MDedge Dermatology

Anthony Rossi, MD, Assistant Attending Physician at Memorial Sloan Kettering Cancer Center, shares several updates in non-melanoma skin cancers emerging from the American Academy of Dermatology’s AAD VMX 2021 meeting.

With PD-1 inhibitors emerging as an immunotherapeutic option in this area, Dr. Rossi discusses a literature review that was conducted to compare the efficacy and safety of pembrolizumab, nivolumab, and cemiplimab in patients with advanced basal cell carcinoma or cutaneous squamous cell carcinoma.

Another review analyzed statin use as a predictor of more aggressive tumor characteristics in squamous cell carcinoma. Dr. Rossi shares that while there were no significant findings when examining the cohort as a whole, the male study population did see an elevated correlation between statin history and high-risk tumors.

Lastly, Dr. Rossi highlights an analysis of tumor burden in patients taking sonidegib 200 mg once daily as part of the 42-month BOLT study. Sonidegib demonstrated durable tumor response and substantial reduction in tumor burden, and safety and tolerability were consistent with earlier data.

--

Anthony Rossi, MD, Assistant Professor, Department of Dermatology, Weill Cornell Medical College; Assistant Attending Physician, Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY

Anthony Rossi, MD, has disclosed the following relevant financial relationships:

Serve(d) as a board member, director, officer, partner, employee, advisor, consultant, or trustee for: DAR Inc; American Society for Dermatologic Surgery Association.

Received research grant from: Regeneron; Biofrontera; Memorial Sloan Kettering Society; Skin Cancer Foundation.

Have a 5% or greater equity interest in: DAR Inc.

Received income in an amount equal to or greater than $250 from: Allergan; Regeneron; Evolus; Cutera; Biofrontera; Iam; DynaMed; Canfield; Merz.

Anthony Rossi, MD, Assistant Attending Physician at Memorial Sloan Kettering Cancer Center, shares several updates in non-melanoma skin cancers emerging from the American Academy of Dermatology’s AAD VMX 2021 meeting.

With PD-1 inhibitors emerging as an immunotherapeutic option in this area, Dr. Rossi discusses a literature review that was conducted to compare the efficacy and safety of pembrolizumab, nivolumab, and cemiplimab in patients with advanced basal cell carcinoma or cutaneous squamous cell carcinoma.

Another review analyzed statin use as a predictor of more aggressive tumor characteristics in squamous cell carcinoma. Dr. Rossi shares that while there were no significant findings when examining the cohort as a whole, the male study population did see an elevated correlation between statin history and high-risk tumors.

Lastly, Dr. Rossi highlights an analysis of tumor burden in patients taking sonidegib 200 mg once daily as part of the 42-month BOLT study. Sonidegib demonstrated durable tumor response and substantial reduction in tumor burden, and safety and tolerability were consistent with earlier data.

--

Anthony Rossi, MD, Assistant Professor, Department of Dermatology, Weill Cornell Medical College; Assistant Attending Physician, Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY

Anthony Rossi, MD, has disclosed the following relevant financial relationships:

Serve(d) as a board member, director, officer, partner, employee, advisor, consultant, or trustee for: DAR Inc; American Society for Dermatologic Surgery Association.

Received research grant from: Regeneron; Biofrontera; Memorial Sloan Kettering Society; Skin Cancer Foundation.

Have a 5% or greater equity interest in: DAR Inc.

Received income in an amount equal to or greater than $250 from: Allergan; Regeneron; Evolus; Cutera; Biofrontera; Iam; DynaMed; Canfield; Merz.

Anthony Rossi, MD, Assistant Attending Physician at Memorial Sloan Kettering Cancer Center, shares several updates in non-melanoma skin cancers emerging from the American Academy of Dermatology’s AAD VMX 2021 meeting.

With PD-1 inhibitors emerging as an immunotherapeutic option in this area, Dr. Rossi discusses a literature review that was conducted to compare the efficacy and safety of pembrolizumab, nivolumab, and cemiplimab in patients with advanced basal cell carcinoma or cutaneous squamous cell carcinoma.

Another review analyzed statin use as a predictor of more aggressive tumor characteristics in squamous cell carcinoma. Dr. Rossi shares that while there were no significant findings when examining the cohort as a whole, the male study population did see an elevated correlation between statin history and high-risk tumors.

Lastly, Dr. Rossi highlights an analysis of tumor burden in patients taking sonidegib 200 mg once daily as part of the 42-month BOLT study. Sonidegib demonstrated durable tumor response and substantial reduction in tumor burden, and safety and tolerability were consistent with earlier data.

--

Anthony Rossi, MD, Assistant Professor, Department of Dermatology, Weill Cornell Medical College; Assistant Attending Physician, Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY

Anthony Rossi, MD, has disclosed the following relevant financial relationships:

Serve(d) as a board member, director, officer, partner, employee, advisor, consultant, or trustee for: DAR Inc; American Society for Dermatologic Surgery Association.

Received research grant from: Regeneron; Biofrontera; Memorial Sloan Kettering Society; Skin Cancer Foundation.

Have a 5% or greater equity interest in: DAR Inc.

Received income in an amount equal to or greater than $250 from: Allergan; Regeneron; Evolus; Cutera; Biofrontera; Iam; DynaMed; Canfield; Merz.

Key studies on psoriasis presented at the American Academy of Dermatology Virtual Meeting Experience (AAD VMX) 2021included data on new topical treatments and biological therapies.

Dr Steven Feldman, of Wake Forest School of Medicine, reviews trial data demonstrating the efficacy of a topical formulation of roflumilast, a phosphodiesterase type 4 (PDE-4) inhibitor previously used in oral systemic form to treat psoriasis.

He also discusses a meta-analysis of the efficacy of biologics favoring newer treatments, such as drugs targeting IL-17 and IL-23.

Dr Feldman reviews the results of two pivotal phase 3 trials presented at the meeting. The POETYK study examined deucravacitinib, a TYK2 inhibitor. In a head-to-head comparison, deucravacitinib was found to be more effective and better tolerated than apremilast in treating psoriasis. BE RADIANT, another head-to-head study, compared the IL-17 blockers bimekizumab and secukinumab. The year-long study favored bimekizumab, though it was associated with a higher risk for candidiasis.

Finally, Dr Feldman discusses the significance of a study showing that psoriasis patients have an approximately 20% higher risk for COVID-19 infection compared with a control group.

--

Steven R. Feldman, MD, PhD, Professor, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina

Steven R. Feldman, MD, PhD, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: AbbVie; Alvotech; Advance Medical; Almirall; Arena; Bristol-Myers Squibb; Caremark; Amgen; Celgene; Galderma Laboratories; Gerson Lehrman Group; Guidepoint Global; Helsinn; Janssen; Kikaku; Leo Pharma; Eli Lilly and Company; Merck; Mylan; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sienna; Sun Pharma; Suncare Research; Xenoport
Serve(d) as a speaker for: AbbVie; Amgen; Celgene; Janssen; Leo Pharma; Eli Lilly and Company; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sun Pharma
Receive(d) grant support from: AbbVie; Amgen; Celgene; Galderma Laboratories; Janssen; Eli Lilly and Company; Novartis; Pfizer; Regeneron; Sanofi
Receive(d) royalties from: Informa; UpToDate; Xlibris
Holds stock in: Causa Technologies; Medical Quality Enhancement Corporation
Serves as founder and chief technology officer for: Causa Technologies

Key studies on psoriasis presented at the American Academy of Dermatology Virtual Meeting Experience (AAD VMX) 2021included data on new topical treatments and biological therapies.

Dr Steven Feldman, of Wake Forest School of Medicine, reviews trial data demonstrating the efficacy of a topical formulation of roflumilast, a phosphodiesterase type 4 (PDE-4) inhibitor previously used in oral systemic form to treat psoriasis.

He also discusses a meta-analysis of the efficacy of biologics favoring newer treatments, such as drugs targeting IL-17 and IL-23.

Dr Feldman reviews the results of two pivotal phase 3 trials presented at the meeting. The POETYK study examined deucravacitinib, a TYK2 inhibitor. In a head-to-head comparison, deucravacitinib was found to be more effective and better tolerated than apremilast in treating psoriasis. BE RADIANT, another head-to-head study, compared the IL-17 blockers bimekizumab and secukinumab. The year-long study favored bimekizumab, though it was associated with a higher risk for candidiasis.

Finally, Dr Feldman discusses the significance of a study showing that psoriasis patients have an approximately 20% higher risk for COVID-19 infection compared with a control group.

--

Steven R. Feldman, MD, PhD, Professor, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina

Steven R. Feldman, MD, PhD, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: AbbVie; Alvotech; Advance Medical; Almirall; Arena; Bristol-Myers Squibb; Caremark; Amgen; Celgene; Galderma Laboratories; Gerson Lehrman Group; Guidepoint Global; Helsinn; Janssen; Kikaku; Leo Pharma; Eli Lilly and Company; Merck; Mylan; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sienna; Sun Pharma; Suncare Research; Xenoport
Serve(d) as a speaker for: AbbVie; Amgen; Celgene; Janssen; Leo Pharma; Eli Lilly and Company; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sun Pharma
Receive(d) grant support from: AbbVie; Amgen; Celgene; Galderma Laboratories; Janssen; Eli Lilly and Company; Novartis; Pfizer; Regeneron; Sanofi
Receive(d) royalties from: Informa; UpToDate; Xlibris
Holds stock in: Causa Technologies; Medical Quality Enhancement Corporation
Serves as founder and chief technology officer for: Causa Technologies

Key studies on psoriasis presented at the American Academy of Dermatology Virtual Meeting Experience (AAD VMX) 2021included data on new topical treatments and biological therapies.

Dr Steven Feldman, of Wake Forest School of Medicine, reviews trial data demonstrating the efficacy of a topical formulation of roflumilast, a phosphodiesterase type 4 (PDE-4) inhibitor previously used in oral systemic form to treat psoriasis.

He also discusses a meta-analysis of the efficacy of biologics favoring newer treatments, such as drugs targeting IL-17 and IL-23.

Dr Feldman reviews the results of two pivotal phase 3 trials presented at the meeting. The POETYK study examined deucravacitinib, a TYK2 inhibitor. In a head-to-head comparison, deucravacitinib was found to be more effective and better tolerated than apremilast in treating psoriasis. BE RADIANT, another head-to-head study, compared the IL-17 blockers bimekizumab and secukinumab. The year-long study favored bimekizumab, though it was associated with a higher risk for candidiasis.

Finally, Dr Feldman discusses the significance of a study showing that psoriasis patients have an approximately 20% higher risk for COVID-19 infection compared with a control group.

--

Steven R. Feldman, MD, PhD, Professor, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina

Steven R. Feldman, MD, PhD, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: AbbVie; Alvotech; Advance Medical; Almirall; Arena; Bristol-Myers Squibb; Caremark; Amgen; Celgene; Galderma Laboratories; Gerson Lehrman Group; Guidepoint Global; Helsinn; Janssen; Kikaku; Leo Pharma; Eli Lilly and Company; Merck; Mylan; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sienna; Sun Pharma; Suncare Research; Xenoport
Serve(d) as a speaker for: AbbVie; Amgen; Celgene; Janssen; Leo Pharma; Eli Lilly and Company; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sun Pharma
Receive(d) grant support from: AbbVie; Amgen; Celgene; Galderma Laboratories; Janssen; Eli Lilly and Company; Novartis; Pfizer; Regeneron; Sanofi
Receive(d) royalties from: Informa; UpToDate; Xlibris
Holds stock in: Causa Technologies; Medical Quality Enhancement Corporation
Serves as founder and chief technology officer for: Causa Technologies

People who are fully vaccinated against COVID-19 are no longer required to wear masks or physically distance, regardless of location or size of the gathering, the CDC announced on May 13.

“Anyone who is fully vaccinated can participate in indoor and outdoor activities, large or small, without wearing a mask or physically distancing,” CDC director Rochelle Walensky, MD, said at a press briefing. “We have all longed for this moment when we can get back to some sense of normalcy.

“This is an exciting and powerful moment,” she added, “It could only happen because of the work from so many who made sure we had the rapid administration of three safe and effective vaccines.”

Dr. Walensky cited three large studies on the effectiveness of COVID-19 vaccines against the original virus and its variants. One study from Israel found the vaccine to be 97% effective against symptomatic infection.

Those who are symptomatic should still wear masks, Dr. Walensky said, and those who are immunocompromised should talk to their doctors for further guidance. The CDC still advises travelers to wear masks while on airplanes or trains.

The COVID-19 death rates are now the lowest they have been since April 2020.

A version of this article first appeared on Medscape.com.

People who are fully vaccinated against COVID-19 are no longer required to wear masks or physically distance, regardless of location or size of the gathering, the CDC announced on May 13.

“Anyone who is fully vaccinated can participate in indoor and outdoor activities, large or small, without wearing a mask or physically distancing,” CDC director Rochelle Walensky, MD, said at a press briefing. “We have all longed for this moment when we can get back to some sense of normalcy.

“This is an exciting and powerful moment,” she added, “It could only happen because of the work from so many who made sure we had the rapid administration of three safe and effective vaccines.”

Dr. Walensky cited three large studies on the effectiveness of COVID-19 vaccines against the original virus and its variants. One study from Israel found the vaccine to be 97% effective against symptomatic infection.

Those who are symptomatic should still wear masks, Dr. Walensky said, and those who are immunocompromised should talk to their doctors for further guidance. The CDC still advises travelers to wear masks while on airplanes or trains.

The COVID-19 death rates are now the lowest they have been since April 2020.

A version of this article first appeared on Medscape.com.

People who are fully vaccinated against COVID-19 are no longer required to wear masks or physically distance, regardless of location or size of the gathering, the CDC announced on May 13.

“Anyone who is fully vaccinated can participate in indoor and outdoor activities, large or small, without wearing a mask or physically distancing,” CDC director Rochelle Walensky, MD, said at a press briefing. “We have all longed for this moment when we can get back to some sense of normalcy.

“This is an exciting and powerful moment,” she added, “It could only happen because of the work from so many who made sure we had the rapid administration of three safe and effective vaccines.”

Dr. Walensky cited three large studies on the effectiveness of COVID-19 vaccines against the original virus and its variants. One study from Israel found the vaccine to be 97% effective against symptomatic infection.

Those who are symptomatic should still wear masks, Dr. Walensky said, and those who are immunocompromised should talk to their doctors for further guidance. The CDC still advises travelers to wear masks while on airplanes or trains.

The COVID-19 death rates are now the lowest they have been since April 2020.

A version of this article first appeared on Medscape.com.

The history of a brownish to pink patch with color change and rapid growth within the first year combined with the exam findings, are suggestive of a tufted angioma, though the findings presented may be nonspecific.

A tufted angioma is a rare vascular tumor of infancy or early childhood, that is present at birth in approximately half of cases. It may initially present as a faint pink to brown plaque, but develops as a firm, red to violaceous nodule or plaque, usually with “lumpiness” or nodularity.^1-3 Lesions usually are infiltrative with indistinct borders. They are named for their histologic appearance, with lobules of capillaries which appear as “tufts” in the dermis and subdermis with “cannonball” appearance, and are considered to be on a spectrum with another vascular tumor called kaposiform hemangioendothelioma (KHE).⁴ These vascular tumors can trigger Kasabach-Merritt syndrome, a disease process in which vascular tumors trap platelets and clotting factors, resulting in a life-threatening thrombocytopenia and consumptive coagulopathy with a high risk of bleeding and high-output heart failure.⁵
 

What’s the differential diagnosis?

