Melanoma

In an update to its 2016 recommendations for skin cancer screening, the U.S. Preventive Services Task Force (USPSTF) has once again determined that there is not enough evidence to recommend for or against screening with a visual skin exam in adolescents and adults without symptoms.

This final recommendation applies to the general public and is not meant for those at higher risk, such as people with a family history of skin cancer or who have any signs or symptoms, such as irregular moles.

“The new recommendations are consistent with those from 2016, and we are unable to balance benefits and harms,” said Task Force member Katrina Donahue, MD, MPH, professor and vice chair of research in the department of family medicine at the University of North Carolina, Chapel Hill. “Unfortunately, there is not enough evidence to recommend for or against screening, and health care professionals should use their judgment when deciding whether or not to screen.”

Dr. Donahue told this news organization that this is a call for more research: “Our recommendations are for patients who present to primary care without symptoms, and after a careful assessment of benefit and harms, we didn’t have evidence to push us towards screening as a benefit. We did look at data from two large screening programs, but they were from Europe and not representative of the U.S. population. They also did not show a benefit for reducing melanoma-related mortality.”

The USPSTF final recommendation statement and corresponding evidence summary have been published online in JAMA, as well as on the USPSTF website.

Skin cancer is the most commonly diagnosed cancer in the United States, but there are different types that vary in their incidence and severity. Basal and squamous cell carcinomas are the most common types of skin cancer, but they infrequently lead to death or substantial morbidity, notes the USPTSF. Melanomas represent about 1% of skin cancer and cause the most skin cancer deaths. An estimated 8,000 individuals in the United States will die of melanoma in 2023.

There are racial differences in melanoma incidence; it is about 30 times more common in White versus Black persons, but disease in persons with darker skin color tends to be diagnosed at a later stage. These disparities may be due to differences in risk factors, access to care, and clinical presentation.

In an accompanying editorial, Maryam M. Asgari, MD, MPH, of the department of dermatology, Massachusetts General Hospital, Boston, and Lori A. Crane, PhD, MPH, of the Colorado School of Public Health, University of Colorado, Aurora, point out that people with darker skin phenotypes also tend to be affected by skin cancers that are not associated with UV radiation, such as acral melanoma, which arises on the palms and soles, and skin cancers that arise in areas of chronic inflammation, such as wounds.

Review of evidence

The USPSTF commissioned a systematic review to evaluate the benefits and harms of screening for skin cancer in asymptomatic adolescents and adults, including evidence for both keratinocyte carcinoma (basal cell carcinoma and squamous cell carcinoma) and cutaneous melanoma.

Foundational evidence showed that the sensitivity of visual skin examination by a clinician to detect melanoma ranged from 40% to 70% and specificity ranged from 86% to 98%. Evidence that evaluated the diagnostic accuracy of visual skin examination to detect keratinocyte carcinoma was limited and inconsistent. There were no new studies reporting on diagnostic accuracy for an asymptomatic screening population.

The USPSTF also reviewed 20 studies in 29 articles (n = 6,053,411). This included three nonrandomized studies evaluating two skin cancer screening programs in Germany, but results were inconsistent. In addition, the ecological and nonrandomized design of the studies limited the conclusions that could be drawn and the applicability to a U.S. population was difficult to assess because of differences in population diversity and health care delivery in the United States.

Other nonrandomized studies that looked at various outcomes, such as harms and stage at diagnosis and melanoma or all-cause mortality, also did not provide sufficient evidence to support screening.
 

Research is needed

In a second accompanying editorial published in JAMA Dermatology, Adewole S. Adamson, MD, MPP, of the division of dermatology and dermatologic surgery at the University of Texas, Austin, pointed out that unlike other cancer screening programs, such as those for breast, colon, and prostate cancer, skin cancer screening programs are somewhat less organized.

The other programs focus on defined groups of the population, generally with easily identifiable characteristics such as age, sex, and family history, and importantly, there are always defined ages for initiation and halting of screening and intervals for screening frequency. None of these basic screening parameters have been widely adopted among dermatologists in the United States, he wrote. “One important reason why skin cancer screening has remained inconsistent is that it is not covered by Medicare or by many commercial insurance companies,” Dr. Adamson told this news organization. “The test, in this case the skin exam, is often performed as part of a routine dermatology visit.”

Dermatologists should take the lead on this, he said. “Dermatologists should push for a high quality prospective clinical trial of skin cancer screening, preferably in a high-risk population.”

Dr. Donahue agrees that research is needed, as noted in the recommendation. For example, studies are needed demonstrating consistent data of the effects of screening on morbidity and mortality or early detection of skin cancer, and clearer descriptions of skin color and inclusion of a full spectrum of skin colors in study participants. Clinical research is also needed on outcomes in participants that reflect the diversity of the U.S. population.

“I hope funding agencies will be interested in this area of study,” she said. “We put out the whole systematic review and point out the gaps. We need consistent evidence in detecting cancer early and reducing complications from skin cancer.”

The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

None of the USPSTF authors report any disclosures. Dr. Asgari reported receiving royalties from UpToDate. Dr. Crane did not make any disclosures. Dr. Adamson reported serving as an expert reviewer for the U.S. Preventive Services Task Force skin cancer screening report, as well as support from the Robert Wood Johnson Foundation, the Dermatology Foundation Public Health Career Development Award, the National Institutes of Health, the American Cancer Society, and Meredith’s Mission for Melanoma.

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

In an update to its 2016 recommendations for skin cancer screening, the U.S. Preventive Services Task Force (USPSTF) has once again determined that there is not enough evidence to recommend for or against screening with a visual skin exam in adolescents and adults without symptoms.

This final recommendation applies to the general public and is not meant for those at higher risk, such as people with a family history of skin cancer or who have any signs or symptoms, such as irregular moles.

“The new recommendations are consistent with those from 2016, and we are unable to balance benefits and harms,” said Task Force member Katrina Donahue, MD, MPH, professor and vice chair of research in the department of family medicine at the University of North Carolina, Chapel Hill. “Unfortunately, there is not enough evidence to recommend for or against screening, and health care professionals should use their judgment when deciding whether or not to screen.”

Dr. Donahue told this news organization that this is a call for more research: “Our recommendations are for patients who present to primary care without symptoms, and after a careful assessment of benefit and harms, we didn’t have evidence to push us towards screening as a benefit. We did look at data from two large screening programs, but they were from Europe and not representative of the U.S. population. They also did not show a benefit for reducing melanoma-related mortality.”

The USPSTF final recommendation statement and corresponding evidence summary have been published online in JAMA, as well as on the USPSTF website.

Skin cancer is the most commonly diagnosed cancer in the United States, but there are different types that vary in their incidence and severity. Basal and squamous cell carcinomas are the most common types of skin cancer, but they infrequently lead to death or substantial morbidity, notes the USPTSF. Melanomas represent about 1% of skin cancer and cause the most skin cancer deaths. An estimated 8,000 individuals in the United States will die of melanoma in 2023.

There are racial differences in melanoma incidence; it is about 30 times more common in White versus Black persons, but disease in persons with darker skin color tends to be diagnosed at a later stage. These disparities may be due to differences in risk factors, access to care, and clinical presentation.

In an accompanying editorial, Maryam M. Asgari, MD, MPH, of the department of dermatology, Massachusetts General Hospital, Boston, and Lori A. Crane, PhD, MPH, of the Colorado School of Public Health, University of Colorado, Aurora, point out that people with darker skin phenotypes also tend to be affected by skin cancers that are not associated with UV radiation, such as acral melanoma, which arises on the palms and soles, and skin cancers that arise in areas of chronic inflammation, such as wounds.

Review of evidence

The USPSTF commissioned a systematic review to evaluate the benefits and harms of screening for skin cancer in asymptomatic adolescents and adults, including evidence for both keratinocyte carcinoma (basal cell carcinoma and squamous cell carcinoma) and cutaneous melanoma.

Foundational evidence showed that the sensitivity of visual skin examination by a clinician to detect melanoma ranged from 40% to 70% and specificity ranged from 86% to 98%. Evidence that evaluated the diagnostic accuracy of visual skin examination to detect keratinocyte carcinoma was limited and inconsistent. There were no new studies reporting on diagnostic accuracy for an asymptomatic screening population.

The USPSTF also reviewed 20 studies in 29 articles (n = 6,053,411). This included three nonrandomized studies evaluating two skin cancer screening programs in Germany, but results were inconsistent. In addition, the ecological and nonrandomized design of the studies limited the conclusions that could be drawn and the applicability to a U.S. population was difficult to assess because of differences in population diversity and health care delivery in the United States.

Other nonrandomized studies that looked at various outcomes, such as harms and stage at diagnosis and melanoma or all-cause mortality, also did not provide sufficient evidence to support screening.
 

Research is needed

In a second accompanying editorial published in JAMA Dermatology, Adewole S. Adamson, MD, MPP, of the division of dermatology and dermatologic surgery at the University of Texas, Austin, pointed out that unlike other cancer screening programs, such as those for breast, colon, and prostate cancer, skin cancer screening programs are somewhat less organized.

The other programs focus on defined groups of the population, generally with easily identifiable characteristics such as age, sex, and family history, and importantly, there are always defined ages for initiation and halting of screening and intervals for screening frequency. None of these basic screening parameters have been widely adopted among dermatologists in the United States, he wrote. “One important reason why skin cancer screening has remained inconsistent is that it is not covered by Medicare or by many commercial insurance companies,” Dr. Adamson told this news organization. “The test, in this case the skin exam, is often performed as part of a routine dermatology visit.”

Dermatologists should take the lead on this, he said. “Dermatologists should push for a high quality prospective clinical trial of skin cancer screening, preferably in a high-risk population.”

Dr. Donahue agrees that research is needed, as noted in the recommendation. For example, studies are needed demonstrating consistent data of the effects of screening on morbidity and mortality or early detection of skin cancer, and clearer descriptions of skin color and inclusion of a full spectrum of skin colors in study participants. Clinical research is also needed on outcomes in participants that reflect the diversity of the U.S. population.

“I hope funding agencies will be interested in this area of study,” she said. “We put out the whole systematic review and point out the gaps. We need consistent evidence in detecting cancer early and reducing complications from skin cancer.”

The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

None of the USPSTF authors report any disclosures. Dr. Asgari reported receiving royalties from UpToDate. Dr. Crane did not make any disclosures. Dr. Adamson reported serving as an expert reviewer for the U.S. Preventive Services Task Force skin cancer screening report, as well as support from the Robert Wood Johnson Foundation, the Dermatology Foundation Public Health Career Development Award, the National Institutes of Health, the American Cancer Society, and Meredith’s Mission for Melanoma.

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

In an update to its 2016 recommendations for skin cancer screening, the U.S. Preventive Services Task Force (USPSTF) has once again determined that there is not enough evidence to recommend for or against screening with a visual skin exam in adolescents and adults without symptoms.

This final recommendation applies to the general public and is not meant for those at higher risk, such as people with a family history of skin cancer or who have any signs or symptoms, such as irregular moles.

“The new recommendations are consistent with those from 2016, and we are unable to balance benefits and harms,” said Task Force member Katrina Donahue, MD, MPH, professor and vice chair of research in the department of family medicine at the University of North Carolina, Chapel Hill. “Unfortunately, there is not enough evidence to recommend for or against screening, and health care professionals should use their judgment when deciding whether or not to screen.”

Dr. Donahue told this news organization that this is a call for more research: “Our recommendations are for patients who present to primary care without symptoms, and after a careful assessment of benefit and harms, we didn’t have evidence to push us towards screening as a benefit. We did look at data from two large screening programs, but they were from Europe and not representative of the U.S. population. They also did not show a benefit for reducing melanoma-related mortality.”

The USPSTF final recommendation statement and corresponding evidence summary have been published online in JAMA, as well as on the USPSTF website.

Skin cancer is the most commonly diagnosed cancer in the United States, but there are different types that vary in their incidence and severity. Basal and squamous cell carcinomas are the most common types of skin cancer, but they infrequently lead to death or substantial morbidity, notes the USPTSF. Melanomas represent about 1% of skin cancer and cause the most skin cancer deaths. An estimated 8,000 individuals in the United States will die of melanoma in 2023.

There are racial differences in melanoma incidence; it is about 30 times more common in White versus Black persons, but disease in persons with darker skin color tends to be diagnosed at a later stage. These disparities may be due to differences in risk factors, access to care, and clinical presentation.

In an accompanying editorial, Maryam M. Asgari, MD, MPH, of the department of dermatology, Massachusetts General Hospital, Boston, and Lori A. Crane, PhD, MPH, of the Colorado School of Public Health, University of Colorado, Aurora, point out that people with darker skin phenotypes also tend to be affected by skin cancers that are not associated with UV radiation, such as acral melanoma, which arises on the palms and soles, and skin cancers that arise in areas of chronic inflammation, such as wounds.

Review of evidence

The USPSTF commissioned a systematic review to evaluate the benefits and harms of screening for skin cancer in asymptomatic adolescents and adults, including evidence for both keratinocyte carcinoma (basal cell carcinoma and squamous cell carcinoma) and cutaneous melanoma.

Foundational evidence showed that the sensitivity of visual skin examination by a clinician to detect melanoma ranged from 40% to 70% and specificity ranged from 86% to 98%. Evidence that evaluated the diagnostic accuracy of visual skin examination to detect keratinocyte carcinoma was limited and inconsistent. There were no new studies reporting on diagnostic accuracy for an asymptomatic screening population.

The USPSTF also reviewed 20 studies in 29 articles (n = 6,053,411). This included three nonrandomized studies evaluating two skin cancer screening programs in Germany, but results were inconsistent. In addition, the ecological and nonrandomized design of the studies limited the conclusions that could be drawn and the applicability to a U.S. population was difficult to assess because of differences in population diversity and health care delivery in the United States.

Other nonrandomized studies that looked at various outcomes, such as harms and stage at diagnosis and melanoma or all-cause mortality, also did not provide sufficient evidence to support screening.
 

Research is needed

In a second accompanying editorial published in JAMA Dermatology, Adewole S. Adamson, MD, MPP, of the division of dermatology and dermatologic surgery at the University of Texas, Austin, pointed out that unlike other cancer screening programs, such as those for breast, colon, and prostate cancer, skin cancer screening programs are somewhat less organized.

The other programs focus on defined groups of the population, generally with easily identifiable characteristics such as age, sex, and family history, and importantly, there are always defined ages for initiation and halting of screening and intervals for screening frequency. None of these basic screening parameters have been widely adopted among dermatologists in the United States, he wrote. “One important reason why skin cancer screening has remained inconsistent is that it is not covered by Medicare or by many commercial insurance companies,” Dr. Adamson told this news organization. “The test, in this case the skin exam, is often performed as part of a routine dermatology visit.”

Dermatologists should take the lead on this, he said. “Dermatologists should push for a high quality prospective clinical trial of skin cancer screening, preferably in a high-risk population.”

