Melanoma

WILLIAMSBURG, VA. — Sentinel lymph node biopsy should be reserved only for squamous cell carcinoma patients whose primary tumors have a high-risk profile, according to Dr. Merrick Ross.

"Clearly, the routine use of sentinel node biopsy is not indicated in these patients, but its selective use in high-risk squamous cell carcinoma [SCC] seems rational," said Dr. Ross at a meeting of the American Society for Mohs Surgery. "This is why it's important for us to continue to define exactly what constitutes a high-risk squamous cell tumor."

High-risk features of SCC include anatomical location, thickness, size, perineural invasion, and the immunocompetence of the patient.

Increasing size is associated with decreased local control and the increased presence of positive lymph nodes. A size of 2 cm "seems to be the most relevant break point," said Dr. Ross, professor of surgical oncology at the University of Texas M.D. Anderson Cancer Center, Houston. "Studies have shown that up to 50% of SCCs larger than that will have nodal involvement. However, to date there is no multivariate analysis that demonstrates size as an independent predictor of nodal disease."

Most studies identify 4-5 cm as the high-risk break point for tumor thickness, he said. In a large German study of 550 patients, only 3% of those with tumors less than 5 mm thick had nodal metastasis, compared with more than 17% of those with thicker tumors, Dr. Ross noted (Cancer 1997;79:915-9).

High-grade tumors are more likely than low-grade tumors to have nodal disease, said Dr. Ross, with 17% of high-grade tumors showing metastasis, compared with 4% of lower-grade tumors. When the German investigators looked at grade distribution according to nodal involvement, 44% of node-positive patients had high-grade primary tumors, whereas only 5% of node-negative patients had high-grade tumors.

Local recurrence is strongly associated with nodal involvement, just as it is with larger size, thicker tumors, narrow excision margins, and anatomical site. Up to 45% of recurrent presentations will have nodal disease, Dr. Ross said.

Lesions that arise on the lip, around the ear, and in the anogenital region are particularly risky. A 2006 study found that 27% of SCCs on the external ear had nodal disease, as did more than 20% of T3- and T4-stage lip lesions (Aust. J Derm. 2006;47:28-33).

The overall health of the patient is another important risk factor. "Patients with HIV [disease] or other immunodeficiency diseases are at an increased risk for metastasis, as are those with any chronic hematologic malignancy" Dr. Ross said.

WILLIAMSBURG, VA. — Sentinel lymph node biopsy should be reserved only for squamous cell carcinoma patients whose primary tumors have a high-risk profile, according to Dr. Merrick Ross.

"Clearly, the routine use of sentinel node biopsy is not indicated in these patients, but its selective use in high-risk squamous cell carcinoma [SCC] seems rational," said Dr. Ross at a meeting of the American Society for Mohs Surgery. "This is why it's important for us to continue to define exactly what constitutes a high-risk squamous cell tumor."

High-risk features of SCC include anatomical location, thickness, size, perineural invasion, and the immunocompetence of the patient.

Increasing size is associated with decreased local control and the increased presence of positive lymph nodes. A size of 2 cm "seems to be the most relevant break point," said Dr. Ross, professor of surgical oncology at the University of Texas M.D. Anderson Cancer Center, Houston. "Studies have shown that up to 50% of SCCs larger than that will have nodal involvement. However, to date there is no multivariate analysis that demonstrates size as an independent predictor of nodal disease."

Most studies identify 4-5 cm as the high-risk break point for tumor thickness, he said. In a large German study of 550 patients, only 3% of those with tumors less than 5 mm thick had nodal metastasis, compared with more than 17% of those with thicker tumors, Dr. Ross noted (Cancer 1997;79:915-9).

High-grade tumors are more likely than low-grade tumors to have nodal disease, said Dr. Ross, with 17% of high-grade tumors showing metastasis, compared with 4% of lower-grade tumors. When the German investigators looked at grade distribution according to nodal involvement, 44% of node-positive patients had high-grade primary tumors, whereas only 5% of node-negative patients had high-grade tumors.

Local recurrence is strongly associated with nodal involvement, just as it is with larger size, thicker tumors, narrow excision margins, and anatomical site. Up to 45% of recurrent presentations will have nodal disease, Dr. Ross said.

Lesions that arise on the lip, around the ear, and in the anogenital region are particularly risky. A 2006 study found that 27% of SCCs on the external ear had nodal disease, as did more than 20% of T3- and T4-stage lip lesions (Aust. J Derm. 2006;47:28-33).

The overall health of the patient is another important risk factor. "Patients with HIV [disease] or other immunodeficiency diseases are at an increased risk for metastasis, as are those with any chronic hematologic malignancy" Dr. Ross said.

WILLIAMSBURG, VA. — Sentinel lymph node biopsy should be reserved only for squamous cell carcinoma patients whose primary tumors have a high-risk profile, according to Dr. Merrick Ross.

"Clearly, the routine use of sentinel node biopsy is not indicated in these patients, but its selective use in high-risk squamous cell carcinoma [SCC] seems rational," said Dr. Ross at a meeting of the American Society for Mohs Surgery. "This is why it's important for us to continue to define exactly what constitutes a high-risk squamous cell tumor."

High-risk features of SCC include anatomical location, thickness, size, perineural invasion, and the immunocompetence of the patient.

Increasing size is associated with decreased local control and the increased presence of positive lymph nodes. A size of 2 cm "seems to be the most relevant break point," said Dr. Ross, professor of surgical oncology at the University of Texas M.D. Anderson Cancer Center, Houston. "Studies have shown that up to 50% of SCCs larger than that will have nodal involvement. However, to date there is no multivariate analysis that demonstrates size as an independent predictor of nodal disease."

Most studies identify 4-5 cm as the high-risk break point for tumor thickness, he said. In a large German study of 550 patients, only 3% of those with tumors less than 5 mm thick had nodal metastasis, compared with more than 17% of those with thicker tumors, Dr. Ross noted (Cancer 1997;79:915-9).

High-grade tumors are more likely than low-grade tumors to have nodal disease, said Dr. Ross, with 17% of high-grade tumors showing metastasis, compared with 4% of lower-grade tumors. When the German investigators looked at grade distribution according to nodal involvement, 44% of node-positive patients had high-grade primary tumors, whereas only 5% of node-negative patients had high-grade tumors.

Local recurrence is strongly associated with nodal involvement, just as it is with larger size, thicker tumors, narrow excision margins, and anatomical site. Up to 45% of recurrent presentations will have nodal disease, Dr. Ross said.

Lesions that arise on the lip, around the ear, and in the anogenital region are particularly risky. A 2006 study found that 27% of SCCs on the external ear had nodal disease, as did more than 20% of T3- and T4-stage lip lesions (Aust. J Derm. 2006;47:28-33).

The overall health of the patient is another important risk factor. "Patients with HIV [disease] or other immunodeficiency diseases are at an increased risk for metastasis, as are those with any chronic hematologic malignancy" Dr. Ross said.

KYOTO, JAPAN — Mycophenolate mofetil-based chronic immunosuppression is associated with a markedly lower risk of skin cancer during the first decade post kidney transplant, compared with alternative regimens aimed at preventing graft rejection, Dr. Irma Wisgerhof said at an international investigative dermatology meeting.

By 13 years post transplant, however, the squamous cell carcinoma risk in mycophenolate mofetil-treated organ recipients is equivalent to that of azathioprine, noted Dr. Wisgerhof of Leiden University (the Netherlands) Medical Center.

The mechanisms underlying these very different arcs of skin cancer risk are unclear. Azathioprine (Imuran) has a direct carcinogenic effect and causes accumulation of 6-thioguanine in cellular DNA. Azathioprine begins causing skin cancer in kidney transplant recipients early, and at a rate that remains steady over time. In contrast, mycophenolate mofetil (CellCept) prevents graft rejection by blocking immune surveillance; it suppresses both cellular and humoral immune responses, she explained.

Dr. Wisgerhof reviewed the experience with nonmelanoma skin cancer in 1,111 kidney transplant recipients who received their first donor kidney at the medical center in 1986-2006.

Through 2007, 6.7% of the patients developed a total of 102 invasive squamous cell carcinomas and 121 basal cell carcinomas. The cumulative incidence of nonmelanoma skin cancer was 3% after 5 years, 6% after 10 years, and 10% after 15 years of graft survival, she said.

The risk of squamous cell carcinoma—but not basal cell carcinoma—varied significantly depending upon the chronic immunosuppression regimen used.

The age- and gender-adjusted risk through the first decade post transplant was 88% lower with mycophenolate mofetil than with azathioprine-based regimens, and 65% less with cyclosporine- or tacrolimus-based regimens than with azathioprine-based immunosuppression, Dr. Wisgerhof said at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Dr. Wisgerhof's study was supported by the Dutch Society of Dermatology and Venereology.

The risk of SCC varied depending upon the chronic immuno-suppression regimen used. DR. WISGERHOF

KYOTO, JAPAN — Mycophenolate mofetil-based chronic immunosuppression is associated with a markedly lower risk of skin cancer during the first decade post kidney transplant, compared with alternative regimens aimed at preventing graft rejection, Dr. Irma Wisgerhof said at an international investigative dermatology meeting.

By 13 years post transplant, however, the squamous cell carcinoma risk in mycophenolate mofetil-treated organ recipients is equivalent to that of azathioprine, noted Dr. Wisgerhof of Leiden University (the Netherlands) Medical Center.

The mechanisms underlying these very different arcs of skin cancer risk are unclear. Azathioprine (Imuran) has a direct carcinogenic effect and causes accumulation of 6-thioguanine in cellular DNA. Azathioprine begins causing skin cancer in kidney transplant recipients early, and at a rate that remains steady over time. In contrast, mycophenolate mofetil (CellCept) prevents graft rejection by blocking immune surveillance; it suppresses both cellular and humoral immune responses, she explained.

Dr. Wisgerhof reviewed the experience with nonmelanoma skin cancer in 1,111 kidney transplant recipients who received their first donor kidney at the medical center in 1986-2006.

Through 2007, 6.7% of the patients developed a total of 102 invasive squamous cell carcinomas and 121 basal cell carcinomas. The cumulative incidence of nonmelanoma skin cancer was 3% after 5 years, 6% after 10 years, and 10% after 15 years of graft survival, she said.