The differential diagnosis of tufted angioma includes other potentially large vascular lesions including infantile hemangioma, congenital hemangioma, port-wine birth marks (capillary malformations), hemangioendotheliomas, and rhabdomyosarcomas.

Infantile hemangiomas (IH) are common vascular tumors of infancy seen in 4%-5% of infants that are characterized by a growth and involution phase. Classically, lesions can be absent or minimally evident at birth, becoming noticeable within the first months of life with a rapid growth phase and typical progression to bright red papules, nodules, or plaques. Deeper hemangiomas may appear more skin colored on the surface with a bluish coloration underneath. They are usually more discreet, with relatively defined borders. Diagnosis is typically clinical and many IHs self-resolve, albeit with residual findings including skin atrophy, scarring, and telangiectasia. Observation or topical timolol are first-line treatment options for more superficial lesions while systemic propranolol is the treatment of choice for deeper IHs or those resulting in possible airway or vision compromise.

Congenital hemangiomas (CH) are another type of vascular growth characterized by a solitary erythematous to violaceous plaque or nodule present at birth with overlying telangiectasia. CHs can be subdivided into categories including rapidly involuting (RICH), partially involuting (PICH), and noninvoluting (NICH). Diagnosis is usually clinical and, depending on the subtype, treatment can involve watchful waiting (for RICHs) or more active intervention such as pulse dye laser or surgical resection (for PICHs or NICHs). The growing nature of this patient’s mass makes a diagnosis of CH unlikely.

Port-wine birth mark, also known as nevus flammeus, is a vascular malformation that appears at birth as a nonpalpable irregular erythematous to violaceous macular plaque. Port-wine stains may be isolated birthmarks, or associated with Sturge-Weber syndrome, complex vascular malformations, or soft-tissue overgrowth. Klippel-Trenauny syndrome (KTS) describes capillary-venous malformations with limb overgrowth, with or without lymphatic malformations, and many are associated with somatic mutations in the PIK3CA gene. While KTS could be considered in this patient, the nodular appearance with lumpy texture and rapid growth makes a vascular tumor more likely.

Rhabdomyosarcoma is a malignancy of skeletal muscle lineage and the most common soft tissue tumor in pediatrics. Cutaneous rhabdomyosarcomas present as erythematous nodules, markedly firm, often “fixed” to deep tissue. A rapidly growing atypical, firm tumor of infancy should raise the consideration of rhabdomyosarcoma and imaging and biopsy are appropriate for evaluation.
 

What should the evaluation and management of this patient be?

Initial workup should include a complete blood count with platelet count as well as coagulation studies including D-dimer, fibrinogen, prothrombin time, and activated partial thromboplastin time, to assess for any thrombocytopenia or coagulopathy.⁶ Ultrasound and/or MRI may also be performed to determine lesion extent. While typical MRI findings might be suggestive of a tufted angioma or hemangioendothelioma, biopsy for histologic examination is usually the approach to diagnosis, which will demonstrate stereotypic round lobules of capillaries in a “tufted” distribution.^2,7 Biopsy may be performed by a surgeon or dermatologist but bleeding at time of biopsy needs to be considered before moving forward with the procedure.

Tufted angiomas of early life may regress spontaneously, though lesions with symptoms, with functional significance, or associated with KHE may require therapy. Surgical excision is one option, but it may be difficult to execute given that these lesions often have poorly defined margins.¹ Other treatment choices include but are not limited to aspirin, systemic corticosteroids, vincristine, interferon-alpha, embolization, and sirolimus.⁸ No specific expert-directed consensus guidelines exist for these lesions, and suspicion of this lesion should prompt urgent referral to a pediatric dermatologist. Concern for Kasabach-Merritt syndrome should trigger immediate referral for rapid evaluation and management.

Complete blood count with platelet count and coagulation studies were normal in our patient. This infant underwent biopsy to confirm the diagnosis of tufted angioma and MRI to determine lesion extent. The lesion slowly involuted spontaneously without recurrence.
 

Mr. Haft is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. He is MS4 at the University of Rochester, N.Y. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Mr. Haft nor Dr. Eichenfield have any relevant financial disclosures.

References

1. Herron MD et al. Pediatr Dermatol. 2002;19(5):394-401.

2. Jones EW and Orkin M. J Am Acad Dermatol. 1989;20(2 Pt 1):214-25.

3. Wong SN and Tay YK. Pediatr Dermatol. 2002;19(5):388-93.

4. Croteau SE and Gupta D. Semin Cutan Med Surg. 2016;35(3):147-52.

5. Kelly M. Pediatr Clin North Am. 2010;57(5):1085-9.

6. Osio A et al. Arch Dermatol. 2010;146(7):758-63.

7. Padilla RS et al. Am J Dermatopathol. 1987;9(4):292-300.

8. Liu XH et al. Int J Cancer. 2016;139(7):1658-66.

The history of a brownish to pink patch with color change and rapid growth within the first year combined with the exam findings, are suggestive of a tufted angioma, though the findings presented may be nonspecific.

A tufted angioma is a rare vascular tumor of infancy or early childhood, that is present at birth in approximately half of cases. It may initially present as a faint pink to brown plaque, but develops as a firm, red to violaceous nodule or plaque, usually with “lumpiness” or nodularity.^1-3 Lesions usually are infiltrative with indistinct borders. They are named for their histologic appearance, with lobules of capillaries which appear as “tufts” in the dermis and subdermis with “cannonball” appearance, and are considered to be on a spectrum with another vascular tumor called kaposiform hemangioendothelioma (KHE).⁴ These vascular tumors can trigger Kasabach-Merritt syndrome, a disease process in which vascular tumors trap platelets and clotting factors, resulting in a life-threatening thrombocytopenia and consumptive coagulopathy with a high risk of bleeding and high-output heart failure.⁵
 

What’s the differential diagnosis?

The differential diagnosis of tufted angioma includes other potentially large vascular lesions including infantile hemangioma, congenital hemangioma, port-wine birth marks (capillary malformations), hemangioendotheliomas, and rhabdomyosarcomas.

Infantile hemangiomas (IH) are common vascular tumors of infancy seen in 4%-5% of infants that are characterized by a growth and involution phase. Classically, lesions can be absent or minimally evident at birth, becoming noticeable within the first months of life with a rapid growth phase and typical progression to bright red papules, nodules, or plaques. Deeper hemangiomas may appear more skin colored on the surface with a bluish coloration underneath. They are usually more discreet, with relatively defined borders. Diagnosis is typically clinical and many IHs self-resolve, albeit with residual findings including skin atrophy, scarring, and telangiectasia. Observation or topical timolol are first-line treatment options for more superficial lesions while systemic propranolol is the treatment of choice for deeper IHs or those resulting in possible airway or vision compromise.

Congenital hemangiomas (CH) are another type of vascular growth characterized by a solitary erythematous to violaceous plaque or nodule present at birth with overlying telangiectasia. CHs can be subdivided into categories including rapidly involuting (RICH), partially involuting (PICH), and noninvoluting (NICH). Diagnosis is usually clinical and, depending on the subtype, treatment can involve watchful waiting (for RICHs) or more active intervention such as pulse dye laser or surgical resection (for PICHs or NICHs). The growing nature of this patient’s mass makes a diagnosis of CH unlikely.

Port-wine birth mark, also known as nevus flammeus, is a vascular malformation that appears at birth as a nonpalpable irregular erythematous to violaceous macular plaque. Port-wine stains may be isolated birthmarks, or associated with Sturge-Weber syndrome, complex vascular malformations, or soft-tissue overgrowth. Klippel-Trenauny syndrome (KTS) describes capillary-venous malformations with limb overgrowth, with or without lymphatic malformations, and many are associated with somatic mutations in the PIK3CA gene. While KTS could be considered in this patient, the nodular appearance with lumpy texture and rapid growth makes a vascular tumor more likely.

Rhabdomyosarcoma is a malignancy of skeletal muscle lineage and the most common soft tissue tumor in pediatrics. Cutaneous rhabdomyosarcomas present as erythematous nodules, markedly firm, often “fixed” to deep tissue. A rapidly growing atypical, firm tumor of infancy should raise the consideration of rhabdomyosarcoma and imaging and biopsy are appropriate for evaluation.
 

What should the evaluation and management of this patient be?

Initial workup should include a complete blood count with platelet count as well as coagulation studies including D-dimer, fibrinogen, prothrombin time, and activated partial thromboplastin time, to assess for any thrombocytopenia or coagulopathy.⁶ Ultrasound and/or MRI may also be performed to determine lesion extent. While typical MRI findings might be suggestive of a tufted angioma or hemangioendothelioma, biopsy for histologic examination is usually the approach to diagnosis, which will demonstrate stereotypic round lobules of capillaries in a “tufted” distribution.^2,7 Biopsy may be performed by a surgeon or dermatologist but bleeding at time of biopsy needs to be considered before moving forward with the procedure.

Tufted angiomas of early life may regress spontaneously, though lesions with symptoms, with functional significance, or associated with KHE may require therapy. Surgical excision is one option, but it may be difficult to execute given that these lesions often have poorly defined margins.¹ Other treatment choices include but are not limited to aspirin, systemic corticosteroids, vincristine, interferon-alpha, embolization, and sirolimus.⁸ No specific expert-directed consensus guidelines exist for these lesions, and suspicion of this lesion should prompt urgent referral to a pediatric dermatologist. Concern for Kasabach-Merritt syndrome should trigger immediate referral for rapid evaluation and management.

Complete blood count with platelet count and coagulation studies were normal in our patient. This infant underwent biopsy to confirm the diagnosis of tufted angioma and MRI to determine lesion extent. The lesion slowly involuted spontaneously without recurrence.
 

Mr. Haft is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. He is MS4 at the University of Rochester, N.Y. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Mr. Haft nor Dr. Eichenfield have any relevant financial disclosures.

References

1. Herron MD et al. Pediatr Dermatol. 2002;19(5):394-401.

2. Jones EW and Orkin M. J Am Acad Dermatol. 1989;20(2 Pt 1):214-25.

3. Wong SN and Tay YK. Pediatr Dermatol. 2002;19(5):388-93.

4. Croteau SE and Gupta D. Semin Cutan Med Surg. 2016;35(3):147-52.

5. Kelly M. Pediatr Clin North Am. 2010;57(5):1085-9.

6. Osio A et al. Arch Dermatol. 2010;146(7):758-63.

7. Padilla RS et al. Am J Dermatopathol. 1987;9(4):292-300.

8. Liu XH et al. Int J Cancer. 2016;139(7):1658-66.

The history of a brownish to pink patch with color change and rapid growth within the first year combined with the exam findings, are suggestive of a tufted angioma, though the findings presented may be nonspecific.

A tufted angioma is a rare vascular tumor of infancy or early childhood, that is present at birth in approximately half of cases. It may initially present as a faint pink to brown plaque, but develops as a firm, red to violaceous nodule or plaque, usually with “lumpiness” or nodularity.^1-3 Lesions usually are infiltrative with indistinct borders. They are named for their histologic appearance, with lobules of capillaries which appear as “tufts” in the dermis and subdermis with “cannonball” appearance, and are considered to be on a spectrum with another vascular tumor called kaposiform hemangioendothelioma (KHE).⁴ These vascular tumors can trigger Kasabach-Merritt syndrome, a disease process in which vascular tumors trap platelets and clotting factors, resulting in a life-threatening thrombocytopenia and consumptive coagulopathy with a high risk of bleeding and high-output heart failure.⁵
 

What’s the differential diagnosis?

The differential diagnosis of tufted angioma includes other potentially large vascular lesions including infantile hemangioma, congenital hemangioma, port-wine birth marks (capillary malformations), hemangioendotheliomas, and rhabdomyosarcomas.

Infantile hemangiomas (IH) are common vascular tumors of infancy seen in 4%-5% of infants that are characterized by a growth and involution phase. Classically, lesions can be absent or minimally evident at birth, becoming noticeable within the first months of life with a rapid growth phase and typical progression to bright red papules, nodules, or plaques. Deeper hemangiomas may appear more skin colored on the surface with a bluish coloration underneath. They are usually more discreet, with relatively defined borders. Diagnosis is typically clinical and many IHs self-resolve, albeit with residual findings including skin atrophy, scarring, and telangiectasia. Observation or topical timolol are first-line treatment options for more superficial lesions while systemic propranolol is the treatment of choice for deeper IHs or those resulting in possible airway or vision compromise.

Congenital hemangiomas (CH) are another type of vascular growth characterized by a solitary erythematous to violaceous plaque or nodule present at birth with overlying telangiectasia. CHs can be subdivided into categories including rapidly involuting (RICH), partially involuting (PICH), and noninvoluting (NICH). Diagnosis is usually clinical and, depending on the subtype, treatment can involve watchful waiting (for RICHs) or more active intervention such as pulse dye laser or surgical resection (for PICHs or NICHs). The growing nature of this patient’s mass makes a diagnosis of CH unlikely.

Port-wine birth mark, also known as nevus flammeus, is a vascular malformation that appears at birth as a nonpalpable irregular erythematous to violaceous macular plaque. Port-wine stains may be isolated birthmarks, or associated with Sturge-Weber syndrome, complex vascular malformations, or soft-tissue overgrowth. Klippel-Trenauny syndrome (KTS) describes capillary-venous malformations with limb overgrowth, with or without lymphatic malformations, and many are associated with somatic mutations in the PIK3CA gene. While KTS could be considered in this patient, the nodular appearance with lumpy texture and rapid growth makes a vascular tumor more likely.

Rhabdomyosarcoma is a malignancy of skeletal muscle lineage and the most common soft tissue tumor in pediatrics. Cutaneous rhabdomyosarcomas present as erythematous nodules, markedly firm, often “fixed” to deep tissue. A rapidly growing atypical, firm tumor of infancy should raise the consideration of rhabdomyosarcoma and imaging and biopsy are appropriate for evaluation.
 

What should the evaluation and management of this patient be?

Initial workup should include a complete blood count with platelet count as well as coagulation studies including D-dimer, fibrinogen, prothrombin time, and activated partial thromboplastin time, to assess for any thrombocytopenia or coagulopathy.⁶ Ultrasound and/or MRI may also be performed to determine lesion extent. While typical MRI findings might be suggestive of a tufted angioma or hemangioendothelioma, biopsy for histologic examination is usually the approach to diagnosis, which will demonstrate stereotypic round lobules of capillaries in a “tufted” distribution.^2,7 Biopsy may be performed by a surgeon or dermatologist but bleeding at time of biopsy needs to be considered before moving forward with the procedure.

Tufted angiomas of early life may regress spontaneously, though lesions with symptoms, with functional significance, or associated with KHE may require therapy. Surgical excision is one option, but it may be difficult to execute given that these lesions often have poorly defined margins.¹ Other treatment choices include but are not limited to aspirin, systemic corticosteroids, vincristine, interferon-alpha, embolization, and sirolimus.⁸ No specific expert-directed consensus guidelines exist for these lesions, and suspicion of this lesion should prompt urgent referral to a pediatric dermatologist. Concern for Kasabach-Merritt syndrome should trigger immediate referral for rapid evaluation and management.

Complete blood count with platelet count and coagulation studies were normal in our patient. This infant underwent biopsy to confirm the diagnosis of tufted angioma and MRI to determine lesion extent. The lesion slowly involuted spontaneously without recurrence.
 

Mr. Haft is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. He is MS4 at the University of Rochester, N.Y. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Mr. Haft nor Dr. Eichenfield have any relevant financial disclosures.

