Melanoma

CHICAGO — KIT gene mutations that are susceptible to imatinib occur in some acral and mucosal melanomas, opening up new therapeutic options for patients with melanoma, according to a study presented as a poster at the annual meeting of the American Society of Clinical Oncology.

KIT mutations were found in 23% of acral melanomas and 16% of mucosal melanomas, reported Dr. Michael C. Heinrich, professor of medicine at the Oregon Health and Science University, Portland, and his colleagues. The mutation frequency was greater among tumors of the anorectum, vulva, and vagina (44%) than among the head and neck (8%).

In contrast, KIT mutations accounted for only 2% of cutaneous melanomas and for 8% of conjunctival melanomas. No mutations were found in an additional 60 choroidal melanomas.

"Based on our study, approximately 40%-50% of all types of melanoma have an oncogenic mutation that could be treated with drugs that are or will be in clinical studies within the next 18 months," Dr. Heinrich said in an interview.

For the study, DNA from archival melanomas was amplified by polymerase-chain reaction (PCR) and the products were screened for mutations in KIT exons 11, 13, 17 (n = 189), BRAF exon 15 (n = 116), and NRAS exons 1 and 2 (n = 117). Mutations were confirmed by direct sequencing.

In addition, immunohistochemistry for CD117 (KIT) was performed on a subset of cases. Lastly, the researchers assessed increases in KIT copy number in specific melanoma subtypes using quantitative real-time PCR.

Six of seven KIT mutations identified were of the type predicted to be sensitive to imatinib (Gleevec). KIT mutations did not overlap with NRAS mutations—which were also common in acral and mucosal tumors—or with BRAF mutations, which were absent in mucosal tumors.

"In the not too distant future, we envision that advanced melanoma tumors would be routinely tested for these types of mutations and the results used to make clinical decisions about the best medical treatment. This would be similar to the existing breast cancer model where ER [estrogen receptor] and HER2 [human epidermal growth factor receptor 2] testing are routine pathology tests that are used to individualize treatment programs," said Dr. Heinrich.

Imatinib is indicated for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia, Philadelphia chromosome-positive acute lymphoblastic leukemia, myelodysplastic/myeloproliferative diseases, hypereosinophilic syndrome and/or chronic eosinophilic leukemia, dermatofibrosarcoma protuberans, and KIT-positive gastrointestinal stromal tumors.

Using a PCR-based assay, the researchers found that KIT was increased in acral and mucosal melanoma cases, though most of the tumors with increased KIT did not have a mutation. Extra KIT copies were not as common in cutaneous and conjunctival tumors. KIT (CD-117) expression was detected in 39% of 105 tumors; however, there was no correlation between CD-117 staining and tumor genotype. KIT mutations of the type known to be sensitive to imatinib do not necessarily correlate with either KIT copy number or CD-117 expression, the researchers noted.

The study was prompted by a recent rectal melanoma case in which a patient with a KIT mutation had a dramatic response to imatinib.

Dr. Heinrich reported that he has received research funding from Novartis and Pfizer Inc., is a consultant for Novartis, and has equity interest in MolecularMD. One of his coauthors has received research funding from Novartis and Pfizer and is a consultant for Novartis.

CHICAGO — KIT gene mutations that are susceptible to imatinib occur in some acral and mucosal melanomas, opening up new therapeutic options for patients with melanoma, according to a study presented as a poster at the annual meeting of the American Society of Clinical Oncology.

KIT mutations were found in 23% of acral melanomas and 16% of mucosal melanomas, reported Dr. Michael C. Heinrich, professor of medicine at the Oregon Health and Science University, Portland, and his colleagues. The mutation frequency was greater among tumors of the anorectum, vulva, and vagina (44%) than among the head and neck (8%).

In contrast, KIT mutations accounted for only 2% of cutaneous melanomas and for 8% of conjunctival melanomas. No mutations were found in an additional 60 choroidal melanomas.

"Based on our study, approximately 40%-50% of all types of melanoma have an oncogenic mutation that could be treated with drugs that are or will be in clinical studies within the next 18 months," Dr. Heinrich said in an interview.

For the study, DNA from archival melanomas was amplified by polymerase-chain reaction (PCR) and the products were screened for mutations in KIT exons 11, 13, 17 (n = 189), BRAF exon 15 (n = 116), and NRAS exons 1 and 2 (n = 117). Mutations were confirmed by direct sequencing.

In addition, immunohistochemistry for CD117 (KIT) was performed on a subset of cases. Lastly, the researchers assessed increases in KIT copy number in specific melanoma subtypes using quantitative real-time PCR.

Six of seven KIT mutations identified were of the type predicted to be sensitive to imatinib (Gleevec). KIT mutations did not overlap with NRAS mutations—which were also common in acral and mucosal tumors—or with BRAF mutations, which were absent in mucosal tumors.

"In the not too distant future, we envision that advanced melanoma tumors would be routinely tested for these types of mutations and the results used to make clinical decisions about the best medical treatment. This would be similar to the existing breast cancer model where ER [estrogen receptor] and HER2 [human epidermal growth factor receptor 2] testing are routine pathology tests that are used to individualize treatment programs," said Dr. Heinrich.

Imatinib is indicated for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia, Philadelphia chromosome-positive acute lymphoblastic leukemia, myelodysplastic/myeloproliferative diseases, hypereosinophilic syndrome and/or chronic eosinophilic leukemia, dermatofibrosarcoma protuberans, and KIT-positive gastrointestinal stromal tumors.

Using a PCR-based assay, the researchers found that KIT was increased in acral and mucosal melanoma cases, though most of the tumors with increased KIT did not have a mutation. Extra KIT copies were not as common in cutaneous and conjunctival tumors. KIT (CD-117) expression was detected in 39% of 105 tumors; however, there was no correlation between CD-117 staining and tumor genotype. KIT mutations of the type known to be sensitive to imatinib do not necessarily correlate with either KIT copy number or CD-117 expression, the researchers noted.

The study was prompted by a recent rectal melanoma case in which a patient with a KIT mutation had a dramatic response to imatinib.

Dr. Heinrich reported that he has received research funding from Novartis and Pfizer Inc., is a consultant for Novartis, and has equity interest in MolecularMD. One of his coauthors has received research funding from Novartis and Pfizer and is a consultant for Novartis.

CHICAGO — KIT gene mutations that are susceptible to imatinib occur in some acral and mucosal melanomas, opening up new therapeutic options for patients with melanoma, according to a study presented as a poster at the annual meeting of the American Society of Clinical Oncology.

KIT mutations were found in 23% of acral melanomas and 16% of mucosal melanomas, reported Dr. Michael C. Heinrich, professor of medicine at the Oregon Health and Science University, Portland, and his colleagues. The mutation frequency was greater among tumors of the anorectum, vulva, and vagina (44%) than among the head and neck (8%).

In contrast, KIT mutations accounted for only 2% of cutaneous melanomas and for 8% of conjunctival melanomas. No mutations were found in an additional 60 choroidal melanomas.

"Based on our study, approximately 40%-50% of all types of melanoma have an oncogenic mutation that could be treated with drugs that are or will be in clinical studies within the next 18 months," Dr. Heinrich said in an interview.

For the study, DNA from archival melanomas was amplified by polymerase-chain reaction (PCR) and the products were screened for mutations in KIT exons 11, 13, 17 (n = 189), BRAF exon 15 (n = 116), and NRAS exons 1 and 2 (n = 117). Mutations were confirmed by direct sequencing.

In addition, immunohistochemistry for CD117 (KIT) was performed on a subset of cases. Lastly, the researchers assessed increases in KIT copy number in specific melanoma subtypes using quantitative real-time PCR.

Six of seven KIT mutations identified were of the type predicted to be sensitive to imatinib (Gleevec). KIT mutations did not overlap with NRAS mutations—which were also common in acral and mucosal tumors—or with BRAF mutations, which were absent in mucosal tumors.

"In the not too distant future, we envision that advanced melanoma tumors would be routinely tested for these types of mutations and the results used to make clinical decisions about the best medical treatment. This would be similar to the existing breast cancer model where ER [estrogen receptor] and HER2 [human epidermal growth factor receptor 2] testing are routine pathology tests that are used to individualize treatment programs," said Dr. Heinrich.

Imatinib is indicated for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia, Philadelphia chromosome-positive acute lymphoblastic leukemia, myelodysplastic/myeloproliferative diseases, hypereosinophilic syndrome and/or chronic eosinophilic leukemia, dermatofibrosarcoma protuberans, and KIT-positive gastrointestinal stromal tumors.

Using a PCR-based assay, the researchers found that KIT was increased in acral and mucosal melanoma cases, though most of the tumors with increased KIT did not have a mutation. Extra KIT copies were not as common in cutaneous and conjunctival tumors. KIT (CD-117) expression was detected in 39% of 105 tumors; however, there was no correlation between CD-117 staining and tumor genotype. KIT mutations of the type known to be sensitive to imatinib do not necessarily correlate with either KIT copy number or CD-117 expression, the researchers noted.

The study was prompted by a recent rectal melanoma case in which a patient with a KIT mutation had a dramatic response to imatinib.

Dr. Heinrich reported that he has received research funding from Novartis and Pfizer Inc., is a consultant for Novartis, and has equity interest in MolecularMD. One of his coauthors has received research funding from Novartis and Pfizer and is a consultant for Novartis.

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

KYOTO, JAPAN — The use of sunless tanning products by women in the United States is on the rise, with the most cited reason by users being the topical products' safety as an alternative to sunbathing and tanning beds.

This is a most welcome trend. Increased public acceptance of sunless tanning products (STPs) holds the potential to cause a substantial reduction in skin cancer rates, Mary Jayne McIlwaine reported at an international investigative dermatology meeting.

"Despite the growing knowledge of the danger of sun exposure and UV tanning, our results suggest that a large proportion of the population still believes tanning is desirable and attractive. Until public opinion changes, it's important to provide the public with suitable ways to tan their skin without the dangers of UV exposure—such as STPs," she added at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

She surveyed 415 women, average age 28 years, regarding their tanning behaviors and beliefs. The women were queried in gyms, swimming pools, and university sororities and dining halls.

