Melanoma

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Pustular infections due to Staphylococcus aureus in the newborn nursery are preventable.

Approximately 4% of all newborns develop an infection in the first 30 days of life. Of these, pustulosis is the second-most common (after nonpneumonia respiratory tract infections), occurring in about 1 in every 100-200 newborns with a peak onset at 10-15 days of life. Most of these infections are due to S. aureus, and increasingly, methicillin-resistant S. aureus (MRSA).

Indeed, outbreaks of neonatal pustular disease should prompt concern about MRSA in the community. Colonization with S. aureus requires very little exposure. The problem can often be traced to crowding and failures of standard infection control practices in the newborn nursery, along with two other specific recently identified risk factors: circumcision and the use of multidose lidocaine vials.

A case-control study investigated 11 newborns who had onset of MRSA skin and soft-tissue infection within 21 days after discharge from a well-infant nursery at a community hospital over an 8-month period. All were term male infants with pustular-vesicular lesions in the groin, Dr. Dao Nguyen and associates at the Centers for Disease Control and Prevention reported (Infect. Control Hosp. Epidemiol. 2007;28:406-11).

Risk factors associated with the MRSA infections were length of stay, circumcision in the nursery, and receipt of lidocaine injections used to anesthetize for the circumcision procedure. Inspection revealed uncovered circumcision equipment, multiple-dose lidocaine vials, and inadequate hand hygiene practices.

Nineteen cases of MRSA infection were reported in neonates born at Beth Israel Deaconess Medical Center in Boston. Of the 19 infants who have become ill with the drug-resistant staphylococcal infection, 15 have been boys, the Boston Public Health Commission reported. Violations of standard infection control practices related to circumcision and postprocedure care were identified as contributing factors.

A literature review of 10 articles reporting on staphylococcal colonization and infection in the newborn period revealed that male infants have a greater risk than do female infants, and that the male to female ratio is even higher in studies where most of the boys are circumcised as infants (Clin. Pediatr. 2007;46:356-8).

But the answer to the neonatal staphylococcal problem is not to stop circumcising babies. Policies and attitudes toward circumcision are currently being revisited. After a decade or so in which a large body of evidence indicating the procedure reduces the risk for the development of a variety of sexually transmitted diseases was largely ignored, the American Academy of Pediatrics is reviewing its policy on the medical benefits of the procedure.

What's needed is better attention to surgical technique and hygiene during circumcision procedures, along with the use of single-dose lidocaine vials.

For newborns who do develop pustular disease in the diaper area, lower abdomen, or any other area, the approach to management varies considerably. Some infants are hospitalized and treated systemically while others are managed with local or topical therapy. An individualized approach would appear necessary as the spectrum of clinical disease is broad. First, the child should be evaluated for other possible etiologies.

If staphylococcal disease is suspected, the presence or absence of systemic signs, abscess, or local cellulitis will help determine whether systemic therapy is needed or if initial local management is appropriate. In all cases, close follow-up is needed to ensure that resolution occurs.

[email protected]

Pustular infections due to Staphylococcus aureus in the newborn nursery are preventable.

Approximately 4% of all newborns develop an infection in the first 30 days of life. Of these, pustulosis is the second-most common (after nonpneumonia respiratory tract infections), occurring in about 1 in every 100-200 newborns with a peak onset at 10-15 days of life. Most of these infections are due to S. aureus, and increasingly, methicillin-resistant S. aureus (MRSA).

Indeed, outbreaks of neonatal pustular disease should prompt concern about MRSA in the community. Colonization with S. aureus requires very little exposure. The problem can often be traced to crowding and failures of standard infection control practices in the newborn nursery, along with two other specific recently identified risk factors: circumcision and the use of multidose lidocaine vials.

A case-control study investigated 11 newborns who had onset of MRSA skin and soft-tissue infection within 21 days after discharge from a well-infant nursery at a community hospital over an 8-month period. All were term male infants with pustular-vesicular lesions in the groin, Dr. Dao Nguyen and associates at the Centers for Disease Control and Prevention reported (Infect. Control Hosp. Epidemiol. 2007;28:406-11).

Risk factors associated with the MRSA infections were length of stay, circumcision in the nursery, and receipt of lidocaine injections used to anesthetize for the circumcision procedure. Inspection revealed uncovered circumcision equipment, multiple-dose lidocaine vials, and inadequate hand hygiene practices.

Nineteen cases of MRSA infection were reported in neonates born at Beth Israel Deaconess Medical Center in Boston. Of the 19 infants who have become ill with the drug-resistant staphylococcal infection, 15 have been boys, the Boston Public Health Commission reported. Violations of standard infection control practices related to circumcision and postprocedure care were identified as contributing factors.

A literature review of 10 articles reporting on staphylococcal colonization and infection in the newborn period revealed that male infants have a greater risk than do female infants, and that the male to female ratio is even higher in studies where most of the boys are circumcised as infants (Clin. Pediatr. 2007;46:356-8).

But the answer to the neonatal staphylococcal problem is not to stop circumcising babies. Policies and attitudes toward circumcision are currently being revisited. After a decade or so in which a large body of evidence indicating the procedure reduces the risk for the development of a variety of sexually transmitted diseases was largely ignored, the American Academy of Pediatrics is reviewing its policy on the medical benefits of the procedure.

What's needed is better attention to surgical technique and hygiene during circumcision procedures, along with the use of single-dose lidocaine vials.

For newborns who do develop pustular disease in the diaper area, lower abdomen, or any other area, the approach to management varies considerably. Some infants are hospitalized and treated systemically while others are managed with local or topical therapy. An individualized approach would appear necessary as the spectrum of clinical disease is broad. First, the child should be evaluated for other possible etiologies.

If staphylococcal disease is suspected, the presence or absence of systemic signs, abscess, or local cellulitis will help determine whether systemic therapy is needed or if initial local management is appropriate. In all cases, close follow-up is needed to ensure that resolution occurs.

[email protected]

Pustular infections due to Staphylococcus aureus in the newborn nursery are preventable.

Approximately 4% of all newborns develop an infection in the first 30 days of life. Of these, pustulosis is the second-most common (after nonpneumonia respiratory tract infections), occurring in about 1 in every 100-200 newborns with a peak onset at 10-15 days of life. Most of these infections are due to S. aureus, and increasingly, methicillin-resistant S. aureus (MRSA).

Indeed, outbreaks of neonatal pustular disease should prompt concern about MRSA in the community. Colonization with S. aureus requires very little exposure. The problem can often be traced to crowding and failures of standard infection control practices in the newborn nursery, along with two other specific recently identified risk factors: circumcision and the use of multidose lidocaine vials.

A case-control study investigated 11 newborns who had onset of MRSA skin and soft-tissue infection within 21 days after discharge from a well-infant nursery at a community hospital over an 8-month period. All were term male infants with pustular-vesicular lesions in the groin, Dr. Dao Nguyen and associates at the Centers for Disease Control and Prevention reported (Infect. Control Hosp. Epidemiol. 2007;28:406-11).

Risk factors associated with the MRSA infections were length of stay, circumcision in the nursery, and receipt of lidocaine injections used to anesthetize for the circumcision procedure. Inspection revealed uncovered circumcision equipment, multiple-dose lidocaine vials, and inadequate hand hygiene practices.

Nineteen cases of MRSA infection were reported in neonates born at Beth Israel Deaconess Medical Center in Boston. Of the 19 infants who have become ill with the drug-resistant staphylococcal infection, 15 have been boys, the Boston Public Health Commission reported. Violations of standard infection control practices related to circumcision and postprocedure care were identified as contributing factors.

A literature review of 10 articles reporting on staphylococcal colonization and infection in the newborn period revealed that male infants have a greater risk than do female infants, and that the male to female ratio is even higher in studies where most of the boys are circumcised as infants (Clin. Pediatr. 2007;46:356-8).

But the answer to the neonatal staphylococcal problem is not to stop circumcising babies. Policies and attitudes toward circumcision are currently being revisited. After a decade or so in which a large body of evidence indicating the procedure reduces the risk for the development of a variety of sexually transmitted diseases was largely ignored, the American Academy of Pediatrics is reviewing its policy on the medical benefits of the procedure.

What's needed is better attention to surgical technique and hygiene during circumcision procedures, along with the use of single-dose lidocaine vials.

For newborns who do develop pustular disease in the diaper area, lower abdomen, or any other area, the approach to management varies considerably. Some infants are hospitalized and treated systemically while others are managed with local or topical therapy. An individualized approach would appear necessary as the spectrum of clinical disease is broad. First, the child should be evaluated for other possible etiologies.

If staphylococcal disease is suspected, the presence or absence of systemic signs, abscess, or local cellulitis will help determine whether systemic therapy is needed or if initial local management is appropriate. In all cases, close follow-up is needed to ensure that resolution occurs.

BOSTON — The threshold for biopsying unexplained nail dystrophy or discoloration should be low, according to Dr. Phoebe Rich.

Although the majority of nail unit lesions are benign, "malignancies are not as obvious to spot clinically as you would think," and a missed or delayed diagnosis can be life threatening, Dr. Rich said at the American Academy of Dermatology's Academy 2009 meeting.

Any unexplained solitary, painful, dystrophic nail, particularly in an elderly patient, should be biopsied to rule out squamous cell carcinoma of the nail bed.

Any pigmented band of unknown etiology, especially in white patients, requires a biopsy to rule out melanoma, said Dr. Rich of the department of dermatology at Oregon Health and Science University in Portland.

The presence of certain clinical signs and symptoms can offer clues to the diagnosis of malignant neoplasms. For example, Dr. Rich said, squamous cell carcinoma of the nail may present as longitudinal erythronychia (a pinkish band extending from the nail matrix); as a nodule or tumor with or without nail loss; as a wartlike periungual lesion with nail splitting and skin fissure; or as a draining subungual mass. Because these presentations mimic other clinical entities, "you have to biopsy to get an accurate diagnosis," she said, stressing that nail surgery should not be intimidating. "Any dermatologist who can do a punch biopsy can do a nail biopsy."

