Melanoma

WAIKOLOA, HAWAII — Researchers, frustrated by more than 3 decades of entirely negative clinical trials that were aimed at establishing new treatments for metastatic melanoma, have pinned their hopes on targeted mitogen-activated protein kinase inhibitors.

"In metastatic melanoma, we have no defensible treatment standard. There are a few treatments that are offered to patients with the possibility of some palliative benefit, but little to no possibility of curative benefit," Dr. Keith T. Flaherty said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

This dismal current state accounts for the hopeful buzz surrounding the investigational targeted mitogen-activated protein (MAP) kinase inhibitors, said Dr. Flaherty, who is on the advisory boards of AstraZeneca Pharmaceuticals LP and Schering-Plough Corp., which are actively pursuing development of targeted inhibitors.

It is unlikely, though, that any of these agents will be effective as single-agent therapy. Multiple concomitant mutations in different signal transduction pathways are a hallmark of metastatic melanoma, so when one pathway is blocked, another is likely to increase compensatory signalling.

"Ultimately, combination targeted therapy is the direction we're going. We think that's what one is going to need to counter the various signal transduction pathways which are simultaneously activated in this disease. It's not a single pathway that drives this disease, and we need to take that complexity into account," said Dr. Flaherty, a medical oncologist who is clinical investigations program leader at the University of Pennsylvania, Philadelphia.

That being said, the field hasn't advanced to the point where definitive clinical trials of combinations of targeted therapies can be done. There simply aren't enough signal transduction inhibitors available.

In the interim, investigators are exploring the therapeutic potential of single-agent MAP kinase pathway inhibitor therapy in combination with conventional chemotherapy. Encouraging preclinical studies suggest that there is a synergistic apoptotic effect, and a few small clinical trials have shown a modest benefit, Dr. Flaherty said.

For example, when sorafenib (Nexavar), the first BRAF inhibitor, was combined with dacarbazine in a phase II randomized trial involving 101 chemotherapy-naive patients, the objective response rate doubled, compared with the 12% figure for dacarbazine alone. Progression-free survival improved from 2.7 months with chemotherapy alone to 4.9 months with combination therapy.

In another randomized phase-II study, however—this one in chemotherapy-refractory patients—the addition of sorafenib brought no benefit over chemotherapy alone. So if sorafenib does enhance the effects of chemotherapy, it's a benefit that seems to be restricted to chemotherapy-naive patients.

The definitive phase III study of this approach is underway: Accrual is nearly complete in a study randomizing 800 metastatic melanoma patients with no prior chemotherapy to carboplatin/paclitaxel alone or combined with sorafenib. The primary end point is overall survival.

Sorafenib has proved to be unimpressive as single-agent therapy in metastatic melanoma. It is an unselective agent that hits numerous other targets in addition to BRAF, and the impedance of these collateral targets may cause toxicity without contributing to efficacy, thereby limiting the ability to deliver enough of the oral drug to inhibit BRAF, Dr. Flaherty explained.

Newer, more potent, and selective orally administered MAP kinase pathway inhibitors are now entering early dose-finding, proof-of-concept clinical trials. These promising agents include RAF265 and PLX4032, by far the most selective of them all, and animal studies suggest that they will be more efficacious than sorafenib.

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

'It's not a single pathway that drives this disease, and we need to take that complexity into account.' DR. FLAHERTY

WAIKOLOA, HAWAII — Researchers, frustrated by more than 3 decades of entirely negative clinical trials that were aimed at establishing new treatments for metastatic melanoma, have pinned their hopes on targeted mitogen-activated protein kinase inhibitors.

"In metastatic melanoma, we have no defensible treatment standard. There are a few treatments that are offered to patients with the possibility of some palliative benefit, but little to no possibility of curative benefit," Dr. Keith T. Flaherty said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

This dismal current state accounts for the hopeful buzz surrounding the investigational targeted mitogen-activated protein (MAP) kinase inhibitors, said Dr. Flaherty, who is on the advisory boards of AstraZeneca Pharmaceuticals LP and Schering-Plough Corp., which are actively pursuing development of targeted inhibitors.

It is unlikely, though, that any of these agents will be effective as single-agent therapy. Multiple concomitant mutations in different signal transduction pathways are a hallmark of metastatic melanoma, so when one pathway is blocked, another is likely to increase compensatory signalling.

"Ultimately, combination targeted therapy is the direction we're going. We think that's what one is going to need to counter the various signal transduction pathways which are simultaneously activated in this disease. It's not a single pathway that drives this disease, and we need to take that complexity into account," said Dr. Flaherty, a medical oncologist who is clinical investigations program leader at the University of Pennsylvania, Philadelphia.

That being said, the field hasn't advanced to the point where definitive clinical trials of combinations of targeted therapies can be done. There simply aren't enough signal transduction inhibitors available.

In the interim, investigators are exploring the therapeutic potential of single-agent MAP kinase pathway inhibitor therapy in combination with conventional chemotherapy. Encouraging preclinical studies suggest that there is a synergistic apoptotic effect, and a few small clinical trials have shown a modest benefit, Dr. Flaherty said.

For example, when sorafenib (Nexavar), the first BRAF inhibitor, was combined with dacarbazine in a phase II randomized trial involving 101 chemotherapy-naive patients, the objective response rate doubled, compared with the 12% figure for dacarbazine alone. Progression-free survival improved from 2.7 months with chemotherapy alone to 4.9 months with combination therapy.

In another randomized phase-II study, however—this one in chemotherapy-refractory patients—the addition of sorafenib brought no benefit over chemotherapy alone. So if sorafenib does enhance the effects of chemotherapy, it's a benefit that seems to be restricted to chemotherapy-naive patients.

The definitive phase III study of this approach is underway: Accrual is nearly complete in a study randomizing 800 metastatic melanoma patients with no prior chemotherapy to carboplatin/paclitaxel alone or combined with sorafenib. The primary end point is overall survival.

Sorafenib has proved to be unimpressive as single-agent therapy in metastatic melanoma. It is an unselective agent that hits numerous other targets in addition to BRAF, and the impedance of these collateral targets may cause toxicity without contributing to efficacy, thereby limiting the ability to deliver enough of the oral drug to inhibit BRAF, Dr. Flaherty explained.

Newer, more potent, and selective orally administered MAP kinase pathway inhibitors are now entering early dose-finding, proof-of-concept clinical trials. These promising agents include RAF265 and PLX4032, by far the most selective of them all, and animal studies suggest that they will be more efficacious than sorafenib.

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

'It's not a single pathway that drives this disease, and we need to take that complexity into account.' DR. FLAHERTY

WAIKOLOA, HAWAII — Researchers, frustrated by more than 3 decades of entirely negative clinical trials that were aimed at establishing new treatments for metastatic melanoma, have pinned their hopes on targeted mitogen-activated protein kinase inhibitors.

"In metastatic melanoma, we have no defensible treatment standard. There are a few treatments that are offered to patients with the possibility of some palliative benefit, but little to no possibility of curative benefit," Dr. Keith T. Flaherty said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

This dismal current state accounts for the hopeful buzz surrounding the investigational targeted mitogen-activated protein (MAP) kinase inhibitors, said Dr. Flaherty, who is on the advisory boards of AstraZeneca Pharmaceuticals LP and Schering-Plough Corp., which are actively pursuing development of targeted inhibitors.

It is unlikely, though, that any of these agents will be effective as single-agent therapy. Multiple concomitant mutations in different signal transduction pathways are a hallmark of metastatic melanoma, so when one pathway is blocked, another is likely to increase compensatory signalling.

"Ultimately, combination targeted therapy is the direction we're going. We think that's what one is going to need to counter the various signal transduction pathways which are simultaneously activated in this disease. It's not a single pathway that drives this disease, and we need to take that complexity into account," said Dr. Flaherty, a medical oncologist who is clinical investigations program leader at the University of Pennsylvania, Philadelphia.

That being said, the field hasn't advanced to the point where definitive clinical trials of combinations of targeted therapies can be done. There simply aren't enough signal transduction inhibitors available.

In the interim, investigators are exploring the therapeutic potential of single-agent MAP kinase pathway inhibitor therapy in combination with conventional chemotherapy. Encouraging preclinical studies suggest that there is a synergistic apoptotic effect, and a few small clinical trials have shown a modest benefit, Dr. Flaherty said.

For example, when sorafenib (Nexavar), the first BRAF inhibitor, was combined with dacarbazine in a phase II randomized trial involving 101 chemotherapy-naive patients, the objective response rate doubled, compared with the 12% figure for dacarbazine alone. Progression-free survival improved from 2.7 months with chemotherapy alone to 4.9 months with combination therapy.

In another randomized phase-II study, however—this one in chemotherapy-refractory patients—the addition of sorafenib brought no benefit over chemotherapy alone. So if sorafenib does enhance the effects of chemotherapy, it's a benefit that seems to be restricted to chemotherapy-naive patients.

The definitive phase III study of this approach is underway: Accrual is nearly complete in a study randomizing 800 metastatic melanoma patients with no prior chemotherapy to carboplatin/paclitaxel alone or combined with sorafenib. The primary end point is overall survival.

