Melanoma

MONTEREY, CALIF. — Cutaneous squamous cell carcinoma can take many forms, with vastly different biological behaviors and risk profiles.

Yet, "with relatively few exceptions, they have a tendency to simply be lumped by the nondermatologist clinician, the general surgeon, and the general pathologist," said Dr. Ronald Barr in calling for a comprehensive clinicopathologic classification of cutaneous SCC subtypes based on malignant potential.

Subtypes of SCC are not "histological curiosities," but distinct entities that offer important clues as to management and prognosis of individual patients, maintained Dr. Barr during a presentation to the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

A system of histologic subtypes of SCC has been proposed by Dr. Barr, professor emeritus of dermatology and pathology at the University of California, Irvine, and his colleagues (J. Cutan. Pathol. 2006;33:191-206, 261-79). The suggested subtypes include low-risk SCCs, which carry a less than 3% risk of metastasis; intermediate-risk SCCs, which have a 3%-10% risk of metastasis; high-risk SCCs, with a greater than 10% risk of metastasis; and SCCs of indeterminate malignant potential, explained Dr. Barr.

These subtype categories would include:

▸ Low-risk, invasive SCCs. These would include SCCs arising in sun-damaged skin of elderly patients (95% of cases), verrucous carcinoma and other human papillomavirus-related SCCs in immunocompetent patients, spindle cell SCC (unrelated to radiation exposure), and trichilemmal carcinoma.

▸ Intermediate-risk SCCs. Suggested category inclusions are acantholytic SCC, lymphoepitheliomalike carcinoma of the skin (LELCS), intraepidermal epithelioma (IEE), and Borst-Jadassohn tumor with invasion.

▸ High-risk SCCs. This subtype category would include invasive Bowen's disease; desmoplastic SCCs; malignant proliferating pilar tumor/cyst; de novo SCC; adenosquamous cell carcinoma; and SCC arising in association with radiation, burn scars, chronic conditions, or immunosuppression.

▸ SCCs of indeterminate malignant potential. Proposed subtypes for this category include signet-ring and clear cell SCC; pigmented, papillary, and follicular SCC; SCC arising in adnexal cysts; and possibly keratoacanthoma.

Dr. Barr acknowledged that many of the tumors he categorized as intermediate- or high-risk are rare, and there have been few studies to accurately determine their malignant poten- tial. However, this classification system would help to structure research by subtype and help to clarify future research by separating out entities that carry a higher risk potential than a superficially invasive, well-differentiated SCC arising within actinic keratoses on sun-damaged skin.

In addition to histologic subtypes, he called for more pathologic reporting of prognostic factors in individual SCC cases including the grade of differentiation (Broders' grades I-IV), tumor size and depth of invasion, and presence or absence of perineural or hematolymphatic invasion.

Fewer than 35% of patients with metastatic SCC survive for 5 years, in stark contrast to the generally excellent prognosis of SCC. "When squamous cell carcinoma metastasizes, the literature just clumps [these cases]," but clearly, individual characteristics make a difference, he said.

With regard to depth of invasion, one study found that tumors less than 2 mm thick never metastasized, those 2 mm to 6 mm metastasized at a rate of 4.5%, and those deeper than 6 mm metastasized at a rate of 15% (Am. J. Clin. Pathol. 1990;94:624-7). Low- versus high-grade differentiation carries a highly variable rate of metastasis as well (33% vs. 9%), Dr. Barr said. Perineural invasion is associated with rates of metastasis between 35% and 80%.

MONTEREY, CALIF. — Cutaneous squamous cell carcinoma can take many forms, with vastly different biological behaviors and risk profiles.

Yet, "with relatively few exceptions, they have a tendency to simply be lumped by the nondermatologist clinician, the general surgeon, and the general pathologist," said Dr. Ronald Barr in calling for a comprehensive clinicopathologic classification of cutaneous SCC subtypes based on malignant potential.

Subtypes of SCC are not "histological curiosities," but distinct entities that offer important clues as to management and prognosis of individual patients, maintained Dr. Barr during a presentation to the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

A system of histologic subtypes of SCC has been proposed by Dr. Barr, professor emeritus of dermatology and pathology at the University of California, Irvine, and his colleagues (J. Cutan. Pathol. 2006;33:191-206, 261-79). The suggested subtypes include low-risk SCCs, which carry a less than 3% risk of metastasis; intermediate-risk SCCs, which have a 3%-10% risk of metastasis; high-risk SCCs, with a greater than 10% risk of metastasis; and SCCs of indeterminate malignant potential, explained Dr. Barr.

These subtype categories would include:

▸ Low-risk, invasive SCCs. These would include SCCs arising in sun-damaged skin of elderly patients (95% of cases), verrucous carcinoma and other human papillomavirus-related SCCs in immunocompetent patients, spindle cell SCC (unrelated to radiation exposure), and trichilemmal carcinoma.

▸ Intermediate-risk SCCs. Suggested category inclusions are acantholytic SCC, lymphoepitheliomalike carcinoma of the skin (LELCS), intraepidermal epithelioma (IEE), and Borst-Jadassohn tumor with invasion.

▸ High-risk SCCs. This subtype category would include invasive Bowen's disease; desmoplastic SCCs; malignant proliferating pilar tumor/cyst; de novo SCC; adenosquamous cell carcinoma; and SCC arising in association with radiation, burn scars, chronic conditions, or immunosuppression.

▸ SCCs of indeterminate malignant potential. Proposed subtypes for this category include signet-ring and clear cell SCC; pigmented, papillary, and follicular SCC; SCC arising in adnexal cysts; and possibly keratoacanthoma.

Dr. Barr acknowledged that many of the tumors he categorized as intermediate- or high-risk are rare, and there have been few studies to accurately determine their malignant poten- tial. However, this classification system would help to structure research by subtype and help to clarify future research by separating out entities that carry a higher risk potential than a superficially invasive, well-differentiated SCC arising within actinic keratoses on sun-damaged skin.

In addition to histologic subtypes, he called for more pathologic reporting of prognostic factors in individual SCC cases including the grade of differentiation (Broders' grades I-IV), tumor size and depth of invasion, and presence or absence of perineural or hematolymphatic invasion.

Fewer than 35% of patients with metastatic SCC survive for 5 years, in stark contrast to the generally excellent prognosis of SCC. "When squamous cell carcinoma metastasizes, the literature just clumps [these cases]," but clearly, individual characteristics make a difference, he said.

With regard to depth of invasion, one study found that tumors less than 2 mm thick never metastasized, those 2 mm to 6 mm metastasized at a rate of 4.5%, and those deeper than 6 mm metastasized at a rate of 15% (Am. J. Clin. Pathol. 1990;94:624-7). Low- versus high-grade differentiation carries a highly variable rate of metastasis as well (33% vs. 9%), Dr. Barr said. Perineural invasion is associated with rates of metastasis between 35% and 80%.

MONTEREY, CALIF. — Cutaneous squamous cell carcinoma can take many forms, with vastly different biological behaviors and risk profiles.

Yet, "with relatively few exceptions, they have a tendency to simply be lumped by the nondermatologist clinician, the general surgeon, and the general pathologist," said Dr. Ronald Barr in calling for a comprehensive clinicopathologic classification of cutaneous SCC subtypes based on malignant potential.

Subtypes of SCC are not "histological curiosities," but distinct entities that offer important clues as to management and prognosis of individual patients, maintained Dr. Barr during a presentation to the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

A system of histologic subtypes of SCC has been proposed by Dr. Barr, professor emeritus of dermatology and pathology at the University of California, Irvine, and his colleagues (J. Cutan. Pathol. 2006;33:191-206, 261-79). The suggested subtypes include low-risk SCCs, which carry a less than 3% risk of metastasis; intermediate-risk SCCs, which have a 3%-10% risk of metastasis; high-risk SCCs, with a greater than 10% risk of metastasis; and SCCs of indeterminate malignant potential, explained Dr. Barr.

These subtype categories would include:

▸ Low-risk, invasive SCCs. These would include SCCs arising in sun-damaged skin of elderly patients (95% of cases), verrucous carcinoma and other human papillomavirus-related SCCs in immunocompetent patients, spindle cell SCC (unrelated to radiation exposure), and trichilemmal carcinoma.

▸ Intermediate-risk SCCs. Suggested category inclusions are acantholytic SCC, lymphoepitheliomalike carcinoma of the skin (LELCS), intraepidermal epithelioma (IEE), and Borst-Jadassohn tumor with invasion.

▸ High-risk SCCs. This subtype category would include invasive Bowen's disease; desmoplastic SCCs; malignant proliferating pilar tumor/cyst; de novo SCC; adenosquamous cell carcinoma; and SCC arising in association with radiation, burn scars, chronic conditions, or immunosuppression.

▸ SCCs of indeterminate malignant potential. Proposed subtypes for this category include signet-ring and clear cell SCC; pigmented, papillary, and follicular SCC; SCC arising in adnexal cysts; and possibly keratoacanthoma.

Dr. Barr acknowledged that many of the tumors he categorized as intermediate- or high-risk are rare, and there have been few studies to accurately determine their malignant poten- tial. However, this classification system would help to structure research by subtype and help to clarify future research by separating out entities that carry a higher risk potential than a superficially invasive, well-differentiated SCC arising within actinic keratoses on sun-damaged skin.

In addition to histologic subtypes, he called for more pathologic reporting of prognostic factors in individual SCC cases including the grade of differentiation (Broders' grades I-IV), tumor size and depth of invasion, and presence or absence of perineural or hematolymphatic invasion.

Fewer than 35% of patients with metastatic SCC survive for 5 years, in stark contrast to the generally excellent prognosis of SCC. "When squamous cell carcinoma metastasizes, the literature just clumps [these cases]," but clearly, individual characteristics make a difference, he said.

With regard to depth of invasion, one study found that tumors less than 2 mm thick never metastasized, those 2 mm to 6 mm metastasized at a rate of 4.5%, and those deeper than 6 mm metastasized at a rate of 15% (Am. J. Clin. Pathol. 1990;94:624-7). Low- versus high-grade differentiation carries a highly variable rate of metastasis as well (33% vs. 9%), Dr. Barr said. Perineural invasion is associated with rates of metastasis between 35% and 80%.

MONTEREY, CALIF. — Melanocytic tumors of unknown malignant potential represent some of the most difficult cases in pediatric dermatology, since little agreement exists about their diagnostic criteria, management, or outcome.