The risk of squamous cell carcinoma—but not basal cell carcinoma—varied significantly depending upon the chronic immunosuppression regimen used.

The age- and gender-adjusted risk through the first decade post transplant was 88% lower with mycophenolate mofetil than with azathioprine-based regimens, and 65% less with cyclosporine- or tacrolimus-based regimens than with azathioprine-based immunosuppression, Dr. Wisgerhof said at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Dr. Wisgerhof's study was supported by the Dutch Society of Dermatology and Venereology.

The risk of SCC varied depending upon the chronic immuno-suppression regimen used. DR. WISGERHOF

KYOTO, JAPAN — Mycophenolate mofetil-based chronic immunosuppression is associated with a markedly lower risk of skin cancer during the first decade post kidney transplant, compared with alternative regimens aimed at preventing graft rejection, Dr. Irma Wisgerhof said at an international investigative dermatology meeting.

By 13 years post transplant, however, the squamous cell carcinoma risk in mycophenolate mofetil-treated organ recipients is equivalent to that of azathioprine, noted Dr. Wisgerhof of Leiden University (the Netherlands) Medical Center.

The mechanisms underlying these very different arcs of skin cancer risk are unclear. Azathioprine (Imuran) has a direct carcinogenic effect and causes accumulation of 6-thioguanine in cellular DNA. Azathioprine begins causing skin cancer in kidney transplant recipients early, and at a rate that remains steady over time. In contrast, mycophenolate mofetil (CellCept) prevents graft rejection by blocking immune surveillance; it suppresses both cellular and humoral immune responses, she explained.

Dr. Wisgerhof reviewed the experience with nonmelanoma skin cancer in 1,111 kidney transplant recipients who received their first donor kidney at the medical center in 1986-2006.

Through 2007, 6.7% of the patients developed a total of 102 invasive squamous cell carcinomas and 121 basal cell carcinomas. The cumulative incidence of nonmelanoma skin cancer was 3% after 5 years, 6% after 10 years, and 10% after 15 years of graft survival, she said.

The risk of squamous cell carcinoma—but not basal cell carcinoma—varied significantly depending upon the chronic immunosuppression regimen used.

The age- and gender-adjusted risk through the first decade post transplant was 88% lower with mycophenolate mofetil than with azathioprine-based regimens, and 65% less with cyclosporine- or tacrolimus-based regimens than with azathioprine-based immunosuppression, Dr. Wisgerhof said at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Dr. Wisgerhof's study was supported by the Dutch Society of Dermatology and Venereology.

The risk of SCC varied depending upon the chronic immuno-suppression regimen used. DR. WISGERHOF

VANCOUVER, B.C. — The epidermal growth factor receptor inhibitor cetuximab alone has been found to produce complete response in patients with advanced cutaneous squamous cell carcinoma.

"To date, there have been no trials using the epidermal growth factor receptor inhibitors for treatment of patients with cutaneous squamous cell carcinoma," said Dr. Matthew E. Halpern at the annual meeting of the American College of Mohs Surgery. A previous trial found that cetuximab (Erbitux) plus radiation was efficacious for treating locally advanced squamous cell carcinoma (SCC) of the head and neck (N. Engl. J. Med. 2006;354:567-78).

Study patients had advanced SCC of the back, scalp, temple, and chest, according to Dr. Halpern, a dermatologic surgeon at New York-Presbyterian Medical Center. Two patients had in-transit metastasis alone, one had both in-transit and axillary metastases, and one had pulmonary metastases. Their treatment consisted of weekly infusions of cetuximab, with a total of four infusions planned.

Two patients had a complete clinical response to cetuximab (Erbitux), Dr. Halpern reported. "Really, like magic, the in-transit metastasis absolutely melted before our eyes," he said, describing one of the patients. Another patient, who received only half of the planned number of infusions because of comorbidities, had a partial response. The remaining patient had merely a limited response.

"As you might expect, side effects of this class of medications are largely cutaneous," Dr. Halpern noted, explaining that patients might develop a characteristic acneiform rash, paronychial inflammation, xerosis, pruritus, and trichomegaly. The study's two complete responders developed a severe rash, and the partial responder developed a moderate rash, while the nonresponder did not develop any rash at all. "Interestingly, even though this is a very small series of patients, patient response seemed to correlate with the severity of acneiform eruption," he observed. "It seemed to be a surrogate marker for therapeutic response."

One of the patients with a complete response was alive at 6 months after treatment, while the other died 7 months afterward from a primary lung cancer. The patient with a partial response died 4 months after treatment from chronic rejection of a lung transplant and had additional metastases at that time. The patient who had a minimal response died 4 months after treatment from brain metastases.

The study had limited follow-up related to the recent treatments patients had received and their comorbidities, Dr. Halpern conceded. Nonetheless, he said, "cetuximab has potential benefit for patients with metastatic cutaneous squamous cell carcinoma and is extremely well tolerated in our hands, with minimal side effects, some of which may be predictive of therapeutic benefit."

Dr. Halpern reported that he had no conflicts of interest in association with the study.

'The severity of acneiform eruption … seemed to be a surrogate marker for therapeutic response.' DR. HALPERN

Biopsy of this nodule revealed infiltrating SCC without epidermal involvement.

The patient's in-transit metastasis and axillary metastases cleared after the third cetuximab infusion. The acneiform rash is characteristic of this drug class. Photos courtesy Dr. Matthew E. Halpern

VANCOUVER, B.C. — The epidermal growth factor receptor inhibitor cetuximab alone has been found to produce complete response in patients with advanced cutaneous squamous cell carcinoma.

"To date, there have been no trials using the epidermal growth factor receptor inhibitors for treatment of patients with cutaneous squamous cell carcinoma," said Dr. Matthew E. Halpern at the annual meeting of the American College of Mohs Surgery. A previous trial found that cetuximab (Erbitux) plus radiation was efficacious for treating locally advanced squamous cell carcinoma (SCC) of the head and neck (N. Engl. J. Med. 2006;354:567-78).

Study patients had advanced SCC of the back, scalp, temple, and chest, according to Dr. Halpern, a dermatologic surgeon at New York-Presbyterian Medical Center. Two patients had in-transit metastasis alone, one had both in-transit and axillary metastases, and one had pulmonary metastases. Their treatment consisted of weekly infusions of cetuximab, with a total of four infusions planned.

Two patients had a complete clinical response to cetuximab (Erbitux), Dr. Halpern reported. "Really, like magic, the in-transit metastasis absolutely melted before our eyes," he said, describing one of the patients. Another patient, who received only half of the planned number of infusions because of comorbidities, had a partial response. The remaining patient had merely a limited response.

"As you might expect, side effects of this class of medications are largely cutaneous," Dr. Halpern noted, explaining that patients might develop a characteristic acneiform rash, paronychial inflammation, xerosis, pruritus, and trichomegaly. The study's two complete responders developed a severe rash, and the partial responder developed a moderate rash, while the nonresponder did not develop any rash at all. "Interestingly, even though this is a very small series of patients, patient response seemed to correlate with the severity of acneiform eruption," he observed. "It seemed to be a surrogate marker for therapeutic response."

One of the patients with a complete response was alive at 6 months after treatment, while the other died 7 months afterward from a primary lung cancer. The patient with a partial response died 4 months after treatment from chronic rejection of a lung transplant and had additional metastases at that time. The patient who had a minimal response died 4 months after treatment from brain metastases.

The study had limited follow-up related to the recent treatments patients had received and their comorbidities, Dr. Halpern conceded. Nonetheless, he said, "cetuximab has potential benefit for patients with metastatic cutaneous squamous cell carcinoma and is extremely well tolerated in our hands, with minimal side effects, some of which may be predictive of therapeutic benefit."

Dr. Halpern reported that he had no conflicts of interest in association with the study.

'The severity of acneiform eruption … seemed to be a surrogate marker for therapeutic response.' DR. HALPERN

Biopsy of this nodule revealed infiltrating SCC without epidermal involvement.

The patient's in-transit metastasis and axillary metastases cleared after the third cetuximab infusion. The acneiform rash is characteristic of this drug class. Photos courtesy Dr. Matthew E. Halpern

VANCOUVER, B.C. — The epidermal growth factor receptor inhibitor cetuximab alone has been found to produce complete response in patients with advanced cutaneous squamous cell carcinoma.

"To date, there have been no trials using the epidermal growth factor receptor inhibitors for treatment of patients with cutaneous squamous cell carcinoma," said Dr. Matthew E. Halpern at the annual meeting of the American College of Mohs Surgery. A previous trial found that cetuximab (Erbitux) plus radiation was efficacious for treating locally advanced squamous cell carcinoma (SCC) of the head and neck (N. Engl. J. Med. 2006;354:567-78).

Study patients had advanced SCC of the back, scalp, temple, and chest, according to Dr. Halpern, a dermatologic surgeon at New York-Presbyterian Medical Center. Two patients had in-transit metastasis alone, one had both in-transit and axillary metastases, and one had pulmonary metastases. Their treatment consisted of weekly infusions of cetuximab, with a total of four infusions planned.

Two patients had a complete clinical response to cetuximab (Erbitux), Dr. Halpern reported. "Really, like magic, the in-transit metastasis absolutely melted before our eyes," he said, describing one of the patients. Another patient, who received only half of the planned number of infusions because of comorbidities, had a partial response. The remaining patient had merely a limited response.

"As you might expect, side effects of this class of medications are largely cutaneous," Dr. Halpern noted, explaining that patients might develop a characteristic acneiform rash, paronychial inflammation, xerosis, pruritus, and trichomegaly. The study's two complete responders developed a severe rash, and the partial responder developed a moderate rash, while the nonresponder did not develop any rash at all. "Interestingly, even though this is a very small series of patients, patient response seemed to correlate with the severity of acneiform eruption," he observed. "It seemed to be a surrogate marker for therapeutic response."

One of the patients with a complete response was alive at 6 months after treatment, while the other died 7 months afterward from a primary lung cancer. The patient with a partial response died 4 months after treatment from chronic rejection of a lung transplant and had additional metastases at that time. The patient who had a minimal response died 4 months after treatment from brain metastases.

The study had limited follow-up related to the recent treatments patients had received and their comorbidities, Dr. Halpern conceded. Nonetheless, he said, "cetuximab has potential benefit for patients with metastatic cutaneous squamous cell carcinoma and is extremely well tolerated in our hands, with minimal side effects, some of which may be predictive of therapeutic benefit."

