Melanoma

SAN DIEGO – Today’s molecular tests for managing melanoma patients are used to reclassify melanoma, identify patients at risk, as well as for diagnosis, prognosis, and treatment, but each one has its specific applications, benefits, and drawbacks, according to Gregory A. Hosler, MD, PhD.

At the annual Cutaneous Malignancy Update, Dr. Hosler, director of dermatopathology for ProPath, highlighted the following molecular tests currently used for the diagnosis of challenging melanocytic lesions:

Comparative genomic hybridization (CGH). This technique allows for the detection of chromosomal copy number changes throughout the tumor genome. “With CGH, test (tumor) DNA and normal DNA are differentially labeled and compared to a reference library. Gains and losses of portions of the tumor genome are determined by comparing the relative signals from these two groups,” said Dr. Hosler, clinical professor of pathology and dermatology at the University of Texas Southwestern Medical Center, Dallas.

“In the past, your library was a metaphase of spread of chromosomes, which introduced technical challenges and made performance of the assay labor intensive. Because of this, CGH is not routinely performed by clinical laboratories and is used more as an exploratory/research technique.”

Array CGH (also known as SNP array). Newer versions of CGH use short DNA sequences that are tiled onto a chip. “The interesting thing about these chips is that you can purchase them or design them on your own,” Dr. Hosler said. “The chips may cover the entire genome or cover specific areas of the genome at higher resolution.” One upside of array CGH, he continued, is that it allows one to detect essentially all gains or losses of chromosomal material in a single reaction. “It is not subject to the artifacts associated with cutting thin sections like with fluorescence in situ hybridization (FISH); it can detect copy number neutral loss of heterozygosity, and it is more scalable,” Dr. Hosler said at the meeting, which was hosted by Scripps MD Anderson Cancer Center.

One downside of array CGH is that does not allow one to analyze specific cells, “so if you have a tumor that’s heterogeneous, the assay is agnostic to this and spits out a result based on all the material provided,” he said. “You can’t parse out different areas of the lesion. It also does not track balanced translocations.” In addition, he said, “there are also questions about reimbursement and these are lab-developed tests, so each lab’s assay is different. Finally, it requires specialized equipment and expertise for interpretation.”

FISH. First-generation melanoma FISH assays, which became available in 2009, used six probes and four colors and had a sensitivity of about 87% and specificity of about 95%, Dr. Hosler said, but there were problems with those assays, particularly related to Spitz nevi. Spitz nevi often duplicate their chromosomes, “so instead of being diploid they’re tetraploid,” he said.

“The second-generation melanoma FISH assays addressed this by adding centromeres to the assay, and targeted probes could be compared to the centromeres on the same chromosome to determine if these were true copy number gains, due to genetic instability, or gains or losses of entire arms or whole chromosomes. This modification and the addition of new targets really improved upon the sensitivity and specificity (94% and 98%, respectively),” he said, noting that this assay is widely used.

Upsides of melanoma FISH assays are that they are a “fairly routine methodology” in large clinical laboratories, he said, and that many labs are familiar with interpretation. “I would say the biggest advantage to FISH is its ability to analyze specific cells, which is useful with small or heterogeneous tumors,” Dr. Hosler said. “Also, there is a genetic reimbursement code for it, and it yields diagnostic and potentially prognostic information.” For example, certain copy number changes have shown to portend a worse prognosis if they’re present in a melanocytic tumor, including alterations in CDKN2A, CCND1, MYC, topoisomerase, and BAP1.

Downsides of melanoma FISH assays are that they are expensive, labor-intensive, and require experts to interpret the results. “The stacking and truncation of cell nuclei innate to paraffin-embedded FISH make interpretation difficult,” he said. “Also, all colors cannot be viewed simultaneously, and each lab’s assay potentially is different, requiring validation. These are not [Food and Drug Administration]-approved tests.”

Next generation sequencing (NGS). Also known as high-throughput sequencing, this technique allows for the generation of millions of sequencing reads that are aligned to a standard human genome, and likely represents the wave of the future. “With NGS you can increase breadth, so you can sequence the entire genome if you want, but you can also increase depth, meaning increasing the number of reads over a single target of the genome,” Dr. Hosler said. “That’s useful if you’re looking for a low frequency mutation.”

For example, NGS allows one to detect alterations of BRAF and KIT and other potentially actionable alterations. It can also be used to detect mutations in benign and malignant melanocytic lesions, including historically diagnostically challenging Spitz and desmoplastic subgroups. Several different NGS technologies exist, and there are different strategies behind each assay, including whole genome sequencing, whole exome sequencing, transcriptome sequencing, and targeted panels. “I’ve seen panels of 10 and I’ve seen panels of 1,500; there’s a wide range,” Dr. Hosler said. “The biggest challenge with NGS, currently, is that it’s difficult to interpret. Trying to figure out what’s important and what’s not important can be challenging. Often you need a team of people who are experts in bioinformatics to interpret these results.”

Slow turnaround time is another downside. “It can take a month to get results, and sometimes clinicians don’t want to wait that long, especially if they think a lesion is melanoma, so that’s an area of focus for NGS laboratories,” he said. “And there are questions on reimbursement. If you run NGS on every unusual melanocytic lesion, that’s not a good use of health care dollars. Who’s paying for it? I don’t have an answer for you. It’s all over the map right now. Each lab’s test and billing practice is different.”

Dr. Hosler reported having no relevant financial disclosures. ProPath is a nationwide pathology practice.

SAN DIEGO – Today’s molecular tests for managing melanoma patients are used to reclassify melanoma, identify patients at risk, as well as for diagnosis, prognosis, and treatment, but each one has its specific applications, benefits, and drawbacks, according to Gregory A. Hosler, MD, PhD.

At the annual Cutaneous Malignancy Update, Dr. Hosler, director of dermatopathology for ProPath, highlighted the following molecular tests currently used for the diagnosis of challenging melanocytic lesions:

Comparative genomic hybridization (CGH). This technique allows for the detection of chromosomal copy number changes throughout the tumor genome. “With CGH, test (tumor) DNA and normal DNA are differentially labeled and compared to a reference library. Gains and losses of portions of the tumor genome are determined by comparing the relative signals from these two groups,” said Dr. Hosler, clinical professor of pathology and dermatology at the University of Texas Southwestern Medical Center, Dallas.

“In the past, your library was a metaphase of spread of chromosomes, which introduced technical challenges and made performance of the assay labor intensive. Because of this, CGH is not routinely performed by clinical laboratories and is used more as an exploratory/research technique.”

Array CGH (also known as SNP array). Newer versions of CGH use short DNA sequences that are tiled onto a chip. “The interesting thing about these chips is that you can purchase them or design them on your own,” Dr. Hosler said. “The chips may cover the entire genome or cover specific areas of the genome at higher resolution.” One upside of array CGH, he continued, is that it allows one to detect essentially all gains or losses of chromosomal material in a single reaction. “It is not subject to the artifacts associated with cutting thin sections like with fluorescence in situ hybridization (FISH); it can detect copy number neutral loss of heterozygosity, and it is more scalable,” Dr. Hosler said at the meeting, which was hosted by Scripps MD Anderson Cancer Center.

One downside of array CGH is that does not allow one to analyze specific cells, “so if you have a tumor that’s heterogeneous, the assay is agnostic to this and spits out a result based on all the material provided,” he said. “You can’t parse out different areas of the lesion. It also does not track balanced translocations.” In addition, he said, “there are also questions about reimbursement and these are lab-developed tests, so each lab’s assay is different. Finally, it requires specialized equipment and expertise for interpretation.”

FISH. First-generation melanoma FISH assays, which became available in 2009, used six probes and four colors and had a sensitivity of about 87% and specificity of about 95%, Dr. Hosler said, but there were problems with those assays, particularly related to Spitz nevi. Spitz nevi often duplicate their chromosomes, “so instead of being diploid they’re tetraploid,” he said.

“The second-generation melanoma FISH assays addressed this by adding centromeres to the assay, and targeted probes could be compared to the centromeres on the same chromosome to determine if these were true copy number gains, due to genetic instability, or gains or losses of entire arms or whole chromosomes. This modification and the addition of new targets really improved upon the sensitivity and specificity (94% and 98%, respectively),” he said, noting that this assay is widely used.

Upsides of melanoma FISH assays are that they are a “fairly routine methodology” in large clinical laboratories, he said, and that many labs are familiar with interpretation. “I would say the biggest advantage to FISH is its ability to analyze specific cells, which is useful with small or heterogeneous tumors,” Dr. Hosler said. “Also, there is a genetic reimbursement code for it, and it yields diagnostic and potentially prognostic information.” For example, certain copy number changes have shown to portend a worse prognosis if they’re present in a melanocytic tumor, including alterations in CDKN2A, CCND1, MYC, topoisomerase, and BAP1.

Downsides of melanoma FISH assays are that they are expensive, labor-intensive, and require experts to interpret the results. “The stacking and truncation of cell nuclei innate to paraffin-embedded FISH make interpretation difficult,” he said. “Also, all colors cannot be viewed simultaneously, and each lab’s assay potentially is different, requiring validation. These are not [Food and Drug Administration]-approved tests.”

Next generation sequencing (NGS). Also known as high-throughput sequencing, this technique allows for the generation of millions of sequencing reads that are aligned to a standard human genome, and likely represents the wave of the future. “With NGS you can increase breadth, so you can sequence the entire genome if you want, but you can also increase depth, meaning increasing the number of reads over a single target of the genome,” Dr. Hosler said. “That’s useful if you’re looking for a low frequency mutation.”

For example, NGS allows one to detect alterations of BRAF and KIT and other potentially actionable alterations. It can also be used to detect mutations in benign and malignant melanocytic lesions, including historically diagnostically challenging Spitz and desmoplastic subgroups. Several different NGS technologies exist, and there are different strategies behind each assay, including whole genome sequencing, whole exome sequencing, transcriptome sequencing, and targeted panels. “I’ve seen panels of 10 and I’ve seen panels of 1,500; there’s a wide range,” Dr. Hosler said. “The biggest challenge with NGS, currently, is that it’s difficult to interpret. Trying to figure out what’s important and what’s not important can be challenging. Often you need a team of people who are experts in bioinformatics to interpret these results.”

Slow turnaround time is another downside. “It can take a month to get results, and sometimes clinicians don’t want to wait that long, especially if they think a lesion is melanoma, so that’s an area of focus for NGS laboratories,” he said. “And there are questions on reimbursement. If you run NGS on every unusual melanocytic lesion, that’s not a good use of health care dollars. Who’s paying for it? I don’t have an answer for you. It’s all over the map right now. Each lab’s test and billing practice is different.”

Dr. Hosler reported having no relevant financial disclosures. ProPath is a nationwide pathology practice.

SAN DIEGO – Today’s molecular tests for managing melanoma patients are used to reclassify melanoma, identify patients at risk, as well as for diagnosis, prognosis, and treatment, but each one has its specific applications, benefits, and drawbacks, according to Gregory A. Hosler, MD, PhD.

At the annual Cutaneous Malignancy Update, Dr. Hosler, director of dermatopathology for ProPath, highlighted the following molecular tests currently used for the diagnosis of challenging melanocytic lesions:

Comparative genomic hybridization (CGH). This technique allows for the detection of chromosomal copy number changes throughout the tumor genome. “With CGH, test (tumor) DNA and normal DNA are differentially labeled and compared to a reference library. Gains and losses of portions of the tumor genome are determined by comparing the relative signals from these two groups,” said Dr. Hosler, clinical professor of pathology and dermatology at the University of Texas Southwestern Medical Center, Dallas.

“In the past, your library was a metaphase of spread of chromosomes, which introduced technical challenges and made performance of the assay labor intensive. Because of this, CGH is not routinely performed by clinical laboratories and is used more as an exploratory/research technique.”

Array CGH (also known as SNP array). Newer versions of CGH use short DNA sequences that are tiled onto a chip. “The interesting thing about these chips is that you can purchase them or design them on your own,” Dr. Hosler said. “The chips may cover the entire genome or cover specific areas of the genome at higher resolution.” One upside of array CGH, he continued, is that it allows one to detect essentially all gains or losses of chromosomal material in a single reaction. “It is not subject to the artifacts associated with cutting thin sections like with fluorescence in situ hybridization (FISH); it can detect copy number neutral loss of heterozygosity, and it is more scalable,” Dr. Hosler said at the meeting, which was hosted by Scripps MD Anderson Cancer Center.

One downside of array CGH is that does not allow one to analyze specific cells, “so if you have a tumor that’s heterogeneous, the assay is agnostic to this and spits out a result based on all the material provided,” he said. “You can’t parse out different areas of the lesion. It also does not track balanced translocations.” In addition, he said, “there are also questions about reimbursement and these are lab-developed tests, so each lab’s assay is different. Finally, it requires specialized equipment and expertise for interpretation.”

FISH. First-generation melanoma FISH assays, which became available in 2009, used six probes and four colors and had a sensitivity of about 87% and specificity of about 95%, Dr. Hosler said, but there were problems with those assays, particularly related to Spitz nevi. Spitz nevi often duplicate their chromosomes, “so instead of being diploid they’re tetraploid,” he said.