For the aforementioned lesions, "you can take a punch or a shave [nail bed] biopsy, and once you have a diagnosis, you can refer the patient for Mohs or, if you feel confident, you can remove it yourself," said Dr. Rich. "We all do skin surgery for squamous cell carcinoma day in and day out. When you remove it, you just have to remember that there is no subcutaneous tissue in the nail, so you are actually removing it at the level just at the periosteum. Check to make sure you have got a nice margin, and you're in good shape."

Subungual melanoma arises from the nail matrix and often presents initially as longitudinal melanonychia, said Dr. Rich. The differential diagnosis for melanonychia is broad, however, and includes benign nevi, lentigo in the nail matrix, genetic and ethnic-type pigmentation, subungual hematoma, drug-induced pigmentation, vitamin deficiency fungal infections, and squamous cell carcinoma in situ, she said.

A high index of suspicion for melanoma should exist with lesions that begin under the nail and extend outward onto healthy skin around the nail (Hutchinson's sign); if there is variability in the pigmentation of the band; if the pigmented band is widening or growing; or if there is bleeding or signs of ulceration, Dr. Rich explained. "In these cases, when you have a pigmented band, you have to open it up, look in there, and get a specimen," she said. "It's critical that you biopsy proximally at the matrix, at the origin of the band, because you need the melanocytes. If you biopsy the nail bed distally in an area where the nail plate is involved, you're not going to get the pigment, and you won't get an accurate diagnosis."

Although pigmentary changes can offer a clue to the presence of melanoma, a certain percentage of nail melanomas are amelanotic, said Dr. Rich. Amelanotic melanomas of the nail bed may resemble chronic paronychia or other benign nail conditions, she said.

For suspected nail melanoma, a nail matrix shave biopsy is sufficient, "unless you suspect advanced melanoma, which is characterized clinically by a dystrophic nail plate in addition to the pigmentation," Dr. Rich said. "In that case, a full thickness biopsy is needed." For large lesions located in the lateral third of the nail, "a longitudinal nail biopsy yields the best information because it samples the nail matrix, nail bed, nail fold, and hyponychium."

Proper preparation of the specimen is also critical to an accurate diagnosis, stressed Dr. Rich, who always orients the specimen on a paper template with a schematic of the nail and fingertip to duplicate its position on the nail unit before dropping it into formalin. "This way, the pathologist knows where the sample comes from," she said.

Because patients are typically apprehensive about nail surgery, the onus is on the clinician to reassure them that it can be done painlessly by using appropriate and effective anesthesia, according to Dr. Rich, who often begins the anesthesia application by having the patient—especially if it is a child—hold a vibrating device. This offers a distraction, she explained, and provides a competing sensation. She then administers an ethyl chloride spray, followed by an injection, via a 30-gauge needle, of lidocaine with epinephrine—which has been proved safe. The addition of bupivacaine or ropivacaine helps to minimize postoperative discomfort.

The anesthesia can be administered using a true digital block, which involves injecting the anesthetic agent into the lateral base of the digit, or through a wing block, whereby the agent is injected into the proximal nail fold. "In my experience, a wing block is quicker, and because it requires a smaller volume of anesthesia, it is safer," said Dr. Rich. "It is also much less painful than a digital block."

Dr. Rich has received advisory board honoraria from Abbott Laboratories and investigator grants from Centocor Inc., Wyeth, and Genentech Inc.

Subungual melanoma often presents initially as longitudinal melanonychia.

Source ©dermnet.com

BOSTON — The threshold for biopsying unexplained nail dystrophy or discoloration should be low, according to Dr. Phoebe Rich.

Although the majority of nail unit lesions are benign, "malignancies are not as obvious to spot clinically as you would think," and a missed or delayed diagnosis can be life threatening, Dr. Rich said at the American Academy of Dermatology's Academy 2009 meeting.

Any unexplained solitary, painful, dystrophic nail, particularly in an elderly patient, should be biopsied to rule out squamous cell carcinoma of the nail bed.

Any pigmented band of unknown etiology, especially in white patients, requires a biopsy to rule out melanoma, said Dr. Rich of the department of dermatology at Oregon Health and Science University in Portland.

The presence of certain clinical signs and symptoms can offer clues to the diagnosis of malignant neoplasms. For example, Dr. Rich said, squamous cell carcinoma of the nail may present as longitudinal erythronychia (a pinkish band extending from the nail matrix); as a nodule or tumor with or without nail loss; as a wartlike periungual lesion with nail splitting and skin fissure; or as a draining subungual mass. Because these presentations mimic other clinical entities, "you have to biopsy to get an accurate diagnosis," she said, stressing that nail surgery should not be intimidating. "Any dermatologist who can do a punch biopsy can do a nail biopsy."

For the aforementioned lesions, "you can take a punch or a shave [nail bed] biopsy, and once you have a diagnosis, you can refer the patient for Mohs or, if you feel confident, you can remove it yourself," said Dr. Rich. "We all do skin surgery for squamous cell carcinoma day in and day out. When you remove it, you just have to remember that there is no subcutaneous tissue in the nail, so you are actually removing it at the level just at the periosteum. Check to make sure you have got a nice margin, and you're in good shape."

Subungual melanoma arises from the nail matrix and often presents initially as longitudinal melanonychia, said Dr. Rich. The differential diagnosis for melanonychia is broad, however, and includes benign nevi, lentigo in the nail matrix, genetic and ethnic-type pigmentation, subungual hematoma, drug-induced pigmentation, vitamin deficiency fungal infections, and squamous cell carcinoma in situ, she said.

A high index of suspicion for melanoma should exist with lesions that begin under the nail and extend outward onto healthy skin around the nail (Hutchinson's sign); if there is variability in the pigmentation of the band; if the pigmented band is widening or growing; or if there is bleeding or signs of ulceration, Dr. Rich explained. "In these cases, when you have a pigmented band, you have to open it up, look in there, and get a specimen," she said. "It's critical that you biopsy proximally at the matrix, at the origin of the band, because you need the melanocytes. If you biopsy the nail bed distally in an area where the nail plate is involved, you're not going to get the pigment, and you won't get an accurate diagnosis."

Although pigmentary changes can offer a clue to the presence of melanoma, a certain percentage of nail melanomas are amelanotic, said Dr. Rich. Amelanotic melanomas of the nail bed may resemble chronic paronychia or other benign nail conditions, she said.

For suspected nail melanoma, a nail matrix shave biopsy is sufficient, "unless you suspect advanced melanoma, which is characterized clinically by a dystrophic nail plate in addition to the pigmentation," Dr. Rich said. "In that case, a full thickness biopsy is needed." For large lesions located in the lateral third of the nail, "a longitudinal nail biopsy yields the best information because it samples the nail matrix, nail bed, nail fold, and hyponychium."

Proper preparation of the specimen is also critical to an accurate diagnosis, stressed Dr. Rich, who always orients the specimen on a paper template with a schematic of the nail and fingertip to duplicate its position on the nail unit before dropping it into formalin. "This way, the pathologist knows where the sample comes from," she said.

Because patients are typically apprehensive about nail surgery, the onus is on the clinician to reassure them that it can be done painlessly by using appropriate and effective anesthesia, according to Dr. Rich, who often begins the anesthesia application by having the patient—especially if it is a child—hold a vibrating device. This offers a distraction, she explained, and provides a competing sensation. She then administers an ethyl chloride spray, followed by an injection, via a 30-gauge needle, of lidocaine with epinephrine—which has been proved safe. The addition of bupivacaine or ropivacaine helps to minimize postoperative discomfort.

The anesthesia can be administered using a true digital block, which involves injecting the anesthetic agent into the lateral base of the digit, or through a wing block, whereby the agent is injected into the proximal nail fold. "In my experience, a wing block is quicker, and because it requires a smaller volume of anesthesia, it is safer," said Dr. Rich. "It is also much less painful than a digital block."

Dr. Rich has received advisory board honoraria from Abbott Laboratories and investigator grants from Centocor Inc., Wyeth, and Genentech Inc.

Subungual melanoma often presents initially as longitudinal melanonychia.

Source ©dermnet.com

BOSTON — The threshold for biopsying unexplained nail dystrophy or discoloration should be low, according to Dr. Phoebe Rich.

Although the majority of nail unit lesions are benign, "malignancies are not as obvious to spot clinically as you would think," and a missed or delayed diagnosis can be life threatening, Dr. Rich said at the American Academy of Dermatology's Academy 2009 meeting.

Any unexplained solitary, painful, dystrophic nail, particularly in an elderly patient, should be biopsied to rule out squamous cell carcinoma of the nail bed.

Any pigmented band of unknown etiology, especially in white patients, requires a biopsy to rule out melanoma, said Dr. Rich of the department of dermatology at Oregon Health and Science University in Portland.

The presence of certain clinical signs and symptoms can offer clues to the diagnosis of malignant neoplasms. For example, Dr. Rich said, squamous cell carcinoma of the nail may present as longitudinal erythronychia (a pinkish band extending from the nail matrix); as a nodule or tumor with or without nail loss; as a wartlike periungual lesion with nail splitting and skin fissure; or as a draining subungual mass. Because these presentations mimic other clinical entities, "you have to biopsy to get an accurate diagnosis," she said, stressing that nail surgery should not be intimidating. "Any dermatologist who can do a punch biopsy can do a nail biopsy."