Dr. Halpern reported that he had no conflicts of interest in association with the study.

'The severity of acneiform eruption … seemed to be a surrogate marker for therapeutic response.' DR. HALPERN

Biopsy of this nodule revealed infiltrating SCC without epidermal involvement.

The patient's in-transit metastasis and axillary metastases cleared after the third cetuximab infusion. The acneiform rash is characteristic of this drug class. Photos courtesy Dr. Matthew E. Halpern

WILLIAMSBURG, VA. — Patients with prosthetic cardiac valves and recently implanted joint prostheses are among the few who should receive prophylactic antibiotics before surgical procedures, according to a dermatologic surgeon.

Prosthetic devices sometimes grow coagulase-negative Staphylococcus aureus, which can cause a life-threatening endocarditis or, in the case of joint prostheses, an intra-articular infection that can necessitate replacement of the device. "If a patient [in these categories] comes to me for surgery and has not been prophylaxed, I will not do the procedure," said Dr. Stephen Spencer of Port Charlotte, Fla.

Neither of the guidelines that address prophylactic antibiotics—the 2007 guidelines for preventing infective carditis and the 2003 guidelines for preventing hematogenous total joint infections—specifically deal with dermatologic surgery, but dermatologists can rationally extrapolate the recommendations to their own patients, Dr. Spencer said at a meeting of the American Society for Mohs Surgery.

For patients with prosthetic cardiac valves, the American Heart Association guidelines recommend 2 g of amoxicillin orally 30-60 minutes before the procedure. Penicillin-allergic patients can take cephalexin, clindamycin, or azithromycin (Circulation 2007;116:1736-54).

Patients who have had a total joint replacement in the past 2 years should take 2 g of cephalexin, cephradine, or amoxicillin 60 minutes before surgery. Penicillin-allergic patients can take clindamycin. Choices for injected antibiotics include clindamycin, cefazolin, or ampicillin, according to guidelines issued by the American Dental Association and the American Academy of Orthopedic Surgeons (J. Am. Dent. Assoc. 2003;134:895-9).

For most other patients, including healthy individuals with joint replacements more than 2 years old, the risks of adverse events associated with antibiotic treatment probably outweigh any potential benefit it might have in preventing infective complications, including infective endocarditis, said Dr. Spencer.

"Very few healthy people need these preoperative antibiotics," he said, citing a 2006 study from Australia that found an extremely low rate of wound infection after dermatologic surgery in the absence of prophylactic antibiotics (Dermatol. Surg. 2006;32:819-26).

The 3-year study included 5,091 lesions treated on 2,424 patients, none of whom received preoperative antibiotics. The overall infection incidence was 1.5%, and many individual procedures had similarly low rates: curettage (0.7%); skin flap repairs (3%); simple excision and closure (0.5%). Skin grafts and wedge excisions had higher rates (9% each).

The investigators concluded that surgery to the nose, ear, fingers, and lips; skin flap surgery; and surgery on diabetics, smokers, and those on anticoagulants did not warrant prophylactic antibiotic treatment. They did recommend antibiotics for procedures below the knee, wedge excisions of lip and ear, all skin grafts, and lesions in the groin, Dr. Spencer noted.

WILLIAMSBURG, VA. — Patients with prosthetic cardiac valves and recently implanted joint prostheses are among the few who should receive prophylactic antibiotics before surgical procedures, according to a dermatologic surgeon.

Prosthetic devices sometimes grow coagulase-negative Staphylococcus aureus, which can cause a life-threatening endocarditis or, in the case of joint prostheses, an intra-articular infection that can necessitate replacement of the device. "If a patient [in these categories] comes to me for surgery and has not been prophylaxed, I will not do the procedure," said Dr. Stephen Spencer of Port Charlotte, Fla.

Neither of the guidelines that address prophylactic antibiotics—the 2007 guidelines for preventing infective carditis and the 2003 guidelines for preventing hematogenous total joint infections—specifically deal with dermatologic surgery, but dermatologists can rationally extrapolate the recommendations to their own patients, Dr. Spencer said at a meeting of the American Society for Mohs Surgery.

For patients with prosthetic cardiac valves, the American Heart Association guidelines recommend 2 g of amoxicillin orally 30-60 minutes before the procedure. Penicillin-allergic patients can take cephalexin, clindamycin, or azithromycin (Circulation 2007;116:1736-54).

Patients who have had a total joint replacement in the past 2 years should take 2 g of cephalexin, cephradine, or amoxicillin 60 minutes before surgery. Penicillin-allergic patients can take clindamycin. Choices for injected antibiotics include clindamycin, cefazolin, or ampicillin, according to guidelines issued by the American Dental Association and the American Academy of Orthopedic Surgeons (J. Am. Dent. Assoc. 2003;134:895-9).

For most other patients, including healthy individuals with joint replacements more than 2 years old, the risks of adverse events associated with antibiotic treatment probably outweigh any potential benefit it might have in preventing infective complications, including infective endocarditis, said Dr. Spencer.

"Very few healthy people need these preoperative antibiotics," he said, citing a 2006 study from Australia that found an extremely low rate of wound infection after dermatologic surgery in the absence of prophylactic antibiotics (Dermatol. Surg. 2006;32:819-26).

The 3-year study included 5,091 lesions treated on 2,424 patients, none of whom received preoperative antibiotics. The overall infection incidence was 1.5%, and many individual procedures had similarly low rates: curettage (0.7%); skin flap repairs (3%); simple excision and closure (0.5%). Skin grafts and wedge excisions had higher rates (9% each).

The investigators concluded that surgery to the nose, ear, fingers, and lips; skin flap surgery; and surgery on diabetics, smokers, and those on anticoagulants did not warrant prophylactic antibiotic treatment. They did recommend antibiotics for procedures below the knee, wedge excisions of lip and ear, all skin grafts, and lesions in the groin, Dr. Spencer noted.

WILLIAMSBURG, VA. — Patients with prosthetic cardiac valves and recently implanted joint prostheses are among the few who should receive prophylactic antibiotics before surgical procedures, according to a dermatologic surgeon.

Prosthetic devices sometimes grow coagulase-negative Staphylococcus aureus, which can cause a life-threatening endocarditis or, in the case of joint prostheses, an intra-articular infection that can necessitate replacement of the device. "If a patient [in these categories] comes to me for surgery and has not been prophylaxed, I will not do the procedure," said Dr. Stephen Spencer of Port Charlotte, Fla.

Neither of the guidelines that address prophylactic antibiotics—the 2007 guidelines for preventing infective carditis and the 2003 guidelines for preventing hematogenous total joint infections—specifically deal with dermatologic surgery, but dermatologists can rationally extrapolate the recommendations to their own patients, Dr. Spencer said at a meeting of the American Society for Mohs Surgery.

For patients with prosthetic cardiac valves, the American Heart Association guidelines recommend 2 g of amoxicillin orally 30-60 minutes before the procedure. Penicillin-allergic patients can take cephalexin, clindamycin, or azithromycin (Circulation 2007;116:1736-54).

Patients who have had a total joint replacement in the past 2 years should take 2 g of cephalexin, cephradine, or amoxicillin 60 minutes before surgery. Penicillin-allergic patients can take clindamycin. Choices for injected antibiotics include clindamycin, cefazolin, or ampicillin, according to guidelines issued by the American Dental Association and the American Academy of Orthopedic Surgeons (J. Am. Dent. Assoc. 2003;134:895-9).

For most other patients, including healthy individuals with joint replacements more than 2 years old, the risks of adverse events associated with antibiotic treatment probably outweigh any potential benefit it might have in preventing infective complications, including infective endocarditis, said Dr. Spencer.

"Very few healthy people need these preoperative antibiotics," he said, citing a 2006 study from Australia that found an extremely low rate of wound infection after dermatologic surgery in the absence of prophylactic antibiotics (Dermatol. Surg. 2006;32:819-26).

The 3-year study included 5,091 lesions treated on 2,424 patients, none of whom received preoperative antibiotics. The overall infection incidence was 1.5%, and many individual procedures had similarly low rates: curettage (0.7%); skin flap repairs (3%); simple excision and closure (0.5%). Skin grafts and wedge excisions had higher rates (9% each).

The investigators concluded that surgery to the nose, ear, fingers, and lips; skin flap surgery; and surgery on diabetics, smokers, and those on anticoagulants did not warrant prophylactic antibiotic treatment. They did recommend antibiotics for procedures below the knee, wedge excisions of lip and ear, all skin grafts, and lesions in the groin, Dr. Spencer noted.

WILLIAMSBURG, VA. — Consistent application of tissue nicks and annotated tissue transfer cards can significantly reduce the chance of error in Mohs surgery.

"Recurrence after Mohs surgery is very low, only 1%-2% at most, but when we look at the reasons behind those recurrences, 75% are due to human error, and of these, 10% are due to incorrect mapping and excision," said Dr. Tri H. Nguyen, director of Mohs micrographic and dermatologic surgery at the University of Texas M.D. Anderson Cancer Center, Houston.

"This includes tissue-orientation mistakes, mapping inaccuracies, mislabeling of sections or slides, and insufficient resection," Dr. Nguyen said at a meeting of the American Society for Mohs Surgery.

He methodically employs a system of identification strategies that nearly eliminates the chance of orientation errors, but an informal survey of fellowship programs showed that few physicians may be using this same level of caution.

Dr. Nguyen asked his residents about orientation techniques taught in the 14 Mohs fellowship programs for which they applied. Only three programs used preprinted maps, and only one used preprinted tissue transfer cards. Only five programs used tissue nicks to orient the sample, and only two of those used double nicks to add an extra layer of security.

"There are tremendous variations in the way we practice mapping and orientation, and probably all are adequate for primary, low-risk, single-stage Mohs resections," he said. "We run into problems with high-risk tumors with multiple convolutions or convexities, and in surgeries with multiple stages and multiple sites."

Anatomical maps and transfer cards can help reduce these problems. The cards have preprinted maps with illustrations of anatomical areas, and they also absorb moisture from specimens, which decreases the chance that they will shift position or fall off during the transfer. Corresponding paper maps have the same information printed on them.

"We have preprinted maps and transfer cards for every conceivable [anatomical area] on the head and neck, and blank ones for drawing locations on the extremities," Dr. Nguyen said.

