New data improve characterization of pediatric melanoma

MIAMI BEACH – Data from several recently published studies have shed new light on the behavior and natural history of melanoma in children and adolescents – and much of the news is good, according to Dr. Sheilagh M. Maguiness.

For example, the findings suggest that the risk of malignant melanoma arising in large congenital nevi is lower than previously thought, at about 2%. Also, outside of the neonatal period the prognosis is excellent for most children diagnosed with melanoma, said Dr. Maguiness of Boston Children’s Hospital.

Data from three of the studies, taken together, show that 36 deaths occurred in 278 cases involving melanoma during childhood or adolescence, for a mortality rate of 13%.

"There was only one death in a child under 10, and that was in the setting of a large congenital nevus," she said at the annual meeting of the American Academy of Dermatology.

Furthermore, the presentation of melanoma in adolescents is similar to that in adults, and the outcomes seem to parallel – and perhaps exceed – those of adults with similar stage tumors, she noted.

The studies do little, however, to clear up controversy about the value of sentinel lymph node biopsy for predicting outcomes in children with melanoma, she said.

Pediatric melanoma represents only about 1%-3% of all melanomas and about 2% of all pediatric malignancies, and it is best considered based on the timing of presentation – presentation during the congenital period, during childhood up to the age of 10 years, and during adolescence – because findings during these stages differ substantially, she said.

Melanoma during the congenital and neonatal period is extremely rare. Four cases involving transplacental metastases from maternal malignant melanoma, nine cases involving large or giant congenital melanocytic nevi, and seven de novo cases have been reported in the literature.

"Unfortunately, when melanoma presents this early, it really does have a poor prognosis, with greater than 50% of the patients dying from their disease," Dr. Maguiness said.

The outlook is much better for older children with melanoma, but any discussion of these cases must include consideration of cases that arise in large congenital melanocytic nevi (LCMN). Controversy has existed over the actual risk of melanoma in these cases, with reports citing risks of anywhere from 7% to 40%, but the studies reviewed by Dr. Maguiness demonstrate that the risk is actually quite low.

A retrospective analysis of data on this topic published in March in the Journal of the American Academy of Dermatology, for example, showed that melanoma developed in only 2% of 2,578 cases of LCMN in 14 studies (J. Am. Acad. Dermatol. 2013;68:493-8.e14).

Other "very, very valuable points" coming out of this data include a finding that 14% of the melanomas occurred viscerally or noncutaneously, and a finding that the mortality rate is high in these patients at about 55%.

"And one of the most important points that I had never appreciated before is a finding that in over 90% of the cases where melanoma developed in these children, satellite nevi were present. Historically we’ve known that the risk of melanoma arising within the satellite nevi itself is quite low – it almost never occurs – but (the finding) that they confer an elevated risk of development of cutaneous melanoma is very interesting," she said.

These findings suggest that a careful examination and regular follow-up is crucial in patients with LCMN, she said.

Findings from three large single-institution studies also have provided interesting new information about pediatric melanoma, she said.

Researchers at the University of Texas Health Science Center at Houston reviewed data on 109 patients under age 19 years with melanoma, including 25 under age 10 years. Seven of 82 patients with adequate follow-up died from their disease, and none of those were in the group under age 10, Dr. Maguiness said.

Among other notable findings from this study: Patients were more likely to be nonwhite, 44% had spitzoid histology, and 52% of those under age 10 who underwent sentinel lymph node biopsy had positive results, compared with 26% in the adolescent cohort (Ann. Surg. 2011;253:1211-15).

The rate of positivity decreased by 13% for each year of increasing age, and because those under age 10 did paradoxically well, the authors suggested that sentinel lymph node positivity does not predict prognosis or outcome in childhood melanoma, Dr. Maguiness noted.

However, investigators from the Moffitt Cancer Center in Tampa concluded, conversely, that sentinel lymph node biopsy does predict outcomes in pediatric melanoma.

Of 126 patients with pediatric melanoma in that retrospective review, 62 underwent sentinel lymph node biopsy and 29% had positive findings. Overall, 19 melanoma-related deaths occurred, for a rate of 16%.

Six patients under the age of 12 were included in the study, but these patients did not undergo sentinel lymph node biopsy. All survived, but there were several late recurrences – after 5 years – even in the node-negative patients, she said.