Sorafenib has proved to be unimpressive as single-agent therapy in metastatic melanoma. It is an unselective agent that hits numerous other targets in addition to BRAF, and the impedance of these collateral targets may cause toxicity without contributing to efficacy, thereby limiting the ability to deliver enough of the oral drug to inhibit BRAF, Dr. Flaherty explained.

Newer, more potent, and selective orally administered MAP kinase pathway inhibitors are now entering early dose-finding, proof-of-concept clinical trials. These promising agents include RAF265 and PLX4032, by far the most selective of them all, and animal studies suggest that they will be more efficacious than sorafenib.

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

'It's not a single pathway that drives this disease, and we need to take that complexity into account.' DR. FLAHERTY

CHICAGO — Isolated limb infusion, a minimally invasive technique to deliver regional chemotherapy, was useful but not optimal in two melanoma studies presented at a symposium sponsored by the Society of Surgical Oncology.

In the largest isolated limb infusion (ILI) series conducted to date, involving 185 patients with advanced metastatic melanoma confined to the limb, the overall survival rate was 84% at a median follow-up of 20 months, said lead investigator Dr. Hidde Kroon, a fellow at the Sydney Melanoma Unit in Australia, where the study was performed and the technique was developed.

He reported the highest rates to date for complete response (38%) and for partial response (46%) to chemotherapy. Stable disease was seen in 10% of patients and progressive disease in 6%.

In the largest study outside Australia, however, U.S. and Taiwanese investigators concluded that isolated limb infusion was an effective way to regionally administer the cytotoxic agent melphalan, but that its efficacy fell short of isolated limb perfusion (ILP).

Sydney Melanoma Unit Experience

Dr. Kroon said that the duration of response was significantly longer in patients achieving a complete response (median 22 months) than was observed overall (median 13 months) in the Australian study.

"Response rates and duration of response after isolated limb infusion are at the lower end of those reported after conventional isolated limb perfusion," Dr. Kroon acknowledged.

"However, ILI was performed in patients with [higher stages] of disease and more comorbidities, which might explain the lower response rates, since stage of disease is a significant risk factor for responses," he said.

Most patients in the study (134, or 72%) had M.D. Anderson stage IIIA or IIIAB disease, with 3% having stage I, 8% stage II, and 16% stage IV disease.

Isolated limb infusion is essentially a low-flow ILP performed without oxygenation via percutaneous catheters. It is a minimally invasive alternative to the more labor-intensive ILP, requires no routine blood transfusion, and can be easily repeated if necessary, Dr. Kroon explained. Results have been promising, but it has not been established whether it is equally effective as isolated limb perfusion.

Patients in the Australian series were treated from 1992 to 2006 with a single isolated limb infusion of melphalan and actinomycin D for 20–30 minutes under mild hyperthermic conditions. Their mean age was 74 years (range, 29–93 years), and the majority (62%) were female. Disease was present in the lower limb in 172 patients, and in the upper limb in 13.

The response rate significantly decreased with increasing stage of disease, Dr. Kroon said.

Response rates were 83% in stage I patients, 53% in stage II, 43% in stage IIIA, 33% in stage IIIAB, and 23% in stage IV.

Median overall survival was 38 months, but increased significantly to 53 months in patients achieving a complete response, he reported.

In a multivariate analysis, independent prognostic factors for complete response were lower disease stage (hazard ratio, 1.69) and greater increase in CO₂ level during the procedure (HR, 1.65).

The procedure was well tolerated, with only five patients developing grade 4 toxicity, and there were no amputations, said Dr. Kroon, who reported no conflicts of interest.

"We conclude that isolated limb infusion is a safe and effective alternative to conventional isolated limb perfusion to treat advanced metastatic melanoma in a limb," he said.

U.S./Taiwanese Experience

Lead investigator Dr. Georgia Beasley of the Duke University Medical Center in Durham, N.C., and associates compared outcomes after 59 ILP treatments in 54 patients against outcomes after 61 ILI treatments in 58 patients, all with in-transit malignant melanoma of the extremity.

Among 50 evaluable ILI patients, complete response was reported in 15 (30%), partial response in 7 (14%), stable disease in 5 (10%), and progressive disease in 23 (46%). The median duration of complete response was 12 months.

Isolated limb perfusion was associated with significantly better response at 3 months (complete response, 57%; partial response, 31%; and no response, 12%); however, significantly more ILP patients had grade 3 or greater toxicity, Dr. Beasley said.

There were nine compartment syndromes and two amputations among ILP patients, versus four compartment syndromes and no amputations among ILI patients.

"In our experience, limb infusion using melphalan did not appear to be as effective as limb perfusion, although the toxicity appears less," Dr. Beasley said.

The investigators noted that correcting the melphalan dose for ideal body weight appeared to minimize toxicity without altering response rates; 66% of ILI patients had their dose corrected, versus only 22% of ILP patients.

CHICAGO — Isolated limb infusion, a minimally invasive technique to deliver regional chemotherapy, was useful but not optimal in two melanoma studies presented at a symposium sponsored by the Society of Surgical Oncology.

In the largest isolated limb infusion (ILI) series conducted to date, involving 185 patients with advanced metastatic melanoma confined to the limb, the overall survival rate was 84% at a median follow-up of 20 months, said lead investigator Dr. Hidde Kroon, a fellow at the Sydney Melanoma Unit in Australia, where the study was performed and the technique was developed.

He reported the highest rates to date for complete response (38%) and for partial response (46%) to chemotherapy. Stable disease was seen in 10% of patients and progressive disease in 6%.

In the largest study outside Australia, however, U.S. and Taiwanese investigators concluded that isolated limb infusion was an effective way to regionally administer the cytotoxic agent melphalan, but that its efficacy fell short of isolated limb perfusion (ILP).

Sydney Melanoma Unit Experience

Dr. Kroon said that the duration of response was significantly longer in patients achieving a complete response (median 22 months) than was observed overall (median 13 months) in the Australian study.

"Response rates and duration of response after isolated limb infusion are at the lower end of those reported after conventional isolated limb perfusion," Dr. Kroon acknowledged.

"However, ILI was performed in patients with [higher stages] of disease and more comorbidities, which might explain the lower response rates, since stage of disease is a significant risk factor for responses," he said.

Most patients in the study (134, or 72%) had M.D. Anderson stage IIIA or IIIAB disease, with 3% having stage I, 8% stage II, and 16% stage IV disease.

Isolated limb infusion is essentially a low-flow ILP performed without oxygenation via percutaneous catheters. It is a minimally invasive alternative to the more labor-intensive ILP, requires no routine blood transfusion, and can be easily repeated if necessary, Dr. Kroon explained. Results have been promising, but it has not been established whether it is equally effective as isolated limb perfusion.

Patients in the Australian series were treated from 1992 to 2006 with a single isolated limb infusion of melphalan and actinomycin D for 20–30 minutes under mild hyperthermic conditions. Their mean age was 74 years (range, 29–93 years), and the majority (62%) were female. Disease was present in the lower limb in 172 patients, and in the upper limb in 13.

The response rate significantly decreased with increasing stage of disease, Dr. Kroon said.

Response rates were 83% in stage I patients, 53% in stage II, 43% in stage IIIA, 33% in stage IIIAB, and 23% in stage IV.

Median overall survival was 38 months, but increased significantly to 53 months in patients achieving a complete response, he reported.

In a multivariate analysis, independent prognostic factors for complete response were lower disease stage (hazard ratio, 1.69) and greater increase in CO₂ level during the procedure (HR, 1.65).

The procedure was well tolerated, with only five patients developing grade 4 toxicity, and there were no amputations, said Dr. Kroon, who reported no conflicts of interest.

"We conclude that isolated limb infusion is a safe and effective alternative to conventional isolated limb perfusion to treat advanced metastatic melanoma in a limb," he said.

U.S./Taiwanese Experience

Lead investigator Dr. Georgia Beasley of the Duke University Medical Center in Durham, N.C., and associates compared outcomes after 59 ILP treatments in 54 patients against outcomes after 61 ILI treatments in 58 patients, all with in-transit malignant melanoma of the extremity.

Among 50 evaluable ILI patients, complete response was reported in 15 (30%), partial response in 7 (14%), stable disease in 5 (10%), and progressive disease in 23 (46%). The median duration of complete response was 12 months.

Isolated limb perfusion was associated with significantly better response at 3 months (complete response, 57%; partial response, 31%; and no response, 12%); however, significantly more ILP patients had grade 3 or greater toxicity, Dr. Beasley said.

There were nine compartment syndromes and two amputations among ILP patients, versus four compartment syndromes and no amputations among ILI patients.

"In our experience, limb infusion using melphalan did not appear to be as effective as limb perfusion, although the toxicity appears less," Dr. Beasley said.

The investigators noted that correcting the melphalan dose for ideal body weight appeared to minimize toxicity without altering response rates; 66% of ILI patients had their dose corrected, versus only 22% of ILP patients.

