Melanoma

GOTHENBURG, SWEDEN – Patients with cutaneous lupus erythematosus appear to have an elevated overall risk of cancer, especially nonmelanoma skin cancer, lung cancer, and non-Hodgkin's lymphoma.

That's the preliminary conclusion from a Swedish national cohort study involving 3,788 Swedes with cutaneous LE (CLE), each matched to three controls and followed for an average of 4.1 years, said Dr. Carina M. Grönhagen at the annual congress of the European Academy of Dermatology and Venereology.

The take-home message from this first-ever look at the cancer risk associated with CLE is that patients with this skin disease need to be followed regularly for the emergence of malignancy. And they need to receive a strong antismoking message.

"Many of these cancers are connected to smoking, and patients with CLE are known to be smokers to a higher degree than in a normal population," observed Dr. Grönhagen, a dermatology resident at Danderyd Hospital and doctoral candidate in medical epidemiology at the Karolinska Institute, Stockholm.

She and her coworkers decided to look at cancer rates in patients with CLE because CLE is an autoimmune disease, and epidemiologic studies indicate other autoimmune diseases are associated with increased cancer risk.

The overall number of cases of cancer documented in the CLE group during the study period was 188, compared with an expected 112. This 67% increased incidence rate ratio remained significant after adjustment for comorbid SLE, which dropped the ratio only to 60%.

The greatest increase in cancer risk seen in the CLE cohort was for nonmelanoma skin cancer, with a 4.3-fold relative risk, compared with controls. The other strongest risk increases were the 2.9-fold increase in lung cancer, the 2.7-fold increase in non-Hodgkin’s lymphoma, and the 2.7-fold rise in buccal cancer.

Asked if she thinks the observed increase in cancer in association with CLE is caused by the skin disease itself, or instead perhaps the immunosuppressive therapies employed in its treatment, Dr. Grönhagen replied that the well-established high rate of smoking among CLE patients is probably a significant contributor. But the immunologic derangement inherent in CLE is also likely to play a role, especially with regard to the increase in nonmelanoma skin cancer.

Dr. Grönhagen said her presentation at the congress was an interim analysis. Assigning three controls per CLE patient is insufficient to draw ironclad conclusions. She reported that with her coworkers, she is in the process of comparing cancer rates in the CLE cohort to those in the entire Swedish population in order to generate standardized incidence rates rather than incidence rate ratios.

She declared having no relevant financial relationships.

GOTHENBURG, SWEDEN – Patients with cutaneous lupus erythematosus appear to have an elevated overall risk of cancer, especially nonmelanoma skin cancer, lung cancer, and non-Hodgkin's lymphoma.

That's the preliminary conclusion from a Swedish national cohort study involving 3,788 Swedes with cutaneous LE (CLE), each matched to three controls and followed for an average of 4.1 years, said Dr. Carina M. Grönhagen at the annual congress of the European Academy of Dermatology and Venereology.

The take-home message from this first-ever look at the cancer risk associated with CLE is that patients with this skin disease need to be followed regularly for the emergence of malignancy. And they need to receive a strong antismoking message.

"Many of these cancers are connected to smoking, and patients with CLE are known to be smokers to a higher degree than in a normal population," observed Dr. Grönhagen, a dermatology resident at Danderyd Hospital and doctoral candidate in medical epidemiology at the Karolinska Institute, Stockholm.

She and her coworkers decided to look at cancer rates in patients with CLE because CLE is an autoimmune disease, and epidemiologic studies indicate other autoimmune diseases are associated with increased cancer risk.

The overall number of cases of cancer documented in the CLE group during the study period was 188, compared with an expected 112. This 67% increased incidence rate ratio remained significant after adjustment for comorbid SLE, which dropped the ratio only to 60%.

The greatest increase in cancer risk seen in the CLE cohort was for nonmelanoma skin cancer, with a 4.3-fold relative risk, compared with controls. The other strongest risk increases were the 2.9-fold increase in lung cancer, the 2.7-fold increase in non-Hodgkin’s lymphoma, and the 2.7-fold rise in buccal cancer.

Asked if she thinks the observed increase in cancer in association with CLE is caused by the skin disease itself, or instead perhaps the immunosuppressive therapies employed in its treatment, Dr. Grönhagen replied that the well-established high rate of smoking among CLE patients is probably a significant contributor. But the immunologic derangement inherent in CLE is also likely to play a role, especially with regard to the increase in nonmelanoma skin cancer.

Dr. Grönhagen said her presentation at the congress was an interim analysis. Assigning three controls per CLE patient is insufficient to draw ironclad conclusions. She reported that with her coworkers, she is in the process of comparing cancer rates in the CLE cohort to those in the entire Swedish population in order to generate standardized incidence rates rather than incidence rate ratios.

She declared having no relevant financial relationships.

GOTHENBURG, SWEDEN – Patients with cutaneous lupus erythematosus appear to have an elevated overall risk of cancer, especially nonmelanoma skin cancer, lung cancer, and non-Hodgkin's lymphoma.

That's the preliminary conclusion from a Swedish national cohort study involving 3,788 Swedes with cutaneous LE (CLE), each matched to three controls and followed for an average of 4.1 years, said Dr. Carina M. Grönhagen at the annual congress of the European Academy of Dermatology and Venereology.

The take-home message from this first-ever look at the cancer risk associated with CLE is that patients with this skin disease need to be followed regularly for the emergence of malignancy. And they need to receive a strong antismoking message.

"Many of these cancers are connected to smoking, and patients with CLE are known to be smokers to a higher degree than in a normal population," observed Dr. Grönhagen, a dermatology resident at Danderyd Hospital and doctoral candidate in medical epidemiology at the Karolinska Institute, Stockholm.

She and her coworkers decided to look at cancer rates in patients with CLE because CLE is an autoimmune disease, and epidemiologic studies indicate other autoimmune diseases are associated with increased cancer risk.

The overall number of cases of cancer documented in the CLE group during the study period was 188, compared with an expected 112. This 67% increased incidence rate ratio remained significant after adjustment for comorbid SLE, which dropped the ratio only to 60%.

The greatest increase in cancer risk seen in the CLE cohort was for nonmelanoma skin cancer, with a 4.3-fold relative risk, compared with controls. The other strongest risk increases were the 2.9-fold increase in lung cancer, the 2.7-fold increase in non-Hodgkin’s lymphoma, and the 2.7-fold rise in buccal cancer.

Asked if she thinks the observed increase in cancer in association with CLE is caused by the skin disease itself, or instead perhaps the immunosuppressive therapies employed in its treatment, Dr. Grönhagen replied that the well-established high rate of smoking among CLE patients is probably a significant contributor. But the immunologic derangement inherent in CLE is also likely to play a role, especially with regard to the increase in nonmelanoma skin cancer.

Dr. Grönhagen said her presentation at the congress was an interim analysis. Assigning three controls per CLE patient is insufficient to draw ironclad conclusions. She reported that with her coworkers, she is in the process of comparing cancer rates in the CLE cohort to those in the entire Swedish population in order to generate standardized incidence rates rather than incidence rate ratios.

She declared having no relevant financial relationships.

SANTA BARBARA, Calif. - The only way to definitively rule out melanoma in a case of melanonychia striata is to perform a biopsy of the nail matrix, according to Dr. Richard K. Scher.

"The source of pigmentation is in the nail matrix, so the biopsy specimen must be taken from there," Dr. Scher said at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Photo courtesy: Dr. Richard K. Scher and Dr. Kenneth Kulp

"It's of no value to do a biopsy of the nail bed. There are almost never melanocytes there, but it's amazing to me how many dermatologists are still doing nail bed biopsies," Dr. Scher, professor of dermatology at the University of North Carolina, Chapel Hill.

While some clinicians prefer to use dermoscopy to inspect cases of melanonychia striata, it is not as accurate or as reliable as microscopic examination.

"At most, dermoscopy should be an aide," he commented.

There are probably too many biopsies being performed, but "I really don't know what the alternative is," Dr. Scher noted. "We need reliable clinical criteria to determine melanoma probability, but we don't have it yet. ... We also need reliable histologic criteria to determine melanoma probability, but we don't always have that, either."

Dr. Scher estimated that 90% of melanocytic bands arise from the distal matrix, which contains more melanocytes than the proximal matrix does. Melanonychia melanoma most commonly occurs in the thumb and the big toe, followed by the index finger. "About 20% of nail melanomas are amelanotic," he said. "That's a number that keeps me awake at night."

Two risk factors for developing melanonychia include older age and being African American. "In general, African Americans do not get melanomas to a great extent, but they do have a lot of benign melanonychia," Dr. Scher noted. "However, acral melanoma is more common in African Americans, compared with other populations."

Other causes of melanonychia include trauma to the nail, infection, and certain medications including antibiotics and chemotherapeutics agents.

Wider, darker nail lesions are more likely to be melanoma, compared with thinner, lighter lesions. "That's true, but I've seen very narrow bands that were melanomas, and I’ve seen very wide bands that were not," Dr. Scher said. "Uniformity of pigment is relatively more reliable than some of the other criteria. So if you see lack of uniformity, think of things like atypical nevi, dysplastic nevi, or melanoma."

In addition, if a patient presents with pigmented nails in four or five digits, "it's not likely that patient will have four or five melanomas," he said. "But if you see a patient particularly a dark-skinned individual who has normal ethnic melanonychia in many digits, but one of them is very different, then you have to become suspicious."

Evolution of the lesion is another worrisome sign. "If the band is changing if it’s getting wider or darker or more streaky then you have to think that you’re dealing with a melanoma."

He emphasized the importance of retrieving the nail plate during the nail biopsy procedure and sending it to the pathologist with the nail matrix specimen, "because sometimes it's hard for the pathologist to find the pigment," he explained. "If the pathologist sends you back a report that there’s no pigment here, the implication is that you missed the lesion. But if you have nail plate there, which has pigment in it, you didn’t miss the lesion. The pathologist did."

Some recent articles in the medical literature suggest that if cases of melanonychia striata in childhood are stable and not atypical in appearance, observation may be an option. However, Dr. Scher urged caution with this approach, saying that "every case must be evaluated individually."

To illustrate his point he discussed the case of a 4-year-old healthy girl who presented to his office with an 8-month history of melanonychia and a 3-month history of possible nail fold pigmentation (see image above). Family history revealed a maternal second cousin with acral melanoma. Dermoscopy was consistent with a nevus diagnosis.

The parents agreed to proceed with a nail biopsy, Dr. Scher said. The pathology report read (in part): "atypical junctional melanocytic proliferation with increased numbers of single melanocytes ...; although this lesion is most probably a nevus, it is recommended that it be completely but conservatively excised."

The girl's parents sought the opinion of seven other pathologists and clinicians at a melanoma conference, and all agreed with complete excision. "In this case, there was not much alternative as to what to do," Dr. Scher said.

The entire nail unit was removed during surgery and the lesion healed with "a terrific cosmetic result," he said.

Dr. Scher said that he had no relevant conflicts to disclose.

SANTA BARBARA, Calif. - The only way to definitively rule out melanoma in a case of melanonychia striata is to perform a biopsy of the nail matrix, according to Dr. Richard K. Scher.

"The source of pigmentation is in the nail matrix, so the biopsy specimen must be taken from there," Dr. Scher said at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Photo courtesy: Dr. Richard K. Scher and Dr. Kenneth Kulp

"It's of no value to do a biopsy of the nail bed. There are almost never melanocytes there, but it's amazing to me how many dermatologists are still doing nail bed biopsies," Dr. Scher, professor of dermatology at the University of North Carolina, Chapel Hill.

While some clinicians prefer to use dermoscopy to inspect cases of melanonychia striata, it is not as accurate or as reliable as microscopic examination.

"At most, dermoscopy should be an aide," he commented.

There are probably too many biopsies being performed, but "I really don't know what the alternative is," Dr. Scher noted. "We need reliable clinical criteria to determine melanoma probability, but we don't have it yet. ... We also need reliable histologic criteria to determine melanoma probability, but we don't always have that, either."

Dr. Scher estimated that 90% of melanocytic bands arise from the distal matrix, which contains more melanocytes than the proximal matrix does. Melanonychia melanoma most commonly occurs in the thumb and the big toe, followed by the index finger. "About 20% of nail melanomas are amelanotic," he said. "That's a number that keeps me awake at night."

Two risk factors for developing melanonychia include older age and being African American. "In general, African Americans do not get melanomas to a great extent, but they do have a lot of benign melanonychia," Dr. Scher noted. "However, acral melanoma is more common in African Americans, compared with other populations."

Other causes of melanonychia include trauma to the nail, infection, and certain medications including antibiotics and chemotherapeutics agents.

Wider, darker nail lesions are more likely to be melanoma, compared with thinner, lighter lesions. "That's true, but I've seen very narrow bands that were melanomas, and I’ve seen very wide bands that were not," Dr. Scher said. "Uniformity of pigment is relatively more reliable than some of the other criteria. So if you see lack of uniformity, think of things like atypical nevi, dysplastic nevi, or melanoma."

In addition, if a patient presents with pigmented nails in four or five digits, "it's not likely that patient will have four or five melanomas," he said. "But if you see a patient particularly a dark-skinned individual who has normal ethnic melanonychia in many digits, but one of them is very different, then you have to become suspicious."

Evolution of the lesion is another worrisome sign. "If the band is changing if it’s getting wider or darker or more streaky then you have to think that you’re dealing with a melanoma."

He emphasized the importance of retrieving the nail plate during the nail biopsy procedure and sending it to the pathologist with the nail matrix specimen, "because sometimes it's hard for the pathologist to find the pigment," he explained. "If the pathologist sends you back a report that there’s no pigment here, the implication is that you missed the lesion. But if you have nail plate there, which has pigment in it, you didn’t miss the lesion. The pathologist did."

Some recent articles in the medical literature suggest that if cases of melanonychia striata in childhood are stable and not atypical in appearance, observation may be an option. However, Dr. Scher urged caution with this approach, saying that "every case must be evaluated individually."

To illustrate his point he discussed the case of a 4-year-old healthy girl who presented to his office with an 8-month history of melanonychia and a 3-month history of possible nail fold pigmentation (see image above). Family history revealed a maternal second cousin with acral melanoma. Dermoscopy was consistent with a nevus diagnosis.

The parents agreed to proceed with a nail biopsy, Dr. Scher said. The pathology report read (in part): "atypical junctional melanocytic proliferation with increased numbers of single melanocytes ...; although this lesion is most probably a nevus, it is recommended that it be completely but conservatively excised."

The girl's parents sought the opinion of seven other pathologists and clinicians at a melanoma conference, and all agreed with complete excision. "In this case, there was not much alternative as to what to do," Dr. Scher said.

The entire nail unit was removed during surgery and the lesion healed with "a terrific cosmetic result," he said.

Dr. Scher said that he had no relevant conflicts to disclose.

SANTA BARBARA, Calif. - The only way to definitively rule out melanoma in a case of melanonychia striata is to perform a biopsy of the nail matrix, according to Dr. Richard K. Scher.

"The source of pigmentation is in the nail matrix, so the biopsy specimen must be taken from there," Dr. Scher said at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Photo courtesy: Dr. Richard K. Scher and Dr. Kenneth Kulp

"It's of no value to do a biopsy of the nail bed. There are almost never melanocytes there, but it's amazing to me how many dermatologists are still doing nail bed biopsies," Dr. Scher, professor of dermatology at the University of North Carolina, Chapel Hill.

