Jeffrey Eisenberg

As a pediatric dermatologist, Dr. Robert A. Silverman is all too familiar with this scenario: A child is referred to him with a diagnosis of nail fungus, and the parents are frustrated that the oral antifungal agents did not work.

What bothers him the most is not the antifungals, but that the patients didn’t need them to begin with because the child didn’t have a fungal infection, he said at the annual Hawaii Dermatology Seminar, sponsored by Skin Disease Education Foundation (SDEF). Several conditions of the nail in children can easily be mistaken for fungal infections.

Dr. Silverman of the department of pediatrics at Georgetown University Medical Center in Washington discussed how to distinguish fungal disease mimics from other pediatric nail conditions in children.

Onychomycosis, the most common nail infection in adults, is not all that common in children, Dr. Silverman said. Studies have shown the prevalence in children to be less than 3% in developed countries, although it is increased among children who have Down syndrome and HIV, or children from households with moccasintype Trichophyton rubrum. Clinical variants are similar to those that occur in adults, such as white superficial onychomycosis, distal lateral subungual onychomycosis, proximal subungual onychomycosis, and endonyx onychomycosis.

Other conditions that may be mistaken for fungal infections include:

• Psoriasis. Nail findings in patients who have psoriasis can be misinterpreted as fungal disease. Telltale signs of psoriasis in the nails, however, are large, irregular pits and the oil spot sign.

• Subungual tumors. These include subungual exostosis and onychomatricoma. These benign growths push on the skin surface, leading to separation of the nail. "Some people think fungus when it’s really a tumor of the underlying bone," Dr. Silverman said.

• Pachyonychia congenita. Though often confused with fungal disease, this condition, which involves a single thickened toenail, is somewhat rare. "If someone came in with a thick toenail, I’d culture him or her," Dr. Silverman said. "If the culture is negative, then you have to start thinking of these other conditions."

• Alopecia areata. Children may have nail signs of alopecia areata before hair loss occurs. In alopecia areata, the nail surface is studded to near confluence with tiny pits, also known as Scotch plaid nails. Also, the nail will have lost its luster and has a sandpaperlike texture.

"If you see what looks like alopecia areata of the nail, but don’t see any hair findings, you ought to scrape the nail to rule out fungus, because fungus can look like alopecia areata of the nails," Dr. Silverman said. "And, of course, then you would want to treat it."

Treatment for fungal infections requires the use of an oral agent for 6-12 weeks, so Dr. Silverman emphasized the importance of obtaining a culture. "If you’re going to treat someone for that length of time, it makes sense to know exactly what you’re treating," he said.

Also, Dr. Silverman said, any time he sees that a child’s parent appears to have a fungal infection, he considers that to be a red flag when trying to diagnose the patient.

As a pediatric dermatologist, Dr. Robert A. Silverman is all too familiar with this scenario: A child is referred to him with a diagnosis of nail fungus, and the parents are frustrated that the oral antifungal agents did not work.

What bothers him the most is not the antifungals, but that the patients didn’t need them to begin with because the child didn’t have a fungal infection, he said at the annual Hawaii Dermatology Seminar, sponsored by Skin Disease Education Foundation (SDEF). Several conditions of the nail in children can easily be mistaken for fungal infections.

Dr. Silverman of the department of pediatrics at Georgetown University Medical Center in Washington discussed how to distinguish fungal disease mimics from other pediatric nail conditions in children.

Onychomycosis, the most common nail infection in adults, is not all that common in children, Dr. Silverman said. Studies have shown the prevalence in children to be less than 3% in developed countries, although it is increased among children who have Down syndrome and HIV, or children from households with moccasintype Trichophyton rubrum. Clinical variants are similar to those that occur in adults, such as white superficial onychomycosis, distal lateral subungual onychomycosis, proximal subungual onychomycosis, and endonyx onychomycosis.

Other conditions that may be mistaken for fungal infections include:

• Psoriasis. Nail findings in patients who have psoriasis can be misinterpreted as fungal disease. Telltale signs of psoriasis in the nails, however, are large, irregular pits and the oil spot sign.

• Subungual tumors. These include subungual exostosis and onychomatricoma. These benign growths push on the skin surface, leading to separation of the nail. "Some people think fungus when it’s really a tumor of the underlying bone," Dr. Silverman said.

• Pachyonychia congenita. Though often confused with fungal disease, this condition, which involves a single thickened toenail, is somewhat rare. "If someone came in with a thick toenail, I’d culture him or her," Dr. Silverman said. "If the culture is negative, then you have to start thinking of these other conditions."

• Alopecia areata. Children may have nail signs of alopecia areata before hair loss occurs. In alopecia areata, the nail surface is studded to near confluence with tiny pits, also known as Scotch plaid nails. Also, the nail will have lost its luster and has a sandpaperlike texture.

"If you see what looks like alopecia areata of the nail, but don’t see any hair findings, you ought to scrape the nail to rule out fungus, because fungus can look like alopecia areata of the nails," Dr. Silverman said. "And, of course, then you would want to treat it."

Treatment for fungal infections requires the use of an oral agent for 6-12 weeks, so Dr. Silverman emphasized the importance of obtaining a culture. "If you’re going to treat someone for that length of time, it makes sense to know exactly what you’re treating," he said.

Also, Dr. Silverman said, any time he sees that a child’s parent appears to have a fungal infection, he considers that to be a red flag when trying to diagnose the patient.

As a pediatric dermatologist, Dr. Robert A. Silverman is all too familiar with this scenario: A child is referred to him with a diagnosis of nail fungus, and the parents are frustrated that the oral antifungal agents did not work.

What bothers him the most is not the antifungals, but that the patients didn’t need them to begin with because the child didn’t have a fungal infection, he said at the annual Hawaii Dermatology Seminar, sponsored by Skin Disease Education Foundation (SDEF). Several conditions of the nail in children can easily be mistaken for fungal infections.

Dr. Silverman of the department of pediatrics at Georgetown University Medical Center in Washington discussed how to distinguish fungal disease mimics from other pediatric nail conditions in children.

