Risk for Melanoma in Kids Not Clear Cut

BOCA RATON, FLA. – The risk factors for melanoma are well established in adults, as is the well-known ABCD method for self-evaluation for the disease, but assessing risk and recognizing melanoma in children are far less clear cut.

The typical risk factors, such as a history of changing moles, white race, and sun sensitivity, don't seem to apply in children to the degree they do in adults, and although the ABCDs (asymmetry, border irregularity, color variations, diameter over 6 mm) have withstood the test of time in adults, for whom they were developed, they don’t necessarily apply in children, Dr. Seth J. Orlow said at the meeting of the Florida Society of Dermatology and Dermatologic Surgery.

The relatively recent addition of an E to the ABCD method adds an element that is applicable to assessment of suspected melanoma in children, noted Dr. Orlow, chair of dermatology and the Samuel Weinberg professor of pediatric dermatology at New York University.

The E stands for evolving, and it refers to any unexpected change in a mole. It is the word "unexpected" that is important when it comes to moles in children, because in many cases – such as with Spitz nevi – some change is normal, he noted.

Adding to the challenge of predicting and diagnosing melanoma in children is the fact that the disease is very rare in this population, he said.

Based on information from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program database from 1973 to 2001, only 95 of 140,206 cases of melanoma were in children under age 10 years. Compared with older children with melanoma, those in this age group who had melanoma were more likely to be nonwhite; have metastatic disease; show nodular histology; have primary tumors on the head, face, and neck; and have a history of other cancer (J. Clin. Oncol. 2005;23:4735-41).

Among the melanoma patients younger than 10 years old, survival was about 90%, which was comparable to that in individuals aged 10-19 years and 20-24 years. Among those under age 20, survival was 100% if the melanoma was in situ, and 96%, 77%, and 57% if it was localized, regional, or distant, respectively.

Dr. Orlow noted that findings from other series over the years have also underscored the rarity of pediatric melanomas: Children's Hospital of Boston reported only 23 cases over 36 years, a Montreal hospital reported only 13 cases over 22 years, and Istituto Nazionale Tumor reported only 33 cases over 25 years. Many of the cases included nodular or amelanotic disease, reinforcing other data suggesting that children tend to have a different presentation than adults. For example, studies have shown that about 20% of melanomas are nodular in adults, compared with 30%-40% in children, and about 10%-20% of melanomas in adults are amelanotic, compared with about 30% in children.

Dr. Orlow noted that his own experience over 21 years underscores the rarity and differences of melanoma in children, compared with adults.

He has encountered only five authentic cases (excluding giant congenital melanocytic nevi), including one that he said "made the most sense" because it involved a 12-year-old boy from Chernobyl, the site of a 1986 large-scale explosion at a nuclear power plant in Ukraine. Radiation levels at that site remain high to this day. The child had a lesion on his lower back and innumerable dysplastic nevi. The boy's mother also had a history of melanoma as a child.

The other cases included one involving a 12-year old Ashkenazic Jewish girl with a less than 1-mm-thick lesion on her shoulder, one involving a 14-year-old Peruvian Indian girl with deeply pigmented skin and a 1-mm-thick lesion on her fingertip, one involving a 15-year old Ashkenazic/Sephardic boy with xeroderma pigmentosum C and two melanomas in situ, and one involving a 16-year-old Jamaican girl with very deeply pigmented skin who had an 8-mm-deep lesion on her posterior thigh and who died of her disease within 3 months.

"I think this list is typical in that it shows you that these are not people you would necessarily predict to have a problem," he said.

Children seem to differ from adults not only in terms of who gets melanoma, but also in terms of how they develop the disease.

Molecular alterations appear to differ in children, Dr. Orlow noted. While BRAF/NRAS pathway genetic mutations are present in 50%-70% of adults with superficial spreading melanomas, and mutations in the c-KIT gene are present in acral lentiginous and mucosal melanomas in adults, in children melanomas appear to have an increased incidence of deletion of c-KIT as well as mutations in the CDKN2A gene, according to one study (J. Invest. Dermatol. 2009;129:1759-68).

The workup and treatment of children with pediatric melanoma are well established. The prognostic value of sentinel lymph node biopsy – which is well established in adults – is also believed to apply in children. There is no evidence regarding lymph node dissection in either adults or children, although it is used frequently. Risks of lymph node dissection include infection and lymphedema, he noted.