Forty-eight percent of respondents reported using STPs at least once in the past year. "That's a much higher percentage than in previous published studies. This suggests STP use may be increasing," according to Ms. McIlwaine, who is a medical student at Emory University in Atlanta.

Encouragingly, 35% of the STP users indicated they employed these "tan-in-a-can" products as at least a partial replacement for sunbathing, and 25% reported using STPs in lieu of tanning beds.

STPs appear to be more popular with younger women. Fifty-four percent of 18-to 25-year-olds reported using them within the past year, compared with 41% of those aged 26-40 years and 40% of respondents over the age of 40.

Only 14% of women with brown or black skin reported STP use, compared with 56% of those with very white/freckled skin and 54% with white/olive skin.

The survey results suggest that, in spite of the growing awareness of the dangers of UV tanning, core ideas regarding the desirability of the tanned look remain largely unchanged. Ninety-three percent of the survey respondents indicated they believe tanned skin is more attractive than untanned skin. Seventy-nine percent said that they feel better about themselves when they have a tan. Seventy-one percent of subjects reported sunbathing at least once during the past year, and 26% used a tanning bed.

Most STPs contain dihydroacetone, which reacts with amino acids in the stratum corneum to produce a temporary brown hue.

Respondents' top reasons for not using STPs were dislike of product color and streakiness. Thus, further technical improvements in product quality might be important in achieving greater public acceptance and more widespread use of STPs as a tool for skin cancer prevention, Ms. McIlwaine concluded.

"Tan-in-a-can" products appear to be more popular with younger women. Shane Wake

KYOTO, JAPAN — The use of sunless tanning products by women in the United States is on the rise, with the most cited reason by users being the topical products' safety as an alternative to sunbathing and tanning beds.

This is a most welcome trend. Increased public acceptance of sunless tanning products (STPs) holds the potential to cause a substantial reduction in skin cancer rates, Mary Jayne McIlwaine reported at an international investigative dermatology meeting.

"Despite the growing knowledge of the danger of sun exposure and UV tanning, our results suggest that a large proportion of the population still believes tanning is desirable and attractive. Until public opinion changes, it's important to provide the public with suitable ways to tan their skin without the dangers of UV exposure—such as STPs," she added at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

She surveyed 415 women, average age 28 years, regarding their tanning behaviors and beliefs. The women were queried in gyms, swimming pools, and university sororities and dining halls.

Forty-eight percent of respondents reported using STPs at least once in the past year. "That's a much higher percentage than in previous published studies. This suggests STP use may be increasing," according to Ms. McIlwaine, who is a medical student at Emory University in Atlanta.

Encouragingly, 35% of the STP users indicated they employed these "tan-in-a-can" products as at least a partial replacement for sunbathing, and 25% reported using STPs in lieu of tanning beds.

STPs appear to be more popular with younger women. Fifty-four percent of 18-to 25-year-olds reported using them within the past year, compared with 41% of those aged 26-40 years and 40% of respondents over the age of 40.

Only 14% of women with brown or black skin reported STP use, compared with 56% of those with very white/freckled skin and 54% with white/olive skin.

The survey results suggest that, in spite of the growing awareness of the dangers of UV tanning, core ideas regarding the desirability of the tanned look remain largely unchanged. Ninety-three percent of the survey respondents indicated they believe tanned skin is more attractive than untanned skin. Seventy-nine percent said that they feel better about themselves when they have a tan. Seventy-one percent of subjects reported sunbathing at least once during the past year, and 26% used a tanning bed.

Most STPs contain dihydroacetone, which reacts with amino acids in the stratum corneum to produce a temporary brown hue.

Respondents' top reasons for not using STPs were dislike of product color and streakiness. Thus, further technical improvements in product quality might be important in achieving greater public acceptance and more widespread use of STPs as a tool for skin cancer prevention, Ms. McIlwaine concluded.

"Tan-in-a-can" products appear to be more popular with younger women. Shane Wake

KYOTO, JAPAN — The use of sunless tanning products by women in the United States is on the rise, with the most cited reason by users being the topical products' safety as an alternative to sunbathing and tanning beds.

This is a most welcome trend. Increased public acceptance of sunless tanning products (STPs) holds the potential to cause a substantial reduction in skin cancer rates, Mary Jayne McIlwaine reported at an international investigative dermatology meeting.

"Despite the growing knowledge of the danger of sun exposure and UV tanning, our results suggest that a large proportion of the population still believes tanning is desirable and attractive. Until public opinion changes, it's important to provide the public with suitable ways to tan their skin without the dangers of UV exposure—such as STPs," she added at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

She surveyed 415 women, average age 28 years, regarding their tanning behaviors and beliefs. The women were queried in gyms, swimming pools, and university sororities and dining halls.

Forty-eight percent of respondents reported using STPs at least once in the past year. "That's a much higher percentage than in previous published studies. This suggests STP use may be increasing," according to Ms. McIlwaine, who is a medical student at Emory University in Atlanta.

Encouragingly, 35% of the STP users indicated they employed these "tan-in-a-can" products as at least a partial replacement for sunbathing, and 25% reported using STPs in lieu of tanning beds.

STPs appear to be more popular with younger women. Fifty-four percent of 18-to 25-year-olds reported using them within the past year, compared with 41% of those aged 26-40 years and 40% of respondents over the age of 40.

Only 14% of women with brown or black skin reported STP use, compared with 56% of those with very white/freckled skin and 54% with white/olive skin.

The survey results suggest that, in spite of the growing awareness of the dangers of UV tanning, core ideas regarding the desirability of the tanned look remain largely unchanged. Ninety-three percent of the survey respondents indicated they believe tanned skin is more attractive than untanned skin. Seventy-nine percent said that they feel better about themselves when they have a tan. Seventy-one percent of subjects reported sunbathing at least once during the past year, and 26% used a tanning bed.

Most STPs contain dihydroacetone, which reacts with amino acids in the stratum corneum to produce a temporary brown hue.

Respondents' top reasons for not using STPs were dislike of product color and streakiness. Thus, further technical improvements in product quality might be important in achieving greater public acceptance and more widespread use of STPs as a tool for skin cancer prevention, Ms. McIlwaine concluded.

"Tan-in-a-can" products appear to be more popular with younger women. Shane Wake

More young adults now say that they value the appearance of a tan than have said so in past years, and their increased use of indoor tanning reflects that attitude, according to Dr. June K. Robinson of Northwestern University, Chicago, and her associates.

Researchers surveyed 100 people who appeared to be aged 18-30 years, and were sitting or lying on a Chicago beach in July of last year, about their knowledge of, attitudes toward, and use of indoor tanning, and compared the results with telephone surveys of 1,000 Illinois residents conducted in 1988 and with 958 teenage and young adult Chicagoans in 1994.

The 38 men and 62 women in the present survey were matched for age and sex with 100 subjects in each earlier survey.

The knowledge that tanning can cause melanoma/skin cancer initially decreased from 42% in the 1988 survey to 38% in the 1994 survey but then increased to 87% in 2007, Dr. Robinson and her associates reported (Arch. Dermatol. 2008;144:484-8).

Nevertheless, they said, "in each successive interval, there was an almost equivalent increase in the perception that people looked better with a tan"—from 58% to 69% and finally to 81% in 2007.

Tanning bed use also rose from 1% in 1988 to 26% in 1994 and 27% in 2007.

In all years surveyed, respondents said that they got most of their information about the general safety of indoor tanning beds from their friends or social group (71%-75%) and half reported that they went to a tanning salon for the first time with their friends. Other sources of information included family (18%-21%) and tanning salon workers (23%-24%).

Adolescents and young adults said their most trusted source of information about indoor tanning was the family physician or dermatologist, but only 15% reported that they had ever discussed the issue with their physicians, Dr. Robinson and her associates found.

"Counseling young adult patients to cease indoor tanning represents an opportunity to prevent UV radiation exposure that may cause melanoma," they noted.

More young adults now say that they value the appearance of a tan than have said so in past years, and their increased use of indoor tanning reflects that attitude, according to Dr. June K. Robinson of Northwestern University, Chicago, and her associates.

Researchers surveyed 100 people who appeared to be aged 18-30 years, and were sitting or lying on a Chicago beach in July of last year, about their knowledge of, attitudes toward, and use of indoor tanning, and compared the results with telephone surveys of 1,000 Illinois residents conducted in 1988 and with 958 teenage and young adult Chicagoans in 1994.

The 38 men and 62 women in the present survey were matched for age and sex with 100 subjects in each earlier survey.

The knowledge that tanning can cause melanoma/skin cancer initially decreased from 42% in the 1988 survey to 38% in the 1994 survey but then increased to 87% in 2007, Dr. Robinson and her associates reported (Arch. Dermatol. 2008;144:484-8).

Nevertheless, they said, "in each successive interval, there was an almost equivalent increase in the perception that people looked better with a tan"—from 58% to 69% and finally to 81% in 2007.

Tanning bed use also rose from 1% in 1988 to 26% in 1994 and 27% in 2007.

In all years surveyed, respondents said that they got most of their information about the general safety of indoor tanning beds from their friends or social group (71%-75%) and half reported that they went to a tanning salon for the first time with their friends. Other sources of information included family (18%-21%) and tanning salon workers (23%-24%).

Adolescents and young adults said their most trusted source of information about indoor tanning was the family physician or dermatologist, but only 15% reported that they had ever discussed the issue with their physicians, Dr. Robinson and her associates found.

"Counseling young adult patients to cease indoor tanning represents an opportunity to prevent UV radiation exposure that may cause melanoma," they noted.

More young adults now say that they value the appearance of a tan than have said so in past years, and their increased use of indoor tanning reflects that attitude, according to Dr. June K. Robinson of Northwestern University, Chicago, and her associates.

Researchers surveyed 100 people who appeared to be aged 18-30 years, and were sitting or lying on a Chicago beach in July of last year, about their knowledge of, attitudes toward, and use of indoor tanning, and compared the results with telephone surveys of 1,000 Illinois residents conducted in 1988 and with 958 teenage and young adult Chicagoans in 1994.

The 38 men and 62 women in the present survey were matched for age and sex with 100 subjects in each earlier survey.

The knowledge that tanning can cause melanoma/skin cancer initially decreased from 42% in the 1988 survey to 38% in the 1994 survey but then increased to 87% in 2007, Dr. Robinson and her associates reported (Arch. Dermatol. 2008;144:484-8).

