Melanoma

The discovery of a genotype associated with a higher risk for cutaneous melanoma in young women could lead to development of an early screening test, according to findings from a pilot study.

Incidence of melanoma is higher among women than men younger than age 40, generally equivalent between men and women aged 40-50, and affects more men than women in people older than 50, according to data from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database.

Investigators proposed that modulation of estrogen levels through a MDM2 single nucleotide polymorphism (SNP) 309 might explain these epidemiologic differences. Dr. Elnaz F. Firoz, of New York University, and his associates assessed MDM2 SNP309 from DNA samples in a prospective study of 227 patients newly diagnosed with melanoma at New York University Medical Center (Clin. Cancer Res. 2009;15:2573-80).

They chose to evaluate this specific genetic polymorphism because, among other research findings, the presence of a specific G allele of MDM2 SNP309 was associated with earlier onset of colorectal cancer, non-small cell lung cancer, and squamous cell carcinoma of the head and neck, compared with patients lacking this allele (Int. J. Cancer 2006;119:718-21; J. Med. Genet. 2005;42:694-8).

Participants were enrolled between August 2002 and November 2006. The study patients were 98% white, a typical percentage for the melanoma population. In addition, the gender distribution in the study—59% men and 41% women—was representative of the melanoma population in the United States (SEER Cancer Statistics Review, 1975-2005).

Of the patients, 75% had stage I disease, 17% had stage II, and 8% had stage III. Median overall age at time of diagnosis was 58 years. However, women with the GG genotype MDM2 SNP309 were diagnosed a median 13 years younger, at 46 years, compared with women with either the TG or TT genotype (diagnosed at a median of 59 years). Median age at diagnosis for men was approximately equal regardless of genotype (60 years for GG, compared with 58 years for TG or TT).

Put another way, women with a GG genotype had a 3.9 times greater chance of being diagnosed before age 50, compared with women with TG or TT genotypes. The greatest likelihood of a diagnosis for women with the GG genotype was before age 40 (odds ratio, 4.6).

"The decrease in the odds ratio from 4.6 to 3.9 as the age cut point increased from age 40 to age 50 may reflect the fact that it is not uncommon for women to undergo menopause prior to the age of 50, but it is rare for this to occur prior to the age of 40," the authors wrote. "These findings, combined with the SEER epidemiologic observation that prior to the age of 40 melanoma is more common among women than men (but not after the age of 50), support the hypothesis that active estrogen signaling in combination with the GG genotype may contribute to melanoma onset in women."

The researchers also assessed histopathologic features of the melanoma tumors and found no associations between MDM2 or p53 genotypes and tumor thickness, histopathologic subtype, anatomic site, or tumor ulceration. In addition, they found no associations between these polymorphisms and recurrence or overall survival.

The lack of a control group of patients who were unaffected by melanoma and patient ancestry data were limitations of the study, as was not having information on patients' menopausal status at the time of diagnosis.

The discovery of a genotype associated with a higher risk for cutaneous melanoma in young women could lead to development of an early screening test, according to findings from a pilot study.

Incidence of melanoma is higher among women than men younger than age 40, generally equivalent between men and women aged 40-50, and affects more men than women in people older than 50, according to data from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database.

Investigators proposed that modulation of estrogen levels through a MDM2 single nucleotide polymorphism (SNP) 309 might explain these epidemiologic differences. Dr. Elnaz F. Firoz, of New York University, and his associates assessed MDM2 SNP309 from DNA samples in a prospective study of 227 patients newly diagnosed with melanoma at New York University Medical Center (Clin. Cancer Res. 2009;15:2573-80).

They chose to evaluate this specific genetic polymorphism because, among other research findings, the presence of a specific G allele of MDM2 SNP309 was associated with earlier onset of colorectal cancer, non-small cell lung cancer, and squamous cell carcinoma of the head and neck, compared with patients lacking this allele (Int. J. Cancer 2006;119:718-21; J. Med. Genet. 2005;42:694-8).

Participants were enrolled between August 2002 and November 2006. The study patients were 98% white, a typical percentage for the melanoma population. In addition, the gender distribution in the study—59% men and 41% women—was representative of the melanoma population in the United States (SEER Cancer Statistics Review, 1975-2005).

Of the patients, 75% had stage I disease, 17% had stage II, and 8% had stage III. Median overall age at time of diagnosis was 58 years. However, women with the GG genotype MDM2 SNP309 were diagnosed a median 13 years younger, at 46 years, compared with women with either the TG or TT genotype (diagnosed at a median of 59 years). Median age at diagnosis for men was approximately equal regardless of genotype (60 years for GG, compared with 58 years for TG or TT).

Put another way, women with a GG genotype had a 3.9 times greater chance of being diagnosed before age 50, compared with women with TG or TT genotypes. The greatest likelihood of a diagnosis for women with the GG genotype was before age 40 (odds ratio, 4.6).

"The decrease in the odds ratio from 4.6 to 3.9 as the age cut point increased from age 40 to age 50 may reflect the fact that it is not uncommon for women to undergo menopause prior to the age of 50, but it is rare for this to occur prior to the age of 40," the authors wrote. "These findings, combined with the SEER epidemiologic observation that prior to the age of 40 melanoma is more common among women than men (but not after the age of 50), support the hypothesis that active estrogen signaling in combination with the GG genotype may contribute to melanoma onset in women."

The researchers also assessed histopathologic features of the melanoma tumors and found no associations between MDM2 or p53 genotypes and tumor thickness, histopathologic subtype, anatomic site, or tumor ulceration. In addition, they found no associations between these polymorphisms and recurrence or overall survival.

The lack of a control group of patients who were unaffected by melanoma and patient ancestry data were limitations of the study, as was not having information on patients' menopausal status at the time of diagnosis.

The discovery of a genotype associated with a higher risk for cutaneous melanoma in young women could lead to development of an early screening test, according to findings from a pilot study.

Incidence of melanoma is higher among women than men younger than age 40, generally equivalent between men and women aged 40-50, and affects more men than women in people older than 50, according to data from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database.

Investigators proposed that modulation of estrogen levels through a MDM2 single nucleotide polymorphism (SNP) 309 might explain these epidemiologic differences. Dr. Elnaz F. Firoz, of New York University, and his associates assessed MDM2 SNP309 from DNA samples in a prospective study of 227 patients newly diagnosed with melanoma at New York University Medical Center (Clin. Cancer Res. 2009;15:2573-80).

They chose to evaluate this specific genetic polymorphism because, among other research findings, the presence of a specific G allele of MDM2 SNP309 was associated with earlier onset of colorectal cancer, non-small cell lung cancer, and squamous cell carcinoma of the head and neck, compared with patients lacking this allele (Int. J. Cancer 2006;119:718-21; J. Med. Genet. 2005;42:694-8).

Participants were enrolled between August 2002 and November 2006. The study patients were 98% white, a typical percentage for the melanoma population. In addition, the gender distribution in the study—59% men and 41% women—was representative of the melanoma population in the United States (SEER Cancer Statistics Review, 1975-2005).

Of the patients, 75% had stage I disease, 17% had stage II, and 8% had stage III. Median overall age at time of diagnosis was 58 years. However, women with the GG genotype MDM2 SNP309 were diagnosed a median 13 years younger, at 46 years, compared with women with either the TG or TT genotype (diagnosed at a median of 59 years). Median age at diagnosis for men was approximately equal regardless of genotype (60 years for GG, compared with 58 years for TG or TT).

Put another way, women with a GG genotype had a 3.9 times greater chance of being diagnosed before age 50, compared with women with TG or TT genotypes. The greatest likelihood of a diagnosis for women with the GG genotype was before age 40 (odds ratio, 4.6).

"The decrease in the odds ratio from 4.6 to 3.9 as the age cut point increased from age 40 to age 50 may reflect the fact that it is not uncommon for women to undergo menopause prior to the age of 50, but it is rare for this to occur prior to the age of 40," the authors wrote. "These findings, combined with the SEER epidemiologic observation that prior to the age of 40 melanoma is more common among women than men (but not after the age of 50), support the hypothesis that active estrogen signaling in combination with the GG genotype may contribute to melanoma onset in women."

The researchers also assessed histopathologic features of the melanoma tumors and found no associations between MDM2 or p53 genotypes and tumor thickness, histopathologic subtype, anatomic site, or tumor ulceration. In addition, they found no associations between these polymorphisms and recurrence or overall survival.

The lack of a control group of patients who were unaffected by melanoma and patient ancestry data were limitations of the study, as was not having information on patients' menopausal status at the time of diagnosis.

SAN FRANCISCO — Recent findings that risk behaviors for skin cancer are most prevalent among 18- to 29-year-olds will be used to create a road map for efforts to curb the rising incidence of melanoma, which has climbed by 4% per year for the past 3 decades.

"We've got enough data epidemiologically now to really see where efforts have to be focused," Dr. Darrell S. Rigel said at the annual meeting of the American Academy of Dermatology. "In the next 10-15 years, we can begin to make an impact on the incidence of melanoma."

Dr. Rigel cited the findings of a landmark study at Fox Chase Cancer Center in Philadelphia, where researchers analyzed trends in skin cancer risk behaviors among 28,235 adults in the 2005 National Health Interview Survey.

The majority of Americans engage in multiple skin cancer risk behaviors. The most common were infrequent use of sun-protective clothing and infrequent use of an SPF-15 or stronger sunscreen.

The prevalence of these two risky behaviors was greatest among 18- to 29-year-olds. So, too, were rates of the other skin cancer risk behaviors tracked in the study: use of indoor tanning, staying in the sun when outside on a sunny day, and getting a sunburn within the past year, said Dr. Rigel of New York University. Indeed, more than 80% of 18- to 29-year-olds reported two or more of these behaviors, and nearly half engaged in three or more (Am. J. Prev. Med. 2008;34:87-93).

A profile emerged of adults at highest risk for skin cancer based on modifiable behaviors: individuals who were younger, male, white, living in the Midwest, smokers, risky drinkers, less educated, and with less sun-sensitive skin. This profile could be particularly helpful in primary care settings, where surveys indicate rates of assessment for skin cancer risk behaviors are low because of time pressure.

A particularly noteworthy study finding was that individuals aged 40-64 years who reported never having had a total skin exam were more than one-third more likely to engage in multiple skin cancer risk behaviors, compared with their contemporaries who had had a screening skin exam. The Fox Chase investigators argued that this observation lends support to recent calls for the creation of a national melanoma screening program targeting all white men aged 50 and older for a whole-body skin screening exam (Arch. Dermatol. 2006;142:504-7).

The Fox Chase team found that although skin cancer risk behaviors were associated with greater levels of physical activity, which often takes place outdoors, higher skin cancer risk is also associated with being overweight or obese. In an accompanying editorial, Dr. Martin A. Weinstock observed that this finding sets the stage for a potential conflict between two worthy goals: preventing skin cancer and maintaining a healthy body weight (Am. J. Prev. Med. 2008;34:171-2).

This conflict can be minimized by promoting the "Slip! Slop! Slap!" public health message developed in Australia in the early 1980s, said Dr. Weinstock, professor of dermatology at Brown University, Providence, R.I.