Onychomycosis, the most common nail infection in adults, is not all that common in children, Dr. Silverman said. Studies have shown the prevalence in children to be less than 3% in developed countries, although it is increased among children who have Down syndrome and HIV, or children from households with moccasintype Trichophyton rubrum. Clinical variants are similar to those that occur in adults, such as white superficial onychomycosis, distal lateral subungual onychomycosis, proximal subungual onychomycosis, and endonyx onychomycosis.

Other conditions that may be mistaken for fungal infections include:

• Psoriasis. Nail findings in patients who have psoriasis can be misinterpreted as fungal disease. Telltale signs of psoriasis in the nails, however, are large, irregular pits and the oil spot sign.

• Subungual tumors. These include subungual exostosis and onychomatricoma. These benign growths push on the skin surface, leading to separation of the nail. "Some people think fungus when it’s really a tumor of the underlying bone," Dr. Silverman said.

• Pachyonychia congenita. Though often confused with fungal disease, this condition, which involves a single thickened toenail, is somewhat rare. "If someone came in with a thick toenail, I’d culture him or her," Dr. Silverman said. "If the culture is negative, then you have to start thinking of these other conditions."

• Alopecia areata. Children may have nail signs of alopecia areata before hair loss occurs. In alopecia areata, the nail surface is studded to near confluence with tiny pits, also known as Scotch plaid nails. Also, the nail will have lost its luster and has a sandpaperlike texture.

"If you see what looks like alopecia areata of the nail, but don’t see any hair findings, you ought to scrape the nail to rule out fungus, because fungus can look like alopecia areata of the nails," Dr. Silverman said. "And, of course, then you would want to treat it."

Treatment for fungal infections requires the use of an oral agent for 6-12 weeks, so Dr. Silverman emphasized the importance of obtaining a culture. "If you’re going to treat someone for that length of time, it makes sense to know exactly what you’re treating," he said.

Also, Dr. Silverman said, any time he sees that a child’s parent appears to have a fungal infection, he considers that to be a red flag when trying to diagnose the patient.

The potential for filter-type embolic protection devices to reduce a patient’s risk of macroemboli during carotid angioplasty and stenting makes them ideal for preventing embolic stroke. Or does it? Based on the literature available, there is not enough evidence to suggest that embolic protection devices (EPDs) should be mandatory when treating carotid artery stenosis (CAS), said Dr. Jos C. van den Berg of Ospedale Regionale di Lugano, Switzerland. And some studies suggest that the use of EPDs when treating carotid artery stenosis increases the risk of complications, including stroke and death.

Dr. van den Berg discussed his literature review and how widely study results varied at the VEITH Symposium.

For example, the World Carotid Artery Stent Registry shows that the stroke and death rate was 5.29% without protection devices versus 2.23% with protection devices.

Elsevier,, Inc. From: Textbook of Intterventional Cardiology, 5th Ed.

The Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial revealed that at 30 days after surgery the stroke rate was 3.9 times higher in unprotected carotid angioplasty and stenting (CAS) (4/15 vs. 5/58).

Other studies show the opposite to be true. For example, in 5,341 patients in the Prospective Registry of Carotid Angioplasty and Stenting (Pro-CAS), periprocedural stroke and death rates with and without protective devices were 3.4% and 3.2%, respectively – an indicator that EPD use is not an independent predictor of adverse outcomes.

In another study, researchers assigned 30 symptomatic patients to filter-protected or unprotected CAS. Magnetic resonance imaging revealed new lesions in 29% of patients treated with EPDs versus 18% in the unprotected group. This difference was sustained at 30 days (26% vs. 12%, respectively).

Meanwhile, secondary analysis of the SPACE (Stent-Supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy) study, which used an EPD in 25% of procedures (145 vs. 418), showed a 30-day ipsilateral stroke and death rate of 6.2% in the unprotected group and 8.3% in the protected group.

Adverse events were significantly lower in patients treated with a closed cell–design stent. In the open cell–design stent group, the use of EPDs showed some benefit. In all, 50% of all adverse events occurred peri-interventionally, 40% after removal of the endovascular device, and 10% during catheter manipulation in the aortic arch.

Other studies show equal outcomes of unprotected stenting and procedures using protection devices. For example, pooled analysis of the SPACE and EVA-3S studies showed no difference in adverse outcomes between the unprotected and protected groups (7.3% for unprotected, 8.1% for protected group).

"Results of filter-protected versus unprotected stenting are similar," Dr. van den Berg said. "Part of the adverse events occur postprocedure. Hyperperfusion will not be prevented, and protection will not prevent contralateral and vertebrobasilar stroke (arch manipulation). A substantial part of strokes do not occur during the procedure." Another consideration is that "protective devices are not free of complications," he said.

Disadvantages to EPDs include additional time needed to perform a procedure, an additional learning curve, and increased costs. In protected CAS (using filter-type devices), predilatation is sometimes necessary and large emboli (1,000 micrometers) may occur when the surgeon passes a distal EPD through the stenosis. Potential EPD complications include vasospasm and dissection, intimal damage, and microemboli during deployment and retrieval.

"There is no level 1 evidence for a beneficial effect of distal filter protection devices," Dr. van den Berg said. "Several studies indicate that carotid artery stenting can be performed at least as safely without (distal) EPD. Carotid stenting with filter-type EPDs leads to more (micro) embolic events. A large part of the procedure remains unprotected anyway, and adverse events related to EPDs do occur." Given these contradictory findings, more studies are needed to decide whether EPDs should become mandatory with CAS, he added.

The potential for filter-type embolic protection devices to reduce a patient’s risk of macroemboli during carotid angioplasty and stenting makes them ideal for preventing embolic stroke. Or does it? Based on the literature available, there is not enough evidence to suggest that embolic protection devices (EPDs) should be mandatory when treating carotid artery stenosis (CAS), said Dr. Jos C. van den Berg of Ospedale Regionale di Lugano, Switzerland. And some studies suggest that the use of EPDs when treating carotid artery stenosis increases the risk of complications, including stroke and death.