For the aforementioned lesions, "you can take a punch or a shave [nail bed] biopsy, and once you have a diagnosis, you can refer the patient for Mohs or, if you feel confident, you can remove it yourself," said Dr. Rich. "We all do skin surgery for squamous cell carcinoma day in and day out. When you remove it, you just have to remember that there is no subcutaneous tissue in the nail, so you are actually removing it at the level just at the periosteum. Check to make sure you have got a nice margin, and you're in good shape."

Subungual melanoma arises from the nail matrix and often presents initially as longitudinal melanonychia, said Dr. Rich. The differential diagnosis for melanonychia is broad, however, and includes benign nevi, lentigo in the nail matrix, genetic and ethnic-type pigmentation, subungual hematoma, drug-induced pigmentation, vitamin deficiency fungal infections, and squamous cell carcinoma in situ, she said.

A high index of suspicion for melanoma should exist with lesions that begin under the nail and extend outward onto healthy skin around the nail (Hutchinson's sign); if there is variability in the pigmentation of the band; if the pigmented band is widening or growing; or if there is bleeding or signs of ulceration, Dr. Rich explained. "In these cases, when you have a pigmented band, you have to open it up, look in there, and get a specimen," she said. "It's critical that you biopsy proximally at the matrix, at the origin of the band, because you need the melanocytes. If you biopsy the nail bed distally in an area where the nail plate is involved, you're not going to get the pigment, and you won't get an accurate diagnosis."

Although pigmentary changes can offer a clue to the presence of melanoma, a certain percentage of nail melanomas are amelanotic, said Dr. Rich. Amelanotic melanomas of the nail bed may resemble chronic paronychia or other benign nail conditions, she said.

For suspected nail melanoma, a nail matrix shave biopsy is sufficient, "unless you suspect advanced melanoma, which is characterized clinically by a dystrophic nail plate in addition to the pigmentation," Dr. Rich said. "In that case, a full thickness biopsy is needed." For large lesions located in the lateral third of the nail, "a longitudinal nail biopsy yields the best information because it samples the nail matrix, nail bed, nail fold, and hyponychium."

Proper preparation of the specimen is also critical to an accurate diagnosis, stressed Dr. Rich, who always orients the specimen on a paper template with a schematic of the nail and fingertip to duplicate its position on the nail unit before dropping it into formalin. "This way, the pathologist knows where the sample comes from," she said.

Because patients are typically apprehensive about nail surgery, the onus is on the clinician to reassure them that it can be done painlessly by using appropriate and effective anesthesia, according to Dr. Rich, who often begins the anesthesia application by having the patient—especially if it is a child—hold a vibrating device. This offers a distraction, she explained, and provides a competing sensation. She then administers an ethyl chloride spray, followed by an injection, via a 30-gauge needle, of lidocaine with epinephrine—which has been proved safe. The addition of bupivacaine or ropivacaine helps to minimize postoperative discomfort.

The anesthesia can be administered using a true digital block, which involves injecting the anesthetic agent into the lateral base of the digit, or through a wing block, whereby the agent is injected into the proximal nail fold. "In my experience, a wing block is quicker, and because it requires a smaller volume of anesthesia, it is safer," said Dr. Rich. "It is also much less painful than a digital block."

Dr. Rich has received advisory board honoraria from Abbott Laboratories and investigator grants from Centocor Inc., Wyeth, and Genentech Inc.

Subungual melanoma often presents initially as longitudinal melanonychia.

Source ©dermnet.com

PORTLAND, ORE. — Skin lesions are a hallmark of Merkel cell carcinoma, yet dermatologists often find themselves out of the loop in diagnosing patients with the disease, said Dr. Paul Nghiem.

"These [lesions] are typically biopsied as a cyst and the patient usually has to argue for one, two, or three doctor's visits to have the lesion biopsied," Dr. Nghiem said at the annual meeting of the Pacific Dermatologic Association. "They're usually biopsied by a reluctant primary care physician who thinks they're taking off a cyst. Then they may be referred to medical oncology or to surgical oncology, but rarely to dermatology."

About 1,500 new cases of Merkel cell carcinoma (MCC) are diagnosed in the United States each year (J. Invest. Dermatol. 2007;127:2100-3), which is about the same incidence as cutaneous T-cell lymphoma or dermatofibrosarcoma protuberans, said Dr. Nghiem, an expert on the disease who is associate professor of dermatology, medicine, and pathology at the University of Washington, Seattle.

MCC is significantly more lethal than melanoma (40% vs. 15%, respectively), and its reported incidence has increased threefold since 1986 (J. Surg. Oncol. 2005;89:1-4).

"A big reason for that is that it's not missed as much," Dr. Nghiem said. "There are better tools for pathologists to use to make the diagnosis."

The three main risk factors for MCC are prolonged sun exposure, immune suppression, and age over 50 years. "Ninety-four percent of all MCC cases are in people aged 50 or older," he said. "There is a very strong synergy with age" (J. Am. Acad. Dermatol. 2008;58:375-81).

Dr. Nghiem said that HIV-positive patients had about a 13-fold increase of MCC in one study (Lancet 2002;359:497-8), while another study showed that solid organ transplant recipients have about a 10-fold increase (Transplantation 1999;68:1717-21).

He and his associates devised the acronym AEIOU to describe the clinical features of Merkel cell carcinoma based on an analysis of 195 patients given the diagnosis between 1980 and 2007 (J. Am. Acad. Dermatol. 2008; 58:375-81). The acronym stands for Asymptomatic, Expanding rapidly, Immune compromised, Older than 50, and UV-exposed, fair skin.

"Under no circumstances do I think that this is a highly specific test," said Dr. Nghiem, whose clinic is based at the Fred Hutchinson Cancer Research Center in Seattle. "It's not going to be up there with the ABCDs of melanoma, but if you see these characteristics together, you may want to think about doing a biopsy."

More than half of the lesions in the 195 patients evaluated (56%) were presumed to be benign at biopsy, and 32% presented on the head and neck, followed by the lower limb (30%), upper limb (20%), trunk (10%), and buttock (8%).

The majority of lesions (81%) presented on sun-exposed skin, but one in six was in a sun-protected site.

Nearly all of the lesions (88%) were asymptomatic ("neither tender nor itchy," he said), 63% doubled in size in the past 3 months, and 8% of the patients were profoundly immune suppressed. "That is a 16-fold increase over the normal population, but still a minority of all Merkel cell cases," he said, noting that 90% of the patients studied were at least 50 years of age and that 98% were fair skinned.

"Taken together, 89% of all Merkel cell carcinomas had three or more of these clinical AEIOU features," he said.

Optimal therapy for MCC is unique among skin cancers, he said, in that sentinel lymph node biopsy (SLNB) is usually indicated and the disease is "exquisitely sensitive" to radiation.

"If I had one modality to treat MCC, it would be radiation," he said.

SLNB is important for prognosis, he added, because it "results in more accurate staging and has therapeutic implications. If it's microscopically positive [the cancer] will very likely develop in that node bed within a few months if you don't do anything."

In Dr. Nghiem's opinion, the best local therapy for MCC is pathologically clear margins when the primary tumor is less than 1 cm, there is no lymphovascular invasion, there is no profound immune suppression, and the SLNB is negative.

"If all of those things are kosher, you are pretty much okay with a negative margin incision," he said. "Otherwise, adjuvant radiation is very helpful."

He described the current staging system for MCC as "a mess." Five staging systems are currently being used, he said, yet all of them are based on studies of fewer than 300 patients and none has been validated.

MCC staging by the American Joint Committee on Cancer is currently performed using the same staging system as for 82 other nonmelanoma skin cancers, including basal cell carcinoma, squamous cell carcinoma, and adnexal neoplasms.

The key histologic feature of MCC is a perinuclear dot pattern of cytokeratin-20, "which is the rule, not the exception," he said.

Dr. Nghiem finds MCC treatment guidelines from the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology to be especially useful. The guidelines are updated annually and are available at www.nccn.org

MCC typically is coded as ICD-9 code 173 (other malignant neoplasm of skin). "Unfortunately, this means that MCC costs can't be tracked at all and, more importantly, patients are denied care," he said. Things should improve on that front shortly, however. Dr. Nghiem said that the CDC is expected to release eight new diagnostic codes specific for MCC this month.

Little is known about MCC biology, but a study from 2008 found that a new polyomavirus is present in the vast majority of cases (Science 2008;319:1096-100). "This is only the sixth example of a virus clearly linked to human cancer," Dr. Nghiem said.

He disclosed that he has received funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American Cancer Society.

The majority of Merkel cell carcinoma lesions appear on sun-exposed skin, but one in six has been found to appear on sun-protected areas.

Merkel cell carcinoma has a significantly higher mortality rate, compared with melanoma, and reported incidence has increased threefold since 1986.

Source Photos courtesy Dr. Paul Nghiem

PORTLAND, ORE. — Skin lesions are a hallmark of Merkel cell carcinoma, yet dermatologists often find themselves out of the loop in diagnosing patients with the disease, said Dr. Paul Nghiem.

"These [lesions] are typically biopsied as a cyst and the patient usually has to argue for one, two, or three doctor's visits to have the lesion biopsied," Dr. Nghiem said at the annual meeting of the Pacific Dermatologic Association. "They're usually biopsied by a reluctant primary care physician who thinks they're taking off a cyst. Then they may be referred to medical oncology or to surgical oncology, but rarely to dermatology."

About 1,500 new cases of Merkel cell carcinoma (MCC) are diagnosed in the United States each year (J. Invest. Dermatol. 2007;127:2100-3), which is about the same incidence as cutaneous T-cell lymphoma or dermatofibrosarcoma protuberans, said Dr. Nghiem, an expert on the disease who is associate professor of dermatology, medicine, and pathology at the University of Washington, Seattle.

MCC is significantly more lethal than melanoma (40% vs. 15%, respectively), and its reported incidence has increased threefold since 1986 (J. Surg. Oncol. 2005;89:1-4).