References

1. Herron MD et al. Pediatr Dermatol. 2002;19(5):394-401.

2. Jones EW and Orkin M. J Am Acad Dermatol. 1989;20(2 Pt 1):214-25.

3. Wong SN and Tay YK. Pediatr Dermatol. 2002;19(5):388-93.

4. Croteau SE and Gupta D. Semin Cutan Med Surg. 2016;35(3):147-52.

5. Kelly M. Pediatr Clin North Am. 2010;57(5):1085-9.

6. Osio A et al. Arch Dermatol. 2010;146(7):758-63.

7. Padilla RS et al. Am J Dermatopathol. 1987;9(4):292-300.

8. Liu XH et al. Int J Cancer. 2016;139(7):1658-66.

You’ve successfully resected a skin cancer lesion, leaving clear margins. Now what?

That’s the question the authors of an evidence-based guideline on reconstruction after skin cancer resection set out to answer.

The guideline – a joint effort of the American Society of Plastic Surgeons, American Society for Dermatologic Surgery, American Academy of Dermatology, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology – Head and Neck Surgery Foundation, American College of Mohs Surgery, American Society for Mohs Surgery, and American Society of Ophthalmic Plastic and Reconstructive Surgery – was published online in the Journal of the American Academy of Dermatology.

From the outset, the panel members realized that to keep the guideline manageable they had to limit recommendations to the practice of reconstruction defined as “cutaneous closure that requires a flap, graft, or tissue rearrangement.”

Other wound closure methods, such as secondary intention healing; simple closures; and complex closures that do not involve flaps, grafts, muscle, or bone, were not covered in the recommendations.

As with similar guidelines, the developers selected seven clinical questions to be addressed, and attempted to find consensus through literature searches, appraisal of the evidence, grading of recommendations, peer review, and public comment.

“We had a very heterogeneous set of things that we were trying to comment on, so we had to keep things somewhat generic,” lead author Andrew Chen, MD, chief of the division of plastic surgery, at the University of Connecticut Health Center, Farmington, said in an interview.

“Skin cancer and reconstruction affect different body areas and areas of different sizes. When we were creating the guidelines, we had to tailor the questions we could ask based on things that would make sense to answer, because obviously we couldn’t ask a question such as: ‘What’s better, a skin graft or a flap?’ Well, there are some things you can’t put a skin graft on – it won’t last, so we couldn’t ask that kind of question,” Dr. Chen said.

Curtis Cetrulo, MD, a plastic and reconstructive surgeon at Massachusetts General Hospital, Boston, who was not involved in the guideline process, said in an interview that the broad recommendations are in keeping with his practice and experience. He also acknowledged, however, the difficulty in creating a guideline that covers the complexity and heterogeneity of reconstructive surgery.

“These are generally good recommendations, but they’re recommendations only, with generally weak levels of evidence. What we really need are clinical trials that can give us definitive answers to some of these questions,” he said.

Recommendations
 

The seven key recommendations, based on the clinical questions raised, are summarized below:

• Delayed (asynchronous) reconstruction is acceptable. Although the quality of the evidence is low and the recommendations are listed as an option, the guideline authors said that depending on the situation, reconstruction can be performed either immediately after resection or delayed by days, weeks, “or even months.”
• Systemic antibiotics should not be routinely prescribed in the interim between resection and reconstruction in adults. Here too, the evidence is low and the recommendation strength is weak, but in “the absence of data showing convincing benefits, systemic antibiotic therapy does not appear necessary or desirable in most cases when there is an interval between cancer resection and reconstruction,” the work group wrote.
• Clinicians may administer perioperative systemic antibiotics in a facility-based setting for adults undergoing reconstruction (3a), but antibiotics should not be routinely prescribed in an office-based setting (3b). The rationale for these recommendations, supported by a moderate level of evidence, is that the risk of surgical-site infection is generally higher in facilities, compared with an office-based setting. Patients who undergo reconstruction in hospitals or surgical centers are more likely to have complex reconstructions or have risks that may make them suitable candidates for antibiotics, but patients in office-based setting may often be spared from the additional costs, side effects, and possible drug interactions from antibiotic use. “There is no evidence in either setting that long-term antibiotic prophylaxis provides infection risk reduction, compared with short-term prophylaxis,” the guideline working group wrote.
• Continue anticoagulant, antithrombotic, and antiplatelet medications for adult patients undergoing reconstruction after skin cancer resection in the office-based setting (4a), and in the facility-based setting should coordinate with the physician managing anticoagulation before modifying the medication prior to surgery (4b). Evidence quality and recommendation strength are both moderate.
• The guideline authors recommend against routine prescription of narcotics as first-line treatment for pain in adults undergoing skin reconstruction (5a), favoring instead acetaminophen and NSAIDs as first-line therapy (5b). Evidence quality and recommendation strength are both moderate.
• In the absence of standardized protocols for the management of pain medications, oral antibiotics, and/or anticoagulants in the perioperative period, clinicians should discuss possible approaches with adult patients. “Educating patients about their perioperative treatment through discussion of treatment strategies may help alleviate anxiety, improve communication, increase patient satisfaction, and maximize patient compliance with the postoperative orders,” the guideline authors wrote.
• The authors suggest that adult patients may be offered follow-up assessments to discuss functional and cosmetic outcomes. “The return of the patient for follow-up visits is an excellent opportunity to better understand and measure these outcomes, improve patient-physician communication, and foster quality improvement. Postoperative follow-up can lead to increased communication between the patient and physician, thereby empowering patients to comment on satisfaction and other important outcomes measures,” they wrote.

What’s next

The guideline developers acknowledged that data are limited regarding reconstructive surgery following skin cancer resection, and that higher-quality studies would help to improve future guidelines. Dr. Chen said that greater use of prospective surgical databases and more systematic collection of patient-reported outcomes could inform further efforts.

The guideline development process was supported by the various groups represented. Dr. Chen and Dr. Cetrulo reported no relevant disclosures.

You’ve successfully resected a skin cancer lesion, leaving clear margins. Now what?

That’s the question the authors of an evidence-based guideline on reconstruction after skin cancer resection set out to answer.

The guideline – a joint effort of the American Society of Plastic Surgeons, American Society for Dermatologic Surgery, American Academy of Dermatology, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology – Head and Neck Surgery Foundation, American College of Mohs Surgery, American Society for Mohs Surgery, and American Society of Ophthalmic Plastic and Reconstructive Surgery – was published online in the Journal of the American Academy of Dermatology.

From the outset, the panel members realized that to keep the guideline manageable they had to limit recommendations to the practice of reconstruction defined as “cutaneous closure that requires a flap, graft, or tissue rearrangement.”

Other wound closure methods, such as secondary intention healing; simple closures; and complex closures that do not involve flaps, grafts, muscle, or bone, were not covered in the recommendations.

As with similar guidelines, the developers selected seven clinical questions to be addressed, and attempted to find consensus through literature searches, appraisal of the evidence, grading of recommendations, peer review, and public comment.

“We had a very heterogeneous set of things that we were trying to comment on, so we had to keep things somewhat generic,” lead author Andrew Chen, MD, chief of the division of plastic surgery, at the University of Connecticut Health Center, Farmington, said in an interview.

“Skin cancer and reconstruction affect different body areas and areas of different sizes. When we were creating the guidelines, we had to tailor the questions we could ask based on things that would make sense to answer, because obviously we couldn’t ask a question such as: ‘What’s better, a skin graft or a flap?’ Well, there are some things you can’t put a skin graft on – it won’t last, so we couldn’t ask that kind of question,” Dr. Chen said.

Curtis Cetrulo, MD, a plastic and reconstructive surgeon at Massachusetts General Hospital, Boston, who was not involved in the guideline process, said in an interview that the broad recommendations are in keeping with his practice and experience. He also acknowledged, however, the difficulty in creating a guideline that covers the complexity and heterogeneity of reconstructive surgery.

“These are generally good recommendations, but they’re recommendations only, with generally weak levels of evidence. What we really need are clinical trials that can give us definitive answers to some of these questions,” he said.

Recommendations
 

The seven key recommendations, based on the clinical questions raised, are summarized below:

• Delayed (asynchronous) reconstruction is acceptable. Although the quality of the evidence is low and the recommendations are listed as an option, the guideline authors said that depending on the situation, reconstruction can be performed either immediately after resection or delayed by days, weeks, “or even months.”
• Systemic antibiotics should not be routinely prescribed in the interim between resection and reconstruction in adults. Here too, the evidence is low and the recommendation strength is weak, but in “the absence of data showing convincing benefits, systemic antibiotic therapy does not appear necessary or desirable in most cases when there is an interval between cancer resection and reconstruction,” the work group wrote.
• Clinicians may administer perioperative systemic antibiotics in a facility-based setting for adults undergoing reconstruction (3a), but antibiotics should not be routinely prescribed in an office-based setting (3b). The rationale for these recommendations, supported by a moderate level of evidence, is that the risk of surgical-site infection is generally higher in facilities, compared with an office-based setting. Patients who undergo reconstruction in hospitals or surgical centers are more likely to have complex reconstructions or have risks that may make them suitable candidates for antibiotics, but patients in office-based setting may often be spared from the additional costs, side effects, and possible drug interactions from antibiotic use. “There is no evidence in either setting that long-term antibiotic prophylaxis provides infection risk reduction, compared with short-term prophylaxis,” the guideline working group wrote.
• Continue anticoagulant, antithrombotic, and antiplatelet medications for adult patients undergoing reconstruction after skin cancer resection in the office-based setting (4a), and in the facility-based setting should coordinate with the physician managing anticoagulation before modifying the medication prior to surgery (4b). Evidence quality and recommendation strength are both moderate.
• The guideline authors recommend against routine prescription of narcotics as first-line treatment for pain in adults undergoing skin reconstruction (5a), favoring instead acetaminophen and NSAIDs as first-line therapy (5b). Evidence quality and recommendation strength are both moderate.
• In the absence of standardized protocols for the management of pain medications, oral antibiotics, and/or anticoagulants in the perioperative period, clinicians should discuss possible approaches with adult patients. “Educating patients about their perioperative treatment through discussion of treatment strategies may help alleviate anxiety, improve communication, increase patient satisfaction, and maximize patient compliance with the postoperative orders,” the guideline authors wrote.
• The authors suggest that adult patients may be offered follow-up assessments to discuss functional and cosmetic outcomes. “The return of the patient for follow-up visits is an excellent opportunity to better understand and measure these outcomes, improve patient-physician communication, and foster quality improvement. Postoperative follow-up can lead to increased communication between the patient and physician, thereby empowering patients to comment on satisfaction and other important outcomes measures,” they wrote.

What’s next

The guideline developers acknowledged that data are limited regarding reconstructive surgery following skin cancer resection, and that higher-quality studies would help to improve future guidelines. Dr. Chen said that greater use of prospective surgical databases and more systematic collection of patient-reported outcomes could inform further efforts.

The guideline development process was supported by the various groups represented. Dr. Chen and Dr. Cetrulo reported no relevant disclosures.

You’ve successfully resected a skin cancer lesion, leaving clear margins. Now what?

That’s the question the authors of an evidence-based guideline on reconstruction after skin cancer resection set out to answer.

The guideline – a joint effort of the American Society of Plastic Surgeons, American Society for Dermatologic Surgery, American Academy of Dermatology, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology – Head and Neck Surgery Foundation, American College of Mohs Surgery, American Society for Mohs Surgery, and American Society of Ophthalmic Plastic and Reconstructive Surgery – was published online in the Journal of the American Academy of Dermatology.

From the outset, the panel members realized that to keep the guideline manageable they had to limit recommendations to the practice of reconstruction defined as “cutaneous closure that requires a flap, graft, or tissue rearrangement.”

Other wound closure methods, such as secondary intention healing; simple closures; and complex closures that do not involve flaps, grafts, muscle, or bone, were not covered in the recommendations.

As with similar guidelines, the developers selected seven clinical questions to be addressed, and attempted to find consensus through literature searches, appraisal of the evidence, grading of recommendations, peer review, and public comment.

“We had a very heterogeneous set of things that we were trying to comment on, so we had to keep things somewhat generic,” lead author Andrew Chen, MD, chief of the division of plastic surgery, at the University of Connecticut Health Center, Farmington, said in an interview.

“Skin cancer and reconstruction affect different body areas and areas of different sizes. When we were creating the guidelines, we had to tailor the questions we could ask based on things that would make sense to answer, because obviously we couldn’t ask a question such as: ‘What’s better, a skin graft or a flap?’ Well, there are some things you can’t put a skin graft on – it won’t last, so we couldn’t ask that kind of question,” Dr. Chen said.

Curtis Cetrulo, MD, a plastic and reconstructive surgeon at Massachusetts General Hospital, Boston, who was not involved in the guideline process, said in an interview that the broad recommendations are in keeping with his practice and experience. He also acknowledged, however, the difficulty in creating a guideline that covers the complexity and heterogeneity of reconstructive surgery.

“These are generally good recommendations, but they’re recommendations only, with generally weak levels of evidence. What we really need are clinical trials that can give us definitive answers to some of these questions,” he said.

Recommendations
 

The seven key recommendations, based on the clinical questions raised, are summarized below:

• Delayed (asynchronous) reconstruction is acceptable. Although the quality of the evidence is low and the recommendations are listed as an option, the guideline authors said that depending on the situation, reconstruction can be performed either immediately after resection or delayed by days, weeks, “or even months.”
• Systemic antibiotics should not be routinely prescribed in the interim between resection and reconstruction in adults. Here too, the evidence is low and the recommendation strength is weak, but in “the absence of data showing convincing benefits, systemic antibiotic therapy does not appear necessary or desirable in most cases when there is an interval between cancer resection and reconstruction,” the work group wrote.
• Clinicians may administer perioperative systemic antibiotics in a facility-based setting for adults undergoing reconstruction (3a), but antibiotics should not be routinely prescribed in an office-based setting (3b). The rationale for these recommendations, supported by a moderate level of evidence, is that the risk of surgical-site infection is generally higher in facilities, compared with an office-based setting. Patients who undergo reconstruction in hospitals or surgical centers are more likely to have complex reconstructions or have risks that may make them suitable candidates for antibiotics, but patients in office-based setting may often be spared from the additional costs, side effects, and possible drug interactions from antibiotic use. “There is no evidence in either setting that long-term antibiotic prophylaxis provides infection risk reduction, compared with short-term prophylaxis,” the guideline working group wrote.
• Continue anticoagulant, antithrombotic, and antiplatelet medications for adult patients undergoing reconstruction after skin cancer resection in the office-based setting (4a), and in the facility-based setting should coordinate with the physician managing anticoagulation before modifying the medication prior to surgery (4b). Evidence quality and recommendation strength are both moderate.
• The guideline authors recommend against routine prescription of narcotics as first-line treatment for pain in adults undergoing skin reconstruction (5a), favoring instead acetaminophen and NSAIDs as first-line therapy (5b). Evidence quality and recommendation strength are both moderate.
• In the absence of standardized protocols for the management of pain medications, oral antibiotics, and/or anticoagulants in the perioperative period, clinicians should discuss possible approaches with adult patients. “Educating patients about their perioperative treatment through discussion of treatment strategies may help alleviate anxiety, improve communication, increase patient satisfaction, and maximize patient compliance with the postoperative orders,” the guideline authors wrote.
• The authors suggest that adult patients may be offered follow-up assessments to discuss functional and cosmetic outcomes. “The return of the patient for follow-up visits is an excellent opportunity to better understand and measure these outcomes, improve patient-physician communication, and foster quality improvement. Postoperative follow-up can lead to increased communication between the patient and physician, thereby empowering patients to comment on satisfaction and other important outcomes measures,” they wrote.

What’s next

The guideline developers acknowledged that data are limited regarding reconstructive surgery following skin cancer resection, and that higher-quality studies would help to improve future guidelines. Dr. Chen said that greater use of prospective surgical databases and more systematic collection of patient-reported outcomes could inform further efforts.

