Nonmelanoma Skin Cancer

Join us on Tuesday, October 8, 2019, at 8:00 pm EST on Twitter at #MDedgeChats as we discuss skin cancer, and what’s new in sunscreen, skin of color, and melanoma. 

Special guests include physicians with expertise in dermatology and skin cancer, Anthony Rossi, MD (@DrAnthonyRossi), Julie Amthor Croley, MD, 15k followers on IG (@Drskinandsmiles), and Candrice Heath, MD (@DrCandriceHeath). Background information about the chat can be found below.

What will the conversation cover?

Q1: What are the most common types of skin cancer? 
Q2: What recent research findings can better inform patients about skin cancer risks?
Q3: What’s the difference between melanoma in fair skin vs. darker skin?
Q4: How does the risk of skin cancer differ in people with darker skin?
Q5: Why should sunscreen be used even in the fall and winter?

About Dr. Rossi: 

Dr. Anthony Rossi (@DrAnthonyRossi) is a board-certified dermatologist with fellowship training in Mohs micrographic surgery, cosmetic and laser surgery, and advanced cutaneous oncology at the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College program, both in New York.  He specializes in skin cancer surgery, cosmetic dermatologic surgery, and laser surgery.  

His research includes quality of life in cancer survivors, the use of noninvasive imaging of the skin, and nonsurgical treatments of skin cancer. Additionally, Dr. Rossi is active in dermatologic organizations and advocacy for medicine.

Research and Publications by Dr. Rossi 

About Dr. Heath:
 

Dr. Candrice Heath (@DrCandriceHeath) is Assistant Professor of Dermatology at the Lewis Katz School of Medicine at Temple University in Philadelphia, Pennsylvania with fellowship training in pediatric dermatology at Johns Hopkins University in Baltimore, Maryland. Dr. Heath is triple board certified in pediatrics, dermatology, and pediatric dermatology. She specializes in adult and pediatric dermatology, skin of color, acne, and eczema. Dr. Heath also enjoys educating primary care physicians on the front lines of health care and delivering easy to understand information to consumers. 

Research and publications by Dr. Heath 
Guest host of MDedge podcast: A sunscreen update with Dr. Vincent DeLeo. 
 

About Dr. Croley:  

Dr. Julie Amthor Croley (@Drskinandsmiles) also known as “Dr. Skin and Smiles” has 15,000 followers on Instagram, and is a Chief Dermatology Resident at the University of Texas Medical Branch in Galveston, Texas. She has a special interest in skin cancer and dermatological surgery and hopes to complete a fellowship in Mohs micrographic surgery after residency. In her free time, Dr. Croley enjoys spending time with her husband (an orthopedic surgeon), running and competing in marathons, and spending time on the beach. 

Media coverage by Dr. Croley

Cutaneous melanoma is the most fatal form of skin cancer and is a considerable public health concern in the United States. Early detection and management of skin cancer can lead to decreased morbidity and mortality from skin cancer. As a result, the American Academy of Dermatology Association supports safe sun-protective practices and diligent self-screening for changing lesions.

Sunscreen use is an essential component of sun protection. New regulations from the US Food and Drug Administration (FDA) have left consumers concerned about the safety of sunscreens. According to a recent Cutis editorial from Vincent A. DeLeo, MD, “There is no question that, as physicians, we want to ‘first, do no harm,’ so we should all be interested in assuring our patients that our sunscreen recommendations are safe and we support the FDA proposal for additional data.”

Patients with skin of color experience disproportionately higher morbidity and mortality when diagnosed with melanoma. “Poor prognosis in patients with skin of color is multifactorial and may be due to poor use of sun protection, misconceptions about melanoma risk, atypical clinical presentation, impaired access to care, and delay in diagnosis,” according to a recent Cutis article. 

Population-based skin cancer screening performed exclusively by dermatologists is not practical. Primary care physicians and other experts in melanoma and public health need to be involved in reducing melanoma mortality. 

In this chat, we will provide expert recommendations on the diagnosis of skin cancer, preventive measures, and the latest research discussed among physicians.

Research & Resources

• “Doctor, Do I Need a Skin Check?”
• Assessing the effectiveness of knowledge-based interventions in skin of color populations.
• Melanoma in US Hispanics
• Podcast: Sunscreen update from Dr. Vincent DeLeo
• Windshield and UV exposure  
• Racial, ethnic minorities often don’t practice sun-protective behaviors.
• Sunscreen regulations and advice for your patients.

Join us on Tuesday, October 8, 2019, at 8:00 pm EST on Twitter at #MDedgeChats as we discuss skin cancer, and what’s new in sunscreen, skin of color, and melanoma. 

Special guests include physicians with expertise in dermatology and skin cancer, Anthony Rossi, MD (@DrAnthonyRossi), Julie Amthor Croley, MD, 15k followers on IG (@Drskinandsmiles), and Candrice Heath, MD (@DrCandriceHeath). Background information about the chat can be found below.

What will the conversation cover?

Q1: What are the most common types of skin cancer? 
Q2: What recent research findings can better inform patients about skin cancer risks?
Q3: What’s the difference between melanoma in fair skin vs. darker skin?
Q4: How does the risk of skin cancer differ in people with darker skin?
Q5: Why should sunscreen be used even in the fall and winter?

About Dr. Rossi: 

Dr. Anthony Rossi (@DrAnthonyRossi) is a board-certified dermatologist with fellowship training in Mohs micrographic surgery, cosmetic and laser surgery, and advanced cutaneous oncology at the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College program, both in New York.  He specializes in skin cancer surgery, cosmetic dermatologic surgery, and laser surgery.  

His research includes quality of life in cancer survivors, the use of noninvasive imaging of the skin, and nonsurgical treatments of skin cancer. Additionally, Dr. Rossi is active in dermatologic organizations and advocacy for medicine.

Research and Publications by Dr. Rossi 

About Dr. Heath:
 

Dr. Candrice Heath (@DrCandriceHeath) is Assistant Professor of Dermatology at the Lewis Katz School of Medicine at Temple University in Philadelphia, Pennsylvania with fellowship training in pediatric dermatology at Johns Hopkins University in Baltimore, Maryland. Dr. Heath is triple board certified in pediatrics, dermatology, and pediatric dermatology. She specializes in adult and pediatric dermatology, skin of color, acne, and eczema. Dr. Heath also enjoys educating primary care physicians on the front lines of health care and delivering easy to understand information to consumers. 

Research and publications by Dr. Heath 
Guest host of MDedge podcast: A sunscreen update with Dr. Vincent DeLeo. 
 

About Dr. Croley:  

Dr. Julie Amthor Croley (@Drskinandsmiles) also known as “Dr. Skin and Smiles” has 15,000 followers on Instagram, and is a Chief Dermatology Resident at the University of Texas Medical Branch in Galveston, Texas. She has a special interest in skin cancer and dermatological surgery and hopes to complete a fellowship in Mohs micrographic surgery after residency. In her free time, Dr. Croley enjoys spending time with her husband (an orthopedic surgeon), running and competing in marathons, and spending time on the beach. 

Media coverage by Dr. Croley

Cutaneous melanoma is the most fatal form of skin cancer and is a considerable public health concern in the United States. Early detection and management of skin cancer can lead to decreased morbidity and mortality from skin cancer. As a result, the American Academy of Dermatology Association supports safe sun-protective practices and diligent self-screening for changing lesions.

Sunscreen use is an essential component of sun protection. New regulations from the US Food and Drug Administration (FDA) have left consumers concerned about the safety of sunscreens. According to a recent Cutis editorial from Vincent A. DeLeo, MD, “There is no question that, as physicians, we want to ‘first, do no harm,’ so we should all be interested in assuring our patients that our sunscreen recommendations are safe and we support the FDA proposal for additional data.”

Patients with skin of color experience disproportionately higher morbidity and mortality when diagnosed with melanoma. “Poor prognosis in patients with skin of color is multifactorial and may be due to poor use of sun protection, misconceptions about melanoma risk, atypical clinical presentation, impaired access to care, and delay in diagnosis,” according to a recent Cutis article. 

Population-based skin cancer screening performed exclusively by dermatologists is not practical. Primary care physicians and other experts in melanoma and public health need to be involved in reducing melanoma mortality. 

In this chat, we will provide expert recommendations on the diagnosis of skin cancer, preventive measures, and the latest research discussed among physicians.

Research & Resources

• “Doctor, Do I Need a Skin Check?”
• Assessing the effectiveness of knowledge-based interventions in skin of color populations.
• Melanoma in US Hispanics
• Podcast: Sunscreen update from Dr. Vincent DeLeo
• Windshield and UV exposure  
• Racial, ethnic minorities often don’t practice sun-protective behaviors.
• Sunscreen regulations and advice for your patients.

Join us on Tuesday, October 8, 2019, at 8:00 pm EST on Twitter at #MDedgeChats as we discuss skin cancer, and what’s new in sunscreen, skin of color, and melanoma. 

Special guests include physicians with expertise in dermatology and skin cancer, Anthony Rossi, MD (@DrAnthonyRossi), Julie Amthor Croley, MD, 15k followers on IG (@Drskinandsmiles), and Candrice Heath, MD (@DrCandriceHeath). Background information about the chat can be found below.

What will the conversation cover?

Q1: What are the most common types of skin cancer? 
Q2: What recent research findings can better inform patients about skin cancer risks?
Q3: What’s the difference between melanoma in fair skin vs. darker skin?
Q4: How does the risk of skin cancer differ in people with darker skin?
Q5: Why should sunscreen be used even in the fall and winter?

About Dr. Rossi: 

Dr. Anthony Rossi (@DrAnthonyRossi) is a board-certified dermatologist with fellowship training in Mohs micrographic surgery, cosmetic and laser surgery, and advanced cutaneous oncology at the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College program, both in New York.  He specializes in skin cancer surgery, cosmetic dermatologic surgery, and laser surgery.  

His research includes quality of life in cancer survivors, the use of noninvasive imaging of the skin, and nonsurgical treatments of skin cancer. Additionally, Dr. Rossi is active in dermatologic organizations and advocacy for medicine.

Research and Publications by Dr. Rossi 

About Dr. Heath:
 

Dr. Candrice Heath (@DrCandriceHeath) is Assistant Professor of Dermatology at the Lewis Katz School of Medicine at Temple University in Philadelphia, Pennsylvania with fellowship training in pediatric dermatology at Johns Hopkins University in Baltimore, Maryland. Dr. Heath is triple board certified in pediatrics, dermatology, and pediatric dermatology. She specializes in adult and pediatric dermatology, skin of color, acne, and eczema. Dr. Heath also enjoys educating primary care physicians on the front lines of health care and delivering easy to understand information to consumers. 

Research and publications by Dr. Heath 
Guest host of MDedge podcast: A sunscreen update with Dr. Vincent DeLeo. 
 

About Dr. Croley:  

Dr. Julie Amthor Croley (@Drskinandsmiles) also known as “Dr. Skin and Smiles” has 15,000 followers on Instagram, and is a Chief Dermatology Resident at the University of Texas Medical Branch in Galveston, Texas. She has a special interest in skin cancer and dermatological surgery and hopes to complete a fellowship in Mohs micrographic surgery after residency. In her free time, Dr. Croley enjoys spending time with her husband (an orthopedic surgeon), running and competing in marathons, and spending time on the beach. 

Media coverage by Dr. Croley

Cutaneous melanoma is the most fatal form of skin cancer and is a considerable public health concern in the United States. Early detection and management of skin cancer can lead to decreased morbidity and mortality from skin cancer. As a result, the American Academy of Dermatology Association supports safe sun-protective practices and diligent self-screening for changing lesions.

Sunscreen use is an essential component of sun protection. New regulations from the US Food and Drug Administration (FDA) have left consumers concerned about the safety of sunscreens. According to a recent Cutis editorial from Vincent A. DeLeo, MD, “There is no question that, as physicians, we want to ‘first, do no harm,’ so we should all be interested in assuring our patients that our sunscreen recommendations are safe and we support the FDA proposal for additional data.”

Patients with skin of color experience disproportionately higher morbidity and mortality when diagnosed with melanoma. “Poor prognosis in patients with skin of color is multifactorial and may be due to poor use of sun protection, misconceptions about melanoma risk, atypical clinical presentation, impaired access to care, and delay in diagnosis,” according to a recent Cutis article. 

Population-based skin cancer screening performed exclusively by dermatologists is not practical. Primary care physicians and other experts in melanoma and public health need to be involved in reducing melanoma mortality. 

In this chat, we will provide expert recommendations on the diagnosis of skin cancer, preventive measures, and the latest research discussed among physicians.

Research & Resources

• “Doctor, Do I Need a Skin Check?”
• Assessing the effectiveness of knowledge-based interventions in skin of color populations.
• Melanoma in US Hispanics
• Podcast: Sunscreen update from Dr. Vincent DeLeo
• Windshield and UV exposure  
• Racial, ethnic minorities often don’t practice sun-protective behaviors.
• Sunscreen regulations and advice for your patients.

Practice Gap

Management of nonmelanoma skin cancer (NMSC) in elderly patients can cause morbidity because these patients frequently struggle to care for their biopsy sites and experience biopsy- and surgery-related complications. To minimize this treatment-related morbidity, we designed a knifeless treatment approach that employs reflectance confocal microscopy (RCM) in lieu of skin biopsy to establish the diagnosis of NMSC, then uses either intralesional or topical chemotherapy or immunotherapy (as appropriate, depending on depth of invasion) to cure the NMSC. With this approach, the patient is spared both biopsy- and surgery-related difficulties, though both intralesional and topical chemotherapy are accompanied by their own risks for adverse effects.

The Technique

Elderly patients, diabetic patients, and patients with lesions suspicious for NMSC on areas prone to poor wound healing or to notable treatment-related morbidity (eg, lower legs, genitals, the face of younger patients) are offered skin biopsy or RCM; the latter is performed during the appointment by an RCM-trained medical assistant. Patients who elect to undergo RCM and who have a diagnosis of superficial basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) in situ are then treated with topical imiquimod or 5-fluorouracil. Patients with an invasive subtype of either BCC, SCC, or keratoacanthoma receive intralesional 5-fluorouracil injected at a concentration of 50 mg/cc at weekly intervals until the lesion blanches, with ongoing follow-up until the lesion is observed to have resolved under dermoscopic inspection.

When resolution is uncertain, RCM is repeated to assess for tumor clearance. Repeat RCM is performed at least 4 weeks after termination of treatment to avoid misinterpretation caused by treatment-related tissue inflammation. Patients who are not cured using this management approach are offered appropriate surgical management.

Practice Implications

Reflectance confocal microscopy has emerged as an effective modality for confirming the diagnosis of NMSC with high sensitivity and specificity.^1,2 Emergence of this technology presents an opportunity for improving the way the NMSC is managed because RCM allows dermatologists to confirm the diagnosis of BCC and SCC by interpretation of RCM mosaics rather than by histopathologic examination of biopsied tissue. Our knifeless approach to skin cancer management is especially beneficial when biopsy and dermatologic surgery are likely to confer notable morbidity, such as managing NMSC on the face of a young adult, in the frail elderly population, or in diabetic patients, and when treating sites on the lower extremity prone to poor wound healing.

Practice Gap

Management of nonmelanoma skin cancer (NMSC) in elderly patients can cause morbidity because these patients frequently struggle to care for their biopsy sites and experience biopsy- and surgery-related complications. To minimize this treatment-related morbidity, we designed a knifeless treatment approach that employs reflectance confocal microscopy (RCM) in lieu of skin biopsy to establish the diagnosis of NMSC, then uses either intralesional or topical chemotherapy or immunotherapy (as appropriate, depending on depth of invasion) to cure the NMSC. With this approach, the patient is spared both biopsy- and surgery-related difficulties, though both intralesional and topical chemotherapy are accompanied by their own risks for adverse effects.

