Melanoma

VANCOUVER, B.C. — Some patients undergoing Mohs micrographic surgery have undiagnosed bleeding disorders, but careful history taking, vigilance during surgery, and tailored management can prevent complications in most cases, according to results of a study of more than 2,500 patients.

Dr. Carl Vinciullo and his colleague, Dr. Ross Baker, both of Royal Perth Hospital in Australia, prospectively assessed the prevalence of bleeding disorders among 2,517 patients undergoing Mohs surgery between 2003 and 2007. The investigators obtained a detailed bleeding history from all patients and performed a hematologic workup in those who had a positive history or who had unexplained excessive bleeding during their Mohs surgery.

A total of 18 patients (0.7%) had a previously undiagnosed bleeding disorder. Eleven of them had a positive bleeding history, while seven had a negative history but bled excessively during surgery. Dr. Vinciullo noted that most of the affected patients had normal routine coagulation profiles on hematologic testing and that one patient had even undergone general surgery uneventfully 2 years earlier.

The hematologic workup further revealed that 6 of the 18 patients had von Willebrand disease (alone or with other abnormalities), three had acquired platelet abnormalities with myelodysplasia and other abnormalities, two had suspected increased capillary fragility, one had a clopidogrel-like platelet secretion defect, and one had suspected impaired vasoconstriction with hereditary hemorrhagic telangiectasia.

Another two patients—one with refractory immune thrombocytopenia and antiplatelet antibodies, and another with disseminated intravascular coagulation, thrombocytopenia, and cancer-associated fibrinogen deficiency—were treated with radiation therapy instead because their disorders were judged to be contraindications to surgery.

Finally, three of the patients had no definable hematologic abnormality. "This does not mean that they do not have a bleeding abnormality," Dr. Vinciullo said of the last group. "It is quite conceivable that there are bleeding abnormalities which are yet not possible to define with the investigations available to us."

Among the patients who were surgical candidates, those with von Willebrand disease were treated with preoperative desmopressin infusion, oral tranexamic acid, or a combination thereof. Those with platelet function abnormalities were all treated with preoperative platelet infusions; one also received desmopressin, and another also received additional platelet cross-matching, recombinant factor VIIa, and tranexamic acid. The remaining patients were given tranexamic acid or were not treated, Dr. Vinciullo reported at the annual meeting of the American College of Mohs Surgery.

With this management approach, 17 of the 18 patients did not experience initial or additional excessive bleeding and did not require further intervention, according to Dr. Vinciullo. The remaining patient, who had an acquired platelet function abnormality, antiplatelet antibodies, low factor XII levels, and myelodysplasia, was hospitalized for 3 days because of surgery-associated bleeding, despite all measures.

Summing up the study's findings, Dr. Vinciullo said that the incidence of undiagnosed bleeding disorders is low in Mohs surgical patients, but physicians nonetheless should be alert for such disorders—even when a bleeding history is negative and the results of routine coagulation studies are normal.

"Hematology assessment is essential, and specialized prophylactic treatment can prevent the vast majority of bleeding complications," he said.

However, he added, routine preoperative hematologic testing is not warranted in patients with a negative bleeding history. "The most sensitive sign is a positive history, so you must take a detailed bleeding history," he emphasized. (See box.) "The sort of questions I listed are the questions you need to ask. It's absolutely incredible how many of these patients have simply never been asked those questions, or the physician knows they bleed but has never done anything about it."

Finally, Dr. Vinciullo advised, "unexplained excessive bleeding during Mohs surgery should be investigated." He noted that a watery consistency of the blood and bleeding from suture holes can be additional telltale signs of underlying bleeding disorders.

"If you have a patient where you place a stitch and blood comes out of the suture hole, to me, that's a reason to send [that person] off for a hematology investigation," he said.

Dr. Vinciullo reported no conflicts of interest in association with the study.

'Hematology assessment is essential, and specialized prophylactic treatment can prevent' bleeding. DR. VINCIULLO

Take a Detailed Bleeding History

Ask patients if they have had excessive bleeding during any of the following:

▸ Menstrual periods or childbirth?

▸ Nosebleeds?

▸ Skin surgery?

▸ Dental work, tonsillectomy, or general surgery? And also ask:

▸ Have you had to return to a physician's office or hospital because of bleeding?

▸ Do you bruise excessively?

▸ Do you take supplements or complementary products (vitamin E, garlic, ginkgo biloba)?

▸ Do you have a family history of bleeding, hemophilia, or von Willebrand disease?

▸ Do you have any blood disorders or leukemia?

Source: Dr. Vinciullo

VANCOUVER, B.C. — Some patients undergoing Mohs micrographic surgery have undiagnosed bleeding disorders, but careful history taking, vigilance during surgery, and tailored management can prevent complications in most cases, according to results of a study of more than 2,500 patients.

Dr. Carl Vinciullo and his colleague, Dr. Ross Baker, both of Royal Perth Hospital in Australia, prospectively assessed the prevalence of bleeding disorders among 2,517 patients undergoing Mohs surgery between 2003 and 2007. The investigators obtained a detailed bleeding history from all patients and performed a hematologic workup in those who had a positive history or who had unexplained excessive bleeding during their Mohs surgery.

A total of 18 patients (0.7%) had a previously undiagnosed bleeding disorder. Eleven of them had a positive bleeding history, while seven had a negative history but bled excessively during surgery. Dr. Vinciullo noted that most of the affected patients had normal routine coagulation profiles on hematologic testing and that one patient had even undergone general surgery uneventfully 2 years earlier.

The hematologic workup further revealed that 6 of the 18 patients had von Willebrand disease (alone or with other abnormalities), three had acquired platelet abnormalities with myelodysplasia and other abnormalities, two had suspected increased capillary fragility, one had a clopidogrel-like platelet secretion defect, and one had suspected impaired vasoconstriction with hereditary hemorrhagic telangiectasia.

Another two patients—one with refractory immune thrombocytopenia and antiplatelet antibodies, and another with disseminated intravascular coagulation, thrombocytopenia, and cancer-associated fibrinogen deficiency—were treated with radiation therapy instead because their disorders were judged to be contraindications to surgery.

Finally, three of the patients had no definable hematologic abnormality. "This does not mean that they do not have a bleeding abnormality," Dr. Vinciullo said of the last group. "It is quite conceivable that there are bleeding abnormalities which are yet not possible to define with the investigations available to us."

Among the patients who were surgical candidates, those with von Willebrand disease were treated with preoperative desmopressin infusion, oral tranexamic acid, or a combination thereof. Those with platelet function abnormalities were all treated with preoperative platelet infusions; one also received desmopressin, and another also received additional platelet cross-matching, recombinant factor VIIa, and tranexamic acid. The remaining patients were given tranexamic acid or were not treated, Dr. Vinciullo reported at the annual meeting of the American College of Mohs Surgery.

With this management approach, 17 of the 18 patients did not experience initial or additional excessive bleeding and did not require further intervention, according to Dr. Vinciullo. The remaining patient, who had an acquired platelet function abnormality, antiplatelet antibodies, low factor XII levels, and myelodysplasia, was hospitalized for 3 days because of surgery-associated bleeding, despite all measures.

Summing up the study's findings, Dr. Vinciullo said that the incidence of undiagnosed bleeding disorders is low in Mohs surgical patients, but physicians nonetheless should be alert for such disorders—even when a bleeding history is negative and the results of routine coagulation studies are normal.

"Hematology assessment is essential, and specialized prophylactic treatment can prevent the vast majority of bleeding complications," he said.

However, he added, routine preoperative hematologic testing is not warranted in patients with a negative bleeding history. "The most sensitive sign is a positive history, so you must take a detailed bleeding history," he emphasized. (See box.) "The sort of questions I listed are the questions you need to ask. It's absolutely incredible how many of these patients have simply never been asked those questions, or the physician knows they bleed but has never done anything about it."

Finally, Dr. Vinciullo advised, "unexplained excessive bleeding during Mohs surgery should be investigated." He noted that a watery consistency of the blood and bleeding from suture holes can be additional telltale signs of underlying bleeding disorders.

"If you have a patient where you place a stitch and blood comes out of the suture hole, to me, that's a reason to send [that person] off for a hematology investigation," he said.

Dr. Vinciullo reported no conflicts of interest in association with the study.

'Hematology assessment is essential, and specialized prophylactic treatment can prevent' bleeding. DR. VINCIULLO

Take a Detailed Bleeding History

Ask patients if they have had excessive bleeding during any of the following:

▸ Menstrual periods or childbirth?

▸ Nosebleeds?

▸ Skin surgery?

▸ Dental work, tonsillectomy, or general surgery? And also ask:

▸ Have you had to return to a physician's office or hospital because of bleeding?

▸ Do you bruise excessively?

▸ Do you take supplements or complementary products (vitamin E, garlic, ginkgo biloba)?

▸ Do you have a family history of bleeding, hemophilia, or von Willebrand disease?

▸ Do you have any blood disorders or leukemia?

Source: Dr. Vinciullo

VANCOUVER, B.C. — Some patients undergoing Mohs micrographic surgery have undiagnosed bleeding disorders, but careful history taking, vigilance during surgery, and tailored management can prevent complications in most cases, according to results of a study of more than 2,500 patients.

Dr. Carl Vinciullo and his colleague, Dr. Ross Baker, both of Royal Perth Hospital in Australia, prospectively assessed the prevalence of bleeding disorders among 2,517 patients undergoing Mohs surgery between 2003 and 2007. The investigators obtained a detailed bleeding history from all patients and performed a hematologic workup in those who had a positive history or who had unexplained excessive bleeding during their Mohs surgery.

A total of 18 patients (0.7%) had a previously undiagnosed bleeding disorder. Eleven of them had a positive bleeding history, while seven had a negative history but bled excessively during surgery. Dr. Vinciullo noted that most of the affected patients had normal routine coagulation profiles on hematologic testing and that one patient had even undergone general surgery uneventfully 2 years earlier.

The hematologic workup further revealed that 6 of the 18 patients had von Willebrand disease (alone or with other abnormalities), three had acquired platelet abnormalities with myelodysplasia and other abnormalities, two had suspected increased capillary fragility, one had a clopidogrel-like platelet secretion defect, and one had suspected impaired vasoconstriction with hereditary hemorrhagic telangiectasia.

Another two patients—one with refractory immune thrombocytopenia and antiplatelet antibodies, and another with disseminated intravascular coagulation, thrombocytopenia, and cancer-associated fibrinogen deficiency—were treated with radiation therapy instead because their disorders were judged to be contraindications to surgery.

Finally, three of the patients had no definable hematologic abnormality. "This does not mean that they do not have a bleeding abnormality," Dr. Vinciullo said of the last group. "It is quite conceivable that there are bleeding abnormalities which are yet not possible to define with the investigations available to us."

Among the patients who were surgical candidates, those with von Willebrand disease were treated with preoperative desmopressin infusion, oral tranexamic acid, or a combination thereof. Those with platelet function abnormalities were all treated with preoperative platelet infusions; one also received desmopressin, and another also received additional platelet cross-matching, recombinant factor VIIa, and tranexamic acid. The remaining patients were given tranexamic acid or were not treated, Dr. Vinciullo reported at the annual meeting of the American College of Mohs Surgery.