The guideline development process was supported by the various groups represented. Dr. Chen and Dr. Cetrulo reported no relevant disclosures.

The American Medical Association has released a 3-year strategic plan to counter longstanding health inequities that hurt marginalized communities and to improve the AMA’s own performance in this regard.

The 82-page report, which was created by the association’s Center for Health Equity, argues for both internal changes at the AMA and changes in how the association addresses race-based inequities in general.

The report was released just 2 months after this news organization reported that a podcast hosted by AMA’s top journal was lambasted as racist and out of touch. In the podcast – entitled “Stuctural Racism for Doctors – What Is It?” – one JAMA editor argued that structural racism doesn’t exist. He eventually resigned and the journal’s top editor was placed on administration leave.

The new AMA report’s strategic framework “is driven by the immense need for equity-centered solutions to confront harms produced by systemic racism and other forms of oppression for Black, Latinx, Indigenous, Asian, and other people of color, as well as people who identify as LGBTQ+ and people with disabilities,” the AMA said in a news release. “Its urgency is underscored by ongoing circumstances including inequities exacerbated by the COVID-19 pandemic, ongoing police brutality, and hate crimes targeting Asian, Black, and Brown communities.”

The plan includes five main approaches to addressing inequities in health care and the AMA:

• Implement antiracist equity strategies through AMA practices, programming, policies, and culture.
• Build alliances with marginalized doctors and other stakeholders to elevate the experiences and ideas of historically marginalized and minority health care leaders.
• Strengthen, empower, and equip doctors with the knowledge and tools to dismantle structural and social health inequities.
• Ensure equitable opportunities in innovation.
• Foster truth, racial healing, reconciliation, and transformation for AMA’s past by accounting for how policies and processes excluded, discriminated, and harmed communities.

As the report acknowledges, the AMA has a long history of exclusion of and discrimination against Black physicians, for which the association publicly apologized in 2008. Within the past year, the AMA has reaffirmed its commitment to addressing this legacy and to be proactive on health equity.

Among other things, the association has described racism as a public health crisis, stated that race has nothing to do with biology, said police brutality is a product of structural racism, and called on the federal government to collect and release COVID-19 race/ethnicity data. It also removed the name of AMA founder Nathan Davis, MD, from an annual award and display because of his contribution to explicit racist practices.
 

Equity-centered solutions

The AMA launched its Center for Health Equity in 2019 with a mandate “to embed health equity across the organization.” Aletha Maybank, MD, was named the AMA’s chief health equity officer to lead the center.

In the report that Dr. Maybank helped write, the AMA discusses the consequences of individual and systemic injustice toward minorities. Among these consequences, the report said, is “segregated and inequitable health care systems.”

The “equity-centered solutions” listed in the report include:

• End segregated health care.
• Establish national health care equity and racial justice standards.
• End the use of race-based clinical decision models.
• Eliminate all forms of discrimination, exclusion and oppression in medical and physician education, training, hiring, and promotion.
• Prevent exclusion of and ensure equal representation of Black, Indigenous and Latinx people in medical school admissions as well as medical school and hospital leadership ranks.
• Ensure equity in innovation, including design, development, implementation along with support for equitable innovation opportunities and entrepreneurship.
• Solidify connections and coordination between health care and public health.
• Acknowledge and repair past harms committed by institutions.
•  

Changing medical education

In an exclusive interview, Gerald E. Harmon, MD, president-elect of the AMA, singled out medical education as an area that is ripe for change. “One of the most threatened phenotypes on the planet is the Black male physician,” he said. “Their numbers among medical school applicants continue to drop. We have increasing numbers of women in medical schools – over 50% of trainees are women – and more Black women are entering medical school, but Black men in medical school are an endangered species.

“We’re trying to get the physician workforce to look like the patient workforce.”

Dr. Harmon cited the “pipeline program” at the Morehouse School of Medicine in Atlanta and the AMA’s “doctors back to school” program as examples of efforts to attract minority high school students to health care careers. Much more needs to be done, he added. “We have to put equity and representation into our medical workforce so we can provide better high quality, more reliable care for underrepresented patients.”
 

Putting the AMA’s house in order

In its report, the AMA also makes recommendations about how it can improve equity within its own organization. Over the next 3 years, among other things, the association plans to improve the diversity of leadership at the AMA and its journal, JAMA; train all staff on equity requirements; and develop a plan to recruit more racial and ethnic minorities, LGBTQ+ people, and disabled people.

Dr. Maybank, the AMA’s chief health equity officer, said in an interview that she wouldn’t describe these efforts as affirmative action. “This is beyond affirmative action. It’s about intentional activity and action to ensure equity and justice within the AMA.”

The AMA has to thoroughly examine its own processes and determine “how inequity shows up on a day-to-day basis,” she said. “Whether it’s through hiring, innovation, publishing or communications, everybody needs to know how inequity shows up and how their own mental models can exacerbate inequities. People need tools to challenge themselves and ask themselves critical questions about racism in their processes and what they can do to mitigate those.”

A version of this article first appeared on WebMD.com.

The American Medical Association has released a 3-year strategic plan to counter longstanding health inequities that hurt marginalized communities and to improve the AMA’s own performance in this regard.

The 82-page report, which was created by the association’s Center for Health Equity, argues for both internal changes at the AMA and changes in how the association addresses race-based inequities in general.

The report was released just 2 months after this news organization reported that a podcast hosted by AMA’s top journal was lambasted as racist and out of touch. In the podcast – entitled “Stuctural Racism for Doctors – What Is It?” – one JAMA editor argued that structural racism doesn’t exist. He eventually resigned and the journal’s top editor was placed on administration leave.

The new AMA report’s strategic framework “is driven by the immense need for equity-centered solutions to confront harms produced by systemic racism and other forms of oppression for Black, Latinx, Indigenous, Asian, and other people of color, as well as people who identify as LGBTQ+ and people with disabilities,” the AMA said in a news release. “Its urgency is underscored by ongoing circumstances including inequities exacerbated by the COVID-19 pandemic, ongoing police brutality, and hate crimes targeting Asian, Black, and Brown communities.”

The plan includes five main approaches to addressing inequities in health care and the AMA:

• Implement antiracist equity strategies through AMA practices, programming, policies, and culture.
• Build alliances with marginalized doctors and other stakeholders to elevate the experiences and ideas of historically marginalized and minority health care leaders.
• Strengthen, empower, and equip doctors with the knowledge and tools to dismantle structural and social health inequities.
• Ensure equitable opportunities in innovation.
• Foster truth, racial healing, reconciliation, and transformation for AMA’s past by accounting for how policies and processes excluded, discriminated, and harmed communities.

As the report acknowledges, the AMA has a long history of exclusion of and discrimination against Black physicians, for which the association publicly apologized in 2008. Within the past year, the AMA has reaffirmed its commitment to addressing this legacy and to be proactive on health equity.

Among other things, the association has described racism as a public health crisis, stated that race has nothing to do with biology, said police brutality is a product of structural racism, and called on the federal government to collect and release COVID-19 race/ethnicity data. It also removed the name of AMA founder Nathan Davis, MD, from an annual award and display because of his contribution to explicit racist practices.
 

Equity-centered solutions

The AMA launched its Center for Health Equity in 2019 with a mandate “to embed health equity across the organization.” Aletha Maybank, MD, was named the AMA’s chief health equity officer to lead the center.

In the report that Dr. Maybank helped write, the AMA discusses the consequences of individual and systemic injustice toward minorities. Among these consequences, the report said, is “segregated and inequitable health care systems.”

The “equity-centered solutions” listed in the report include:

• End segregated health care.
• Establish national health care equity and racial justice standards.
• End the use of race-based clinical decision models.
• Eliminate all forms of discrimination, exclusion and oppression in medical and physician education, training, hiring, and promotion.
• Prevent exclusion of and ensure equal representation of Black, Indigenous and Latinx people in medical school admissions as well as medical school and hospital leadership ranks.
• Ensure equity in innovation, including design, development, implementation along with support for equitable innovation opportunities and entrepreneurship.
• Solidify connections and coordination between health care and public health.
• Acknowledge and repair past harms committed by institutions.
•  

Changing medical education

In an exclusive interview, Gerald E. Harmon, MD, president-elect of the AMA, singled out medical education as an area that is ripe for change. “One of the most threatened phenotypes on the planet is the Black male physician,” he said. “Their numbers among medical school applicants continue to drop. We have increasing numbers of women in medical schools – over 50% of trainees are women – and more Black women are entering medical school, but Black men in medical school are an endangered species.

“We’re trying to get the physician workforce to look like the patient workforce.”

Dr. Harmon cited the “pipeline program” at the Morehouse School of Medicine in Atlanta and the AMA’s “doctors back to school” program as examples of efforts to attract minority high school students to health care careers. Much more needs to be done, he added. “We have to put equity and representation into our medical workforce so we can provide better high quality, more reliable care for underrepresented patients.”
 

Putting the AMA’s house in order

In its report, the AMA also makes recommendations about how it can improve equity within its own organization. Over the next 3 years, among other things, the association plans to improve the diversity of leadership at the AMA and its journal, JAMA; train all staff on equity requirements; and develop a plan to recruit more racial and ethnic minorities, LGBTQ+ people, and disabled people.

Dr. Maybank, the AMA’s chief health equity officer, said in an interview that she wouldn’t describe these efforts as affirmative action. “This is beyond affirmative action. It’s about intentional activity and action to ensure equity and justice within the AMA.”

The AMA has to thoroughly examine its own processes and determine “how inequity shows up on a day-to-day basis,” she said. “Whether it’s through hiring, innovation, publishing or communications, everybody needs to know how inequity shows up and how their own mental models can exacerbate inequities. People need tools to challenge themselves and ask themselves critical questions about racism in their processes and what they can do to mitigate those.”

A version of this article first appeared on WebMD.com.

The American Medical Association has released a 3-year strategic plan to counter longstanding health inequities that hurt marginalized communities and to improve the AMA’s own performance in this regard.

The 82-page report, which was created by the association’s Center for Health Equity, argues for both internal changes at the AMA and changes in how the association addresses race-based inequities in general.

The report was released just 2 months after this news organization reported that a podcast hosted by AMA’s top journal was lambasted as racist and out of touch. In the podcast – entitled “Stuctural Racism for Doctors – What Is It?” – one JAMA editor argued that structural racism doesn’t exist. He eventually resigned and the journal’s top editor was placed on administration leave.

The new AMA report’s strategic framework “is driven by the immense need for equity-centered solutions to confront harms produced by systemic racism and other forms of oppression for Black, Latinx, Indigenous, Asian, and other people of color, as well as people who identify as LGBTQ+ and people with disabilities,” the AMA said in a news release. “Its urgency is underscored by ongoing circumstances including inequities exacerbated by the COVID-19 pandemic, ongoing police brutality, and hate crimes targeting Asian, Black, and Brown communities.”

The plan includes five main approaches to addressing inequities in health care and the AMA:

• Implement antiracist equity strategies through AMA practices, programming, policies, and culture.
• Build alliances with marginalized doctors and other stakeholders to elevate the experiences and ideas of historically marginalized and minority health care leaders.
• Strengthen, empower, and equip doctors with the knowledge and tools to dismantle structural and social health inequities.
• Ensure equitable opportunities in innovation.
• Foster truth, racial healing, reconciliation, and transformation for AMA’s past by accounting for how policies and processes excluded, discriminated, and harmed communities.

As the report acknowledges, the AMA has a long history of exclusion of and discrimination against Black physicians, for which the association publicly apologized in 2008. Within the past year, the AMA has reaffirmed its commitment to addressing this legacy and to be proactive on health equity.

Among other things, the association has described racism as a public health crisis, stated that race has nothing to do with biology, said police brutality is a product of structural racism, and called on the federal government to collect and release COVID-19 race/ethnicity data. It also removed the name of AMA founder Nathan Davis, MD, from an annual award and display because of his contribution to explicit racist practices.
 

Equity-centered solutions

The AMA launched its Center for Health Equity in 2019 with a mandate “to embed health equity across the organization.” Aletha Maybank, MD, was named the AMA’s chief health equity officer to lead the center.

In the report that Dr. Maybank helped write, the AMA discusses the consequences of individual and systemic injustice toward minorities. Among these consequences, the report said, is “segregated and inequitable health care systems.”

The “equity-centered solutions” listed in the report include:

• End segregated health care.
• Establish national health care equity and racial justice standards.
• End the use of race-based clinical decision models.
• Eliminate all forms of discrimination, exclusion and oppression in medical and physician education, training, hiring, and promotion.
• Prevent exclusion of and ensure equal representation of Black, Indigenous and Latinx people in medical school admissions as well as medical school and hospital leadership ranks.
• Ensure equity in innovation, including design, development, implementation along with support for equitable innovation opportunities and entrepreneurship.
• Solidify connections and coordination between health care and public health.
• Acknowledge and repair past harms committed by institutions.
•  

Changing medical education

In an exclusive interview, Gerald E. Harmon, MD, president-elect of the AMA, singled out medical education as an area that is ripe for change. “One of the most threatened phenotypes on the planet is the Black male physician,” he said. “Their numbers among medical school applicants continue to drop. We have increasing numbers of women in medical schools – over 50% of trainees are women – and more Black women are entering medical school, but Black men in medical school are an endangered species.

“We’re trying to get the physician workforce to look like the patient workforce.”

Dr. Harmon cited the “pipeline program” at the Morehouse School of Medicine in Atlanta and the AMA’s “doctors back to school” program as examples of efforts to attract minority high school students to health care careers. Much more needs to be done, he added. “We have to put equity and representation into our medical workforce so we can provide better high quality, more reliable care for underrepresented patients.”
 

Putting the AMA’s house in order

In its report, the AMA also makes recommendations about how it can improve equity within its own organization. Over the next 3 years, among other things, the association plans to improve the diversity of leadership at the AMA and its journal, JAMA; train all staff on equity requirements; and develop a plan to recruit more racial and ethnic minorities, LGBTQ+ people, and disabled people.

Dr. Maybank, the AMA’s chief health equity officer, said in an interview that she wouldn’t describe these efforts as affirmative action. “This is beyond affirmative action. It’s about intentional activity and action to ensure equity and justice within the AMA.”

The AMA has to thoroughly examine its own processes and determine “how inequity shows up on a day-to-day basis,” she said. “Whether it’s through hiring, innovation, publishing or communications, everybody needs to know how inequity shows up and how their own mental models can exacerbate inequities. People need tools to challenge themselves and ask themselves critical questions about racism in their processes and what they can do to mitigate those.”

A version of this article first appeared on WebMD.com.

Dermatologists and other clinicians should advise their patients with skin of color to practice sensible sun protection, including wearing protective clothing, staying in the shade when outdoors, and applying a tinted sunscreen with an SPF of 30 or greater to exposed areas, according to Henry W. Lim, MD.

In addition, “with rigorous photoprotection, vitamin D supplementation should be advised to patients,” Dr. Lim, a former chair of the department of dermatology at Henry Ford Health System, Detroit, said during the Society for Pediatric Dermatology pre-AAD meeting. “One multivitamin a day should be sufficient for most patients. This is especially relevant because we do know that skin of color patients tend to have lower vitamin D levels to start with.”

Photoprotection for people of color helps minimize the development of photodermatoses, postinflammatory hyperpigmentation, polymorphous light eruption, and chronic actinic dermatitis, he said. In a retrospective chart review of 1,080 people conducted at four academic medical centers in the United States, Dr. Lim and colleagues found a higher proportion of polymorphous light eruption and chronic actinic dermatitis in Black individuals, and a higher proportion of photoallergic contact dermatitis, phototoxic drug eruptions, phytophotodermatitis, porphyria, and solar urticaria in White individuals.