When the investigators looked at recurrence-free survival, they found that node-positive patients had significantly worse recurrence-free survival and melanoma-specific survival than that of node-negative patients (60% vs.94% and 78% vs. 97%, respectively) at a median follow-up of 5 years (Ann. Surg. Oncol. 2012;19:3888-95).

A study by investigators at the University of California, San Francisco, focused more on historical data, finding that many of the 70 patients included in the study had putative risk factors for melanoma. For example, 20% had numerous nevi, 27% had a positive family history, and 25% had a history of sunburn. Also, this study was the only one of the three to address the presence of LCMN, and only three patients had melanoma arising in a nevus, providing further evidence of a low risk of melanoma in LCMN.

The diagnosis of pediatric melanoma was delayed by about a year in more than 60% of the patients.

The investigators noted that primary lesion characteristics differed from those seen in adults, and they concluded that the conventional ABCDE criteria used to help in the diagnosis of melanoma did not capture melanoma in about 60% of the childhood cases and 40% of the adolescent cases.

Lesions in this study were much more likely to be amelanotic in children, and of uniform color in adolescents. Lesional evolution was nearly universal, and bleeding, bumps, variable diameter, and de novo development were common.

On histopathology, a majority of tumors were not superficial spreading type; more were unclassified spitzoid and other histopathologic subtypes, she noted.

Ten patients (14%) died from their melanoma, and of these, 7 had amelanotic melanoma. Only 1 patient under age 10 years died, and that was in the setting of a large congenital melanocytic nevus.

Based on their findings, the investigators suggested pediatric-specific ABCD criteria (A = amelanotic, B = bleeding, bumps, C = color uniformity, and D = de novo and any diameter) to be used along with the conventional ABCDE criteria to facilitate earlier recognition and treatment of pediatric melanoma (J. Am. Acad. Dermatol. 2013 [doi:10.1016/j.jaad.2012.12.953]).

Although there are some conflicting findings in these three studies – including differing conclusions with respect to the value of sentinel lymph node biopsy for predicting outcomes – there also are some consistent findings, Dr. Maguiness said.

Prepubertal melanoma tends to involve thicker tumors, and darker skin types are overrepresented. Also, lesions in all ages in the pediatric population tend to be amelanotic with spitzoid histology, and tend to have higher rates of positive sentinel lymph node biopsies, compared with adult cases. Prepubertal cases have the highest rates of node positivity, she said.

"So, in conclusion, the risk of malignant melanoma within large congenital nevi seems to be lower than we thought, and the diagnosis of malignant melanoma of childhood has excellent prognosis – speaking to the unique natural history and biology of these tumors, which we probably don’t fully understand," she said, adding that adolescent presentations of melanoma seem to be similar to those in adults, with a slightly better overall prognosis.

Dr. Maguiness reported having no disclosures.

MIAMI BEACH – Data from several recently published studies have shed new light on the behavior and natural history of melanoma in children and adolescents – and much of the news is good, according to Dr. Sheilagh M. Maguiness.

For example, the findings suggest that the risk of malignant melanoma arising in large congenital nevi is lower than previously thought, at about 2%. Also, outside of the neonatal period the prognosis is excellent for most children diagnosed with melanoma, said Dr. Maguiness of Boston Children’s Hospital.

Data from three of the studies, taken together, show that 36 deaths occurred in 278 cases involving melanoma during childhood or adolescence, for a mortality rate of 13%.

"There was only one death in a child under 10, and that was in the setting of a large congenital nevus," she said at the annual meeting of the American Academy of Dermatology.

Furthermore, the presentation of melanoma in adolescents is similar to that in adults, and the outcomes seem to parallel – and perhaps exceed – those of adults with similar stage tumors, she noted.

The studies do little, however, to clear up controversy about the value of sentinel lymph node biopsy for predicting outcomes in children with melanoma, she said.

Pediatric melanoma represents only about 1%-3% of all melanomas and about 2% of all pediatric malignancies, and it is best considered based on the timing of presentation – presentation during the congenital period, during childhood up to the age of 10 years, and during adolescence – because findings during these stages differ substantially, she said.