With this management approach, 17 of the 18 patients did not experience initial or additional excessive bleeding and did not require further intervention, according to Dr. Vinciullo. The remaining patient, who had an acquired platelet function abnormality, antiplatelet antibodies, low factor XII levels, and myelodysplasia, was hospitalized for 3 days because of surgery-associated bleeding, despite all measures.

Summing up the study's findings, Dr. Vinciullo said that the incidence of undiagnosed bleeding disorders is low in Mohs surgical patients, but physicians nonetheless should be alert for such disorders—even when a bleeding history is negative and the results of routine coagulation studies are normal.

"Hematology assessment is essential, and specialized prophylactic treatment can prevent the vast majority of bleeding complications," he said.

However, he added, routine preoperative hematologic testing is not warranted in patients with a negative bleeding history. "The most sensitive sign is a positive history, so you must take a detailed bleeding history," he emphasized. (See box.) "The sort of questions I listed are the questions you need to ask. It's absolutely incredible how many of these patients have simply never been asked those questions, or the physician knows they bleed but has never done anything about it."

Finally, Dr. Vinciullo advised, "unexplained excessive bleeding during Mohs surgery should be investigated." He noted that a watery consistency of the blood and bleeding from suture holes can be additional telltale signs of underlying bleeding disorders.

"If you have a patient where you place a stitch and blood comes out of the suture hole, to me, that's a reason to send [that person] off for a hematology investigation," he said.

Dr. Vinciullo reported no conflicts of interest in association with the study.

'Hematology assessment is essential, and specialized prophylactic treatment can prevent' bleeding. DR. VINCIULLO

Take a Detailed Bleeding History

Ask patients if they have had excessive bleeding during any of the following:

▸ Menstrual periods or childbirth?

▸ Nosebleeds?

▸ Skin surgery?

▸ Dental work, tonsillectomy, or general surgery? And also ask:

▸ Have you had to return to a physician's office or hospital because of bleeding?

▸ Do you bruise excessively?

▸ Do you take supplements or complementary products (vitamin E, garlic, ginkgo biloba)?

▸ Do you have a family history of bleeding, hemophilia, or von Willebrand disease?

▸ Do you have any blood disorders or leukemia?

Source: Dr. Vinciullo

CHICAGO — The modified Keystone Island skin flap avoids the need for skin grafting in most patients with lower limb primary melanoma, a prospective study from Australia suggests.

The flap, which takes its name from architectural terminology because of its curvilinear, trapezoidal shape, is technically straightforward to perform, substantially reduces hospitalization, and affords better cosmesis compared with skin grafting, investigator Marc Moncrieff said at a symposium sponsored by the Society of Surgical Oncology. The flap also can be used in patients with significant comorbidities that are often regarded as contraindications for fasciocutaneous flap reconstruction in the lower limb.

"Defects resulting from incision of primary melanomas in the lower limb can usually be reconstructed using the modified Keystone flap," he said. "In our experience, a skin graft is rarely required."

Dr. Moncrieff and associates reported on a prospective cohort of 176 consecutive patients, mean age 57 years (range 21–93), with stage I or II invasive primary cutaneous melanoma treated over a 3-year-period at the Sydney Melanoma Unit, where Dr. Moncrieff is a fellow and the Keystone flap is the standard reconstruction technique for lower limb primary melanoma defects.

Major complications were reported in 5 (2.8%) patients. These included one partial flap necrosis, one total flap loss, two infections, and one deep vein thrombosis. Minor complications, including transient neuralgia, minor wound problems, and seroma, were reported in 8 patients (4.5%).

At baseline, the average Breslow thickness was 1.33 mm (range in situ to 9.0 mm), average radial margin 1.5 cm (0.5–2.0 cm), and average defect width 3 cm (1.1–6.3 cm).

The flaps were performed from the proximal lower leg to the dorsum of the foot, with 14% performed on the upper-third of the lower leg, 45% on the middle-third, and 41% on the lower-third. There was no significant increase in complications in the distal third of the limb, a traditionally difficult area to close because of its anatomical tightness, he said.

The reconstructions included 106 standard Keystone flaps, 65 modified, and 5 double-opposing type flaps. Modification of the flap design significantly reduced the major complication rate, and all double-opposing flaps healed without incident.

The standard Keystone flap originally reported by fellow Australian Dr. Felix Behan (ANZ J Surg. 2003;73:112–20) is essentially two conjoined V-Y flaps end to side that are advanced to fill the defect.

Surgeons at the Sydney Melanoma Unit modified the flap by dividing the lateral deep fascia margin to allow for adequate advancement of the flap and to improve vascularity. For larger defects, two opposing Keystone flaps can be used to fill the defect. In all three types, once the skin is incised, the subcutaneous tissue is divided by blunt dissection to preserve the integrity of the vascular network, including the fascial and muscular perforators.

Because the skin is taken from the surrounding tissue, the color match is superior to that of split-thickness skin grafts, which are typically taken from the abdomen, and can result in a crocodile-like appearance of the skin and lengthy rehabilitation, Dr. Moncrieff said.

Dr. Michael Sabel, session moderator, acknowledged that the Keystone flap is "a great improvement" over the split-thickness skin graft, but that the full-thickness skin graft is a simple and widely used technique that provides well-matched tissue from the sentinel lymph node biopsy site or abdomen, with its main disadvantage being that patients are typically immobilized for 5 days.

Dr. Moncrieff responded that the Keystone flap can be performed in the same amount of time as a full-thickness graft and that most patients elevate their limb overnight and return home and walk the next day. Of the 176 patients, 39 (22%) had the procedure performed in a day-case setting.

An audience member questioned whether the technique can be used to fill larger defects or upper limb defects. The modified Keystone flap has been used to reconstruct distal upper limb defects, and requires no special allowances when closing larger defects, said Dr. Moncrieff, who reported no conflicts of interest.

CHICAGO — The modified Keystone Island skin flap avoids the need for skin grafting in most patients with lower limb primary melanoma, a prospective study from Australia suggests.

The flap, which takes its name from architectural terminology because of its curvilinear, trapezoidal shape, is technically straightforward to perform, substantially reduces hospitalization, and affords better cosmesis compared with skin grafting, investigator Marc Moncrieff said at a symposium sponsored by the Society of Surgical Oncology. The flap also can be used in patients with significant comorbidities that are often regarded as contraindications for fasciocutaneous flap reconstruction in the lower limb.

"Defects resulting from incision of primary melanomas in the lower limb can usually be reconstructed using the modified Keystone flap," he said. "In our experience, a skin graft is rarely required."

Dr. Moncrieff and associates reported on a prospective cohort of 176 consecutive patients, mean age 57 years (range 21–93), with stage I or II invasive primary cutaneous melanoma treated over a 3-year-period at the Sydney Melanoma Unit, where Dr. Moncrieff is a fellow and the Keystone flap is the standard reconstruction technique for lower limb primary melanoma defects.

Major complications were reported in 5 (2.8%) patients. These included one partial flap necrosis, one total flap loss, two infections, and one deep vein thrombosis. Minor complications, including transient neuralgia, minor wound problems, and seroma, were reported in 8 patients (4.5%).

At baseline, the average Breslow thickness was 1.33 mm (range in situ to 9.0 mm), average radial margin 1.5 cm (0.5–2.0 cm), and average defect width 3 cm (1.1–6.3 cm).

The flaps were performed from the proximal lower leg to the dorsum of the foot, with 14% performed on the upper-third of the lower leg, 45% on the middle-third, and 41% on the lower-third. There was no significant increase in complications in the distal third of the limb, a traditionally difficult area to close because of its anatomical tightness, he said.

The reconstructions included 106 standard Keystone flaps, 65 modified, and 5 double-opposing type flaps. Modification of the flap design significantly reduced the major complication rate, and all double-opposing flaps healed without incident.

The standard Keystone flap originally reported by fellow Australian Dr. Felix Behan (ANZ J Surg. 2003;73:112–20) is essentially two conjoined V-Y flaps end to side that are advanced to fill the defect.

Surgeons at the Sydney Melanoma Unit modified the flap by dividing the lateral deep fascia margin to allow for adequate advancement of the flap and to improve vascularity. For larger defects, two opposing Keystone flaps can be used to fill the defect. In all three types, once the skin is incised, the subcutaneous tissue is divided by blunt dissection to preserve the integrity of the vascular network, including the fascial and muscular perforators.

Because the skin is taken from the surrounding tissue, the color match is superior to that of split-thickness skin grafts, which are typically taken from the abdomen, and can result in a crocodile-like appearance of the skin and lengthy rehabilitation, Dr. Moncrieff said.

Dr. Michael Sabel, session moderator, acknowledged that the Keystone flap is "a great improvement" over the split-thickness skin graft, but that the full-thickness skin graft is a simple and widely used technique that provides well-matched tissue from the sentinel lymph node biopsy site or abdomen, with its main disadvantage being that patients are typically immobilized for 5 days.

Dr. Moncrieff responded that the Keystone flap can be performed in the same amount of time as a full-thickness graft and that most patients elevate their limb overnight and return home and walk the next day. Of the 176 patients, 39 (22%) had the procedure performed in a day-case setting.

An audience member questioned whether the technique can be used to fill larger defects or upper limb defects. The modified Keystone flap has been used to reconstruct distal upper limb defects, and requires no special allowances when closing larger defects, said Dr. Moncrieff, who reported no conflicts of interest.

CHICAGO — The modified Keystone Island skin flap avoids the need for skin grafting in most patients with lower limb primary melanoma, a prospective study from Australia suggests.

The flap, which takes its name from architectural terminology because of its curvilinear, trapezoidal shape, is technically straightforward to perform, substantially reduces hospitalization, and affords better cosmesis compared with skin grafting, investigator Marc Moncrieff said at a symposium sponsored by the Society of Surgical Oncology. The flap also can be used in patients with significant comorbidities that are often regarded as contraindications for fasciocutaneous flap reconstruction in the lower limb.

"Defects resulting from incision of primary melanomas in the lower limb can usually be reconstructed using the modified Keystone flap," he said. "In our experience, a skin graft is rarely required."

Dr. Moncrieff and associates reported on a prospective cohort of 176 consecutive patients, mean age 57 years (range 21–93), with stage I or II invasive primary cutaneous melanoma treated over a 3-year-period at the Sydney Melanoma Unit, where Dr. Moncrieff is a fellow and the Keystone flap is the standard reconstruction technique for lower limb primary melanoma defects.

Major complications were reported in 5 (2.8%) patients. These included one partial flap necrosis, one total flap loss, two infections, and one deep vein thrombosis. Minor complications, including transient neuralgia, minor wound problems, and seroma, were reported in 8 patients (4.5%).

At baseline, the average Breslow thickness was 1.33 mm (range in situ to 9.0 mm), average radial margin 1.5 cm (0.5–2.0 cm), and average defect width 3 cm (1.1–6.3 cm).