Dr. Donahue agrees that research is needed, as noted in the recommendation. For example, studies are needed demonstrating consistent data of the effects of screening on morbidity and mortality or early detection of skin cancer, and clearer descriptions of skin color and inclusion of a full spectrum of skin colors in study participants. Clinical research is also needed on outcomes in participants that reflect the diversity of the U.S. population.

“I hope funding agencies will be interested in this area of study,” she said. “We put out the whole systematic review and point out the gaps. We need consistent evidence in detecting cancer early and reducing complications from skin cancer.”

The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

None of the USPSTF authors report any disclosures. Dr. Asgari reported receiving royalties from UpToDate. Dr. Crane did not make any disclosures. Dr. Adamson reported serving as an expert reviewer for the U.S. Preventive Services Task Force skin cancer screening report, as well as support from the Robert Wood Johnson Foundation, the Dermatology Foundation Public Health Career Development Award, the National Institutes of Health, the American Cancer Society, and Meredith’s Mission for Melanoma.

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

Among patients with unresectable desmoplastic melanoma (DM), a prospective trial showed that single-agent treatment with the programmed death 1 (PD-1) inhibitor pembrolizumab led to a dramatic overall response rate.

The findings could represent a new standard of treatment for this extremely rare tumor.

The study was inspired by a previous retrospective analysis which found an overall response rate of 77% and a complete response of 32% to anti–PD-1 monotherapy.

The ORR is about double what is seen in melanoma more generally, according to Kari Kendra, MD, PhD, who presented the study at the annual meeting of the American Association for Cancer Research.

“Our study was a positive study. Of note, in the retrospective study, they saw a complete response rate of 32%, which was amazingly similar to what we found. [The findings support] the use of single agent anti–PD-1 immunotherapy as first line treatment for most patients with unresectable desmoplastic melanoma. [There was 89% overall response and we saw] dramatic responses across the board,” said Dr. Kendra, who is a medical oncologist at Ohio State University Wexner Medical Center, Columbus.

The findings drew a strong reaction. “In a rare tumor session, to see response curves like that, it’s just outstanding,” said the session’s cochair Brian Van Tine, MD, PhD, who is a professor of medical oncology at Washington University in St. Louis.

“This really is one of the highest tumor response rates to immunotherapy that we are seeing in any cancer. And I think may also highlight the fact that we shouldn’t think of all cutaneous melanomas as one disease, given the heterogeneity in tumor responses based on some of the pathologic and molecular characteristics,” said Zeynep Aroglu, MD, who served as a discussant but was also one of the investigators who enrolled patients for the trial.

Desmoplastic melanoma represents about 4% of all cutaneous melanoma diagnoses, and its unique pathology can make it difficult to diagnose. That often leads to a late diagnosis, according to Dr. Aroglu. They typically occur in elderly patients, in the head and neck area, and are associated with sun exposure. DM also tends to have a high mutation burden, Dr. Aroglu said during the session.

It remains to be seen why there is such a high response rate in this tumor type, even among tumor types with mutation burdens that are nearly as high. DM tumors are often driven by neurofibromatosis type 1, but other tumors driven by NF-1 don’t have as high of a response rate to immunotherapy. The tumor environment could also play a role, she said.

“Is it a combination of all these factors? I think some of the ongoing analysis of tumor samples that Dr. Kendra mentioned may help to answer some of these questions,” Dr. Aroglu continued.

She also noted that the melanoma field is increasingly turning to combination of anti–PD-1 therapy with agents like that target LAG3 or CTLA4. Such combinations can achieve higher response rates, but at a cost of higher rates of grade 3-4 adverse events than anti–PD-1 inhibitors alone. “I wonder if for desmoplastic melanomas in light of this data, do we consider de-escalating therapy, given these very high response rates to PD-1 alone, given also the elderly age of many of these patients, because even the PD-1–LAG3 combo still has a higher rate of toxicity than PD-1 monotherapy. Perhaps the immunotherapy combinations can be reserved for those rare desmoplastic patients who are resistant to PD-1 alone,” said Dr. Aroglu.
 

Study details and adverse events

Twenty-seven patients were enrolled in the study; 93% were male, all were White, and 22% had elevated baseline lactate dehydrogenase. About 63% had disease located in the head and neck area, 33% experienced a complete response (P < .001), and 56% had a partial response for an ORR of 89%. The result surpassed the primary endpoint target of at least a 20% complete response rate.

The 2-year progression-free survival was 74%, and 2-year overall survival was 89%. The most common toxicities were fatigue (56%), diarrhea (33%), maculopapular rash (30%), pruritus (22%), anemia (19%), arthralgia (19%), and decreased lymphocyte count (19%). There were two grade 4 adverse events: a lipase increase and a lung infection accompanied by sepsis.

The researchers also carried out whole exome sequencing of biopsies and found that 67% had NF-1 loss of function mutations.

Dr. Aroglu has served on advisory boards for Pfizer, Array, Eisai, Genentech, Natera, Novartis, OncoSec, and Regeneron. She has received research support from Boehringer Ingelheim, Pfizer, and Novartis. Dr. Kendra has received institutional support from Bristol Myers-Squibb and trial support from CheckMate Pharmaceuticals, GlaxoSmithKline, Immunocore, Medspace, Merck, Novartis, and Varian Medical Systems. Dr. Van Tine has financial relationships with a wide range of pharmaceutical companies.

Among patients with unresectable desmoplastic melanoma (DM), a prospective trial showed that single-agent treatment with the programmed death 1 (PD-1) inhibitor pembrolizumab led to a dramatic overall response rate.

The findings could represent a new standard of treatment for this extremely rare tumor.

The study was inspired by a previous retrospective analysis which found an overall response rate of 77% and a complete response of 32% to anti–PD-1 monotherapy.

The ORR is about double what is seen in melanoma more generally, according to Kari Kendra, MD, PhD, who presented the study at the annual meeting of the American Association for Cancer Research.

“Our study was a positive study. Of note, in the retrospective study, they saw a complete response rate of 32%, which was amazingly similar to what we found. [The findings support] the use of single agent anti–PD-1 immunotherapy as first line treatment for most patients with unresectable desmoplastic melanoma. [There was 89% overall response and we saw] dramatic responses across the board,” said Dr. Kendra, who is a medical oncologist at Ohio State University Wexner Medical Center, Columbus.

The findings drew a strong reaction. “In a rare tumor session, to see response curves like that, it’s just outstanding,” said the session’s cochair Brian Van Tine, MD, PhD, who is a professor of medical oncology at Washington University in St. Louis.

“This really is one of the highest tumor response rates to immunotherapy that we are seeing in any cancer. And I think may also highlight the fact that we shouldn’t think of all cutaneous melanomas as one disease, given the heterogeneity in tumor responses based on some of the pathologic and molecular characteristics,” said Zeynep Aroglu, MD, who served as a discussant but was also one of the investigators who enrolled patients for the trial.

Desmoplastic melanoma represents about 4% of all cutaneous melanoma diagnoses, and its unique pathology can make it difficult to diagnose. That often leads to a late diagnosis, according to Dr. Aroglu. They typically occur in elderly patients, in the head and neck area, and are associated with sun exposure. DM also tends to have a high mutation burden, Dr. Aroglu said during the session.

It remains to be seen why there is such a high response rate in this tumor type, even among tumor types with mutation burdens that are nearly as high. DM tumors are often driven by neurofibromatosis type 1, but other tumors driven by NF-1 don’t have as high of a response rate to immunotherapy. The tumor environment could also play a role, she said.

“Is it a combination of all these factors? I think some of the ongoing analysis of tumor samples that Dr. Kendra mentioned may help to answer some of these questions,” Dr. Aroglu continued.

She also noted that the melanoma field is increasingly turning to combination of anti–PD-1 therapy with agents like that target LAG3 or CTLA4. Such combinations can achieve higher response rates, but at a cost of higher rates of grade 3-4 adverse events than anti–PD-1 inhibitors alone. “I wonder if for desmoplastic melanomas in light of this data, do we consider de-escalating therapy, given these very high response rates to PD-1 alone, given also the elderly age of many of these patients, because even the PD-1–LAG3 combo still has a higher rate of toxicity than PD-1 monotherapy. Perhaps the immunotherapy combinations can be reserved for those rare desmoplastic patients who are resistant to PD-1 alone,” said Dr. Aroglu.
 

Study details and adverse events

Twenty-seven patients were enrolled in the study; 93% were male, all were White, and 22% had elevated baseline lactate dehydrogenase. About 63% had disease located in the head and neck area, 33% experienced a complete response (P < .001), and 56% had a partial response for an ORR of 89%. The result surpassed the primary endpoint target of at least a 20% complete response rate.

The 2-year progression-free survival was 74%, and 2-year overall survival was 89%. The most common toxicities were fatigue (56%), diarrhea (33%), maculopapular rash (30%), pruritus (22%), anemia (19%), arthralgia (19%), and decreased lymphocyte count (19%). There were two grade 4 adverse events: a lipase increase and a lung infection accompanied by sepsis.

The researchers also carried out whole exome sequencing of biopsies and found that 67% had NF-1 loss of function mutations.

Dr. Aroglu has served on advisory boards for Pfizer, Array, Eisai, Genentech, Natera, Novartis, OncoSec, and Regeneron. She has received research support from Boehringer Ingelheim, Pfizer, and Novartis. Dr. Kendra has received institutional support from Bristol Myers-Squibb and trial support from CheckMate Pharmaceuticals, GlaxoSmithKline, Immunocore, Medspace, Merck, Novartis, and Varian Medical Systems. Dr. Van Tine has financial relationships with a wide range of pharmaceutical companies.

Among patients with unresectable desmoplastic melanoma (DM), a prospective trial showed that single-agent treatment with the programmed death 1 (PD-1) inhibitor pembrolizumab led to a dramatic overall response rate.

The findings could represent a new standard of treatment for this extremely rare tumor.

The study was inspired by a previous retrospective analysis which found an overall response rate of 77% and a complete response of 32% to anti–PD-1 monotherapy.

The ORR is about double what is seen in melanoma more generally, according to Kari Kendra, MD, PhD, who presented the study at the annual meeting of the American Association for Cancer Research.

“Our study was a positive study. Of note, in the retrospective study, they saw a complete response rate of 32%, which was amazingly similar to what we found. [The findings support] the use of single agent anti–PD-1 immunotherapy as first line treatment for most patients with unresectable desmoplastic melanoma. [There was 89% overall response and we saw] dramatic responses across the board,” said Dr. Kendra, who is a medical oncologist at Ohio State University Wexner Medical Center, Columbus.

The findings drew a strong reaction. “In a rare tumor session, to see response curves like that, it’s just outstanding,” said the session’s cochair Brian Van Tine, MD, PhD, who is a professor of medical oncology at Washington University in St. Louis.

“This really is one of the highest tumor response rates to immunotherapy that we are seeing in any cancer. And I think may also highlight the fact that we shouldn’t think of all cutaneous melanomas as one disease, given the heterogeneity in tumor responses based on some of the pathologic and molecular characteristics,” said Zeynep Aroglu, MD, who served as a discussant but was also one of the investigators who enrolled patients for the trial.

Desmoplastic melanoma represents about 4% of all cutaneous melanoma diagnoses, and its unique pathology can make it difficult to diagnose. That often leads to a late diagnosis, according to Dr. Aroglu. They typically occur in elderly patients, in the head and neck area, and are associated with sun exposure. DM also tends to have a high mutation burden, Dr. Aroglu said during the session.

It remains to be seen why there is such a high response rate in this tumor type, even among tumor types with mutation burdens that are nearly as high. DM tumors are often driven by neurofibromatosis type 1, but other tumors driven by NF-1 don’t have as high of a response rate to immunotherapy. The tumor environment could also play a role, she said.

“Is it a combination of all these factors? I think some of the ongoing analysis of tumor samples that Dr. Kendra mentioned may help to answer some of these questions,” Dr. Aroglu continued.

She also noted that the melanoma field is increasingly turning to combination of anti–PD-1 therapy with agents like that target LAG3 or CTLA4. Such combinations can achieve higher response rates, but at a cost of higher rates of grade 3-4 adverse events than anti–PD-1 inhibitors alone. “I wonder if for desmoplastic melanomas in light of this data, do we consider de-escalating therapy, given these very high response rates to PD-1 alone, given also the elderly age of many of these patients, because even the PD-1–LAG3 combo still has a higher rate of toxicity than PD-1 monotherapy. Perhaps the immunotherapy combinations can be reserved for those rare desmoplastic patients who are resistant to PD-1 alone,” said Dr. Aroglu.
 

Study details and adverse events

Twenty-seven patients were enrolled in the study; 93% were male, all were White, and 22% had elevated baseline lactate dehydrogenase. About 63% had disease located in the head and neck area, 33% experienced a complete response (P < .001), and 56% had a partial response for an ORR of 89%. The result surpassed the primary endpoint target of at least a 20% complete response rate.

The 2-year progression-free survival was 74%, and 2-year overall survival was 89%. The most common toxicities were fatigue (56%), diarrhea (33%), maculopapular rash (30%), pruritus (22%), anemia (19%), arthralgia (19%), and decreased lymphocyte count (19%). There were two grade 4 adverse events: a lipase increase and a lung infection accompanied by sepsis.

The researchers also carried out whole exome sequencing of biopsies and found that 67% had NF-1 loss of function mutations.

Dr. Aroglu has served on advisory boards for Pfizer, Array, Eisai, Genentech, Natera, Novartis, OncoSec, and Regeneron. She has received research support from Boehringer Ingelheim, Pfizer, and Novartis. Dr. Kendra has received institutional support from Bristol Myers-Squibb and trial support from CheckMate Pharmaceuticals, GlaxoSmithKline, Immunocore, Medspace, Merck, Novartis, and Varian Medical Systems. Dr. Van Tine has financial relationships with a wide range of pharmaceutical companies.

Current U.S., European, and Australian guidelines recommend 10-mm safety margins for radical excision of primary melanomas, but for patients with early-stage cutaneous melanoma in critical areas of the body, excision with 5-mm margins may not significantly increase risk for recurrence or melanoma-specific mortality (MSM), results of a retrospective study suggest.

Among 1,179 patients with stage T1a melanomas near the face, scalp, external genitalia, or other critical areas, the weighted 10-year local recurrence rate for patients who underwent resection with 10-mm margins was 5.7%, compared with 6.7% for those who had resections with 5-mm margins, a nonsignificant difference.

Weighted 10-year melanoma-specific mortality was 1.8% for patients treated with wide margins, vs. 4.2% for those treated with narrow margins, also a nonsignificant difference. Patients treated with narrow margins did have significantly fewer reconstructive surgeries than patients treated with wide margins, reported Andrea Maurichi, MD, and colleagues at the National Cancer Institute of Italy in Milan.

“Because this association was found in melanomas of the head and neck, acral, and genital sites, there is no plausible reason why it could not be extrapolated to other locations. The findings also support the need for prospective randomized clinical trials to definitively answer the important question about appropriate excision margins for T1a melanoma,” they wrote in the study, published online in JAMA Dermatology.