Melanoma during the congenital and neonatal period is extremely rare. Four cases involving transplacental metastases from maternal malignant melanoma, nine cases involving large or giant congenital melanocytic nevi, and seven de novo cases have been reported in the literature.

"Unfortunately, when melanoma presents this early, it really does have a poor prognosis, with greater than 50% of the patients dying from their disease," Dr. Maguiness said.

The outlook is much better for older children with melanoma, but any discussion of these cases must include consideration of cases that arise in large congenital melanocytic nevi (LCMN). Controversy has existed over the actual risk of melanoma in these cases, with reports citing risks of anywhere from 7% to 40%, but the studies reviewed by Dr. Maguiness demonstrate that the risk is actually quite low.

A retrospective analysis of data on this topic published in March in the Journal of the American Academy of Dermatology, for example, showed that melanoma developed in only 2% of 2,578 cases of LCMN in 14 studies (J. Am. Acad. Dermatol. 2013;68:493-8.e14).

Other "very, very valuable points" coming out of this data include a finding that 14% of the melanomas occurred viscerally or noncutaneously, and a finding that the mortality rate is high in these patients at about 55%.

"And one of the most important points that I had never appreciated before is a finding that in over 90% of the cases where melanoma developed in these children, satellite nevi were present. Historically we’ve known that the risk of melanoma arising within the satellite nevi itself is quite low – it almost never occurs – but (the finding) that they confer an elevated risk of development of cutaneous melanoma is very interesting," she said.

These findings suggest that a careful examination and regular follow-up is crucial in patients with LCMN, she said.

Findings from three large single-institution studies also have provided interesting new information about pediatric melanoma, she said.

Researchers at the University of Texas Health Science Center at Houston reviewed data on 109 patients under age 19 years with melanoma, including 25 under age 10 years. Seven of 82 patients with adequate follow-up died from their disease, and none of those were in the group under age 10, Dr. Maguiness said.

Among other notable findings from this study: Patients were more likely to be nonwhite, 44% had spitzoid histology, and 52% of those under age 10 who underwent sentinel lymph node biopsy had positive results, compared with 26% in the adolescent cohort (Ann. Surg. 2011;253:1211-15).

The rate of positivity decreased by 13% for each year of increasing age, and because those under age 10 did paradoxically well, the authors suggested that sentinel lymph node positivity does not predict prognosis or outcome in childhood melanoma, Dr. Maguiness noted.

However, investigators from the Moffitt Cancer Center in Tampa concluded, conversely, that sentinel lymph node biopsy does predict outcomes in pediatric melanoma.

Of 126 patients with pediatric melanoma in that retrospective review, 62 underwent sentinel lymph node biopsy and 29% had positive findings. Overall, 19 melanoma-related deaths occurred, for a rate of 16%.

Six patients under the age of 12 were included in the study, but these patients did not undergo sentinel lymph node biopsy. All survived, but there were several late recurrences – after 5 years – even in the node-negative patients, she said.

When the investigators looked at recurrence-free survival, they found that node-positive patients had significantly worse recurrence-free survival and melanoma-specific survival than that of node-negative patients (60% vs.94% and 78% vs. 97%, respectively) at a median follow-up of 5 years (Ann. Surg. Oncol. 2012;19:3888-95).

A study by investigators at the University of California, San Francisco, focused more on historical data, finding that many of the 70 patients included in the study had putative risk factors for melanoma. For example, 20% had numerous nevi, 27% had a positive family history, and 25% had a history of sunburn. Also, this study was the only one of the three to address the presence of LCMN, and only three patients had melanoma arising in a nevus, providing further evidence of a low risk of melanoma in LCMN.

The diagnosis of pediatric melanoma was delayed by about a year in more than 60% of the patients.

The investigators noted that primary lesion characteristics differed from those seen in adults, and they concluded that the conventional ABCDE criteria used to help in the diagnosis of melanoma did not capture melanoma in about 60% of the childhood cases and 40% of the adolescent cases.

Lesions in this study were much more likely to be amelanotic in children, and of uniform color in adolescents. Lesional evolution was nearly universal, and bleeding, bumps, variable diameter, and de novo development were common.

On histopathology, a majority of tumors were not superficial spreading type; more were unclassified spitzoid and other histopathologic subtypes, she noted.