Nevertheless, they said, "in each successive interval, there was an almost equivalent increase in the perception that people looked better with a tan"—from 58% to 69% and finally to 81% in 2007.

Tanning bed use also rose from 1% in 1988 to 26% in 1994 and 27% in 2007.

In all years surveyed, respondents said that they got most of their information about the general safety of indoor tanning beds from their friends or social group (71%-75%) and half reported that they went to a tanning salon for the first time with their friends. Other sources of information included family (18%-21%) and tanning salon workers (23%-24%).

Adolescents and young adults said their most trusted source of information about indoor tanning was the family physician or dermatologist, but only 15% reported that they had ever discussed the issue with their physicians, Dr. Robinson and her associates found.

"Counseling young adult patients to cease indoor tanning represents an opportunity to prevent UV radiation exposure that may cause melanoma," they noted.

CHICAGO — The Sunbelt melanoma study did not meet its primary end point of showing a benefit of high-dose interferon in melanoma patients with a single positive sentinel lymph node, reported the principal investigator at the annual meeting of the American Society of Clinical Oncology.

In neither of two protocols comparing high-dose interferon to observation did the treatment arms show a significant benefit in either 5-year disease-free survival or overall survival among patients with a single positive node confirmed by histology or molecular studies.

Dr. Kelly McMasters, chief of the division of surgical oncology at the University of Louisville (Ky.), presented the data on behalf of his colleagues in the Sunbelt Melanoma Trial Group. The investigator-initiated trial, which involved 79 centers in the United States and Canada, registered 3,619 patients from the ages of 18 to 70 years with cutaneous melanomas with a thickness of at least 1 mm and no clinical evidence of regional nodal or distant metastases. Of these 1,781 were reported in the intention-to-treat analyses.

The patients were stratified according to Breslow thickness: 1.0-2.0 mm, 2-4 mm, and greater than 4 mm, and the presence or absence of ulceration.

The trial had two protocol arms and an unusually complex design. All patients underwent sentinel node biopsy, and those with a node that was confirmed positive on histology were eligible for protocol A, which involved completion lymph node dissection.

Patients with only one microscopically positive node were then randomized to either an observation arm (arm 1, with 112 patients) or to a treatment arm with high-dose interferon alfa-2b (Intron A) for 12 months (arm 2, 106 patients).

Patients with more than one positive lymph node or extracapsular extension were assigned to receive high-dose interferon for 12 months and were followed (arm 3, with 99 patients).

In protocol B, those patients who had histologically negative results after sentinel node biopsy subsequently had their sample tested with reverse transcriptase-polymerase chain reaction (RT-PCR) for molecular staging to detect the presence of occult melanoma cells. Those who were RT-PCR-positive were then randomized to either observation (arm 4, with 180 patients), completion lymph node dissection (arm 5, with 192 patients), or completion lymph node dissection plus interferon (arm 6, with 184 patients). Patients who were RT-PCR-negative were assigned to observation alone (arm 7, with 908 patients).

Dr. McMasters presented intention-to-treat analyses for each protocol. In protocol A, for patients with a single histologically positive sentinel node, the 5-year disease-free survival was 70.2% for arm 1 (the observation group) and 73.2% for arm 2 (the interferon group) (log-rank P = .4589). Five-year overall survival in these patients was 75.4% among patients on observation vs. 72.9% for those on interferon (P = .9033).

There were, however, statistically significant decreases in both disease-free and overall survival for patients in protocol A with more than one positive lymph node (arm 3), compared with arms 1 and 2. The 5-year disease-free survival for patients in arm 3 was 44.5% (P less than .0001 vs. arms 1 and 2), and overall survival was 52.9% (P = .0004).

In the disease-free survival analysis in protocol B, there were similarly no significant differences among patients randomized to observation, completion lymph node dissection, or completion lymph node dissection with interferon, with rates of 83.9%, 85.2%, and 83.7%, respectively.

For the same groups in the overall survival analysis, there were no significant differences, with rates of 85.5% for the observation arm, 85.3% for the node dissection alone arm, and 86.8% for the node dissection plus IFN arm. Similarly, there were no significant differences in either disease-free survival in protocol B between patients who were node-negative or node-positive on RT-PCR, or in overall survival, which indicated that PCR testing for melanoma cells was not prognostically significant in this study, Dr. McMasters remarked.

A comparison of all the patient treatment arms in the study showed that patients who were histologically node-negative (those in arms 4, 5, 6, and 7 combined) had a better overall survival rate than those with a single positive sentinel node (patients in arms 1 and 2 combined), who in turn did better than those who had more than one positive node or extracapsular extension (those in arm 3) (P less than .0001).

In protocol A, "our results did not support the use of high-dose interferon for patients with a single microscopically positive sentinel node," Dr. McMasters said.

In protocol B, the results do not support the use of completion lymph node dissection or interferon for node-negative patients, and indicate that RT-PCR staging of sentinel lymph nodes was not predictive of worse outcome.

Dr. McMasters noted that the study was underpowered to detect small differences in disease-free survival and overall survival, "but we also did not observe significant trends, and even large sample size will not make differences appear if they don't exist."

The study was supported by a grant from Schering Oncology Biotech. Dr. McMasters and several other investigators have been on the speakers bureau.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — The Sunbelt melanoma study did not meet its primary end point of showing a benefit of high-dose interferon in melanoma patients with a single positive sentinel lymph node, reported the principal investigator at the annual meeting of the American Society of Clinical Oncology.

In neither of two protocols comparing high-dose interferon to observation did the treatment arms show a significant benefit in either 5-year disease-free survival or overall survival among patients with a single positive node confirmed by histology or molecular studies.

Dr. Kelly McMasters, chief of the division of surgical oncology at the University of Louisville (Ky.), presented the data on behalf of his colleagues in the Sunbelt Melanoma Trial Group. The investigator-initiated trial, which involved 79 centers in the United States and Canada, registered 3,619 patients from the ages of 18 to 70 years with cutaneous melanomas with a thickness of at least 1 mm and no clinical evidence of regional nodal or distant metastases. Of these 1,781 were reported in the intention-to-treat analyses.

The patients were stratified according to Breslow thickness: 1.0-2.0 mm, 2-4 mm, and greater than 4 mm, and the presence or absence of ulceration.

The trial had two protocol arms and an unusually complex design. All patients underwent sentinel node biopsy, and those with a node that was confirmed positive on histology were eligible for protocol A, which involved completion lymph node dissection.

Patients with only one microscopically positive node were then randomized to either an observation arm (arm 1, with 112 patients) or to a treatment arm with high-dose interferon alfa-2b (Intron A) for 12 months (arm 2, 106 patients).

Patients with more than one positive lymph node or extracapsular extension were assigned to receive high-dose interferon for 12 months and were followed (arm 3, with 99 patients).

In protocol B, those patients who had histologically negative results after sentinel node biopsy subsequently had their sample tested with reverse transcriptase-polymerase chain reaction (RT-PCR) for molecular staging to detect the presence of occult melanoma cells. Those who were RT-PCR-positive were then randomized to either observation (arm 4, with 180 patients), completion lymph node dissection (arm 5, with 192 patients), or completion lymph node dissection plus interferon (arm 6, with 184 patients). Patients who were RT-PCR-negative were assigned to observation alone (arm 7, with 908 patients).

Dr. McMasters presented intention-to-treat analyses for each protocol. In protocol A, for patients with a single histologically positive sentinel node, the 5-year disease-free survival was 70.2% for arm 1 (the observation group) and 73.2% for arm 2 (the interferon group) (log-rank P = .4589). Five-year overall survival in these patients was 75.4% among patients on observation vs. 72.9% for those on interferon (P = .9033).

There were, however, statistically significant decreases in both disease-free and overall survival for patients in protocol A with more than one positive lymph node (arm 3), compared with arms 1 and 2. The 5-year disease-free survival for patients in arm 3 was 44.5% (P less than .0001 vs. arms 1 and 2), and overall survival was 52.9% (P = .0004).

In the disease-free survival analysis in protocol B, there were similarly no significant differences among patients randomized to observation, completion lymph node dissection, or completion lymph node dissection with interferon, with rates of 83.9%, 85.2%, and 83.7%, respectively.

For the same groups in the overall survival analysis, there were no significant differences, with rates of 85.5% for the observation arm, 85.3% for the node dissection alone arm, and 86.8% for the node dissection plus IFN arm. Similarly, there were no significant differences in either disease-free survival in protocol B between patients who were node-negative or node-positive on RT-PCR, or in overall survival, which indicated that PCR testing for melanoma cells was not prognostically significant in this study, Dr. McMasters remarked.

A comparison of all the patient treatment arms in the study showed that patients who were histologically node-negative (those in arms 4, 5, 6, and 7 combined) had a better overall survival rate than those with a single positive sentinel node (patients in arms 1 and 2 combined), who in turn did better than those who had more than one positive node or extracapsular extension (those in arm 3) (P less than .0001).

In protocol A, "our results did not support the use of high-dose interferon for patients with a single microscopically positive sentinel node," Dr. McMasters said.

In protocol B, the results do not support the use of completion lymph node dissection or interferon for node-negative patients, and indicate that RT-PCR staging of sentinel lymph nodes was not predictive of worse outcome.

Dr. McMasters noted that the study was underpowered to detect small differences in disease-free survival and overall survival, "but we also did not observe significant trends, and even large sample size will not make differences appear if they don't exist."

The study was supported by a grant from Schering Oncology Biotech. Dr. McMasters and several other investigators have been on the speakers bureau.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — The Sunbelt melanoma study did not meet its primary end point of showing a benefit of high-dose interferon in melanoma patients with a single positive sentinel lymph node, reported the principal investigator at the annual meeting of the American Society of Clinical Oncology.

In neither of two protocols comparing high-dose interferon to observation did the treatment arms show a significant benefit in either 5-year disease-free survival or overall survival among patients with a single positive node confirmed by histology or molecular studies.