The authors also found, however, that Breslow thickness greater than 0.4 mm and mitotic rate greater than 1/mm­­² were associated with worse MSM, and that acral lentiginous melanoma, lentigo maligna melanoma, and increasing Breslow thickness were associated with a higher incidence of local recurrence.

A melanoma expert who was not involved in the study said that despite these findings, wider margins are always preferable.

“There is always a conversation around these general [critical] areas, but as a rule we try to get larger margins,” said Ryan J. Sullivan, MD, of Mass General Cancer Center in Boston.

In an interview, Dr. Sullivan said that the finding about lower frequency of reconstructive procedures in the narrow margins groups may be more of a concern for younger patients than for the elderly.

Study design

The investigators conducted a retrospective cohort study of consecutive patients aged 18 or older at the National Cancer Institute of Milan who were diagnosed with T1a cutaneous melanoma close to critical areas from 2001 through 2020.

Patients with primary cutaneous melanoma of the head and face areas with functional or cosmetic considerations, acral areas (plantar, palmar, digital and interdigital areas), external genitalia, or periumbilical and perineal areas were eligible for inclusion.

The cohort comprised 1,179 patients with a median age of 50 and equal sex distribution. Of these patients, 626 (53%) had a wide excision, of whom 434 had a linear repair, and 192 had a flap of graft reconstruction. The remaining 553 patients had narrow excisions, 491 with linear repair, and 62 with flap or graft reconstruction.

Analyses were adjusted to account for imbalances between the surgical groups.

The study was supported by the nonprofit foundation Emme Rouge. The authors and Dr. Sullivan reported having no relevant conflicts of interest to disclose.

Current U.S., European, and Australian guidelines recommend 10-mm safety margins for radical excision of primary melanomas, but for patients with early-stage cutaneous melanoma in critical areas of the body, excision with 5-mm margins may not significantly increase risk for recurrence or melanoma-specific mortality (MSM), results of a retrospective study suggest.

Among 1,179 patients with stage T1a melanomas near the face, scalp, external genitalia, or other critical areas, the weighted 10-year local recurrence rate for patients who underwent resection with 10-mm margins was 5.7%, compared with 6.7% for those who had resections with 5-mm margins, a nonsignificant difference.

Weighted 10-year melanoma-specific mortality was 1.8% for patients treated with wide margins, vs. 4.2% for those treated with narrow margins, also a nonsignificant difference. Patients treated with narrow margins did have significantly fewer reconstructive surgeries than patients treated with wide margins, reported Andrea Maurichi, MD, and colleagues at the National Cancer Institute of Italy in Milan.

“Because this association was found in melanomas of the head and neck, acral, and genital sites, there is no plausible reason why it could not be extrapolated to other locations. The findings also support the need for prospective randomized clinical trials to definitively answer the important question about appropriate excision margins for T1a melanoma,” they wrote in the study, published online in JAMA Dermatology.

The authors also found, however, that Breslow thickness greater than 0.4 mm and mitotic rate greater than 1/mm­­² were associated with worse MSM, and that acral lentiginous melanoma, lentigo maligna melanoma, and increasing Breslow thickness were associated with a higher incidence of local recurrence.

A melanoma expert who was not involved in the study said that despite these findings, wider margins are always preferable.

“There is always a conversation around these general [critical] areas, but as a rule we try to get larger margins,” said Ryan J. Sullivan, MD, of Mass General Cancer Center in Boston.

In an interview, Dr. Sullivan said that the finding about lower frequency of reconstructive procedures in the narrow margins groups may be more of a concern for younger patients than for the elderly.

Study design

The investigators conducted a retrospective cohort study of consecutive patients aged 18 or older at the National Cancer Institute of Milan who were diagnosed with T1a cutaneous melanoma close to critical areas from 2001 through 2020.

Patients with primary cutaneous melanoma of the head and face areas with functional or cosmetic considerations, acral areas (plantar, palmar, digital and interdigital areas), external genitalia, or periumbilical and perineal areas were eligible for inclusion.

The cohort comprised 1,179 patients with a median age of 50 and equal sex distribution. Of these patients, 626 (53%) had a wide excision, of whom 434 had a linear repair, and 192 had a flap of graft reconstruction. The remaining 553 patients had narrow excisions, 491 with linear repair, and 62 with flap or graft reconstruction.

Analyses were adjusted to account for imbalances between the surgical groups.

The study was supported by the nonprofit foundation Emme Rouge. The authors and Dr. Sullivan reported having no relevant conflicts of interest to disclose.

Current U.S., European, and Australian guidelines recommend 10-mm safety margins for radical excision of primary melanomas, but for patients with early-stage cutaneous melanoma in critical areas of the body, excision with 5-mm margins may not significantly increase risk for recurrence or melanoma-specific mortality (MSM), results of a retrospective study suggest.

Among 1,179 patients with stage T1a melanomas near the face, scalp, external genitalia, or other critical areas, the weighted 10-year local recurrence rate for patients who underwent resection with 10-mm margins was 5.7%, compared with 6.7% for those who had resections with 5-mm margins, a nonsignificant difference.

Weighted 10-year melanoma-specific mortality was 1.8% for patients treated with wide margins, vs. 4.2% for those treated with narrow margins, also a nonsignificant difference. Patients treated with narrow margins did have significantly fewer reconstructive surgeries than patients treated with wide margins, reported Andrea Maurichi, MD, and colleagues at the National Cancer Institute of Italy in Milan.

“Because this association was found in melanomas of the head and neck, acral, and genital sites, there is no plausible reason why it could not be extrapolated to other locations. The findings also support the need for prospective randomized clinical trials to definitively answer the important question about appropriate excision margins for T1a melanoma,” they wrote in the study, published online in JAMA Dermatology.

The authors also found, however, that Breslow thickness greater than 0.4 mm and mitotic rate greater than 1/mm­­² were associated with worse MSM, and that acral lentiginous melanoma, lentigo maligna melanoma, and increasing Breslow thickness were associated with a higher incidence of local recurrence.

A melanoma expert who was not involved in the study said that despite these findings, wider margins are always preferable.

“There is always a conversation around these general [critical] areas, but as a rule we try to get larger margins,” said Ryan J. Sullivan, MD, of Mass General Cancer Center in Boston.

In an interview, Dr. Sullivan said that the finding about lower frequency of reconstructive procedures in the narrow margins groups may be more of a concern for younger patients than for the elderly.

Study design

The investigators conducted a retrospective cohort study of consecutive patients aged 18 or older at the National Cancer Institute of Milan who were diagnosed with T1a cutaneous melanoma close to critical areas from 2001 through 2020.

Patients with primary cutaneous melanoma of the head and face areas with functional or cosmetic considerations, acral areas (plantar, palmar, digital and interdigital areas), external genitalia, or periumbilical and perineal areas were eligible for inclusion.

The cohort comprised 1,179 patients with a median age of 50 and equal sex distribution. Of these patients, 626 (53%) had a wide excision, of whom 434 had a linear repair, and 192 had a flap of graft reconstruction. The remaining 553 patients had narrow excisions, 491 with linear repair, and 62 with flap or graft reconstruction.

Analyses were adjusted to account for imbalances between the surgical groups.

The study was supported by the nonprofit foundation Emme Rouge. The authors and Dr. Sullivan reported having no relevant conflicts of interest to disclose.

PHOENIX – During the incidental treatment of melanocytic nevi during laser hair removal, common clinical changes include regression and decreased size, while common histologic changes include mild atypia and thermal damage, according to results from a systematic review of literature on the topic. To date, no severe cases of severe dysplasia or melanoma have been reported.

“That’s reassuring,” study author Ahuva Cices, MD, said in an interview at the annual conference of the American Society for Laser Medicine and Surgery, where she presented the results during an abstract session. “But, with that in mind, we want to avoid treating nevi with laser hair removal to avoid changes that could be concerning. We also recommend baseline skin exams so we know what we’re looking at before we start treating with lasers, and any changes can be recognized from that baseline status. It’s important to keep an eye out for changes and always be evaluating.”

Doug Brunk/MDedge News

In December of 2022, Dr. Cices, chief dermatology resident at Mount Sinai Health System, New York, searched PubMed for articles that evaluated changes in melanocytic nevi after laser hair removal procedures. She used the search terms “nevi laser hair removal,” “nevi diode,” “nevi long pulse alexandrite,” “nevi long pulse neodymium doped yttrium aluminum garnet,” and “melanoma laser hair removal,” and limited the analysis to English language patient-based reports that discussed incidental treatment of melanocytic nevi while undergoing hair removal with a laser.

Reports excluded from the analysis were those that focused on changes following hair removal with nonlaser devices such as intense pulsed light (IPL), those evaluating nonmelanocytic nevi such as Becker’s nevus or nevus of Ota, and those evaluating the intentional ablation or removal of melanocytic lesions.

The search yielded 10 relevant studies for systematic review: seven case reports or series and three observational trials, two of which were prospective and one retrospective.

The results of the review, according to Dr. Cices, revealed that clinical and dermoscopic changes were noted to present as early as 15 days after treatment and persist to the maximum follow up time, at 3 years. Commonly reported changes included regression, decreased size, laser-induced asymmetry, bleaching, darkening, and altered pattern on dermoscopy. Histologic changes included mild atypia, thermal damage, scar formation, and regression.

“Although some of the clinical and dermoscopic alterations may be concerning for malignancy, to our knowledge, there are no documented cases of malignant transformation of nevi following treatment with laser hair removal,” she wrote in the abstract.

Dr. Cices acknowledged certain limitations of the systematic review, including the low number of relevant reports and their generally small sample size, many of which were limited to single cases.

Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford, who was asked to comment on the review, characterized the findings as important because laser hair removal is such a commonly performed procedure.

While the study is limited by the small number of studies on the subject matter, “it brings up an important discussion,” Dr. Ibrahimi said in an interview. “Generally speaking, we know that most hair removal lasers do indeed target melanin pigment and can be absorbed by melanocytes. While the wavelengths used for LHR [laser hair removal] will not result in DNA damage or cause mutations that can lead to melanoma, they can sometimes alter the appearance of pigmented lesions and that may change the dermatologist’s ability to monitor them for atypia,” he noted.

“For that reason, I would recommend all patients see a dermatologist for evaluation of their nevi prior to any treatments and they consider very carefully where they get their laser treatments. If they have any atypical pigmented lesions, then that information should be disclosed with the person performing the laser hair removal procedure particularly if there are lesions that are being specifically monitored.”

Dr. Cices reported having no disclosures. Dr. Ibrahimi disclosed that he is a member of the advisory board for Accure Acne, AbbVie, Cutera, Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero. He also holds stock in many device and pharmaceutical companies.

PHOENIX – During the incidental treatment of melanocytic nevi during laser hair removal, common clinical changes include regression and decreased size, while common histologic changes include mild atypia and thermal damage, according to results from a systematic review of literature on the topic. To date, no severe cases of severe dysplasia or melanoma have been reported.

“That’s reassuring,” study author Ahuva Cices, MD, said in an interview at the annual conference of the American Society for Laser Medicine and Surgery, where she presented the results during an abstract session. “But, with that in mind, we want to avoid treating nevi with laser hair removal to avoid changes that could be concerning. We also recommend baseline skin exams so we know what we’re looking at before we start treating with lasers, and any changes can be recognized from that baseline status. It’s important to keep an eye out for changes and always be evaluating.”

Doug Brunk/MDedge News

In December of 2022, Dr. Cices, chief dermatology resident at Mount Sinai Health System, New York, searched PubMed for articles that evaluated changes in melanocytic nevi after laser hair removal procedures. She used the search terms “nevi laser hair removal,” “nevi diode,” “nevi long pulse alexandrite,” “nevi long pulse neodymium doped yttrium aluminum garnet,” and “melanoma laser hair removal,” and limited the analysis to English language patient-based reports that discussed incidental treatment of melanocytic nevi while undergoing hair removal with a laser.

Reports excluded from the analysis were those that focused on changes following hair removal with nonlaser devices such as intense pulsed light (IPL), those evaluating nonmelanocytic nevi such as Becker’s nevus or nevus of Ota, and those evaluating the intentional ablation or removal of melanocytic lesions.

The search yielded 10 relevant studies for systematic review: seven case reports or series and three observational trials, two of which were prospective and one retrospective.

The results of the review, according to Dr. Cices, revealed that clinical and dermoscopic changes were noted to present as early as 15 days after treatment and persist to the maximum follow up time, at 3 years. Commonly reported changes included regression, decreased size, laser-induced asymmetry, bleaching, darkening, and altered pattern on dermoscopy. Histologic changes included mild atypia, thermal damage, scar formation, and regression.

“Although some of the clinical and dermoscopic alterations may be concerning for malignancy, to our knowledge, there are no documented cases of malignant transformation of nevi following treatment with laser hair removal,” she wrote in the abstract.

Dr. Cices acknowledged certain limitations of the systematic review, including the low number of relevant reports and their generally small sample size, many of which were limited to single cases.

Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford, who was asked to comment on the review, characterized the findings as important because laser hair removal is such a commonly performed procedure.

While the study is limited by the small number of studies on the subject matter, “it brings up an important discussion,” Dr. Ibrahimi said in an interview. “Generally speaking, we know that most hair removal lasers do indeed target melanin pigment and can be absorbed by melanocytes. While the wavelengths used for LHR [laser hair removal] will not result in DNA damage or cause mutations that can lead to melanoma, they can sometimes alter the appearance of pigmented lesions and that may change the dermatologist’s ability to monitor them for atypia,” he noted.

“For that reason, I would recommend all patients see a dermatologist for evaluation of their nevi prior to any treatments and they consider very carefully where they get their laser treatments. If they have any atypical pigmented lesions, then that information should be disclosed with the person performing the laser hair removal procedure particularly if there are lesions that are being specifically monitored.”

Dr. Cices reported having no disclosures. Dr. Ibrahimi disclosed that he is a member of the advisory board for Accure Acne, AbbVie, Cutera, Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero. He also holds stock in many device and pharmaceutical companies.

PHOENIX – During the incidental treatment of melanocytic nevi during laser hair removal, common clinical changes include regression and decreased size, while common histologic changes include mild atypia and thermal damage, according to results from a systematic review of literature on the topic. To date, no severe cases of severe dysplasia or melanoma have been reported.

“That’s reassuring,” study author Ahuva Cices, MD, said in an interview at the annual conference of the American Society for Laser Medicine and Surgery, where she presented the results during an abstract session. “But, with that in mind, we want to avoid treating nevi with laser hair removal to avoid changes that could be concerning. We also recommend baseline skin exams so we know what we’re looking at before we start treating with lasers, and any changes can be recognized from that baseline status. It’s important to keep an eye out for changes and always be evaluating.”

Doug Brunk/MDedge News

In December of 2022, Dr. Cices, chief dermatology resident at Mount Sinai Health System, New York, searched PubMed for articles that evaluated changes in melanocytic nevi after laser hair removal procedures. She used the search terms “nevi laser hair removal,” “nevi diode,” “nevi long pulse alexandrite,” “nevi long pulse neodymium doped yttrium aluminum garnet,” and “melanoma laser hair removal,” and limited the analysis to English language patient-based reports that discussed incidental treatment of melanocytic nevi while undergoing hair removal with a laser.