Dr. van den Berg discussed his literature review and how widely study results varied at the VEITH Symposium.

For example, the World Carotid Artery Stent Registry shows that the stroke and death rate was 5.29% without protection devices versus 2.23% with protection devices.

Elsevier,, Inc. From: Textbook of Intterventional Cardiology, 5th Ed.

The Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial revealed that at 30 days after surgery the stroke rate was 3.9 times higher in unprotected carotid angioplasty and stenting (CAS) (4/15 vs. 5/58).

Other studies show the opposite to be true. For example, in 5,341 patients in the Prospective Registry of Carotid Angioplasty and Stenting (Pro-CAS), periprocedural stroke and death rates with and without protective devices were 3.4% and 3.2%, respectively – an indicator that EPD use is not an independent predictor of adverse outcomes.

In another study, researchers assigned 30 symptomatic patients to filter-protected or unprotected CAS. Magnetic resonance imaging revealed new lesions in 29% of patients treated with EPDs versus 18% in the unprotected group. This difference was sustained at 30 days (26% vs. 12%, respectively).

Meanwhile, secondary analysis of the SPACE (Stent-Supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy) study, which used an EPD in 25% of procedures (145 vs. 418), showed a 30-day ipsilateral stroke and death rate of 6.2% in the unprotected group and 8.3% in the protected group.

Adverse events were significantly lower in patients treated with a closed cell–design stent. In the open cell–design stent group, the use of EPDs showed some benefit. In all, 50% of all adverse events occurred peri-interventionally, 40% after removal of the endovascular device, and 10% during catheter manipulation in the aortic arch.

Other studies show equal outcomes of unprotected stenting and procedures using protection devices. For example, pooled analysis of the SPACE and EVA-3S studies showed no difference in adverse outcomes between the unprotected and protected groups (7.3% for unprotected, 8.1% for protected group).

"Results of filter-protected versus unprotected stenting are similar," Dr. van den Berg said. "Part of the adverse events occur postprocedure. Hyperperfusion will not be prevented, and protection will not prevent contralateral and vertebrobasilar stroke (arch manipulation). A substantial part of strokes do not occur during the procedure." Another consideration is that "protective devices are not free of complications," he said.

Disadvantages to EPDs include additional time needed to perform a procedure, an additional learning curve, and increased costs. In protected CAS (using filter-type devices), predilatation is sometimes necessary and large emboli (1,000 micrometers) may occur when the surgeon passes a distal EPD through the stenosis. Potential EPD complications include vasospasm and dissection, intimal damage, and microemboli during deployment and retrieval.

"There is no level 1 evidence for a beneficial effect of distal filter protection devices," Dr. van den Berg said. "Several studies indicate that carotid artery stenting can be performed at least as safely without (distal) EPD. Carotid stenting with filter-type EPDs leads to more (micro) embolic events. A large part of the procedure remains unprotected anyway, and adverse events related to EPDs do occur." Given these contradictory findings, more studies are needed to decide whether EPDs should become mandatory with CAS, he added.

The potential for filter-type embolic protection devices to reduce a patient’s risk of macroemboli during carotid angioplasty and stenting makes them ideal for preventing embolic stroke. Or does it? Based on the literature available, there is not enough evidence to suggest that embolic protection devices (EPDs) should be mandatory when treating carotid artery stenosis (CAS), said Dr. Jos C. van den Berg of Ospedale Regionale di Lugano, Switzerland. And some studies suggest that the use of EPDs when treating carotid artery stenosis increases the risk of complications, including stroke and death.

Dr. van den Berg discussed his literature review and how widely study results varied at the VEITH Symposium.

For example, the World Carotid Artery Stent Registry shows that the stroke and death rate was 5.29% without protection devices versus 2.23% with protection devices.

Elsevier,, Inc. From: Textbook of Intterventional Cardiology, 5th Ed.

The Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial revealed that at 30 days after surgery the stroke rate was 3.9 times higher in unprotected carotid angioplasty and stenting (CAS) (4/15 vs. 5/58).

Other studies show the opposite to be true. For example, in 5,341 patients in the Prospective Registry of Carotid Angioplasty and Stenting (Pro-CAS), periprocedural stroke and death rates with and without protective devices were 3.4% and 3.2%, respectively – an indicator that EPD use is not an independent predictor of adverse outcomes.

In another study, researchers assigned 30 symptomatic patients to filter-protected or unprotected CAS. Magnetic resonance imaging revealed new lesions in 29% of patients treated with EPDs versus 18% in the unprotected group. This difference was sustained at 30 days (26% vs. 12%, respectively).

Meanwhile, secondary analysis of the SPACE (Stent-Supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy) study, which used an EPD in 25% of procedures (145 vs. 418), showed a 30-day ipsilateral stroke and death rate of 6.2% in the unprotected group and 8.3% in the protected group.

Adverse events were significantly lower in patients treated with a closed cell–design stent. In the open cell–design stent group, the use of EPDs showed some benefit. In all, 50% of all adverse events occurred peri-interventionally, 40% after removal of the endovascular device, and 10% during catheter manipulation in the aortic arch.

Other studies show equal outcomes of unprotected stenting and procedures using protection devices. For example, pooled analysis of the SPACE and EVA-3S studies showed no difference in adverse outcomes between the unprotected and protected groups (7.3% for unprotected, 8.1% for protected group).

"Results of filter-protected versus unprotected stenting are similar," Dr. van den Berg said. "Part of the adverse events occur postprocedure. Hyperperfusion will not be prevented, and protection will not prevent contralateral and vertebrobasilar stroke (arch manipulation). A substantial part of strokes do not occur during the procedure." Another consideration is that "protective devices are not free of complications," he said.

Disadvantages to EPDs include additional time needed to perform a procedure, an additional learning curve, and increased costs. In protected CAS (using filter-type devices), predilatation is sometimes necessary and large emboli (1,000 micrometers) may occur when the surgeon passes a distal EPD through the stenosis. Potential EPD complications include vasospasm and dissection, intimal damage, and microemboli during deployment and retrieval.