While some clinicians prefer to use dermoscopy to inspect cases of melanonychia striata, it is not as accurate or as reliable as microscopic examination.

"At most, dermoscopy should be an aide," he commented.

There are probably too many biopsies being performed, but "I really don't know what the alternative is," Dr. Scher noted. "We need reliable clinical criteria to determine melanoma probability, but we don't have it yet. ... We also need reliable histologic criteria to determine melanoma probability, but we don't always have that, either."

Dr. Scher estimated that 90% of melanocytic bands arise from the distal matrix, which contains more melanocytes than the proximal matrix does. Melanonychia melanoma most commonly occurs in the thumb and the big toe, followed by the index finger. "About 20% of nail melanomas are amelanotic," he said. "That's a number that keeps me awake at night."

Two risk factors for developing melanonychia include older age and being African American. "In general, African Americans do not get melanomas to a great extent, but they do have a lot of benign melanonychia," Dr. Scher noted. "However, acral melanoma is more common in African Americans, compared with other populations."

Other causes of melanonychia include trauma to the nail, infection, and certain medications including antibiotics and chemotherapeutics agents.

Wider, darker nail lesions are more likely to be melanoma, compared with thinner, lighter lesions. "That's true, but I've seen very narrow bands that were melanomas, and I’ve seen very wide bands that were not," Dr. Scher said. "Uniformity of pigment is relatively more reliable than some of the other criteria. So if you see lack of uniformity, think of things like atypical nevi, dysplastic nevi, or melanoma."

In addition, if a patient presents with pigmented nails in four or five digits, "it's not likely that patient will have four or five melanomas," he said. "But if you see a patient particularly a dark-skinned individual who has normal ethnic melanonychia in many digits, but one of them is very different, then you have to become suspicious."

Evolution of the lesion is another worrisome sign. "If the band is changing if it’s getting wider or darker or more streaky then you have to think that you’re dealing with a melanoma."

He emphasized the importance of retrieving the nail plate during the nail biopsy procedure and sending it to the pathologist with the nail matrix specimen, "because sometimes it's hard for the pathologist to find the pigment," he explained. "If the pathologist sends you back a report that there’s no pigment here, the implication is that you missed the lesion. But if you have nail plate there, which has pigment in it, you didn’t miss the lesion. The pathologist did."

Some recent articles in the medical literature suggest that if cases of melanonychia striata in childhood are stable and not atypical in appearance, observation may be an option. However, Dr. Scher urged caution with this approach, saying that "every case must be evaluated individually."

To illustrate his point he discussed the case of a 4-year-old healthy girl who presented to his office with an 8-month history of melanonychia and a 3-month history of possible nail fold pigmentation (see image above). Family history revealed a maternal second cousin with acral melanoma. Dermoscopy was consistent with a nevus diagnosis.

The parents agreed to proceed with a nail biopsy, Dr. Scher said. The pathology report read (in part): "atypical junctional melanocytic proliferation with increased numbers of single melanocytes ...; although this lesion is most probably a nevus, it is recommended that it be completely but conservatively excised."

The girl's parents sought the opinion of seven other pathologists and clinicians at a melanoma conference, and all agreed with complete excision. "In this case, there was not much alternative as to what to do," Dr. Scher said.

The entire nail unit was removed during surgery and the lesion healed with "a terrific cosmetic result," he said.

Dr. Scher said that he had no relevant conflicts to disclose.

GOTHENBURG, Sweden - A novel, topically applied inhibitor of the hedgehog signaling pathway showed considerable promise for the treatment of nevoid basal cell carcinoma syndrome in a pilot study.

The 0.75% cream, LDE225, is a potent and selective inhibitor of the protein "smoothened," a key player in the hedgehog signaling pathway, according to Dr. Hans Skvara.

The hedgehog pathway is important in embryonic development and tissue homeostasis. Its uncontrolled overactivity is responsible for the formation of the multiple aggressive basal cell carcinomas (BCCs) characteristic of nevoid basal cell carcinoma syndrome, an autosomal dominant disorder also known as Gorlin-Goltz syndrome, Dr. Skvara said at the annual congress of the European Academy of Dermatology and Venereology.

Twice-daily application of LDE225 for 4 weeks resulted in complete clinical response in 3 of 13 treated BCCs in eight patients and partial clinical response in another 9 tumors. Only one treated BCC showed no clinical response, according to Dr. Skvara of the Medical University of Vienna.

Of the 14 vehicle-treated BCCs in the same eight participants in this randomized, double-blind, 4-week, proof-of-concept study, only one showed a partial clinical response.

Mean tumor volume decreased by 50% in the smoothened inhibitor–treated BCCs, with no significant change over time in the vehicle-treated lesions.

Tumors treated with LDE225 showed downregulation of key genes in the hedgehog pathway, including PTCH 1 and 2 and Gli 1 and 2, in six of eight patients.

Histopathology, however, revealed nests of detectable BCC cells in all treated lesions after 4 weeks of therapy. "Four weeks was probably too short a treatment," Dr. Skvara noted.

The topical smoothened inhibitor was well tolerated, without the marked irritation characteristic of current topical therapies for BCC, such as imiquimod and 5-fluorouracil, he said. If further studies show the smoothened antagonist is able to microscopically eradicate BCC tumor nests, it could become a valuable treatment modality.

"These are some very exciting results. I’m impressed," commented session chair Dr. Jean-Paul Claudel of the University of Tours (France). He asked Dr. Skvara about next steps.

Dr. Skvara replied that a study is underway comparing 6 versus 9 weeks of treatment with two different strengths of the LDE225 cream: the 0.75% formulation used in the pilot study and a slightly lower concentration.

Dr. Skvara declared that he received a research grant from Novartis, which is developing LDE225, to conduct the pilot study.

GOTHENBURG, Sweden - A novel, topically applied inhibitor of the hedgehog signaling pathway showed considerable promise for the treatment of nevoid basal cell carcinoma syndrome in a pilot study.

The 0.75% cream, LDE225, is a potent and selective inhibitor of the protein "smoothened," a key player in the hedgehog signaling pathway, according to Dr. Hans Skvara.

The hedgehog pathway is important in embryonic development and tissue homeostasis. Its uncontrolled overactivity is responsible for the formation of the multiple aggressive basal cell carcinomas (BCCs) characteristic of nevoid basal cell carcinoma syndrome, an autosomal dominant disorder also known as Gorlin-Goltz syndrome, Dr. Skvara said at the annual congress of the European Academy of Dermatology and Venereology.

Twice-daily application of LDE225 for 4 weeks resulted in complete clinical response in 3 of 13 treated BCCs in eight patients and partial clinical response in another 9 tumors. Only one treated BCC showed no clinical response, according to Dr. Skvara of the Medical University of Vienna.

Of the 14 vehicle-treated BCCs in the same eight participants in this randomized, double-blind, 4-week, proof-of-concept study, only one showed a partial clinical response.

Mean tumor volume decreased by 50% in the smoothened inhibitor–treated BCCs, with no significant change over time in the vehicle-treated lesions.

Tumors treated with LDE225 showed downregulation of key genes in the hedgehog pathway, including PTCH 1 and 2 and Gli 1 and 2, in six of eight patients.

Histopathology, however, revealed nests of detectable BCC cells in all treated lesions after 4 weeks of therapy. "Four weeks was probably too short a treatment," Dr. Skvara noted.

The topical smoothened inhibitor was well tolerated, without the marked irritation characteristic of current topical therapies for BCC, such as imiquimod and 5-fluorouracil, he said. If further studies show the smoothened antagonist is able to microscopically eradicate BCC tumor nests, it could become a valuable treatment modality.

"These are some very exciting results. I’m impressed," commented session chair Dr. Jean-Paul Claudel of the University of Tours (France). He asked Dr. Skvara about next steps.

Dr. Skvara replied that a study is underway comparing 6 versus 9 weeks of treatment with two different strengths of the LDE225 cream: the 0.75% formulation used in the pilot study and a slightly lower concentration.

Dr. Skvara declared that he received a research grant from Novartis, which is developing LDE225, to conduct the pilot study.

GOTHENBURG, Sweden - A novel, topically applied inhibitor of the hedgehog signaling pathway showed considerable promise for the treatment of nevoid basal cell carcinoma syndrome in a pilot study.

The 0.75% cream, LDE225, is a potent and selective inhibitor of the protein "smoothened," a key player in the hedgehog signaling pathway, according to Dr. Hans Skvara.

The hedgehog pathway is important in embryonic development and tissue homeostasis. Its uncontrolled overactivity is responsible for the formation of the multiple aggressive basal cell carcinomas (BCCs) characteristic of nevoid basal cell carcinoma syndrome, an autosomal dominant disorder also known as Gorlin-Goltz syndrome, Dr. Skvara said at the annual congress of the European Academy of Dermatology and Venereology.

Twice-daily application of LDE225 for 4 weeks resulted in complete clinical response in 3 of 13 treated BCCs in eight patients and partial clinical response in another 9 tumors. Only one treated BCC showed no clinical response, according to Dr. Skvara of the Medical University of Vienna.

Of the 14 vehicle-treated BCCs in the same eight participants in this randomized, double-blind, 4-week, proof-of-concept study, only one showed a partial clinical response.

Mean tumor volume decreased by 50% in the smoothened inhibitor–treated BCCs, with no significant change over time in the vehicle-treated lesions.

Tumors treated with LDE225 showed downregulation of key genes in the hedgehog pathway, including PTCH 1 and 2 and Gli 1 and 2, in six of eight patients.

Histopathology, however, revealed nests of detectable BCC cells in all treated lesions after 4 weeks of therapy. "Four weeks was probably too short a treatment," Dr. Skvara noted.

The topical smoothened inhibitor was well tolerated, without the marked irritation characteristic of current topical therapies for BCC, such as imiquimod and 5-fluorouracil, he said. If further studies show the smoothened antagonist is able to microscopically eradicate BCC tumor nests, it could become a valuable treatment modality.

"These are some very exciting results. I’m impressed," commented session chair Dr. Jean-Paul Claudel of the University of Tours (France). He asked Dr. Skvara about next steps.

Dr. Skvara replied that a study is underway comparing 6 versus 9 weeks of treatment with two different strengths of the LDE225 cream: the 0.75% formulation used in the pilot study and a slightly lower concentration.

Dr. Skvara declared that he received a research grant from Novartis, which is developing LDE225, to conduct the pilot study.

When a handful of oncologists from competing institutions gathered their expertise and egos together in a joint effort to define appropriate care of patients with cancer, it wasn’t entirely clear the endeavor would work. Shared concerns about HMOs had brought them together in the mid 1990s, but they also vied for the same grants, philanthropic gifts, and patients.

Under the deft leadership of the late Dr. Roger J. Winn, the National Comprehensive Cancer Network (NCCN) has parlayed that first guideline, published in 1995, into the most widely used clinical practice guidelines in oncology. By the NCCN’s own account, the guidelines cover 97% of all patients with cancer. Last year alone, nearly 3.3 million PDF copies were downloaded, with select editions now available in 10 languages including Mandarin and Turkish.

The NCCN, which has seen its original budget increase from $2 million to a little more than $30 million, also successfully flexed its political muscle in recent months over the issue of risk evaluation and mitigation strategies (or REMs), and expanded its global reach through conferences in Beijing, Brazil, and Abu Dhabi.

Membership in the not-for-profit alliance was capped 2 years ago at 21 cancer centers in the United States. These member institutions fund the guidelines through dues and millions of dollars worth of free time, said Dr. David S. Ettinger, the Alex Grass professor of oncology at Johns Hopkins University, Baltimore, and chair of the NCCN’s non–small cell lung cancer and occult primary clinical practice panels.

“Fifteen years later, although there may still be some differences, the guidelines are as specific as you can get,” he said.

They also hold tremendous sway with public and private insurers, raising concerns over how they are being used and whether strict adherence can lead to “cookbook” medicine.

Insurers Base Coverage on Guidelines

The NCCN tracks and monitors guideline compliance for breast, colorectal, non-Hodgkin’s lymphoma, non–small cell lung cancer and, most recently, ovarian cancer, with compliance at about 90%-92% for recommendations with level 1 evidence and 85% overall, said NCCN chief executive officer William T. McGivney, Ph.D. For the remaining 15%, patient characteristics, patient preference, and physician disagreement with the guidelines will direct care. The transparency of the guidelines allows physicians to review the references, the category of evidence, and level of consensus, and decide on their own to use them or not, he said. Still, Dr. Ettinger acknowledges that treatment “decisions are made not wanting to fight insurance companies.”

The NCCN noticed early on that its guidelines were being used as the basis for setting coverage policy, prompting the creation in 2004 of the first NCCN Drugs and Biologics Compendium, Dr. McGivney said. The compendium is now used by such key stakeholders as the Centers for Medicare and Medicaid Services and UnitedHealthcare Inc., one of the nation’s largest private insurers.

“On the private side, you see payers basically saying “If it’s in the NCCN Compendium, it’s covered,’ which is critically important for clinicians and patients,” he said. “We have tremendous influence and collaborative influence I think, with payers.”

If a physician uses a drug covered by the compendium to treat any of the 20,000 patients UnitedHealthcare (UHC) has on active chemotherapy in any given year, the drug is automatically covered, said Dr. Lee N. Newcomer, senior vice president, oncology, for the Minnesota-based insurer. Cases involving drugs not covered by the compendium are reviewed by a medical director who looks at state laws and regulations and the employer’s specific requirements. If an employer requires that any chemotherapy recommended by a physician is covered, then the drug would be covered by UHC, even if it’s not in the compendium, he said.

Prior to UHC’s adopting the compendium, 15% of treatments given by its oncologists didn’t match NCCN recommendations. “I would argue that this was both waste and exposing patients to toxicity and drugs that wouldn’t help them,” said Dr. Newcomer, adding that noncompliance is now less than 1%.

Oncologists Rated on Quality of Care

Earlier this year, UHC unveiled the Oncology Care Analysis program that uses clinical and claims data from about 2,600 oncologists and 14,000 patients from across the country with breast, colon and lung cancer to gauge quality of care based on adherence to NCCN guidelines. Oncologists receive a report showing their individual results along with aggregate national results.

Dr. Newcomer dismisses concerns that the program could pressure oncologists into making treatment decisions based on their standing with UHC rather than the best choice for patients who don’t fit the guidelines because such patients are excluded from the analysis. Moreover, there are no financial incentives or penalties associated with the program. “UHC has always emphasized that the information is for quality improvement,” he said. “We let physicians decide how to act on the information.”

The first pass at the data shows that compliance with the NCCN guidelines is stronger in the treatment of breast than colon or lung cancer, but also that about one-third of breast cancer patients prescribed tamoxifen or an aromatase inhibitor aren’t renewing their prescriptions. “We can bring that information back to the physician, and they can have a discussion with their patient about why they aren’t taking that medicine,” he said.

Feedback from physicians has also identified coding problems for carcinoid tumors of the colon and disagreement over whether bevacizumab (Avastin) is truly contraindicated in patients with lung cancer and brain metastases. UHC shares these concerns, along with the national aggregate data, with the NCCN.

Dr. Eric P. Winer, director of the Breast Oncology Center at the Dana-Farber Cancer Institute in Boston and chief scientific adviser for Susan G. Komen for the Cure, said that of all the guidelines to use, the NCCN guidelines make the most sense, but that oncologists would hear and listen more closely to the message that their practice is out of line if it were delivered by a state or national accreditation program.