Reports excluded from the analysis were those that focused on changes following hair removal with nonlaser devices such as intense pulsed light (IPL), those evaluating nonmelanocytic nevi such as Becker’s nevus or nevus of Ota, and those evaluating the intentional ablation or removal of melanocytic lesions.

The search yielded 10 relevant studies for systematic review: seven case reports or series and three observational trials, two of which were prospective and one retrospective.

The results of the review, according to Dr. Cices, revealed that clinical and dermoscopic changes were noted to present as early as 15 days after treatment and persist to the maximum follow up time, at 3 years. Commonly reported changes included regression, decreased size, laser-induced asymmetry, bleaching, darkening, and altered pattern on dermoscopy. Histologic changes included mild atypia, thermal damage, scar formation, and regression.

“Although some of the clinical and dermoscopic alterations may be concerning for malignancy, to our knowledge, there are no documented cases of malignant transformation of nevi following treatment with laser hair removal,” she wrote in the abstract.

Dr. Cices acknowledged certain limitations of the systematic review, including the low number of relevant reports and their generally small sample size, many of which were limited to single cases.

Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford, who was asked to comment on the review, characterized the findings as important because laser hair removal is such a commonly performed procedure.

While the study is limited by the small number of studies on the subject matter, “it brings up an important discussion,” Dr. Ibrahimi said in an interview. “Generally speaking, we know that most hair removal lasers do indeed target melanin pigment and can be absorbed by melanocytes. While the wavelengths used for LHR [laser hair removal] will not result in DNA damage or cause mutations that can lead to melanoma, they can sometimes alter the appearance of pigmented lesions and that may change the dermatologist’s ability to monitor them for atypia,” he noted.

“For that reason, I would recommend all patients see a dermatologist for evaluation of their nevi prior to any treatments and they consider very carefully where they get their laser treatments. If they have any atypical pigmented lesions, then that information should be disclosed with the person performing the laser hair removal procedure particularly if there are lesions that are being specifically monitored.”

Dr. Cices reported having no disclosures. Dr. Ibrahimi disclosed that he is a member of the advisory board for Accure Acne, AbbVie, Cutera, Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero. He also holds stock in many device and pharmaceutical companies.

Results of a study recently published in Nature Communications suggests that radiation from ultraviolet nail polish dryers could induce cell death and trigger molecular changes linked to cancer in human cells. According to two experts, these findings raise concerns regarding the safety of frequent use of these nail dryers.

In the study, human and mouse cells were exposed to radiation from UV nail dryers. Exposing human and mice skin cells to UVA light for 20 minutes resulted in the death of 20%-30% of cells; three consecutive 20-minute sessions resulted in the death of 65%-70% of cells. Additionally, surviving cells suffered oxidative damage to their DNA and mitochondria, with mutational patterns similar to those seen in skin cancer, study investigator Maria Zhivagui, PhD, of the University of California, San Diego, and associates reported.  

“This study showed that irradiation of human and mouse cell lines using UV nail polish dryers resulted in DNA damage and genome mutations,” Shari Lipner, MD, PhD, director of the nail division at New York–Presbyterian Hospital/Weill Cornell Medicine, New York, said in an interview. The study “ties together exposure to UV light from nail polish dryers and genetic mutations that are associated with skin cancers,” added Dr. Lipner, who was not involved with the study.

UV nail lamps are commonly used to dry and harden gel nail polish formulas. Often referred to as “mini tanning beds,” these devices emit UVA radiation, classified as a Group 1 Carcinogen by the International Agency for Research on Cancer.

“Both UVA and UVB are main drivers of both melanoma and keratinocyte carcinomas (basal cell carcinoma and squamous cell carcinoma),” said Anthony Rossi, MD, a dermatologic surgeon at Memorial Sloan Kettering Cancer Center, New York, who was also not a study investigator. UV irradiance “produces DNA mutations that are specific to forming types of skin cancer,” he said in an interview.

UVA wavelengths commonly used in nail dryers can penetrate all layers of the epidermis, the top layer of the skin, potentially affecting stem cells in the skin, according to the study.

Dr. Lipner noted that “there have been several case reports of patients with histories of gel manicures using UV nail polish dryers who later developed squamous cell carcinomas on the dorsal hands, fingers, and nails, and articles describing high UV emissions from nail polish dryers, but the direct connection between UV dryers and skin cancer development was tenuous.” The first of its kind, the new study investigated the impact of UV nail drying devices at a cellular level.

The results of this study, in combination with previous case reports suggesting the development of skin cancers following UVA dryer use, raise concern regarding the safety of these commonly used devices. The study, the authors wrote, “does not provide direct evidence for an increased cancer risk in human beings,” but their findings and “prior evidence strongly suggest that radiation emitted by UV nail polish dryers may cause cancers of the hand and that UV nail polish dryers, similar to tanning beds, may increase the risk of early onset skin cancer.”

Courtesy MSKCC

Dr. Rossi said that, “while this study shows that the UV exposure does affect human cells and causes mutations, the study was not done in vivo in human beings, so further studies are needed to know at what dose and frequency gel manicures would be needed to cause detrimental effects.” However, for people who regularly receive gel manicures involving UV nail dryers, both Dr. Lipner and Dr. Rossi recommend applying a broad-spectrum sunscreen to protect the dorsal hands, fingertips, and skin surrounding the nails, or wearing UV-protective gloves.

The study was supported by an Alfred B. Sloan Research Fellowship to one of the authors and grants from the National Institutes of Health to two authors. One author reported being a compensated consultant and having an equity interest in io9. Dr. Lipner and Dr. Rossi reported no relevant financial relationships.

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

Results of a study recently published in Nature Communications suggests that radiation from ultraviolet nail polish dryers could induce cell death and trigger molecular changes linked to cancer in human cells. According to two experts, these findings raise concerns regarding the safety of frequent use of these nail dryers.

In the study, human and mouse cells were exposed to radiation from UV nail dryers. Exposing human and mice skin cells to UVA light for 20 minutes resulted in the death of 20%-30% of cells; three consecutive 20-minute sessions resulted in the death of 65%-70% of cells. Additionally, surviving cells suffered oxidative damage to their DNA and mitochondria, with mutational patterns similar to those seen in skin cancer, study investigator Maria Zhivagui, PhD, of the University of California, San Diego, and associates reported.  

“This study showed that irradiation of human and mouse cell lines using UV nail polish dryers resulted in DNA damage and genome mutations,” Shari Lipner, MD, PhD, director of the nail division at New York–Presbyterian Hospital/Weill Cornell Medicine, New York, said in an interview. The study “ties together exposure to UV light from nail polish dryers and genetic mutations that are associated with skin cancers,” added Dr. Lipner, who was not involved with the study.

UV nail lamps are commonly used to dry and harden gel nail polish formulas. Often referred to as “mini tanning beds,” these devices emit UVA radiation, classified as a Group 1 Carcinogen by the International Agency for Research on Cancer.

“Both UVA and UVB are main drivers of both melanoma and keratinocyte carcinomas (basal cell carcinoma and squamous cell carcinoma),” said Anthony Rossi, MD, a dermatologic surgeon at Memorial Sloan Kettering Cancer Center, New York, who was also not a study investigator. UV irradiance “produces DNA mutations that are specific to forming types of skin cancer,” he said in an interview.

UVA wavelengths commonly used in nail dryers can penetrate all layers of the epidermis, the top layer of the skin, potentially affecting stem cells in the skin, according to the study.

Dr. Lipner noted that “there have been several case reports of patients with histories of gel manicures using UV nail polish dryers who later developed squamous cell carcinomas on the dorsal hands, fingers, and nails, and articles describing high UV emissions from nail polish dryers, but the direct connection between UV dryers and skin cancer development was tenuous.” The first of its kind, the new study investigated the impact of UV nail drying devices at a cellular level.

The results of this study, in combination with previous case reports suggesting the development of skin cancers following UVA dryer use, raise concern regarding the safety of these commonly used devices. The study, the authors wrote, “does not provide direct evidence for an increased cancer risk in human beings,” but their findings and “prior evidence strongly suggest that radiation emitted by UV nail polish dryers may cause cancers of the hand and that UV nail polish dryers, similar to tanning beds, may increase the risk of early onset skin cancer.”

Courtesy MSKCC

Dr. Rossi said that, “while this study shows that the UV exposure does affect human cells and causes mutations, the study was not done in vivo in human beings, so further studies are needed to know at what dose and frequency gel manicures would be needed to cause detrimental effects.” However, for people who regularly receive gel manicures involving UV nail dryers, both Dr. Lipner and Dr. Rossi recommend applying a broad-spectrum sunscreen to protect the dorsal hands, fingertips, and skin surrounding the nails, or wearing UV-protective gloves.

The study was supported by an Alfred B. Sloan Research Fellowship to one of the authors and grants from the National Institutes of Health to two authors. One author reported being a compensated consultant and having an equity interest in io9. Dr. Lipner and Dr. Rossi reported no relevant financial relationships.

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

Results of a study recently published in Nature Communications suggests that radiation from ultraviolet nail polish dryers could induce cell death and trigger molecular changes linked to cancer in human cells. According to two experts, these findings raise concerns regarding the safety of frequent use of these nail dryers.

In the study, human and mouse cells were exposed to radiation from UV nail dryers. Exposing human and mice skin cells to UVA light for 20 minutes resulted in the death of 20%-30% of cells; three consecutive 20-minute sessions resulted in the death of 65%-70% of cells. Additionally, surviving cells suffered oxidative damage to their DNA and mitochondria, with mutational patterns similar to those seen in skin cancer, study investigator Maria Zhivagui, PhD, of the University of California, San Diego, and associates reported.  

“This study showed that irradiation of human and mouse cell lines using UV nail polish dryers resulted in DNA damage and genome mutations,” Shari Lipner, MD, PhD, director of the nail division at New York–Presbyterian Hospital/Weill Cornell Medicine, New York, said in an interview. The study “ties together exposure to UV light from nail polish dryers and genetic mutations that are associated with skin cancers,” added Dr. Lipner, who was not involved with the study.

UV nail lamps are commonly used to dry and harden gel nail polish formulas. Often referred to as “mini tanning beds,” these devices emit UVA radiation, classified as a Group 1 Carcinogen by the International Agency for Research on Cancer.

“Both UVA and UVB are main drivers of both melanoma and keratinocyte carcinomas (basal cell carcinoma and squamous cell carcinoma),” said Anthony Rossi, MD, a dermatologic surgeon at Memorial Sloan Kettering Cancer Center, New York, who was also not a study investigator. UV irradiance “produces DNA mutations that are specific to forming types of skin cancer,” he said in an interview.

UVA wavelengths commonly used in nail dryers can penetrate all layers of the epidermis, the top layer of the skin, potentially affecting stem cells in the skin, according to the study.

Dr. Lipner noted that “there have been several case reports of patients with histories of gel manicures using UV nail polish dryers who later developed squamous cell carcinomas on the dorsal hands, fingers, and nails, and articles describing high UV emissions from nail polish dryers, but the direct connection between UV dryers and skin cancer development was tenuous.” The first of its kind, the new study investigated the impact of UV nail drying devices at a cellular level.

The results of this study, in combination with previous case reports suggesting the development of skin cancers following UVA dryer use, raise concern regarding the safety of these commonly used devices. The study, the authors wrote, “does not provide direct evidence for an increased cancer risk in human beings,” but their findings and “prior evidence strongly suggest that radiation emitted by UV nail polish dryers may cause cancers of the hand and that UV nail polish dryers, similar to tanning beds, may increase the risk of early onset skin cancer.”

Courtesy MSKCC

Dr. Rossi said that, “while this study shows that the UV exposure does affect human cells and causes mutations, the study was not done in vivo in human beings, so further studies are needed to know at what dose and frequency gel manicures would be needed to cause detrimental effects.” However, for people who regularly receive gel manicures involving UV nail dryers, both Dr. Lipner and Dr. Rossi recommend applying a broad-spectrum sunscreen to protect the dorsal hands, fingertips, and skin surrounding the nails, or wearing UV-protective gloves.

The study was supported by an Alfred B. Sloan Research Fellowship to one of the authors and grants from the National Institutes of Health to two authors. One author reported being a compensated consultant and having an equity interest in io9. Dr. Lipner and Dr. Rossi reported no relevant financial relationships.

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

Over the past 30 years, more than 80 new systemic therapies for cancer have been approved, and many patients diagnosed with localized disease have benefited with improved progression-free and overall survival. The same can be said for some – but by no means all – patients with metastatic disease at diagnosis, a new study indicates.

“Our results show that the survival of patients with de novo metastatic cancer improved slowly over 30 years but that these gains were typically modest and unevenly distributed among cancers,” comment the authors, led by Marianne Luyendijk, MSc, from the Netherlands Comprehensive Cancer Organization, Utrecht.

The study was published online  in the Journal of the National Cancer Institute.

The retrospective study compared survival data of patients with de novo metastatic disease diagnosed from 1989 through 1993 with those of patients diagnosed from 2014 to 2018.

The results show that 5-year survival increased by 15% or more among patients with metastatic gastrointestinal stromal tumors; neuroendocrine tumors; melanoma; and cancers of the prostate, breast, thyroid, and testes.

For patients with other cancers, however, the gains in survival were more modest. For example, over the study period, 5-year survival of patients with metastatic non–small cell lung cancer increased by only 6%, a disappointing finding, given the advent of targeted therapies and immunotherapy during the most recent period, the authors note.

In contrast, there was a 16% improvement in long-term survival of patients with metastatic melanoma, likely owing to the introduction of immune checkpoint inhibitors and targeted therapies, such as tyrosine kinase inhibitors.

The data also showed differences over time in the proportion of patients diagnosed with de novo metastatic disease; some cancers, such as NSCLC and small cell lung cancer, were more frequently diagnosed at late stages in the more recent era, possibly owing to increased screening and the use of technology such as FDG-PET imaging.

On the other end of the spectrum, cancers of the prostate, rectum, uterine cervix, breast, gallbladder, and bile ducts were more likely to be caught at an earlier stage during later years of the study period.

The authors say that among the possible explanations for a less than robust reduction over time in metastatic disease is that new drugs do not always translate into improved survival. They cite a 2017 study showing that among 53 new cancer drugs approved by U.S., European, or Australian drug regulators, fewer than half improved overall survival by at least 3 months, and an additional 26% offered survival advantages that were either shorter than 3 months or of unknown benefit.

“This may also explain why the 1- and 5-year survival rates of some cancers have changed little in the last 30 years,” they write. “Nevertheless, even minor benefits in survival or other outcomes (for example, quality of life) may represent progress in treating patients with metastatic cancer.”

The investigators recommend that to improve understanding of the effect of new therapies on survival of metastatic disease, cancer registries include data on therapies used beyond the first line, as well as comorbidities and quality-of-life measures.

