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Extramammary Paget Disease: Making the Correct Diagnosis

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Registry data provide evidence that Mohs surgery remains underutilized

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– Analysis of U.S. national cancer registry data shows that, contrary to expectation, the use of Mohs micrographic surgery for treatment of melanoma in situ did not increase following adoption of the Affordable Care Act, Sean Condon, MD, reported at the annual meeting of the American College of Mohs Surgery.

Ditto for the use of Mohs in patients with the rare cutaneous malignancies for which published evidence clearly demonstrates Mohs outperforms wide local excision, which is employed seven times more frequently than Mohs in such situations.

Bruce Jancin/MDedge News
Dr. Sean Condon


“Mohs utilization did not increase after the Affordable Care Act [ACA], despite new health insurance coverage for 20 million previously uninsured adults,” Dr. Condon said. “Surprisingly, after the ACA we actually saw a decrease in Mohs use for melanoma in situ.”

Indeed, his retrospective study of more than 25,000 patients in the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registries showed that the proportion of patients with melanoma in situ treated with Mohs declined from 13.9% during 2008-2009 – prior to ACA implementation – to 12.3% in 2011-2013, after the ACA took effect. That’s a statistically significant 13% drop, even though numerous published studies have shown outcomes in melanoma in situ are better with Mohs, said the dermatologist, who conducted the study while completing a Mohs surgery fellowship at the Cleveland Clinic. He is now in private practice in Thousand Oaks, Calif.

His analysis included 19,013 patients treated in 2008-2014 for melanoma in situ and 6,309 others treated for rare cutaneous malignancies deemed appropriate for Mohs according to the criteria formally developed jointly by the American Academy of Dermatology, the American College of Mohs Surgery, the American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery (J Am Acad Dermatol. 2012 Oct;67[4]:531-50). These rare malignancies include adnexal carcinoma, Merkel cell carcinoma, dermatofibrosarcoma, extramammary Paget disease, sebaceous adenocarcinoma, and leiomyosarcoma.



“These rare cutaneous malignancies were historically treated with wide local excision. However, numerous studies have lately shown that lower recurrence rates were found with Mohs compared with wide local excision,” Dr. Condon noted.

Nonetheless, the proportion of the rare cutaneous malignancies treated using Mohs was unaffected by implementation of the ACA. Nor was it influenced one way or the other by publication of the joint Mohs appropriate use criteria in 2012: The Mohs-treated proportion of such cases was 15.25% in 2010-2011 and 14.6% in 2013-2014.

Similarly, even though the appropriate use criteria identified melanoma in situ as Mohs appropriate, the proportion of those malignancies treated via Mohs was the same before and after the 2012 release of the criteria.

“It’s commonly thought that Mohs is overused. However, our study and our data clearly identify that Mohs is being underutilized for melanoma in situ and for rare cutaneous malignancies. This represents a knowledge gap for other specialties regarding best-practice therapy,” Dr. Condon said.

He and his coinvestigators searched for socioeconomic predictors of Mohs utilization by matching the nationally representative SEER data with U.S. census data. They examined the impact of three metrics: insurance status, income, and poverty. They found that low-income patients and those in the highest quartile of poverty were significantly less likely to have Mohs surgery for their melanoma in situ and rare cutaneous malignancies throughout the study years. Lack of health insurance had no impact on Mohs utilization for melanoma in situ but was independently associated with decreased likelihood of Mohs for the rare cutaneous malignancies. White patients were 2-fold to 2.4-fold more likely to have Mohs surgery for their rare cutaneous malignancies than were black patients.

“One can conclude that Mohs micrographic surgery may be skewed toward more affluent patients, and lower socioeconomic status areas have less Mohs access. So our data from this study support a role for targeted education and improved patient access to Mohs,” Dr. Condon said.

He noted that because the SEER registries don’t track squamous or basal cell carcinomas, it’s unknown whether Mohs is also underutilized for the higher-risk forms of these most common of all skin cancers.

Dr. Condon reported having no financial conflicts regarding his study, conducted free of commercial support.

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– Analysis of U.S. national cancer registry data shows that, contrary to expectation, the use of Mohs micrographic surgery for treatment of melanoma in situ did not increase following adoption of the Affordable Care Act, Sean Condon, MD, reported at the annual meeting of the American College of Mohs Surgery.

Ditto for the use of Mohs in patients with the rare cutaneous malignancies for which published evidence clearly demonstrates Mohs outperforms wide local excision, which is employed seven times more frequently than Mohs in such situations.

Bruce Jancin/MDedge News
Dr. Sean Condon


“Mohs utilization did not increase after the Affordable Care Act [ACA], despite new health insurance coverage for 20 million previously uninsured adults,” Dr. Condon said. “Surprisingly, after the ACA we actually saw a decrease in Mohs use for melanoma in situ.”

Indeed, his retrospective study of more than 25,000 patients in the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registries showed that the proportion of patients with melanoma in situ treated with Mohs declined from 13.9% during 2008-2009 – prior to ACA implementation – to 12.3% in 2011-2013, after the ACA took effect. That’s a statistically significant 13% drop, even though numerous published studies have shown outcomes in melanoma in situ are better with Mohs, said the dermatologist, who conducted the study while completing a Mohs surgery fellowship at the Cleveland Clinic. He is now in private practice in Thousand Oaks, Calif.

His analysis included 19,013 patients treated in 2008-2014 for melanoma in situ and 6,309 others treated for rare cutaneous malignancies deemed appropriate for Mohs according to the criteria formally developed jointly by the American Academy of Dermatology, the American College of Mohs Surgery, the American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery (J Am Acad Dermatol. 2012 Oct;67[4]:531-50). These rare malignancies include adnexal carcinoma, Merkel cell carcinoma, dermatofibrosarcoma, extramammary Paget disease, sebaceous adenocarcinoma, and leiomyosarcoma.



“These rare cutaneous malignancies were historically treated with wide local excision. However, numerous studies have lately shown that lower recurrence rates were found with Mohs compared with wide local excision,” Dr. Condon noted.

Nonetheless, the proportion of the rare cutaneous malignancies treated using Mohs was unaffected by implementation of the ACA. Nor was it influenced one way or the other by publication of the joint Mohs appropriate use criteria in 2012: The Mohs-treated proportion of such cases was 15.25% in 2010-2011 and 14.6% in 2013-2014.

Similarly, even though the appropriate use criteria identified melanoma in situ as Mohs appropriate, the proportion of those malignancies treated via Mohs was the same before and after the 2012 release of the criteria.

“It’s commonly thought that Mohs is overused. However, our study and our data clearly identify that Mohs is being underutilized for melanoma in situ and for rare cutaneous malignancies. This represents a knowledge gap for other specialties regarding best-practice therapy,” Dr. Condon said.

He and his coinvestigators searched for socioeconomic predictors of Mohs utilization by matching the nationally representative SEER data with U.S. census data. They examined the impact of three metrics: insurance status, income, and poverty. They found that low-income patients and those in the highest quartile of poverty were significantly less likely to have Mohs surgery for their melanoma in situ and rare cutaneous malignancies throughout the study years. Lack of health insurance had no impact on Mohs utilization for melanoma in situ but was independently associated with decreased likelihood of Mohs for the rare cutaneous malignancies. White patients were 2-fold to 2.4-fold more likely to have Mohs surgery for their rare cutaneous malignancies than were black patients.

“One can conclude that Mohs micrographic surgery may be skewed toward more affluent patients, and lower socioeconomic status areas have less Mohs access. So our data from this study support a role for targeted education and improved patient access to Mohs,” Dr. Condon said.

He noted that because the SEER registries don’t track squamous or basal cell carcinomas, it’s unknown whether Mohs is also underutilized for the higher-risk forms of these most common of all skin cancers.

Dr. Condon reported having no financial conflicts regarding his study, conducted free of commercial support.

 

– Analysis of U.S. national cancer registry data shows that, contrary to expectation, the use of Mohs micrographic surgery for treatment of melanoma in situ did not increase following adoption of the Affordable Care Act, Sean Condon, MD, reported at the annual meeting of the American College of Mohs Surgery.

Ditto for the use of Mohs in patients with the rare cutaneous malignancies for which published evidence clearly demonstrates Mohs outperforms wide local excision, which is employed seven times more frequently than Mohs in such situations.

Bruce Jancin/MDedge News
Dr. Sean Condon


“Mohs utilization did not increase after the Affordable Care Act [ACA], despite new health insurance coverage for 20 million previously uninsured adults,” Dr. Condon said. “Surprisingly, after the ACA we actually saw a decrease in Mohs use for melanoma in situ.”

Indeed, his retrospective study of more than 25,000 patients in the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registries showed that the proportion of patients with melanoma in situ treated with Mohs declined from 13.9% during 2008-2009 – prior to ACA implementation – to 12.3% in 2011-2013, after the ACA took effect. That’s a statistically significant 13% drop, even though numerous published studies have shown outcomes in melanoma in situ are better with Mohs, said the dermatologist, who conducted the study while completing a Mohs surgery fellowship at the Cleveland Clinic. He is now in private practice in Thousand Oaks, Calif.

His analysis included 19,013 patients treated in 2008-2014 for melanoma in situ and 6,309 others treated for rare cutaneous malignancies deemed appropriate for Mohs according to the criteria formally developed jointly by the American Academy of Dermatology, the American College of Mohs Surgery, the American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery (J Am Acad Dermatol. 2012 Oct;67[4]:531-50). These rare malignancies include adnexal carcinoma, Merkel cell carcinoma, dermatofibrosarcoma, extramammary Paget disease, sebaceous adenocarcinoma, and leiomyosarcoma.



“These rare cutaneous malignancies were historically treated with wide local excision. However, numerous studies have lately shown that lower recurrence rates were found with Mohs compared with wide local excision,” Dr. Condon noted.

Nonetheless, the proportion of the rare cutaneous malignancies treated using Mohs was unaffected by implementation of the ACA. Nor was it influenced one way or the other by publication of the joint Mohs appropriate use criteria in 2012: The Mohs-treated proportion of such cases was 15.25% in 2010-2011 and 14.6% in 2013-2014.

Similarly, even though the appropriate use criteria identified melanoma in situ as Mohs appropriate, the proportion of those malignancies treated via Mohs was the same before and after the 2012 release of the criteria.

“It’s commonly thought that Mohs is overused. However, our study and our data clearly identify that Mohs is being underutilized for melanoma in situ and for rare cutaneous malignancies. This represents a knowledge gap for other specialties regarding best-practice therapy,” Dr. Condon said.

He and his coinvestigators searched for socioeconomic predictors of Mohs utilization by matching the nationally representative SEER data with U.S. census data. They examined the impact of three metrics: insurance status, income, and poverty. They found that low-income patients and those in the highest quartile of poverty were significantly less likely to have Mohs surgery for their melanoma in situ and rare cutaneous malignancies throughout the study years. Lack of health insurance had no impact on Mohs utilization for melanoma in situ but was independently associated with decreased likelihood of Mohs for the rare cutaneous malignancies. White patients were 2-fold to 2.4-fold more likely to have Mohs surgery for their rare cutaneous malignancies than were black patients.

“One can conclude that Mohs micrographic surgery may be skewed toward more affluent patients, and lower socioeconomic status areas have less Mohs access. So our data from this study support a role for targeted education and improved patient access to Mohs,” Dr. Condon said.

He noted that because the SEER registries don’t track squamous or basal cell carcinomas, it’s unknown whether Mohs is also underutilized for the higher-risk forms of these most common of all skin cancers.

Dr. Condon reported having no financial conflicts regarding his study, conducted free of commercial support.

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REPORTING FROM THE ACMS 50TH ANNUAL MEETING

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Key clinical point: Mohs micrographic surgery remains seriously underutilized for the skin cancers for which it is most advantageous.

