Melanoma

SAN FRANCISCO — Mycosis fungoides is classically considered a disease of middle-aged white men, but onset prior to age 40 years is significantly more common in black women than in white men or women, according to the experience at M.D. Anderson Cancer Center.

Moreover, young black women with mycosis fungoides (MF) are particularly likely to have rapid progression with a poor prognosis, Patricia Sun reported at the annual meeting of the American Academy of Dermatology.

"We would like people to consider more aggressive therapy in African American women who present with MF before age 40—including allogeneic transplantation—earlier than you would think of it in other patients," said Ms. Sun of M.D. Anderson and the University of Texas, Houston.

MF is the most common form of cutaneous T-cell lymphoma, with an annual incidence of 6.4 cases per million population. The peak age at presentation is 60–69 years. The ratio of men to women with MF is roughly 2:1. The disease is most often characterized by an indolent course, and in one large series, median survival was 10 years. MF is more common in whites than blacks.

However, when the cutaneous T-cell lymphoma team at M.D. Anderson recently noticed a small cluster of young black women who presented with MF of an aggressive nature, it enlisted Ms. Sun to lead a study aimed at learning whether these cases were simply a fluke or were representative of a consistent yet previously unrecognized trend.

Ms. Sun analyzed the prospectively collected data on 1,074 MF patients who presented to the cancer center during 1969–2007. She noted onset prior to age 40 years in 33% of black patients, 36% of Hispanics, and 13% of whites. Women presented with MF prior to age 40 significantly more often than did men. Indeed, 35% of the 40 black women with MF in the series presented before age 40, as did 48% of 40 affected Hispanic women and less than 15% of 550 white women.

Aggressive disease—defined as rapid progression from stable, mild disease to stage IV in the span of less than a year at any time during the disease course—occurred in nine women with early-onset MF. Eight of these women were black and one was white. Six of the eight black women with aggressive early-onset MF died of their disease; the two survivors underwent allogeneic transplantation.

Why the poorer outcome in black women with MF before the age of 40? "Our thought is vitamin D," Ms. Sun said. "I know everybody's talking about vitamin D now, but many of our African American patients are vitamin-D deficient."

One audience member cautioned that MF is notoriously difficult to diagnose, particularly in darker-skinned individuals, and there's probably a bias for the more severe cases to be referred to M.D. Anderson.

SAN FRANCISCO — Mycosis fungoides is classically considered a disease of middle-aged white men, but onset prior to age 40 years is significantly more common in black women than in white men or women, according to the experience at M.D. Anderson Cancer Center.

Moreover, young black women with mycosis fungoides (MF) are particularly likely to have rapid progression with a poor prognosis, Patricia Sun reported at the annual meeting of the American Academy of Dermatology.

"We would like people to consider more aggressive therapy in African American women who present with MF before age 40—including allogeneic transplantation—earlier than you would think of it in other patients," said Ms. Sun of M.D. Anderson and the University of Texas, Houston.

MF is the most common form of cutaneous T-cell lymphoma, with an annual incidence of 6.4 cases per million population. The peak age at presentation is 60–69 years. The ratio of men to women with MF is roughly 2:1. The disease is most often characterized by an indolent course, and in one large series, median survival was 10 years. MF is more common in whites than blacks.

However, when the cutaneous T-cell lymphoma team at M.D. Anderson recently noticed a small cluster of young black women who presented with MF of an aggressive nature, it enlisted Ms. Sun to lead a study aimed at learning whether these cases were simply a fluke or were representative of a consistent yet previously unrecognized trend.

Ms. Sun analyzed the prospectively collected data on 1,074 MF patients who presented to the cancer center during 1969–2007. She noted onset prior to age 40 years in 33% of black patients, 36% of Hispanics, and 13% of whites. Women presented with MF prior to age 40 significantly more often than did men. Indeed, 35% of the 40 black women with MF in the series presented before age 40, as did 48% of 40 affected Hispanic women and less than 15% of 550 white women.

Aggressive disease—defined as rapid progression from stable, mild disease to stage IV in the span of less than a year at any time during the disease course—occurred in nine women with early-onset MF. Eight of these women were black and one was white. Six of the eight black women with aggressive early-onset MF died of their disease; the two survivors underwent allogeneic transplantation.

Why the poorer outcome in black women with MF before the age of 40? "Our thought is vitamin D," Ms. Sun said. "I know everybody's talking about vitamin D now, but many of our African American patients are vitamin-D deficient."

One audience member cautioned that MF is notoriously difficult to diagnose, particularly in darker-skinned individuals, and there's probably a bias for the more severe cases to be referred to M.D. Anderson.

SAN FRANCISCO — Mycosis fungoides is classically considered a disease of middle-aged white men, but onset prior to age 40 years is significantly more common in black women than in white men or women, according to the experience at M.D. Anderson Cancer Center.

Moreover, young black women with mycosis fungoides (MF) are particularly likely to have rapid progression with a poor prognosis, Patricia Sun reported at the annual meeting of the American Academy of Dermatology.

"We would like people to consider more aggressive therapy in African American women who present with MF before age 40—including allogeneic transplantation—earlier than you would think of it in other patients," said Ms. Sun of M.D. Anderson and the University of Texas, Houston.

MF is the most common form of cutaneous T-cell lymphoma, with an annual incidence of 6.4 cases per million population. The peak age at presentation is 60–69 years. The ratio of men to women with MF is roughly 2:1. The disease is most often characterized by an indolent course, and in one large series, median survival was 10 years. MF is more common in whites than blacks.

However, when the cutaneous T-cell lymphoma team at M.D. Anderson recently noticed a small cluster of young black women who presented with MF of an aggressive nature, it enlisted Ms. Sun to lead a study aimed at learning whether these cases were simply a fluke or were representative of a consistent yet previously unrecognized trend.

Ms. Sun analyzed the prospectively collected data on 1,074 MF patients who presented to the cancer center during 1969–2007. She noted onset prior to age 40 years in 33% of black patients, 36% of Hispanics, and 13% of whites. Women presented with MF prior to age 40 significantly more often than did men. Indeed, 35% of the 40 black women with MF in the series presented before age 40, as did 48% of 40 affected Hispanic women and less than 15% of 550 white women.

Aggressive disease—defined as rapid progression from stable, mild disease to stage IV in the span of less than a year at any time during the disease course—occurred in nine women with early-onset MF. Eight of these women were black and one was white. Six of the eight black women with aggressive early-onset MF died of their disease; the two survivors underwent allogeneic transplantation.

Why the poorer outcome in black women with MF before the age of 40? "Our thought is vitamin D," Ms. Sun said. "I know everybody's talking about vitamin D now, but many of our African American patients are vitamin-D deficient."

One audience member cautioned that MF is notoriously difficult to diagnose, particularly in darker-skinned individuals, and there's probably a bias for the more severe cases to be referred to M.D. Anderson.

MAUI, HAWAII — Immunohistochemical staining for p75 nerve growth factor receptor is a helpful tool for establishing the diagnosis of desmoplastic melanoma in cases where histopathology is inconclusive and S-100 staining is weak or absent, according to Dr. Maxwell A. Fung. "This stain is one that even a lot of dermatopathlogists have never heard of," he said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

The p75 nerve growth factor receptor is a marker of Schwannian differentiation. It's worth becoming familiar with p75 nerve growth factor receptor because the insurance industry has identified unrecognized desmoplastic melanoma as one of the top-10 causes of malpractice lawsuits involving melanoma, said Dr. Fung of the University of California, Davis.

"S-100 staining is our workhorse, our most sensitive stain for identification of melanomas. But when it's focal or absent, consider p75 nerve growth factor receptor. It's a very sensitive marker for desmoplastic melanoma," said Dr. Fung.

"It's very nonspecific—it'll stain a nevus or a neurofibroma—but in the context of trying to make a diagnosis of desmoplastic melanoma, if this is positive, it's going to make the diagnosis," he added.

Dr. Fung noted that dermatopath-ologists at Boston University have proposed incorporating p75 nerve growth factor receptor and S-100 staining as a primary immunohistochemical test panel for the diagnosis of desmoplastic melanoma (Am. J. Dermatopathol. 2006;28:162–7).

In a separate presentation, Dr. Jeffrey E. Gershenwald raised the possibility that desmoplastic melanoma may in fact not be a melanoma at all.

"There is evolving new genetic data that certainly suggests this may be a different disease. It may actually behave more like a sarcoma," said Dr. Gershenwald of the M.D. Anderson Cancer Center in Houston.

He and his colleagues recently demonstrated how differently desmoplastic melanomas behave in an analysis of the M.D. Anderson database of melanoma patients undergoing wide local excision and sentinel lymph node biopsy.

The investigators divided patients into three subgroups: 1,785 whose melanomas lacked desmoplastic features, 19 with mixed desmoplastic melanoma, and 46 with pure desmoplastic melanoma.

The pure desmoplastic melanomas were significantly thicker and far less likely to be ulcerated than were the nondesmoplastic or mixed desmoplastic melanomas. (See box.)

Moreover, in contrast to the 16%-17% rates of sentinel lymph node positivity in patients with nondesmoplastic or mixed desmoplastic melanoma, the rate of sentinel lymph node involvement in patients with pure desmoplastic melanoma was "almost insignificant," Dr. Gershenwald said. However, the management approach should be the same as for those with all other types of melanoma.

SDEF and this newspaper are owned by Elsevier.

ELSEVIER GLOBAL MEDICAL NEWS

MAUI, HAWAII — Immunohistochemical staining for p75 nerve growth factor receptor is a helpful tool for establishing the diagnosis of desmoplastic melanoma in cases where histopathology is inconclusive and S-100 staining is weak or absent, according to Dr. Maxwell A. Fung. "This stain is one that even a lot of dermatopathlogists have never heard of," he said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

The p75 nerve growth factor receptor is a marker of Schwannian differentiation. It's worth becoming familiar with p75 nerve growth factor receptor because the insurance industry has identified unrecognized desmoplastic melanoma as one of the top-10 causes of malpractice lawsuits involving melanoma, said Dr. Fung of the University of California, Davis.