"There is no level 1 evidence for a beneficial effect of distal filter protection devices," Dr. van den Berg said. "Several studies indicate that carotid artery stenting can be performed at least as safely without (distal) EPD. Carotid stenting with filter-type EPDs leads to more (micro) embolic events. A large part of the procedure remains unprotected anyway, and adverse events related to EPDs do occur." Given these contradictory findings, more studies are needed to decide whether EPDs should become mandatory with CAS, he added.

Theories of how nevi develop have received little attention in the last 100 years, but that appears to be changing, according to Dr. Ashfaq A. Marghoob.

Dr. Marghoob, a dermatologist at Memorial Sloan-Kettering Cancer Center in New York, discussed what is currently known about nevogenesis. "Since nevi are associated with an increased risk of melanoma, understanding nevogenesis may help to unravel some of the mysteries of melanomagenesis," he noted at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

German physician Paul Gerson Unna proposed the "Abtropfung" theory of nevogenesis in 1893. The theory holds that melanocytic nevus cells develop in the epidermis and drop off to the dermis over time. "For almost a century this theory of nevogenesis was accepted as truth and remained uncontested," Dr. Marghoob said.

During the past few decades, however, newly acquired observations from histopathology and embryogenesis have led some researchers to question the validity of the "Abtropfung" theory in favor of the "Hochsteigerung" theory.

Dr. Stewart F. Cramer, a pathologist, proposed the latter in 1984. It essentially is the reverse of the Abtropfung theory, meaning that nevus cells migrate from the dermis to the epidermis.

Photo courtesy Dr. Ashfaq A. Marghoob

For example, in one histopathology study, no child younger than 10 had a purely junctional nevus, 52% had compound nevi, and 48% had dermal nevi (Am. J. Dermatopathol. 1998;20:135-9). In patients older than age 60, 12% had junctional nevi, 23% had compound nevi, and 65% had dermal nevi. Had the Abtropfung theory been correct, most childhood nevi would be junctional, and most nevi in late adult life would be intradermal. The researchers said their findings better fit the theory of upward migration of nevus cells.

In another study, researchers reviewed all biopsy reports for junctional nevi from 2001 at the Penn State Milton S. Hershey Medical Center and found that these lesions occur with similar frequency in the young and in the elderly (J. Am. Acad. Dermatol 2007;56:825-7).

Photo courtesy Dr. Ashfaq A. Marghoob

"However, new insights gained from the epidemiology of nevi, cross-sectional and longitudinal study of nevi, dermoscopy and confocal microscopy investigation of nevi, as well as the cellular and molecular study of nevi, brings into question the aforementioned theories," Dr. Marghoob says.

In fact, he added, there is insufficient evidence that either theory is the norm in postnatal life. More longitudinal studies are needed to determine nevus evolution.

Dr. Marghoob reported having no relevant conflicts of interest. SDEF and this news organization are owned by Elsevier.

Theories of how nevi develop have received little attention in the last 100 years, but that appears to be changing, according to Dr. Ashfaq A. Marghoob.

Dr. Marghoob, a dermatologist at Memorial Sloan-Kettering Cancer Center in New York, discussed what is currently known about nevogenesis. "Since nevi are associated with an increased risk of melanoma, understanding nevogenesis may help to unravel some of the mysteries of melanomagenesis," he noted at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

German physician Paul Gerson Unna proposed the "Abtropfung" theory of nevogenesis in 1893. The theory holds that melanocytic nevus cells develop in the epidermis and drop off to the dermis over time. "For almost a century this theory of nevogenesis was accepted as truth and remained uncontested," Dr. Marghoob said.

During the past few decades, however, newly acquired observations from histopathology and embryogenesis have led some researchers to question the validity of the "Abtropfung" theory in favor of the "Hochsteigerung" theory.

Dr. Stewart F. Cramer, a pathologist, proposed the latter in 1984. It essentially is the reverse of the Abtropfung theory, meaning that nevus cells migrate from the dermis to the epidermis.

Photo courtesy Dr. Ashfaq A. Marghoob

For example, in one histopathology study, no child younger than 10 had a purely junctional nevus, 52% had compound nevi, and 48% had dermal nevi (Am. J. Dermatopathol. 1998;20:135-9). In patients older than age 60, 12% had junctional nevi, 23% had compound nevi, and 65% had dermal nevi. Had the Abtropfung theory been correct, most childhood nevi would be junctional, and most nevi in late adult life would be intradermal. The researchers said their findings better fit the theory of upward migration of nevus cells.

In another study, researchers reviewed all biopsy reports for junctional nevi from 2001 at the Penn State Milton S. Hershey Medical Center and found that these lesions occur with similar frequency in the young and in the elderly (J. Am. Acad. Dermatol 2007;56:825-7).

Photo courtesy Dr. Ashfaq A. Marghoob

"However, new insights gained from the epidemiology of nevi, cross-sectional and longitudinal study of nevi, dermoscopy and confocal microscopy investigation of nevi, as well as the cellular and molecular study of nevi, brings into question the aforementioned theories," Dr. Marghoob says.

In fact, he added, there is insufficient evidence that either theory is the norm in postnatal life. More longitudinal studies are needed to determine nevus evolution.

Dr. Marghoob reported having no relevant conflicts of interest. SDEF and this news organization are owned by Elsevier.

Theories of how nevi develop have received little attention in the last 100 years, but that appears to be changing, according to Dr. Ashfaq A. Marghoob.

Dr. Marghoob, a dermatologist at Memorial Sloan-Kettering Cancer Center in New York, discussed what is currently known about nevogenesis. "Since nevi are associated with an increased risk of melanoma, understanding nevogenesis may help to unravel some of the mysteries of melanomagenesis," he noted at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

German physician Paul Gerson Unna proposed the "Abtropfung" theory of nevogenesis in 1893. The theory holds that melanocytic nevus cells develop in the epidermis and drop off to the dermis over time. "For almost a century this theory of nevogenesis was accepted as truth and remained uncontested," Dr. Marghoob said.