'We've got enough data epidemiologically now to really see where efforts have to be focused.' DR. RIGEL

SAN FRANCISCO — Recent findings that risk behaviors for skin cancer are most prevalent among 18- to 29-year-olds will be used to create a road map for efforts to curb the rising incidence of melanoma, which has climbed by 4% per year for the past 3 decades.

"We've got enough data epidemiologically now to really see where efforts have to be focused," Dr. Darrell S. Rigel said at the annual meeting of the American Academy of Dermatology. "In the next 10-15 years, we can begin to make an impact on the incidence of melanoma."

Dr. Rigel cited the findings of a landmark study at Fox Chase Cancer Center in Philadelphia, where researchers analyzed trends in skin cancer risk behaviors among 28,235 adults in the 2005 National Health Interview Survey.

The majority of Americans engage in multiple skin cancer risk behaviors. The most common were infrequent use of sun-protective clothing and infrequent use of an SPF-15 or stronger sunscreen.

The prevalence of these two risky behaviors was greatest among 18- to 29-year-olds. So, too, were rates of the other skin cancer risk behaviors tracked in the study: use of indoor tanning, staying in the sun when outside on a sunny day, and getting a sunburn within the past year, said Dr. Rigel of New York University. Indeed, more than 80% of 18- to 29-year-olds reported two or more of these behaviors, and nearly half engaged in three or more (Am. J. Prev. Med. 2008;34:87-93).

A profile emerged of adults at highest risk for skin cancer based on modifiable behaviors: individuals who were younger, male, white, living in the Midwest, smokers, risky drinkers, less educated, and with less sun-sensitive skin. This profile could be particularly helpful in primary care settings, where surveys indicate rates of assessment for skin cancer risk behaviors are low because of time pressure.

A particularly noteworthy study finding was that individuals aged 40-64 years who reported never having had a total skin exam were more than one-third more likely to engage in multiple skin cancer risk behaviors, compared with their contemporaries who had had a screening skin exam. The Fox Chase investigators argued that this observation lends support to recent calls for the creation of a national melanoma screening program targeting all white men aged 50 and older for a whole-body skin screening exam (Arch. Dermatol. 2006;142:504-7).

The Fox Chase team found that although skin cancer risk behaviors were associated with greater levels of physical activity, which often takes place outdoors, higher skin cancer risk is also associated with being overweight or obese. In an accompanying editorial, Dr. Martin A. Weinstock observed that this finding sets the stage for a potential conflict between two worthy goals: preventing skin cancer and maintaining a healthy body weight (Am. J. Prev. Med. 2008;34:171-2).

This conflict can be minimized by promoting the "Slip! Slop! Slap!" public health message developed in Australia in the early 1980s, said Dr. Weinstock, professor of dermatology at Brown University, Providence, R.I.

'We've got enough data epidemiologically now to really see where efforts have to be focused.' DR. RIGEL

SAN FRANCISCO — Recent findings that risk behaviors for skin cancer are most prevalent among 18- to 29-year-olds will be used to create a road map for efforts to curb the rising incidence of melanoma, which has climbed by 4% per year for the past 3 decades.

"We've got enough data epidemiologically now to really see where efforts have to be focused," Dr. Darrell S. Rigel said at the annual meeting of the American Academy of Dermatology. "In the next 10-15 years, we can begin to make an impact on the incidence of melanoma."

Dr. Rigel cited the findings of a landmark study at Fox Chase Cancer Center in Philadelphia, where researchers analyzed trends in skin cancer risk behaviors among 28,235 adults in the 2005 National Health Interview Survey.

The majority of Americans engage in multiple skin cancer risk behaviors. The most common were infrequent use of sun-protective clothing and infrequent use of an SPF-15 or stronger sunscreen.

The prevalence of these two risky behaviors was greatest among 18- to 29-year-olds. So, too, were rates of the other skin cancer risk behaviors tracked in the study: use of indoor tanning, staying in the sun when outside on a sunny day, and getting a sunburn within the past year, said Dr. Rigel of New York University. Indeed, more than 80% of 18- to 29-year-olds reported two or more of these behaviors, and nearly half engaged in three or more (Am. J. Prev. Med. 2008;34:87-93).

A profile emerged of adults at highest risk for skin cancer based on modifiable behaviors: individuals who were younger, male, white, living in the Midwest, smokers, risky drinkers, less educated, and with less sun-sensitive skin. This profile could be particularly helpful in primary care settings, where surveys indicate rates of assessment for skin cancer risk behaviors are low because of time pressure.

A particularly noteworthy study finding was that individuals aged 40-64 years who reported never having had a total skin exam were more than one-third more likely to engage in multiple skin cancer risk behaviors, compared with their contemporaries who had had a screening skin exam. The Fox Chase investigators argued that this observation lends support to recent calls for the creation of a national melanoma screening program targeting all white men aged 50 and older for a whole-body skin screening exam (Arch. Dermatol. 2006;142:504-7).

The Fox Chase team found that although skin cancer risk behaviors were associated with greater levels of physical activity, which often takes place outdoors, higher skin cancer risk is also associated with being overweight or obese. In an accompanying editorial, Dr. Martin A. Weinstock observed that this finding sets the stage for a potential conflict between two worthy goals: preventing skin cancer and maintaining a healthy body weight (Am. J. Prev. Med. 2008;34:171-2).

This conflict can be minimized by promoting the "Slip! Slop! Slap!" public health message developed in Australia in the early 1980s, said Dr. Weinstock, professor of dermatology at Brown University, Providence, R.I.

'We've got enough data epidemiologically now to really see where efforts have to be focused.' DR. RIGEL

SAN FRANCISCO — Intralesional rituximab appears to be an effective and nontoxic therapeutic option for patients with multiple noncontiguous lesions of CD20-positive primary cutaneous B-cell lymphoma, according to Dr. Marco Ardigo.

Rituximab (Rituxanin North America and Japan; MabTheraelsewhere) is a chimeric monoclonal antibody directed against the CD20 antigen. It is often administered intravenously for the treatment of primary cutaneous B-cell lymphoma (CBCL). But the investigational use of intralesional rituximab has several compelling advantages: Notably, it does not produce systemic immunosuppression, and the cost is far lower because a much smaller amount of drug is used and prophylactic antibiotics are not required to prevent severe infections, Dr. Ardigo said at the annual meeting of the American Academy of Dermatology.

He reported on two patients with follicular CBCL and one with marginal zone CBCL whose multiple noncontiguous skin lesions made the prospect of local radiotherapy or surgical excision problematic. All three patients were free of systemic involvement. Their 15 nodular lesions up to 2.5 cm in diameter were treated with 20 mg of rituximab injected subcutaneously into each lesion three times per week, 1 week per month for 2 months. The maximum cumulative dose was 120 mg per lesion, in contrast to the usual intravenous regimen of 375 mg/m

Complete remission occurred by 2 months. The three patients have remained in remission through 10 months of ongoing follow-up.

No systemic side effects were noted, and no reduction in peripheral CD20-positive T cells occurred in the weeks following intralesional therapy. The only side effect reported was local pain during the injections, said Dr. Ardigo of the San Gallicano Dermatological Institute, Rome.

He noted that several other small case series have reported similarly favorable experiences with intralesional rituximab for primary CBCL, including one from the University of Zurich (Arch. Dermatol. 2000;136:374-8) and another from Geneva University (Br. J. Dermatol. 2006;155:1197-200).

Dr. Ardigo reported no financial conflicts of interest with commercial entities.

SAN FRANCISCO — Intralesional rituximab appears to be an effective and nontoxic therapeutic option for patients with multiple noncontiguous lesions of CD20-positive primary cutaneous B-cell lymphoma, according to Dr. Marco Ardigo.

Rituximab (Rituxanin North America and Japan; MabTheraelsewhere) is a chimeric monoclonal antibody directed against the CD20 antigen. It is often administered intravenously for the treatment of primary cutaneous B-cell lymphoma (CBCL). But the investigational use of intralesional rituximab has several compelling advantages: Notably, it does not produce systemic immunosuppression, and the cost is far lower because a much smaller amount of drug is used and prophylactic antibiotics are not required to prevent severe infections, Dr. Ardigo said at the annual meeting of the American Academy of Dermatology.

He reported on two patients with follicular CBCL and one with marginal zone CBCL whose multiple noncontiguous skin lesions made the prospect of local radiotherapy or surgical excision problematic. All three patients were free of systemic involvement. Their 15 nodular lesions up to 2.5 cm in diameter were treated with 20 mg of rituximab injected subcutaneously into each lesion three times per week, 1 week per month for 2 months. The maximum cumulative dose was 120 mg per lesion, in contrast to the usual intravenous regimen of 375 mg/m

Complete remission occurred by 2 months. The three patients have remained in remission through 10 months of ongoing follow-up.

No systemic side effects were noted, and no reduction in peripheral CD20-positive T cells occurred in the weeks following intralesional therapy. The only side effect reported was local pain during the injections, said Dr. Ardigo of the San Gallicano Dermatological Institute, Rome.

He noted that several other small case series have reported similarly favorable experiences with intralesional rituximab for primary CBCL, including one from the University of Zurich (Arch. Dermatol. 2000;136:374-8) and another from Geneva University (Br. J. Dermatol. 2006;155:1197-200).

Dr. Ardigo reported no financial conflicts of interest with commercial entities.

SAN FRANCISCO — Intralesional rituximab appears to be an effective and nontoxic therapeutic option for patients with multiple noncontiguous lesions of CD20-positive primary cutaneous B-cell lymphoma, according to Dr. Marco Ardigo.

Rituximab (Rituxanin North America and Japan; MabTheraelsewhere) is a chimeric monoclonal antibody directed against the CD20 antigen. It is often administered intravenously for the treatment of primary cutaneous B-cell lymphoma (CBCL). But the investigational use of intralesional rituximab has several compelling advantages: Notably, it does not produce systemic immunosuppression, and the cost is far lower because a much smaller amount of drug is used and prophylactic antibiotics are not required to prevent severe infections, Dr. Ardigo said at the annual meeting of the American Academy of Dermatology.

He reported on two patients with follicular CBCL and one with marginal zone CBCL whose multiple noncontiguous skin lesions made the prospect of local radiotherapy or surgical excision problematic. All three patients were free of systemic involvement. Their 15 nodular lesions up to 2.5 cm in diameter were treated with 20 mg of rituximab injected subcutaneously into each lesion three times per week, 1 week per month for 2 months. The maximum cumulative dose was 120 mg per lesion, in contrast to the usual intravenous regimen of 375 mg/m

Complete remission occurred by 2 months. The three patients have remained in remission through 10 months of ongoing follow-up.

No systemic side effects were noted, and no reduction in peripheral CD20-positive T cells occurred in the weeks following intralesional therapy. The only side effect reported was local pain during the injections, said Dr. Ardigo of the San Gallicano Dermatological Institute, Rome.

He noted that several other small case series have reported similarly favorable experiences with intralesional rituximab for primary CBCL, including one from the University of Zurich (Arch. Dermatol. 2000;136:374-8) and another from Geneva University (Br. J. Dermatol. 2006;155:1197-200).

Dr. Ardigo reported no financial conflicts of interest with commercial entities.