"S-100 staining is our workhorse, our most sensitive stain for identification of melanomas. But when it's focal or absent, consider p75 nerve growth factor receptor. It's a very sensitive marker for desmoplastic melanoma," said Dr. Fung.

"It's very nonspecific—it'll stain a nevus or a neurofibroma—but in the context of trying to make a diagnosis of desmoplastic melanoma, if this is positive, it's going to make the diagnosis," he added.

Dr. Fung noted that dermatopath-ologists at Boston University have proposed incorporating p75 nerve growth factor receptor and S-100 staining as a primary immunohistochemical test panel for the diagnosis of desmoplastic melanoma (Am. J. Dermatopathol. 2006;28:162–7).

In a separate presentation, Dr. Jeffrey E. Gershenwald raised the possibility that desmoplastic melanoma may in fact not be a melanoma at all.

"There is evolving new genetic data that certainly suggests this may be a different disease. It may actually behave more like a sarcoma," said Dr. Gershenwald of the M.D. Anderson Cancer Center in Houston.

He and his colleagues recently demonstrated how differently desmoplastic melanomas behave in an analysis of the M.D. Anderson database of melanoma patients undergoing wide local excision and sentinel lymph node biopsy.

The investigators divided patients into three subgroups: 1,785 whose melanomas lacked desmoplastic features, 19 with mixed desmoplastic melanoma, and 46 with pure desmoplastic melanoma.

The pure desmoplastic melanomas were significantly thicker and far less likely to be ulcerated than were the nondesmoplastic or mixed desmoplastic melanomas. (See box.)

Moreover, in contrast to the 16%-17% rates of sentinel lymph node positivity in patients with nondesmoplastic or mixed desmoplastic melanoma, the rate of sentinel lymph node involvement in patients with pure desmoplastic melanoma was "almost insignificant," Dr. Gershenwald said. However, the management approach should be the same as for those with all other types of melanoma.

SDEF and this newspaper are owned by Elsevier.

ELSEVIER GLOBAL MEDICAL NEWS

MAUI, HAWAII — Immunohistochemical staining for p75 nerve growth factor receptor is a helpful tool for establishing the diagnosis of desmoplastic melanoma in cases where histopathology is inconclusive and S-100 staining is weak or absent, according to Dr. Maxwell A. Fung. "This stain is one that even a lot of dermatopathlogists have never heard of," he said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

The p75 nerve growth factor receptor is a marker of Schwannian differentiation. It's worth becoming familiar with p75 nerve growth factor receptor because the insurance industry has identified unrecognized desmoplastic melanoma as one of the top-10 causes of malpractice lawsuits involving melanoma, said Dr. Fung of the University of California, Davis.

"S-100 staining is our workhorse, our most sensitive stain for identification of melanomas. But when it's focal or absent, consider p75 nerve growth factor receptor. It's a very sensitive marker for desmoplastic melanoma," said Dr. Fung.

"It's very nonspecific—it'll stain a nevus or a neurofibroma—but in the context of trying to make a diagnosis of desmoplastic melanoma, if this is positive, it's going to make the diagnosis," he added.

Dr. Fung noted that dermatopath-ologists at Boston University have proposed incorporating p75 nerve growth factor receptor and S-100 staining as a primary immunohistochemical test panel for the diagnosis of desmoplastic melanoma (Am. J. Dermatopathol. 2006;28:162–7).

In a separate presentation, Dr. Jeffrey E. Gershenwald raised the possibility that desmoplastic melanoma may in fact not be a melanoma at all.

"There is evolving new genetic data that certainly suggests this may be a different disease. It may actually behave more like a sarcoma," said Dr. Gershenwald of the M.D. Anderson Cancer Center in Houston.

He and his colleagues recently demonstrated how differently desmoplastic melanomas behave in an analysis of the M.D. Anderson database of melanoma patients undergoing wide local excision and sentinel lymph node biopsy.

The investigators divided patients into three subgroups: 1,785 whose melanomas lacked desmoplastic features, 19 with mixed desmoplastic melanoma, and 46 with pure desmoplastic melanoma.

The pure desmoplastic melanomas were significantly thicker and far less likely to be ulcerated than were the nondesmoplastic or mixed desmoplastic melanomas. (See box.)

Moreover, in contrast to the 16%-17% rates of sentinel lymph node positivity in patients with nondesmoplastic or mixed desmoplastic melanoma, the rate of sentinel lymph node involvement in patients with pure desmoplastic melanoma was "almost insignificant," Dr. Gershenwald said. However, the management approach should be the same as for those with all other types of melanoma.

SDEF and this newspaper are owned by Elsevier.

ELSEVIER GLOBAL MEDICAL NEWS

Ralph M. Trüeb, MD

Few dermatologic conditions carry as much emotional distress as chemotherapy-induced alopecia (CIA). The prerequisite for successful development of strategies for CIA prevention is the understanding of the pathobiology of CIA. The incidence and severity of CIA are variable and related to the particular chemotherapeutic protocol. CIA is traditionally categorized as acute diffuse hair loss caused by dystrophic anagen effluvium; however, CIA presents with different clinical patterns of hair loss. When an arrest of mitotic activity occurs, obviously numerous and interacting factors influence the shedding pattern. The major approach to minimize CIA is by scalp cooling. Unfortunately, most published data on scalp cooling are of poor quality. Several experimental approaches to the development of pharmacologic agents are under evaluation and include drug-specific antibodies, hair growth cycle modifiers, cytokines and growth factors, antioxidants, inhibitors of apoptosis, and cell-cycle and proliferation modifiers. Ultimately, the protection should be selective to the hair follicle; for example, topical application, such that the anticancer efficacy of chemotherapy is not hampered. Among the few agents that have been evaluated so far in humans, AS101 and minoxidil were able to reduce the severity or shorten the duration of CIA, but could not prevent CIA.

*For a PDF of the full article, click on the link to the left of this introduction.

Ralph M. Trüeb, MD

Few dermatologic conditions carry as much emotional distress as chemotherapy-induced alopecia (CIA). The prerequisite for successful development of strategies for CIA prevention is the understanding of the pathobiology of CIA. The incidence and severity of CIA are variable and related to the particular chemotherapeutic protocol. CIA is traditionally categorized as acute diffuse hair loss caused by dystrophic anagen effluvium; however, CIA presents with different clinical patterns of hair loss. When an arrest of mitotic activity occurs, obviously numerous and interacting factors influence the shedding pattern. The major approach to minimize CIA is by scalp cooling. Unfortunately, most published data on scalp cooling are of poor quality. Several experimental approaches to the development of pharmacologic agents are under evaluation and include drug-specific antibodies, hair growth cycle modifiers, cytokines and growth factors, antioxidants, inhibitors of apoptosis, and cell-cycle and proliferation modifiers. Ultimately, the protection should be selective to the hair follicle; for example, topical application, such that the anticancer efficacy of chemotherapy is not hampered. Among the few agents that have been evaluated so far in humans, AS101 and minoxidil were able to reduce the severity or shorten the duration of CIA, but could not prevent CIA.

*For a PDF of the full article, click on the link to the left of this introduction.

Ralph M. Trüeb, MD

Few dermatologic conditions carry as much emotional distress as chemotherapy-induced alopecia (CIA). The prerequisite for successful development of strategies for CIA prevention is the understanding of the pathobiology of CIA. The incidence and severity of CIA are variable and related to the particular chemotherapeutic protocol. CIA is traditionally categorized as acute diffuse hair loss caused by dystrophic anagen effluvium; however, CIA presents with different clinical patterns of hair loss. When an arrest of mitotic activity occurs, obviously numerous and interacting factors influence the shedding pattern. The major approach to minimize CIA is by scalp cooling. Unfortunately, most published data on scalp cooling are of poor quality. Several experimental approaches to the development of pharmacologic agents are under evaluation and include drug-specific antibodies, hair growth cycle modifiers, cytokines and growth factors, antioxidants, inhibitors of apoptosis, and cell-cycle and proliferation modifiers. Ultimately, the protection should be selective to the hair follicle; for example, topical application, such that the anticancer efficacy of chemotherapy is not hampered. Among the few agents that have been evaluated so far in humans, AS101 and minoxidil were able to reduce the severity or shorten the duration of CIA, but could not prevent CIA.

*For a PDF of the full article, click on the link to the left of this introduction.

Each beach vacation from birth to age 6 by white Colorado children was associated with a 5% increase in small nevi when the children were examined at age 7, but not with large nevi development.

In addition, the total estimated UV dose received on waterside vacations and the number of days spent on vacation were not significantly related to nevi count, suggesting that a threshold dose of UV exposure is received relatively early during each waterside vacation, such that 3-day-long getaways may have the same effect on nevi development as 10-day trips, according to the authors.

Although it is the larger nevi (greater than or equal to 2 mm) that are most commonly associated with skin cancer, increased numbers of small nevi in childhood also confer melanoma risk.

“Parents should be aware of the effect that vacations may have on their children's risk for developing melanoma as adults, and they should be cautious about selection of vacation locations,” wrote Dr. Kelly J. Pettijohn, the study's lead author, from the department of community and behavioral health at the Colorado School of Public Health, Denver, and associates.

A total of 681 children born in 1998 who were lifetime residents of Colorado were studied.

Patients' parents were asked in 20- to 30-minute phone interviews about the child's vacation history, sunburn history, and demographic data. Skin exams were also conducted in 2005, when the patients were 7 years old, and nevi were grouped into two categories: less than 2 mm, or greater than or equal to 2 mm (Cancer Epidemiol. Biomarkers Prev. 2009;18:454–63).

Vacations were classified as either “waterside” or “nonwaterside” depending on their location.

For example, all vacations to Miami were considered waterside because it is assumed that the child would have spent a large amount of time in the sun with minimal clothing coverage. Some locations were considered waterside only in the summer season—for example, Duck, N.C.