The Technique

Elderly patients, diabetic patients, and patients with lesions suspicious for NMSC on areas prone to poor wound healing or to notable treatment-related morbidity (eg, lower legs, genitals, the face of younger patients) are offered skin biopsy or RCM; the latter is performed during the appointment by an RCM-trained medical assistant. Patients who elect to undergo RCM and who have a diagnosis of superficial basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) in situ are then treated with topical imiquimod or 5-fluorouracil. Patients with an invasive subtype of either BCC, SCC, or keratoacanthoma receive intralesional 5-fluorouracil injected at a concentration of 50 mg/cc at weekly intervals until the lesion blanches, with ongoing follow-up until the lesion is observed to have resolved under dermoscopic inspection.

When resolution is uncertain, RCM is repeated to assess for tumor clearance. Repeat RCM is performed at least 4 weeks after termination of treatment to avoid misinterpretation caused by treatment-related tissue inflammation. Patients who are not cured using this management approach are offered appropriate surgical management.

Practice Implications

Reflectance confocal microscopy has emerged as an effective modality for confirming the diagnosis of NMSC with high sensitivity and specificity.^1,2 Emergence of this technology presents an opportunity for improving the way the NMSC is managed because RCM allows dermatologists to confirm the diagnosis of BCC and SCC by interpretation of RCM mosaics rather than by histopathologic examination of biopsied tissue. Our knifeless approach to skin cancer management is especially beneficial when biopsy and dermatologic surgery are likely to confer notable morbidity, such as managing NMSC on the face of a young adult, in the frail elderly population, or in diabetic patients, and when treating sites on the lower extremity prone to poor wound healing.

Practice Gap

Management of nonmelanoma skin cancer (NMSC) in elderly patients can cause morbidity because these patients frequently struggle to care for their biopsy sites and experience biopsy- and surgery-related complications. To minimize this treatment-related morbidity, we designed a knifeless treatment approach that employs reflectance confocal microscopy (RCM) in lieu of skin biopsy to establish the diagnosis of NMSC, then uses either intralesional or topical chemotherapy or immunotherapy (as appropriate, depending on depth of invasion) to cure the NMSC. With this approach, the patient is spared both biopsy- and surgery-related difficulties, though both intralesional and topical chemotherapy are accompanied by their own risks for adverse effects.

The Technique

Elderly patients, diabetic patients, and patients with lesions suspicious for NMSC on areas prone to poor wound healing or to notable treatment-related morbidity (eg, lower legs, genitals, the face of younger patients) are offered skin biopsy or RCM; the latter is performed during the appointment by an RCM-trained medical assistant. Patients who elect to undergo RCM and who have a diagnosis of superficial basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) in situ are then treated with topical imiquimod or 5-fluorouracil. Patients with an invasive subtype of either BCC, SCC, or keratoacanthoma receive intralesional 5-fluorouracil injected at a concentration of 50 mg/cc at weekly intervals until the lesion blanches, with ongoing follow-up until the lesion is observed to have resolved under dermoscopic inspection.

When resolution is uncertain, RCM is repeated to assess for tumor clearance. Repeat RCM is performed at least 4 weeks after termination of treatment to avoid misinterpretation caused by treatment-related tissue inflammation. Patients who are not cured using this management approach are offered appropriate surgical management.

Practice Implications

Reflectance confocal microscopy has emerged as an effective modality for confirming the diagnosis of NMSC with high sensitivity and specificity.^1,2 Emergence of this technology presents an opportunity for improving the way the NMSC is managed because RCM allows dermatologists to confirm the diagnosis of BCC and SCC by interpretation of RCM mosaics rather than by histopathologic examination of biopsied tissue. Our knifeless approach to skin cancer management is especially beneficial when biopsy and dermatologic surgery are likely to confer notable morbidity, such as managing NMSC on the face of a young adult, in the frail elderly population, or in diabetic patients, and when treating sites on the lower extremity prone to poor wound healing.

SAN DIEGO – Using laser and light sources to treat nonaggressive basal cell carcinoma (BCC) is emerging as a promising treatment option, especially for those with multiple tumors and those who are poor surgical candidates, Arisa E. Ortiz, MD, said at the annual Masters of Aesthetics Symposium.

“Topical therapies often result in recurrence, so there really is a need for an alternative [to surgery] that’s effective, efficient, and carries a low risk of side effects,” said Dr. Ortiz, who is director of laser and cosmetic dermatology at the University of California, San Diego,

“The prototypic feature of BCC is the presence of telangiectatic vessels,” she explained, and the postulated mechanism of action is selective photothermolysis of the tumor vasculature. “These vessels are slightly larger in caliber, compared with normal skin – 40 micrometers versus 15 micrometers – and more fragile. You can tailor your pulse duration to the size of the vessels. Theoretically, by targeting the vasculature then you get tumor regression with sparing of normal tissue.”

Initial studies of this approach have used the 595-nm pulsed-dye laser, which is well absorbed by oxyhemoglobin, but more recent studies have used the 1064-nm Nd:YAG to reach deep arterial vessels. In a prospective, open-label study, 10 patients with 13 BCCs less than 1.5 cm in diameter received one treatment with a 10-ms pulsed 1064-nm Nd:YAG laser delivered on the trunk or extremities at a fluence of 80-120 J/cm² (Lasers Surg Med. 2015;47[2]:106-10). Dr. Ortiz and her colleagues observed a 92% clearance rate overall.

She described other earlier studies of the approach as flawed, because they relied on confirmation of clearance rates with clinical exam or biopsy rather than with surgical excision. “Also, some of the protocols weren’t standardized, multiple treatments were required, and subjects with suboptimal response were currently on anticoagulation,” she said. “Intravascular coagulation is important for effective treatment with vascular lasers, so anticoagulation may interfere with efficacy.”

In a more recent multicenter study, Dr. Ortiz and her colleagues treated 33 BCCs once with the long-pulsed 1064-nm Nd:YAG laser delivered with a 5-6 mm spot size at a fluence of 125-140 J/cm² and a 7-10 ms pulse duration (Laser Surgery Med. Feb 13 2018. doi: 10.1002/lsm.22803). Standard surgical excision with 5-mm margins was performed 4 weeks after laser treatment. Among 31 subjects who completed the study, 28 of 31 BCC tumors (90%) cleared after one treatment.

“The treatments were performed without anesthesia, because we didn’t want the vasculature to be affected, but in clinical practice I am now using lidocaine with no epinephrine,” Dr. Ortiz said. She characterized the results as “at least comparable to, if not superior to” common modalities including methyl aminolevulinate–PDT (72.8%), imiquimod cream (83.4%), and fluorouracil cream (80.1%). “One criticism I hear is that with such high fluences, you’re probably getting some bulk heating,” she said. “Maybe so, but it seems to work and there’s no scarring, which suggests otherwise.”

Advantages of using a 1064-nm Nd:YAG for treating nonaggressive BCCs are that it requires just one treatment, it takes about 5 minutes, and there is no significant downtime, with no limitations in posttreatment activity. “Potentially there is a relatively decreased risk for complications, including infection and bleeding,” she added. “It’s a good alternative for treating patients with multiple tumors or those who are poor surgical candidates.”

She and her colleagues are currently performing a long-term follow-up study of 35 BCC lesions. Only one has potentially recurred, but that recurrence has not yet been confirmed.

Dr. Ortiz treats BCCs with a standard 5-mm margin and uses lidocaine without epinephrine to avoid vasoconstriction. She typically uses a 1064-nm Cutera excel V laser delivered at a pulse duration of 8 ms and a fluence of 140 J/cm^2, with no cooling. “Theoretically, any 1064-nm pulsed-dye laser could work, but the way the pulse is delivered is different, depending on which device” is used, she said.

“I always like waiting between passes to avoid any bulk heating. The immediate endpoint to strive for is slight graying and slight contraction,” she said. Billing codes for malignant destruction/electrodesiccation and curettage can be used (codes 17260-17266 for the trunk and 17280-17283 for the face).

In order to determine the mechanism of cell death and to optimize results, Dr. Ortiz said that further studies need to be conducted in vitro and in vivo. In order to determine treatment efficacy, clinical studies involving various heat sources and low concentrations of lidocaine are also required.

Dr. Ortiz disclosed having financial relationships with numerous pharmaceutical and device companies. She is also cochair of the MOAS.

[email protected]

SAN DIEGO – Using laser and light sources to treat nonaggressive basal cell carcinoma (BCC) is emerging as a promising treatment option, especially for those with multiple tumors and those who are poor surgical candidates, Arisa E. Ortiz, MD, said at the annual Masters of Aesthetics Symposium.

“Topical therapies often result in recurrence, so there really is a need for an alternative [to surgery] that’s effective, efficient, and carries a low risk of side effects,” said Dr. Ortiz, who is director of laser and cosmetic dermatology at the University of California, San Diego,

“The prototypic feature of BCC is the presence of telangiectatic vessels,” she explained, and the postulated mechanism of action is selective photothermolysis of the tumor vasculature. “These vessels are slightly larger in caliber, compared with normal skin – 40 micrometers versus 15 micrometers – and more fragile. You can tailor your pulse duration to the size of the vessels. Theoretically, by targeting the vasculature then you get tumor regression with sparing of normal tissue.”

Initial studies of this approach have used the 595-nm pulsed-dye laser, which is well absorbed by oxyhemoglobin, but more recent studies have used the 1064-nm Nd:YAG to reach deep arterial vessels. In a prospective, open-label study, 10 patients with 13 BCCs less than 1.5 cm in diameter received one treatment with a 10-ms pulsed 1064-nm Nd:YAG laser delivered on the trunk or extremities at a fluence of 80-120 J/cm² (Lasers Surg Med. 2015;47[2]:106-10). Dr. Ortiz and her colleagues observed a 92% clearance rate overall.

She described other earlier studies of the approach as flawed, because they relied on confirmation of clearance rates with clinical exam or biopsy rather than with surgical excision. “Also, some of the protocols weren’t standardized, multiple treatments were required, and subjects with suboptimal response were currently on anticoagulation,” she said. “Intravascular coagulation is important for effective treatment with vascular lasers, so anticoagulation may interfere with efficacy.”

In a more recent multicenter study, Dr. Ortiz and her colleagues treated 33 BCCs once with the long-pulsed 1064-nm Nd:YAG laser delivered with a 5-6 mm spot size at a fluence of 125-140 J/cm² and a 7-10 ms pulse duration (Laser Surgery Med. Feb 13 2018. doi: 10.1002/lsm.22803). Standard surgical excision with 5-mm margins was performed 4 weeks after laser treatment. Among 31 subjects who completed the study, 28 of 31 BCC tumors (90%) cleared after one treatment.

“The treatments were performed without anesthesia, because we didn’t want the vasculature to be affected, but in clinical practice I am now using lidocaine with no epinephrine,” Dr. Ortiz said. She characterized the results as “at least comparable to, if not superior to” common modalities including methyl aminolevulinate–PDT (72.8%), imiquimod cream (83.4%), and fluorouracil cream (80.1%). “One criticism I hear is that with such high fluences, you’re probably getting some bulk heating,” she said. “Maybe so, but it seems to work and there’s no scarring, which suggests otherwise.”

Advantages of using a 1064-nm Nd:YAG for treating nonaggressive BCCs are that it requires just one treatment, it takes about 5 minutes, and there is no significant downtime, with no limitations in posttreatment activity. “Potentially there is a relatively decreased risk for complications, including infection and bleeding,” she added. “It’s a good alternative for treating patients with multiple tumors or those who are poor surgical candidates.”

She and her colleagues are currently performing a long-term follow-up study of 35 BCC lesions. Only one has potentially recurred, but that recurrence has not yet been confirmed.

Dr. Ortiz treats BCCs with a standard 5-mm margin and uses lidocaine without epinephrine to avoid vasoconstriction. She typically uses a 1064-nm Cutera excel V laser delivered at a pulse duration of 8 ms and a fluence of 140 J/cm^2, with no cooling. “Theoretically, any 1064-nm pulsed-dye laser could work, but the way the pulse is delivered is different, depending on which device” is used, she said.

“I always like waiting between passes to avoid any bulk heating. The immediate endpoint to strive for is slight graying and slight contraction,” she said. Billing codes for malignant destruction/electrodesiccation and curettage can be used (codes 17260-17266 for the trunk and 17280-17283 for the face).

In order to determine the mechanism of cell death and to optimize results, Dr. Ortiz said that further studies need to be conducted in vitro and in vivo. In order to determine treatment efficacy, clinical studies involving various heat sources and low concentrations of lidocaine are also required.

Dr. Ortiz disclosed having financial relationships with numerous pharmaceutical and device companies. She is also cochair of the MOAS.

[email protected]

SAN DIEGO – Using laser and light sources to treat nonaggressive basal cell carcinoma (BCC) is emerging as a promising treatment option, especially for those with multiple tumors and those who are poor surgical candidates, Arisa E. Ortiz, MD, said at the annual Masters of Aesthetics Symposium.

“Topical therapies often result in recurrence, so there really is a need for an alternative [to surgery] that’s effective, efficient, and carries a low risk of side effects,” said Dr. Ortiz, who is director of laser and cosmetic dermatology at the University of California, San Diego,

“The prototypic feature of BCC is the presence of telangiectatic vessels,” she explained, and the postulated mechanism of action is selective photothermolysis of the tumor vasculature. “These vessels are slightly larger in caliber, compared with normal skin – 40 micrometers versus 15 micrometers – and more fragile. You can tailor your pulse duration to the size of the vessels. Theoretically, by targeting the vasculature then you get tumor regression with sparing of normal tissue.”

Initial studies of this approach have used the 595-nm pulsed-dye laser, which is well absorbed by oxyhemoglobin, but more recent studies have used the 1064-nm Nd:YAG to reach deep arterial vessels. In a prospective, open-label study, 10 patients with 13 BCCs less than 1.5 cm in diameter received one treatment with a 10-ms pulsed 1064-nm Nd:YAG laser delivered on the trunk or extremities at a fluence of 80-120 J/cm² (Lasers Surg Med. 2015;47[2]:106-10). Dr. Ortiz and her colleagues observed a 92% clearance rate overall.

She described other earlier studies of the approach as flawed, because they relied on confirmation of clearance rates with clinical exam or biopsy rather than with surgical excision. “Also, some of the protocols weren’t standardized, multiple treatments were required, and subjects with suboptimal response were currently on anticoagulation,” she said. “Intravascular coagulation is important for effective treatment with vascular lasers, so anticoagulation may interfere with efficacy.”

In a more recent multicenter study, Dr. Ortiz and her colleagues treated 33 BCCs once with the long-pulsed 1064-nm Nd:YAG laser delivered with a 5-6 mm spot size at a fluence of 125-140 J/cm² and a 7-10 ms pulse duration (Laser Surgery Med. Feb 13 2018. doi: 10.1002/lsm.22803). Standard surgical excision with 5-mm margins was performed 4 weeks after laser treatment. Among 31 subjects who completed the study, 28 of 31 BCC tumors (90%) cleared after one treatment.

“The treatments were performed without anesthesia, because we didn’t want the vasculature to be affected, but in clinical practice I am now using lidocaine with no epinephrine,” Dr. Ortiz said. She characterized the results as “at least comparable to, if not superior to” common modalities including methyl aminolevulinate–PDT (72.8%), imiquimod cream (83.4%), and fluorouracil cream (80.1%). “One criticism I hear is that with such high fluences, you’re probably getting some bulk heating,” she said. “Maybe so, but it seems to work and there’s no scarring, which suggests otherwise.”