SAN FRANCISCO — Dermatologists and oncologists have long fretted over when to pull out the therapeutic big guns for patients with early-stage cutaneous T-cell lymphoma.

Gene expression profiling of lesional skin may provide the answer.

"We want to know who's going to progress in a high-risk way and who's not. And we're looking to see which patients will respond to which therapies. We think we can begin to do so by looking at some of these genes," Dr. Thomas S. Kupper said at the annual meeting of the American Academy of Dermatology.

The great majority of patients with stage IA and many with stage IB cutaneous T-cell lymphoma (CTCL) have indolent, skin-limited disease, but others have rapidly progressive and often fatal disease. Lesional skin gene expression profiling may eventually make it possible to employ, in proactive fashion, the more aggressive and toxic systemic therapies in selected high-risk patients with early-stage disease, according to Dr. Kupper, Thomas B. Fitzpatrick Professor of Dermatology at Harvard Medical School and chair of the department of dermatology at Brigham and Women's Hospital, Boston.

He and a multidisciplinary team profiled gene expression on 63 lesional skin biopsies from 62 patients with all stages of CTCL. Thirteen patients had stage IA disease—that is, limited patches and plaques over less than 10% of their body surface area—while 29 had stage IB CTCL, 8 had stage IIB, and 12 had stage III.

The investigators identified 593 markedly upregulated genes grouped within three distinct patterns or clusters of gene expression, with roughly one-third of patients falling within each cluster.

The dominant genes upregulated in cluster 1 included many genes involved in T-cell activation and the immune response, including the T-cell alpha and beta chains, interleukin-2 receptor, lymphocyte-specific protein kinase, CD8+ T-cell markers, tumor necrosis factor pathway genes, downstream members of the WNT signaling pathway, and several B-cell-related genes.

Cluster 2 was rich in upregulated genes involved in keratinocyte and epidermal differentiation and proliferation. All but two patients in cluster 2 had stage IA or IB disease. Cluster 2 patients were generally extremely treatment-responsive; indeed, all but three cluster 2 patients were maintained in remission or under good control with only topical therapies. The sole stage IIB patient in cluster 2 went into remission on PUVA alone.

Cluster 3 featured upregulation of several T-cell-specific genes as well as genes related to keratinocyte function. Like cluster 1, cluster 3 was distinguished by more aggressive, less treatment-responsive disease. Seven of 12 stage III patients fell into cluster 3, as did only 1 patient with IA disease.

During roughly 3 years of follow-up, there were seven deaths, three cases of disease progression despite systemic therapies, and one large-cell transformation.

None occurred in cluster 2 patients. In contrast, the event-free survival rate was 80% in cluster 3 and less than 60% in cluster 1. One cluster 1 patient with stage IA disease at the time of gene profiling progressed to large-cell transformation unresponsive to total skin electron beam therapy, denileukin diftitox (Ontak), and suberoylanilide hydroxamic acid.

Nine of 11 stage IB patients in cluster 2 were maintained on intermittent topical therapies. In contrast, the more difficult to treat stage IB patients tended to fall into clusters 1 and 3; indeed, 7 of 18 patients with IB CTCL in clusters 1 and 3 required systemic therapies after a variety of topical therapies failed. One stage IB patient in cluster 1 developed metastatic disease and died despite oral bexarotene, denileukin diftitox, total skin electron beam irradiation, interferon, photopheresis, and multiagent chemotherapy.

Prospective studies with larger numbers of CTCL patients will be required to characterize the gene profile clusters more fully and zero in on individual genes having particularly potent predictive power, Dr. Kupper said.

The gene profiling study was sponsored by the National Institutes of Health.

SAN FRANCISCO — Dermatologists and oncologists have long fretted over when to pull out the therapeutic big guns for patients with early-stage cutaneous T-cell lymphoma.

Gene expression profiling of lesional skin may provide the answer.

"We want to know who's going to progress in a high-risk way and who's not. And we're looking to see which patients will respond to which therapies. We think we can begin to do so by looking at some of these genes," Dr. Thomas S. Kupper said at the annual meeting of the American Academy of Dermatology.

The great majority of patients with stage IA and many with stage IB cutaneous T-cell lymphoma (CTCL) have indolent, skin-limited disease, but others have rapidly progressive and often fatal disease. Lesional skin gene expression profiling may eventually make it possible to employ, in proactive fashion, the more aggressive and toxic systemic therapies in selected high-risk patients with early-stage disease, according to Dr. Kupper, Thomas B. Fitzpatrick Professor of Dermatology at Harvard Medical School and chair of the department of dermatology at Brigham and Women's Hospital, Boston.

He and a multidisciplinary team profiled gene expression on 63 lesional skin biopsies from 62 patients with all stages of CTCL. Thirteen patients had stage IA disease—that is, limited patches and plaques over less than 10% of their body surface area—while 29 had stage IB CTCL, 8 had stage IIB, and 12 had stage III.

The investigators identified 593 markedly upregulated genes grouped within three distinct patterns or clusters of gene expression, with roughly one-third of patients falling within each cluster.

The dominant genes upregulated in cluster 1 included many genes involved in T-cell activation and the immune response, including the T-cell alpha and beta chains, interleukin-2 receptor, lymphocyte-specific protein kinase, CD8+ T-cell markers, tumor necrosis factor pathway genes, downstream members of the WNT signaling pathway, and several B-cell-related genes.

Cluster 2 was rich in upregulated genes involved in keratinocyte and epidermal differentiation and proliferation. All but two patients in cluster 2 had stage IA or IB disease. Cluster 2 patients were generally extremely treatment-responsive; indeed, all but three cluster 2 patients were maintained in remission or under good control with only topical therapies. The sole stage IIB patient in cluster 2 went into remission on PUVA alone.

Cluster 3 featured upregulation of several T-cell-specific genes as well as genes related to keratinocyte function. Like cluster 1, cluster 3 was distinguished by more aggressive, less treatment-responsive disease. Seven of 12 stage III patients fell into cluster 3, as did only 1 patient with IA disease.

During roughly 3 years of follow-up, there were seven deaths, three cases of disease progression despite systemic therapies, and one large-cell transformation.

None occurred in cluster 2 patients. In contrast, the event-free survival rate was 80% in cluster 3 and less than 60% in cluster 1. One cluster 1 patient with stage IA disease at the time of gene profiling progressed to large-cell transformation unresponsive to total skin electron beam therapy, denileukin diftitox (Ontak), and suberoylanilide hydroxamic acid.

Nine of 11 stage IB patients in cluster 2 were maintained on intermittent topical therapies. In contrast, the more difficult to treat stage IB patients tended to fall into clusters 1 and 3; indeed, 7 of 18 patients with IB CTCL in clusters 1 and 3 required systemic therapies after a variety of topical therapies failed. One stage IB patient in cluster 1 developed metastatic disease and died despite oral bexarotene, denileukin diftitox, total skin electron beam irradiation, interferon, photopheresis, and multiagent chemotherapy.

Prospective studies with larger numbers of CTCL patients will be required to characterize the gene profile clusters more fully and zero in on individual genes having particularly potent predictive power, Dr. Kupper said.

The gene profiling study was sponsored by the National Institutes of Health.

SAN FRANCISCO — Dermatologists and oncologists have long fretted over when to pull out the therapeutic big guns for patients with early-stage cutaneous T-cell lymphoma.

Gene expression profiling of lesional skin may provide the answer.

"We want to know who's going to progress in a high-risk way and who's not. And we're looking to see which patients will respond to which therapies. We think we can begin to do so by looking at some of these genes," Dr. Thomas S. Kupper said at the annual meeting of the American Academy of Dermatology.

The great majority of patients with stage IA and many with stage IB cutaneous T-cell lymphoma (CTCL) have indolent, skin-limited disease, but others have rapidly progressive and often fatal disease. Lesional skin gene expression profiling may eventually make it possible to employ, in proactive fashion, the more aggressive and toxic systemic therapies in selected high-risk patients with early-stage disease, according to Dr. Kupper, Thomas B. Fitzpatrick Professor of Dermatology at Harvard Medical School and chair of the department of dermatology at Brigham and Women's Hospital, Boston.

He and a multidisciplinary team profiled gene expression on 63 lesional skin biopsies from 62 patients with all stages of CTCL. Thirteen patients had stage IA disease—that is, limited patches and plaques over less than 10% of their body surface area—while 29 had stage IB CTCL, 8 had stage IIB, and 12 had stage III.

The investigators identified 593 markedly upregulated genes grouped within three distinct patterns or clusters of gene expression, with roughly one-third of patients falling within each cluster.

The dominant genes upregulated in cluster 1 included many genes involved in T-cell activation and the immune response, including the T-cell alpha and beta chains, interleukin-2 receptor, lymphocyte-specific protein kinase, CD8+ T-cell markers, tumor necrosis factor pathway genes, downstream members of the WNT signaling pathway, and several B-cell-related genes.

Cluster 2 was rich in upregulated genes involved in keratinocyte and epidermal differentiation and proliferation. All but two patients in cluster 2 had stage IA or IB disease. Cluster 2 patients were generally extremely treatment-responsive; indeed, all but three cluster 2 patients were maintained in remission or under good control with only topical therapies. The sole stage IIB patient in cluster 2 went into remission on PUVA alone.

Cluster 3 featured upregulation of several T-cell-specific genes as well as genes related to keratinocyte function. Like cluster 1, cluster 3 was distinguished by more aggressive, less treatment-responsive disease. Seven of 12 stage III patients fell into cluster 3, as did only 1 patient with IA disease.

During roughly 3 years of follow-up, there were seven deaths, three cases of disease progression despite systemic therapies, and one large-cell transformation.

None occurred in cluster 2 patients. In contrast, the event-free survival rate was 80% in cluster 3 and less than 60% in cluster 1. One cluster 1 patient with stage IA disease at the time of gene profiling progressed to large-cell transformation unresponsive to total skin electron beam therapy, denileukin diftitox (Ontak), and suberoylanilide hydroxamic acid.

Nine of 11 stage IB patients in cluster 2 were maintained on intermittent topical therapies. In contrast, the more difficult to treat stage IB patients tended to fall into clusters 1 and 3; indeed, 7 of 18 patients with IB CTCL in clusters 1 and 3 required systemic therapies after a variety of topical therapies failed. One stage IB patient in cluster 1 developed metastatic disease and died despite oral bexarotene, denileukin diftitox, total skin electron beam irradiation, interferon, photopheresis, and multiagent chemotherapy.

Prospective studies with larger numbers of CTCL patients will be required to characterize the gene profile clusters more fully and zero in on individual genes having particularly potent predictive power, Dr. Kupper said.

The gene profiling study was sponsored by the National Institutes of Health.

By Greg Feero, M.D.

The American Cancer Society and the National Cancer Institute estimate that 62,480 people in the United States will be diagnosed with melanoma this year, and that 8,420 people will die from it.

Although melanoma rates have risen steadily in recent decades, data from the Centers for Disease Control show that those rates are particularly high among young women, probably because of the increase in suntanning and use of tanning booths in that population.

Many public health campaigns have focused on exposure to ultraviolet light as a risk factor for melanoma. However, many melanomas occur in areas of the skin that are not exposed to high levels of sun, and many arise outside of previously existing nevi.