The authors did not report a study funding source. Ms. Luyendijk has disclosed no relevant financial relationships. Several co-authors reported financial relationships with pharmaceutical companies.

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

Over the past 30 years, more than 80 new systemic therapies for cancer have been approved, and many patients diagnosed with localized disease have benefited with improved progression-free and overall survival. The same can be said for some – but by no means all – patients with metastatic disease at diagnosis, a new study indicates.

“Our results show that the survival of patients with de novo metastatic cancer improved slowly over 30 years but that these gains were typically modest and unevenly distributed among cancers,” comment the authors, led by Marianne Luyendijk, MSc, from the Netherlands Comprehensive Cancer Organization, Utrecht.

The study was published online  in the Journal of the National Cancer Institute.

The retrospective study compared survival data of patients with de novo metastatic disease diagnosed from 1989 through 1993 with those of patients diagnosed from 2014 to 2018.

The results show that 5-year survival increased by 15% or more among patients with metastatic gastrointestinal stromal tumors; neuroendocrine tumors; melanoma; and cancers of the prostate, breast, thyroid, and testes.

For patients with other cancers, however, the gains in survival were more modest. For example, over the study period, 5-year survival of patients with metastatic non–small cell lung cancer increased by only 6%, a disappointing finding, given the advent of targeted therapies and immunotherapy during the most recent period, the authors note.

In contrast, there was a 16% improvement in long-term survival of patients with metastatic melanoma, likely owing to the introduction of immune checkpoint inhibitors and targeted therapies, such as tyrosine kinase inhibitors.

The data also showed differences over time in the proportion of patients diagnosed with de novo metastatic disease; some cancers, such as NSCLC and small cell lung cancer, were more frequently diagnosed at late stages in the more recent era, possibly owing to increased screening and the use of technology such as FDG-PET imaging.

On the other end of the spectrum, cancers of the prostate, rectum, uterine cervix, breast, gallbladder, and bile ducts were more likely to be caught at an earlier stage during later years of the study period.

The authors say that among the possible explanations for a less than robust reduction over time in metastatic disease is that new drugs do not always translate into improved survival. They cite a 2017 study showing that among 53 new cancer drugs approved by U.S., European, or Australian drug regulators, fewer than half improved overall survival by at least 3 months, and an additional 26% offered survival advantages that were either shorter than 3 months or of unknown benefit.

“This may also explain why the 1- and 5-year survival rates of some cancers have changed little in the last 30 years,” they write. “Nevertheless, even minor benefits in survival or other outcomes (for example, quality of life) may represent progress in treating patients with metastatic cancer.”

The investigators recommend that to improve understanding of the effect of new therapies on survival of metastatic disease, cancer registries include data on therapies used beyond the first line, as well as comorbidities and quality-of-life measures.

The authors did not report a study funding source. Ms. Luyendijk has disclosed no relevant financial relationships. Several co-authors reported financial relationships with pharmaceutical companies.

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

Over the past 30 years, more than 80 new systemic therapies for cancer have been approved, and many patients diagnosed with localized disease have benefited with improved progression-free and overall survival. The same can be said for some – but by no means all – patients with metastatic disease at diagnosis, a new study indicates.

“Our results show that the survival of patients with de novo metastatic cancer improved slowly over 30 years but that these gains were typically modest and unevenly distributed among cancers,” comment the authors, led by Marianne Luyendijk, MSc, from the Netherlands Comprehensive Cancer Organization, Utrecht.

The study was published online  in the Journal of the National Cancer Institute.

The retrospective study compared survival data of patients with de novo metastatic disease diagnosed from 1989 through 1993 with those of patients diagnosed from 2014 to 2018.

The results show that 5-year survival increased by 15% or more among patients with metastatic gastrointestinal stromal tumors; neuroendocrine tumors; melanoma; and cancers of the prostate, breast, thyroid, and testes.

For patients with other cancers, however, the gains in survival were more modest. For example, over the study period, 5-year survival of patients with metastatic non–small cell lung cancer increased by only 6%, a disappointing finding, given the advent of targeted therapies and immunotherapy during the most recent period, the authors note.

In contrast, there was a 16% improvement in long-term survival of patients with metastatic melanoma, likely owing to the introduction of immune checkpoint inhibitors and targeted therapies, such as tyrosine kinase inhibitors.

The data also showed differences over time in the proportion of patients diagnosed with de novo metastatic disease; some cancers, such as NSCLC and small cell lung cancer, were more frequently diagnosed at late stages in the more recent era, possibly owing to increased screening and the use of technology such as FDG-PET imaging.

On the other end of the spectrum, cancers of the prostate, rectum, uterine cervix, breast, gallbladder, and bile ducts were more likely to be caught at an earlier stage during later years of the study period.

The authors say that among the possible explanations for a less than robust reduction over time in metastatic disease is that new drugs do not always translate into improved survival. They cite a 2017 study showing that among 53 new cancer drugs approved by U.S., European, or Australian drug regulators, fewer than half improved overall survival by at least 3 months, and an additional 26% offered survival advantages that were either shorter than 3 months or of unknown benefit.

“This may also explain why the 1- and 5-year survival rates of some cancers have changed little in the last 30 years,” they write. “Nevertheless, even minor benefits in survival or other outcomes (for example, quality of life) may represent progress in treating patients with metastatic cancer.”

The investigators recommend that to improve understanding of the effect of new therapies on survival of metastatic disease, cancer registries include data on therapies used beyond the first line, as well as comorbidities and quality-of-life measures.

The authors did not report a study funding source. Ms. Luyendijk has disclosed no relevant financial relationships. Several co-authors reported financial relationships with pharmaceutical companies.

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

The Diagnosis: Porokeratosis Plantaris Palmaris et Disseminata

A 3-mm punch biopsy of the right upper arm showed incipient cornoid lamellae formation, pigment incontinence, and sparse dermal lymphocytic inflammation (Figure), suggestive of porokeratosis plantaris palmaris et disseminata (PPPD). The dermatopathologist recommended a second biopsy to confirm the diagnosis and to confirm that the lesions on the palms and soles also were suggestive of porokeratosis. A second 4-mm punch biopsy of the left palm was consistent with PPPD.

The risks of PPPD as a precancerous entity along with the benefits and side effects of the various management options were discussed with our patient. We recommended that he start low-dose isotretinoin (20 mg/d) due to the large body surface area affected, making focal and field treatments likely insufficient. However, our patient opted not to treat and did not return for follow-up.

Subtypes of porokeratosis, including disseminated superficial actinic porokeratosis (DSAP) and PPPD, are conditions that disrupt the normal maturation of keratin and present clinically with symmetric, crusted, annular papules.¹ The signature but nonspecific histopathologic feature shared among the subtypes is the presence of a cornoid lamellae.² Several triggers of porokeratosis have been proposed, including trauma and exposure to UV and ionizing radiation.^2,3 The clinical variants of porokeratosis are important conditions to diagnose correctly because they portend a risk for Bowen disease and invasive squamous cell carcinoma and may indicate the presence of an underlying hematologic and/or solid organ malignancy.⁴ Management of porokeratosis is difficult, as treatments have shown limited efficacy and variable recurrence rates. Treatment options include focal, field, and systemic options, such as 5-fluorouracil, topical compound of cholesterol and lovastatin, isotretinoin, and acitretin.^1,2

Porokeratoses may arise from gene mutations in the mevalonate pathway,⁵ which is essential for the production of cholesterol.⁶ Topical cholesterol alone has not been shown to improve porokeratosis, but the combination topical therapy of cholesterol and lovastatin is promising. It is theorized to deliver benefit by both providing the essential end product of the pathway and simultaneously reducing the number of potentially toxic intermediates.⁶

Porokeratosis plantaris palmaris et disseminata (also known as porokeratosis plantaris) is unique among the subtypes of porokeratosis in that its annular, red-pink, papular rash with scaling and a keratotic border tends to start distally, involving the palms and soles, and progresses proximally to the trunk with smaller lesions.^1,7 This centripetal progression can take years, as was seen in our patient.¹ The disease is uncommon, with a dearth of published reports on PPPD.² However, case reports have shown that PPPD is strongly linked to family history and may have an autosomal-dominant inheritance pattern. Penetrance is greater in men than in women, as PPPD is twice as common in men.⁸ Most cases of PPPD have been diagnosed in patients in their 20s and 30s, but Hartman et al9 reported a case wherein a patient was diagnosed with PPPD after 65 years of age, similar to our patient.

Although the lesions in DSAP can appear similar to those in PPPD, DSAP is more common among the family of porokeratotic conditions, affecting women twice as often as men, with a sporadic pattern of inheritance.² These same features are present in some other types of porokeratosis but not PPPD. Furthermore, DSAP progresses proximally to distally but often with truncal sparing.²

Akin to PPPD, pityriasis rubra pilaris (PRP) often presents with palmoplantar keratoderma.¹⁰ There are at least 6 types of PRP with varying degrees of similarity to PPPD. However, in many cases PRP is associated with a background of diffuse erythema on the body with islands of spared skin. In addition, cases of PRP have been linked to extracutaneous findings such as ectropion and joint pain.¹¹

Darier disease, especially the acrokeratosis verruciformis of Hopf variant, is more common in men and involves younger populations, as in PPPD.¹¹ However, the crusted lesions seen in Darier disease frequently involve the skin folds. These intertriginous lesions may coalesce, mimicking warts in appearance, and are at risk for secondary infection. Nail findings in Darier disease also are distinct and include longitudinal white or red stripes running along the nail bed, in addition to V-shaped nicks at the nail tips.

Psoriasis can occur anywhere on the body and is associated with silver scaling atop a salmon-colored dermatitis.¹² It results from aberrant proliferation of keratinocytes. Some distinguishing features of psoriasis include a disease course that waxes and wanes as well as pitting of the nails.

Although PPPD typically affects young adults, we presented a case of PPPD in an older man. Porokeratosis plantaris palmaris et disseminata in older adults may represent a delayed diagnosis, imply a broader range for the age of onset, or suggest its manifestation secondary to radiation treatment or another phenomenon. For example, our patient received 35 radiotherapy cycles for tongue cancer more than 5 years prior to the onset of PPPD.

The Diagnosis: Porokeratosis Plantaris Palmaris et Disseminata

A 3-mm punch biopsy of the right upper arm showed incipient cornoid lamellae formation, pigment incontinence, and sparse dermal lymphocytic inflammation (Figure), suggestive of porokeratosis plantaris palmaris et disseminata (PPPD). The dermatopathologist recommended a second biopsy to confirm the diagnosis and to confirm that the lesions on the palms and soles also were suggestive of porokeratosis. A second 4-mm punch biopsy of the left palm was consistent with PPPD.

The risks of PPPD as a precancerous entity along with the benefits and side effects of the various management options were discussed with our patient. We recommended that he start low-dose isotretinoin (20 mg/d) due to the large body surface area affected, making focal and field treatments likely insufficient. However, our patient opted not to treat and did not return for follow-up.

Subtypes of porokeratosis, including disseminated superficial actinic porokeratosis (DSAP) and PPPD, are conditions that disrupt the normal maturation of keratin and present clinically with symmetric, crusted, annular papules.¹ The signature but nonspecific histopathologic feature shared among the subtypes is the presence of a cornoid lamellae.² Several triggers of porokeratosis have been proposed, including trauma and exposure to UV and ionizing radiation.^2,3 The clinical variants of porokeratosis are important conditions to diagnose correctly because they portend a risk for Bowen disease and invasive squamous cell carcinoma and may indicate the presence of an underlying hematologic and/or solid organ malignancy.⁴ Management of porokeratosis is difficult, as treatments have shown limited efficacy and variable recurrence rates. Treatment options include focal, field, and systemic options, such as 5-fluorouracil, topical compound of cholesterol and lovastatin, isotretinoin, and acitretin.^1,2

Porokeratoses may arise from gene mutations in the mevalonate pathway,⁵ which is essential for the production of cholesterol.⁶ Topical cholesterol alone has not been shown to improve porokeratosis, but the combination topical therapy of cholesterol and lovastatin is promising. It is theorized to deliver benefit by both providing the essential end product of the pathway and simultaneously reducing the number of potentially toxic intermediates.⁶

Porokeratosis plantaris palmaris et disseminata (also known as porokeratosis plantaris) is unique among the subtypes of porokeratosis in that its annular, red-pink, papular rash with scaling and a keratotic border tends to start distally, involving the palms and soles, and progresses proximally to the trunk with smaller lesions.^1,7 This centripetal progression can take years, as was seen in our patient.¹ The disease is uncommon, with a dearth of published reports on PPPD.² However, case reports have shown that PPPD is strongly linked to family history and may have an autosomal-dominant inheritance pattern. Penetrance is greater in men than in women, as PPPD is twice as common in men.⁸ Most cases of PPPD have been diagnosed in patients in their 20s and 30s, but Hartman et al9 reported a case wherein a patient was diagnosed with PPPD after 65 years of age, similar to our patient.

Although the lesions in DSAP can appear similar to those in PPPD, DSAP is more common among the family of porokeratotic conditions, affecting women twice as often as men, with a sporadic pattern of inheritance.² These same features are present in some other types of porokeratosis but not PPPD. Furthermore, DSAP progresses proximally to distally but often with truncal sparing.²

Akin to PPPD, pityriasis rubra pilaris (PRP) often presents with palmoplantar keratoderma.¹⁰ There are at least 6 types of PRP with varying degrees of similarity to PPPD. However, in many cases PRP is associated with a background of diffuse erythema on the body with islands of spared skin. In addition, cases of PRP have been linked to extracutaneous findings such as ectropion and joint pain.¹¹

Darier disease, especially the acrokeratosis verruciformis of Hopf variant, is more common in men and involves younger populations, as in PPPD.¹¹ However, the crusted lesions seen in Darier disease frequently involve the skin folds. These intertriginous lesions may coalesce, mimicking warts in appearance, and are at risk for secondary infection. Nail findings in Darier disease also are distinct and include longitudinal white or red stripes running along the nail bed, in addition to V-shaped nicks at the nail tips.

Psoriasis can occur anywhere on the body and is associated with silver scaling atop a salmon-colored dermatitis.¹² It results from aberrant proliferation of keratinocytes. Some distinguishing features of psoriasis include a disease course that waxes and wanes as well as pitting of the nails.

Although PPPD typically affects young adults, we presented a case of PPPD in an older man. Porokeratosis plantaris palmaris et disseminata in older adults may represent a delayed diagnosis, imply a broader range for the age of onset, or suggest its manifestation secondary to radiation treatment or another phenomenon. For example, our patient received 35 radiotherapy cycles for tongue cancer more than 5 years prior to the onset of PPPD.

The Diagnosis: Porokeratosis Plantaris Palmaris et Disseminata

A 3-mm punch biopsy of the right upper arm showed incipient cornoid lamellae formation, pigment incontinence, and sparse dermal lymphocytic inflammation (Figure), suggestive of porokeratosis plantaris palmaris et disseminata (PPPD). The dermatopathologist recommended a second biopsy to confirm the diagnosis and to confirm that the lesions on the palms and soles also were suggestive of porokeratosis. A second 4-mm punch biopsy of the left palm was consistent with PPPD.