Advantages of using a 1064-nm Nd:YAG for treating nonaggressive BCCs are that it requires just one treatment, it takes about 5 minutes, and there is no significant downtime, with no limitations in posttreatment activity. “Potentially there is a relatively decreased risk for complications, including infection and bleeding,” she added. “It’s a good alternative for treating patients with multiple tumors or those who are poor surgical candidates.”

She and her colleagues are currently performing a long-term follow-up study of 35 BCC lesions. Only one has potentially recurred, but that recurrence has not yet been confirmed.

Dr. Ortiz treats BCCs with a standard 5-mm margin and uses lidocaine without epinephrine to avoid vasoconstriction. She typically uses a 1064-nm Cutera excel V laser delivered at a pulse duration of 8 ms and a fluence of 140 J/cm^2, with no cooling. “Theoretically, any 1064-nm pulsed-dye laser could work, but the way the pulse is delivered is different, depending on which device” is used, she said.

“I always like waiting between passes to avoid any bulk heating. The immediate endpoint to strive for is slight graying and slight contraction,” she said. Billing codes for malignant destruction/electrodesiccation and curettage can be used (codes 17260-17266 for the trunk and 17280-17283 for the face).

In order to determine the mechanism of cell death and to optimize results, Dr. Ortiz said that further studies need to be conducted in vitro and in vivo. In order to determine treatment efficacy, clinical studies involving various heat sources and low concentrations of lidocaine are also required.

Dr. Ortiz disclosed having financial relationships with numerous pharmaceutical and device companies. She is also cochair of the MOAS.

[email protected]

To the Editor:

A 43-year-old woman presented with a mole on the central back that had been present since childhood and had changed and grown over the last few years. The patient reported that her 2-year-old rescue dog frequently sniffed the mole and would subsequently get agitated and try to scratch and bite the lesion. This behavior prompted the patient to visit a dermatologist.

She reported no personal history of melanoma or nonmelanoma skin cancer, tanning booth exposure, blistering sunburns, or use of immunosuppressant medications. Her family history was remarkable for basal cell carcinoma in her father but no family history of melanoma. Physical examination revealed a 1.2×1.5-cm brown patch along with a 1×1-cm ulcerated nodule on the lower aspect of the lesion (Figure 1). Dermoscopy showed a blue-white veil and an irregular vascular pattern (Figure 2). No cervical, axillary, or inguinal lymphadenopathy was appreciated on physical examination. Reflectance confocal microscopy showed pagetoid spread of atypical round melanocytes as well as melanocytes in the stratum corneum (Figure 3).

The patient was referred to a surgical oncologist for wide local excision and sentinel lymph node biopsy. Pathology showed a 4-mm-thick melanoma with numerous positive lymph nodes (Figure 4). The patient subsequently underwent a right axillary lymphadenectomy and was diagnosed with stage IIIB malignant melanoma. After surgery, the patient reported that her dog would now sniff her back and calmly rest his head in her lap.

Both anecdotal and systematic evidence have emerged on the role of canine olfaction in the detection of lung, breast, colorectal, ovarian, prostate, and skin cancers, including malignant melanoma.^1-6 A 1989 case report described a woman who was prompted to seek dermatologic evaluation of a pigmented lesion because her dog consistently targeted the lesion. Excision and subsequent histopathologic examination of the lesion revealed that it was malignant melanoma.⁵ Another case report described a patient whose dog, which was not trained to detect cancers in humans, persistently licked a lesion behind the patient’s ear that eventually was found to be malignant melanoma.⁶ These reports have inspired considerable research interest regarding canine olfaction as a potential method to noninvasively screen for and even diagnose malignant melanomas in humans.

Both physiologic and pathologic metabolic processes result in the production of volatile organic compounds (VOCs), or small odorant molecules that evaporate at normal temperatures and pressures.¹ Individual cells release VOCs in extremely low concentrations into the blood, urine, feces, and breath, as well as onto the skin’s surface, but there are methods for detecting these VOCs, including gas chromatography–mass spectrometry and canine olfaction.^7,8 Pathologic processes, such as infection and malignancy, result in irregular protein synthesis and metabolism, producing new VOCs or differing concentrations of VOCs as compared to normal processes.¹

Dimethyl disulfide and dimethyl trisulfide compounds have been identified in malignant melanoma, and these compounds are not produced by normal melanocytes.⁷ Furthermore, malignant melanoma produces differing quantities of these compounds as compared to normal melanocytes, including isovaleric acid, 2-methylbutyric acid, isoamyl alcohol (3-methyl-1-butanol), and 2-methyl-1-butanol, resulting in a distinct odorant profile that previously has been detected via canine olfaction.⁷ Canine olfaction can identify odorant molecules at up to 1 part per trillion (a magnitude more sensitive than the currently available gas chromatography–mass spectrometry technologies) and can detect the production of new VOCs or altered VOC ratios due to pathologic processes.¹ Systematic studies with dogs that are trained to detect cancers in humans have shown that canine olfaction correctly identified malignant melanomas against healthy skin, benign nevi, and even basal cell carcinomas at higher rates than what would have been expected by chance alone.^2,3

Canine olfaction can identify new or altered ratios of odorant VOCs associated with pathologic metabolic processes, and canines can be trained to target odor profiles associated with specific diseases.¹ Canine olfaction for melanoma screening and diagnosis may seem appealing, as it provides an easily transportable, real-time, low-cost method compared to other techniques such as gas chromatography–mass spectrometry.¹ Although preliminary results have shown that canine olfaction detects melanoma at higher rates than would be expected by chance alone, these findings have not approached clinical utility for the widespread use of canine olfaction as a screening method for melanoma.^2,3,9 Further studies are needed to understand the role of canine olfaction in melanoma screening and diagnosis as well as to explore methods to optimize sensitivity and specificity. Until then, patients and dermatologists should not ignore the behavior of dogs toward skin lesions. Dogs may be beneficial in the detection of melanoma and help save lives, as was seen in our case.

To the Editor:

A 43-year-old woman presented with a mole on the central back that had been present since childhood and had changed and grown over the last few years. The patient reported that her 2-year-old rescue dog frequently sniffed the mole and would subsequently get agitated and try to scratch and bite the lesion. This behavior prompted the patient to visit a dermatologist.

She reported no personal history of melanoma or nonmelanoma skin cancer, tanning booth exposure, blistering sunburns, or use of immunosuppressant medications. Her family history was remarkable for basal cell carcinoma in her father but no family history of melanoma. Physical examination revealed a 1.2×1.5-cm brown patch along with a 1×1-cm ulcerated nodule on the lower aspect of the lesion (Figure 1). Dermoscopy showed a blue-white veil and an irregular vascular pattern (Figure 2). No cervical, axillary, or inguinal lymphadenopathy was appreciated on physical examination. Reflectance confocal microscopy showed pagetoid spread of atypical round melanocytes as well as melanocytes in the stratum corneum (Figure 3).

The patient was referred to a surgical oncologist for wide local excision and sentinel lymph node biopsy. Pathology showed a 4-mm-thick melanoma with numerous positive lymph nodes (Figure 4). The patient subsequently underwent a right axillary lymphadenectomy and was diagnosed with stage IIIB malignant melanoma. After surgery, the patient reported that her dog would now sniff her back and calmly rest his head in her lap.

Both anecdotal and systematic evidence have emerged on the role of canine olfaction in the detection of lung, breast, colorectal, ovarian, prostate, and skin cancers, including malignant melanoma.^1-6 A 1989 case report described a woman who was prompted to seek dermatologic evaluation of a pigmented lesion because her dog consistently targeted the lesion. Excision and subsequent histopathologic examination of the lesion revealed that it was malignant melanoma.⁵ Another case report described a patient whose dog, which was not trained to detect cancers in humans, persistently licked a lesion behind the patient’s ear that eventually was found to be malignant melanoma.⁶ These reports have inspired considerable research interest regarding canine olfaction as a potential method to noninvasively screen for and even diagnose malignant melanomas in humans.

Both physiologic and pathologic metabolic processes result in the production of volatile organic compounds (VOCs), or small odorant molecules that evaporate at normal temperatures and pressures.¹ Individual cells release VOCs in extremely low concentrations into the blood, urine, feces, and breath, as well as onto the skin’s surface, but there are methods for detecting these VOCs, including gas chromatography–mass spectrometry and canine olfaction.^7,8 Pathologic processes, such as infection and malignancy, result in irregular protein synthesis and metabolism, producing new VOCs or differing concentrations of VOCs as compared to normal processes.¹

Dimethyl disulfide and dimethyl trisulfide compounds have been identified in malignant melanoma, and these compounds are not produced by normal melanocytes.⁷ Furthermore, malignant melanoma produces differing quantities of these compounds as compared to normal melanocytes, including isovaleric acid, 2-methylbutyric acid, isoamyl alcohol (3-methyl-1-butanol), and 2-methyl-1-butanol, resulting in a distinct odorant profile that previously has been detected via canine olfaction.⁷ Canine olfaction can identify odorant molecules at up to 1 part per trillion (a magnitude more sensitive than the currently available gas chromatography–mass spectrometry technologies) and can detect the production of new VOCs or altered VOC ratios due to pathologic processes.¹ Systematic studies with dogs that are trained to detect cancers in humans have shown that canine olfaction correctly identified malignant melanomas against healthy skin, benign nevi, and even basal cell carcinomas at higher rates than what would have been expected by chance alone.^2,3

Canine olfaction can identify new or altered ratios of odorant VOCs associated with pathologic metabolic processes, and canines can be trained to target odor profiles associated with specific diseases.¹ Canine olfaction for melanoma screening and diagnosis may seem appealing, as it provides an easily transportable, real-time, low-cost method compared to other techniques such as gas chromatography–mass spectrometry.¹ Although preliminary results have shown that canine olfaction detects melanoma at higher rates than would be expected by chance alone, these findings have not approached clinical utility for the widespread use of canine olfaction as a screening method for melanoma.^2,3,9 Further studies are needed to understand the role of canine olfaction in melanoma screening and diagnosis as well as to explore methods to optimize sensitivity and specificity. Until then, patients and dermatologists should not ignore the behavior of dogs toward skin lesions. Dogs may be beneficial in the detection of melanoma and help save lives, as was seen in our case.

To the Editor:

A 43-year-old woman presented with a mole on the central back that had been present since childhood and had changed and grown over the last few years. The patient reported that her 2-year-old rescue dog frequently sniffed the mole and would subsequently get agitated and try to scratch and bite the lesion. This behavior prompted the patient to visit a dermatologist.

She reported no personal history of melanoma or nonmelanoma skin cancer, tanning booth exposure, blistering sunburns, or use of immunosuppressant medications. Her family history was remarkable for basal cell carcinoma in her father but no family history of melanoma. Physical examination revealed a 1.2×1.5-cm brown patch along with a 1×1-cm ulcerated nodule on the lower aspect of the lesion (Figure 1). Dermoscopy showed a blue-white veil and an irregular vascular pattern (Figure 2). No cervical, axillary, or inguinal lymphadenopathy was appreciated on physical examination. Reflectance confocal microscopy showed pagetoid spread of atypical round melanocytes as well as melanocytes in the stratum corneum (Figure 3).

The patient was referred to a surgical oncologist for wide local excision and sentinel lymph node biopsy. Pathology showed a 4-mm-thick melanoma with numerous positive lymph nodes (Figure 4). The patient subsequently underwent a right axillary lymphadenectomy and was diagnosed with stage IIIB malignant melanoma. After surgery, the patient reported that her dog would now sniff her back and calmly rest his head in her lap.

Both anecdotal and systematic evidence have emerged on the role of canine olfaction in the detection of lung, breast, colorectal, ovarian, prostate, and skin cancers, including malignant melanoma.^1-6 A 1989 case report described a woman who was prompted to seek dermatologic evaluation of a pigmented lesion because her dog consistently targeted the lesion. Excision and subsequent histopathologic examination of the lesion revealed that it was malignant melanoma.⁵ Another case report described a patient whose dog, which was not trained to detect cancers in humans, persistently licked a lesion behind the patient’s ear that eventually was found to be malignant melanoma.⁶ These reports have inspired considerable research interest regarding canine olfaction as a potential method to noninvasively screen for and even diagnose malignant melanomas in humans.

Both physiologic and pathologic metabolic processes result in the production of volatile organic compounds (VOCs), or small odorant molecules that evaporate at normal temperatures and pressures.¹ Individual cells release VOCs in extremely low concentrations into the blood, urine, feces, and breath, as well as onto the skin’s surface, but there are methods for detecting these VOCs, including gas chromatography–mass spectrometry and canine olfaction.^7,8 Pathologic processes, such as infection and malignancy, result in irregular protein synthesis and metabolism, producing new VOCs or differing concentrations of VOCs as compared to normal processes.¹

Dimethyl disulfide and dimethyl trisulfide compounds have been identified in malignant melanoma, and these compounds are not produced by normal melanocytes.⁷ Furthermore, malignant melanoma produces differing quantities of these compounds as compared to normal melanocytes, including isovaleric acid, 2-methylbutyric acid, isoamyl alcohol (3-methyl-1-butanol), and 2-methyl-1-butanol, resulting in a distinct odorant profile that previously has been detected via canine olfaction.⁷ Canine olfaction can identify odorant molecules at up to 1 part per trillion (a magnitude more sensitive than the currently available gas chromatography–mass spectrometry technologies) and can detect the production of new VOCs or altered VOC ratios due to pathologic processes.¹ Systematic studies with dogs that are trained to detect cancers in humans have shown that canine olfaction correctly identified malignant melanomas against healthy skin, benign nevi, and even basal cell carcinomas at higher rates than what would have been expected by chance alone.^2,3

Canine olfaction can identify new or altered ratios of odorant VOCs associated with pathologic metabolic processes, and canines can be trained to target odor profiles associated with specific diseases.¹ Canine olfaction for melanoma screening and diagnosis may seem appealing, as it provides an easily transportable, real-time, low-cost method compared to other techniques such as gas chromatography–mass spectrometry.¹ Although preliminary results have shown that canine olfaction detects melanoma at higher rates than would be expected by chance alone, these findings have not approached clinical utility for the widespread use of canine olfaction as a screening method for melanoma.^2,3,9 Further studies are needed to understand the role of canine olfaction in melanoma screening and diagnosis as well as to explore methods to optimize sensitivity and specificity. Until then, patients and dermatologists should not ignore the behavior of dogs toward skin lesions. Dogs may be beneficial in the detection of melanoma and help save lives, as was seen in our case.

To the Editor:

Verrucous carcinoma (VC) is a rare type of squamous cell carcinoma characterized by a well-differentiated low-grade tumor with a high degree of keratinization. First described by Ackerman¹ in 1948, VC presents on the skin or oral and genital mucosae with minimal atypical cytologic findings.^1-3 It most commonly is seen in late middle-aged men (85% of cases) and presents as a slow-growing mass, often of more than 10 years’ duration.^2,3 Verrucous carcinoma frequently is observed at 3 particular anatomic sites: the oral cavity, known as oral florid papillomatosis; the anogenital area, known as Buschke-Löwenstein tumor; and on the plantar surface, known as epithelioma cuniculatum.^2-13

A 19-year-old man presented with an ulcerous lesion on the right big toe of 2 years’ duration. He reported that the lesion had gradually increased in size and was painful when walking. Physical examination revealed an ulcerated lesion on the right big toe with purulent inflammation and necrosis, unclear edges, and border nodules containing a fatty, yellowish, foul-smelling material (Figure 1). Histologic examination of purulent material from deep within the primary lesion revealed gram-negative rods and gram-positive diplococci. Erlich-Ziehl-Neelsen staining and culture in Lowenstein-Jensen medium were negative for mycobacteria. Histologic examination and fungal culture were not diagnostic for fungal infection.