Major finding: The use of Mohs micrographic surgery to treat melanoma in situ declined significantly after passage of the Affordable Care Act.

Study details: This was a retrospective study of national SEER data on more than 25,000 patients treated for melanoma in situ or rare cutaneous malignancies during 2008-2014.

Disclosures: The presenter reported having no financial conflicts regarding his study, conducted free of commercial support.

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Study pinpoints skin cancer risk factors after hematopoietic cell transplant

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– The 10-year incidence rates for both squamous cell carcinoma and basal cell carcinoma arising after hematopoietic cell transplantation are impressively high at 17%-plus for each, but the malignancies occur on two very different timelines, according to Jeffrey F. Scott, MD, a fellow in micrographic surgery and dermatologic oncology at Case Western Reserve University in Cleveland.

Most of the squamous cell carcinomas (SCCs) in a large multicenter retrospective study developed within the first 5 years following hematopoietic cell transplantation (HCT), while the majority of the basal cell carcinomas (BCCs) occurred after that point, Dr. Scott reported at the annual meeting of the American College of Mohs Surgery.

He presented the results of the study, which included 876 HCT recipients followed for a mean of 6.1 years. The study objective was to pin down the risk factors for skin cancer after HCT, especially the patient-specific ones. This has become a pressing issue because the use of HCT is steadily growing, and the 5-year survival rate now exceeds 50%.

The transplant-specific risk factors have previously been fairly well described by others. They include the donor source, type of disease, the conditioning regimen, whether whole body irradiation was used, immunosuppression, graft versus host disease (GVHD), and others.

The patient-centric risk factors, in contrast, have not been well characterized. And it’s critical to thoroughly understand these risk factors in order to develop targeted prevention and surveillance strategies, Dr. Scott said.

“There remains a significant knowledge gap within our field. I would venture that the majority of this audience has treated a patient with skin cancer who has had a transplant,” he said. “Yet when a patient asks us, ‘Doc, what is my risk for skin cancer after my HCT?’ we’re really unable to give them an accurate and complete assessment of that risk. That’s because we’re missing the second major category of risk factors: the patient-specific risk factors.”

The reason for that, he added, is that the major population-based studies and national HCT registries are run by hematologists and oncologists, and they haven’t adequately captured the patient-specific skin cancer risk factors. But these are variables very familiar to dermatologists. They include skin phenotype, history of UV radiation exposure, and history of pre-HCT skin cancer.

Dr. Scott said the multicenter study he presented has two major advantages over prior studies: its large size and thorough followup. Nearly all 876 patients were followed by both an oncologist and a dermatologist at the same institution.

During followup, the HCT recipients collectively developed 63 SCCs, 55 BCCs, and 16 malignant melanomas. The 5- and 10-year incidence rates for SCC were 10.6% and 17.2%. For BCC, the 5- and 10-year rates were 5.7% and 17.6%. All 16 cases of melanoma occurred within 5 years after HCT.

In multivariate Cox proportional hazard analyses, photodamage documented on examination was independently associated with a 3.2-fold increased risk of post-HCT SCC and a 3.5-fold increased risk of BCC.

A pre-transplant history of BCC was associated with a 3.9-fold increased likelihood of developing a BCC afterwards. Similarly, a pre-HCT history of SCC conferred a 4.2-fold increased risk of post-transplant SCC and was also independently associated with a 6.6-fold increased risk of developing melanoma post-HCT.

Fitzpatrick skin types I and II were respectively associated with 9.3- and 7.2-fold increased risks of post-HCT nonmelanoma skin cancer, compared with skin types III-VI.

Acute GVHD wasn’t associated with an increased risk of nonmelanoma skin cancer after HCT. However, in an observation that hasn’t previously been reported by others, chronic GVHD with skin involvement was associated with a 2.7-fold increased likelihood of SCC post-HCT, Dr. Scott noted.

What’s next for Dr. Scott and his coinvestigators? “Our ultimate goal with this project is to develop an interactive risk assessment tool like the National Cancer Institute’s Breast Cancer Risk Assessment Tool that can be online and used by patients and providers to estimate their individualized risk of basal cell carcinoma, squamous cell carcinoma, and melanoma after HCT,” he said.

Dr. Scott reported having no financial conflicts related to the study.

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– The 10-year incidence rates for both squamous cell carcinoma and basal cell carcinoma arising after hematopoietic cell transplantation are impressively high at 17%-plus for each, but the malignancies occur on two very different timelines, according to Jeffrey F. Scott, MD, a fellow in micrographic surgery and dermatologic oncology at Case Western Reserve University in Cleveland.

Most of the squamous cell carcinomas (SCCs) in a large multicenter retrospective study developed within the first 5 years following hematopoietic cell transplantation (HCT), while the majority of the basal cell carcinomas (BCCs) occurred after that point, Dr. Scott reported at the annual meeting of the American College of Mohs Surgery.

He presented the results of the study, which included 876 HCT recipients followed for a mean of 6.1 years. The study objective was to pin down the risk factors for skin cancer after HCT, especially the patient-specific ones. This has become a pressing issue because the use of HCT is steadily growing, and the 5-year survival rate now exceeds 50%.

The transplant-specific risk factors have previously been fairly well described by others. They include the donor source, type of disease, the conditioning regimen, whether whole body irradiation was used, immunosuppression, graft versus host disease (GVHD), and others.

The patient-centric risk factors, in contrast, have not been well characterized. And it’s critical to thoroughly understand these risk factors in order to develop targeted prevention and surveillance strategies, Dr. Scott said.

“There remains a significant knowledge gap within our field. I would venture that the majority of this audience has treated a patient with skin cancer who has had a transplant,” he said. “Yet when a patient asks us, ‘Doc, what is my risk for skin cancer after my HCT?’ we’re really unable to give them an accurate and complete assessment of that risk. That’s because we’re missing the second major category of risk factors: the patient-specific risk factors.”

The reason for that, he added, is that the major population-based studies and national HCT registries are run by hematologists and oncologists, and they haven’t adequately captured the patient-specific skin cancer risk factors. But these are variables very familiar to dermatologists. They include skin phenotype, history of UV radiation exposure, and history of pre-HCT skin cancer.

Dr. Scott said the multicenter study he presented has two major advantages over prior studies: its large size and thorough followup. Nearly all 876 patients were followed by both an oncologist and a dermatologist at the same institution.

During followup, the HCT recipients collectively developed 63 SCCs, 55 BCCs, and 16 malignant melanomas. The 5- and 10-year incidence rates for SCC were 10.6% and 17.2%. For BCC, the 5- and 10-year rates were 5.7% and 17.6%. All 16 cases of melanoma occurred within 5 years after HCT.

In multivariate Cox proportional hazard analyses, photodamage documented on examination was independently associated with a 3.2-fold increased risk of post-HCT SCC and a 3.5-fold increased risk of BCC.

A pre-transplant history of BCC was associated with a 3.9-fold increased likelihood of developing a BCC afterwards. Similarly, a pre-HCT history of SCC conferred a 4.2-fold increased risk of post-transplant SCC and was also independently associated with a 6.6-fold increased risk of developing melanoma post-HCT.

Fitzpatrick skin types I and II were respectively associated with 9.3- and 7.2-fold increased risks of post-HCT nonmelanoma skin cancer, compared with skin types III-VI.

Acute GVHD wasn’t associated with an increased risk of nonmelanoma skin cancer after HCT. However, in an observation that hasn’t previously been reported by others, chronic GVHD with skin involvement was associated with a 2.7-fold increased likelihood of SCC post-HCT, Dr. Scott noted.

What’s next for Dr. Scott and his coinvestigators? “Our ultimate goal with this project is to develop an interactive risk assessment tool like the National Cancer Institute’s Breast Cancer Risk Assessment Tool that can be online and used by patients and providers to estimate their individualized risk of basal cell carcinoma, squamous cell carcinoma, and melanoma after HCT,” he said.

Dr. Scott reported having no financial conflicts related to the study.

– The 10-year incidence rates for both squamous cell carcinoma and basal cell carcinoma arising after hematopoietic cell transplantation are impressively high at 17%-plus for each, but the malignancies occur on two very different timelines, according to Jeffrey F. Scott, MD, a fellow in micrographic surgery and dermatologic oncology at Case Western Reserve University in Cleveland.

Most of the squamous cell carcinomas (SCCs) in a large multicenter retrospective study developed within the first 5 years following hematopoietic cell transplantation (HCT), while the majority of the basal cell carcinomas (BCCs) occurred after that point, Dr. Scott reported at the annual meeting of the American College of Mohs Surgery.

He presented the results of the study, which included 876 HCT recipients followed for a mean of 6.1 years. The study objective was to pin down the risk factors for skin cancer after HCT, especially the patient-specific ones. This has become a pressing issue because the use of HCT is steadily growing, and the 5-year survival rate now exceeds 50%.

The transplant-specific risk factors have previously been fairly well described by others. They include the donor source, type of disease, the conditioning regimen, whether whole body irradiation was used, immunosuppression, graft versus host disease (GVHD), and others.

The patient-centric risk factors, in contrast, have not been well characterized. And it’s critical to thoroughly understand these risk factors in order to develop targeted prevention and surveillance strategies, Dr. Scott said.

“There remains a significant knowledge gap within our field. I would venture that the majority of this audience has treated a patient with skin cancer who has had a transplant,” he said. “Yet when a patient asks us, ‘Doc, what is my risk for skin cancer after my HCT?’ we’re really unable to give them an accurate and complete assessment of that risk. That’s because we’re missing the second major category of risk factors: the patient-specific risk factors.”

The reason for that, he added, is that the major population-based studies and national HCT registries are run by hematologists and oncologists, and they haven’t adequately captured the patient-specific skin cancer risk factors. But these are variables very familiar to dermatologists. They include skin phenotype, history of UV radiation exposure, and history of pre-HCT skin cancer.

Dr. Scott said the multicenter study he presented has two major advantages over prior studies: its large size and thorough followup. Nearly all 876 patients were followed by both an oncologist and a dermatologist at the same institution.

During followup, the HCT recipients collectively developed 63 SCCs, 55 BCCs, and 16 malignant melanomas. The 5- and 10-year incidence rates for SCC were 10.6% and 17.2%. For BCC, the 5- and 10-year rates were 5.7% and 17.6%. All 16 cases of melanoma occurred within 5 years after HCT.

In multivariate Cox proportional hazard analyses, photodamage documented on examination was independently associated with a 3.2-fold increased risk of post-HCT SCC and a 3.5-fold increased risk of BCC.

A pre-transplant history of BCC was associated with a 3.9-fold increased likelihood of developing a BCC afterwards. Similarly, a pre-HCT history of SCC conferred a 4.2-fold increased risk of post-transplant SCC and was also independently associated with a 6.6-fold increased risk of developing melanoma post-HCT.

Fitzpatrick skin types I and II were respectively associated with 9.3- and 7.2-fold increased risks of post-HCT nonmelanoma skin cancer, compared with skin types III-VI.

Acute GVHD wasn’t associated with an increased risk of nonmelanoma skin cancer after HCT. However, in an observation that hasn’t previously been reported by others, chronic GVHD with skin involvement was associated with a 2.7-fold increased likelihood of SCC post-HCT, Dr. Scott noted.

What’s next for Dr. Scott and his coinvestigators? “Our ultimate goal with this project is to develop an interactive risk assessment tool like the National Cancer Institute’s Breast Cancer Risk Assessment Tool that can be online and used by patients and providers to estimate their individualized risk of basal cell carcinoma, squamous cell carcinoma, and melanoma after HCT,” he said.

Dr. Scott reported having no financial conflicts related to the study.

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REPORTING FROM THE ACMS ANNUAL MEETING

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Key clinical point: Individualized risk assessment for skin cancer after hematopoietic cell transplantation may be close at hand.

