need to interrupt an ongoing excision or closure to convey the status of the case. These systems may then permit enhanced clinic and workflow efficiency, which may help to shorten patient wait times.

Conclusion

Our study supports the use of light-based communication systems in MMS suites to improve efficiency in the clinic. Based on our analysis, light-based communication methods were significantly associated with improved time savings (P=.0482). Our study did not show an improvement in provider-reported satisfaction with any of the current systems used in MMS clinics. We hope that this information will help guide providers in implementing new communication techniques to improve clinic efficiency. 



Acknowledgments
The authors would like to thank Ms. Kathy Kyler (Oklahoma City, Oklahoma) for her assistance in preparing this manuscript. Support for Dr. Chen and Mr. Stubblefield was provided through National Institutes of Health, National Institute of General Medical Sciences [Grant 2U54GM104938-06, PI Judith James].

Women had about a twofold higher risk than that of men of developing dermatologic adverse events while taking immune checkpoint inhibitors for metastatic melanoma in a review of 235 patients at Dana Farber Cancer Center, Boston.
 

Overall, 62.4% of the 93 women in the review and 48.6% of the 142 men experienced confirmed skin reactions, for an odds ratio (OR) of 2.11 for women compared with men (P = .01).

“Clinicians should consider these results in counseling female patients regarding an elevated risk of dermatologic adverse events” when taking checkpoint inhibitors, said investigators led by Harvard University medical student Jordan Said, who presented the results at the American Academy of Dermatology Virtual Meeting Experience.

Autoimmune-like adverse events are common with checkpoint inhibitors. Dermatologic side effects occur in about half of people receiving monotherapy and more than that among patients receiving combination therapy.

Skin reactions can include psoriasiform dermatitis, lichenoid reactions, vitiligo, and bullous pemphigoid and may require hospitalization and prolonged steroid treatment.

Not much is known about risk factors for these reactions. A higher incidence among women has been previously reported. A 2019 study found a higher risk for pneumonitis and endocrinopathy, including hypophysitis, among women who underwent treatment for non–small cell lung cancer or metastatic melanoma.

The 2019 study found that the risk was higher among premenopausal women than postmenopausal women, which led some to suggest that estrogen may play a role.

The results of the Dana Farber review argue against that notion. In their review, the investigators found that the risk was similarly elevated among the 27 premenopausal women (OR, 1.97; P = .40) and the 66 postmenopausal women (OR, 2.17, P = .05). In the study, women who were aged 52 years or older at the start of treatment were considered to be postmenopausal.

“This suggests that factors beyond sex hormones are likely contributory” to the difference in risk between men and women. It’s known that women are at higher risk for autoimmune disease overall, which might be related to the increased odds of autoimmune-like reactions, and it may be that sex-related differences in innate and adoptive immunity are at work, Mr. Said noted.

When asked for comment, Douglas Johnson, MD, assistant professor of hematology/oncology at Vanderbilt University, Nashville, Tenn., said that although some studies have reported a greater risk for side effects among women, others have not. “Additional research is needed to determine the interactions between sex and effects of immune checkpoint inhibitors, as well as many other possible triggers of immune-related adverse events,” he said.

“Continued work in this area will be so important to help determine how to best counsel women and to ensure early recognition and intervention for dermatologic side effects,” said Bernice Kwong, MD, director of the Supportive Dermato-Oncology Program at Stanford (Calif.) University.

The patients in the review were treated from 2011 to 2016 and underwent at least monthly evaluations by their medical teams. They were taking either nivolumab, pembrolizumab, or ipilimumab or a nivolumab/ipilimumab combination.

The median age of the men in the study was 65 years; the median age of women was 60 years. Almost 98% of the participants were White. The majority received one to three infusions, most commonly with pembrolizumab monotherapy.

No funding for the study was reported. Mr. Said has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Women had about a twofold higher risk than that of men of developing dermatologic adverse events while taking immune checkpoint inhibitors for metastatic melanoma in a review of 235 patients at Dana Farber Cancer Center, Boston.
 

Overall, 62.4% of the 93 women in the review and 48.6% of the 142 men experienced confirmed skin reactions, for an odds ratio (OR) of 2.11 for women compared with men (P = .01).

“Clinicians should consider these results in counseling female patients regarding an elevated risk of dermatologic adverse events” when taking checkpoint inhibitors, said investigators led by Harvard University medical student Jordan Said, who presented the results at the American Academy of Dermatology Virtual Meeting Experience.

Autoimmune-like adverse events are common with checkpoint inhibitors. Dermatologic side effects occur in about half of people receiving monotherapy and more than that among patients receiving combination therapy.

Skin reactions can include psoriasiform dermatitis, lichenoid reactions, vitiligo, and bullous pemphigoid and may require hospitalization and prolonged steroid treatment.