And other locations, though technically waterside, were included in the nonwaterside category because they are not typically associated with water activities that lead to sun exposure in any season of the year; San Francisco fell into this category.

A history of severe sunburn, of sunscreen use, of hat use, or of sun sensitivity failed to predict the development of nevi. “The only significant linear relationship between vacations and nevi less than 2 mm was for number of waterside vacations before age 6,” wrote the authors. Each vacation was associated with a 5% increase in these small nevi after other factors were controlled for.

In addition, the authors found that waterside vacations taken within 1 year of the skin exam did not affect small nevi counts.

This finding suggests a time lag of at least 1 year may be necessary for the effects of sun exposure during waterside vacations to result in new nevi, they noted. Alternatively, the finding could be due to a physiologic change in childrens' melanocytes, “which become less susceptible to the intense sun exposure received on waterside vacations as [children] age.”

The obvious limitations of this study, including the lack of behavioral information (for instance, on the exact amount of time spent outside while on vacation, the type of clothing worn, or the sun protection practices used), as well as reliance on parent recall, are countered by the study's strengths. “It is one of the few large longitudinal cohort studies of nevus development in children,” said the authors, and it is the only one to report the link between vacations and nevi in North American subjects.

The authors reported no potential conflicts of interest related to this story.

“Parents should be aware of the effect that vacations may have on their children's” melanoma risk, warned an investigator. LOUISE A. KOENIG/ELSEVIER GLOBAL MEDICAL NEWS

Each beach vacation from birth to age 6 by white Colorado children was associated with a 5% increase in small nevi when the children were examined at age 7, but not with large nevi development.

In addition, the total estimated UV dose received on waterside vacations and the number of days spent on vacation were not significantly related to nevi count, suggesting that a threshold dose of UV exposure is received relatively early during each waterside vacation, such that 3-day-long getaways may have the same effect on nevi development as 10-day trips, according to the authors.

Although it is the larger nevi (greater than or equal to 2 mm) that are most commonly associated with skin cancer, increased numbers of small nevi in childhood also confer melanoma risk.

“Parents should be aware of the effect that vacations may have on their children's risk for developing melanoma as adults, and they should be cautious about selection of vacation locations,” wrote Dr. Kelly J. Pettijohn, the study's lead author, from the department of community and behavioral health at the Colorado School of Public Health, Denver, and associates.

A total of 681 children born in 1998 who were lifetime residents of Colorado were studied.

Patients' parents were asked in 20- to 30-minute phone interviews about the child's vacation history, sunburn history, and demographic data. Skin exams were also conducted in 2005, when the patients were 7 years old, and nevi were grouped into two categories: less than 2 mm, or greater than or equal to 2 mm (Cancer Epidemiol. Biomarkers Prev. 2009;18:454–63).

Vacations were classified as either “waterside” or “nonwaterside” depending on their location.

For example, all vacations to Miami were considered waterside because it is assumed that the child would have spent a large amount of time in the sun with minimal clothing coverage. Some locations were considered waterside only in the summer season—for example, Duck, N.C.

And other locations, though technically waterside, were included in the nonwaterside category because they are not typically associated with water activities that lead to sun exposure in any season of the year; San Francisco fell into this category.

A history of severe sunburn, of sunscreen use, of hat use, or of sun sensitivity failed to predict the development of nevi. “The only significant linear relationship between vacations and nevi less than 2 mm was for number of waterside vacations before age 6,” wrote the authors. Each vacation was associated with a 5% increase in these small nevi after other factors were controlled for.

In addition, the authors found that waterside vacations taken within 1 year of the skin exam did not affect small nevi counts.

This finding suggests a time lag of at least 1 year may be necessary for the effects of sun exposure during waterside vacations to result in new nevi, they noted. Alternatively, the finding could be due to a physiologic change in childrens' melanocytes, “which become less susceptible to the intense sun exposure received on waterside vacations as [children] age.”

The obvious limitations of this study, including the lack of behavioral information (for instance, on the exact amount of time spent outside while on vacation, the type of clothing worn, or the sun protection practices used), as well as reliance on parent recall, are countered by the study's strengths. “It is one of the few large longitudinal cohort studies of nevus development in children,” said the authors, and it is the only one to report the link between vacations and nevi in North American subjects.

The authors reported no potential conflicts of interest related to this story.

“Parents should be aware of the effect that vacations may have on their children's” melanoma risk, warned an investigator. LOUISE A. KOENIG/ELSEVIER GLOBAL MEDICAL NEWS

Each beach vacation from birth to age 6 by white Colorado children was associated with a 5% increase in small nevi when the children were examined at age 7, but not with large nevi development.

In addition, the total estimated UV dose received on waterside vacations and the number of days spent on vacation were not significantly related to nevi count, suggesting that a threshold dose of UV exposure is received relatively early during each waterside vacation, such that 3-day-long getaways may have the same effect on nevi development as 10-day trips, according to the authors.

Although it is the larger nevi (greater than or equal to 2 mm) that are most commonly associated with skin cancer, increased numbers of small nevi in childhood also confer melanoma risk.

“Parents should be aware of the effect that vacations may have on their children's risk for developing melanoma as adults, and they should be cautious about selection of vacation locations,” wrote Dr. Kelly J. Pettijohn, the study's lead author, from the department of community and behavioral health at the Colorado School of Public Health, Denver, and associates.

A total of 681 children born in 1998 who were lifetime residents of Colorado were studied.

Patients' parents were asked in 20- to 30-minute phone interviews about the child's vacation history, sunburn history, and demographic data. Skin exams were also conducted in 2005, when the patients were 7 years old, and nevi were grouped into two categories: less than 2 mm, or greater than or equal to 2 mm (Cancer Epidemiol. Biomarkers Prev. 2009;18:454–63).

Vacations were classified as either “waterside” or “nonwaterside” depending on their location.

For example, all vacations to Miami were considered waterside because it is assumed that the child would have spent a large amount of time in the sun with minimal clothing coverage. Some locations were considered waterside only in the summer season—for example, Duck, N.C.

And other locations, though technically waterside, were included in the nonwaterside category because they are not typically associated with water activities that lead to sun exposure in any season of the year; San Francisco fell into this category.

A history of severe sunburn, of sunscreen use, of hat use, or of sun sensitivity failed to predict the development of nevi. “The only significant linear relationship between vacations and nevi less than 2 mm was for number of waterside vacations before age 6,” wrote the authors. Each vacation was associated with a 5% increase in these small nevi after other factors were controlled for.

In addition, the authors found that waterside vacations taken within 1 year of the skin exam did not affect small nevi counts.

This finding suggests a time lag of at least 1 year may be necessary for the effects of sun exposure during waterside vacations to result in new nevi, they noted. Alternatively, the finding could be due to a physiologic change in childrens' melanocytes, “which become less susceptible to the intense sun exposure received on waterside vacations as [children] age.”

The obvious limitations of this study, including the lack of behavioral information (for instance, on the exact amount of time spent outside while on vacation, the type of clothing worn, or the sun protection practices used), as well as reliance on parent recall, are countered by the study's strengths. “It is one of the few large longitudinal cohort studies of nevus development in children,” said the authors, and it is the only one to report the link between vacations and nevi in North American subjects.

The authors reported no potential conflicts of interest related to this story.

“Parents should be aware of the effect that vacations may have on their children's” melanoma risk, warned an investigator. LOUISE A. KOENIG/ELSEVIER GLOBAL MEDICAL NEWS

PALM BEACH, FLA. — Regional chemotherapy via isolated limb infusion is an acceptable and minimally invasive alternative to hyperthermic isolated limb perfusion to combat in-transit extremity melanoma, according to a review.

"Perfusion is appropriate with lymph node involvement. For all others, infusion should be considered," Dr. Georgia M. Beasley said. She, Dr. Douglas S. Tyler, and their colleagues reviewed response and toxicity for 166 isolated limb infusions in 157 patients with advanced extremity melanoma. At 3 months after the infusion of melphalan, patients' responses were fairly evenly divided among complete response, partial response, and no response. In cases when the melphalan dose was adjusted for ideal body weight (IBW), the rate of grade 3 or higher toxicity fell more than half, with no effect on complete response rate.

Melphalan (Alkeran) was administered at eight centers, representing the majority of institutions performing limb infusions in the United States, Dr. Beasley said at the annual meeting of the Southern Surgical Association.

Patients received melphalan at doses of 7.5 mg/L for advanced melanoma of the lower extremity and 10 mg/L for the upper extremity. Mean ischemic time was 72 minutes. Papaverine was also administered in 60% of procedures. "We currently recommend use of papaverine in conjunction with adjustment of melphalan for ideal body weight to minimize toxicity," Dr. Beasley said.

Among the 122 evaluable patients, 31% experienced a complete response at 3 months according to RECIST (Response Evaluation Criteria in Solid Tumors), modified for cutaneous lesions. Another 33% of patients had a partial response, and 36% did not respond at 3 months. The complete response rate for hyperthermic isolated limb perfusion is generally accepted to be 40%-80%, Dr. Beasley said. Discussant Dr. Kirby I. Bland drew attention to the 36% rate of nonresponders. "You were still unable to control local disease in [almost] 40% of that population," said Dr. Bland, chair of the surgery department at the University of Alabama at Birmingham.

"For extensive in-transit disease in the lower extremity, I would recommend infusion, even though one-third of patients are not expected to have a response," responded Dr. Beasley, a first-year general surgery resident at Duke University Medical Center, Durham, N.C. "This allows reservation of perfusion for those who do not respond. Also, repeat perfusions are more difficult to do."

Dr. Beasley said that 36% of cases were associated with grade 3 or higher clinical toxicity. In 42% of the procedures, melphalan was adjusted for IBW. This modification reduced grade 3 or greater toxicities from 47% to 21%. At the same time, it did not alter the complete response rate. "By the end of the series, we were correcting everyone [at Duke] for ideal body weight," Dr. Beasley said. She cautioned that the dose adjustment did reduce the partial response rate, however.

