Nonmelanoma Skin Cancer

Surgical therapies remain the preferred treatment for the management of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), according to new practice guidelines issued by the American Academy of Dermatology.

Nonsurgical approaches such as cryotherapy, photodynamic therapy, and radiation may be considered for low-risk cancers if surgery is contraindicated, but these methods have lower cure rates, according to the guidelines. Christopher K. Bichakjian, MD, professor of dermatology, University of Michigan, Ann Arbor, and Murad Alam, MD, professor of dermatology, Northwestern University, Chicago, cochaired the work groups that developed the guidelines.

dermnews@frontlinemedcom.com

Surgical therapies remain the preferred treatment for the management of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), according to new practice guidelines issued by the American Academy of Dermatology.

Nonsurgical approaches such as cryotherapy, photodynamic therapy, and radiation may be considered for low-risk cancers if surgery is contraindicated, but these methods have lower cure rates, according to the guidelines. Christopher K. Bichakjian, MD, professor of dermatology, University of Michigan, Ann Arbor, and Murad Alam, MD, professor of dermatology, Northwestern University, Chicago, cochaired the work groups that developed the guidelines.

dermnews@frontlinemedcom.com

Surgical therapies remain the preferred treatment for the management of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), according to new practice guidelines issued by the American Academy of Dermatology.

Nonsurgical approaches such as cryotherapy, photodynamic therapy, and radiation may be considered for low-risk cancers if surgery is contraindicated, but these methods have lower cure rates, according to the guidelines. Christopher K. Bichakjian, MD, professor of dermatology, University of Michigan, Ann Arbor, and Murad Alam, MD, professor of dermatology, Northwestern University, Chicago, cochaired the work groups that developed the guidelines.

dermnews@frontlinemedcom.com

To the Editor:

A 53-year-old woman was referred by her oncologist to our dermatology office with lesions on the face and body that presented 8 days after starting vemurafenib 960 mg twice daily for metastatic melanoma. The patient denied any symptoms from the lesions but was concerned they would spread to cover her entire face and body.

The patient's medical history included a diagnosis of metastatic melanoma 6 years prior to presentation. She stated that the primary cutaneous melanoma site was unknown. The patient had endured numerous surgeries to excise lymph node tumors, with some lesions up to 3 cm. The patient recently started vemurafenib, a treatment for BRAF V600E mutation-positive metastatic melanoma. The patient's personal history was notable for hepatitis A, B, and C, and her family history revealed her mother had metastatic lung cancer.

Physical examination revealed numerous 2- to 3-mm, round-oval, flesh-colored to light-brown papules on the cheeks, chest, abdomen (Figure 1), back, and both arms and legs. Some papules were inflamed and some had a stuck-on appearance. Lesions on the chest between the breasts and inframammary region were slightly inflamed. Two skin biopsies were performed. Biopsy of the lesion on the right lateral back revealed solar lentigo, early macular seborrheic keratosis, and a focus of inflamed mild solar keratosis. The dermis showed a mild superficial perivascular and interstitial inflammatory infiltrate composed mostly of lymphocytes, histiocytes, and eosinophils. There were occasional melanophages present (Figure 2). Biopsy of the lesion between the breasts revealed inflamed verrucous seborrheic keratosis (Figure 3).

We treated the lesion on the right lateral back with cycles of cryotherapy and explained to the patient that the lesion between the breasts was benign. We also reiterated to the patient the importance of wearing sun-protective clothing and UVA/UVB sunblock with a sun protection factor of 30 or higher.

Our patient was diagnosed with pneumonia and subsequently had to discontinue vemurafenib. During the period of nontreatment, the keratotic lesions cleared with postinflammatory hyperpigmentation and no epidermal changes, which showed a possible inference of a direct relationship between the vemurafenib and the appearance of the nonmalignant cutaneous lesions. Although this report only represents 1 patient, other patients possibly can benefit from a modified dose of vemurafenib, which either would resolve or lessen the quantity of these lesions.