“The practicing physician is less likely to trust that the insurer has a clear understanding of what the optimal practice would be,” he said. “It’s just not a credible source in the way that a committee of one’s peers might be.”

Dr. Newcomer said he’d love to see other groups take on the task but has not seen similar published quality data coming out of medical groups. “We are filling a void that’s there,” he said.

Is the Fast Lane Too Broad?

Dr. Ira Klein, clinical head of oncology condition analysis for Aetna Inc., said it doesn’t rely exclusively on the NCCN for the development of guidelines and payment. Aetna has covered drugs for indications in NCCN’s Compendium with a consensus rating of 2b or greater but looks to a variety of sources including top-tier journals and outside opinions when creating guidelines and their clinical practice policy bulletins.

“Relying solely on the NCCN would be like using the Cliff Notes,” he said.

Dr. Klein went on to say that the strength of the NCCN guidelines is that they are evidence based and very good at bringing experts together for consensus-based care when the evidence isn’t particularly strong. Their weakness is that they “could be likened to a 50-lane highway” in cases where multiple treatment options would be appropriate for one disease at one stage, Dr. Klein said.

Dr. Newcomer echoed this sentiment, faulting the NCCN for not assigning a hierarchy to its decisions. He cited the array of recommended chemotherapy regimens for breast cancer, and said, “Where I’d like to see the NCCN guidelines go is to say that of these 14, these 2 are the best.”

Still, both insurers are looking to the NCCN regarding coverage of bevacizumab, following the FDA’s Oncologic Drugs Advisory Committee July vote recommending against its use for the first-line treatment of metastatic breast cancer. Dr. Newcomer said UHC will continue to cover the drug for this indication until the NCCN makes its recommendation following the FDA’s final vote. Dr. Klein said if the FDA removes breast cancer as an indication for bevacizumab, Aetna would consider dropping its existing coverage for the drug and would take the NCCN’s position into consideration in its decision.

The speed at which the NCCN can make such a revision to its guidelines is part of what makes them so unusual. “They are assiduously up to date,” Dr. McGivney said. Staff members track the literature, news of large clinical trials, and FDA filings in order to stay abreast of changes in the evidence, with some 2010 guidelines already in their third or fourth edition.

“We really are in the information age and, of all the areas of medicine, cancer care is probably the most rapidly advancing with respect to the science and research,” he said.

This point was driven home when the American Society of Clinical Oncology (ASCO) published guidelines for stage IV non–small cell lung cancer earlier this year without encompassing emerging data on the importance of epidermal growth factor receptor mutations in treatment response.

“The advantage of systematic review-based guidelines like ASCO uses is that they are more evidence-based, strictly speaking, but take longer to conduct and require methodological expertise,” said Dr. Ethan M. Basch, chair of ASCO’s clinical practice guidelines committee. “The advantage of narrative review with consensus-based guidelines such as used by NCCN is that they can be conducted more rapidly, but are less evidence-based in terms of their degree of systematic approach and hence may be more subject to the biases of panel members.”

When a handful of oncologists from competing institutions gathered their expertise and egos together in a joint effort to define appropriate care of patients with cancer, it wasn’t entirely clear the endeavor would work. Shared concerns about HMOs had brought them together in the mid 1990s, but they also vied for the same grants, philanthropic gifts, and patients.

Under the deft leadership of the late Dr. Roger J. Winn, the National Comprehensive Cancer Network (NCCN) has parlayed that first guideline, published in 1995, into the most widely used clinical practice guidelines in oncology. By the NCCN’s own account, the guidelines cover 97% of all patients with cancer. Last year alone, nearly 3.3 million PDF copies were downloaded, with select editions now available in 10 languages including Mandarin and Turkish.

The NCCN, which has seen its original budget increase from $2 million to a little more than $30 million, also successfully flexed its political muscle in recent months over the issue of risk evaluation and mitigation strategies (or REMs), and expanded its global reach through conferences in Beijing, Brazil, and Abu Dhabi.

Membership in the not-for-profit alliance was capped 2 years ago at 21 cancer centers in the United States. These member institutions fund the guidelines through dues and millions of dollars worth of free time, said Dr. David S. Ettinger, the Alex Grass professor of oncology at Johns Hopkins University, Baltimore, and chair of the NCCN’s non–small cell lung cancer and occult primary clinical practice panels.

“Fifteen years later, although there may still be some differences, the guidelines are as specific as you can get,” he said.

They also hold tremendous sway with public and private insurers, raising concerns over how they are being used and whether strict adherence can lead to “cookbook” medicine.

Insurers Base Coverage on Guidelines

The NCCN tracks and monitors guideline compliance for breast, colorectal, non-Hodgkin’s lymphoma, non–small cell lung cancer and, most recently, ovarian cancer, with compliance at about 90%-92% for recommendations with level 1 evidence and 85% overall, said NCCN chief executive officer William T. McGivney, Ph.D. For the remaining 15%, patient characteristics, patient preference, and physician disagreement with the guidelines will direct care. The transparency of the guidelines allows physicians to review the references, the category of evidence, and level of consensus, and decide on their own to use them or not, he said. Still, Dr. Ettinger acknowledges that treatment “decisions are made not wanting to fight insurance companies.”

The NCCN noticed early on that its guidelines were being used as the basis for setting coverage policy, prompting the creation in 2004 of the first NCCN Drugs and Biologics Compendium, Dr. McGivney said. The compendium is now used by such key stakeholders as the Centers for Medicare and Medicaid Services and UnitedHealthcare Inc., one of the nation’s largest private insurers.

“On the private side, you see payers basically saying “If it’s in the NCCN Compendium, it’s covered,’ which is critically important for clinicians and patients,” he said. “We have tremendous influence and collaborative influence I think, with payers.”

If a physician uses a drug covered by the compendium to treat any of the 20,000 patients UnitedHealthcare (UHC) has on active chemotherapy in any given year, the drug is automatically covered, said Dr. Lee N. Newcomer, senior vice president, oncology, for the Minnesota-based insurer. Cases involving drugs not covered by the compendium are reviewed by a medical director who looks at state laws and regulations and the employer’s specific requirements. If an employer requires that any chemotherapy recommended by a physician is covered, then the drug would be covered by UHC, even if it’s not in the compendium, he said.

Prior to UHC’s adopting the compendium, 15% of treatments given by its oncologists didn’t match NCCN recommendations. “I would argue that this was both waste and exposing patients to toxicity and drugs that wouldn’t help them,” said Dr. Newcomer, adding that noncompliance is now less than 1%.

Oncologists Rated on Quality of Care

Earlier this year, UHC unveiled the Oncology Care Analysis program that uses clinical and claims data from about 2,600 oncologists and 14,000 patients from across the country with breast, colon and lung cancer to gauge quality of care based on adherence to NCCN guidelines. Oncologists receive a report showing their individual results along with aggregate national results.

Dr. Newcomer dismisses concerns that the program could pressure oncologists into making treatment decisions based on their standing with UHC rather than the best choice for patients who don’t fit the guidelines because such patients are excluded from the analysis. Moreover, there are no financial incentives or penalties associated with the program. “UHC has always emphasized that the information is for quality improvement,” he said. “We let physicians decide how to act on the information.”

The first pass at the data shows that compliance with the NCCN guidelines is stronger in the treatment of breast than colon or lung cancer, but also that about one-third of breast cancer patients prescribed tamoxifen or an aromatase inhibitor aren’t renewing their prescriptions. “We can bring that information back to the physician, and they can have a discussion with their patient about why they aren’t taking that medicine,” he said.

Feedback from physicians has also identified coding problems for carcinoid tumors of the colon and disagreement over whether bevacizumab (Avastin) is truly contraindicated in patients with lung cancer and brain metastases. UHC shares these concerns, along with the national aggregate data, with the NCCN.

Dr. Eric P. Winer, director of the Breast Oncology Center at the Dana-Farber Cancer Institute in Boston and chief scientific adviser for Susan G. Komen for the Cure, said that of all the guidelines to use, the NCCN guidelines make the most sense, but that oncologists would hear and listen more closely to the message that their practice is out of line if it were delivered by a state or national accreditation program.

“The practicing physician is less likely to trust that the insurer has a clear understanding of what the optimal practice would be,” he said. “It’s just not a credible source in the way that a committee of one’s peers might be.”

Dr. Newcomer said he’d love to see other groups take on the task but has not seen similar published quality data coming out of medical groups. “We are filling a void that’s there,” he said.

Is the Fast Lane Too Broad?

Dr. Ira Klein, clinical head of oncology condition analysis for Aetna Inc., said it doesn’t rely exclusively on the NCCN for the development of guidelines and payment. Aetna has covered drugs for indications in NCCN’s Compendium with a consensus rating of 2b or greater but looks to a variety of sources including top-tier journals and outside opinions when creating guidelines and their clinical practice policy bulletins.

“Relying solely on the NCCN would be like using the Cliff Notes,” he said.

Dr. Klein went on to say that the strength of the NCCN guidelines is that they are evidence based and very good at bringing experts together for consensus-based care when the evidence isn’t particularly strong. Their weakness is that they “could be likened to a 50-lane highway” in cases where multiple treatment options would be appropriate for one disease at one stage, Dr. Klein said.

Dr. Newcomer echoed this sentiment, faulting the NCCN for not assigning a hierarchy to its decisions. He cited the array of recommended chemotherapy regimens for breast cancer, and said, “Where I’d like to see the NCCN guidelines go is to say that of these 14, these 2 are the best.”

Still, both insurers are looking to the NCCN regarding coverage of bevacizumab, following the FDA’s Oncologic Drugs Advisory Committee July vote recommending against its use for the first-line treatment of metastatic breast cancer. Dr. Newcomer said UHC will continue to cover the drug for this indication until the NCCN makes its recommendation following the FDA’s final vote. Dr. Klein said if the FDA removes breast cancer as an indication for bevacizumab, Aetna would consider dropping its existing coverage for the drug and would take the NCCN’s position into consideration in its decision.

The speed at which the NCCN can make such a revision to its guidelines is part of what makes them so unusual. “They are assiduously up to date,” Dr. McGivney said. Staff members track the literature, news of large clinical trials, and FDA filings in order to stay abreast of changes in the evidence, with some 2010 guidelines already in their third or fourth edition.

“We really are in the information age and, of all the areas of medicine, cancer care is probably the most rapidly advancing with respect to the science and research,” he said.

This point was driven home when the American Society of Clinical Oncology (ASCO) published guidelines for stage IV non–small cell lung cancer earlier this year without encompassing emerging data on the importance of epidermal growth factor receptor mutations in treatment response.

“The advantage of systematic review-based guidelines like ASCO uses is that they are more evidence-based, strictly speaking, but take longer to conduct and require methodological expertise,” said Dr. Ethan M. Basch, chair of ASCO’s clinical practice guidelines committee. “The advantage of narrative review with consensus-based guidelines such as used by NCCN is that they can be conducted more rapidly, but are less evidence-based in terms of their degree of systematic approach and hence may be more subject to the biases of panel members.”

When a handful of oncologists from competing institutions gathered their expertise and egos together in a joint effort to define appropriate care of patients with cancer, it wasn’t entirely clear the endeavor would work. Shared concerns about HMOs had brought them together in the mid 1990s, but they also vied for the same grants, philanthropic gifts, and patients.

Under the deft leadership of the late Dr. Roger J. Winn, the National Comprehensive Cancer Network (NCCN) has parlayed that first guideline, published in 1995, into the most widely used clinical practice guidelines in oncology. By the NCCN’s own account, the guidelines cover 97% of all patients with cancer. Last year alone, nearly 3.3 million PDF copies were downloaded, with select editions now available in 10 languages including Mandarin and Turkish.

The NCCN, which has seen its original budget increase from $2 million to a little more than $30 million, also successfully flexed its political muscle in recent months over the issue of risk evaluation and mitigation strategies (or REMs), and expanded its global reach through conferences in Beijing, Brazil, and Abu Dhabi.

Membership in the not-for-profit alliance was capped 2 years ago at 21 cancer centers in the United States. These member institutions fund the guidelines through dues and millions of dollars worth of free time, said Dr. David S. Ettinger, the Alex Grass professor of oncology at Johns Hopkins University, Baltimore, and chair of the NCCN’s non–small cell lung cancer and occult primary clinical practice panels.

“Fifteen years later, although there may still be some differences, the guidelines are as specific as you can get,” he said.

They also hold tremendous sway with public and private insurers, raising concerns over how they are being used and whether strict adherence can lead to “cookbook” medicine.

Insurers Base Coverage on Guidelines

The NCCN tracks and monitors guideline compliance for breast, colorectal, non-Hodgkin’s lymphoma, non–small cell lung cancer and, most recently, ovarian cancer, with compliance at about 90%-92% for recommendations with level 1 evidence and 85% overall, said NCCN chief executive officer William T. McGivney, Ph.D. For the remaining 15%, patient characteristics, patient preference, and physician disagreement with the guidelines will direct care. The transparency of the guidelines allows physicians to review the references, the category of evidence, and level of consensus, and decide on their own to use them or not, he said. Still, Dr. Ettinger acknowledges that treatment “decisions are made not wanting to fight insurance companies.”

The NCCN noticed early on that its guidelines were being used as the basis for setting coverage policy, prompting the creation in 2004 of the first NCCN Drugs and Biologics Compendium, Dr. McGivney said. The compendium is now used by such key stakeholders as the Centers for Medicare and Medicaid Services and UnitedHealthcare Inc., one of the nation’s largest private insurers.

“On the private side, you see payers basically saying “If it’s in the NCCN Compendium, it’s covered,’ which is critically important for clinicians and patients,” he said. “We have tremendous influence and collaborative influence I think, with payers.”

If a physician uses a drug covered by the compendium to treat any of the 20,000 patients UnitedHealthcare (UHC) has on active chemotherapy in any given year, the drug is automatically covered, said Dr. Lee N. Newcomer, senior vice president, oncology, for the Minnesota-based insurer. Cases involving drugs not covered by the compendium are reviewed by a medical director who looks at state laws and regulations and the employer’s specific requirements. If an employer requires that any chemotherapy recommended by a physician is covered, then the drug would be covered by UHC, even if it’s not in the compendium, he said.

Prior to UHC’s adopting the compendium, 15% of treatments given by its oncologists didn’t match NCCN recommendations. “I would argue that this was both waste and exposing patients to toxicity and drugs that wouldn’t help them,” said Dr. Newcomer, adding that noncompliance is now less than 1%.

Oncologists Rated on Quality of Care

Earlier this year, UHC unveiled the Oncology Care Analysis program that uses clinical and claims data from about 2,600 oncologists and 14,000 patients from across the country with breast, colon and lung cancer to gauge quality of care based on adherence to NCCN guidelines. Oncologists receive a report showing their individual results along with aggregate national results.

Dr. Newcomer dismisses concerns that the program could pressure oncologists into making treatment decisions based on their standing with UHC rather than the best choice for patients who don’t fit the guidelines because such patients are excluded from the analysis. Moreover, there are no financial incentives or penalties associated with the program. “UHC has always emphasized that the information is for quality improvement,” he said. “We let physicians decide how to act on the information.”

The first pass at the data shows that compliance with the NCCN guidelines is stronger in the treatment of breast than colon or lung cancer, but also that about one-third of breast cancer patients prescribed tamoxifen or an aromatase inhibitor aren’t renewing their prescriptions. “We can bring that information back to the physician, and they can have a discussion with their patient about why they aren’t taking that medicine,” he said.