Limb infusion and perfusion exhibit major differences in the rates of grade 5 toxicity, Dr. Beasley said. Even though one limb infusion patient had an amputation, the rate of grade 5 toxicity "appears to be nearly 10-fold higher with perfusion," based on all the published data for isolated limb infusion. The study did not directly compare rates of grade 3 and 4 toxicity in infusion and perfusion, but the rates appear to be somewhat similar, she said, with dose correction for IBW significantly reducing toxicity.

"How many patients had compartment syndrome, and what are your recommendations for monitoring?" asked Dr. Kelly M. McMasters, a study discussant and chair of surgery at the University of Louisville (Ky.). Nine cases of compartment syndrome were reported, Dr. Beasley replied. She recommended daily creatine phosphokinase measurements and close clinical monitoring.

Only two U.S. studies previously assessed isolated limb infusion, with both reporting single-center experience (Ann. Surg. Oncol. 2008;15:2195–205; Ann. Surg. Oncol. 2006;13:1123–9).

None of the researchers in the current study had any relevant disclosures.

PALM BEACH, FLA. — Regional chemotherapy via isolated limb infusion is an acceptable and minimally invasive alternative to hyperthermic isolated limb perfusion to combat in-transit extremity melanoma, according to a review.

"Perfusion is appropriate with lymph node involvement. For all others, infusion should be considered," Dr. Georgia M. Beasley said. She, Dr. Douglas S. Tyler, and their colleagues reviewed response and toxicity for 166 isolated limb infusions in 157 patients with advanced extremity melanoma. At 3 months after the infusion of melphalan, patients' responses were fairly evenly divided among complete response, partial response, and no response. In cases when the melphalan dose was adjusted for ideal body weight (IBW), the rate of grade 3 or higher toxicity fell more than half, with no effect on complete response rate.

Melphalan (Alkeran) was administered at eight centers, representing the majority of institutions performing limb infusions in the United States, Dr. Beasley said at the annual meeting of the Southern Surgical Association.

Patients received melphalan at doses of 7.5 mg/L for advanced melanoma of the lower extremity and 10 mg/L for the upper extremity. Mean ischemic time was 72 minutes. Papaverine was also administered in 60% of procedures. "We currently recommend use of papaverine in conjunction with adjustment of melphalan for ideal body weight to minimize toxicity," Dr. Beasley said.

Among the 122 evaluable patients, 31% experienced a complete response at 3 months according to RECIST (Response Evaluation Criteria in Solid Tumors), modified for cutaneous lesions. Another 33% of patients had a partial response, and 36% did not respond at 3 months. The complete response rate for hyperthermic isolated limb perfusion is generally accepted to be 40%-80%, Dr. Beasley said. Discussant Dr. Kirby I. Bland drew attention to the 36% rate of nonresponders. "You were still unable to control local disease in [almost] 40% of that population," said Dr. Bland, chair of the surgery department at the University of Alabama at Birmingham.

"For extensive in-transit disease in the lower extremity, I would recommend infusion, even though one-third of patients are not expected to have a response," responded Dr. Beasley, a first-year general surgery resident at Duke University Medical Center, Durham, N.C. "This allows reservation of perfusion for those who do not respond. Also, repeat perfusions are more difficult to do."

Dr. Beasley said that 36% of cases were associated with grade 3 or higher clinical toxicity. In 42% of the procedures, melphalan was adjusted for IBW. This modification reduced grade 3 or greater toxicities from 47% to 21%. At the same time, it did not alter the complete response rate. "By the end of the series, we were correcting everyone [at Duke] for ideal body weight," Dr. Beasley said. She cautioned that the dose adjustment did reduce the partial response rate, however.

Limb infusion and perfusion exhibit major differences in the rates of grade 5 toxicity, Dr. Beasley said. Even though one limb infusion patient had an amputation, the rate of grade 5 toxicity "appears to be nearly 10-fold higher with perfusion," based on all the published data for isolated limb infusion. The study did not directly compare rates of grade 3 and 4 toxicity in infusion and perfusion, but the rates appear to be somewhat similar, she said, with dose correction for IBW significantly reducing toxicity.

"How many patients had compartment syndrome, and what are your recommendations for monitoring?" asked Dr. Kelly M. McMasters, a study discussant and chair of surgery at the University of Louisville (Ky.). Nine cases of compartment syndrome were reported, Dr. Beasley replied. She recommended daily creatine phosphokinase measurements and close clinical monitoring.

Only two U.S. studies previously assessed isolated limb infusion, with both reporting single-center experience (Ann. Surg. Oncol. 2008;15:2195–205; Ann. Surg. Oncol. 2006;13:1123–9).

None of the researchers in the current study had any relevant disclosures.

PALM BEACH, FLA. — Regional chemotherapy via isolated limb infusion is an acceptable and minimally invasive alternative to hyperthermic isolated limb perfusion to combat in-transit extremity melanoma, according to a review.

"Perfusion is appropriate with lymph node involvement. For all others, infusion should be considered," Dr. Georgia M. Beasley said. She, Dr. Douglas S. Tyler, and their colleagues reviewed response and toxicity for 166 isolated limb infusions in 157 patients with advanced extremity melanoma. At 3 months after the infusion of melphalan, patients' responses were fairly evenly divided among complete response, partial response, and no response. In cases when the melphalan dose was adjusted for ideal body weight (IBW), the rate of grade 3 or higher toxicity fell more than half, with no effect on complete response rate.

Melphalan (Alkeran) was administered at eight centers, representing the majority of institutions performing limb infusions in the United States, Dr. Beasley said at the annual meeting of the Southern Surgical Association.

Patients received melphalan at doses of 7.5 mg/L for advanced melanoma of the lower extremity and 10 mg/L for the upper extremity. Mean ischemic time was 72 minutes. Papaverine was also administered in 60% of procedures. "We currently recommend use of papaverine in conjunction with adjustment of melphalan for ideal body weight to minimize toxicity," Dr. Beasley said.

Among the 122 evaluable patients, 31% experienced a complete response at 3 months according to RECIST (Response Evaluation Criteria in Solid Tumors), modified for cutaneous lesions. Another 33% of patients had a partial response, and 36% did not respond at 3 months. The complete response rate for hyperthermic isolated limb perfusion is generally accepted to be 40%-80%, Dr. Beasley said. Discussant Dr. Kirby I. Bland drew attention to the 36% rate of nonresponders. "You were still unable to control local disease in [almost] 40% of that population," said Dr. Bland, chair of the surgery department at the University of Alabama at Birmingham.

"For extensive in-transit disease in the lower extremity, I would recommend infusion, even though one-third of patients are not expected to have a response," responded Dr. Beasley, a first-year general surgery resident at Duke University Medical Center, Durham, N.C. "This allows reservation of perfusion for those who do not respond. Also, repeat perfusions are more difficult to do."

Dr. Beasley said that 36% of cases were associated with grade 3 or higher clinical toxicity. In 42% of the procedures, melphalan was adjusted for IBW. This modification reduced grade 3 or greater toxicities from 47% to 21%. At the same time, it did not alter the complete response rate. "By the end of the series, we were correcting everyone [at Duke] for ideal body weight," Dr. Beasley said. She cautioned that the dose adjustment did reduce the partial response rate, however.

Limb infusion and perfusion exhibit major differences in the rates of grade 5 toxicity, Dr. Beasley said. Even though one limb infusion patient had an amputation, the rate of grade 5 toxicity "appears to be nearly 10-fold higher with perfusion," based on all the published data for isolated limb infusion. The study did not directly compare rates of grade 3 and 4 toxicity in infusion and perfusion, but the rates appear to be somewhat similar, she said, with dose correction for IBW significantly reducing toxicity.

"How many patients had compartment syndrome, and what are your recommendations for monitoring?" asked Dr. Kelly M. McMasters, a study discussant and chair of surgery at the University of Louisville (Ky.). Nine cases of compartment syndrome were reported, Dr. Beasley replied. She recommended daily creatine phosphokinase measurements and close clinical monitoring.

Only two U.S. studies previously assessed isolated limb infusion, with both reporting single-center experience (Ann. Surg. Oncol. 2008;15:2195–205; Ann. Surg. Oncol. 2006;13:1123–9).

None of the researchers in the current study had any relevant disclosures.

SANTA FE, N.M. — Physicians at the John Wayne Cancer Institute in Los Angeles have developed a scoring system to help identify the small number of thin melanomas most at risk of nodal recurrence and in need of evaluation by sentinel lymph node biopsy.

The system uses three parameters—Breslow thickness, age, and sex—that emerged as significant predictors in a multivariate analysis of 1,732 patients prospectively followed at the institute after treatment with excision alone within 6 months of their melanoma diagnosis. Patients with clinically evident nodal disease or nodal staging were excluded from the study.

Only 2.9% had regional nodal basin recurrence at a mean follow-up of 13.2 years, Dr. Mark B. Faries reported in a presentation of the system at the annual meeting of the Western Surgical Association. Risk increased with Breslow thickness (odds ratio, 2.5; P less than .0001) and male sex (OR, 3.5; P = .0005), but decreased with age above 50 years (OR, 0.45; P = .0019).

Predicted probabilities of recurrence ranged from 0.1% to 17.4% in the 18-step scoring system shown by Dr. Faries, a surgical oncologist at the institute. The lowest risk would be in a female patient over 70 years old with a melanoma less than 0.5 mm thick. The highest risk was assigned to a hypothetical male patient less than 50 years of age with a melanoma 0.76–0.99 mm in Breslow thickness.

"Most patients can be classified as very low risk, but others have a more substantial risk of nodal disease," he said. "The risk of clinical nodal recurrence can be estimated for patients with thin melanoma based on very simple and reproducible parameters."

Men accounted for slightly more than half, 51%, of the study population. Mean age was 48.5 years; mean Breslow thickness was 0.5 mm. Most melanomas were on the trunk (43%) or extremities (41%); just 16% were on the head or neck.