During the past few decades, however, newly acquired observations from histopathology and embryogenesis have led some researchers to question the validity of the "Abtropfung" theory in favor of the "Hochsteigerung" theory.

Dr. Stewart F. Cramer, a pathologist, proposed the latter in 1984. It essentially is the reverse of the Abtropfung theory, meaning that nevus cells migrate from the dermis to the epidermis.

Photo courtesy Dr. Ashfaq A. Marghoob

For example, in one histopathology study, no child younger than 10 had a purely junctional nevus, 52% had compound nevi, and 48% had dermal nevi (Am. J. Dermatopathol. 1998;20:135-9). In patients older than age 60, 12% had junctional nevi, 23% had compound nevi, and 65% had dermal nevi. Had the Abtropfung theory been correct, most childhood nevi would be junctional, and most nevi in late adult life would be intradermal. The researchers said their findings better fit the theory of upward migration of nevus cells.

In another study, researchers reviewed all biopsy reports for junctional nevi from 2001 at the Penn State Milton S. Hershey Medical Center and found that these lesions occur with similar frequency in the young and in the elderly (J. Am. Acad. Dermatol 2007;56:825-7).

Photo courtesy Dr. Ashfaq A. Marghoob

"However, new insights gained from the epidemiology of nevi, cross-sectional and longitudinal study of nevi, dermoscopy and confocal microscopy investigation of nevi, as well as the cellular and molecular study of nevi, brings into question the aforementioned theories," Dr. Marghoob says.

In fact, he added, there is insufficient evidence that either theory is the norm in postnatal life. More longitudinal studies are needed to determine nevus evolution.

Dr. Marghoob reported having no relevant conflicts of interest. SDEF and this news organization are owned by Elsevier.

During the past 30 years, only two drugs – dacarbazine and interleukin-2 – have been approved by the Food and Drug Administration for treating metastatic melanoma, and while these drugs help control the disease in a small percentage of patients, they do not appear to improve survival.

However, agents introduced within the last 2 years are reported to improve survival, Dr. Richard D. Carvajal of Memorial Sloan-Kettering Cancer Center, said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The first is ipilimumab (also known as MDX-010 or MDX-101), a monoclonal antibody that binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). Normally, CTLA-4 slows the immune system, but this treatment allows the immune system to recognize melanoma, Dr. Carvajal said.

In one study reported last year, ipilimumab improved overall survival in patients with previously treated metastatic melanoma (N. Engl. J. Med. 2010;363;711-23). Specifically, patients who received ipilimumab plus glycoprotein 100 (gp100) had an overall survival of 10 months, while those who received gp100 alone had a survival rate of 6.4 months. The median overall survival for patients taking ipilimumab alone was 10.1 months.

The second treatment, PLX4032 (also known as RG7204 or RO5185426), works by inhibiting the mutated BRAF protein found in about half of all cases of metastatic melanoma. In January, the manufacturer, Plexxikon, announced that a phase III clinical study showed a significant survival benefit in people with previously untreated BRAF V600 mutation-positive metastatic melanoma.

Study participants who received PLX4032 lived longer (overall survival) and also lived longer without their disease getting worse (progression-free survival), compared with participants who received dacarbazine, the current standard of care, Dr. Carvajal said, adding "these are really large breakthroughs."

Dr. Carvajal disclosed that he has served as a consultant for Novartis. SDEF and this news organization are owned by Elsevier.

During the past 30 years, only two drugs – dacarbazine and interleukin-2 – have been approved by the Food and Drug Administration for treating metastatic melanoma, and while these drugs help control the disease in a small percentage of patients, they do not appear to improve survival.

However, agents introduced within the last 2 years are reported to improve survival, Dr. Richard D. Carvajal of Memorial Sloan-Kettering Cancer Center, said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The first is ipilimumab (also known as MDX-010 or MDX-101), a monoclonal antibody that binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). Normally, CTLA-4 slows the immune system, but this treatment allows the immune system to recognize melanoma, Dr. Carvajal said.

In one study reported last year, ipilimumab improved overall survival in patients with previously treated metastatic melanoma (N. Engl. J. Med. 2010;363;711-23). Specifically, patients who received ipilimumab plus glycoprotein 100 (gp100) had an overall survival of 10 months, while those who received gp100 alone had a survival rate of 6.4 months. The median overall survival for patients taking ipilimumab alone was 10.1 months.

The second treatment, PLX4032 (also known as RG7204 or RO5185426), works by inhibiting the mutated BRAF protein found in about half of all cases of metastatic melanoma. In January, the manufacturer, Plexxikon, announced that a phase III clinical study showed a significant survival benefit in people with previously untreated BRAF V600 mutation-positive metastatic melanoma.

Study participants who received PLX4032 lived longer (overall survival) and also lived longer without their disease getting worse (progression-free survival), compared with participants who received dacarbazine, the current standard of care, Dr. Carvajal said, adding "these are really large breakthroughs."

Dr. Carvajal disclosed that he has served as a consultant for Novartis. SDEF and this news organization are owned by Elsevier.

During the past 30 years, only two drugs – dacarbazine and interleukin-2 – have been approved by the Food and Drug Administration for treating metastatic melanoma, and while these drugs help control the disease in a small percentage of patients, they do not appear to improve survival.

However, agents introduced within the last 2 years are reported to improve survival, Dr. Richard D. Carvajal of Memorial Sloan-Kettering Cancer Center, said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The first is ipilimumab (also known as MDX-010 or MDX-101), a monoclonal antibody that binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). Normally, CTLA-4 slows the immune system, but this treatment allows the immune system to recognize melanoma, Dr. Carvajal said.

In one study reported last year, ipilimumab improved overall survival in patients with previously treated metastatic melanoma (N. Engl. J. Med. 2010;363;711-23). Specifically, patients who received ipilimumab plus glycoprotein 100 (gp100) had an overall survival of 10 months, while those who received gp100 alone had a survival rate of 6.4 months. The median overall survival for patients taking ipilimumab alone was 10.1 months.