"They cause everyone, including pathologists, referring dermatologists, and surgeons, to lose sleep," said Dr. Susan Swetter, director of Stanford (Calif.) University's pigmented lesion and cutaneous melanoma clinic, at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Dr. Swetter described the management of an 8-mm raised, blue-black nodule that appeared behind the right ear of an 11-year-old girl. Satellite blue-black macules appeared on the periphery of the lesion.

A partial 5-mm punch biopsy was reviewed by pathologists at Stanford; the University of California, San Francisco; and Massachusetts General Hospital, Boston. The conclusion was that the lesion was a melanocytic tumor of unknown malignant potential (MELTUMP) with decidedly mixed signals: no ulceration but a relatively high mitotic rate (4/mm2) and probable angiolymphatic invasion.

Differential diagnoses included a pigmented epithelioid melanocytoma, an agminated Spitz nevus, or a "low-grade" melanoma. The patient underwent a "fairly intuitive" comprehensive work-up, including a thorough personal and family history, a review of the timing and speed of growth of the lesion, and a total body skin examination and physical examination, including palpation of regional lymph node basins to assess for metastasis.

Melanoma experts agree that MELTUMP lesions should be completely excised, but the specifics about recommended margins remain hazy, Dr. Swetter explained. Some experts would decide to perform a wide excision in such a case, perhaps including sentinel lymph node biopsy, as if they were treating a melanoma.

At Stanford, where the patient was seen, the decision was made to take a 1-cm margin, narrower than the 2-cm margin that would be appropriate for a 3.7-mm melanoma, and to await the pathology results before deciding whether to perform a sentinel lymph node biopsy or lymph node dissection.

The histology on the wide excision specimen showed that the lesion was symmetrical and well circumscribed with a polypoid proliferation of darkly pigmented melanocytes and a mitotic rate "well below 1/mm2."

Dr. Swetter described the applicable histology images as revealing "deeply pigmented epithelial spindle cells and unmistakable angiolymphatic invasion."

"Our pathologists thought this was most consistent with a melanocytoma diagnosis," and noted its rarity as well as its "uncertain biological behavior," said Dr. Swetter.

A comparative genomic hybridization study was ordered from the UCSF laboratory, but results were estimated to take 6–8 weeks, a period of time that could compromise afferent lymphatic drainage from a scalp lesion and reduce the accuracy of the sentinel node biopsy.

After extensive discussions with the child's parents, the Stanford team elected to perform a sentinel lymph node biopsy but to await the outcome of the comparative genomic hybridization studies prior to performing complete lymph node dissection in the event that the sentinel node specimen was positive. A metastatic work-up with PET/CT scanning was performed "in part … to allay some of the parental concern about metastatic disease." Parenthetically, Dr. Swetter noted that such a scan would not generally be indicated in an asymptomatic patient with no signs of metastatic disease and would not preclude the possibility of a positive sentinel node biopsy. The scans were negative.

Two sentinel lymph nodes were identified and removed in the right cervical neck. One was positive for subcapsular and parenchymal metastatic foci of pigmented epithelioid melanocytoma and stained strongly positive for S100, MelanA, and HMB45.

Ironically, MELTUMP lesions have been associated with a very high rate of sentinel lymph node positivity in the two largest retrospective studies to date (44%–50%, compared with approximately 20% for typical melanomas with Breslow thickness greater than 1 mm).

However, the picture is confusing, because studies also associate atypical Spitz tumors with a very high survival rate despite apparent micrometastases.

In the case of Dr. Swetter's patient, a comparative genomic hybridization offered what appeared to be optimistic information, since the lesion contained aberrations on chromosome 11, a finding that has been exclusively associated with Spitz nevi in comparative studies with other benign nevi and melanomas. No complete lymph node dissection was performed and the patient has been followed for more than a year without evidence of recurrent disease.

Fatal outcomes have resulted in cases where several pathologists concurred with a diagnosis of Spitz nevus or atypical Spitzoid tumors, suggesting that these cases represented unrecognized melanoma, although this scenario does not appear to be the norm. The lesions should be completely excised, and treated similarly to melanomas when they are characterized by frank atypia or uncertain biologic behavior.

Until more information can be gathered from the national pediatric melanoma and melanocytic neoplasms database organized by Dr. Bruce Overbook at Case Western Reserve University in Cleveland, Dr. Swetter urged open and frank discussions among medical professionals and families about the diagnostic uncertainty regarding these lesions.

An 8-mm raised, blue-black nodule on an 11-year-old raised uncertainty among Stanford University specialists. Stanford University Departments of Dermatology and Pathology and the Melanoma Care Coalition, Pharmadura, LLC

MONTEREY, CALIF. — Melanocytic tumors of unknown malignant potential represent some of the most difficult cases in pediatric dermatology, since little agreement exists about their diagnostic criteria, management, or outcome.

"They cause everyone, including pathologists, referring dermatologists, and surgeons, to lose sleep," said Dr. Susan Swetter, director of Stanford (Calif.) University's pigmented lesion and cutaneous melanoma clinic, at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Dr. Swetter described the management of an 8-mm raised, blue-black nodule that appeared behind the right ear of an 11-year-old girl. Satellite blue-black macules appeared on the periphery of the lesion.

A partial 5-mm punch biopsy was reviewed by pathologists at Stanford; the University of California, San Francisco; and Massachusetts General Hospital, Boston. The conclusion was that the lesion was a melanocytic tumor of unknown malignant potential (MELTUMP) with decidedly mixed signals: no ulceration but a relatively high mitotic rate (4/mm2) and probable angiolymphatic invasion.

Differential diagnoses included a pigmented epithelioid melanocytoma, an agminated Spitz nevus, or a "low-grade" melanoma. The patient underwent a "fairly intuitive" comprehensive work-up, including a thorough personal and family history, a review of the timing and speed of growth of the lesion, and a total body skin examination and physical examination, including palpation of regional lymph node basins to assess for metastasis.

Melanoma experts agree that MELTUMP lesions should be completely excised, but the specifics about recommended margins remain hazy, Dr. Swetter explained. Some experts would decide to perform a wide excision in such a case, perhaps including sentinel lymph node biopsy, as if they were treating a melanoma.

At Stanford, where the patient was seen, the decision was made to take a 1-cm margin, narrower than the 2-cm margin that would be appropriate for a 3.7-mm melanoma, and to await the pathology results before deciding whether to perform a sentinel lymph node biopsy or lymph node dissection.

The histology on the wide excision specimen showed that the lesion was symmetrical and well circumscribed with a polypoid proliferation of darkly pigmented melanocytes and a mitotic rate "well below 1/mm2."

Dr. Swetter described the applicable histology images as revealing "deeply pigmented epithelial spindle cells and unmistakable angiolymphatic invasion."

"Our pathologists thought this was most consistent with a melanocytoma diagnosis," and noted its rarity as well as its "uncertain biological behavior," said Dr. Swetter.

A comparative genomic hybridization study was ordered from the UCSF laboratory, but results were estimated to take 6–8 weeks, a period of time that could compromise afferent lymphatic drainage from a scalp lesion and reduce the accuracy of the sentinel node biopsy.

After extensive discussions with the child's parents, the Stanford team elected to perform a sentinel lymph node biopsy but to await the outcome of the comparative genomic hybridization studies prior to performing complete lymph node dissection in the event that the sentinel node specimen was positive. A metastatic work-up with PET/CT scanning was performed "in part … to allay some of the parental concern about metastatic disease." Parenthetically, Dr. Swetter noted that such a scan would not generally be indicated in an asymptomatic patient with no signs of metastatic disease and would not preclude the possibility of a positive sentinel node biopsy. The scans were negative.

Two sentinel lymph nodes were identified and removed in the right cervical neck. One was positive for subcapsular and parenchymal metastatic foci of pigmented epithelioid melanocytoma and stained strongly positive for S100, MelanA, and HMB45.

Ironically, MELTUMP lesions have been associated with a very high rate of sentinel lymph node positivity in the two largest retrospective studies to date (44%–50%, compared with approximately 20% for typical melanomas with Breslow thickness greater than 1 mm).

However, the picture is confusing, because studies also associate atypical Spitz tumors with a very high survival rate despite apparent micrometastases.

In the case of Dr. Swetter's patient, a comparative genomic hybridization offered what appeared to be optimistic information, since the lesion contained aberrations on chromosome 11, a finding that has been exclusively associated with Spitz nevi in comparative studies with other benign nevi and melanomas. No complete lymph node dissection was performed and the patient has been followed for more than a year without evidence of recurrent disease.

Fatal outcomes have resulted in cases where several pathologists concurred with a diagnosis of Spitz nevus or atypical Spitzoid tumors, suggesting that these cases represented unrecognized melanoma, although this scenario does not appear to be the norm. The lesions should be completely excised, and treated similarly to melanomas when they are characterized by frank atypia or uncertain biologic behavior.

Until more information can be gathered from the national pediatric melanoma and melanocytic neoplasms database organized by Dr. Bruce Overbook at Case Western Reserve University in Cleveland, Dr. Swetter urged open and frank discussions among medical professionals and families about the diagnostic uncertainty regarding these lesions.

An 8-mm raised, blue-black nodule on an 11-year-old raised uncertainty among Stanford University specialists. Stanford University Departments of Dermatology and Pathology and the Melanoma Care Coalition, Pharmadura, LLC

MONTEREY, CALIF. — Melanocytic tumors of unknown malignant potential represent some of the most difficult cases in pediatric dermatology, since little agreement exists about their diagnostic criteria, management, or outcome.

"They cause everyone, including pathologists, referring dermatologists, and surgeons, to lose sleep," said Dr. Susan Swetter, director of Stanford (Calif.) University's pigmented lesion and cutaneous melanoma clinic, at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Dr. Swetter described the management of an 8-mm raised, blue-black nodule that appeared behind the right ear of an 11-year-old girl. Satellite blue-black macules appeared on the periphery of the lesion.

A partial 5-mm punch biopsy was reviewed by pathologists at Stanford; the University of California, San Francisco; and Massachusetts General Hospital, Boston. The conclusion was that the lesion was a melanocytic tumor of unknown malignant potential (MELTUMP) with decidedly mixed signals: no ulceration but a relatively high mitotic rate (4/mm2) and probable angiolymphatic invasion.

Differential diagnoses included a pigmented epithelioid melanocytoma, an agminated Spitz nevus, or a "low-grade" melanoma. The patient underwent a "fairly intuitive" comprehensive work-up, including a thorough personal and family history, a review of the timing and speed of growth of the lesion, and a total body skin examination and physical examination, including palpation of regional lymph node basins to assess for metastasis.