The risks of PPPD as a precancerous entity along with the benefits and side effects of the various management options were discussed with our patient. We recommended that he start low-dose isotretinoin (20 mg/d) due to the large body surface area affected, making focal and field treatments likely insufficient. However, our patient opted not to treat and did not return for follow-up.

Subtypes of porokeratosis, including disseminated superficial actinic porokeratosis (DSAP) and PPPD, are conditions that disrupt the normal maturation of keratin and present clinically with symmetric, crusted, annular papules.¹ The signature but nonspecific histopathologic feature shared among the subtypes is the presence of a cornoid lamellae.² Several triggers of porokeratosis have been proposed, including trauma and exposure to UV and ionizing radiation.^2,3 The clinical variants of porokeratosis are important conditions to diagnose correctly because they portend a risk for Bowen disease and invasive squamous cell carcinoma and may indicate the presence of an underlying hematologic and/or solid organ malignancy.⁴ Management of porokeratosis is difficult, as treatments have shown limited efficacy and variable recurrence rates. Treatment options include focal, field, and systemic options, such as 5-fluorouracil, topical compound of cholesterol and lovastatin, isotretinoin, and acitretin.^1,2

Porokeratoses may arise from gene mutations in the mevalonate pathway,⁵ which is essential for the production of cholesterol.⁶ Topical cholesterol alone has not been shown to improve porokeratosis, but the combination topical therapy of cholesterol and lovastatin is promising. It is theorized to deliver benefit by both providing the essential end product of the pathway and simultaneously reducing the number of potentially toxic intermediates.⁶

Porokeratosis plantaris palmaris et disseminata (also known as porokeratosis plantaris) is unique among the subtypes of porokeratosis in that its annular, red-pink, papular rash with scaling and a keratotic border tends to start distally, involving the palms and soles, and progresses proximally to the trunk with smaller lesions.^1,7 This centripetal progression can take years, as was seen in our patient.¹ The disease is uncommon, with a dearth of published reports on PPPD.² However, case reports have shown that PPPD is strongly linked to family history and may have an autosomal-dominant inheritance pattern. Penetrance is greater in men than in women, as PPPD is twice as common in men.⁸ Most cases of PPPD have been diagnosed in patients in their 20s and 30s, but Hartman et al9 reported a case wherein a patient was diagnosed with PPPD after 65 years of age, similar to our patient.

Although the lesions in DSAP can appear similar to those in PPPD, DSAP is more common among the family of porokeratotic conditions, affecting women twice as often as men, with a sporadic pattern of inheritance.² These same features are present in some other types of porokeratosis but not PPPD. Furthermore, DSAP progresses proximally to distally but often with truncal sparing.²

Akin to PPPD, pityriasis rubra pilaris (PRP) often presents with palmoplantar keratoderma.¹⁰ There are at least 6 types of PRP with varying degrees of similarity to PPPD. However, in many cases PRP is associated with a background of diffuse erythema on the body with islands of spared skin. In addition, cases of PRP have been linked to extracutaneous findings such as ectropion and joint pain.¹¹

Darier disease, especially the acrokeratosis verruciformis of Hopf variant, is more common in men and involves younger populations, as in PPPD.¹¹ However, the crusted lesions seen in Darier disease frequently involve the skin folds. These intertriginous lesions may coalesce, mimicking warts in appearance, and are at risk for secondary infection. Nail findings in Darier disease also are distinct and include longitudinal white or red stripes running along the nail bed, in addition to V-shaped nicks at the nail tips.

Psoriasis can occur anywhere on the body and is associated with silver scaling atop a salmon-colored dermatitis.¹² It results from aberrant proliferation of keratinocytes. Some distinguishing features of psoriasis include a disease course that waxes and wanes as well as pitting of the nails.

Although PPPD typically affects young adults, we presented a case of PPPD in an older man. Porokeratosis plantaris palmaris et disseminata in older adults may represent a delayed diagnosis, imply a broader range for the age of onset, or suggest its manifestation secondary to radiation treatment or another phenomenon. For example, our patient received 35 radiotherapy cycles for tongue cancer more than 5 years prior to the onset of PPPD.

To the Editor:

An 85-year-old man with a history of hypertension and chronic kidney disease presented with a localized darkening patch of hair on the left parietal scalp that had progressed over the last 7 years (Figure 1A). He had no prior history of skin cancer. Physical examination revealed the remainder of the hair was gray. There was an irregularly pigmented plaque on the skin underlying the darkened hair measuring 5.0 cm in diameter that was confirmed to be melanoma (Figure 1B). He underwent a staged excision to remove the lesion. The surgical defect was closed via a 5.0×6.0-cm full-thickness skin graft. 

The initial biopsy showed melanoma in situ. However, the final pathology report following the excision revealed an invasive melanoma with a Breslow depth of 1.0 mm (Clark level IV; American Joint Committee on Cancer T1b).¹ Histopathology showed pigment deposition with surrounding deep follicular extension of melanoma (Figure 2).

The patient declined a sentinel lymph node biopsy and agreed to a genetic profile assessment.² The results of the test identified the patient had a low probability of a positive sentinel lymph node and the lowest risk of melanoma recurrence within 5 years. The patient was clear of disease at 12-month follow-up.

Based on a PubMed search of articles indexed for MEDLINE using the terms hair repigmentation and melanoma, there have been 11 other reported cases of hair repigmentation associated with melanoma (Table).^3-13 It initially was suspected that this rare phenomenon primarily existed in the female population, as the first 5 cases were reported solely in females,^3-7 possibly due to the prevalence of androgenetic alopecia in males.¹¹ However, 6 cases of repigmentation associated with melanoma were later reported in males^8-13; our patient represents an additional reported case in a male. It is unknown if there is a higher prevalence of this phenomenon among males or females.

Most previously reported cases of repigmentation were associated with melanoma in situ, lentigo maligna type. Repigmentation also has been reported in malignant melanoma, as documented in our patient, as well as desmoplastic and amelanotic melanoma.^5,6 In every case, the color of the repigmentation was darker than the rest of the patient’s hair; however, the repigmentation color can be different from the patient’s original hair color from their youth.^4,5,11

The exact mechanism responsible for hair repigmentation in the setting of melanoma is unclear. It has been speculated from prior cases that repigmentation may be caused by paracrine stimulation from melanoma cells activating adjacent benign hair follicle melanocytes to produce melanin.^7,14,15 This process likely is due to cytokines or growth factors, such as c-kit ligand.^14,15 Several neural and immune networks and mediators activate the receptor tyrosine kinase KIT, which is thought to play a role in activating melanogenesis within the hair bulb.¹⁴ These signals also could originate from changes in the microenvironment instead of the melanoma cells themselves.⁶ Another possible mechanism is that repigmentation was caused by melanin-producing malignant melanocytes.⁴

Because this phenomenon typically occurs in older patients, the cause of repigmentation also could be related to chronic sun damage, which may result in upregulation of stem cell factor and α-melanocyte–stimulating hormone, as well as other molecules associated with melanogenesis, such as c-KIT receptor and tyrosinase.^15,16 Upregulation of these molecules can lead to an increased number of melanocytes within the hair bulb. In addition, UVA and narrowband UVB have been recognized as major players in melanocyte stimulation. Phototherapy with UVA or narrowband UVB has been used for repigmentation in vitiligo patients.¹⁷

In cases without invasion of hair follicles by malignant cells, repigmentation more likely results from external signals stimulating benign bulbar melanocytes to produce melanin rather than melanoma cell growth extending into the hair bulb.⁶ In these cases, there is an increase in the number of hair bulbar melanocytes with a lack of malignant morphology in the hair bulb.⁸ If the signals are directly from melanoma cells in the hair bulb, it is unknown how the malignant cells upregulated melanogenesis in adjacent benign melanocytes or which specific signals required for normal pigmentation were involved in these repigmentation cases.⁶

Use of medications was ruled out as an underlying cause of the repigmentation in our patient. Drug-related repigmentation of the hair typically is observed in a diffuse generalized pattern. In our case, the repigmentation was localized to the area of the underlying dark patch, and the patient was not on any medications that could cause hair hyperpigmentation. Hyperpigmentation has been associated with acitretin, lenalidomide, corticosteroids, erlotinib, latanoprost, verapamil, tamoxifen, levodopa, thalidomide, PD-1 inhibitors, and tumor necrosis α inhibitors.^18-30 Repigmentation also has been reported after local radiotherapy and herpes zoster infection.^31,32

The underlying melanoma in our patient was removed by staged square excision. Excision was the treatment of choice for most similar reported cases. Radiotherapy was utilized in two different cases.^3,4 In one case, radiotherapy was successfully used to treat melanoma in situ, lentigo maligna type; the patient’s hair grew back to its original color, which suggests that normal hair physiology was restored once melanoma cells were eliminated.³ One reported case demonstrated successful treatment of lentigo maligna type–melanoma with imiquimod cream 5% applied 6 times weekly for 9 months with a positive cosmetic result.⁹ The exact mechanism of imiquimod is not fully understood. Imiquimod induces cytokines to stimulate the production of IFN-α via activation of toll-like receptor 7.³³ There was complete clearing of the lesion as well as the hair pigmentation,⁹ which suggests that the treatment also eliminated deeper cells influencing pigmentation. A case of malignant amelanotic melanoma was successfully treated with anti–PD-1 antibody pembrolizumab (2 mg/kg every 3 weeks), with no recurrence at 12 months. Pembrolizumab acts as an immune checkpoint inhibitor by binding to the PD-1 receptor and allowing the immune system to recognize and attack melanoma cells. After 5 doses of pembrolizumab, the patient was clear of disease and his hair color returned to gray.⁵

In 2022, melanoma was estimated to be the fifth most commonly diagnosed cancer among men and women in the United States.³⁴ Early melanoma detection is a critical factor in achieving positive patient outcomes. Hair repigmentation is a potentially serious phenomenon that warrants a physician visit. Melanoma lesions under the hair may be overlooked because of limited visibility. Physicians must inspect spontaneous hair repigmentation with high suspicion and interpret the change as a possible indirect result of melanoma. Overall, it is important to increase public awareness of regular skin checks and melanoma warning signs.

To the Editor:

An 85-year-old man with a history of hypertension and chronic kidney disease presented with a localized darkening patch of hair on the left parietal scalp that had progressed over the last 7 years (Figure 1A). He had no prior history of skin cancer. Physical examination revealed the remainder of the hair was gray. There was an irregularly pigmented plaque on the skin underlying the darkened hair measuring 5.0 cm in diameter that was confirmed to be melanoma (Figure 1B). He underwent a staged excision to remove the lesion. The surgical defect was closed via a 5.0×6.0-cm full-thickness skin graft. 

The initial biopsy showed melanoma in situ. However, the final pathology report following the excision revealed an invasive melanoma with a Breslow depth of 1.0 mm (Clark level IV; American Joint Committee on Cancer T1b).¹ Histopathology showed pigment deposition with surrounding deep follicular extension of melanoma (Figure 2).

The patient declined a sentinel lymph node biopsy and agreed to a genetic profile assessment.² The results of the test identified the patient had a low probability of a positive sentinel lymph node and the lowest risk of melanoma recurrence within 5 years. The patient was clear of disease at 12-month follow-up.

Based on a PubMed search of articles indexed for MEDLINE using the terms hair repigmentation and melanoma, there have been 11 other reported cases of hair repigmentation associated with melanoma (Table).^3-13 It initially was suspected that this rare phenomenon primarily existed in the female population, as the first 5 cases were reported solely in females,^3-7 possibly due to the prevalence of androgenetic alopecia in males.¹¹ However, 6 cases of repigmentation associated with melanoma were later reported in males^8-13; our patient represents an additional reported case in a male. It is unknown if there is a higher prevalence of this phenomenon among males or females.

Most previously reported cases of repigmentation were associated with melanoma in situ, lentigo maligna type. Repigmentation also has been reported in malignant melanoma, as documented in our patient, as well as desmoplastic and amelanotic melanoma.^5,6 In every case, the color of the repigmentation was darker than the rest of the patient’s hair; however, the repigmentation color can be different from the patient’s original hair color from their youth.^4,5,11

The exact mechanism responsible for hair repigmentation in the setting of melanoma is unclear. It has been speculated from prior cases that repigmentation may be caused by paracrine stimulation from melanoma cells activating adjacent benign hair follicle melanocytes to produce melanin.^7,14,15 This process likely is due to cytokines or growth factors, such as c-kit ligand.^14,15 Several neural and immune networks and mediators activate the receptor tyrosine kinase KIT, which is thought to play a role in activating melanogenesis within the hair bulb.¹⁴ These signals also could originate from changes in the microenvironment instead of the melanoma cells themselves.⁶ Another possible mechanism is that repigmentation was caused by melanin-producing malignant melanocytes.⁴

Because this phenomenon typically occurs in older patients, the cause of repigmentation also could be related to chronic sun damage, which may result in upregulation of stem cell factor and α-melanocyte–stimulating hormone, as well as other molecules associated with melanogenesis, such as c-KIT receptor and tyrosinase.^15,16 Upregulation of these molecules can lead to an increased number of melanocytes within the hair bulb. In addition, UVA and narrowband UVB have been recognized as major players in melanocyte stimulation. Phototherapy with UVA or narrowband UVB has been used for repigmentation in vitiligo patients.¹⁷

In cases without invasion of hair follicles by malignant cells, repigmentation more likely results from external signals stimulating benign bulbar melanocytes to produce melanin rather than melanoma cell growth extending into the hair bulb.⁶ In these cases, there is an increase in the number of hair bulbar melanocytes with a lack of malignant morphology in the hair bulb.⁸ If the signals are directly from melanoma cells in the hair bulb, it is unknown how the malignant cells upregulated melanogenesis in adjacent benign melanocytes or which specific signals required for normal pigmentation were involved in these repigmentation cases.⁶

Use of medications was ruled out as an underlying cause of the repigmentation in our patient. Drug-related repigmentation of the hair typically is observed in a diffuse generalized pattern. In our case, the repigmentation was localized to the area of the underlying dark patch, and the patient was not on any medications that could cause hair hyperpigmentation. Hyperpigmentation has been associated with acitretin, lenalidomide, corticosteroids, erlotinib, latanoprost, verapamil, tamoxifen, levodopa, thalidomide, PD-1 inhibitors, and tumor necrosis α inhibitors.^18-30 Repigmentation also has been reported after local radiotherapy and herpes zoster infection.^31,32

The underlying melanoma in our patient was removed by staged square excision. Excision was the treatment of choice for most similar reported cases. Radiotherapy was utilized in two different cases.^3,4 In one case, radiotherapy was successfully used to treat melanoma in situ, lentigo maligna type; the patient’s hair grew back to its original color, which suggests that normal hair physiology was restored once melanoma cells were eliminated.³ One reported case demonstrated successful treatment of lentigo maligna type–melanoma with imiquimod cream 5% applied 6 times weekly for 9 months with a positive cosmetic result.⁹ The exact mechanism of imiquimod is not fully understood. Imiquimod induces cytokines to stimulate the production of IFN-α via activation of toll-like receptor 7.³³ There was complete clearing of the lesion as well as the hair pigmentation,⁹ which suggests that the treatment also eliminated deeper cells influencing pigmentation. A case of malignant amelanotic melanoma was successfully treated with anti–PD-1 antibody pembrolizumab (2 mg/kg every 3 weeks), with no recurrence at 12 months. Pembrolizumab acts as an immune checkpoint inhibitor by binding to the PD-1 receptor and allowing the immune system to recognize and attack melanoma cells. After 5 doses of pembrolizumab, the patient was clear of disease and his hair color returned to gray.⁵

In 2022, melanoma was estimated to be the fifth most commonly diagnosed cancer among men and women in the United States.³⁴ Early melanoma detection is a critical factor in achieving positive patient outcomes. Hair repigmentation is a potentially serious phenomenon that warrants a physician visit. Melanoma lesions under the hair may be overlooked because of limited visibility. Physicians must inspect spontaneous hair repigmentation with high suspicion and interpret the change as a possible indirect result of melanoma. Overall, it is important to increase public awareness of regular skin checks and melanoma warning signs.