Vemurafenib is the first US Food and Drug Administration-approved treatment for nonresectable metastatic melanoma with the BRAF V600E mutation as detected by a US Food and Drug Administration-approved test.^1,2 Mutated BRAF is present in approximately 60% of cutaneous melanomas.³ Vemurafenib targets the oncogenic BRAF V600E making the protein inactive, thus inhibiting cell proliferation and leading to apoptosis and shrinkage of the metastatic tumors.^3-5 Vemurafenib has a response rate of more than 50% and is associated with rapid improvement in quality of life.³

Cutaneous side effects include increased incidence of squamous cell carcinoma and keratoacanthomas, appearing approximately 7 to 8 weeks after starting vemurafenib.⁴ The incidence of these lesions increases in patients 65 years and older and in patients with prior skin cancer and chronic sun exposure. The paradoxical activation of the mitogen-activated protein kinase pathway by mutant BRAF-selective inhibitors provides an explanation of the induction of squamous cell carcinomas.⁴ Prior to the initiation of vemurafenib, all patients should receive a total-body skin examination and every 2 months thereafter while on treatment. After discontinuation of the medicine, the patient should continue to receive total-body skin evaluations every 6 months indefinitely.

Patients should be aware of the potential for mild to severe photosensitivity reactions. They should be advised to limit their sun exposure time and to wear sun-protective clothing when outdoors. The use of broad-spectrum UVA/UVB sunscreen and lip protectant with a sun protection factor of 30 or higher also should be stressed.^6,7 Patients should be aware that UVA rays penetrate glass; therefore, UV-protective clothing should be worn throughout the day and during all seasons.⁷

In clinical trials of vemurafenib, Stevens-Johnson syndrome and toxic epidermal necrolysis was reported in 2 patients.^8,9 Clinical trials also reported patients developing new primary malignant melanoma lesions.¹⁰ These findings further emphasize the need for patients to undergo total-body skin examinations during and after treatment.

Other possible dermatologic reactions include a generalized rash, erythema, alopecia, and pruritus.^2,3 The development of benign growths associated with patients on vemurafenib include follicular plugging seen in keratosis pilaris, palmar and plantar hyperkeratosis, seborrheic dermatitis-like rashes, verrucous keratosis, and acantholytic dyskeratosis.^8,11,12

We report a case of nonmalignant growths occurring 8 days after starting vemurafenib. This case illustrates potential cutaneous adverse reactions that were benign yet still of great concern to our patient. Many of these nonmalignant cutaneous findings are associated with abnormal follicular keratinization thought to be secondary to abnormal signaling of the mitogen-activated protein kinase pathway that occurs with the use of BRAF inhibitors.⁸ Although in this case malignant lesions were not discovered, the need for total-body skin examinations exists during all stages of treatment. Supportive care and reassurance should be given to patients along with local treatments including topical therapies (steroids, retinoids), cryotherapy, and biopsies or excisions when necessary.^13,14

To the Editor:

A 53-year-old woman was referred by her oncologist to our dermatology office with lesions on the face and body that presented 8 days after starting vemurafenib 960 mg twice daily for metastatic melanoma. The patient denied any symptoms from the lesions but was concerned they would spread to cover her entire face and body.

The patient's medical history included a diagnosis of metastatic melanoma 6 years prior to presentation. She stated that the primary cutaneous melanoma site was unknown. The patient had endured numerous surgeries to excise lymph node tumors, with some lesions up to 3 cm. The patient recently started vemurafenib, a treatment for BRAF V600E mutation-positive metastatic melanoma. The patient's personal history was notable for hepatitis A, B, and C, and her family history revealed her mother had metastatic lung cancer.