“Another pediatric photodermatosis, actinic prurigo, tends to occur most often in Mestizo individuals, patients of American Indian heritage,” he added. “This is a significant issue, especially in Latin America.”

In a systematic review of 20 studies in the medical literature, researchers assessed the quality of life and psychological impact of photodermatoses in affected patients. Studies included in the review drew from 2,487 adults and 119 children. Among adults, the self-administered Dermatology Life Quality Index (DLQI) revealed that photodermatoses adversely affected employment, education, and leisure activities in adults. Among children, the condition adversely affected outdoor activities and exacerbated symptoms in those with erythropoietic protoporphyria (EPP).

As for skin cancer risk, the association between UV light exposure and the development of melanoma is not as strong in people with skin of color, compared with light-skinned individuals. In a recent systematic review of 13 studies on the topic, 11 showed no association, one showed a small positive relationship in Black males and 1 showed a weak association in Hispanic males.

“The conclusion from this review is that UV protection for melanoma prevention in people of color is not supported by most studies,” said Dr. Lim, who was not affiliated with the review. “The authors also noted, however, that the evidence is of moderate to low quality. Larger studies should be done.”

The association between UV exposure and the development to squamous cell cancer in skin of color is also not strong. “However, we do know that sun exposure is associated with the development of basal cell carcinoma in this population,” he said.

Sunscreen ingredient studies

Dr. Lim also highlighted findings from two studies related to the effect of sunscreen application on plasma concentration of sunscreen active ingredients, both in adults. In the most recent analysis, scientists at the Food and Drug Administration and colleagues conducted a randomized clinical trial in 48 individuals with skin types II-IV.

Participants applied sunscreen at 2 mg/cm² to 75% of body surface area at 0 hours on day 1 and 4 times on day 2 through day 4 at 2-hour intervals. Over the course of 21 days, the researchers collected 34 blood samples from each participant, and evaluated six active ingredients in four sunscreen products: avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate.

For all active ingredients, levels of greater than 0.5 ng/mL were detected after a single application on day 1. Levels of greater than 0.5 ng/mL were detected up to day 7, and up to day 21 for oxybenzone. All were detected in skin on days 7 and 14 via tape stripping. The authors called for further studies to determine the clinical significance of these findings and emphasized that the results “do not indicate that individuals should refrain from the use of sunscreen.”

The FDA is asking for additional studies on the safety of these 12 filters, noted Dr. Lim, who is a past president of the American Academy of Dermatology. On Feb. 26, 2019, the FDA issued a proposed rule regarding sunscreen drug products for over-the-counter human use. It proposes that the 16 UV filters be classified into one of 3 categories. Category I would include zinc oxide and titanium dioxide, which are generally recognized as safe and effective (GRASE). Category II would include PABA and trolamine salicylate, which are not used in the United States and are not GRASE. Category III would include 12 filters that lack insufficient safety data to make a determination regarding GRASE.

The final FDA rule was scheduled to be released in September of 2020, but a result of the Coronavirus Aid, Relief, and Economic Security (CARES) Act, the FDA “will be moving from a laborious rulemaking process to an administrative order process, which means it should not take as long to implement a monograph,” Dr. Lim said. “The FDA has decided that there will not be a final rule regarding sunscreen drug products,” but is required to issue a proposed administrative order by Sept. 27, 2021, he said.

When the final administrative order has been issued, manufacturers would have at least 1 year to comply with sunscreen products offered in the United States. “The approximate timeline is probably going to be 2023,” he said.

Dr. Lim disclosed that he is an investigator for Incyte, L’Oreal, Pfizer, and the Patient-centered Outcomes Research Institute, and a consultant for Pierre Fabre, ISDIN, Ferndale, La Roche–Posay, and Beiersdorf. He has been a speaker at general educational sessions sponsored by La Roche–Posay and Cantabria Labs.

[email protected]

Dermatologists and other clinicians should advise their patients with skin of color to practice sensible sun protection, including wearing protective clothing, staying in the shade when outdoors, and applying a tinted sunscreen with an SPF of 30 or greater to exposed areas, according to Henry W. Lim, MD.

In addition, “with rigorous photoprotection, vitamin D supplementation should be advised to patients,” Dr. Lim, a former chair of the department of dermatology at Henry Ford Health System, Detroit, said during the Society for Pediatric Dermatology pre-AAD meeting. “One multivitamin a day should be sufficient for most patients. This is especially relevant because we do know that skin of color patients tend to have lower vitamin D levels to start with.”

Photoprotection for people of color helps minimize the development of photodermatoses, postinflammatory hyperpigmentation, polymorphous light eruption, and chronic actinic dermatitis, he said. In a retrospective chart review of 1,080 people conducted at four academic medical centers in the United States, Dr. Lim and colleagues found a higher proportion of polymorphous light eruption and chronic actinic dermatitis in Black individuals, and a higher proportion of photoallergic contact dermatitis, phototoxic drug eruptions, phytophotodermatitis, porphyria, and solar urticaria in White individuals.

“Another pediatric photodermatosis, actinic prurigo, tends to occur most often in Mestizo individuals, patients of American Indian heritage,” he added. “This is a significant issue, especially in Latin America.”

In a systematic review of 20 studies in the medical literature, researchers assessed the quality of life and psychological impact of photodermatoses in affected patients. Studies included in the review drew from 2,487 adults and 119 children. Among adults, the self-administered Dermatology Life Quality Index (DLQI) revealed that photodermatoses adversely affected employment, education, and leisure activities in adults. Among children, the condition adversely affected outdoor activities and exacerbated symptoms in those with erythropoietic protoporphyria (EPP).

As for skin cancer risk, the association between UV light exposure and the development of melanoma is not as strong in people with skin of color, compared with light-skinned individuals. In a recent systematic review of 13 studies on the topic, 11 showed no association, one showed a small positive relationship in Black males and 1 showed a weak association in Hispanic males.

“The conclusion from this review is that UV protection for melanoma prevention in people of color is not supported by most studies,” said Dr. Lim, who was not affiliated with the review. “The authors also noted, however, that the evidence is of moderate to low quality. Larger studies should be done.”

The association between UV exposure and the development to squamous cell cancer in skin of color is also not strong. “However, we do know that sun exposure is associated with the development of basal cell carcinoma in this population,” he said.

Sunscreen ingredient studies

Dr. Lim also highlighted findings from two studies related to the effect of sunscreen application on plasma concentration of sunscreen active ingredients, both in adults. In the most recent analysis, scientists at the Food and Drug Administration and colleagues conducted a randomized clinical trial in 48 individuals with skin types II-IV.

Participants applied sunscreen at 2 mg/cm² to 75% of body surface area at 0 hours on day 1 and 4 times on day 2 through day 4 at 2-hour intervals. Over the course of 21 days, the researchers collected 34 blood samples from each participant, and evaluated six active ingredients in four sunscreen products: avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate.

For all active ingredients, levels of greater than 0.5 ng/mL were detected after a single application on day 1. Levels of greater than 0.5 ng/mL were detected up to day 7, and up to day 21 for oxybenzone. All were detected in skin on days 7 and 14 via tape stripping. The authors called for further studies to determine the clinical significance of these findings and emphasized that the results “do not indicate that individuals should refrain from the use of sunscreen.”

The FDA is asking for additional studies on the safety of these 12 filters, noted Dr. Lim, who is a past president of the American Academy of Dermatology. On Feb. 26, 2019, the FDA issued a proposed rule regarding sunscreen drug products for over-the-counter human use. It proposes that the 16 UV filters be classified into one of 3 categories. Category I would include zinc oxide and titanium dioxide, which are generally recognized as safe and effective (GRASE). Category II would include PABA and trolamine salicylate, which are not used in the United States and are not GRASE. Category III would include 12 filters that lack insufficient safety data to make a determination regarding GRASE.

The final FDA rule was scheduled to be released in September of 2020, but a result of the Coronavirus Aid, Relief, and Economic Security (CARES) Act, the FDA “will be moving from a laborious rulemaking process to an administrative order process, which means it should not take as long to implement a monograph,” Dr. Lim said. “The FDA has decided that there will not be a final rule regarding sunscreen drug products,” but is required to issue a proposed administrative order by Sept. 27, 2021, he said.

When the final administrative order has been issued, manufacturers would have at least 1 year to comply with sunscreen products offered in the United States. “The approximate timeline is probably going to be 2023,” he said.

Dr. Lim disclosed that he is an investigator for Incyte, L’Oreal, Pfizer, and the Patient-centered Outcomes Research Institute, and a consultant for Pierre Fabre, ISDIN, Ferndale, La Roche–Posay, and Beiersdorf. He has been a speaker at general educational sessions sponsored by La Roche–Posay and Cantabria Labs.

[email protected]

Dermatologists and other clinicians should advise their patients with skin of color to practice sensible sun protection, including wearing protective clothing, staying in the shade when outdoors, and applying a tinted sunscreen with an SPF of 30 or greater to exposed areas, according to Henry W. Lim, MD.

In addition, “with rigorous photoprotection, vitamin D supplementation should be advised to patients,” Dr. Lim, a former chair of the department of dermatology at Henry Ford Health System, Detroit, said during the Society for Pediatric Dermatology pre-AAD meeting. “One multivitamin a day should be sufficient for most patients. This is especially relevant because we do know that skin of color patients tend to have lower vitamin D levels to start with.”

Photoprotection for people of color helps minimize the development of photodermatoses, postinflammatory hyperpigmentation, polymorphous light eruption, and chronic actinic dermatitis, he said. In a retrospective chart review of 1,080 people conducted at four academic medical centers in the United States, Dr. Lim and colleagues found a higher proportion of polymorphous light eruption and chronic actinic dermatitis in Black individuals, and a higher proportion of photoallergic contact dermatitis, phototoxic drug eruptions, phytophotodermatitis, porphyria, and solar urticaria in White individuals.

“Another pediatric photodermatosis, actinic prurigo, tends to occur most often in Mestizo individuals, patients of American Indian heritage,” he added. “This is a significant issue, especially in Latin America.”

In a systematic review of 20 studies in the medical literature, researchers assessed the quality of life and psychological impact of photodermatoses in affected patients. Studies included in the review drew from 2,487 adults and 119 children. Among adults, the self-administered Dermatology Life Quality Index (DLQI) revealed that photodermatoses adversely affected employment, education, and leisure activities in adults. Among children, the condition adversely affected outdoor activities and exacerbated symptoms in those with erythropoietic protoporphyria (EPP).

As for skin cancer risk, the association between UV light exposure and the development of melanoma is not as strong in people with skin of color, compared with light-skinned individuals. In a recent systematic review of 13 studies on the topic, 11 showed no association, one showed a small positive relationship in Black males and 1 showed a weak association in Hispanic males.

“The conclusion from this review is that UV protection for melanoma prevention in people of color is not supported by most studies,” said Dr. Lim, who was not affiliated with the review. “The authors also noted, however, that the evidence is of moderate to low quality. Larger studies should be done.”

The association between UV exposure and the development to squamous cell cancer in skin of color is also not strong. “However, we do know that sun exposure is associated with the development of basal cell carcinoma in this population,” he said.

Sunscreen ingredient studies

Dr. Lim also highlighted findings from two studies related to the effect of sunscreen application on plasma concentration of sunscreen active ingredients, both in adults. In the most recent analysis, scientists at the Food and Drug Administration and colleagues conducted a randomized clinical trial in 48 individuals with skin types II-IV.

Participants applied sunscreen at 2 mg/cm² to 75% of body surface area at 0 hours on day 1 and 4 times on day 2 through day 4 at 2-hour intervals. Over the course of 21 days, the researchers collected 34 blood samples from each participant, and evaluated six active ingredients in four sunscreen products: avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate.

For all active ingredients, levels of greater than 0.5 ng/mL were detected after a single application on day 1. Levels of greater than 0.5 ng/mL were detected up to day 7, and up to day 21 for oxybenzone. All were detected in skin on days 7 and 14 via tape stripping. The authors called for further studies to determine the clinical significance of these findings and emphasized that the results “do not indicate that individuals should refrain from the use of sunscreen.”

The FDA is asking for additional studies on the safety of these 12 filters, noted Dr. Lim, who is a past president of the American Academy of Dermatology. On Feb. 26, 2019, the FDA issued a proposed rule regarding sunscreen drug products for over-the-counter human use. It proposes that the 16 UV filters be classified into one of 3 categories. Category I would include zinc oxide and titanium dioxide, which are generally recognized as safe and effective (GRASE). Category II would include PABA and trolamine salicylate, which are not used in the United States and are not GRASE. Category III would include 12 filters that lack insufficient safety data to make a determination regarding GRASE.

The final FDA rule was scheduled to be released in September of 2020, but a result of the Coronavirus Aid, Relief, and Economic Security (CARES) Act, the FDA “will be moving from a laborious rulemaking process to an administrative order process, which means it should not take as long to implement a monograph,” Dr. Lim said. “The FDA has decided that there will not be a final rule regarding sunscreen drug products,” but is required to issue a proposed administrative order by Sept. 27, 2021, he said.

When the final administrative order has been issued, manufacturers would have at least 1 year to comply with sunscreen products offered in the United States. “The approximate timeline is probably going to be 2023,” he said.

Dr. Lim disclosed that he is an investigator for Incyte, L’Oreal, Pfizer, and the Patient-centered Outcomes Research Institute, and a consultant for Pierre Fabre, ISDIN, Ferndale, La Roche–Posay, and Beiersdorf. He has been a speaker at general educational sessions sponsored by La Roche–Posay and Cantabria Labs.

[email protected]

Lower blood sugar with sardines

Brand X Pictures/thinkstock.com

If you’ve ever turned your nose up at someone eating sardines straight from the can, you could be the one missing out on a good way to boost your own health.

New research from Open University of Catalonia (Spain) has found that eating two cans of whole sardines a week can help prevent people from developing type 2 diabetes (T2D). Now you might be thinking: That’s a lot of fish, can’t I just take a supplement pill? Actually, no.

“Nutrients can play an essential role in the prevention and treatment of many different pathologies, but their effect is usually caused by the synergy that exists between them and the food that they are contained in,” study coauthor Diana Rizzolo, PhD, said in a written statement. See, we told you.

In a study of 152 patients with prediabetes, each participant was put on a specific diet to reduce their chances of developing T2D. Among the patients who were not given sardines each week, the proportion considered to be at the highest risk fell from 27% to 22% after 1 year, but for those who did get the sardines, the size of the high-risk group shrank from 37% to just 8%.

Suggesting sardines during checkups could make eating them more widely accepted, Dr. Rizzolo and associates said. Sardines are cheap, easy to find, and also have the benefits of other oily fish, like boosting insulin resistance and increasing good cholesterol.

So why not have a can with a couple of saltine crackers for lunch? Your blood sugar will thank you. Just please avoid indulging on a plane or in your office, where workers are slowly returning – no need to give them another excuse to avoid their cubicle.
 

Come for the torture, stay for the vaccine

MMZ84 from Pixabay

Bran Castle. Home of Dracula and Vlad the Impaler (at least in pop culture’s eyes). A moody Gothic structure atop a hill. You can practically hear the ancient screams of thousands of tortured souls as you wander the grounds and its cursed halls. Naturally, it’s a major tourist destination.

Unfortunately for Romania, the pandemic has rather put a damper on tourism. The restrictions have done their damage, but here’s a quick LOTME theory: Perhaps people don’t want to be reminded of medieval tortures when we’ve got plenty of modern-day ones right now.