The flaps were performed from the proximal lower leg to the dorsum of the foot, with 14% performed on the upper-third of the lower leg, 45% on the middle-third, and 41% on the lower-third. There was no significant increase in complications in the distal third of the limb, a traditionally difficult area to close because of its anatomical tightness, he said.

The reconstructions included 106 standard Keystone flaps, 65 modified, and 5 double-opposing type flaps. Modification of the flap design significantly reduced the major complication rate, and all double-opposing flaps healed without incident.

The standard Keystone flap originally reported by fellow Australian Dr. Felix Behan (ANZ J Surg. 2003;73:112–20) is essentially two conjoined V-Y flaps end to side that are advanced to fill the defect.

Surgeons at the Sydney Melanoma Unit modified the flap by dividing the lateral deep fascia margin to allow for adequate advancement of the flap and to improve vascularity. For larger defects, two opposing Keystone flaps can be used to fill the defect. In all three types, once the skin is incised, the subcutaneous tissue is divided by blunt dissection to preserve the integrity of the vascular network, including the fascial and muscular perforators.

Because the skin is taken from the surrounding tissue, the color match is superior to that of split-thickness skin grafts, which are typically taken from the abdomen, and can result in a crocodile-like appearance of the skin and lengthy rehabilitation, Dr. Moncrieff said.

Dr. Michael Sabel, session moderator, acknowledged that the Keystone flap is "a great improvement" over the split-thickness skin graft, but that the full-thickness skin graft is a simple and widely used technique that provides well-matched tissue from the sentinel lymph node biopsy site or abdomen, with its main disadvantage being that patients are typically immobilized for 5 days.

Dr. Moncrieff responded that the Keystone flap can be performed in the same amount of time as a full-thickness graft and that most patients elevate their limb overnight and return home and walk the next day. Of the 176 patients, 39 (22%) had the procedure performed in a day-case setting.

An audience member questioned whether the technique can be used to fill larger defects or upper limb defects. The modified Keystone flap has been used to reconstruct distal upper limb defects, and requires no special allowances when closing larger defects, said Dr. Moncrieff, who reported no conflicts of interest.

The Women's Dermatologic Society has launched a campaign in conjunction with the Ladies' Professional Golf Association to promote proper skin protection during outdoor activities. The campaign, "Play Safe in the Sun," is part of a 3-year outreach program sponsored by L'Oreal USA and involves outreach at a series of LPGA events. The activities include free skin cancer screenings, sun damage assessment, free sunscreen, and sun safety education information for all tournament attendees. In addition, local volunteer dermatologists will provide free, private skin cancer screenings for LPGA players, caddies, and media personnel. For more information, contact the Women's Dermatologic Society by visiting www.womensderm.orgwww.playsafeinthesun.org

The Women's Dermatologic Society has launched a campaign in conjunction with the Ladies' Professional Golf Association to promote proper skin protection during outdoor activities. The campaign, "Play Safe in the Sun," is part of a 3-year outreach program sponsored by L'Oreal USA and involves outreach at a series of LPGA events. The activities include free skin cancer screenings, sun damage assessment, free sunscreen, and sun safety education information for all tournament attendees. In addition, local volunteer dermatologists will provide free, private skin cancer screenings for LPGA players, caddies, and media personnel. For more information, contact the Women's Dermatologic Society by visiting www.womensderm.orgwww.playsafeinthesun.org

The Women's Dermatologic Society has launched a campaign in conjunction with the Ladies' Professional Golf Association to promote proper skin protection during outdoor activities. The campaign, "Play Safe in the Sun," is part of a 3-year outreach program sponsored by L'Oreal USA and involves outreach at a series of LPGA events. The activities include free skin cancer screenings, sun damage assessment, free sunscreen, and sun safety education information for all tournament attendees. In addition, local volunteer dermatologists will provide free, private skin cancer screenings for LPGA players, caddies, and media personnel. For more information, contact the Women's Dermatologic Society by visiting www.womensderm.orgwww.playsafeinthesun.org

WAIKOLOA, HAWAII — The incidence of cutaneous T-cell lymphoma has risen dramatically since the early 1970s for reasons that are not known, Dr. Joan Guitart said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

Moreover, the best available numbers probably underestimate the true incidence because of reporting delay. Diagnosis of early mycosis fungoides, which is the most common type of cutaneous T-cell lymphoma (CTCL), can be quite difficult as the disease often mimics psoriasis, eczema, and other benign dermatoses, he said.

"Clearly, in the future we will be seeing a lot more CTCL," predicted Dr. Guitart, professor of dermatology at Northwestern University, Chicago.

He cited a population-based study that was conducted by dermatoepidemiologists at Brown University, Providence, R.I. Utilizing registry data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program, the investigators showed that the annual incidence of CTCL in the United States increased more than threefold from 1973 to 2002.

The researchers found marked racial differences in CTCL.

The annual incidence in blacks was 9.0 cases per 1 million, compared with 6.1 per million in whites. The disease was also substantially more common in men, with an annual incidence of 8.7 per million, compared with 4.6 per million in women.

The racial disparity diminished with age. In contrast, the difference between genders became more pronounced with advancing age but decreased over the course of the study period (Arch. Dermatol. 2007;143:854–9).

The investigators identified substantial geographic differences in CTCL incidence that were consistent with theories holding that environmental or viral exposures may play an etiologic role in the disease.

They also found that higher CTCL rates were associated with indicators of greater socioeconomic status, including median family income, median home value, and percentage of the population with a bachelor's degree or higher, Dr. Guitart noted.

There was no association between the incidence of CTCL and population density, but rates were strongly correlated with physician density, said Dr. Guitart.

The researchers concluded that improved diagnostic tools for CTCL and changes in International Classification of Diseases for Oncology schemes over the years may have contributed to the rising patient numbers but are not sufficient to account for the bulk of the marked increase.

Skin Disease Education Foundation and SKIN &ALLERGY NEWS are wholly owned subsidiaries of Elsevier.

The annual incidence of CTCLin the U.S. increased more than threefold from 1973 to 2002. DR. GUITART

WAIKOLOA, HAWAII — The incidence of cutaneous T-cell lymphoma has risen dramatically since the early 1970s for reasons that are not known, Dr. Joan Guitart said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

Moreover, the best available numbers probably underestimate the true incidence because of reporting delay. Diagnosis of early mycosis fungoides, which is the most common type of cutaneous T-cell lymphoma (CTCL), can be quite difficult as the disease often mimics psoriasis, eczema, and other benign dermatoses, he said.

"Clearly, in the future we will be seeing a lot more CTCL," predicted Dr. Guitart, professor of dermatology at Northwestern University, Chicago.

He cited a population-based study that was conducted by dermatoepidemiologists at Brown University, Providence, R.I. Utilizing registry data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program, the investigators showed that the annual incidence of CTCL in the United States increased more than threefold from 1973 to 2002.

The researchers found marked racial differences in CTCL.

The annual incidence in blacks was 9.0 cases per 1 million, compared with 6.1 per million in whites. The disease was also substantially more common in men, with an annual incidence of 8.7 per million, compared with 4.6 per million in women.

The racial disparity diminished with age. In contrast, the difference between genders became more pronounced with advancing age but decreased over the course of the study period (Arch. Dermatol. 2007;143:854–9).

The investigators identified substantial geographic differences in CTCL incidence that were consistent with theories holding that environmental or viral exposures may play an etiologic role in the disease.

They also found that higher CTCL rates were associated with indicators of greater socioeconomic status, including median family income, median home value, and percentage of the population with a bachelor's degree or higher, Dr. Guitart noted.

There was no association between the incidence of CTCL and population density, but rates were strongly correlated with physician density, said Dr. Guitart.

The researchers concluded that improved diagnostic tools for CTCL and changes in International Classification of Diseases for Oncology schemes over the years may have contributed to the rising patient numbers but are not sufficient to account for the bulk of the marked increase.

Skin Disease Education Foundation and SKIN &ALLERGY NEWS are wholly owned subsidiaries of Elsevier.

The annual incidence of CTCLin the U.S. increased more than threefold from 1973 to 2002. DR. GUITART

WAIKOLOA, HAWAII — The incidence of cutaneous T-cell lymphoma has risen dramatically since the early 1970s for reasons that are not known, Dr. Joan Guitart said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

Moreover, the best available numbers probably underestimate the true incidence because of reporting delay. Diagnosis of early mycosis fungoides, which is the most common type of cutaneous T-cell lymphoma (CTCL), can be quite difficult as the disease often mimics psoriasis, eczema, and other benign dermatoses, he said.

"Clearly, in the future we will be seeing a lot more CTCL," predicted Dr. Guitart, professor of dermatology at Northwestern University, Chicago.

He cited a population-based study that was conducted by dermatoepidemiologists at Brown University, Providence, R.I. Utilizing registry data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program, the investigators showed that the annual incidence of CTCL in the United States increased more than threefold from 1973 to 2002.

The researchers found marked racial differences in CTCL.

The annual incidence in blacks was 9.0 cases per 1 million, compared with 6.1 per million in whites. The disease was also substantially more common in men, with an annual incidence of 8.7 per million, compared with 4.6 per million in women.

The racial disparity diminished with age. In contrast, the difference between genders became more pronounced with advancing age but decreased over the course of the study period (Arch. Dermatol. 2007;143:854–9).

The investigators identified substantial geographic differences in CTCL incidence that were consistent with theories holding that environmental or viral exposures may play an etiologic role in the disease.

They also found that higher CTCL rates were associated with indicators of greater socioeconomic status, including median family income, median home value, and percentage of the population with a bachelor's degree or higher, Dr. Guitart noted.

There was no association between the incidence of CTCL and population density, but rates were strongly correlated with physician density, said Dr. Guitart.

The researchers concluded that improved diagnostic tools for CTCL and changes in International Classification of Diseases for Oncology schemes over the years may have contributed to the rising patient numbers but are not sufficient to account for the bulk of the marked increase.

Skin Disease Education Foundation and SKIN &ALLERGY NEWS are wholly owned subsidiaries of Elsevier.

The annual incidence of CTCLin the U.S. increased more than threefold from 1973 to 2002. DR. GUITART

WAIKOLOA, HAWAII — The phrase "cutaneous T-cell lymphoid dyscrasia" could serve as a novel unifying term for a variety of chronic skin conditions characterized by persistent T-cell clonality without meeting the histologic or clinical criteria for mycosis fungoides, Dr. Joan Guitart proposed at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

Cutaneous T-cell lymphoid dyscrasias encompass eight distinct clinicopathologic precancerous entities, and is a better term than "precutaneous T-cell lymphoma" or "premycotic" because most affected patients will in fact have an innocuous, indolent clinical course without ever progressing to overt cutaneous T-cell lymphoma (Arch. Dermatol. 2007;143:921–32).

For example, long-term studies demonstrate that only 10%–15% of patients with parapsoriasis—one form of cutaneous T-cell lymphoid dyscrasia—evolve into mycosis fungoides, explained Dr. Guitart, professor of dermatology at Northwestern University, Chicago. He proposed the following criteria as requisite for cutaneous T-cell lymphoid dyscrasia:

▸ The condition is chronic with a tendency to relapse following topical therapy.