Melanoma experts agree that MELTUMP lesions should be completely excised, but the specifics about recommended margins remain hazy, Dr. Swetter explained. Some experts would decide to perform a wide excision in such a case, perhaps including sentinel lymph node biopsy, as if they were treating a melanoma.

At Stanford, where the patient was seen, the decision was made to take a 1-cm margin, narrower than the 2-cm margin that would be appropriate for a 3.7-mm melanoma, and to await the pathology results before deciding whether to perform a sentinel lymph node biopsy or lymph node dissection.

The histology on the wide excision specimen showed that the lesion was symmetrical and well circumscribed with a polypoid proliferation of darkly pigmented melanocytes and a mitotic rate "well below 1/mm2."

Dr. Swetter described the applicable histology images as revealing "deeply pigmented epithelial spindle cells and unmistakable angiolymphatic invasion."

"Our pathologists thought this was most consistent with a melanocytoma diagnosis," and noted its rarity as well as its "uncertain biological behavior," said Dr. Swetter.

A comparative genomic hybridization study was ordered from the UCSF laboratory, but results were estimated to take 6–8 weeks, a period of time that could compromise afferent lymphatic drainage from a scalp lesion and reduce the accuracy of the sentinel node biopsy.

After extensive discussions with the child's parents, the Stanford team elected to perform a sentinel lymph node biopsy but to await the outcome of the comparative genomic hybridization studies prior to performing complete lymph node dissection in the event that the sentinel node specimen was positive. A metastatic work-up with PET/CT scanning was performed "in part … to allay some of the parental concern about metastatic disease." Parenthetically, Dr. Swetter noted that such a scan would not generally be indicated in an asymptomatic patient with no signs of metastatic disease and would not preclude the possibility of a positive sentinel node biopsy. The scans were negative.

Two sentinel lymph nodes were identified and removed in the right cervical neck. One was positive for subcapsular and parenchymal metastatic foci of pigmented epithelioid melanocytoma and stained strongly positive for S100, MelanA, and HMB45.

Ironically, MELTUMP lesions have been associated with a very high rate of sentinel lymph node positivity in the two largest retrospective studies to date (44%–50%, compared with approximately 20% for typical melanomas with Breslow thickness greater than 1 mm).

However, the picture is confusing, because studies also associate atypical Spitz tumors with a very high survival rate despite apparent micrometastases.

In the case of Dr. Swetter's patient, a comparative genomic hybridization offered what appeared to be optimistic information, since the lesion contained aberrations on chromosome 11, a finding that has been exclusively associated with Spitz nevi in comparative studies with other benign nevi and melanomas. No complete lymph node dissection was performed and the patient has been followed for more than a year without evidence of recurrent disease.

Fatal outcomes have resulted in cases where several pathologists concurred with a diagnosis of Spitz nevus or atypical Spitzoid tumors, suggesting that these cases represented unrecognized melanoma, although this scenario does not appear to be the norm. The lesions should be completely excised, and treated similarly to melanomas when they are characterized by frank atypia or uncertain biologic behavior.

Until more information can be gathered from the national pediatric melanoma and melanocytic neoplasms database organized by Dr. Bruce Overbook at Case Western Reserve University in Cleveland, Dr. Swetter urged open and frank discussions among medical professionals and families about the diagnostic uncertainty regarding these lesions.

An 8-mm raised, blue-black nodule on an 11-year-old raised uncertainty among Stanford University specialists. Stanford University Departments of Dermatology and Pathology and the Melanoma Care Coalition, Pharmadura, LLC

ORLANDO — Vascular structures visualized on dermoscopy aid in the diagnosis of both benign and malignant nonpigmented tumors of the skin, Dr. Brian Katz said at the annual meeting of the Florida Society of Dermatologic Surgeons.

In fact, associated vasculature should be evaluated carefully to avoid missing a malignancy, said Dr. Katz of Mount Sinai Medical Center, Miami Beach.

When using conventional dermoscopy for nonpigmented lesions, be careful about the amount of pressure applied because a blanching of the vessels can occur and impede diagnostic efforts. Also, consider using ultrasound gel rather than alcohol with dermoscopy, he suggested, because it helps prevent compression of vessels. (See box at right.)

This is important because special morphologic types of vessels are associated with different skin tumors. Various studies show which types of vessels are suggestive of which diagnoses, he said.

In nonpigmented basal cell carcinomas, arborizing vessels are a major feature visualized on dermoscopy, and these were shown in at least one study to have a 90% positive predictive value for basal cell carcinoma. Pink-white to white shiny areas and ulceration also are characteristic in these lesions.

With superficial basal cell carcinoma, two main dermoscopic features typically are observed: shiny pink to white structureless areas and short, fine telangiectasias.

Dr. Katz discussed other types of malignant lesions, along with their associated vasculature on dermoscopy:

PISquamous cell carcinoma in situ/Bowen's disease. These lesions are characterized by glomerular vessels and scaly surface on dermoscopy.

PISquamous cell carcinoma (more invasive types). Characterized by polymorphous vessels, which are mainly glomerular or hairpin vessels and are irregularly distributed and which have a whitish halo.

PIAmelanotic melanoma. Characterized by the presence of mainly dotted and linear irregular polymorphous vessels or by hairpin polymorphous vessels with milky-red globules/areas and ulceration. A whitish-pink background also may be seen on dermoscopy.

A rule of thumb is the more vessels seen, the more likely it is to be a malignant lesion, Dr. Katz said.

Vasculature visualized on dermoscopy is helpful for diagnosing benign nonpigmented lesions, including pyogenic granuloma (characterized by milky red homogenous areas separated with white intersecting lines with a white collarette at the periphery) and intradermal nevi (commalike vessels with a regular distribution throughout the lesion, a pink or pale structureless background, and sometimes pigmentary remnants).

Nonpigmented seborrheic keratosis also can be diagnosed with dermoscopy. It is characterized vascularly by regularly distributed hairpin loop vessels; dermoscopic features of keratinization; and dermoscopic features including comedolike opening, milialike cysts, sharp borders, fissures, and ridges. Yellow scaling and whitish halo also may be noted.

Other benign lesions that can be diagnosed include sebaceous hyperplasia—aggregated white to yellow central globularlike structures and surrounding, scarcely branching crown vessels at the periphery that never cross the center of the neoplasm—and Spitz nevus, which is characterized by dotted vessels, regular distribution, and a pink background, Dr. Katz said.

Dermoscopy of a malignant neoplasm reveals multiple arborizing vessels on a pink, whiteshiny background. Courtesy Dr. Brian Katz

Ultrasound Gel a Better Choice in Some Situations

Research on the use of dermoscopy has shown that although alcohol is the "best all around" fluid to use for dermoscopy, ultrasound gel is a better option in some instances, Dr. Katz noted.

For examining melanonychia of the nail plate, gel works best. Similarly, for nonpigmented tumors of the skin, in which visualization of the vasculature is important for making a correct diagnosis, gel helps mitigate the effects of some of the pressure that is applied with conventional contact dermoscopy.

In a comparison of contact dermoscopy with gel versus alcohol for a malignant melanoma, the gel clearly allowed much better visualization of the vasculature, while the alcohol allowed more compression—and thus blanching—of the vessels, he said.

The effect was strictly caused by the pressure applied, he said at the meeting, noting that pressure should be minimal with contact dermoscopy.

An option to circumvent this problem altogether is to use a polarized dermatoscope in noncontact mode, which has been shown to be the best option for visualizing blood vessels, Dr. Katz said.

Dermoscopy with ultrasound gel (left) allows for better visualization than with alcohol (right) because there is less vessel compression. PHOTOS COURTESY DR. HAROLD RABINOVITZ

ORLANDO — Vascular structures visualized on dermoscopy aid in the diagnosis of both benign and malignant nonpigmented tumors of the skin, Dr. Brian Katz said at the annual meeting of the Florida Society of Dermatologic Surgeons.

In fact, associated vasculature should be evaluated carefully to avoid missing a malignancy, said Dr. Katz of Mount Sinai Medical Center, Miami Beach.

When using conventional dermoscopy for nonpigmented lesions, be careful about the amount of pressure applied because a blanching of the vessels can occur and impede diagnostic efforts. Also, consider using ultrasound gel rather than alcohol with dermoscopy, he suggested, because it helps prevent compression of vessels. (See box at right.)

This is important because special morphologic types of vessels are associated with different skin tumors. Various studies show which types of vessels are suggestive of which diagnoses, he said.

In nonpigmented basal cell carcinomas, arborizing vessels are a major feature visualized on dermoscopy, and these were shown in at least one study to have a 90% positive predictive value for basal cell carcinoma. Pink-white to white shiny areas and ulceration also are characteristic in these lesions.

With superficial basal cell carcinoma, two main dermoscopic features typically are observed: shiny pink to white structureless areas and short, fine telangiectasias.

Dr. Katz discussed other types of malignant lesions, along with their associated vasculature on dermoscopy:

PISquamous cell carcinoma in situ/Bowen's disease. These lesions are characterized by glomerular vessels and scaly surface on dermoscopy.

PISquamous cell carcinoma (more invasive types). Characterized by polymorphous vessels, which are mainly glomerular or hairpin vessels and are irregularly distributed and which have a whitish halo.

PIAmelanotic melanoma. Characterized by the presence of mainly dotted and linear irregular polymorphous vessels or by hairpin polymorphous vessels with milky-red globules/areas and ulceration. A whitish-pink background also may be seen on dermoscopy.

A rule of thumb is the more vessels seen, the more likely it is to be a malignant lesion, Dr. Katz said.

Vasculature visualized on dermoscopy is helpful for diagnosing benign nonpigmented lesions, including pyogenic granuloma (characterized by milky red homogenous areas separated with white intersecting lines with a white collarette at the periphery) and intradermal nevi (commalike vessels with a regular distribution throughout the lesion, a pink or pale structureless background, and sometimes pigmentary remnants).

Nonpigmented seborrheic keratosis also can be diagnosed with dermoscopy. It is characterized vascularly by regularly distributed hairpin loop vessels; dermoscopic features of keratinization; and dermoscopic features including comedolike opening, milialike cysts, sharp borders, fissures, and ridges. Yellow scaling and whitish halo also may be noted.

Other benign lesions that can be diagnosed include sebaceous hyperplasia—aggregated white to yellow central globularlike structures and surrounding, scarcely branching crown vessels at the periphery that never cross the center of the neoplasm—and Spitz nevus, which is characterized by dotted vessels, regular distribution, and a pink background, Dr. Katz said.