“The second-generation melanoma FISH assays addressed this by adding centromeres to the assay, and targeted probes could be compared to the centromeres on the same chromosome to determine if these were true copy number gains, due to genetic instability, or gains or losses of entire arms or whole chromosomes. This modification and the addition of new targets really improved upon the sensitivity and specificity (94% and 98%, respectively),” he said, noting that this assay is widely used.

Upsides of melanoma FISH assays are that they are a “fairly routine methodology” in large clinical laboratories, he said, and that many labs are familiar with interpretation. “I would say the biggest advantage to FISH is its ability to analyze specific cells, which is useful with small or heterogeneous tumors,” Dr. Hosler said. “Also, there is a genetic reimbursement code for it, and it yields diagnostic and potentially prognostic information.” For example, certain copy number changes have shown to portend a worse prognosis if they’re present in a melanocytic tumor, including alterations in CDKN2A, CCND1, MYC, topoisomerase, and BAP1.

Downsides of melanoma FISH assays are that they are expensive, labor-intensive, and require experts to interpret the results. “The stacking and truncation of cell nuclei innate to paraffin-embedded FISH make interpretation difficult,” he said. “Also, all colors cannot be viewed simultaneously, and each lab’s assay potentially is different, requiring validation. These are not [Food and Drug Administration]-approved tests.”

Next generation sequencing (NGS). Also known as high-throughput sequencing, this technique allows for the generation of millions of sequencing reads that are aligned to a standard human genome, and likely represents the wave of the future. “With NGS you can increase breadth, so you can sequence the entire genome if you want, but you can also increase depth, meaning increasing the number of reads over a single target of the genome,” Dr. Hosler said. “That’s useful if you’re looking for a low frequency mutation.”

For example, NGS allows one to detect alterations of BRAF and KIT and other potentially actionable alterations. It can also be used to detect mutations in benign and malignant melanocytic lesions, including historically diagnostically challenging Spitz and desmoplastic subgroups. Several different NGS technologies exist, and there are different strategies behind each assay, including whole genome sequencing, whole exome sequencing, transcriptome sequencing, and targeted panels. “I’ve seen panels of 10 and I’ve seen panels of 1,500; there’s a wide range,” Dr. Hosler said. “The biggest challenge with NGS, currently, is that it’s difficult to interpret. Trying to figure out what’s important and what’s not important can be challenging. Often you need a team of people who are experts in bioinformatics to interpret these results.”

Slow turnaround time is another downside. “It can take a month to get results, and sometimes clinicians don’t want to wait that long, especially if they think a lesion is melanoma, so that’s an area of focus for NGS laboratories,” he said. “And there are questions on reimbursement. If you run NGS on every unusual melanocytic lesion, that’s not a good use of health care dollars. Who’s paying for it? I don’t have an answer for you. It’s all over the map right now. Each lab’s test and billing practice is different.”

Dr. Hosler reported having no relevant financial disclosures. ProPath is a nationwide pathology practice.

SAN DIEGO – When parents bring their children to Caroline Piggott, MD, to evaluate a suspicious mole on the scalp or other body location, the vast majority turn out to be benign, because the incidence of melanoma is rare, especially before puberty.

“Only 1%-2% of all melanomas in the world are in children, so most of my job is to provide reassurance,” Dr. Piggott, a pediatric dermatologist at Scripps MD Anderson Cancer Center, San Diego, said at the annual Cutaneous Malignancy Update. “Few pediatric studies exist. Why? Because children are excluded from most melanoma clinical trials. Our management is based mainly on adult National Comprehensive Cancer Network guidelines.”

Doug Brunk/MDedge News

To help parents identify melanoma, clinicians typically recommend the “ABCDE” rule, for Asymmetry, Border irregularity, Color variation (especially dark or multiple colors), Diameter greater than 6 mm, and Evolving (is it changing, bleeding or painful?).

While Dr. Piggott considers the standard ABCDE rules as important – especially in older children and teenagers – researchers led by Kelly M. Cordoro, MD, professor of dermatology at the University of California, San Francisco, proposed a modified ABCD criteria based on evaluating a cohort of 60 children who were diagnosed with melanoma and 10 who were diagnosed with ambiguous melanocytic tumors treated as melanoma before age 20 years at UCSF from 1984 to 2009.

The researchers divided patients into two groups: those aged 0-10 years (19; group A) and those aged 11-19 years (51; group B), and found that 60% of children in group A and 40% of those in group B did not present with conventional ABCDE criteria for children. Of the 60 melanoma patients, 10 died. Of these, 9 were older than age 10, and 70% had amelanotic lesions. Based on their analysis of clinical, histopathologic, and outcomes data, Dr. Cordoro and colleagues proposed additional ABCD criteria in which A stands for stands Amelanotic; B for Bleeding or Bump; C for Color uniformity, and D for De novo or any Diameter.

“This doesn’t mean you throw the old ABCDE criteria out the window,” Dr. Piggott said. “It means that you use this modified criteria in conjunction with the conventional ABCDE rules.”

Risk factors for melanoma in children are like those in adults, and include a family history of melanoma, large/giant congenital nevi, the presence of many atypical appearing nevi, having Fitzpatrick skin types I or II, a history of blistering sunburns, and the presence of genetic anomalies such as xeroderma pigmentosum.

According to an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program, melanoma incidence increased in all individuals in the United States aged 0-19 years from 1973 to 2009. Key risk factors included White race, female sex, and living in a SEER registry categorized as low UVB exposure. Over the study period, boys experienced increased incidence rates of melanoma on the face and trunk, while girls experienced increased incidence rates of melanoma on the lower limbs and hip.

More recently, researchers extracted data from 988,103 cases of invasive melanoma in the 2001-2015 SEER database to determine the age-specific incidence of melanoma in the United States. In 2015, 83,362 cases of invasive melanoma were reported for all ages. Of these, only 67 cases were younger than age 10, while 251 were between the ages of 10 and 19 and 1,973 were young adults between the ages of 20 and 29.

In other findings, between 2006 and 2015, the overall incidence of invasive melanoma for all ages increased from 200 million to 229 cases per million person-years. “However, there were statistically significant decreases in melanoma incidence for individuals aged 10-19 years and for those aged 10-29 years,” said Dr. Piggott, who was not involved with the study. “The hypothesis is that public health efforts encouraging against sun exposure and tanning bed use may be influencing melanoma incidence in younger populations. What is interesting, though, is that young adult women have twice the melanoma risk as young adult men.”

In a separate study, researchers prospectively followed 60 melanoma-prone families for up to 40 years to evaluate the risk of pediatric melanoma in those with and without cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations. Regardless of their CDKN2A status, the percentage of pediatric melanoma cases was 6- to 28-fold higher among melanoma-prone families, compared with the general population. In addition, families who were CDKN2A positive had a significantly higher rate of pediatric melanoma cases compared with those who were CDKN2A negative (11.1% vs. 2.5%; P = .004).

As for treating pediatric melanoma, the standard of care is similar to that for adults: usually wide local surgical excision of the primary lesion, depending on depth. Clinicians typically follow adult parameters for sentinel lymph node biopsy, such as lesion depth and ulceration.

“We know that a positive sentinel node does have prognostic value, but there is great debate on whether to do a lymph node dissection if the sentinel lymph node is positive,” Dr. Piggott said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “This is determined on a case-by-case basis. We consider factors such as, are the nodes palpable? Is there evidence on ultrasound? But there are no formal guidelines.”

Limited studies of systemic therapy in children exist because this population is excluded from most melanoma clinical trials. “In the past, interferon was sometimes used,” she said. “But in recent years, as with adults, we have started to use targeted immunologic therapy. This is usually managed by a tertiary academic oncology center.”

The chance of surviving pediatric melanoma is good if caught early. As in adults, the stage correlates strongly with survival, and distant metastases carry a poor prognosis.

In 2020, researchers published a retrospective, multicenter review of 38 cases of fatal pediatric melanoma between 1994 and 2017. The analysis was limited to individuals 20 years of age and younger who were cared for at 12 academic medical centers. Of the 38 patients, 42% were male, 58% were female, and 57% were White. In addition, 19% were Hispanic, “which is a larger percentage than fatalities in adult [Hispanic] populations with melanoma,” said Dr. Piggott, who was not involved in the study.

The mean age at diagnosis was 12.7 years, the mean age at death was 15.6 , and the mean survival time after diagnosis was about 35 months. Of the 16 cases with known identifiable subtypes, 50% were nodular, 31% were superficial spreading, and 19% were spitzoid melanoma. In addition, one-quarter of melanomas arose in association with congenital melanocytic nevi.

“The good news is that there are only 38 total cases of fatal pediatric melanoma between 12 academic centers over a 23-year period,” Dr. Piggott said. “Thanks goodness the number is that low.”

Dr. Piggott reported having no relevant disclosures.

SAN DIEGO – When parents bring their children to Caroline Piggott, MD, to evaluate a suspicious mole on the scalp or other body location, the vast majority turn out to be benign, because the incidence of melanoma is rare, especially before puberty.

“Only 1%-2% of all melanomas in the world are in children, so most of my job is to provide reassurance,” Dr. Piggott, a pediatric dermatologist at Scripps MD Anderson Cancer Center, San Diego, said at the annual Cutaneous Malignancy Update. “Few pediatric studies exist. Why? Because children are excluded from most melanoma clinical trials. Our management is based mainly on adult National Comprehensive Cancer Network guidelines.”

Doug Brunk/MDedge News

To help parents identify melanoma, clinicians typically recommend the “ABCDE” rule, for Asymmetry, Border irregularity, Color variation (especially dark or multiple colors), Diameter greater than 6 mm, and Evolving (is it changing, bleeding or painful?).

While Dr. Piggott considers the standard ABCDE rules as important – especially in older children and teenagers – researchers led by Kelly M. Cordoro, MD, professor of dermatology at the University of California, San Francisco, proposed a modified ABCD criteria based on evaluating a cohort of 60 children who were diagnosed with melanoma and 10 who were diagnosed with ambiguous melanocytic tumors treated as melanoma before age 20 years at UCSF from 1984 to 2009.

The researchers divided patients into two groups: those aged 0-10 years (19; group A) and those aged 11-19 years (51; group B), and found that 60% of children in group A and 40% of those in group B did not present with conventional ABCDE criteria for children. Of the 60 melanoma patients, 10 died. Of these, 9 were older than age 10, and 70% had amelanotic lesions. Based on their analysis of clinical, histopathologic, and outcomes data, Dr. Cordoro and colleagues proposed additional ABCD criteria in which A stands for stands Amelanotic; B for Bleeding or Bump; C for Color uniformity, and D for De novo or any Diameter.

“This doesn’t mean you throw the old ABCDE criteria out the window,” Dr. Piggott said. “It means that you use this modified criteria in conjunction with the conventional ABCDE rules.”

Risk factors for melanoma in children are like those in adults, and include a family history of melanoma, large/giant congenital nevi, the presence of many atypical appearing nevi, having Fitzpatrick skin types I or II, a history of blistering sunburns, and the presence of genetic anomalies such as xeroderma pigmentosum.

According to an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program, melanoma incidence increased in all individuals in the United States aged 0-19 years from 1973 to 2009. Key risk factors included White race, female sex, and living in a SEER registry categorized as low UVB exposure. Over the study period, boys experienced increased incidence rates of melanoma on the face and trunk, while girls experienced increased incidence rates of melanoma on the lower limbs and hip.

More recently, researchers extracted data from 988,103 cases of invasive melanoma in the 2001-2015 SEER database to determine the age-specific incidence of melanoma in the United States. In 2015, 83,362 cases of invasive melanoma were reported for all ages. Of these, only 67 cases were younger than age 10, while 251 were between the ages of 10 and 19 and 1,973 were young adults between the ages of 20 and 29.

In other findings, between 2006 and 2015, the overall incidence of invasive melanoma for all ages increased from 200 million to 229 cases per million person-years. “However, there were statistically significant decreases in melanoma incidence for individuals aged 10-19 years and for those aged 10-29 years,” said Dr. Piggott, who was not involved with the study. “The hypothesis is that public health efforts encouraging against sun exposure and tanning bed use may be influencing melanoma incidence in younger populations. What is interesting, though, is that young adult women have twice the melanoma risk as young adult men.”

In a separate study, researchers prospectively followed 60 melanoma-prone families for up to 40 years to evaluate the risk of pediatric melanoma in those with and without cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations. Regardless of their CDKN2A status, the percentage of pediatric melanoma cases was 6- to 28-fold higher among melanoma-prone families, compared with the general population. In addition, families who were CDKN2A positive had a significantly higher rate of pediatric melanoma cases compared with those who were CDKN2A negative (11.1% vs. 2.5%; P = .004).

As for treating pediatric melanoma, the standard of care is similar to that for adults: usually wide local surgical excision of the primary lesion, depending on depth. Clinicians typically follow adult parameters for sentinel lymph node biopsy, such as lesion depth and ulceration.

“We know that a positive sentinel node does have prognostic value, but there is great debate on whether to do a lymph node dissection if the sentinel lymph node is positive,” Dr. Piggott said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “This is determined on a case-by-case basis. We consider factors such as, are the nodes palpable? Is there evidence on ultrasound? But there are no formal guidelines.”