▸ There is no known triggering event, such as the occurrence of T-cell clones in conjunction with rheumatoid arthritis, lupus erythematosus, organ transplants, or other states of long-term immunostimulation. There also is no evidence of allergic reaction, hypersensitivity, or connective-tissue disorder.

▸ There is the presence of one or a few T-cell clones defined by reduced CD7 and CD62L expression in skin specimens.

▸ There is a lack of morphologic evidence for T-cell lymphoma. The dominant lymphocyte is small or intermediate in size.

Other skin disorders fitting the definition include pityriasis lichenoides chronica, idiopathic follicular mucinosis, atypical lymphocytic lobular panniculitis, clonal erythroderma, pigmented purpuric variant, syringolymphoid hyperplasia with alopecia, and hypopigmented interface variant.

SDEF and SKIN & ALLERGY NEWS are wholly owned subsidiaries of Elsevier.

WAIKOLOA, HAWAII — The phrase "cutaneous T-cell lymphoid dyscrasia" could serve as a novel unifying term for a variety of chronic skin conditions characterized by persistent T-cell clonality without meeting the histologic or clinical criteria for mycosis fungoides, Dr. Joan Guitart proposed at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

Cutaneous T-cell lymphoid dyscrasias encompass eight distinct clinicopathologic precancerous entities, and is a better term than "precutaneous T-cell lymphoma" or "premycotic" because most affected patients will in fact have an innocuous, indolent clinical course without ever progressing to overt cutaneous T-cell lymphoma (Arch. Dermatol. 2007;143:921–32).

For example, long-term studies demonstrate that only 10%–15% of patients with parapsoriasis—one form of cutaneous T-cell lymphoid dyscrasia—evolve into mycosis fungoides, explained Dr. Guitart, professor of dermatology at Northwestern University, Chicago. He proposed the following criteria as requisite for cutaneous T-cell lymphoid dyscrasia:

▸ The condition is chronic with a tendency to relapse following topical therapy.

▸ There is no known triggering event, such as the occurrence of T-cell clones in conjunction with rheumatoid arthritis, lupus erythematosus, organ transplants, or other states of long-term immunostimulation. There also is no evidence of allergic reaction, hypersensitivity, or connective-tissue disorder.

▸ There is the presence of one or a few T-cell clones defined by reduced CD7 and CD62L expression in skin specimens.

▸ There is a lack of morphologic evidence for T-cell lymphoma. The dominant lymphocyte is small or intermediate in size.

Other skin disorders fitting the definition include pityriasis lichenoides chronica, idiopathic follicular mucinosis, atypical lymphocytic lobular panniculitis, clonal erythroderma, pigmented purpuric variant, syringolymphoid hyperplasia with alopecia, and hypopigmented interface variant.

SDEF and SKIN & ALLERGY NEWS are wholly owned subsidiaries of Elsevier.

WAIKOLOA, HAWAII — The phrase "cutaneous T-cell lymphoid dyscrasia" could serve as a novel unifying term for a variety of chronic skin conditions characterized by persistent T-cell clonality without meeting the histologic or clinical criteria for mycosis fungoides, Dr. Joan Guitart proposed at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

Cutaneous T-cell lymphoid dyscrasias encompass eight distinct clinicopathologic precancerous entities, and is a better term than "precutaneous T-cell lymphoma" or "premycotic" because most affected patients will in fact have an innocuous, indolent clinical course without ever progressing to overt cutaneous T-cell lymphoma (Arch. Dermatol. 2007;143:921–32).

For example, long-term studies demonstrate that only 10%–15% of patients with parapsoriasis—one form of cutaneous T-cell lymphoid dyscrasia—evolve into mycosis fungoides, explained Dr. Guitart, professor of dermatology at Northwestern University, Chicago. He proposed the following criteria as requisite for cutaneous T-cell lymphoid dyscrasia:

▸ The condition is chronic with a tendency to relapse following topical therapy.

▸ There is no known triggering event, such as the occurrence of T-cell clones in conjunction with rheumatoid arthritis, lupus erythematosus, organ transplants, or other states of long-term immunostimulation. There also is no evidence of allergic reaction, hypersensitivity, or connective-tissue disorder.

▸ There is the presence of one or a few T-cell clones defined by reduced CD7 and CD62L expression in skin specimens.

▸ There is a lack of morphologic evidence for T-cell lymphoma. The dominant lymphocyte is small or intermediate in size.

Other skin disorders fitting the definition include pityriasis lichenoides chronica, idiopathic follicular mucinosis, atypical lymphocytic lobular panniculitis, clonal erythroderma, pigmented purpuric variant, syringolymphoid hyperplasia with alopecia, and hypopigmented interface variant.

SDEF and SKIN & ALLERGY NEWS are wholly owned subsidiaries of Elsevier.

WAIKOLOA, HAWAII — The standardized, points-based diagnostic algorithm for early mycosis fungoides developed by the International Society for Cutaneous Lymphoma can be helpful in approaching the ambiguous patient with a patchy, thin-plaque rash and some atypia in the biopsy, Dr. Kimberly Bohjanen said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

In the past, such a patient might visit four different physicians and variously receive a diagnosis of parapsoriasis, atopic dermatitis, contact dermatitis, or early classic cutaneous T-cell lymphoma (CTCL), noted Dr. Bohjanen of the University of Minnesota, Minneapolis.

Although the algorithm—codeveloped by the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer—might seem confusing at first, it really is not. In fact, it's akin to the scoring system rheumatologists developed to define systemic lupus, she said.

Four points are required to diagnose early mycosis fungoides. Up to two can come from the clinical exam. The basic clinical criterion is the presence of persistent and/or progressive patches and thin plaques. The additional clinical criteria are a non-sun-exposed "bathing suit"-type lesion distribution, poikiloderma, and variation in lesion size and shape. A patient gets one point for presenting with the basic clinical criterion plus one of the additional criteria, or two points for presenting with the basic criterion plus any two additional clinical criteria.

Up to two points can be awarded based on the histopathologic findings on biopsy.

The basic histopathologic criterion is the presence of a superficial lymphoid infiltrate. If this, plus either of the two additional criteria—epidermotropism without spongiosis, and lymphoid atypia as defined by enlarged, irregular, hyperchromatic nuclei—are met, that's worth one point. If the basic and both additional criteria are present, that's worth two points.

"So basically if you have someone with a classic presentation of CTCL that meets the criteria on clinical exam and then you have a biopsy with all of these features, you've made the diagnosis of CTCL without even going on to immunotyping or T-cell gene rearrangement," she said.

All of this presupposes that the possibility of drug eruption has been ruled out from the outset.

A subsequent biopsy is used to gather material for T-cell gene rearrangement and immunopathologic studies. These studies need to be done routinely because of their value in staging, even in patients who already have four points.

One additional point is awarded for evidence of clonality on T-cell gene rearrangement. The algorithm gives another point if at least one of the following three immunopathologic markers of CTCL is present on the cell surface: less than 50% CD2-positive, CD3-positive, or CD5-positive T cells; less than 10% CD7-positive T cells; and discordance between the epidermal and dermal population of CD2, CD3, CD5, or CD7 T cells, with the antigen deficiency being confined to the epidermis (J. Am. Acad. Dermatol. 2005;53:1053–63).

The new system follows the T (tumor), N (lymph nodes), M (visceral metastases), and B (blood—with or without circulating Sézary cells) format (Blood 2007;110:1713–22). The biggest change was in lymph node staging, which now incorporates clonality, she said.

Dr. Bohjanen disclosed being on the speakers bureau for Abbott Laboratories.

SDEF and SKIN & ALLERGY NEWS are wholly owned subsidiaries of Elsevier.

WAIKOLOA, HAWAII — The standardized, points-based diagnostic algorithm for early mycosis fungoides developed by the International Society for Cutaneous Lymphoma can be helpful in approaching the ambiguous patient with a patchy, thin-plaque rash and some atypia in the biopsy, Dr. Kimberly Bohjanen said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

In the past, such a patient might visit four different physicians and variously receive a diagnosis of parapsoriasis, atopic dermatitis, contact dermatitis, or early classic cutaneous T-cell lymphoma (CTCL), noted Dr. Bohjanen of the University of Minnesota, Minneapolis.

Although the algorithm—codeveloped by the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer—might seem confusing at first, it really is not. In fact, it's akin to the scoring system rheumatologists developed to define systemic lupus, she said.

Four points are required to diagnose early mycosis fungoides. Up to two can come from the clinical exam. The basic clinical criterion is the presence of persistent and/or progressive patches and thin plaques. The additional clinical criteria are a non-sun-exposed "bathing suit"-type lesion distribution, poikiloderma, and variation in lesion size and shape. A patient gets one point for presenting with the basic clinical criterion plus one of the additional criteria, or two points for presenting with the basic criterion plus any two additional clinical criteria.

Up to two points can be awarded based on the histopathologic findings on biopsy.

The basic histopathologic criterion is the presence of a superficial lymphoid infiltrate. If this, plus either of the two additional criteria—epidermotropism without spongiosis, and lymphoid atypia as defined by enlarged, irregular, hyperchromatic nuclei—are met, that's worth one point. If the basic and both additional criteria are present, that's worth two points.

"So basically if you have someone with a classic presentation of CTCL that meets the criteria on clinical exam and then you have a biopsy with all of these features, you've made the diagnosis of CTCL without even going on to immunotyping or T-cell gene rearrangement," she said.

All of this presupposes that the possibility of drug eruption has been ruled out from the outset.

A subsequent biopsy is used to gather material for T-cell gene rearrangement and immunopathologic studies. These studies need to be done routinely because of their value in staging, even in patients who already have four points.

One additional point is awarded for evidence of clonality on T-cell gene rearrangement. The algorithm gives another point if at least one of the following three immunopathologic markers of CTCL is present on the cell surface: less than 50% CD2-positive, CD3-positive, or CD5-positive T cells; less than 10% CD7-positive T cells; and discordance between the epidermal and dermal population of CD2, CD3, CD5, or CD7 T cells, with the antigen deficiency being confined to the epidermis (J. Am. Acad. Dermatol. 2005;53:1053–63).

The new system follows the T (tumor), N (lymph nodes), M (visceral metastases), and B (blood—with or without circulating Sézary cells) format (Blood 2007;110:1713–22). The biggest change was in lymph node staging, which now incorporates clonality, she said.

Dr. Bohjanen disclosed being on the speakers bureau for Abbott Laboratories.

SDEF and SKIN & ALLERGY NEWS are wholly owned subsidiaries of Elsevier.

WAIKOLOA, HAWAII — The standardized, points-based diagnostic algorithm for early mycosis fungoides developed by the International Society for Cutaneous Lymphoma can be helpful in approaching the ambiguous patient with a patchy, thin-plaque rash and some atypia in the biopsy, Dr. Kimberly Bohjanen said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

In the past, such a patient might visit four different physicians and variously receive a diagnosis of parapsoriasis, atopic dermatitis, contact dermatitis, or early classic cutaneous T-cell lymphoma (CTCL), noted Dr. Bohjanen of the University of Minnesota, Minneapolis.