CHICAGO — Isolated limb infusion, a minimally invasive technique to deliver regional chemotherapy, was useful but not optimal in two melanoma studies presented at a symposium sponsored by the Society of Surgical Oncology.

In the largest isolated limb infusion (ILI) series conducted to date, involving 185 patients with advanced metastatic melanoma confined to the limb, the overall survival rate was 84% at a median follow-up of 20 months, said lead investigator Dr. Hidde Kroon, a fellow at the Sydney Melanoma Unit in Australia, where the study was performed and the technique was developed.

He reported the highest rates to date for complete response (38%) and for partial response (46%) to chemotherapy. Stable disease was seen in 10% of patients and progressive disease in 6%.

In the largest study outside Australia, however, U.S. and Taiwanese investigators concluded that isolated limb infusion was an effective way to regionally administer the cytotoxic agent melphalan, but that its efficacy fell short of isolated limb perfusion (ILP).

Sydney Melanoma Unit Experience

Dr. Kroon said that the duration of response was significantly longer in patients achieving a complete response (median 22 months) than was observed overall (median 13 months) in the Australian study.

"Response rates and duration of response after isolated limb infusion are at the lower end of those reported after conventional isolated limb perfusion," Dr. Kroon acknowledged.

"However, ILI was performed in patients with [higher stages] of disease and more comorbidities, which might explain the lower response rates, since stage of disease is a significant risk factor for responses," he said.

Most patients in the study (134, or 72%) had M.D. Anderson stage IIIA or IIIAB disease, with 3% having stage I, 8% stage II, and 16% stage IV disease.

Isolated limb infusion is essentially a low-flow ILP performed without oxygenation via percutaneous catheters. It is a minimally invasive alternative to the more labor-intensive ILP, requires no routine blood transfusion, and can be easily repeated if necessary, Dr. Kroon explained. Results have been promising, but it has not been established whether it is equally effective as isolated limb perfusion.

Patients in the Australian series were treated from 1992 to 2006 with a single isolated limb infusion of melphalan and actinomycin D for 20–30 minutes under mild hyperthermic conditions. Their mean age was 74 years (range, 29–93 years), and the majority (62%) were female. Disease was present in the lower limb in 172 patients, and in the upper limb in 13.

The response rate significantly decreased with increasing stage of disease, Dr. Kroon said.

Response rates were 83% in stage I patients, 53% in stage II, 43% in stage IIIA, 33% in stage IIIAB, and 23% in stage IV.

Median overall survival was 38 months, but increased significantly to 53 months in patients achieving a complete response, he reported.

In a multivariate analysis, independent prognostic factors for complete response were lower disease stage (hazard ratio, 1.69) and greater increase in CO₂ level during the procedure (HR, 1.65).

The procedure was well tolerated, with only five patients developing grade 4 toxicity, and there were no amputations, said Dr. Kroon, who reported no conflicts of interest.

"We conclude that isolated limb infusion is a safe and effective alternative to conventional isolated limb perfusion to treat advanced metastatic melanoma in a limb," he said.

U.S./Taiwanese Experience

Lead investigator Dr. Georgia Beasley of the Duke University Medical Center in Durham, N.C., and associates compared outcomes after 59 ILP treatments in 54 patients against outcomes after 61 ILI treatments in 58 patients, all with in-transit malignant melanoma of the extremity.

Among 50 evaluable ILI patients, complete response was reported in 15 (30%), partial response in 7 (14%), stable disease in 5 (10%), and progressive disease in 23 (46%). The median duration of complete response was 12 months.

Isolated limb perfusion was associated with significantly better response at 3 months (complete response, 57%; partial response, 31%; and no response, 12%); however, significantly more ILP patients had grade 3 or greater toxicity, Dr. Beasley said.

There were nine compartment syndromes and two amputations among ILP patients, versus four compartment syndromes and no amputations among ILI patients.

"In our experience, limb infusion using melphalan did not appear to be as effective as limb perfusion, although the toxicity appears less," Dr. Beasley said.

The investigators noted that correcting the melphalan dose for ideal body weight appeared to minimize toxicity without altering response rates; 66% of ILI patients had their dose corrected, versus only 22% of ILP patients.

SAN ANTONIO — The treatment of most patients who have mycosis fungoides is well within the purview of dermatologists.

"It's very rewarding caring for these patients, because they respond to so many different therapies," Dr. L. Frank Glass said at the annual meeting of the American Academy of Dermatology.

In fact, most patients do very well and don't die from this disease, which is the most common of the cutaneous T-cell lymphomas. Its treatment resembles that of a chronic disease, such as psoriasis, more than that of a terminal illness, said Dr. Glass of the University of South Florida, Tampa.

From topical steroids and retinoids to alkylating agents and phototherapy, the range of treatments for cutaneous T-cell lymphomas is expansive and provides options for successfully treating the many variants of the disease. Furthermore, these are treatments with which dermatologists, compared with other specialists, have the most extensive experience.

"We're used to using retinoids orally," he said, noting that even imiquimod—another drug with which dermatologists have extensive experience—is considered an off-label option for the treatment of mycosis fungoides.

Dermatologists will mainly see patients with disease up to the limited patch-plaque stage. Disease progression in these patients tends to be limited, and some patients with very early-stage disease have been shown to have the same survival as the general population.

At least one study has shown that those patients who receive conservative sequential therapy do as well as those patients who receive aggressive chemotherapy and radiation treatment, Dr. Glass explained.

Even with patients who have more advanced tumor-stage disease that requires multispecialty care, dermatologists can continue to play a role in treatment, thanks to the following modalities now available:

▸ Topical corticosteroids. Class I corticosteroids tend to work best for mycosis fungoides patients, but should be avoided in those with atrophic disease variants. When they are appropriate, corticosteroids tend to work well for itching and redness. Corticosteroids are particularly useful as adjuvants with other therapies.

▸ Phototherapy. PUVA is best, but narrow-band phototherapy offers more convenience and also has good results. The choice depends on the stage and type of lesion, as well as patient risk factors, Dr. Glass said.

Although response rates are similar with PUVA and narrow-band light, there are some questions about the durability of response with narrow-band light and whether thicker lesions respond as well to this form of phototherapy. In those with higher melanoma risk, however, narrow-band light may be safer.

Phototherapy is great as a maintenance therapy, but in those with progressive disease, relapse rates increase and combination therapy with a systemic agent may be necessary.

▸ Extracorporeal photophoresis. This treatment is quite effective, particularly in patients with erythrodermic mycosis fungoides and Sézary syndrome. It is the treatment of choice for the former, and is "the beginning of treatment" for the latter, he said.

▸ Bexarotene. Topical bexarotene is promising, with a similar mechanism of action to other retinoids, but at nearly $2,000 per tube it is too expensive to be considered a viable option at this time, Dr. Glass noted.

Oral bexarotene is more accessible and works well in combination with other therapies, such as PUVA.

Using oral bexarotene in a combination allows the dosage of both agents to be reduced, thus maintaining good response but reducing the risk of adverse effects, such as hypertriglyceridemia and hypothyroidism.

However, Dr. Glass noted that when he uses bexarotene in combination with another treatment for sustained therapy, he brings in an internist to ensure that the patient doesn't have an increased cardiac risk or a metabolic problem "down the road."

Nonetheless, combination therapy is "pretty effective and can certainly be initiated" by dermatologists with fewer side effects, he said.

SAN ANTONIO — The treatment of most patients who have mycosis fungoides is well within the purview of dermatologists.

"It's very rewarding caring for these patients, because they respond to so many different therapies," Dr. L. Frank Glass said at the annual meeting of the American Academy of Dermatology.

In fact, most patients do very well and don't die from this disease, which is the most common of the cutaneous T-cell lymphomas. Its treatment resembles that of a chronic disease, such as psoriasis, more than that of a terminal illness, said Dr. Glass of the University of South Florida, Tampa.

From topical steroids and retinoids to alkylating agents and phototherapy, the range of treatments for cutaneous T-cell lymphomas is expansive and provides options for successfully treating the many variants of the disease. Furthermore, these are treatments with which dermatologists, compared with other specialists, have the most extensive experience.

"We're used to using retinoids orally," he said, noting that even imiquimod—another drug with which dermatologists have extensive experience—is considered an off-label option for the treatment of mycosis fungoides.

Dermatologists will mainly see patients with disease up to the limited patch-plaque stage. Disease progression in these patients tends to be limited, and some patients with very early-stage disease have been shown to have the same survival as the general population.

At least one study has shown that those patients who receive conservative sequential therapy do as well as those patients who receive aggressive chemotherapy and radiation treatment, Dr. Glass explained.

Even with patients who have more advanced tumor-stage disease that requires multispecialty care, dermatologists can continue to play a role in treatment, thanks to the following modalities now available:

▸ Topical corticosteroids. Class I corticosteroids tend to work best for mycosis fungoides patients, but should be avoided in those with atrophic disease variants. When they are appropriate, corticosteroids tend to work well for itching and redness. Corticosteroids are particularly useful as adjuvants with other therapies.