Limited studies of systemic therapy in children exist because this population is excluded from most melanoma clinical trials. “In the past, interferon was sometimes used,” she said. “But in recent years, as with adults, we have started to use targeted immunologic therapy. This is usually managed by a tertiary academic oncology center.”

The chance of surviving pediatric melanoma is good if caught early. As in adults, the stage correlates strongly with survival, and distant metastases carry a poor prognosis.

In 2020, researchers published a retrospective, multicenter review of 38 cases of fatal pediatric melanoma between 1994 and 2017. The analysis was limited to individuals 20 years of age and younger who were cared for at 12 academic medical centers. Of the 38 patients, 42% were male, 58% were female, and 57% were White. In addition, 19% were Hispanic, “which is a larger percentage than fatalities in adult [Hispanic] populations with melanoma,” said Dr. Piggott, who was not involved in the study.

The mean age at diagnosis was 12.7 years, the mean age at death was 15.6 , and the mean survival time after diagnosis was about 35 months. Of the 16 cases with known identifiable subtypes, 50% were nodular, 31% were superficial spreading, and 19% were spitzoid melanoma. In addition, one-quarter of melanomas arose in association with congenital melanocytic nevi.

“The good news is that there are only 38 total cases of fatal pediatric melanoma between 12 academic centers over a 23-year period,” Dr. Piggott said. “Thanks goodness the number is that low.”

Dr. Piggott reported having no relevant disclosures.

SAN DIEGO – When parents bring their children to Caroline Piggott, MD, to evaluate a suspicious mole on the scalp or other body location, the vast majority turn out to be benign, because the incidence of melanoma is rare, especially before puberty.

“Only 1%-2% of all melanomas in the world are in children, so most of my job is to provide reassurance,” Dr. Piggott, a pediatric dermatologist at Scripps MD Anderson Cancer Center, San Diego, said at the annual Cutaneous Malignancy Update. “Few pediatric studies exist. Why? Because children are excluded from most melanoma clinical trials. Our management is based mainly on adult National Comprehensive Cancer Network guidelines.”

Doug Brunk/MDedge News

To help parents identify melanoma, clinicians typically recommend the “ABCDE” rule, for Asymmetry, Border irregularity, Color variation (especially dark or multiple colors), Diameter greater than 6 mm, and Evolving (is it changing, bleeding or painful?).

While Dr. Piggott considers the standard ABCDE rules as important – especially in older children and teenagers – researchers led by Kelly M. Cordoro, MD, professor of dermatology at the University of California, San Francisco, proposed a modified ABCD criteria based on evaluating a cohort of 60 children who were diagnosed with melanoma and 10 who were diagnosed with ambiguous melanocytic tumors treated as melanoma before age 20 years at UCSF from 1984 to 2009.

The researchers divided patients into two groups: those aged 0-10 years (19; group A) and those aged 11-19 years (51; group B), and found that 60% of children in group A and 40% of those in group B did not present with conventional ABCDE criteria for children. Of the 60 melanoma patients, 10 died. Of these, 9 were older than age 10, and 70% had amelanotic lesions. Based on their analysis of clinical, histopathologic, and outcomes data, Dr. Cordoro and colleagues proposed additional ABCD criteria in which A stands for stands Amelanotic; B for Bleeding or Bump; C for Color uniformity, and D for De novo or any Diameter.

“This doesn’t mean you throw the old ABCDE criteria out the window,” Dr. Piggott said. “It means that you use this modified criteria in conjunction with the conventional ABCDE rules.”

Risk factors for melanoma in children are like those in adults, and include a family history of melanoma, large/giant congenital nevi, the presence of many atypical appearing nevi, having Fitzpatrick skin types I or II, a history of blistering sunburns, and the presence of genetic anomalies such as xeroderma pigmentosum.

According to an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program, melanoma incidence increased in all individuals in the United States aged 0-19 years from 1973 to 2009. Key risk factors included White race, female sex, and living in a SEER registry categorized as low UVB exposure. Over the study period, boys experienced increased incidence rates of melanoma on the face and trunk, while girls experienced increased incidence rates of melanoma on the lower limbs and hip.

More recently, researchers extracted data from 988,103 cases of invasive melanoma in the 2001-2015 SEER database to determine the age-specific incidence of melanoma in the United States. In 2015, 83,362 cases of invasive melanoma were reported for all ages. Of these, only 67 cases were younger than age 10, while 251 were between the ages of 10 and 19 and 1,973 were young adults between the ages of 20 and 29.

In other findings, between 2006 and 2015, the overall incidence of invasive melanoma for all ages increased from 200 million to 229 cases per million person-years. “However, there were statistically significant decreases in melanoma incidence for individuals aged 10-19 years and for those aged 10-29 years,” said Dr. Piggott, who was not involved with the study. “The hypothesis is that public health efforts encouraging against sun exposure and tanning bed use may be influencing melanoma incidence in younger populations. What is interesting, though, is that young adult women have twice the melanoma risk as young adult men.”

In a separate study, researchers prospectively followed 60 melanoma-prone families for up to 40 years to evaluate the risk of pediatric melanoma in those with and without cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations. Regardless of their CDKN2A status, the percentage of pediatric melanoma cases was 6- to 28-fold higher among melanoma-prone families, compared with the general population. In addition, families who were CDKN2A positive had a significantly higher rate of pediatric melanoma cases compared with those who were CDKN2A negative (11.1% vs. 2.5%; P = .004).

As for treating pediatric melanoma, the standard of care is similar to that for adults: usually wide local surgical excision of the primary lesion, depending on depth. Clinicians typically follow adult parameters for sentinel lymph node biopsy, such as lesion depth and ulceration.

“We know that a positive sentinel node does have prognostic value, but there is great debate on whether to do a lymph node dissection if the sentinel lymph node is positive,” Dr. Piggott said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “This is determined on a case-by-case basis. We consider factors such as, are the nodes palpable? Is there evidence on ultrasound? But there are no formal guidelines.”

Limited studies of systemic therapy in children exist because this population is excluded from most melanoma clinical trials. “In the past, interferon was sometimes used,” she said. “But in recent years, as with adults, we have started to use targeted immunologic therapy. This is usually managed by a tertiary academic oncology center.”

The chance of surviving pediatric melanoma is good if caught early. As in adults, the stage correlates strongly with survival, and distant metastases carry a poor prognosis.

In 2020, researchers published a retrospective, multicenter review of 38 cases of fatal pediatric melanoma between 1994 and 2017. The analysis was limited to individuals 20 years of age and younger who were cared for at 12 academic medical centers. Of the 38 patients, 42% were male, 58% were female, and 57% were White. In addition, 19% were Hispanic, “which is a larger percentage than fatalities in adult [Hispanic] populations with melanoma,” said Dr. Piggott, who was not involved in the study.

The mean age at diagnosis was 12.7 years, the mean age at death was 15.6 , and the mean survival time after diagnosis was about 35 months. Of the 16 cases with known identifiable subtypes, 50% were nodular, 31% were superficial spreading, and 19% were spitzoid melanoma. In addition, one-quarter of melanomas arose in association with congenital melanocytic nevi.

“The good news is that there are only 38 total cases of fatal pediatric melanoma between 12 academic centers over a 23-year period,” Dr. Piggott said. “Thanks goodness the number is that low.”

Dr. Piggott reported having no relevant disclosures.

San Diego – The way Benjamin Kelley, MD, sees it, the term dysplastic nevi (DN) suffers from an identity crisis, with different clinicians using different terms to describe a subset of melanocytic nevi that are clinically atypical.

Doug Brunk/MDedge News

“There’s a confusion in the terminology, a term the late A. Bernard Ackerman, MD, called ‘patho-babel,’ ” Dr. Kelley, a Mohs micrographic surgeon and dermatopathologist in La Jolla, Calif., said at the annual Cutaneous Malignancy Update. “The idea of DN was originally used to describe a clinical melanoma syndrome. Now we use it for individual lesions, not just clinically but histologically. Some dermatologists refer to DN as ‘pre-melanoma,’ which is a negative framing,” he noted.

“We also refer to common nevi as ‘benign,’ which implies that DN are not benign,” he added. “The good news is that regardless of what they are called, the histologic criteria is generally agreed upon. The names can be used interchangeably.”

The bad news, he continued, is that there is less-than-perfect interobserver variability for grading DN lesions and significant variability in the treatment recommendations that pathologists give to clinicians. In one study, a group of pathology experts was asked to review 48 photomicrographs of melanocytic lesions and provide their diagnosis and treatment recommendations based on the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis scheme. For one, which showed a broad lesion with irregular epidermal thinning and thickening, the diagnoses ranged from solar lentigo to melanoma in situ. Treatment recommendations ranged from no treatment to re-excise with appropriate margins.

“This is an extreme example, but it shows you how difficult [establishing a diagnosis] can be,” Dr. Kelley said.

In a more recent study, researchers analyzed interobserver reproducibility in grading 179 DN cases among three observers who applied the 2018 World Health Organization grading criteria. The observers showed moderate to good agreement for most of the architectural features, except for criteria regarding focal continuous basal proliferation of melanocytes, density of non-nested junctional melanocytes, and presence of dyscohesive nests of intraepidermal melanocytes, whereas fair agreement was achieved for the cytological criteria. “So, it sounds to me like there was not a whole lot of agreement,” Dr. Kelley said.

An earlier single-center study titled “Clinicians Are From Mars and Pathologists Are From Venus” found that surgeons misunderstood the pathologist’s report 30% of the time.

In Dr. Kelly’s opinion, management of DNs will be successful if clinicians have a good working relationship with their dermatopathologists, if they biopsy to ensure an adequate, representative specimen, and if that they know what the terminology on the pathology report means and what actions to take. “The biopsy method matters,” he emphasized.

In a 14-year follow-up survey, investigators assessed DN management trends among 703 U.S. dermatologists. One key finding was that 69% of dermatologists in 2015 performed total removals when biopsying DN to achieve clear margins, compared with 86% in 2001.

A subsequent survey of 213 New England–based dermatologists found that the degree of clinical suspicion for melanoma was important in DN biopsy technique, with more respondents favoring shave biopsies for lesions with low suspicion and full-thickness biopsies for highly suspicious lesions.

“Misdiagnosis is more common for melanomas that have been assessed with punch and shave biopsies than with an excisional biopsy,” Dr. Kelley said. “I’m not too much of a stickler. I don’t require everyone to send me a giant excision, but I do want a representative sample.”

What about re-excision of DN considered to be mild or moderate? In 2015, members of the Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group published a consensus statement on DN management recommendations for clinically atypical nevi/DN based on a review of published evidence. The subcommittee members concluded that mildly and moderately DN with clear margins do not need to be re-excised, and that mildly DN biopsied with positive histologic margins without clinical residual pigmentation may be safely observed rather than re-excised.

For moderately DN with positive histologic margins without clinically apparent residual pigmentation, the subcommittee members concluded that observation may be reasonable.

In his own informal analysis, Dr. Kelley compiled data from published studies he could find on DN management and divided them into two groups: the observation group, in which researchers from eight studies biopsied the DN lesion and watched the patients over time to see what happened, and the re-excision group, in which researchers from seven studies biopsied the DN lesion and subsequently re-excised it. There were about 1,500 patients in both groups. No deaths occurred in either group, he said, but 15 patients in the re-excision group developed a melanoma at the site of the original biopsy (1%), compared with 7 in the observation group (0.5%).

Six of seven melanomas in the observation group came from one article conducted at a VA clinic. In the study, 6 of 304 observed DN subsequently developed melanoma at the site of the lesion. “However, five of six that developed melanoma had an original biopsy that was a partial biopsy with grossly positive margins; I think that’s where the problem lies,” Dr. Kelley said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “All five grew lentigo maligna type melanoma, which we know can extend multiple millimeters beyond the clinically apparent lesion.”

The findings support mounting evidence that re-excising mild and moderate DN, regardless of border involvement, may not be necessary. “Currently, most clinicians still re-excise moderate and severe DN involving margins, especially if there is residual pigment,” Dr. Kelley said. “Most re-excise severe DN regardless of margin involvement, but beware if your biopsy was a partial sample of a larger lesion.”

He acknowledged limitations to pathologic studies of DN, including the potential for diagnostic uncertainty. “That doesn’t necessarily mean that the pathologist got the diagnosis wrong. It could be, what is the risk that the portion of tissue not visualized contains melanoma? If you give me a 5 mm sample of a DN, and I cut it into 4-micrometer sections, I’m only looking at less than 1% of the actual nevus. That’s compounded if the pathologist only receives a partial sample.”

Dr. Kelley reported having no relevant disclosures.

San Diego – The way Benjamin Kelley, MD, sees it, the term dysplastic nevi (DN) suffers from an identity crisis, with different clinicians using different terms to describe a subset of melanocytic nevi that are clinically atypical.