Strategic tissue nicking adds a second layer of security to the surgery. "The argument over tissue nicks is pointless. There is no doubt that a properly made nick of the patient and the excised tissue leaves an indelible mark to go back and orient your sample," he said.

Single nicks, however, aren't sufficient. "With a single, there is always a chance the tissue will get dropped or shifted and you will lose the accuracy of your orientation. If you have a second nick consistently placed, you will always know exactly how the tissue is oriented. Two nicks ensure specimen orientation with or without" an anatomical transfer card, Dr. Nguyen said.

In double nicking, there should be a little space between the incisions. "If you place the second nick close to the peripheral edge, you are prone to tissue folding, which can mask tumor," he said.

WILLIAMSBURG, VA. — Consistent application of tissue nicks and annotated tissue transfer cards can significantly reduce the chance of error in Mohs surgery.

"Recurrence after Mohs surgery is very low, only 1%-2% at most, but when we look at the reasons behind those recurrences, 75% are due to human error, and of these, 10% are due to incorrect mapping and excision," said Dr. Tri H. Nguyen, director of Mohs micrographic and dermatologic surgery at the University of Texas M.D. Anderson Cancer Center, Houston.

"This includes tissue-orientation mistakes, mapping inaccuracies, mislabeling of sections or slides, and insufficient resection," Dr. Nguyen said at a meeting of the American Society for Mohs Surgery.

He methodically employs a system of identification strategies that nearly eliminates the chance of orientation errors, but an informal survey of fellowship programs showed that few physicians may be using this same level of caution.

Dr. Nguyen asked his residents about orientation techniques taught in the 14 Mohs fellowship programs for which they applied. Only three programs used preprinted maps, and only one used preprinted tissue transfer cards. Only five programs used tissue nicks to orient the sample, and only two of those used double nicks to add an extra layer of security.

"There are tremendous variations in the way we practice mapping and orientation, and probably all are adequate for primary, low-risk, single-stage Mohs resections," he said. "We run into problems with high-risk tumors with multiple convolutions or convexities, and in surgeries with multiple stages and multiple sites."

Anatomical maps and transfer cards can help reduce these problems. The cards have preprinted maps with illustrations of anatomical areas, and they also absorb moisture from specimens, which decreases the chance that they will shift position or fall off during the transfer. Corresponding paper maps have the same information printed on them.

"We have preprinted maps and transfer cards for every conceivable [anatomical area] on the head and neck, and blank ones for drawing locations on the extremities," Dr. Nguyen said.

Strategic tissue nicking adds a second layer of security to the surgery. "The argument over tissue nicks is pointless. There is no doubt that a properly made nick of the patient and the excised tissue leaves an indelible mark to go back and orient your sample," he said.

Single nicks, however, aren't sufficient. "With a single, there is always a chance the tissue will get dropped or shifted and you will lose the accuracy of your orientation. If you have a second nick consistently placed, you will always know exactly how the tissue is oriented. Two nicks ensure specimen orientation with or without" an anatomical transfer card, Dr. Nguyen said.

In double nicking, there should be a little space between the incisions. "If you place the second nick close to the peripheral edge, you are prone to tissue folding, which can mask tumor," he said.

WILLIAMSBURG, VA. — Consistent application of tissue nicks and annotated tissue transfer cards can significantly reduce the chance of error in Mohs surgery.

"Recurrence after Mohs surgery is very low, only 1%-2% at most, but when we look at the reasons behind those recurrences, 75% are due to human error, and of these, 10% are due to incorrect mapping and excision," said Dr. Tri H. Nguyen, director of Mohs micrographic and dermatologic surgery at the University of Texas M.D. Anderson Cancer Center, Houston.

"This includes tissue-orientation mistakes, mapping inaccuracies, mislabeling of sections or slides, and insufficient resection," Dr. Nguyen said at a meeting of the American Society for Mohs Surgery.

He methodically employs a system of identification strategies that nearly eliminates the chance of orientation errors, but an informal survey of fellowship programs showed that few physicians may be using this same level of caution.

Dr. Nguyen asked his residents about orientation techniques taught in the 14 Mohs fellowship programs for which they applied. Only three programs used preprinted maps, and only one used preprinted tissue transfer cards. Only five programs used tissue nicks to orient the sample, and only two of those used double nicks to add an extra layer of security.

"There are tremendous variations in the way we practice mapping and orientation, and probably all are adequate for primary, low-risk, single-stage Mohs resections," he said. "We run into problems with high-risk tumors with multiple convolutions or convexities, and in surgeries with multiple stages and multiple sites."

Anatomical maps and transfer cards can help reduce these problems. The cards have preprinted maps with illustrations of anatomical areas, and they also absorb moisture from specimens, which decreases the chance that they will shift position or fall off during the transfer. Corresponding paper maps have the same information printed on them.

"We have preprinted maps and transfer cards for every conceivable [anatomical area] on the head and neck, and blank ones for drawing locations on the extremities," Dr. Nguyen said.

Strategic tissue nicking adds a second layer of security to the surgery. "The argument over tissue nicks is pointless. There is no doubt that a properly made nick of the patient and the excised tissue leaves an indelible mark to go back and orient your sample," he said.

Single nicks, however, aren't sufficient. "With a single, there is always a chance the tissue will get dropped or shifted and you will lose the accuracy of your orientation. If you have a second nick consistently placed, you will always know exactly how the tissue is oriented. Two nicks ensure specimen orientation with or without" an anatomical transfer card, Dr. Nguyen said.

In double nicking, there should be a little space between the incisions. "If you place the second nick close to the peripheral edge, you are prone to tissue folding, which can mask tumor," he said.

VANCOUVER, B.C. — Photographing cutaneous lesions before biopsy can help prevent wrong-site surgery when the lesions prove to be malignant and patients must undergo Mohs excision of the remaining tumor, according to an observational study of 271 biopsy sites.

Factors such as healing and actinic skin damage can make it difficult to identify biopsy sites at the time of Mohs surgery, Dr. Jamie L. McGinness, a dermatologic surgeon in Leawood, Kan., and Lee's Summit, Mo., said at the annual meeting of American College of Mohs Surgery.

In a previous survey of Mohs surgeons, other investigators found that 11% of the 300 respondents had been sued and that performing surgery on the wrong site was a leading reason for the malpractice claims, accounting for 14% (Dermatol. Surg. 2006;32:79-83).

For their study, Dr. McGinness and his coinvestigators enrolled patients who were undergoing Mohs surgery with any of four physicians at the center for a previously biopsied, malignant cutaneous lesion who could see their biopsy site using a mirror, and who had preoperative photographs of their biopsy site. Those with conditions that impair memory were excluded.

On the day of Mohs surgery, patients were given a mirror and asked to identify their biopsy site. Next, their Mohs surgeons were asked to identify the site using the anatomic information on the pathology report, the diagrammed location, and palpation. Neither the patient nor the physician was further assisted with the identification process.

In all, 271 biopsy sites were evaluated. Fully 16.6% of sites were incorrectly identified by patients and 5.9% were incorrectly identified by physicians. About 4.4% were incorrectly identified by both parties. In contrast, all sites were correctly identified with the use of preoperative photos. The results suggest that neither patients—even confident ones—nor diagrams are reliable means for identifying biopsy sites, Dr. McGinness said.

If a biopsy site cannot be identified at the time of surgery, the options are to proceed anyway—at the risk of wrong-site surgery—or to cancel surgery. "When surgeries are cancelled, this leads to higher patient inconvenience, untreated tumors that could metastasize, larger tumors when they again become observable, and increased patient morbidity," Dr. McGinness commented.

All of the patients underwent surgery an average of 2-3 weeks after biopsy, and he recommended that future research evaluate the role of this time interval. "With longer wait times between biopsy and surgery, lesions could heal and the rates [of incorrect identification] could actually be even higher," he explained.

Dr. McGinness reported no conflicts of interest related to the study.

Performing surgery on the wrong site was behind 14% of the lawsuits brought against Mohs surgeons. DR. MCGINNESS

Healing and actinic skin damage can make it hard to identify the biopsy site before surgery.

By using a prebiopsy photograph, the surgeon located the biopsy site and removed the tumor. Photos courtesy Dr. Jamie L. McGinness

VANCOUVER, B.C. — Photographing cutaneous lesions before biopsy can help prevent wrong-site surgery when the lesions prove to be malignant and patients must undergo Mohs excision of the remaining tumor, according to an observational study of 271 biopsy sites.

Factors such as healing and actinic skin damage can make it difficult to identify biopsy sites at the time of Mohs surgery, Dr. Jamie L. McGinness, a dermatologic surgeon in Leawood, Kan., and Lee's Summit, Mo., said at the annual meeting of American College of Mohs Surgery.

In a previous survey of Mohs surgeons, other investigators found that 11% of the 300 respondents had been sued and that performing surgery on the wrong site was a leading reason for the malpractice claims, accounting for 14% (Dermatol. Surg. 2006;32:79-83).

For their study, Dr. McGinness and his coinvestigators enrolled patients who were undergoing Mohs surgery with any of four physicians at the center for a previously biopsied, malignant cutaneous lesion who could see their biopsy site using a mirror, and who had preoperative photographs of their biopsy site. Those with conditions that impair memory were excluded.

On the day of Mohs surgery, patients were given a mirror and asked to identify their biopsy site. Next, their Mohs surgeons were asked to identify the site using the anatomic information on the pathology report, the diagrammed location, and palpation. Neither the patient nor the physician was further assisted with the identification process.

In all, 271 biopsy sites were evaluated. Fully 16.6% of sites were incorrectly identified by patients and 5.9% were incorrectly identified by physicians. About 4.4% were incorrectly identified by both parties. In contrast, all sites were correctly identified with the use of preoperative photos. The results suggest that neither patients—even confident ones—nor diagrams are reliable means for identifying biopsy sites, Dr. McGinness said.

If a biopsy site cannot be identified at the time of surgery, the options are to proceed anyway—at the risk of wrong-site surgery—or to cancel surgery. "When surgeries are cancelled, this leads to higher patient inconvenience, untreated tumors that could metastasize, larger tumors when they again become observable, and increased patient morbidity," Dr. McGinness commented.