▸ Phototherapy. PUVA is best, but narrow-band phototherapy offers more convenience and also has good results. The choice depends on the stage and type of lesion, as well as patient risk factors, Dr. Glass said.

Although response rates are similar with PUVA and narrow-band light, there are some questions about the durability of response with narrow-band light and whether thicker lesions respond as well to this form of phototherapy. In those with higher melanoma risk, however, narrow-band light may be safer.

Phototherapy is great as a maintenance therapy, but in those with progressive disease, relapse rates increase and combination therapy with a systemic agent may be necessary.

▸ Extracorporeal photophoresis. This treatment is quite effective, particularly in patients with erythrodermic mycosis fungoides and Sézary syndrome. It is the treatment of choice for the former, and is "the beginning of treatment" for the latter, he said.

▸ Bexarotene. Topical bexarotene is promising, with a similar mechanism of action to other retinoids, but at nearly $2,000 per tube it is too expensive to be considered a viable option at this time, Dr. Glass noted.

Oral bexarotene is more accessible and works well in combination with other therapies, such as PUVA.

Using oral bexarotene in a combination allows the dosage of both agents to be reduced, thus maintaining good response but reducing the risk of adverse effects, such as hypertriglyceridemia and hypothyroidism.

However, Dr. Glass noted that when he uses bexarotene in combination with another treatment for sustained therapy, he brings in an internist to ensure that the patient doesn't have an increased cardiac risk or a metabolic problem "down the road."

Nonetheless, combination therapy is "pretty effective and can certainly be initiated" by dermatologists with fewer side effects, he said.

SAN ANTONIO — The treatment of most patients who have mycosis fungoides is well within the purview of dermatologists.

"It's very rewarding caring for these patients, because they respond to so many different therapies," Dr. L. Frank Glass said at the annual meeting of the American Academy of Dermatology.

In fact, most patients do very well and don't die from this disease, which is the most common of the cutaneous T-cell lymphomas. Its treatment resembles that of a chronic disease, such as psoriasis, more than that of a terminal illness, said Dr. Glass of the University of South Florida, Tampa.

From topical steroids and retinoids to alkylating agents and phototherapy, the range of treatments for cutaneous T-cell lymphomas is expansive and provides options for successfully treating the many variants of the disease. Furthermore, these are treatments with which dermatologists, compared with other specialists, have the most extensive experience.

"We're used to using retinoids orally," he said, noting that even imiquimod—another drug with which dermatologists have extensive experience—is considered an off-label option for the treatment of mycosis fungoides.

Dermatologists will mainly see patients with disease up to the limited patch-plaque stage. Disease progression in these patients tends to be limited, and some patients with very early-stage disease have been shown to have the same survival as the general population.

At least one study has shown that those patients who receive conservative sequential therapy do as well as those patients who receive aggressive chemotherapy and radiation treatment, Dr. Glass explained.

Even with patients who have more advanced tumor-stage disease that requires multispecialty care, dermatologists can continue to play a role in treatment, thanks to the following modalities now available:

▸ Topical corticosteroids. Class I corticosteroids tend to work best for mycosis fungoides patients, but should be avoided in those with atrophic disease variants. When they are appropriate, corticosteroids tend to work well for itching and redness. Corticosteroids are particularly useful as adjuvants with other therapies.

▸ Phototherapy. PUVA is best, but narrow-band phototherapy offers more convenience and also has good results. The choice depends on the stage and type of lesion, as well as patient risk factors, Dr. Glass said.

Although response rates are similar with PUVA and narrow-band light, there are some questions about the durability of response with narrow-band light and whether thicker lesions respond as well to this form of phototherapy. In those with higher melanoma risk, however, narrow-band light may be safer.

Phototherapy is great as a maintenance therapy, but in those with progressive disease, relapse rates increase and combination therapy with a systemic agent may be necessary.

▸ Extracorporeal photophoresis. This treatment is quite effective, particularly in patients with erythrodermic mycosis fungoides and Sézary syndrome. It is the treatment of choice for the former, and is "the beginning of treatment" for the latter, he said.

▸ Bexarotene. Topical bexarotene is promising, with a similar mechanism of action to other retinoids, but at nearly $2,000 per tube it is too expensive to be considered a viable option at this time, Dr. Glass noted.

Oral bexarotene is more accessible and works well in combination with other therapies, such as PUVA.

Using oral bexarotene in a combination allows the dosage of both agents to be reduced, thus maintaining good response but reducing the risk of adverse effects, such as hypertriglyceridemia and hypothyroidism.

However, Dr. Glass noted that when he uses bexarotene in combination with another treatment for sustained therapy, he brings in an internist to ensure that the patient doesn't have an increased cardiac risk or a metabolic problem "down the road."

Nonetheless, combination therapy is "pretty effective and can certainly be initiated" by dermatologists with fewer side effects, he said.

SAN ANTONIO — The use of total body photography as a surveillance tool for melanoma has great potential to reduce the number of unnecessary biopsies, Dr. Allan C. Halpern said at the annual meeting of the American Academy of Dermatology.

When used appropriately in conjunction with self-examination and regular follow-up, total body photography (TBP) can also increase the likelihood of detecting thinner melanomas, said Dr. Halpern, chief of dermatology at Memorial Sloan-Kettering Cancer Center, New York.

Although it does have some disadvantages—namely the possibility of raising the threshold for removal of lesions in favor of follow-up in patients who may not return for follow-up—it also has a number of possible advantages for both patients and physicians, he said.

The key is to use TBP cautiously. The first visit is not the time to raise the threshold for removing a suspicious lesion in anticipation of using TBP for surveillance. Instead, build a relationship before relying on the patient to perform self-evaluations and come in for routine follow-up visits. Once a relationship is established and the patient is compliant, TBP can be a great tool for engaging patients in their own care and increasing patient satisfaction, he noted.

The sensitivity and specificity of TBP for melanoma are increased in those who do come back. Studies have shown that patients who are engaged in their care because they receive copies of the photos and are asked to do monthly self-examinations by comparing lesions with the photos are more likely to do self-examinations and are more likely to be effective when performing self-examinations than are patients who do not receive photos, Dr. Halpern said.

As a result, the use of TBP is increasing. A survey of AAD members showed 63% of 105 residency programs use TBP and 49% of AAD members use it at least some of the time in patients with dysplastic nevi. Furthermore, 83% of programs with specialized pigmented lesions clinics and 49% of those without such a clinic are using TBP.

Those who don't use TBP cite perceived logistical difficulties, financial constraints, and doubt about its benefits as reasons for not using it, he said.

The use of TBP requires only a digital camera of at least 6–12 megapixels (although he uses one with 40 megapixels), a computer, and a space with good lighting and the availability of a blue or black backdrop, Dr. Halpern explained, also noting that a CPT code for TBP exists.

As for benefits, one small study showed no difference in detection of melanoma for those who used and didn't use TBP. It did show an increase in sensitivity and specificity for detection of nonmelanomas, and another showed that twice as many patients who received photos were compliant with recommended care, including self-examination, than those who were not.

The actual taking of the photographs can be uncomfortable for the patient, so it is a good idea to perform a physical examination first. Dr. Halpern always starts with the patient facing away from him to allow the patient time to acclimate to the discomfort of the situation and to allow himself time to regain composure before facing the patient should he encounter an alarming lesion.

Photos can be taken by the physician, a specially trained nurse, or a medical photographer. Some practices have a photographer on staff, and hospitals may employ photographers and be accommodating when it comes to TBP services. "You can achieve very high-quality pictures if you nail down a system and use it in a sufficiently standardized fashion," Dr. Halpern said, noting that there are papers in the literature to provide guidance for using TBP.

Basically, as much of the body surface as possible should be photographed, and positioning should be chosen to allow this.

Side-by-side (photos and patient) examinations can then be conducted at follow-up visits. He recommended examining patients while they are standing, which makes it easier to compare lesions against those in the photos.

Patient privacy needs to be carefully protected, so photos kept on office computers should be encrypted, he said.

Patients should be provided with hard copies and a compact disk along with a photo-marking pen that they can use to mark the photographs if they find something of concern on their monthly self-examination.

It is important to inform patients that their role in performing self-examinations is not meant to be anxiety provoking; rather it should be an exercise in becoming familiar with the big picture so they can recognize obvious changes and fast-growing lesions that might be of concern.

Dr. Halpern used a night-sky analogy to describe how patients should view their photos. If they become familiar with their own "constellations," they will notice when something new appears in the field, or if something other than the North Star is shining brightest. The patient's job is to notice the obvious changes; the physician's job is to find the subtle changes, he said.

As for which patients are the best candidates for TBP, he suggested using it for those with dysplastic nevi who have undergone many excisions and those with a familial or personal history of melanoma. No prospective data exist to guide how often patients should be seen, but every 6 months has been a good interval in Dr. Halpern's experience. "We do find the vast majority of melanomas in surveillance with these patients. … This is one of the major reasons for doing total body photograph."