Doug Brunk/MDedge News

“There’s a confusion in the terminology, a term the late A. Bernard Ackerman, MD, called ‘patho-babel,’ ” Dr. Kelley, a Mohs micrographic surgeon and dermatopathologist in La Jolla, Calif., said at the annual Cutaneous Malignancy Update. “The idea of DN was originally used to describe a clinical melanoma syndrome. Now we use it for individual lesions, not just clinically but histologically. Some dermatologists refer to DN as ‘pre-melanoma,’ which is a negative framing,” he noted.

“We also refer to common nevi as ‘benign,’ which implies that DN are not benign,” he added. “The good news is that regardless of what they are called, the histologic criteria is generally agreed upon. The names can be used interchangeably.”

The bad news, he continued, is that there is less-than-perfect interobserver variability for grading DN lesions and significant variability in the treatment recommendations that pathologists give to clinicians. In one study, a group of pathology experts was asked to review 48 photomicrographs of melanocytic lesions and provide their diagnosis and treatment recommendations based on the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis scheme. For one, which showed a broad lesion with irregular epidermal thinning and thickening, the diagnoses ranged from solar lentigo to melanoma in situ. Treatment recommendations ranged from no treatment to re-excise with appropriate margins.

“This is an extreme example, but it shows you how difficult [establishing a diagnosis] can be,” Dr. Kelley said.

In a more recent study, researchers analyzed interobserver reproducibility in grading 179 DN cases among three observers who applied the 2018 World Health Organization grading criteria. The observers showed moderate to good agreement for most of the architectural features, except for criteria regarding focal continuous basal proliferation of melanocytes, density of non-nested junctional melanocytes, and presence of dyscohesive nests of intraepidermal melanocytes, whereas fair agreement was achieved for the cytological criteria. “So, it sounds to me like there was not a whole lot of agreement,” Dr. Kelley said.

An earlier single-center study titled “Clinicians Are From Mars and Pathologists Are From Venus” found that surgeons misunderstood the pathologist’s report 30% of the time.

In Dr. Kelly’s opinion, management of DNs will be successful if clinicians have a good working relationship with their dermatopathologists, if they biopsy to ensure an adequate, representative specimen, and if that they know what the terminology on the pathology report means and what actions to take. “The biopsy method matters,” he emphasized.

In a 14-year follow-up survey, investigators assessed DN management trends among 703 U.S. dermatologists. One key finding was that 69% of dermatologists in 2015 performed total removals when biopsying DN to achieve clear margins, compared with 86% in 2001.

A subsequent survey of 213 New England–based dermatologists found that the degree of clinical suspicion for melanoma was important in DN biopsy technique, with more respondents favoring shave biopsies for lesions with low suspicion and full-thickness biopsies for highly suspicious lesions.

“Misdiagnosis is more common for melanomas that have been assessed with punch and shave biopsies than with an excisional biopsy,” Dr. Kelley said. “I’m not too much of a stickler. I don’t require everyone to send me a giant excision, but I do want a representative sample.”

What about re-excision of DN considered to be mild or moderate? In 2015, members of the Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group published a consensus statement on DN management recommendations for clinically atypical nevi/DN based on a review of published evidence. The subcommittee members concluded that mildly and moderately DN with clear margins do not need to be re-excised, and that mildly DN biopsied with positive histologic margins without clinical residual pigmentation may be safely observed rather than re-excised.

For moderately DN with positive histologic margins without clinically apparent residual pigmentation, the subcommittee members concluded that observation may be reasonable.

In his own informal analysis, Dr. Kelley compiled data from published studies he could find on DN management and divided them into two groups: the observation group, in which researchers from eight studies biopsied the DN lesion and watched the patients over time to see what happened, and the re-excision group, in which researchers from seven studies biopsied the DN lesion and subsequently re-excised it. There were about 1,500 patients in both groups. No deaths occurred in either group, he said, but 15 patients in the re-excision group developed a melanoma at the site of the original biopsy (1%), compared with 7 in the observation group (0.5%).

Six of seven melanomas in the observation group came from one article conducted at a VA clinic. In the study, 6 of 304 observed DN subsequently developed melanoma at the site of the lesion. “However, five of six that developed melanoma had an original biopsy that was a partial biopsy with grossly positive margins; I think that’s where the problem lies,” Dr. Kelley said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “All five grew lentigo maligna type melanoma, which we know can extend multiple millimeters beyond the clinically apparent lesion.”

The findings support mounting evidence that re-excising mild and moderate DN, regardless of border involvement, may not be necessary. “Currently, most clinicians still re-excise moderate and severe DN involving margins, especially if there is residual pigment,” Dr. Kelley said. “Most re-excise severe DN regardless of margin involvement, but beware if your biopsy was a partial sample of a larger lesion.”

He acknowledged limitations to pathologic studies of DN, including the potential for diagnostic uncertainty. “That doesn’t necessarily mean that the pathologist got the diagnosis wrong. It could be, what is the risk that the portion of tissue not visualized contains melanoma? If you give me a 5 mm sample of a DN, and I cut it into 4-micrometer sections, I’m only looking at less than 1% of the actual nevus. That’s compounded if the pathologist only receives a partial sample.”

Dr. Kelley reported having no relevant disclosures.

San Diego – The way Benjamin Kelley, MD, sees it, the term dysplastic nevi (DN) suffers from an identity crisis, with different clinicians using different terms to describe a subset of melanocytic nevi that are clinically atypical.

Doug Brunk/MDedge News

“There’s a confusion in the terminology, a term the late A. Bernard Ackerman, MD, called ‘patho-babel,’ ” Dr. Kelley, a Mohs micrographic surgeon and dermatopathologist in La Jolla, Calif., said at the annual Cutaneous Malignancy Update. “The idea of DN was originally used to describe a clinical melanoma syndrome. Now we use it for individual lesions, not just clinically but histologically. Some dermatologists refer to DN as ‘pre-melanoma,’ which is a negative framing,” he noted.

“We also refer to common nevi as ‘benign,’ which implies that DN are not benign,” he added. “The good news is that regardless of what they are called, the histologic criteria is generally agreed upon. The names can be used interchangeably.”

The bad news, he continued, is that there is less-than-perfect interobserver variability for grading DN lesions and significant variability in the treatment recommendations that pathologists give to clinicians. In one study, a group of pathology experts was asked to review 48 photomicrographs of melanocytic lesions and provide their diagnosis and treatment recommendations based on the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis scheme. For one, which showed a broad lesion with irregular epidermal thinning and thickening, the diagnoses ranged from solar lentigo to melanoma in situ. Treatment recommendations ranged from no treatment to re-excise with appropriate margins.

“This is an extreme example, but it shows you how difficult [establishing a diagnosis] can be,” Dr. Kelley said.

In a more recent study, researchers analyzed interobserver reproducibility in grading 179 DN cases among three observers who applied the 2018 World Health Organization grading criteria. The observers showed moderate to good agreement for most of the architectural features, except for criteria regarding focal continuous basal proliferation of melanocytes, density of non-nested junctional melanocytes, and presence of dyscohesive nests of intraepidermal melanocytes, whereas fair agreement was achieved for the cytological criteria. “So, it sounds to me like there was not a whole lot of agreement,” Dr. Kelley said.

An earlier single-center study titled “Clinicians Are From Mars and Pathologists Are From Venus” found that surgeons misunderstood the pathologist’s report 30% of the time.

In Dr. Kelly’s opinion, management of DNs will be successful if clinicians have a good working relationship with their dermatopathologists, if they biopsy to ensure an adequate, representative specimen, and if that they know what the terminology on the pathology report means and what actions to take. “The biopsy method matters,” he emphasized.

In a 14-year follow-up survey, investigators assessed DN management trends among 703 U.S. dermatologists. One key finding was that 69% of dermatologists in 2015 performed total removals when biopsying DN to achieve clear margins, compared with 86% in 2001.

A subsequent survey of 213 New England–based dermatologists found that the degree of clinical suspicion for melanoma was important in DN biopsy technique, with more respondents favoring shave biopsies for lesions with low suspicion and full-thickness biopsies for highly suspicious lesions.

“Misdiagnosis is more common for melanomas that have been assessed with punch and shave biopsies than with an excisional biopsy,” Dr. Kelley said. “I’m not too much of a stickler. I don’t require everyone to send me a giant excision, but I do want a representative sample.”

What about re-excision of DN considered to be mild or moderate? In 2015, members of the Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group published a consensus statement on DN management recommendations for clinically atypical nevi/DN based on a review of published evidence. The subcommittee members concluded that mildly and moderately DN with clear margins do not need to be re-excised, and that mildly DN biopsied with positive histologic margins without clinical residual pigmentation may be safely observed rather than re-excised.

For moderately DN with positive histologic margins without clinically apparent residual pigmentation, the subcommittee members concluded that observation may be reasonable.

In his own informal analysis, Dr. Kelley compiled data from published studies he could find on DN management and divided them into two groups: the observation group, in which researchers from eight studies biopsied the DN lesion and watched the patients over time to see what happened, and the re-excision group, in which researchers from seven studies biopsied the DN lesion and subsequently re-excised it. There were about 1,500 patients in both groups. No deaths occurred in either group, he said, but 15 patients in the re-excision group developed a melanoma at the site of the original biopsy (1%), compared with 7 in the observation group (0.5%).

Six of seven melanomas in the observation group came from one article conducted at a VA clinic. In the study, 6 of 304 observed DN subsequently developed melanoma at the site of the lesion. “However, five of six that developed melanoma had an original biopsy that was a partial biopsy with grossly positive margins; I think that’s where the problem lies,” Dr. Kelley said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “All five grew lentigo maligna type melanoma, which we know can extend multiple millimeters beyond the clinically apparent lesion.”

The findings support mounting evidence that re-excising mild and moderate DN, regardless of border involvement, may not be necessary. “Currently, most clinicians still re-excise moderate and severe DN involving margins, especially if there is residual pigment,” Dr. Kelley said. “Most re-excise severe DN regardless of margin involvement, but beware if your biopsy was a partial sample of a larger lesion.”

He acknowledged limitations to pathologic studies of DN, including the potential for diagnostic uncertainty. “That doesn’t necessarily mean that the pathologist got the diagnosis wrong. It could be, what is the risk that the portion of tissue not visualized contains melanoma? If you give me a 5 mm sample of a DN, and I cut it into 4-micrometer sections, I’m only looking at less than 1% of the actual nevus. That’s compounded if the pathologist only receives a partial sample.”

Dr. Kelley reported having no relevant disclosures.

SAN DIEGO – According to the latest American Cancer Society (ACS) data, cutaneous melanoma was the 5th most common cancer in 2022, with an estimated 99,780 new cases and 7,650 deaths, following cancer of the colorectal area, lung and bronchus, prostate, and breast.

“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist who practices in Macon, Ga., said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”

In 2023, the ACS estimates that about 97,610 new melanomas will be diagnosed in the United States (58,120 men and 39,490 women), and about 7,990 people are expected to die of melanoma (5,420 men and 2,570 women). In addition, ACS data from 2017-2019 project that about 2.1% of men and women will be diagnosed with cutaneous melanoma in their lifetime. To date, more than 1.3 million people in the United States live with cutaneous melanoma, and the overall 5-year survival is 93.7%.

Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due primarily to sun exposure and to changing recreational behaviors and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3% to 7% per year, “which translates into a doubling of rates every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.

While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color. Blacks present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.

Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1, and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.

The main environmental risk factor for melanoma is exposure to ultraviolet radiation. “You can break it down in terms of whether this exposure is lifetime, intermittent intense UV exposure, from the use of tanning beds, or due to sunburns during childhood,” Dr. Kent said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. Other environmental risk factors include distance from the equator, having a high socioeconomic status, being immunosuppressed, and exposure to heavy metals, insecticides, or hormones.

In a recently published study, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1,212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than were first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than were first melanomas.

In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio [HR], 6.36 vs. 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03).

Second melanomas were also more strongly associated with a history of multiple skin cancer excisions than were first melanomas (HR, 2.63 vs. 1.86; P = .05). “Interestingly, there were no differences in UV exposure between the first primary and second primary melanoma groups,” said Dr. Kent, who was not involved with the study.

He noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey (NAMCS) found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits – even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said. “We as dermatologists have work to do to help educate them.”

Dr. Kent reported having no relevant disclosures.

SAN DIEGO – According to the latest American Cancer Society (ACS) data, cutaneous melanoma was the 5th most common cancer in 2022, with an estimated 99,780 new cases and 7,650 deaths, following cancer of the colorectal area, lung and bronchus, prostate, and breast.

“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist who practices in Macon, Ga., said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”

In 2023, the ACS estimates that about 97,610 new melanomas will be diagnosed in the United States (58,120 men and 39,490 women), and about 7,990 people are expected to die of melanoma (5,420 men and 2,570 women). In addition, ACS data from 2017-2019 project that about 2.1% of men and women will be diagnosed with cutaneous melanoma in their lifetime. To date, more than 1.3 million people in the United States live with cutaneous melanoma, and the overall 5-year survival is 93.7%.

Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due primarily to sun exposure and to changing recreational behaviors and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3% to 7% per year, “which translates into a doubling of rates every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.

While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color. Blacks present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.

Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1, and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.