As for treatment, adjuvant therapy includes high-dose interferon-alpha, which is approved for use in adults but not children. It has been used in several case series in children. Risks include fever, malaise, neutropenia, and abnormal liver function tests.

While there remains a great deal to learn about melanoma in children, there are several fallacies about the disease that dermatologists should know. The top five falacies, according to Dr. Orlow, are:

• Any new mole that appears suddenly in a child, or a mole that has grown over the past 6 months, should prompt concern about melanoma just as it does in adults. Reality: The appearance of new nevi in children is normal, and it is also normal for nevi to grow and evolve until they reach their zenith.

• Nevi on the scalp are particularly worrisome and should be removed because they are difficult to follow. Reality: The scalp is a common site for nevi to arise in white children. Such nevi will often have a targetlike appearance or resemble a fried egg. Many resolve by adulthood.

• All atypical/dysplastic nevi must be removed. Reality: Even in patients with the highest risk, such as those with familial atypical mole melanoma syndrome, more than 50% of melanomas will not have any evidence of a preexisting nevus.

• If melanocytic cells are found in a sentinel lymph node biopsy, it must be melanoma. Reality: Such cells can be found in the lymph nodes of children with Spitz nevi, atypical spitzoid melanocytic tumors, and blue nevi.

• We can prevent most prepubertal melanomas by applying our experience with melanoma and melanoma risk in adults. Reality: Such melanomas are unusual both clinically and with respect to the patients in whom they arise.

Dr. Orlow had no disclosures relevant to his presentation.

BOCA RATON, FLA. – The risk factors for melanoma are well established in adults, as is the well-known ABCD method for self-evaluation for the disease, but assessing risk and recognizing melanoma in children are far less clear cut.

The typical risk factors, such as a history of changing moles, white race, and sun sensitivity, don't seem to apply in children to the degree they do in adults, and although the ABCDs (asymmetry, border irregularity, color variations, diameter over 6 mm) have withstood the test of time in adults, for whom they were developed, they don’t necessarily apply in children, Dr. Seth J. Orlow said at the meeting of the Florida Society of Dermatology and Dermatologic Surgery.

The relatively recent addition of an E to the ABCD method adds an element that is applicable to assessment of suspected melanoma in children, noted Dr. Orlow, chair of dermatology and the Samuel Weinberg professor of pediatric dermatology at New York University.

The E stands for evolving, and it refers to any unexpected change in a mole. It is the word "unexpected" that is important when it comes to moles in children, because in many cases – such as with Spitz nevi – some change is normal, he noted.

Adding to the challenge of predicting and diagnosing melanoma in children is the fact that the disease is very rare in this population, he said.

Based on information from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program database from 1973 to 2001, only 95 of 140,206 cases of melanoma were in children under age 10 years. Compared with older children with melanoma, those in this age group who had melanoma were more likely to be nonwhite; have metastatic disease; show nodular histology; have primary tumors on the head, face, and neck; and have a history of other cancer (J. Clin. Oncol. 2005;23:4735-41).

Among the melanoma patients younger than 10 years old, survival was about 90%, which was comparable to that in individuals aged 10-19 years and 20-24 years. Among those under age 20, survival was 100% if the melanoma was in situ, and 96%, 77%, and 57% if it was localized, regional, or distant, respectively.

Dr. Orlow noted that findings from other series over the years have also underscored the rarity of pediatric melanomas: Children's Hospital of Boston reported only 23 cases over 36 years, a Montreal hospital reported only 13 cases over 22 years, and Istituto Nazionale Tumor reported only 33 cases over 25 years. Many of the cases included nodular or amelanotic disease, reinforcing other data suggesting that children tend to have a different presentation than adults. For example, studies have shown that about 20% of melanomas are nodular in adults, compared with 30%-40% in children, and about 10%-20% of melanomas in adults are amelanotic, compared with about 30% in children.

Dr. Orlow noted that his own experience over 21 years underscores the rarity and differences of melanoma in children, compared with adults.

He has encountered only five authentic cases (excluding giant congenital melanocytic nevi), including one that he said "made the most sense" because it involved a 12-year-old boy from Chernobyl, the site of a 1986 large-scale explosion at a nuclear power plant in Ukraine. Radiation levels at that site remain high to this day. The child had a lesion on his lower back and innumerable dysplastic nevi. The boy's mother also had a history of melanoma as a child.