To the Editor:

An 85-year-old man with a history of hypertension and chronic kidney disease presented with a localized darkening patch of hair on the left parietal scalp that had progressed over the last 7 years (Figure 1A). He had no prior history of skin cancer. Physical examination revealed the remainder of the hair was gray. There was an irregularly pigmented plaque on the skin underlying the darkened hair measuring 5.0 cm in diameter that was confirmed to be melanoma (Figure 1B). He underwent a staged excision to remove the lesion. The surgical defect was closed via a 5.0×6.0-cm full-thickness skin graft. 

The initial biopsy showed melanoma in situ. However, the final pathology report following the excision revealed an invasive melanoma with a Breslow depth of 1.0 mm (Clark level IV; American Joint Committee on Cancer T1b).¹ Histopathology showed pigment deposition with surrounding deep follicular extension of melanoma (Figure 2).

The patient declined a sentinel lymph node biopsy and agreed to a genetic profile assessment.² The results of the test identified the patient had a low probability of a positive sentinel lymph node and the lowest risk of melanoma recurrence within 5 years. The patient was clear of disease at 12-month follow-up.

Based on a PubMed search of articles indexed for MEDLINE using the terms hair repigmentation and melanoma, there have been 11 other reported cases of hair repigmentation associated with melanoma (Table).^3-13 It initially was suspected that this rare phenomenon primarily existed in the female population, as the first 5 cases were reported solely in females,^3-7 possibly due to the prevalence of androgenetic alopecia in males.¹¹ However, 6 cases of repigmentation associated with melanoma were later reported in males^8-13; our patient represents an additional reported case in a male. It is unknown if there is a higher prevalence of this phenomenon among males or females.

Most previously reported cases of repigmentation were associated with melanoma in situ, lentigo maligna type. Repigmentation also has been reported in malignant melanoma, as documented in our patient, as well as desmoplastic and amelanotic melanoma.^5,6 In every case, the color of the repigmentation was darker than the rest of the patient’s hair; however, the repigmentation color can be different from the patient’s original hair color from their youth.^4,5,11

The exact mechanism responsible for hair repigmentation in the setting of melanoma is unclear. It has been speculated from prior cases that repigmentation may be caused by paracrine stimulation from melanoma cells activating adjacent benign hair follicle melanocytes to produce melanin.^7,14,15 This process likely is due to cytokines or growth factors, such as c-kit ligand.^14,15 Several neural and immune networks and mediators activate the receptor tyrosine kinase KIT, which is thought to play a role in activating melanogenesis within the hair bulb.¹⁴ These signals also could originate from changes in the microenvironment instead of the melanoma cells themselves.⁶ Another possible mechanism is that repigmentation was caused by melanin-producing malignant melanocytes.⁴

Because this phenomenon typically occurs in older patients, the cause of repigmentation also could be related to chronic sun damage, which may result in upregulation of stem cell factor and α-melanocyte–stimulating hormone, as well as other molecules associated with melanogenesis, such as c-KIT receptor and tyrosinase.^15,16 Upregulation of these molecules can lead to an increased number of melanocytes within the hair bulb. In addition, UVA and narrowband UVB have been recognized as major players in melanocyte stimulation. Phototherapy with UVA or narrowband UVB has been used for repigmentation in vitiligo patients.¹⁷

In cases without invasion of hair follicles by malignant cells, repigmentation more likely results from external signals stimulating benign bulbar melanocytes to produce melanin rather than melanoma cell growth extending into the hair bulb.⁶ In these cases, there is an increase in the number of hair bulbar melanocytes with a lack of malignant morphology in the hair bulb.⁸ If the signals are directly from melanoma cells in the hair bulb, it is unknown how the malignant cells upregulated melanogenesis in adjacent benign melanocytes or which specific signals required for normal pigmentation were involved in these repigmentation cases.⁶

Use of medications was ruled out as an underlying cause of the repigmentation in our patient. Drug-related repigmentation of the hair typically is observed in a diffuse generalized pattern. In our case, the repigmentation was localized to the area of the underlying dark patch, and the patient was not on any medications that could cause hair hyperpigmentation. Hyperpigmentation has been associated with acitretin, lenalidomide, corticosteroids, erlotinib, latanoprost, verapamil, tamoxifen, levodopa, thalidomide, PD-1 inhibitors, and tumor necrosis α inhibitors.^18-30 Repigmentation also has been reported after local radiotherapy and herpes zoster infection.^31,32

The underlying melanoma in our patient was removed by staged square excision. Excision was the treatment of choice for most similar reported cases. Radiotherapy was utilized in two different cases.^3,4 In one case, radiotherapy was successfully used to treat melanoma in situ, lentigo maligna type; the patient’s hair grew back to its original color, which suggests that normal hair physiology was restored once melanoma cells were eliminated.³ One reported case demonstrated successful treatment of lentigo maligna type–melanoma with imiquimod cream 5% applied 6 times weekly for 9 months with a positive cosmetic result.⁹ The exact mechanism of imiquimod is not fully understood. Imiquimod induces cytokines to stimulate the production of IFN-α via activation of toll-like receptor 7.³³ There was complete clearing of the lesion as well as the hair pigmentation,⁹ which suggests that the treatment also eliminated deeper cells influencing pigmentation. A case of malignant amelanotic melanoma was successfully treated with anti–PD-1 antibody pembrolizumab (2 mg/kg every 3 weeks), with no recurrence at 12 months. Pembrolizumab acts as an immune checkpoint inhibitor by binding to the PD-1 receptor and allowing the immune system to recognize and attack melanoma cells. After 5 doses of pembrolizumab, the patient was clear of disease and his hair color returned to gray.⁵

In 2022, melanoma was estimated to be the fifth most commonly diagnosed cancer among men and women in the United States.³⁴ Early melanoma detection is a critical factor in achieving positive patient outcomes. Hair repigmentation is a potentially serious phenomenon that warrants a physician visit. Melanoma lesions under the hair may be overlooked because of limited visibility. Physicians must inspect spontaneous hair repigmentation with high suspicion and interpret the change as a possible indirect result of melanoma. Overall, it is important to increase public awareness of regular skin checks and melanoma warning signs.

New data released by the U.S. Department of Defense show that the incidence of many types of cancer is higher among military pilots and aviation support personnel in comparison with the general population.

“Military aircrew and ground crew were overall more likely to be diagnosed with cancer, but less likely to die from cancer compared to the U.S. population,” the report concludes.

The study involved 156,050 aircrew and 737,891 ground crew. Participants were followed between 1992 and 2017. Both groups were predominantly male and non-Hispanic.

Data on cancer incidence and mortality for these two groups were compared with data from groups of similar age in the general population through use of the Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute.

For aircrew, the study found an 87% higher rate of melanoma, a 39% higher rate of thyroid cancer, a 16% higher rate of prostate cancer, and a 24% higher rate of cancer for all sites combined.

A higher rate of melanoma and prostate cancer among aircrew has been reported previously, but the increased rate of thyroid cancer is a new finding, the authors note.

The uptick in melanoma has also been reported in studies of civilian pilots and cabin crew. It has been attributed to exposure to hazardous ultraviolet and cosmic radiation.

For ground crew members, the analysis found a 19% higher rate of cancers of the brain and nervous system, a 15% higher rate of thyroid cancer, a 9% higher rate of melanoma and of kidney and renal pelvis cancers, and a 3% higher rate of cancer for all sites combined.

There is little to compare these findings with: This is the first time that cancer risk has been evaluated in such a large population of military ground crew.
 

Lower rates of cancer mortality

In contrast to the increase in cancer incidence, the report found a decrease in cancer mortality.

When compared with a demographically similar U.S. population, the mortality rate among aircrew was 56% lower for all cancer sites; for ground crew, the mortality rate was 35% lower.

However, the report authors emphasize that “it is important to note that the military study population was relatively young.”

The median age at the end of follow-up for the cancer incidence analysis was 41 years for aircrew and 26 years for ground crew. The median age at the end of follow-up for the cancer mortality analysis was 48 years for aircrew and 41 years for ground crew.

“Results may have differed if additional older former Service members had been included in the study, since cancer risk and mortality rates increase with age,” the authors comment.

Other studies have found an increase in deaths from melanoma as well as an increase in the incidence of melanoma. A meta-analysis published in 2019 in the British Journal of Dermatology found that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population. Pilots are also more likely to die from melanoma.
 

Further study underway

The findings on military air and ground crew come from phase 1 of a study that was required by Congress in the 2021 defense bill. Because the investigators found an increase in the incidence of cancer, phase 2 of the study is now necessary.

The report authors explain that phase 2 will consist of identifying the carcinogenic toxicants or hazardous materials associated with military flight operations; identifying operating environments that could be associated with increased amounts of ionizing and nonionizing radiation; identifying specific duties, dates of service, and types of aircraft flown that could have increased the risk for cancer; identifying duty locations associated with a higher incidence of cancers; identifying potential exposures through military service that are not related to aviation; and determining the appropriate age to begin screening military aircrew and ground crew for cancers.

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

New data released by the U.S. Department of Defense show that the incidence of many types of cancer is higher among military pilots and aviation support personnel in comparison with the general population.

“Military aircrew and ground crew were overall more likely to be diagnosed with cancer, but less likely to die from cancer compared to the U.S. population,” the report concludes.

The study involved 156,050 aircrew and 737,891 ground crew. Participants were followed between 1992 and 2017. Both groups were predominantly male and non-Hispanic.

Data on cancer incidence and mortality for these two groups were compared with data from groups of similar age in the general population through use of the Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute.

For aircrew, the study found an 87% higher rate of melanoma, a 39% higher rate of thyroid cancer, a 16% higher rate of prostate cancer, and a 24% higher rate of cancer for all sites combined.

A higher rate of melanoma and prostate cancer among aircrew has been reported previously, but the increased rate of thyroid cancer is a new finding, the authors note.

The uptick in melanoma has also been reported in studies of civilian pilots and cabin crew. It has been attributed to exposure to hazardous ultraviolet and cosmic radiation.

For ground crew members, the analysis found a 19% higher rate of cancers of the brain and nervous system, a 15% higher rate of thyroid cancer, a 9% higher rate of melanoma and of kidney and renal pelvis cancers, and a 3% higher rate of cancer for all sites combined.

There is little to compare these findings with: This is the first time that cancer risk has been evaluated in such a large population of military ground crew.
 

Lower rates of cancer mortality

In contrast to the increase in cancer incidence, the report found a decrease in cancer mortality.

When compared with a demographically similar U.S. population, the mortality rate among aircrew was 56% lower for all cancer sites; for ground crew, the mortality rate was 35% lower.

However, the report authors emphasize that “it is important to note that the military study population was relatively young.”

The median age at the end of follow-up for the cancer incidence analysis was 41 years for aircrew and 26 years for ground crew. The median age at the end of follow-up for the cancer mortality analysis was 48 years for aircrew and 41 years for ground crew.

“Results may have differed if additional older former Service members had been included in the study, since cancer risk and mortality rates increase with age,” the authors comment.

Other studies have found an increase in deaths from melanoma as well as an increase in the incidence of melanoma. A meta-analysis published in 2019 in the British Journal of Dermatology found that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population. Pilots are also more likely to die from melanoma.
 

Further study underway

The findings on military air and ground crew come from phase 1 of a study that was required by Congress in the 2021 defense bill. Because the investigators found an increase in the incidence of cancer, phase 2 of the study is now necessary.

The report authors explain that phase 2 will consist of identifying the carcinogenic toxicants or hazardous materials associated with military flight operations; identifying operating environments that could be associated with increased amounts of ionizing and nonionizing radiation; identifying specific duties, dates of service, and types of aircraft flown that could have increased the risk for cancer; identifying duty locations associated with a higher incidence of cancers; identifying potential exposures through military service that are not related to aviation; and determining the appropriate age to begin screening military aircrew and ground crew for cancers.

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

New data released by the U.S. Department of Defense show that the incidence of many types of cancer is higher among military pilots and aviation support personnel in comparison with the general population.

“Military aircrew and ground crew were overall more likely to be diagnosed with cancer, but less likely to die from cancer compared to the U.S. population,” the report concludes.

The study involved 156,050 aircrew and 737,891 ground crew. Participants were followed between 1992 and 2017. Both groups were predominantly male and non-Hispanic.

Data on cancer incidence and mortality for these two groups were compared with data from groups of similar age in the general population through use of the Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute.

For aircrew, the study found an 87% higher rate of melanoma, a 39% higher rate of thyroid cancer, a 16% higher rate of prostate cancer, and a 24% higher rate of cancer for all sites combined.

A higher rate of melanoma and prostate cancer among aircrew has been reported previously, but the increased rate of thyroid cancer is a new finding, the authors note.

The uptick in melanoma has also been reported in studies of civilian pilots and cabin crew. It has been attributed to exposure to hazardous ultraviolet and cosmic radiation.

For ground crew members, the analysis found a 19% higher rate of cancers of the brain and nervous system, a 15% higher rate of thyroid cancer, a 9% higher rate of melanoma and of kidney and renal pelvis cancers, and a 3% higher rate of cancer for all sites combined.

There is little to compare these findings with: This is the first time that cancer risk has been evaluated in such a large population of military ground crew.
 

Lower rates of cancer mortality

In contrast to the increase in cancer incidence, the report found a decrease in cancer mortality.

When compared with a demographically similar U.S. population, the mortality rate among aircrew was 56% lower for all cancer sites; for ground crew, the mortality rate was 35% lower.

However, the report authors emphasize that “it is important to note that the military study population was relatively young.”

The median age at the end of follow-up for the cancer incidence analysis was 41 years for aircrew and 26 years for ground crew. The median age at the end of follow-up for the cancer mortality analysis was 48 years for aircrew and 41 years for ground crew.