Ten patients (14%) died from their melanoma, and of these, 7 had amelanotic melanoma. Only 1 patient under age 10 years died, and that was in the setting of a large congenital melanocytic nevus.

Based on their findings, the investigators suggested pediatric-specific ABCD criteria (A = amelanotic, B = bleeding, bumps, C = color uniformity, and D = de novo and any diameter) to be used along with the conventional ABCDE criteria to facilitate earlier recognition and treatment of pediatric melanoma (J. Am. Acad. Dermatol. 2013 [doi:10.1016/j.jaad.2012.12.953]).

Although there are some conflicting findings in these three studies – including differing conclusions with respect to the value of sentinel lymph node biopsy for predicting outcomes – there also are some consistent findings, Dr. Maguiness said.

Prepubertal melanoma tends to involve thicker tumors, and darker skin types are overrepresented. Also, lesions in all ages in the pediatric population tend to be amelanotic with spitzoid histology, and tend to have higher rates of positive sentinel lymph node biopsies, compared with adult cases. Prepubertal cases have the highest rates of node positivity, she said.

"So, in conclusion, the risk of malignant melanoma within large congenital nevi seems to be lower than we thought, and the diagnosis of malignant melanoma of childhood has excellent prognosis – speaking to the unique natural history and biology of these tumors, which we probably don’t fully understand," she said, adding that adolescent presentations of melanoma seem to be similar to those in adults, with a slightly better overall prognosis.

Dr. Maguiness reported having no disclosures.

MIAMI BEACH – Data from several recently published studies have shed new light on the behavior and natural history of melanoma in children and adolescents – and much of the news is good, according to Dr. Sheilagh M. Maguiness.

For example, the findings suggest that the risk of malignant melanoma arising in large congenital nevi is lower than previously thought, at about 2%. Also, outside of the neonatal period the prognosis is excellent for most children diagnosed with melanoma, said Dr. Maguiness of Boston Children’s Hospital.

Data from three of the studies, taken together, show that 36 deaths occurred in 278 cases involving melanoma during childhood or adolescence, for a mortality rate of 13%.

"There was only one death in a child under 10, and that was in the setting of a large congenital nevus," she said at the annual meeting of the American Academy of Dermatology.

Furthermore, the presentation of melanoma in adolescents is similar to that in adults, and the outcomes seem to parallel – and perhaps exceed – those of adults with similar stage tumors, she noted.

The studies do little, however, to clear up controversy about the value of sentinel lymph node biopsy for predicting outcomes in children with melanoma, she said.

Pediatric melanoma represents only about 1%-3% of all melanomas and about 2% of all pediatric malignancies, and it is best considered based on the timing of presentation – presentation during the congenital period, during childhood up to the age of 10 years, and during adolescence – because findings during these stages differ substantially, she said.

Melanoma during the congenital and neonatal period is extremely rare. Four cases involving transplacental metastases from maternal malignant melanoma, nine cases involving large or giant congenital melanocytic nevi, and seven de novo cases have been reported in the literature.

"Unfortunately, when melanoma presents this early, it really does have a poor prognosis, with greater than 50% of the patients dying from their disease," Dr. Maguiness said.

The outlook is much better for older children with melanoma, but any discussion of these cases must include consideration of cases that arise in large congenital melanocytic nevi (LCMN). Controversy has existed over the actual risk of melanoma in these cases, with reports citing risks of anywhere from 7% to 40%, but the studies reviewed by Dr. Maguiness demonstrate that the risk is actually quite low.

A retrospective analysis of data on this topic published in March in the Journal of the American Academy of Dermatology, for example, showed that melanoma developed in only 2% of 2,578 cases of LCMN in 14 studies (J. Am. Acad. Dermatol. 2013;68:493-8.e14).

Other "very, very valuable points" coming out of this data include a finding that 14% of the melanomas occurred viscerally or noncutaneously, and a finding that the mortality rate is high in these patients at about 55%.

"And one of the most important points that I had never appreciated before is a finding that in over 90% of the cases where melanoma developed in these children, satellite nevi were present. Historically we’ve known that the risk of melanoma arising within the satellite nevi itself is quite low – it almost never occurs – but (the finding) that they confer an elevated risk of development of cutaneous melanoma is very interesting," she said.