Although the algorithm—codeveloped by the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer—might seem confusing at first, it really is not. In fact, it's akin to the scoring system rheumatologists developed to define systemic lupus, she said.

Four points are required to diagnose early mycosis fungoides. Up to two can come from the clinical exam. The basic clinical criterion is the presence of persistent and/or progressive patches and thin plaques. The additional clinical criteria are a non-sun-exposed "bathing suit"-type lesion distribution, poikiloderma, and variation in lesion size and shape. A patient gets one point for presenting with the basic clinical criterion plus one of the additional criteria, or two points for presenting with the basic criterion plus any two additional clinical criteria.

Up to two points can be awarded based on the histopathologic findings on biopsy.

The basic histopathologic criterion is the presence of a superficial lymphoid infiltrate. If this, plus either of the two additional criteria—epidermotropism without spongiosis, and lymphoid atypia as defined by enlarged, irregular, hyperchromatic nuclei—are met, that's worth one point. If the basic and both additional criteria are present, that's worth two points.

"So basically if you have someone with a classic presentation of CTCL that meets the criteria on clinical exam and then you have a biopsy with all of these features, you've made the diagnosis of CTCL without even going on to immunotyping or T-cell gene rearrangement," she said.

All of this presupposes that the possibility of drug eruption has been ruled out from the outset.

A subsequent biopsy is used to gather material for T-cell gene rearrangement and immunopathologic studies. These studies need to be done routinely because of their value in staging, even in patients who already have four points.

One additional point is awarded for evidence of clonality on T-cell gene rearrangement. The algorithm gives another point if at least one of the following three immunopathologic markers of CTCL is present on the cell surface: less than 50% CD2-positive, CD3-positive, or CD5-positive T cells; less than 10% CD7-positive T cells; and discordance between the epidermal and dermal population of CD2, CD3, CD5, or CD7 T cells, with the antigen deficiency being confined to the epidermis (J. Am. Acad. Dermatol. 2005;53:1053–63).

The new system follows the T (tumor), N (lymph nodes), M (visceral metastases), and B (blood—with or without circulating Sézary cells) format (Blood 2007;110:1713–22). The biggest change was in lymph node staging, which now incorporates clonality, she said.

Dr. Bohjanen disclosed being on the speakers bureau for Abbott Laboratories.

SDEF and SKIN & ALLERGY NEWS are wholly owned subsidiaries of Elsevier.

Early stages of mycosis fungoides should be managed by dermatologists, not ceded to oncologists, as often happens. I would hate to see our great specialty demoted to the treatment of acne warts and cosmetic conditions. Let's not give away this disease, too. It belongs to us.

Especially early on, there's a very important role for skin-directed therapy—and we dermatologists are the experts, not the oncologists.

Abundant evidence shows that pathogenetic events leading to tumor progression in myosis fungoides (MF) occur in the skin, and that skin-directed therapy can induce prolonged remissions.

That's a point particularly worth emphasizing in light of the European Organisation for Research and Treatment of Cancer's current recommendation that "expectant management" is a legitimate option in patients with stage IA disease because they have a normal life expectancy. This recommendation is based on a misinterpretation of the data. What the guideline writers failed to realize is that these stage IA MF patients in the major reported series who are doing so well are actually receiving skin-directed treatment. We really don't have good data on the natural history of mycosis fungoides without treatment, so their conclusions are based on faulty information.

Patients with cutaneous T-cell lymphoma (CTCL) face numerous problems in which dermatologists have special expertise: severe pruritus, xerosis, cosmetic issues, an increase in skin cancers, and numerous cutaneous infectious complications.

In one study of 356 patients with MF or Sézary syndrome, the incidence of cutaneous bacterial infection was 17% per year (JAMA 1992;267:1354–8). The combined annual rate of cutaneous herpes simplex and herpes zoster infections was 3.8%. Extracutaneous CTCL involvement independently predicted a 12-fold increased risk of recurrent bacterial skin infection, a 28-fold increase in disseminated herpesvirus infection, and a rather remarkable 15-fold increase in death from infection.

We, as dermatologists, are very well qualified to manage these infections.

A study recently completed at Northwestern University in Chicago showed roughly a 40% Staphylococcus aureus colonization rate in CTCL patients. Worsening of the skin lesions or a new flare of erythroderma in CTCL patients may be related to a cutaneous infection rather than tumor progression.

At Northwestern, we recommend culturing patients often and utilizing frequent dilute bleach baths to help control S. aureus colonization levels. That's important because S. aureus superantigen has been shown to stimulate tumor-infiltrating lymphocytes, thus encouraging growth of malignant T cells. Treating a concurrent S. aureus skin infection may be sufficient to curtain a Sézary syndrome crisis, for example.

The quality of life issues raised by CTCL are often striking and here again dermatologists can be uniquely helpful. A survey of the Mycosis Fungoides Foundation membership found that 62% of respondents indicated their disease made them feel unattractive. A profound distress over health concerns was nearly universal (Cancer 2006;107:2504–11).

With skin-directed therapies, it is important to apply agents such as topical steroids, nitrogen mustard, and retinoids not only to the actual lesions but for a few centimeters beyond the actual clinical borders. Oncologists generally handle systemic therapies for CTCL, but there has been considerable interest among dermatologists in vorinostat (Zolinza), an oral inhibitor of histone deacetylase (HDAC) approved by the Food and Drug Administration in 2006 for the treatment of CTCL.

I have been less than favorably impressed by the low response rates—24% and 30% in two published trials—as well as the short duration of response and extensive side effects. In general, I think dermatologists feel comfortable prescribing oral treatment, but I would recommend caution on its use. The risk-benefit ratio is not that great, and in any case new HDACs with perhaps a better safety profile and efficacy are in the pipeline.

Dermatology has lost control of too many important diseases like sexually transmitted diseases, connective vascular conditions, and other allergy/immunology conditions. We should not lose track of mycosis fungoides, too.

Early stages of mycosis fungoides should be managed by dermatologists, not ceded to oncologists, as often happens. I would hate to see our great specialty demoted to the treatment of acne warts and cosmetic conditions. Let's not give away this disease, too. It belongs to us.

Especially early on, there's a very important role for skin-directed therapy—and we dermatologists are the experts, not the oncologists.

Abundant evidence shows that pathogenetic events leading to tumor progression in myosis fungoides (MF) occur in the skin, and that skin-directed therapy can induce prolonged remissions.

That's a point particularly worth emphasizing in light of the European Organisation for Research and Treatment of Cancer's current recommendation that "expectant management" is a legitimate option in patients with stage IA disease because they have a normal life expectancy. This recommendation is based on a misinterpretation of the data. What the guideline writers failed to realize is that these stage IA MF patients in the major reported series who are doing so well are actually receiving skin-directed treatment. We really don't have good data on the natural history of mycosis fungoides without treatment, so their conclusions are based on faulty information.

Patients with cutaneous T-cell lymphoma (CTCL) face numerous problems in which dermatologists have special expertise: severe pruritus, xerosis, cosmetic issues, an increase in skin cancers, and numerous cutaneous infectious complications.

In one study of 356 patients with MF or Sézary syndrome, the incidence of cutaneous bacterial infection was 17% per year (JAMA 1992;267:1354–8). The combined annual rate of cutaneous herpes simplex and herpes zoster infections was 3.8%. Extracutaneous CTCL involvement independently predicted a 12-fold increased risk of recurrent bacterial skin infection, a 28-fold increase in disseminated herpesvirus infection, and a rather remarkable 15-fold increase in death from infection.

We, as dermatologists, are very well qualified to manage these infections.

A study recently completed at Northwestern University in Chicago showed roughly a 40% Staphylococcus aureus colonization rate in CTCL patients. Worsening of the skin lesions or a new flare of erythroderma in CTCL patients may be related to a cutaneous infection rather than tumor progression.

At Northwestern, we recommend culturing patients often and utilizing frequent dilute bleach baths to help control S. aureus colonization levels. That's important because S. aureus superantigen has been shown to stimulate tumor-infiltrating lymphocytes, thus encouraging growth of malignant T cells. Treating a concurrent S. aureus skin infection may be sufficient to curtain a Sézary syndrome crisis, for example.

The quality of life issues raised by CTCL are often striking and here again dermatologists can be uniquely helpful. A survey of the Mycosis Fungoides Foundation membership found that 62% of respondents indicated their disease made them feel unattractive. A profound distress over health concerns was nearly universal (Cancer 2006;107:2504–11).

With skin-directed therapies, it is important to apply agents such as topical steroids, nitrogen mustard, and retinoids not only to the actual lesions but for a few centimeters beyond the actual clinical borders. Oncologists generally handle systemic therapies for CTCL, but there has been considerable interest among dermatologists in vorinostat (Zolinza), an oral inhibitor of histone deacetylase (HDAC) approved by the Food and Drug Administration in 2006 for the treatment of CTCL.

I have been less than favorably impressed by the low response rates—24% and 30% in two published trials—as well as the short duration of response and extensive side effects. In general, I think dermatologists feel comfortable prescribing oral treatment, but I would recommend caution on its use. The risk-benefit ratio is not that great, and in any case new HDACs with perhaps a better safety profile and efficacy are in the pipeline.

Dermatology has lost control of too many important diseases like sexually transmitted diseases, connective vascular conditions, and other allergy/immunology conditions. We should not lose track of mycosis fungoides, too.

Early stages of mycosis fungoides should be managed by dermatologists, not ceded to oncologists, as often happens. I would hate to see our great specialty demoted to the treatment of acne warts and cosmetic conditions. Let's not give away this disease, too. It belongs to us.

Especially early on, there's a very important role for skin-directed therapy—and we dermatologists are the experts, not the oncologists.

Abundant evidence shows that pathogenetic events leading to tumor progression in myosis fungoides (MF) occur in the skin, and that skin-directed therapy can induce prolonged remissions.

That's a point particularly worth emphasizing in light of the European Organisation for Research and Treatment of Cancer's current recommendation that "expectant management" is a legitimate option in patients with stage IA disease because they have a normal life expectancy. This recommendation is based on a misinterpretation of the data. What the guideline writers failed to realize is that these stage IA MF patients in the major reported series who are doing so well are actually receiving skin-directed treatment. We really don't have good data on the natural history of mycosis fungoides without treatment, so their conclusions are based on faulty information.

Patients with cutaneous T-cell lymphoma (CTCL) face numerous problems in which dermatologists have special expertise: severe pruritus, xerosis, cosmetic issues, an increase in skin cancers, and numerous cutaneous infectious complications.

In one study of 356 patients with MF or Sézary syndrome, the incidence of cutaneous bacterial infection was 17% per year (JAMA 1992;267:1354–8). The combined annual rate of cutaneous herpes simplex and herpes zoster infections was 3.8%. Extracutaneous CTCL involvement independently predicted a 12-fold increased risk of recurrent bacterial skin infection, a 28-fold increase in disseminated herpesvirus infection, and a rather remarkable 15-fold increase in death from infection.

We, as dermatologists, are very well qualified to manage these infections.