All of the patients underwent surgery an average of 2-3 weeks after biopsy, and he recommended that future research evaluate the role of this time interval. "With longer wait times between biopsy and surgery, lesions could heal and the rates [of incorrect identification] could actually be even higher," he explained.

Dr. McGinness reported no conflicts of interest related to the study.

Performing surgery on the wrong site was behind 14% of the lawsuits brought against Mohs surgeons. DR. MCGINNESS

Healing and actinic skin damage can make it hard to identify the biopsy site before surgery.

By using a prebiopsy photograph, the surgeon located the biopsy site and removed the tumor. Photos courtesy Dr. Jamie L. McGinness

VANCOUVER, B.C. — Photographing cutaneous lesions before biopsy can help prevent wrong-site surgery when the lesions prove to be malignant and patients must undergo Mohs excision of the remaining tumor, according to an observational study of 271 biopsy sites.

Factors such as healing and actinic skin damage can make it difficult to identify biopsy sites at the time of Mohs surgery, Dr. Jamie L. McGinness, a dermatologic surgeon in Leawood, Kan., and Lee's Summit, Mo., said at the annual meeting of American College of Mohs Surgery.

In a previous survey of Mohs surgeons, other investigators found that 11% of the 300 respondents had been sued and that performing surgery on the wrong site was a leading reason for the malpractice claims, accounting for 14% (Dermatol. Surg. 2006;32:79-83).

For their study, Dr. McGinness and his coinvestigators enrolled patients who were undergoing Mohs surgery with any of four physicians at the center for a previously biopsied, malignant cutaneous lesion who could see their biopsy site using a mirror, and who had preoperative photographs of their biopsy site. Those with conditions that impair memory were excluded.

On the day of Mohs surgery, patients were given a mirror and asked to identify their biopsy site. Next, their Mohs surgeons were asked to identify the site using the anatomic information on the pathology report, the diagrammed location, and palpation. Neither the patient nor the physician was further assisted with the identification process.

In all, 271 biopsy sites were evaluated. Fully 16.6% of sites were incorrectly identified by patients and 5.9% were incorrectly identified by physicians. About 4.4% were incorrectly identified by both parties. In contrast, all sites were correctly identified with the use of preoperative photos. The results suggest that neither patients—even confident ones—nor diagrams are reliable means for identifying biopsy sites, Dr. McGinness said.

If a biopsy site cannot be identified at the time of surgery, the options are to proceed anyway—at the risk of wrong-site surgery—or to cancel surgery. "When surgeries are cancelled, this leads to higher patient inconvenience, untreated tumors that could metastasize, larger tumors when they again become observable, and increased patient morbidity," Dr. McGinness commented.

All of the patients underwent surgery an average of 2-3 weeks after biopsy, and he recommended that future research evaluate the role of this time interval. "With longer wait times between biopsy and surgery, lesions could heal and the rates [of incorrect identification] could actually be even higher," he explained.

Dr. McGinness reported no conflicts of interest related to the study.

Performing surgery on the wrong site was behind 14% of the lawsuits brought against Mohs surgeons. DR. MCGINNESS

Healing and actinic skin damage can make it hard to identify the biopsy site before surgery.

By using a prebiopsy photograph, the surgeon located the biopsy site and removed the tumor. Photos courtesy Dr. Jamie L. McGinness

KYOTO, JAPAN — Blue-light phototherapy for neonatal jaundice could promote development of dysplastic nevi, Dr. Zsanett Csoma asserted at an international investigative dermatology meeting.

His latest contribution to the controversial issue was in the form of a study of 618 healthy Hungarian patients aged 21-71 years. Patients born since 1968—when blue-light phototherapy for neonatal jaundice was introduced in Hungary—were found to have a 2.1-fold greater prevalence of dysplastic nevi than those who were born earlier, Dr. Csoma said at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

In an earlier cross-sectional study involving 747 patients aged 14-18 years, he found the prevalence of clinically dysplastic nevi to be 19% in those with no history of phototherapy for neonatal jaundice, compared with 25% in patients with such a history.

The proposed mechanism for the increase in dysplastic nevi lies in the emission spectrum of blue-light photo lamps, according to Dr. Csoma of the University of Szeged (Hungary). Although the spectrum centers on 450 nm, a small proportion of the emitted light—less than 1%—is UVA. Ultraviolet light not only induces melanocyte proliferation, it also has profound immunosuppressive and immunomodulatory effects in the skin and is sufficient to induce melanoma precursors in animals. These immunosuppressive effects could be magnified in the immature skin of neonates, he said.

When the earlier study was published (Pediatrics 2007;119:1036-7), it drew fire from Dr. Phyllis A. Dennery and Dr. Scott Lorch of the University of Pennsylvania, Philadelphia, and Children's Hospital of Philadelphia, who wrote that they found the data unconvincing (Pediatrics 2007;120:247-8).

"We need to remember the devastating consequences of our reduced vigilance for hyperbilirubinemia in the late 1980s and early 1990s. We must seriously weigh the resurgence of kernicterus against the potential for moles and nevi until more strategies are available to prevent hyperbilirubinemia," they cautioned.

Separately, French investigators reported that neonatal phototherapy was associated with a significant increase in melanocytic nevi 2-5 mm in diameter in a study involving 58 children aged 8-9 years. They suggested melanoma surveillance in exposed children (Arch. Dermatol. 2006;142:1599-604).

The French recommendation was deemed "premature" in a follow-up commentary by Dr. Thomas B. Newman of the University of California, San Francisco, and Dr. M. Jeffrey Maisels, chairman of the department of pediatrics at William Beaumont Hospital, Royal Oak, Mich.

"Counseling families of infants exposed to phototherapy that their child needs to be watched for melanoma is not a trivial matter. Much more evidence than was provided … is needed before it can be recommended," they wrote (Arch. Dermatol. 2007;143:1216).

Dr. Csoma's study was supported by the National Fund of the Hungarian Ministry of Health.

KYOTO, JAPAN — Blue-light phototherapy for neonatal jaundice could promote development of dysplastic nevi, Dr. Zsanett Csoma asserted at an international investigative dermatology meeting.

His latest contribution to the controversial issue was in the form of a study of 618 healthy Hungarian patients aged 21-71 years. Patients born since 1968—when blue-light phototherapy for neonatal jaundice was introduced in Hungary—were found to have a 2.1-fold greater prevalence of dysplastic nevi than those who were born earlier, Dr. Csoma said at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

In an earlier cross-sectional study involving 747 patients aged 14-18 years, he found the prevalence of clinically dysplastic nevi to be 19% in those with no history of phototherapy for neonatal jaundice, compared with 25% in patients with such a history.

The proposed mechanism for the increase in dysplastic nevi lies in the emission spectrum of blue-light photo lamps, according to Dr. Csoma of the University of Szeged (Hungary). Although the spectrum centers on 450 nm, a small proportion of the emitted light—less than 1%—is UVA. Ultraviolet light not only induces melanocyte proliferation, it also has profound immunosuppressive and immunomodulatory effects in the skin and is sufficient to induce melanoma precursors in animals. These immunosuppressive effects could be magnified in the immature skin of neonates, he said.

When the earlier study was published (Pediatrics 2007;119:1036-7), it drew fire from Dr. Phyllis A. Dennery and Dr. Scott Lorch of the University of Pennsylvania, Philadelphia, and Children's Hospital of Philadelphia, who wrote that they found the data unconvincing (Pediatrics 2007;120:247-8).

"We need to remember the devastating consequences of our reduced vigilance for hyperbilirubinemia in the late 1980s and early 1990s. We must seriously weigh the resurgence of kernicterus against the potential for moles and nevi until more strategies are available to prevent hyperbilirubinemia," they cautioned.

Separately, French investigators reported that neonatal phototherapy was associated with a significant increase in melanocytic nevi 2-5 mm in diameter in a study involving 58 children aged 8-9 years. They suggested melanoma surveillance in exposed children (Arch. Dermatol. 2006;142:1599-604).

The French recommendation was deemed "premature" in a follow-up commentary by Dr. Thomas B. Newman of the University of California, San Francisco, and Dr. M. Jeffrey Maisels, chairman of the department of pediatrics at William Beaumont Hospital, Royal Oak, Mich.

"Counseling families of infants exposed to phototherapy that their child needs to be watched for melanoma is not a trivial matter. Much more evidence than was provided … is needed before it can be recommended," they wrote (Arch. Dermatol. 2007;143:1216).

Dr. Csoma's study was supported by the National Fund of the Hungarian Ministry of Health.

KYOTO, JAPAN — Blue-light phototherapy for neonatal jaundice could promote development of dysplastic nevi, Dr. Zsanett Csoma asserted at an international investigative dermatology meeting.

His latest contribution to the controversial issue was in the form of a study of 618 healthy Hungarian patients aged 21-71 years. Patients born since 1968—when blue-light phototherapy for neonatal jaundice was introduced in Hungary—were found to have a 2.1-fold greater prevalence of dysplastic nevi than those who were born earlier, Dr. Csoma said at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

In an earlier cross-sectional study involving 747 patients aged 14-18 years, he found the prevalence of clinically dysplastic nevi to be 19% in those with no history of phototherapy for neonatal jaundice, compared with 25% in patients with such a history.

The proposed mechanism for the increase in dysplastic nevi lies in the emission spectrum of blue-light photo lamps, according to Dr. Csoma of the University of Szeged (Hungary). Although the spectrum centers on 450 nm, a small proportion of the emitted light—less than 1%—is UVA. Ultraviolet light not only induces melanocyte proliferation, it also has profound immunosuppressive and immunomodulatory effects in the skin and is sufficient to induce melanoma precursors in animals. These immunosuppressive effects could be magnified in the immature skin of neonates, he said.

When the earlier study was published (Pediatrics 2007;119:1036-7), it drew fire from Dr. Phyllis A. Dennery and Dr. Scott Lorch of the University of Pennsylvania, Philadelphia, and Children's Hospital of Philadelphia, who wrote that they found the data unconvincing (Pediatrics 2007;120:247-8).

"We need to remember the devastating consequences of our reduced vigilance for hyperbilirubinemia in the late 1980s and early 1990s. We must seriously weigh the resurgence of kernicterus against the potential for moles and nevi until more strategies are available to prevent hyperbilirubinemia," they cautioned.