At the initial presentation, radiography of the right big toe revealed porotic signs and cortical irregularity of the distal phalanx. A deep incisional biopsy of the lesion was performed for pathologic and microbiologic analysis. Erlich-Ziehl-Neelsen staining was negative, fungal elements could not be observed, and there was no growth in Lowenstein-Jensen medium or Sabouraud dextrose agar. Polymerase chain reaction for human papillomavirus, M tuberculosis, and atypical mycobacterium was negative. Periodic acid–Schiff staining was negative for fungal elements. Histopathologic examination revealed an exophytic as well as endophytic squamous cell proliferation infiltrating deeper layers of the dermis with a desmoplastic stroma (Figure 2). Slight cytologic atypia was noted. A diagnosis of VC was made based on the clinical and histopathologic findings. The patient’s right big toe was amputated by plastic surgery 6 months after the initial presentation.

Histopathologic examination, especially of superficial biopsies, generally reveals squamous cell proliferation demonstrating minimal pleomorphism and cytologic atypia with sparse mitotic figures.^4-6 Diagnosis of VC can be challenging if the endophytic proliferation, which characteristically pushes into the dermis and even deeper tissues at the base of the lesion, is not seen. This feature is uncommon in squamous cell carcinomas.^3,4,6 Histopathologic detection of koilocytes can lead to difficulty in distinguishing VC from warts.⁵ The growth of lesions is exophytic in plantar verrucae, whereas in VC it may be either exophytic or endophytic.⁴ At early stages, it is too difficult to distinguish VC from pseudoepitheliomatous hyperplasia caused by chronic inflammation, as well as from tuberculosis and subcutaneous mycoses.^3,6 In these situations, possible responsible microorganisms must be sought out. Amelanotic malignant melanoma and eccrine poroma also should be considered in the differential diagnosis.^3,5 If the biopsy specimen is obtained superficially and is fragmented, the diagnosis is more difficult, making deep biopsies essential in suspicious cases.⁴ Excision is the best treatment, and Mohs micrographic surgery may be required in some cases.^2,3,11 It is important to consider that radiotherapy may lead to anaplastic transformation and metastasis.² Metastasis to lymph nodes is very rare, and the prognosis is excellent when complete excision is performed.² Recurrence may be observed.⁴

Our case of plantar VC is notable because of the patient’s young age, which is uncommon, as the typical age for developing VC is late middle age (ie, fifth and sixth decades of life). A long-standing lesion that is therapy resistant and without a detectable microorganism should be investigated for malignancy by repetitive deep biopsy regardless of the patient’s age, as demonstrated in our case.

To the Editor:

Verrucous carcinoma (VC) is a rare type of squamous cell carcinoma characterized by a well-differentiated low-grade tumor with a high degree of keratinization. First described by Ackerman¹ in 1948, VC presents on the skin or oral and genital mucosae with minimal atypical cytologic findings.^1-3 It most commonly is seen in late middle-aged men (85% of cases) and presents as a slow-growing mass, often of more than 10 years’ duration.^2,3 Verrucous carcinoma frequently is observed at 3 particular anatomic sites: the oral cavity, known as oral florid papillomatosis; the anogenital area, known as Buschke-Löwenstein tumor; and on the plantar surface, known as epithelioma cuniculatum.^2-13

A 19-year-old man presented with an ulcerous lesion on the right big toe of 2 years’ duration. He reported that the lesion had gradually increased in size and was painful when walking. Physical examination revealed an ulcerated lesion on the right big toe with purulent inflammation and necrosis, unclear edges, and border nodules containing a fatty, yellowish, foul-smelling material (Figure 1). Histologic examination of purulent material from deep within the primary lesion revealed gram-negative rods and gram-positive diplococci. Erlich-Ziehl-Neelsen staining and culture in Lowenstein-Jensen medium were negative for mycobacteria. Histologic examination and fungal culture were not diagnostic for fungal infection.

At the initial presentation, radiography of the right big toe revealed porotic signs and cortical irregularity of the distal phalanx. A deep incisional biopsy of the lesion was performed for pathologic and microbiologic analysis. Erlich-Ziehl-Neelsen staining was negative, fungal elements could not be observed, and there was no growth in Lowenstein-Jensen medium or Sabouraud dextrose agar. Polymerase chain reaction for human papillomavirus, M tuberculosis, and atypical mycobacterium was negative. Periodic acid–Schiff staining was negative for fungal elements. Histopathologic examination revealed an exophytic as well as endophytic squamous cell proliferation infiltrating deeper layers of the dermis with a desmoplastic stroma (Figure 2). Slight cytologic atypia was noted. A diagnosis of VC was made based on the clinical and histopathologic findings. The patient’s right big toe was amputated by plastic surgery 6 months after the initial presentation.

Histopathologic examination, especially of superficial biopsies, generally reveals squamous cell proliferation demonstrating minimal pleomorphism and cytologic atypia with sparse mitotic figures.^4-6 Diagnosis of VC can be challenging if the endophytic proliferation, which characteristically pushes into the dermis and even deeper tissues at the base of the lesion, is not seen. This feature is uncommon in squamous cell carcinomas.^3,4,6 Histopathologic detection of koilocytes can lead to difficulty in distinguishing VC from warts.⁵ The growth of lesions is exophytic in plantar verrucae, whereas in VC it may be either exophytic or endophytic.⁴ At early stages, it is too difficult to distinguish VC from pseudoepitheliomatous hyperplasia caused by chronic inflammation, as well as from tuberculosis and subcutaneous mycoses.^3,6 In these situations, possible responsible microorganisms must be sought out. Amelanotic malignant melanoma and eccrine poroma also should be considered in the differential diagnosis.^3,5 If the biopsy specimen is obtained superficially and is fragmented, the diagnosis is more difficult, making deep biopsies essential in suspicious cases.⁴ Excision is the best treatment, and Mohs micrographic surgery may be required in some cases.^2,3,11 It is important to consider that radiotherapy may lead to anaplastic transformation and metastasis.² Metastasis to lymph nodes is very rare, and the prognosis is excellent when complete excision is performed.² Recurrence may be observed.⁴

Our case of plantar VC is notable because of the patient’s young age, which is uncommon, as the typical age for developing VC is late middle age (ie, fifth and sixth decades of life). A long-standing lesion that is therapy resistant and without a detectable microorganism should be investigated for malignancy by repetitive deep biopsy regardless of the patient’s age, as demonstrated in our case.

To the Editor:

Verrucous carcinoma (VC) is a rare type of squamous cell carcinoma characterized by a well-differentiated low-grade tumor with a high degree of keratinization. First described by Ackerman¹ in 1948, VC presents on the skin or oral and genital mucosae with minimal atypical cytologic findings.^1-3 It most commonly is seen in late middle-aged men (85% of cases) and presents as a slow-growing mass, often of more than 10 years’ duration.^2,3 Verrucous carcinoma frequently is observed at 3 particular anatomic sites: the oral cavity, known as oral florid papillomatosis; the anogenital area, known as Buschke-Löwenstein tumor; and on the plantar surface, known as epithelioma cuniculatum.^2-13

A 19-year-old man presented with an ulcerous lesion on the right big toe of 2 years’ duration. He reported that the lesion had gradually increased in size and was painful when walking. Physical examination revealed an ulcerated lesion on the right big toe with purulent inflammation and necrosis, unclear edges, and border nodules containing a fatty, yellowish, foul-smelling material (Figure 1). Histologic examination of purulent material from deep within the primary lesion revealed gram-negative rods and gram-positive diplococci. Erlich-Ziehl-Neelsen staining and culture in Lowenstein-Jensen medium were negative for mycobacteria. Histologic examination and fungal culture were not diagnostic for fungal infection.

At the initial presentation, radiography of the right big toe revealed porotic signs and cortical irregularity of the distal phalanx. A deep incisional biopsy of the lesion was performed for pathologic and microbiologic analysis. Erlich-Ziehl-Neelsen staining was negative, fungal elements could not be observed, and there was no growth in Lowenstein-Jensen medium or Sabouraud dextrose agar. Polymerase chain reaction for human papillomavirus, M tuberculosis, and atypical mycobacterium was negative. Periodic acid–Schiff staining was negative for fungal elements. Histopathologic examination revealed an exophytic as well as endophytic squamous cell proliferation infiltrating deeper layers of the dermis with a desmoplastic stroma (Figure 2). Slight cytologic atypia was noted. A diagnosis of VC was made based on the clinical and histopathologic findings. The patient’s right big toe was amputated by plastic surgery 6 months after the initial presentation.

Histopathologic examination, especially of superficial biopsies, generally reveals squamous cell proliferation demonstrating minimal pleomorphism and cytologic atypia with sparse mitotic figures.^4-6 Diagnosis of VC can be challenging if the endophytic proliferation, which characteristically pushes into the dermis and even deeper tissues at the base of the lesion, is not seen. This feature is uncommon in squamous cell carcinomas.^3,4,6 Histopathologic detection of koilocytes can lead to difficulty in distinguishing VC from warts.⁵ The growth of lesions is exophytic in plantar verrucae, whereas in VC it may be either exophytic or endophytic.⁴ At early stages, it is too difficult to distinguish VC from pseudoepitheliomatous hyperplasia caused by chronic inflammation, as well as from tuberculosis and subcutaneous mycoses.^3,6 In these situations, possible responsible microorganisms must be sought out. Amelanotic malignant melanoma and eccrine poroma also should be considered in the differential diagnosis.^3,5 If the biopsy specimen is obtained superficially and is fragmented, the diagnosis is more difficult, making deep biopsies essential in suspicious cases.⁴ Excision is the best treatment, and Mohs micrographic surgery may be required in some cases.^2,3,11 It is important to consider that radiotherapy may lead to anaplastic transformation and metastasis.² Metastasis to lymph nodes is very rare, and the prognosis is excellent when complete excision is performed.² Recurrence may be observed.⁴

Our case of plantar VC is notable because of the patient’s young age, which is uncommon, as the typical age for developing VC is late middle age (ie, fifth and sixth decades of life). A long-standing lesion that is therapy resistant and without a detectable microorganism should be investigated for malignancy by repetitive deep biopsy regardless of the patient’s age, as demonstrated in our case.

Case Report

A 63-year-old man was evaluated in the Mohs clinic for a lesion on the right supraclavicular neck, which he described as a linear asymptomatic “birthmark” that had been present since childhood and stable for many years. It began to enlarge approximately 5 years prior, became increasingly red, and had occasional crusting. The lesion also gradually became more irritated with repeated mild trauma when he carried a backpack while hiking. On physical examination, a 10×2-cm, linear, pink plaque with an irregular border, translucent rolled edges, and central smooth atrophic skin was seen on the right supraclavicular neck (Figure). There was no visible epidermal nevus or nevus sebaceous in the area. A shave biopsy of the lesion confirmed the pathologic diagnosis of basal cell carcinoma, nodular type, along with the morphologic diagnosis of linear basal cell carcinoma (LBCC). The tumor was completely removed with standard excision using 5-mm margins.

Approximately 10 months after the original excision, the patient developed an irritated erosion that occasionally bled when his backpack rubbed against it. He returned to the clinic after the erosion failed to heal. Physical examination revealed a 1.4×0.7-cm, eroded, pink papule with large telangiectases at the superior pole of the excision scar. A shave biopsy confirmed the diagnosis of a recurrent infiltrative basal cell carcinoma. The tumor was then completely excised using Mohs micrographic surgery.

Comment

Linear basal cell carcinoma, first described by Lewis¹ in 1985, is a rare morphologic variant of basal cell carcinoma. In 2011, Al-Niaimi and Lyon² performed a comprehensive literature search on LBCC (1985-2008) and found only 39 cases (including 2 of their own) had been published since the pioneer case in 1985. It was determined that the most common sites affected were the periorbital area and neck (n=13 each [67%]), and the majority were histologically nodular (n=27 [69%]). Mohs micrographic surgery was the most common treatment method (n=23 [59%]), followed by primary excision (n=17 [44%]). A history of trauma, radiotherapy, or prior operation in association with the site of the LBCC was discovered in only 7 cases (18%).² Although Peschen et al³ proposed that trauma—both physical and surgical—and radiotherapy may play a role in the development of LBCCs, the low incidence reported suggests that other factors may be involved. To determine if genetic factors were contributing to the development of LBCCs, Yamaguchi et al⁴ investigated the expression of p27 and PCTAIRE1, both known to contribute to tumorigenesis when mutated, as well as somatic gene mutations using deep sequencing in a case of LBCC; they found no associated genetic mutation.

Reported Cases of LBCC
According to a PubMed search of articles indexed for MEDLINE using the terms linear and basal cell carcinoma, 67 cases (including the current case) of LBCC have been published since 1985. The patient demographics, anatomic location, histologic subtype, treatment methods, and frequency of recurrence for all reported cases of LBCC are summarized in the Table.^1-24 There were 36 women and 31 men, with an average age of 70 years (range, 40–92 years). The most commonly affected sites were the periocular region (n=27) and neck (n=18). Histologically, most LBCCs were nodular (n=35), with the next most common histologic subtype being infiltrative (n=20), which included the morphoeic, metatypical, and micronodular subtypes under the overarching infiltrative subtype. The most frequently chosen treatment option was primary excision (n=38 [57%]), followed by Mohs micrographic surgery (n=28 [42%]). Risk factors previously identified by Al-Niaimi and Lyon,² including trauma, radiotherapy, or prior operation, were reported in 12 of 67 cases. Recurrence was reported in only 2 of 67 cases, 1 being the current case; however, an accurate recurrence rate could not be calculated due to lack of follow-up or short length of follow-up in most of the reported cases.

Conclusion

Linear basal cell carcinoma should be considered a distinct morphologic variant of basal cell carcinoma. Although likely underreported, this variant is uncommon. It presents most often in the periocular and neck regions. The most common histologic subtypes are nodular and infiltrative. Because of the likelihood of subclinical spread, LBCC should be regarded as a high-risk subtype. As such, Mohs micrographic surgery or excision with complete circumferential peripheral and deep margin assessment is recommended as first-line treatment of LBCC.⁶

Case Report

A 63-year-old man was evaluated in the Mohs clinic for a lesion on the right supraclavicular neck, which he described as a linear asymptomatic “birthmark” that had been present since childhood and stable for many years. It began to enlarge approximately 5 years prior, became increasingly red, and had occasional crusting. The lesion also gradually became more irritated with repeated mild trauma when he carried a backpack while hiking. On physical examination, a 10×2-cm, linear, pink plaque with an irregular border, translucent rolled edges, and central smooth atrophic skin was seen on the right supraclavicular neck (Figure). There was no visible epidermal nevus or nevus sebaceous in the area. A shave biopsy of the lesion confirmed the pathologic diagnosis of basal cell carcinoma, nodular type, along with the morphologic diagnosis of linear basal cell carcinoma (LBCC). The tumor was completely removed with standard excision using 5-mm margins.

Approximately 10 months after the original excision, the patient developed an irritated erosion that occasionally bled when his backpack rubbed against it. He returned to the clinic after the erosion failed to heal. Physical examination revealed a 1.4×0.7-cm, eroded, pink papule with large telangiectases at the superior pole of the excision scar. A shave biopsy confirmed the diagnosis of a recurrent infiltrative basal cell carcinoma. The tumor was then completely excised using Mohs micrographic surgery.