The other cases included one involving a 12-year old Ashkenazic Jewish girl with a less than 1-mm-thick lesion on her shoulder, one involving a 14-year-old Peruvian Indian girl with deeply pigmented skin and a 1-mm-thick lesion on her fingertip, one involving a 15-year old Ashkenazic/Sephardic boy with xeroderma pigmentosum C and two melanomas in situ, and one involving a 16-year-old Jamaican girl with very deeply pigmented skin who had an 8-mm-deep lesion on her posterior thigh and who died of her disease within 3 months.

"I think this list is typical in that it shows you that these are not people you would necessarily predict to have a problem," he said.

Children seem to differ from adults not only in terms of who gets melanoma, but also in terms of how they develop the disease.

Molecular alterations appear to differ in children, Dr. Orlow noted. While BRAF/NRAS pathway genetic mutations are present in 50%-70% of adults with superficial spreading melanomas, and mutations in the c-KIT gene are present in acral lentiginous and mucosal melanomas in adults, in children melanomas appear to have an increased incidence of deletion of c-KIT as well as mutations in the CDKN2A gene, according to one study (J. Invest. Dermatol. 2009;129:1759-68).

The workup and treatment of children with pediatric melanoma are well established. The prognostic value of sentinel lymph node biopsy – which is well established in adults – is also believed to apply in children. There is no evidence regarding lymph node dissection in either adults or children, although it is used frequently. Risks of lymph node dissection include infection and lymphedema, he noted.

As for treatment, adjuvant therapy includes high-dose interferon-alpha, which is approved for use in adults but not children. It has been used in several case series in children. Risks include fever, malaise, neutropenia, and abnormal liver function tests.

While there remains a great deal to learn about melanoma in children, there are several fallacies about the disease that dermatologists should know. The top five falacies, according to Dr. Orlow, are:

• Any new mole that appears suddenly in a child, or a mole that has grown over the past 6 months, should prompt concern about melanoma just as it does in adults. Reality: The appearance of new nevi in children is normal, and it is also normal for nevi to grow and evolve until they reach their zenith.

• Nevi on the scalp are particularly worrisome and should be removed because they are difficult to follow. Reality: The scalp is a common site for nevi to arise in white children. Such nevi will often have a targetlike appearance or resemble a fried egg. Many resolve by adulthood.

• All atypical/dysplastic nevi must be removed. Reality: Even in patients with the highest risk, such as those with familial atypical mole melanoma syndrome, more than 50% of melanomas will not have any evidence of a preexisting nevus.

• If melanocytic cells are found in a sentinel lymph node biopsy, it must be melanoma. Reality: Such cells can be found in the lymph nodes of children with Spitz nevi, atypical spitzoid melanocytic tumors, and blue nevi.

• We can prevent most prepubertal melanomas by applying our experience with melanoma and melanoma risk in adults. Reality: Such melanomas are unusual both clinically and with respect to the patients in whom they arise.

Dr. Orlow had no disclosures relevant to his presentation.

BOCA RATON, FLA. – The risk factors for melanoma are well established in adults, as is the well-known ABCD method for self-evaluation for the disease, but assessing risk and recognizing melanoma in children are far less clear cut.

The typical risk factors, such as a history of changing moles, white race, and sun sensitivity, don't seem to apply in children to the degree they do in adults, and although the ABCDs (asymmetry, border irregularity, color variations, diameter over 6 mm) have withstood the test of time in adults, for whom they were developed, they don’t necessarily apply in children, Dr. Seth J. Orlow said at the meeting of the Florida Society of Dermatology and Dermatologic Surgery.

The relatively recent addition of an E to the ABCD method adds an element that is applicable to assessment of suspected melanoma in children, noted Dr. Orlow, chair of dermatology and the Samuel Weinberg professor of pediatric dermatology at New York University.

The E stands for evolving, and it refers to any unexpected change in a mole. It is the word "unexpected" that is important when it comes to moles in children, because in many cases – such as with Spitz nevi – some change is normal, he noted.

Adding to the challenge of predicting and diagnosing melanoma in children is the fact that the disease is very rare in this population, he said.

Based on information from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program database from 1973 to 2001, only 95 of 140,206 cases of melanoma were in children under age 10 years. Compared with older children with melanoma, those in this age group who had melanoma were more likely to be nonwhite; have metastatic disease; show nodular histology; have primary tumors on the head, face, and neck; and have a history of other cancer (J. Clin. Oncol. 2005;23:4735-41).