Physical examination revealed numerous 2- to 3-mm, round-oval, flesh-colored to light-brown papules on the cheeks, chest, abdomen (Figure 1), back, and both arms and legs. Some papules were inflamed and some had a stuck-on appearance. Lesions on the chest between the breasts and inframammary region were slightly inflamed. Two skin biopsies were performed. Biopsy of the lesion on the right lateral back revealed solar lentigo, early macular seborrheic keratosis, and a focus of inflamed mild solar keratosis. The dermis showed a mild superficial perivascular and interstitial inflammatory infiltrate composed mostly of lymphocytes, histiocytes, and eosinophils. There were occasional melanophages present (Figure 2). Biopsy of the lesion between the breasts revealed inflamed verrucous seborrheic keratosis (Figure 3).

We treated the lesion on the right lateral back with cycles of cryotherapy and explained to the patient that the lesion between the breasts was benign. We also reiterated to the patient the importance of wearing sun-protective clothing and UVA/UVB sunblock with a sun protection factor of 30 or higher.

Our patient was diagnosed with pneumonia and subsequently had to discontinue vemurafenib. During the period of nontreatment, the keratotic lesions cleared with postinflammatory hyperpigmentation and no epidermal changes, which showed a possible inference of a direct relationship between the vemurafenib and the appearance of the nonmalignant cutaneous lesions. Although this report only represents 1 patient, other patients possibly can benefit from a modified dose of vemurafenib, which either would resolve or lessen the quantity of these lesions.

Vemurafenib is the first US Food and Drug Administration-approved treatment for nonresectable metastatic melanoma with the BRAF V600E mutation as detected by a US Food and Drug Administration-approved test.^1,2 Mutated BRAF is present in approximately 60% of cutaneous melanomas.³ Vemurafenib targets the oncogenic BRAF V600E making the protein inactive, thus inhibiting cell proliferation and leading to apoptosis and shrinkage of the metastatic tumors.^3-5 Vemurafenib has a response rate of more than 50% and is associated with rapid improvement in quality of life.³

Cutaneous side effects include increased incidence of squamous cell carcinoma and keratoacanthomas, appearing approximately 7 to 8 weeks after starting vemurafenib.⁴ The incidence of these lesions increases in patients 65 years and older and in patients with prior skin cancer and chronic sun exposure. The paradoxical activation of the mitogen-activated protein kinase pathway by mutant BRAF-selective inhibitors provides an explanation of the induction of squamous cell carcinomas.⁴ Prior to the initiation of vemurafenib, all patients should receive a total-body skin examination and every 2 months thereafter while on treatment. After discontinuation of the medicine, the patient should continue to receive total-body skin evaluations every 6 months indefinitely.

Patients should be aware of the potential for mild to severe photosensitivity reactions. They should be advised to limit their sun exposure time and to wear sun-protective clothing when outdoors. The use of broad-spectrum UVA/UVB sunscreen and lip protectant with a sun protection factor of 30 or higher also should be stressed.^6,7 Patients should be aware that UVA rays penetrate glass; therefore, UV-protective clothing should be worn throughout the day and during all seasons.⁷

In clinical trials of vemurafenib, Stevens-Johnson syndrome and toxic epidermal necrolysis was reported in 2 patients.^8,9 Clinical trials also reported patients developing new primary malignant melanoma lesions.¹⁰ These findings further emphasize the need for patients to undergo total-body skin examinations during and after treatment.

Other possible dermatologic reactions include a generalized rash, erythema, alopecia, and pruritus.^2,3 The development of benign growths associated with patients on vemurafenib include follicular plugging seen in keratosis pilaris, palmar and plantar hyperkeratosis, seborrheic dermatitis-like rashes, verrucous keratosis, and acantholytic dyskeratosis.^8,11,12

We report a case of nonmalignant growths occurring 8 days after starting vemurafenib. This case illustrates potential cutaneous adverse reactions that were benign yet still of great concern to our patient. Many of these nonmalignant cutaneous findings are associated with abnormal follicular keratinization thought to be secondary to abnormal signaling of the mitogen-activated protein kinase pathway that occurs with the use of BRAF inhibitors.⁸ Although in this case malignant lesions were not discovered, the need for total-body skin examinations exists during all stages of treatment. Supportive care and reassurance should be given to patients along with local treatments including topical therapies (steroids, retinoids), cryotherapy, and biopsies or excisions when necessary.^13,14

To the Editor:

A 53-year-old woman was referred by her oncologist to our dermatology office with lesions on the face and body that presented 8 days after starting vemurafenib 960 mg twice daily for metastatic melanoma. The patient denied any symptoms from the lesions but was concerned they would spread to cover her entire face and body.