Separately, French investigators reported that neonatal phototherapy was associated with a significant increase in melanocytic nevi 2-5 mm in diameter in a study involving 58 children aged 8-9 years. They suggested melanoma surveillance in exposed children (Arch. Dermatol. 2006;142:1599-604).

The French recommendation was deemed "premature" in a follow-up commentary by Dr. Thomas B. Newman of the University of California, San Francisco, and Dr. M. Jeffrey Maisels, chairman of the department of pediatrics at William Beaumont Hospital, Royal Oak, Mich.

"Counseling families of infants exposed to phototherapy that their child needs to be watched for melanoma is not a trivial matter. Much more evidence than was provided … is needed before it can be recommended," they wrote (Arch. Dermatol. 2007;143:1216).

Dr. Csoma's study was supported by the National Fund of the Hungarian Ministry of Health.

WILLIAMSBURG, VA. — Although large numbers of nevi—especially dysplastic nevi—are clearly associated with an increased melanoma risk, the lesions themselves do not appear to become cancerous, Dr. Terry L. Barrett said at the annual meeting of the American Society for Mohs Surgery.

"I remain unconvinced that either the common acquired nevus or the dysplastic nevus develops into melanoma," said Dr. Barrett, professor of pathology and dermatology at the University of Texas, Dallas. "I think they are both benign lesions the majority of the time. Usually, melanomas in these patients arise on normal-appearing skin and not the site of the nevus. When that happens, I think it's coincidental, not a nevus gone bad."

Few studies have actually investigated this point, although Dr. Barrett did mention a 2007 in vitro study that looked at levels of polycomb group protein EZH2, a cell regulatory protein markedly elevated in malignant skin lesions (J. Cutan. Pathol. 2007;34:597-600). The level in both in situ and invasive melanoma was almost three times that seen in acquired and dysplastic nevi—a finding that seems to support Dr. Barrett's opinion.

Regardless of the source, however, patients with large numbers of nevi are at a significantly increased risk of melanoma and other malignancies. The two commonly recognized nevi syndromes carry different risks, Dr. Barrett said.

Familial atypical mole/melanoma syndrome is an autosomal dominant disorder that increases the lifetime risk of melanoma by almost 100%. Sporadic dysplastic nevus syndrome is a spontaneous mutation that increases the relative risk of malignancy up to 46 times that of the general population, he said.

For patients with the sporadic syndrome, sun exposure seems to play a key role in the development of melanoma. "It's been suggested that intermittent sun exposure manifests the phenotype of the dysplastic nevi [and its attendant increased melanoma risk], while patients without sun exposure manifest the common acquired nevi," Dr. Barrett noted.

"There is no clear agreement among dermatologists about how these lesions should be handled," he said. "If you think a lesion is premalignant, you'll want to excise it, and if the report comes back 'severely atypical,' you'll probably want to have negative margins. If you think the lesions aren't premalignant, then after you exclude a diagnosis of melanoma, you probably won't do anything. We have people in our practice who do both."

The phase in which a dermatologist "catches" the nevus probably influences treatment decisions. "These lesions are dynamic, change throughout life, and can be acquired at any age. I think what's happening is that if we biopsy them in a quiescent phase, we don't see cytological atypia. And if we catch them in a dynamic phase, they have different cellular characteristics, which we then have to define as mild or severe atypia," Dr. Barrett said.

Since the lesions are so changeable, and patients are at such a significantly increased risk of melanoma, close follow-up at 3- to 11-month intervals is crucial. It's probably a good idea to screen first-degree relatives, too, he suggested.

WILLIAMSBURG, VA. — Although large numbers of nevi—especially dysplastic nevi—are clearly associated with an increased melanoma risk, the lesions themselves do not appear to become cancerous, Dr. Terry L. Barrett said at the annual meeting of the American Society for Mohs Surgery.

"I remain unconvinced that either the common acquired nevus or the dysplastic nevus develops into melanoma," said Dr. Barrett, professor of pathology and dermatology at the University of Texas, Dallas. "I think they are both benign lesions the majority of the time. Usually, melanomas in these patients arise on normal-appearing skin and not the site of the nevus. When that happens, I think it's coincidental, not a nevus gone bad."

Few studies have actually investigated this point, although Dr. Barrett did mention a 2007 in vitro study that looked at levels of polycomb group protein EZH2, a cell regulatory protein markedly elevated in malignant skin lesions (J. Cutan. Pathol. 2007;34:597-600). The level in both in situ and invasive melanoma was almost three times that seen in acquired and dysplastic nevi—a finding that seems to support Dr. Barrett's opinion.

Regardless of the source, however, patients with large numbers of nevi are at a significantly increased risk of melanoma and other malignancies. The two commonly recognized nevi syndromes carry different risks, Dr. Barrett said.

Familial atypical mole/melanoma syndrome is an autosomal dominant disorder that increases the lifetime risk of melanoma by almost 100%. Sporadic dysplastic nevus syndrome is a spontaneous mutation that increases the relative risk of malignancy up to 46 times that of the general population, he said.

For patients with the sporadic syndrome, sun exposure seems to play a key role in the development of melanoma. "It's been suggested that intermittent sun exposure manifests the phenotype of the dysplastic nevi [and its attendant increased melanoma risk], while patients without sun exposure manifest the common acquired nevi," Dr. Barrett noted.

"There is no clear agreement among dermatologists about how these lesions should be handled," he said. "If you think a lesion is premalignant, you'll want to excise it, and if the report comes back 'severely atypical,' you'll probably want to have negative margins. If you think the lesions aren't premalignant, then after you exclude a diagnosis of melanoma, you probably won't do anything. We have people in our practice who do both."

The phase in which a dermatologist "catches" the nevus probably influences treatment decisions. "These lesions are dynamic, change throughout life, and can be acquired at any age. I think what's happening is that if we biopsy them in a quiescent phase, we don't see cytological atypia. And if we catch them in a dynamic phase, they have different cellular characteristics, which we then have to define as mild or severe atypia," Dr. Barrett said.

Since the lesions are so changeable, and patients are at such a significantly increased risk of melanoma, close follow-up at 3- to 11-month intervals is crucial. It's probably a good idea to screen first-degree relatives, too, he suggested.

WILLIAMSBURG, VA. — Although large numbers of nevi—especially dysplastic nevi—are clearly associated with an increased melanoma risk, the lesions themselves do not appear to become cancerous, Dr. Terry L. Barrett said at the annual meeting of the American Society for Mohs Surgery.

"I remain unconvinced that either the common acquired nevus or the dysplastic nevus develops into melanoma," said Dr. Barrett, professor of pathology and dermatology at the University of Texas, Dallas. "I think they are both benign lesions the majority of the time. Usually, melanomas in these patients arise on normal-appearing skin and not the site of the nevus. When that happens, I think it's coincidental, not a nevus gone bad."

Few studies have actually investigated this point, although Dr. Barrett did mention a 2007 in vitro study that looked at levels of polycomb group protein EZH2, a cell regulatory protein markedly elevated in malignant skin lesions (J. Cutan. Pathol. 2007;34:597-600). The level in both in situ and invasive melanoma was almost three times that seen in acquired and dysplastic nevi—a finding that seems to support Dr. Barrett's opinion.

Regardless of the source, however, patients with large numbers of nevi are at a significantly increased risk of melanoma and other malignancies. The two commonly recognized nevi syndromes carry different risks, Dr. Barrett said.

Familial atypical mole/melanoma syndrome is an autosomal dominant disorder that increases the lifetime risk of melanoma by almost 100%. Sporadic dysplastic nevus syndrome is a spontaneous mutation that increases the relative risk of malignancy up to 46 times that of the general population, he said.

For patients with the sporadic syndrome, sun exposure seems to play a key role in the development of melanoma. "It's been suggested that intermittent sun exposure manifests the phenotype of the dysplastic nevi [and its attendant increased melanoma risk], while patients without sun exposure manifest the common acquired nevi," Dr. Barrett noted.

"There is no clear agreement among dermatologists about how these lesions should be handled," he said. "If you think a lesion is premalignant, you'll want to excise it, and if the report comes back 'severely atypical,' you'll probably want to have negative margins. If you think the lesions aren't premalignant, then after you exclude a diagnosis of melanoma, you probably won't do anything. We have people in our practice who do both."

The phase in which a dermatologist "catches" the nevus probably influences treatment decisions. "These lesions are dynamic, change throughout life, and can be acquired at any age. I think what's happening is that if we biopsy them in a quiescent phase, we don't see cytological atypia. And if we catch them in a dynamic phase, they have different cellular characteristics, which we then have to define as mild or severe atypia," Dr. Barrett said.

Since the lesions are so changeable, and patients are at such a significantly increased risk of melanoma, close follow-up at 3- to 11-month intervals is crucial. It's probably a good idea to screen first-degree relatives, too, he suggested.

CHICAGO — The investigational agent ipilimumab showed activity against all stages of advanced metastatic melanoma, but was also associated with colitis and diarrhea that were not controlled by oral prophylaxis with the anti-inflammatory budesonide, investigators reported at the annual meeting of the American Society of Clinical Oncology.

"Ipilimumab, which in my opinion is an active drug in melanoma, is associated with autoinflammatory side effects, so-called immune-related adverse events," said Dr. Jeffrey S. Weber of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla.

The hypothesis of the study, funded by Bristol-Myers Squibb, joint developer of the monoclonal antibody ipilimumab, was that prophylactic oral budesonide (Entocort EC), an anti-inflammatory approved for treatment of Crohn's disease, might reduce the rate of grade 2 or greater gastrointestinal immune-related adverse events associated with ipilimumab therapy.

The idea did not pan out and the study did not reach its primary end point, although it did meet several of the secondary end points of melanoma control in both previously treated and treatment-naïve patients, reported Dr. Weber, who shares a patent with the University of Southern California and Bristol-Myers Squibb/Medarex.

Budesonide was chosen because it is a controlled-release oral steroid with minimal systemic corticosteroid exposure, Dr. Weber noted.

The primary end point of the study was diarrhea of grade 2 severity or greater among patients receiving 10 mg/kg of ipilimumab and either placebo or budesonide.

Secondary end points included best overall response rate per modified World Health Organization criteria, disease control rate (a composite of complete and partial response rates and stable disease), overall and 1-year survival, and biologic and pharmacokinetic parameters.