Patients who receive copies of their photos, and are asked to do monthly self-exams, are more likely to do the exams and be effective in doing so, said Dr. Allan C. Halpern. Daphne Demas/MSKCC Dermatology

SAN ANTONIO — The use of total body photography as a surveillance tool for melanoma has great potential to reduce the number of unnecessary biopsies, Dr. Allan C. Halpern said at the annual meeting of the American Academy of Dermatology.

When used appropriately in conjunction with self-examination and regular follow-up, total body photography (TBP) can also increase the likelihood of detecting thinner melanomas, said Dr. Halpern, chief of dermatology at Memorial Sloan-Kettering Cancer Center, New York.

Although it does have some disadvantages—namely the possibility of raising the threshold for removal of lesions in favor of follow-up in patients who may not return for follow-up—it also has a number of possible advantages for both patients and physicians, he said.

The key is to use TBP cautiously. The first visit is not the time to raise the threshold for removing a suspicious lesion in anticipation of using TBP for surveillance. Instead, build a relationship before relying on the patient to perform self-evaluations and come in for routine follow-up visits. Once a relationship is established and the patient is compliant, TBP can be a great tool for engaging patients in their own care and increasing patient satisfaction, he noted.

The sensitivity and specificity of TBP for melanoma are increased in those who do come back. Studies have shown that patients who are engaged in their care because they receive copies of the photos and are asked to do monthly self-examinations by comparing lesions with the photos are more likely to do self-examinations and are more likely to be effective when performing self-examinations than are patients who do not receive photos, Dr. Halpern said.

As a result, the use of TBP is increasing. A survey of AAD members showed 63% of 105 residency programs use TBP and 49% of AAD members use it at least some of the time in patients with dysplastic nevi. Furthermore, 83% of programs with specialized pigmented lesions clinics and 49% of those without such a clinic are using TBP.

Those who don't use TBP cite perceived logistical difficulties, financial constraints, and doubt about its benefits as reasons for not using it, he said.

The use of TBP requires only a digital camera of at least 6–12 megapixels (although he uses one with 40 megapixels), a computer, and a space with good lighting and the availability of a blue or black backdrop, Dr. Halpern explained, also noting that a CPT code for TBP exists.

As for benefits, one small study showed no difference in detection of melanoma for those who used and didn't use TBP. It did show an increase in sensitivity and specificity for detection of nonmelanomas, and another showed that twice as many patients who received photos were compliant with recommended care, including self-examination, than those who were not.

The actual taking of the photographs can be uncomfortable for the patient, so it is a good idea to perform a physical examination first. Dr. Halpern always starts with the patient facing away from him to allow the patient time to acclimate to the discomfort of the situation and to allow himself time to regain composure before facing the patient should he encounter an alarming lesion.

Photos can be taken by the physician, a specially trained nurse, or a medical photographer. Some practices have a photographer on staff, and hospitals may employ photographers and be accommodating when it comes to TBP services. "You can achieve very high-quality pictures if you nail down a system and use it in a sufficiently standardized fashion," Dr. Halpern said, noting that there are papers in the literature to provide guidance for using TBP.

Basically, as much of the body surface as possible should be photographed, and positioning should be chosen to allow this.

Side-by-side (photos and patient) examinations can then be conducted at follow-up visits. He recommended examining patients while they are standing, which makes it easier to compare lesions against those in the photos.

Patient privacy needs to be carefully protected, so photos kept on office computers should be encrypted, he said.

Patients should be provided with hard copies and a compact disk along with a photo-marking pen that they can use to mark the photographs if they find something of concern on their monthly self-examination.

It is important to inform patients that their role in performing self-examinations is not meant to be anxiety provoking; rather it should be an exercise in becoming familiar with the big picture so they can recognize obvious changes and fast-growing lesions that might be of concern.

Dr. Halpern used a night-sky analogy to describe how patients should view their photos. If they become familiar with their own "constellations," they will notice when something new appears in the field, or if something other than the North Star is shining brightest. The patient's job is to notice the obvious changes; the physician's job is to find the subtle changes, he said.

As for which patients are the best candidates for TBP, he suggested using it for those with dysplastic nevi who have undergone many excisions and those with a familial or personal history of melanoma. No prospective data exist to guide how often patients should be seen, but every 6 months has been a good interval in Dr. Halpern's experience. "We do find the vast majority of melanomas in surveillance with these patients. … This is one of the major reasons for doing total body photograph."

Patients who receive copies of their photos, and are asked to do monthly self-exams, are more likely to do the exams and be effective in doing so, said Dr. Allan C. Halpern. Daphne Demas/MSKCC Dermatology

SAN ANTONIO — The use of total body photography as a surveillance tool for melanoma has great potential to reduce the number of unnecessary biopsies, Dr. Allan C. Halpern said at the annual meeting of the American Academy of Dermatology.

When used appropriately in conjunction with self-examination and regular follow-up, total body photography (TBP) can also increase the likelihood of detecting thinner melanomas, said Dr. Halpern, chief of dermatology at Memorial Sloan-Kettering Cancer Center, New York.

Although it does have some disadvantages—namely the possibility of raising the threshold for removal of lesions in favor of follow-up in patients who may not return for follow-up—it also has a number of possible advantages for both patients and physicians, he said.

The key is to use TBP cautiously. The first visit is not the time to raise the threshold for removing a suspicious lesion in anticipation of using TBP for surveillance. Instead, build a relationship before relying on the patient to perform self-evaluations and come in for routine follow-up visits. Once a relationship is established and the patient is compliant, TBP can be a great tool for engaging patients in their own care and increasing patient satisfaction, he noted.

The sensitivity and specificity of TBP for melanoma are increased in those who do come back. Studies have shown that patients who are engaged in their care because they receive copies of the photos and are asked to do monthly self-examinations by comparing lesions with the photos are more likely to do self-examinations and are more likely to be effective when performing self-examinations than are patients who do not receive photos, Dr. Halpern said.

As a result, the use of TBP is increasing. A survey of AAD members showed 63% of 105 residency programs use TBP and 49% of AAD members use it at least some of the time in patients with dysplastic nevi. Furthermore, 83% of programs with specialized pigmented lesions clinics and 49% of those without such a clinic are using TBP.

Those who don't use TBP cite perceived logistical difficulties, financial constraints, and doubt about its benefits as reasons for not using it, he said.

The use of TBP requires only a digital camera of at least 6–12 megapixels (although he uses one with 40 megapixels), a computer, and a space with good lighting and the availability of a blue or black backdrop, Dr. Halpern explained, also noting that a CPT code for TBP exists.

As for benefits, one small study showed no difference in detection of melanoma for those who used and didn't use TBP. It did show an increase in sensitivity and specificity for detection of nonmelanomas, and another showed that twice as many patients who received photos were compliant with recommended care, including self-examination, than those who were not.

The actual taking of the photographs can be uncomfortable for the patient, so it is a good idea to perform a physical examination first. Dr. Halpern always starts with the patient facing away from him to allow the patient time to acclimate to the discomfort of the situation and to allow himself time to regain composure before facing the patient should he encounter an alarming lesion.

Photos can be taken by the physician, a specially trained nurse, or a medical photographer. Some practices have a photographer on staff, and hospitals may employ photographers and be accommodating when it comes to TBP services. "You can achieve very high-quality pictures if you nail down a system and use it in a sufficiently standardized fashion," Dr. Halpern said, noting that there are papers in the literature to provide guidance for using TBP.

Basically, as much of the body surface as possible should be photographed, and positioning should be chosen to allow this.

Side-by-side (photos and patient) examinations can then be conducted at follow-up visits. He recommended examining patients while they are standing, which makes it easier to compare lesions against those in the photos.

Patient privacy needs to be carefully protected, so photos kept on office computers should be encrypted, he said.

Patients should be provided with hard copies and a compact disk along with a photo-marking pen that they can use to mark the photographs if they find something of concern on their monthly self-examination.

It is important to inform patients that their role in performing self-examinations is not meant to be anxiety provoking; rather it should be an exercise in becoming familiar with the big picture so they can recognize obvious changes and fast-growing lesions that might be of concern.

Dr. Halpern used a night-sky analogy to describe how patients should view their photos. If they become familiar with their own "constellations," they will notice when something new appears in the field, or if something other than the North Star is shining brightest. The patient's job is to notice the obvious changes; the physician's job is to find the subtle changes, he said.

As for which patients are the best candidates for TBP, he suggested using it for those with dysplastic nevi who have undergone many excisions and those with a familial or personal history of melanoma. No prospective data exist to guide how often patients should be seen, but every 6 months has been a good interval in Dr. Halpern's experience. "We do find the vast majority of melanomas in surveillance with these patients. … This is one of the major reasons for doing total body photograph."

Patients who receive copies of their photos, and are asked to do monthly self-exams, are more likely to do the exams and be effective in doing so, said Dr. Allan C. Halpern. Daphne Demas/MSKCC Dermatology

SAN DIEGO — Extracutaneous melanomas are rare—they make up only 15% of all melanomas—but small primary lesions can be easily overlooked during a routine skin exam, according to one expert.

Sites that require close inspection include the scalp, nail beds, interdigital folds, and perianal skin. These areas "are easily accessible to clinical exam and can make a big difference for your patients," Dr. Terence C. O'Grady said at an update on melanoma sponsored by the Scripps Clinic.