Among the melanoma patients younger than 10 years old, survival was about 90%, which was comparable to that in individuals aged 10-19 years and 20-24 years. Among those under age 20, survival was 100% if the melanoma was in situ, and 96%, 77%, and 57% if it was localized, regional, or distant, respectively.

Dr. Orlow noted that findings from other series over the years have also underscored the rarity of pediatric melanomas: Children's Hospital of Boston reported only 23 cases over 36 years, a Montreal hospital reported only 13 cases over 22 years, and Istituto Nazionale Tumor reported only 33 cases over 25 years. Many of the cases included nodular or amelanotic disease, reinforcing other data suggesting that children tend to have a different presentation than adults. For example, studies have shown that about 20% of melanomas are nodular in adults, compared with 30%-40% in children, and about 10%-20% of melanomas in adults are amelanotic, compared with about 30% in children.

Dr. Orlow noted that his own experience over 21 years underscores the rarity and differences of melanoma in children, compared with adults.

He has encountered only five authentic cases (excluding giant congenital melanocytic nevi), including one that he said "made the most sense" because it involved a 12-year-old boy from Chernobyl, the site of a 1986 large-scale explosion at a nuclear power plant in Ukraine. Radiation levels at that site remain high to this day. The child had a lesion on his lower back and innumerable dysplastic nevi. The boy's mother also had a history of melanoma as a child.

The other cases included one involving a 12-year old Ashkenazic Jewish girl with a less than 1-mm-thick lesion on her shoulder, one involving a 14-year-old Peruvian Indian girl with deeply pigmented skin and a 1-mm-thick lesion on her fingertip, one involving a 15-year old Ashkenazic/Sephardic boy with xeroderma pigmentosum C and two melanomas in situ, and one involving a 16-year-old Jamaican girl with very deeply pigmented skin who had an 8-mm-deep lesion on her posterior thigh and who died of her disease within 3 months.

"I think this list is typical in that it shows you that these are not people you would necessarily predict to have a problem," he said.

Children seem to differ from adults not only in terms of who gets melanoma, but also in terms of how they develop the disease.

Molecular alterations appear to differ in children, Dr. Orlow noted. While BRAF/NRAS pathway genetic mutations are present in 50%-70% of adults with superficial spreading melanomas, and mutations in the c-KIT gene are present in acral lentiginous and mucosal melanomas in adults, in children melanomas appear to have an increased incidence of deletion of c-KIT as well as mutations in the CDKN2A gene, according to one study (J. Invest. Dermatol. 2009;129:1759-68).

The workup and treatment of children with pediatric melanoma are well established. The prognostic value of sentinel lymph node biopsy – which is well established in adults – is also believed to apply in children. There is no evidence regarding lymph node dissection in either adults or children, although it is used frequently. Risks of lymph node dissection include infection and lymphedema, he noted.

As for treatment, adjuvant therapy includes high-dose interferon-alpha, which is approved for use in adults but not children. It has been used in several case series in children. Risks include fever, malaise, neutropenia, and abnormal liver function tests.

While there remains a great deal to learn about melanoma in children, there are several fallacies about the disease that dermatologists should know. The top five falacies, according to Dr. Orlow, are:

• Any new mole that appears suddenly in a child, or a mole that has grown over the past 6 months, should prompt concern about melanoma just as it does in adults. Reality: The appearance of new nevi in children is normal, and it is also normal for nevi to grow and evolve until they reach their zenith.

• Nevi on the scalp are particularly worrisome and should be removed because they are difficult to follow. Reality: The scalp is a common site for nevi to arise in white children. Such nevi will often have a targetlike appearance or resemble a fried egg. Many resolve by adulthood.

• All atypical/dysplastic nevi must be removed. Reality: Even in patients with the highest risk, such as those with familial atypical mole melanoma syndrome, more than 50% of melanomas will not have any evidence of a preexisting nevus.

• If melanocytic cells are found in a sentinel lymph node biopsy, it must be melanoma. Reality: Such cells can be found in the lymph nodes of children with Spitz nevi, atypical spitzoid melanocytic tumors, and blue nevi.

• We can prevent most prepubertal melanomas by applying our experience with melanoma and melanoma risk in adults. Reality: Such melanomas are unusual both clinically and with respect to the patients in whom they arise.

Dr. Orlow had no disclosures relevant to his presentation.