Comment

Linear basal cell carcinoma, first described by Lewis¹ in 1985, is a rare morphologic variant of basal cell carcinoma. In 2011, Al-Niaimi and Lyon² performed a comprehensive literature search on LBCC (1985-2008) and found only 39 cases (including 2 of their own) had been published since the pioneer case in 1985. It was determined that the most common sites affected were the periorbital area and neck (n=13 each [67%]), and the majority were histologically nodular (n=27 [69%]). Mohs micrographic surgery was the most common treatment method (n=23 [59%]), followed by primary excision (n=17 [44%]). A history of trauma, radiotherapy, or prior operation in association with the site of the LBCC was discovered in only 7 cases (18%).² Although Peschen et al³ proposed that trauma—both physical and surgical—and radiotherapy may play a role in the development of LBCCs, the low incidence reported suggests that other factors may be involved. To determine if genetic factors were contributing to the development of LBCCs, Yamaguchi et al⁴ investigated the expression of p27 and PCTAIRE1, both known to contribute to tumorigenesis when mutated, as well as somatic gene mutations using deep sequencing in a case of LBCC; they found no associated genetic mutation.

Reported Cases of LBCC
According to a PubMed search of articles indexed for MEDLINE using the terms linear and basal cell carcinoma, 67 cases (including the current case) of LBCC have been published since 1985. The patient demographics, anatomic location, histologic subtype, treatment methods, and frequency of recurrence for all reported cases of LBCC are summarized in the Table.^1-24 There were 36 women and 31 men, with an average age of 70 years (range, 40–92 years). The most commonly affected sites were the periocular region (n=27) and neck (n=18). Histologically, most LBCCs were nodular (n=35), with the next most common histologic subtype being infiltrative (n=20), which included the morphoeic, metatypical, and micronodular subtypes under the overarching infiltrative subtype. The most frequently chosen treatment option was primary excision (n=38 [57%]), followed by Mohs micrographic surgery (n=28 [42%]). Risk factors previously identified by Al-Niaimi and Lyon,² including trauma, radiotherapy, or prior operation, were reported in 12 of 67 cases. Recurrence was reported in only 2 of 67 cases, 1 being the current case; however, an accurate recurrence rate could not be calculated due to lack of follow-up or short length of follow-up in most of the reported cases.

Conclusion

Linear basal cell carcinoma should be considered a distinct morphologic variant of basal cell carcinoma. Although likely underreported, this variant is uncommon. It presents most often in the periocular and neck regions. The most common histologic subtypes are nodular and infiltrative. Because of the likelihood of subclinical spread, LBCC should be regarded as a high-risk subtype. As such, Mohs micrographic surgery or excision with complete circumferential peripheral and deep margin assessment is recommended as first-line treatment of LBCC.⁶

Case Report

A 63-year-old man was evaluated in the Mohs clinic for a lesion on the right supraclavicular neck, which he described as a linear asymptomatic “birthmark” that had been present since childhood and stable for many years. It began to enlarge approximately 5 years prior, became increasingly red, and had occasional crusting. The lesion also gradually became more irritated with repeated mild trauma when he carried a backpack while hiking. On physical examination, a 10×2-cm, linear, pink plaque with an irregular border, translucent rolled edges, and central smooth atrophic skin was seen on the right supraclavicular neck (Figure). There was no visible epidermal nevus or nevus sebaceous in the area. A shave biopsy of the lesion confirmed the pathologic diagnosis of basal cell carcinoma, nodular type, along with the morphologic diagnosis of linear basal cell carcinoma (LBCC). The tumor was completely removed with standard excision using 5-mm margins.

Approximately 10 months after the original excision, the patient developed an irritated erosion that occasionally bled when his backpack rubbed against it. He returned to the clinic after the erosion failed to heal. Physical examination revealed a 1.4×0.7-cm, eroded, pink papule with large telangiectases at the superior pole of the excision scar. A shave biopsy confirmed the diagnosis of a recurrent infiltrative basal cell carcinoma. The tumor was then completely excised using Mohs micrographic surgery.

Comment

Linear basal cell carcinoma, first described by Lewis¹ in 1985, is a rare morphologic variant of basal cell carcinoma. In 2011, Al-Niaimi and Lyon² performed a comprehensive literature search on LBCC (1985-2008) and found only 39 cases (including 2 of their own) had been published since the pioneer case in 1985. It was determined that the most common sites affected were the periorbital area and neck (n=13 each [67%]), and the majority were histologically nodular (n=27 [69%]). Mohs micrographic surgery was the most common treatment method (n=23 [59%]), followed by primary excision (n=17 [44%]). A history of trauma, radiotherapy, or prior operation in association with the site of the LBCC was discovered in only 7 cases (18%).² Although Peschen et al³ proposed that trauma—both physical and surgical—and radiotherapy may play a role in the development of LBCCs, the low incidence reported suggests that other factors may be involved. To determine if genetic factors were contributing to the development of LBCCs, Yamaguchi et al⁴ investigated the expression of p27 and PCTAIRE1, both known to contribute to tumorigenesis when mutated, as well as somatic gene mutations using deep sequencing in a case of LBCC; they found no associated genetic mutation.

Reported Cases of LBCC
According to a PubMed search of articles indexed for MEDLINE using the terms linear and basal cell carcinoma, 67 cases (including the current case) of LBCC have been published since 1985. The patient demographics, anatomic location, histologic subtype, treatment methods, and frequency of recurrence for all reported cases of LBCC are summarized in the Table.^1-24 There were 36 women and 31 men, with an average age of 70 years (range, 40–92 years). The most commonly affected sites were the periocular region (n=27) and neck (n=18). Histologically, most LBCCs were nodular (n=35), with the next most common histologic subtype being infiltrative (n=20), which included the morphoeic, metatypical, and micronodular subtypes under the overarching infiltrative subtype. The most frequently chosen treatment option was primary excision (n=38 [57%]), followed by Mohs micrographic surgery (n=28 [42%]). Risk factors previously identified by Al-Niaimi and Lyon,² including trauma, radiotherapy, or prior operation, were reported in 12 of 67 cases. Recurrence was reported in only 2 of 67 cases, 1 being the current case; however, an accurate recurrence rate could not be calculated due to lack of follow-up or short length of follow-up in most of the reported cases.

Conclusion

Linear basal cell carcinoma should be considered a distinct morphologic variant of basal cell carcinoma. Although likely underreported, this variant is uncommon. It presents most often in the periocular and neck regions. The most common histologic subtypes are nodular and infiltrative. Because of the likelihood of subclinical spread, LBCC should be regarded as a high-risk subtype. As such, Mohs micrographic surgery or excision with complete circumferential peripheral and deep margin assessment is recommended as first-line treatment of LBCC.⁶

Traditionally, diagnosis of skin disease relies on clinical inspection, often followed by biopsy and histopathologic examination. In recent years, new noninvasive tools have emerged that can aid in clinical diagnosis and reduce the number of unnecessary benign biopsies. Although there has been a surge in noninvasive diagnostic technologies, many tools are still in research and development phases, with few tools widely adopted and used in regular clinical practice. In this article, we discuss the use of dermoscopy, reflectance confocal microscopy (RCM), and optical coherence tomography (OCT) in the diagnosis and management of skin disease.

Dermoscopy

Dermoscopy, also known as epiluminescence light microscopy and previously known as dermatoscopy, utilizes a ×10 to ×100 microscope objective with a light source to magnify and visualize structures present below the skin’s surface, such as melanin and blood vessels. There are 3 types of dermoscopy: conventional nonpolarized dermoscopy, polarized contact dermoscopy, and nonpolarized contact dermoscopy (Figure 1). Traditional nonpolarized dermoscopy requires a liquid medium and direct contact with the skin, and it relies on light reflection and refraction properties.¹ Cross-polarized light sources allow visualization of deeper structures, either with or without a liquid medium and contact with the skin surface. Although there is overall concurrence among the different types of dermoscopy, subtle differences in the appearance of color, features, and structure are present.¹

Dermoscopy offers many benefits for dermatologists and other providers. It can be used to aid in the diagnosis of cutaneous neoplasms and other skin diseases. Numerous low-cost dermatoscopes currently are commercially available. The handheld, easily transportable nature of dermatoscopes have resulted in widespread practice integration. Approximately 84% of attending dermatologists in US academic settings reported using dermoscopy, and many refer to the dermatoscope as “the dermatologist’s stethoscope.”² In addition, 6% to 15% of other US providers, including family physicians, internal medicine physicians, and plastic surgeons, have reported using dermoscopy in their clinical practices. Limitations of dermoscopy include visualization of the skin surface only and not deeper structures within the tissue, the need for training for adequate interpretation of dermoscopic images, and lack of reimbursement for dermoscopic examination.³

Many dermoscopic structures that correspond well with histopathology have been described. Dermoscopy has a sensitivity of 79% to 96% and specificity of 69% to 99% in the diagnosis of melanoma.⁴ There is variable data on the specificity of dermoscopy in the diagnosis of melanoma, with one meta-analysis finding no statistically significant difference in specificity compared to naked eye examination,⁵ while other studies report increased specificity and subsequent reduction in biopsy of benign lesions.^6,7 Dermoscopy also can aid in the diagnosis of keratinocytic neoplasms, and dermoscopy also results in a sensitivity of 78.6% to 100% and a specificity of 53.8% to 100% in the diagnosis of basal cell carcinoma (BCC).⁸ Limitations of dermoscopy include false-positive diagnoses, commonly seborrheic keratoses and nevi, resulting in unnecessary biopsies, as well as false-negative diagnoses, commonly amelanotic and nevoid melanoma, resulting in delays in skin cancer diagnosis and resultant poor outcomes.⁹ Dermoscopy also is used to aid in the diagnosis of inflammatory and infectious skin diseases, as well as scalp, hair, and nail disorders.¹⁰

Reflectance Confocal Microscopy

Reflectance confocal microscopy utilizes an 830-nm laser to capture horizontal en face images of the skin with high resolution. Different structures of the skin have varying indices of refraction: keratin, melanin, and collagen appear bright white, while other components appear dark, generating black-and-white RCM images.¹¹ Currently, there are 2 reflectance confocal microscopes that are commercially available in the United States. The Vivascope 1500 (Caliber ID) is the traditional model that captures 8×8-mm images, and the Vivascope 3000 (Caliber ID) is a smaller handheld model that captures 0.5×0.5-mm images. The traditional model provides the advantages of higher-resolution images and the ability to capture larger surface areas but is best suited to image flat areas of skin to which a square window can be adhered. The handheld model allows improved contact with the varying topography of skin; does not require an adhesive window; and can be used to image cartilaginous, mucosal, and sensitive surfaces. However, it can be difficult to correlate individual images captured by the handheld RCM with the location relative to the lesion, as it is exquisitely sensitive to motion and also is operator dependent. Although complex algorithms are under development to stitch individual images to provide better correlation with the geography of the lesion, such programs are not yet widely available.¹²

Reflectance confocal microscopy affords many benefits for patients and providers. It is noninvasive and painless and is capable of imaging in vivo live skin as compared to clinical examination and dermoscopy, which only allow for visualization of the skin’s surface. Reflectance confocal microscopy also is time efficient, as imaging of a single lesion can be completed in 10 to 15 minutes. This technology generates high-resolution images, and RCM diagnosis has consistently demonstrated high sensitivity and specificity when compared to histopathology.¹³ Additionally, RCM imaging can spare biopsy and resultant scarring on cosmetically sensitive areas. Recently, RCM imaging of the skin has been granted Category I Current Procedural Terminology reimbursement codes that allow provider reimbursement and integration of RCM into daily practice¹⁴; however, private insurance coverage in the United States is variable. Limitations of RCM include a maximum depth of 200 to 300 µm, high cost to procure a reflectance confocal microscope, and the need for considerable training and practice to accurately interpret grayscale en face images.¹⁵

There has been extensive research regarding the use of RCM in the evaluation of cutaneous neoplasms and other skin diseases. Numerous features and patterns have been identified and described that correspond with different skin diseases and correspond well with histopathology (Figure 2).^13,16,17 Reflectance confocal microscopy has demonstrated consistently high accuracy in the diagnosis of melanocytic lesions, with a sensitivity of 93% to 100% and a specificity of 75% to 99%.^18-21 Reflectance confocal microscopy is especially useful in the evaluation of clinically or dermoscopically equivocal pigmented lesions due to greater specificity, resulting in a reduction of unnecessary biopsies.^22,23 It also has high accuracy in the diagnosis of keratinocytic neoplasms, with a sensitivity of 82% to 100% and a specificity of 78% to 97% in the diagnosis of BCC,²⁴ and a sensitivity of 74% to 100% and specificity of 78% to 100% in the diagnosis of squamous cell carcinoma (SCC).^25,26 Evaluation of SCC and actinic keratosis (AK) using RCM may be limited by considerable hyperkeratosis and ulceration. In addition, it can be challenging to differentiate AK and SCC on RCM, and considerable expertise is required to accurately grade cytologic and architectural atypia.²⁷ However, RCM has been used to discriminate between in situ and invasive proliferations.²⁸ Reflectance confocal microscopy has wide applications in the diagnosis and management of cutaneous infections^29,30 and inflammatory skin diseases.^29,31-33 Recent RCM research explored the use of RCM to identify biopsy sites,³⁴ delineate presurgical tumor margins,^35,36 and monitor response to noninvasive treatments.^37,38

Optical Coherence Tomography

Optical coherence tomography is an imaging modality that utilizes light backscatter from infrared light to produce grayscale cross-sectional or vertical images and horizontal en face images.³⁹ Optical coherence tomography can visualize structures in the epidermis, dermoepidermal junction, and upper dermis.⁴⁰ It can image boundaries of structures but cannot visualize individual cells.

There are different types of OCT devices available, including frequency-domain OCT (FD-OCT), or conventional OCT, and high-definition OCT (HD-OCT). With FD-OCT, images are captured at a maximum depth of 1 to 2 mm but with limited resolution. High-definition OCT has superior resolution compared to FD-OCT but is restricted to a shallower depth of 750 μm.³⁹ The main advantage of OCT is the ability to noninvasively image live tissue and visualize 2- to 5-times greater depth as compared to RCM. Several OCT devices have obtained US Food and Drug Administration approval; however, OCT has not been widely adopted into clinical practice and is available only in tertiary academic centers. Additionally, OCT imaging in dermatology is rarely reimbursed. Other limitations of OCT include poor resolution of images, high cost to procure an OCT device, and the need for advanced training and experience to accurately interpret images.^40,41

Optical coherence tomography primarily is used to diagnose cutaneous neoplasms. The best evidence of the diagnostic accuracy of OCT is in the setting of BCC, with a recent systematic review reporting a sensitivity of 66% to 96% and a specificity of 75% to 86% for conventional FD-OCT.⁴² The use of FD-OCT results in an increase in specificity without a significant change in sensitivity when compared to dermoscopy in the diagnosis of BCC.⁴³ Melanoma is difficult to diagnose via FD-OCT, as the visualization of architectural features often is limited by poor resolution.⁴⁴ A study of HD-OCT in the diagnosis of melanoma with a limited sample size reported a sensitivity of 74% to 80% and a specificity of 92% to 93%.⁴⁵ Similarly, a study of HD-OCT used in the diagnosis of AK and SCC revealed a sensitivity and specificity of 81.6% and 92.6%, respectively, for AK and 93.8% and 98.9%, respectively, for SCC.⁴⁶

Numerous algorithms and scoring systems have been developed to further explore the utility of OCT in the diagnosis of cutaneous neoplasms.^47,48 Recent research investigated the utility of dynamic OCT, which can evaluate microvasculature in the diagnosis of cutaneous neoplasms (Figure 3)⁴⁹; the combination of OCT with other imaging modalities^50,51; the use of OCT to delineate presurgical margins^52,53; and the role of OCT in the diagnosis and monitoring of inflammatory and infectious skin diseases.^54,55

Final Thoughts

In recent years, there has been a surge of interest in noninvasive techniques for diagnosis and management of skin diseases; however, noninvasive tools exist on a spectrum in dermatology. Dermoscopy provides low-cost imaging of the skin’s surface and has been widely adopted by dermatologists and other providers to aid in clinical diagnosis. Reflectance confocal microscopy provides reimbursable in vivo imaging of live tissue with cellular-level resolution but is limited by depth, cost, and need for advanced training; thus, RCM has only been adopted in some clinical practices. Optical coherence tomography offers in vivo imaging of live tissue with substantial depth but poor resolution, high cost, need for advanced training, and rare reimbursement for providers. Future directions include combination of complementary imaging modalities, increased clinical practice integration, and education and reimbursement for providers.