Feedback from physicians has also identified coding problems for carcinoid tumors of the colon and disagreement over whether bevacizumab (Avastin) is truly contraindicated in patients with lung cancer and brain metastases. UHC shares these concerns, along with the national aggregate data, with the NCCN.

Dr. Eric P. Winer, director of the Breast Oncology Center at the Dana-Farber Cancer Institute in Boston and chief scientific adviser for Susan G. Komen for the Cure, said that of all the guidelines to use, the NCCN guidelines make the most sense, but that oncologists would hear and listen more closely to the message that their practice is out of line if it were delivered by a state or national accreditation program.

“The practicing physician is less likely to trust that the insurer has a clear understanding of what the optimal practice would be,” he said. “It’s just not a credible source in the way that a committee of one’s peers might be.”

Dr. Newcomer said he’d love to see other groups take on the task but has not seen similar published quality data coming out of medical groups. “We are filling a void that’s there,” he said.

Is the Fast Lane Too Broad?

Dr. Ira Klein, clinical head of oncology condition analysis for Aetna Inc., said it doesn’t rely exclusively on the NCCN for the development of guidelines and payment. Aetna has covered drugs for indications in NCCN’s Compendium with a consensus rating of 2b or greater but looks to a variety of sources including top-tier journals and outside opinions when creating guidelines and their clinical practice policy bulletins.

“Relying solely on the NCCN would be like using the Cliff Notes,” he said.

Dr. Klein went on to say that the strength of the NCCN guidelines is that they are evidence based and very good at bringing experts together for consensus-based care when the evidence isn’t particularly strong. Their weakness is that they “could be likened to a 50-lane highway” in cases where multiple treatment options would be appropriate for one disease at one stage, Dr. Klein said.

Dr. Newcomer echoed this sentiment, faulting the NCCN for not assigning a hierarchy to its decisions. He cited the array of recommended chemotherapy regimens for breast cancer, and said, “Where I’d like to see the NCCN guidelines go is to say that of these 14, these 2 are the best.”

Still, both insurers are looking to the NCCN regarding coverage of bevacizumab, following the FDA’s Oncologic Drugs Advisory Committee July vote recommending against its use for the first-line treatment of metastatic breast cancer. Dr. Newcomer said UHC will continue to cover the drug for this indication until the NCCN makes its recommendation following the FDA’s final vote. Dr. Klein said if the FDA removes breast cancer as an indication for bevacizumab, Aetna would consider dropping its existing coverage for the drug and would take the NCCN’s position into consideration in its decision.

The speed at which the NCCN can make such a revision to its guidelines is part of what makes them so unusual. “They are assiduously up to date,” Dr. McGivney said. Staff members track the literature, news of large clinical trials, and FDA filings in order to stay abreast of changes in the evidence, with some 2010 guidelines already in their third or fourth edition.

“We really are in the information age and, of all the areas of medicine, cancer care is probably the most rapidly advancing with respect to the science and research,” he said.

This point was driven home when the American Society of Clinical Oncology (ASCO) published guidelines for stage IV non–small cell lung cancer earlier this year without encompassing emerging data on the importance of epidermal growth factor receptor mutations in treatment response.

“The advantage of systematic review-based guidelines like ASCO uses is that they are more evidence-based, strictly speaking, but take longer to conduct and require methodological expertise,” said Dr. Ethan M. Basch, chair of ASCO’s clinical practice guidelines committee. “The advantage of narrative review with consensus-based guidelines such as used by NCCN is that they can be conducted more rapidly, but are less evidence-based in terms of their degree of systematic approach and hence may be more subject to the biases of panel members.”

SANTA BARBARA, Calif. – Current American Joint Committee on Cancer melanoma staging criteria incorporate a mitotic rate of 1/mm2 or greater into the T1b classification, recognizing mitotic rate as an independent prognostic factor in patients with primary melanoma.

This change, which went into effect in January,"is going to have a profound impact in whom we consider eligible for staging with sentinel lymph node biopsy" Dr. Susan Swetter predicted at the annual meeting of the California Society of Dermatology and Dermatologic Surgery. "The reason is that only about 6%-8% of these T1 tumors (1.0 mm) are ulcerated, but it is estimated that up to 30%-40% will have an elevated mitotic rate of 1.0 or more per square millimeter. This leaves us with a conundrum: Are all of these patients going to be eligible for sentinel lymph node biopsy?"

Current AJCC melanoma staging criteria are based on data analysis from the 2008 AJCC collaborative melanoma staging database from 14 cancer centers and cooperative oncology organizations worldwide, said Dr. Swetter, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford University Medical Center/VA Palo Alto Health Care System, Calif.

The criteria are based on prognostic factor analysis of nearly 60,000 patients to validate staging criteria and groupings for the 7th edition of the AJCC Cancer Staging Manual (Springer, New York), which was published in the fall of 2009 and became active in January 2010.

"The concept is that each stage grouping has a uniform risk for survival, and there are a wealth of patients per tumor node metastasis (TNM) categories, with more than 27,000 with stage I and II disease, more than 3,400 with stage III disease, and more than 7,600 with stage IV disease," Dr. Swetter said.

The newest revision of the AJCC staging for melanoma involves no major changes for TNM and stage grouping criteria, with the exception of mitotic rate.

Other changes involve more advanced disease. For example, "immunohistochemical detection of nodal metastases is now acceptable, whereas only routine histology was used previously," Dr. Swetter said. "Also, there is no longer a lower limit to designate node-positive disease. The size of the isolated tumor cells is no longer used, although that is quite controversial."

Thickness of tumors is potentially a marker of duration of growth, with increasing tumor thickness correlating adversely with survival. According to the 2008 AJCC Melanoma Database, patients with tumor thickness of 0.01-0.55 mm have a 10-year survival rate of 95%, while those with a tumor thickness of 4.01-6.0 mm have a 10-year survival rate of 54%.

The most relevant correlate of a mitotic rate increase and its effect on prognosis appears to be in thin tumors, Dr. Swetter said. "This is why the new AJCC guidelines incorporate mitotic rate in tumors that are less than or equal to 1.0 mm thick."

Survival data from the 2008 AJCC Melanoma Database suggest there is little to no value in promoting sentinel lymph node biopsy in patients who have tumors up to 0.50 mm in depth, regardless of mitotic rate, because the survival rate in these patients is excellent. Currently, the T1b designation is used for staging in terms of survival. "It is not a criterion in itself to perform sentinel lymph node biopsy," Dr. Swetter emphasized. "There is some evolving data suggesting that mitotic rate as a continuous variable may be predictive of occult regional nodal disease."

One published study suggests that sentinel lymph node biopsy is appropriate for patients with T1b melanomas, including those defined by mitotic rate (J. Natl. Compr. Canc. Netw. 2009;7:308-17). "We are now awaiting publication of a larger analysis of patients with thin melanoma," Dr. Swetter said. "Both the National Comprehensive Cancer Network and the AAD [American Academy of Dermatology] melanoma panels are weighing in to establish an appropriate threshold in these T1b patients."

Dr. Swetter, who serves on both of the panels, noted that there is currently "very little enthusiasm from a surgical perspective to be pursuing sentinel lymph node biopsy on every patient who is T1b by virtue of mitotic rate."

The National Comprehensive Cancer Network recommends that clinicians "discuss and offer" sentinel lymph node biopsy for patients with stage IB and stage II cutaneous melanoma, "recognizing that the sentinel node biopsy is an important staging tool, but its impact on overall survival is unclear," Dr. Swetter said.

The procedure should also be considered for stage IA melanomas with adverse features including positive deep margins, lymphovascular invasion, thickness of 0.75 mm or greater, or younger age.

The decision not to perform sentinel lymph node biopsy can be based on significant patient comorbidities, patient preference, or other factors.

An unresolved question is whether or not sentinel lymph node biopsy is a valid staging technique in older patients. "Older age is associated with worse prognosis, but lower rates of sentinel lymph node positivity," Dr. Swetter said. "The question is, why? One issue is whether there is different biology of melanoma in the elderly, or whether host immune factors come into play. Another [factor] could be delayed lymphatic spread, or it might be that tumors are more likely to disseminate hematogenously in older patients, compared with younger patients."

In the future, Dr. Swetter predicted the emergence of individualized prognoses based on novel weighted mathematical equations using AJCC staging and other factors. A Web-based predictive tool for prognosis developed by the AJCC Melanoma Database is currently available at www.melanomaprognosis.org.

Dr. Swetter stated having no relevant financial conflicts to disclose.

SANTA BARBARA, Calif. – Current American Joint Committee on Cancer melanoma staging criteria incorporate a mitotic rate of 1/mm2 or greater into the T1b classification, recognizing mitotic rate as an independent prognostic factor in patients with primary melanoma.

This change, which went into effect in January,"is going to have a profound impact in whom we consider eligible for staging with sentinel lymph node biopsy" Dr. Susan Swetter predicted at the annual meeting of the California Society of Dermatology and Dermatologic Surgery. "The reason is that only about 6%-8% of these T1 tumors (1.0 mm) are ulcerated, but it is estimated that up to 30%-40% will have an elevated mitotic rate of 1.0 or more per square millimeter. This leaves us with a conundrum: Are all of these patients going to be eligible for sentinel lymph node biopsy?"

Current AJCC melanoma staging criteria are based on data analysis from the 2008 AJCC collaborative melanoma staging database from 14 cancer centers and cooperative oncology organizations worldwide, said Dr. Swetter, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford University Medical Center/VA Palo Alto Health Care System, Calif.

The criteria are based on prognostic factor analysis of nearly 60,000 patients to validate staging criteria and groupings for the 7th edition of the AJCC Cancer Staging Manual (Springer, New York), which was published in the fall of 2009 and became active in January 2010.

"The concept is that each stage grouping has a uniform risk for survival, and there are a wealth of patients per tumor node metastasis (TNM) categories, with more than 27,000 with stage I and II disease, more than 3,400 with stage III disease, and more than 7,600 with stage IV disease," Dr. Swetter said.

The newest revision of the AJCC staging for melanoma involves no major changes for TNM and stage grouping criteria, with the exception of mitotic rate.

Other changes involve more advanced disease. For example, "immunohistochemical detection of nodal metastases is now acceptable, whereas only routine histology was used previously," Dr. Swetter said. "Also, there is no longer a lower limit to designate node-positive disease. The size of the isolated tumor cells is no longer used, although that is quite controversial."

Thickness of tumors is potentially a marker of duration of growth, with increasing tumor thickness correlating adversely with survival. According to the 2008 AJCC Melanoma Database, patients with tumor thickness of 0.01-0.55 mm have a 10-year survival rate of 95%, while those with a tumor thickness of 4.01-6.0 mm have a 10-year survival rate of 54%.

The most relevant correlate of a mitotic rate increase and its effect on prognosis appears to be in thin tumors, Dr. Swetter said. "This is why the new AJCC guidelines incorporate mitotic rate in tumors that are less than or equal to 1.0 mm thick."

Survival data from the 2008 AJCC Melanoma Database suggest there is little to no value in promoting sentinel lymph node biopsy in patients who have tumors up to 0.50 mm in depth, regardless of mitotic rate, because the survival rate in these patients is excellent. Currently, the T1b designation is used for staging in terms of survival. "It is not a criterion in itself to perform sentinel lymph node biopsy," Dr. Swetter emphasized. "There is some evolving data suggesting that mitotic rate as a continuous variable may be predictive of occult regional nodal disease."

One published study suggests that sentinel lymph node biopsy is appropriate for patients with T1b melanomas, including those defined by mitotic rate (J. Natl. Compr. Canc. Netw. 2009;7:308-17). "We are now awaiting publication of a larger analysis of patients with thin melanoma," Dr. Swetter said. "Both the National Comprehensive Cancer Network and the AAD [American Academy of Dermatology] melanoma panels are weighing in to establish an appropriate threshold in these T1b patients."

Dr. Swetter, who serves on both of the panels, noted that there is currently "very little enthusiasm from a surgical perspective to be pursuing sentinel lymph node biopsy on every patient who is T1b by virtue of mitotic rate."

The National Comprehensive Cancer Network recommends that clinicians "discuss and offer" sentinel lymph node biopsy for patients with stage IB and stage II cutaneous melanoma, "recognizing that the sentinel node biopsy is an important staging tool, but its impact on overall survival is unclear," Dr. Swetter said.

The procedure should also be considered for stage IA melanomas with adverse features including positive deep margins, lymphovascular invasion, thickness of 0.75 mm or greater, or younger age.

The decision not to perform sentinel lymph node biopsy can be based on significant patient comorbidities, patient preference, or other factors.

An unresolved question is whether or not sentinel lymph node biopsy is a valid staging technique in older patients. "Older age is associated with worse prognosis, but lower rates of sentinel lymph node positivity," Dr. Swetter said. "The question is, why? One issue is whether there is different biology of melanoma in the elderly, or whether host immune factors come into play. Another [factor] could be delayed lymphatic spread, or it might be that tumors are more likely to disseminate hematogenously in older patients, compared with younger patients."

In the future, Dr. Swetter predicted the emergence of individualized prognoses based on novel weighted mathematical equations using AJCC staging and other factors. A Web-based predictive tool for prognosis developed by the AJCC Melanoma Database is currently available at www.melanomaprognosis.org.

Dr. Swetter stated having no relevant financial conflicts to disclose.

SANTA BARBARA, Calif. – Current American Joint Committee on Cancer melanoma staging criteria incorporate a mitotic rate of 1/mm2 or greater into the T1b classification, recognizing mitotic rate as an independent prognostic factor in patients with primary melanoma.

This change, which went into effect in January,"is going to have a profound impact in whom we consider eligible for staging with sentinel lymph node biopsy" Dr. Susan Swetter predicted at the annual meeting of the California Society of Dermatology and Dermatologic Surgery. "The reason is that only about 6%-8% of these T1 tumors (1.0 mm) are ulcerated, but it is estimated that up to 30%-40% will have an elevated mitotic rate of 1.0 or more per square millimeter. This leaves us with a conundrum: Are all of these patients going to be eligible for sentinel lymph node biopsy?"

Current AJCC melanoma staging criteria are based on data analysis from the 2008 AJCC collaborative melanoma staging database from 14 cancer centers and cooperative oncology organizations worldwide, said Dr. Swetter, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford University Medical Center/VA Palo Alto Health Care System, Calif.

The criteria are based on prognostic factor analysis of nearly 60,000 patients to validate staging criteria and groupings for the 7th edition of the AJCC Cancer Staging Manual (Springer, New York), which was published in the fall of 2009 and became active in January 2010.

"The concept is that each stage grouping has a uniform risk for survival, and there are a wealth of patients per tumor node metastasis (TNM) categories, with more than 27,000 with stage I and II disease, more than 3,400 with stage III disease, and more than 7,600 with stage IV disease," Dr. Swetter said.

The newest revision of the AJCC staging for melanoma involves no major changes for TNM and stage grouping criteria, with the exception of mitotic rate.

Other changes involve more advanced disease. For example, "immunohistochemical detection of nodal metastases is now acceptable, whereas only routine histology was used previously," Dr. Swetter said. "Also, there is no longer a lower limit to designate node-positive disease. The size of the isolated tumor cells is no longer used, although that is quite controversial."

Thickness of tumors is potentially a marker of duration of growth, with increasing tumor thickness correlating adversely with survival. According to the 2008 AJCC Melanoma Database, patients with tumor thickness of 0.01-0.55 mm have a 10-year survival rate of 95%, while those with a tumor thickness of 4.01-6.0 mm have a 10-year survival rate of 54%.