“Results may have differed if additional older former Service members had been included in the study, since cancer risk and mortality rates increase with age,” the authors comment.

Other studies have found an increase in deaths from melanoma as well as an increase in the incidence of melanoma. A meta-analysis published in 2019 in the British Journal of Dermatology found that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population. Pilots are also more likely to die from melanoma.
 

Further study underway

The findings on military air and ground crew come from phase 1 of a study that was required by Congress in the 2021 defense bill. Because the investigators found an increase in the incidence of cancer, phase 2 of the study is now necessary.

The report authors explain that phase 2 will consist of identifying the carcinogenic toxicants or hazardous materials associated with military flight operations; identifying operating environments that could be associated with increased amounts of ionizing and nonionizing radiation; identifying specific duties, dates of service, and types of aircraft flown that could have increased the risk for cancer; identifying duty locations associated with a higher incidence of cancers; identifying potential exposures through military service that are not related to aviation; and determining the appropriate age to begin screening military aircrew and ground crew for cancers.

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

Detecting melanoma early, when it is easier to treat, remains a “paramount goal,” but guidelines surrounding optimal melanoma screening practices and diagnostic evaluations need greater clarity, according to the authors of a new consensus statement.

That is why a group of expert panelists evaluated the existing evidence and a range of clinical scenarios to help clarify the optimal strategies for early detection and assessment of cutaneous melanoma.

Overall, the panelists agreed that a risk-stratified approach is likely the most appropriate strategy for melanoma screening and follow-up and supported the use of visual and dermoscopic examination. However, the panelists did not reach consensus on the role for gene expression profile (GEP) testing in clinical decision-making, citing the need for these assays to be validated in large randomized clinical trials.

In an accompanying editorial, two experts highlighted the importance of carefully evaluating the role of diagnostic tests.

“Diagnostic tests such as GEP must face critical scrutiny; if not, there are immediate concerns for patient care, such as the patient being erroneously informed that they do not have cancer or told that they do have cancer when they do not,” write Alan C. Geller, MPH, RN, from the Harvard T.H. Chan School of Public Health, Boston, and Marvin A. Weinstock, MD, PhD, from Brown University, Providence, R.I.

The consensus statement was published online in JAMA Dermatology.
 

The need for guidance

Although focusing melanoma screening on higher-risk populations may be cost effective, compared with population-based screening, the major guidelines lack consistent guidance to support a risk-stratified approach to skin cancer screening and best practices on diagnosing cutaneous melanoma.

In the prebiopsy setting, the appropriate use of diagnostic tools for evaluating the need for biopsy remain poorly defined, and, in the post-biopsy setting, questions remain concerning the diagnostic accuracy of molecular techniques, diagnostic GEP testing, next-generation sequencing, and immunohistochemical assessment for various markers of melanoma.

To provide consensus recommendations on optimal screening practices, prebiopsy and postbiopsy diagnostics, and prognostic assessment of cutaneous melanoma, a group of 42 panelists voted on hypothetical scenarios via an emailed survey. The panel then came together for a consensus conference, which included 51 experts who discussed their approach to the various clinical case scenarios. Most attendees (45 of the 51) answered a follow-up survey for their final recommendations.

The panelists reached a consensus, with 70% agreement, to support a risk-stratified approach to melanoma screening in clinical settings and public screening events. The experts agreed that higher-risk individuals (those with a relative risk of 5 or greater) could be appropriately screened by a general dermatologist or pigmented lesion evaluation. Higher-risk individuals included those with severe skin damage from the sun, systemic immunosuppression, or a personal history of nonmelanoma or melanoma skin cancer.

Panelists agreed that those at general or lower risk (RR < 2) could be screened by a primary care provider or through regular self- or partner examinations, whereas those at moderate risk could be screened by their primary care clinician or general dermatologist. The experts observed “a shift in acceptance” of primary care physicians screening the general population, and an acknowledgement of the importance of self- and partner examinations as screening adjuncts for all populations.

In the prebiopsy setting, panelists reached consensus that visual and dermoscopic examination was appropriate for evaluating patients with “no new, changing, or unusual skin lesions or with a new lesion that is not visually concerning.”

The panelists also reached consensus that lesions deemed clinically suspicious for cancer or showing features of cancer on reflectance confocal microscopy should be biopsied. Although most respondents (86%) did not currently use epidermal tape stripping routinely, they agreed that, in a hypothetical situation where epidermal tape stripping was used, that lesions positive for PRAME or LINC should be biopsied.

In the postbiopsy setting, views on the use of GEP scores varied. Although panelists agreed that a low-risk prognostic GEP score should not outweigh concerning histologic features when patients are selected to undergo sentinel lymph node biopsy (SLNB), they did not reach consensus for imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status.

“The panelists await future, well-designed prospective studies to determine if use of these and newer technologies improves the care of patients with melanoma,” the panelists write.

In the editorial, Mr. Geller and Dr. Weinstock highlighted concerns about the cost and potential access issues associated with these newer technologies, given that the current cost of GEP testing exceeds $7,000.

The editorialists also emphasize that “going forward, the field should be advanced by tackling one of the more pressing, common, potentially morbid, and costly procedures – the prognostic use of sentinel lymph node biopsy.”

Of critical importance is “whether GEP can reduce morbidity and cost by safely reducing the number of SLNBs performed,” Mr. Geller and Dr. Weinstock write.

The funding for the administration and facilitation of the consensus development conference and the development of the manuscript was provided by Dermtech, in an unrestricted award overseen by the Melanoma Research Foundation and managed and executed at UPMC by the principal investigator. Several of the coauthors disclosed relationships with industry. Mr. Geller is a contributor to UptoDate for which he receives royalties. Dr. Weinstock receives consulting fees from AbbVie.

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

Detecting melanoma early, when it is easier to treat, remains a “paramount goal,” but guidelines surrounding optimal melanoma screening practices and diagnostic evaluations need greater clarity, according to the authors of a new consensus statement.

That is why a group of expert panelists evaluated the existing evidence and a range of clinical scenarios to help clarify the optimal strategies for early detection and assessment of cutaneous melanoma.

Overall, the panelists agreed that a risk-stratified approach is likely the most appropriate strategy for melanoma screening and follow-up and supported the use of visual and dermoscopic examination. However, the panelists did not reach consensus on the role for gene expression profile (GEP) testing in clinical decision-making, citing the need for these assays to be validated in large randomized clinical trials.

In an accompanying editorial, two experts highlighted the importance of carefully evaluating the role of diagnostic tests.

“Diagnostic tests such as GEP must face critical scrutiny; if not, there are immediate concerns for patient care, such as the patient being erroneously informed that they do not have cancer or told that they do have cancer when they do not,” write Alan C. Geller, MPH, RN, from the Harvard T.H. Chan School of Public Health, Boston, and Marvin A. Weinstock, MD, PhD, from Brown University, Providence, R.I.

The consensus statement was published online in JAMA Dermatology.
 

The need for guidance

Although focusing melanoma screening on higher-risk populations may be cost effective, compared with population-based screening, the major guidelines lack consistent guidance to support a risk-stratified approach to skin cancer screening and best practices on diagnosing cutaneous melanoma.

In the prebiopsy setting, the appropriate use of diagnostic tools for evaluating the need for biopsy remain poorly defined, and, in the post-biopsy setting, questions remain concerning the diagnostic accuracy of molecular techniques, diagnostic GEP testing, next-generation sequencing, and immunohistochemical assessment for various markers of melanoma.

To provide consensus recommendations on optimal screening practices, prebiopsy and postbiopsy diagnostics, and prognostic assessment of cutaneous melanoma, a group of 42 panelists voted on hypothetical scenarios via an emailed survey. The panel then came together for a consensus conference, which included 51 experts who discussed their approach to the various clinical case scenarios. Most attendees (45 of the 51) answered a follow-up survey for their final recommendations.

The panelists reached a consensus, with 70% agreement, to support a risk-stratified approach to melanoma screening in clinical settings and public screening events. The experts agreed that higher-risk individuals (those with a relative risk of 5 or greater) could be appropriately screened by a general dermatologist or pigmented lesion evaluation. Higher-risk individuals included those with severe skin damage from the sun, systemic immunosuppression, or a personal history of nonmelanoma or melanoma skin cancer.

Panelists agreed that those at general or lower risk (RR < 2) could be screened by a primary care provider or through regular self- or partner examinations, whereas those at moderate risk could be screened by their primary care clinician or general dermatologist. The experts observed “a shift in acceptance” of primary care physicians screening the general population, and an acknowledgement of the importance of self- and partner examinations as screening adjuncts for all populations.

In the prebiopsy setting, panelists reached consensus that visual and dermoscopic examination was appropriate for evaluating patients with “no new, changing, or unusual skin lesions or with a new lesion that is not visually concerning.”

The panelists also reached consensus that lesions deemed clinically suspicious for cancer or showing features of cancer on reflectance confocal microscopy should be biopsied. Although most respondents (86%) did not currently use epidermal tape stripping routinely, they agreed that, in a hypothetical situation where epidermal tape stripping was used, that lesions positive for PRAME or LINC should be biopsied.

In the postbiopsy setting, views on the use of GEP scores varied. Although panelists agreed that a low-risk prognostic GEP score should not outweigh concerning histologic features when patients are selected to undergo sentinel lymph node biopsy (SLNB), they did not reach consensus for imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status.

“The panelists await future, well-designed prospective studies to determine if use of these and newer technologies improves the care of patients with melanoma,” the panelists write.

In the editorial, Mr. Geller and Dr. Weinstock highlighted concerns about the cost and potential access issues associated with these newer technologies, given that the current cost of GEP testing exceeds $7,000.

The editorialists also emphasize that “going forward, the field should be advanced by tackling one of the more pressing, common, potentially morbid, and costly procedures – the prognostic use of sentinel lymph node biopsy.”

Of critical importance is “whether GEP can reduce morbidity and cost by safely reducing the number of SLNBs performed,” Mr. Geller and Dr. Weinstock write.

The funding for the administration and facilitation of the consensus development conference and the development of the manuscript was provided by Dermtech, in an unrestricted award overseen by the Melanoma Research Foundation and managed and executed at UPMC by the principal investigator. Several of the coauthors disclosed relationships with industry. Mr. Geller is a contributor to UptoDate for which he receives royalties. Dr. Weinstock receives consulting fees from AbbVie.

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

Detecting melanoma early, when it is easier to treat, remains a “paramount goal,” but guidelines surrounding optimal melanoma screening practices and diagnostic evaluations need greater clarity, according to the authors of a new consensus statement.

That is why a group of expert panelists evaluated the existing evidence and a range of clinical scenarios to help clarify the optimal strategies for early detection and assessment of cutaneous melanoma.

Overall, the panelists agreed that a risk-stratified approach is likely the most appropriate strategy for melanoma screening and follow-up and supported the use of visual and dermoscopic examination. However, the panelists did not reach consensus on the role for gene expression profile (GEP) testing in clinical decision-making, citing the need for these assays to be validated in large randomized clinical trials.

In an accompanying editorial, two experts highlighted the importance of carefully evaluating the role of diagnostic tests.

“Diagnostic tests such as GEP must face critical scrutiny; if not, there are immediate concerns for patient care, such as the patient being erroneously informed that they do not have cancer or told that they do have cancer when they do not,” write Alan C. Geller, MPH, RN, from the Harvard T.H. Chan School of Public Health, Boston, and Marvin A. Weinstock, MD, PhD, from Brown University, Providence, R.I.

The consensus statement was published online in JAMA Dermatology.
 

The need for guidance

Although focusing melanoma screening on higher-risk populations may be cost effective, compared with population-based screening, the major guidelines lack consistent guidance to support a risk-stratified approach to skin cancer screening and best practices on diagnosing cutaneous melanoma.

In the prebiopsy setting, the appropriate use of diagnostic tools for evaluating the need for biopsy remain poorly defined, and, in the post-biopsy setting, questions remain concerning the diagnostic accuracy of molecular techniques, diagnostic GEP testing, next-generation sequencing, and immunohistochemical assessment for various markers of melanoma.

To provide consensus recommendations on optimal screening practices, prebiopsy and postbiopsy diagnostics, and prognostic assessment of cutaneous melanoma, a group of 42 panelists voted on hypothetical scenarios via an emailed survey. The panel then came together for a consensus conference, which included 51 experts who discussed their approach to the various clinical case scenarios. Most attendees (45 of the 51) answered a follow-up survey for their final recommendations.

The panelists reached a consensus, with 70% agreement, to support a risk-stratified approach to melanoma screening in clinical settings and public screening events. The experts agreed that higher-risk individuals (those with a relative risk of 5 or greater) could be appropriately screened by a general dermatologist or pigmented lesion evaluation. Higher-risk individuals included those with severe skin damage from the sun, systemic immunosuppression, or a personal history of nonmelanoma or melanoma skin cancer.

Panelists agreed that those at general or lower risk (RR < 2) could be screened by a primary care provider or through regular self- or partner examinations, whereas those at moderate risk could be screened by their primary care clinician or general dermatologist. The experts observed “a shift in acceptance” of primary care physicians screening the general population, and an acknowledgement of the importance of self- and partner examinations as screening adjuncts for all populations.

In the prebiopsy setting, panelists reached consensus that visual and dermoscopic examination was appropriate for evaluating patients with “no new, changing, or unusual skin lesions or with a new lesion that is not visually concerning.”

The panelists also reached consensus that lesions deemed clinically suspicious for cancer or showing features of cancer on reflectance confocal microscopy should be biopsied. Although most respondents (86%) did not currently use epidermal tape stripping routinely, they agreed that, in a hypothetical situation where epidermal tape stripping was used, that lesions positive for PRAME or LINC should be biopsied.

In the postbiopsy setting, views on the use of GEP scores varied. Although panelists agreed that a low-risk prognostic GEP score should not outweigh concerning histologic features when patients are selected to undergo sentinel lymph node biopsy (SLNB), they did not reach consensus for imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status.

“The panelists await future, well-designed prospective studies to determine if use of these and newer technologies improves the care of patients with melanoma,” the panelists write.

In the editorial, Mr. Geller and Dr. Weinstock highlighted concerns about the cost and potential access issues associated with these newer technologies, given that the current cost of GEP testing exceeds $7,000.

The editorialists also emphasize that “going forward, the field should be advanced by tackling one of the more pressing, common, potentially morbid, and costly procedures – the prognostic use of sentinel lymph node biopsy.”

Of critical importance is “whether GEP can reduce morbidity and cost by safely reducing the number of SLNBs performed,” Mr. Geller and Dr. Weinstock write.

The funding for the administration and facilitation of the consensus development conference and the development of the manuscript was provided by Dermtech, in an unrestricted award overseen by the Melanoma Research Foundation and managed and executed at UPMC by the principal investigator. Several of the coauthors disclosed relationships with industry. Mr. Geller is a contributor to UptoDate for which he receives royalties. Dr. Weinstock receives consulting fees from AbbVie.

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