Traditionally, diagnosis of skin disease relies on clinical inspection, often followed by biopsy and histopathologic examination. In recent years, new noninvasive tools have emerged that can aid in clinical diagnosis and reduce the number of unnecessary benign biopsies. Although there has been a surge in noninvasive diagnostic technologies, many tools are still in research and development phases, with few tools widely adopted and used in regular clinical practice. In this article, we discuss the use of dermoscopy, reflectance confocal microscopy (RCM), and optical coherence tomography (OCT) in the diagnosis and management of skin disease.

Dermoscopy

Dermoscopy, also known as epiluminescence light microscopy and previously known as dermatoscopy, utilizes a ×10 to ×100 microscope objective with a light source to magnify and visualize structures present below the skin’s surface, such as melanin and blood vessels. There are 3 types of dermoscopy: conventional nonpolarized dermoscopy, polarized contact dermoscopy, and nonpolarized contact dermoscopy (Figure 1). Traditional nonpolarized dermoscopy requires a liquid medium and direct contact with the skin, and it relies on light reflection and refraction properties.¹ Cross-polarized light sources allow visualization of deeper structures, either with or without a liquid medium and contact with the skin surface. Although there is overall concurrence among the different types of dermoscopy, subtle differences in the appearance of color, features, and structure are present.¹

Dermoscopy offers many benefits for dermatologists and other providers. It can be used to aid in the diagnosis of cutaneous neoplasms and other skin diseases. Numerous low-cost dermatoscopes currently are commercially available. The handheld, easily transportable nature of dermatoscopes have resulted in widespread practice integration. Approximately 84% of attending dermatologists in US academic settings reported using dermoscopy, and many refer to the dermatoscope as “the dermatologist’s stethoscope.”² In addition, 6% to 15% of other US providers, including family physicians, internal medicine physicians, and plastic surgeons, have reported using dermoscopy in their clinical practices. Limitations of dermoscopy include visualization of the skin surface only and not deeper structures within the tissue, the need for training for adequate interpretation of dermoscopic images, and lack of reimbursement for dermoscopic examination.³

Many dermoscopic structures that correspond well with histopathology have been described. Dermoscopy has a sensitivity of 79% to 96% and specificity of 69% to 99% in the diagnosis of melanoma.⁴ There is variable data on the specificity of dermoscopy in the diagnosis of melanoma, with one meta-analysis finding no statistically significant difference in specificity compared to naked eye examination,⁵ while other studies report increased specificity and subsequent reduction in biopsy of benign lesions.^6,7 Dermoscopy also can aid in the diagnosis of keratinocytic neoplasms, and dermoscopy also results in a sensitivity of 78.6% to 100% and a specificity of 53.8% to 100% in the diagnosis of basal cell carcinoma (BCC).⁸ Limitations of dermoscopy include false-positive diagnoses, commonly seborrheic keratoses and nevi, resulting in unnecessary biopsies, as well as false-negative diagnoses, commonly amelanotic and nevoid melanoma, resulting in delays in skin cancer diagnosis and resultant poor outcomes.⁹ Dermoscopy also is used to aid in the diagnosis of inflammatory and infectious skin diseases, as well as scalp, hair, and nail disorders.¹⁰

Reflectance Confocal Microscopy

Reflectance confocal microscopy utilizes an 830-nm laser to capture horizontal en face images of the skin with high resolution. Different structures of the skin have varying indices of refraction: keratin, melanin, and collagen appear bright white, while other components appear dark, generating black-and-white RCM images.¹¹ Currently, there are 2 reflectance confocal microscopes that are commercially available in the United States. The Vivascope 1500 (Caliber ID) is the traditional model that captures 8×8-mm images, and the Vivascope 3000 (Caliber ID) is a smaller handheld model that captures 0.5×0.5-mm images. The traditional model provides the advantages of higher-resolution images and the ability to capture larger surface areas but is best suited to image flat areas of skin to which a square window can be adhered. The handheld model allows improved contact with the varying topography of skin; does not require an adhesive window; and can be used to image cartilaginous, mucosal, and sensitive surfaces. However, it can be difficult to correlate individual images captured by the handheld RCM with the location relative to the lesion, as it is exquisitely sensitive to motion and also is operator dependent. Although complex algorithms are under development to stitch individual images to provide better correlation with the geography of the lesion, such programs are not yet widely available.¹²

Reflectance confocal microscopy affords many benefits for patients and providers. It is noninvasive and painless and is capable of imaging in vivo live skin as compared to clinical examination and dermoscopy, which only allow for visualization of the skin’s surface. Reflectance confocal microscopy also is time efficient, as imaging of a single lesion can be completed in 10 to 15 minutes. This technology generates high-resolution images, and RCM diagnosis has consistently demonstrated high sensitivity and specificity when compared to histopathology.¹³ Additionally, RCM imaging can spare biopsy and resultant scarring on cosmetically sensitive areas. Recently, RCM imaging of the skin has been granted Category I Current Procedural Terminology reimbursement codes that allow provider reimbursement and integration of RCM into daily practice¹⁴; however, private insurance coverage in the United States is variable. Limitations of RCM include a maximum depth of 200 to 300 µm, high cost to procure a reflectance confocal microscope, and the need for considerable training and practice to accurately interpret grayscale en face images.¹⁵

There has been extensive research regarding the use of RCM in the evaluation of cutaneous neoplasms and other skin diseases. Numerous features and patterns have been identified and described that correspond with different skin diseases and correspond well with histopathology (Figure 2).^13,16,17 Reflectance confocal microscopy has demonstrated consistently high accuracy in the diagnosis of melanocytic lesions, with a sensitivity of 93% to 100% and a specificity of 75% to 99%.^18-21 Reflectance confocal microscopy is especially useful in the evaluation of clinically or dermoscopically equivocal pigmented lesions due to greater specificity, resulting in a reduction of unnecessary biopsies.^22,23 It also has high accuracy in the diagnosis of keratinocytic neoplasms, with a sensitivity of 82% to 100% and a specificity of 78% to 97% in the diagnosis of BCC,²⁴ and a sensitivity of 74% to 100% and specificity of 78% to 100% in the diagnosis of squamous cell carcinoma (SCC).^25,26 Evaluation of SCC and actinic keratosis (AK) using RCM may be limited by considerable hyperkeratosis and ulceration. In addition, it can be challenging to differentiate AK and SCC on RCM, and considerable expertise is required to accurately grade cytologic and architectural atypia.²⁷ However, RCM has been used to discriminate between in situ and invasive proliferations.²⁸ Reflectance confocal microscopy has wide applications in the diagnosis and management of cutaneous infections^29,30 and inflammatory skin diseases.^29,31-33 Recent RCM research explored the use of RCM to identify biopsy sites,³⁴ delineate presurgical tumor margins,^35,36 and monitor response to noninvasive treatments.^37,38

Optical Coherence Tomography

Optical coherence tomography is an imaging modality that utilizes light backscatter from infrared light to produce grayscale cross-sectional or vertical images and horizontal en face images.³⁹ Optical coherence tomography can visualize structures in the epidermis, dermoepidermal junction, and upper dermis.⁴⁰ It can image boundaries of structures but cannot visualize individual cells.

There are different types of OCT devices available, including frequency-domain OCT (FD-OCT), or conventional OCT, and high-definition OCT (HD-OCT). With FD-OCT, images are captured at a maximum depth of 1 to 2 mm but with limited resolution. High-definition OCT has superior resolution compared to FD-OCT but is restricted to a shallower depth of 750 μm.³⁹ The main advantage of OCT is the ability to noninvasively image live tissue and visualize 2- to 5-times greater depth as compared to RCM. Several OCT devices have obtained US Food and Drug Administration approval; however, OCT has not been widely adopted into clinical practice and is available only in tertiary academic centers. Additionally, OCT imaging in dermatology is rarely reimbursed. Other limitations of OCT include poor resolution of images, high cost to procure an OCT device, and the need for advanced training and experience to accurately interpret images.^40,41

Optical coherence tomography primarily is used to diagnose cutaneous neoplasms. The best evidence of the diagnostic accuracy of OCT is in the setting of BCC, with a recent systematic review reporting a sensitivity of 66% to 96% and a specificity of 75% to 86% for conventional FD-OCT.⁴² The use of FD-OCT results in an increase in specificity without a significant change in sensitivity when compared to dermoscopy in the diagnosis of BCC.⁴³ Melanoma is difficult to diagnose via FD-OCT, as the visualization of architectural features often is limited by poor resolution.⁴⁴ A study of HD-OCT in the diagnosis of melanoma with a limited sample size reported a sensitivity of 74% to 80% and a specificity of 92% to 93%.⁴⁵ Similarly, a study of HD-OCT used in the diagnosis of AK and SCC revealed a sensitivity and specificity of 81.6% and 92.6%, respectively, for AK and 93.8% and 98.9%, respectively, for SCC.⁴⁶

Numerous algorithms and scoring systems have been developed to further explore the utility of OCT in the diagnosis of cutaneous neoplasms.^47,48 Recent research investigated the utility of dynamic OCT, which can evaluate microvasculature in the diagnosis of cutaneous neoplasms (Figure 3)⁴⁹; the combination of OCT with other imaging modalities^50,51; the use of OCT to delineate presurgical margins^52,53; and the role of OCT in the diagnosis and monitoring of inflammatory and infectious skin diseases.^54,55

Final Thoughts

In recent years, there has been a surge of interest in noninvasive techniques for diagnosis and management of skin diseases; however, noninvasive tools exist on a spectrum in dermatology. Dermoscopy provides low-cost imaging of the skin’s surface and has been widely adopted by dermatologists and other providers to aid in clinical diagnosis. Reflectance confocal microscopy provides reimbursable in vivo imaging of live tissue with cellular-level resolution but is limited by depth, cost, and need for advanced training; thus, RCM has only been adopted in some clinical practices. Optical coherence tomography offers in vivo imaging of live tissue with substantial depth but poor resolution, high cost, need for advanced training, and rare reimbursement for providers. Future directions include combination of complementary imaging modalities, increased clinical practice integration, and education and reimbursement for providers.

Traditionally, diagnosis of skin disease relies on clinical inspection, often followed by biopsy and histopathologic examination. In recent years, new noninvasive tools have emerged that can aid in clinical diagnosis and reduce the number of unnecessary benign biopsies. Although there has been a surge in noninvasive diagnostic technologies, many tools are still in research and development phases, with few tools widely adopted and used in regular clinical practice. In this article, we discuss the use of dermoscopy, reflectance confocal microscopy (RCM), and optical coherence tomography (OCT) in the diagnosis and management of skin disease.

Dermoscopy

Dermoscopy, also known as epiluminescence light microscopy and previously known as dermatoscopy, utilizes a ×10 to ×100 microscope objective with a light source to magnify and visualize structures present below the skin’s surface, such as melanin and blood vessels. There are 3 types of dermoscopy: conventional nonpolarized dermoscopy, polarized contact dermoscopy, and nonpolarized contact dermoscopy (Figure 1). Traditional nonpolarized dermoscopy requires a liquid medium and direct contact with the skin, and it relies on light reflection and refraction properties.¹ Cross-polarized light sources allow visualization of deeper structures, either with or without a liquid medium and contact with the skin surface. Although there is overall concurrence among the different types of dermoscopy, subtle differences in the appearance of color, features, and structure are present.¹

Dermoscopy offers many benefits for dermatologists and other providers. It can be used to aid in the diagnosis of cutaneous neoplasms and other skin diseases. Numerous low-cost dermatoscopes currently are commercially available. The handheld, easily transportable nature of dermatoscopes have resulted in widespread practice integration. Approximately 84% of attending dermatologists in US academic settings reported using dermoscopy, and many refer to the dermatoscope as “the dermatologist’s stethoscope.”² In addition, 6% to 15% of other US providers, including family physicians, internal medicine physicians, and plastic surgeons, have reported using dermoscopy in their clinical practices. Limitations of dermoscopy include visualization of the skin surface only and not deeper structures within the tissue, the need for training for adequate interpretation of dermoscopic images, and lack of reimbursement for dermoscopic examination.³

Many dermoscopic structures that correspond well with histopathology have been described. Dermoscopy has a sensitivity of 79% to 96% and specificity of 69% to 99% in the diagnosis of melanoma.⁴ There is variable data on the specificity of dermoscopy in the diagnosis of melanoma, with one meta-analysis finding no statistically significant difference in specificity compared to naked eye examination,⁵ while other studies report increased specificity and subsequent reduction in biopsy of benign lesions.^6,7 Dermoscopy also can aid in the diagnosis of keratinocytic neoplasms, and dermoscopy also results in a sensitivity of 78.6% to 100% and a specificity of 53.8% to 100% in the diagnosis of basal cell carcinoma (BCC).⁸ Limitations of dermoscopy include false-positive diagnoses, commonly seborrheic keratoses and nevi, resulting in unnecessary biopsies, as well as false-negative diagnoses, commonly amelanotic and nevoid melanoma, resulting in delays in skin cancer diagnosis and resultant poor outcomes.⁹ Dermoscopy also is used to aid in the diagnosis of inflammatory and infectious skin diseases, as well as scalp, hair, and nail disorders.¹⁰

Reflectance Confocal Microscopy

Reflectance confocal microscopy utilizes an 830-nm laser to capture horizontal en face images of the skin with high resolution. Different structures of the skin have varying indices of refraction: keratin, melanin, and collagen appear bright white, while other components appear dark, generating black-and-white RCM images.¹¹ Currently, there are 2 reflectance confocal microscopes that are commercially available in the United States. The Vivascope 1500 (Caliber ID) is the traditional model that captures 8×8-mm images, and the Vivascope 3000 (Caliber ID) is a smaller handheld model that captures 0.5×0.5-mm images. The traditional model provides the advantages of higher-resolution images and the ability to capture larger surface areas but is best suited to image flat areas of skin to which a square window can be adhered. The handheld model allows improved contact with the varying topography of skin; does not require an adhesive window; and can be used to image cartilaginous, mucosal, and sensitive surfaces. However, it can be difficult to correlate individual images captured by the handheld RCM with the location relative to the lesion, as it is exquisitely sensitive to motion and also is operator dependent. Although complex algorithms are under development to stitch individual images to provide better correlation with the geography of the lesion, such programs are not yet widely available.¹²

Reflectance confocal microscopy affords many benefits for patients and providers. It is noninvasive and painless and is capable of imaging in vivo live skin as compared to clinical examination and dermoscopy, which only allow for visualization of the skin’s surface. Reflectance confocal microscopy also is time efficient, as imaging of a single lesion can be completed in 10 to 15 minutes. This technology generates high-resolution images, and RCM diagnosis has consistently demonstrated high sensitivity and specificity when compared to histopathology.¹³ Additionally, RCM imaging can spare biopsy and resultant scarring on cosmetically sensitive areas. Recently, RCM imaging of the skin has been granted Category I Current Procedural Terminology reimbursement codes that allow provider reimbursement and integration of RCM into daily practice¹⁴; however, private insurance coverage in the United States is variable. Limitations of RCM include a maximum depth of 200 to 300 µm, high cost to procure a reflectance confocal microscope, and the need for considerable training and practice to accurately interpret grayscale en face images.¹⁵

There has been extensive research regarding the use of RCM in the evaluation of cutaneous neoplasms and other skin diseases. Numerous features and patterns have been identified and described that correspond with different skin diseases and correspond well with histopathology (Figure 2).^13,16,17 Reflectance confocal microscopy has demonstrated consistently high accuracy in the diagnosis of melanocytic lesions, with a sensitivity of 93% to 100% and a specificity of 75% to 99%.^18-21 Reflectance confocal microscopy is especially useful in the evaluation of clinically or dermoscopically equivocal pigmented lesions due to greater specificity, resulting in a reduction of unnecessary biopsies.^22,23 It also has high accuracy in the diagnosis of keratinocytic neoplasms, with a sensitivity of 82% to 100% and a specificity of 78% to 97% in the diagnosis of BCC,²⁴ and a sensitivity of 74% to 100% and specificity of 78% to 100% in the diagnosis of squamous cell carcinoma (SCC).^25,26 Evaluation of SCC and actinic keratosis (AK) using RCM may be limited by considerable hyperkeratosis and ulceration. In addition, it can be challenging to differentiate AK and SCC on RCM, and considerable expertise is required to accurately grade cytologic and architectural atypia.²⁷ However, RCM has been used to discriminate between in situ and invasive proliferations.²⁸ Reflectance confocal microscopy has wide applications in the diagnosis and management of cutaneous infections^29,30 and inflammatory skin diseases.^29,31-33 Recent RCM research explored the use of RCM to identify biopsy sites,³⁴ delineate presurgical tumor margins,^35,36 and monitor response to noninvasive treatments.^37,38

Optical Coherence Tomography

Optical coherence tomography is an imaging modality that utilizes light backscatter from infrared light to produce grayscale cross-sectional or vertical images and horizontal en face images.³⁹ Optical coherence tomography can visualize structures in the epidermis, dermoepidermal junction, and upper dermis.⁴⁰ It can image boundaries of structures but cannot visualize individual cells.