Dermoscopy of a malignant neoplasm reveals multiple arborizing vessels on a pink, whiteshiny background. Courtesy Dr. Brian Katz

Ultrasound Gel a Better Choice in Some Situations

Research on the use of dermoscopy has shown that although alcohol is the "best all around" fluid to use for dermoscopy, ultrasound gel is a better option in some instances, Dr. Katz noted.

For examining melanonychia of the nail plate, gel works best. Similarly, for nonpigmented tumors of the skin, in which visualization of the vasculature is important for making a correct diagnosis, gel helps mitigate the effects of some of the pressure that is applied with conventional contact dermoscopy.

In a comparison of contact dermoscopy with gel versus alcohol for a malignant melanoma, the gel clearly allowed much better visualization of the vasculature, while the alcohol allowed more compression—and thus blanching—of the vessels, he said.

The effect was strictly caused by the pressure applied, he said at the meeting, noting that pressure should be minimal with contact dermoscopy.

An option to circumvent this problem altogether is to use a polarized dermatoscope in noncontact mode, which has been shown to be the best option for visualizing blood vessels, Dr. Katz said.

Dermoscopy with ultrasound gel (left) allows for better visualization than with alcohol (right) because there is less vessel compression. PHOTOS COURTESY DR. HAROLD RABINOVITZ

ORLANDO — Vascular structures visualized on dermoscopy aid in the diagnosis of both benign and malignant nonpigmented tumors of the skin, Dr. Brian Katz said at the annual meeting of the Florida Society of Dermatologic Surgeons.

In fact, associated vasculature should be evaluated carefully to avoid missing a malignancy, said Dr. Katz of Mount Sinai Medical Center, Miami Beach.

When using conventional dermoscopy for nonpigmented lesions, be careful about the amount of pressure applied because a blanching of the vessels can occur and impede diagnostic efforts. Also, consider using ultrasound gel rather than alcohol with dermoscopy, he suggested, because it helps prevent compression of vessels. (See box at right.)

This is important because special morphologic types of vessels are associated with different skin tumors. Various studies show which types of vessels are suggestive of which diagnoses, he said.

In nonpigmented basal cell carcinomas, arborizing vessels are a major feature visualized on dermoscopy, and these were shown in at least one study to have a 90% positive predictive value for basal cell carcinoma. Pink-white to white shiny areas and ulceration also are characteristic in these lesions.

With superficial basal cell carcinoma, two main dermoscopic features typically are observed: shiny pink to white structureless areas and short, fine telangiectasias.

Dr. Katz discussed other types of malignant lesions, along with their associated vasculature on dermoscopy:

PISquamous cell carcinoma in situ/Bowen's disease. These lesions are characterized by glomerular vessels and scaly surface on dermoscopy.

PISquamous cell carcinoma (more invasive types). Characterized by polymorphous vessels, which are mainly glomerular or hairpin vessels and are irregularly distributed and which have a whitish halo.

PIAmelanotic melanoma. Characterized by the presence of mainly dotted and linear irregular polymorphous vessels or by hairpin polymorphous vessels with milky-red globules/areas and ulceration. A whitish-pink background also may be seen on dermoscopy.

A rule of thumb is the more vessels seen, the more likely it is to be a malignant lesion, Dr. Katz said.

Vasculature visualized on dermoscopy is helpful for diagnosing benign nonpigmented lesions, including pyogenic granuloma (characterized by milky red homogenous areas separated with white intersecting lines with a white collarette at the periphery) and intradermal nevi (commalike vessels with a regular distribution throughout the lesion, a pink or pale structureless background, and sometimes pigmentary remnants).

Nonpigmented seborrheic keratosis also can be diagnosed with dermoscopy. It is characterized vascularly by regularly distributed hairpin loop vessels; dermoscopic features of keratinization; and dermoscopic features including comedolike opening, milialike cysts, sharp borders, fissures, and ridges. Yellow scaling and whitish halo also may be noted.

Other benign lesions that can be diagnosed include sebaceous hyperplasia—aggregated white to yellow central globularlike structures and surrounding, scarcely branching crown vessels at the periphery that never cross the center of the neoplasm—and Spitz nevus, which is characterized by dotted vessels, regular distribution, and a pink background, Dr. Katz said.

Dermoscopy of a malignant neoplasm reveals multiple arborizing vessels on a pink, whiteshiny background. Courtesy Dr. Brian Katz

Ultrasound Gel a Better Choice in Some Situations

Research on the use of dermoscopy has shown that although alcohol is the "best all around" fluid to use for dermoscopy, ultrasound gel is a better option in some instances, Dr. Katz noted.

For examining melanonychia of the nail plate, gel works best. Similarly, for nonpigmented tumors of the skin, in which visualization of the vasculature is important for making a correct diagnosis, gel helps mitigate the effects of some of the pressure that is applied with conventional contact dermoscopy.

In a comparison of contact dermoscopy with gel versus alcohol for a malignant melanoma, the gel clearly allowed much better visualization of the vasculature, while the alcohol allowed more compression—and thus blanching—of the vessels, he said.

The effect was strictly caused by the pressure applied, he said at the meeting, noting that pressure should be minimal with contact dermoscopy.

An option to circumvent this problem altogether is to use a polarized dermatoscope in noncontact mode, which has been shown to be the best option for visualizing blood vessels, Dr. Katz said.

Dermoscopy with ultrasound gel (left) allows for better visualization than with alcohol (right) because there is less vessel compression. PHOTOS COURTESY DR. HAROLD RABINOVITZ

ORLANDO — The field of dermoscopy is expanding rapidly, as demonstrated both by the increase in published papers on the topic in recent years and by the increasing number of uses for the technology, Dr. Brian Katz said at the annual meeting of the Florida Society of Dermatologic Surgeons.

A recent study noted that 450 papers were published on the topic between 2000 and 2005, compared with 100 between 1987 and 1999, said Dr. Katz of Mount Sinai Medical Center, Miami Beach.

His own review of more recent literature showed that about 250 papers on dermoscopy were published in the last year alone.

Additionally, dermoscopy now is being used to predict and/or monitor treatment response in a variety of conditions.

Patients being treated with topical corticosteroids for lichen planus and psoriasis, for example, are being monitored for early signs of atrophy, according to Dr. Katz.

It also appears that patterns seen on dermoscopy in port-wine stains of the face can predict response to pulsed dye laser treatment, Dr. Katz said.

One study of 33 children demonstrated that those with a superficial pattern involving multiple dotted or globularlike vessels were more likely to have a good response. The children with deeper patterns involving linear vessels, which were sometimes reticular in appearance, had much poorer response (Pediatr. Dermatol. 2004;21:589–96).

The study also showed that an undefined pattern on dermoscopy was an indication that no further response would be achieved with treatment. This type of finding typically occurred after multiple treatments, and the investigators suggested it should mark the end point of treatment.

Dermoscopy has been shown to be useful in guiding resection of lentigo maligna of the head and neck.

In a study of 26 patients with lesions that clinically appeared to have an uninvolved border, dermoscopy distinguished those with an anular pattern that histologically corresponded to melanoma in situ from those with findings indicative of the melanocytic hyperplasia commonly seen in sun-damaged skin (Arch. Dermatol. 2004;140:1095–110).

More recently, dermoscopy has been reported to be useful for monitoring the progress of patients treated with tazarotene for superficial basal cell carcinomas.

In a study of 41 patients, with slightly more than half achieving a complete response, dermoscopy showed progressive loss of dermoscopic structures over the course of treatment until the end point was achieved and all leaflike areas, arborizing vessels, and pink/white background had resolved (Dermatol. Surg. 2005;31:217–20).

In a case report published in 2006, dermoscopy was used successfully to monitor the response to imiquimod in a patient treated for lentigo maligna. Over a 12-week treatment course, progressive loss of dermoscopic features of facial lentigo maligna, such as asymmetrically pigmented hair follicle openings and rhomboidal structures around hair follicles, all had resolved (Arch. Dermatol. 2006;142:530–1). The patient was followed for 2 years with no recurrence, Dr. Katz said.

ORLANDO — The field of dermoscopy is expanding rapidly, as demonstrated both by the increase in published papers on the topic in recent years and by the increasing number of uses for the technology, Dr. Brian Katz said at the annual meeting of the Florida Society of Dermatologic Surgeons.

A recent study noted that 450 papers were published on the topic between 2000 and 2005, compared with 100 between 1987 and 1999, said Dr. Katz of Mount Sinai Medical Center, Miami Beach.

His own review of more recent literature showed that about 250 papers on dermoscopy were published in the last year alone.

Additionally, dermoscopy now is being used to predict and/or monitor treatment response in a variety of conditions.

Patients being treated with topical corticosteroids for lichen planus and psoriasis, for example, are being monitored for early signs of atrophy, according to Dr. Katz.

It also appears that patterns seen on dermoscopy in port-wine stains of the face can predict response to pulsed dye laser treatment, Dr. Katz said.

One study of 33 children demonstrated that those with a superficial pattern involving multiple dotted or globularlike vessels were more likely to have a good response. The children with deeper patterns involving linear vessels, which were sometimes reticular in appearance, had much poorer response (Pediatr. Dermatol. 2004;21:589–96).

The study also showed that an undefined pattern on dermoscopy was an indication that no further response would be achieved with treatment. This type of finding typically occurred after multiple treatments, and the investigators suggested it should mark the end point of treatment.

Dermoscopy has been shown to be useful in guiding resection of lentigo maligna of the head and neck.

In a study of 26 patients with lesions that clinically appeared to have an uninvolved border, dermoscopy distinguished those with an anular pattern that histologically corresponded to melanoma in situ from those with findings indicative of the melanocytic hyperplasia commonly seen in sun-damaged skin (Arch. Dermatol. 2004;140:1095–110).

More recently, dermoscopy has been reported to be useful for monitoring the progress of patients treated with tazarotene for superficial basal cell carcinomas.

In a study of 41 patients, with slightly more than half achieving a complete response, dermoscopy showed progressive loss of dermoscopic structures over the course of treatment until the end point was achieved and all leaflike areas, arborizing vessels, and pink/white background had resolved (Dermatol. Surg. 2005;31:217–20).

In a case report published in 2006, dermoscopy was used successfully to monitor the response to imiquimod in a patient treated for lentigo maligna. Over a 12-week treatment course, progressive loss of dermoscopic features of facial lentigo maligna, such as asymmetrically pigmented hair follicle openings and rhomboidal structures around hair follicles, all had resolved (Arch. Dermatol. 2006;142:530–1). The patient was followed for 2 years with no recurrence, Dr. Katz said.