Dr. Kelly McMasters, chief of the division of surgical oncology at the University of Louisville (Ky.), presented the data on behalf of his colleagues in the Sunbelt Melanoma Trial Group. The investigator-initiated trial, which involved 79 centers in the United States and Canada, registered 3,619 patients from the ages of 18 to 70 years with cutaneous melanomas with a thickness of at least 1 mm and no clinical evidence of regional nodal or distant metastases. Of these 1,781 were reported in the intention-to-treat analyses.

The patients were stratified according to Breslow thickness: 1.0-2.0 mm, 2-4 mm, and greater than 4 mm, and the presence or absence of ulceration.

The trial had two protocol arms and an unusually complex design. All patients underwent sentinel node biopsy, and those with a node that was confirmed positive on histology were eligible for protocol A, which involved completion lymph node dissection.

Patients with only one microscopically positive node were then randomized to either an observation arm (arm 1, with 112 patients) or to a treatment arm with high-dose interferon alfa-2b (Intron A) for 12 months (arm 2, 106 patients).

Patients with more than one positive lymph node or extracapsular extension were assigned to receive high-dose interferon for 12 months and were followed (arm 3, with 99 patients).

In protocol B, those patients who had histologically negative results after sentinel node biopsy subsequently had their sample tested with reverse transcriptase-polymerase chain reaction (RT-PCR) for molecular staging to detect the presence of occult melanoma cells. Those who were RT-PCR-positive were then randomized to either observation (arm 4, with 180 patients), completion lymph node dissection (arm 5, with 192 patients), or completion lymph node dissection plus interferon (arm 6, with 184 patients). Patients who were RT-PCR-negative were assigned to observation alone (arm 7, with 908 patients).

Dr. McMasters presented intention-to-treat analyses for each protocol. In protocol A, for patients with a single histologically positive sentinel node, the 5-year disease-free survival was 70.2% for arm 1 (the observation group) and 73.2% for arm 2 (the interferon group) (log-rank P = .4589). Five-year overall survival in these patients was 75.4% among patients on observation vs. 72.9% for those on interferon (P = .9033).

There were, however, statistically significant decreases in both disease-free and overall survival for patients in protocol A with more than one positive lymph node (arm 3), compared with arms 1 and 2. The 5-year disease-free survival for patients in arm 3 was 44.5% (P less than .0001 vs. arms 1 and 2), and overall survival was 52.9% (P = .0004).

In the disease-free survival analysis in protocol B, there were similarly no significant differences among patients randomized to observation, completion lymph node dissection, or completion lymph node dissection with interferon, with rates of 83.9%, 85.2%, and 83.7%, respectively.

For the same groups in the overall survival analysis, there were no significant differences, with rates of 85.5% for the observation arm, 85.3% for the node dissection alone arm, and 86.8% for the node dissection plus IFN arm. Similarly, there were no significant differences in either disease-free survival in protocol B between patients who were node-negative or node-positive on RT-PCR, or in overall survival, which indicated that PCR testing for melanoma cells was not prognostically significant in this study, Dr. McMasters remarked.

A comparison of all the patient treatment arms in the study showed that patients who were histologically node-negative (those in arms 4, 5, 6, and 7 combined) had a better overall survival rate than those with a single positive sentinel node (patients in arms 1 and 2 combined), who in turn did better than those who had more than one positive node or extracapsular extension (those in arm 3) (P less than .0001).

In protocol A, "our results did not support the use of high-dose interferon for patients with a single microscopically positive sentinel node," Dr. McMasters said.

In protocol B, the results do not support the use of completion lymph node dissection or interferon for node-negative patients, and indicate that RT-PCR staging of sentinel lymph nodes was not predictive of worse outcome.

Dr. McMasters noted that the study was underpowered to detect small differences in disease-free survival and overall survival, "but we also did not observe significant trends, and even large sample size will not make differences appear if they don't exist."

The study was supported by a grant from Schering Oncology Biotech. Dr. McMasters and several other investigators have been on the speakers bureau.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — Add tremelimumab monotherapy to the list of treatments that showed potential for improving metastatic melanoma survival but have failed thus far to live up to their promise, investigators reported at the annual meeting of the American Society of Clinical Oncology.

In an international multicenter phase III trial comparing the investigational antibody tremelimumab with standard single-agent chemotherapy, tremelimumab did not improve overall survival versus either temozolomide (Temodar) or dacarbazine (DTC), said Dr. Antoni Ribas, a medical oncologist at the University of California at Los Angeles Medical Center.

While tremelimumab didn't surpass standard chemotherapy, patients who received it had objective responses to the agent, many of which were sustained, Dr. Ribas said, concluding that it warrants further investigation for treatment of metastatic melanoma.

Tremelimumab is a fully humanized monoclonal antibody specific for cytotoxic T lymphocyte-associated antigen 4 (CTLA4). It blocks negative CTLA4 signaling, and has been shown in animal models and in vitro studies to induce significant activation of T cells at concentrations of 30 mcg/mL.

In a phase I/II clinical trial in 112 patients with measurable melanoma, tremelimumab produced objective responses in 11% of patients, and ongoing durable responses of 32-64 months in 8% of patients.

The phase III study was designed to test the hypothesis that tremelimumab could improve survival in patients with surgically incurable metastatic melanoma. It was funded by Pfizer Inc., developer of tremelimumab. The investigators chose a dose of 15 mg/kg on day 1 and then every 90 days.

The primary end point was overall survival with an improvement of at least 33% over the comparator, with secondary end points including best overall response, durable response, duration of tumor response, progression-free survival 6 months after randomization, and safety.

Stages IIIc and IV melanoma patients were randomized in a 1:1:1 ratio to either tremelimumab or to single-agent chemotherapy with either 1,000 mg/m

The analysis was conducted on 324 patients who were assigned to receive tremelimumab and 319 assigned to the two chemotherapy regimens.

The trial was halted early after the second interim analysis in March 2008, when the data safety monitoring board determined that the study crossed the predetermined adjusted boundary for futility (P greater than .473), with a P value of .729.

A Kaplan-Meier estimate of overall survival among all patients in an intention-to-treat analysis showed median survival rates of 11.8 months for tremelimumab and 10.7 months for chemotherapy.

In an exploratory analysis of factors associated with overall survival, the authors found that "contrary to what had been anticipated, there is a trend toward better survival in the subset of patients with less advanced disease when treated with chemotherapy as opposed to tremelimumab," Dr. Ribas said.

In an intention-to-treat analysis of responses to therapy and 6-month progression-free survival, the complete response rate among 328 patients on tremelimumab was 1.5%, compared with 1.8% for 327 patients on chemotherapy. The partial response rates were 7.6% for patients who received the antibody and 8.3% for those on chemotherapy. The objective response rates (complete and partial responses combined) were 9.1% and 10.1%, respectively.

Six-month objective response rates (complete and partial responses combined) were 9.1% and 10.1%, respectively. Six-month progression-free survival was 18.6% for tremelimumab, vs. 14.1% for chemotherapy; this difference was not statistically significant.

Dr. Patrick Hwu, professor and chairman of medical oncology at the University of Texas M.D. Anderson Cancer Center, Houston, questioned whether overall survival was the best end point for the study, given that a subgroup of patients had a durable response to the anti-CTLA4 antibody.

Dr. Ribas has received honoraria, research funding, and served in an advisory role to Pfizer. Three of his coauthors are employees of the company.

CHICAGO — Add tremelimumab monotherapy to the list of treatments that showed potential for improving metastatic melanoma survival but have failed thus far to live up to their promise, investigators reported at the annual meeting of the American Society of Clinical Oncology.

In an international multicenter phase III trial comparing the investigational antibody tremelimumab with standard single-agent chemotherapy, tremelimumab did not improve overall survival versus either temozolomide (Temodar) or dacarbazine (DTC), said Dr. Antoni Ribas, a medical oncologist at the University of California at Los Angeles Medical Center.

While tremelimumab didn't surpass standard chemotherapy, patients who received it had objective responses to the agent, many of which were sustained, Dr. Ribas said, concluding that it warrants further investigation for treatment of metastatic melanoma.

Tremelimumab is a fully humanized monoclonal antibody specific for cytotoxic T lymphocyte-associated antigen 4 (CTLA4). It blocks negative CTLA4 signaling, and has been shown in animal models and in vitro studies to induce significant activation of T cells at concentrations of 30 mcg/mL.

In a phase I/II clinical trial in 112 patients with measurable melanoma, tremelimumab produced objective responses in 11% of patients, and ongoing durable responses of 32-64 months in 8% of patients.

The phase III study was designed to test the hypothesis that tremelimumab could improve survival in patients with surgically incurable metastatic melanoma. It was funded by Pfizer Inc., developer of tremelimumab. The investigators chose a dose of 15 mg/kg on day 1 and then every 90 days.

The primary end point was overall survival with an improvement of at least 33% over the comparator, with secondary end points including best overall response, durable response, duration of tumor response, progression-free survival 6 months after randomization, and safety.

Stages IIIc and IV melanoma patients were randomized in a 1:1:1 ratio to either tremelimumab or to single-agent chemotherapy with either 1,000 mg/m

The analysis was conducted on 324 patients who were assigned to receive tremelimumab and 319 assigned to the two chemotherapy regimens.

The trial was halted early after the second interim analysis in March 2008, when the data safety monitoring board determined that the study crossed the predetermined adjusted boundary for futility (P greater than .473), with a P value of .729.

A Kaplan-Meier estimate of overall survival among all patients in an intention-to-treat analysis showed median survival rates of 11.8 months for tremelimumab and 10.7 months for chemotherapy.

In an exploratory analysis of factors associated with overall survival, the authors found that "contrary to what had been anticipated, there is a trend toward better survival in the subset of patients with less advanced disease when treated with chemotherapy as opposed to tremelimumab," Dr. Ribas said.

In an intention-to-treat analysis of responses to therapy and 6-month progression-free survival, the complete response rate among 328 patients on tremelimumab was 1.5%, compared with 1.8% for 327 patients on chemotherapy. The partial response rates were 7.6% for patients who received the antibody and 8.3% for those on chemotherapy. The objective response rates (complete and partial responses combined) were 9.1% and 10.1%, respectively.

Six-month objective response rates (complete and partial responses combined) were 9.1% and 10.1%, respectively. Six-month progression-free survival was 18.6% for tremelimumab, vs. 14.1% for chemotherapy; this difference was not statistically significant.