The most commonly affected sites for extracutaneous melanoma include the ocular or juxtacutaneous mucosal membranes, said Dr. O'Grady, who directs the dermatology residency program at the University of California, San Diego.

The three most common metastatic locations include the lungs (70%), the liver (68%), and the bowels (58%). Other sites include the pancreas (50%), the adrenal gland (50%), the heart (49%), kidneys (45%), brain (39%), thyroid (39%), and spleen (36%), he said.

Melanoma can metastasize to these sites in a number of ways. A melanoma could have been completely removed without histologic examination.

"You could also have a completely regressed melanoma at another site that was not treated," he said.

"This can be a real problem because there is no evidence of a pre-existing lesion. In our clinic, if we don't see a primary lesion we do a Wood's light exam and look for hypopigmented areas that may represent previously regressed lesions. Unfortunately, when you biopsy these regressed areas, the only thing you usually see is pigment incontinence on the histology, so there's no evidence that the melanoma was ever there," Dr. O'Grady said.

Because it's rare to find primary melanomas in these locations, he continued, "it's more probable that these lesions are metastatic to that site rather than being a primary lesion."

The five most common locations of primary extracutaneous melanoma include the eye (79%), the vulva (7%), soft tissues (3%), anorectum (2%), and the vagina (2%), according to Dr. O'Grady. "Many of us loathe to do an exam of the genitalia, but [lesions in this area] do occur," he said. "I usually tell patients that have had a melanoma or are at high risk for melanoma to bring this point up with other physicians they [may see], so they can have those areas examined."

Dr. O'Grady said that he begins his skin examinations at the scalp and works his way down to the feet.

"I always tell patients who wear nail polish to have that removed for the exam so I can see the nail bed," he said. "I look at the interdigital folds and at the bottom of the feet. Patients always wonder, 'What are you looking for in between my toes?' I tell them, 'You can get pigmented lesions in those areas. You can also get melanomas in those areas.'"

He also emphasized the importance of biopsying lesions detected in subungual areas. "These lesions can be impossible to diagnose without a biopsy, but a lot of [clinicians] don't feel comfortably doing a nail biopsy," said Dr. O'Grady.

"Not only is that a problem, but when you send it to pathology and you don't have someone who knows how to handle nail specimens, you're going to end up with a very nondiagnostic specimen. You want to see the skin on top of the nail, the nail plate, and the subungual tissue," he said.

SAN DIEGO — Extracutaneous melanomas are rare—they make up only 15% of all melanomas—but small primary lesions can be easily overlooked during a routine skin exam, according to one expert.

Sites that require close inspection include the scalp, nail beds, interdigital folds, and perianal skin. These areas "are easily accessible to clinical exam and can make a big difference for your patients," Dr. Terence C. O'Grady said at an update on melanoma sponsored by the Scripps Clinic.

The most commonly affected sites for extracutaneous melanoma include the ocular or juxtacutaneous mucosal membranes, said Dr. O'Grady, who directs the dermatology residency program at the University of California, San Diego.

The three most common metastatic locations include the lungs (70%), the liver (68%), and the bowels (58%). Other sites include the pancreas (50%), the adrenal gland (50%), the heart (49%), kidneys (45%), brain (39%), thyroid (39%), and spleen (36%), he said.

Melanoma can metastasize to these sites in a number of ways. A melanoma could have been completely removed without histologic examination.

"You could also have a completely regressed melanoma at another site that was not treated," he said.

"This can be a real problem because there is no evidence of a pre-existing lesion. In our clinic, if we don't see a primary lesion we do a Wood's light exam and look for hypopigmented areas that may represent previously regressed lesions. Unfortunately, when you biopsy these regressed areas, the only thing you usually see is pigment incontinence on the histology, so there's no evidence that the melanoma was ever there," Dr. O'Grady said.

Because it's rare to find primary melanomas in these locations, he continued, "it's more probable that these lesions are metastatic to that site rather than being a primary lesion."

The five most common locations of primary extracutaneous melanoma include the eye (79%), the vulva (7%), soft tissues (3%), anorectum (2%), and the vagina (2%), according to Dr. O'Grady. "Many of us loathe to do an exam of the genitalia, but [lesions in this area] do occur," he said. "I usually tell patients that have had a melanoma or are at high risk for melanoma to bring this point up with other physicians they [may see], so they can have those areas examined."

Dr. O'Grady said that he begins his skin examinations at the scalp and works his way down to the feet.

"I always tell patients who wear nail polish to have that removed for the exam so I can see the nail bed," he said. "I look at the interdigital folds and at the bottom of the feet. Patients always wonder, 'What are you looking for in between my toes?' I tell them, 'You can get pigmented lesions in those areas. You can also get melanomas in those areas.'"

He also emphasized the importance of biopsying lesions detected in subungual areas. "These lesions can be impossible to diagnose without a biopsy, but a lot of [clinicians] don't feel comfortably doing a nail biopsy," said Dr. O'Grady.

"Not only is that a problem, but when you send it to pathology and you don't have someone who knows how to handle nail specimens, you're going to end up with a very nondiagnostic specimen. You want to see the skin on top of the nail, the nail plate, and the subungual tissue," he said.

SAN DIEGO — Extracutaneous melanomas are rare—they make up only 15% of all melanomas—but small primary lesions can be easily overlooked during a routine skin exam, according to one expert.

Sites that require close inspection include the scalp, nail beds, interdigital folds, and perianal skin. These areas "are easily accessible to clinical exam and can make a big difference for your patients," Dr. Terence C. O'Grady said at an update on melanoma sponsored by the Scripps Clinic.

The most commonly affected sites for extracutaneous melanoma include the ocular or juxtacutaneous mucosal membranes, said Dr. O'Grady, who directs the dermatology residency program at the University of California, San Diego.

The three most common metastatic locations include the lungs (70%), the liver (68%), and the bowels (58%). Other sites include the pancreas (50%), the adrenal gland (50%), the heart (49%), kidneys (45%), brain (39%), thyroid (39%), and spleen (36%), he said.

Melanoma can metastasize to these sites in a number of ways. A melanoma could have been completely removed without histologic examination.

"You could also have a completely regressed melanoma at another site that was not treated," he said.

"This can be a real problem because there is no evidence of a pre-existing lesion. In our clinic, if we don't see a primary lesion we do a Wood's light exam and look for hypopigmented areas that may represent previously regressed lesions. Unfortunately, when you biopsy these regressed areas, the only thing you usually see is pigment incontinence on the histology, so there's no evidence that the melanoma was ever there," Dr. O'Grady said.

Because it's rare to find primary melanomas in these locations, he continued, "it's more probable that these lesions are metastatic to that site rather than being a primary lesion."

The five most common locations of primary extracutaneous melanoma include the eye (79%), the vulva (7%), soft tissues (3%), anorectum (2%), and the vagina (2%), according to Dr. O'Grady. "Many of us loathe to do an exam of the genitalia, but [lesions in this area] do occur," he said. "I usually tell patients that have had a melanoma or are at high risk for melanoma to bring this point up with other physicians they [may see], so they can have those areas examined."

Dr. O'Grady said that he begins his skin examinations at the scalp and works his way down to the feet.

"I always tell patients who wear nail polish to have that removed for the exam so I can see the nail bed," he said. "I look at the interdigital folds and at the bottom of the feet. Patients always wonder, 'What are you looking for in between my toes?' I tell them, 'You can get pigmented lesions in those areas. You can also get melanomas in those areas.'"

He also emphasized the importance of biopsying lesions detected in subungual areas. "These lesions can be impossible to diagnose without a biopsy, but a lot of [clinicians] don't feel comfortably doing a nail biopsy," said Dr. O'Grady.

"Not only is that a problem, but when you send it to pathology and you don't have someone who knows how to handle nail specimens, you're going to end up with a very nondiagnostic specimen. You want to see the skin on top of the nail, the nail plate, and the subungual tissue," he said.

WAIKOLOA, HAWAII — Dermatologic surveillance following diagnosis of a primary melanoma is often overly intensive, Dr. Daniel G. Coit asserted at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

"The key recommendation for melanoma patients is that they ought to go on lifetime dermatologic surveillance. But I'm here to help you, not to hurt you. We find a lot of patients who are fairly low risk undergoing dermatologic surveillance every 3 months for the rest of their lives. I think this needlessly imposes an unreasonable burden on the shoulders of my teammates in dermatology," noted Dr. Coit, a surgeon who is coleader of the melanoma disease management team at Memorial Sloan-Kettering Cancer Center in New York and a member of the American Joint Committee on Cancer melanoma staging committee.

"You don't need to follow up everybody three or four times a year," he emphasized. Indeed, annual skin surveillance is entirely appropriate in melanoma patients who are not in a subgroup at elevated risk for another primary melanoma, he said.

And who are these high-risk subgroups? Most notably, melanoma patients who have dysplastic nevi, who have a positive family history for melanoma, or who have already been diagnosed with a second primary tumor, Dr. Coit continued.