"A big reason for that is that it's not missed as much," Dr. Nghiem said. "There are better tools for pathologists to use to make the diagnosis."

The three main risk factors for MCC are prolonged sun exposure, immune suppression, and age over 50 years. "Ninety-four percent of all MCC cases are in people aged 50 or older," he said. "There is a very strong synergy with age" (J. Am. Acad. Dermatol. 2008;58:375-81).

Dr. Nghiem said that HIV-positive patients had about a 13-fold increase of MCC in one study (Lancet 2002;359:497-8), while another study showed that solid organ transplant recipients have about a 10-fold increase (Transplantation 1999;68:1717-21).

He and his associates devised the acronym AEIOU to describe the clinical features of Merkel cell carcinoma based on an analysis of 195 patients given the diagnosis between 1980 and 2007 (J. Am. Acad. Dermatol. 2008; 58:375-81). The acronym stands for Asymptomatic, Expanding rapidly, Immune compromised, Older than 50, and UV-exposed, fair skin.

"Under no circumstances do I think that this is a highly specific test," said Dr. Nghiem, whose clinic is based at the Fred Hutchinson Cancer Research Center in Seattle. "It's not going to be up there with the ABCDs of melanoma, but if you see these characteristics together, you may want to think about doing a biopsy."

More than half of the lesions in the 195 patients evaluated (56%) were presumed to be benign at biopsy, and 32% presented on the head and neck, followed by the lower limb (30%), upper limb (20%), trunk (10%), and buttock (8%).

The majority of lesions (81%) presented on sun-exposed skin, but one in six was in a sun-protected site.

Nearly all of the lesions (88%) were asymptomatic ("neither tender nor itchy," he said), 63% doubled in size in the past 3 months, and 8% of the patients were profoundly immune suppressed. "That is a 16-fold increase over the normal population, but still a minority of all Merkel cell cases," he said, noting that 90% of the patients studied were at least 50 years of age and that 98% were fair skinned.

"Taken together, 89% of all Merkel cell carcinomas had three or more of these clinical AEIOU features," he said.

Optimal therapy for MCC is unique among skin cancers, he said, in that sentinel lymph node biopsy (SLNB) is usually indicated and the disease is "exquisitely sensitive" to radiation.

"If I had one modality to treat MCC, it would be radiation," he said.

SLNB is important for prognosis, he added, because it "results in more accurate staging and has therapeutic implications. If it's microscopically positive [the cancer] will very likely develop in that node bed within a few months if you don't do anything."

In Dr. Nghiem's opinion, the best local therapy for MCC is pathologically clear margins when the primary tumor is less than 1 cm, there is no lymphovascular invasion, there is no profound immune suppression, and the SLNB is negative.

"If all of those things are kosher, you are pretty much okay with a negative margin incision," he said. "Otherwise, adjuvant radiation is very helpful."

He described the current staging system for MCC as "a mess." Five staging systems are currently being used, he said, yet all of them are based on studies of fewer than 300 patients and none has been validated.

MCC staging by the American Joint Committee on Cancer is currently performed using the same staging system as for 82 other nonmelanoma skin cancers, including basal cell carcinoma, squamous cell carcinoma, and adnexal neoplasms.

The key histologic feature of MCC is a perinuclear dot pattern of cytokeratin-20, "which is the rule, not the exception," he said.

Dr. Nghiem finds MCC treatment guidelines from the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology to be especially useful. The guidelines are updated annually and are available at www.nccn.org

MCC typically is coded as ICD-9 code 173 (other malignant neoplasm of skin). "Unfortunately, this means that MCC costs can't be tracked at all and, more importantly, patients are denied care," he said. Things should improve on that front shortly, however. Dr. Nghiem said that the CDC is expected to release eight new diagnostic codes specific for MCC this month.

Little is known about MCC biology, but a study from 2008 found that a new polyomavirus is present in the vast majority of cases (Science 2008;319:1096-100). "This is only the sixth example of a virus clearly linked to human cancer," Dr. Nghiem said.

He disclosed that he has received funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American Cancer Society.

The majority of Merkel cell carcinoma lesions appear on sun-exposed skin, but one in six has been found to appear on sun-protected areas.

Merkel cell carcinoma has a significantly higher mortality rate, compared with melanoma, and reported incidence has increased threefold since 1986.

Source Photos courtesy Dr. Paul Nghiem

PORTLAND, ORE. — Skin lesions are a hallmark of Merkel cell carcinoma, yet dermatologists often find themselves out of the loop in diagnosing patients with the disease, said Dr. Paul Nghiem.

"These [lesions] are typically biopsied as a cyst and the patient usually has to argue for one, two, or three doctor's visits to have the lesion biopsied," Dr. Nghiem said at the annual meeting of the Pacific Dermatologic Association. "They're usually biopsied by a reluctant primary care physician who thinks they're taking off a cyst. Then they may be referred to medical oncology or to surgical oncology, but rarely to dermatology."

About 1,500 new cases of Merkel cell carcinoma (MCC) are diagnosed in the United States each year (J. Invest. Dermatol. 2007;127:2100-3), which is about the same incidence as cutaneous T-cell lymphoma or dermatofibrosarcoma protuberans, said Dr. Nghiem, an expert on the disease who is associate professor of dermatology, medicine, and pathology at the University of Washington, Seattle.

MCC is significantly more lethal than melanoma (40% vs. 15%, respectively), and its reported incidence has increased threefold since 1986 (J. Surg. Oncol. 2005;89:1-4).

"A big reason for that is that it's not missed as much," Dr. Nghiem said. "There are better tools for pathologists to use to make the diagnosis."

The three main risk factors for MCC are prolonged sun exposure, immune suppression, and age over 50 years. "Ninety-four percent of all MCC cases are in people aged 50 or older," he said. "There is a very strong synergy with age" (J. Am. Acad. Dermatol. 2008;58:375-81).

Dr. Nghiem said that HIV-positive patients had about a 13-fold increase of MCC in one study (Lancet 2002;359:497-8), while another study showed that solid organ transplant recipients have about a 10-fold increase (Transplantation 1999;68:1717-21).

He and his associates devised the acronym AEIOU to describe the clinical features of Merkel cell carcinoma based on an analysis of 195 patients given the diagnosis between 1980 and 2007 (J. Am. Acad. Dermatol. 2008; 58:375-81). The acronym stands for Asymptomatic, Expanding rapidly, Immune compromised, Older than 50, and UV-exposed, fair skin.

"Under no circumstances do I think that this is a highly specific test," said Dr. Nghiem, whose clinic is based at the Fred Hutchinson Cancer Research Center in Seattle. "It's not going to be up there with the ABCDs of melanoma, but if you see these characteristics together, you may want to think about doing a biopsy."

More than half of the lesions in the 195 patients evaluated (56%) were presumed to be benign at biopsy, and 32% presented on the head and neck, followed by the lower limb (30%), upper limb (20%), trunk (10%), and buttock (8%).

The majority of lesions (81%) presented on sun-exposed skin, but one in six was in a sun-protected site.

Nearly all of the lesions (88%) were asymptomatic ("neither tender nor itchy," he said), 63% doubled in size in the past 3 months, and 8% of the patients were profoundly immune suppressed. "That is a 16-fold increase over the normal population, but still a minority of all Merkel cell cases," he said, noting that 90% of the patients studied were at least 50 years of age and that 98% were fair skinned.

"Taken together, 89% of all Merkel cell carcinomas had three or more of these clinical AEIOU features," he said.

Optimal therapy for MCC is unique among skin cancers, he said, in that sentinel lymph node biopsy (SLNB) is usually indicated and the disease is "exquisitely sensitive" to radiation.

"If I had one modality to treat MCC, it would be radiation," he said.

SLNB is important for prognosis, he added, because it "results in more accurate staging and has therapeutic implications. If it's microscopically positive [the cancer] will very likely develop in that node bed within a few months if you don't do anything."

In Dr. Nghiem's opinion, the best local therapy for MCC is pathologically clear margins when the primary tumor is less than 1 cm, there is no lymphovascular invasion, there is no profound immune suppression, and the SLNB is negative.

"If all of those things are kosher, you are pretty much okay with a negative margin incision," he said. "Otherwise, adjuvant radiation is very helpful."

He described the current staging system for MCC as "a mess." Five staging systems are currently being used, he said, yet all of them are based on studies of fewer than 300 patients and none has been validated.

MCC staging by the American Joint Committee on Cancer is currently performed using the same staging system as for 82 other nonmelanoma skin cancers, including basal cell carcinoma, squamous cell carcinoma, and adnexal neoplasms.

The key histologic feature of MCC is a perinuclear dot pattern of cytokeratin-20, "which is the rule, not the exception," he said.

Dr. Nghiem finds MCC treatment guidelines from the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology to be especially useful. The guidelines are updated annually and are available at www.nccn.org

MCC typically is coded as ICD-9 code 173 (other malignant neoplasm of skin). "Unfortunately, this means that MCC costs can't be tracked at all and, more importantly, patients are denied care," he said. Things should improve on that front shortly, however. Dr. Nghiem said that the CDC is expected to release eight new diagnostic codes specific for MCC this month.

Little is known about MCC biology, but a study from 2008 found that a new polyomavirus is present in the vast majority of cases (Science 2008;319:1096-100). "This is only the sixth example of a virus clearly linked to human cancer," Dr. Nghiem said.

He disclosed that he has received funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American Cancer Society.

The majority of Merkel cell carcinoma lesions appear on sun-exposed skin, but one in six has been found to appear on sun-protected areas.

Merkel cell carcinoma has a significantly higher mortality rate, compared with melanoma, and reported incidence has increased threefold since 1986.