A study recently completed at Northwestern University in Chicago showed roughly a 40% Staphylococcus aureus colonization rate in CTCL patients. Worsening of the skin lesions or a new flare of erythroderma in CTCL patients may be related to a cutaneous infection rather than tumor progression.

At Northwestern, we recommend culturing patients often and utilizing frequent dilute bleach baths to help control S. aureus colonization levels. That's important because S. aureus superantigen has been shown to stimulate tumor-infiltrating lymphocytes, thus encouraging growth of malignant T cells. Treating a concurrent S. aureus skin infection may be sufficient to curtain a Sézary syndrome crisis, for example.

The quality of life issues raised by CTCL are often striking and here again dermatologists can be uniquely helpful. A survey of the Mycosis Fungoides Foundation membership found that 62% of respondents indicated their disease made them feel unattractive. A profound distress over health concerns was nearly universal (Cancer 2006;107:2504–11).

With skin-directed therapies, it is important to apply agents such as topical steroids, nitrogen mustard, and retinoids not only to the actual lesions but for a few centimeters beyond the actual clinical borders. Oncologists generally handle systemic therapies for CTCL, but there has been considerable interest among dermatologists in vorinostat (Zolinza), an oral inhibitor of histone deacetylase (HDAC) approved by the Food and Drug Administration in 2006 for the treatment of CTCL.

I have been less than favorably impressed by the low response rates—24% and 30% in two published trials—as well as the short duration of response and extensive side effects. In general, I think dermatologists feel comfortable prescribing oral treatment, but I would recommend caution on its use. The risk-benefit ratio is not that great, and in any case new HDACs with perhaps a better safety profile and efficacy are in the pipeline.

Dermatology has lost control of too many important diseases like sexually transmitted diseases, connective vascular conditions, and other allergy/immunology conditions. We should not lose track of mycosis fungoides, too.

CHICAGO — Adherence to national cancer treatment guidelines was associated with decreased local and regional recurrence, improved disease-free and overall survival, and decreased treatment-associated morbidity in a study of 327 consecutive clinically node-negative melanoma patients.

A review of cancer registry data at Rush North Shore Medical Center in Skokie, Ill., revealed that 72% of patients were treated in compliance with National Comprehensive Cancer Network (NCCN) recommendations for margins of excision, Dr. Jennifer Erickson Foster and colleagues reported at a symposium sponsored by the Society of Surgical Oncology.

Appropriate lymph node staging and treatment was received by 271 patients or 83%. Interestingly, when treatment was performed by a surgical oncologist, margin compliance was 95% and lymph node compliance 92%, said Dr. Foster, the lead investigator. A recommended completion lymph node dissection was performed for a positive sentinel lymph node in 78% of patients.

Patients treated in a noncompliant fashion with regard to margins had a threefold increase in postoperative complications in comparison with those treated in a compliant fashion. Similarly, patients treated in a lymph node-noncompliant fashion were 2.4 times more likely to have a postoperative complication. Both findings were statistically significant, said Dr. Erickson Foster, who reported no conflicts of interest for the investigators.

Noncompliance with NCCN guidelines for margins of excision was associated with increased locoregional (26% vs. 6%) and distant recurrence (8% vs. 6%), as compared with compliant cases. Locoregional disease alone as the first site of relapse was seen in 33% of lymph node-noncompliant cases vs. 6% of lymph node-compliant cases.

Five-year disease-free survival was higher among margin-compliant cases, compared with margin-noncompliant cases (86% vs. 68%), as was 5-year overall survival (93% vs. 83%). Similar increases in disease-free (85% vs. 54%) and overall (95% vs. 66%) survival were observed with compliance to lymph node staging and treatment recommendations.

The mean follow-up was 51 months (minimum 18 months) and mean age 66 years; 53% of the patients were women, and 32% of melanomas were located on the trunk, a finding consistent with cutaneous melanoma. Postoperative complications were reported in 55 patients (17%), with major complications in 4%, including one myocardial infarction, one pneumothorax, two cases of lymphedema, and two cases of facial nerve injury.

"These findings are provocative and suggest that compliance with NCCN guidelines improves outcomes in clinically node-negative melanoma patients," senior author Dr. Tina J. Hieken, of Rush Medical College, in Chicago, said in an interview. "We recommend that clinicians treating melanoma patients become familiar with these guidelines and utilize them to assist clinical decision making."

During the question-and-answer session, Dr. Foster noted that 20 different physicians representing nine specialties performed melanoma treatment in the study. Compliance did improve among specialties as time went on, but only surgical oncologists had greater than 90% compliance for margins of excision and lymph node staging and treatment.

Audience member Dr. Daniel G. Coit, who cochaired the NCCN guideline committee for melanoma, stressed that noncompliance with recommendations should not be equated with poor medical care. "Guidelines don't define best medical care; the doctors and patients define best medical care," he said.

Both Dr. Foster and Dr. Hieken agreed that physicians regularly depart from guidelines for a variety of reasons, such as aesthetic considerations, patient preferences, patient comorbidities, and tumor features.

"Guidelines are a point of departure," said Dr. Coit of Memorial Sloan-Kettering Cancer Center in New York. "They are not how we must do it, and we need to be very careful about how we define that, because there are other people who don't know that and will be looking at these kinds of presentations very carefully, and they're going to come to the wrong conclusion."

CHICAGO — Adherence to national cancer treatment guidelines was associated with decreased local and regional recurrence, improved disease-free and overall survival, and decreased treatment-associated morbidity in a study of 327 consecutive clinically node-negative melanoma patients.

A review of cancer registry data at Rush North Shore Medical Center in Skokie, Ill., revealed that 72% of patients were treated in compliance with National Comprehensive Cancer Network (NCCN) recommendations for margins of excision, Dr. Jennifer Erickson Foster and colleagues reported at a symposium sponsored by the Society of Surgical Oncology.

Appropriate lymph node staging and treatment was received by 271 patients or 83%. Interestingly, when treatment was performed by a surgical oncologist, margin compliance was 95% and lymph node compliance 92%, said Dr. Foster, the lead investigator. A recommended completion lymph node dissection was performed for a positive sentinel lymph node in 78% of patients.

Patients treated in a noncompliant fashion with regard to margins had a threefold increase in postoperative complications in comparison with those treated in a compliant fashion. Similarly, patients treated in a lymph node-noncompliant fashion were 2.4 times more likely to have a postoperative complication. Both findings were statistically significant, said Dr. Erickson Foster, who reported no conflicts of interest for the investigators.

Noncompliance with NCCN guidelines for margins of excision was associated with increased locoregional (26% vs. 6%) and distant recurrence (8% vs. 6%), as compared with compliant cases. Locoregional disease alone as the first site of relapse was seen in 33% of lymph node-noncompliant cases vs. 6% of lymph node-compliant cases.

Five-year disease-free survival was higher among margin-compliant cases, compared with margin-noncompliant cases (86% vs. 68%), as was 5-year overall survival (93% vs. 83%). Similar increases in disease-free (85% vs. 54%) and overall (95% vs. 66%) survival were observed with compliance to lymph node staging and treatment recommendations.

The mean follow-up was 51 months (minimum 18 months) and mean age 66 years; 53% of the patients were women, and 32% of melanomas were located on the trunk, a finding consistent with cutaneous melanoma. Postoperative complications were reported in 55 patients (17%), with major complications in 4%, including one myocardial infarction, one pneumothorax, two cases of lymphedema, and two cases of facial nerve injury.

"These findings are provocative and suggest that compliance with NCCN guidelines improves outcomes in clinically node-negative melanoma patients," senior author Dr. Tina J. Hieken, of Rush Medical College, in Chicago, said in an interview. "We recommend that clinicians treating melanoma patients become familiar with these guidelines and utilize them to assist clinical decision making."

During the question-and-answer session, Dr. Foster noted that 20 different physicians representing nine specialties performed melanoma treatment in the study. Compliance did improve among specialties as time went on, but only surgical oncologists had greater than 90% compliance for margins of excision and lymph node staging and treatment.

Audience member Dr. Daniel G. Coit, who cochaired the NCCN guideline committee for melanoma, stressed that noncompliance with recommendations should not be equated with poor medical care. "Guidelines don't define best medical care; the doctors and patients define best medical care," he said.

Both Dr. Foster and Dr. Hieken agreed that physicians regularly depart from guidelines for a variety of reasons, such as aesthetic considerations, patient preferences, patient comorbidities, and tumor features.

"Guidelines are a point of departure," said Dr. Coit of Memorial Sloan-Kettering Cancer Center in New York. "They are not how we must do it, and we need to be very careful about how we define that, because there are other people who don't know that and will be looking at these kinds of presentations very carefully, and they're going to come to the wrong conclusion."

CHICAGO — Adherence to national cancer treatment guidelines was associated with decreased local and regional recurrence, improved disease-free and overall survival, and decreased treatment-associated morbidity in a study of 327 consecutive clinically node-negative melanoma patients.

A review of cancer registry data at Rush North Shore Medical Center in Skokie, Ill., revealed that 72% of patients were treated in compliance with National Comprehensive Cancer Network (NCCN) recommendations for margins of excision, Dr. Jennifer Erickson Foster and colleagues reported at a symposium sponsored by the Society of Surgical Oncology.

Appropriate lymph node staging and treatment was received by 271 patients or 83%. Interestingly, when treatment was performed by a surgical oncologist, margin compliance was 95% and lymph node compliance 92%, said Dr. Foster, the lead investigator. A recommended completion lymph node dissection was performed for a positive sentinel lymph node in 78% of patients.

Patients treated in a noncompliant fashion with regard to margins had a threefold increase in postoperative complications in comparison with those treated in a compliant fashion. Similarly, patients treated in a lymph node-noncompliant fashion were 2.4 times more likely to have a postoperative complication. Both findings were statistically significant, said Dr. Erickson Foster, who reported no conflicts of interest for the investigators.

Noncompliance with NCCN guidelines for margins of excision was associated with increased locoregional (26% vs. 6%) and distant recurrence (8% vs. 6%), as compared with compliant cases. Locoregional disease alone as the first site of relapse was seen in 33% of lymph node-noncompliant cases vs. 6% of lymph node-compliant cases.

Five-year disease-free survival was higher among margin-compliant cases, compared with margin-noncompliant cases (86% vs. 68%), as was 5-year overall survival (93% vs. 83%). Similar increases in disease-free (85% vs. 54%) and overall (95% vs. 66%) survival were observed with compliance to lymph node staging and treatment recommendations.

The mean follow-up was 51 months (minimum 18 months) and mean age 66 years; 53% of the patients were women, and 32% of melanomas were located on the trunk, a finding consistent with cutaneous melanoma. Postoperative complications were reported in 55 patients (17%), with major complications in 4%, including one myocardial infarction, one pneumothorax, two cases of lymphedema, and two cases of facial nerve injury.

"These findings are provocative and suggest that compliance with NCCN guidelines improves outcomes in clinically node-negative melanoma patients," senior author Dr. Tina J. Hieken, of Rush Medical College, in Chicago, said in an interview. "We recommend that clinicians treating melanoma patients become familiar with these guidelines and utilize them to assist clinical decision making."