Ulceration was recorded in only 39 patients—2.3% of the study population (among whom only 1,282 had ulceration data available)—but Dr. Faries reported it greatly increased risk of nodal recurrence. The recurrence rate reached 7.7% in patients with ulceration, vs. 2.7% in the absence of ulceration.

This led Dr. James A. Recaberen of Huntington Memorial Hospital in Pasadena, Calif., to observe from the audience, "The most important thing I take away is that anyone with ulceration should be a candidate for nodal investigation." Dr. Faries concurred that while ulceration is infrequent, it can be cause by itself to proceed with a nodal biopsy.

Another lesson, he said, was the need for long follow-up of thin melanomas. About a third of recurrences occurred after 5 years of follow-up. Mean time to nodal recurrence was 38.3 months.

The small number of recurrences relative to the large number of patients with thin melanomas presents a particularly challenging problem, according to Dr. Faries and other speakers. "Melanoma is increasing in incidence faster than virtually any other solid tumor," he said, noting that about 70% of new lesions are less than 1 mm in thickness.

As with thicker melanoma, lymph node status is the most significant prognostic factor Dr. Faries noted. "However, use of sentinel node biopsy in all cases of thin melanoma is not reasonable," he cautioned, citing the large number of patients involved.

Indeed, in his discussion of the presentation, Dr. Richard Thirlby suggested that indiscriminate use of sentinel node dissection could result in a cost of $1 million to find one nodal recurrence.

Dr. Thirlby of Virginia Mason Medical Center in Seattle praised the analysis; however, he noted that it did not give thresholds for ordering a biopsy. To that end, he called for a decision-tree analysis that could help physicians use the system to decide when to recommend a sentinel node procedure.

Decision-tree and cost analyses are excellent suggestions, Dr. Faries agreed, but "I don't know that we can make a bottom line based on any predictive system."

Dr. Faries reported no relevant conflicts of interest.

SANTA FE, N.M. — Physicians at the John Wayne Cancer Institute in Los Angeles have developed a scoring system to help identify the small number of thin melanomas most at risk of nodal recurrence and in need of evaluation by sentinel lymph node biopsy.

The system uses three parameters—Breslow thickness, age, and sex—that emerged as significant predictors in a multivariate analysis of 1,732 patients prospectively followed at the institute after treatment with excision alone within 6 months of their melanoma diagnosis. Patients with clinically evident nodal disease or nodal staging were excluded from the study.

Only 2.9% had regional nodal basin recurrence at a mean follow-up of 13.2 years, Dr. Mark B. Faries reported in a presentation of the system at the annual meeting of the Western Surgical Association. Risk increased with Breslow thickness (odds ratio, 2.5; P less than .0001) and male sex (OR, 3.5; P = .0005), but decreased with age above 50 years (OR, 0.45; P = .0019).

Predicted probabilities of recurrence ranged from 0.1% to 17.4% in the 18-step scoring system shown by Dr. Faries, a surgical oncologist at the institute. The lowest risk would be in a female patient over 70 years old with a melanoma less than 0.5 mm thick. The highest risk was assigned to a hypothetical male patient less than 50 years of age with a melanoma 0.76–0.99 mm in Breslow thickness.

"Most patients can be classified as very low risk, but others have a more substantial risk of nodal disease," he said. "The risk of clinical nodal recurrence can be estimated for patients with thin melanoma based on very simple and reproducible parameters."

Men accounted for slightly more than half, 51%, of the study population. Mean age was 48.5 years; mean Breslow thickness was 0.5 mm. Most melanomas were on the trunk (43%) or extremities (41%); just 16% were on the head or neck.

Ulceration was recorded in only 39 patients—2.3% of the study population (among whom only 1,282 had ulceration data available)—but Dr. Faries reported it greatly increased risk of nodal recurrence. The recurrence rate reached 7.7% in patients with ulceration, vs. 2.7% in the absence of ulceration.

This led Dr. James A. Recaberen of Huntington Memorial Hospital in Pasadena, Calif., to observe from the audience, "The most important thing I take away is that anyone with ulceration should be a candidate for nodal investigation." Dr. Faries concurred that while ulceration is infrequent, it can be cause by itself to proceed with a nodal biopsy.

Another lesson, he said, was the need for long follow-up of thin melanomas. About a third of recurrences occurred after 5 years of follow-up. Mean time to nodal recurrence was 38.3 months.

The small number of recurrences relative to the large number of patients with thin melanomas presents a particularly challenging problem, according to Dr. Faries and other speakers. "Melanoma is increasing in incidence faster than virtually any other solid tumor," he said, noting that about 70% of new lesions are less than 1 mm in thickness.

As with thicker melanoma, lymph node status is the most significant prognostic factor Dr. Faries noted. "However, use of sentinel node biopsy in all cases of thin melanoma is not reasonable," he cautioned, citing the large number of patients involved.

Indeed, in his discussion of the presentation, Dr. Richard Thirlby suggested that indiscriminate use of sentinel node dissection could result in a cost of $1 million to find one nodal recurrence.

Dr. Thirlby of Virginia Mason Medical Center in Seattle praised the analysis; however, he noted that it did not give thresholds for ordering a biopsy. To that end, he called for a decision-tree analysis that could help physicians use the system to decide when to recommend a sentinel node procedure.

Decision-tree and cost analyses are excellent suggestions, Dr. Faries agreed, but "I don't know that we can make a bottom line based on any predictive system."

Dr. Faries reported no relevant conflicts of interest.

SANTA FE, N.M. — Physicians at the John Wayne Cancer Institute in Los Angeles have developed a scoring system to help identify the small number of thin melanomas most at risk of nodal recurrence and in need of evaluation by sentinel lymph node biopsy.

The system uses three parameters—Breslow thickness, age, and sex—that emerged as significant predictors in a multivariate analysis of 1,732 patients prospectively followed at the institute after treatment with excision alone within 6 months of their melanoma diagnosis. Patients with clinically evident nodal disease or nodal staging were excluded from the study.

Only 2.9% had regional nodal basin recurrence at a mean follow-up of 13.2 years, Dr. Mark B. Faries reported in a presentation of the system at the annual meeting of the Western Surgical Association. Risk increased with Breslow thickness (odds ratio, 2.5; P less than .0001) and male sex (OR, 3.5; P = .0005), but decreased with age above 50 years (OR, 0.45; P = .0019).

Predicted probabilities of recurrence ranged from 0.1% to 17.4% in the 18-step scoring system shown by Dr. Faries, a surgical oncologist at the institute. The lowest risk would be in a female patient over 70 years old with a melanoma less than 0.5 mm thick. The highest risk was assigned to a hypothetical male patient less than 50 years of age with a melanoma 0.76–0.99 mm in Breslow thickness.

"Most patients can be classified as very low risk, but others have a more substantial risk of nodal disease," he said. "The risk of clinical nodal recurrence can be estimated for patients with thin melanoma based on very simple and reproducible parameters."

Men accounted for slightly more than half, 51%, of the study population. Mean age was 48.5 years; mean Breslow thickness was 0.5 mm. Most melanomas were on the trunk (43%) or extremities (41%); just 16% were on the head or neck.

Ulceration was recorded in only 39 patients—2.3% of the study population (among whom only 1,282 had ulceration data available)—but Dr. Faries reported it greatly increased risk of nodal recurrence. The recurrence rate reached 7.7% in patients with ulceration, vs. 2.7% in the absence of ulceration.

This led Dr. James A. Recaberen of Huntington Memorial Hospital in Pasadena, Calif., to observe from the audience, "The most important thing I take away is that anyone with ulceration should be a candidate for nodal investigation." Dr. Faries concurred that while ulceration is infrequent, it can be cause by itself to proceed with a nodal biopsy.

Another lesson, he said, was the need for long follow-up of thin melanomas. About a third of recurrences occurred after 5 years of follow-up. Mean time to nodal recurrence was 38.3 months.

The small number of recurrences relative to the large number of patients with thin melanomas presents a particularly challenging problem, according to Dr. Faries and other speakers. "Melanoma is increasing in incidence faster than virtually any other solid tumor," he said, noting that about 70% of new lesions are less than 1 mm in thickness.

As with thicker melanoma, lymph node status is the most significant prognostic factor Dr. Faries noted. "However, use of sentinel node biopsy in all cases of thin melanoma is not reasonable," he cautioned, citing the large number of patients involved.

Indeed, in his discussion of the presentation, Dr. Richard Thirlby suggested that indiscriminate use of sentinel node dissection could result in a cost of $1 million to find one nodal recurrence.

Dr. Thirlby of Virginia Mason Medical Center in Seattle praised the analysis; however, he noted that it did not give thresholds for ordering a biopsy. To that end, he called for a decision-tree analysis that could help physicians use the system to decide when to recommend a sentinel node procedure.

Decision-tree and cost analyses are excellent suggestions, Dr. Faries agreed, but "I don't know that we can make a bottom line based on any predictive system."

Dr. Faries reported no relevant conflicts of interest.

Vitamin D, skin cancer screening, and chemoprevention top the list of current melanoma prevention controversies, according to Dr. Clara Curiel-Lewandowski.

Vitamin D has been a contentious subject for many years with its being suggested that increased sun protection may be associated with lower vitamin D levels, noted Dr. Lewandowski at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation in Maui.

"A decrease in the serum level of vitamin D has been observed in the general population, particularly here in the United States.

"The challenge is to understand to which degree each modulating factor—such as vitamin D dietary intake, photoprotection, body mass index, and geographical location—contributes to the observed decline in serum levels," she said in an interview.

"There is no randomized prospective study linking vitamin D deficiency to excessive photoprotection. Those studies are very difficult to carry out," said Dr. Curiel-Lewandowski, who is director of the pigmented lesion clinic and multidisciplinary oncology at the Arizona Cancer Center in Tucson.

Another component in declining vitamin D levels is that humans produce less vitamin D as they age. Therefore, rising life expectancy may have a role in decreased vitamin D levels. "We're now living to 60, 70, 80 years and we are converting less vitamin D, irrespective of other sources," she said.