Source Photos courtesy Dr. Paul Nghiem

A new drug that inhibits the hedgehog signaling pathway has shown "remarkable" antitumor activity against basal cell carcinoma and medulloblastoma, according to two reports.

The hedgehog signaling pathway regulates cell growth and differentiation during early development but is inactive in healthy adults. However, it appears that mutations in components of the pathway can cause malignant growth in some cases of medulloblastoma, the most common brain cancer in children, and in several cancers in adults, notably basal cell carcinoma.

The hedgehog pathway derived its name from its signaling molecule, a polypeptide ligand called Hedgehog [Hh] because the mutation it caused when it was first discovered in fruit flies produced stubby, hairy-looking larvae resembling hedgehogs.

The new oral agent, GDC-0449, was developed to selectively and potently inhibit hedgehog signaling without producing the adverse effects common with conventional chemotherapy. It appears to have done so in a phase I clinical trial of patients with advanced or metastatic basal cell carcinoma and in a single case study testing it against medulloblastoma refractory to all other treatments. Both studies were supported by Genentech Inc., developer of GDC-0449.

These results indicate that targeting the hedgehog signaling pathway may be a promising avenue for a whole new class of cancer therapies, Dr. Andrzej A. Dlugosz and Dr. Moshe Talpaz of the University of Michigan, Ann Arbor, said in an editorial comment accompanying the two reports.

"Although the total number of patients with advanced or metastatic basal cell carcinoma is small, these studies should ignite renewed interest in testing hedgehog pathway inhibitors in patients with typical basal cell carcinoma" as well as other cancers, they said.

"For patients at especially high risk for multiple basal cell tumors, an effective medical treatment would be a welcome alternative to repeated surgical procedures, which can be especially disfiguring when the tumors occur on the face," Dr. Dlugosz and Dr. Talpaz said (N. Engl. J. Med. 2009 [doi: 10.1056/NEJMe0906092

Alternatively, tumor debulking with the use of hedgehog inhibitors, followed by surgical excision, might prove beneficial in many patients, they added.

In the clinical trial, Dr. Daniel D. Von Hoff of the Translational Genomics Research Institute in Scottsdale, Ariz., and his associates assessed GDC-0449 in 18 patients with metastatic and 15 patients with locally advanced basal cell carcinoma that had been refractory to surgery, radiotherapy, and chemotherapy.

A total of 18 patients showed a clinical response, 11 showed stable disease for up to 10 months, and 4 had disease progression, Dr. Von Hoff and his colleagues reported (N. Engl. J. Med. 2009 [doi: 10.1056/NEJMoa0905360

The overall response rate was 55%. Dr. Dlugosz and Dr. Talpaz termed the 50% response rate among patients with metastatic disease "remarkable."

There were no dose-limiting toxic effects or grade-5 adverse events during the study. One grade-4 event occurred (asymptomatic hyponatremia) and several patients reported a variety of problems that may or may not have been related to treatment, such as fatigue and weight loss. Only one patient discontinued treatment after 8 months, citing abdominal pain, fatigue, weight loss, anorexia, and dysgeusia.

In the case study, Dr. Charles M. Rudin of Johns Hopkins University, Baltimore, and his associates assessed GDC-0449 in a 26-year-old man with a 4-year history of medulloblastoma. The patient had undergone gross total resection of the tumor, craniospinal irradiation, extensive chemotherapy, autologous stem-cell transplantation, and additional systemic treatment with temozolomide and bevacizumab, but nevertheless had widespread skeletal and soft tissue metastases. With no alternative therapies left, he was offered CDC-0449.

Within 1 month, supraclavicular lymphadenopathy resolved, sternal masses regressed, and the patient reported that his intractable pain had resolved. After a few more weeks, more nodules regressed and the patient had returned to a normal level of activity. After a few more weeks, further metastases were markedly diminished or, in the case of a disabling epidural mass at C7, no longer detectable.

After 3 months of treatment, however, there was renewed tumor activity, including new lesions as well as regrowth of old lesions. The patient progressed rapidly, despite a series of subsequent therapies, and died.

"The tumor had a remarkable, although incomplete, and rapid, although transient, response to inhibition of the hedgehog pathway with GDC-0449," Dr. Rudin and his colleagues noted (N. Engl. J. Med. 2009 [doi:10.1056/NEJMoa0902903

"The regression is notable because of the tumor burden and the extent of metastasis in this patient, with substantial soft tissue and bony tissue involvement and clinically significant bone marrow compromise, and underscores the primary role that the hedgehog pathway played in maintaining and driving the growth of this patient's tumor," they added.

Examining the possibility of acquired resistance to hedgehog pathway inhibitors will be key in future studies, they noted. The potential adverse effects of hedgehog pathway blockade in children must also be delineated, as they are the largest population of patients with medulloblastoma.

Dr. Dlugosz reported receiving consulting fees from Merck & Co. and grant support from Pfizer Inc. Dr. Von Hoff reported receiving clinical research funding from Genentech Inc. Dr. Rudin reported receiving research funding and a BioOncology Grant Program Award from Genentech, as well as a clinical scientist award in translational research from Burroughs Wellcome Fund. Dr. Talpaz had no conflicts to report.

A new drug that inhibits the hedgehog signaling pathway has shown "remarkable" antitumor activity against basal cell carcinoma and medulloblastoma, according to two reports.

The hedgehog signaling pathway regulates cell growth and differentiation during early development but is inactive in healthy adults. However, it appears that mutations in components of the pathway can cause malignant growth in some cases of medulloblastoma, the most common brain cancer in children, and in several cancers in adults, notably basal cell carcinoma.

The hedgehog pathway derived its name from its signaling molecule, a polypeptide ligand called Hedgehog [Hh] because the mutation it caused when it was first discovered in fruit flies produced stubby, hairy-looking larvae resembling hedgehogs.

The new oral agent, GDC-0449, was developed to selectively and potently inhibit hedgehog signaling without producing the adverse effects common with conventional chemotherapy. It appears to have done so in a phase I clinical trial of patients with advanced or metastatic basal cell carcinoma and in a single case study testing it against medulloblastoma refractory to all other treatments. Both studies were supported by Genentech Inc., developer of GDC-0449.

These results indicate that targeting the hedgehog signaling pathway may be a promising avenue for a whole new class of cancer therapies, Dr. Andrzej A. Dlugosz and Dr. Moshe Talpaz of the University of Michigan, Ann Arbor, said in an editorial comment accompanying the two reports.

"Although the total number of patients with advanced or metastatic basal cell carcinoma is small, these studies should ignite renewed interest in testing hedgehog pathway inhibitors in patients with typical basal cell carcinoma" as well as other cancers, they said.

"For patients at especially high risk for multiple basal cell tumors, an effective medical treatment would be a welcome alternative to repeated surgical procedures, which can be especially disfiguring when the tumors occur on the face," Dr. Dlugosz and Dr. Talpaz said (N. Engl. J. Med. 2009 [doi: 10.1056/NEJMe0906092

Alternatively, tumor debulking with the use of hedgehog inhibitors, followed by surgical excision, might prove beneficial in many patients, they added.

In the clinical trial, Dr. Daniel D. Von Hoff of the Translational Genomics Research Institute in Scottsdale, Ariz., and his associates assessed GDC-0449 in 18 patients with metastatic and 15 patients with locally advanced basal cell carcinoma that had been refractory to surgery, radiotherapy, and chemotherapy.

A total of 18 patients showed a clinical response, 11 showed stable disease for up to 10 months, and 4 had disease progression, Dr. Von Hoff and his colleagues reported (N. Engl. J. Med. 2009 [doi: 10.1056/NEJMoa0905360

The overall response rate was 55%. Dr. Dlugosz and Dr. Talpaz termed the 50% response rate among patients with metastatic disease "remarkable."

There were no dose-limiting toxic effects or grade-5 adverse events during the study. One grade-4 event occurred (asymptomatic hyponatremia) and several patients reported a variety of problems that may or may not have been related to treatment, such as fatigue and weight loss. Only one patient discontinued treatment after 8 months, citing abdominal pain, fatigue, weight loss, anorexia, and dysgeusia.

In the case study, Dr. Charles M. Rudin of Johns Hopkins University, Baltimore, and his associates assessed GDC-0449 in a 26-year-old man with a 4-year history of medulloblastoma. The patient had undergone gross total resection of the tumor, craniospinal irradiation, extensive chemotherapy, autologous stem-cell transplantation, and additional systemic treatment with temozolomide and bevacizumab, but nevertheless had widespread skeletal and soft tissue metastases. With no alternative therapies left, he was offered CDC-0449.

Within 1 month, supraclavicular lymphadenopathy resolved, sternal masses regressed, and the patient reported that his intractable pain had resolved. After a few more weeks, more nodules regressed and the patient had returned to a normal level of activity. After a few more weeks, further metastases were markedly diminished or, in the case of a disabling epidural mass at C7, no longer detectable.

After 3 months of treatment, however, there was renewed tumor activity, including new lesions as well as regrowth of old lesions. The patient progressed rapidly, despite a series of subsequent therapies, and died.

"The tumor had a remarkable, although incomplete, and rapid, although transient, response to inhibition of the hedgehog pathway with GDC-0449," Dr. Rudin and his colleagues noted (N. Engl. J. Med. 2009 [doi:10.1056/NEJMoa0902903

"The regression is notable because of the tumor burden and the extent of metastasis in this patient, with substantial soft tissue and bony tissue involvement and clinically significant bone marrow compromise, and underscores the primary role that the hedgehog pathway played in maintaining and driving the growth of this patient's tumor," they added.

Examining the possibility of acquired resistance to hedgehog pathway inhibitors will be key in future studies, they noted. The potential adverse effects of hedgehog pathway blockade in children must also be delineated, as they are the largest population of patients with medulloblastoma.