Dr. Patrick Hwu, professor and chairman of medical oncology at the University of Texas M.D. Anderson Cancer Center, Houston, questioned whether overall survival was the best end point for the study, given that a subgroup of patients had a durable response to the anti-CTLA4 antibody.

Dr. Ribas has received honoraria, research funding, and served in an advisory role to Pfizer. Three of his coauthors are employees of the company.

CHICAGO — Add tremelimumab monotherapy to the list of treatments that showed potential for improving metastatic melanoma survival but have failed thus far to live up to their promise, investigators reported at the annual meeting of the American Society of Clinical Oncology.

In an international multicenter phase III trial comparing the investigational antibody tremelimumab with standard single-agent chemotherapy, tremelimumab did not improve overall survival versus either temozolomide (Temodar) or dacarbazine (DTC), said Dr. Antoni Ribas, a medical oncologist at the University of California at Los Angeles Medical Center.

While tremelimumab didn't surpass standard chemotherapy, patients who received it had objective responses to the agent, many of which were sustained, Dr. Ribas said, concluding that it warrants further investigation for treatment of metastatic melanoma.

Tremelimumab is a fully humanized monoclonal antibody specific for cytotoxic T lymphocyte-associated antigen 4 (CTLA4). It blocks negative CTLA4 signaling, and has been shown in animal models and in vitro studies to induce significant activation of T cells at concentrations of 30 mcg/mL.

In a phase I/II clinical trial in 112 patients with measurable melanoma, tremelimumab produced objective responses in 11% of patients, and ongoing durable responses of 32-64 months in 8% of patients.

The phase III study was designed to test the hypothesis that tremelimumab could improve survival in patients with surgically incurable metastatic melanoma. It was funded by Pfizer Inc., developer of tremelimumab. The investigators chose a dose of 15 mg/kg on day 1 and then every 90 days.

The primary end point was overall survival with an improvement of at least 33% over the comparator, with secondary end points including best overall response, durable response, duration of tumor response, progression-free survival 6 months after randomization, and safety.

Stages IIIc and IV melanoma patients were randomized in a 1:1:1 ratio to either tremelimumab or to single-agent chemotherapy with either 1,000 mg/m

The analysis was conducted on 324 patients who were assigned to receive tremelimumab and 319 assigned to the two chemotherapy regimens.

The trial was halted early after the second interim analysis in March 2008, when the data safety monitoring board determined that the study crossed the predetermined adjusted boundary for futility (P greater than .473), with a P value of .729.

A Kaplan-Meier estimate of overall survival among all patients in an intention-to-treat analysis showed median survival rates of 11.8 months for tremelimumab and 10.7 months for chemotherapy.

In an exploratory analysis of factors associated with overall survival, the authors found that "contrary to what had been anticipated, there is a trend toward better survival in the subset of patients with less advanced disease when treated with chemotherapy as opposed to tremelimumab," Dr. Ribas said.

In an intention-to-treat analysis of responses to therapy and 6-month progression-free survival, the complete response rate among 328 patients on tremelimumab was 1.5%, compared with 1.8% for 327 patients on chemotherapy. The partial response rates were 7.6% for patients who received the antibody and 8.3% for those on chemotherapy. The objective response rates (complete and partial responses combined) were 9.1% and 10.1%, respectively.

Six-month objective response rates (complete and partial responses combined) were 9.1% and 10.1%, respectively. Six-month progression-free survival was 18.6% for tremelimumab, vs. 14.1% for chemotherapy; this difference was not statistically significant.

Dr. Patrick Hwu, professor and chairman of medical oncology at the University of Texas M.D. Anderson Cancer Center, Houston, questioned whether overall survival was the best end point for the study, given that a subgroup of patients had a durable response to the anti-CTLA4 antibody.

Dr. Ribas has received honoraria, research funding, and served in an advisory role to Pfizer. Three of his coauthors are employees of the company.

WILLIAMSBURG, VA. — More than half of patients who undergo organ transplantation will develop a skin cancer, often within the first 5 years after surgery, according to Dr. Henry Randle.

Most of the cancers associated with transplant surgery are squamous cell carcinomas (SCC), which tend to appear as multiple lesions that grow rapidly and exhibit a high rate of recurrence, said Dr. Randle of the Mayo Clinic, Jacksonville, Fla.

"These tumors are very aggressive and 5%-8% more likely to metastasize. They require aggressive treatment and frequent follow-up—like every 1-3 months. Don't let these patients get by without seeing you every 6 months to 1 year," he said at a meeting of the American Society for Mohs Surgery.

SCCs are up to 250 times more likely to develop in transplant patients than the rest of the population, according to Dr. Randle. These patients also have a 10-fold increased risk of basal cell carcinoma (BCC), a 3- to 5-fold increased risk of malignant melanoma, and up to an 85-fold increased risk of Kaposi sarcoma.

"It is now recognized that skin cancer constitutes 37%-50% of all de novo neoplasms in transplant patients. The typical patient has multiple actinic keratoses and warts, a reversal of the basal cell:squamous cell carcinoma ratio, and aggressive squamous cell carcinomas that may metastasize and cause death within months to years after the transplant."

He cited three severity groups:

▸ Isolated carcinogenesis. Patients have a few lesions scattered about, which can be treated with basic therapies.

▸ Moderate carcinogenesis. Patients have up to 10 skin cancers per year. They need more aggressive treatment (usually Mohs surgery), and more frequent follow-up.

▸ Catastrophic carcinogenesis. These patients can get more than 100 SCCs each year and are likely to die from the tumors. They require frequent visits and very aggressive treatment, perhaps with "megasessions," in which several lesions are removed with Mohs surgery in one treatment. This can be problematic as it usually requires general anesthesia and the sessions can be quite long, Dr. Randle said.

Mohs is not the only treatment that can benefit transplant patients, however. "We need to use all our options to treat them. That includes excisional surgery, Mohs, topical anticancer creams, and chemotherapy and radiation in selected patients," he said.

For superficial, low-risk SCC lesions, aggressive electrodesiccation and curettage or laser surgery should suffice. For large lesions, wide excision including the subcutaneous fat is necessary.

For high-risk, rapidly growing, or recurrent SCCs, Mohs is probably the choice. However, because these lesions are more prone to metastasize, a sentinel node biopsy should be considered, Dr. Randle said.

SCC lesions with in-transit metastases will require a wide excision plus radiation, "and very close follow-up, because this treatment will probably fail," Dr. Randle said.

Transplant patients with skin cancers will do better if they can reduce or eliminate their immunosuppressive medications, "but the transplant surgeons don't like that suggestion, of course. You need to walk a tightrope between rejection and skin cancer, and it's not easy," he said.

WILLIAMSBURG, VA. — More than half of patients who undergo organ transplantation will develop a skin cancer, often within the first 5 years after surgery, according to Dr. Henry Randle.

Most of the cancers associated with transplant surgery are squamous cell carcinomas (SCC), which tend to appear as multiple lesions that grow rapidly and exhibit a high rate of recurrence, said Dr. Randle of the Mayo Clinic, Jacksonville, Fla.

"These tumors are very aggressive and 5%-8% more likely to metastasize. They require aggressive treatment and frequent follow-up—like every 1-3 months. Don't let these patients get by without seeing you every 6 months to 1 year," he said at a meeting of the American Society for Mohs Surgery.

SCCs are up to 250 times more likely to develop in transplant patients than the rest of the population, according to Dr. Randle. These patients also have a 10-fold increased risk of basal cell carcinoma (BCC), a 3- to 5-fold increased risk of malignant melanoma, and up to an 85-fold increased risk of Kaposi sarcoma.

"It is now recognized that skin cancer constitutes 37%-50% of all de novo neoplasms in transplant patients. The typical patient has multiple actinic keratoses and warts, a reversal of the basal cell:squamous cell carcinoma ratio, and aggressive squamous cell carcinomas that may metastasize and cause death within months to years after the transplant."

He cited three severity groups:

▸ Isolated carcinogenesis. Patients have a few lesions scattered about, which can be treated with basic therapies.

▸ Moderate carcinogenesis. Patients have up to 10 skin cancers per year. They need more aggressive treatment (usually Mohs surgery), and more frequent follow-up.

▸ Catastrophic carcinogenesis. These patients can get more than 100 SCCs each year and are likely to die from the tumors. They require frequent visits and very aggressive treatment, perhaps with "megasessions," in which several lesions are removed with Mohs surgery in one treatment. This can be problematic as it usually requires general anesthesia and the sessions can be quite long, Dr. Randle said.

Mohs is not the only treatment that can benefit transplant patients, however. "We need to use all our options to treat them. That includes excisional surgery, Mohs, topical anticancer creams, and chemotherapy and radiation in selected patients," he said.

For superficial, low-risk SCC lesions, aggressive electrodesiccation and curettage or laser surgery should suffice. For large lesions, wide excision including the subcutaneous fat is necessary.

For high-risk, rapidly growing, or recurrent SCCs, Mohs is probably the choice. However, because these lesions are more prone to metastasize, a sentinel node biopsy should be considered, Dr. Randle said.

SCC lesions with in-transit metastases will require a wide excision plus radiation, "and very close follow-up, because this treatment will probably fail," Dr. Randle said.

Transplant patients with skin cancers will do better if they can reduce or eliminate their immunosuppressive medications, "but the transplant surgeons don't like that suggestion, of course. You need to walk a tightrope between rejection and skin cancer, and it's not easy," he said.

WILLIAMSBURG, VA. — More than half of patients who undergo organ transplantation will develop a skin cancer, often within the first 5 years after surgery, according to Dr. Henry Randle.

Most of the cancers associated with transplant surgery are squamous cell carcinomas (SCC), which tend to appear as multiple lesions that grow rapidly and exhibit a high rate of recurrence, said Dr. Randle of the Mayo Clinic, Jacksonville, Fla.

"These tumors are very aggressive and 5%-8% more likely to metastasize. They require aggressive treatment and frequent follow-up—like every 1-3 months. Don't let these patients get by without seeing you every 6 months to 1 year," he said at a meeting of the American Society for Mohs Surgery.