In addition, normal levels of serum 25(OH)D are now in the 70-nmol/L range, where it used to be 35–40 nmol/L, she said. With all of these variables, it is very difficult to tease out which of the components are responsible for declining vitamin D levels.

Advice to skin cancer patients about vitamin D should be based on common sense, said Dr. Curiel-Lewandowski.

She recommends that patients pursue a balanced diet, take daily vitamin D supplements above 400 IU if needed, and limit sun exposure to early morning and late afternoon hours. The specific dose supplementation for individuals with suspected risk factors for vitamin D deficiency should be based on their serum 25(OH)D levels.

Skin Cancer Screening

It's important to make the distinction between screening the general population and screening specific high-risk groups for skin cancer, said Dr. Curiel-Lewandowski.

"Cost effectiveness of massive skin cancer screening in the general population has been questioned," she said. An agreement needs to be reached on who is at risk for melanoma and how to target them for skin cancer screening.

The United States Preventive Services Task Force just released new recommendations on skin cancer screening for the general population (Ann. Intern. Med. 2009;150:188–93).

The task force said that there is insufficient evidence to recommend for or against skin cancer screening in the general population. (See story on pg. 4.)

"It is important to understand—no one is against skin cancer screening," said Dr. Curiel-Lewandowski. There simply are not enough data to recommend for or against it in the general population.

"In order to properly validate the effectiveness of massive or selective screening, randomized prospective studies will need to be completed. However, the incidence of melanoma is lower compared with other cancers and in order to get significance, you need more than 400,000 subjects involved and followed for over 10 years to achieve reasonable outcome data. … It's a very difficult study to accomplish," she said.

The task force did identify high-risk groups of individuals: fair-skinned men and women older than 65 years, patients with atypical nevi, patients with more than 50 nevi, and those with a family history of melanoma.

"What's not clear from this message is what to do with people that are known to be at high risk," she said, noting that the new recommendations identify these groups "but they don't tell you the type of screening and frequency that is recommended."

These are precisely the patients that many dermatologists see—patients with atypical nevi, those with a family history of melanoma, and transplant patients. Screenings should be done for these individuals, said Dr. Curiel-Lewandowski.

Chemoprevention

"The reason why the concept of melanoma chemoprevention is emerging is because new alternatives are necessary to decrease the burden of disease, especially in high risk individuals. This rationale is particularly compelling since we haven't been successful in decreasing mortality rates. … It opens up another option, which is trying to identify systemic agents that can be used in individuals at higher risk for melanoma to slow down the development of disease or even prevent it," Dr. Curiel-Lewandowski commented.

In the 1980s, studies were performed using topical retinoids for atypical nevi. In the late 1990s, statins became the hot topic. Neither option panned out. "What is emerging now among several candidate agents are nonsteroidal anti-inflammatories and green tea derivatives" she said.

The idea of using NSAIDs for the chemoprevention of melanoma comes from experimental and limited epidemiologic and clinical data suggesting that the extended use of NSAIDs decreases the risk of melanoma development. Ongoing larger epidemiologic studies looking in more detail at the strength of this association are expected to be released within the next year.

"Since multiple melanoma pathways have been identified, the effectiveness of a specific chemopreventive agent in a given high-risk population needs to be carefully thought out," Dr. Curiel-Lewandowski said.

Some have advanced this as an argument against chemoprevention.

SDEF and this newspaper are owned by Elsevier.

Vitamin D, skin cancer screening, and chemoprevention top the list of current melanoma prevention controversies, according to Dr. Clara Curiel-Lewandowski.

Vitamin D has been a contentious subject for many years with its being suggested that increased sun protection may be associated with lower vitamin D levels, noted Dr. Lewandowski at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation in Maui.

"A decrease in the serum level of vitamin D has been observed in the general population, particularly here in the United States.

"The challenge is to understand to which degree each modulating factor—such as vitamin D dietary intake, photoprotection, body mass index, and geographical location—contributes to the observed decline in serum levels," she said in an interview.

"There is no randomized prospective study linking vitamin D deficiency to excessive photoprotection. Those studies are very difficult to carry out," said Dr. Curiel-Lewandowski, who is director of the pigmented lesion clinic and multidisciplinary oncology at the Arizona Cancer Center in Tucson.

Another component in declining vitamin D levels is that humans produce less vitamin D as they age. Therefore, rising life expectancy may have a role in decreased vitamin D levels. "We're now living to 60, 70, 80 years and we are converting less vitamin D, irrespective of other sources," she said.

In addition, normal levels of serum 25(OH)D are now in the 70-nmol/L range, where it used to be 35–40 nmol/L, she said. With all of these variables, it is very difficult to tease out which of the components are responsible for declining vitamin D levels.

Advice to skin cancer patients about vitamin D should be based on common sense, said Dr. Curiel-Lewandowski.

She recommends that patients pursue a balanced diet, take daily vitamin D supplements above 400 IU if needed, and limit sun exposure to early morning and late afternoon hours. The specific dose supplementation for individuals with suspected risk factors for vitamin D deficiency should be based on their serum 25(OH)D levels.

Skin Cancer Screening

It's important to make the distinction between screening the general population and screening specific high-risk groups for skin cancer, said Dr. Curiel-Lewandowski.

"Cost effectiveness of massive skin cancer screening in the general population has been questioned," she said. An agreement needs to be reached on who is at risk for melanoma and how to target them for skin cancer screening.

The United States Preventive Services Task Force just released new recommendations on skin cancer screening for the general population (Ann. Intern. Med. 2009;150:188–93).

The task force said that there is insufficient evidence to recommend for or against skin cancer screening in the general population. (See story on pg. 4.)

"It is important to understand—no one is against skin cancer screening," said Dr. Curiel-Lewandowski. There simply are not enough data to recommend for or against it in the general population.

"In order to properly validate the effectiveness of massive or selective screening, randomized prospective studies will need to be completed. However, the incidence of melanoma is lower compared with other cancers and in order to get significance, you need more than 400,000 subjects involved and followed for over 10 years to achieve reasonable outcome data. … It's a very difficult study to accomplish," she said.

The task force did identify high-risk groups of individuals: fair-skinned men and women older than 65 years, patients with atypical nevi, patients with more than 50 nevi, and those with a family history of melanoma.

"What's not clear from this message is what to do with people that are known to be at high risk," she said, noting that the new recommendations identify these groups "but they don't tell you the type of screening and frequency that is recommended."

These are precisely the patients that many dermatologists see—patients with atypical nevi, those with a family history of melanoma, and transplant patients. Screenings should be done for these individuals, said Dr. Curiel-Lewandowski.

Chemoprevention

"The reason why the concept of melanoma chemoprevention is emerging is because new alternatives are necessary to decrease the burden of disease, especially in high risk individuals. This rationale is particularly compelling since we haven't been successful in decreasing mortality rates. … It opens up another option, which is trying to identify systemic agents that can be used in individuals at higher risk for melanoma to slow down the development of disease or even prevent it," Dr. Curiel-Lewandowski commented.

In the 1980s, studies were performed using topical retinoids for atypical nevi. In the late 1990s, statins became the hot topic. Neither option panned out. "What is emerging now among several candidate agents are nonsteroidal anti-inflammatories and green tea derivatives" she said.

The idea of using NSAIDs for the chemoprevention of melanoma comes from experimental and limited epidemiologic and clinical data suggesting that the extended use of NSAIDs decreases the risk of melanoma development. Ongoing larger epidemiologic studies looking in more detail at the strength of this association are expected to be released within the next year.

"Since multiple melanoma pathways have been identified, the effectiveness of a specific chemopreventive agent in a given high-risk population needs to be carefully thought out," Dr. Curiel-Lewandowski said.

Some have advanced this as an argument against chemoprevention.

SDEF and this newspaper are owned by Elsevier.

Vitamin D, skin cancer screening, and chemoprevention top the list of current melanoma prevention controversies, according to Dr. Clara Curiel-Lewandowski.

Vitamin D has been a contentious subject for many years with its being suggested that increased sun protection may be associated with lower vitamin D levels, noted Dr. Lewandowski at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation in Maui.

"A decrease in the serum level of vitamin D has been observed in the general population, particularly here in the United States.

"The challenge is to understand to which degree each modulating factor—such as vitamin D dietary intake, photoprotection, body mass index, and geographical location—contributes to the observed decline in serum levels," she said in an interview.

"There is no randomized prospective study linking vitamin D deficiency to excessive photoprotection. Those studies are very difficult to carry out," said Dr. Curiel-Lewandowski, who is director of the pigmented lesion clinic and multidisciplinary oncology at the Arizona Cancer Center in Tucson.

Another component in declining vitamin D levels is that humans produce less vitamin D as they age. Therefore, rising life expectancy may have a role in decreased vitamin D levels. "We're now living to 60, 70, 80 years and we are converting less vitamin D, irrespective of other sources," she said.

In addition, normal levels of serum 25(OH)D are now in the 70-nmol/L range, where it used to be 35–40 nmol/L, she said. With all of these variables, it is very difficult to tease out which of the components are responsible for declining vitamin D levels.

Advice to skin cancer patients about vitamin D should be based on common sense, said Dr. Curiel-Lewandowski.

She recommends that patients pursue a balanced diet, take daily vitamin D supplements above 400 IU if needed, and limit sun exposure to early morning and late afternoon hours. The specific dose supplementation for individuals with suspected risk factors for vitamin D deficiency should be based on their serum 25(OH)D levels.

Skin Cancer Screening

It's important to make the distinction between screening the general population and screening specific high-risk groups for skin cancer, said Dr. Curiel-Lewandowski.

"Cost effectiveness of massive skin cancer screening in the general population has been questioned," she said. An agreement needs to be reached on who is at risk for melanoma and how to target them for skin cancer screening.

The United States Preventive Services Task Force just released new recommendations on skin cancer screening for the general population (Ann. Intern. Med. 2009;150:188–93).