Dr. Dlugosz reported receiving consulting fees from Merck & Co. and grant support from Pfizer Inc. Dr. Von Hoff reported receiving clinical research funding from Genentech Inc. Dr. Rudin reported receiving research funding and a BioOncology Grant Program Award from Genentech, as well as a clinical scientist award in translational research from Burroughs Wellcome Fund. Dr. Talpaz had no conflicts to report.

A new drug that inhibits the hedgehog signaling pathway has shown "remarkable" antitumor activity against basal cell carcinoma and medulloblastoma, according to two reports.

The hedgehog signaling pathway regulates cell growth and differentiation during early development but is inactive in healthy adults. However, it appears that mutations in components of the pathway can cause malignant growth in some cases of medulloblastoma, the most common brain cancer in children, and in several cancers in adults, notably basal cell carcinoma.

The hedgehog pathway derived its name from its signaling molecule, a polypeptide ligand called Hedgehog [Hh] because the mutation it caused when it was first discovered in fruit flies produced stubby, hairy-looking larvae resembling hedgehogs.

The new oral agent, GDC-0449, was developed to selectively and potently inhibit hedgehog signaling without producing the adverse effects common with conventional chemotherapy. It appears to have done so in a phase I clinical trial of patients with advanced or metastatic basal cell carcinoma and in a single case study testing it against medulloblastoma refractory to all other treatments. Both studies were supported by Genentech Inc., developer of GDC-0449.

These results indicate that targeting the hedgehog signaling pathway may be a promising avenue for a whole new class of cancer therapies, Dr. Andrzej A. Dlugosz and Dr. Moshe Talpaz of the University of Michigan, Ann Arbor, said in an editorial comment accompanying the two reports.

"Although the total number of patients with advanced or metastatic basal cell carcinoma is small, these studies should ignite renewed interest in testing hedgehog pathway inhibitors in patients with typical basal cell carcinoma" as well as other cancers, they said.

"For patients at especially high risk for multiple basal cell tumors, an effective medical treatment would be a welcome alternative to repeated surgical procedures, which can be especially disfiguring when the tumors occur on the face," Dr. Dlugosz and Dr. Talpaz said (N. Engl. J. Med. 2009 [doi: 10.1056/NEJMe0906092

Alternatively, tumor debulking with the use of hedgehog inhibitors, followed by surgical excision, might prove beneficial in many patients, they added.

In the clinical trial, Dr. Daniel D. Von Hoff of the Translational Genomics Research Institute in Scottsdale, Ariz., and his associates assessed GDC-0449 in 18 patients with metastatic and 15 patients with locally advanced basal cell carcinoma that had been refractory to surgery, radiotherapy, and chemotherapy.

A total of 18 patients showed a clinical response, 11 showed stable disease for up to 10 months, and 4 had disease progression, Dr. Von Hoff and his colleagues reported (N. Engl. J. Med. 2009 [doi: 10.1056/NEJMoa0905360

The overall response rate was 55%. Dr. Dlugosz and Dr. Talpaz termed the 50% response rate among patients with metastatic disease "remarkable."

There were no dose-limiting toxic effects or grade-5 adverse events during the study. One grade-4 event occurred (asymptomatic hyponatremia) and several patients reported a variety of problems that may or may not have been related to treatment, such as fatigue and weight loss. Only one patient discontinued treatment after 8 months, citing abdominal pain, fatigue, weight loss, anorexia, and dysgeusia.

In the case study, Dr. Charles M. Rudin of Johns Hopkins University, Baltimore, and his associates assessed GDC-0449 in a 26-year-old man with a 4-year history of medulloblastoma. The patient had undergone gross total resection of the tumor, craniospinal irradiation, extensive chemotherapy, autologous stem-cell transplantation, and additional systemic treatment with temozolomide and bevacizumab, but nevertheless had widespread skeletal and soft tissue metastases. With no alternative therapies left, he was offered CDC-0449.

Within 1 month, supraclavicular lymphadenopathy resolved, sternal masses regressed, and the patient reported that his intractable pain had resolved. After a few more weeks, more nodules regressed and the patient had returned to a normal level of activity. After a few more weeks, further metastases were markedly diminished or, in the case of a disabling epidural mass at C7, no longer detectable.

After 3 months of treatment, however, there was renewed tumor activity, including new lesions as well as regrowth of old lesions. The patient progressed rapidly, despite a series of subsequent therapies, and died.

"The tumor had a remarkable, although incomplete, and rapid, although transient, response to inhibition of the hedgehog pathway with GDC-0449," Dr. Rudin and his colleagues noted (N. Engl. J. Med. 2009 [doi:10.1056/NEJMoa0902903

"The regression is notable because of the tumor burden and the extent of metastasis in this patient, with substantial soft tissue and bony tissue involvement and clinically significant bone marrow compromise, and underscores the primary role that the hedgehog pathway played in maintaining and driving the growth of this patient's tumor," they added.

Examining the possibility of acquired resistance to hedgehog pathway inhibitors will be key in future studies, they noted. The potential adverse effects of hedgehog pathway blockade in children must also be delineated, as they are the largest population of patients with medulloblastoma.

Dr. Dlugosz reported receiving consulting fees from Merck & Co. and grant support from Pfizer Inc. Dr. Von Hoff reported receiving clinical research funding from Genentech Inc. Dr. Rudin reported receiving research funding and a BioOncology Grant Program Award from Genentech, as well as a clinical scientist award in translational research from Burroughs Wellcome Fund. Dr. Talpaz had no conflicts to report.

Two years after the American Academy of Dermatology's Seal of Recognition program was launched, six products have been recognized for their sun protection benefits.

In an interview, Dr. James M. Spencer, who oversees the program, said that he expected the list of recognized products “to be somewhat larger” by now. He acknowledged that part of the slow start may stem from controversy the program generated at the AAD's annual meeting in 2008, most notably by the late dermatopathologist A. Bernard Ackerman.

“He did not feel that sunlight causes melanoma,” recalled Dr. Spencer, who also chairs the AAD's Melanoma/Skin Cancer Committee. “If you have that position, why would you want to encourage people to wear sun protection products? He also felt that [the Seal of Recognition program] was a conflict of interest financially; that it tainted the AAD. We're all sensitive to that. Potential conflicts of interest come up in practice all the time. Professionalism means putting your duty ahead of your personal benefit.”

Dr. Spencer of Mount Sinai School of Medicine, New York, went on to emphasize that while he is sensitive to the arguments against the program, “at the end of the day it's like giving a medication: We weigh the risks versus the benefits. The benefits are, if we can get people to use effective sun protection products more, that's a benefit. The risks are that it may make us appear like we've sold out somehow. We have to weigh those two against each other. To me, the benefits to society of driving sun protection products outweigh any potential risks. Life's full of decisions like that, isn't it?”

To have a product considered for the program, the manufacturer must pay a $5,000 application fee, followed by a $10,000 annual license fee upon approval of the application.

“This program was never intended to be a fund-raiser,” said Dr. Spencer. “If there's any money left over [from the application fees] after program expenses, it goes solely to public education for skin cancer.”

Loosely modeled after product endorsement programs established by the American Dental Association and the Skin Cancer Foundation, the AAD's Seal of Recognition program has a twofold purpose, Dr. Spencer said: to let consumers know that the product they're buying has a sun protection benefit, and “to raise awareness about the importance of sun protection. According to recent surveys the use of sunscreen is going down.”

Each product undergoes a review every 2 years to ensure that it still meets evidence-based criteria as set forth by the AAD. “It is a fairly high hurdle for a product to have these independent studies, to be reviewed and accepted,” Dr. Spencer said.

The Seal of Recognition program reflects the academy's efforts “to do everything possible to reduce the incidence of skin cancer on all fronts. Among those fronts is to encourage the use of effective sun protection products. That's the genesis of this effort,” he said.

The ongoing debate about the benefits of vitamin D and the call by some clinicians to seek out unprotected exposure to the sun is not helping the Seal of Recognition program from a public relations standpoint, either. “Dermatologists need to be aware that sun protection has become a controversial issue, specifically because of vitamin D,” he said. “Weighing the evidence overall, our advocacy of regular sun protection is still the way to go, and I would encourage our colleagues to continue their advocacy for sun protection.”

By accepting application fees from companies that manufacture sun protection products, the Seal of Recognition program “can be misinterpreted as a conflict of interest by the medical or general public,” said Dr. Peter C. Lombardo of the department of dermatology at Columbia University, New York. A recent article about professional medical associations and their relationships with industry calls the propriety of endorsing commercial products “highly suspect” (JAMA 2009;301:1367-72).

“My objection is that money is involved in the granting of the seal, and this is where the misconception of the AAD's motives arises,” said Dr. Lombardo. “If this were not the case, I would have no objection to [the program]. I believe the AAD is the premier academic institution of America's dermatologists and as such it should be 'like Caesar's wife': above reproach.”

Ron Cummings, founder and owner of Newport Beach, Calif.–based AminoGenesis Skin Care, called the Seal of Recognition program a “long-overdue” development. “What made this good is that it was a third-party verification process, extremely documented and very rigorous,” he said. “You had to put together a formula that was great, and we were able to do that. Consumers have responded very well, because when they use a product with this AAD seal, they know that it has some level of credibility behind it. It's a certain level of assurance.”

The manufacturer must contract with an independent laboratory to test the product in accordance with stringent, evidence-based criteria, including UVA protection, which is not yet required by the Food and Drug Administration. The independent laboratory test results are reviewed by an independent scientist who holds a PhD degree in photobiology and is based in New York City. (The AAD would not disclose the name of this person to ensure that the review of products being considered for the seal remains independent.) That person provides a recommendation about whether the product meets the program's criteria to the AAD's Melanoma/Skin Cancer Committee, which makes the final call on acceptance.