The patient's medical history included a diagnosis of metastatic melanoma 6 years prior to presentation. She stated that the primary cutaneous melanoma site was unknown. The patient had endured numerous surgeries to excise lymph node tumors, with some lesions up to 3 cm. The patient recently started vemurafenib, a treatment for BRAF V600E mutation-positive metastatic melanoma. The patient's personal history was notable for hepatitis A, B, and C, and her family history revealed her mother had metastatic lung cancer.

Physical examination revealed numerous 2- to 3-mm, round-oval, flesh-colored to light-brown papules on the cheeks, chest, abdomen (Figure 1), back, and both arms and legs. Some papules were inflamed and some had a stuck-on appearance. Lesions on the chest between the breasts and inframammary region were slightly inflamed. Two skin biopsies were performed. Biopsy of the lesion on the right lateral back revealed solar lentigo, early macular seborrheic keratosis, and a focus of inflamed mild solar keratosis. The dermis showed a mild superficial perivascular and interstitial inflammatory infiltrate composed mostly of lymphocytes, histiocytes, and eosinophils. There were occasional melanophages present (Figure 2). Biopsy of the lesion between the breasts revealed inflamed verrucous seborrheic keratosis (Figure 3).

We treated the lesion on the right lateral back with cycles of cryotherapy and explained to the patient that the lesion between the breasts was benign. We also reiterated to the patient the importance of wearing sun-protective clothing and UVA/UVB sunblock with a sun protection factor of 30 or higher.

Our patient was diagnosed with pneumonia and subsequently had to discontinue vemurafenib. During the period of nontreatment, the keratotic lesions cleared with postinflammatory hyperpigmentation and no epidermal changes, which showed a possible inference of a direct relationship between the vemurafenib and the appearance of the nonmalignant cutaneous lesions. Although this report only represents 1 patient, other patients possibly can benefit from a modified dose of vemurafenib, which either would resolve or lessen the quantity of these lesions.

Vemurafenib is the first US Food and Drug Administration-approved treatment for nonresectable metastatic melanoma with the BRAF V600E mutation as detected by a US Food and Drug Administration-approved test.^1,2 Mutated BRAF is present in approximately 60% of cutaneous melanomas.³ Vemurafenib targets the oncogenic BRAF V600E making the protein inactive, thus inhibiting cell proliferation and leading to apoptosis and shrinkage of the metastatic tumors.^3-5 Vemurafenib has a response rate of more than 50% and is associated with rapid improvement in quality of life.³

Cutaneous side effects include increased incidence of squamous cell carcinoma and keratoacanthomas, appearing approximately 7 to 8 weeks after starting vemurafenib.⁴ The incidence of these lesions increases in patients 65 years and older and in patients with prior skin cancer and chronic sun exposure. The paradoxical activation of the mitogen-activated protein kinase pathway by mutant BRAF-selective inhibitors provides an explanation of the induction of squamous cell carcinomas.⁴ Prior to the initiation of vemurafenib, all patients should receive a total-body skin examination and every 2 months thereafter while on treatment. After discontinuation of the medicine, the patient should continue to receive total-body skin evaluations every 6 months indefinitely.

Patients should be aware of the potential for mild to severe photosensitivity reactions. They should be advised to limit their sun exposure time and to wear sun-protective clothing when outdoors. The use of broad-spectrum UVA/UVB sunscreen and lip protectant with a sun protection factor of 30 or higher also should be stressed.^6,7 Patients should be aware that UVA rays penetrate glass; therefore, UV-protective clothing should be worn throughout the day and during all seasons.⁷

In clinical trials of vemurafenib, Stevens-Johnson syndrome and toxic epidermal necrolysis was reported in 2 patients.^8,9 Clinical trials also reported patients developing new primary malignant melanoma lesions.¹⁰ These findings further emphasize the need for patients to undergo total-body skin examinations during and after treatment.