Several years ago he and his Sloan-Kettering colleagues examined this issue of second primary melanomas in detail. They reported on 4,484 patients with primary melanoma followed prospectively at the tertiary cancer center; 8.6% went on to have two or more primary melanomas. Patients with more than one primary melanoma averaged 2.3.

The estimated cumulative 5-year risk of a second primary melanoma was 11.4%. Fifty-nine percent of patients presented with their second primary tumor within 1 year of their first. After that first year, the incidence in patients without a family history of dysplastic nevi leveled off at about 0.3% per year, less than many physicians might expect. Interestingly, that low long-term annual rate was quite similar to the figure reported in an earlier analysis of the Duke University (Durham, N.C.) melanoma database, Dr. Coit noted (Surgery 1993;113:330–9).

Not only were the majority of second primary melanomas detected during the first year of surveillance in the Sloan-Kettering series, but most of those diagnosed in the first year were found at the time the initial primary was diagnosed.

"With the heightened awareness created by finding a primary melanoma, these patients undergo a complete and very thorough review, and other suspicious lesions are biopsied. After that the slope of the curve [of incident second primary melanoma] is actually pretty flat," according to Dr. Coit.

This was not the case, however, in the high-risk subgroups. In such patients, a case can be made for lifetime dermatologic surveillance more often than annually, he said.

In the Sloan-Kettering study, the subgroup of melanoma patients at highest risk of another primary tumor consisted of patients who had already been diagnosed with a second primary melanoma; they had a 15.6% incidence of a third primary tumor within 1 year of their second and a 31% probability of developing a third primary within 5 years (JAMA 2005;294:1647–54).

Forty-nine percent of patients had their second primary melanoma on the same body site as their first. The greatest site concordance was 60% for lesions on the extremities.

Dr. Keith T. Flaherty observed that the risk over time is not linear. It depends, instead, upon the stage of the first primary melanoma. The risk is greatest early on for those with high-risk disease and much more spread out over time in patients with early-stage disease.

"That needs to inform our surveillance," said Dr. Flaherty, who is a medical oncologist at the University of Pennsylvania in Philadelphia.

Dr. Coit concurred. "I'd go so far as to say that almost no one with early-stage disease recurs early, and almost no one with late-stage disease recurs late," he added.

Skin Disease Education Foundation and this news organization are wholly owned subsidiaries of Elsevier.

WAIKOLOA, HAWAII — Dermatologic surveillance following diagnosis of a primary melanoma is often overly intensive, Dr. Daniel G. Coit asserted at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

"The key recommendation for melanoma patients is that they ought to go on lifetime dermatologic surveillance. But I'm here to help you, not to hurt you. We find a lot of patients who are fairly low risk undergoing dermatologic surveillance every 3 months for the rest of their lives. I think this needlessly imposes an unreasonable burden on the shoulders of my teammates in dermatology," noted Dr. Coit, a surgeon who is coleader of the melanoma disease management team at Memorial Sloan-Kettering Cancer Center in New York and a member of the American Joint Committee on Cancer melanoma staging committee.

"You don't need to follow up everybody three or four times a year," he emphasized. Indeed, annual skin surveillance is entirely appropriate in melanoma patients who are not in a subgroup at elevated risk for another primary melanoma, he said.

And who are these high-risk subgroups? Most notably, melanoma patients who have dysplastic nevi, who have a positive family history for melanoma, or who have already been diagnosed with a second primary tumor, Dr. Coit continued.

Several years ago he and his Sloan-Kettering colleagues examined this issue of second primary melanomas in detail. They reported on 4,484 patients with primary melanoma followed prospectively at the tertiary cancer center; 8.6% went on to have two or more primary melanomas. Patients with more than one primary melanoma averaged 2.3.

The estimated cumulative 5-year risk of a second primary melanoma was 11.4%. Fifty-nine percent of patients presented with their second primary tumor within 1 year of their first. After that first year, the incidence in patients without a family history of dysplastic nevi leveled off at about 0.3% per year, less than many physicians might expect. Interestingly, that low long-term annual rate was quite similar to the figure reported in an earlier analysis of the Duke University (Durham, N.C.) melanoma database, Dr. Coit noted (Surgery 1993;113:330–9).

Not only were the majority of second primary melanomas detected during the first year of surveillance in the Sloan-Kettering series, but most of those diagnosed in the first year were found at the time the initial primary was diagnosed.

"With the heightened awareness created by finding a primary melanoma, these patients undergo a complete and very thorough review, and other suspicious lesions are biopsied. After that the slope of the curve [of incident second primary melanoma] is actually pretty flat," according to Dr. Coit.

This was not the case, however, in the high-risk subgroups. In such patients, a case can be made for lifetime dermatologic surveillance more often than annually, he said.

In the Sloan-Kettering study, the subgroup of melanoma patients at highest risk of another primary tumor consisted of patients who had already been diagnosed with a second primary melanoma; they had a 15.6% incidence of a third primary tumor within 1 year of their second and a 31% probability of developing a third primary within 5 years (JAMA 2005;294:1647–54).

Forty-nine percent of patients had their second primary melanoma on the same body site as their first. The greatest site concordance was 60% for lesions on the extremities.

Dr. Keith T. Flaherty observed that the risk over time is not linear. It depends, instead, upon the stage of the first primary melanoma. The risk is greatest early on for those with high-risk disease and much more spread out over time in patients with early-stage disease.

"That needs to inform our surveillance," said Dr. Flaherty, who is a medical oncologist at the University of Pennsylvania in Philadelphia.

Dr. Coit concurred. "I'd go so far as to say that almost no one with early-stage disease recurs early, and almost no one with late-stage disease recurs late," he added.

Skin Disease Education Foundation and this news organization are wholly owned subsidiaries of Elsevier.

WAIKOLOA, HAWAII — Dermatologic surveillance following diagnosis of a primary melanoma is often overly intensive, Dr. Daniel G. Coit asserted at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

"The key recommendation for melanoma patients is that they ought to go on lifetime dermatologic surveillance. But I'm here to help you, not to hurt you. We find a lot of patients who are fairly low risk undergoing dermatologic surveillance every 3 months for the rest of their lives. I think this needlessly imposes an unreasonable burden on the shoulders of my teammates in dermatology," noted Dr. Coit, a surgeon who is coleader of the melanoma disease management team at Memorial Sloan-Kettering Cancer Center in New York and a member of the American Joint Committee on Cancer melanoma staging committee.

"You don't need to follow up everybody three or four times a year," he emphasized. Indeed, annual skin surveillance is entirely appropriate in melanoma patients who are not in a subgroup at elevated risk for another primary melanoma, he said.

And who are these high-risk subgroups? Most notably, melanoma patients who have dysplastic nevi, who have a positive family history for melanoma, or who have already been diagnosed with a second primary tumor, Dr. Coit continued.

Several years ago he and his Sloan-Kettering colleagues examined this issue of second primary melanomas in detail. They reported on 4,484 patients with primary melanoma followed prospectively at the tertiary cancer center; 8.6% went on to have two or more primary melanomas. Patients with more than one primary melanoma averaged 2.3.

The estimated cumulative 5-year risk of a second primary melanoma was 11.4%. Fifty-nine percent of patients presented with their second primary tumor within 1 year of their first. After that first year, the incidence in patients without a family history of dysplastic nevi leveled off at about 0.3% per year, less than many physicians might expect. Interestingly, that low long-term annual rate was quite similar to the figure reported in an earlier analysis of the Duke University (Durham, N.C.) melanoma database, Dr. Coit noted (Surgery 1993;113:330–9).

Not only were the majority of second primary melanomas detected during the first year of surveillance in the Sloan-Kettering series, but most of those diagnosed in the first year were found at the time the initial primary was diagnosed.

"With the heightened awareness created by finding a primary melanoma, these patients undergo a complete and very thorough review, and other suspicious lesions are biopsied. After that the slope of the curve [of incident second primary melanoma] is actually pretty flat," according to Dr. Coit.

This was not the case, however, in the high-risk subgroups. In such patients, a case can be made for lifetime dermatologic surveillance more often than annually, he said.

In the Sloan-Kettering study, the subgroup of melanoma patients at highest risk of another primary tumor consisted of patients who had already been diagnosed with a second primary melanoma; they had a 15.6% incidence of a third primary tumor within 1 year of their second and a 31% probability of developing a third primary within 5 years (JAMA 2005;294:1647–54).

Forty-nine percent of patients had their second primary melanoma on the same body site as their first. The greatest site concordance was 60% for lesions on the extremities.

Dr. Keith T. Flaherty observed that the risk over time is not linear. It depends, instead, upon the stage of the first primary melanoma. The risk is greatest early on for those with high-risk disease and much more spread out over time in patients with early-stage disease.

"That needs to inform our surveillance," said Dr. Flaherty, who is a medical oncologist at the University of Pennsylvania in Philadelphia.

Dr. Coit concurred. "I'd go so far as to say that almost no one with early-stage disease recurs early, and almost no one with late-stage disease recurs late," he added.