The second treatment, PLX4032 (also known as RG7204 or RO5185426), works by inhibiting the mutated BRAF protein found in about half of all cases of metastatic melanoma. In January, the manufacturer, Plexxikon, announced that a phase III clinical study showed a significant survival benefit in people with previously untreated BRAF V600 mutation-positive metastatic melanoma.

Study participants who received PLX4032 lived longer (overall survival) and also lived longer without their disease getting worse (progression-free survival), compared with participants who received dacarbazine, the current standard of care, Dr. Carvajal said, adding "these are really large breakthroughs."

Dr. Carvajal disclosed that he has served as a consultant for Novartis. SDEF and this news organization are owned by Elsevier.

During the past 30 years, only two drugs – dacarbazine and interleukin-2 – have been approved by the Food and Drug Administration for treating metastatic melanoma, and while these drugs help control the disease in a small percentage of patients, they do not appear to improve survival.

However, agents introduced within the last 2 years are reported to improve survival, Dr. Richard D. Carvajal of Memorial Sloan-Kettering Cancer Center, said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The first is ipilimumab (also known as MDX-010 or MDX-101), a monoclonal antibody that binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). Normally, CTLA-4 slows the immune system, but this treatment allows the immune system to recognize melanoma, Dr. Carvajal said.

In one study reported last year, ipilimumab improved overall survival in patients with previously treated metastatic melanoma (N. Engl. J. Med. 2010;363;711-23). Specifically, patients who received ipilimumab plus glycoprotein 100 (gp100) had an overall survival of 10 months, while those who received gp100 alone had a survival rate of 6.4 months. The median overall survival for patients taking ipilimumab alone was 10.1 months.

The second treatment, PLX4032 (also known as RG7204 or RO5185426), works by inhibiting the mutated BRAF protein found in about half of all cases of metastatic melanoma. In January, the manufacturer, Plexxikon, announced that a phase III clinical study showed a significant survival benefit in people with previously untreated BRAF V600 mutation-positive metastatic melanoma.

Study participants who received PLX4032 lived longer (overall survival) and also lived longer without their disease getting worse (progression-free survival), compared with participants who received dacarbazine, the current standard of care, Dr. Carvajal said, adding "these are really large breakthroughs."

Dr. Carvajal disclosed that he has served as a consultant for Novartis. SDEF and this news organization are owned by Elsevier.

During the past 30 years, only two drugs – dacarbazine and interleukin-2 – have been approved by the Food and Drug Administration for treating metastatic melanoma, and while these drugs help control the disease in a small percentage of patients, they do not appear to improve survival.

However, agents introduced within the last 2 years are reported to improve survival, Dr. Richard D. Carvajal of Memorial Sloan-Kettering Cancer Center, said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The first is ipilimumab (also known as MDX-010 or MDX-101), a monoclonal antibody that binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). Normally, CTLA-4 slows the immune system, but this treatment allows the immune system to recognize melanoma, Dr. Carvajal said.

In one study reported last year, ipilimumab improved overall survival in patients with previously treated metastatic melanoma (N. Engl. J. Med. 2010;363;711-23). Specifically, patients who received ipilimumab plus glycoprotein 100 (gp100) had an overall survival of 10 months, while those who received gp100 alone had a survival rate of 6.4 months. The median overall survival for patients taking ipilimumab alone was 10.1 months.

The second treatment, PLX4032 (also known as RG7204 or RO5185426), works by inhibiting the mutated BRAF protein found in about half of all cases of metastatic melanoma. In January, the manufacturer, Plexxikon, announced that a phase III clinical study showed a significant survival benefit in people with previously untreated BRAF V600 mutation-positive metastatic melanoma.

Study participants who received PLX4032 lived longer (overall survival) and also lived longer without their disease getting worse (progression-free survival), compared with participants who received dacarbazine, the current standard of care, Dr. Carvajal said, adding "these are really large breakthroughs."

Dr. Carvajal disclosed that he has served as a consultant for Novartis. SDEF and this news organization are owned by Elsevier.

During the past 30 years, only two drugs – dacarbazine and interleukin-2 – have been approved by the Food and Drug Administration for treating metastatic melanoma, and while these drugs help control the disease in a small percentage of patients, they do not appear to improve survival.

However, agents introduced within the last 2 years are reported to improve survival, Dr. Richard D. Carvajal of Memorial Sloan-Kettering Cancer Center, said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The first is ipilimumab (also known as MDX-010 or MDX-101), a monoclonal antibody that binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). Normally, CTLA-4 slows the immune system, but this treatment allows the immune system to recognize melanoma, Dr. Carvajal said.

In one study reported last year, ipilimumab improved overall survival in patients with previously treated metastatic melanoma (N. Engl. J. Med. 2010;363;711-23). Specifically, patients who received ipilimumab plus glycoprotein 100 (gp100) had an overall survival of 10 months, while those who received gp100 alone had a survival rate of 6.4 months. The median overall survival for patients taking ipilimumab alone was 10.1 months.

The second treatment, PLX4032 (also known as RG7204 or RO5185426), works by inhibiting the mutated BRAF protein found in about half of all cases of metastatic melanoma. In January, the manufacturer, Plexxikon, announced that a phase III clinical study showed a significant survival benefit in people with previously untreated BRAF V600 mutation-positive metastatic melanoma.

Study participants who received PLX4032 lived longer (overall survival) and also lived longer without their disease getting worse (progression-free survival), compared with participants who received dacarbazine, the current standard of care, Dr. Carvajal said, adding "these are really large breakthroughs."

Dr. Carvajal disclosed that he has served as a consultant for Novartis. SDEF and this news organization are owned by Elsevier.

During the past 30 years, only two drugs – dacarbazine and interleukin-2 – have been approved by the Food and Drug Administration for treating metastatic melanoma, and while these drugs help control the disease in a small percentage of patients, they do not appear to improve survival.