The main environmental risk factor for melanoma is exposure to ultraviolet radiation. “You can break it down in terms of whether this exposure is lifetime, intermittent intense UV exposure, from the use of tanning beds, or due to sunburns during childhood,” Dr. Kent said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. Other environmental risk factors include distance from the equator, having a high socioeconomic status, being immunosuppressed, and exposure to heavy metals, insecticides, or hormones.

In a recently published study, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1,212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than were first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than were first melanomas.

In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio [HR], 6.36 vs. 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03).

Second melanomas were also more strongly associated with a history of multiple skin cancer excisions than were first melanomas (HR, 2.63 vs. 1.86; P = .05). “Interestingly, there were no differences in UV exposure between the first primary and second primary melanoma groups,” said Dr. Kent, who was not involved with the study.

He noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey (NAMCS) found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits – even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said. “We as dermatologists have work to do to help educate them.”

Dr. Kent reported having no relevant disclosures.

SAN DIEGO – According to the latest American Cancer Society (ACS) data, cutaneous melanoma was the 5th most common cancer in 2022, with an estimated 99,780 new cases and 7,650 deaths, following cancer of the colorectal area, lung and bronchus, prostate, and breast.

“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist who practices in Macon, Ga., said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”

In 2023, the ACS estimates that about 97,610 new melanomas will be diagnosed in the United States (58,120 men and 39,490 women), and about 7,990 people are expected to die of melanoma (5,420 men and 2,570 women). In addition, ACS data from 2017-2019 project that about 2.1% of men and women will be diagnosed with cutaneous melanoma in their lifetime. To date, more than 1.3 million people in the United States live with cutaneous melanoma, and the overall 5-year survival is 93.7%.

Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due primarily to sun exposure and to changing recreational behaviors and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3% to 7% per year, “which translates into a doubling of rates every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.

While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color. Blacks present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.

Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1, and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.

The main environmental risk factor for melanoma is exposure to ultraviolet radiation. “You can break it down in terms of whether this exposure is lifetime, intermittent intense UV exposure, from the use of tanning beds, or due to sunburns during childhood,” Dr. Kent said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. Other environmental risk factors include distance from the equator, having a high socioeconomic status, being immunosuppressed, and exposure to heavy metals, insecticides, or hormones.

In a recently published study, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1,212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than were first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than were first melanomas.

In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio [HR], 6.36 vs. 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03).

Second melanomas were also more strongly associated with a history of multiple skin cancer excisions than were first melanomas (HR, 2.63 vs. 1.86; P = .05). “Interestingly, there were no differences in UV exposure between the first primary and second primary melanoma groups,” said Dr. Kent, who was not involved with the study.

He noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey (NAMCS) found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits – even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said. “We as dermatologists have work to do to help educate them.”

Dr. Kent reported having no relevant disclosures.

San Diego – Despite advances in dermoscopy and other techniques for diagnosing cutaneous melanoma, histology remains the gold standard.

“I don’t think that’s going to change in the short term,” Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, said at the annual Cutaneous Malignancy Update. “But I do think we can supplement that with other modalities that will improve the clinical examination and help dermatopathologists as they assess and evaluate these lesions,” he said, adding: “The reality is, histopathology, while it may be the gold standard, is not necessarily a consistently reproducible evaluation. That raises the question: What can we do better?”

Christoph Burgstedt/Science Photo Library/Getty Images

According to Dr. Blalock, the future may include more routine use of noninvasive genetic molecular assays to assist with the diagnostics challenges linked to the visual image and pattern recognition approach of detecting cutaneous melanoma. For example, a two-gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions obtained noninvasively via adhesive patch biopsy.

“Today, you can pick up a kit from your local pharmacy that can tell you a bit about broad genetic susceptibilities,” he said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. He predicted that using adhesive patch biopsies to assess suspicious melanocytic lesions “is likely the wave of the future.” This may increase patient understanding “as to the types of risks they have, the different lesions they have, and minimize invasive disease, but it also will pose different challenges for us when it comes to deploying patient-centered health care. For example, in a patient with multiple different lesions, how are you going to keep track of them all?”

Dermoscopy

In Dr. Blalock’s clinical opinion, dermoscopy improves the sensitivity of human visual detection of melanoma and may allow detection before a lesion displays classical features described with the “ABCDE rule.” However, the learning curve for dermoscopy is steep, he added, and whether the technique should be considered a first-line tool or as a supplement to other methods of examining cutaneous lesions remains a matter of debate.

“Dermoscopy is our version of the stethoscope,” he said. “We need to figure out when we’re going to use it. Should we be using it all of the time or only some of the time? Based on the clinical setting, maybe it’s a personal choice, but this can be a helpful skill and art in your practice if you’re willing to take the time to learn.”

In 2007, the International Dermoscopy Society (IDS) established a proposal for the standardization and recommended criteria necessary to effectively convey dermoscopic findings to consulting physicians and colleagues. The document includes 10 points categorized as either recommended or optional for a standardized dermoscopy report.

“The first step is to assess the lesion to determine whether or not it’s melanocytic in the first place,” said Dr. Blalock. “There are many different features – the mile-high [global features] evaluation of the lesions – then more specific local features that may clue you in to specific diagnoses,” he noted. “Once we get past that first step of determining that a lesion is melanocytic, it’s not enough to stop there, because we don’t want to biopsy every single lesion that’s melanocytic,” so there is a need to determine which ones require intervention, which is where dermoscopy “gets trickier and a little more challenging.”

According to the IDS, a standard dermoscopy report should include the patient’s age, relevant history pertaining to the lesion, pertinent personal and family history (recommended); clinical description of the lesion (recommended); the two-step method of dermoscopy differentiating melanocytic from nonmelanocytic tumors (recommended); and the use of standardized terms to describe structures as defined by the Dermoscopy Consensus Report published in 2003.

For new terms, the document states, “it would be helpful” for the physician to provide a working definition (recommended); the dermoscopic algorithm used should be mentioned (optional); information on the imaging equipment and magnification (recommended); clinical and dermoscopic images of the tumor (recommended); a diagnosis or differential diagnosis (recommended); decision concerning management (recommended), and specific comments for the pathologist when excision and histopathologic examination are recommended (optional).

The 2007 IDS document also includes a proposed seven-point checklist to differentiate between benign and melanocytic lesions on dermoscopy. Three major criteria are worth two points each: The presence of an atypical pigment network, gray-blue areas (commonly known as the veil), and an atypical vascular pattern. Four minor criteria are worth one point each: Irregular streaks, irregular dots/globules, irregular pigmentation, and regression structures. A minimum total score of 3 is required to establish a diagnosis of melanoma.

Another diagnostic technique, digital mole mapping, involves the use of photography to detect new or changing lesions. Dr. Blalock described this approach as rife with limitations, including variations in quality, challenges of storing and maintaining records, cost, time required to evaluate them, and determining which patients are appropriate candidates.

Other techniques being evaluated include computer algorithms to help dermatologists determine the diagnosis of melanoma from dermoscopic images, electrical impedance spectroscopy for noninvasive evaluation of atypical pigmented lesions, and ultrasound for staging of cutaneous malignant tumors.

Ultimately, “I think we’ll have multiple tools in our belt,” Dr. Blalock said, adding, “How do we pull them out at the right time to improve the lives of our patients? Are we going to use ultrasound? Dermoscopy? Integrate them with some of the genetic findings?”

Dr. Blalock disclosed that he has served as a principal investigator for Castle Biosciences.

San Diego – Despite advances in dermoscopy and other techniques for diagnosing cutaneous melanoma, histology remains the gold standard.

“I don’t think that’s going to change in the short term,” Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, said at the annual Cutaneous Malignancy Update. “But I do think we can supplement that with other modalities that will improve the clinical examination and help dermatopathologists as they assess and evaluate these lesions,” he said, adding: “The reality is, histopathology, while it may be the gold standard, is not necessarily a consistently reproducible evaluation. That raises the question: What can we do better?”

Christoph Burgstedt/Science Photo Library/Getty Images

According to Dr. Blalock, the future may include more routine use of noninvasive genetic molecular assays to assist with the diagnostics challenges linked to the visual image and pattern recognition approach of detecting cutaneous melanoma. For example, a two-gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions obtained noninvasively via adhesive patch biopsy.

“Today, you can pick up a kit from your local pharmacy that can tell you a bit about broad genetic susceptibilities,” he said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. He predicted that using adhesive patch biopsies to assess suspicious melanocytic lesions “is likely the wave of the future.” This may increase patient understanding “as to the types of risks they have, the different lesions they have, and minimize invasive disease, but it also will pose different challenges for us when it comes to deploying patient-centered health care. For example, in a patient with multiple different lesions, how are you going to keep track of them all?”

Dermoscopy

In Dr. Blalock’s clinical opinion, dermoscopy improves the sensitivity of human visual detection of melanoma and may allow detection before a lesion displays classical features described with the “ABCDE rule.” However, the learning curve for dermoscopy is steep, he added, and whether the technique should be considered a first-line tool or as a supplement to other methods of examining cutaneous lesions remains a matter of debate.

“Dermoscopy is our version of the stethoscope,” he said. “We need to figure out when we’re going to use it. Should we be using it all of the time or only some of the time? Based on the clinical setting, maybe it’s a personal choice, but this can be a helpful skill and art in your practice if you’re willing to take the time to learn.”

In 2007, the International Dermoscopy Society (IDS) established a proposal for the standardization and recommended criteria necessary to effectively convey dermoscopic findings to consulting physicians and colleagues. The document includes 10 points categorized as either recommended or optional for a standardized dermoscopy report.

“The first step is to assess the lesion to determine whether or not it’s melanocytic in the first place,” said Dr. Blalock. “There are many different features – the mile-high [global features] evaluation of the lesions – then more specific local features that may clue you in to specific diagnoses,” he noted. “Once we get past that first step of determining that a lesion is melanocytic, it’s not enough to stop there, because we don’t want to biopsy every single lesion that’s melanocytic,” so there is a need to determine which ones require intervention, which is where dermoscopy “gets trickier and a little more challenging.”

According to the IDS, a standard dermoscopy report should include the patient’s age, relevant history pertaining to the lesion, pertinent personal and family history (recommended); clinical description of the lesion (recommended); the two-step method of dermoscopy differentiating melanocytic from nonmelanocytic tumors (recommended); and the use of standardized terms to describe structures as defined by the Dermoscopy Consensus Report published in 2003.

For new terms, the document states, “it would be helpful” for the physician to provide a working definition (recommended); the dermoscopic algorithm used should be mentioned (optional); information on the imaging equipment and magnification (recommended); clinical and dermoscopic images of the tumor (recommended); a diagnosis or differential diagnosis (recommended); decision concerning management (recommended), and specific comments for the pathologist when excision and histopathologic examination are recommended (optional).

The 2007 IDS document also includes a proposed seven-point checklist to differentiate between benign and melanocytic lesions on dermoscopy. Three major criteria are worth two points each: The presence of an atypical pigment network, gray-blue areas (commonly known as the veil), and an atypical vascular pattern. Four minor criteria are worth one point each: Irregular streaks, irregular dots/globules, irregular pigmentation, and regression structures. A minimum total score of 3 is required to establish a diagnosis of melanoma.

Another diagnostic technique, digital mole mapping, involves the use of photography to detect new or changing lesions. Dr. Blalock described this approach as rife with limitations, including variations in quality, challenges of storing and maintaining records, cost, time required to evaluate them, and determining which patients are appropriate candidates.

Other techniques being evaluated include computer algorithms to help dermatologists determine the diagnosis of melanoma from dermoscopic images, electrical impedance spectroscopy for noninvasive evaluation of atypical pigmented lesions, and ultrasound for staging of cutaneous malignant tumors.

Ultimately, “I think we’ll have multiple tools in our belt,” Dr. Blalock said, adding, “How do we pull them out at the right time to improve the lives of our patients? Are we going to use ultrasound? Dermoscopy? Integrate them with some of the genetic findings?”

Dr. Blalock disclosed that he has served as a principal investigator for Castle Biosciences.

San Diego – Despite advances in dermoscopy and other techniques for diagnosing cutaneous melanoma, histology remains the gold standard.

“I don’t think that’s going to change in the short term,” Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, said at the annual Cutaneous Malignancy Update. “But I do think we can supplement that with other modalities that will improve the clinical examination and help dermatopathologists as they assess and evaluate these lesions,” he said, adding: “The reality is, histopathology, while it may be the gold standard, is not necessarily a consistently reproducible evaluation. That raises the question: What can we do better?”

Christoph Burgstedt/Science Photo Library/Getty Images

According to Dr. Blalock, the future may include more routine use of noninvasive genetic molecular assays to assist with the diagnostics challenges linked to the visual image and pattern recognition approach of detecting cutaneous melanoma. For example, a two-gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions obtained noninvasively via adhesive patch biopsy.

“Today, you can pick up a kit from your local pharmacy that can tell you a bit about broad genetic susceptibilities,” he said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. He predicted that using adhesive patch biopsies to assess suspicious melanocytic lesions “is likely the wave of the future.” This may increase patient understanding “as to the types of risks they have, the different lesions they have, and minimize invasive disease, but it also will pose different challenges for us when it comes to deploying patient-centered health care. For example, in a patient with multiple different lesions, how are you going to keep track of them all?”