These findings suggest that a careful examination and regular follow-up is crucial in patients with LCMN, she said.

Findings from three large single-institution studies also have provided interesting new information about pediatric melanoma, she said.

Researchers at the University of Texas Health Science Center at Houston reviewed data on 109 patients under age 19 years with melanoma, including 25 under age 10 years. Seven of 82 patients with adequate follow-up died from their disease, and none of those were in the group under age 10, Dr. Maguiness said.

Among other notable findings from this study: Patients were more likely to be nonwhite, 44% had spitzoid histology, and 52% of those under age 10 who underwent sentinel lymph node biopsy had positive results, compared with 26% in the adolescent cohort (Ann. Surg. 2011;253:1211-15).

The rate of positivity decreased by 13% for each year of increasing age, and because those under age 10 did paradoxically well, the authors suggested that sentinel lymph node positivity does not predict prognosis or outcome in childhood melanoma, Dr. Maguiness noted.

However, investigators from the Moffitt Cancer Center in Tampa concluded, conversely, that sentinel lymph node biopsy does predict outcomes in pediatric melanoma.

Of 126 patients with pediatric melanoma in that retrospective review, 62 underwent sentinel lymph node biopsy and 29% had positive findings. Overall, 19 melanoma-related deaths occurred, for a rate of 16%.

Six patients under the age of 12 were included in the study, but these patients did not undergo sentinel lymph node biopsy. All survived, but there were several late recurrences – after 5 years – even in the node-negative patients, she said.

When the investigators looked at recurrence-free survival, they found that node-positive patients had significantly worse recurrence-free survival and melanoma-specific survival than that of node-negative patients (60% vs.94% and 78% vs. 97%, respectively) at a median follow-up of 5 years (Ann. Surg. Oncol. 2012;19:3888-95).

A study by investigators at the University of California, San Francisco, focused more on historical data, finding that many of the 70 patients included in the study had putative risk factors for melanoma. For example, 20% had numerous nevi, 27% had a positive family history, and 25% had a history of sunburn. Also, this study was the only one of the three to address the presence of LCMN, and only three patients had melanoma arising in a nevus, providing further evidence of a low risk of melanoma in LCMN.

The diagnosis of pediatric melanoma was delayed by about a year in more than 60% of the patients.

The investigators noted that primary lesion characteristics differed from those seen in adults, and they concluded that the conventional ABCDE criteria used to help in the diagnosis of melanoma did not capture melanoma in about 60% of the childhood cases and 40% of the adolescent cases.

Lesions in this study were much more likely to be amelanotic in children, and of uniform color in adolescents. Lesional evolution was nearly universal, and bleeding, bumps, variable diameter, and de novo development were common.

On histopathology, a majority of tumors were not superficial spreading type; more were unclassified spitzoid and other histopathologic subtypes, she noted.

Ten patients (14%) died from their melanoma, and of these, 7 had amelanotic melanoma. Only 1 patient under age 10 years died, and that was in the setting of a large congenital melanocytic nevus.

Based on their findings, the investigators suggested pediatric-specific ABCD criteria (A = amelanotic, B = bleeding, bumps, C = color uniformity, and D = de novo and any diameter) to be used along with the conventional ABCDE criteria to facilitate earlier recognition and treatment of pediatric melanoma (J. Am. Acad. Dermatol. 2013 [doi:10.1016/j.jaad.2012.12.953]).

Although there are some conflicting findings in these three studies – including differing conclusions with respect to the value of sentinel lymph node biopsy for predicting outcomes – there also are some consistent findings, Dr. Maguiness said.

Prepubertal melanoma tends to involve thicker tumors, and darker skin types are overrepresented. Also, lesions in all ages in the pediatric population tend to be amelanotic with spitzoid histology, and tend to have higher rates of positive sentinel lymph node biopsies, compared with adult cases. Prepubertal cases have the highest rates of node positivity, she said.

"So, in conclusion, the risk of malignant melanoma within large congenital nevi seems to be lower than we thought, and the diagnosis of malignant melanoma of childhood has excellent prognosis – speaking to the unique natural history and biology of these tumors, which we probably don’t fully understand," she said, adding that adolescent presentations of melanoma seem to be similar to those in adults, with a slightly better overall prognosis.

Dr. Maguiness reported having no disclosures.