Budesonide was administered at a dose of 9 mg/day during ipilimumab induction every 3 weeks in four cycles over 12 weeks, after which budesonide was tapered. A total of 58 patients received the monoclonal antibody plus budesonide, and 57 received ipilimumab plus placebo.

The authors found that grade 2 or greater diarrhea occurred in 19 of the 58 (32.83%) of patients on budesonide, and 20 of 57 (35.1%) of those on placebo; the difference was not statistically significant, Dr. Weber said.

Objective tumor response to ipilimumab was seen in both the budesonide and control arms, at 15.8% and 12.1% of patients, respectively. Response rates were similar among previously treated and treatment-naïve patients, and in patients with stage M1a, M1b, and M1c disease. At the time of the analysis, 24 months, median overall survival had not been reached. The 1-year survival rate was similar in both groups, at 58.8% among patients on budesonide, and 59.1% of controls.

A Kaplan-Meier estimate for overall survival suggested that at about 20 months the survival rate for previously untreated patients would be 67.2%, and the rate for treatment-experienced patients would be 48.8%.

Among patients with melanoma metastatic to brain, two had a partial response, three had stable disease, one had disease progression, and one patient's status was unknown. Of these patients, one survived less than 6 months after being started on ipilimumab, four lived between 6 and 9 months, and seven were still alive from 10.4 to 19.4 months, the point of most recent follow-up.

Central nervous system adverse events related to ipilimumab were reported in two patients, with grade 2 headache and grade 1 dizziness. Immune-related adverse events were the most common toxicities seen with ipilimumab; 40% were grade 3 or 4 events. There were no bowel perforations or treatment-related deaths.

"My conclusion as to the secondary end points is that ipilimumab showed significant efficacy with an excellent estimated median overall survival in patients who got or did not receive prophylactic budesonide, previously treated or untreated patients, patients at all M stages, and including the 50% who had M1c disease," Dr. Weber said.

CHICAGO — The investigational agent ipilimumab showed activity against all stages of advanced metastatic melanoma, but was also associated with colitis and diarrhea that were not controlled by oral prophylaxis with the anti-inflammatory budesonide, investigators reported at the annual meeting of the American Society of Clinical Oncology.

"Ipilimumab, which in my opinion is an active drug in melanoma, is associated with autoinflammatory side effects, so-called immune-related adverse events," said Dr. Jeffrey S. Weber of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla.

The hypothesis of the study, funded by Bristol-Myers Squibb, joint developer of the monoclonal antibody ipilimumab, was that prophylactic oral budesonide (Entocort EC), an anti-inflammatory approved for treatment of Crohn's disease, might reduce the rate of grade 2 or greater gastrointestinal immune-related adverse events associated with ipilimumab therapy.

The idea did not pan out and the study did not reach its primary end point, although it did meet several of the secondary end points of melanoma control in both previously treated and treatment-naïve patients, reported Dr. Weber, who shares a patent with the University of Southern California and Bristol-Myers Squibb/Medarex.

Budesonide was chosen because it is a controlled-release oral steroid with minimal systemic corticosteroid exposure, Dr. Weber noted.

The primary end point of the study was diarrhea of grade 2 severity or greater among patients receiving 10 mg/kg of ipilimumab and either placebo or budesonide.

Secondary end points included best overall response rate per modified World Health Organization criteria, disease control rate (a composite of complete and partial response rates and stable disease), overall and 1-year survival, and biologic and pharmacokinetic parameters.

Budesonide was administered at a dose of 9 mg/day during ipilimumab induction every 3 weeks in four cycles over 12 weeks, after which budesonide was tapered. A total of 58 patients received the monoclonal antibody plus budesonide, and 57 received ipilimumab plus placebo.

The authors found that grade 2 or greater diarrhea occurred in 19 of the 58 (32.83%) of patients on budesonide, and 20 of 57 (35.1%) of those on placebo; the difference was not statistically significant, Dr. Weber said.

Objective tumor response to ipilimumab was seen in both the budesonide and control arms, at 15.8% and 12.1% of patients, respectively. Response rates were similar among previously treated and treatment-naïve patients, and in patients with stage M1a, M1b, and M1c disease. At the time of the analysis, 24 months, median overall survival had not been reached. The 1-year survival rate was similar in both groups, at 58.8% among patients on budesonide, and 59.1% of controls.

A Kaplan-Meier estimate for overall survival suggested that at about 20 months the survival rate for previously untreated patients would be 67.2%, and the rate for treatment-experienced patients would be 48.8%.

Among patients with melanoma metastatic to brain, two had a partial response, three had stable disease, one had disease progression, and one patient's status was unknown. Of these patients, one survived less than 6 months after being started on ipilimumab, four lived between 6 and 9 months, and seven were still alive from 10.4 to 19.4 months, the point of most recent follow-up.

Central nervous system adverse events related to ipilimumab were reported in two patients, with grade 2 headache and grade 1 dizziness. Immune-related adverse events were the most common toxicities seen with ipilimumab; 40% were grade 3 or 4 events. There were no bowel perforations or treatment-related deaths.

"My conclusion as to the secondary end points is that ipilimumab showed significant efficacy with an excellent estimated median overall survival in patients who got or did not receive prophylactic budesonide, previously treated or untreated patients, patients at all M stages, and including the 50% who had M1c disease," Dr. Weber said.

CHICAGO — The investigational agent ipilimumab showed activity against all stages of advanced metastatic melanoma, but was also associated with colitis and diarrhea that were not controlled by oral prophylaxis with the anti-inflammatory budesonide, investigators reported at the annual meeting of the American Society of Clinical Oncology.

"Ipilimumab, which in my opinion is an active drug in melanoma, is associated with autoinflammatory side effects, so-called immune-related adverse events," said Dr. Jeffrey S. Weber of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla.

The hypothesis of the study, funded by Bristol-Myers Squibb, joint developer of the monoclonal antibody ipilimumab, was that prophylactic oral budesonide (Entocort EC), an anti-inflammatory approved for treatment of Crohn's disease, might reduce the rate of grade 2 or greater gastrointestinal immune-related adverse events associated with ipilimumab therapy.

The idea did not pan out and the study did not reach its primary end point, although it did meet several of the secondary end points of melanoma control in both previously treated and treatment-naïve patients, reported Dr. Weber, who shares a patent with the University of Southern California and Bristol-Myers Squibb/Medarex.

Budesonide was chosen because it is a controlled-release oral steroid with minimal systemic corticosteroid exposure, Dr. Weber noted.

The primary end point of the study was diarrhea of grade 2 severity or greater among patients receiving 10 mg/kg of ipilimumab and either placebo or budesonide.

Secondary end points included best overall response rate per modified World Health Organization criteria, disease control rate (a composite of complete and partial response rates and stable disease), overall and 1-year survival, and biologic and pharmacokinetic parameters.

Budesonide was administered at a dose of 9 mg/day during ipilimumab induction every 3 weeks in four cycles over 12 weeks, after which budesonide was tapered. A total of 58 patients received the monoclonal antibody plus budesonide, and 57 received ipilimumab plus placebo.

The authors found that grade 2 or greater diarrhea occurred in 19 of the 58 (32.83%) of patients on budesonide, and 20 of 57 (35.1%) of those on placebo; the difference was not statistically significant, Dr. Weber said.

Objective tumor response to ipilimumab was seen in both the budesonide and control arms, at 15.8% and 12.1% of patients, respectively. Response rates were similar among previously treated and treatment-naïve patients, and in patients with stage M1a, M1b, and M1c disease. At the time of the analysis, 24 months, median overall survival had not been reached. The 1-year survival rate was similar in both groups, at 58.8% among patients on budesonide, and 59.1% of controls.

A Kaplan-Meier estimate for overall survival suggested that at about 20 months the survival rate for previously untreated patients would be 67.2%, and the rate for treatment-experienced patients would be 48.8%.

Among patients with melanoma metastatic to brain, two had a partial response, three had stable disease, one had disease progression, and one patient's status was unknown. Of these patients, one survived less than 6 months after being started on ipilimumab, four lived between 6 and 9 months, and seven were still alive from 10.4 to 19.4 months, the point of most recent follow-up.

Central nervous system adverse events related to ipilimumab were reported in two patients, with grade 2 headache and grade 1 dizziness. Immune-related adverse events were the most common toxicities seen with ipilimumab; 40% were grade 3 or 4 events. There were no bowel perforations or treatment-related deaths.

"My conclusion as to the secondary end points is that ipilimumab showed significant efficacy with an excellent estimated median overall survival in patients who got or did not receive prophylactic budesonide, previously treated or untreated patients, patients at all M stages, and including the 50% who had M1c disease," Dr. Weber said.

NEW ORLEANS — Although the concept of checking the skin for melanoma may be to "find the ugly duckling," the first challenge is to identify the signature nevus in order to determine the patient's particular phenotype, said Dr. Jean Bolognia.

"Identifying the signature nevus will reduce the number of biopsies you perform," said Dr. Bolognia.

She discussed several varieties of signature melanocytic nevi at a dermatology update sponsored by Tulane University. She highlighted a few of the more common types as well as the two most challenging.

Solid brown nevi, she said, are easier to manage. "This type of signature nevus is easy to follow, as it is symmetric and uniform in color," noted Dr. Bolognia, professor of dermatology at Yale University, New Haven, Conn.

Because of their size, the large moles that resemble fried eggs and are often found on the back are frequently of concern to patients and their relatives as well as to non-dermatologists. These "sensational" nevi are benign, and rather than being labeled as precursors of melanoma, they should be viewed as a phenotypic marker, alerting the physician that the patient's entire skin is at risk and should therefore be carefully examined.

"A melanoma can arise in this type of nevus, just as it can any other compound nevus," she said. "Do look for superimposed changes, but in and of themselves, these nevi are benign." Prophylactic excision is not recommended for fried-egg nevi, as scarring can be significant given their size and truncal location. In addition, these nevi age over time with gradual fading of the shoulder component into the surrounding skin and formation of a skin-colored intradermal nevus centrally.

On other hand, the "cheetah" phenotype, represented by numerous small, dark nevi, can be very difficult to manage, she noted. The signature nevus is a dark brown-black compound or junctional lentiginous nevus that may or may not have a thin medium brown rim. The center of the lesion is extremely dark and solid, without a visible pigment pattern by dermoscopy.