There are different types of OCT devices available, including frequency-domain OCT (FD-OCT), or conventional OCT, and high-definition OCT (HD-OCT). With FD-OCT, images are captured at a maximum depth of 1 to 2 mm but with limited resolution. High-definition OCT has superior resolution compared to FD-OCT but is restricted to a shallower depth of 750 μm.³⁹ The main advantage of OCT is the ability to noninvasively image live tissue and visualize 2- to 5-times greater depth as compared to RCM. Several OCT devices have obtained US Food and Drug Administration approval; however, OCT has not been widely adopted into clinical practice and is available only in tertiary academic centers. Additionally, OCT imaging in dermatology is rarely reimbursed. Other limitations of OCT include poor resolution of images, high cost to procure an OCT device, and the need for advanced training and experience to accurately interpret images.^40,41

Optical coherence tomography primarily is used to diagnose cutaneous neoplasms. The best evidence of the diagnostic accuracy of OCT is in the setting of BCC, with a recent systematic review reporting a sensitivity of 66% to 96% and a specificity of 75% to 86% for conventional FD-OCT.⁴² The use of FD-OCT results in an increase in specificity without a significant change in sensitivity when compared to dermoscopy in the diagnosis of BCC.⁴³ Melanoma is difficult to diagnose via FD-OCT, as the visualization of architectural features often is limited by poor resolution.⁴⁴ A study of HD-OCT in the diagnosis of melanoma with a limited sample size reported a sensitivity of 74% to 80% and a specificity of 92% to 93%.⁴⁵ Similarly, a study of HD-OCT used in the diagnosis of AK and SCC revealed a sensitivity and specificity of 81.6% and 92.6%, respectively, for AK and 93.8% and 98.9%, respectively, for SCC.⁴⁶

Numerous algorithms and scoring systems have been developed to further explore the utility of OCT in the diagnosis of cutaneous neoplasms.^47,48 Recent research investigated the utility of dynamic OCT, which can evaluate microvasculature in the diagnosis of cutaneous neoplasms (Figure 3)⁴⁹; the combination of OCT with other imaging modalities^50,51; the use of OCT to delineate presurgical margins^52,53; and the role of OCT in the diagnosis and monitoring of inflammatory and infectious skin diseases.^54,55

Final Thoughts

In recent years, there has been a surge of interest in noninvasive techniques for diagnosis and management of skin diseases; however, noninvasive tools exist on a spectrum in dermatology. Dermoscopy provides low-cost imaging of the skin’s surface and has been widely adopted by dermatologists and other providers to aid in clinical diagnosis. Reflectance confocal microscopy provides reimbursable in vivo imaging of live tissue with cellular-level resolution but is limited by depth, cost, and need for advanced training; thus, RCM has only been adopted in some clinical practices. Optical coherence tomography offers in vivo imaging of live tissue with substantial depth but poor resolution, high cost, need for advanced training, and rare reimbursement for providers. Future directions include combination of complementary imaging modalities, increased clinical practice integration, and education and reimbursement for providers.

NEW YORK – Sunscreens remain the front-line strategy for preventing skin cancers of all types, but there is a growing array of chemopreventive agents for keratinocyte carcinomas (KCs) that deserves to be considered for selective use in at-risk patients, according to an update at the American Academy of Dermatology summer meeting.

In providing her perspective on the available options, Rebecca Hartman, MD, MPH, director of melanoma epidemiology at Brigham and Women’s Hospital, Boston, emphasized that the therapies are not interchangeable but deserve to be used selectively according to their relative protection and relative risks.

Of oral agents, she characterized two, nicotinamide and acitretin, as “clinic-ready.” Acitretin is “an oldie but goodie,” but there is an important issue of tolerability. In the published studies, 15%-39% of patients withdrew because of adverse events, according to Dr. Hartman, which suggests the need for a motivated patient.

In addition, acitretin can be esterified into etretinate, a teratogen that can persist as long as 3 years after the drug is discontinued, making this drug contraindicated in women of childbearing potential, she noted.

However, most patients in need of prophylaxis for KCs are older, so teratogenicity is not an issue. In her practice, she offers acitretin to patients who are developing three or more KCs per year, as well as in situations of extensive skin damage in which a course of acitretin might provide some degree of clearing.

“When you are faced with the potential of a large number of biopsies, you could start acitretin to see if lesions can be reduced,” Dr. Hartman said .

Prevention of KCs became somewhat more attractive as a routine practice following publication of a phase 3 trial with nicotinamide. In this study, nicotinamide, an over-the-counter water-soluble form of vitamin B3, was associated with significantly reduced nonmelanoma skin cancers, including KCs and actinic keratoses, relative to placebo (N Engl J Med. 2015 Oct 22;373[17]:1618-26). Importantly, there was no greater risk of adverse events relative to placebo.

When assessed individually, the relative reduction in squamous cell carcinomas (SCCs; P = .05) and basal cell carcinomas (P = .12) fell short of statistical significance, but there was a highly significant 13% reduction in actinic keratoses after 12 months (P less than .001). An increase in SCCs was observed after therapy was stopped, which led Dr. Hartman to conclude that nicotinamide must be used on a “use-it-or-lose-it” basis. However, she does routinely offer this option.

“When do I recommend nicotinamide? Any patient with multiple actinic keratoses who wants to get ahead of the game and wants something that is relative safe,” Dr. Hartman explained. She uses the same dosing employed in the study, which was 500 mg twice daily.

There are other options for chemoprevention of KCs, but they are less attractive.

For example, capecitabine is effective, but tolerability is an even greater issue with this agent than it is for acitretin. According to Dr. Hartman, “we use this therapy very rarely and only in select cases.” As an alternative to the 14 days on and 7 days off schedule used for treatment of cancer, capecitabine is sometimes better tolerated in a 7 day on and 7 day off schedule, she said.

Topical 5-fluorouracil with or without calcipotriol is another chemoprevention option for those who can tolerate a skin reaction that lasts several days, Dr. Hartman said. She cited one study that associated this therapy with a nearly 80% reduction in face and scalp SCC.

Ultimately, she offers 5-fluorouracil with or without calcipotriol to “patients who want an evidence-based chemoprevention,” but she indicated that patients must be motivated to endure the adverse effects.

Many remain unaware of the array of options for chemoprevention of KCs, but Dr. Hartman emphasized that this is an area of active research with new options expected.

“I am really excited about the future direction of chemoprevention in skin cancer,” said Dr. Hartman, citing ongoing work to develop vitamin A, polypodium leucotomas extract, and human papillomavirus vaccine as options.

“If we can stop skin cancer in the first place, avoiding the morbidity and mortality of treatment, we will also hopefully save costs as well,” she commented. So far, essentially all of the strategies for chemoprevention, other than sunscreen, involve KCs, which leaves a large unmet need for better ways to prevent melanoma. However, Dr. Hartman noted that KCs represent the most common type of cancer of any type.

Just days after Dr. Hartman spoke at the meeting, a prospective study of vitamin A that found an inverse association between vitamin A intake and cutaneous SCC risk was, in fact, published in JAMA Dermatology (2019 Jul 31. doi: 10.1001/jamadermatol.2019.1937).

Dr. Hartman reported no financial relationships relevant to her presentation.

 

NEW YORK – Sunscreens remain the front-line strategy for preventing skin cancers of all types, but there is a growing array of chemopreventive agents for keratinocyte carcinomas (KCs) that deserves to be considered for selective use in at-risk patients, according to an update at the American Academy of Dermatology summer meeting.

In providing her perspective on the available options, Rebecca Hartman, MD, MPH, director of melanoma epidemiology at Brigham and Women’s Hospital, Boston, emphasized that the therapies are not interchangeable but deserve to be used selectively according to their relative protection and relative risks.

Of oral agents, she characterized two, nicotinamide and acitretin, as “clinic-ready.” Acitretin is “an oldie but goodie,” but there is an important issue of tolerability. In the published studies, 15%-39% of patients withdrew because of adverse events, according to Dr. Hartman, which suggests the need for a motivated patient.

In addition, acitretin can be esterified into etretinate, a teratogen that can persist as long as 3 years after the drug is discontinued, making this drug contraindicated in women of childbearing potential, she noted.

However, most patients in need of prophylaxis for KCs are older, so teratogenicity is not an issue. In her practice, she offers acitretin to patients who are developing three or more KCs per year, as well as in situations of extensive skin damage in which a course of acitretin might provide some degree of clearing.

“When you are faced with the potential of a large number of biopsies, you could start acitretin to see if lesions can be reduced,” Dr. Hartman said .

Prevention of KCs became somewhat more attractive as a routine practice following publication of a phase 3 trial with nicotinamide. In this study, nicotinamide, an over-the-counter water-soluble form of vitamin B3, was associated with significantly reduced nonmelanoma skin cancers, including KCs and actinic keratoses, relative to placebo (N Engl J Med. 2015 Oct 22;373[17]:1618-26). Importantly, there was no greater risk of adverse events relative to placebo.

When assessed individually, the relative reduction in squamous cell carcinomas (SCCs; P = .05) and basal cell carcinomas (P = .12) fell short of statistical significance, but there was a highly significant 13% reduction in actinic keratoses after 12 months (P less than .001). An increase in SCCs was observed after therapy was stopped, which led Dr. Hartman to conclude that nicotinamide must be used on a “use-it-or-lose-it” basis. However, she does routinely offer this option.

“When do I recommend nicotinamide? Any patient with multiple actinic keratoses who wants to get ahead of the game and wants something that is relative safe,” Dr. Hartman explained. She uses the same dosing employed in the study, which was 500 mg twice daily.

There are other options for chemoprevention of KCs, but they are less attractive.

For example, capecitabine is effective, but tolerability is an even greater issue with this agent than it is for acitretin. According to Dr. Hartman, “we use this therapy very rarely and only in select cases.” As an alternative to the 14 days on and 7 days off schedule used for treatment of cancer, capecitabine is sometimes better tolerated in a 7 day on and 7 day off schedule, she said.

Topical 5-fluorouracil with or without calcipotriol is another chemoprevention option for those who can tolerate a skin reaction that lasts several days, Dr. Hartman said. She cited one study that associated this therapy with a nearly 80% reduction in face and scalp SCC.

Ultimately, she offers 5-fluorouracil with or without calcipotriol to “patients who want an evidence-based chemoprevention,” but she indicated that patients must be motivated to endure the adverse effects.

Many remain unaware of the array of options for chemoprevention of KCs, but Dr. Hartman emphasized that this is an area of active research with new options expected.

“I am really excited about the future direction of chemoprevention in skin cancer,” said Dr. Hartman, citing ongoing work to develop vitamin A, polypodium leucotomas extract, and human papillomavirus vaccine as options.

“If we can stop skin cancer in the first place, avoiding the morbidity and mortality of treatment, we will also hopefully save costs as well,” she commented. So far, essentially all of the strategies for chemoprevention, other than sunscreen, involve KCs, which leaves a large unmet need for better ways to prevent melanoma. However, Dr. Hartman noted that KCs represent the most common type of cancer of any type.

Just days after Dr. Hartman spoke at the meeting, a prospective study of vitamin A that found an inverse association between vitamin A intake and cutaneous SCC risk was, in fact, published in JAMA Dermatology (2019 Jul 31. doi: 10.1001/jamadermatol.2019.1937).

Dr. Hartman reported no financial relationships relevant to her presentation.

 

NEW YORK – Sunscreens remain the front-line strategy for preventing skin cancers of all types, but there is a growing array of chemopreventive agents for keratinocyte carcinomas (KCs) that deserves to be considered for selective use in at-risk patients, according to an update at the American Academy of Dermatology summer meeting.

In providing her perspective on the available options, Rebecca Hartman, MD, MPH, director of melanoma epidemiology at Brigham and Women’s Hospital, Boston, emphasized that the therapies are not interchangeable but deserve to be used selectively according to their relative protection and relative risks.

Of oral agents, she characterized two, nicotinamide and acitretin, as “clinic-ready.” Acitretin is “an oldie but goodie,” but there is an important issue of tolerability. In the published studies, 15%-39% of patients withdrew because of adverse events, according to Dr. Hartman, which suggests the need for a motivated patient.

In addition, acitretin can be esterified into etretinate, a teratogen that can persist as long as 3 years after the drug is discontinued, making this drug contraindicated in women of childbearing potential, she noted.

However, most patients in need of prophylaxis for KCs are older, so teratogenicity is not an issue. In her practice, she offers acitretin to patients who are developing three or more KCs per year, as well as in situations of extensive skin damage in which a course of acitretin might provide some degree of clearing.

“When you are faced with the potential of a large number of biopsies, you could start acitretin to see if lesions can be reduced,” Dr. Hartman said .

Prevention of KCs became somewhat more attractive as a routine practice following publication of a phase 3 trial with nicotinamide. In this study, nicotinamide, an over-the-counter water-soluble form of vitamin B3, was associated with significantly reduced nonmelanoma skin cancers, including KCs and actinic keratoses, relative to placebo (N Engl J Med. 2015 Oct 22;373[17]:1618-26). Importantly, there was no greater risk of adverse events relative to placebo.

When assessed individually, the relative reduction in squamous cell carcinomas (SCCs; P = .05) and basal cell carcinomas (P = .12) fell short of statistical significance, but there was a highly significant 13% reduction in actinic keratoses after 12 months (P less than .001). An increase in SCCs was observed after therapy was stopped, which led Dr. Hartman to conclude that nicotinamide must be used on a “use-it-or-lose-it” basis. However, she does routinely offer this option.

“When do I recommend nicotinamide? Any patient with multiple actinic keratoses who wants to get ahead of the game and wants something that is relative safe,” Dr. Hartman explained. She uses the same dosing employed in the study, which was 500 mg twice daily.

There are other options for chemoprevention of KCs, but they are less attractive.

For example, capecitabine is effective, but tolerability is an even greater issue with this agent than it is for acitretin. According to Dr. Hartman, “we use this therapy very rarely and only in select cases.” As an alternative to the 14 days on and 7 days off schedule used for treatment of cancer, capecitabine is sometimes better tolerated in a 7 day on and 7 day off schedule, she said.