The management of Bran Castle has developed a new gimmick to drum up attendance – come to Bran Castle and get your COVID vaccine. Anyone can come and get jabbed with the Pfizer vaccine on all weekends in May, and when they do, they gain free admittance to the castle and the exhibit within, home to 52 medieval torture instruments. “The idea … was to show how people got jabbed 500-600 years ago in Europe,” the castle’s marketing director said.

While it may not be kind of the jabbing ole Vladdy got his name for – fully impaling people on hundreds of wooden stakes while you eat a nice dinner isn’t exactly smiled upon in today’s world – we’re sure he’d approve of this more limited but ultimately beneficial version. Jabbing people while helping them really is the dream.
 

Fuzzy little COVID detectors

temmuzcan/Getty Images

Before we get started, we need a moment to get our deep, movie trailer announcer-type voice ready. Okay, here goes.

“In a world where an organism too tiny to see brings entire economies to a standstill and pits scientists against doofuses, who can humanity turn to for help?”

How about bees? That’s right, we said bees. But not just any bees. Specially trained bees. Specially trained Dutch bees. Bees trained to sniff out our greatest nemesis. No, we’re not talking about Ted Cruz anymore. Let it go, that was just a joke. We’re talking COVID.

We’ll let Wim van der Poel, professor of virology at Wageningen (the Netherlands) University, explain the process: “We collect normal honeybees from a beekeeper, and we put the bees in harnesses.” And you thought their tulips were pretty great – the Dutch are putting harnesses on bees! (Which is much better than our previous story of bees involving a Taiwanese patient.)

The researchers presented the bees with two types of samples: COVID infected and non–COVID infected. The infected samples came with a sugary water reward and the noninfected samples did not, so the bees quickly learned to tell the difference.

The bees, then, could cut the waiting time for test results down to seconds, and at a fraction of the cost, making them an option in countries without a lot of testing infrastructure, the research team suggested.

The plan is not without its flaws, of course, but we’re convinced. More than that, we are true bee-lievers.
 

A little slice of … well, not heaven

risalbudiman006/Pixaby

If you’ve been around for the last 2 decades, you’ve seen your share of Internet trends: Remember the ice bucket challenge? Tide pod eating? We know what you’re thinking: Sigh, what could they be doing now?

Well, people are eating old meat, and before you think about the expired ground beef you got on special from the grocery store yesterday, that’s not quite what we mean. We all know expiration dates are “suggestions,” like yield signs and yellow lights. People are eating rotten, decomposing, borderline moldy meat.

They claim that the meat tastes better. We’re not so sure, but don’t worry, because it gets weirder. Some folks, apparently, are getting high from eating this meat, experiencing a feeling of euphoria. Personally, we think that rotten fumes probably knocked these people out and made them hallucinate.

Singaporean dietitian Naras Lapsys says that eating rotten meat can possibly cause a person to go into another state of consciousness, but it’s not a good thing. We don’t think you have to be a dietitian to know that.

It has not been definitively proven that eating rotting meat makes you high, but it’s definitely proven that this is disgusting … and very dangerous.
 

Lower blood sugar with sardines

Brand X Pictures/thinkstock.com

If you’ve ever turned your nose up at someone eating sardines straight from the can, you could be the one missing out on a good way to boost your own health.

New research from Open University of Catalonia (Spain) has found that eating two cans of whole sardines a week can help prevent people from developing type 2 diabetes (T2D). Now you might be thinking: That’s a lot of fish, can’t I just take a supplement pill? Actually, no.

“Nutrients can play an essential role in the prevention and treatment of many different pathologies, but their effect is usually caused by the synergy that exists between them and the food that they are contained in,” study coauthor Diana Rizzolo, PhD, said in a written statement. See, we told you.

In a study of 152 patients with prediabetes, each participant was put on a specific diet to reduce their chances of developing T2D. Among the patients who were not given sardines each week, the proportion considered to be at the highest risk fell from 27% to 22% after 1 year, but for those who did get the sardines, the size of the high-risk group shrank from 37% to just 8%.

Suggesting sardines during checkups could make eating them more widely accepted, Dr. Rizzolo and associates said. Sardines are cheap, easy to find, and also have the benefits of other oily fish, like boosting insulin resistance and increasing good cholesterol.

So why not have a can with a couple of saltine crackers for lunch? Your blood sugar will thank you. Just please avoid indulging on a plane or in your office, where workers are slowly returning – no need to give them another excuse to avoid their cubicle.
 

Come for the torture, stay for the vaccine

MMZ84 from Pixabay

Bran Castle. Home of Dracula and Vlad the Impaler (at least in pop culture’s eyes). A moody Gothic structure atop a hill. You can practically hear the ancient screams of thousands of tortured souls as you wander the grounds and its cursed halls. Naturally, it’s a major tourist destination.

Unfortunately for Romania, the pandemic has rather put a damper on tourism. The restrictions have done their damage, but here’s a quick LOTME theory: Perhaps people don’t want to be reminded of medieval tortures when we’ve got plenty of modern-day ones right now.

The management of Bran Castle has developed a new gimmick to drum up attendance – come to Bran Castle and get your COVID vaccine. Anyone can come and get jabbed with the Pfizer vaccine on all weekends in May, and when they do, they gain free admittance to the castle and the exhibit within, home to 52 medieval torture instruments. “The idea … was to show how people got jabbed 500-600 years ago in Europe,” the castle’s marketing director said.

While it may not be kind of the jabbing ole Vladdy got his name for – fully impaling people on hundreds of wooden stakes while you eat a nice dinner isn’t exactly smiled upon in today’s world – we’re sure he’d approve of this more limited but ultimately beneficial version. Jabbing people while helping them really is the dream.
 

Fuzzy little COVID detectors

temmuzcan/Getty Images

Before we get started, we need a moment to get our deep, movie trailer announcer-type voice ready. Okay, here goes.

“In a world where an organism too tiny to see brings entire economies to a standstill and pits scientists against doofuses, who can humanity turn to for help?”

How about bees? That’s right, we said bees. But not just any bees. Specially trained bees. Specially trained Dutch bees. Bees trained to sniff out our greatest nemesis. No, we’re not talking about Ted Cruz anymore. Let it go, that was just a joke. We’re talking COVID.

We’ll let Wim van der Poel, professor of virology at Wageningen (the Netherlands) University, explain the process: “We collect normal honeybees from a beekeeper, and we put the bees in harnesses.” And you thought their tulips were pretty great – the Dutch are putting harnesses on bees! (Which is much better than our previous story of bees involving a Taiwanese patient.)

The researchers presented the bees with two types of samples: COVID infected and non–COVID infected. The infected samples came with a sugary water reward and the noninfected samples did not, so the bees quickly learned to tell the difference.

The bees, then, could cut the waiting time for test results down to seconds, and at a fraction of the cost, making them an option in countries without a lot of testing infrastructure, the research team suggested.

The plan is not without its flaws, of course, but we’re convinced. More than that, we are true bee-lievers.
 

A little slice of … well, not heaven

risalbudiman006/Pixaby

If you’ve been around for the last 2 decades, you’ve seen your share of Internet trends: Remember the ice bucket challenge? Tide pod eating? We know what you’re thinking: Sigh, what could they be doing now?

Well, people are eating old meat, and before you think about the expired ground beef you got on special from the grocery store yesterday, that’s not quite what we mean. We all know expiration dates are “suggestions,” like yield signs and yellow lights. People are eating rotten, decomposing, borderline moldy meat.

They claim that the meat tastes better. We’re not so sure, but don’t worry, because it gets weirder. Some folks, apparently, are getting high from eating this meat, experiencing a feeling of euphoria. Personally, we think that rotten fumes probably knocked these people out and made them hallucinate.

Singaporean dietitian Naras Lapsys says that eating rotten meat can possibly cause a person to go into another state of consciousness, but it’s not a good thing. We don’t think you have to be a dietitian to know that.

It has not been definitively proven that eating rotting meat makes you high, but it’s definitely proven that this is disgusting … and very dangerous.
 

Lower blood sugar with sardines

Brand X Pictures/thinkstock.com

If you’ve ever turned your nose up at someone eating sardines straight from the can, you could be the one missing out on a good way to boost your own health.

New research from Open University of Catalonia (Spain) has found that eating two cans of whole sardines a week can help prevent people from developing type 2 diabetes (T2D). Now you might be thinking: That’s a lot of fish, can’t I just take a supplement pill? Actually, no.

“Nutrients can play an essential role in the prevention and treatment of many different pathologies, but their effect is usually caused by the synergy that exists between them and the food that they are contained in,” study coauthor Diana Rizzolo, PhD, said in a written statement. See, we told you.

In a study of 152 patients with prediabetes, each participant was put on a specific diet to reduce their chances of developing T2D. Among the patients who were not given sardines each week, the proportion considered to be at the highest risk fell from 27% to 22% after 1 year, but for those who did get the sardines, the size of the high-risk group shrank from 37% to just 8%.

Suggesting sardines during checkups could make eating them more widely accepted, Dr. Rizzolo and associates said. Sardines are cheap, easy to find, and also have the benefits of other oily fish, like boosting insulin resistance and increasing good cholesterol.

So why not have a can with a couple of saltine crackers for lunch? Your blood sugar will thank you. Just please avoid indulging on a plane or in your office, where workers are slowly returning – no need to give them another excuse to avoid their cubicle.
 

Come for the torture, stay for the vaccine

MMZ84 from Pixabay

Bran Castle. Home of Dracula and Vlad the Impaler (at least in pop culture’s eyes). A moody Gothic structure atop a hill. You can practically hear the ancient screams of thousands of tortured souls as you wander the grounds and its cursed halls. Naturally, it’s a major tourist destination.

Unfortunately for Romania, the pandemic has rather put a damper on tourism. The restrictions have done their damage, but here’s a quick LOTME theory: Perhaps people don’t want to be reminded of medieval tortures when we’ve got plenty of modern-day ones right now.

The management of Bran Castle has developed a new gimmick to drum up attendance – come to Bran Castle and get your COVID vaccine. Anyone can come and get jabbed with the Pfizer vaccine on all weekends in May, and when they do, they gain free admittance to the castle and the exhibit within, home to 52 medieval torture instruments. “The idea … was to show how people got jabbed 500-600 years ago in Europe,” the castle’s marketing director said.

While it may not be kind of the jabbing ole Vladdy got his name for – fully impaling people on hundreds of wooden stakes while you eat a nice dinner isn’t exactly smiled upon in today’s world – we’re sure he’d approve of this more limited but ultimately beneficial version. Jabbing people while helping them really is the dream.
 

Fuzzy little COVID detectors

temmuzcan/Getty Images

Before we get started, we need a moment to get our deep, movie trailer announcer-type voice ready. Okay, here goes.

“In a world where an organism too tiny to see brings entire economies to a standstill and pits scientists against doofuses, who can humanity turn to for help?”

How about bees? That’s right, we said bees. But not just any bees. Specially trained bees. Specially trained Dutch bees. Bees trained to sniff out our greatest nemesis. No, we’re not talking about Ted Cruz anymore. Let it go, that was just a joke. We’re talking COVID.

We’ll let Wim van der Poel, professor of virology at Wageningen (the Netherlands) University, explain the process: “We collect normal honeybees from a beekeeper, and we put the bees in harnesses.” And you thought their tulips were pretty great – the Dutch are putting harnesses on bees! (Which is much better than our previous story of bees involving a Taiwanese patient.)

The researchers presented the bees with two types of samples: COVID infected and non–COVID infected. The infected samples came with a sugary water reward and the noninfected samples did not, so the bees quickly learned to tell the difference.

The bees, then, could cut the waiting time for test results down to seconds, and at a fraction of the cost, making them an option in countries without a lot of testing infrastructure, the research team suggested.

The plan is not without its flaws, of course, but we’re convinced. More than that, we are true bee-lievers.
 

A little slice of … well, not heaven

risalbudiman006/Pixaby

If you’ve been around for the last 2 decades, you’ve seen your share of Internet trends: Remember the ice bucket challenge? Tide pod eating? We know what you’re thinking: Sigh, what could they be doing now?

Well, people are eating old meat, and before you think about the expired ground beef you got on special from the grocery store yesterday, that’s not quite what we mean. We all know expiration dates are “suggestions,” like yield signs and yellow lights. People are eating rotten, decomposing, borderline moldy meat.

They claim that the meat tastes better. We’re not so sure, but don’t worry, because it gets weirder. Some folks, apparently, are getting high from eating this meat, experiencing a feeling of euphoria. Personally, we think that rotten fumes probably knocked these people out and made them hallucinate.

Singaporean dietitian Naras Lapsys says that eating rotten meat can possibly cause a person to go into another state of consciousness, but it’s not a good thing. We don’t think you have to be a dietitian to know that.

It has not been definitively proven that eating rotting meat makes you high, but it’s definitely proven that this is disgusting … and very dangerous.
 

The Diagnosis: Granular Cell Tumor 

Histopathologic analysis from the axillary excision demonstrated cords and sheets of large polygonal cells in the dermis with uniform, oval, hyperchromatic nuclei and ample pink granular-staining cytoplasm (quiz images). An infiltrative growth pattern was noted; however, there was no evidence of conspicuous mitoses, nuclear pleomorphism, or necrosis. These results in conjunction with the immunohistochemistry findings were consistent with a benign granular cell tumor (GCT), a rare neoplasm considered to have neural/Schwann cell origin.^1-3 

Our case demonstrates the difficulty in clinically diagnosing cutaneous GCTs. The tumor often presents as a solitary, 0.5- to 3-cm, asymptomatic, firm nodule^4,5; however, GCTs also can appear verrucous, eroded, or with other variable morphologies, which can create diagnostic challenges.^5,6 Accordingly, a 1980 study of 110 patients with GCTs found that the preoperative clinical diagnosis was incorrect in all but 3 cases,⁷ emphasizing the need for histologic evaluation. Benign GCTs tend to exhibit sheets of polygonal tumor cells with eosinophilic granular cytoplasm and small central nuclei.^3,5 The cytoplasmic granules are periodic acid-Schiff positive and diastase resistant.⁶ Many cases feature pseudoepitheliomatous hyperplasia, which can misleadingly resemble squamous cell carcinoma.^3,5,6 Of note, invasive growth patterns on histology can occur with benign GCTs, as in our patient's case, and do not impact prognosis.^3,4 On immunohistochemistry, benign, atypical, and malignant GCTs often stain positive for S-100 protein, vimentin, neuron-specific enolase, SOX10, and CD68.^1,3  

Although our patient's GCTs were benign, an estimated 1% to 2% are malignant.^1,4 In 1998, Fanburg-Smith et al¹ defined 6 histologic criteria that characterize malignant GCTs: necrosis, tumor cell spindling, vesicular nuclei with large nucleoli, high nuclear to cytoplasmic ratio, increased mitosis, and pleomorphism. Neoplasms with 3 or more of these features are classified as malignant, those with 1 or 2 are considered atypical, and those with only pleomorphism or no other criteria met are diagnosed as benign.¹  