Skin Disease Education Foundation and this news organization are wholly owned subsidiaries of Elsevier.

Azadeh Esmaeili, MS, IV, Alon Scope, MD, Allan C. Halpern, MD, and Ashfaq A. Marghoob, MD

The ability to detect early melanoma remains of paramount importance in our efforts to curtail deaths related to this malignancy. Fortunately, our clinical skills at recognizing the varied clinical presentation of early melanomas are continuously improving. Our enhanced clinical acumen together with improved awareness of the danger signs of melanoma has resulted in a greater proportion of thin melanomas being diagnosed today as compared to the past. The implementation and utilization of in vivo imaging technologies in clinical practice promises to further enhance our ability to detect melanoma while this cancer is still thin and easily curable. This article describes the utility and application of the in vivo imaging technologies that are currently in clinical use today including dermoscopy, total body photography, individual lesion photography, and reflectance confocal microscopy.

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

Azadeh Esmaeili, MS, IV, Alon Scope, MD, Allan C. Halpern, MD, and Ashfaq A. Marghoob, MD

The ability to detect early melanoma remains of paramount importance in our efforts to curtail deaths related to this malignancy. Fortunately, our clinical skills at recognizing the varied clinical presentation of early melanomas are continuously improving. Our enhanced clinical acumen together with improved awareness of the danger signs of melanoma has resulted in a greater proportion of thin melanomas being diagnosed today as compared to the past. The implementation and utilization of in vivo imaging technologies in clinical practice promises to further enhance our ability to detect melanoma while this cancer is still thin and easily curable. This article describes the utility and application of the in vivo imaging technologies that are currently in clinical use today including dermoscopy, total body photography, individual lesion photography, and reflectance confocal microscopy.

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

Azadeh Esmaeili, MS, IV, Alon Scope, MD, Allan C. Halpern, MD, and Ashfaq A. Marghoob, MD

The ability to detect early melanoma remains of paramount importance in our efforts to curtail deaths related to this malignancy. Fortunately, our clinical skills at recognizing the varied clinical presentation of early melanomas are continuously improving. Our enhanced clinical acumen together with improved awareness of the danger signs of melanoma has resulted in a greater proportion of thin melanomas being diagnosed today as compared to the past. The implementation and utilization of in vivo imaging technologies in clinical practice promises to further enhance our ability to detect melanoma while this cancer is still thin and easily curable. This article describes the utility and application of the in vivo imaging technologies that are currently in clinical use today including dermoscopy, total body photography, individual lesion photography, and reflectance confocal microscopy.

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

Andreas Blum, MD, Iris Zalaudek, MD, and Giuseppe Argenziano, MD

Between 1987 and 2007, different groups developed digital image analysis systems for the diagnosis of benign and malignant skin tumors. As the result of significant differences in the technical devices, the number, the nature and benign/malignant ratio of included skin tumors, different variables and statistical methods any comparison of these different systems and their results is difficult. For the use and comparison of the diagnostic performance of different digital image analysis systems in the future, some principle basic conditions are required: All used systems should have a standardized recording system and calibration. First, melanocytic and nonmelanocytic lesions should be included for the development of the diagnostic algorithms. Critical analyses of the results should answer the question if in future only melanocytic lesions should be analyzed or all pigmented and nonpigmented lesions. This will also lead to the answer if only dermatologists or all specialities of medical doctors will use such a system. All artifacts (eg, hairs, air bubbles) should be removed. The number of variables should be chosen according to the number of included melanomas. A high number of benign skin lesions should be included. Of all lesions only 10% or better less should be invasive melanomas. Each system should be developed by a training-set and controlled by an independent test-set. Each system should be controlled by the user with the final decision and responsibility and tested by independent users without any conflict of financial interest.

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

Andreas Blum, MD, Iris Zalaudek, MD, and Giuseppe Argenziano, MD

Between 1987 and 2007, different groups developed digital image analysis systems for the diagnosis of benign and malignant skin tumors. As the result of significant differences in the technical devices, the number, the nature and benign/malignant ratio of included skin tumors, different variables and statistical methods any comparison of these different systems and their results is difficult. For the use and comparison of the diagnostic performance of different digital image analysis systems in the future, some principle basic conditions are required: All used systems should have a standardized recording system and calibration. First, melanocytic and nonmelanocytic lesions should be included for the development of the diagnostic algorithms. Critical analyses of the results should answer the question if in future only melanocytic lesions should be analyzed or all pigmented and nonpigmented lesions. This will also lead to the answer if only dermatologists or all specialities of medical doctors will use such a system. All artifacts (eg, hairs, air bubbles) should be removed. The number of variables should be chosen according to the number of included melanomas. A high number of benign skin lesions should be included. Of all lesions only 10% or better less should be invasive melanomas. Each system should be developed by a training-set and controlled by an independent test-set. Each system should be controlled by the user with the final decision and responsibility and tested by independent users without any conflict of financial interest.

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

Andreas Blum, MD, Iris Zalaudek, MD, and Giuseppe Argenziano, MD

Between 1987 and 2007, different groups developed digital image analysis systems for the diagnosis of benign and malignant skin tumors. As the result of significant differences in the technical devices, the number, the nature and benign/malignant ratio of included skin tumors, different variables and statistical methods any comparison of these different systems and their results is difficult. For the use and comparison of the diagnostic performance of different digital image analysis systems in the future, some principle basic conditions are required: All used systems should have a standardized recording system and calibration. First, melanocytic and nonmelanocytic lesions should be included for the development of the diagnostic algorithms. Critical analyses of the results should answer the question if in future only melanocytic lesions should be analyzed or all pigmented and nonpigmented lesions. This will also lead to the answer if only dermatologists or all specialities of medical doctors will use such a system. All artifacts (eg, hairs, air bubbles) should be removed. The number of variables should be chosen according to the number of included melanomas. A high number of benign skin lesions should be included. Of all lesions only 10% or better less should be invasive melanomas. Each system should be developed by a training-set and controlled by an independent test-set. Each system should be controlled by the user with the final decision and responsibility and tested by independent users without any conflict of financial interest.

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

Malene E. Vestergaard, MD, and Scott W. Menzies, MB, BS, PhD

The objective of this review is to report and discuss the evidence for fully automated diagnostic instruments for cutaneous melanoma tested in a real-world clinical setting directly compared with human diagnosis.  A systematic review was performed and articles excluded when studies did not report sensitivity or specificity for melanoma directly compared with humans on an independent test set.  Only 3 instruments have had their diagnostic accuracy compared with a human diagnosis in the clinical field with a meaningful sample size that could allow some generalization with the wider clinical arena.  Two of these instruments showed a significantly inferior specificity for the diagnosis of melanoma compared with specialists.  In one of these studies, the sensitivity for diagnosis, although superior to the specialist diagnosis, did not reach statistical significance. In contrast, one instrument had an equivalent specificity and trended superior but not significantly for sensitivity for the diagnosis of melanoma. Other image based non clinic studies and studies comparing clinical management as the endpoint rather than diagnosis are also reviewed.

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

Malene E. Vestergaard, MD, and Scott W. Menzies, MB, BS, PhD

The objective of this review is to report and discuss the evidence for fully automated diagnostic instruments for cutaneous melanoma tested in a real-world clinical setting directly compared with human diagnosis.  A systematic review was performed and articles excluded when studies did not report sensitivity or specificity for melanoma directly compared with humans on an independent test set.  Only 3 instruments have had their diagnostic accuracy compared with a human diagnosis in the clinical field with a meaningful sample size that could allow some generalization with the wider clinical arena.  Two of these instruments showed a significantly inferior specificity for the diagnosis of melanoma compared with specialists.  In one of these studies, the sensitivity for diagnosis, although superior to the specialist diagnosis, did not reach statistical significance. In contrast, one instrument had an equivalent specificity and trended superior but not significantly for sensitivity for the diagnosis of melanoma. Other image based non clinic studies and studies comparing clinical management as the endpoint rather than diagnosis are also reviewed.

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

Malene E. Vestergaard, MD, and Scott W. Menzies, MB, BS, PhD

The objective of this review is to report and discuss the evidence for fully automated diagnostic instruments for cutaneous melanoma tested in a real-world clinical setting directly compared with human diagnosis.  A systematic review was performed and articles excluded when studies did not report sensitivity or specificity for melanoma directly compared with humans on an independent test set.  Only 3 instruments have had their diagnostic accuracy compared with a human diagnosis in the clinical field with a meaningful sample size that could allow some generalization with the wider clinical arena.  Two of these instruments showed a significantly inferior specificity for the diagnosis of melanoma compared with specialists.  In one of these studies, the sensitivity for diagnosis, although superior to the specialist diagnosis, did not reach statistical significance. In contrast, one instrument had an equivalent specificity and trended superior but not significantly for sensitivity for the diagnosis of melanoma. Other image based non clinic studies and studies comparing clinical management as the endpoint rather than diagnosis are also reviewed.

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

Mollie A. MacCormack, MD

Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease.

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

Mollie A. MacCormack, MD

Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease.

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

Mollie A. MacCormack, MD

Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease.

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