Not much is known about risk factors for these reactions. A higher incidence among women has been previously reported. A 2019 study found a higher risk for pneumonitis and endocrinopathy, including hypophysitis, among women who underwent treatment for non–small cell lung cancer or metastatic melanoma.

The 2019 study found that the risk was higher among premenopausal women than postmenopausal women, which led some to suggest that estrogen may play a role.

The results of the Dana Farber review argue against that notion. In their review, the investigators found that the risk was similarly elevated among the 27 premenopausal women (OR, 1.97; P = .40) and the 66 postmenopausal women (OR, 2.17, P = .05). In the study, women who were aged 52 years or older at the start of treatment were considered to be postmenopausal.

“This suggests that factors beyond sex hormones are likely contributory” to the difference in risk between men and women. It’s known that women are at higher risk for autoimmune disease overall, which might be related to the increased odds of autoimmune-like reactions, and it may be that sex-related differences in innate and adoptive immunity are at work, Mr. Said noted.

When asked for comment, Douglas Johnson, MD, assistant professor of hematology/oncology at Vanderbilt University, Nashville, Tenn., said that although some studies have reported a greater risk for side effects among women, others have not. “Additional research is needed to determine the interactions between sex and effects of immune checkpoint inhibitors, as well as many other possible triggers of immune-related adverse events,” he said.

“Continued work in this area will be so important to help determine how to best counsel women and to ensure early recognition and intervention for dermatologic side effects,” said Bernice Kwong, MD, director of the Supportive Dermato-Oncology Program at Stanford (Calif.) University.

The patients in the review were treated from 2011 to 2016 and underwent at least monthly evaluations by their medical teams. They were taking either nivolumab, pembrolizumab, or ipilimumab or a nivolumab/ipilimumab combination.

The median age of the men in the study was 65 years; the median age of women was 60 years. Almost 98% of the participants were White. The majority received one to three infusions, most commonly with pembrolizumab monotherapy.

No funding for the study was reported. Mr. Said has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Women had about a twofold higher risk than that of men of developing dermatologic adverse events while taking immune checkpoint inhibitors for metastatic melanoma in a review of 235 patients at Dana Farber Cancer Center, Boston.
 

Overall, 62.4% of the 93 women in the review and 48.6% of the 142 men experienced confirmed skin reactions, for an odds ratio (OR) of 2.11 for women compared with men (P = .01).

“Clinicians should consider these results in counseling female patients regarding an elevated risk of dermatologic adverse events” when taking checkpoint inhibitors, said investigators led by Harvard University medical student Jordan Said, who presented the results at the American Academy of Dermatology Virtual Meeting Experience.

Autoimmune-like adverse events are common with checkpoint inhibitors. Dermatologic side effects occur in about half of people receiving monotherapy and more than that among patients receiving combination therapy.

Skin reactions can include psoriasiform dermatitis, lichenoid reactions, vitiligo, and bullous pemphigoid and may require hospitalization and prolonged steroid treatment.

Not much is known about risk factors for these reactions. A higher incidence among women has been previously reported. A 2019 study found a higher risk for pneumonitis and endocrinopathy, including hypophysitis, among women who underwent treatment for non–small cell lung cancer or metastatic melanoma.

The 2019 study found that the risk was higher among premenopausal women than postmenopausal women, which led some to suggest that estrogen may play a role.

The results of the Dana Farber review argue against that notion. In their review, the investigators found that the risk was similarly elevated among the 27 premenopausal women (OR, 1.97; P = .40) and the 66 postmenopausal women (OR, 2.17, P = .05). In the study, women who were aged 52 years or older at the start of treatment were considered to be postmenopausal.

“This suggests that factors beyond sex hormones are likely contributory” to the difference in risk between men and women. It’s known that women are at higher risk for autoimmune disease overall, which might be related to the increased odds of autoimmune-like reactions, and it may be that sex-related differences in innate and adoptive immunity are at work, Mr. Said noted.

When asked for comment, Douglas Johnson, MD, assistant professor of hematology/oncology at Vanderbilt University, Nashville, Tenn., said that although some studies have reported a greater risk for side effects among women, others have not. “Additional research is needed to determine the interactions between sex and effects of immune checkpoint inhibitors, as well as many other possible triggers of immune-related adverse events,” he said.

“Continued work in this area will be so important to help determine how to best counsel women and to ensure early recognition and intervention for dermatologic side effects,” said Bernice Kwong, MD, director of the Supportive Dermato-Oncology Program at Stanford (Calif.) University.

The patients in the review were treated from 2011 to 2016 and underwent at least monthly evaluations by their medical teams. They were taking either nivolumab, pembrolizumab, or ipilimumab or a nivolumab/ipilimumab combination.

The median age of the men in the study was 65 years; the median age of women was 60 years. Almost 98% of the participants were White. The majority received one to three infusions, most commonly with pembrolizumab monotherapy.

No funding for the study was reported. Mr. Said has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.