Major finding: Photodamage documented on examination more than triples the risk of developing nonmelanoma skin cancer after hematopoietic cell transplantation.

Study details: A multicenter retrospective study of 876 hematopoietic cell recipients followed for a mean of 6.1 years.

Disclosures: The presenter reported having no financial conflicts related to the study, which was conducted without commercial support.

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New Guidelines for Nonmelanoma Skin Cancer: What You Need to Know

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Nevus count tied to BCC risk

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– The more nevi a person has, the greater the risk of basal cell carcinoma, according to a review of over 200,000 subjects in decades-long health professional cohorts.

It’s well known that nevi increase the risk of melanoma, and the study confirmed that fact. The basal cell carcinoma finding, however, is novel. “The relationship between nevi and non-melanoma skin cancer has not [previously] been clearly demonstrated in large population cohorts,” said lead investigator Erin X. Wei, MD, a dermatologist at Brigham and Women’s Hospital, Boston.

“Nevus count serves as a convenient maker to identify patients at risk for both melanoma and basal cell carcinoma. Providers should be aware of these increased risks in patients with any nevi on the extremity, particularly 15 or more,” she said at the International Investigative Dermatology meeting.

There was no association, meanwhile, between nevus counts and squamous cell carcinoma (SCC).

The team reviewed 176,317 women in the Nurses’ Health Study 1 and 2, as well as 32,383 men in the Health Professionals Follow-up Study. Subjects were enrolled in the 1980s and followed through 2012. They reported nevus counts on their arms or legs at baseline, and filled out questionnaires on a regular basis that, among many other things, asked about new skin cancer diagnoses.

Overall, there were 30,457 incident basal cell carcinomas (BCCs), 1,704 incident melanomas, and 2,296 incident SCCs. Melanomas and SCCs – as well as a portion of BCCs – were confirmed by histology.

The team correlated the skin cancer incidence with how many moles subjects reported at baseline: zero, 1-5, 6-14, or 15 or more.

 

 


“Surprisingly, having any nevi on an extremity was associated with a significant increase in the risk of basal cell carcinoma,” in a dose-dependent manner, with 15 or more conferring a 40% increased risk of BCC, compared to subjects with no extremity nevi, Dr. Wei said (P less than .0001).

Even one mole also increased the risk of melanoma; having six or more nearly tripled it, again in a dose-dependent fashion (P less than .0001). Extremity nevi increased the risk of melanoma across all anatomic sites, including head, neck, and trunk.

The findings were statistically significant, and adjusted for age, body mass index, smoking, sun exposure, sunburn history, and other confounders.

There was no industry funding for the work, and the investigators had no relevant disclosures.

SOURCE: Wei EX et al. 2018 International Investigative Dermatology meeting abstract 233

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– The more nevi a person has, the greater the risk of basal cell carcinoma, according to a review of over 200,000 subjects in decades-long health professional cohorts.

It’s well known that nevi increase the risk of melanoma, and the study confirmed that fact. The basal cell carcinoma finding, however, is novel. “The relationship between nevi and non-melanoma skin cancer has not [previously] been clearly demonstrated in large population cohorts,” said lead investigator Erin X. Wei, MD, a dermatologist at Brigham and Women’s Hospital, Boston.

“Nevus count serves as a convenient maker to identify patients at risk for both melanoma and basal cell carcinoma. Providers should be aware of these increased risks in patients with any nevi on the extremity, particularly 15 or more,” she said at the International Investigative Dermatology meeting.

There was no association, meanwhile, between nevus counts and squamous cell carcinoma (SCC).

The team reviewed 176,317 women in the Nurses’ Health Study 1 and 2, as well as 32,383 men in the Health Professionals Follow-up Study. Subjects were enrolled in the 1980s and followed through 2012. They reported nevus counts on their arms or legs at baseline, and filled out questionnaires on a regular basis that, among many other things, asked about new skin cancer diagnoses.

Overall, there were 30,457 incident basal cell carcinomas (BCCs), 1,704 incident melanomas, and 2,296 incident SCCs. Melanomas and SCCs – as well as a portion of BCCs – were confirmed by histology.

The team correlated the skin cancer incidence with how many moles subjects reported at baseline: zero, 1-5, 6-14, or 15 or more.

 

 


“Surprisingly, having any nevi on an extremity was associated with a significant increase in the risk of basal cell carcinoma,” in a dose-dependent manner, with 15 or more conferring a 40% increased risk of BCC, compared to subjects with no extremity nevi, Dr. Wei said (P less than .0001).

Even one mole also increased the risk of melanoma; having six or more nearly tripled it, again in a dose-dependent fashion (P less than .0001). Extremity nevi increased the risk of melanoma across all anatomic sites, including head, neck, and trunk.

The findings were statistically significant, and adjusted for age, body mass index, smoking, sun exposure, sunburn history, and other confounders.

There was no industry funding for the work, and the investigators had no relevant disclosures.

SOURCE: Wei EX et al. 2018 International Investigative Dermatology meeting abstract 233

 

– The more nevi a person has, the greater the risk of basal cell carcinoma, according to a review of over 200,000 subjects in decades-long health professional cohorts.

It’s well known that nevi increase the risk of melanoma, and the study confirmed that fact. The basal cell carcinoma finding, however, is novel. “The relationship between nevi and non-melanoma skin cancer has not [previously] been clearly demonstrated in large population cohorts,” said lead investigator Erin X. Wei, MD, a dermatologist at Brigham and Women’s Hospital, Boston.

“Nevus count serves as a convenient maker to identify patients at risk for both melanoma and basal cell carcinoma. Providers should be aware of these increased risks in patients with any nevi on the extremity, particularly 15 or more,” she said at the International Investigative Dermatology meeting.

There was no association, meanwhile, between nevus counts and squamous cell carcinoma (SCC).

The team reviewed 176,317 women in the Nurses’ Health Study 1 and 2, as well as 32,383 men in the Health Professionals Follow-up Study. Subjects were enrolled in the 1980s and followed through 2012. They reported nevus counts on their arms or legs at baseline, and filled out questionnaires on a regular basis that, among many other things, asked about new skin cancer diagnoses.

Overall, there were 30,457 incident basal cell carcinomas (BCCs), 1,704 incident melanomas, and 2,296 incident SCCs. Melanomas and SCCs – as well as a portion of BCCs – were confirmed by histology.

The team correlated the skin cancer incidence with how many moles subjects reported at baseline: zero, 1-5, 6-14, or 15 or more.

 

 


“Surprisingly, having any nevi on an extremity was associated with a significant increase in the risk of basal cell carcinoma,” in a dose-dependent manner, with 15 or more conferring a 40% increased risk of BCC, compared to subjects with no extremity nevi, Dr. Wei said (P less than .0001).

Even one mole also increased the risk of melanoma; having six or more nearly tripled it, again in a dose-dependent fashion (P less than .0001). Extremity nevi increased the risk of melanoma across all anatomic sites, including head, neck, and trunk.

The findings were statistically significant, and adjusted for age, body mass index, smoking, sun exposure, sunburn history, and other confounders.

There was no industry funding for the work, and the investigators had no relevant disclosures.

SOURCE: Wei EX et al. 2018 International Investigative Dermatology meeting abstract 233

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Key clinical point: The more nevi a person has, the greater the risk of basal cell carcinoma.

Major finding: Having 15 or more moles on the arms and legs increased the risk 40% (P less than .0001).

Study details: Review of over 200,000 subjects in decades-long health professional cohorts

Disclosures: There was no industry funding for the work, and the investigators had no relevant disclosures.

Source: Wei EX et al. 2018 International Investigative Dermatology meeting abstract 233

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Unusual Presentation of Ectopic Extramammary Paget Disease

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Unusual Presentation of Ectopic Extramammary Paget Disease

Extramammary Paget disease (EMPD) is a malignant epithelial tumor that most commonly affects the anogenital region and less frequently arises in the axillae. Most cases occur in locations where apocrine glands predominate.1 Few cases of EMPD arising in nonapocrine-bearing regions, or ectopic EMPD, have been reported.2 We describe a case of primary ectopic EMPD with an infiltrative growth pattern arising on the back of a 67-year-old Thai man.

Case Report

A 67-year-old Thai man presented to the dermatology clinic for evaluation of a persistent rash on the right lower back of approximately 30 years’ duration. He reported that the eruption had started out as a small coin-shaped area but had slowly increased in size. Over the last 2 years, the area had grown more rapidly and became pruritic. His medical history was remarkable for hypertension treated with losartan, but he was otherwise healthy. He had no history of cancer or gastrointestinal tract or genitourinary symptoms, and he had no recent fever, weight loss, or night sweats.

On physical examination a well-demarcated, asymmetric, erythematous to brown plaque was noted on the right lower back. The plaque was surfaced by scale and contained a central hyperkeratotic papule (Figure 1). The skin examination was otherwise unremarkable. The patient had no lymphadenopathy.

Figure1
Figure 1. Ectopic extramammary Paget disease presenting as a well-demarcated, asymmetric, erythematous to brown plaque on the right lower back with associated scale and a central hyperkeratotic papule.

Two punch biopsies were performed. On low power, acanthosis and hyperkeratosis of the epidermis were noted. The epidermis contained a proliferation of large (tumor) cells with pleomorphic nuclei, prominent nucleoli, and abundant pale to clear cytoplasm. The cells were present singularly as well as in clusters and were most prominent along the basal layer but many were also seen extending to more superficial levels of the epidermis (Figure 2A). In one biopsy, the tumor cells were found in the dermis with an infiltrative growth pattern (Figure 2B). Immunohistochemistry (IHC) studies for cytokeratin 7 (Figure 3A and 3B) and carcinoembryonic antigen (Figure 3C) labeled the tumor cells. An IHC study for gross cystic disease fluid protein 15 labeled some of the tumor cells. Immunohistochemistry studies for S-100, human melanoma black 45 (HMB-45), p16, and renal cell carcinoma did not label the tumor cells. An IHC study for MIB-1 labeled many of the tumor cells, indicating a notably increased mitotic index. The patient was diagnosed with ectopic EMPD. He underwent an endoscopy, colonoscopy, and cystoscopy, all of which were normal.

Figure2
Figure 2. Proliferation of large cells with pleomorphic nuclei, prominent nucleoli, and abundant pale to clear cytoplasm confined to the epidermis in ectopic extramammary Paget disease (A)(H&E, original magnification ×10). The tumor cells demonstrated an infiltrative growth pattern in another biopsy from the plaque (B)(H&E, original magnification ×4).

Figure3
Figure 3. Immunohistochemical studies for cytokeratin 7 (A and B)(original magnifications ×10 and ×4) and carcinoembryonic antigen labeled the tumor cells strongly and diffusely (C)(original magnification ×10).
 

 

Comment

Extramammary Paget disease is a malignant tumor typically found in apocrine-rich areas of the skin, particularly the anogenital skin. It is categorized as primary or secondary EMPD. Primary EMPD arises as an intraepithelial adenocarcinoma, with the Toker cell as the cell of origin.3 Secondary EMPD represents a cutaneous extension of an underlying malignancy (eg, colorectal, urothelial, prostatic, gynecologic).4

Ectopic EMPD arises in nonapocrine-bearing areas, specifically the nongerminative milk line. A review of the literature using Google Scholar and the search term ectopic extramammary Paget disease showed that there have been at least 30 cases of ectopic EMPD reported. Older men are more commonly affected, with a mean age at diagnosis of approximately 68 years. Although the tumor is most commonly seen on the trunk, cases on the head, arms, and legs have been reported.5

This tumor is most frequently seen in Asian individuals, as in our patient, with a ratio of approximately 3:1.5 Interestingly, triple or quadruple EMPD was reported in 68 Japanese patients but rarely has been reported outside of Japan.6 It is thought that some germinative apocrine-differentiating cells might preferentially exist on the trunk of Asians, leading to an increased incidence of EMPD in this population5; however, the exact reason for this racial preference is not completely understood, and more studies are needed to investigate this association.