Multiple GCTs have been reported in 10% to 25% of cases and, as highlighted in our case, can occur in both a metachronous and synchronous manner.^2-4,6 Our patient developed a solitary GCT on the inferior lip 3 years prior to the appearance of 2 additional GCTs within 6 months of each other. The presence of multiple GCTs has been associated with genetic syndromes, such as neurofibromatosis type 1 and Noonan syndrome with multiple lentigines^3,8; however, as our case demonstrates, multiple GCTs can occur in nonsyndromic patients as well. When multiple GCTs develop at distant sites, they can resemble metastasis.³ To differentiate these clinical scenarios, Machado et al³ proposed utilizing histology and anatomic location. Multiple tumors with benign characteristics on histology likely represent multiple GCTs, whereas tumors arising at sites common to GCT metastasis, such as lymph node, bone, or viscera, are more concerning for metastatic disease. It has been suggested that patients with multiple GCTs should be monitored with physical examination and repeat magnetic resonance imaging or computed tomography every 6 to 12 months.² Given our patient's presentation with new tumors arising within 6 months of one another, we recommended a 6-month follow-up interval rather than 1 year. Due to the rarity of GCTs, clinical trials to define treatment guidelines and recommendations have not been performed.³ However, the most commonly utilized treatment modality is wide local excision, as performed in our patient.^2,4 

Melanoma, atypical fibroxanthoma (AFX), xanthoma, and leiomyosarcoma may be difficult to distinguish from GCT.^1,3,4 Melanoma incidence has increased dramatically over the last several decades, with rates in the United States rising from 6.8 cases per 100,000 individuals in the 1970s to 20.¹ in the early 2000s. Risk factors for its development include UV radiation exposure and particularly severe sunburns during childhood, along with a number of host risk factors such as total number of melanocytic nevi, family history, and fair complexion.⁹ Histologically, it often demonstrates irregularly distributed, poorly defined melanocytes with pagetoid spread and dyscohesive nests (Figure 1).¹⁰ Melanoma metastasis occasionally can present as a soft-tissue mass and often stains positive for S-100 and vimentin, thus resembling GCT^1,4; however, unlike melanoma, GCTs lack melanosomes and stain negative for more specific melanocyte markers, such as melanoma antigen recognized by T cells 1 (MART-1).^1,3,4 
Atypical fibroxanthoma is a cutaneous neoplasm with fibrohistiocytic mesenchymal origin.¹¹ These tumors typically arise on the head and neck in elderly individuals, particularly men with sun-damaged skin. They often present as superficial, rapidly growing nodules with the potential to ulcerate and bleed.^11,12 Histologic features include pleomorphic spindle and epithelioid cells, whose nuclei appear hyperchromatic with atypical mitoses (Figure 2).¹² Granular cell changes occur infrequently with AFXs, but in such cases immunohistochemistry can readily distinguish AFX from GCT. Although both tend to stain positive for CD68 and vimentin, AFXs lack S-100 protein and SOX10 expression that frequently is observed in GCTs.^3,12  

Xanthomas are localized lipid deposits in the connective tissue of the skin that often arise in association with dyslipidemia.¹³ They typically present as soft to semisolid yellow papules, plaques, or nodules. Their clinical appearance can resemble GCTs; however, histologic analysis enables differentiation with ease, as xanthomas demonstrate characteristic foam cells, consisting of lipid-laden macrophages (Figure 3).¹³  

Cutaneous leiomyosarcoma is a rare dermal neoplasm, accounting for 2% to 3% of all sarcomas.¹⁴ They typically occur in White males during the fifth to seventh decades of life and often present as asymptomatic lesions on the lower extremities. They frequently arise from pilar smooth muscle. Unlike uterine and soft-tissue leiomyosarcoma, cutaneous leiomyosarcoma tends to follow an indolent course and rarely metastasizes.¹⁴ Histologically, these tumors display intersecting, well-defined, spindle-cell fascicles with abundant eosinophilic cytoplasm and cigar-shaped, blunt-ended nuclei (Figure 4).¹⁵ Occasionally, leiomyosarcomas can demonstrate cytoplasmic granularity due to lysosome accumulation⁴; nevertheless, the diagnosis usually can be elucidated by examining more typical histologic areas and utilizing immunohistochemistry, which often stains positive for α-smooth muscle actin, desmin, and h-caldesmon.^4,15 

The Diagnosis: Granular Cell Tumor 

Histopathologic analysis from the axillary excision demonstrated cords and sheets of large polygonal cells in the dermis with uniform, oval, hyperchromatic nuclei and ample pink granular-staining cytoplasm (quiz images). An infiltrative growth pattern was noted; however, there was no evidence of conspicuous mitoses, nuclear pleomorphism, or necrosis. These results in conjunction with the immunohistochemistry findings were consistent with a benign granular cell tumor (GCT), a rare neoplasm considered to have neural/Schwann cell origin.^1-3 

Our case demonstrates the difficulty in clinically diagnosing cutaneous GCTs. The tumor often presents as a solitary, 0.5- to 3-cm, asymptomatic, firm nodule^4,5; however, GCTs also can appear verrucous, eroded, or with other variable morphologies, which can create diagnostic challenges.^5,6 Accordingly, a 1980 study of 110 patients with GCTs found that the preoperative clinical diagnosis was incorrect in all but 3 cases,⁷ emphasizing the need for histologic evaluation. Benign GCTs tend to exhibit sheets of polygonal tumor cells with eosinophilic granular cytoplasm and small central nuclei.^3,5 The cytoplasmic granules are periodic acid-Schiff positive and diastase resistant.⁶ Many cases feature pseudoepitheliomatous hyperplasia, which can misleadingly resemble squamous cell carcinoma.^3,5,6 Of note, invasive growth patterns on histology can occur with benign GCTs, as in our patient's case, and do not impact prognosis.^3,4 On immunohistochemistry, benign, atypical, and malignant GCTs often stain positive for S-100 protein, vimentin, neuron-specific enolase, SOX10, and CD68.^1,3  

Although our patient's GCTs were benign, an estimated 1% to 2% are malignant.^1,4 In 1998, Fanburg-Smith et al¹ defined 6 histologic criteria that characterize malignant GCTs: necrosis, tumor cell spindling, vesicular nuclei with large nucleoli, high nuclear to cytoplasmic ratio, increased mitosis, and pleomorphism. Neoplasms with 3 or more of these features are classified as malignant, those with 1 or 2 are considered atypical, and those with only pleomorphism or no other criteria met are diagnosed as benign.¹  

Multiple GCTs have been reported in 10% to 25% of cases and, as highlighted in our case, can occur in both a metachronous and synchronous manner.^2-4,6 Our patient developed a solitary GCT on the inferior lip 3 years prior to the appearance of 2 additional GCTs within 6 months of each other. The presence of multiple GCTs has been associated with genetic syndromes, such as neurofibromatosis type 1 and Noonan syndrome with multiple lentigines^3,8; however, as our case demonstrates, multiple GCTs can occur in nonsyndromic patients as well. When multiple GCTs develop at distant sites, they can resemble metastasis.³ To differentiate these clinical scenarios, Machado et al³ proposed utilizing histology and anatomic location. Multiple tumors with benign characteristics on histology likely represent multiple GCTs, whereas tumors arising at sites common to GCT metastasis, such as lymph node, bone, or viscera, are more concerning for metastatic disease. It has been suggested that patients with multiple GCTs should be monitored with physical examination and repeat magnetic resonance imaging or computed tomography every 6 to 12 months.² Given our patient's presentation with new tumors arising within 6 months of one another, we recommended a 6-month follow-up interval rather than 1 year. Due to the rarity of GCTs, clinical trials to define treatment guidelines and recommendations have not been performed.³ However, the most commonly utilized treatment modality is wide local excision, as performed in our patient.^2,4 

Melanoma, atypical fibroxanthoma (AFX), xanthoma, and leiomyosarcoma may be difficult to distinguish from GCT.^1,3,4 Melanoma incidence has increased dramatically over the last several decades, with rates in the United States rising from 6.8 cases per 100,000 individuals in the 1970s to 20.¹ in the early 2000s. Risk factors for its development include UV radiation exposure and particularly severe sunburns during childhood, along with a number of host risk factors such as total number of melanocytic nevi, family history, and fair complexion.⁹ Histologically, it often demonstrates irregularly distributed, poorly defined melanocytes with pagetoid spread and dyscohesive nests (Figure 1).¹⁰ Melanoma metastasis occasionally can present as a soft-tissue mass and often stains positive for S-100 and vimentin, thus resembling GCT^1,4; however, unlike melanoma, GCTs lack melanosomes and stain negative for more specific melanocyte markers, such as melanoma antigen recognized by T cells 1 (MART-1).^1,3,4 
Atypical fibroxanthoma is a cutaneous neoplasm with fibrohistiocytic mesenchymal origin.¹¹ These tumors typically arise on the head and neck in elderly individuals, particularly men with sun-damaged skin. They often present as superficial, rapidly growing nodules with the potential to ulcerate and bleed.^11,12 Histologic features include pleomorphic spindle and epithelioid cells, whose nuclei appear hyperchromatic with atypical mitoses (Figure 2).¹² Granular cell changes occur infrequently with AFXs, but in such cases immunohistochemistry can readily distinguish AFX from GCT. Although both tend to stain positive for CD68 and vimentin, AFXs lack S-100 protein and SOX10 expression that frequently is observed in GCTs.^3,12  

Xanthomas are localized lipid deposits in the connective tissue of the skin that often arise in association with dyslipidemia.¹³ They typically present as soft to semisolid yellow papules, plaques, or nodules. Their clinical appearance can resemble GCTs; however, histologic analysis enables differentiation with ease, as xanthomas demonstrate characteristic foam cells, consisting of lipid-laden macrophages (Figure 3).¹³  

Cutaneous leiomyosarcoma is a rare dermal neoplasm, accounting for 2% to 3% of all sarcomas.¹⁴ They typically occur in White males during the fifth to seventh decades of life and often present as asymptomatic lesions on the lower extremities. They frequently arise from pilar smooth muscle. Unlike uterine and soft-tissue leiomyosarcoma, cutaneous leiomyosarcoma tends to follow an indolent course and rarely metastasizes.¹⁴ Histologically, these tumors display intersecting, well-defined, spindle-cell fascicles with abundant eosinophilic cytoplasm and cigar-shaped, blunt-ended nuclei (Figure 4).¹⁵ Occasionally, leiomyosarcomas can demonstrate cytoplasmic granularity due to lysosome accumulation⁴; nevertheless, the diagnosis usually can be elucidated by examining more typical histologic areas and utilizing immunohistochemistry, which often stains positive for α-smooth muscle actin, desmin, and h-caldesmon.^4,15 

The Diagnosis: Granular Cell Tumor 

Histopathologic analysis from the axillary excision demonstrated cords and sheets of large polygonal cells in the dermis with uniform, oval, hyperchromatic nuclei and ample pink granular-staining cytoplasm (quiz images). An infiltrative growth pattern was noted; however, there was no evidence of conspicuous mitoses, nuclear pleomorphism, or necrosis. These results in conjunction with the immunohistochemistry findings were consistent with a benign granular cell tumor (GCT), a rare neoplasm considered to have neural/Schwann cell origin.^1-3 

Our case demonstrates the difficulty in clinically diagnosing cutaneous GCTs. The tumor often presents as a solitary, 0.5- to 3-cm, asymptomatic, firm nodule^4,5; however, GCTs also can appear verrucous, eroded, or with other variable morphologies, which can create diagnostic challenges.^5,6 Accordingly, a 1980 study of 110 patients with GCTs found that the preoperative clinical diagnosis was incorrect in all but 3 cases,⁷ emphasizing the need for histologic evaluation. Benign GCTs tend to exhibit sheets of polygonal tumor cells with eosinophilic granular cytoplasm and small central nuclei.^3,5 The cytoplasmic granules are periodic acid-Schiff positive and diastase resistant.⁶ Many cases feature pseudoepitheliomatous hyperplasia, which can misleadingly resemble squamous cell carcinoma.^3,5,6 Of note, invasive growth patterns on histology can occur with benign GCTs, as in our patient's case, and do not impact prognosis.^3,4 On immunohistochemistry, benign, atypical, and malignant GCTs often stain positive for S-100 protein, vimentin, neuron-specific enolase, SOX10, and CD68.^1,3  

Although our patient's GCTs were benign, an estimated 1% to 2% are malignant.^1,4 In 1998, Fanburg-Smith et al¹ defined 6 histologic criteria that characterize malignant GCTs: necrosis, tumor cell spindling, vesicular nuclei with large nucleoli, high nuclear to cytoplasmic ratio, increased mitosis, and pleomorphism. Neoplasms with 3 or more of these features are classified as malignant, those with 1 or 2 are considered atypical, and those with only pleomorphism or no other criteria met are diagnosed as benign.¹  

Multiple GCTs have been reported in 10% to 25% of cases and, as highlighted in our case, can occur in both a metachronous and synchronous manner.^2-4,6 Our patient developed a solitary GCT on the inferior lip 3 years prior to the appearance of 2 additional GCTs within 6 months of each other. The presence of multiple GCTs has been associated with genetic syndromes, such as neurofibromatosis type 1 and Noonan syndrome with multiple lentigines^3,8; however, as our case demonstrates, multiple GCTs can occur in nonsyndromic patients as well. When multiple GCTs develop at distant sites, they can resemble metastasis.³ To differentiate these clinical scenarios, Machado et al³ proposed utilizing histology and anatomic location. Multiple tumors with benign characteristics on histology likely represent multiple GCTs, whereas tumors arising at sites common to GCT metastasis, such as lymph node, bone, or viscera, are more concerning for metastatic disease. It has been suggested that patients with multiple GCTs should be monitored with physical examination and repeat magnetic resonance imaging or computed tomography every 6 to 12 months.² Given our patient's presentation with new tumors arising within 6 months of one another, we recommended a 6-month follow-up interval rather than 1 year. Due to the rarity of GCTs, clinical trials to define treatment guidelines and recommendations have not been performed.³ However, the most commonly utilized treatment modality is wide local excision, as performed in our patient.^2,4 

Melanoma, atypical fibroxanthoma (AFX), xanthoma, and leiomyosarcoma may be difficult to distinguish from GCT.^1,3,4 Melanoma incidence has increased dramatically over the last several decades, with rates in the United States rising from 6.8 cases per 100,000 individuals in the 1970s to 20.¹ in the early 2000s. Risk factors for its development include UV radiation exposure and particularly severe sunburns during childhood, along with a number of host risk factors such as total number of melanocytic nevi, family history, and fair complexion.⁹ Histologically, it often demonstrates irregularly distributed, poorly defined melanocytes with pagetoid spread and dyscohesive nests (Figure 1).¹⁰ Melanoma metastasis occasionally can present as a soft-tissue mass and often stains positive for S-100 and vimentin, thus resembling GCT^1,4; however, unlike melanoma, GCTs lack melanosomes and stain negative for more specific melanocyte markers, such as melanoma antigen recognized by T cells 1 (MART-1).^1,3,4 
Atypical fibroxanthoma is a cutaneous neoplasm with fibrohistiocytic mesenchymal origin.¹¹ These tumors typically arise on the head and neck in elderly individuals, particularly men with sun-damaged skin. They often present as superficial, rapidly growing nodules with the potential to ulcerate and bleed.^11,12 Histologic features include pleomorphic spindle and epithelioid cells, whose nuclei appear hyperchromatic with atypical mitoses (Figure 2).¹² Granular cell changes occur infrequently with AFXs, but in such cases immunohistochemistry can readily distinguish AFX from GCT. Although both tend to stain positive for CD68 and vimentin, AFXs lack S-100 protein and SOX10 expression that frequently is observed in GCTs.^3,12  

Xanthomas are localized lipid deposits in the connective tissue of the skin that often arise in association with dyslipidemia.¹³ They typically present as soft to semisolid yellow papules, plaques, or nodules. Their clinical appearance can resemble GCTs; however, histologic analysis enables differentiation with ease, as xanthomas demonstrate characteristic foam cells, consisting of lipid-laden macrophages (Figure 3).¹³  

Cutaneous leiomyosarcoma is a rare dermal neoplasm, accounting for 2% to 3% of all sarcomas.¹⁴ They typically occur in White males during the fifth to seventh decades of life and often present as asymptomatic lesions on the lower extremities. They frequently arise from pilar smooth muscle. Unlike uterine and soft-tissue leiomyosarcoma, cutaneous leiomyosarcoma tends to follow an indolent course and rarely metastasizes.¹⁴ Histologically, these tumors display intersecting, well-defined, spindle-cell fascicles with abundant eosinophilic cytoplasm and cigar-shaped, blunt-ended nuclei (Figure 4).¹⁵ Occasionally, leiomyosarcomas can demonstrate cytoplasmic granularity due to lysosome accumulation⁴; nevertheless, the diagnosis usually can be elucidated by examining more typical histologic areas and utilizing immunohistochemistry, which often stains positive for α-smooth muscle actin, desmin, and h-caldesmon.^4,15 

Emerging data suggest that molecular classification of vascular anomalies can improve prognostication and treatment for babies born with these malformations, according to Beth Drolet, MD.