In general, the risk factors for melanoma include a history of severe sunburn, numbers of nevi, pale skin, red or blonde hair, light-colored eyes, freckles, history of dysplastic nevi or melanoma, exposure to sunny climates, age, gender, and of course, genetics.

For example, if you are a fair-skinned male living in Australia, your lifetime risk for developing melanoma may be as high as 4%. In the United States, one's lifetime risk of melanoma is about 1%, and this risk almost doubles with a family history of the disorder. If one has a family history of melanoma and a personal history of dysplastic nevi, one's risk for melanoma soars, so that someone with two relatives with melanoma and who has dysplastic nevi has an estimated 500-fold risk of developing a melanoma.

Dysplastic nevus syndrome is a distinct disorder that is inherited in an autosomal dominant manner. Dysplastic nevi are a precursor to malignant melanoma, though only about 5% of all melanomas arise from such high-risk settings.

Genetic testing in these high-risk cases is available but is not routinely recommended. Four loci—CDKN2A, CDK, ARF, and chromosome 1p22—have been associated with dysplastic nevus syndrome. The risk incurred by mutations in CDKN2A, which accounts for about 10%-40% of the families with dysplastic nevus syndrome, confers a roughly 76% lifetime risk of developing melanoma.

Findings from a recent study suggested some value in conducting genetic testing in these families by showing that individuals with a positive test result increased their self-screening beyond recommended levels. Of course, this could lead to more false-positive biopsies, but that may be a reasonable trade-off in this population. There is no indication to use this type of genetic testing in a screening setting, but taking a family history in routine care might identify those needing specialized—and potentially lifesaving—surveillance.

Over the last year or so, genome-wide association studies have begun to shed some light on the underpinnings of sporadic cases of melanoma. Some of the associations are not that surprising because genes that seem to be related to traits such as fair skin or eye color (ASIP, TYR, and TYRP1) turn up as melanoma risk factors.

More recently, an area on chromosome 20q11.22 that contains a number of potentially important genes has been identified.

As with most results from genome-wide association studies, the effect sizes are very small (odds ratio less than 2) but are highly significant. In addition, we are finding that seemingly unrelated disorders can share common genetic defects. A most striking example of this is the shared association found for melanoma, diabetes, and heart disease with the CDKN2A/2B genes.

What mechanistic relationship do these disorders share? Could it be a link though immune function?

It is increasingly likely that in a few years we will have more answers and perhaps be able to develop more effective treatments. In the meantime, advise your patients to cover up—especially when visiting Australia—and watch out for those who have a family history of this serious disorder.

Dr. Greg Feero is a family physician with a doctorate in human genetics from the University of Pittsburgh. He is a senior adviser for genomic medicine in the Office of the Director at the National Human Genome Research Institute.

By Greg Feero, M.D.

The American Cancer Society and the National Cancer Institute estimate that 62,480 people in the United States will be diagnosed with melanoma this year, and that 8,420 people will die from it.

Although melanoma rates have risen steadily in recent decades, data from the Centers for Disease Control show that those rates are particularly high among young women, probably because of the increase in suntanning and use of tanning booths in that population.

Many public health campaigns have focused on exposure to ultraviolet light as a risk factor for melanoma. However, many melanomas occur in areas of the skin that are not exposed to high levels of sun, and many arise outside of previously existing nevi.

In general, the risk factors for melanoma include a history of severe sunburn, numbers of nevi, pale skin, red or blonde hair, light-colored eyes, freckles, history of dysplastic nevi or melanoma, exposure to sunny climates, age, gender, and of course, genetics.

For example, if you are a fair-skinned male living in Australia, your lifetime risk for developing melanoma may be as high as 4%. In the United States, one's lifetime risk of melanoma is about 1%, and this risk almost doubles with a family history of the disorder. If one has a family history of melanoma and a personal history of dysplastic nevi, one's risk for melanoma soars, so that someone with two relatives with melanoma and who has dysplastic nevi has an estimated 500-fold risk of developing a melanoma.

Dysplastic nevus syndrome is a distinct disorder that is inherited in an autosomal dominant manner. Dysplastic nevi are a precursor to malignant melanoma, though only about 5% of all melanomas arise from such high-risk settings.

Genetic testing in these high-risk cases is available but is not routinely recommended. Four loci—CDKN2A, CDK, ARF, and chromosome 1p22—have been associated with dysplastic nevus syndrome. The risk incurred by mutations in CDKN2A, which accounts for about 10%-40% of the families with dysplastic nevus syndrome, confers a roughly 76% lifetime risk of developing melanoma.

Findings from a recent study suggested some value in conducting genetic testing in these families by showing that individuals with a positive test result increased their self-screening beyond recommended levels. Of course, this could lead to more false-positive biopsies, but that may be a reasonable trade-off in this population. There is no indication to use this type of genetic testing in a screening setting, but taking a family history in routine care might identify those needing specialized—and potentially lifesaving—surveillance.

Over the last year or so, genome-wide association studies have begun to shed some light on the underpinnings of sporadic cases of melanoma. Some of the associations are not that surprising because genes that seem to be related to traits such as fair skin or eye color (ASIP, TYR, and TYRP1) turn up as melanoma risk factors.

More recently, an area on chromosome 20q11.22 that contains a number of potentially important genes has been identified.

As with most results from genome-wide association studies, the effect sizes are very small (odds ratio less than 2) but are highly significant. In addition, we are finding that seemingly unrelated disorders can share common genetic defects. A most striking example of this is the shared association found for melanoma, diabetes, and heart disease with the CDKN2A/2B genes.

What mechanistic relationship do these disorders share? Could it be a link though immune function?

It is increasingly likely that in a few years we will have more answers and perhaps be able to develop more effective treatments. In the meantime, advise your patients to cover up—especially when visiting Australia—and watch out for those who have a family history of this serious disorder.

Dr. Greg Feero is a family physician with a doctorate in human genetics from the University of Pittsburgh. He is a senior adviser for genomic medicine in the Office of the Director at the National Human Genome Research Institute.

By Greg Feero, M.D.

The American Cancer Society and the National Cancer Institute estimate that 62,480 people in the United States will be diagnosed with melanoma this year, and that 8,420 people will die from it.

Although melanoma rates have risen steadily in recent decades, data from the Centers for Disease Control show that those rates are particularly high among young women, probably because of the increase in suntanning and use of tanning booths in that population.

Many public health campaigns have focused on exposure to ultraviolet light as a risk factor for melanoma. However, many melanomas occur in areas of the skin that are not exposed to high levels of sun, and many arise outside of previously existing nevi.

In general, the risk factors for melanoma include a history of severe sunburn, numbers of nevi, pale skin, red or blonde hair, light-colored eyes, freckles, history of dysplastic nevi or melanoma, exposure to sunny climates, age, gender, and of course, genetics.

For example, if you are a fair-skinned male living in Australia, your lifetime risk for developing melanoma may be as high as 4%. In the United States, one's lifetime risk of melanoma is about 1%, and this risk almost doubles with a family history of the disorder. If one has a family history of melanoma and a personal history of dysplastic nevi, one's risk for melanoma soars, so that someone with two relatives with melanoma and who has dysplastic nevi has an estimated 500-fold risk of developing a melanoma.

Dysplastic nevus syndrome is a distinct disorder that is inherited in an autosomal dominant manner. Dysplastic nevi are a precursor to malignant melanoma, though only about 5% of all melanomas arise from such high-risk settings.

Genetic testing in these high-risk cases is available but is not routinely recommended. Four loci—CDKN2A, CDK, ARF, and chromosome 1p22—have been associated with dysplastic nevus syndrome. The risk incurred by mutations in CDKN2A, which accounts for about 10%-40% of the families with dysplastic nevus syndrome, confers a roughly 76% lifetime risk of developing melanoma.

Findings from a recent study suggested some value in conducting genetic testing in these families by showing that individuals with a positive test result increased their self-screening beyond recommended levels. Of course, this could lead to more false-positive biopsies, but that may be a reasonable trade-off in this population. There is no indication to use this type of genetic testing in a screening setting, but taking a family history in routine care might identify those needing specialized—and potentially lifesaving—surveillance.

Over the last year or so, genome-wide association studies have begun to shed some light on the underpinnings of sporadic cases of melanoma. Some of the associations are not that surprising because genes that seem to be related to traits such as fair skin or eye color (ASIP, TYR, and TYRP1) turn up as melanoma risk factors.

More recently, an area on chromosome 20q11.22 that contains a number of potentially important genes has been identified.

As with most results from genome-wide association studies, the effect sizes are very small (odds ratio less than 2) but are highly significant. In addition, we are finding that seemingly unrelated disorders can share common genetic defects. A most striking example of this is the shared association found for melanoma, diabetes, and heart disease with the CDKN2A/2B genes.

What mechanistic relationship do these disorders share? Could it be a link though immune function?

It is increasingly likely that in a few years we will have more answers and perhaps be able to develop more effective treatments. In the meantime, advise your patients to cover up—especially when visiting Australia—and watch out for those who have a family history of this serious disorder.

Dr. Greg Feero is a family physician with a doctorate in human genetics from the University of Pittsburgh. He is a senior adviser for genomic medicine in the Office of the Director at the National Human Genome Research Institute.

SAN FRANCISCO — The prevalence of skin cancer screening among U.S. adults inched higher during the first half of this decade, according to the Centers for Disease Control and Prevention.

In 2000, one in seven adults said they had ever undergone a head-to-toe skin exam by a dermatologist or other physician. By 2005, this figure rose to one in six, Naheed A. Lakhani reported at the annual meeting of the American Academy of Dermatology.

Skin cancer screening appropriately was more common among groups at greater risk, including whites, individuals over age 50 years, and those with a personal or family history of skin cancer, noted Ms. Lakhani of the Coordinating Office for Global Health at the CDC.

She presented an analysis of data from the National Health Interview Survey conducted in 2000 and 2005. Each survey embraced a nationally representative sample composed of roughly 30,000 civilian noninstitutionalized adults.

In 2000, 15% of U.S. adults reported ever having had a total body skin screening exam given by a physician. By 2005, this figure had reached 17%. The prevalence of skin cancer screening was 16% among men and significantly higher at 18% in women, who in general are believed to be at higher risk because of their greater use of tanning beds.

Skin cancer screening prevalence was highest, at 69%, among individuals with a personal history of any form of skin cancer. People with a family history of melanoma were more than 2.4-fold more likely to have ever had a physician-administered total body skin exam, compared with individuals without such a history.

Those with a family history of nonmelanoma skin cancer were 1.76-fold more likely to have undergone a screening exam.

Nearly one in five white adults reported ever having been screened for skin cancer. That's a significantly higher rate than for other racial and ethnic groups. Screening prevalence rose with adults' education level, physical activity, number of sunburns in the past year, sun sensitivity, and frequency of using sunscreen and/or sun-protective clothing, she continued.

One in five Americans will develop skin cancer during their lifetime. Since 1985, the American Academy of Dermatology has offered skin screening exams conducted by academy members through the AAD Melanoma/Skin Cancer Screening Program. The American Cancer Society also recommends total body skin exams.