Diagnosis of ectopic EMPD is made histologically. Tumor cells have abundant pale cytoplasm and large pleomorphic nuclei with prominent nucleoli. The cells are arranged in small groups or singly within the basal regions of the epidermis. In longstanding lesions, the entire thickness of the epidermis may be involved. Uncommonly, the tumor cells may invade the dermis, such as in our patient. On immunohistochemistry, the tumor cells stain positive for carcinoembryonic antigen, epithelial membrane antigen, and low-molecular-weight cytokeratins (eg, cytokeratin 7). Many of the tumor cells also express gross cystic disease fluid protein 15, which helps exclude cutaneous invasion of secondary EMPD.7-9 Cases of primary cutaneous apocrine carcinoma can have similar histologic and immunohistochemical findings to invasive EMPD, which further supports the possible apocrine derivation of Paget disease. In our patient, we considered the diagnosis of primary cutaneous apocrine adenocarcinoma with epidermotropism; however, we favored the diagnosis of ectopic EMPD with dermal invasion given the extensive epidermal-only involvement seen in one of the biopsies, which would be unusual for primary cutaneous apocrine adenocarcinoma.

Our patient had no identified underlying malignancy upon further workup; however, many cases of EMPD have been associated with an underlying malignancy.9-15 Several authors have reported a range of underlying malignancies associated with EMPD, with the incidence ranging from 11% to 45%.9-15 The location of the underlying internal malignancy appears to be closely related to the location of the EMPD.11 It is recommended that a thorough workup for internal malignancies be performed, including a full skin examination, lymph node examination, colonoscopy, cystoscopy, and gynecologic/prostate examination, among others.

No known differences in the prognosis or associated underlying malignancies between ectopic and ordinary EMPD have been reported; however, it has been noted that EMPD with invasion into the dermis does correlate with a more aggressive course and worse prognosis.8 Treatment includes surgical removal by Mohs micrographic surgery or wide local excision. Long-term follow-up is required since recurrences can be frequent.11-15

References
  1. Mazoujian G, Pinkus GS, Haagensen DE Jr. Extramammary Paget’s disease—evidence for an apocrine origin: an immunoperoxidase study of gross cystic disease fluid protein-15, carcinoembryonic antigen, and keratin proteins. Am J Surg Pathol. 1984;8:43-50.
  2. Saida T, Iwata M. “Ectopic” extramammary Paget’s disease affecting the lower anterior aspect of the chest. J Am Acad Dermatol. 1987;17(5, pt 2):910-913.
  3. Willman JH, Golitz LE, Fitzpatrick JE. Vulvar clear cells of Toker: precursors of extramammary Paget’s disease. Am J Dermatopathol. 2005;27:185-188.
  4. Lloyd J, Flanagan AM. Mammary and extramammary Paget’s disease.J Clin Pathol. 2000;53:742-749.
  5. Sawada Y, Bito T, Kabashima R, et al. Ectopic extramammary Paget’s disease: case report and literature review. Acta Derm Venereol. 2010;90:502-505.
  6. Abe S, Kabashima K, Nishio D, et al. Quadruple extramammary Paget’s disease. Acta Derm Venereol. 2007;87:80-81.
  7. Kanitakis J. Mammary and extramammary Paget’s disease. J Eur Acad Dermatol Venereol. 2007;21:581-590.
  8. Goldblum JR, Hart WR. Vulvar Paget’s disease: a clinicopathologic and immunohistochemical study of 19 cases. Am J Surg Pathol. 1997;21:1178-1187.
  9. Goldblum JR, Hart WR. Perianal Paget’s disease: a histologic and immunohistochemical study of 11 cases with and without associated rectal adenocarcinoma. Am J Surg Pathol. 1998;22:170-179.
  10. Shepherd V, Davidson EJ, Davies‐Humphreys J. Extramammary Paget’s disease. BJOG. 2005;112:273-279.
  11. Chanda JJ. Extramammary Paget’s disease: prognosis and relationship to internal malignancy. J Am Acad Dermatol. 1985;13:1009-1014.
  12. Besa P, Rich TA, Delclos L, et al. Extramammary Paget’s disease of the perineal skin: role of radiotherapy. Int J Radiat Oncol Biol Phys. 1992;24:73-78.
  13. Fanning J, Lambert HC, Hale TM, et al. Paget’s disease of the vulva: prevalence of associated vulvar adenocarcinoma, invasive Paget’s disease, and recurrence after surgical excision. Am J Obstet Gynecol. 1999;180:24-27.
  14. Parker LP, Parker JR, Bodurka-Bevers D, et al. Paget’s disease of the vulva: pathology, pattern of involvement, and prognosis. Gynecol Oncol. 2000;77:183-189.
  15. Marchesa P, Fazio VW, Oliart S, et al. Long-term outcome of patients with perianal Paget’s disease. Ann Surg Oncol. 1997;4:475-480.
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Correspondence: Brandon McNally, MD, Department of Pathology: Anatomic Pathology, 12605 E 16th Ave, Campus Box F768, Aurora, CO 80045 ([email protected]).

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Extramammary Paget disease (EMPD) is a malignant epithelial tumor that most commonly affects the anogenital region and less frequently arises in the axillae. Most cases occur in locations where apocrine glands predominate.1 Few cases of EMPD arising in nonapocrine-bearing regions, or ectopic EMPD, have been reported.2 We describe a case of primary ectopic EMPD with an infiltrative growth pattern arising on the back of a 67-year-old Thai man.

Case Report

A 67-year-old Thai man presented to the dermatology clinic for evaluation of a persistent rash on the right lower back of approximately 30 years’ duration. He reported that the eruption had started out as a small coin-shaped area but had slowly increased in size. Over the last 2 years, the area had grown more rapidly and became pruritic. His medical history was remarkable for hypertension treated with losartan, but he was otherwise healthy. He had no history of cancer or gastrointestinal tract or genitourinary symptoms, and he had no recent fever, weight loss, or night sweats.

On physical examination a well-demarcated, asymmetric, erythematous to brown plaque was noted on the right lower back. The plaque was surfaced by scale and contained a central hyperkeratotic papule (Figure 1). The skin examination was otherwise unremarkable. The patient had no lymphadenopathy.

Figure1
Figure 1. Ectopic extramammary Paget disease presenting as a well-demarcated, asymmetric, erythematous to brown plaque on the right lower back with associated scale and a central hyperkeratotic papule.

Two punch biopsies were performed. On low power, acanthosis and hyperkeratosis of the epidermis were noted. The epidermis contained a proliferation of large (tumor) cells with pleomorphic nuclei, prominent nucleoli, and abundant pale to clear cytoplasm. The cells were present singularly as well as in clusters and were most prominent along the basal layer but many were also seen extending to more superficial levels of the epidermis (Figure 2A). In one biopsy, the tumor cells were found in the dermis with an infiltrative growth pattern (Figure 2B). Immunohistochemistry (IHC) studies for cytokeratin 7 (Figure 3A and 3B) and carcinoembryonic antigen (Figure 3C) labeled the tumor cells. An IHC study for gross cystic disease fluid protein 15 labeled some of the tumor cells. Immunohistochemistry studies for S-100, human melanoma black 45 (HMB-45), p16, and renal cell carcinoma did not label the tumor cells. An IHC study for MIB-1 labeled many of the tumor cells, indicating a notably increased mitotic index. The patient was diagnosed with ectopic EMPD. He underwent an endoscopy, colonoscopy, and cystoscopy, all of which were normal.

Figure2
Figure 2. Proliferation of large cells with pleomorphic nuclei, prominent nucleoli, and abundant pale to clear cytoplasm confined to the epidermis in ectopic extramammary Paget disease (A)(H&E, original magnification ×10). The tumor cells demonstrated an infiltrative growth pattern in another biopsy from the plaque (B)(H&E, original magnification ×4).

Figure3
Figure 3. Immunohistochemical studies for cytokeratin 7 (A and B)(original magnifications ×10 and ×4) and carcinoembryonic antigen labeled the tumor cells strongly and diffusely (C)(original magnification ×10).
 

 

Comment

Extramammary Paget disease is a malignant tumor typically found in apocrine-rich areas of the skin, particularly the anogenital skin. It is categorized as primary or secondary EMPD. Primary EMPD arises as an intraepithelial adenocarcinoma, with the Toker cell as the cell of origin.3 Secondary EMPD represents a cutaneous extension of an underlying malignancy (eg, colorectal, urothelial, prostatic, gynecologic).4

Ectopic EMPD arises in nonapocrine-bearing areas, specifically the nongerminative milk line. A review of the literature using Google Scholar and the search term ectopic extramammary Paget disease showed that there have been at least 30 cases of ectopic EMPD reported. Older men are more commonly affected, with a mean age at diagnosis of approximately 68 years. Although the tumor is most commonly seen on the trunk, cases on the head, arms, and legs have been reported.5

This tumor is most frequently seen in Asian individuals, as in our patient, with a ratio of approximately 3:1.5 Interestingly, triple or quadruple EMPD was reported in 68 Japanese patients but rarely has been reported outside of Japan.6 It is thought that some germinative apocrine-differentiating cells might preferentially exist on the trunk of Asians, leading to an increased incidence of EMPD in this population5; however, the exact reason for this racial preference is not completely understood, and more studies are needed to investigate this association.

Diagnosis of ectopic EMPD is made histologically. Tumor cells have abundant pale cytoplasm and large pleomorphic nuclei with prominent nucleoli. The cells are arranged in small groups or singly within the basal regions of the epidermis. In longstanding lesions, the entire thickness of the epidermis may be involved. Uncommonly, the tumor cells may invade the dermis, such as in our patient. On immunohistochemistry, the tumor cells stain positive for carcinoembryonic antigen, epithelial membrane antigen, and low-molecular-weight cytokeratins (eg, cytokeratin 7). Many of the tumor cells also express gross cystic disease fluid protein 15, which helps exclude cutaneous invasion of secondary EMPD.7-9 Cases of primary cutaneous apocrine carcinoma can have similar histologic and immunohistochemical findings to invasive EMPD, which further supports the possible apocrine derivation of Paget disease. In our patient, we considered the diagnosis of primary cutaneous apocrine adenocarcinoma with epidermotropism; however, we favored the diagnosis of ectopic EMPD with dermal invasion given the extensive epidermal-only involvement seen in one of the biopsies, which would be unusual for primary cutaneous apocrine adenocarcinoma.

Our patient had no identified underlying malignancy upon further workup; however, many cases of EMPD have been associated with an underlying malignancy.9-15 Several authors have reported a range of underlying malignancies associated with EMPD, with the incidence ranging from 11% to 45%.9-15 The location of the underlying internal malignancy appears to be closely related to the location of the EMPD.11 It is recommended that a thorough workup for internal malignancies be performed, including a full skin examination, lymph node examination, colonoscopy, cystoscopy, and gynecologic/prostate examination, among others.

No known differences in the prognosis or associated underlying malignancies between ectopic and ordinary EMPD have been reported; however, it has been noted that EMPD with invasion into the dermis does correlate with a more aggressive course and worse prognosis.8 Treatment includes surgical removal by Mohs micrographic surgery or wide local excision. Long-term follow-up is required since recurrences can be frequent.11-15

Extramammary Paget disease (EMPD) is a malignant epithelial tumor that most commonly affects the anogenital region and less frequently arises in the axillae. Most cases occur in locations where apocrine glands predominate.1 Few cases of EMPD arising in nonapocrine-bearing regions, or ectopic EMPD, have been reported.2 We describe a case of primary ectopic EMPD with an infiltrative growth pattern arising on the back of a 67-year-old Thai man.