Dr. Spencer disclosed that he is a consultant for L'Oréal, Neutrogena, and IVAX.

Products Bearing AAD Seal of Recognition

AminoGenesis Anti-Aging Day Cream with SPF 18

AminoGenesis Derma Scyne Wrinkle Arrest with SPF 18

Coolibar Sun Protection Clothing UPF 50+

Aveeno Continuous Protection Sunblock SPF 55

Aveeno Baby Continuous Protection Sunblock SPF 55

Mederma Cream plus SPF 30

Two years after the American Academy of Dermatology's Seal of Recognition program was launched, six products have been recognized for their sun protection benefits.

In an interview, Dr. James M. Spencer, who oversees the program, said that he expected the list of recognized products “to be somewhat larger” by now. He acknowledged that part of the slow start may stem from controversy the program generated at the AAD's annual meeting in 2008, most notably by the late dermatopathologist A. Bernard Ackerman.

“He did not feel that sunlight causes melanoma,” recalled Dr. Spencer, who also chairs the AAD's Melanoma/Skin Cancer Committee. “If you have that position, why would you want to encourage people to wear sun protection products? He also felt that [the Seal of Recognition program] was a conflict of interest financially; that it tainted the AAD. We're all sensitive to that. Potential conflicts of interest come up in practice all the time. Professionalism means putting your duty ahead of your personal benefit.”

Dr. Spencer of Mount Sinai School of Medicine, New York, went on to emphasize that while he is sensitive to the arguments against the program, “at the end of the day it's like giving a medication: We weigh the risks versus the benefits. The benefits are, if we can get people to use effective sun protection products more, that's a benefit. The risks are that it may make us appear like we've sold out somehow. We have to weigh those two against each other. To me, the benefits to society of driving sun protection products outweigh any potential risks. Life's full of decisions like that, isn't it?”

To have a product considered for the program, the manufacturer must pay a $5,000 application fee, followed by a $10,000 annual license fee upon approval of the application.

“This program was never intended to be a fund-raiser,” said Dr. Spencer. “If there's any money left over [from the application fees] after program expenses, it goes solely to public education for skin cancer.”

Loosely modeled after product endorsement programs established by the American Dental Association and the Skin Cancer Foundation, the AAD's Seal of Recognition program has a twofold purpose, Dr. Spencer said: to let consumers know that the product they're buying has a sun protection benefit, and “to raise awareness about the importance of sun protection. According to recent surveys the use of sunscreen is going down.”

Each product undergoes a review every 2 years to ensure that it still meets evidence-based criteria as set forth by the AAD. “It is a fairly high hurdle for a product to have these independent studies, to be reviewed and accepted,” Dr. Spencer said.

The Seal of Recognition program reflects the academy's efforts “to do everything possible to reduce the incidence of skin cancer on all fronts. Among those fronts is to encourage the use of effective sun protection products. That's the genesis of this effort,” he said.

The ongoing debate about the benefits of vitamin D and the call by some clinicians to seek out unprotected exposure to the sun is not helping the Seal of Recognition program from a public relations standpoint, either. “Dermatologists need to be aware that sun protection has become a controversial issue, specifically because of vitamin D,” he said. “Weighing the evidence overall, our advocacy of regular sun protection is still the way to go, and I would encourage our colleagues to continue their advocacy for sun protection.”

By accepting application fees from companies that manufacture sun protection products, the Seal of Recognition program “can be misinterpreted as a conflict of interest by the medical or general public,” said Dr. Peter C. Lombardo of the department of dermatology at Columbia University, New York. A recent article about professional medical associations and their relationships with industry calls the propriety of endorsing commercial products “highly suspect” (JAMA 2009;301:1367-72).

“My objection is that money is involved in the granting of the seal, and this is where the misconception of the AAD's motives arises,” said Dr. Lombardo. “If this were not the case, I would have no objection to [the program]. I believe the AAD is the premier academic institution of America's dermatologists and as such it should be 'like Caesar's wife': above reproach.”

Ron Cummings, founder and owner of Newport Beach, Calif.–based AminoGenesis Skin Care, called the Seal of Recognition program a “long-overdue” development. “What made this good is that it was a third-party verification process, extremely documented and very rigorous,” he said. “You had to put together a formula that was great, and we were able to do that. Consumers have responded very well, because when they use a product with this AAD seal, they know that it has some level of credibility behind it. It's a certain level of assurance.”

The manufacturer must contract with an independent laboratory to test the product in accordance with stringent, evidence-based criteria, including UVA protection, which is not yet required by the Food and Drug Administration. The independent laboratory test results are reviewed by an independent scientist who holds a PhD degree in photobiology and is based in New York City. (The AAD would not disclose the name of this person to ensure that the review of products being considered for the seal remains independent.) That person provides a recommendation about whether the product meets the program's criteria to the AAD's Melanoma/Skin Cancer Committee, which makes the final call on acceptance.

Dr. Spencer disclosed that he is a consultant for L'Oréal, Neutrogena, and IVAX.

Products Bearing AAD Seal of Recognition

AminoGenesis Anti-Aging Day Cream with SPF 18

AminoGenesis Derma Scyne Wrinkle Arrest with SPF 18

Coolibar Sun Protection Clothing UPF 50+

Aveeno Continuous Protection Sunblock SPF 55

Aveeno Baby Continuous Protection Sunblock SPF 55

Mederma Cream plus SPF 30

Two years after the American Academy of Dermatology's Seal of Recognition program was launched, six products have been recognized for their sun protection benefits.

In an interview, Dr. James M. Spencer, who oversees the program, said that he expected the list of recognized products “to be somewhat larger” by now. He acknowledged that part of the slow start may stem from controversy the program generated at the AAD's annual meeting in 2008, most notably by the late dermatopathologist A. Bernard Ackerman.

“He did not feel that sunlight causes melanoma,” recalled Dr. Spencer, who also chairs the AAD's Melanoma/Skin Cancer Committee. “If you have that position, why would you want to encourage people to wear sun protection products? He also felt that [the Seal of Recognition program] was a conflict of interest financially; that it tainted the AAD. We're all sensitive to that. Potential conflicts of interest come up in practice all the time. Professionalism means putting your duty ahead of your personal benefit.”

Dr. Spencer of Mount Sinai School of Medicine, New York, went on to emphasize that while he is sensitive to the arguments against the program, “at the end of the day it's like giving a medication: We weigh the risks versus the benefits. The benefits are, if we can get people to use effective sun protection products more, that's a benefit. The risks are that it may make us appear like we've sold out somehow. We have to weigh those two against each other. To me, the benefits to society of driving sun protection products outweigh any potential risks. Life's full of decisions like that, isn't it?”

To have a product considered for the program, the manufacturer must pay a $5,000 application fee, followed by a $10,000 annual license fee upon approval of the application.

“This program was never intended to be a fund-raiser,” said Dr. Spencer. “If there's any money left over [from the application fees] after program expenses, it goes solely to public education for skin cancer.”

Loosely modeled after product endorsement programs established by the American Dental Association and the Skin Cancer Foundation, the AAD's Seal of Recognition program has a twofold purpose, Dr. Spencer said: to let consumers know that the product they're buying has a sun protection benefit, and “to raise awareness about the importance of sun protection. According to recent surveys the use of sunscreen is going down.”

Each product undergoes a review every 2 years to ensure that it still meets evidence-based criteria as set forth by the AAD. “It is a fairly high hurdle for a product to have these independent studies, to be reviewed and accepted,” Dr. Spencer said.

The Seal of Recognition program reflects the academy's efforts “to do everything possible to reduce the incidence of skin cancer on all fronts. Among those fronts is to encourage the use of effective sun protection products. That's the genesis of this effort,” he said.

The ongoing debate about the benefits of vitamin D and the call by some clinicians to seek out unprotected exposure to the sun is not helping the Seal of Recognition program from a public relations standpoint, either. “Dermatologists need to be aware that sun protection has become a controversial issue, specifically because of vitamin D,” he said. “Weighing the evidence overall, our advocacy of regular sun protection is still the way to go, and I would encourage our colleagues to continue their advocacy for sun protection.”

By accepting application fees from companies that manufacture sun protection products, the Seal of Recognition program “can be misinterpreted as a conflict of interest by the medical or general public,” said Dr. Peter C. Lombardo of the department of dermatology at Columbia University, New York. A recent article about professional medical associations and their relationships with industry calls the propriety of endorsing commercial products “highly suspect” (JAMA 2009;301:1367-72).

“My objection is that money is involved in the granting of the seal, and this is where the misconception of the AAD's motives arises,” said Dr. Lombardo. “If this were not the case, I would have no objection to [the program]. I believe the AAD is the premier academic institution of America's dermatologists and as such it should be 'like Caesar's wife': above reproach.”

Ron Cummings, founder and owner of Newport Beach, Calif.–based AminoGenesis Skin Care, called the Seal of Recognition program a “long-overdue” development. “What made this good is that it was a third-party verification process, extremely documented and very rigorous,” he said. “You had to put together a formula that was great, and we were able to do that. Consumers have responded very well, because when they use a product with this AAD seal, they know that it has some level of credibility behind it. It's a certain level of assurance.”

The manufacturer must contract with an independent laboratory to test the product in accordance with stringent, evidence-based criteria, including UVA protection, which is not yet required by the Food and Drug Administration. The independent laboratory test results are reviewed by an independent scientist who holds a PhD degree in photobiology and is based in New York City. (The AAD would not disclose the name of this person to ensure that the review of products being considered for the seal remains independent.) That person provides a recommendation about whether the product meets the program's criteria to the AAD's Melanoma/Skin Cancer Committee, which makes the final call on acceptance.

Dr. Spencer disclosed that he is a consultant for L'Oréal, Neutrogena, and IVAX.