However, earlier this year, in a move criticized by many dermatologists, the U.S. Preventive Services Task Force concluded that insufficient evidence exists to recommend for or against routine skin cancer screening.

SAN FRANCISCO — The prevalence of skin cancer screening among U.S. adults inched higher during the first half of this decade, according to the Centers for Disease Control and Prevention.

In 2000, one in seven adults said they had ever undergone a head-to-toe skin exam by a dermatologist or other physician. By 2005, this figure rose to one in six, Naheed A. Lakhani reported at the annual meeting of the American Academy of Dermatology.

Skin cancer screening appropriately was more common among groups at greater risk, including whites, individuals over age 50 years, and those with a personal or family history of skin cancer, noted Ms. Lakhani of the Coordinating Office for Global Health at the CDC.

She presented an analysis of data from the National Health Interview Survey conducted in 2000 and 2005. Each survey embraced a nationally representative sample composed of roughly 30,000 civilian noninstitutionalized adults.

In 2000, 15% of U.S. adults reported ever having had a total body skin screening exam given by a physician. By 2005, this figure had reached 17%. The prevalence of skin cancer screening was 16% among men and significantly higher at 18% in women, who in general are believed to be at higher risk because of their greater use of tanning beds.

Skin cancer screening prevalence was highest, at 69%, among individuals with a personal history of any form of skin cancer. People with a family history of melanoma were more than 2.4-fold more likely to have ever had a physician-administered total body skin exam, compared with individuals without such a history.

Those with a family history of nonmelanoma skin cancer were 1.76-fold more likely to have undergone a screening exam.

Nearly one in five white adults reported ever having been screened for skin cancer. That's a significantly higher rate than for other racial and ethnic groups. Screening prevalence rose with adults' education level, physical activity, number of sunburns in the past year, sun sensitivity, and frequency of using sunscreen and/or sun-protective clothing, she continued.

One in five Americans will develop skin cancer during their lifetime. Since 1985, the American Academy of Dermatology has offered skin screening exams conducted by academy members through the AAD Melanoma/Skin Cancer Screening Program. The American Cancer Society also recommends total body skin exams.

However, earlier this year, in a move criticized by many dermatologists, the U.S. Preventive Services Task Force concluded that insufficient evidence exists to recommend for or against routine skin cancer screening.

SAN FRANCISCO — The prevalence of skin cancer screening among U.S. adults inched higher during the first half of this decade, according to the Centers for Disease Control and Prevention.

In 2000, one in seven adults said they had ever undergone a head-to-toe skin exam by a dermatologist or other physician. By 2005, this figure rose to one in six, Naheed A. Lakhani reported at the annual meeting of the American Academy of Dermatology.

Skin cancer screening appropriately was more common among groups at greater risk, including whites, individuals over age 50 years, and those with a personal or family history of skin cancer, noted Ms. Lakhani of the Coordinating Office for Global Health at the CDC.

She presented an analysis of data from the National Health Interview Survey conducted in 2000 and 2005. Each survey embraced a nationally representative sample composed of roughly 30,000 civilian noninstitutionalized adults.

In 2000, 15% of U.S. adults reported ever having had a total body skin screening exam given by a physician. By 2005, this figure had reached 17%. The prevalence of skin cancer screening was 16% among men and significantly higher at 18% in women, who in general are believed to be at higher risk because of their greater use of tanning beds.

Skin cancer screening prevalence was highest, at 69%, among individuals with a personal history of any form of skin cancer. People with a family history of melanoma were more than 2.4-fold more likely to have ever had a physician-administered total body skin exam, compared with individuals without such a history.

Those with a family history of nonmelanoma skin cancer were 1.76-fold more likely to have undergone a screening exam.

Nearly one in five white adults reported ever having been screened for skin cancer. That's a significantly higher rate than for other racial and ethnic groups. Screening prevalence rose with adults' education level, physical activity, number of sunburns in the past year, sun sensitivity, and frequency of using sunscreen and/or sun-protective clothing, she continued.

One in five Americans will develop skin cancer during their lifetime. Since 1985, the American Academy of Dermatology has offered skin screening exams conducted by academy members through the AAD Melanoma/Skin Cancer Screening Program. The American Cancer Society also recommends total body skin exams.

However, earlier this year, in a move criticized by many dermatologists, the U.S. Preventive Services Task Force concluded that insufficient evidence exists to recommend for or against routine skin cancer screening.

MAUI, HAWAII — A topical trolamine/sodium alginate emulsion resulted in significantly faster healing than topical antibiotics after a variety of common procedures without promoting bacterial resistance or causing contact dermatitis, according to Dr. Leon H. Kircik.

"We can utilize it in most of the simple procedures we perform every day: shave biopsies, cryosurgery, topical [5-fluorouracil], Mohs surgery. I think your patients will welcome having to wear a Band-Aid on their face for a couple days less," he said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

Dr. Kircik conducted an investigator-blinded randomized trial comparing twice-daily Biafine (trolamine/sodium alginate emulsion, Ortho-McNeil Pharmaceuticals Inc.) with twice-daily Polysporin ointment (bacitracin zinc and polymyxin B sulfate, Pfizer Inc.) for second-intention healing following Mohs micrographic surgery for nonmelanoma skin cancers on the face of 25 patients.

The Biafine-treated wound sites healed significantly faster. Mean wound size decreased from 112 mm₂ at baseline to 22.1 mm₂ at week 3 with complete healing in all patients by week 6. In contrast, the topical antibiotic-treated wounds averaged 102 mm₂ at baseline, 28.9 mm₂ at week 3, and 3.8 mm₂ at week 6. Two patients in the topical antibiotic group rated their wound treatment as ineffective at week 3.

The 13 patients in the Biafine arm were assessed as having significantly less erythema, erosion, and inflammation at week 3 than the 12 patients in the topical antibiotic arm.

Dr. Kircik has shown that Biafine speeded healing of shave biopsy sites among 15 patients in another study, and he also found that Biafine outperformed white petrolatum in reducing the marked skin irritation caused by 5-FU therapy for actinic keratoses in a 23-patient investigator-blinded trial. In none of his studies did a single Biafine-treated patient develop contact dermatitis.

Dr. Kircik noted that Dr. James Q. Del Rosso of the University of Nevada, Las Vegas, has shown in a randomized investigator-blinded trial that Biafine resulted in significantly faster healing of multiple cryotherapy-treated actinic keratoses than did a nonmedicated petrolatum-based ointment.

Biafine-treated sites on the dorsal hands were completely healed in a mean of 9 days, compared with 11 days in the control group in Dr. Del Rosso's study. Lesions on the dorsal forearms healed in 10 days with Biafine and 13 days with petrolatum. Those on the cheek healed completely in 9 days with Biafine, versus 11 days with petrolatum, and lesions on the forehead healed in 9 days with Biafine, compared with 13 days with petrolatum.

"You may say, '2 days, 3 days, what's the big deal?' But if you look back at the Valtrex [valacyclovir] trials for herpes simplex, the improvement in healing time was around a day, sometimes less. So, really, if you're helping your patients heal 2 or 3 days faster it's a big advantage for them," said Dr. Kircik, who is in private practice in Louisville, Ky., and is a member of the faculty at Indiana University, Indianapolis.

Biafine is widely used in Europe for the treatment of radiation dermatitis, which occurs in close to 90% of women undergoing radiation therapy for breast cancer. The skin complication usually begins in the third week of radiotherapy and peaks a week or two after the course of radiation is completed.

The progression is from erythema to inflammation to desquamation—a grade 3 complication—to skin necrosis and ulceration. Biafine has been shown to reduce the rate of progression to grade 3/4 toxicity, enabling patients to complete their cancer treatment without delays.

"The bottom line is radiation dermatitis is really not a dermatitis. It becomes a complex open wound at grades 3 and 4, and it has to be treated like an open wound—and that's where this topical agent comes into play," Dr. Kircik said.

Biafine is approved in the United States as a prescription medical device. In vitro studies have shown that trolamine/sodium alginate induces a 3- to 10-fold increase in macrophage proliferation. The macrophages, in turn, stimulate fibroblasts to promote epithelial cell multiplication and growth. The product contains demineralized water, which penetrates to the dermal layer within 1 hour of application, he explained.

Dr. Kircik uses Biafine routinely in numerous situations he encounters in daily clinical practice. "I'm really trying to get away from using topical antibiotics because of all we hear about bacterial resistance, and also the contact dermatitis problem," he said in an interview.

Dr. Kircik disclosed that he is a consultant to, and on the speakers bureau of, OrthoNeutrogena, which markets Biafine and is a division of Ortho-McNeil.

SDEF and this newspaper are owned by Elsevier.

ELSEVIER GLOBAL MEDICAL NEWS

Healing progression of a topical trolamine/sodium alginate emulsion-treated wound on a patient's left clavicle is shown from baseline to 1 month. PHOTOS COURTESY DR. LEON H. KIRCIK

MAUI, HAWAII — A topical trolamine/sodium alginate emulsion resulted in significantly faster healing than topical antibiotics after a variety of common procedures without promoting bacterial resistance or causing contact dermatitis, according to Dr. Leon H. Kircik.

"We can utilize it in most of the simple procedures we perform every day: shave biopsies, cryosurgery, topical [5-fluorouracil], Mohs surgery. I think your patients will welcome having to wear a Band-Aid on their face for a couple days less," he said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

Dr. Kircik conducted an investigator-blinded randomized trial comparing twice-daily Biafine (trolamine/sodium alginate emulsion, Ortho-McNeil Pharmaceuticals Inc.) with twice-daily Polysporin ointment (bacitracin zinc and polymyxin B sulfate, Pfizer Inc.) for second-intention healing following Mohs micrographic surgery for nonmelanoma skin cancers on the face of 25 patients.

The Biafine-treated wound sites healed significantly faster. Mean wound size decreased from 112 mm₂ at baseline to 22.1 mm₂ at week 3 with complete healing in all patients by week 6. In contrast, the topical antibiotic-treated wounds averaged 102 mm₂ at baseline, 28.9 mm₂ at week 3, and 3.8 mm₂ at week 6. Two patients in the topical antibiotic group rated their wound treatment as ineffective at week 3.

The 13 patients in the Biafine arm were assessed as having significantly less erythema, erosion, and inflammation at week 3 than the 12 patients in the topical antibiotic arm.

Dr. Kircik has shown that Biafine speeded healing of shave biopsy sites among 15 patients in another study, and he also found that Biafine outperformed white petrolatum in reducing the marked skin irritation caused by 5-FU therapy for actinic keratoses in a 23-patient investigator-blinded trial. In none of his studies did a single Biafine-treated patient develop contact dermatitis.

Dr. Kircik noted that Dr. James Q. Del Rosso of the University of Nevada, Las Vegas, has shown in a randomized investigator-blinded trial that Biafine resulted in significantly faster healing of multiple cryotherapy-treated actinic keratoses than did a nonmedicated petrolatum-based ointment.

Biafine-treated sites on the dorsal hands were completely healed in a mean of 9 days, compared with 11 days in the control group in Dr. Del Rosso's study. Lesions on the dorsal forearms healed in 10 days with Biafine and 13 days with petrolatum. Those on the cheek healed completely in 9 days with Biafine, versus 11 days with petrolatum, and lesions on the forehead healed in 9 days with Biafine, compared with 13 days with petrolatum.