The most relevant correlate of a mitotic rate increase and its effect on prognosis appears to be in thin tumors, Dr. Swetter said. "This is why the new AJCC guidelines incorporate mitotic rate in tumors that are less than or equal to 1.0 mm thick."

Survival data from the 2008 AJCC Melanoma Database suggest there is little to no value in promoting sentinel lymph node biopsy in patients who have tumors up to 0.50 mm in depth, regardless of mitotic rate, because the survival rate in these patients is excellent. Currently, the T1b designation is used for staging in terms of survival. "It is not a criterion in itself to perform sentinel lymph node biopsy," Dr. Swetter emphasized. "There is some evolving data suggesting that mitotic rate as a continuous variable may be predictive of occult regional nodal disease."

One published study suggests that sentinel lymph node biopsy is appropriate for patients with T1b melanomas, including those defined by mitotic rate (J. Natl. Compr. Canc. Netw. 2009;7:308-17). "We are now awaiting publication of a larger analysis of patients with thin melanoma," Dr. Swetter said. "Both the National Comprehensive Cancer Network and the AAD [American Academy of Dermatology] melanoma panels are weighing in to establish an appropriate threshold in these T1b patients."

Dr. Swetter, who serves on both of the panels, noted that there is currently "very little enthusiasm from a surgical perspective to be pursuing sentinel lymph node biopsy on every patient who is T1b by virtue of mitotic rate."

The National Comprehensive Cancer Network recommends that clinicians "discuss and offer" sentinel lymph node biopsy for patients with stage IB and stage II cutaneous melanoma, "recognizing that the sentinel node biopsy is an important staging tool, but its impact on overall survival is unclear," Dr. Swetter said.

The procedure should also be considered for stage IA melanomas with adverse features including positive deep margins, lymphovascular invasion, thickness of 0.75 mm or greater, or younger age.

The decision not to perform sentinel lymph node biopsy can be based on significant patient comorbidities, patient preference, or other factors.

An unresolved question is whether or not sentinel lymph node biopsy is a valid staging technique in older patients. "Older age is associated with worse prognosis, but lower rates of sentinel lymph node positivity," Dr. Swetter said. "The question is, why? One issue is whether there is different biology of melanoma in the elderly, or whether host immune factors come into play. Another [factor] could be delayed lymphatic spread, or it might be that tumors are more likely to disseminate hematogenously in older patients, compared with younger patients."

In the future, Dr. Swetter predicted the emergence of individualized prognoses based on novel weighted mathematical equations using AJCC staging and other factors. A Web-based predictive tool for prognosis developed by the AJCC Melanoma Database is currently available at www.melanomaprognosis.org.

Dr. Swetter stated having no relevant financial conflicts to disclose.

Melanocytic nevi – spitz, congenital, and acquired – can pose diagnostic challenges for the pediatric dermatologist.

Dr. Jonathan A. Dyer offered a review of the latest literature on these pediatric melanomas at a seminar on women's and pediatric dermatology sponsored by Skin Disease Education Foundation.

Atypical Spitzoid Melanocytic Tumors (ASMT)

Data suggest that a positive sentinel lymph node biopsy (SLNB) in ASMT does not necessarily mean poor prognosis, according to Dr. Dyer, who is an assistant professor of clinical dermatology at the University of Missouri in Columbia.

Positive SLNB is not uncommon in ASMT, occurring in 28%-50% of cases. Nodal lesion morphology appears to be what matters – typical-appearing subcapsular cells versus ugly cells that replace a significant portion of the node (Am. J. Surg. Pathol. 2009;33:1386-95).

In a series of six published studies with more than 100 patients, no patient with ASMT and positive SLNB died of disease, he reported. However, follow-up was limited in many reports (median 10 months). Most malignant melanomas recur within 36 months.

In the Multicenter Selective Lymphadenectomy Trial (MSLT), the 5-year survival rate for patients younger than 19 years with malignant melanoma with a positive SLN was 68%, compared with 59% for adults.

Congenital Melanocytic Nevi (CMN)

A 19-year prospective study at Great Ormond Street Hospital in London provided a plethora of information on CMN (Br. J. Dermatol. 2009;160:143-50). The study included 349 families with CMN and 79 control families. Poor maternal health (threatened miscarriage, maternal hypertension, or severe nausea/vomiting) was associated with an increased incidence of CMN.

The researchers also found a possible positive association between maternal smoking and projected adult size and overall CMN incidence. CMN was more likely in females, while maternal freckling was independently associated with smaller projected adult size. A quarter of those with CMN had a second-degree relative with CMN, noted Dr. Dyer.

Furthermore, it is estimated that 5%-30% of patients with large CMN have asymptomatic neurocutaneous melanosis (NCM). NCM symptoms – increased intracranial pressure or seizures – typically occur in the first 2 years of life, he reported. It is possible for patients to convert from asymptomatic NCM to symptomatic but it is unclear how common it is (J. Clin. Oncol. 2009;27:e136).

Occasionally NCM symptoms are temporary or controllable; however, prognosis of symptomatic NCM is guarded. MRI is sensitive for NCM in the first 4-6 months but small deposits can be missed.

In terms of risk, satellites appear to be a major risk factor for NCM in patients with CMN. If there are no satellites, the risk of NCM is very low, summarized Dr. Dyer. In addition, CMN size appears to matter more than location. Based on several studies, the risk of NCM tends to be about 20%.

It has been suggested that up to two-thirds of pediatric patients with NCM go on to develop leptomeningeal tumors. Some patients may develop symptomatic NCM as a result, reported Dr. Dyer. An estimated 50%-90% of these patients die within 3 years of symptom onset. It is also estimated that 50% develop malignant melanoma of the central nervous system (Clin. Dermatol. 2009;27:529-36) .

Many CMN improve with time, he noted. In the Great Ormond Street study, for example, the majority of untreated lesions lightened during the follow-up period (Br. J. Dermatol. 2009;160:387-92). Surgery and the presence of satellites at birth were independently associated with darkening.

Satisfaction with surgery was high for patients with CMN of less than 20 cm and for those with facial lesions. However, satisfaction was reduced with increasing projected adult size. Girls were more likely to have surgery.

Treatment seemed to increase the darkening of remaining or later-developing nevi, independent of type, timing, or nevus. Tissue expansion appeared to be associated with increased satellite development, noted Dr. Dyer. Projected adult size was associated with satellite number but not treatment type.

Childhood Melanoma

Melanoma accounts for 1%-3% of childhood malignancies. The incidence increased by 2.9% per year from 1973 to 2001 (Clin. Dermatol. 2009;27:529-36). Melanoma is seven times more common in the second decade than in the first, said Dr. Dyer. It is estimated that teens aged 15-19 years account for 73%-79% of cases.

Interestingly, there is a slight male predominance in young children that changes to a slight female predominance in older groups. Adolescent white girls with a history of ultraviolet exposure have the greatest melanoma risk, particularly on the trunk and lower extremities, he pointed out.

Approximately 30% of childhood melanomas arise with giant CMN. Lifetime risk appears to be bimodal, with the first peak in the first decade of life (usually in the first 5 years). It is estimated that 50%-70% arise before puberty. Head and neck melanomas are more common at age 1-4 years, while melanomas on the trunk are more common with increasing age. Early-life melanomas tend to be dermal with poorer outcomes. The second peak occurs in adulthood, reported Dr. Dyer.

Approximately 20% of childhood melanomas occur with other melanocytic lesions. Malignant melanomas from small CMN typically occur after puberty. These are more similar to adult malignant melanomas.

Childhood melanomas are associated with an increased incidence of amelanotic and nodular lesions. Risk factors include the following: intermittent intense sun exposure, tendency to sunburn, tendency to freckle, fair skin, blue/green eyes, blonde/red hair, xeroderma pigmentosum, giant CMN, dysplastic nevus syndrome, atypical nevi, a family history of malignant melanoma, and immunosuppression.

The risk of transformation for CMN is associated with size. Small to medium CMN (less than 20 cm) have a 1%-5% risk of transformation, while large/giant CMN (greater than 20 cm) have at least a 5%-10% risk; however, the risk may be as great as 20%.

Some studies suggest that 30%-75% of pediatric malignant melanoma originated in giant CMN, and one-third are fatal, reported Dr. Dyer. Excision does not completely eliminate the risk. In one study, 8% of patients developed extracutaneous malignant melanoma after CMN excision.

He noted that the risk of childhood melanoma is associated with immunodeficiency. The risk is six times greater if immunodeficiency is genetic in origin; the risk is four times greater if immunodeficiency is acquired.

The indications for sentinel lymph node biopsy in children are the same as in adults, he noted. Children have a higher incidence positive sentinel lymph node. However, this does not predict likelihood of recurrence or prognosis in children.

Surgical excision should use the same margins as in adults whenever possible. Thickness, ulceration, and stage at diagnosis are all prognostic factors.

Disclosures: Dr. Dyer reported having no conflicts of interest. SDEF and this news organization are owned by Elsevier.

Melanocytic nevi – spitz, congenital, and acquired – can pose diagnostic challenges for the pediatric dermatologist.

Dr. Jonathan A. Dyer offered a review of the latest literature on these pediatric melanomas at a seminar on women's and pediatric dermatology sponsored by Skin Disease Education Foundation.

Atypical Spitzoid Melanocytic Tumors (ASMT)

Data suggest that a positive sentinel lymph node biopsy (SLNB) in ASMT does not necessarily mean poor prognosis, according to Dr. Dyer, who is an assistant professor of clinical dermatology at the University of Missouri in Columbia.

Positive SLNB is not uncommon in ASMT, occurring in 28%-50% of cases. Nodal lesion morphology appears to be what matters – typical-appearing subcapsular cells versus ugly cells that replace a significant portion of the node (Am. J. Surg. Pathol. 2009;33:1386-95).

In a series of six published studies with more than 100 patients, no patient with ASMT and positive SLNB died of disease, he reported. However, follow-up was limited in many reports (median 10 months). Most malignant melanomas recur within 36 months.

In the Multicenter Selective Lymphadenectomy Trial (MSLT), the 5-year survival rate for patients younger than 19 years with malignant melanoma with a positive SLN was 68%, compared with 59% for adults.

Congenital Melanocytic Nevi (CMN)

A 19-year prospective study at Great Ormond Street Hospital in London provided a plethora of information on CMN (Br. J. Dermatol. 2009;160:143-50). The study included 349 families with CMN and 79 control families. Poor maternal health (threatened miscarriage, maternal hypertension, or severe nausea/vomiting) was associated with an increased incidence of CMN.

The researchers also found a possible positive association between maternal smoking and projected adult size and overall CMN incidence. CMN was more likely in females, while maternal freckling was independently associated with smaller projected adult size. A quarter of those with CMN had a second-degree relative with CMN, noted Dr. Dyer.

Furthermore, it is estimated that 5%-30% of patients with large CMN have asymptomatic neurocutaneous melanosis (NCM). NCM symptoms – increased intracranial pressure or seizures – typically occur in the first 2 years of life, he reported. It is possible for patients to convert from asymptomatic NCM to symptomatic but it is unclear how common it is (J. Clin. Oncol. 2009;27:e136).

Occasionally NCM symptoms are temporary or controllable; however, prognosis of symptomatic NCM is guarded. MRI is sensitive for NCM in the first 4-6 months but small deposits can be missed.

In terms of risk, satellites appear to be a major risk factor for NCM in patients with CMN. If there are no satellites, the risk of NCM is very low, summarized Dr. Dyer. In addition, CMN size appears to matter more than location. Based on several studies, the risk of NCM tends to be about 20%.

It has been suggested that up to two-thirds of pediatric patients with NCM go on to develop leptomeningeal tumors. Some patients may develop symptomatic NCM as a result, reported Dr. Dyer. An estimated 50%-90% of these patients die within 3 years of symptom onset. It is also estimated that 50% develop malignant melanoma of the central nervous system (Clin. Dermatol. 2009;27:529-36) .

Many CMN improve with time, he noted. In the Great Ormond Street study, for example, the majority of untreated lesions lightened during the follow-up period (Br. J. Dermatol. 2009;160:387-92). Surgery and the presence of satellites at birth were independently associated with darkening.

Satisfaction with surgery was high for patients with CMN of less than 20 cm and for those with facial lesions. However, satisfaction was reduced with increasing projected adult size. Girls were more likely to have surgery.

Treatment seemed to increase the darkening of remaining or later-developing nevi, independent of type, timing, or nevus. Tissue expansion appeared to be associated with increased satellite development, noted Dr. Dyer. Projected adult size was associated with satellite number but not treatment type.

Childhood Melanoma

Melanoma accounts for 1%-3% of childhood malignancies. The incidence increased by 2.9% per year from 1973 to 2001 (Clin. Dermatol. 2009;27:529-36). Melanoma is seven times more common in the second decade than in the first, said Dr. Dyer. It is estimated that teens aged 15-19 years account for 73%-79% of cases.

Interestingly, there is a slight male predominance in young children that changes to a slight female predominance in older groups. Adolescent white girls with a history of ultraviolet exposure have the greatest melanoma risk, particularly on the trunk and lower extremities, he pointed out.

Approximately 30% of childhood melanomas arise with giant CMN. Lifetime risk appears to be bimodal, with the first peak in the first decade of life (usually in the first 5 years). It is estimated that 50%-70% arise before puberty. Head and neck melanomas are more common at age 1-4 years, while melanomas on the trunk are more common with increasing age. Early-life melanomas tend to be dermal with poorer outcomes. The second peak occurs in adulthood, reported Dr. Dyer.

Approximately 20% of childhood melanomas occur with other melanocytic lesions. Malignant melanomas from small CMN typically occur after puberty. These are more similar to adult malignant melanomas.

Childhood melanomas are associated with an increased incidence of amelanotic and nodular lesions. Risk factors include the following: intermittent intense sun exposure, tendency to sunburn, tendency to freckle, fair skin, blue/green eyes, blonde/red hair, xeroderma pigmentosum, giant CMN, dysplastic nevus syndrome, atypical nevi, a family history of malignant melanoma, and immunosuppression.

The risk of transformation for CMN is associated with size. Small to medium CMN (less than 20 cm) have a 1%-5% risk of transformation, while large/giant CMN (greater than 20 cm) have at least a 5%-10% risk; however, the risk may be as great as 20%.

Some studies suggest that 30%-75% of pediatric malignant melanoma originated in giant CMN, and one-third are fatal, reported Dr. Dyer. Excision does not completely eliminate the risk. In one study, 8% of patients developed extracutaneous malignant melanoma after CMN excision.

He noted that the risk of childhood melanoma is associated with immunodeficiency. The risk is six times greater if immunodeficiency is genetic in origin; the risk is four times greater if immunodeficiency is acquired.

The indications for sentinel lymph node biopsy in children are the same as in adults, he noted. Children have a higher incidence positive sentinel lymph node. However, this does not predict likelihood of recurrence or prognosis in children.

Surgical excision should use the same margins as in adults whenever possible. Thickness, ulceration, and stage at diagnosis are all prognostic factors.

Disclosures: Dr. Dyer reported having no conflicts of interest. SDEF and this news organization are owned by Elsevier.

Melanocytic nevi – spitz, congenital, and acquired – can pose diagnostic challenges for the pediatric dermatologist.