Case Report

A 67-year-old Thai man presented to the dermatology clinic for evaluation of a persistent rash on the right lower back of approximately 30 years’ duration. He reported that the eruption had started out as a small coin-shaped area but had slowly increased in size. Over the last 2 years, the area had grown more rapidly and became pruritic. His medical history was remarkable for hypertension treated with losartan, but he was otherwise healthy. He had no history of cancer or gastrointestinal tract or genitourinary symptoms, and he had no recent fever, weight loss, or night sweats.

On physical examination a well-demarcated, asymmetric, erythematous to brown plaque was noted on the right lower back. The plaque was surfaced by scale and contained a central hyperkeratotic papule (Figure 1). The skin examination was otherwise unremarkable. The patient had no lymphadenopathy.

Figure1
Figure 1. Ectopic extramammary Paget disease presenting as a well-demarcated, asymmetric, erythematous to brown plaque on the right lower back with associated scale and a central hyperkeratotic papule.

Two punch biopsies were performed. On low power, acanthosis and hyperkeratosis of the epidermis were noted. The epidermis contained a proliferation of large (tumor) cells with pleomorphic nuclei, prominent nucleoli, and abundant pale to clear cytoplasm. The cells were present singularly as well as in clusters and were most prominent along the basal layer but many were also seen extending to more superficial levels of the epidermis (Figure 2A). In one biopsy, the tumor cells were found in the dermis with an infiltrative growth pattern (Figure 2B). Immunohistochemistry (IHC) studies for cytokeratin 7 (Figure 3A and 3B) and carcinoembryonic antigen (Figure 3C) labeled the tumor cells. An IHC study for gross cystic disease fluid protein 15 labeled some of the tumor cells. Immunohistochemistry studies for S-100, human melanoma black 45 (HMB-45), p16, and renal cell carcinoma did not label the tumor cells. An IHC study for MIB-1 labeled many of the tumor cells, indicating a notably increased mitotic index. The patient was diagnosed with ectopic EMPD. He underwent an endoscopy, colonoscopy, and cystoscopy, all of which were normal.

Figure2
Figure 2. Proliferation of large cells with pleomorphic nuclei, prominent nucleoli, and abundant pale to clear cytoplasm confined to the epidermis in ectopic extramammary Paget disease (A)(H&E, original magnification ×10). The tumor cells demonstrated an infiltrative growth pattern in another biopsy from the plaque (B)(H&E, original magnification ×4).

Figure3
Figure 3. Immunohistochemical studies for cytokeratin 7 (A and B)(original magnifications ×10 and ×4) and carcinoembryonic antigen labeled the tumor cells strongly and diffusely (C)(original magnification ×10).
 

 

Comment

Extramammary Paget disease is a malignant tumor typically found in apocrine-rich areas of the skin, particularly the anogenital skin. It is categorized as primary or secondary EMPD. Primary EMPD arises as an intraepithelial adenocarcinoma, with the Toker cell as the cell of origin.3 Secondary EMPD represents a cutaneous extension of an underlying malignancy (eg, colorectal, urothelial, prostatic, gynecologic).4

Ectopic EMPD arises in nonapocrine-bearing areas, specifically the nongerminative milk line. A review of the literature using Google Scholar and the search term ectopic extramammary Paget disease showed that there have been at least 30 cases of ectopic EMPD reported. Older men are more commonly affected, with a mean age at diagnosis of approximately 68 years. Although the tumor is most commonly seen on the trunk, cases on the head, arms, and legs have been reported.5

This tumor is most frequently seen in Asian individuals, as in our patient, with a ratio of approximately 3:1.5 Interestingly, triple or quadruple EMPD was reported in 68 Japanese patients but rarely has been reported outside of Japan.6 It is thought that some germinative apocrine-differentiating cells might preferentially exist on the trunk of Asians, leading to an increased incidence of EMPD in this population5; however, the exact reason for this racial preference is not completely understood, and more studies are needed to investigate this association.

Diagnosis of ectopic EMPD is made histologically. Tumor cells have abundant pale cytoplasm and large pleomorphic nuclei with prominent nucleoli. The cells are arranged in small groups or singly within the basal regions of the epidermis. In longstanding lesions, the entire thickness of the epidermis may be involved. Uncommonly, the tumor cells may invade the dermis, such as in our patient. On immunohistochemistry, the tumor cells stain positive for carcinoembryonic antigen, epithelial membrane antigen, and low-molecular-weight cytokeratins (eg, cytokeratin 7). Many of the tumor cells also express gross cystic disease fluid protein 15, which helps exclude cutaneous invasion of secondary EMPD.7-9 Cases of primary cutaneous apocrine carcinoma can have similar histologic and immunohistochemical findings to invasive EMPD, which further supports the possible apocrine derivation of Paget disease. In our patient, we considered the diagnosis of primary cutaneous apocrine adenocarcinoma with epidermotropism; however, we favored the diagnosis of ectopic EMPD with dermal invasion given the extensive epidermal-only involvement seen in one of the biopsies, which would be unusual for primary cutaneous apocrine adenocarcinoma.

Our patient had no identified underlying malignancy upon further workup; however, many cases of EMPD have been associated with an underlying malignancy.9-15 Several authors have reported a range of underlying malignancies associated with EMPD, with the incidence ranging from 11% to 45%.9-15 The location of the underlying internal malignancy appears to be closely related to the location of the EMPD.11 It is recommended that a thorough workup for internal malignancies be performed, including a full skin examination, lymph node examination, colonoscopy, cystoscopy, and gynecologic/prostate examination, among others.

No known differences in the prognosis or associated underlying malignancies between ectopic and ordinary EMPD have been reported; however, it has been noted that EMPD with invasion into the dermis does correlate with a more aggressive course and worse prognosis.8 Treatment includes surgical removal by Mohs micrographic surgery or wide local excision. Long-term follow-up is required since recurrences can be frequent.11-15

References
  1. Mazoujian G, Pinkus GS, Haagensen DE Jr. Extramammary Paget’s disease—evidence for an apocrine origin: an immunoperoxidase study of gross cystic disease fluid protein-15, carcinoembryonic antigen, and keratin proteins. Am J Surg Pathol. 1984;8:43-50.
  2. Saida T, Iwata M. “Ectopic” extramammary Paget’s disease affecting the lower anterior aspect of the chest. J Am Acad Dermatol. 1987;17(5, pt 2):910-913.
  3. Willman JH, Golitz LE, Fitzpatrick JE. Vulvar clear cells of Toker: precursors of extramammary Paget’s disease. Am J Dermatopathol. 2005;27:185-188.
  4. Lloyd J, Flanagan AM. Mammary and extramammary Paget’s disease.J Clin Pathol. 2000;53:742-749.
  5. Sawada Y, Bito T, Kabashima R, et al. Ectopic extramammary Paget’s disease: case report and literature review. Acta Derm Venereol. 2010;90:502-505.
  6. Abe S, Kabashima K, Nishio D, et al. Quadruple extramammary Paget’s disease. Acta Derm Venereol. 2007;87:80-81.
  7. Kanitakis J. Mammary and extramammary Paget’s disease. J Eur Acad Dermatol Venereol. 2007;21:581-590.
  8. Goldblum JR, Hart WR. Vulvar Paget’s disease: a clinicopathologic and immunohistochemical study of 19 cases. Am J Surg Pathol. 1997;21:1178-1187.
  9. Goldblum JR, Hart WR. Perianal Paget’s disease: a histologic and immunohistochemical study of 11 cases with and without associated rectal adenocarcinoma. Am J Surg Pathol. 1998;22:170-179.
  10. Shepherd V, Davidson EJ, Davies‐Humphreys J. Extramammary Paget’s disease. BJOG. 2005;112:273-279.
  11. Chanda JJ. Extramammary Paget’s disease: prognosis and relationship to internal malignancy. J Am Acad Dermatol. 1985;13:1009-1014.
  12. Besa P, Rich TA, Delclos L, et al. Extramammary Paget’s disease of the perineal skin: role of radiotherapy. Int J Radiat Oncol Biol Phys. 1992;24:73-78.
  13. Fanning J, Lambert HC, Hale TM, et al. Paget’s disease of the vulva: prevalence of associated vulvar adenocarcinoma, invasive Paget’s disease, and recurrence after surgical excision. Am J Obstet Gynecol. 1999;180:24-27.
  14. Parker LP, Parker JR, Bodurka-Bevers D, et al. Paget’s disease of the vulva: pathology, pattern of involvement, and prognosis. Gynecol Oncol. 2000;77:183-189.
  15. Marchesa P, Fazio VW, Oliart S, et al. Long-term outcome of patients with perianal Paget’s disease. Ann Surg Oncol. 1997;4:475-480.
References
  1. Mazoujian G, Pinkus GS, Haagensen DE Jr. Extramammary Paget’s disease—evidence for an apocrine origin: an immunoperoxidase study of gross cystic disease fluid protein-15, carcinoembryonic antigen, and keratin proteins. Am J Surg Pathol. 1984;8:43-50.
  2. Saida T, Iwata M. “Ectopic” extramammary Paget’s disease affecting the lower anterior aspect of the chest. J Am Acad Dermatol. 1987;17(5, pt 2):910-913.
  3. Willman JH, Golitz LE, Fitzpatrick JE. Vulvar clear cells of Toker: precursors of extramammary Paget’s disease. Am J Dermatopathol. 2005;27:185-188.
  4. Lloyd J, Flanagan AM. Mammary and extramammary Paget’s disease.J Clin Pathol. 2000;53:742-749.
  5. Sawada Y, Bito T, Kabashima R, et al. Ectopic extramammary Paget’s disease: case report and literature review. Acta Derm Venereol. 2010;90:502-505.
  6. Abe S, Kabashima K, Nishio D, et al. Quadruple extramammary Paget’s disease. Acta Derm Venereol. 2007;87:80-81.
  7. Kanitakis J. Mammary and extramammary Paget’s disease. J Eur Acad Dermatol Venereol. 2007;21:581-590.
  8. Goldblum JR, Hart WR. Vulvar Paget’s disease: a clinicopathologic and immunohistochemical study of 19 cases. Am J Surg Pathol. 1997;21:1178-1187.
  9. Goldblum JR, Hart WR. Perianal Paget’s disease: a histologic and immunohistochemical study of 11 cases with and without associated rectal adenocarcinoma. Am J Surg Pathol. 1998;22:170-179.
  10. Shepherd V, Davidson EJ, Davies‐Humphreys J. Extramammary Paget’s disease. BJOG. 2005;112:273-279.
  11. Chanda JJ. Extramammary Paget’s disease: prognosis and relationship to internal malignancy. J Am Acad Dermatol. 1985;13:1009-1014.
  12. Besa P, Rich TA, Delclos L, et al. Extramammary Paget’s disease of the perineal skin: role of radiotherapy. Int J Radiat Oncol Biol Phys. 1992;24:73-78.
  13. Fanning J, Lambert HC, Hale TM, et al. Paget’s disease of the vulva: prevalence of associated vulvar adenocarcinoma, invasive Paget’s disease, and recurrence after surgical excision. Am J Obstet Gynecol. 1999;180:24-27.
  14. Parker LP, Parker JR, Bodurka-Bevers D, et al. Paget’s disease of the vulva: pathology, pattern of involvement, and prognosis. Gynecol Oncol. 2000;77:183-189.
  15. Marchesa P, Fazio VW, Oliart S, et al. Long-term outcome of patients with perianal Paget’s disease. Ann Surg Oncol. 1997;4:475-480.
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  • Ectopic extramammary Paget disease (EMPD) is a rare presentation of EMPD that is histologically identical to EMPD.
  • Ectopic EMPD can be associated with underlying malignancy and therefore warrants a thorough workup.
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Checkpoint inhibitor shows promise in advanced squamous-cell carcinoma

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An immune checkpoint inhibitor that targets the PD-1 receptor has shown “robust” efficacy among patients with advanced cutaneous squamous-cell carcinoma, according to researchers.