ORLANDO — The field of dermoscopy is expanding rapidly, as demonstrated both by the increase in published papers on the topic in recent years and by the increasing number of uses for the technology, Dr. Brian Katz said at the annual meeting of the Florida Society of Dermatologic Surgeons.

A recent study noted that 450 papers were published on the topic between 2000 and 2005, compared with 100 between 1987 and 1999, said Dr. Katz of Mount Sinai Medical Center, Miami Beach.

His own review of more recent literature showed that about 250 papers on dermoscopy were published in the last year alone.

Additionally, dermoscopy now is being used to predict and/or monitor treatment response in a variety of conditions.

Patients being treated with topical corticosteroids for lichen planus and psoriasis, for example, are being monitored for early signs of atrophy, according to Dr. Katz.

It also appears that patterns seen on dermoscopy in port-wine stains of the face can predict response to pulsed dye laser treatment, Dr. Katz said.

One study of 33 children demonstrated that those with a superficial pattern involving multiple dotted or globularlike vessels were more likely to have a good response. The children with deeper patterns involving linear vessels, which were sometimes reticular in appearance, had much poorer response (Pediatr. Dermatol. 2004;21:589–96).

The study also showed that an undefined pattern on dermoscopy was an indication that no further response would be achieved with treatment. This type of finding typically occurred after multiple treatments, and the investigators suggested it should mark the end point of treatment.

Dermoscopy has been shown to be useful in guiding resection of lentigo maligna of the head and neck.

In a study of 26 patients with lesions that clinically appeared to have an uninvolved border, dermoscopy distinguished those with an anular pattern that histologically corresponded to melanoma in situ from those with findings indicative of the melanocytic hyperplasia commonly seen in sun-damaged skin (Arch. Dermatol. 2004;140:1095–110).

More recently, dermoscopy has been reported to be useful for monitoring the progress of patients treated with tazarotene for superficial basal cell carcinomas.

In a study of 41 patients, with slightly more than half achieving a complete response, dermoscopy showed progressive loss of dermoscopic structures over the course of treatment until the end point was achieved and all leaflike areas, arborizing vessels, and pink/white background had resolved (Dermatol. Surg. 2005;31:217–20).

In a case report published in 2006, dermoscopy was used successfully to monitor the response to imiquimod in a patient treated for lentigo maligna. Over a 12-week treatment course, progressive loss of dermoscopic features of facial lentigo maligna, such as asymmetrically pigmented hair follicle openings and rhomboidal structures around hair follicles, all had resolved (Arch. Dermatol. 2006;142:530–1). The patient was followed for 2 years with no recurrence, Dr. Katz said.

ZURICH — In vivo confocal laser scanning microscopy is a useful diagnostic tool for pigmented skin lesions that are clinically and dermoscopically equivocal, Dr. Verena Ahlgrimm-Siess said at the annual meeting of the European Society for Dermatological Research.

"The ability to noninvasively analyze the architecture and cytomorphology of pigmented skin lesions permits a preliminary diagnostic evaluation and allows, in context with the clinical and dermoscopic impression, a judgment on the need for biopsy or excision for definitive diagnosis," according to Dr. Ahlgrimm-Siess of the Medical University of Graz (Austria).

Early detection of melanoma is one of the greatest challenges in dermatology, according to Dr. Ahlgrimm-Siess. Studies indicate the sensitivity of clinical diagnosis with the unaided eye is about 65%.

Dermoscopy improves diagnostic accuracy, but it takes a fair amount of time and practice to become skillful. The 10x magnification is another limitation.

Confocal laser scanning microscopy permits real-time noninvasive visualization of epidermal and dermal microanatomic structures and cellular details at a resolution comparable to that obtained in examination of histologic specimens under a conventional microscope.

The novel imaging technology utilizes a near-infrared diode laser at 830 nm wavelength and sufficiently low power—less than 35 mW at the tissue level—that no tissue damage occurs.

Physicians can be taught to use confocal laser scanning microscopy in a 1-hour presentation.

Among the diagnostic features of the laser scanning technique that have proved most helpful to physicians in distinguishing melanomas are monomorphic melanocytic cells, disarray of the melanocytic architecture, and bright collagen fiber bundles.

In a prior study, investigators reported 97.6% sensitivity and 88.2% specificity for confocal laser scanning microscopy in discriminating malignant from benign pigmented skin lesions (J. Invest. Dermatol. 2005;124:493–8) and a positive predictive value of 94.2% in another (Cancer 2006;107:193–200). However, these were lesions in which the distinction using conventional means was relatively clear cut, noted Dr. Ahlgrimm-Siess.

The physician presented a more clinically realistic study involving 50 challenging equivocal pigmented lesions in which melanoma could not be ruled out clinically or dermoscopically. There were 16 melanomas, 3 basal cell carcinomas, 25 melanocytic nevi, and 6 nonmelanocytic pigmented lesions.

Relying solely on the laser scanning microscope images, blinded physicians missed two melanomas, for a diagnostic sensitivity of 89.4% and a specificity of 64.5%.

However, with access to the clinical and dermoscopic images as well as laser scanning microscopy, the specificity climbed to 87% while the sensitivity remained at 89.4%.

Discrimination of benign nevi from early melanoma in situ up to 0.75 mm in thickness could be made in 9 of 11 cases with the laser scanning microscopy alone, for a sensitivity of 81.8% and a specificity of 84%, Dr. Ahlgrimm-Siess added.

The jump in diagnostic specificity from 64.5% with laser scanning microscopy alone to 87% in combination with dermoscopic and clinical evaluation wasn't enough to satisfy the session cochair, Dr. Hywel Williams.

He indicated that he doesn't consider the laser scanning technique ready for prime time as a means of sparing patients from undergoing negative skin biopsies.

"I would be, as a clinician, certainly not happy to be missing 13% or 14% of malignant lesions," said Dr. Williams, professor of dermato-epidemiology at the University of Nottingham (England).

ZURICH — In vivo confocal laser scanning microscopy is a useful diagnostic tool for pigmented skin lesions that are clinically and dermoscopically equivocal, Dr. Verena Ahlgrimm-Siess said at the annual meeting of the European Society for Dermatological Research.

"The ability to noninvasively analyze the architecture and cytomorphology of pigmented skin lesions permits a preliminary diagnostic evaluation and allows, in context with the clinical and dermoscopic impression, a judgment on the need for biopsy or excision for definitive diagnosis," according to Dr. Ahlgrimm-Siess of the Medical University of Graz (Austria).

Early detection of melanoma is one of the greatest challenges in dermatology, according to Dr. Ahlgrimm-Siess. Studies indicate the sensitivity of clinical diagnosis with the unaided eye is about 65%.

Dermoscopy improves diagnostic accuracy, but it takes a fair amount of time and practice to become skillful. The 10x magnification is another limitation.

Confocal laser scanning microscopy permits real-time noninvasive visualization of epidermal and dermal microanatomic structures and cellular details at a resolution comparable to that obtained in examination of histologic specimens under a conventional microscope.

The novel imaging technology utilizes a near-infrared diode laser at 830 nm wavelength and sufficiently low power—less than 35 mW at the tissue level—that no tissue damage occurs.

Physicians can be taught to use confocal laser scanning microscopy in a 1-hour presentation.

Among the diagnostic features of the laser scanning technique that have proved most helpful to physicians in distinguishing melanomas are monomorphic melanocytic cells, disarray of the melanocytic architecture, and bright collagen fiber bundles.

In a prior study, investigators reported 97.6% sensitivity and 88.2% specificity for confocal laser scanning microscopy in discriminating malignant from benign pigmented skin lesions (J. Invest. Dermatol. 2005;124:493–8) and a positive predictive value of 94.2% in another (Cancer 2006;107:193–200). However, these were lesions in which the distinction using conventional means was relatively clear cut, noted Dr. Ahlgrimm-Siess.

The physician presented a more clinically realistic study involving 50 challenging equivocal pigmented lesions in which melanoma could not be ruled out clinically or dermoscopically. There were 16 melanomas, 3 basal cell carcinomas, 25 melanocytic nevi, and 6 nonmelanocytic pigmented lesions.

Relying solely on the laser scanning microscope images, blinded physicians missed two melanomas, for a diagnostic sensitivity of 89.4% and a specificity of 64.5%.

However, with access to the clinical and dermoscopic images as well as laser scanning microscopy, the specificity climbed to 87% while the sensitivity remained at 89.4%.

Discrimination of benign nevi from early melanoma in situ up to 0.75 mm in thickness could be made in 9 of 11 cases with the laser scanning microscopy alone, for a sensitivity of 81.8% and a specificity of 84%, Dr. Ahlgrimm-Siess added.

The jump in diagnostic specificity from 64.5% with laser scanning microscopy alone to 87% in combination with dermoscopic and clinical evaluation wasn't enough to satisfy the session cochair, Dr. Hywel Williams.

He indicated that he doesn't consider the laser scanning technique ready for prime time as a means of sparing patients from undergoing negative skin biopsies.

"I would be, as a clinician, certainly not happy to be missing 13% or 14% of malignant lesions," said Dr. Williams, professor of dermato-epidemiology at the University of Nottingham (England).

ZURICH — In vivo confocal laser scanning microscopy is a useful diagnostic tool for pigmented skin lesions that are clinically and dermoscopically equivocal, Dr. Verena Ahlgrimm-Siess said at the annual meeting of the European Society for Dermatological Research.

"The ability to noninvasively analyze the architecture and cytomorphology of pigmented skin lesions permits a preliminary diagnostic evaluation and allows, in context with the clinical and dermoscopic impression, a judgment on the need for biopsy or excision for definitive diagnosis," according to Dr. Ahlgrimm-Siess of the Medical University of Graz (Austria).

Early detection of melanoma is one of the greatest challenges in dermatology, according to Dr. Ahlgrimm-Siess. Studies indicate the sensitivity of clinical diagnosis with the unaided eye is about 65%.

Dermoscopy improves diagnostic accuracy, but it takes a fair amount of time and practice to become skillful. The 10x magnification is another limitation.

Confocal laser scanning microscopy permits real-time noninvasive visualization of epidermal and dermal microanatomic structures and cellular details at a resolution comparable to that obtained in examination of histologic specimens under a conventional microscope.

The novel imaging technology utilizes a near-infrared diode laser at 830 nm wavelength and sufficiently low power—less than 35 mW at the tissue level—that no tissue damage occurs.