However, agents introduced within the last 2 years are reported to improve survival, Dr. Richard D. Carvajal of Memorial Sloan-Kettering Cancer Center, said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The first is ipilimumab (also known as MDX-010), a monoclonal antibody that binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA4). Normally, CTLA4 functions as one of several negative feedback mechanisms within the immune system. Treatment with ipilimumab takes away this negative feedback mechanism and allows the immune system to recognize and combat melanoma, Dr. Carvajal said.

In one study reported last year, ipilimumab improved overall survival in patients with previously treated metastatic melanoma (N. Engl. J. Med. 2010;363;711-23). Specifically, patients who received ipilimumab plus glycoprotein 100 (gp100) vaccine had an overall survival of 10 months, while those who received gp100 alone had a survival rate of 6.4 months. The median overall survival for patients taking ipilimumab alone was 10.1 months.

Even more striking, the 1-year overall survival rate for patients receiving ipilimumab alone or in combination with the vaccine was approximately 45%, significantly better than the 1-year overall survival rate of 25% achieved with the vaccine alone.

The second agent, PLX4032 (also known as RG7204 or RO5185426), works by inhibiting the mutated BRAF protein found in about half of all cases of metastatic melanoma. In January, the manufacturer, Plexxikon, announced that a phase III clinical study showed a significant survival benefit in people with previously untreated BRAF V600 mutation-positive metastatic melanoma.

Study participants who received PLX4032 lived longer (overall survival) and also lived longer without their disease getting worse (progression-free survival), compared with participants who received dacarbazine, the current standard of care.

"As these are the first two drugs ever demonstrated to improve survival in patients with advanced melanoma, these recent developments are extremely significant breakthroughs for the management of this disease," Dr. Carvajal said.

Dr. Carvajal disclosed that he has served as a consultant for Novartis. SDEF and this news organization are owned by Elsevier.

During the past 30 years, only two drugs – dacarbazine and interleukin-2 – have been approved by the Food and Drug Administration for treating metastatic melanoma, and while these drugs help control the disease in a small percentage of patients, they do not appear to improve survival.

However, agents introduced within the last 2 years are reported to improve survival, Dr. Richard D. Carvajal of Memorial Sloan-Kettering Cancer Center, said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The first is ipilimumab (also known as MDX-010), a monoclonal antibody that binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA4). Normally, CTLA4 functions as one of several negative feedback mechanisms within the immune system. Treatment with ipilimumab takes away this negative feedback mechanism and allows the immune system to recognize and combat melanoma, Dr. Carvajal said.

In one study reported last year, ipilimumab improved overall survival in patients with previously treated metastatic melanoma (N. Engl. J. Med. 2010;363;711-23). Specifically, patients who received ipilimumab plus glycoprotein 100 (gp100) vaccine had an overall survival of 10 months, while those who received gp100 alone had a survival rate of 6.4 months. The median overall survival for patients taking ipilimumab alone was 10.1 months.

Even more striking, the 1-year overall survival rate for patients receiving ipilimumab alone or in combination with the vaccine was approximately 45%, significantly better than the 1-year overall survival rate of 25% achieved with the vaccine alone.

The second agent, PLX4032 (also known as RG7204 or RO5185426), works by inhibiting the mutated BRAF protein found in about half of all cases of metastatic melanoma. In January, the manufacturer, Plexxikon, announced that a phase III clinical study showed a significant survival benefit in people with previously untreated BRAF V600 mutation-positive metastatic melanoma.

Study participants who received PLX4032 lived longer (overall survival) and also lived longer without their disease getting worse (progression-free survival), compared with participants who received dacarbazine, the current standard of care.

"As these are the first two drugs ever demonstrated to improve survival in patients with advanced melanoma, these recent developments are extremely significant breakthroughs for the management of this disease," Dr. Carvajal said.

Dr. Carvajal disclosed that he has served as a consultant for Novartis. SDEF and this news organization are owned by Elsevier.

During the past 30 years, only two drugs – dacarbazine and interleukin-2 – have been approved by the Food and Drug Administration for treating metastatic melanoma, and while these drugs help control the disease in a small percentage of patients, they do not appear to improve survival.

However, agents introduced within the last 2 years are reported to improve survival, Dr. Richard D. Carvajal of Memorial Sloan-Kettering Cancer Center, said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The first is ipilimumab (also known as MDX-010), a monoclonal antibody that binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA4). Normally, CTLA4 functions as one of several negative feedback mechanisms within the immune system. Treatment with ipilimumab takes away this negative feedback mechanism and allows the immune system to recognize and combat melanoma, Dr. Carvajal said.

In one study reported last year, ipilimumab improved overall survival in patients with previously treated metastatic melanoma (N. Engl. J. Med. 2010;363;711-23). Specifically, patients who received ipilimumab plus glycoprotein 100 (gp100) vaccine had an overall survival of 10 months, while those who received gp100 alone had a survival rate of 6.4 months. The median overall survival for patients taking ipilimumab alone was 10.1 months.

Even more striking, the 1-year overall survival rate for patients receiving ipilimumab alone or in combination with the vaccine was approximately 45%, significantly better than the 1-year overall survival rate of 25% achieved with the vaccine alone.

The second agent, PLX4032 (also known as RG7204 or RO5185426), works by inhibiting the mutated BRAF protein found in about half of all cases of metastatic melanoma. In January, the manufacturer, Plexxikon, announced that a phase III clinical study showed a significant survival benefit in people with previously untreated BRAF V600 mutation-positive metastatic melanoma.

Study participants who received PLX4032 lived longer (overall survival) and also lived longer without their disease getting worse (progression-free survival), compared with participants who received dacarbazine, the current standard of care.

"As these are the first two drugs ever demonstrated to improve survival in patients with advanced melanoma, these recent developments are extremely significant breakthroughs for the management of this disease," Dr. Carvajal said.

Dr. Carvajal disclosed that he has served as a consultant for Novartis. SDEF and this news organization are owned by Elsevier.

Clinical observation calls into question some of the preconceived notions about melanoma pathogenesis, according to Dr. James M. Grichnik.