A combined phase 1/phase 2 study, published in the New England Journal of Medicine and presented simultaneously at the annual meeting of the American Society of Clinical Oncology, looked at the effect of monoclonal antibody cemiplimab in an expansion cohort of 26 patients with locally-advanced or metastatic cutaneous squamous-cell carcinoma who were not eligible for surgery. The phase 2 component involved 59 patients with metastatic disease.

Patients were treated with intravenous cemiplimab every 2 weeks for 48 weeks in the phase 1 study, and up to 96 weeks – or until unacceptable toxicity or disease progression – in the phase 2 study.

In the phase 1 study, researchers saw a response rate of 50% and a 65% rate of durable disease control, after a median follow-up of 11 months (1.1-17). The median time to response was 2.3 months, and more than half the patients (54%) who showed a response maintained that response past 6 months.

In the phase 2 study in patients with metastatic disease, 47% responded to the treatment – 24 patients showed a partial response and 4 showed a complete response. Of those who responded, 61% showed durable disease control after a median follow-up of 7.9 months.

The median time to response in this group of patients was 1.9 months, and 57% of those who did respond still showed a response at 6 months. However neither median progression-free survival nor median overall survival had been reached at the point of data cut-off.

The treatment showed similar effects in patients with regional and distant metastatic disease.

Advanced cutaneous squamous-cell carcinoma was thought to be an ideal target for immunotherapy because the high mutation burden in the tumor meant it would be sensitive to effector T cell attack, wrote Michael R. Migden, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his coauthors.

 

 


“In addition, the dramatically increased risk of cutaneous squamous-cell carcinoma among people with immunosuppression pointed to an important role for immune surveillance with this cancer,” the authors wrote.

In the phase 2 study, 29% of patients experienced a serious adverse event – including two cases of pneumonitis – and three patients (5%) discontinued treatment. There were three deaths due to adverse events: One patient died from pneumonia complications, one died in his sleep, and one patient died following hypercalcemia and deep vein thrombosis.

Aside from these, most adverse events were grade 1 or 2. Around one-quarter of patients experienced diarrhea (27%) or fatigue (24%), while the other most common adverse events were nausea (17%), constipation (15%) and rash (15%). The authors noted that these adverse events were similar to those seen in other PD-1 inhibitors.

“Our results are consistent with an emerging theme regarding the high efficacy of immune checkpoint blockade for the treatment of hypermutated cancers, since the mutation burden of cutaneous squamous-cell carcinoma is similar to that reported for advanced solid tumors with microsatellite instability,” the authors wrote.
 

 

Cemiplimab is now being tested in a phase 2 trial in patients with advanced basal cell carcinoma.

The study was supported by Regeneron Pharmaceuticals and Sanofi. Eight authors declared funding from Regeneron to conduct the trial. Ten authors were employees of Regeneron. Fifteen authors also declared funding and payments from pharmaceutical companies outside the submitted work. Four had nothing to disclose.

SOURCE: Migden M et al. NEJM, 2018; June 4. doi: 10.1056/NEJMoa1805131.

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An immune checkpoint inhibitor that targets the PD-1 receptor has shown “robust” efficacy among patients with advanced cutaneous squamous-cell carcinoma, according to researchers.

A combined phase 1/phase 2 study, published in the New England Journal of Medicine and presented simultaneously at the annual meeting of the American Society of Clinical Oncology, looked at the effect of monoclonal antibody cemiplimab in an expansion cohort of 26 patients with locally-advanced or metastatic cutaneous squamous-cell carcinoma who were not eligible for surgery. The phase 2 component involved 59 patients with metastatic disease.

Patients were treated with intravenous cemiplimab every 2 weeks for 48 weeks in the phase 1 study, and up to 96 weeks – or until unacceptable toxicity or disease progression – in the phase 2 study.

In the phase 1 study, researchers saw a response rate of 50% and a 65% rate of durable disease control, after a median follow-up of 11 months (1.1-17). The median time to response was 2.3 months, and more than half the patients (54%) who showed a response maintained that response past 6 months.

In the phase 2 study in patients with metastatic disease, 47% responded to the treatment – 24 patients showed a partial response and 4 showed a complete response. Of those who responded, 61% showed durable disease control after a median follow-up of 7.9 months.

The median time to response in this group of patients was 1.9 months, and 57% of those who did respond still showed a response at 6 months. However neither median progression-free survival nor median overall survival had been reached at the point of data cut-off.

The treatment showed similar effects in patients with regional and distant metastatic disease.

Advanced cutaneous squamous-cell carcinoma was thought to be an ideal target for immunotherapy because the high mutation burden in the tumor meant it would be sensitive to effector T cell attack, wrote Michael R. Migden, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his coauthors.

 

 


“In addition, the dramatically increased risk of cutaneous squamous-cell carcinoma among people with immunosuppression pointed to an important role for immune surveillance with this cancer,” the authors wrote.

In the phase 2 study, 29% of patients experienced a serious adverse event – including two cases of pneumonitis – and three patients (5%) discontinued treatment. There were three deaths due to adverse events: One patient died from pneumonia complications, one died in his sleep, and one patient died following hypercalcemia and deep vein thrombosis.

Aside from these, most adverse events were grade 1 or 2. Around one-quarter of patients experienced diarrhea (27%) or fatigue (24%), while the other most common adverse events were nausea (17%), constipation (15%) and rash (15%). The authors noted that these adverse events were similar to those seen in other PD-1 inhibitors.

“Our results are consistent with an emerging theme regarding the high efficacy of immune checkpoint blockade for the treatment of hypermutated cancers, since the mutation burden of cutaneous squamous-cell carcinoma is similar to that reported for advanced solid tumors with microsatellite instability,” the authors wrote.
 

 

Cemiplimab is now being tested in a phase 2 trial in patients with advanced basal cell carcinoma.

The study was supported by Regeneron Pharmaceuticals and Sanofi. Eight authors declared funding from Regeneron to conduct the trial. Ten authors were employees of Regeneron. Fifteen authors also declared funding and payments from pharmaceutical companies outside the submitted work. Four had nothing to disclose.

SOURCE: Migden M et al. NEJM, 2018; June 4. doi: 10.1056/NEJMoa1805131.

An immune checkpoint inhibitor that targets the PD-1 receptor has shown “robust” efficacy among patients with advanced cutaneous squamous-cell carcinoma, according to researchers.

A combined phase 1/phase 2 study, published in the New England Journal of Medicine and presented simultaneously at the annual meeting of the American Society of Clinical Oncology, looked at the effect of monoclonal antibody cemiplimab in an expansion cohort of 26 patients with locally-advanced or metastatic cutaneous squamous-cell carcinoma who were not eligible for surgery. The phase 2 component involved 59 patients with metastatic disease.

Patients were treated with intravenous cemiplimab every 2 weeks for 48 weeks in the phase 1 study, and up to 96 weeks – or until unacceptable toxicity or disease progression – in the phase 2 study.

In the phase 1 study, researchers saw a response rate of 50% and a 65% rate of durable disease control, after a median follow-up of 11 months (1.1-17). The median time to response was 2.3 months, and more than half the patients (54%) who showed a response maintained that response past 6 months.

In the phase 2 study in patients with metastatic disease, 47% responded to the treatment – 24 patients showed a partial response and 4 showed a complete response. Of those who responded, 61% showed durable disease control after a median follow-up of 7.9 months.

The median time to response in this group of patients was 1.9 months, and 57% of those who did respond still showed a response at 6 months. However neither median progression-free survival nor median overall survival had been reached at the point of data cut-off.

The treatment showed similar effects in patients with regional and distant metastatic disease.

Advanced cutaneous squamous-cell carcinoma was thought to be an ideal target for immunotherapy because the high mutation burden in the tumor meant it would be sensitive to effector T cell attack, wrote Michael R. Migden, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his coauthors.

 

 


“In addition, the dramatically increased risk of cutaneous squamous-cell carcinoma among people with immunosuppression pointed to an important role for immune surveillance with this cancer,” the authors wrote.

In the phase 2 study, 29% of patients experienced a serious adverse event – including two cases of pneumonitis – and three patients (5%) discontinued treatment. There were three deaths due to adverse events: One patient died from pneumonia complications, one died in his sleep, and one patient died following hypercalcemia and deep vein thrombosis.

Aside from these, most adverse events were grade 1 or 2. Around one-quarter of patients experienced diarrhea (27%) or fatigue (24%), while the other most common adverse events were nausea (17%), constipation (15%) and rash (15%). The authors noted that these adverse events were similar to those seen in other PD-1 inhibitors.

“Our results are consistent with an emerging theme regarding the high efficacy of immune checkpoint blockade for the treatment of hypermutated cancers, since the mutation burden of cutaneous squamous-cell carcinoma is similar to that reported for advanced solid tumors with microsatellite instability,” the authors wrote.
 

 

Cemiplimab is now being tested in a phase 2 trial in patients with advanced basal cell carcinoma.

The study was supported by Regeneron Pharmaceuticals and Sanofi. Eight authors declared funding from Regeneron to conduct the trial. Ten authors were employees of Regeneron. Fifteen authors also declared funding and payments from pharmaceutical companies outside the submitted work. Four had nothing to disclose.

SOURCE: Migden M et al. NEJM, 2018; June 4. doi: 10.1056/NEJMoa1805131.

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Key clinical point: PD-1 inhibitor cemiplimab shows significant response in advanced squamous-cell carcinoma.

Major finding: Around half of patients with advanced squamous-cell carcinoma responded to checkpoint inhibitor cemiplimab.

Study details: Phase 1 expanded cohort study of 26 patients with advanced cutaneous squamous-cell carcinoma and phase 2 study of 59 patients with metastatic squamous-cell carcinoma.

Disclosures: The study was supported by Regeneron Pharmaceuticals and Sanofi. Eight authors declared funding from Regeneron to conduct the trial. Ten authors were employees of Regeneron. Fifteen authors declared funding and payments from pharmaceutical companies outside the submitted work. Four had nothing to disclose.

Source: Migden M et al. N Engl J Med. 2018 June 4. doi: 10.1056/NEJMoa1805131.

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Psoriasis therapy with biologics not linked to increased cancer risk

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Biologic treatments were not associated with an increased risk of cancer among patients with psoriasis in the medium term, in a study that analyzed data from patient registries.

“Cumulative length of exposure to biologics was not associated with the risk of developing cancers, even after controlling for the effect of age, gender, location,” as well as for previous exposure to methotrexate, cyclosporine, and phototherapy; duration of psoriasis; and comorbidities, reported Ignacio García-Doval, MD, of the Fundación Academia Española de Dermatología y Venereología, Madrid, and his associates.

Christine Langer-p?schel/Thinkstock
Data from four studies in Psonet from Israel, Italy, Spain, and the United Kingdom were analyzed, with each cancer case matched with up to four cancer-free controls in each cohort. Exposure to biologic therapies, methotrexate, and cyclosporine were calculated as cumulative years of exposure, as were other expected confounders such as duration of psoriasis, length of exposure to phototherapy, and the modified Charlson Comorbidity Index. There were data on 579 cancer cases and 2,671 matched controls; this included 41 cases of squamous cell carcinoma and 108 cases of basal cell carcinoma. Psonet is a surveillance network in Europe that is monitoring the longterm effectiveness and safety of systemic agents in patients with psoriasis.