Topical 5-fluorouracil with or without calcipotriol is another chemoprevention option for those who can tolerate a skin reaction that lasts several days, Dr. Hartman said. She cited one study that associated this therapy with a nearly 80% reduction in face and scalp SCC.

Ultimately, she offers 5-fluorouracil with or without calcipotriol to “patients who want an evidence-based chemoprevention,” but she indicated that patients must be motivated to endure the adverse effects.

Many remain unaware of the array of options for chemoprevention of KCs, but Dr. Hartman emphasized that this is an area of active research with new options expected.

“I am really excited about the future direction of chemoprevention in skin cancer,” said Dr. Hartman, citing ongoing work to develop vitamin A, polypodium leucotomas extract, and human papillomavirus vaccine as options.

“If we can stop skin cancer in the first place, avoiding the morbidity and mortality of treatment, we will also hopefully save costs as well,” she commented. So far, essentially all of the strategies for chemoprevention, other than sunscreen, involve KCs, which leaves a large unmet need for better ways to prevent melanoma. However, Dr. Hartman noted that KCs represent the most common type of cancer of any type.

Just days after Dr. Hartman spoke at the meeting, a prospective study of vitamin A that found an inverse association between vitamin A intake and cutaneous SCC risk was, in fact, published in JAMA Dermatology (2019 Jul 31. doi: 10.1001/jamadermatol.2019.1937).

Dr. Hartman reported no financial relationships relevant to her presentation.

 

Higher intake of dietary vitamin A was associated with a reduced risk of cutaneous squamous cell carcinoma (SCC), in a large prospective study published in JAMA Dermatology.

There was also an inverse association between intake of carotenoids and risk of cutaneous SCC over the follow-up period of 26-28 years. The results of the study support “the protective role of vitamin A against SCC development,” wrote Jongwoo Kim, MD, of Brown University, Providence, R.I., and Inje University, Seoul, South Korea, and coauthors. “Our data further support the contention that supplemental and dietary vitamin A may be beneficial in preventing SCC,” they added.

The study evaluated intake of vitamin A and carotenoids and SCC risk with data from the Health Professionals Follow-Up Study (1986-2012) of 48,400 men, and the Nurses’ Health Study (1984-2012) of 75,170 women. Participants in those studies completed questionnaires based on lifestyle and medical history. Only white participants were included, because of the low number of SCC cases and low SCC risk in nonwhite participants, and participants who did not report diet and those who had a history of melanoma, SCC, or other cancer diagnoses at baseline were excluded.

Over the follow-up of 26-28 years, a total of 3,978 SCC cases were confirmed using pathological records. The investigators used different quintiles based on the median total amount of vitamin A intake. Using quintile 1 (lowest intake) as a reference, the pooled multivariate hazard ratios of vitamin A intake were 0.97, 0.97, 0.93, and 0.83 for quintiles 2, 3, 4, and 5, respectively (P less than .001 for the trend, in order of increasing quintiles).

In addition, they reported that greater intakes of retinol and several carotenoids were also significantly associated with a lower SCC risk.

The results were “generally consistent between men and women,” and “the inverse associations appeared to be more prominent among those with moles and those with burn or blistering sunburn reaction as children or adolescents,” they wrote.

The large sample size, prospective design, and confirmation of SCC cases by histology are among the strengths of the study, while a key limitation of the study was the homogeneous nature of the study population, which “may limit the generalizability of our findings,” the authors wrote.

The study was funded by the National Institutes of Health and Inje University (South Korea). One author reported serving as a consultant for AbbVie, Amgen, the Centers for Disease Control and Prevention, Janssen, Merck, Novartis, and Pfizer; and as a compensated investigator for Amgen, Regeneron, and Sanofi. Dr. Kim and the remaining three authors reported no disclosures.

SOURCE: Kim J et al. JAMA Dermatol. 2019 Jul 31. doi: 10.1001/jamadermatol.2019.1937.


 

Higher intake of dietary vitamin A was associated with a reduced risk of cutaneous squamous cell carcinoma (SCC), in a large prospective study published in JAMA Dermatology.

There was also an inverse association between intake of carotenoids and risk of cutaneous SCC over the follow-up period of 26-28 years. The results of the study support “the protective role of vitamin A against SCC development,” wrote Jongwoo Kim, MD, of Brown University, Providence, R.I., and Inje University, Seoul, South Korea, and coauthors. “Our data further support the contention that supplemental and dietary vitamin A may be beneficial in preventing SCC,” they added.

The study evaluated intake of vitamin A and carotenoids and SCC risk with data from the Health Professionals Follow-Up Study (1986-2012) of 48,400 men, and the Nurses’ Health Study (1984-2012) of 75,170 women. Participants in those studies completed questionnaires based on lifestyle and medical history. Only white participants were included, because of the low number of SCC cases and low SCC risk in nonwhite participants, and participants who did not report diet and those who had a history of melanoma, SCC, or other cancer diagnoses at baseline were excluded.

Over the follow-up of 26-28 years, a total of 3,978 SCC cases were confirmed using pathological records. The investigators used different quintiles based on the median total amount of vitamin A intake. Using quintile 1 (lowest intake) as a reference, the pooled multivariate hazard ratios of vitamin A intake were 0.97, 0.97, 0.93, and 0.83 for quintiles 2, 3, 4, and 5, respectively (P less than .001 for the trend, in order of increasing quintiles).

In addition, they reported that greater intakes of retinol and several carotenoids were also significantly associated with a lower SCC risk.

The results were “generally consistent between men and women,” and “the inverse associations appeared to be more prominent among those with moles and those with burn or blistering sunburn reaction as children or adolescents,” they wrote.

The large sample size, prospective design, and confirmation of SCC cases by histology are among the strengths of the study, while a key limitation of the study was the homogeneous nature of the study population, which “may limit the generalizability of our findings,” the authors wrote.

The study was funded by the National Institutes of Health and Inje University (South Korea). One author reported serving as a consultant for AbbVie, Amgen, the Centers for Disease Control and Prevention, Janssen, Merck, Novartis, and Pfizer; and as a compensated investigator for Amgen, Regeneron, and Sanofi. Dr. Kim and the remaining three authors reported no disclosures.

SOURCE: Kim J et al. JAMA Dermatol. 2019 Jul 31. doi: 10.1001/jamadermatol.2019.1937.


 

Higher intake of dietary vitamin A was associated with a reduced risk of cutaneous squamous cell carcinoma (SCC), in a large prospective study published in JAMA Dermatology.

There was also an inverse association between intake of carotenoids and risk of cutaneous SCC over the follow-up period of 26-28 years. The results of the study support “the protective role of vitamin A against SCC development,” wrote Jongwoo Kim, MD, of Brown University, Providence, R.I., and Inje University, Seoul, South Korea, and coauthors. “Our data further support the contention that supplemental and dietary vitamin A may be beneficial in preventing SCC,” they added.

The study evaluated intake of vitamin A and carotenoids and SCC risk with data from the Health Professionals Follow-Up Study (1986-2012) of 48,400 men, and the Nurses’ Health Study (1984-2012) of 75,170 women. Participants in those studies completed questionnaires based on lifestyle and medical history. Only white participants were included, because of the low number of SCC cases and low SCC risk in nonwhite participants, and participants who did not report diet and those who had a history of melanoma, SCC, or other cancer diagnoses at baseline were excluded.

Over the follow-up of 26-28 years, a total of 3,978 SCC cases were confirmed using pathological records. The investigators used different quintiles based on the median total amount of vitamin A intake. Using quintile 1 (lowest intake) as a reference, the pooled multivariate hazard ratios of vitamin A intake were 0.97, 0.97, 0.93, and 0.83 for quintiles 2, 3, 4, and 5, respectively (P less than .001 for the trend, in order of increasing quintiles).

In addition, they reported that greater intakes of retinol and several carotenoids were also significantly associated with a lower SCC risk.

The results were “generally consistent between men and women,” and “the inverse associations appeared to be more prominent among those with moles and those with burn or blistering sunburn reaction as children or adolescents,” they wrote.

The large sample size, prospective design, and confirmation of SCC cases by histology are among the strengths of the study, while a key limitation of the study was the homogeneous nature of the study population, which “may limit the generalizability of our findings,” the authors wrote.

The study was funded by the National Institutes of Health and Inje University (South Korea). One author reported serving as a consultant for AbbVie, Amgen, the Centers for Disease Control and Prevention, Janssen, Merck, Novartis, and Pfizer; and as a compensated investigator for Amgen, Regeneron, and Sanofi. Dr. Kim and the remaining three authors reported no disclosures.

SOURCE: Kim J et al. JAMA Dermatol. 2019 Jul 31. doi: 10.1001/jamadermatol.2019.1937.


 

To the Editor:

A 34-year-old woman with a history of adamantinoma of the right tibia that had been surgically resected with tibial reconstruction 5 years prior presented with a mildly tender, enlarging lesion on the right distal shin of 6 months’ duration that had started to change color. Review of systems was otherwise negative. Physical examination revealed an 8-mm, slightly tender, rubbery, pink papule adjacent to the surgical scar over the right tibia (Figure 1). Given the rapid growth of the lesion and its proximity to the surgical site, a punch biopsy was performed.

Histopathologic examination demonstrated a densely cellular dermal tumor composed of spindle cells with large hyperchromatic nuclei, numerous mitotic figures, and minimal eosinophilic cytoplasm (Figure 2A). Immunohistochemical studies revealed that approximately 40% of the tumor nuclei were immunoreactive to Ki-67 (Figure 2B), and total cytokeratin was focally positive (Figure 2C). A diagnosis of metastatic adamantinoma was made. Positron emission tomography and magnetic resonance imaging revealed new lytic lesions involving the T10 and L2 vertebrae (without frank spinal cord compression) and the right superior sacrum. Additionally, a small pulmonary nodule on the left upper lobe was noted on positron emission tomography, but it was below the size threshold for reliable detection. A computed tomography–guided biopsy of the T10 lesion demonstrated metastatic adamantinoma. The patient underwent a spinal stabilization procedure and discussed options regarding further oncologic and palliative management.

Adamantinomas are slow growing, and as a result, patients often present with gradual onset of pain and swelling that persists for years.^3,4 Metastasis occurs in 10% to 30% of patients, typically located in regional lymph nodes, the lungs, and distant bone.^1,4 Our case represents a rare instance of adamantinoma metastasis to the skin. Although primary adamantinomas consist of both epithelial and stromal components, the typical metastatic lesions of adamantinomas are solely epithelial (often in a spindle-cell pattern),¹ as was seen in our patient.

Operative removal via amputation or en bloc resection with limb salvage is the current treatment of choice. Adamantinomas are highly radioresistant, and chemotherapy has shown minimal efficacy.^3,5

In conclusion, the presence of cutaneous metastasis from an adamantinoma is rare. Our case emphasizes this tumor’s potential for late metastasis as well as late recurrence.^3,6 Most importantly, dermatologists should be made aware of this rare bone tumor and its unusual presentation, as early detection can aid in prognosis.

To the Editor:

A 34-year-old woman with a history of adamantinoma of the right tibia that had been surgically resected with tibial reconstruction 5 years prior presented with a mildly tender, enlarging lesion on the right distal shin of 6 months’ duration that had started to change color. Review of systems was otherwise negative. Physical examination revealed an 8-mm, slightly tender, rubbery, pink papule adjacent to the surgical scar over the right tibia (Figure 1). Given the rapid growth of the lesion and its proximity to the surgical site, a punch biopsy was performed.

Histopathologic examination demonstrated a densely cellular dermal tumor composed of spindle cells with large hyperchromatic nuclei, numerous mitotic figures, and minimal eosinophilic cytoplasm (Figure 2A). Immunohistochemical studies revealed that approximately 40% of the tumor nuclei were immunoreactive to Ki-67 (Figure 2B), and total cytokeratin was focally positive (Figure 2C). A diagnosis of metastatic adamantinoma was made. Positron emission tomography and magnetic resonance imaging revealed new lytic lesions involving the T10 and L2 vertebrae (without frank spinal cord compression) and the right superior sacrum. Additionally, a small pulmonary nodule on the left upper lobe was noted on positron emission tomography, but it was below the size threshold for reliable detection. A computed tomography–guided biopsy of the T10 lesion demonstrated metastatic adamantinoma. The patient underwent a spinal stabilization procedure and discussed options regarding further oncologic and palliative management.

Adamantinomas are slow growing, and as a result, patients often present with gradual onset of pain and swelling that persists for years.^3,4 Metastasis occurs in 10% to 30% of patients, typically located in regional lymph nodes, the lungs, and distant bone.^1,4 Our case represents a rare instance of adamantinoma metastasis to the skin. Although primary adamantinomas consist of both epithelial and stromal components, the typical metastatic lesions of adamantinomas are solely epithelial (often in a spindle-cell pattern),¹ as was seen in our patient.

Operative removal via amputation or en bloc resection with limb salvage is the current treatment of choice. Adamantinomas are highly radioresistant, and chemotherapy has shown minimal efficacy.^3,5

In conclusion, the presence of cutaneous metastasis from an adamantinoma is rare. Our case emphasizes this tumor’s potential for late metastasis as well as late recurrence.^3,6 Most importantly, dermatologists should be made aware of this rare bone tumor and its unusual presentation, as early detection can aid in prognosis.

To the Editor:

A 34-year-old woman with a history of adamantinoma of the right tibia that had been surgically resected with tibial reconstruction 5 years prior presented with a mildly tender, enlarging lesion on the right distal shin of 6 months’ duration that had started to change color. Review of systems was otherwise negative. Physical examination revealed an 8-mm, slightly tender, rubbery, pink papule adjacent to the surgical scar over the right tibia (Figure 1). Given the rapid growth of the lesion and its proximity to the surgical site, a punch biopsy was performed.

Histopathologic examination demonstrated a densely cellular dermal tumor composed of spindle cells with large hyperchromatic nuclei, numerous mitotic figures, and minimal eosinophilic cytoplasm (Figure 2A). Immunohistochemical studies revealed that approximately 40% of the tumor nuclei were immunoreactive to Ki-67 (Figure 2B), and total cytokeratin was focally positive (Figure 2C). A diagnosis of metastatic adamantinoma was made. Positron emission tomography and magnetic resonance imaging revealed new lytic lesions involving the T10 and L2 vertebrae (without frank spinal cord compression) and the right superior sacrum. Additionally, a small pulmonary nodule on the left upper lobe was noted on positron emission tomography, but it was below the size threshold for reliable detection. A computed tomography–guided biopsy of the T10 lesion demonstrated metastatic adamantinoma. The patient underwent a spinal stabilization procedure and discussed options regarding further oncologic and palliative management.

Adamantinomas are slow growing, and as a result, patients often present with gradual onset of pain and swelling that persists for years.^3,4 Metastasis occurs in 10% to 30% of patients, typically located in regional lymph nodes, the lungs, and distant bone.^1,4 Our case represents a rare instance of adamantinoma metastasis to the skin. Although primary adamantinomas consist of both epithelial and stromal components, the typical metastatic lesions of adamantinomas are solely epithelial (often in a spindle-cell pattern),¹ as was seen in our patient.

Operative removal via amputation or en bloc resection with limb salvage is the current treatment of choice. Adamantinomas are highly radioresistant, and chemotherapy has shown minimal efficacy.^3,5

In conclusion, the presence of cutaneous metastasis from an adamantinoma is rare. Our case emphasizes this tumor’s potential for late metastasis as well as late recurrence.^3,6 Most importantly, dermatologists should be made aware of this rare bone tumor and its unusual presentation, as early detection can aid in prognosis.