Products Bearing AAD Seal of Recognition

AminoGenesis Anti-Aging Day Cream with SPF 18

AminoGenesis Derma Scyne Wrinkle Arrest with SPF 18

Coolibar Sun Protection Clothing UPF 50+

Aveeno Continuous Protection Sunblock SPF 55

Aveeno Baby Continuous Protection Sunblock SPF 55

Mederma Cream plus SPF 30

“We are beginning to move away from clinicopathologic diagnosis into an era of clinicoimaging diagnosis.” This vision became a fact, as the dermatoscope represents nowadays the dermatologist stethoscope. This is not only because dermoscopy reveals a new and fascinating morphologic dimension of pigmented and nonpigmented skin tumors, but also because it improves the recognition of a growing number of skin symptoms in general dermatology. Melanoma detection remains the most important indication of dermoscopy and in melanoma screening the aim of dermoscopy is to maximize early detection while minimizing the unnecessary excision of benign skin tumors. In the last few years, 3 meta-analyses and 2 randomized studies have definitely proven that dermoscopy allows improving sensitivity for melanoma as compared to the naked eye examination alone. This is the consequence of at least 3 issues: first, the presence of early dermoscopy signs that are visible in melanoma much before the appearance of the classical clinical features; second, an increased attitude of  clinicians to check more closely clinically banal-looking lesions; third, an improved attitude of clinicians to monitor their patients. 

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

“We are beginning to move away from clinicopathologic diagnosis into an era of clinicoimaging diagnosis.” This vision became a fact, as the dermatoscope represents nowadays the dermatologist stethoscope. This is not only because dermoscopy reveals a new and fascinating morphologic dimension of pigmented and nonpigmented skin tumors, but also because it improves the recognition of a growing number of skin symptoms in general dermatology. Melanoma detection remains the most important indication of dermoscopy and in melanoma screening the aim of dermoscopy is to maximize early detection while minimizing the unnecessary excision of benign skin tumors. In the last few years, 3 meta-analyses and 2 randomized studies have definitely proven that dermoscopy allows improving sensitivity for melanoma as compared to the naked eye examination alone. This is the consequence of at least 3 issues: first, the presence of early dermoscopy signs that are visible in melanoma much before the appearance of the classical clinical features; second, an increased attitude of  clinicians to check more closely clinically banal-looking lesions; third, an improved attitude of clinicians to monitor their patients. 

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

“We are beginning to move away from clinicopathologic diagnosis into an era of clinicoimaging diagnosis.” This vision became a fact, as the dermatoscope represents nowadays the dermatologist stethoscope. This is not only because dermoscopy reveals a new and fascinating morphologic dimension of pigmented and nonpigmented skin tumors, but also because it improves the recognition of a growing number of skin symptoms in general dermatology. Melanoma detection remains the most important indication of dermoscopy and in melanoma screening the aim of dermoscopy is to maximize early detection while minimizing the unnecessary excision of benign skin tumors. In the last few years, 3 meta-analyses and 2 randomized studies have definitely proven that dermoscopy allows improving sensitivity for melanoma as compared to the naked eye examination alone. This is the consequence of at least 3 issues: first, the presence of early dermoscopy signs that are visible in melanoma much before the appearance of the classical clinical features; second, an increased attitude of  clinicians to check more closely clinically banal-looking lesions; third, an improved attitude of clinicians to monitor their patients. 

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

Different types of nevi do exist in relation to their epidemiology, morphology, evolution, and associated melanoma risk. The introduction of dermoscopy opened a new dimension of the morphologic universe of nevi and allowed clinicians to observe colors and structures within nevi that are otherwise not visible to the unaided eye. Because most of these colors and structures correspond to well-defined histopathologic correlates, dermoscopy enables clinicians to date to more precisely predict the histopathology diagnosis and thereby improve on their clinical diagnostic accuracy. Besides the diagnostic impact, the in vivo observation of thousands of nevi using dermoscopy and digital dermoscopic follow-up has opened new understanding about the evolution of nevi and factors influencing the nevus pattern. In consequence, a new nevus classification has been proposed, subdividing nevi into 7 categories, which are as follows: (1) globular/cobblestone nevi, (2) reticular nevi, (3) starburst nevi, (4) homogeneous blue nevi, (5) nevi on special body sites, (6) nevi with special features, and (7) and unclassifiable melanocytic proliferations. This article provides an overview on the morphologic classification of nevi and the factors influencing the nevus pattern.

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

Different types of nevi do exist in relation to their epidemiology, morphology, evolution, and associated melanoma risk. The introduction of dermoscopy opened a new dimension of the morphologic universe of nevi and allowed clinicians to observe colors and structures within nevi that are otherwise not visible to the unaided eye. Because most of these colors and structures correspond to well-defined histopathologic correlates, dermoscopy enables clinicians to date to more precisely predict the histopathology diagnosis and thereby improve on their clinical diagnostic accuracy. Besides the diagnostic impact, the in vivo observation of thousands of nevi using dermoscopy and digital dermoscopic follow-up has opened new understanding about the evolution of nevi and factors influencing the nevus pattern. In consequence, a new nevus classification has been proposed, subdividing nevi into 7 categories, which are as follows: (1) globular/cobblestone nevi, (2) reticular nevi, (3) starburst nevi, (4) homogeneous blue nevi, (5) nevi on special body sites, (6) nevi with special features, and (7) and unclassifiable melanocytic proliferations. This article provides an overview on the morphologic classification of nevi and the factors influencing the nevus pattern.

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

Different types of nevi do exist in relation to their epidemiology, morphology, evolution, and associated melanoma risk. The introduction of dermoscopy opened a new dimension of the morphologic universe of nevi and allowed clinicians to observe colors and structures within nevi that are otherwise not visible to the unaided eye. Because most of these colors and structures correspond to well-defined histopathologic correlates, dermoscopy enables clinicians to date to more precisely predict the histopathology diagnosis and thereby improve on their clinical diagnostic accuracy. Besides the diagnostic impact, the in vivo observation of thousands of nevi using dermoscopy and digital dermoscopic follow-up has opened new understanding about the evolution of nevi and factors influencing the nevus pattern. In consequence, a new nevus classification has been proposed, subdividing nevi into 7 categories, which are as follows: (1) globular/cobblestone nevi, (2) reticular nevi, (3) starburst nevi, (4) homogeneous blue nevi, (5) nevi on special body sites, (6) nevi with special features, and (7) and unclassifiable melanocytic proliferations. This article provides an overview on the morphologic classification of nevi and the factors influencing the nevus pattern.

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

The increasing use of dermoscopy in preoperative diagnosis of melanocytic skin neoplasms is impacting on routine histopathology to a relevant extent. We herein present the dermoscopic-pathologic features of 6 cases of histopathologically controversial melanocytic skin neoplasms. By illustrating these cases, we emphasize at least 3 different fields of interest for a combined (clinico-)dermoscopic-pathologic diagnostic approach, namely, information about the evolution of lesions; detection of gross sampling errors; definition of peculiar clinicopathologic entities. The theoretic and practical aspects of a close interaction among dermoscopists and histopathologists are itemized in detail.

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

The increasing use of dermoscopy in preoperative diagnosis of melanocytic skin neoplasms is impacting on routine histopathology to a relevant extent. We herein present the dermoscopic-pathologic features of 6 cases of histopathologically controversial melanocytic skin neoplasms. By illustrating these cases, we emphasize at least 3 different fields of interest for a combined (clinico-)dermoscopic-pathologic diagnostic approach, namely, information about the evolution of lesions; detection of gross sampling errors; definition of peculiar clinicopathologic entities. The theoretic and practical aspects of a close interaction among dermoscopists and histopathologists are itemized in detail.

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

The increasing use of dermoscopy in preoperative diagnosis of melanocytic skin neoplasms is impacting on routine histopathology to a relevant extent. We herein present the dermoscopic-pathologic features of 6 cases of histopathologically controversial melanocytic skin neoplasms. By illustrating these cases, we emphasize at least 3 different fields of interest for a combined (clinico-)dermoscopic-pathologic diagnostic approach, namely, information about the evolution of lesions; detection of gross sampling errors; definition of peculiar clinicopathologic entities. The theoretic and practical aspects of a close interaction among dermoscopists and histopathologists are itemized in detail.

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

Dermoscopy increases the clinician’s diagnostic accuracy by as much as 30% over that of unaided visual clinical inspection alone and has been confirmed in 3 separate evidencebased publications using a meta-analysis of the literature. It can be viewed as an in vivo bridge between clinical morphology and histopathology. This “bridge” has provided clinician researchers with many new insights into morphology and tumor biology. In this article, we provide the reader with an overview of the different aspects of dermoscopy as a research tool. We cover different aspects, such as the new equipment, new structures, the importance of blood vessels, etc.

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

Dermoscopy increases the clinician’s diagnostic accuracy by as much as 30% over that of unaided visual clinical inspection alone and has been confirmed in 3 separate evidencebased publications using a meta-analysis of the literature. It can be viewed as an in vivo bridge between clinical morphology and histopathology. This “bridge” has provided clinician researchers with many new insights into morphology and tumor biology. In this article, we provide the reader with an overview of the different aspects of dermoscopy as a research tool. We cover different aspects, such as the new equipment, new structures, the importance of blood vessels, etc.

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

Dermoscopy increases the clinician’s diagnostic accuracy by as much as 30% over that of unaided visual clinical inspection alone and has been confirmed in 3 separate evidencebased publications using a meta-analysis of the literature. It can be viewed as an in vivo bridge between clinical morphology and histopathology. This “bridge” has provided clinician researchers with many new insights into morphology and tumor biology. In this article, we provide the reader with an overview of the different aspects of dermoscopy as a research tool. We cover different aspects, such as the new equipment, new structures, the importance of blood vessels, etc.

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