The pooled adjusted odds ratio of cancer per year of biologic exposure was 1.02 (95% confidence interval, 0.92-1.13), demonstrating no significantly increased risk of cancer per cumulative year of biologic exposure for psoriasis therapy, Dr. García-Doval and his associates reported in the study, published in the British Journal of Dermatology. This was true even when broken down within the registries for comparison, and when analyzed by type of cancers, such as squamous cell carcinoma and basal cell carcinoma.

A limitation of the study was inadequate power to detect and compare risk between individual biologics, they said. Also, “as our data describe limited follow-up and latencies, it is still possible that a risk after longer periods of exposure and latencies exists.”

Most of the authors had numerous financial disclosures related to pharmaceutical companies. Psonet was supported with funds from the European Association of Venereology and Dermatology and the Italian Drug Agency. Funding for the individual registries includes support from pharmaceutical companies.

SOURCE: García-Doval I et al. Br J Dermatol. 2018 May 3. doi: 10.1111/bjd.16715.

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Biologic treatments were not associated with an increased risk of cancer among patients with psoriasis in the medium term, in a study that analyzed data from patient registries.

“Cumulative length of exposure to biologics was not associated with the risk of developing cancers, even after controlling for the effect of age, gender, location,” as well as for previous exposure to methotrexate, cyclosporine, and phototherapy; duration of psoriasis; and comorbidities, reported Ignacio García-Doval, MD, of the Fundación Academia Española de Dermatología y Venereología, Madrid, and his associates.

Christine Langer-p?schel/Thinkstock
Data from four studies in Psonet from Israel, Italy, Spain, and the United Kingdom were analyzed, with each cancer case matched with up to four cancer-free controls in each cohort. Exposure to biologic therapies, methotrexate, and cyclosporine were calculated as cumulative years of exposure, as were other expected confounders such as duration of psoriasis, length of exposure to phototherapy, and the modified Charlson Comorbidity Index. There were data on 579 cancer cases and 2,671 matched controls; this included 41 cases of squamous cell carcinoma and 108 cases of basal cell carcinoma. Psonet is a surveillance network in Europe that is monitoring the longterm effectiveness and safety of systemic agents in patients with psoriasis.



The pooled adjusted odds ratio of cancer per year of biologic exposure was 1.02 (95% confidence interval, 0.92-1.13), demonstrating no significantly increased risk of cancer per cumulative year of biologic exposure for psoriasis therapy, Dr. García-Doval and his associates reported in the study, published in the British Journal of Dermatology. This was true even when broken down within the registries for comparison, and when analyzed by type of cancers, such as squamous cell carcinoma and basal cell carcinoma.

A limitation of the study was inadequate power to detect and compare risk between individual biologics, they said. Also, “as our data describe limited follow-up and latencies, it is still possible that a risk after longer periods of exposure and latencies exists.”

Most of the authors had numerous financial disclosures related to pharmaceutical companies. Psonet was supported with funds from the European Association of Venereology and Dermatology and the Italian Drug Agency. Funding for the individual registries includes support from pharmaceutical companies.

SOURCE: García-Doval I et al. Br J Dermatol. 2018 May 3. doi: 10.1111/bjd.16715.

 

Biologic treatments were not associated with an increased risk of cancer among patients with psoriasis in the medium term, in a study that analyzed data from patient registries.

“Cumulative length of exposure to biologics was not associated with the risk of developing cancers, even after controlling for the effect of age, gender, location,” as well as for previous exposure to methotrexate, cyclosporine, and phototherapy; duration of psoriasis; and comorbidities, reported Ignacio García-Doval, MD, of the Fundación Academia Española de Dermatología y Venereología, Madrid, and his associates.

Christine Langer-p?schel/Thinkstock
Data from four studies in Psonet from Israel, Italy, Spain, and the United Kingdom were analyzed, with each cancer case matched with up to four cancer-free controls in each cohort. Exposure to biologic therapies, methotrexate, and cyclosporine were calculated as cumulative years of exposure, as were other expected confounders such as duration of psoriasis, length of exposure to phototherapy, and the modified Charlson Comorbidity Index. There were data on 579 cancer cases and 2,671 matched controls; this included 41 cases of squamous cell carcinoma and 108 cases of basal cell carcinoma. Psonet is a surveillance network in Europe that is monitoring the longterm effectiveness and safety of systemic agents in patients with psoriasis.



The pooled adjusted odds ratio of cancer per year of biologic exposure was 1.02 (95% confidence interval, 0.92-1.13), demonstrating no significantly increased risk of cancer per cumulative year of biologic exposure for psoriasis therapy, Dr. García-Doval and his associates reported in the study, published in the British Journal of Dermatology. This was true even when broken down within the registries for comparison, and when analyzed by type of cancers, such as squamous cell carcinoma and basal cell carcinoma.

A limitation of the study was inadequate power to detect and compare risk between individual biologics, they said. Also, “as our data describe limited follow-up and latencies, it is still possible that a risk after longer periods of exposure and latencies exists.”

Most of the authors had numerous financial disclosures related to pharmaceutical companies. Psonet was supported with funds from the European Association of Venereology and Dermatology and the Italian Drug Agency. Funding for the individual registries includes support from pharmaceutical companies.

SOURCE: García-Doval I et al. Br J Dermatol. 2018 May 3. doi: 10.1111/bjd.16715.

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FROM THE BRITISH JOURNAL OF DERMATOLOGY

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Key clinical point: There was no significantly increased risk of cancer per cumulative year of exposure to biologics for psoriasis treatment.

Major finding: The pooled adjusted odds ratio of cancer per year of biologic exposure was 1.02.

Study details: Patient data were drawn from four national databases within Psonet, which included 579 cancer cases and 2,671 matched controls.

Disclosures: Most of the authors had numerous financial disclosures related to pharmaceutical companies. Psonet was supported with funds from the European Association of Venereology and Dermatology and the Italian Drug Agency. Funding for the individual registries includes support from pharmaceutical companies.

Source: García-Doval I et al. Br J Dermatol. 2018 May 3. doi: 10.1111/bjd.16715.

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Regular skin exams reduced advanced KCs in posttransplant patients

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– Annual skin exams reduced the rate of advanced keratinocyte carcinoma (KC) after solid organ transplant by 34%, according to a review of 10,198 transplant patients in Ontario, Canada.

Transplant patients have a far higher risk of KC than the general public because of immunosuppression: A quarter of patients are affected within 5 years. Transplant guidelines have recommended annual skin exams.

M. Alexander Otto/MDedge News
Dr. An-Wen Chan
But just 2.1% of the patients in the review had annual exams, and less than half saw a dermatologist even once during an average of 5 years of follow-up.

Other studies have reported adherence rates of up to 50%, but the numbers were based largely on patient self-report. Instead, the Ontario study used billing codes and other administrative data to get an idea of how many patients actually followed through.

“I would be surprised if other jurisdictions have significantly better rates of adherence,” said lead investigator An-Wen Chan, MD, of the division of dermatology at the University of Toronto and director of a transplant dermatology clinic at the University Health Network.

Part of the problem is that there’s just not a lot of evidence that annual screenings improve KC outcomes, he noted.

To help plug that evidence gap, Dr. Chan and his team reviewed transplant cases in Ontario going back to the mid-1990s; 62% of the patients had kidney transplants, 24% had liver transplants, and the rest had heart or lung transplants. The patients were all aged over 18 years; 60% were white, 15% Asian, 4% black, and the rest unknown. About two-thirds were men.
 

 


Adherence to annual dermatology checkups at least 75% of the time was associated with a marked reduction in the development of advanced KC, defined as lesions greater than 2 cm and requiring reconstruction and lymphadenectomy (adjusted hazard ratio, 0.66; 95% CI, 0.48-0.92).

Increasing age at transplant, white race, male sex, and past history of skin cancer were among the factors that were associated with increased risk. There was a trend toward increased risk with liver, lung, and heart transplants, as opposed to kidney transplants. Results were adjusted for demographic, transplant, and other variables.

In short, “adherence to annual dermatology assessments ... reduced KC-related morbidity and death. The highest risk patients were not necessarily the ones that saw their dermatologist annually,” Dr. Chan said.

Rates of adherence varied across transplant sites. It’s probably less of a problem at the University of Toronto, where Dr. Chan is embedded with the transplant team and where he can educate patients and providers on the importance of annual screening and help ensure that it’s done.
 

 


“We have a rigorous skin referral policy in place and really target transplant patients to be seen within a year. Having a dermatologist dedicated to transplant dermatology really helps,” he said. The next step is to define the optimal frequency of posttransplant skin cancer screening and to address barriers to screening.

There was no industry funding for the work, and Dr. Chan had no relevant disclosures.

SOURCE: Chan A et al. IID 2018, Abstract 522.

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– Annual skin exams reduced the rate of advanced keratinocyte carcinoma (KC) after solid organ transplant by 34%, according to a review of 10,198 transplant patients in Ontario, Canada.

Transplant patients have a far higher risk of KC than the general public because of immunosuppression: A quarter of patients are affected within 5 years. Transplant guidelines have recommended annual skin exams.

M. Alexander Otto/MDedge News
Dr. An-Wen Chan
But just 2.1% of the patients in the review had annual exams, and less than half saw a dermatologist even once during an average of 5 years of follow-up.

Other studies have reported adherence rates of up to 50%, but the numbers were based largely on patient self-report. Instead, the Ontario study used billing codes and other administrative data to get an idea of how many patients actually followed through.

“I would be surprised if other jurisdictions have significantly better rates of adherence,” said lead investigator An-Wen Chan, MD, of the division of dermatology at the University of Toronto and director of a transplant dermatology clinic at the University Health Network.

Part of the problem is that there’s just not a lot of evidence that annual screenings improve KC outcomes, he noted.

To help plug that evidence gap, Dr. Chan and his team reviewed transplant cases in Ontario going back to the mid-1990s; 62% of the patients had kidney transplants, 24% had liver transplants, and the rest had heart or lung transplants. The patients were all aged over 18 years; 60% were white, 15% Asian, 4% black, and the rest unknown. About two-thirds were men.
 

 


Adherence to annual dermatology checkups at least 75% of the time was associated with a marked reduction in the development of advanced KC, defined as lesions greater than 2 cm and requiring reconstruction and lymphadenectomy (adjusted hazard ratio, 0.66; 95% CI, 0.48-0.92).

Increasing age at transplant, white race, male sex, and past history of skin cancer were among the factors that were associated with increased risk. There was a trend toward increased risk with liver, lung, and heart transplants, as opposed to kidney transplants. Results were adjusted for demographic, transplant, and other variables.

In short, “adherence to annual dermatology assessments ... reduced KC-related morbidity and death. The highest risk patients were not necessarily the ones that saw their dermatologist annually,” Dr. Chan said.

Rates of adherence varied across transplant sites. It’s probably less of a problem at the University of Toronto, where Dr. Chan is embedded with the transplant team and where he can educate patients and providers on the importance of annual screening and help ensure that it’s done.
 

 


“We have a rigorous skin referral policy in place and really target transplant patients to be seen within a year. Having a dermatologist dedicated to transplant dermatology really helps,” he said. The next step is to define the optimal frequency of posttransplant skin cancer screening and to address barriers to screening.

There was no industry funding for the work, and Dr. Chan had no relevant disclosures.

SOURCE: Chan A et al. IID 2018, Abstract 522.

 

– Annual skin exams reduced the rate of advanced keratinocyte carcinoma (KC) after solid organ transplant by 34%, according to a review of 10,198 transplant patients in Ontario, Canada.

Transplant patients have a far higher risk of KC than the general public because of immunosuppression: A quarter of patients are affected within 5 years. Transplant guidelines have recommended annual skin exams.

M. Alexander Otto/MDedge News
Dr. An-Wen Chan
But just 2.1% of the patients in the review had annual exams, and less than half saw a dermatologist even once during an average of 5 years of follow-up.