Other possible dermatologic reactions include a generalized rash, erythema, alopecia, and pruritus.^2,3 The development of benign growths associated with patients on vemurafenib include follicular plugging seen in keratosis pilaris, palmar and plantar hyperkeratosis, seborrheic dermatitis-like rashes, verrucous keratosis, and acantholytic dyskeratosis.^8,11,12

We report a case of nonmalignant growths occurring 8 days after starting vemurafenib. This case illustrates potential cutaneous adverse reactions that were benign yet still of great concern to our patient. Many of these nonmalignant cutaneous findings are associated with abnormal follicular keratinization thought to be secondary to abnormal signaling of the mitogen-activated protein kinase pathway that occurs with the use of BRAF inhibitors.⁸ Although in this case malignant lesions were not discovered, the need for total-body skin examinations exists during all stages of treatment. Supportive care and reassurance should be given to patients along with local treatments including topical therapies (steroids, retinoids), cryotherapy, and biopsies or excisions when necessary.^13,14

Dermoscopy increases diagnostic accuracy in the analysis of skin growths.^1,2 Recently the use of dermoscopy has broadened to include inflammatory dermatoses and skin infections.³ To substantiate the value of dermoscopy in assessing psoriasis, we performed a systematic review of the literature and briefly reviewed 31 articles. We also report a case that highlights the differences between psoriasis and basal cell carcinoma (BCC) under dermoscopic examination, and we discuss the literature on the dermoscopic findings of psoriasis with an emphasis on the relative sensitivities and specificities of dermoscopic findings for psoriasis and for BCC.

Case Report

A 63-year-old man with psoriasis and a history of BCC presented for follow-up of psoriasis, which was well-controlled on etanercept. The physical examination was remarkable for scaly pink papules scattered on the trunk and extremities. A new larger red-pink patch was located on the left lower back (Figure 1). Dermoscopic evaluation of the new patch revealed shiny white lines and branching blood vessels (Figure 2). Pathology results of a shave biopsy revealed superficial BCC. The skin cancer was treated with electrodesiccation and curettage.

Comment

The clinical morphology of psoriasis and BCC can be similar, and dermoscopy can help in differentiating between the 2 conditions.

Literature Search on Dermoscopy and Psoriasis
We performed a PubMed search of articles indexed for MEDLINE to review the published literature on dermoscopy and psoriasis. Two reviewers (C.H. and L.C.) searched for psoriasis paired with the terms dermoscopy or dermatoscopy or epiluminescence microscopy. Only English-language articles published between 1996 and 2016 were included in the search. Articles that focused solely on confocal microscopy were excluded. Article titles and abstracts were evaluated and articles that omitted mention of dermoscopy and psoriasis were excluded, yielding a total of 31 articles. Of these articles, only 2 discussed the specificity or sensitivity of the dermoscopic findings of psoriasis.^4,5 Most of the articles were case reports and descriptive cross-sectional studies. The reports addressed multiple subtypes of psoriasis, but reports on psoriasis vulgaris and scalp psoriasis were most common (Table). Lallas et al⁶ provided a comprehensive descriptive review of the main findings on dermoscopy for psoriasis and other inflammatory skin conditions, but it lacked a comparison between psoriasis and BCC or data on the sensitivity and specificity of the findings. Two studies reported sensitivity and specificity values for the dermoscopic findings of psoriasis.^4,5 Pan et al⁵ reported a 98% diagnostic probability of psoriasis if red dots, homogeneous vascular pattern, and a light red background are all present. Additionally, they reported that the presence of 4 of 6 criteria for BCC—scattered vascular pattern, arborizing microvessels, telangiectatic or atypical vessels, milky-pink background, and brown dots⁄globules—yielded a diagnostic probability of 99%.⁵ Similarly, Lallas et al⁶ demonstrated that the presence of dotted vessels alone is not sufficient to presume a diagnosis of psoriasis, as this finding can be seen in other inflammatory skin conditions. However, “the combination of regularly distributed dotted vessels over a light red background associated with diffuse white scales was highly predictive of [plaque psoriasis] and allowed a correct diagnosis with 88.0% specificity and 84.9% sensitivity.”⁴ Figure 3 shows a dermoscopic image of plaque psoriasis that demonstrates these findings. The remaining literature corroborated this evidence, with the most commonly reported dermoscopic findings of psoriasis being red dots, red globules, glomerular vessels (also known as twisted capillary loops), red globular rings, and white scale.^7-12