Physicians can be taught to use confocal laser scanning microscopy in a 1-hour presentation.

Among the diagnostic features of the laser scanning technique that have proved most helpful to physicians in distinguishing melanomas are monomorphic melanocytic cells, disarray of the melanocytic architecture, and bright collagen fiber bundles.

In a prior study, investigators reported 97.6% sensitivity and 88.2% specificity for confocal laser scanning microscopy in discriminating malignant from benign pigmented skin lesions (J. Invest. Dermatol. 2005;124:493–8) and a positive predictive value of 94.2% in another (Cancer 2006;107:193–200). However, these were lesions in which the distinction using conventional means was relatively clear cut, noted Dr. Ahlgrimm-Siess.

The physician presented a more clinically realistic study involving 50 challenging equivocal pigmented lesions in which melanoma could not be ruled out clinically or dermoscopically. There were 16 melanomas, 3 basal cell carcinomas, 25 melanocytic nevi, and 6 nonmelanocytic pigmented lesions.

Relying solely on the laser scanning microscope images, blinded physicians missed two melanomas, for a diagnostic sensitivity of 89.4% and a specificity of 64.5%.

However, with access to the clinical and dermoscopic images as well as laser scanning microscopy, the specificity climbed to 87% while the sensitivity remained at 89.4%.

Discrimination of benign nevi from early melanoma in situ up to 0.75 mm in thickness could be made in 9 of 11 cases with the laser scanning microscopy alone, for a sensitivity of 81.8% and a specificity of 84%, Dr. Ahlgrimm-Siess added.

The jump in diagnostic specificity from 64.5% with laser scanning microscopy alone to 87% in combination with dermoscopic and clinical evaluation wasn't enough to satisfy the session cochair, Dr. Hywel Williams.

He indicated that he doesn't consider the laser scanning technique ready for prime time as a means of sparing patients from undergoing negative skin biopsies.

"I would be, as a clinician, certainly not happy to be missing 13% or 14% of malignant lesions," said Dr. Williams, professor of dermato-epidemiology at the University of Nottingham (England).

AMSTERDAM — A panel of immunohistochemical stains, including human epidermal growth factor receptor 2/neu and CDX2, is useful in distinguishing extramammary Paget disease that is limited to the skin versus the subset of secondary extramammary Paget disease that is associated specifically with concurrent or future anogenital cancer, Dr. Jared Abbott said at the 11th World Congress on Cancers of the Skin.

Other investigators have postulated that the triad of cytokeratin 7 (CK7), CK20, and BRST-2 immunohistochemical stains is broadly useful in distinguishing extramammary Paget disease (EMPD) that is limited to the skin—known as primary EMPD—from all forms of secondary extramammary Paget disease, but Dr. Abbott did not find this to be the case in his own large series. Indeed, caution should be exercised in relying upon the triad of immunostains for this purpose, said Dr. Abbott of the Mayo Clinic, Rochester, Minn.

EMPD is an uncommon condition occurring primarily in the elderly, with more women than men affected. It arises as a cutaneous adenocarcinoma with a proclivity for sites rich in apocrine glands. Patients with EMPD often present with a prominent solitary plaque lesion in the anogenital or vulvar region. The lesion is erythematous, eczematous, and often pruritic. The course is often locally aggressive, with frequent recurrences.

The classic histopathologic findings of EMPD consist of clusters of epithelial cells with pagetoid extension throughout the epidermis, often accompanied by a superficial lymphocytic inflammatory infiltrate, he said at the congress, which was sponsored by the Skin Cancer Foundation and Erasmus University.

The distinction between primary and secondary EMPD is important because the prognoses are entirely different. Primary EMPD, which accounts for at least three-quarters of cases, has a good prognosis, whereas secondary EMPD has a very poor prognosis because the skin disorder is often accompanied—or, in the months to come, followed—by a gastrointestinal or genitourinary malignancy. Unfortunately, primary and secondary EMPD can't be differentiated based upon histopathology.

"Their [hematoxylin and eosin stains] look exactly alike," Dr. Abbott said.

Other investigators have turned to immunohistochemical staining patterns in an effort to make the distinction. It has been reported that primary EMPD is often CK7- and BRST-2-positive and CK20-negative, whereas secondary EMPD is BRST-2-negative, CK20-positive, and equivocal in terms of CK7.

To see if he could verify this finding, and to assess the utility of some newer immunohistochemical stains, Dr. Abbott studied excisional biopsy specimens from 61 Mayo Clinic patients with EMPD. The median age at diagnosis was 73 years, and 44 patients were women. A total of 45 patients had primary EMPD. The 16 with secondary EMPD, as determined during a median 4-year follow-up, consisted of seven patients with anorectal carcinomas, four with prostate cancer, and five with urothelial cell cancer.

All patients in both the primary and secondary EMPD groups were CK7-positive, so that was of no help, he said. In addition, CK20, BRST-2, androgen receptor, and cyclin D1 did not prove to be of much assistance in distinguishing primary from secondary EMPD. (See box.)

In contrast, HER2/neu and CDX2 were quite helpful in separating primary from secondary EMPD involving anorectal malignancy. Five of the seven patients with lower GI cancer stained positive for CDX2, and all seven were HER2/neu negative. Unfortunately, no staining pattern proved useful in identifying patients with prostate or urothelial cell cancer.

The finding that more than two-thirds of patients with primary EMPD were HER2/neu-positive, and that the positivity rate was even higher among those with recurrent primary EMPD, raises the possibility that Herceptin (trastuzumab) might be effective in these individuals, although that has never been studied, Dr. Abbott said.

ELSEVIER GLOBAL MEDICAL NEWS

AMSTERDAM — A panel of immunohistochemical stains, including human epidermal growth factor receptor 2/neu and CDX2, is useful in distinguishing extramammary Paget disease that is limited to the skin versus the subset of secondary extramammary Paget disease that is associated specifically with concurrent or future anogenital cancer, Dr. Jared Abbott said at the 11th World Congress on Cancers of the Skin.

Other investigators have postulated that the triad of cytokeratin 7 (CK7), CK20, and BRST-2 immunohistochemical stains is broadly useful in distinguishing extramammary Paget disease (EMPD) that is limited to the skin—known as primary EMPD—from all forms of secondary extramammary Paget disease, but Dr. Abbott did not find this to be the case in his own large series. Indeed, caution should be exercised in relying upon the triad of immunostains for this purpose, said Dr. Abbott of the Mayo Clinic, Rochester, Minn.

EMPD is an uncommon condition occurring primarily in the elderly, with more women than men affected. It arises as a cutaneous adenocarcinoma with a proclivity for sites rich in apocrine glands. Patients with EMPD often present with a prominent solitary plaque lesion in the anogenital or vulvar region. The lesion is erythematous, eczematous, and often pruritic. The course is often locally aggressive, with frequent recurrences.

The classic histopathologic findings of EMPD consist of clusters of epithelial cells with pagetoid extension throughout the epidermis, often accompanied by a superficial lymphocytic inflammatory infiltrate, he said at the congress, which was sponsored by the Skin Cancer Foundation and Erasmus University.

The distinction between primary and secondary EMPD is important because the prognoses are entirely different. Primary EMPD, which accounts for at least three-quarters of cases, has a good prognosis, whereas secondary EMPD has a very poor prognosis because the skin disorder is often accompanied—or, in the months to come, followed—by a gastrointestinal or genitourinary malignancy. Unfortunately, primary and secondary EMPD can't be differentiated based upon histopathology.

"Their [hematoxylin and eosin stains] look exactly alike," Dr. Abbott said.

Other investigators have turned to immunohistochemical staining patterns in an effort to make the distinction. It has been reported that primary EMPD is often CK7- and BRST-2-positive and CK20-negative, whereas secondary EMPD is BRST-2-negative, CK20-positive, and equivocal in terms of CK7.

To see if he could verify this finding, and to assess the utility of some newer immunohistochemical stains, Dr. Abbott studied excisional biopsy specimens from 61 Mayo Clinic patients with EMPD. The median age at diagnosis was 73 years, and 44 patients were women. A total of 45 patients had primary EMPD. The 16 with secondary EMPD, as determined during a median 4-year follow-up, consisted of seven patients with anorectal carcinomas, four with prostate cancer, and five with urothelial cell cancer.

All patients in both the primary and secondary EMPD groups were CK7-positive, so that was of no help, he said. In addition, CK20, BRST-2, androgen receptor, and cyclin D1 did not prove to be of much assistance in distinguishing primary from secondary EMPD. (See box.)

In contrast, HER2/neu and CDX2 were quite helpful in separating primary from secondary EMPD involving anorectal malignancy. Five of the seven patients with lower GI cancer stained positive for CDX2, and all seven were HER2/neu negative. Unfortunately, no staining pattern proved useful in identifying patients with prostate or urothelial cell cancer.

The finding that more than two-thirds of patients with primary EMPD were HER2/neu-positive, and that the positivity rate was even higher among those with recurrent primary EMPD, raises the possibility that Herceptin (trastuzumab) might be effective in these individuals, although that has never been studied, Dr. Abbott said.

ELSEVIER GLOBAL MEDICAL NEWS

AMSTERDAM — A panel of immunohistochemical stains, including human epidermal growth factor receptor 2/neu and CDX2, is useful in distinguishing extramammary Paget disease that is limited to the skin versus the subset of secondary extramammary Paget disease that is associated specifically with concurrent or future anogenital cancer, Dr. Jared Abbott said at the 11th World Congress on Cancers of the Skin.

Other investigators have postulated that the triad of cytokeratin 7 (CK7), CK20, and BRST-2 immunohistochemical stains is broadly useful in distinguishing extramammary Paget disease (EMPD) that is limited to the skin—known as primary EMPD—from all forms of secondary extramammary Paget disease, but Dr. Abbott did not find this to be the case in his own large series. Indeed, caution should be exercised in relying upon the triad of immunostains for this purpose, said Dr. Abbott of the Mayo Clinic, Rochester, Minn.

EMPD is an uncommon condition occurring primarily in the elderly, with more women than men affected. It arises as a cutaneous adenocarcinoma with a proclivity for sites rich in apocrine glands. Patients with EMPD often present with a prominent solitary plaque lesion in the anogenital or vulvar region. The lesion is erythematous, eczematous, and often pruritic. The course is often locally aggressive, with frequent recurrences.

The classic histopathologic findings of EMPD consist of clusters of epithelial cells with pagetoid extension throughout the epidermis, often accompanied by a superficial lymphocytic inflammatory infiltrate, he said at the congress, which was sponsored by the Skin Cancer Foundation and Erasmus University.