SCCs are up to 250 times more likely to develop in transplant patients than the rest of the population, according to Dr. Randle. These patients also have a 10-fold increased risk of basal cell carcinoma (BCC), a 3- to 5-fold increased risk of malignant melanoma, and up to an 85-fold increased risk of Kaposi sarcoma.

"It is now recognized that skin cancer constitutes 37%-50% of all de novo neoplasms in transplant patients. The typical patient has multiple actinic keratoses and warts, a reversal of the basal cell:squamous cell carcinoma ratio, and aggressive squamous cell carcinomas that may metastasize and cause death within months to years after the transplant."

He cited three severity groups:

▸ Isolated carcinogenesis. Patients have a few lesions scattered about, which can be treated with basic therapies.

▸ Moderate carcinogenesis. Patients have up to 10 skin cancers per year. They need more aggressive treatment (usually Mohs surgery), and more frequent follow-up.

▸ Catastrophic carcinogenesis. These patients can get more than 100 SCCs each year and are likely to die from the tumors. They require frequent visits and very aggressive treatment, perhaps with "megasessions," in which several lesions are removed with Mohs surgery in one treatment. This can be problematic as it usually requires general anesthesia and the sessions can be quite long, Dr. Randle said.

Mohs is not the only treatment that can benefit transplant patients, however. "We need to use all our options to treat them. That includes excisional surgery, Mohs, topical anticancer creams, and chemotherapy and radiation in selected patients," he said.

For superficial, low-risk SCC lesions, aggressive electrodesiccation and curettage or laser surgery should suffice. For large lesions, wide excision including the subcutaneous fat is necessary.

For high-risk, rapidly growing, or recurrent SCCs, Mohs is probably the choice. However, because these lesions are more prone to metastasize, a sentinel node biopsy should be considered, Dr. Randle said.

SCC lesions with in-transit metastases will require a wide excision plus radiation, "and very close follow-up, because this treatment will probably fail," Dr. Randle said.

Transplant patients with skin cancers will do better if they can reduce or eliminate their immunosuppressive medications, "but the transplant surgeons don't like that suggestion, of course. You need to walk a tightrope between rejection and skin cancer, and it's not easy," he said.

SCOTTSDALE, ARIZ. — If there was an award given for "oldies but goodies" in the dermatologic armamentarium, Dr. Haines Ely would surely nominate bleomycin, a medication he has long relied upon for difficult squamous and Merkel cell lesions.

"My love affair with bleomycin began when I was a senior medical student," he recalled at the annual meeting of the Noah Worcester Dermatological Society.

The experience exposed him to two near-miraculous responses to intralesional bleomycin: the first, in a patient who refused a penectomy for advanced squamous cell carcinoma (SCC) of the penis.

And the second, in a patient with multiple fast-growing metastatic skin lesions from SCC of the lung that had left the patient "screaming in agony" on the hospital ward where Dr. Ely was moonlighting as a phlebotomist.

"By morning, those tumors had resolved. He was sitting up and eating breakfast," said Dr. Ely, a dermatologist in private practice in Grass Valley, Calif.

Through the years, Dr. Ely's reliance on bleomycin in tough cases has been reconfirmed.

The drug has a profound antiviral effect, demonstrated by the drug's effectiveness for treating Kaposi's sarcoma patients in the early days of HIV therapy.

It has also been useful for treating aggressive acantholytic SCC patients who refused surgery or were poor surgical candidates, he said. But perhaps its greatest utility is in treating patients with Merkel cell carcinoma (MCC), which has recently been linked to a previously unknown polyomavirus that may prove susceptible to bleomycin (Science 2008;319:1096-100).

"The treatment of choice is still surgery," he emphasized, but patients are often unable to undergo surgery because of their advanced age, comorbidities, and immunocompromised state. In several cases he presented, radiation therapy proved unsuccessful or resulted in profound complications.

One such case involved an 84-year-old woman residing in a nursing home who was seen for a "cyst" on her cheek that proved to be a 6-cm MCC. "I called several plastic surgeons in town, but nobody would touch it," he said.

Radiation was followed by "tremendous regrowth," prompting Dr. Ely to inject bleomycin directly into the tumor base in two treatments, 1 week apart.

The tumor resolved. "She lived 5 years with no recurrences," he said.

For tumors that strongly resemble MCC, "I don't even fool around," said Dr. Ely, noting that he injects 3 IU of bleomycin with lidocaine prior to biopsying the site. In one such case sent for referral following prebiopsy intralesional bleomycin, no evidence could be found of MCC by the time of excision.

Dr. Ely said his experience has led him to add to the recently described acronym AEIOU associated with features of MCC: asymptomatic/lack of tenderness, expanding rapidly, immune suppression, older than age 50, and UV-exposed site in a fair-skinned person (J. Am. Acad. Dermatol. 2008;58:375-81).

His own acronym, AEIOU-VB, includes "viral associated" and "bleomycin sensitive."

He cautioned that patients must have adequate renal function for bleomycin to be considered, and some patients may have transient side effects such as chills and fever following intralesional injections of the medication. The most serious, albeit rare, complication of bleomycin is pulmonary fibrosis, more commonly seen in elderly patients and those receiving high doses of the chemotherapy.

Dr. Ely reported having no conflicts of interest.

'My love affair with bleomycin began when Iwas a senior medical student.' DR. ELY

SCOTTSDALE, ARIZ. — If there was an award given for "oldies but goodies" in the dermatologic armamentarium, Dr. Haines Ely would surely nominate bleomycin, a medication he has long relied upon for difficult squamous and Merkel cell lesions.

"My love affair with bleomycin began when I was a senior medical student," he recalled at the annual meeting of the Noah Worcester Dermatological Society.

The experience exposed him to two near-miraculous responses to intralesional bleomycin: the first, in a patient who refused a penectomy for advanced squamous cell carcinoma (SCC) of the penis.

And the second, in a patient with multiple fast-growing metastatic skin lesions from SCC of the lung that had left the patient "screaming in agony" on the hospital ward where Dr. Ely was moonlighting as a phlebotomist.

"By morning, those tumors had resolved. He was sitting up and eating breakfast," said Dr. Ely, a dermatologist in private practice in Grass Valley, Calif.

Through the years, Dr. Ely's reliance on bleomycin in tough cases has been reconfirmed.

The drug has a profound antiviral effect, demonstrated by the drug's effectiveness for treating Kaposi's sarcoma patients in the early days of HIV therapy.

It has also been useful for treating aggressive acantholytic SCC patients who refused surgery or were poor surgical candidates, he said. But perhaps its greatest utility is in treating patients with Merkel cell carcinoma (MCC), which has recently been linked to a previously unknown polyomavirus that may prove susceptible to bleomycin (Science 2008;319:1096-100).

"The treatment of choice is still surgery," he emphasized, but patients are often unable to undergo surgery because of their advanced age, comorbidities, and immunocompromised state. In several cases he presented, radiation therapy proved unsuccessful or resulted in profound complications.

One such case involved an 84-year-old woman residing in a nursing home who was seen for a "cyst" on her cheek that proved to be a 6-cm MCC. "I called several plastic surgeons in town, but nobody would touch it," he said.

Radiation was followed by "tremendous regrowth," prompting Dr. Ely to inject bleomycin directly into the tumor base in two treatments, 1 week apart.

The tumor resolved. "She lived 5 years with no recurrences," he said.

For tumors that strongly resemble MCC, "I don't even fool around," said Dr. Ely, noting that he injects 3 IU of bleomycin with lidocaine prior to biopsying the site. In one such case sent for referral following prebiopsy intralesional bleomycin, no evidence could be found of MCC by the time of excision.

Dr. Ely said his experience has led him to add to the recently described acronym AEIOU associated with features of MCC: asymptomatic/lack of tenderness, expanding rapidly, immune suppression, older than age 50, and UV-exposed site in a fair-skinned person (J. Am. Acad. Dermatol. 2008;58:375-81).

His own acronym, AEIOU-VB, includes "viral associated" and "bleomycin sensitive."

He cautioned that patients must have adequate renal function for bleomycin to be considered, and some patients may have transient side effects such as chills and fever following intralesional injections of the medication. The most serious, albeit rare, complication of bleomycin is pulmonary fibrosis, more commonly seen in elderly patients and those receiving high doses of the chemotherapy.

Dr. Ely reported having no conflicts of interest.

'My love affair with bleomycin began when Iwas a senior medical student.' DR. ELY

SCOTTSDALE, ARIZ. — If there was an award given for "oldies but goodies" in the dermatologic armamentarium, Dr. Haines Ely would surely nominate bleomycin, a medication he has long relied upon for difficult squamous and Merkel cell lesions.

"My love affair with bleomycin began when I was a senior medical student," he recalled at the annual meeting of the Noah Worcester Dermatological Society.

The experience exposed him to two near-miraculous responses to intralesional bleomycin: the first, in a patient who refused a penectomy for advanced squamous cell carcinoma (SCC) of the penis.

And the second, in a patient with multiple fast-growing metastatic skin lesions from SCC of the lung that had left the patient "screaming in agony" on the hospital ward where Dr. Ely was moonlighting as a phlebotomist.

"By morning, those tumors had resolved. He was sitting up and eating breakfast," said Dr. Ely, a dermatologist in private practice in Grass Valley, Calif.

Through the years, Dr. Ely's reliance on bleomycin in tough cases has been reconfirmed.

The drug has a profound antiviral effect, demonstrated by the drug's effectiveness for treating Kaposi's sarcoma patients in the early days of HIV therapy.

It has also been useful for treating aggressive acantholytic SCC patients who refused surgery or were poor surgical candidates, he said. But perhaps its greatest utility is in treating patients with Merkel cell carcinoma (MCC), which has recently been linked to a previously unknown polyomavirus that may prove susceptible to bleomycin (Science 2008;319:1096-100).

"The treatment of choice is still surgery," he emphasized, but patients are often unable to undergo surgery because of their advanced age, comorbidities, and immunocompromised state. In several cases he presented, radiation therapy proved unsuccessful or resulted in profound complications.

One such case involved an 84-year-old woman residing in a nursing home who was seen for a "cyst" on her cheek that proved to be a 6-cm MCC. "I called several plastic surgeons in town, but nobody would touch it," he said.

Radiation was followed by "tremendous regrowth," prompting Dr. Ely to inject bleomycin directly into the tumor base in two treatments, 1 week apart.