"You may say, '2 days, 3 days, what's the big deal?' But if you look back at the Valtrex [valacyclovir] trials for herpes simplex, the improvement in healing time was around a day, sometimes less. So, really, if you're helping your patients heal 2 or 3 days faster it's a big advantage for them," said Dr. Kircik, who is in private practice in Louisville, Ky., and is a member of the faculty at Indiana University, Indianapolis.

Biafine is widely used in Europe for the treatment of radiation dermatitis, which occurs in close to 90% of women undergoing radiation therapy for breast cancer. The skin complication usually begins in the third week of radiotherapy and peaks a week or two after the course of radiation is completed.

The progression is from erythema to inflammation to desquamation—a grade 3 complication—to skin necrosis and ulceration. Biafine has been shown to reduce the rate of progression to grade 3/4 toxicity, enabling patients to complete their cancer treatment without delays.

"The bottom line is radiation dermatitis is really not a dermatitis. It becomes a complex open wound at grades 3 and 4, and it has to be treated like an open wound—and that's where this topical agent comes into play," Dr. Kircik said.

Biafine is approved in the United States as a prescription medical device. In vitro studies have shown that trolamine/sodium alginate induces a 3- to 10-fold increase in macrophage proliferation. The macrophages, in turn, stimulate fibroblasts to promote epithelial cell multiplication and growth. The product contains demineralized water, which penetrates to the dermal layer within 1 hour of application, he explained.

Dr. Kircik uses Biafine routinely in numerous situations he encounters in daily clinical practice. "I'm really trying to get away from using topical antibiotics because of all we hear about bacterial resistance, and also the contact dermatitis problem," he said in an interview.

Dr. Kircik disclosed that he is a consultant to, and on the speakers bureau of, OrthoNeutrogena, which markets Biafine and is a division of Ortho-McNeil.

SDEF and this newspaper are owned by Elsevier.

ELSEVIER GLOBAL MEDICAL NEWS

Healing progression of a topical trolamine/sodium alginate emulsion-treated wound on a patient's left clavicle is shown from baseline to 1 month. PHOTOS COURTESY DR. LEON H. KIRCIK

MAUI, HAWAII — A topical trolamine/sodium alginate emulsion resulted in significantly faster healing than topical antibiotics after a variety of common procedures without promoting bacterial resistance or causing contact dermatitis, according to Dr. Leon H. Kircik.

"We can utilize it in most of the simple procedures we perform every day: shave biopsies, cryosurgery, topical [5-fluorouracil], Mohs surgery. I think your patients will welcome having to wear a Band-Aid on their face for a couple days less," he said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

Dr. Kircik conducted an investigator-blinded randomized trial comparing twice-daily Biafine (trolamine/sodium alginate emulsion, Ortho-McNeil Pharmaceuticals Inc.) with twice-daily Polysporin ointment (bacitracin zinc and polymyxin B sulfate, Pfizer Inc.) for second-intention healing following Mohs micrographic surgery for nonmelanoma skin cancers on the face of 25 patients.

The Biafine-treated wound sites healed significantly faster. Mean wound size decreased from 112 mm₂ at baseline to 22.1 mm₂ at week 3 with complete healing in all patients by week 6. In contrast, the topical antibiotic-treated wounds averaged 102 mm₂ at baseline, 28.9 mm₂ at week 3, and 3.8 mm₂ at week 6. Two patients in the topical antibiotic group rated their wound treatment as ineffective at week 3.

The 13 patients in the Biafine arm were assessed as having significantly less erythema, erosion, and inflammation at week 3 than the 12 patients in the topical antibiotic arm.

Dr. Kircik has shown that Biafine speeded healing of shave biopsy sites among 15 patients in another study, and he also found that Biafine outperformed white petrolatum in reducing the marked skin irritation caused by 5-FU therapy for actinic keratoses in a 23-patient investigator-blinded trial. In none of his studies did a single Biafine-treated patient develop contact dermatitis.

Dr. Kircik noted that Dr. James Q. Del Rosso of the University of Nevada, Las Vegas, has shown in a randomized investigator-blinded trial that Biafine resulted in significantly faster healing of multiple cryotherapy-treated actinic keratoses than did a nonmedicated petrolatum-based ointment.

Biafine-treated sites on the dorsal hands were completely healed in a mean of 9 days, compared with 11 days in the control group in Dr. Del Rosso's study. Lesions on the dorsal forearms healed in 10 days with Biafine and 13 days with petrolatum. Those on the cheek healed completely in 9 days with Biafine, versus 11 days with petrolatum, and lesions on the forehead healed in 9 days with Biafine, compared with 13 days with petrolatum.

"You may say, '2 days, 3 days, what's the big deal?' But if you look back at the Valtrex [valacyclovir] trials for herpes simplex, the improvement in healing time was around a day, sometimes less. So, really, if you're helping your patients heal 2 or 3 days faster it's a big advantage for them," said Dr. Kircik, who is in private practice in Louisville, Ky., and is a member of the faculty at Indiana University, Indianapolis.

Biafine is widely used in Europe for the treatment of radiation dermatitis, which occurs in close to 90% of women undergoing radiation therapy for breast cancer. The skin complication usually begins in the third week of radiotherapy and peaks a week or two after the course of radiation is completed.

The progression is from erythema to inflammation to desquamation—a grade 3 complication—to skin necrosis and ulceration. Biafine has been shown to reduce the rate of progression to grade 3/4 toxicity, enabling patients to complete their cancer treatment without delays.

"The bottom line is radiation dermatitis is really not a dermatitis. It becomes a complex open wound at grades 3 and 4, and it has to be treated like an open wound—and that's where this topical agent comes into play," Dr. Kircik said.

Biafine is approved in the United States as a prescription medical device. In vitro studies have shown that trolamine/sodium alginate induces a 3- to 10-fold increase in macrophage proliferation. The macrophages, in turn, stimulate fibroblasts to promote epithelial cell multiplication and growth. The product contains demineralized water, which penetrates to the dermal layer within 1 hour of application, he explained.

Dr. Kircik uses Biafine routinely in numerous situations he encounters in daily clinical practice. "I'm really trying to get away from using topical antibiotics because of all we hear about bacterial resistance, and also the contact dermatitis problem," he said in an interview.

Dr. Kircik disclosed that he is a consultant to, and on the speakers bureau of, OrthoNeutrogena, which markets Biafine and is a division of Ortho-McNeil.

SDEF and this newspaper are owned by Elsevier.

ELSEVIER GLOBAL MEDICAL NEWS

Healing progression of a topical trolamine/sodium alginate emulsion-treated wound on a patient's left clavicle is shown from baseline to 1 month. PHOTOS COURTESY DR. LEON H. KIRCIK

SANTA BARBARA, CALIF. — Squamous cell carcinoma of the oral cavity, particularly of the tongue, is not a diagnosis seen only in smokers aged 65 and older, reports in the literature suggest.

"We're seeing a surge of cases among younger people," Dr. Janellen Smith said at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Current literature from around the world documents the story: a puzzling rise of oral squamous cell carcinoma (SCC) cases in people as young as their 20s, often in the absence of traditional risk factors such as years of smoking, tobacco chewing, or alcohol use.

Among the young as well as older patients, the tongue is the most common intraoral site for SCC, at 40% of newly diagnosed cases.

Theories abound as to what may be driving this increase of cancer cases, said Dr. Smith, professor of dermatology at the University of California, Irvine.

Marijuana use, chewing tobacco, and human papillomavirus are all considered potential contributors.

Factors predicting prognosis include stage of the cancer, tumor location, and whether the cancer has spread.

It is important is to diagnose SCC in its early stages, while it is treatable. The 5-year survival in cases diagnosed late "has not changed in years and years," and hovers around 50%. "As dermatologists, we are in a position to diagnose this early," she said.

"We know this is not lichen planus," she added, describing the rosy red macules and plaques of erythroplakia, a sign of SCC.

White patches and plaques of leukoplakia are other telltale signs.

Common early presentations are along the posterolateral border and the ventral surface of the tongue—regions of thin, nonkeratinized mucosa and saliva pooling, she said.

Studies show that such SCCs frequently drain to cervical nodes, 66% of which are positive at the time of diagnosis.

Although the precise cause of an uptick in cases is unknown, the theoretical involvement of HPV makes vaccination of young women all the more sensible, Dr. Smith said at a second lecture during a seminar held in Las Vegas and sponsored by Skin Disease Education Foundation.

"We are actually quite anxious to see that people get vaccinated," she said.

Dr. Smith reported no potential conflicts of interest regarding her lectures.

SDEF and this newspaper are owned by Elsevier.

SANTA BARBARA, CALIF. — Squamous cell carcinoma of the oral cavity, particularly of the tongue, is not a diagnosis seen only in smokers aged 65 and older, reports in the literature suggest.

"We're seeing a surge of cases among younger people," Dr. Janellen Smith said at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Current literature from around the world documents the story: a puzzling rise of oral squamous cell carcinoma (SCC) cases in people as young as their 20s, often in the absence of traditional risk factors such as years of smoking, tobacco chewing, or alcohol use.

Among the young as well as older patients, the tongue is the most common intraoral site for SCC, at 40% of newly diagnosed cases.

Theories abound as to what may be driving this increase of cancer cases, said Dr. Smith, professor of dermatology at the University of California, Irvine.

Marijuana use, chewing tobacco, and human papillomavirus are all considered potential contributors.

Factors predicting prognosis include stage of the cancer, tumor location, and whether the cancer has spread.

It is important is to diagnose SCC in its early stages, while it is treatable. The 5-year survival in cases diagnosed late "has not changed in years and years," and hovers around 50%. "As dermatologists, we are in a position to diagnose this early," she said.

"We know this is not lichen planus," she added, describing the rosy red macules and plaques of erythroplakia, a sign of SCC.

White patches and plaques of leukoplakia are other telltale signs.

Common early presentations are along the posterolateral border and the ventral surface of the tongue—regions of thin, nonkeratinized mucosa and saliva pooling, she said.

Studies show that such SCCs frequently drain to cervical nodes, 66% of which are positive at the time of diagnosis.

Although the precise cause of an uptick in cases is unknown, the theoretical involvement of HPV makes vaccination of young women all the more sensible, Dr. Smith said at a second lecture during a seminar held in Las Vegas and sponsored by Skin Disease Education Foundation.

"We are actually quite anxious to see that people get vaccinated," she said.

Dr. Smith reported no potential conflicts of interest regarding her lectures.

SDEF and this newspaper are owned by Elsevier.

SANTA BARBARA, CALIF. — Squamous cell carcinoma of the oral cavity, particularly of the tongue, is not a diagnosis seen only in smokers aged 65 and older, reports in the literature suggest.

"We're seeing a surge of cases among younger people," Dr. Janellen Smith said at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Current literature from around the world documents the story: a puzzling rise of oral squamous cell carcinoma (SCC) cases in people as young as their 20s, often in the absence of traditional risk factors such as years of smoking, tobacco chewing, or alcohol use.

Among the young as well as older patients, the tongue is the most common intraoral site for SCC, at 40% of newly diagnosed cases.