The distinction between primary and secondary EMPD is important because the prognoses are entirely different. Primary EMPD, which accounts for at least three-quarters of cases, has a good prognosis, whereas secondary EMPD has a very poor prognosis because the skin disorder is often accompanied—or, in the months to come, followed—by a gastrointestinal or genitourinary malignancy. Unfortunately, primary and secondary EMPD can't be differentiated based upon histopathology.

"Their [hematoxylin and eosin stains] look exactly alike," Dr. Abbott said.

Other investigators have turned to immunohistochemical staining patterns in an effort to make the distinction. It has been reported that primary EMPD is often CK7- and BRST-2-positive and CK20-negative, whereas secondary EMPD is BRST-2-negative, CK20-positive, and equivocal in terms of CK7.

To see if he could verify this finding, and to assess the utility of some newer immunohistochemical stains, Dr. Abbott studied excisional biopsy specimens from 61 Mayo Clinic patients with EMPD. The median age at diagnosis was 73 years, and 44 patients were women. A total of 45 patients had primary EMPD. The 16 with secondary EMPD, as determined during a median 4-year follow-up, consisted of seven patients with anorectal carcinomas, four with prostate cancer, and five with urothelial cell cancer.

All patients in both the primary and secondary EMPD groups were CK7-positive, so that was of no help, he said. In addition, CK20, BRST-2, androgen receptor, and cyclin D1 did not prove to be of much assistance in distinguishing primary from secondary EMPD. (See box.)

In contrast, HER2/neu and CDX2 were quite helpful in separating primary from secondary EMPD involving anorectal malignancy. Five of the seven patients with lower GI cancer stained positive for CDX2, and all seven were HER2/neu negative. Unfortunately, no staining pattern proved useful in identifying patients with prostate or urothelial cell cancer.

The finding that more than two-thirds of patients with primary EMPD were HER2/neu-positive, and that the positivity rate was even higher among those with recurrent primary EMPD, raises the possibility that Herceptin (trastuzumab) might be effective in these individuals, although that has never been studied, Dr. Abbott said.

ELSEVIER GLOBAL MEDICAL NEWS

CORONADO, CALIF. — The side effects associated with epidermal growth factor receptor inhibitors can be so awful that several cancer patients have told Dr. Jonathan Cotliar that they would rather die than continue taking them.

"That's significant when you hear that from many people," Dr. Cotliar said at the annual meeting of the Pacific Dermatologic Association.

One side effect that occurs in 60%–80% of cancer patients who take epidermal growth factor receptor inhibitors (EGFRIs) is skin toxicity, mostly in the form of papulopustular lesions. Paronychia, fissures, xerosis, alopecia, eyelash trichomegaly, telangiectasias, and photosensitivity also can occur.

"I think the companies that developed these drugs underestimated the significance of cutaneous toxicity," said Dr. Cotliar, director of inpatient dermatology services in the division of dermatology at the University of California, Los Angeles.

The incidence of skin toxicity among patients who take the monoclonal antibodies cetuximab (Erbitux) or panitumumab (Vectibix) is somewhat higher compared with those who take the tyrosine kinase inhibitors erlotinib (Tarceva) or gefitinib (Iressa). All of the agents cause apoptosis of keratinocytes. "That's probably the major event that allows for what we see clinically in these patients," he said.

"We also know that there is early initiation of keratinocyte differentiation. In theory, that allows the stratum corneum to become impaired, which leads to many of these toxicities. We also know that inhibition of epidermal growth factor leads to epithelial cell production of proinflammatory mediators. That allows for the adaptive immune response to take hold," he explained.

Papulopustular lesions commonly occur on the face, chest, back, and scalp. The palms and soles are spared.

Histology reveals a thinned stratum corneum, dilated follicular infundibula, necrotic keratinocytes, and mixed inflammation in the upper dermis. "In addition, you may see acantholysis of the follicular epithelium," Dr. Cotliar said.

Ironically, skin toxicity—specifically the papulopustular lesions—is a surrogate marker for treatment efficacy of EGFRIs. "We know that this eruption is more severe and incidence is greater in responders to these medications than in those who don't respond," said Dr. Cotliar, who disclosed that he is a consultant for Amgen Inc., which manufactures panitumumab, and has received honoraria from the company.

"We also know that there is a nice correlation between survival, both overall and progression free, [and] severity of the rash. We don't know if this is an epiphenomenon or if there's something about the cutaneous toxicity that's allowing the immune response to percolate and fight the underlying cancer," he noted.

The severity of papulopustular lesions seems to be linked to the EGFRI dose. "We also know that patients typically develop these lesions 1–3 weeks after their first infusion or their first pills," he said. "The maximal toxicity occurs by weeks 3–5."

Once patients stop taking the EGFRI, the cutaneous side effects usually resolve within a couple of weeks.

There is no current standard for treating skin toxicity associated with EGFRI use. A proposed treatment algorithm was recently published (Oncologist 2007;12:610–21), but "everything we know about treating these patients is based on case reports," Dr. Cotliar said.

A first approach might involve modifying the dose of the EGFRI by following package insert instructions. Most patients referred to Dr. Cotliar and his associates are started on 1% or 2% hydrocortisone or sometimes tetracycline or doxycycline.

"A lot of times I will start patients on doxycycline 100 mg b.i.d.," he said. "I also typically start—for the first week or two—with a mid- to high-potency topical corticosteroid."

One "black hole" among possible treatment options is isotretinoin. "Nobody's sure what effect it has on tumor biology," he said. "We're also not sure of its effect on EGFRIs. We need to know more about that. We do know from case reports that 20–30 mg/day is successful in helping resolve some of these lesions."

Other potential treatments for papulopustular lesions include colloidal oatmeal lotion, topical erythromycin, clindamycin, metronidazole, and topical retinoids.

Potential treatments for xerosis and pruritus triggered by the use of EGFRIs include bland emollients and antihistamines.

Potential treatments for paronychia and fissures include aluminum acetate soaks, 4% thymol, emollients, topical corticosteroids, intralesional steroids, systemic antibiotics, electrodesiccation, cryosurgery, surgical debridement, and nail plate avulsion, Dr. Cotliar said.

Lastly, pulsed dye lasers can be used to treat telangiectasias.

Papulopustular lesions are commonly seen in patients who are taking epidermal growth factor inhibitors. Courtesy Dr. Jonathan Cotliar

CORONADO, CALIF. — The side effects associated with epidermal growth factor receptor inhibitors can be so awful that several cancer patients have told Dr. Jonathan Cotliar that they would rather die than continue taking them.

"That's significant when you hear that from many people," Dr. Cotliar said at the annual meeting of the Pacific Dermatologic Association.

One side effect that occurs in 60%–80% of cancer patients who take epidermal growth factor receptor inhibitors (EGFRIs) is skin toxicity, mostly in the form of papulopustular lesions. Paronychia, fissures, xerosis, alopecia, eyelash trichomegaly, telangiectasias, and photosensitivity also can occur.

"I think the companies that developed these drugs underestimated the significance of cutaneous toxicity," said Dr. Cotliar, director of inpatient dermatology services in the division of dermatology at the University of California, Los Angeles.

The incidence of skin toxicity among patients who take the monoclonal antibodies cetuximab (Erbitux) or panitumumab (Vectibix) is somewhat higher compared with those who take the tyrosine kinase inhibitors erlotinib (Tarceva) or gefitinib (Iressa). All of the agents cause apoptosis of keratinocytes. "That's probably the major event that allows for what we see clinically in these patients," he said.

"We also know that there is early initiation of keratinocyte differentiation. In theory, that allows the stratum corneum to become impaired, which leads to many of these toxicities. We also know that inhibition of epidermal growth factor leads to epithelial cell production of proinflammatory mediators. That allows for the adaptive immune response to take hold," he explained.

Papulopustular lesions commonly occur on the face, chest, back, and scalp. The palms and soles are spared.

Histology reveals a thinned stratum corneum, dilated follicular infundibula, necrotic keratinocytes, and mixed inflammation in the upper dermis. "In addition, you may see acantholysis of the follicular epithelium," Dr. Cotliar said.

Ironically, skin toxicity—specifically the papulopustular lesions—is a surrogate marker for treatment efficacy of EGFRIs. "We know that this eruption is more severe and incidence is greater in responders to these medications than in those who don't respond," said Dr. Cotliar, who disclosed that he is a consultant for Amgen Inc., which manufactures panitumumab, and has received honoraria from the company.

"We also know that there is a nice correlation between survival, both overall and progression free, [and] severity of the rash. We don't know if this is an epiphenomenon or if there's something about the cutaneous toxicity that's allowing the immune response to percolate and fight the underlying cancer," he noted.

The severity of papulopustular lesions seems to be linked to the EGFRI dose. "We also know that patients typically develop these lesions 1–3 weeks after their first infusion or their first pills," he said. "The maximal toxicity occurs by weeks 3–5."

Once patients stop taking the EGFRI, the cutaneous side effects usually resolve within a couple of weeks.

There is no current standard for treating skin toxicity associated with EGFRI use. A proposed treatment algorithm was recently published (Oncologist 2007;12:610–21), but "everything we know about treating these patients is based on case reports," Dr. Cotliar said.

A first approach might involve modifying the dose of the EGFRI by following package insert instructions. Most patients referred to Dr. Cotliar and his associates are started on 1% or 2% hydrocortisone or sometimes tetracycline or doxycycline.

"A lot of times I will start patients on doxycycline 100 mg b.i.d.," he said. "I also typically start—for the first week or two—with a mid- to high-potency topical corticosteroid."

One "black hole" among possible treatment options is isotretinoin. "Nobody's sure what effect it has on tumor biology," he said. "We're also not sure of its effect on EGFRIs. We need to know more about that. We do know from case reports that 20–30 mg/day is successful in helping resolve some of these lesions."

Other potential treatments for papulopustular lesions include colloidal oatmeal lotion, topical erythromycin, clindamycin, metronidazole, and topical retinoids.

Potential treatments for xerosis and pruritus triggered by the use of EGFRIs include bland emollients and antihistamines.

Potential treatments for paronychia and fissures include aluminum acetate soaks, 4% thymol, emollients, topical corticosteroids, intralesional steroids, systemic antibiotics, electrodesiccation, cryosurgery, surgical debridement, and nail plate avulsion, Dr. Cotliar said.

Lastly, pulsed dye lasers can be used to treat telangiectasias.