Dr. Jonathan A. Dyer offered a review of the latest literature on these pediatric melanomas at a seminar on women's and pediatric dermatology sponsored by Skin Disease Education Foundation.

Atypical Spitzoid Melanocytic Tumors (ASMT)

Data suggest that a positive sentinel lymph node biopsy (SLNB) in ASMT does not necessarily mean poor prognosis, according to Dr. Dyer, who is an assistant professor of clinical dermatology at the University of Missouri in Columbia.

Positive SLNB is not uncommon in ASMT, occurring in 28%-50% of cases. Nodal lesion morphology appears to be what matters – typical-appearing subcapsular cells versus ugly cells that replace a significant portion of the node (Am. J. Surg. Pathol. 2009;33:1386-95).

In a series of six published studies with more than 100 patients, no patient with ASMT and positive SLNB died of disease, he reported. However, follow-up was limited in many reports (median 10 months). Most malignant melanomas recur within 36 months.

In the Multicenter Selective Lymphadenectomy Trial (MSLT), the 5-year survival rate for patients younger than 19 years with malignant melanoma with a positive SLN was 68%, compared with 59% for adults.

Congenital Melanocytic Nevi (CMN)

A 19-year prospective study at Great Ormond Street Hospital in London provided a plethora of information on CMN (Br. J. Dermatol. 2009;160:143-50). The study included 349 families with CMN and 79 control families. Poor maternal health (threatened miscarriage, maternal hypertension, or severe nausea/vomiting) was associated with an increased incidence of CMN.

The researchers also found a possible positive association between maternal smoking and projected adult size and overall CMN incidence. CMN was more likely in females, while maternal freckling was independently associated with smaller projected adult size. A quarter of those with CMN had a second-degree relative with CMN, noted Dr. Dyer.

Furthermore, it is estimated that 5%-30% of patients with large CMN have asymptomatic neurocutaneous melanosis (NCM). NCM symptoms – increased intracranial pressure or seizures – typically occur in the first 2 years of life, he reported. It is possible for patients to convert from asymptomatic NCM to symptomatic but it is unclear how common it is (J. Clin. Oncol. 2009;27:e136).

Occasionally NCM symptoms are temporary or controllable; however, prognosis of symptomatic NCM is guarded. MRI is sensitive for NCM in the first 4-6 months but small deposits can be missed.

In terms of risk, satellites appear to be a major risk factor for NCM in patients with CMN. If there are no satellites, the risk of NCM is very low, summarized Dr. Dyer. In addition, CMN size appears to matter more than location. Based on several studies, the risk of NCM tends to be about 20%.

It has been suggested that up to two-thirds of pediatric patients with NCM go on to develop leptomeningeal tumors. Some patients may develop symptomatic NCM as a result, reported Dr. Dyer. An estimated 50%-90% of these patients die within 3 years of symptom onset. It is also estimated that 50% develop malignant melanoma of the central nervous system (Clin. Dermatol. 2009;27:529-36) .

Many CMN improve with time, he noted. In the Great Ormond Street study, for example, the majority of untreated lesions lightened during the follow-up period (Br. J. Dermatol. 2009;160:387-92). Surgery and the presence of satellites at birth were independently associated with darkening.

Satisfaction with surgery was high for patients with CMN of less than 20 cm and for those with facial lesions. However, satisfaction was reduced with increasing projected adult size. Girls were more likely to have surgery.

Treatment seemed to increase the darkening of remaining or later-developing nevi, independent of type, timing, or nevus. Tissue expansion appeared to be associated with increased satellite development, noted Dr. Dyer. Projected adult size was associated with satellite number but not treatment type.

Childhood Melanoma

Melanoma accounts for 1%-3% of childhood malignancies. The incidence increased by 2.9% per year from 1973 to 2001 (Clin. Dermatol. 2009;27:529-36). Melanoma is seven times more common in the second decade than in the first, said Dr. Dyer. It is estimated that teens aged 15-19 years account for 73%-79% of cases.

Interestingly, there is a slight male predominance in young children that changes to a slight female predominance in older groups. Adolescent white girls with a history of ultraviolet exposure have the greatest melanoma risk, particularly on the trunk and lower extremities, he pointed out.

Approximately 30% of childhood melanomas arise with giant CMN. Lifetime risk appears to be bimodal, with the first peak in the first decade of life (usually in the first 5 years). It is estimated that 50%-70% arise before puberty. Head and neck melanomas are more common at age 1-4 years, while melanomas on the trunk are more common with increasing age. Early-life melanomas tend to be dermal with poorer outcomes. The second peak occurs in adulthood, reported Dr. Dyer.

Approximately 20% of childhood melanomas occur with other melanocytic lesions. Malignant melanomas from small CMN typically occur after puberty. These are more similar to adult malignant melanomas.

Childhood melanomas are associated with an increased incidence of amelanotic and nodular lesions. Risk factors include the following: intermittent intense sun exposure, tendency to sunburn, tendency to freckle, fair skin, blue/green eyes, blonde/red hair, xeroderma pigmentosum, giant CMN, dysplastic nevus syndrome, atypical nevi, a family history of malignant melanoma, and immunosuppression.

The risk of transformation for CMN is associated with size. Small to medium CMN (less than 20 cm) have a 1%-5% risk of transformation, while large/giant CMN (greater than 20 cm) have at least a 5%-10% risk; however, the risk may be as great as 20%.

Some studies suggest that 30%-75% of pediatric malignant melanoma originated in giant CMN, and one-third are fatal, reported Dr. Dyer. Excision does not completely eliminate the risk. In one study, 8% of patients developed extracutaneous malignant melanoma after CMN excision.

He noted that the risk of childhood melanoma is associated with immunodeficiency. The risk is six times greater if immunodeficiency is genetic in origin; the risk is four times greater if immunodeficiency is acquired.

The indications for sentinel lymph node biopsy in children are the same as in adults, he noted. Children have a higher incidence positive sentinel lymph node. However, this does not predict likelihood of recurrence or prognosis in children.

Surgical excision should use the same margins as in adults whenever possible. Thickness, ulceration, and stage at diagnosis are all prognostic factors.

Disclosures: Dr. Dyer reported having no conflicts of interest. SDEF and this news organization are owned by Elsevier.

While dermoscopy can enhance the diagnosis of a number of skin conditions, it is especially useful in determining whether neoplasms should undergo biopsy.

"Patients are becoming aware of the technique and more and more are expecting their dermatologists to be skilled in its application," Dr. David L. Swanson said in an interview.

Photo courtesy Dr. David L. Swanson

However, fewer than half of academic dermatologists and less than a quarter of practicing dermatologists use dermoscopy in the United States, according to Dr. Swanson, chief of medical dermatology at the Mayo Clinic in Scottsdale, Ariz. In comparison, dermoscopy is taught to primary care physicians in Europe and Australia.

He discussed methods for assessing whether a lesion should be biopsied.

With the two-step pattern recognition method, the dermoscopist must first determine whether a neoplasm is a melanocytic proliferative one, such as a nevus or melanoma. "The reason that the first step is to consider nevi or melanomas is the importance of identifying the latter – especially melanomas that are not obvious with the naked eye," said Dr. Swanson at a seminar on women's and pediatric dermatology sponsored by Skin Disease Education Foundation.

If the lesion is melanocytic proliferative, the dermoscopist then applies the methods of interpretation for nevi or melanoma – such as pattern recognition or an algorithm. "If it isn't, then there are other diagnostic features that are used to lead to a clinical impression," he said.

The dermoscopy three-point rule has a high sensitivity for melanoma, he said. If a pigmented lesion has any two of the three criteria – atypical asymmetry, atypical pigment network, or blue-white structures – there is a likelihood of melanoma, and the lesion should be biopsied.

"The three-point rule is easier to learn and apply but as with all algorithms, there are a lot of exceptions to the rules. So one has to be willing to learn those exceptions and step out of the algorithm if they aren't certain," said Dr. Swanson. "One specific problem with the three-point method is that it doesn't take into account an atypical vasculature. Any dermoscopist using the three-point rule has to keep that in mind as an additional feature."

The seven-point algorithm – developed by Dr. Giuseppe Argenziano and others – is aimed at helping the novice dermoscopist. "It is a fairly reproducible method with very good specificity and sensitivity for making a decision to biopsy a melanocytic lesion. The three-point algorithm actually was derived from it as a method to simplify," said Dr. Swanson. "Most experienced dermoscopists only use algorithms occasionally, because with experience they become comfortable with pattern recognition."

The seven-point algorithm includes the criteria of the three-point rule, plus four minor criteria: streaks, regression pattern, irregular diffuse pigmentation, and irregular dot and globules.

Disclosures: Dr. Swanson reported having none. SDEF and this news organization are owned by Elsevier.

While dermoscopy can enhance the diagnosis of a number of skin conditions, it is especially useful in determining whether neoplasms should undergo biopsy.

"Patients are becoming aware of the technique and more and more are expecting their dermatologists to be skilled in its application," Dr. David L. Swanson said in an interview.

Photo courtesy Dr. David L. Swanson

However, fewer than half of academic dermatologists and less than a quarter of practicing dermatologists use dermoscopy in the United States, according to Dr. Swanson, chief of medical dermatology at the Mayo Clinic in Scottsdale, Ariz. In comparison, dermoscopy is taught to primary care physicians in Europe and Australia.

He discussed methods for assessing whether a lesion should be biopsied.

With the two-step pattern recognition method, the dermoscopist must first determine whether a neoplasm is a melanocytic proliferative one, such as a nevus or melanoma. "The reason that the first step is to consider nevi or melanomas is the importance of identifying the latter – especially melanomas that are not obvious with the naked eye," said Dr. Swanson at a seminar on women's and pediatric dermatology sponsored by Skin Disease Education Foundation.

If the lesion is melanocytic proliferative, the dermoscopist then applies the methods of interpretation for nevi or melanoma – such as pattern recognition or an algorithm. "If it isn't, then there are other diagnostic features that are used to lead to a clinical impression," he said.

The dermoscopy three-point rule has a high sensitivity for melanoma, he said. If a pigmented lesion has any two of the three criteria – atypical asymmetry, atypical pigment network, or blue-white structures – there is a likelihood of melanoma, and the lesion should be biopsied.

"The three-point rule is easier to learn and apply but as with all algorithms, there are a lot of exceptions to the rules. So one has to be willing to learn those exceptions and step out of the algorithm if they aren't certain," said Dr. Swanson. "One specific problem with the three-point method is that it doesn't take into account an atypical vasculature. Any dermoscopist using the three-point rule has to keep that in mind as an additional feature."

The seven-point algorithm – developed by Dr. Giuseppe Argenziano and others – is aimed at helping the novice dermoscopist. "It is a fairly reproducible method with very good specificity and sensitivity for making a decision to biopsy a melanocytic lesion. The three-point algorithm actually was derived from it as a method to simplify," said Dr. Swanson. "Most experienced dermoscopists only use algorithms occasionally, because with experience they become comfortable with pattern recognition."

The seven-point algorithm includes the criteria of the three-point rule, plus four minor criteria: streaks, regression pattern, irregular diffuse pigmentation, and irregular dot and globules.

Disclosures: Dr. Swanson reported having none. SDEF and this news organization are owned by Elsevier.

While dermoscopy can enhance the diagnosis of a number of skin conditions, it is especially useful in determining whether neoplasms should undergo biopsy.

"Patients are becoming aware of the technique and more and more are expecting their dermatologists to be skilled in its application," Dr. David L. Swanson said in an interview.

Photo courtesy Dr. David L. Swanson

However, fewer than half of academic dermatologists and less than a quarter of practicing dermatologists use dermoscopy in the United States, according to Dr. Swanson, chief of medical dermatology at the Mayo Clinic in Scottsdale, Ariz. In comparison, dermoscopy is taught to primary care physicians in Europe and Australia.

He discussed methods for assessing whether a lesion should be biopsied.

With the two-step pattern recognition method, the dermoscopist must first determine whether a neoplasm is a melanocytic proliferative one, such as a nevus or melanoma. "The reason that the first step is to consider nevi or melanomas is the importance of identifying the latter – especially melanomas that are not obvious with the naked eye," said Dr. Swanson at a seminar on women's and pediatric dermatology sponsored by Skin Disease Education Foundation.

If the lesion is melanocytic proliferative, the dermoscopist then applies the methods of interpretation for nevi or melanoma – such as pattern recognition or an algorithm. "If it isn't, then there are other diagnostic features that are used to lead to a clinical impression," he said.

The dermoscopy three-point rule has a high sensitivity for melanoma, he said. If a pigmented lesion has any two of the three criteria – atypical asymmetry, atypical pigment network, or blue-white structures – there is a likelihood of melanoma, and the lesion should be biopsied.

"The three-point rule is easier to learn and apply but as with all algorithms, there are a lot of exceptions to the rules. So one has to be willing to learn those exceptions and step out of the algorithm if they aren't certain," said Dr. Swanson. "One specific problem with the three-point method is that it doesn't take into account an atypical vasculature. Any dermoscopist using the three-point rule has to keep that in mind as an additional feature."

The seven-point algorithm – developed by Dr. Giuseppe Argenziano and others – is aimed at helping the novice dermoscopist. "It is a fairly reproducible method with very good specificity and sensitivity for making a decision to biopsy a melanocytic lesion. The three-point algorithm actually was derived from it as a method to simplify," said Dr. Swanson. "Most experienced dermoscopists only use algorithms occasionally, because with experience they become comfortable with pattern recognition."

The seven-point algorithm includes the criteria of the three-point rule, plus four minor criteria: streaks, regression pattern, irregular diffuse pigmentation, and irregular dot and globules.

Disclosures: Dr. Swanson reported having none. SDEF and this news organization are owned by Elsevier.

A cosmetics industry panel, prompted by recent criticism of sunscreen ingredients vitamin A and oxybenzone, plans to consider new safety data for the substances in 2011.

The Cosmetic Ingredient Review (CIR) Expert Panel added the ingredients to its re-review list at the group's Aug. 31 meeting.

©mark wragg/iStockphoto.com

The CIR team plans to re-review retinyl palmitate after the National Toxicology Program (NTP) releases a report on the vitamin A compound, expected in 2011. CIR Director Alan Andersen said the reviewers will use "caution that we do not proceed beyond the new data."

In its 2010 sunscreen report released in May, the Environmental Working Group offered its read on preliminary NTP data, suggesting that findings from rodent studies show retinyl palmitate is photocarcinogenic.

The organization advised consumers to avoid sunscreens containing both retinyl palmitate and oxybenzone, which it suggests is a potential hormone disrupter.

Looking to "dismiss the misinformation that sunscreens are not safe" and reinforce the idea they protect against sun damage and cancer, the American Academy of Dermatology issued a report, maintaining there is no evidence that retinyl palmitate in sunscreens causes cancer.

Dr. Steven Q. Wang of Memorial Sloan-Kettering Cancer Center, New York, and his colleagues evaluated the compound from several points of view (J. Amer. Acad. Dermatol. 2010 [doi:10.1016/j.jaad.2010.07.015]), and concluded that "there is no convincing evidence" that retinyl palmitate, a form of vitamin A, is carcinogenic in sunscreens" (see "Editorial Refutes EWG's Sunscreen Finding").

The council, with support from FDA and the Consumer Federation of America, established CIR in 1976 to review and assesses the safety of ingredients used in cosmetics in an open, unbiased, and expert manner, and publishes the results in peer-reviewed scientific literature, according to CIR's website.