The tumor resolved. "She lived 5 years with no recurrences," he said.

For tumors that strongly resemble MCC, "I don't even fool around," said Dr. Ely, noting that he injects 3 IU of bleomycin with lidocaine prior to biopsying the site. In one such case sent for referral following prebiopsy intralesional bleomycin, no evidence could be found of MCC by the time of excision.

Dr. Ely said his experience has led him to add to the recently described acronym AEIOU associated with features of MCC: asymptomatic/lack of tenderness, expanding rapidly, immune suppression, older than age 50, and UV-exposed site in a fair-skinned person (J. Am. Acad. Dermatol. 2008;58:375-81).

His own acronym, AEIOU-VB, includes "viral associated" and "bleomycin sensitive."

He cautioned that patients must have adequate renal function for bleomycin to be considered, and some patients may have transient side effects such as chills and fever following intralesional injections of the medication. The most serious, albeit rare, complication of bleomycin is pulmonary fibrosis, more commonly seen in elderly patients and those receiving high doses of the chemotherapy.

Dr. Ely reported having no conflicts of interest.

'My love affair with bleomycin began when Iwas a senior medical student.' DR. ELY

VANCOUVER, B.C. — Capecitabine, an oral prodrug of 5-fluorouracil, can be used to control advanced squamous cell carcinoma of the skin when conventional treatment options have run out, according to the results of two studies involving a total of five patients.

Capecitabine (Xeloda) "was designed to improve upon existing 5-fluorouracil by having increased efficacy, an improved side-effect profile, and increased ease of administration," Dr. Mariah R. Brown, lead investigator of one study, explained at the annual meeting of the American College of Mohs Surgery.

Although capecitabine is currently approved only for treatment of colorectal cancer and breast cancer, research suggests a possible role for the drug in managing several other malignancies, including skin cancer, she noted.

Dr. Brown and her colleagues at the University of Colorado, Denver, studied three patients (two women and one man) aged 60-73 years who had locally advanced squamous cell carcinoma (SCC) of the head and neck. In each case, the cancer was inoperable because of tumor size or limitations imposed by prior surgery or radiation therapy; patients also wanted to avoid aggressive therapy. None of the patients had evidence of metastases.

The patients were treated with multiple courses of capecitabine (1,500 mg twice daily), with each course consisting of 2 weeks on the drug and 1 week off. The total duration of treatment ranged from 2 to 6 months.

All patients had a clinical response, with visible shrinkage of tumors by more than 50% and response beginning within the first course of therapy, Dr. Brown reported.

One patient was clinically disease-free after four courses of therapy. She continued taking capecitabine, albeit at a lower dose, because she experienced severe hand-foot syndrome, and was stable 6 months after starting the lower-dose therapy. Another patient had to discontinue the drug after 21/2 courses because of adverse effects (neutropenia and diarrhea) and experienced rapid regrowth of her tumor. The remaining patient was free of disease after four courses but was then lost to follow-up.

"Capecitabine demonstrates some initial positive results in advanced cutaneous squamous cell carcinoma," Dr. Brown said. "The medication was relatively well tolerated, but side effects may necessitate dose reduction or discontinuation."

The second study, presented as a poster by Dr. Jeffrey E. Petersen of Wright State University in Dayton, Ohio, described use of capecitabine in two patients with SCC.

The first patient was an 87-year-old man who had multiple recurrent SCCs of the scalp and had undergone previous cryotherapy, topical 5-fluorouracil treatment, and multiple excisions including a Mohs procedure. The cancer progressed, despite treatment with a maximum dose of radiation therapy. The patient declined extensive surgery.

The second patient was an 84-year-old man who had previously undergone Mohs surgery down to bone for SCC of the scalp but experienced a recurrence. He had already received radiation to that area. The patient had severe Alzheimer's disease, and his family declined further surgery.

Both patients were treated with capecitabine at 50% of the standard dose of 1,250 mg/m

Although the patients experienced mild nausea and reduced taste while on treatment, the drug was otherwise well tolerated, he noted.

In addition to improving visible disease, capecitabine may be acting on disease that is not yet clinically evident. "Because it's a systemic drug, … in the large tumors where there is a high risk of metastatic disease you may be also treating that microscopic metastatic disease," he explained.

"Capecitabine gives you an option sometimes when you are looking at a patient and thinking, 'I don't have any more options, I don't have anything more to offer these people.' And [now] we do," Dr. Petersen said.

Dr. Brown and Dr. Petersen reported that they had no conflicts of interest in association with their studies.

This 87-year-old patient's recurrent SCC had progressed despite treatment with a maximum dose of radiation.

There is marked improvement of the scalp after four courses of capecitabine, although some ulcers are still present. Photos courtesy Dr. Jeffrey E. Petersen

VANCOUVER, B.C. — Capecitabine, an oral prodrug of 5-fluorouracil, can be used to control advanced squamous cell carcinoma of the skin when conventional treatment options have run out, according to the results of two studies involving a total of five patients.

Capecitabine (Xeloda) "was designed to improve upon existing 5-fluorouracil by having increased efficacy, an improved side-effect profile, and increased ease of administration," Dr. Mariah R. Brown, lead investigator of one study, explained at the annual meeting of the American College of Mohs Surgery.

Although capecitabine is currently approved only for treatment of colorectal cancer and breast cancer, research suggests a possible role for the drug in managing several other malignancies, including skin cancer, she noted.

Dr. Brown and her colleagues at the University of Colorado, Denver, studied three patients (two women and one man) aged 60-73 years who had locally advanced squamous cell carcinoma (SCC) of the head and neck. In each case, the cancer was inoperable because of tumor size or limitations imposed by prior surgery or radiation therapy; patients also wanted to avoid aggressive therapy. None of the patients had evidence of metastases.

The patients were treated with multiple courses of capecitabine (1,500 mg twice daily), with each course consisting of 2 weeks on the drug and 1 week off. The total duration of treatment ranged from 2 to 6 months.

All patients had a clinical response, with visible shrinkage of tumors by more than 50% and response beginning within the first course of therapy, Dr. Brown reported.

One patient was clinically disease-free after four courses of therapy. She continued taking capecitabine, albeit at a lower dose, because she experienced severe hand-foot syndrome, and was stable 6 months after starting the lower-dose therapy. Another patient had to discontinue the drug after 21/2 courses because of adverse effects (neutropenia and diarrhea) and experienced rapid regrowth of her tumor. The remaining patient was free of disease after four courses but was then lost to follow-up.

"Capecitabine demonstrates some initial positive results in advanced cutaneous squamous cell carcinoma," Dr. Brown said. "The medication was relatively well tolerated, but side effects may necessitate dose reduction or discontinuation."

The second study, presented as a poster by Dr. Jeffrey E. Petersen of Wright State University in Dayton, Ohio, described use of capecitabine in two patients with SCC.

The first patient was an 87-year-old man who had multiple recurrent SCCs of the scalp and had undergone previous cryotherapy, topical 5-fluorouracil treatment, and multiple excisions including a Mohs procedure. The cancer progressed, despite treatment with a maximum dose of radiation therapy. The patient declined extensive surgery.

The second patient was an 84-year-old man who had previously undergone Mohs surgery down to bone for SCC of the scalp but experienced a recurrence. He had already received radiation to that area. The patient had severe Alzheimer's disease, and his family declined further surgery.

Both patients were treated with capecitabine at 50% of the standard dose of 1,250 mg/m

Although the patients experienced mild nausea and reduced taste while on treatment, the drug was otherwise well tolerated, he noted.

In addition to improving visible disease, capecitabine may be acting on disease that is not yet clinically evident. "Because it's a systemic drug, … in the large tumors where there is a high risk of metastatic disease you may be also treating that microscopic metastatic disease," he explained.

"Capecitabine gives you an option sometimes when you are looking at a patient and thinking, 'I don't have any more options, I don't have anything more to offer these people.' And [now] we do," Dr. Petersen said.

Dr. Brown and Dr. Petersen reported that they had no conflicts of interest in association with their studies.

This 87-year-old patient's recurrent SCC had progressed despite treatment with a maximum dose of radiation.

There is marked improvement of the scalp after four courses of capecitabine, although some ulcers are still present. Photos courtesy Dr. Jeffrey E. Petersen

VANCOUVER, B.C. — Capecitabine, an oral prodrug of 5-fluorouracil, can be used to control advanced squamous cell carcinoma of the skin when conventional treatment options have run out, according to the results of two studies involving a total of five patients.

Capecitabine (Xeloda) "was designed to improve upon existing 5-fluorouracil by having increased efficacy, an improved side-effect profile, and increased ease of administration," Dr. Mariah R. Brown, lead investigator of one study, explained at the annual meeting of the American College of Mohs Surgery.

Although capecitabine is currently approved only for treatment of colorectal cancer and breast cancer, research suggests a possible role for the drug in managing several other malignancies, including skin cancer, she noted.

Dr. Brown and her colleagues at the University of Colorado, Denver, studied three patients (two women and one man) aged 60-73 years who had locally advanced squamous cell carcinoma (SCC) of the head and neck. In each case, the cancer was inoperable because of tumor size or limitations imposed by prior surgery or radiation therapy; patients also wanted to avoid aggressive therapy. None of the patients had evidence of metastases.

The patients were treated with multiple courses of capecitabine (1,500 mg twice daily), with each course consisting of 2 weeks on the drug and 1 week off. The total duration of treatment ranged from 2 to 6 months.

All patients had a clinical response, with visible shrinkage of tumors by more than 50% and response beginning within the first course of therapy, Dr. Brown reported.

One patient was clinically disease-free after four courses of therapy. She continued taking capecitabine, albeit at a lower dose, because she experienced severe hand-foot syndrome, and was stable 6 months after starting the lower-dose therapy. Another patient had to discontinue the drug after 21/2 courses because of adverse effects (neutropenia and diarrhea) and experienced rapid regrowth of her tumor. The remaining patient was free of disease after four courses but was then lost to follow-up.

"Capecitabine demonstrates some initial positive results in advanced cutaneous squamous cell carcinoma," Dr. Brown said. "The medication was relatively well tolerated, but side effects may necessitate dose reduction or discontinuation."