Papulopustular lesions are commonly seen in patients who are taking epidermal growth factor inhibitors. Courtesy Dr. Jonathan Cotliar

CORONADO, CALIF. — The side effects associated with epidermal growth factor receptor inhibitors can be so awful that several cancer patients have told Dr. Jonathan Cotliar that they would rather die than continue taking them.

"That's significant when you hear that from many people," Dr. Cotliar said at the annual meeting of the Pacific Dermatologic Association.

One side effect that occurs in 60%–80% of cancer patients who take epidermal growth factor receptor inhibitors (EGFRIs) is skin toxicity, mostly in the form of papulopustular lesions. Paronychia, fissures, xerosis, alopecia, eyelash trichomegaly, telangiectasias, and photosensitivity also can occur.

"I think the companies that developed these drugs underestimated the significance of cutaneous toxicity," said Dr. Cotliar, director of inpatient dermatology services in the division of dermatology at the University of California, Los Angeles.

The incidence of skin toxicity among patients who take the monoclonal antibodies cetuximab (Erbitux) or panitumumab (Vectibix) is somewhat higher compared with those who take the tyrosine kinase inhibitors erlotinib (Tarceva) or gefitinib (Iressa). All of the agents cause apoptosis of keratinocytes. "That's probably the major event that allows for what we see clinically in these patients," he said.

"We also know that there is early initiation of keratinocyte differentiation. In theory, that allows the stratum corneum to become impaired, which leads to many of these toxicities. We also know that inhibition of epidermal growth factor leads to epithelial cell production of proinflammatory mediators. That allows for the adaptive immune response to take hold," he explained.

Papulopustular lesions commonly occur on the face, chest, back, and scalp. The palms and soles are spared.

Histology reveals a thinned stratum corneum, dilated follicular infundibula, necrotic keratinocytes, and mixed inflammation in the upper dermis. "In addition, you may see acantholysis of the follicular epithelium," Dr. Cotliar said.

Ironically, skin toxicity—specifically the papulopustular lesions—is a surrogate marker for treatment efficacy of EGFRIs. "We know that this eruption is more severe and incidence is greater in responders to these medications than in those who don't respond," said Dr. Cotliar, who disclosed that he is a consultant for Amgen Inc., which manufactures panitumumab, and has received honoraria from the company.

"We also know that there is a nice correlation between survival, both overall and progression free, [and] severity of the rash. We don't know if this is an epiphenomenon or if there's something about the cutaneous toxicity that's allowing the immune response to percolate and fight the underlying cancer," he noted.

The severity of papulopustular lesions seems to be linked to the EGFRI dose. "We also know that patients typically develop these lesions 1–3 weeks after their first infusion or their first pills," he said. "The maximal toxicity occurs by weeks 3–5."

Once patients stop taking the EGFRI, the cutaneous side effects usually resolve within a couple of weeks.

There is no current standard for treating skin toxicity associated with EGFRI use. A proposed treatment algorithm was recently published (Oncologist 2007;12:610–21), but "everything we know about treating these patients is based on case reports," Dr. Cotliar said.

A first approach might involve modifying the dose of the EGFRI by following package insert instructions. Most patients referred to Dr. Cotliar and his associates are started on 1% or 2% hydrocortisone or sometimes tetracycline or doxycycline.

"A lot of times I will start patients on doxycycline 100 mg b.i.d.," he said. "I also typically start—for the first week or two—with a mid- to high-potency topical corticosteroid."

One "black hole" among possible treatment options is isotretinoin. "Nobody's sure what effect it has on tumor biology," he said. "We're also not sure of its effect on EGFRIs. We need to know more about that. We do know from case reports that 20–30 mg/day is successful in helping resolve some of these lesions."

Other potential treatments for papulopustular lesions include colloidal oatmeal lotion, topical erythromycin, clindamycin, metronidazole, and topical retinoids.

Potential treatments for xerosis and pruritus triggered by the use of EGFRIs include bland emollients and antihistamines.

Potential treatments for paronychia and fissures include aluminum acetate soaks, 4% thymol, emollients, topical corticosteroids, intralesional steroids, systemic antibiotics, electrodesiccation, cryosurgery, surgical debridement, and nail plate avulsion, Dr. Cotliar said.

Lastly, pulsed dye lasers can be used to treat telangiectasias.

Papulopustular lesions are commonly seen in patients who are taking epidermal growth factor inhibitors. Courtesy Dr. Jonathan Cotliar

CORONADO, CALIF. — Topical red wine, green tea, and caffeine polyphenols may play a role as chemopreventive agents for actinic keratoses and photodamaged skin, results from a small pilot study suggest.

The first part of the study was designed to assess the safety and efficacy of the individual polyphenols. The second part of the study was designed to assess the efficacy of combination therapy (green tea polyphenols plus vitamin C or red wine polyphenols plus caffeine), Dr. Karen F. Han said at the annual meeting of the Pacific Dermatologic Association.

Patients were eligible for the study if they had at least three actinic keratoses on each forearm, each dorsal hand, or the face/scalp/neck area, and were otherwise in good health.

In a double-blind, left-to-right placebo-controlled trial, the subjects were randomly assigned to one of the tested gels and a placebo gel. Patients were instructed to apply the gels twice a day for 12 weeks.

Before and after clinical photographs were taken, shave or 2-mm punch biopsies were obtained, and the patients were followed monthly for a total of four visits.

At each monthly follow-up visit, Dr. Han, a dermatologist in group practice in Palo Alto, Calif., mapped and counted actinic keratoses, took clinical photographs, and reviewed each patient's self-assessment form. The main outcome measure was the total number of residual actinic keratoses; the secondary outcome measure was an assessment of signs of photodamage, including dyschromia, wrinkling, texture, and telangiectasia.

In part 1 of the study, Dr. Han saw a statistically significant difference between the treatment sides and placebo sides in 11 of 14 patients. Of those 14 patients, 7 (50%) had reduced numbers of actinic keratoses that favored the treatment side. The reduction ranged from 60% to 100% clearance.

In part 2 of the study, Dr. Han observed a statistically significant difference between the treatment sides and the placebo sides in eight of nine patients who completed this component of the trial. Of those nine patients, seven (78%) had reduced numbers of actinic keratoses that favored the treatment side. The reduction ranged from 50% to 85% clearance.

Shantel Medical Supply Corp. supplied the gels used for the trial, but Dr. Han did not receive any financial support from the company.

Seven of nine patients had significantlyfewer actinic keratoses on the combination therapy side. DR. HAN

CORONADO, CALIF. — Topical red wine, green tea, and caffeine polyphenols may play a role as chemopreventive agents for actinic keratoses and photodamaged skin, results from a small pilot study suggest.

The first part of the study was designed to assess the safety and efficacy of the individual polyphenols. The second part of the study was designed to assess the efficacy of combination therapy (green tea polyphenols plus vitamin C or red wine polyphenols plus caffeine), Dr. Karen F. Han said at the annual meeting of the Pacific Dermatologic Association.

Patients were eligible for the study if they had at least three actinic keratoses on each forearm, each dorsal hand, or the face/scalp/neck area, and were otherwise in good health.

In a double-blind, left-to-right placebo-controlled trial, the subjects were randomly assigned to one of the tested gels and a placebo gel. Patients were instructed to apply the gels twice a day for 12 weeks.

Before and after clinical photographs were taken, shave or 2-mm punch biopsies were obtained, and the patients were followed monthly for a total of four visits.

At each monthly follow-up visit, Dr. Han, a dermatologist in group practice in Palo Alto, Calif., mapped and counted actinic keratoses, took clinical photographs, and reviewed each patient's self-assessment form. The main outcome measure was the total number of residual actinic keratoses; the secondary outcome measure was an assessment of signs of photodamage, including dyschromia, wrinkling, texture, and telangiectasia.

In part 1 of the study, Dr. Han saw a statistically significant difference between the treatment sides and placebo sides in 11 of 14 patients. Of those 14 patients, 7 (50%) had reduced numbers of actinic keratoses that favored the treatment side. The reduction ranged from 60% to 100% clearance.

In part 2 of the study, Dr. Han observed a statistically significant difference between the treatment sides and the placebo sides in eight of nine patients who completed this component of the trial. Of those nine patients, seven (78%) had reduced numbers of actinic keratoses that favored the treatment side. The reduction ranged from 50% to 85% clearance.

Shantel Medical Supply Corp. supplied the gels used for the trial, but Dr. Han did not receive any financial support from the company.

Seven of nine patients had significantlyfewer actinic keratoses on the combination therapy side. DR. HAN

CORONADO, CALIF. — Topical red wine, green tea, and caffeine polyphenols may play a role as chemopreventive agents for actinic keratoses and photodamaged skin, results from a small pilot study suggest.

The first part of the study was designed to assess the safety and efficacy of the individual polyphenols. The second part of the study was designed to assess the efficacy of combination therapy (green tea polyphenols plus vitamin C or red wine polyphenols plus caffeine), Dr. Karen F. Han said at the annual meeting of the Pacific Dermatologic Association.

Patients were eligible for the study if they had at least three actinic keratoses on each forearm, each dorsal hand, or the face/scalp/neck area, and were otherwise in good health.

In a double-blind, left-to-right placebo-controlled trial, the subjects were randomly assigned to one of the tested gels and a placebo gel. Patients were instructed to apply the gels twice a day for 12 weeks.

Before and after clinical photographs were taken, shave or 2-mm punch biopsies were obtained, and the patients were followed monthly for a total of four visits.

At each monthly follow-up visit, Dr. Han, a dermatologist in group practice in Palo Alto, Calif., mapped and counted actinic keratoses, took clinical photographs, and reviewed each patient's self-assessment form. The main outcome measure was the total number of residual actinic keratoses; the secondary outcome measure was an assessment of signs of photodamage, including dyschromia, wrinkling, texture, and telangiectasia.

In part 1 of the study, Dr. Han saw a statistically significant difference between the treatment sides and placebo sides in 11 of 14 patients. Of those 14 patients, 7 (50%) had reduced numbers of actinic keratoses that favored the treatment side. The reduction ranged from 60% to 100% clearance.

In part 2 of the study, Dr. Han observed a statistically significant difference between the treatment sides and the placebo sides in eight of nine patients who completed this component of the trial. Of those nine patients, seven (78%) had reduced numbers of actinic keratoses that favored the treatment side. The reduction ranged from 50% to 85% clearance.

Shantel Medical Supply Corp. supplied the gels used for the trial, but Dr. Han did not receive any financial support from the company.

Seven of nine patients had significantlyfewer actinic keratoses on the combination therapy side. DR. HAN