During the question-and-answer session, Dr. Foster noted that 20 different physicians representing nine specialties performed melanoma treatment in the study. Compliance did improve among specialties as time went on, but only surgical oncologists had greater than 90% compliance for margins of excision and lymph node staging and treatment.

Audience member Dr. Daniel G. Coit, who cochaired the NCCN guideline committee for melanoma, stressed that noncompliance with recommendations should not be equated with poor medical care. "Guidelines don't define best medical care; the doctors and patients define best medical care," he said.

Both Dr. Foster and Dr. Hieken agreed that physicians regularly depart from guidelines for a variety of reasons, such as aesthetic considerations, patient preferences, patient comorbidities, and tumor features.

"Guidelines are a point of departure," said Dr. Coit of Memorial Sloan-Kettering Cancer Center in New York. "They are not how we must do it, and we need to be very careful about how we define that, because there are other people who don't know that and will be looking at these kinds of presentations very carefully, and they're going to come to the wrong conclusion."

WAIKOLOA, HAWAII — The "ugly duckling" sign showed impressive sensitivity for melanoma when applied by physicians as well as nonmedically trained individuals for rating melanocytic lesions, according to Dr. Ashfaq A. Marghoob.

The results of this study suggest the ugly duckling sign may be a valuable melanoma screening tool readily teachable to primary care physicians, nurse practitioners, and patients performing periodic skin self-examination, Dr. Marghoob reported at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

"Could this be a new public health message?" he asked. "For the last 20 or 30 years we've been talking about the ABCD features, but maybe we could add something along the lines of, 'Look for the ABCD features, but if you see a lesion on your skin that looks different than the surrounding lesions on your skin—even if it doesn't have the ABCDs—see a dermatologist.'"

The ugly duckling sign was first described in 1998 by Dr. Jean-Jacques Grob of the University of Marseille in Provence, France. It holds that nevi on a given individual tend to resemble each other: "Moles breed true," said Dr. Marghoob, a dermatologist at Memorial Sloan-Kettering Cancer Center, New York.

The ugly duckling—the outlier, the exceptional nevus, the one that looks different from the others—is more likely to be a melanoma, even if it does not exhibit the classic features ascribed to melanoma in the ABCD rule.

The ABCD acronym "has served us well" in the early recognition of melanoma, said Dr. Marghoob, but it has shortcomings: There is morphologic overlap with dysplastic nevi, resulting in many unnecessary excisions. Also, the ABCD criterion does not fit for many thin melanomas.

To test the utility of the ugly duckling sign when applied by a diverse group of people, Dr. Marghoob and coinvestigators assembled a portfolio of digital photographs of the backs of 12 patients at high risk for melanoma. Each of the patients had at least eight dysplastic nevi on their back.

In five patients, one of the skin lesions was a melanoma which was removed and histologically confirmed after the pictures were taken. The photo spread included whole-back overview images as well as clinical closeups of a total of 145 lesions.

The lesion raters consisted of 13 general dermatologists, 8 dermatologists with special expertise in pigmented lesions, 5 nurses, and 8 secretaries and other nonclinical hospital staff. They were asked if any of the 145 nevi differed from the others on the patients' backs.

There was excellent agreement on the ugly duckling sign among observers. All five melanomas but only 3 of 140 benign nevi were identified as ugly duckling lesions by at least two-thirds of the raters. The sensitivity of the ugly duckling sign—that is, the percentage of melanomas identified as "different"—was 100% for the experts, 89% for the general dermatologists, 88% for the nurses, and 85% for the nonclinicians. For the overall group, the sensitivity of the ugly duckling sign was 90% (Arch. Dermatol. 2008;144:58–64).

That 85% sensitivity when the ugly duckling sign was applied by nonclinicians is much higher than the percentage seen in studies of the ABCD method, Dr. Marghoob observed.

He noted that the overall melanoma survival rate in the United States has soared from less than 60% in 1970 to greater than 90% in 2008. This extremely impressive gain is mainly a result of improved detection of early disease, since there are still no effective systemic therapies for advanced melanoma.

Widespread adoption of the ugly duckling sign could be a further step forward in early diagnosis of melanoma. Total body photography, dermoscopy, and confocal microscopy are additional tools likely to lead to further improvements, he said.

SDEF and SKIN & ALLERGY NEWS are wholly owned subsidiaries of Elsevier.

The ABCD acronym 'has served us well' in the early recognition of melanoma, but it has shortcomings. DR. MARGHOOB

WAIKOLOA, HAWAII — The "ugly duckling" sign showed impressive sensitivity for melanoma when applied by physicians as well as nonmedically trained individuals for rating melanocytic lesions, according to Dr. Ashfaq A. Marghoob.

The results of this study suggest the ugly duckling sign may be a valuable melanoma screening tool readily teachable to primary care physicians, nurse practitioners, and patients performing periodic skin self-examination, Dr. Marghoob reported at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

"Could this be a new public health message?" he asked. "For the last 20 or 30 years we've been talking about the ABCD features, but maybe we could add something along the lines of, 'Look for the ABCD features, but if you see a lesion on your skin that looks different than the surrounding lesions on your skin—even if it doesn't have the ABCDs—see a dermatologist.'"

The ugly duckling sign was first described in 1998 by Dr. Jean-Jacques Grob of the University of Marseille in Provence, France. It holds that nevi on a given individual tend to resemble each other: "Moles breed true," said Dr. Marghoob, a dermatologist at Memorial Sloan-Kettering Cancer Center, New York.

The ugly duckling—the outlier, the exceptional nevus, the one that looks different from the others—is more likely to be a melanoma, even if it does not exhibit the classic features ascribed to melanoma in the ABCD rule.

The ABCD acronym "has served us well" in the early recognition of melanoma, said Dr. Marghoob, but it has shortcomings: There is morphologic overlap with dysplastic nevi, resulting in many unnecessary excisions. Also, the ABCD criterion does not fit for many thin melanomas.

To test the utility of the ugly duckling sign when applied by a diverse group of people, Dr. Marghoob and coinvestigators assembled a portfolio of digital photographs of the backs of 12 patients at high risk for melanoma. Each of the patients had at least eight dysplastic nevi on their back.

In five patients, one of the skin lesions was a melanoma which was removed and histologically confirmed after the pictures were taken. The photo spread included whole-back overview images as well as clinical closeups of a total of 145 lesions.

The lesion raters consisted of 13 general dermatologists, 8 dermatologists with special expertise in pigmented lesions, 5 nurses, and 8 secretaries and other nonclinical hospital staff. They were asked if any of the 145 nevi differed from the others on the patients' backs.

There was excellent agreement on the ugly duckling sign among observers. All five melanomas but only 3 of 140 benign nevi were identified as ugly duckling lesions by at least two-thirds of the raters. The sensitivity of the ugly duckling sign—that is, the percentage of melanomas identified as "different"—was 100% for the experts, 89% for the general dermatologists, 88% for the nurses, and 85% for the nonclinicians. For the overall group, the sensitivity of the ugly duckling sign was 90% (Arch. Dermatol. 2008;144:58–64).

That 85% sensitivity when the ugly duckling sign was applied by nonclinicians is much higher than the percentage seen in studies of the ABCD method, Dr. Marghoob observed.

He noted that the overall melanoma survival rate in the United States has soared from less than 60% in 1970 to greater than 90% in 2008. This extremely impressive gain is mainly a result of improved detection of early disease, since there are still no effective systemic therapies for advanced melanoma.

Widespread adoption of the ugly duckling sign could be a further step forward in early diagnosis of melanoma. Total body photography, dermoscopy, and confocal microscopy are additional tools likely to lead to further improvements, he said.

SDEF and SKIN & ALLERGY NEWS are wholly owned subsidiaries of Elsevier.

The ABCD acronym 'has served us well' in the early recognition of melanoma, but it has shortcomings. DR. MARGHOOB

WAIKOLOA, HAWAII — The "ugly duckling" sign showed impressive sensitivity for melanoma when applied by physicians as well as nonmedically trained individuals for rating melanocytic lesions, according to Dr. Ashfaq A. Marghoob.

The results of this study suggest the ugly duckling sign may be a valuable melanoma screening tool readily teachable to primary care physicians, nurse practitioners, and patients performing periodic skin self-examination, Dr. Marghoob reported at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

"Could this be a new public health message?" he asked. "For the last 20 or 30 years we've been talking about the ABCD features, but maybe we could add something along the lines of, 'Look for the ABCD features, but if you see a lesion on your skin that looks different than the surrounding lesions on your skin—even if it doesn't have the ABCDs—see a dermatologist.'"

The ugly duckling sign was first described in 1998 by Dr. Jean-Jacques Grob of the University of Marseille in Provence, France. It holds that nevi on a given individual tend to resemble each other: "Moles breed true," said Dr. Marghoob, a dermatologist at Memorial Sloan-Kettering Cancer Center, New York.

The ugly duckling—the outlier, the exceptional nevus, the one that looks different from the others—is more likely to be a melanoma, even if it does not exhibit the classic features ascribed to melanoma in the ABCD rule.

The ABCD acronym "has served us well" in the early recognition of melanoma, said Dr. Marghoob, but it has shortcomings: There is morphologic overlap with dysplastic nevi, resulting in many unnecessary excisions. Also, the ABCD criterion does not fit for many thin melanomas.

To test the utility of the ugly duckling sign when applied by a diverse group of people, Dr. Marghoob and coinvestigators assembled a portfolio of digital photographs of the backs of 12 patients at high risk for melanoma. Each of the patients had at least eight dysplastic nevi on their back.

In five patients, one of the skin lesions was a melanoma which was removed and histologically confirmed after the pictures were taken. The photo spread included whole-back overview images as well as clinical closeups of a total of 145 lesions.

The lesion raters consisted of 13 general dermatologists, 8 dermatologists with special expertise in pigmented lesions, 5 nurses, and 8 secretaries and other nonclinical hospital staff. They were asked if any of the 145 nevi differed from the others on the patients' backs.

There was excellent agreement on the ugly duckling sign among observers. All five melanomas but only 3 of 140 benign nevi were identified as ugly duckling lesions by at least two-thirds of the raters. The sensitivity of the ugly duckling sign—that is, the percentage of melanomas identified as "different"—was 100% for the experts, 89% for the general dermatologists, 88% for the nurses, and 85% for the nonclinicians. For the overall group, the sensitivity of the ugly duckling sign was 90% (Arch. Dermatol. 2008;144:58–64).

That 85% sensitivity when the ugly duckling sign was applied by nonclinicians is much higher than the percentage seen in studies of the ABCD method, Dr. Marghoob observed.

He noted that the overall melanoma survival rate in the United States has soared from less than 60% in 1970 to greater than 90% in 2008. This extremely impressive gain is mainly a result of improved detection of early disease, since there are still no effective systemic therapies for advanced melanoma.

Widespread adoption of the ugly duckling sign could be a further step forward in early diagnosis of melanoma. Total body photography, dermoscopy, and confocal microscopy are additional tools likely to lead to further improvements, he said.

SDEF and SKIN & ALLERGY NEWS are wholly owned subsidiaries of Elsevier.