Theories abound as to what may be driving this increase of cancer cases, said Dr. Smith, professor of dermatology at the University of California, Irvine.

Marijuana use, chewing tobacco, and human papillomavirus are all considered potential contributors.

Factors predicting prognosis include stage of the cancer, tumor location, and whether the cancer has spread.

It is important is to diagnose SCC in its early stages, while it is treatable. The 5-year survival in cases diagnosed late "has not changed in years and years," and hovers around 50%. "As dermatologists, we are in a position to diagnose this early," she said.

"We know this is not lichen planus," she added, describing the rosy red macules and plaques of erythroplakia, a sign of SCC.

White patches and plaques of leukoplakia are other telltale signs.

Common early presentations are along the posterolateral border and the ventral surface of the tongue—regions of thin, nonkeratinized mucosa and saliva pooling, she said.

Studies show that such SCCs frequently drain to cervical nodes, 66% of which are positive at the time of diagnosis.

Although the precise cause of an uptick in cases is unknown, the theoretical involvement of HPV makes vaccination of young women all the more sensible, Dr. Smith said at a second lecture during a seminar held in Las Vegas and sponsored by Skin Disease Education Foundation.

"We are actually quite anxious to see that people get vaccinated," she said.

Dr. Smith reported no potential conflicts of interest regarding her lectures.

SDEF and this newspaper are owned by Elsevier.

SAN FRANCISCO — People who worked at outdoor summer jobs as teenagers for three years or more had twice the risk of developing malignant melanoma later in life as those who did not, according to a case-control study by Dr. Darrell S. Rigel.

Dr. Rigel, of New York University Medical Center, presented preliminary results of his study at the annual meeting of the American Academy of Dermatology.

The study identified six independent risk factors, each of which increased the risk of malignant melanoma between two- and threefold. In addition to the outdoor summer job, the other five were history of blistering sunburns, red or blonde hair, marked freckling of the upper back, a family history of melanoma, and a history of actinic keratoses.

The study involved 300 consecutive patients with malignant melanoma who were seen at Dr. Rigel's clinic. They were compared with 302 age- and gender-matched controls who were seen for acne, psoriasis, eczema, or other reasons unrelated to pigmented lesions. The average age of the patients was about 50 years, with a range from 18 years to the mid-70s.

Dr. Rigel and his colleagues evaluated all patients for the presence of 43 potential risk factors. Only six emerged as independent risk factors in the multivariate analysis.

In an interview, Dr. Rigel said there was at least one potential risk factor that was conspicuous by its absence from that list: The study found no increase in risk with increasing age. "The model tended to predict early on in life what was going to happen later in life," he said.

The lifetime risk of melanoma in the U.S. population is about 1.5%, Dr. Rigel said. The presence of any one of the six risk factors increased the lifetime risk to 3%-5%. The presence of two or more of the risk factors increases the lifetime risk 5–10 times over that of the general population. Those with three or more have a 10-fold to 20-fold increase in risk.

"You want to come up with a model that focuses as effectively as possible on those at high risk," Dr. Rigel said. "Eventually, if you think about it, these are not the models we want. We're using surrogates. We're using factors that are not really the cause. The cause is genetic susceptibility and exposure to UV. … I believe that 5 or 10 years from now we'll have a genetic screen for melanoma."

According to Dr. Rigel, this study carries an important message to primary-care physicians. "There's only 9,000 dermatologists [in the U.S.]. Only one-third of dermatologic disease is treated by dermatologists. That means two-thirds are going to [primary care physicians]. We want those melanomas to be detected early. So models like this may let the primary care physician also focus on who they should focus their efforts on."

Dr. Rigel disclosed having no relevant financial disclosures, and noted that the study was privately funded.

'The model tended to predict early on in life what was going to happen later in life.' DR. RIGEL

Teens with outdoor jobs for at least 3 summers double their melanoma risk. ©Reuben Schulz/iStockphoto.com

SAN FRANCISCO — People who worked at outdoor summer jobs as teenagers for three years or more had twice the risk of developing malignant melanoma later in life as those who did not, according to a case-control study by Dr. Darrell S. Rigel.

Dr. Rigel, of New York University Medical Center, presented preliminary results of his study at the annual meeting of the American Academy of Dermatology.

The study identified six independent risk factors, each of which increased the risk of malignant melanoma between two- and threefold. In addition to the outdoor summer job, the other five were history of blistering sunburns, red or blonde hair, marked freckling of the upper back, a family history of melanoma, and a history of actinic keratoses.

The study involved 300 consecutive patients with malignant melanoma who were seen at Dr. Rigel's clinic. They were compared with 302 age- and gender-matched controls who were seen for acne, psoriasis, eczema, or other reasons unrelated to pigmented lesions. The average age of the patients was about 50 years, with a range from 18 years to the mid-70s.

Dr. Rigel and his colleagues evaluated all patients for the presence of 43 potential risk factors. Only six emerged as independent risk factors in the multivariate analysis.

In an interview, Dr. Rigel said there was at least one potential risk factor that was conspicuous by its absence from that list: The study found no increase in risk with increasing age. "The model tended to predict early on in life what was going to happen later in life," he said.

The lifetime risk of melanoma in the U.S. population is about 1.5%, Dr. Rigel said. The presence of any one of the six risk factors increased the lifetime risk to 3%-5%. The presence of two or more of the risk factors increases the lifetime risk 5–10 times over that of the general population. Those with three or more have a 10-fold to 20-fold increase in risk.

"You want to come up with a model that focuses as effectively as possible on those at high risk," Dr. Rigel said. "Eventually, if you think about it, these are not the models we want. We're using surrogates. We're using factors that are not really the cause. The cause is genetic susceptibility and exposure to UV. … I believe that 5 or 10 years from now we'll have a genetic screen for melanoma."

According to Dr. Rigel, this study carries an important message to primary-care physicians. "There's only 9,000 dermatologists [in the U.S.]. Only one-third of dermatologic disease is treated by dermatologists. That means two-thirds are going to [primary care physicians]. We want those melanomas to be detected early. So models like this may let the primary care physician also focus on who they should focus their efforts on."

Dr. Rigel disclosed having no relevant financial disclosures, and noted that the study was privately funded.

'The model tended to predict early on in life what was going to happen later in life.' DR. RIGEL

Teens with outdoor jobs for at least 3 summers double their melanoma risk. ©Reuben Schulz/iStockphoto.com

SAN FRANCISCO — People who worked at outdoor summer jobs as teenagers for three years or more had twice the risk of developing malignant melanoma later in life as those who did not, according to a case-control study by Dr. Darrell S. Rigel.

Dr. Rigel, of New York University Medical Center, presented preliminary results of his study at the annual meeting of the American Academy of Dermatology.

The study identified six independent risk factors, each of which increased the risk of malignant melanoma between two- and threefold. In addition to the outdoor summer job, the other five were history of blistering sunburns, red or blonde hair, marked freckling of the upper back, a family history of melanoma, and a history of actinic keratoses.

The study involved 300 consecutive patients with malignant melanoma who were seen at Dr. Rigel's clinic. They were compared with 302 age- and gender-matched controls who were seen for acne, psoriasis, eczema, or other reasons unrelated to pigmented lesions. The average age of the patients was about 50 years, with a range from 18 years to the mid-70s.

Dr. Rigel and his colleagues evaluated all patients for the presence of 43 potential risk factors. Only six emerged as independent risk factors in the multivariate analysis.

In an interview, Dr. Rigel said there was at least one potential risk factor that was conspicuous by its absence from that list: The study found no increase in risk with increasing age. "The model tended to predict early on in life what was going to happen later in life," he said.

The lifetime risk of melanoma in the U.S. population is about 1.5%, Dr. Rigel said. The presence of any one of the six risk factors increased the lifetime risk to 3%-5%. The presence of two or more of the risk factors increases the lifetime risk 5–10 times over that of the general population. Those with three or more have a 10-fold to 20-fold increase in risk.

"You want to come up with a model that focuses as effectively as possible on those at high risk," Dr. Rigel said. "Eventually, if you think about it, these are not the models we want. We're using surrogates. We're using factors that are not really the cause. The cause is genetic susceptibility and exposure to UV. … I believe that 5 or 10 years from now we'll have a genetic screen for melanoma."

According to Dr. Rigel, this study carries an important message to primary-care physicians. "There's only 9,000 dermatologists [in the U.S.]. Only one-third of dermatologic disease is treated by dermatologists. That means two-thirds are going to [primary care physicians]. We want those melanomas to be detected early. So models like this may let the primary care physician also focus on who they should focus their efforts on."

Dr. Rigel disclosed having no relevant financial disclosures, and noted that the study was privately funded.

'The model tended to predict early on in life what was going to happen later in life.' DR. RIGEL

Teens with outdoor jobs for at least 3 summers double their melanoma risk. ©Reuben Schulz/iStockphoto.com

HOLLYWOOD, FLA. — The differential diagnosis and management of primary cutaneous lymphoma rely to a great extent on whether lesions appear on the leg or elsewhere, according to the first guidelines released by the National Comprehensive Cancer Network.

"Diffuse B-cell lymphoma on the leg often leads to death," Dr. Steven M. Horwitz said. In contrast, other forms of primary cutaneous lymphoma, including follicle center and marginal zone disease, generally are indolent, and a majority of patients survive a decade or more after diagnosis.

"One of the questions is: Why have a guideline? Why not just treat this like other lymphomas?" Dr. Horwitz said at the annual conference of the National Comprehensive Cancer Network (NCCN). "A take-home point is there are notable differences between cutaneous B-cell lymphomas that affect treatment."

The genesis of the first guidelines was an observational study that found 5-year survival was 94% for non-leg-type cutaneous lymphoma patients versus 52% for leg-type disease (J. Clin. Oncol. 2001;19:3602–10). "Keep in mind the leg patients tend to be older," Dr. Horwitz said. Another study by the European Organization for Research and Treatment of Cancer (EORTC) confirmed this overall survival disparity out to 11 years (Curr. Opin. Oncol. 2006;18:425–31).

Clinical presentation, pathology, imaging, and "more and more" immunophenotyping can aid diagnosis, he said. For example, primary cutaneous follicle center lymphoma (FCL) is more common than the deadlier primary cutaneous diffuse large B-cell lymphoma (DLBCL), leg type. "In lymphoma we are not shy about giving things really long names," said Dr. Horwitz of Memorial Sloan-Kettering Cancer Center, New York.

FCL is typically an erythematous nodule with smooth skin on top. "And it doesn't have to be a small lesion, even though it's indolent," Dr. Horwitz said. In addition, FCL has a predilection for the scalp and forehead and tends to grow slowly and spontaneously regress.

In contrast, DLBCL leg-type is associated with rapid growth and features frequent mitosis. "But be a little careful. It could be a pseudolymphoma. Just a high proliferation rate only does not automatically mean leg disease," said Dr. Horwitz.

Histopathology differences are outlined in the guidelines. It is essential that a pathologist with expertise in diagnosis of primary cutaneous B-cell lymphoma review all tumor slides. A punch, incisional, or excisional biopsy is recommended. "Shave biopsies we don't like because the infiltrate is dermal," said Dr. Horwitz, a member of the NCCN panel that developed the guidelines.