“We now know that 75%-80% of vascular malformations have gene mutations that make the cells either live longer, grow faster, or make them bigger in size,” Dr. Drolet, professor and chair of dermatology at the University of Wisconsin–Madison, said during the Society for Pediatric Dermatology pre-AAD meeting. “The basic binary premise of the current ISSVA [International Society for the Study of Vascular Anomalies] classification dividing vascular anomalies into tumors and malformations is wrong; the biology is not that straightforward. It may be helpful to differentiate between an infantile hemangioma and a capillary malformation during infancy as the hemangioma will grow in the next month, but we now know that patients with capillary malformations also have significant overgrowth of their tissue. We’ve all seen that; it just takes years, not months for us to notice it.”

The change in thinking about the root causes of vascular anomalies, she noted, stems from scientific advances in the understanding of embryonic mosaicism, DNA variation that happens after the zygote is formed, but before birth. “We know that each cell in a zygote will undergo 40 cell divisions before a baby is born,” she said. “Those cell divisions are not as neat as we thought they were. That cell and DNA duplication is actually quite messy, so there are mutations that happen purely because of embryonic cell division.”

Everyone is born with 120 somatic mutations per cell, she continued, “so we have multiple genomes in one human. Not all of those mutations are going to cause disease. Not all of those are going to be functional. About 10% of those mutations will actually be in a coding region of the gene and have the potential to change the function of the protein. If it changes the function of the protein so that the cell can’t survive, that cell dies off, but it gives the cell an advantage. It grows a little bit faster, let’s say. That cell survives, divides, producing a line of cells that can cause disease.”

In 2011, Dr. Drolet and colleagues from the Hemangioma Investigator Group and the Pediatric Dermatology Research Alliance (PeDRA) launched a multisite collaborative group to investigate the role of mosaic genetics in patients with vascular anomalies and discrepancy of growth. To date, 365 patients are enrolled, and the researchers have sequenced 97 of 165 affected tissue samples collected. “What’s nice about the registry is that we enrolled a wide spectrum of diseases: very mild diseases that might be treated by dermatologists to complex, syndromic diseases that might end up in an interdisciplinary vascular anomalies clinic,” she said.

For gene sequencing, the researchers drew from solid tumor biology and used next-generation sequencing with semi-target hybrid capture, “so we’re only looking at a subset of genes,” she said. “Right now, the chip we’re using has 180 cancer-related genes. It sequences the entire exome of the gene with a high depth of coverage, usually over 1,000 X. We use a specific pipeline that can detect very low allele frequency mutation: down to 1%, and robust criteria to determine variant pathogenicity.”

In 75% of tissue samples so far, the researchers have found a gene mutation in one of 13 genes: AKT1, AKT3, BRAF, GNA11, GNAQ, KRAS, MAP2K1, NRAS, PIK3CA, PIK3R1, PTPN11, RASA1, and TEK. According to Dr. Drolet, the common thread in these 13 genes is that they are implicated in cancer and have direct control over the cell cycle. “They’re intracellular proteins that control the cell cycle,” she explained. “These are proteins that are in the cell but interact with transmembrane proteins that receive extracellular messengers of cell growth”.

Understanding and recognizing genetic conditions is complicated, she said, because it involves determining which gene is altered, where in the DNA the gene is altered, how the gene variation will influence the function of the protein, and what tissue expresses that gene. “Then you get your phenotype,” Dr. Drolet said. “If you add mosaicism onto that, you have several additional variables. You need to know: When in embryogenesis did the mutation occur? What region of the body is affected? What cell lineage is affected? That predicts what phenotype you’re going to have.”

While molecular classification efforts continue to be refined, Dr. Drolet incorporates genotyping at every opportunity, like when she counsels parents of a baby born with a vascular stain on its face. “What can we tell them about what else might be wrong? What can we tell them about how this will change over time? What can we tell them about how we can treat it? I think genotyping absolutely helps to clarify that for me,” she said. “I can’t use that alone, but it gives me another piece of evidence to help do a better job in predicting when I need to screen, what I need to screen for, and what might happen in the future. If you combine your genotype with your clinical exam, I really do believe we can start to offer some prognostication for our families, to say, ‘this is the degree of overgrowth we may see over time; these are the complications I predict that you might have.’ ”

Even the vascular stain can give you a clue. “If it’s light and lacey, you probably don’t have a lot of cell cycle activation,” Dr. Drolet said. “If it’s dark and there’s blebs and you’ve got some bleeding at a young age, you’ve got a highly activated mutation, and there’s everything in between.”

Dr. Drolet disclosed that she is a consultant for Venthera and Novartis and is a board member for the Isthmus Project. She also holds intellectual property rights in and is a patent holder for Peds Derm Development Group. Dr. Drolet has also received funding from the Spirit Foundation, Kayleigh’s Crew Endowment, the SPD, PeDRA, and the National Institutes of Health.

[email protected]

Emerging data suggest that molecular classification of vascular anomalies can improve prognostication and treatment for babies born with these malformations, according to Beth Drolet, MD.

“We now know that 75%-80% of vascular malformations have gene mutations that make the cells either live longer, grow faster, or make them bigger in size,” Dr. Drolet, professor and chair of dermatology at the University of Wisconsin–Madison, said during the Society for Pediatric Dermatology pre-AAD meeting. “The basic binary premise of the current ISSVA [International Society for the Study of Vascular Anomalies] classification dividing vascular anomalies into tumors and malformations is wrong; the biology is not that straightforward. It may be helpful to differentiate between an infantile hemangioma and a capillary malformation during infancy as the hemangioma will grow in the next month, but we now know that patients with capillary malformations also have significant overgrowth of their tissue. We’ve all seen that; it just takes years, not months for us to notice it.”

The change in thinking about the root causes of vascular anomalies, she noted, stems from scientific advances in the understanding of embryonic mosaicism, DNA variation that happens after the zygote is formed, but before birth. “We know that each cell in a zygote will undergo 40 cell divisions before a baby is born,” she said. “Those cell divisions are not as neat as we thought they were. That cell and DNA duplication is actually quite messy, so there are mutations that happen purely because of embryonic cell division.”

Everyone is born with 120 somatic mutations per cell, she continued, “so we have multiple genomes in one human. Not all of those mutations are going to cause disease. Not all of those are going to be functional. About 10% of those mutations will actually be in a coding region of the gene and have the potential to change the function of the protein. If it changes the function of the protein so that the cell can’t survive, that cell dies off, but it gives the cell an advantage. It grows a little bit faster, let’s say. That cell survives, divides, producing a line of cells that can cause disease.”

In 2011, Dr. Drolet and colleagues from the Hemangioma Investigator Group and the Pediatric Dermatology Research Alliance (PeDRA) launched a multisite collaborative group to investigate the role of mosaic genetics in patients with vascular anomalies and discrepancy of growth. To date, 365 patients are enrolled, and the researchers have sequenced 97 of 165 affected tissue samples collected. “What’s nice about the registry is that we enrolled a wide spectrum of diseases: very mild diseases that might be treated by dermatologists to complex, syndromic diseases that might end up in an interdisciplinary vascular anomalies clinic,” she said.

For gene sequencing, the researchers drew from solid tumor biology and used next-generation sequencing with semi-target hybrid capture, “so we’re only looking at a subset of genes,” she said. “Right now, the chip we’re using has 180 cancer-related genes. It sequences the entire exome of the gene with a high depth of coverage, usually over 1,000 X. We use a specific pipeline that can detect very low allele frequency mutation: down to 1%, and robust criteria to determine variant pathogenicity.”

In 75% of tissue samples so far, the researchers have found a gene mutation in one of 13 genes: AKT1, AKT3, BRAF, GNA11, GNAQ, KRAS, MAP2K1, NRAS, PIK3CA, PIK3R1, PTPN11, RASA1, and TEK. According to Dr. Drolet, the common thread in these 13 genes is that they are implicated in cancer and have direct control over the cell cycle. “They’re intracellular proteins that control the cell cycle,” she explained. “These are proteins that are in the cell but interact with transmembrane proteins that receive extracellular messengers of cell growth”.

Understanding and recognizing genetic conditions is complicated, she said, because it involves determining which gene is altered, where in the DNA the gene is altered, how the gene variation will influence the function of the protein, and what tissue expresses that gene. “Then you get your phenotype,” Dr. Drolet said. “If you add mosaicism onto that, you have several additional variables. You need to know: When in embryogenesis did the mutation occur? What region of the body is affected? What cell lineage is affected? That predicts what phenotype you’re going to have.”

While molecular classification efforts continue to be refined, Dr. Drolet incorporates genotyping at every opportunity, like when she counsels parents of a baby born with a vascular stain on its face. “What can we tell them about what else might be wrong? What can we tell them about how this will change over time? What can we tell them about how we can treat it? I think genotyping absolutely helps to clarify that for me,” she said. “I can’t use that alone, but it gives me another piece of evidence to help do a better job in predicting when I need to screen, what I need to screen for, and what might happen in the future. If you combine your genotype with your clinical exam, I really do believe we can start to offer some prognostication for our families, to say, ‘this is the degree of overgrowth we may see over time; these are the complications I predict that you might have.’ ”

Even the vascular stain can give you a clue. “If it’s light and lacey, you probably don’t have a lot of cell cycle activation,” Dr. Drolet said. “If it’s dark and there’s blebs and you’ve got some bleeding at a young age, you’ve got a highly activated mutation, and there’s everything in between.”

Dr. Drolet disclosed that she is a consultant for Venthera and Novartis and is a board member for the Isthmus Project. She also holds intellectual property rights in and is a patent holder for Peds Derm Development Group. Dr. Drolet has also received funding from the Spirit Foundation, Kayleigh’s Crew Endowment, the SPD, PeDRA, and the National Institutes of Health.

[email protected]

Emerging data suggest that molecular classification of vascular anomalies can improve prognostication and treatment for babies born with these malformations, according to Beth Drolet, MD.

“We now know that 75%-80% of vascular malformations have gene mutations that make the cells either live longer, grow faster, or make them bigger in size,” Dr. Drolet, professor and chair of dermatology at the University of Wisconsin–Madison, said during the Society for Pediatric Dermatology pre-AAD meeting. “The basic binary premise of the current ISSVA [International Society for the Study of Vascular Anomalies] classification dividing vascular anomalies into tumors and malformations is wrong; the biology is not that straightforward. It may be helpful to differentiate between an infantile hemangioma and a capillary malformation during infancy as the hemangioma will grow in the next month, but we now know that patients with capillary malformations also have significant overgrowth of their tissue. We’ve all seen that; it just takes years, not months for us to notice it.”

The change in thinking about the root causes of vascular anomalies, she noted, stems from scientific advances in the understanding of embryonic mosaicism, DNA variation that happens after the zygote is formed, but before birth. “We know that each cell in a zygote will undergo 40 cell divisions before a baby is born,” she said. “Those cell divisions are not as neat as we thought they were. That cell and DNA duplication is actually quite messy, so there are mutations that happen purely because of embryonic cell division.”

Everyone is born with 120 somatic mutations per cell, she continued, “so we have multiple genomes in one human. Not all of those mutations are going to cause disease. Not all of those are going to be functional. About 10% of those mutations will actually be in a coding region of the gene and have the potential to change the function of the protein. If it changes the function of the protein so that the cell can’t survive, that cell dies off, but it gives the cell an advantage. It grows a little bit faster, let’s say. That cell survives, divides, producing a line of cells that can cause disease.”

In 2011, Dr. Drolet and colleagues from the Hemangioma Investigator Group and the Pediatric Dermatology Research Alliance (PeDRA) launched a multisite collaborative group to investigate the role of mosaic genetics in patients with vascular anomalies and discrepancy of growth. To date, 365 patients are enrolled, and the researchers have sequenced 97 of 165 affected tissue samples collected. “What’s nice about the registry is that we enrolled a wide spectrum of diseases: very mild diseases that might be treated by dermatologists to complex, syndromic diseases that might end up in an interdisciplinary vascular anomalies clinic,” she said.

For gene sequencing, the researchers drew from solid tumor biology and used next-generation sequencing with semi-target hybrid capture, “so we’re only looking at a subset of genes,” she said. “Right now, the chip we’re using has 180 cancer-related genes. It sequences the entire exome of the gene with a high depth of coverage, usually over 1,000 X. We use a specific pipeline that can detect very low allele frequency mutation: down to 1%, and robust criteria to determine variant pathogenicity.”

In 75% of tissue samples so far, the researchers have found a gene mutation in one of 13 genes: AKT1, AKT3, BRAF, GNA11, GNAQ, KRAS, MAP2K1, NRAS, PIK3CA, PIK3R1, PTPN11, RASA1, and TEK. According to Dr. Drolet, the common thread in these 13 genes is that they are implicated in cancer and have direct control over the cell cycle. “They’re intracellular proteins that control the cell cycle,” she explained. “These are proteins that are in the cell but interact with transmembrane proteins that receive extracellular messengers of cell growth”.

Understanding and recognizing genetic conditions is complicated, she said, because it involves determining which gene is altered, where in the DNA the gene is altered, how the gene variation will influence the function of the protein, and what tissue expresses that gene. “Then you get your phenotype,” Dr. Drolet said. “If you add mosaicism onto that, you have several additional variables. You need to know: When in embryogenesis did the mutation occur? What region of the body is affected? What cell lineage is affected? That predicts what phenotype you’re going to have.”

While molecular classification efforts continue to be refined, Dr. Drolet incorporates genotyping at every opportunity, like when she counsels parents of a baby born with a vascular stain on its face. “What can we tell them about what else might be wrong? What can we tell them about how this will change over time? What can we tell them about how we can treat it? I think genotyping absolutely helps to clarify that for me,” she said. “I can’t use that alone, but it gives me another piece of evidence to help do a better job in predicting when I need to screen, what I need to screen for, and what might happen in the future. If you combine your genotype with your clinical exam, I really do believe we can start to offer some prognostication for our families, to say, ‘this is the degree of overgrowth we may see over time; these are the complications I predict that you might have.’ ”

Even the vascular stain can give you a clue. “If it’s light and lacey, you probably don’t have a lot of cell cycle activation,” Dr. Drolet said. “If it’s dark and there’s blebs and you’ve got some bleeding at a young age, you’ve got a highly activated mutation, and there’s everything in between.”

Dr. Drolet disclosed that she is a consultant for Venthera and Novartis and is a board member for the Isthmus Project. She also holds intellectual property rights in and is a patent holder for Peds Derm Development Group. Dr. Drolet has also received funding from the Spirit Foundation, Kayleigh’s Crew Endowment, the SPD, PeDRA, and the National Institutes of Health.

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