The CIR panel will re-review seven other ingredient groups in 2011. Typically the group considers rereviewing ingredients every 15 years, as well as any substances that it feels should be re-examined on account of emerging science or public debate.

Hair colorants HC Red No. 1 and 4-chlororesorcinol both will receive another look next year, as well as foaming agent cocomide DEA and preservatives glutaral and methyldibromo glutaronitrile.

Ingredients reviewed in 1996 that the panel will not review in 2011 include butoxyethanol, dibutyl adipate, di-t-butylhydroquinone, disperse yellow 3 and sodium m-nitrobenzenesulfonate.

Not all ingredients on priority lists are reviewed by the panel. Ingredients from the 2009 and 2010 lists that are not being reviewed actively include amino acids, chamomile and talc. Amino acids have been "reprioritized," while work on chamomile and talc has been tabled, CIR says.

FDA currently is reviewing talc and talc-containing cosmetic products in the U.S. for asbestos contamination following reports of the carcinogen in cosmetics overseas. Its survey is expected to continue through 2010.

Disclosures: Skin & Allergy News Digital Network and "The Pink Sheet" are published by Elsevier.

A cosmetics industry panel, prompted by recent criticism of sunscreen ingredients vitamin A and oxybenzone, plans to consider new safety data for the substances in 2011.

The Cosmetic Ingredient Review (CIR) Expert Panel added the ingredients to its re-review list at the group's Aug. 31 meeting.

©mark wragg/iStockphoto.com

The CIR team plans to re-review retinyl palmitate after the National Toxicology Program (NTP) releases a report on the vitamin A compound, expected in 2011. CIR Director Alan Andersen said the reviewers will use "caution that we do not proceed beyond the new data."

In its 2010 sunscreen report released in May, the Environmental Working Group offered its read on preliminary NTP data, suggesting that findings from rodent studies show retinyl palmitate is photocarcinogenic.

The organization advised consumers to avoid sunscreens containing both retinyl palmitate and oxybenzone, which it suggests is a potential hormone disrupter.

Looking to "dismiss the misinformation that sunscreens are not safe" and reinforce the idea they protect against sun damage and cancer, the American Academy of Dermatology issued a report, maintaining there is no evidence that retinyl palmitate in sunscreens causes cancer.

Dr. Steven Q. Wang of Memorial Sloan-Kettering Cancer Center, New York, and his colleagues evaluated the compound from several points of view (J. Amer. Acad. Dermatol. 2010 [doi:10.1016/j.jaad.2010.07.015]), and concluded that "there is no convincing evidence" that retinyl palmitate, a form of vitamin A, is carcinogenic in sunscreens" (see "Editorial Refutes EWG's Sunscreen Finding").

The council, with support from FDA and the Consumer Federation of America, established CIR in 1976 to review and assesses the safety of ingredients used in cosmetics in an open, unbiased, and expert manner, and publishes the results in peer-reviewed scientific literature, according to CIR's website.

The CIR panel will re-review seven other ingredient groups in 2011. Typically the group considers rereviewing ingredients every 15 years, as well as any substances that it feels should be re-examined on account of emerging science or public debate.

Hair colorants HC Red No. 1 and 4-chlororesorcinol both will receive another look next year, as well as foaming agent cocomide DEA and preservatives glutaral and methyldibromo glutaronitrile.

Ingredients reviewed in 1996 that the panel will not review in 2011 include butoxyethanol, dibutyl adipate, di-t-butylhydroquinone, disperse yellow 3 and sodium m-nitrobenzenesulfonate.

Not all ingredients on priority lists are reviewed by the panel. Ingredients from the 2009 and 2010 lists that are not being reviewed actively include amino acids, chamomile and talc. Amino acids have been "reprioritized," while work on chamomile and talc has been tabled, CIR says.

FDA currently is reviewing talc and talc-containing cosmetic products in the U.S. for asbestos contamination following reports of the carcinogen in cosmetics overseas. Its survey is expected to continue through 2010.

Disclosures: Skin & Allergy News Digital Network and "The Pink Sheet" are published by Elsevier.

A cosmetics industry panel, prompted by recent criticism of sunscreen ingredients vitamin A and oxybenzone, plans to consider new safety data for the substances in 2011.

The Cosmetic Ingredient Review (CIR) Expert Panel added the ingredients to its re-review list at the group's Aug. 31 meeting.

©mark wragg/iStockphoto.com

The CIR team plans to re-review retinyl palmitate after the National Toxicology Program (NTP) releases a report on the vitamin A compound, expected in 2011. CIR Director Alan Andersen said the reviewers will use "caution that we do not proceed beyond the new data."

In its 2010 sunscreen report released in May, the Environmental Working Group offered its read on preliminary NTP data, suggesting that findings from rodent studies show retinyl palmitate is photocarcinogenic.

The organization advised consumers to avoid sunscreens containing both retinyl palmitate and oxybenzone, which it suggests is a potential hormone disrupter.

Looking to "dismiss the misinformation that sunscreens are not safe" and reinforce the idea they protect against sun damage and cancer, the American Academy of Dermatology issued a report, maintaining there is no evidence that retinyl palmitate in sunscreens causes cancer.

Dr. Steven Q. Wang of Memorial Sloan-Kettering Cancer Center, New York, and his colleagues evaluated the compound from several points of view (J. Amer. Acad. Dermatol. 2010 [doi:10.1016/j.jaad.2010.07.015]), and concluded that "there is no convincing evidence" that retinyl palmitate, a form of vitamin A, is carcinogenic in sunscreens" (see "Editorial Refutes EWG's Sunscreen Finding").

The council, with support from FDA and the Consumer Federation of America, established CIR in 1976 to review and assesses the safety of ingredients used in cosmetics in an open, unbiased, and expert manner, and publishes the results in peer-reviewed scientific literature, according to CIR's website.

The CIR panel will re-review seven other ingredient groups in 2011. Typically the group considers rereviewing ingredients every 15 years, as well as any substances that it feels should be re-examined on account of emerging science or public debate.

Hair colorants HC Red No. 1 and 4-chlororesorcinol both will receive another look next year, as well as foaming agent cocomide DEA and preservatives glutaral and methyldibromo glutaronitrile.

Ingredients reviewed in 1996 that the panel will not review in 2011 include butoxyethanol, dibutyl adipate, di-t-butylhydroquinone, disperse yellow 3 and sodium m-nitrobenzenesulfonate.

Not all ingredients on priority lists are reviewed by the panel. Ingredients from the 2009 and 2010 lists that are not being reviewed actively include amino acids, chamomile and talc. Amino acids have been "reprioritized," while work on chamomile and talc has been tabled, CIR says.

FDA currently is reviewing talc and talc-containing cosmetic products in the U.S. for asbestos contamination following reports of the carcinogen in cosmetics overseas. Its survey is expected to continue through 2010.

Disclosures: Skin & Allergy News Digital Network and "The Pink Sheet" are published by Elsevier.

An intervention promoting the use of a “sunless” tanning product among women at a beach reduced their sunbathing behavior and sunburns acquired for the remainder of the summer, according to a report in the September issue of the Archives of Dermatology.

The intervention also had a long-term effect, as many of the women reported that they decreased their sunbathing and used the fake tanning product again the following summer, said Sherry L. Pagoto, Ph.D., of the University of Massachusetts Medical School, Worcester, and her associates

The researchers assessed the intervention in women who visited two public beaches in Massachusetts in June and July of 2006 and agreed to participate in a study of sunbathing. A total of 125 subjects at one beach were assigned to the intervention and 125 at the other beach served as a control group. The mean age was 31 years.

The intervention included completing a brief questionnaire on sunbathing behavior, receiving written and verbal instructions on the use of a sunless tanning product and free samples of the product, receiving a pamphlet about skin cancer, having their photograph taken with an instant UV-filtered camera to demonstrate sun damage on their skin, receiving free samples of sunscreen, and being strongly encouraged to use sunless tanning rather than sunbathing. The control subjects completed the questionnaire, had their picture taken with a regular instant camera, and were given free cosmetic samples unrelated to skin health.

All study subjects had a 2-month follow-up for assessment of the short-term effects of the intervention, as well as at 1 year for long-term assessment.

At short-term follow-up, women in the intervention group reported that they had reduced their sunbathing by 33%, compared with a 10% decrease reported by the control subjects. The intervention group also said they had acquired 73% fewer sunburns, compared with 37% fewer reported by the control subjects. In addition, the intervention group said they had increased their use of protective clothing by 32%, while the control group said they had done so by only 2%. All of these between-group differences were statistically significant.

At long-term follow-up, the intervention group still reported a significant decrease in sunbathing behavior and showed a significant increase in the use of sunless tanning products, compared with the control group. The differences in the number of sunburns and the use of protective clothing did not persist.

The use of sunscreen increased slightly in both groups at short-term follow-up, but the difference between groups was not significant. And the increased use of sunscreen did not persist the following year.

These findings suggest that “promoting sunless tanning to sunbathers in the context of a skin cancer prevention public health message may be helpful in reducing sunbathing and sunburns and in promoting the use of protective clothing,” Dr. Pagoto and her colleagues wrote (Arch. Dermatol. 2010;146:979-84).

“Physicians might be reluctant to recommend sunless tanning due to concerns that it might inadvertently reinforce the patient’s desire to be tan,” they noted. However, these results suggest that instead, physicians should encourage patients who sunbathe to consider safer alternatives such as sunless tanning.

This study was limited in that nearly half of the women who were approached to participate in the study refused to do so, which could have contributed to selection bias. Also, the outcome measures relied on self-report, which may have contributed to social desirability bias. Finally, studies on the safety of the long-term use of sunless tanning products are lacking, and the long-term effects on the epidermis of dihydroxyacetone, the principal component of such products, remain unknown, the investigators noted.

An intervention promoting the use of a “sunless” tanning product among women at a beach reduced their sunbathing behavior and sunburns acquired for the remainder of the summer, according to a report in the September issue of the Archives of Dermatology.

The intervention also had a long-term effect, as many of the women reported that they decreased their sunbathing and used the fake tanning product again the following summer, said Sherry L. Pagoto, Ph.D., of the University of Massachusetts Medical School, Worcester, and her associates

The researchers assessed the intervention in women who visited two public beaches in Massachusetts in June and July of 2006 and agreed to participate in a study of sunbathing. A total of 125 subjects at one beach were assigned to the intervention and 125 at the other beach served as a control group. The mean age was 31 years.

The intervention included completing a brief questionnaire on sunbathing behavior, receiving written and verbal instructions on the use of a sunless tanning product and free samples of the product, receiving a pamphlet about skin cancer, having their photograph taken with an instant UV-filtered camera to demonstrate sun damage on their skin, receiving free samples of sunscreen, and being strongly encouraged to use sunless tanning rather than sunbathing. The control subjects completed the questionnaire, had their picture taken with a regular instant camera, and were given free cosmetic samples unrelated to skin health.

All study subjects had a 2-month follow-up for assessment of the short-term effects of the intervention, as well as at 1 year for long-term assessment.

At short-term follow-up, women in the intervention group reported that they had reduced their sunbathing by 33%, compared with a 10% decrease reported by the control subjects. The intervention group also said they had acquired 73% fewer sunburns, compared with 37% fewer reported by the control subjects. In addition, the intervention group said they had increased their use of protective clothing by 32%, while the control group said they had done so by only 2%. All of these between-group differences were statistically significant.

At long-term follow-up, the intervention group still reported a significant decrease in sunbathing behavior and showed a significant increase in the use of sunless tanning products, compared with the control group. The differences in the number of sunburns and the use of protective clothing did not persist.

The use of sunscreen increased slightly in both groups at short-term follow-up, but the difference between groups was not significant. And the increased use of sunscreen did not persist the following year.

These findings suggest that “promoting sunless tanning to sunbathers in the context of a skin cancer prevention public health message may be helpful in reducing sunbathing and sunburns and in promoting the use of protective clothing,” Dr. Pagoto and her colleagues wrote (Arch. Dermatol. 2010;146:979-84).

“Physicians might be reluctant to recommend sunless tanning due to concerns that it might inadvertently reinforce the patient’s desire to be tan,” they noted. However, these results suggest that instead, physicians should encourage patients who sunbathe to consider safer alternatives such as sunless tanning.

This study was limited in that nearly half of the women who were approached to participate in the study refused to do so, which could have contributed to selection bias. Also, the outcome measures relied on self-report, which may have contributed to social desirability bias. Finally, studies on the safety of the long-term use of sunless tanning products are lacking, and the long-term effects on the epidermis of dihydroxyacetone, the principal component of such products, remain unknown, the investigators noted.

An intervention promoting the use of a “sunless” tanning product among women at a beach reduced their sunbathing behavior and sunburns acquired for the remainder of the summer, according to a report in the September issue of the Archives of Dermatology.

The intervention also had a long-term effect, as many of the women reported that they decreased their sunbathing and used the fake tanning product again the following summer, said Sherry L. Pagoto, Ph.D., of the University of Massachusetts Medical School, Worcester, and her associates

The researchers assessed the intervention in women who visited two public beaches in Massachusetts in June and July of 2006 and agreed to participate in a study of sunbathing. A total of 125 subjects at one beach were assigned to the intervention and 125 at the other beach served as a control group. The mean age was 31 years.

The intervention included completing a brief questionnaire on sunbathing behavior, receiving written and verbal instructions on the use of a sunless tanning product and free samples of the product, receiving a pamphlet about skin cancer, having their photograph taken with an instant UV-filtered camera to demonstrate sun damage on their skin, receiving free samples of sunscreen, and being strongly encouraged to use sunless tanning rather than sunbathing. The control subjects completed the questionnaire, had their picture taken with a regular instant camera, and were given free cosmetic samples unrelated to skin health.

All study subjects had a 2-month follow-up for assessment of the short-term effects of the intervention, as well as at 1 year for long-term assessment.

At short-term follow-up, women in the intervention group reported that they had reduced their sunbathing by 33%, compared with a 10% decrease reported by the control subjects. The intervention group also said they had acquired 73% fewer sunburns, compared with 37% fewer reported by the control subjects. In addition, the intervention group said they had increased their use of protective clothing by 32%, while the control group said they had done so by only 2%. All of these between-group differences were statistically significant.

At long-term follow-up, the intervention group still reported a significant decrease in sunbathing behavior and showed a significant increase in the use of sunless tanning products, compared with the control group. The differences in the number of sunburns and the use of protective clothing did not persist.

The use of sunscreen increased slightly in both groups at short-term follow-up, but the difference between groups was not significant. And the increased use of sunscreen did not persist the following year.

These findings suggest that “promoting sunless tanning to sunbathers in the context of a skin cancer prevention public health message may be helpful in reducing sunbathing and sunburns and in promoting the use of protective clothing,” Dr. Pagoto and her colleagues wrote (Arch. Dermatol. 2010;146:979-84).

“Physicians might be reluctant to recommend sunless tanning due to concerns that it might inadvertently reinforce the patient’s desire to be tan,” they noted. However, these results suggest that instead, physicians should encourage patients who sunbathe to consider safer alternatives such as sunless tanning.

This study was limited in that nearly half of the women who were approached to participate in the study refused to do so, which could have contributed to selection bias. Also, the outcome measures relied on self-report, which may have contributed to social desirability bias. Finally, studies on the safety of the long-term use of sunless tanning products are lacking, and the long-term effects on the epidermis of dihydroxyacetone, the principal component of such products, remain unknown, the investigators noted.

PASADENA, Calif. - Dermatologists tend to use too many different names for a single entity with a defined clinical spectrum - toxic erythema of chemotherapy.