The task force said that there is insufficient evidence to recommend for or against skin cancer screening in the general population. (See story on pg. 4.)

"It is important to understand—no one is against skin cancer screening," said Dr. Curiel-Lewandowski. There simply are not enough data to recommend for or against it in the general population.

"In order to properly validate the effectiveness of massive or selective screening, randomized prospective studies will need to be completed. However, the incidence of melanoma is lower compared with other cancers and in order to get significance, you need more than 400,000 subjects involved and followed for over 10 years to achieve reasonable outcome data. … It's a very difficult study to accomplish," she said.

The task force did identify high-risk groups of individuals: fair-skinned men and women older than 65 years, patients with atypical nevi, patients with more than 50 nevi, and those with a family history of melanoma.

"What's not clear from this message is what to do with people that are known to be at high risk," she said, noting that the new recommendations identify these groups "but they don't tell you the type of screening and frequency that is recommended."

These are precisely the patients that many dermatologists see—patients with atypical nevi, those with a family history of melanoma, and transplant patients. Screenings should be done for these individuals, said Dr. Curiel-Lewandowski.

Chemoprevention

"The reason why the concept of melanoma chemoprevention is emerging is because new alternatives are necessary to decrease the burden of disease, especially in high risk individuals. This rationale is particularly compelling since we haven't been successful in decreasing mortality rates. … It opens up another option, which is trying to identify systemic agents that can be used in individuals at higher risk for melanoma to slow down the development of disease or even prevent it," Dr. Curiel-Lewandowski commented.

In the 1980s, studies were performed using topical retinoids for atypical nevi. In the late 1990s, statins became the hot topic. Neither option panned out. "What is emerging now among several candidate agents are nonsteroidal anti-inflammatories and green tea derivatives" she said.

The idea of using NSAIDs for the chemoprevention of melanoma comes from experimental and limited epidemiologic and clinical data suggesting that the extended use of NSAIDs decreases the risk of melanoma development. Ongoing larger epidemiologic studies looking in more detail at the strength of this association are expected to be released within the next year.

"Since multiple melanoma pathways have been identified, the effectiveness of a specific chemopreventive agent in a given high-risk population needs to be carefully thought out," Dr. Curiel-Lewandowski said.

Some have advanced this as an argument against chemoprevention.

SDEF and this newspaper are owned by Elsevier.

PALM BEACH, FLA. — The presence of microscopic or even submicroscopic melanoma in a sentinel lymph node may be clinically relevant, a retrospective study has shown.

"We believe patients with microscopic deposits of metastatic melanoma have biologically relevant, potentially life-threatening disease," Dr. David W. Ollila said at the annual meeting of the Southern Surgical Association.

Although other investigators have proposed that submicroscopic disease (a sentinel node tumor that is less than 0.1 mm) is not associated with a significantly increased risk of recurrence or death (Br. J. Surg. 2007;94:1293–9), Dr. Ollila and his associates hypothesized that any sentinel node evidence of metastatic melanoma, regardless of size or stage, may be a cause for concern.

He and his associates retrospectively studied 586 patients (mean age, 55 years) with invasive melanoma and a sentinel node biopsy from 1998 to 2007 in a prospectively maintained database. They classified the 322 men and 264 women as node negative or as having a tumor burden of less than 0.1 mm, 0.1–1.0 mm, or greater than 1.0 mm.

The investigators found a statistically significant difference in recurrence of any type between node-negative patients and those with a tumor burden less than 0.1 mm. During a mean follow-up of 2.7 years, 57 (11%) of the 496 node-negative patients had a recurrence, compared with 8 (24%) of the 33 patients with a sentinel node tumor less than 0.1 mm.

"We [also] found a significant difference in disease-free survival between sentinel node-negative [patients] and the submicroscopic group. They cannot be considered equivalent," said Dr. Ollila, director of the sentinel node program and codirector of the multidisciplinary melanoma program at the University of North Carolina at Chapel Hill.

In the node-negative group, 51 patients (10%) died, as did 5 (15%) of those with a tumor burden less than 0.1 mm, 6 of 27 patients (22%) in the 0.1- to 1.0-mm group, and 12 of 30 patients (40%) who had tumors larger than 1.0 mm.

Dr. Ollila pointed out that the stepwise decrease in survival with increasing diameter of the metastatic deposit was statistically different among the four groups. "This is an interesting [finding], contrary to Rotterdam criteria. I submit to you that these patients are on a continuum, and this is clinically relevant disease," he said.

An increased sentinel node tumor burden was also associated with a greater risk of metastatic disease in other nodes. A total of 7% of node-negative patients had distant recurrence, as did 15% of those with tumors less than 0.1 mm, 22% of the 0.1- to 1.0-mm group, and 47% of those with tumors larger than 1.0 mm.

Dr. Marshall M. Urist, professor of surgery, University of Alabama at Birmingham, commented that this is an excellent study and asked, "Why did you measure these metastases in a two-dimensional way for a three-dimensional process?"

Dr. Ollila replied: "Point well taken. It's a volume disease. It would be more representative if we could do volumetric measures." The two-dimensional measurement was a limitation of the database used in the study, he said.

PALM BEACH, FLA. — The presence of microscopic or even submicroscopic melanoma in a sentinel lymph node may be clinically relevant, a retrospective study has shown.

"We believe patients with microscopic deposits of metastatic melanoma have biologically relevant, potentially life-threatening disease," Dr. David W. Ollila said at the annual meeting of the Southern Surgical Association.

Although other investigators have proposed that submicroscopic disease (a sentinel node tumor that is less than 0.1 mm) is not associated with a significantly increased risk of recurrence or death (Br. J. Surg. 2007;94:1293–9), Dr. Ollila and his associates hypothesized that any sentinel node evidence of metastatic melanoma, regardless of size or stage, may be a cause for concern.

He and his associates retrospectively studied 586 patients (mean age, 55 years) with invasive melanoma and a sentinel node biopsy from 1998 to 2007 in a prospectively maintained database. They classified the 322 men and 264 women as node negative or as having a tumor burden of less than 0.1 mm, 0.1–1.0 mm, or greater than 1.0 mm.

The investigators found a statistically significant difference in recurrence of any type between node-negative patients and those with a tumor burden less than 0.1 mm. During a mean follow-up of 2.7 years, 57 (11%) of the 496 node-negative patients had a recurrence, compared with 8 (24%) of the 33 patients with a sentinel node tumor less than 0.1 mm.

"We [also] found a significant difference in disease-free survival between sentinel node-negative [patients] and the submicroscopic group. They cannot be considered equivalent," said Dr. Ollila, director of the sentinel node program and codirector of the multidisciplinary melanoma program at the University of North Carolina at Chapel Hill.

In the node-negative group, 51 patients (10%) died, as did 5 (15%) of those with a tumor burden less than 0.1 mm, 6 of 27 patients (22%) in the 0.1- to 1.0-mm group, and 12 of 30 patients (40%) who had tumors larger than 1.0 mm.

Dr. Ollila pointed out that the stepwise decrease in survival with increasing diameter of the metastatic deposit was statistically different among the four groups. "This is an interesting [finding], contrary to Rotterdam criteria. I submit to you that these patients are on a continuum, and this is clinically relevant disease," he said.

An increased sentinel node tumor burden was also associated with a greater risk of metastatic disease in other nodes. A total of 7% of node-negative patients had distant recurrence, as did 15% of those with tumors less than 0.1 mm, 22% of the 0.1- to 1.0-mm group, and 47% of those with tumors larger than 1.0 mm.

Dr. Marshall M. Urist, professor of surgery, University of Alabama at Birmingham, commented that this is an excellent study and asked, "Why did you measure these metastases in a two-dimensional way for a three-dimensional process?"

Dr. Ollila replied: "Point well taken. It's a volume disease. It would be more representative if we could do volumetric measures." The two-dimensional measurement was a limitation of the database used in the study, he said.

PALM BEACH, FLA. — The presence of microscopic or even submicroscopic melanoma in a sentinel lymph node may be clinically relevant, a retrospective study has shown.

"We believe patients with microscopic deposits of metastatic melanoma have biologically relevant, potentially life-threatening disease," Dr. David W. Ollila said at the annual meeting of the Southern Surgical Association.

Although other investigators have proposed that submicroscopic disease (a sentinel node tumor that is less than 0.1 mm) is not associated with a significantly increased risk of recurrence or death (Br. J. Surg. 2007;94:1293–9), Dr. Ollila and his associates hypothesized that any sentinel node evidence of metastatic melanoma, regardless of size or stage, may be a cause for concern.

He and his associates retrospectively studied 586 patients (mean age, 55 years) with invasive melanoma and a sentinel node biopsy from 1998 to 2007 in a prospectively maintained database. They classified the 322 men and 264 women as node negative or as having a tumor burden of less than 0.1 mm, 0.1–1.0 mm, or greater than 1.0 mm.

The investigators found a statistically significant difference in recurrence of any type between node-negative patients and those with a tumor burden less than 0.1 mm. During a mean follow-up of 2.7 years, 57 (11%) of the 496 node-negative patients had a recurrence, compared with 8 (24%) of the 33 patients with a sentinel node tumor less than 0.1 mm.

"We [also] found a significant difference in disease-free survival between sentinel node-negative [patients] and the submicroscopic group. They cannot be considered equivalent," said Dr. Ollila, director of the sentinel node program and codirector of the multidisciplinary melanoma program at the University of North Carolina at Chapel Hill.

In the node-negative group, 51 patients (10%) died, as did 5 (15%) of those with a tumor burden less than 0.1 mm, 6 of 27 patients (22%) in the 0.1- to 1.0-mm group, and 12 of 30 patients (40%) who had tumors larger than 1.0 mm.

Dr. Ollila pointed out that the stepwise decrease in survival with increasing diameter of the metastatic deposit was statistically different among the four groups. "This is an interesting [finding], contrary to Rotterdam criteria. I submit to you that these patients are on a continuum, and this is clinically relevant disease," he said.