The ABCD acronym 'has served us well' in the early recognition of melanoma, but it has shortcomings. DR. MARGHOOB

SAN DIEGO — A custom-designed inhibitor of a mutation in the Hedgehog signaling pathway stimulated antitumor activity in eight of nine patients with locally advanced, multifocal, or metastatic basal cell carcinoma in phase I interim trial results presented at the annual meeting of the American Association for Cancer Research.

Patients in the small, ongoing trial experienced healing of their lesions, diminishment of pain and fatigue, and improvement in dyspnea while taking the study drug GDC-0449 for periods ranging from 120 to 438 days.

"These responses were pretty dramatic, [beginning] within 2–3 weeks of starting the drug," said Dr. Daniel D. Von Hoff, senior investigator and director of translational research for the Translational Genomics Research Institute in Scottsdale, Ariz.

Basal cell carcinoma is the most common malignancy in humans, diagnosed in approximately 1 million U.S. patients per year. While it typically grows slowly and can be managed by local excision or ionizing radiation, it may infiltrate surrounding tissue. In rare cases (less than 0.1%), it becomes metastatic, most commonly to the lung, liver, and/or bone.

The first three patients enrolled in the study received daily doses of 150 mg, 270 mg, and 540 mg, respectively, of GDC-0449, a synthetic, revved-up version of the naturally occurring Hedgehog pathway antagonist cyclopamine. When antitumor activity was confirmed, six more patients were enrolled, all receiving the 150-mg/day dose.

The average patient was aged 61 years (range 42–85 years). Eight were men.

All had undergone surgery (some as many as 20 operations) for their basal cell carcinoma. Four had received radiation, and three were given chemotherapy. Five patients had metastatic disease, two had locally advanced disease of the ear, and two had multifocal disease.

Among four of the patients with metastatic disease, two had a confirmed partial response, one had stable disease, and one progressed while on the study drug and died of his disease. It is too early to assess the response of one recently enrolled patient with metastatic disease, according to Dr. Von Hoff.

In four patients with clinically evaluable locally advanced or multifocal disease, two had a complete response and two had stable disease, meaning that their skin lesions were not advancing.

Metabolic responses to chemotherapy were demonstrated in all five patients who had undergone positron emission tomography evaluations at the time of the presentation, Dr. Van Hoff reported during a late-breaking session.

"Toxicities were relatively mild," he said; they included dysgeusia, an alteration in taste sensations; mild alopecia; mild weight loss; and hyponatremia.

The drug's development represented what Dr. Von Hoff called, "the essence of translational medicine." Molecular biologists first discovered that aberrance in the Hedgehog signaling pathway triggered when patched (PTCH) or smoothened (SMO) gene mutations caused an acceleration of cell growth that proved instrumental in the development of either sporadic or hereditary basal cell carcinoma.

Nature then played a role, he noted.

Serendipitously, it was discovered that cyclopamine, a naturally occurring inhibitor of the SMO mutation, could be found in pregnant ewes that ate corn lilies in the western United States and subsequently gave birth to cyclopslike lambs with oversize heads and a single, central eye.

Genentech Inc., in conjunction with the Curis Inc., developed a synthetic version of cyclopamine 100 times more potent than the version found in corn lilies, naming the agent GDC-0449.

Patients, including Subject #1 in the phase I study, "knew the drug was coming and hung on." Although metastatic basal cell carcinoma is very rare, its prognosis is poor, with a mean survival of approximately 5 months, said Dr. Von Hoff.

Formal discussant Dr. Ervin Epstein of the Children's Hospital Oakland (Calif.) Research Institute noted that many unanswered questions remain about GDC-0449, but he said that, as a "card-carrying dermatologist," he is "full of optimism … that help is on the way."

Dr. Von Hoff receives research grant support from Genentech, developer of GDC-0449. Dr. Epstein is a consultant for Genentech and owns stock in Curis.

SAN DIEGO — A custom-designed inhibitor of a mutation in the Hedgehog signaling pathway stimulated antitumor activity in eight of nine patients with locally advanced, multifocal, or metastatic basal cell carcinoma in phase I interim trial results presented at the annual meeting of the American Association for Cancer Research.

Patients in the small, ongoing trial experienced healing of their lesions, diminishment of pain and fatigue, and improvement in dyspnea while taking the study drug GDC-0449 for periods ranging from 120 to 438 days.

"These responses were pretty dramatic, [beginning] within 2–3 weeks of starting the drug," said Dr. Daniel D. Von Hoff, senior investigator and director of translational research for the Translational Genomics Research Institute in Scottsdale, Ariz.

Basal cell carcinoma is the most common malignancy in humans, diagnosed in approximately 1 million U.S. patients per year. While it typically grows slowly and can be managed by local excision or ionizing radiation, it may infiltrate surrounding tissue. In rare cases (less than 0.1%), it becomes metastatic, most commonly to the lung, liver, and/or bone.

The first three patients enrolled in the study received daily doses of 150 mg, 270 mg, and 540 mg, respectively, of GDC-0449, a synthetic, revved-up version of the naturally occurring Hedgehog pathway antagonist cyclopamine. When antitumor activity was confirmed, six more patients were enrolled, all receiving the 150-mg/day dose.

The average patient was aged 61 years (range 42–85 years). Eight were men.

All had undergone surgery (some as many as 20 operations) for their basal cell carcinoma. Four had received radiation, and three were given chemotherapy. Five patients had metastatic disease, two had locally advanced disease of the ear, and two had multifocal disease.

Among four of the patients with metastatic disease, two had a confirmed partial response, one had stable disease, and one progressed while on the study drug and died of his disease. It is too early to assess the response of one recently enrolled patient with metastatic disease, according to Dr. Von Hoff.

In four patients with clinically evaluable locally advanced or multifocal disease, two had a complete response and two had stable disease, meaning that their skin lesions were not advancing.

Metabolic responses to chemotherapy were demonstrated in all five patients who had undergone positron emission tomography evaluations at the time of the presentation, Dr. Van Hoff reported during a late-breaking session.

"Toxicities were relatively mild," he said; they included dysgeusia, an alteration in taste sensations; mild alopecia; mild weight loss; and hyponatremia.

The drug's development represented what Dr. Von Hoff called, "the essence of translational medicine." Molecular biologists first discovered that aberrance in the Hedgehog signaling pathway triggered when patched (PTCH) or smoothened (SMO) gene mutations caused an acceleration of cell growth that proved instrumental in the development of either sporadic or hereditary basal cell carcinoma.

Nature then played a role, he noted.

Serendipitously, it was discovered that cyclopamine, a naturally occurring inhibitor of the SMO mutation, could be found in pregnant ewes that ate corn lilies in the western United States and subsequently gave birth to cyclopslike lambs with oversize heads and a single, central eye.

Genentech Inc., in conjunction with the Curis Inc., developed a synthetic version of cyclopamine 100 times more potent than the version found in corn lilies, naming the agent GDC-0449.

Patients, including Subject #1 in the phase I study, "knew the drug was coming and hung on." Although metastatic basal cell carcinoma is very rare, its prognosis is poor, with a mean survival of approximately 5 months, said Dr. Von Hoff.

Formal discussant Dr. Ervin Epstein of the Children's Hospital Oakland (Calif.) Research Institute noted that many unanswered questions remain about GDC-0449, but he said that, as a "card-carrying dermatologist," he is "full of optimism … that help is on the way."

Dr. Von Hoff receives research grant support from Genentech, developer of GDC-0449. Dr. Epstein is a consultant for Genentech and owns stock in Curis.

SAN DIEGO — A custom-designed inhibitor of a mutation in the Hedgehog signaling pathway stimulated antitumor activity in eight of nine patients with locally advanced, multifocal, or metastatic basal cell carcinoma in phase I interim trial results presented at the annual meeting of the American Association for Cancer Research.

Patients in the small, ongoing trial experienced healing of their lesions, diminishment of pain and fatigue, and improvement in dyspnea while taking the study drug GDC-0449 for periods ranging from 120 to 438 days.

"These responses were pretty dramatic, [beginning] within 2–3 weeks of starting the drug," said Dr. Daniel D. Von Hoff, senior investigator and director of translational research for the Translational Genomics Research Institute in Scottsdale, Ariz.

Basal cell carcinoma is the most common malignancy in humans, diagnosed in approximately 1 million U.S. patients per year. While it typically grows slowly and can be managed by local excision or ionizing radiation, it may infiltrate surrounding tissue. In rare cases (less than 0.1%), it becomes metastatic, most commonly to the lung, liver, and/or bone.

The first three patients enrolled in the study received daily doses of 150 mg, 270 mg, and 540 mg, respectively, of GDC-0449, a synthetic, revved-up version of the naturally occurring Hedgehog pathway antagonist cyclopamine. When antitumor activity was confirmed, six more patients were enrolled, all receiving the 150-mg/day dose.

The average patient was aged 61 years (range 42–85 years). Eight were men.

All had undergone surgery (some as many as 20 operations) for their basal cell carcinoma. Four had received radiation, and three were given chemotherapy. Five patients had metastatic disease, two had locally advanced disease of the ear, and two had multifocal disease.

Among four of the patients with metastatic disease, two had a confirmed partial response, one had stable disease, and one progressed while on the study drug and died of his disease. It is too early to assess the response of one recently enrolled patient with metastatic disease, according to Dr. Von Hoff.

In four patients with clinically evaluable locally advanced or multifocal disease, two had a complete response and two had stable disease, meaning that their skin lesions were not advancing.

Metabolic responses to chemotherapy were demonstrated in all five patients who had undergone positron emission tomography evaluations at the time of the presentation, Dr. Van Hoff reported during a late-breaking session.

"Toxicities were relatively mild," he said; they included dysgeusia, an alteration in taste sensations; mild alopecia; mild weight loss; and hyponatremia.

The drug's development represented what Dr. Von Hoff called, "the essence of translational medicine." Molecular biologists first discovered that aberrance in the Hedgehog signaling pathway triggered when patched (PTCH) or smoothened (SMO) gene mutations caused an acceleration of cell growth that proved instrumental in the development of either sporadic or hereditary basal cell carcinoma.

Nature then played a role, he noted.

Serendipitously, it was discovered that cyclopamine, a naturally occurring inhibitor of the SMO mutation, could be found in pregnant ewes that ate corn lilies in the western United States and subsequently gave birth to cyclopslike lambs with oversize heads and a single, central eye.

Genentech Inc., in conjunction with the Curis Inc., developed a synthetic version of cyclopamine 100 times more potent than the version found in corn lilies, naming the agent GDC-0449.

Patients, including Subject #1 in the phase I study, "knew the drug was coming and hung on." Although metastatic basal cell carcinoma is very rare, its prognosis is poor, with a mean survival of approximately 5 months, said Dr. Von Hoff.

Formal discussant Dr. Ervin Epstein of the Children's Hospital Oakland (Calif.) Research Institute noted that many unanswered questions remain about GDC-0449, but he said that, as a "card-carrying dermatologist," he is "full of optimism … that help is on the way."

Dr. Von Hoff receives research grant support from Genentech, developer of GDC-0449. Dr. Epstein is a consultant for Genentech and owns stock in Curis.