The second study, presented as a poster by Dr. Jeffrey E. Petersen of Wright State University in Dayton, Ohio, described use of capecitabine in two patients with SCC.

The first patient was an 87-year-old man who had multiple recurrent SCCs of the scalp and had undergone previous cryotherapy, topical 5-fluorouracil treatment, and multiple excisions including a Mohs procedure. The cancer progressed, despite treatment with a maximum dose of radiation therapy. The patient declined extensive surgery.

The second patient was an 84-year-old man who had previously undergone Mohs surgery down to bone for SCC of the scalp but experienced a recurrence. He had already received radiation to that area. The patient had severe Alzheimer's disease, and his family declined further surgery.

Both patients were treated with capecitabine at 50% of the standard dose of 1,250 mg/m

Although the patients experienced mild nausea and reduced taste while on treatment, the drug was otherwise well tolerated, he noted.

In addition to improving visible disease, capecitabine may be acting on disease that is not yet clinically evident. "Because it's a systemic drug, … in the large tumors where there is a high risk of metastatic disease you may be also treating that microscopic metastatic disease," he explained.

"Capecitabine gives you an option sometimes when you are looking at a patient and thinking, 'I don't have any more options, I don't have anything more to offer these people.' And [now] we do," Dr. Petersen said.

Dr. Brown and Dr. Petersen reported that they had no conflicts of interest in association with their studies.

This 87-year-old patient's recurrent SCC had progressed despite treatment with a maximum dose of radiation.

There is marked improvement of the scalp after four courses of capecitabine, although some ulcers are still present. Photos courtesy Dr. Jeffrey E. Petersen

VANCOUVER, B.C. — Adenosquamous carcinoma is an often misdiagnosed and more aggressive type of skin cancer that requires close follow-up for possible recurrences, according to a review that identified 27 patients with primary disease.

"We are starting to get the sense that it can be very clinically aggressive and, in fact, may be more aggressive than conventional cutaneous squamous cell carcinoma [SCC], with a high risk of local recurrence," Dr. Jennifer M. Fu said at the annual meeting of the American College of Mohs Surgery.

A rise in the number of cases at her institution in recent years, with some of them proving to be very locally aggressive, prompted a closer look at this cancer. Dr. Fu and her colleagues searched their institution's records for the past 10 years to identify cases of adenosquamous carcinoma (ASC) diagnosed there. The search identified 27 patients with primary ASC, 7 of whom experienced a recurrence. The patients had a mean age of 74 years (range 50-97 years), and 70% were men.

Some 56% of the primary tumors were on the face, 15% were on the scalp, and 15% were on the arm or shoulder. "Clinically, this was a very difficult diagnosis for people to make, often presenting just as a firm papule or plaque and not infrequently ulcerated," observed Dr. Fu, a dermatology resident at the University of California, San Francisco.

"Most of the clinicians diagnosed this as something else—as basal cell carcinoma, scar, metastatic carcinoma, rosacea in one case, and a spider bite in another case," she said. "In no case was adenosquamous carcinoma correctly diagnosed."

Histopathologically, many of the features of ASC overlap those of desmoplastic SCC, but ASC differs in having glandular differentiation. "At least at our institution, we feel that adenosquamous carcinoma is probably best considered a variant of SCC and on a spectrum of desmoplastic SCC," Dr. Fu said.

The tumors evaluated in the study typically had an infiltrative pattern with dermal fibrosis or sclerosis: 61% showed elastosis, while 30% were ulcerated. Squamous differentiation was universal, with all tumors exhibiting cytoplasmic cornification and 41% having keratinizing cysts.

Most tumors (92%) had ductular elements, while 58% had glandular elements. Even when a tumor had glandular elements, the percentage of that tumor showing those elements varied from roughly 5% to 80%. In fact, two of the cases were initially interpreted to be SCC but were subsequently determined to have glandular differentiation more consistent with ASC. In such equivocal cases, immunostaining for carcinoembryonic antigen or cytokeratin 7 may help identify glandular foci, she noted.

Clinical outcomes were assessed in the six patients who received most of their treatment at her hospital. Five were immunosuppressed. All underwent Mohs surgery at least once, and two received adjuvant radiation therapy and cetuximab (Erbitux) for locally advanced disease. For these patients, "the Mohs defect postoperatively far exceeded what was evident clinically," said Dr. Fu, who had no conflicts of interest in association with the study.

In this patient, recurrent nodules and plaques of adenosquamous carcinoma are visible at the edge of a scar from previous treatment. University of California, San Francisco/Department of Dermatology

VANCOUVER, B.C. — Adenosquamous carcinoma is an often misdiagnosed and more aggressive type of skin cancer that requires close follow-up for possible recurrences, according to a review that identified 27 patients with primary disease.

"We are starting to get the sense that it can be very clinically aggressive and, in fact, may be more aggressive than conventional cutaneous squamous cell carcinoma [SCC], with a high risk of local recurrence," Dr. Jennifer M. Fu said at the annual meeting of the American College of Mohs Surgery.

A rise in the number of cases at her institution in recent years, with some of them proving to be very locally aggressive, prompted a closer look at this cancer. Dr. Fu and her colleagues searched their institution's records for the past 10 years to identify cases of adenosquamous carcinoma (ASC) diagnosed there. The search identified 27 patients with primary ASC, 7 of whom experienced a recurrence. The patients had a mean age of 74 years (range 50-97 years), and 70% were men.

Some 56% of the primary tumors were on the face, 15% were on the scalp, and 15% were on the arm or shoulder. "Clinically, this was a very difficult diagnosis for people to make, often presenting just as a firm papule or plaque and not infrequently ulcerated," observed Dr. Fu, a dermatology resident at the University of California, San Francisco.

"Most of the clinicians diagnosed this as something else—as basal cell carcinoma, scar, metastatic carcinoma, rosacea in one case, and a spider bite in another case," she said. "In no case was adenosquamous carcinoma correctly diagnosed."

Histopathologically, many of the features of ASC overlap those of desmoplastic SCC, but ASC differs in having glandular differentiation. "At least at our institution, we feel that adenosquamous carcinoma is probably best considered a variant of SCC and on a spectrum of desmoplastic SCC," Dr. Fu said.

The tumors evaluated in the study typically had an infiltrative pattern with dermal fibrosis or sclerosis: 61% showed elastosis, while 30% were ulcerated. Squamous differentiation was universal, with all tumors exhibiting cytoplasmic cornification and 41% having keratinizing cysts.

Most tumors (92%) had ductular elements, while 58% had glandular elements. Even when a tumor had glandular elements, the percentage of that tumor showing those elements varied from roughly 5% to 80%. In fact, two of the cases were initially interpreted to be SCC but were subsequently determined to have glandular differentiation more consistent with ASC. In such equivocal cases, immunostaining for carcinoembryonic antigen or cytokeratin 7 may help identify glandular foci, she noted.

Clinical outcomes were assessed in the six patients who received most of their treatment at her hospital. Five were immunosuppressed. All underwent Mohs surgery at least once, and two received adjuvant radiation therapy and cetuximab (Erbitux) for locally advanced disease. For these patients, "the Mohs defect postoperatively far exceeded what was evident clinically," said Dr. Fu, who had no conflicts of interest in association with the study.

In this patient, recurrent nodules and plaques of adenosquamous carcinoma are visible at the edge of a scar from previous treatment. University of California, San Francisco/Department of Dermatology

VANCOUVER, B.C. — Adenosquamous carcinoma is an often misdiagnosed and more aggressive type of skin cancer that requires close follow-up for possible recurrences, according to a review that identified 27 patients with primary disease.

"We are starting to get the sense that it can be very clinically aggressive and, in fact, may be more aggressive than conventional cutaneous squamous cell carcinoma [SCC], with a high risk of local recurrence," Dr. Jennifer M. Fu said at the annual meeting of the American College of Mohs Surgery.

A rise in the number of cases at her institution in recent years, with some of them proving to be very locally aggressive, prompted a closer look at this cancer. Dr. Fu and her colleagues searched their institution's records for the past 10 years to identify cases of adenosquamous carcinoma (ASC) diagnosed there. The search identified 27 patients with primary ASC, 7 of whom experienced a recurrence. The patients had a mean age of 74 years (range 50-97 years), and 70% were men.

Some 56% of the primary tumors were on the face, 15% were on the scalp, and 15% were on the arm or shoulder. "Clinically, this was a very difficult diagnosis for people to make, often presenting just as a firm papule or plaque and not infrequently ulcerated," observed Dr. Fu, a dermatology resident at the University of California, San Francisco.

"Most of the clinicians diagnosed this as something else—as basal cell carcinoma, scar, metastatic carcinoma, rosacea in one case, and a spider bite in another case," she said. "In no case was adenosquamous carcinoma correctly diagnosed."

Histopathologically, many of the features of ASC overlap those of desmoplastic SCC, but ASC differs in having glandular differentiation. "At least at our institution, we feel that adenosquamous carcinoma is probably best considered a variant of SCC and on a spectrum of desmoplastic SCC," Dr. Fu said.

The tumors evaluated in the study typically had an infiltrative pattern with dermal fibrosis or sclerosis: 61% showed elastosis, while 30% were ulcerated. Squamous differentiation was universal, with all tumors exhibiting cytoplasmic cornification and 41% having keratinizing cysts.

Most tumors (92%) had ductular elements, while 58% had glandular elements. Even when a tumor had glandular elements, the percentage of that tumor showing those elements varied from roughly 5% to 80%. In fact, two of the cases were initially interpreted to be SCC but were subsequently determined to have glandular differentiation more consistent with ASC. In such equivocal cases, immunostaining for carcinoembryonic antigen or cytokeratin 7 may help identify glandular foci, she noted.

Clinical outcomes were assessed in the six patients who received most of their treatment at her hospital. Five were immunosuppressed. All underwent Mohs surgery at least once, and two received adjuvant radiation therapy and cetuximab (Erbitux) for locally advanced disease. For these patients, "the Mohs defect postoperatively far exceeded what was evident clinically," said Dr. Fu, who had no conflicts of interest in association with the study.

In this patient, recurrent nodules and plaques of adenosquamous carcinoma are visible at the edge of a scar from previous treatment. University of California, San Francisco/Department of Dermatology