Also essential to differential diagnosis is an immunophenotyping panel. For example, "A CD5 positive result means it is probably a skin manifestation of a systemic lymphoma," Dr. Horwitz said. Primary cutaneous lymphoma is a definition of exclusion, diagnosed when there is no evidence of extracutaneous disease on complete staging with physical examination, CT, bone marrow biopsy, and/or PET scan.

Diagnostic methods "useful in certain circumstances" include peripheral blood flow cytometry, molecular genetic testing for antigen receptor gene rearrangements, and cytogenetics or fluorescent in situ hybridization assays.

Work-up is also divided into essential and sometimes useful strategies. Complete history and physical examination, including a complete skin exam, are essential, for example. "I know it slows you down, but you really want to get patients to take all their clothes off and look at all of their skin. Even ask them to take their socks off and examine their feet," Dr. Horwitz said.

Order a complete blood count with differential, comprehensive metabolic panel, lactase dehydrogenase assay, and test for hepatitis B, if treatment includes rituximab (Rituxan, Genenetch).

Essential imaging includes a chest/abdominal/pelvic CT scan. A PET-CT scan is useful in certain circumstances. Dr. Horwitz said, "If you really think the person has local disease, PET is probably better for finding evidence of extracutaneous disease."

A bone marrow biopsy is considered essential with DLBCL, leg type. It also is useful for patients with FCL but is optional if the patient has marginal zone lymphoma (MZL), the other major form of indolent primary cutaneous disease.

The NCCN guidelines include a section to identify appropriate candidates for localized radiation therapy. Solitary skin involvement, regional disease, and systemic disease are differentiated according to clinical judgment. For solitary or regional T1-T2 FCL and MZL disease, for example, "almost all patients will respond" to locoregional radiation therapy or excision, he said.

Dr. Horwitz is a consultant for Eisai, Genenetch Inc., Merck & Co., and Therakos. He also is on the speakers bureau for Merck and receives grant and research support from Allos Therapeutics, Genzyme Corp., and Gloucester Pharmaceuticals.

'I know it slows you down, but you really want to get patients to take all their clothes off and look at all of their skin.' DR. HORWITZ

HOLLYWOOD, FLA. — The differential diagnosis and management of primary cutaneous lymphoma rely to a great extent on whether lesions appear on the leg or elsewhere, according to the first guidelines released by the National Comprehensive Cancer Network.

"Diffuse B-cell lymphoma on the leg often leads to death," Dr. Steven M. Horwitz said. In contrast, other forms of primary cutaneous lymphoma, including follicle center and marginal zone disease, generally are indolent, and a majority of patients survive a decade or more after diagnosis.

"One of the questions is: Why have a guideline? Why not just treat this like other lymphomas?" Dr. Horwitz said at the annual conference of the National Comprehensive Cancer Network (NCCN). "A take-home point is there are notable differences between cutaneous B-cell lymphomas that affect treatment."

The genesis of the first guidelines was an observational study that found 5-year survival was 94% for non-leg-type cutaneous lymphoma patients versus 52% for leg-type disease (J. Clin. Oncol. 2001;19:3602–10). "Keep in mind the leg patients tend to be older," Dr. Horwitz said. Another study by the European Organization for Research and Treatment of Cancer (EORTC) confirmed this overall survival disparity out to 11 years (Curr. Opin. Oncol. 2006;18:425–31).

Clinical presentation, pathology, imaging, and "more and more" immunophenotyping can aid diagnosis, he said. For example, primary cutaneous follicle center lymphoma (FCL) is more common than the deadlier primary cutaneous diffuse large B-cell lymphoma (DLBCL), leg type. "In lymphoma we are not shy about giving things really long names," said Dr. Horwitz of Memorial Sloan-Kettering Cancer Center, New York.

FCL is typically an erythematous nodule with smooth skin on top. "And it doesn't have to be a small lesion, even though it's indolent," Dr. Horwitz said. In addition, FCL has a predilection for the scalp and forehead and tends to grow slowly and spontaneously regress.

In contrast, DLBCL leg-type is associated with rapid growth and features frequent mitosis. "But be a little careful. It could be a pseudolymphoma. Just a high proliferation rate only does not automatically mean leg disease," said Dr. Horwitz.

Histopathology differences are outlined in the guidelines. It is essential that a pathologist with expertise in diagnosis of primary cutaneous B-cell lymphoma review all tumor slides. A punch, incisional, or excisional biopsy is recommended. "Shave biopsies we don't like because the infiltrate is dermal," said Dr. Horwitz, a member of the NCCN panel that developed the guidelines.

Also essential to differential diagnosis is an immunophenotyping panel. For example, "A CD5 positive result means it is probably a skin manifestation of a systemic lymphoma," Dr. Horwitz said. Primary cutaneous lymphoma is a definition of exclusion, diagnosed when there is no evidence of extracutaneous disease on complete staging with physical examination, CT, bone marrow biopsy, and/or PET scan.

Diagnostic methods "useful in certain circumstances" include peripheral blood flow cytometry, molecular genetic testing for antigen receptor gene rearrangements, and cytogenetics or fluorescent in situ hybridization assays.

Work-up is also divided into essential and sometimes useful strategies. Complete history and physical examination, including a complete skin exam, are essential, for example. "I know it slows you down, but you really want to get patients to take all their clothes off and look at all of their skin. Even ask them to take their socks off and examine their feet," Dr. Horwitz said.

Order a complete blood count with differential, comprehensive metabolic panel, lactase dehydrogenase assay, and test for hepatitis B, if treatment includes rituximab (Rituxan, Genenetch).

Essential imaging includes a chest/abdominal/pelvic CT scan. A PET-CT scan is useful in certain circumstances. Dr. Horwitz said, "If you really think the person has local disease, PET is probably better for finding evidence of extracutaneous disease."

A bone marrow biopsy is considered essential with DLBCL, leg type. It also is useful for patients with FCL but is optional if the patient has marginal zone lymphoma (MZL), the other major form of indolent primary cutaneous disease.

The NCCN guidelines include a section to identify appropriate candidates for localized radiation therapy. Solitary skin involvement, regional disease, and systemic disease are differentiated according to clinical judgment. For solitary or regional T1-T2 FCL and MZL disease, for example, "almost all patients will respond" to locoregional radiation therapy or excision, he said.

Dr. Horwitz is a consultant for Eisai, Genenetch Inc., Merck & Co., and Therakos. He also is on the speakers bureau for Merck and receives grant and research support from Allos Therapeutics, Genzyme Corp., and Gloucester Pharmaceuticals.

'I know it slows you down, but you really want to get patients to take all their clothes off and look at all of their skin.' DR. HORWITZ

HOLLYWOOD, FLA. — The differential diagnosis and management of primary cutaneous lymphoma rely to a great extent on whether lesions appear on the leg or elsewhere, according to the first guidelines released by the National Comprehensive Cancer Network.

"Diffuse B-cell lymphoma on the leg often leads to death," Dr. Steven M. Horwitz said. In contrast, other forms of primary cutaneous lymphoma, including follicle center and marginal zone disease, generally are indolent, and a majority of patients survive a decade or more after diagnosis.

"One of the questions is: Why have a guideline? Why not just treat this like other lymphomas?" Dr. Horwitz said at the annual conference of the National Comprehensive Cancer Network (NCCN). "A take-home point is there are notable differences between cutaneous B-cell lymphomas that affect treatment."

The genesis of the first guidelines was an observational study that found 5-year survival was 94% for non-leg-type cutaneous lymphoma patients versus 52% for leg-type disease (J. Clin. Oncol. 2001;19:3602–10). "Keep in mind the leg patients tend to be older," Dr. Horwitz said. Another study by the European Organization for Research and Treatment of Cancer (EORTC) confirmed this overall survival disparity out to 11 years (Curr. Opin. Oncol. 2006;18:425–31).

Clinical presentation, pathology, imaging, and "more and more" immunophenotyping can aid diagnosis, he said. For example, primary cutaneous follicle center lymphoma (FCL) is more common than the deadlier primary cutaneous diffuse large B-cell lymphoma (DLBCL), leg type. "In lymphoma we are not shy about giving things really long names," said Dr. Horwitz of Memorial Sloan-Kettering Cancer Center, New York.

FCL is typically an erythematous nodule with smooth skin on top. "And it doesn't have to be a small lesion, even though it's indolent," Dr. Horwitz said. In addition, FCL has a predilection for the scalp and forehead and tends to grow slowly and spontaneously regress.

In contrast, DLBCL leg-type is associated with rapid growth and features frequent mitosis. "But be a little careful. It could be a pseudolymphoma. Just a high proliferation rate only does not automatically mean leg disease," said Dr. Horwitz.

Histopathology differences are outlined in the guidelines. It is essential that a pathologist with expertise in diagnosis of primary cutaneous B-cell lymphoma review all tumor slides. A punch, incisional, or excisional biopsy is recommended. "Shave biopsies we don't like because the infiltrate is dermal," said Dr. Horwitz, a member of the NCCN panel that developed the guidelines.

Also essential to differential diagnosis is an immunophenotyping panel. For example, "A CD5 positive result means it is probably a skin manifestation of a systemic lymphoma," Dr. Horwitz said. Primary cutaneous lymphoma is a definition of exclusion, diagnosed when there is no evidence of extracutaneous disease on complete staging with physical examination, CT, bone marrow biopsy, and/or PET scan.

Diagnostic methods "useful in certain circumstances" include peripheral blood flow cytometry, molecular genetic testing for antigen receptor gene rearrangements, and cytogenetics or fluorescent in situ hybridization assays.

Work-up is also divided into essential and sometimes useful strategies. Complete history and physical examination, including a complete skin exam, are essential, for example. "I know it slows you down, but you really want to get patients to take all their clothes off and look at all of their skin. Even ask them to take their socks off and examine their feet," Dr. Horwitz said.

Order a complete blood count with differential, comprehensive metabolic panel, lactase dehydrogenase assay, and test for hepatitis B, if treatment includes rituximab (Rituxan, Genenetch).

Essential imaging includes a chest/abdominal/pelvic CT scan. A PET-CT scan is useful in certain circumstances. Dr. Horwitz said, "If you really think the person has local disease, PET is probably better for finding evidence of extracutaneous disease."

A bone marrow biopsy is considered essential with DLBCL, leg type. It also is useful for patients with FCL but is optional if the patient has marginal zone lymphoma (MZL), the other major form of indolent primary cutaneous disease.

The NCCN guidelines include a section to identify appropriate candidates for localized radiation therapy. Solitary skin involvement, regional disease, and systemic disease are differentiated according to clinical judgment. For solitary or regional T1-T2 FCL and MZL disease, for example, "almost all patients will respond" to locoregional radiation therapy or excision, he said.

Dr. Horwitz is a consultant for Eisai, Genenetch Inc., Merck & Co., and Therakos. He also is on the speakers bureau for Merck and receives grant and research support from Allos Therapeutics, Genzyme Corp., and Gloucester Pharmaceuticals.

'I know it slows you down, but you really want to get patients to take all their clothes off and look at all of their skin.' DR. HORWITZ