The traditional model is that melanomas initially develop from differentiated melanocytes in the epidermis and then invade the dermis. This is largely based on pathologic features, said Dr. Grichnik, director of the melanoma program at Sylvester Cancer Comprehensive Center, and professor of dermatology at the University of Miami. Specifically, the lowest-risk melanoma in situ tumors are thought to remain in the epidermis, while higher-risk tumors invade the deeper dermal tissues.

However, there is a newer model of melanomagenesis that is based on stem cell biology, Dr. Grichnik said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF). The model suggests that stem cells in the dermis can become mature epidermal melanocytes, and that early epigenetic or genetic alterations leading to transformation may take place in the dermis rather than in the epidermis (J. Invest. Dermatol. 2008;128:2365-80).

Also, stem cell markers CD166, CD133, and nestin are expressed at significantly higher levels in melanoma compared to banal nevi. Nestin was found to be significantly increased in metastatic melanoma, compared with primary melanoma, suggesting this subpopulation of cells may be particularly virulent (Mod. Pathol. 2007;20:102-7).

The problem with tumor stem cell components, however, is that they may not have normal antigens, and components may escape into the lymph system rather than adhere to the lymph nodes.

"So, the immune system doesn't do a good job of catching them," Dr. Grichnik said, adding that tumors contain a heterogeneous population of cells. "They're trying to differentiate towards a normal pigment of cells, the melanocytes. Some of the heterogeneous population has the antigens that the immune system destroys, but the stem cell population doesn't."

Recognition of these pathways may lead to better diagnostic and therapeutic tools. A multiple treatment approach most likely will be needed.

"One approach is to destroy proliferative cells and another is to destroy the nonproliferative tumor stem cells," Dr. Grichnik said. "We'll have to develop therapies that are specific to the tumor stem cells."

Dr. Grichnik disclosed that he is a major shareholder and founder of DigitalDerm, and serves in a consultant role for Electro-Optical Systems and Spectral Image.

SDEF and this news organization are owned by Elsevier.

Clinical observation calls into question some of the preconceived notions about melanoma pathogenesis, according to Dr. James M. Grichnik.

The traditional model is that melanomas initially develop from differentiated melanocytes in the epidermis and then invade the dermis. This is largely based on pathologic features, said Dr. Grichnik, director of the melanoma program at Sylvester Cancer Comprehensive Center, and professor of dermatology at the University of Miami. Specifically, the lowest-risk melanoma in situ tumors are thought to remain in the epidermis, while higher-risk tumors invade the deeper dermal tissues.

However, there is a newer model of melanomagenesis that is based on stem cell biology, Dr. Grichnik said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF). The model suggests that stem cells in the dermis can become mature epidermal melanocytes, and that early epigenetic or genetic alterations leading to transformation may take place in the dermis rather than in the epidermis (J. Invest. Dermatol. 2008;128:2365-80).

Also, stem cell markers CD166, CD133, and nestin are expressed at significantly higher levels in melanoma compared to banal nevi. Nestin was found to be significantly increased in metastatic melanoma, compared with primary melanoma, suggesting this subpopulation of cells may be particularly virulent (Mod. Pathol. 2007;20:102-7).

The problem with tumor stem cell components, however, is that they may not have normal antigens, and components may escape into the lymph system rather than adhere to the lymph nodes.

"So, the immune system doesn't do a good job of catching them," Dr. Grichnik said, adding that tumors contain a heterogeneous population of cells. "They're trying to differentiate towards a normal pigment of cells, the melanocytes. Some of the heterogeneous population has the antigens that the immune system destroys, but the stem cell population doesn't."

Recognition of these pathways may lead to better diagnostic and therapeutic tools. A multiple treatment approach most likely will be needed.

"One approach is to destroy proliferative cells and another is to destroy the nonproliferative tumor stem cells," Dr. Grichnik said. "We'll have to develop therapies that are specific to the tumor stem cells."

Dr. Grichnik disclosed that he is a major shareholder and founder of DigitalDerm, and serves in a consultant role for Electro-Optical Systems and Spectral Image.

SDEF and this news organization are owned by Elsevier.

Clinical observation calls into question some of the preconceived notions about melanoma pathogenesis, according to Dr. James M. Grichnik.

The traditional model is that melanomas initially develop from differentiated melanocytes in the epidermis and then invade the dermis. This is largely based on pathologic features, said Dr. Grichnik, director of the melanoma program at Sylvester Cancer Comprehensive Center, and professor of dermatology at the University of Miami. Specifically, the lowest-risk melanoma in situ tumors are thought to remain in the epidermis, while higher-risk tumors invade the deeper dermal tissues.

However, there is a newer model of melanomagenesis that is based on stem cell biology, Dr. Grichnik said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF). The model suggests that stem cells in the dermis can become mature epidermal melanocytes, and that early epigenetic or genetic alterations leading to transformation may take place in the dermis rather than in the epidermis (J. Invest. Dermatol. 2008;128:2365-80).

Also, stem cell markers CD166, CD133, and nestin are expressed at significantly higher levels in melanoma compared to banal nevi. Nestin was found to be significantly increased in metastatic melanoma, compared with primary melanoma, suggesting this subpopulation of cells may be particularly virulent (Mod. Pathol. 2007;20:102-7).

The problem with tumor stem cell components, however, is that they may not have normal antigens, and components may escape into the lymph system rather than adhere to the lymph nodes.

"So, the immune system doesn't do a good job of catching them," Dr. Grichnik said, adding that tumors contain a heterogeneous population of cells. "They're trying to differentiate towards a normal pigment of cells, the melanocytes. Some of the heterogeneous population has the antigens that the immune system destroys, but the stem cell population doesn't."

Recognition of these pathways may lead to better diagnostic and therapeutic tools. A multiple treatment approach most likely will be needed.

"One approach is to destroy proliferative cells and another is to destroy the nonproliferative tumor stem cells," Dr. Grichnik said. "We'll have to develop therapies that are specific to the tumor stem cells."

Dr. Grichnik disclosed that he is a major shareholder and founder of DigitalDerm, and serves in a consultant role for Electro-Optical Systems and Spectral Image.

SDEF and this news organization are owned by Elsevier.