Dermoscopy

In Dr. Blalock’s clinical opinion, dermoscopy improves the sensitivity of human visual detection of melanoma and may allow detection before a lesion displays classical features described with the “ABCDE rule.” However, the learning curve for dermoscopy is steep, he added, and whether the technique should be considered a first-line tool or as a supplement to other methods of examining cutaneous lesions remains a matter of debate.

“Dermoscopy is our version of the stethoscope,” he said. “We need to figure out when we’re going to use it. Should we be using it all of the time or only some of the time? Based on the clinical setting, maybe it’s a personal choice, but this can be a helpful skill and art in your practice if you’re willing to take the time to learn.”

In 2007, the International Dermoscopy Society (IDS) established a proposal for the standardization and recommended criteria necessary to effectively convey dermoscopic findings to consulting physicians and colleagues. The document includes 10 points categorized as either recommended or optional for a standardized dermoscopy report.

“The first step is to assess the lesion to determine whether or not it’s melanocytic in the first place,” said Dr. Blalock. “There are many different features – the mile-high [global features] evaluation of the lesions – then more specific local features that may clue you in to specific diagnoses,” he noted. “Once we get past that first step of determining that a lesion is melanocytic, it’s not enough to stop there, because we don’t want to biopsy every single lesion that’s melanocytic,” so there is a need to determine which ones require intervention, which is where dermoscopy “gets trickier and a little more challenging.”

According to the IDS, a standard dermoscopy report should include the patient’s age, relevant history pertaining to the lesion, pertinent personal and family history (recommended); clinical description of the lesion (recommended); the two-step method of dermoscopy differentiating melanocytic from nonmelanocytic tumors (recommended); and the use of standardized terms to describe structures as defined by the Dermoscopy Consensus Report published in 2003.

For new terms, the document states, “it would be helpful” for the physician to provide a working definition (recommended); the dermoscopic algorithm used should be mentioned (optional); information on the imaging equipment and magnification (recommended); clinical and dermoscopic images of the tumor (recommended); a diagnosis or differential diagnosis (recommended); decision concerning management (recommended), and specific comments for the pathologist when excision and histopathologic examination are recommended (optional).

The 2007 IDS document also includes a proposed seven-point checklist to differentiate between benign and melanocytic lesions on dermoscopy. Three major criteria are worth two points each: The presence of an atypical pigment network, gray-blue areas (commonly known as the veil), and an atypical vascular pattern. Four minor criteria are worth one point each: Irregular streaks, irregular dots/globules, irregular pigmentation, and regression structures. A minimum total score of 3 is required to establish a diagnosis of melanoma.

Another diagnostic technique, digital mole mapping, involves the use of photography to detect new or changing lesions. Dr. Blalock described this approach as rife with limitations, including variations in quality, challenges of storing and maintaining records, cost, time required to evaluate them, and determining which patients are appropriate candidates.

Other techniques being evaluated include computer algorithms to help dermatologists determine the diagnosis of melanoma from dermoscopic images, electrical impedance spectroscopy for noninvasive evaluation of atypical pigmented lesions, and ultrasound for staging of cutaneous malignant tumors.

Ultimately, “I think we’ll have multiple tools in our belt,” Dr. Blalock said, adding, “How do we pull them out at the right time to improve the lives of our patients? Are we going to use ultrasound? Dermoscopy? Integrate them with some of the genetic findings?”

Dr. Blalock disclosed that he has served as a principal investigator for Castle Biosciences.

A case series of epidermal growth factor receptor (EGFR) exon 20 insertion–mutated advanced non–small cell lung cancer patients with dermatologic adverse events (dAEs) subsequent to treatment with amivantamab showed classic toxic effects associated with EGFR inhibitors and atypical presentations. Toxic effects, however, were mitigated by dose interruptions, dAE management, and amivantamab dose reductions, allowing for cancer therapy continuation in all cases. Amivantamab doses were reduced in 5 out of 6 cases, according to a research letter published in JAMA Dermatology.

The EGFR exon 20 insertion–mutation portends insensitivity to EGFR tyrosine kinase inhibitors and poor prognosis. Amivantamab, a bispecific monoclonal antibody targeting EGFR and mesenchymal epithelial transition factor (MET) is Food and Drug Administration approved for this population. Acneiform eruptions and pruritus are the most common dAEs associated with EGFR inhibitors, with xerosis, fissures, and nail and hair changes occurring additionally. While no FDA-approved monoclonal antibody targets MET exclusively, capmatinib and tepotinib (both tyrosine kinase inhibitors) inhibit MET. They have been associated with photosensitivity, acneiform rash, paronychia, xerosis, pruritus, and mucositis.

The Belzer et al. letter reviewed six consecutive cases (mean age, 58) of dAEs associated with amivantamab at two academic health centers (treated June 2021 to August 2022) in order to describe dAEs associated with amivantamab use. “I suspect the rate of dAEs with amivantamab is similar to the rate of dAEs associated with first- and second-generation EGFR inhibitors, where the majority of patients, actually 75%-90%, develop cutaneous toxicity,” said Jonathan Leventhal, MD, Yale University, New Haven, Conn., corresponding author for the Belzer et al. letter.

Time from treatment initiation with amivantamab to dAE ranged from less than 1 month to 4 months. All dAEs were grade 2 or 3 and all included acneiform eruptions. These were widespread in four cases and in another case complicated by impetiginization (culture results positive for methicillin-susceptible Staphylococcus aureus), and a further case was limited to the scalp, face, upper back, and upper chest. Others with widespread acneiform eruption included the face with hyperkeratotic crust of the scalp and dermatitis of the posterior neck. Fissuring of the palms and soles was noted in two cases with widespread acneiform eruptions. Paronychia with pyogenic granulomas was reported in four cases. Another case included onycholysis with suppurative paronychia.

In five cases amivantamab was stopped but successfully reinitiated at 67%-75% of the original dose. In one case amivantamab was continued at the original dose.

Doxycycline at 100 mg twice daily was included among all of the treatments for cutaneous dAEs. Silver nitrate cautery was applied for pyogenic granulomas in clinic. The case of grade 3 acneiform eruption of the scalp and face was treated with hydrogen peroxide soaks with debridement in clinic, doxycycline, aluminum acetate soaks, and triamcinolone ointment. All dermatologic cases resolved fully without scarring.

“It is very likely that this series highlights the more severe and unusual presentations of dAEs which were referred to oncodermatology. I suspect milder presentations were likely managed by oncologists,” Dr. Leventhal said in the interview.

“It is important for dermatologists and oncologists to be aware of the more severe and atypical dAEs associated with this novel FDA-approved targeted therapy.” Dr. Belzer said. “As amivantamab use increases, oncologists and dermatologists need to collaborate to ensure swift diagnosis and management of dAEs.”

One trial, the authors stated, revealed more than half of patients receiving EGFR inhibitors taking preemptive treatment with moisturizers, sunscreen, topical corticosteroids, and an oral tetracycline to have more than a 50% reduction in grade 2 or higher dAEs. Belzer et al. concluded that prophylactic treatment, including sun protection, should be considered before initiating treatment with amivantamab.

A limitation of the study, Belzer et al. acknowledged, was the small sample size.

Dr. Leventhal reported receiving personal fees from the advisory boards of Sanofi, Regeneron, and La Roche-Posay as well as clinical trial funding from Azitra and OnQuality Pharmaceuticals outside the submitted work.

A case series of epidermal growth factor receptor (EGFR) exon 20 insertion–mutated advanced non–small cell lung cancer patients with dermatologic adverse events (dAEs) subsequent to treatment with amivantamab showed classic toxic effects associated with EGFR inhibitors and atypical presentations. Toxic effects, however, were mitigated by dose interruptions, dAE management, and amivantamab dose reductions, allowing for cancer therapy continuation in all cases. Amivantamab doses were reduced in 5 out of 6 cases, according to a research letter published in JAMA Dermatology.

The EGFR exon 20 insertion–mutation portends insensitivity to EGFR tyrosine kinase inhibitors and poor prognosis. Amivantamab, a bispecific monoclonal antibody targeting EGFR and mesenchymal epithelial transition factor (MET) is Food and Drug Administration approved for this population. Acneiform eruptions and pruritus are the most common dAEs associated with EGFR inhibitors, with xerosis, fissures, and nail and hair changes occurring additionally. While no FDA-approved monoclonal antibody targets MET exclusively, capmatinib and tepotinib (both tyrosine kinase inhibitors) inhibit MET. They have been associated with photosensitivity, acneiform rash, paronychia, xerosis, pruritus, and mucositis.

The Belzer et al. letter reviewed six consecutive cases (mean age, 58) of dAEs associated with amivantamab at two academic health centers (treated June 2021 to August 2022) in order to describe dAEs associated with amivantamab use. “I suspect the rate of dAEs with amivantamab is similar to the rate of dAEs associated with first- and second-generation EGFR inhibitors, where the majority of patients, actually 75%-90%, develop cutaneous toxicity,” said Jonathan Leventhal, MD, Yale University, New Haven, Conn., corresponding author for the Belzer et al. letter.

Time from treatment initiation with amivantamab to dAE ranged from less than 1 month to 4 months. All dAEs were grade 2 or 3 and all included acneiform eruptions. These were widespread in four cases and in another case complicated by impetiginization (culture results positive for methicillin-susceptible Staphylococcus aureus), and a further case was limited to the scalp, face, upper back, and upper chest. Others with widespread acneiform eruption included the face with hyperkeratotic crust of the scalp and dermatitis of the posterior neck. Fissuring of the palms and soles was noted in two cases with widespread acneiform eruptions. Paronychia with pyogenic granulomas was reported in four cases. Another case included onycholysis with suppurative paronychia.

In five cases amivantamab was stopped but successfully reinitiated at 67%-75% of the original dose. In one case amivantamab was continued at the original dose.

Doxycycline at 100 mg twice daily was included among all of the treatments for cutaneous dAEs. Silver nitrate cautery was applied for pyogenic granulomas in clinic. The case of grade 3 acneiform eruption of the scalp and face was treated with hydrogen peroxide soaks with debridement in clinic, doxycycline, aluminum acetate soaks, and triamcinolone ointment. All dermatologic cases resolved fully without scarring.

“It is very likely that this series highlights the more severe and unusual presentations of dAEs which were referred to oncodermatology. I suspect milder presentations were likely managed by oncologists,” Dr. Leventhal said in the interview.

“It is important for dermatologists and oncologists to be aware of the more severe and atypical dAEs associated with this novel FDA-approved targeted therapy.” Dr. Belzer said. “As amivantamab use increases, oncologists and dermatologists need to collaborate to ensure swift diagnosis and management of dAEs.”

One trial, the authors stated, revealed more than half of patients receiving EGFR inhibitors taking preemptive treatment with moisturizers, sunscreen, topical corticosteroids, and an oral tetracycline to have more than a 50% reduction in grade 2 or higher dAEs. Belzer et al. concluded that prophylactic treatment, including sun protection, should be considered before initiating treatment with amivantamab.

A limitation of the study, Belzer et al. acknowledged, was the small sample size.

Dr. Leventhal reported receiving personal fees from the advisory boards of Sanofi, Regeneron, and La Roche-Posay as well as clinical trial funding from Azitra and OnQuality Pharmaceuticals outside the submitted work.

A case series of epidermal growth factor receptor (EGFR) exon 20 insertion–mutated advanced non–small cell lung cancer patients with dermatologic adverse events (dAEs) subsequent to treatment with amivantamab showed classic toxic effects associated with EGFR inhibitors and atypical presentations. Toxic effects, however, were mitigated by dose interruptions, dAE management, and amivantamab dose reductions, allowing for cancer therapy continuation in all cases. Amivantamab doses were reduced in 5 out of 6 cases, according to a research letter published in JAMA Dermatology.

The EGFR exon 20 insertion–mutation portends insensitivity to EGFR tyrosine kinase inhibitors and poor prognosis. Amivantamab, a bispecific monoclonal antibody targeting EGFR and mesenchymal epithelial transition factor (MET) is Food and Drug Administration approved for this population. Acneiform eruptions and pruritus are the most common dAEs associated with EGFR inhibitors, with xerosis, fissures, and nail and hair changes occurring additionally. While no FDA-approved monoclonal antibody targets MET exclusively, capmatinib and tepotinib (both tyrosine kinase inhibitors) inhibit MET. They have been associated with photosensitivity, acneiform rash, paronychia, xerosis, pruritus, and mucositis.

The Belzer et al. letter reviewed six consecutive cases (mean age, 58) of dAEs associated with amivantamab at two academic health centers (treated June 2021 to August 2022) in order to describe dAEs associated with amivantamab use. “I suspect the rate of dAEs with amivantamab is similar to the rate of dAEs associated with first- and second-generation EGFR inhibitors, where the majority of patients, actually 75%-90%, develop cutaneous toxicity,” said Jonathan Leventhal, MD, Yale University, New Haven, Conn., corresponding author for the Belzer et al. letter.