Other studies have reported adherence rates of up to 50%, but the numbers were based largely on patient self-report. Instead, the Ontario study used billing codes and other administrative data to get an idea of how many patients actually followed through.

“I would be surprised if other jurisdictions have significantly better rates of adherence,” said lead investigator An-Wen Chan, MD, of the division of dermatology at the University of Toronto and director of a transplant dermatology clinic at the University Health Network.

Part of the problem is that there’s just not a lot of evidence that annual screenings improve KC outcomes, he noted.

To help plug that evidence gap, Dr. Chan and his team reviewed transplant cases in Ontario going back to the mid-1990s; 62% of the patients had kidney transplants, 24% had liver transplants, and the rest had heart or lung transplants. The patients were all aged over 18 years; 60% were white, 15% Asian, 4% black, and the rest unknown. About two-thirds were men.
 

 


Adherence to annual dermatology checkups at least 75% of the time was associated with a marked reduction in the development of advanced KC, defined as lesions greater than 2 cm and requiring reconstruction and lymphadenectomy (adjusted hazard ratio, 0.66; 95% CI, 0.48-0.92).

Increasing age at transplant, white race, male sex, and past history of skin cancer were among the factors that were associated with increased risk. There was a trend toward increased risk with liver, lung, and heart transplants, as opposed to kidney transplants. Results were adjusted for demographic, transplant, and other variables.

In short, “adherence to annual dermatology assessments ... reduced KC-related morbidity and death. The highest risk patients were not necessarily the ones that saw their dermatologist annually,” Dr. Chan said.

Rates of adherence varied across transplant sites. It’s probably less of a problem at the University of Toronto, where Dr. Chan is embedded with the transplant team and where he can educate patients and providers on the importance of annual screening and help ensure that it’s done.
 

 


“We have a rigorous skin referral policy in place and really target transplant patients to be seen within a year. Having a dermatologist dedicated to transplant dermatology really helps,” he said. The next step is to define the optimal frequency of posttransplant skin cancer screening and to address barriers to screening.

There was no industry funding for the work, and Dr. Chan had no relevant disclosures.

SOURCE: Chan A et al. IID 2018, Abstract 522.

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Key clinical point: Transplant patients need help to ensure they get annual dermatology checkups.

Major finding: Just 2.1% of the patients in the review had annual exams, and less than half saw a dermatologist even once during an average of 5-years follow-up.

Study details: A review of 10,198 solid organ transplant cases.

Disclosures: There was no industry funding, and the lead investigator had no disclosures.

Source: Chan A et al. IID 2018, Abstract 522

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Keratinocyte carcinoma added no VTE risk in cohort study

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Keratinocyte carcinoma patients were not at increased risk of venous thromboembolism (VTE) compared with controls in a recent population-based study of more than 700,000 insurance claims, according to investigators.

That finding suggests that clinicians should more carefully consider use of prophylactic anticoagulation in patients with squamous or basal cell carcinoma, said Shannon F. Rudy, MD, of Stanford (Calif.) University, and her coinvestigators. The report was published in JAMA Facial Plastic Surgery.

“While chemoprophylaxis is important when treating patients with an increased risk of VTE, it is equally important that such agents are not administered inappropriately because they can lead to perioperative complications,” wrote Dr. Rudy and her coauthors.

In current practice, patients with keratinocyte carcinomas (i.e., squamous cell carcinoma or basal cell carcinoma) are routinely classified at higher risk of thromboembolic events because of their diagnosis. That subsequently impacts treatment decisions regarding perioperative anticoagulation, the investigators noted.

Their population-based, retrospective analysis was based on insurance claims made between Jan. 1, 2007, and Dec. 31, 2014. The investigators identified three cohorts: 417,839 keratinocyte carcinoma patients, 314,736 controls at average risk of VTE, and 7,671 individuals considered to be at high risk of VTE because of a prior diagnosis of acute myeloid leukemia or pancreatic cancer.

In the keratinocyte carcinoma cohort, investigators found VTE risk was lower compared with the high-risk cohort in univariable analysis, multivariable analysis, and after matching patient characteristics and risk factors (odds ratio, 0.52; 95% confidence interval, 0.35-0.78; P = .001).

Compared with the control cohort, the keratinocyte carcinoma cohort had a higher risk of VTE in univariable analysis; however, the risk was lower in multivariable analysis, and not statistically different when patient characteristics and risk factors were matched (OR, 0.95; 95% CI, 0.89-1.01; P = .08).

 

 


“These results argue for careful consideration of risk assessment models, such as the Caprini score, when a surgical procedure is planned for a patient with keratinocyte carcinoma and no other risk factors for VTE in order to limit unnecessary exposure to the potential risk of VTE chemoprophylaxis,” Dr. Rudy and her coauthors wrote.

The Caprini score is a commonly used, validated, VTE risk stratification model that assigns points to specific risk factors, producing a score that can be used to decide on prophylaxis regimens, they noted.

A present or previous cancer diagnosis is worth 2 points in the Caprini system, which would put a patient at the upper end of the “low risk” category, while one additional risk factor such as planned minor surgery would indicate moderate risk.

“Recently, Caprini has begun to exclude basal cell carcinoma from this calculation, but no reference to evidence is given,” the researchers wrote.

Dr. Rudy and her coauthors had no conflicts of interest to disclose.

SOURCE: Rudy SF et al. JAMA Facial Plast Surg. 2018 May 24. doi: 10.1001/jamafacial.2018.0331.

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Keratinocyte carcinoma patients were not at increased risk of venous thromboembolism (VTE) compared with controls in a recent population-based study of more than 700,000 insurance claims, according to investigators.

That finding suggests that clinicians should more carefully consider use of prophylactic anticoagulation in patients with squamous or basal cell carcinoma, said Shannon F. Rudy, MD, of Stanford (Calif.) University, and her coinvestigators. The report was published in JAMA Facial Plastic Surgery.

“While chemoprophylaxis is important when treating patients with an increased risk of VTE, it is equally important that such agents are not administered inappropriately because they can lead to perioperative complications,” wrote Dr. Rudy and her coauthors.

In current practice, patients with keratinocyte carcinomas (i.e., squamous cell carcinoma or basal cell carcinoma) are routinely classified at higher risk of thromboembolic events because of their diagnosis. That subsequently impacts treatment decisions regarding perioperative anticoagulation, the investigators noted.

Their population-based, retrospective analysis was based on insurance claims made between Jan. 1, 2007, and Dec. 31, 2014. The investigators identified three cohorts: 417,839 keratinocyte carcinoma patients, 314,736 controls at average risk of VTE, and 7,671 individuals considered to be at high risk of VTE because of a prior diagnosis of acute myeloid leukemia or pancreatic cancer.

In the keratinocyte carcinoma cohort, investigators found VTE risk was lower compared with the high-risk cohort in univariable analysis, multivariable analysis, and after matching patient characteristics and risk factors (odds ratio, 0.52; 95% confidence interval, 0.35-0.78; P = .001).

Compared with the control cohort, the keratinocyte carcinoma cohort had a higher risk of VTE in univariable analysis; however, the risk was lower in multivariable analysis, and not statistically different when patient characteristics and risk factors were matched (OR, 0.95; 95% CI, 0.89-1.01; P = .08).

 

 


“These results argue for careful consideration of risk assessment models, such as the Caprini score, when a surgical procedure is planned for a patient with keratinocyte carcinoma and no other risk factors for VTE in order to limit unnecessary exposure to the potential risk of VTE chemoprophylaxis,” Dr. Rudy and her coauthors wrote.

The Caprini score is a commonly used, validated, VTE risk stratification model that assigns points to specific risk factors, producing a score that can be used to decide on prophylaxis regimens, they noted.

A present or previous cancer diagnosis is worth 2 points in the Caprini system, which would put a patient at the upper end of the “low risk” category, while one additional risk factor such as planned minor surgery would indicate moderate risk.

“Recently, Caprini has begun to exclude basal cell carcinoma from this calculation, but no reference to evidence is given,” the researchers wrote.

Dr. Rudy and her coauthors had no conflicts of interest to disclose.

SOURCE: Rudy SF et al. JAMA Facial Plast Surg. 2018 May 24. doi: 10.1001/jamafacial.2018.0331.

 

Keratinocyte carcinoma patients were not at increased risk of venous thromboembolism (VTE) compared with controls in a recent population-based study of more than 700,000 insurance claims, according to investigators.

That finding suggests that clinicians should more carefully consider use of prophylactic anticoagulation in patients with squamous or basal cell carcinoma, said Shannon F. Rudy, MD, of Stanford (Calif.) University, and her coinvestigators. The report was published in JAMA Facial Plastic Surgery.

“While chemoprophylaxis is important when treating patients with an increased risk of VTE, it is equally important that such agents are not administered inappropriately because they can lead to perioperative complications,” wrote Dr. Rudy and her coauthors.

In current practice, patients with keratinocyte carcinomas (i.e., squamous cell carcinoma or basal cell carcinoma) are routinely classified at higher risk of thromboembolic events because of their diagnosis. That subsequently impacts treatment decisions regarding perioperative anticoagulation, the investigators noted.

Their population-based, retrospective analysis was based on insurance claims made between Jan. 1, 2007, and Dec. 31, 2014. The investigators identified three cohorts: 417,839 keratinocyte carcinoma patients, 314,736 controls at average risk of VTE, and 7,671 individuals considered to be at high risk of VTE because of a prior diagnosis of acute myeloid leukemia or pancreatic cancer.

In the keratinocyte carcinoma cohort, investigators found VTE risk was lower compared with the high-risk cohort in univariable analysis, multivariable analysis, and after matching patient characteristics and risk factors (odds ratio, 0.52; 95% confidence interval, 0.35-0.78; P = .001).

Compared with the control cohort, the keratinocyte carcinoma cohort had a higher risk of VTE in univariable analysis; however, the risk was lower in multivariable analysis, and not statistically different when patient characteristics and risk factors were matched (OR, 0.95; 95% CI, 0.89-1.01; P = .08).

 

 


“These results argue for careful consideration of risk assessment models, such as the Caprini score, when a surgical procedure is planned for a patient with keratinocyte carcinoma and no other risk factors for VTE in order to limit unnecessary exposure to the potential risk of VTE chemoprophylaxis,” Dr. Rudy and her coauthors wrote.

The Caprini score is a commonly used, validated, VTE risk stratification model that assigns points to specific risk factors, producing a score that can be used to decide on prophylaxis regimens, they noted.

A present or previous cancer diagnosis is worth 2 points in the Caprini system, which would put a patient at the upper end of the “low risk” category, while one additional risk factor such as planned minor surgery would indicate moderate risk.

“Recently, Caprini has begun to exclude basal cell carcinoma from this calculation, but no reference to evidence is given,” the researchers wrote.

Dr. Rudy and her coauthors had no conflicts of interest to disclose.

SOURCE: Rudy SF et al. JAMA Facial Plast Surg. 2018 May 24. doi: 10.1001/jamafacial.2018.0331.

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Key clinical point: Keratinocyte patients had no increased risk of venous thromboembolism (VTE) versus controls, suggesting the need to carefully consider whether prophylactic anticoagulation is needed at the time of surgery in these patients.

Major finding: Risk of VTE in the keratinocyte carcinoma cohort was not different compared with controls after adjustment for patient characteristics and risk factors (OR, 0.95; 95% CI, 0.89-1.01; P = .08).

Study details: A population-based retrospective analysis of insurance claims made between Jan. 1, 2007, and Dec. 31, 2014, including 417,839 keratinocyte carcinoma patients, 314,736 controls, and a high-risk cohort of 7,671 individuals.

Disclosures: The authors declared no conflicts of interest.

Source: Rudy SF et al. JAMA Facial Plast Surg. 2018 May 24. doi: 10.1001/jamafacial.2018.0331.

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