“We have too many names for one disease,” and this complicates clinical communication and decisions about management, Dr. Jean Bolognia said at the annual meeting of the Pacific Dermatologic Association.

If dermatologists used the term “toxic erythema of chemotherapy” (TEC), they would improve discussions with hematologists, oncologists, and internists, said Dr. Bolognia, professor of dermatology at Yale University, New Haven, Conn. Other terms sometimes used in place of TEC include eccrine squamous syringometaplasia and epidermal dysmaturation. While some alternative terms may be histologically accurate, they can be confusing to nondermatologists as diagnoses.

The term TEC indicates that the patient is not having an allergic reaction or an infectious process. It tells clinicians that the dermatologic problem will resolve spontaneously but can recur if the patient again uses a similar or higher dosage of the drug that caused it, noted Dr. Bolognia.

Cytarabine (Ara C) and anthracyclines are “at the top of the list” of drugs associated with TEC, so patients with acute myelogenous leukemia commonly develop TEC. The liposomal form of doxorubicin is “kinder and gentler when it comes to your bone marrow and your hair, but is worse when it comes to producing TEC,” she said.

Other drugs most commonly associated with TEC include taxanes (often used to treat breast cancer), methotrexate, multikinase inhibitors, gemcitabine, clofarabine, pralatrexate, 5-fluorouracil (5-FU), and prodrugs that turn into 5-FU in the body (like capecitabine).

Busulfan, until recently, was an oral chemotherapeutic drug that caused nausea and vomiting, which lead to underdosing. Now that it is administered intravenously, it is more likely to give rise to TEC, she said. If called upon to evaluate a possible case of erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis in a patient who has received IV busulfan in the past several weeks, consider TEC.

Image courtesy of Dr. Jean Bolognia.

Clinically, signs and symptoms of TEC can occur a month or so after the drug is given. TEC appears as erythematous or violaceous patches or edematous plaques. “They’re going to appear on hands and feet, elbows and knees, axillae and groin, including the scrotum, and occasionally on the ears,” she said. When it’s severe, a good portion of the skin surface can have the appearance of a sunburn.

Once you know the distribution pattern for TEC bullae “you can make the diagnosis at the bedside,” she added.

The lesions are associated with pain and burning more than with pruritus, suggesting a toxic reaction. Their dusky hue can contribute to misdiagnoses, such as toxic erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis.

The lesions may become purpuric, especially in the setting of thrombocytopenia, leading to the misdiagnosis of vasculitis. Sterile bullae followed by erosions also develop within the plaques, followed by desquamation and spontaneous resolution regardless of the therapy chosen. Of note, the desquamation is dry on the palms and soles or elbows and knees, but is moist in the major body folds.

Dr. Bolognia said she would especially like to see dermatologists stop using the term “acral erythrodysesthesia,” or “hand-foot syndrome,” because patients often have additional sites of involvement and trying to explain the cutaneous findings in these areas can lead to erroneous diagnoses. For example, the lesions on the elbows and knees may be misdiagnosed as dermatitis or involvement of the axillae and groin as cutaneous candidiasis, even though the patient is already receiving voriconazole.

Image courtesy of Dr. Jean Bolognia.

“By simply saying you have TEC, you have a unifying diagnosis,” she said. “Histologic findings include atypia and apoptosis of keratinocytes, as well as some loss of polarity of epidermal cells and crowding of keratinocytes. There is vacuolar degeneration of the basal layer, which may lead the dermatopathologist to raise the possibility of erythema multiforme, Stevens-Johnson syndrome, or graft-versus-host disease.”

Additional findings include eccrine squamous syringometaplasia and eccrine hidradenitis. Distinguishing TEC from graft-versus-host disease or erythema multiforme/Stevens-Johnson syndrome superimposed upon chemotherapy-induced changes may be difficult histologically, but the dermatologist can do the clinicopathologic correlation and arrive at the diagnosis, she said. For example, on the palmar surface of the hands, a clinical clue to the diagnosis of TEC is accentuation of erythema and bullae within the creases of the digits, a finding not seen in the differential diagnoses.

Pseudocellulitis (or erysipeloid reaction) also falls within the spectrum of TEC. Large patches or plaques of burning erythema appear and tense bullae may develop. The bullae do not spontaneously slough, and there is no Nikolsky’s sign. Pseudocellulitis is seen primarily following exposure to gemcitabine, but also to clofarabine, a newer drug being used as a second- or third-line agent for leukemia.

Lastly, chemotherapy-induced eccrine hidradenitis clearly falls within the histologic spectrum of TEC, she said, but clinically there are some patients who have a Sweet’s syndrome–like presentation, and these could be categorized separately.

TEC can be misdiagnosed as several other entities including cellulitis, herpetic viral infections, vasculitis, graft-versus-host disease (especially when the patient also has diarrhea), or a hypersensitivity drug reaction. It is important to note that TEC can be a skin sign of systemic disease in that severe cutaneous disease can be associated with severe cytotoxicity of the bowel, leading to sepsis caused by GI flora, she said. The team caring for the patient should be made aware of this possibility.

Disclosures: Dr. Bolognia said she has no pertinent conflicts of interest.

PASADENA, Calif. - Dermatologists tend to use too many different names for a single entity with a defined clinical spectrum - toxic erythema of chemotherapy.

“We have too many names for one disease,” and this complicates clinical communication and decisions about management, Dr. Jean Bolognia said at the annual meeting of the Pacific Dermatologic Association.

If dermatologists used the term “toxic erythema of chemotherapy” (TEC), they would improve discussions with hematologists, oncologists, and internists, said Dr. Bolognia, professor of dermatology at Yale University, New Haven, Conn. Other terms sometimes used in place of TEC include eccrine squamous syringometaplasia and epidermal dysmaturation. While some alternative terms may be histologically accurate, they can be confusing to nondermatologists as diagnoses.

The term TEC indicates that the patient is not having an allergic reaction or an infectious process. It tells clinicians that the dermatologic problem will resolve spontaneously but can recur if the patient again uses a similar or higher dosage of the drug that caused it, noted Dr. Bolognia.

Cytarabine (Ara C) and anthracyclines are “at the top of the list” of drugs associated with TEC, so patients with acute myelogenous leukemia commonly develop TEC. The liposomal form of doxorubicin is “kinder and gentler when it comes to your bone marrow and your hair, but is worse when it comes to producing TEC,” she said.

Other drugs most commonly associated with TEC include taxanes (often used to treat breast cancer), methotrexate, multikinase inhibitors, gemcitabine, clofarabine, pralatrexate, 5-fluorouracil (5-FU), and prodrugs that turn into 5-FU in the body (like capecitabine).

Busulfan, until recently, was an oral chemotherapeutic drug that caused nausea and vomiting, which lead to underdosing. Now that it is administered intravenously, it is more likely to give rise to TEC, she said. If called upon to evaluate a possible case of erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis in a patient who has received IV busulfan in the past several weeks, consider TEC.

Image courtesy of Dr. Jean Bolognia.

Clinically, signs and symptoms of TEC can occur a month or so after the drug is given. TEC appears as erythematous or violaceous patches or edematous plaques. “They’re going to appear on hands and feet, elbows and knees, axillae and groin, including the scrotum, and occasionally on the ears,” she said. When it’s severe, a good portion of the skin surface can have the appearance of a sunburn.

Once you know the distribution pattern for TEC bullae “you can make the diagnosis at the bedside,” she added.

The lesions are associated with pain and burning more than with pruritus, suggesting a toxic reaction. Their dusky hue can contribute to misdiagnoses, such as toxic erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis.

The lesions may become purpuric, especially in the setting of thrombocytopenia, leading to the misdiagnosis of vasculitis. Sterile bullae followed by erosions also develop within the plaques, followed by desquamation and spontaneous resolution regardless of the therapy chosen. Of note, the desquamation is dry on the palms and soles or elbows and knees, but is moist in the major body folds.

Dr. Bolognia said she would especially like to see dermatologists stop using the term “acral erythrodysesthesia,” or “hand-foot syndrome,” because patients often have additional sites of involvement and trying to explain the cutaneous findings in these areas can lead to erroneous diagnoses. For example, the lesions on the elbows and knees may be misdiagnosed as dermatitis or involvement of the axillae and groin as cutaneous candidiasis, even though the patient is already receiving voriconazole.

Image courtesy of Dr. Jean Bolognia.

“By simply saying you have TEC, you have a unifying diagnosis,” she said. “Histologic findings include atypia and apoptosis of keratinocytes, as well as some loss of polarity of epidermal cells and crowding of keratinocytes. There is vacuolar degeneration of the basal layer, which may lead the dermatopathologist to raise the possibility of erythema multiforme, Stevens-Johnson syndrome, or graft-versus-host disease.”

Additional findings include eccrine squamous syringometaplasia and eccrine hidradenitis. Distinguishing TEC from graft-versus-host disease or erythema multiforme/Stevens-Johnson syndrome superimposed upon chemotherapy-induced changes may be difficult histologically, but the dermatologist can do the clinicopathologic correlation and arrive at the diagnosis, she said. For example, on the palmar surface of the hands, a clinical clue to the diagnosis of TEC is accentuation of erythema and bullae within the creases of the digits, a finding not seen in the differential diagnoses.

Pseudocellulitis (or erysipeloid reaction) also falls within the spectrum of TEC. Large patches or plaques of burning erythema appear and tense bullae may develop. The bullae do not spontaneously slough, and there is no Nikolsky’s sign. Pseudocellulitis is seen primarily following exposure to gemcitabine, but also to clofarabine, a newer drug being used as a second- or third-line agent for leukemia.

Lastly, chemotherapy-induced eccrine hidradenitis clearly falls within the histologic spectrum of TEC, she said, but clinically there are some patients who have a Sweet’s syndrome–like presentation, and these could be categorized separately.

TEC can be misdiagnosed as several other entities including cellulitis, herpetic viral infections, vasculitis, graft-versus-host disease (especially when the patient also has diarrhea), or a hypersensitivity drug reaction. It is important to note that TEC can be a skin sign of systemic disease in that severe cutaneous disease can be associated with severe cytotoxicity of the bowel, leading to sepsis caused by GI flora, she said. The team caring for the patient should be made aware of this possibility.

Disclosures: Dr. Bolognia said she has no pertinent conflicts of interest.

PASADENA, Calif. - Dermatologists tend to use too many different names for a single entity with a defined clinical spectrum - toxic erythema of chemotherapy.

“We have too many names for one disease,” and this complicates clinical communication and decisions about management, Dr. Jean Bolognia said at the annual meeting of the Pacific Dermatologic Association.

If dermatologists used the term “toxic erythema of chemotherapy” (TEC), they would improve discussions with hematologists, oncologists, and internists, said Dr. Bolognia, professor of dermatology at Yale University, New Haven, Conn. Other terms sometimes used in place of TEC include eccrine squamous syringometaplasia and epidermal dysmaturation. While some alternative terms may be histologically accurate, they can be confusing to nondermatologists as diagnoses.

The term TEC indicates that the patient is not having an allergic reaction or an infectious process. It tells clinicians that the dermatologic problem will resolve spontaneously but can recur if the patient again uses a similar or higher dosage of the drug that caused it, noted Dr. Bolognia.

Cytarabine (Ara C) and anthracyclines are “at the top of the list” of drugs associated with TEC, so patients with acute myelogenous leukemia commonly develop TEC. The liposomal form of doxorubicin is “kinder and gentler when it comes to your bone marrow and your hair, but is worse when it comes to producing TEC,” she said.

Other drugs most commonly associated with TEC include taxanes (often used to treat breast cancer), methotrexate, multikinase inhibitors, gemcitabine, clofarabine, pralatrexate, 5-fluorouracil (5-FU), and prodrugs that turn into 5-FU in the body (like capecitabine).

Busulfan, until recently, was an oral chemotherapeutic drug that caused nausea and vomiting, which lead to underdosing. Now that it is administered intravenously, it is more likely to give rise to TEC, she said. If called upon to evaluate a possible case of erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis in a patient who has received IV busulfan in the past several weeks, consider TEC.

Image courtesy of Dr. Jean Bolognia.

Clinically, signs and symptoms of TEC can occur a month or so after the drug is given. TEC appears as erythematous or violaceous patches or edematous plaques. “They’re going to appear on hands and feet, elbows and knees, axillae and groin, including the scrotum, and occasionally on the ears,” she said. When it’s severe, a good portion of the skin surface can have the appearance of a sunburn.

Once you know the distribution pattern for TEC bullae “you can make the diagnosis at the bedside,” she added.

The lesions are associated with pain and burning more than with pruritus, suggesting a toxic reaction. Their dusky hue can contribute to misdiagnoses, such as toxic erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis.

The lesions may become purpuric, especially in the setting of thrombocytopenia, leading to the misdiagnosis of vasculitis. Sterile bullae followed by erosions also develop within the plaques, followed by desquamation and spontaneous resolution regardless of the therapy chosen. Of note, the desquamation is dry on the palms and soles or elbows and knees, but is moist in the major body folds.

Dr. Bolognia said she would especially like to see dermatologists stop using the term “acral erythrodysesthesia,” or “hand-foot syndrome,” because patients often have additional sites of involvement and trying to explain the cutaneous findings in these areas can lead to erroneous diagnoses. For example, the lesions on the elbows and knees may be misdiagnosed as dermatitis or involvement of the axillae and groin as cutaneous candidiasis, even though the patient is already receiving voriconazole.

Image courtesy of Dr. Jean Bolognia.

“By simply saying you have TEC, you have a unifying diagnosis,” she said. “Histologic findings include atypia and apoptosis of keratinocytes, as well as some loss of polarity of epidermal cells and crowding of keratinocytes. There is vacuolar degeneration of the basal layer, which may lead the dermatopathologist to raise the possibility of erythema multiforme, Stevens-Johnson syndrome, or graft-versus-host disease.”

Additional findings include eccrine squamous syringometaplasia and eccrine hidradenitis. Distinguishing TEC from graft-versus-host disease or erythema multiforme/Stevens-Johnson syndrome superimposed upon chemotherapy-induced changes may be difficult histologically, but the dermatologist can do the clinicopathologic correlation and arrive at the diagnosis, she said. For example, on the palmar surface of the hands, a clinical clue to the diagnosis of TEC is accentuation of erythema and bullae within the creases of the digits, a finding not seen in the differential diagnoses.

Pseudocellulitis (or erysipeloid reaction) also falls within the spectrum of TEC. Large patches or plaques of burning erythema appear and tense bullae may develop. The bullae do not spontaneously slough, and there is no Nikolsky’s sign. Pseudocellulitis is seen primarily following exposure to gemcitabine, but also to clofarabine, a newer drug being used as a second- or third-line agent for leukemia.

Lastly, chemotherapy-induced eccrine hidradenitis clearly falls within the histologic spectrum of TEC, she said, but clinically there are some patients who have a Sweet’s syndrome–like presentation, and these could be categorized separately.

TEC can be misdiagnosed as several other entities including cellulitis, herpetic viral infections, vasculitis, graft-versus-host disease (especially when the patient also has diarrhea), or a hypersensitivity drug reaction. It is important to note that TEC can be a skin sign of systemic disease in that severe cutaneous disease can be associated with severe cytotoxicity of the bowel, leading to sepsis caused by GI flora, she said. The team caring for the patient should be made aware of this possibility.

Disclosures: Dr. Bolognia said she has no pertinent conflicts of interest.