An increased sentinel node tumor burden was also associated with a greater risk of metastatic disease in other nodes. A total of 7% of node-negative patients had distant recurrence, as did 15% of those with tumors less than 0.1 mm, 22% of the 0.1- to 1.0-mm group, and 47% of those with tumors larger than 1.0 mm.

Dr. Marshall M. Urist, professor of surgery, University of Alabama at Birmingham, commented that this is an excellent study and asked, "Why did you measure these metastases in a two-dimensional way for a three-dimensional process?"

Dr. Ollila replied: "Point well taken. It's a volume disease. It would be more representative if we could do volumetric measures." The two-dimensional measurement was a limitation of the database used in the study, he said.

LAS VEGAS — Early-stage mycosis fungoides appears to be a lympho-accumulative disorder, driven by defects in apoptosis mechanisms designed to regulate T-cell populations in the skin, according to Dr. Gary Wood.

Cell cycle defects that lead to the classic "unchecked growth" that characterizes lymphoproliferative diseases do occur in mycosis fungoides, but likely not until its later stages, Dr. Wood, who is chairman of dermatology at the University of Wisconsin, Madison, said during a dermatology seminar that was sponsored by Skin Disease Education Foundation.

In the beginning, mycosis fungoides demonstrate a low rate of apoptosis, with "cells not growing particularly quickly, but also not dying—like guests that you invite that don't go home," he commented.

Many additional clues point to early mycosis fungoides as a lympho-accumulative, rather than a lympho-proliferative, disorder, he said, including:

▸ An indolent clinical course.

▸ Development of patches, not tumor masses.

▸ Low proliferative rate and mitotic counts.

▸ Relative resistance to chemotherapy, because mycosis fungoides cells are "quite similar to normal T cells. Anything that will kill them will kill the rest of the patient."

▸ Poor growth in vitro.

Research of late has buoyed the theory of lympho-accumulation.

One or more death receptor defects have been identified in the majority of patients with cutaneous T-cell lymphoma, including defects in FAS; TNFR (R1, R2, or the antiapoptotic TRAF1 receptor); or TRAIL (DR4, DR5, DcR1, or DcR2).

Dr. Wood's team and others have found further defects in the death receptor antagonist cFLIP, which is a key player in the death receptor pathway, he noted.

He and his colleagues found low FAS expression in 30 of the 31 patients with cutaneous T-cell lymphoma and in 5 of the 6 patients with large plaque parapsoriasis, a precursor of mycosis fungoides or Sézary syndrome (J. Invest. Dermatol. 2008 Oct. 16 [Epub doi:10.1038/jid.2008.309

No such abnormality was seen in the 15 patients with chronic dermatoses, he noted at the meeting.

A more targeted look identified four cutaneous T-cell lymphoma cell lines (MyLa, HH, SZ4, and SeAx) in which resistance to apoptosis correlated with levels of FAS transcripts and proteins.

Taking it one step further, Dr. Woods and his associates found that, when they triggered FAS upregulation by transfecting genes with a wild-type FAS construct, apoptosis was restored, including spontaneous FAS pathway apoptosis, in which FAS ligands, in essence, self-destruct.

"You can see a big uptake in the amount of killing," he pointed out, demonstrating the effect in each of the four tested cell lines using real time polymerase chain reaction (RT/PCR) technology.

While Dr. Wood's team has focused on FAS transfection to prime FAS and cutaneous T-cell lymphoma cells to self-destruct or to become targets of tumor-infiltrating lymphocytes, there are other ways to upregulate FAS as well.

These include interleukin-2 and bryostatin; interferon-α and -γ; and even epigallocatechin gallate (EGCG), which is the polyphenol antioxidant in green tea, he said.

"In the future, these may be useful therapeutic targets," Dr. Wood said.

SDEF and this newspaper are owned by Elsevier.

LAS VEGAS — Early-stage mycosis fungoides appears to be a lympho-accumulative disorder, driven by defects in apoptosis mechanisms designed to regulate T-cell populations in the skin, according to Dr. Gary Wood.

Cell cycle defects that lead to the classic "unchecked growth" that characterizes lymphoproliferative diseases do occur in mycosis fungoides, but likely not until its later stages, Dr. Wood, who is chairman of dermatology at the University of Wisconsin, Madison, said during a dermatology seminar that was sponsored by Skin Disease Education Foundation.

In the beginning, mycosis fungoides demonstrate a low rate of apoptosis, with "cells not growing particularly quickly, but also not dying—like guests that you invite that don't go home," he commented.

Many additional clues point to early mycosis fungoides as a lympho-accumulative, rather than a lympho-proliferative, disorder, he said, including:

▸ An indolent clinical course.

▸ Development of patches, not tumor masses.

▸ Low proliferative rate and mitotic counts.

▸ Relative resistance to chemotherapy, because mycosis fungoides cells are "quite similar to normal T cells. Anything that will kill them will kill the rest of the patient."

▸ Poor growth in vitro.

Research of late has buoyed the theory of lympho-accumulation.

One or more death receptor defects have been identified in the majority of patients with cutaneous T-cell lymphoma, including defects in FAS; TNFR (R1, R2, or the antiapoptotic TRAF1 receptor); or TRAIL (DR4, DR5, DcR1, or DcR2).

Dr. Wood's team and others have found further defects in the death receptor antagonist cFLIP, which is a key player in the death receptor pathway, he noted.

He and his colleagues found low FAS expression in 30 of the 31 patients with cutaneous T-cell lymphoma and in 5 of the 6 patients with large plaque parapsoriasis, a precursor of mycosis fungoides or Sézary syndrome (J. Invest. Dermatol. 2008 Oct. 16 [Epub doi:10.1038/jid.2008.309

No such abnormality was seen in the 15 patients with chronic dermatoses, he noted at the meeting.

A more targeted look identified four cutaneous T-cell lymphoma cell lines (MyLa, HH, SZ4, and SeAx) in which resistance to apoptosis correlated with levels of FAS transcripts and proteins.

Taking it one step further, Dr. Woods and his associates found that, when they triggered FAS upregulation by transfecting genes with a wild-type FAS construct, apoptosis was restored, including spontaneous FAS pathway apoptosis, in which FAS ligands, in essence, self-destruct.

"You can see a big uptake in the amount of killing," he pointed out, demonstrating the effect in each of the four tested cell lines using real time polymerase chain reaction (RT/PCR) technology.

While Dr. Wood's team has focused on FAS transfection to prime FAS and cutaneous T-cell lymphoma cells to self-destruct or to become targets of tumor-infiltrating lymphocytes, there are other ways to upregulate FAS as well.

These include interleukin-2 and bryostatin; interferon-α and -γ; and even epigallocatechin gallate (EGCG), which is the polyphenol antioxidant in green tea, he said.

"In the future, these may be useful therapeutic targets," Dr. Wood said.

SDEF and this newspaper are owned by Elsevier.

LAS VEGAS — Early-stage mycosis fungoides appears to be a lympho-accumulative disorder, driven by defects in apoptosis mechanisms designed to regulate T-cell populations in the skin, according to Dr. Gary Wood.

Cell cycle defects that lead to the classic "unchecked growth" that characterizes lymphoproliferative diseases do occur in mycosis fungoides, but likely not until its later stages, Dr. Wood, who is chairman of dermatology at the University of Wisconsin, Madison, said during a dermatology seminar that was sponsored by Skin Disease Education Foundation.

In the beginning, mycosis fungoides demonstrate a low rate of apoptosis, with "cells not growing particularly quickly, but also not dying—like guests that you invite that don't go home," he commented.

Many additional clues point to early mycosis fungoides as a lympho-accumulative, rather than a lympho-proliferative, disorder, he said, including:

▸ An indolent clinical course.

▸ Development of patches, not tumor masses.

▸ Low proliferative rate and mitotic counts.

▸ Relative resistance to chemotherapy, because mycosis fungoides cells are "quite similar to normal T cells. Anything that will kill them will kill the rest of the patient."

▸ Poor growth in vitro.

Research of late has buoyed the theory of lympho-accumulation.

One or more death receptor defects have been identified in the majority of patients with cutaneous T-cell lymphoma, including defects in FAS; TNFR (R1, R2, or the antiapoptotic TRAF1 receptor); or TRAIL (DR4, DR5, DcR1, or DcR2).

Dr. Wood's team and others have found further defects in the death receptor antagonist cFLIP, which is a key player in the death receptor pathway, he noted.

He and his colleagues found low FAS expression in 30 of the 31 patients with cutaneous T-cell lymphoma and in 5 of the 6 patients with large plaque parapsoriasis, a precursor of mycosis fungoides or Sézary syndrome (J. Invest. Dermatol. 2008 Oct. 16 [Epub doi:10.1038/jid.2008.309

No such abnormality was seen in the 15 patients with chronic dermatoses, he noted at the meeting.

A more targeted look identified four cutaneous T-cell lymphoma cell lines (MyLa, HH, SZ4, and SeAx) in which resistance to apoptosis correlated with levels of FAS transcripts and proteins.

Taking it one step further, Dr. Woods and his associates found that, when they triggered FAS upregulation by transfecting genes with a wild-type FAS construct, apoptosis was restored, including spontaneous FAS pathway apoptosis, in which FAS ligands, in essence, self-destruct.

"You can see a big uptake in the amount of killing," he pointed out, demonstrating the effect in each of the four tested cell lines using real time polymerase chain reaction (RT/PCR) technology.

While Dr. Wood's team has focused on FAS transfection to prime FAS and cutaneous T-cell lymphoma cells to self-destruct or to become targets of tumor-infiltrating lymphocytes, there are other ways to upregulate FAS as well.

These include interleukin-2 and bryostatin; interferon-α and -γ; and even epigallocatechin gallate (EGCG), which is the polyphenol antioxidant in green tea, he said.

"In the future, these may be useful therapeutic targets," Dr. Wood said.

SDEF and this newspaper are owned by Elsevier.