"Usually, the patient has 200 or more of these nevi, often admixed with solar lentigines. The anticipation is that this patient will undergo multiple biopsies, with a lower 'hit rate' for cutaneous melanoma than with other types of nevi," she said. "I share these patients with another dermatologist. Having two sets of eyes doing a skin examination is my solution to the difficult 'cheetah' phenotype."

The "eclipse" nevi resemble a solar eclipse, with a solid tan center and a brown rim that is often stellate. The rim may also be discontinuous, leading to asymmetry. They are often seen on the scalp of children, and can be the first sign that a child will be "moley."

"These nevi are benign but they get attention because of their irregular outline and variation in color. Unless there is a superimposed change, they should not elicit concern," she noted. "When the signature nevus is an eclipse nevus, you should focus on the 10 to 15 other nevi that are not in this 'family' and look for the one with the most atypical features."

Dr. Bolognia does not recommend surgically removing eclipse nevi on the scalp because others will probably develop and parents will expect these to be removed as well. Cockarde or "target" nevi are in the same family as eclipse nevi; these types are often seen together.

Another difficult, though rare, phenotype is represented by multiple pink nevi. These patients tend to be skin type 1 or 2 and they produce little, if any, melanin in their nevi. "In this patient the pigment pattern is missing, the road signs are gone, and these nevi can be difficult to evaluate clinically," she said.

"If the nevus has substance (not soft like an aging dermal nevus), I take a second look. And I also look for the nevus with the darkest pink color or any red lesion. I usually biopsy the latter, unless it is clearly acneiform, and like with the 'cheetah' phenotype, share these patients with another dermatologist," she said.

Multiple halo nevi, seen most often in patients in their late teens and early 20s, can also be problematic. There are four stages of halo nevi, with stages I and II being characterized by a depigmented halo surrounding either a pigmented nevus (I) or a pink nevus (II). Stage III appears as an area of depigmentation that is oval or circular in shape (with no central nevus), thus resembling a patch of vitiligo, while stage IV represents complete repigmentation. While everyone with multiple halo nevi deserves a total body examination, if an older adult presents with multiple halo nevi, the possibility of an immune reaction to an ocular (or cutaneous) melanoma needs to be considered, Dr. Bolognia said.

Exams of the "cheetah" phenotype, represented by numerous small, dark nevi, are best conducted with two sets of eyes. Courtesy Dr. Jean Bolognia

NEW ORLEANS — Although the concept of checking the skin for melanoma may be to "find the ugly duckling," the first challenge is to identify the signature nevus in order to determine the patient's particular phenotype, said Dr. Jean Bolognia.

"Identifying the signature nevus will reduce the number of biopsies you perform," said Dr. Bolognia.

She discussed several varieties of signature melanocytic nevi at a dermatology update sponsored by Tulane University. She highlighted a few of the more common types as well as the two most challenging.

Solid brown nevi, she said, are easier to manage. "This type of signature nevus is easy to follow, as it is symmetric and uniform in color," noted Dr. Bolognia, professor of dermatology at Yale University, New Haven, Conn.

Because of their size, the large moles that resemble fried eggs and are often found on the back are frequently of concern to patients and their relatives as well as to non-dermatologists. These "sensational" nevi are benign, and rather than being labeled as precursors of melanoma, they should be viewed as a phenotypic marker, alerting the physician that the patient's entire skin is at risk and should therefore be carefully examined.

"A melanoma can arise in this type of nevus, just as it can any other compound nevus," she said. "Do look for superimposed changes, but in and of themselves, these nevi are benign." Prophylactic excision is not recommended for fried-egg nevi, as scarring can be significant given their size and truncal location. In addition, these nevi age over time with gradual fading of the shoulder component into the surrounding skin and formation of a skin-colored intradermal nevus centrally.

On other hand, the "cheetah" phenotype, represented by numerous small, dark nevi, can be very difficult to manage, she noted. The signature nevus is a dark brown-black compound or junctional lentiginous nevus that may or may not have a thin medium brown rim. The center of the lesion is extremely dark and solid, without a visible pigment pattern by dermoscopy.

"Usually, the patient has 200 or more of these nevi, often admixed with solar lentigines. The anticipation is that this patient will undergo multiple biopsies, with a lower 'hit rate' for cutaneous melanoma than with other types of nevi," she said. "I share these patients with another dermatologist. Having two sets of eyes doing a skin examination is my solution to the difficult 'cheetah' phenotype."

The "eclipse" nevi resemble a solar eclipse, with a solid tan center and a brown rim that is often stellate. The rim may also be discontinuous, leading to asymmetry. They are often seen on the scalp of children, and can be the first sign that a child will be "moley."

"These nevi are benign but they get attention because of their irregular outline and variation in color. Unless there is a superimposed change, they should not elicit concern," she noted. "When the signature nevus is an eclipse nevus, you should focus on the 10 to 15 other nevi that are not in this 'family' and look for the one with the most atypical features."

Dr. Bolognia does not recommend surgically removing eclipse nevi on the scalp because others will probably develop and parents will expect these to be removed as well. Cockarde or "target" nevi are in the same family as eclipse nevi; these types are often seen together.

Another difficult, though rare, phenotype is represented by multiple pink nevi. These patients tend to be skin type 1 or 2 and they produce little, if any, melanin in their nevi. "In this patient the pigment pattern is missing, the road signs are gone, and these nevi can be difficult to evaluate clinically," she said.

"If the nevus has substance (not soft like an aging dermal nevus), I take a second look. And I also look for the nevus with the darkest pink color or any red lesion. I usually biopsy the latter, unless it is clearly acneiform, and like with the 'cheetah' phenotype, share these patients with another dermatologist," she said.

Multiple halo nevi, seen most often in patients in their late teens and early 20s, can also be problematic. There are four stages of halo nevi, with stages I and II being characterized by a depigmented halo surrounding either a pigmented nevus (I) or a pink nevus (II). Stage III appears as an area of depigmentation that is oval or circular in shape (with no central nevus), thus resembling a patch of vitiligo, while stage IV represents complete repigmentation. While everyone with multiple halo nevi deserves a total body examination, if an older adult presents with multiple halo nevi, the possibility of an immune reaction to an ocular (or cutaneous) melanoma needs to be considered, Dr. Bolognia said.

Exams of the "cheetah" phenotype, represented by numerous small, dark nevi, are best conducted with two sets of eyes. Courtesy Dr. Jean Bolognia

NEW ORLEANS — Although the concept of checking the skin for melanoma may be to "find the ugly duckling," the first challenge is to identify the signature nevus in order to determine the patient's particular phenotype, said Dr. Jean Bolognia.

"Identifying the signature nevus will reduce the number of biopsies you perform," said Dr. Bolognia.

She discussed several varieties of signature melanocytic nevi at a dermatology update sponsored by Tulane University. She highlighted a few of the more common types as well as the two most challenging.

Solid brown nevi, she said, are easier to manage. "This type of signature nevus is easy to follow, as it is symmetric and uniform in color," noted Dr. Bolognia, professor of dermatology at Yale University, New Haven, Conn.

Because of their size, the large moles that resemble fried eggs and are often found on the back are frequently of concern to patients and their relatives as well as to non-dermatologists. These "sensational" nevi are benign, and rather than being labeled as precursors of melanoma, they should be viewed as a phenotypic marker, alerting the physician that the patient's entire skin is at risk and should therefore be carefully examined.

"A melanoma can arise in this type of nevus, just as it can any other compound nevus," she said. "Do look for superimposed changes, but in and of themselves, these nevi are benign." Prophylactic excision is not recommended for fried-egg nevi, as scarring can be significant given their size and truncal location. In addition, these nevi age over time with gradual fading of the shoulder component into the surrounding skin and formation of a skin-colored intradermal nevus centrally.

On other hand, the "cheetah" phenotype, represented by numerous small, dark nevi, can be very difficult to manage, she noted. The signature nevus is a dark brown-black compound or junctional lentiginous nevus that may or may not have a thin medium brown rim. The center of the lesion is extremely dark and solid, without a visible pigment pattern by dermoscopy.

"Usually, the patient has 200 or more of these nevi, often admixed with solar lentigines. The anticipation is that this patient will undergo multiple biopsies, with a lower 'hit rate' for cutaneous melanoma than with other types of nevi," she said. "I share these patients with another dermatologist. Having two sets of eyes doing a skin examination is my solution to the difficult 'cheetah' phenotype."

The "eclipse" nevi resemble a solar eclipse, with a solid tan center and a brown rim that is often stellate. The rim may also be discontinuous, leading to asymmetry. They are often seen on the scalp of children, and can be the first sign that a child will be "moley."

"These nevi are benign but they get attention because of their irregular outline and variation in color. Unless there is a superimposed change, they should not elicit concern," she noted. "When the signature nevus is an eclipse nevus, you should focus on the 10 to 15 other nevi that are not in this 'family' and look for the one with the most atypical features."

Dr. Bolognia does not recommend surgically removing eclipse nevi on the scalp because others will probably develop and parents will expect these to be removed as well. Cockarde or "target" nevi are in the same family as eclipse nevi; these types are often seen together.

Another difficult, though rare, phenotype is represented by multiple pink nevi. These patients tend to be skin type 1 or 2 and they produce little, if any, melanin in their nevi. "In this patient the pigment pattern is missing, the road signs are gone, and these nevi can be difficult to evaluate clinically," she said.

"If the nevus has substance (not soft like an aging dermal nevus), I take a second look. And I also look for the nevus with the darkest pink color or any red lesion. I usually biopsy the latter, unless it is clearly acneiform, and like with the 'cheetah' phenotype, share these patients with another dermatologist," she said.

Multiple halo nevi, seen most often in patients in their late teens and early 20s, can also be problematic. There are four stages of halo nevi, with stages I and II being characterized by a depigmented halo surrounding either a pigmented nevus (I) or a pink nevus (II). Stage III appears as an area of depigmentation that is oval or circular in shape (with no central nevus), thus resembling a patch of vitiligo, while stage IV represents complete repigmentation. While everyone with multiple halo nevi deserves a total body examination, if an older adult presents with multiple halo nevi, the possibility of an immune reaction to an ocular (or cutaneous) melanoma needs to be considered, Dr. Bolognia said.

Exams of the "cheetah" phenotype, represented by numerous small, dark nevi, are best conducted with two sets of eyes. Courtesy Dr. Jean Bolognia