Time from treatment initiation with amivantamab to dAE ranged from less than 1 month to 4 months. All dAEs were grade 2 or 3 and all included acneiform eruptions. These were widespread in four cases and in another case complicated by impetiginization (culture results positive for methicillin-susceptible Staphylococcus aureus), and a further case was limited to the scalp, face, upper back, and upper chest. Others with widespread acneiform eruption included the face with hyperkeratotic crust of the scalp and dermatitis of the posterior neck. Fissuring of the palms and soles was noted in two cases with widespread acneiform eruptions. Paronychia with pyogenic granulomas was reported in four cases. Another case included onycholysis with suppurative paronychia.

In five cases amivantamab was stopped but successfully reinitiated at 67%-75% of the original dose. In one case amivantamab was continued at the original dose.

Doxycycline at 100 mg twice daily was included among all of the treatments for cutaneous dAEs. Silver nitrate cautery was applied for pyogenic granulomas in clinic. The case of grade 3 acneiform eruption of the scalp and face was treated with hydrogen peroxide soaks with debridement in clinic, doxycycline, aluminum acetate soaks, and triamcinolone ointment. All dermatologic cases resolved fully without scarring.

“It is very likely that this series highlights the more severe and unusual presentations of dAEs which were referred to oncodermatology. I suspect milder presentations were likely managed by oncologists,” Dr. Leventhal said in the interview.

“It is important for dermatologists and oncologists to be aware of the more severe and atypical dAEs associated with this novel FDA-approved targeted therapy.” Dr. Belzer said. “As amivantamab use increases, oncologists and dermatologists need to collaborate to ensure swift diagnosis and management of dAEs.”

One trial, the authors stated, revealed more than half of patients receiving EGFR inhibitors taking preemptive treatment with moisturizers, sunscreen, topical corticosteroids, and an oral tetracycline to have more than a 50% reduction in grade 2 or higher dAEs. Belzer et al. concluded that prophylactic treatment, including sun protection, should be considered before initiating treatment with amivantamab.

A limitation of the study, Belzer et al. acknowledged, was the small sample size.

Dr. Leventhal reported receiving personal fees from the advisory boards of Sanofi, Regeneron, and La Roche-Posay as well as clinical trial funding from Azitra and OnQuality Pharmaceuticals outside the submitted work.

SAN DIEGO – Evidence of melanoma in the ancient past is rare, but according to James W. Patterson, MD, signs of melanoma with cutaneous lesions and diffuse bony metastases have been discovered in Peruvian Inca mummies.

“Radiocarbon dating indicated that these mummies were 2,400 years old,” Dr. Patterson, professor emeritus of pathology and dermatology at the University of Virginia, Charlottesville, said at the annual Cutaneous Malignancy Update.

In 1820, William Norris, a general practitioner from Stourbridge, England, published the first English language report of melanoma in the Edinburgh Medical and Surgical Journal. “The report was titled ‘A case of fungoid disease,’ so it appears that melanoma was often regarded as a fungal infection back then,” Dr. Patterson said. In the report, Dr. Norris described the tumor in a 59-year-old man as “nearly half the size of a hen’s egg, of a deep brown color, of a firm and fleshy feel, [and] ulcerated on its surface.” Dr. Norris authored a later work titled “Eight cases of melanosis, with pathological and therapeutical remarks on that disease.”

In 1840, a full 2 decades following the first published report from Dr. Norris, the British surgeon Samuel Cooper published a book titled “First Lines of Theory and Practice of Surgery,” in which he described patients with advanced stage melanoma as untreatable and postulated that the only chance for survival was early removal of the tumor.

Dr. Patterson reported having no relevant disclosures.

SAN DIEGO – Evidence of melanoma in the ancient past is rare, but according to James W. Patterson, MD, signs of melanoma with cutaneous lesions and diffuse bony metastases have been discovered in Peruvian Inca mummies.

“Radiocarbon dating indicated that these mummies were 2,400 years old,” Dr. Patterson, professor emeritus of pathology and dermatology at the University of Virginia, Charlottesville, said at the annual Cutaneous Malignancy Update.

In 1820, William Norris, a general practitioner from Stourbridge, England, published the first English language report of melanoma in the Edinburgh Medical and Surgical Journal. “The report was titled ‘A case of fungoid disease,’ so it appears that melanoma was often regarded as a fungal infection back then,” Dr. Patterson said. In the report, Dr. Norris described the tumor in a 59-year-old man as “nearly half the size of a hen’s egg, of a deep brown color, of a firm and fleshy feel, [and] ulcerated on its surface.” Dr. Norris authored a later work titled “Eight cases of melanosis, with pathological and therapeutical remarks on that disease.”

In 1840, a full 2 decades following the first published report from Dr. Norris, the British surgeon Samuel Cooper published a book titled “First Lines of Theory and Practice of Surgery,” in which he described patients with advanced stage melanoma as untreatable and postulated that the only chance for survival was early removal of the tumor.

Dr. Patterson reported having no relevant disclosures.

SAN DIEGO – Evidence of melanoma in the ancient past is rare, but according to James W. Patterson, MD, signs of melanoma with cutaneous lesions and diffuse bony metastases have been discovered in Peruvian Inca mummies.

“Radiocarbon dating indicated that these mummies were 2,400 years old,” Dr. Patterson, professor emeritus of pathology and dermatology at the University of Virginia, Charlottesville, said at the annual Cutaneous Malignancy Update.

In 1820, William Norris, a general practitioner from Stourbridge, England, published the first English language report of melanoma in the Edinburgh Medical and Surgical Journal. “The report was titled ‘A case of fungoid disease,’ so it appears that melanoma was often regarded as a fungal infection back then,” Dr. Patterson said. In the report, Dr. Norris described the tumor in a 59-year-old man as “nearly half the size of a hen’s egg, of a deep brown color, of a firm and fleshy feel, [and] ulcerated on its surface.” Dr. Norris authored a later work titled “Eight cases of melanosis, with pathological and therapeutical remarks on that disease.”

In 1840, a full 2 decades following the first published report from Dr. Norris, the British surgeon Samuel Cooper published a book titled “First Lines of Theory and Practice of Surgery,” in which he described patients with advanced stage melanoma as untreatable and postulated that the only chance for survival was early removal of the tumor.

Dr. Patterson reported having no relevant disclosures.

SAN DIEGO – As with many markers for the evaluation of challenging melanocytic lesions, preferentially expressed antigen in melanoma (PRAME) has its benefits and drawbacks, according to Cora Humberson, MD.

“I’m a fan, but there are issues with it,” Dr. Humberson, dermatopathology coordinator in the department of pathology at Scripps MD Anderson Cancer Center, San Diego, said at the annual Cutaneous Malignancy Update. “It’s all in how you use it.”

PRAME is part of the cancer/testis (CT) antigens, of which more than 40 have now been identified. They are encoded by genes that are normally expressed only in the human germ line, but are also expressed in various tumor types, including melanoma and carcinomas of the bladder, lung, and liver. “The biological function of these antigens is not fully understood, but they may act as a repressor of retinoic acid, potentially inhibiting differentiation, inhibiting proliferation arrest – things that we associate with malignancy,” she said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “These immunogenic proteins are being pursued as targets for therapeutic cancer vaccines,” she noted.

CT antigens are also being evaluated for their role in oncogenesis, she added. Recapitulation of portions of the germline gene-expression might contribute characteristic features to the neoplastic phenotype, including immortality, invasiveness, immune evasion, and metastatic capacity.

According to Dr. Humberson, PRAME can be used to differentiate comingled nevus and melanoma, to distinguish between nevoid melanoma and nevus, and for melanoma margin assessment in sun-damaged skin. One potential pitfall is that sun-damaged melanocytes may express PRAME. “The older the person and the more sun damage [they have], the more likely you are to see this, but the melanocytes won’t be grouped, they’ll be scattered,” she said.

Another pitfall is that less than 15% of nevi may express PRAME. “PRAME can be expressed in scars, so if you’re looking at a spindle cell lesion, be aware that you might be looking at a scar if you’re seeing PRAME expression,” she added. She also noted that PRAME immunohistochemistry (IHC) expression is not a prognostic biomarker in thin melanomas.

If fewer than 25% of cells in a melanocytic lesion express PRAME, most published assessments of PRAME IHC favor nevi as the diagnosis. “If more than 75% are expressing it, it favors melanoma,” Dr. Humberson said. “There’s a big category in between. It’s not that 30% is more likely benign or that 60% is more likely malignant; you can’t really depend upon [PRAME] if you’re in this range.”

A diagnostic accuracy study found that when more than 75% of cells express PRAME, the marker has a sensitivity of 0.63 and a specificity of 0.97.

Selected PRAME-related published references she recommended include: J Cutan Pathol. 2021;48(9):1115-23; Diagnostics. 2022 Sep 9; 12(9):2197, and J Cutan Pathol. 2022;49(9):829-32.

Dr. Humberson reported having no relevant disclosures.

SAN DIEGO – As with many markers for the evaluation of challenging melanocytic lesions, preferentially expressed antigen in melanoma (PRAME) has its benefits and drawbacks, according to Cora Humberson, MD.

“I’m a fan, but there are issues with it,” Dr. Humberson, dermatopathology coordinator in the department of pathology at Scripps MD Anderson Cancer Center, San Diego, said at the annual Cutaneous Malignancy Update. “It’s all in how you use it.”

PRAME is part of the cancer/testis (CT) antigens, of which more than 40 have now been identified. They are encoded by genes that are normally expressed only in the human germ line, but are also expressed in various tumor types, including melanoma and carcinomas of the bladder, lung, and liver. “The biological function of these antigens is not fully understood, but they may act as a repressor of retinoic acid, potentially inhibiting differentiation, inhibiting proliferation arrest – things that we associate with malignancy,” she said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “These immunogenic proteins are being pursued as targets for therapeutic cancer vaccines,” she noted.

CT antigens are also being evaluated for their role in oncogenesis, she added. Recapitulation of portions of the germline gene-expression might contribute characteristic features to the neoplastic phenotype, including immortality, invasiveness, immune evasion, and metastatic capacity.

According to Dr. Humberson, PRAME can be used to differentiate comingled nevus and melanoma, to distinguish between nevoid melanoma and nevus, and for melanoma margin assessment in sun-damaged skin. One potential pitfall is that sun-damaged melanocytes may express PRAME. “The older the person and the more sun damage [they have], the more likely you are to see this, but the melanocytes won’t be grouped, they’ll be scattered,” she said.

Another pitfall is that less than 15% of nevi may express PRAME. “PRAME can be expressed in scars, so if you’re looking at a spindle cell lesion, be aware that you might be looking at a scar if you’re seeing PRAME expression,” she added. She also noted that PRAME immunohistochemistry (IHC) expression is not a prognostic biomarker in thin melanomas.

If fewer than 25% of cells in a melanocytic lesion express PRAME, most published assessments of PRAME IHC favor nevi as the diagnosis. “If more than 75% are expressing it, it favors melanoma,” Dr. Humberson said. “There’s a big category in between. It’s not that 30% is more likely benign or that 60% is more likely malignant; you can’t really depend upon [PRAME] if you’re in this range.”

A diagnostic accuracy study found that when more than 75% of cells express PRAME, the marker has a sensitivity of 0.63 and a specificity of 0.97.

Selected PRAME-related published references she recommended include: J Cutan Pathol. 2021;48(9):1115-23; Diagnostics. 2022 Sep 9; 12(9):2197, and J Cutan Pathol. 2022;49(9):829-32.

Dr. Humberson reported having no relevant disclosures.

SAN DIEGO – As with many markers for the evaluation of challenging melanocytic lesions, preferentially expressed antigen in melanoma (PRAME) has its benefits and drawbacks, according to Cora Humberson, MD.

“I’m a fan, but there are issues with it,” Dr. Humberson, dermatopathology coordinator in the department of pathology at Scripps MD Anderson Cancer Center, San Diego, said at the annual Cutaneous Malignancy Update. “It’s all in how you use it.”

PRAME is part of the cancer/testis (CT) antigens, of which more than 40 have now been identified. They are encoded by genes that are normally expressed only in the human germ line, but are also expressed in various tumor types, including melanoma and carcinomas of the bladder, lung, and liver. “The biological function of these antigens is not fully understood, but they may act as a repressor of retinoic acid, potentially inhibiting differentiation, inhibiting proliferation arrest – things that we associate with malignancy,” she said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “These immunogenic proteins are being pursued as targets for therapeutic cancer vaccines,” she noted.

CT antigens are also being evaluated for their role in oncogenesis, she added. Recapitulation of portions of the germline gene-expression might contribute characteristic features to the neoplastic phenotype, including immortality, invasiveness, immune evasion, and metastatic capacity.

According to Dr. Humberson, PRAME can be used to differentiate comingled nevus and melanoma, to distinguish between nevoid melanoma and nevus, and for melanoma margin assessment in sun-damaged skin. One potential pitfall is that sun-damaged melanocytes may express PRAME. “The older the person and the more sun damage [they have], the more likely you are to see this, but the melanocytes won’t be grouped, they’ll be scattered,” she said.

Another pitfall is that less than 15% of nevi may express PRAME. “PRAME can be expressed in scars, so if you’re looking at a spindle cell lesion, be aware that you might be looking at a scar if you’re seeing PRAME expression,” she added. She also noted that PRAME immunohistochemistry (IHC) expression is not a prognostic biomarker in thin melanomas.

If fewer than 25% of cells in a melanocytic lesion express PRAME, most published assessments of PRAME IHC favor nevi as the diagnosis. “If more than 75% are expressing it, it favors melanoma,” Dr. Humberson said. “There’s a big category in between. It’s not that 30% is more likely benign or that 60% is more likely malignant; you can’t really depend upon [PRAME] if you’re in this range.”

A diagnostic accuracy study found that when more than 75% of cells express PRAME, the marker has a sensitivity of 0.63 and a specificity of 0.97.

Selected PRAME-related published references she recommended include: J Cutan Pathol. 2021;48(9):1115-23; Diagnostics. 2022 Sep 9; 12(9):2197, and J Cutan Pathol. 2022;49(9):829-32.

Dr. Humberson reported having no relevant disclosures.

I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.

Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.

There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
 

When should a patient be referred to palliative care?

Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.

For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.

But don’t get me wrong. I’m not discouraging referrals to palliative care, instead I’m suggesting the careful triage of patients.
 

Palliative care for all?

In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.

The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.

This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.

In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.

Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
 

When should patients be referred to a specialty palliative care program?

I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.

A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.

At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.

Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.

There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
 

When should a patient be referred to palliative care?

Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.

For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.

But don’t get me wrong. I’m not discouraging referrals to palliative care, instead I’m suggesting the careful triage of patients.
 

Palliative care for all?

In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.

The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.

This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.

In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.

Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
 

When should patients be referred to a specialty palliative care program?

I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.

A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.

At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.

Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.

There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
 

When should a patient be referred to palliative care?

Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.

For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.

But don’t get me wrong. I’m not discouraging referrals to palliative care, instead I’m suggesting the careful triage of patients.
 

Palliative care for all?

In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.

The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.

This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.

In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.

Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
 

When should patients be referred to a specialty palliative care program?

I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.

A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.

At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

Individuals who regularly take vitamin D supplements are significantly less likely to have a history of malignant melanoma or any type of skin cancers than are nonusers, say Finnish investigators. They also found a trend for benefit with occasional use.

The study, published in Melanoma Research, involved almost 500 individuals attending a dermatology clinic who reported on their use of vitamin D supplements.

Zbynek Pospisil/Getty Images

Regular users had a significant 55% reduction in the odds of having a past or present melanoma diagnosis, while occasional use was associated with a nonsignificant 46% reduction. The reduction was similar for all skin cancer types.

However, senior author Ilkka T. Harvima, MD, PhD, department of dermatology, University of Eastern Finland and Kuopio (Finland) University Hospital, warned there are limitations to the study.

Despite adjustment for several possible confounding factors, “it is still possible that some other, yet unidentified or untested, factors can still confound the present result,” he said.

Consequently, “the causal link between vitamin D and melanoma cannot be confirmed by the present results,” Dr. Harvima said in a statement.

Even if the link were to be proven, “the question about the optimal dose of oral vitamin D in order to for it to have beneficial effects remains to be answered,” he said.

“Until we know more, national intake recommendations should be followed.”

The incidence of cutaneous malignant melanoma and other skin cancers has been increasing steadily in Western populations, particularly in immunosuppressed individuals, the authors pointed out, and they attributed the rise to an increased exposure to ultraviolet radiation.

While ultraviolet radiation exposure is a well-known risk factor, “the other side of the coin is that public sun protection campaigns have led to alerts that insufficient sun exposure is a significant public health problem, resulting in insufficient vitamin D status.”

For their study, the team reviewed the records of 498 patients aged 21-79 years at a  dermatology outpatient clinic who were deemed by an experienced dermatologist to be at risk of any type of skin cancer.

Among these patients, 295 individuals had a history of past or present cutaneous malignancy, with 100 diagnosed with melanoma, 213 with basal cell carcinoma, and 41 with squamous cell carcinoma. A further 70 subjects had cancer elsewhere, including breast, prostate, kidney, bladder, intestine, and blood cancers.

A subgroup of 96 patients were immunocompromised and were considered separately.

The 402 remaining patients were categorized, based on their self-reported use of oral vitamin D preparations, as nonusers (n = 99), occasional users (n = 126), and regular users (n = 177).

Regular use of vitamin D was associated with being more educated (P = .032), less frequent outdoor working (P = .003), lower tobacco pack years (P = .001), and more frequent solarium exposure (P = .002).

There was no significant association between vitamin D use and photoaging, actinic keratoses, nevi, basal or squamous cell carcinoma, body mass index, or self-estimated lifetime exposure to sunlight or sunburns.

However, there were significant associations between regular use of vitamin D and a lower incidence of melanoma and other cancer types.

There were significantly fewer individuals in the regular vitamin D use group with a past or present history of melanoma when compared with the nonuse group, at 18.1% vs. 32.3% (P = .021), or any type of skin cancer, at 62.1% vs. 74.7% (P = .027).

Multivariate logistic regression analysis revealed that regular vitamin D use was significantly associated with a reduced melanoma risk, at an odds ratio vs. nonuse of 0.447 (P = .016).

Occasional use was associated with a reduced, albeit nonsignificant, risk, with an odds ratio versus nonuse of 0.540 (P = .08).

For any type of skin cancers, regular vitamin D use was associated with an odds ratio vs. nonuse of 0.478 (P = .032), while that for occasional vitamin D use was 0.543 (P = .061).

“Somewhat similar” results were obtained when the investigators looked at the subgroup of immunocompromised individuals, although they note that “the number of subjects was low.”

The study was supported by the Cancer Center of Eastern Finland of the University of Eastern Finland, the Finnish Cancer Research Foundation, and the VTR-funding of Kuopio University Hospital. The authors report no relevant financial relationships.

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

Individuals who regularly take vitamin D supplements are significantly less likely to have a history of malignant melanoma or any type of skin cancers than are nonusers, say Finnish investigators. They also found a trend for benefit with occasional use.

The study, published in Melanoma Research, involved almost 500 individuals attending a dermatology clinic who reported on their use of vitamin D supplements.

Zbynek Pospisil/Getty Images

Regular users had a significant 55% reduction in the odds of having a past or present melanoma diagnosis, while occasional use was associated with a nonsignificant 46% reduction. The reduction was similar for all skin cancer types.

However, senior author Ilkka T. Harvima, MD, PhD, department of dermatology, University of Eastern Finland and Kuopio (Finland) University Hospital, warned there are limitations to the study.

Despite adjustment for several possible confounding factors, “it is still possible that some other, yet unidentified or untested, factors can still confound the present result,” he said.

Consequently, “the causal link between vitamin D and melanoma cannot be confirmed by the present results,” Dr. Harvima said in a statement.

Even if the link were to be proven, “the question about the optimal dose of oral vitamin D in order to for it to have beneficial effects remains to be answered,” he said.

“Until we know more, national intake recommendations should be followed.”

The incidence of cutaneous malignant melanoma and other skin cancers has been increasing steadily in Western populations, particularly in immunosuppressed individuals, the authors pointed out, and they attributed the rise to an increased exposure to ultraviolet radiation.

While ultraviolet radiation exposure is a well-known risk factor, “the other side of the coin is that public sun protection campaigns have led to alerts that insufficient sun exposure is a significant public health problem, resulting in insufficient vitamin D status.”

For their study, the team reviewed the records of 498 patients aged 21-79 years at a  dermatology outpatient clinic who were deemed by an experienced dermatologist to be at risk of any type of skin cancer.

Among these patients, 295 individuals had a history of past or present cutaneous malignancy, with 100 diagnosed with melanoma, 213 with basal cell carcinoma, and 41 with squamous cell carcinoma. A further 70 subjects had cancer elsewhere, including breast, prostate, kidney, bladder, intestine, and blood cancers.

A subgroup of 96 patients were immunocompromised and were considered separately.

The 402 remaining patients were categorized, based on their self-reported use of oral vitamin D preparations, as nonusers (n = 99), occasional users (n = 126), and regular users (n = 177).

Regular use of vitamin D was associated with being more educated (P = .032), less frequent outdoor working (P = .003), lower tobacco pack years (P = .001), and more frequent solarium exposure (P = .002).

There was no significant association between vitamin D use and photoaging, actinic keratoses, nevi, basal or squamous cell carcinoma, body mass index, or self-estimated lifetime exposure to sunlight or sunburns.

However, there were significant associations between regular use of vitamin D and a lower incidence of melanoma and other cancer types.

There were significantly fewer individuals in the regular vitamin D use group with a past or present history of melanoma when compared with the nonuse group, at 18.1% vs. 32.3% (P = .021), or any type of skin cancer, at 62.1% vs. 74.7% (P = .027).

Multivariate logistic regression analysis revealed that regular vitamin D use was significantly associated with a reduced melanoma risk, at an odds ratio vs. nonuse of 0.447 (P = .016).

Occasional use was associated with a reduced, albeit nonsignificant, risk, with an odds ratio versus nonuse of 0.540 (P = .08).

For any type of skin cancers, regular vitamin D use was associated with an odds ratio vs. nonuse of 0.478 (P = .032), while that for occasional vitamin D use was 0.543 (P = .061).

“Somewhat similar” results were obtained when the investigators looked at the subgroup of immunocompromised individuals, although they note that “the number of subjects was low.”

The study was supported by the Cancer Center of Eastern Finland of the University of Eastern Finland, the Finnish Cancer Research Foundation, and the VTR-funding of Kuopio University Hospital. The authors report no relevant financial relationships.

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

Individuals who regularly take vitamin D supplements are significantly less likely to have a history of malignant melanoma or any type of skin cancers than are nonusers, say Finnish investigators. They also found a trend for benefit with occasional use.

The study, published in Melanoma Research, involved almost 500 individuals attending a dermatology clinic who reported on their use of vitamin D supplements.

Zbynek Pospisil/Getty Images

Regular users had a significant 55% reduction in the odds of having a past or present melanoma diagnosis, while occasional use was associated with a nonsignificant 46% reduction. The reduction was similar for all skin cancer types.

However, senior author Ilkka T. Harvima, MD, PhD, department of dermatology, University of Eastern Finland and Kuopio (Finland) University Hospital, warned there are limitations to the study.

Despite adjustment for several possible confounding factors, “it is still possible that some other, yet unidentified or untested, factors can still confound the present result,” he said.

Consequently, “the causal link between vitamin D and melanoma cannot be confirmed by the present results,” Dr. Harvima said in a statement.

Even if the link were to be proven, “the question about the optimal dose of oral vitamin D in order to for it to have beneficial effects remains to be answered,” he said.

“Until we know more, national intake recommendations should be followed.”

The incidence of cutaneous malignant melanoma and other skin cancers has been increasing steadily in Western populations, particularly in immunosuppressed individuals, the authors pointed out, and they attributed the rise to an increased exposure to ultraviolet radiation.

While ultraviolet radiation exposure is a well-known risk factor, “the other side of the coin is that public sun protection campaigns have led to alerts that insufficient sun exposure is a significant public health problem, resulting in insufficient vitamin D status.”

For their study, the team reviewed the records of 498 patients aged 21-79 years at a  dermatology outpatient clinic who were deemed by an experienced dermatologist to be at risk of any type of skin cancer.

Among these patients, 295 individuals had a history of past or present cutaneous malignancy, with 100 diagnosed with melanoma, 213 with basal cell carcinoma, and 41 with squamous cell carcinoma. A further 70 subjects had cancer elsewhere, including breast, prostate, kidney, bladder, intestine, and blood cancers.

A subgroup of 96 patients were immunocompromised and were considered separately.

The 402 remaining patients were categorized, based on their self-reported use of oral vitamin D preparations, as nonusers (n = 99), occasional users (n = 126), and regular users (n = 177).

Regular use of vitamin D was associated with being more educated (P = .032), less frequent outdoor working (P = .003), lower tobacco pack years (P = .001), and more frequent solarium exposure (P = .002).

There was no significant association between vitamin D use and photoaging, actinic keratoses, nevi, basal or squamous cell carcinoma, body mass index, or self-estimated lifetime exposure to sunlight or sunburns.

However, there were significant associations between regular use of vitamin D and a lower incidence of melanoma and other cancer types.

There were significantly fewer individuals in the regular vitamin D use group with a past or present history of melanoma when compared with the nonuse group, at 18.1% vs. 32.3% (P = .021), or any type of skin cancer, at 62.1% vs. 74.7% (P = .027).

Multivariate logistic regression analysis revealed that regular vitamin D use was significantly associated with a reduced melanoma risk, at an odds ratio vs. nonuse of 0.447 (P = .016).

Occasional use was associated with a reduced, albeit nonsignificant, risk, with an odds ratio versus nonuse of 0.540 (P = .08).

For any type of skin cancers, regular vitamin D use was associated with an odds ratio vs. nonuse of 0.478 (P = .032), while that for occasional vitamin D use was 0.543 (P = .061).

“Somewhat similar” results were obtained when the investigators looked at the subgroup of immunocompromised individuals, although they note that “the number of subjects was low.”

The study was supported by the Cancer Center of Eastern Finland of the University of Eastern Finland, the Finnish Cancer Research Foundation, and the VTR-funding of Kuopio University Hospital. The authors report no relevant financial relationships.

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