Dermoscopy and BCC
Much has been published on the dermoscopic findings of BCC.^5,13-15 The dermoscopic findings of BCC include large blue-gray ovoid nests, leaflike areas, spoke-wheel–like areas, arborizing vessels (telangiectasia), and ulceration.¹⁵ Superficial BCC is characterized by short fine or arborizing telangiectasia, shallow erosions, and shiny white areas.¹⁵ The positive predictive value of dermoscopy in BCC is as high as 97%.¹⁶ Additionally, multiple studies report a sensitivity of 95% to 99%^5,13,14 and a specificity of 79% to 99% in the use of dermoscopy for identifying BCC. According to Pan et al,⁵ the most sensitive finding for BCC is a scattered vascular pattern (97%), while the most specific finding is arborizing microvessels (99%).

Utility of Dermoscopy
Our case of a 63-year-old man with a history of psoriasis and BCC highlights the usefulness of dermoscopy in accurately determining the features of each condition. Additionally, dermoscopy aids in differentiating between psoriasis and squamous cell carcinoma. In contrast to the dotted vessels seen in psoriasis, squamous cell carcinomas often have peripheral hairpin (glomerular) vessels.¹⁷

If future reports confirm dermoscopy’s utility in accurately diagnosing psoriasis, fewer biopsies may be needed when evaluating patients with new rashes. Furthermore, dermoscopy may expedite treatment of psoriasis (as it can for malignant conditions) by obviating the wait for pathology results currently needed to initiate systemic treatment. For patients with psoriasis who also have sun-damaged skin, dermoscopy may assist in differentiating pink patches and plaques of psoriasis from skin cancer, such as superficial BCCs, which often have shiny white lines not seen in psoriasis.¹⁵

Dermoscopy increases diagnostic accuracy in the analysis of skin growths.^1,2 Recently the use of dermoscopy has broadened to include inflammatory dermatoses and skin infections.³ To substantiate the value of dermoscopy in assessing psoriasis, we performed a systematic review of the literature and briefly reviewed 31 articles. We also report a case that highlights the differences between psoriasis and basal cell carcinoma (BCC) under dermoscopic examination, and we discuss the literature on the dermoscopic findings of psoriasis with an emphasis on the relative sensitivities and specificities of dermoscopic findings for psoriasis and for BCC.

Case Report

A 63-year-old man with psoriasis and a history of BCC presented for follow-up of psoriasis, which was well-controlled on etanercept. The physical examination was remarkable for scaly pink papules scattered on the trunk and extremities. A new larger red-pink patch was located on the left lower back (Figure 1). Dermoscopic evaluation of the new patch revealed shiny white lines and branching blood vessels (Figure 2). Pathology results of a shave biopsy revealed superficial BCC. The skin cancer was treated with electrodesiccation and curettage.

Comment

The clinical morphology of psoriasis and BCC can be similar, and dermoscopy can help in differentiating between the 2 conditions.

Literature Search on Dermoscopy and Psoriasis
We performed a PubMed search of articles indexed for MEDLINE to review the published literature on dermoscopy and psoriasis. Two reviewers (C.H. and L.C.) searched for psoriasis paired with the terms dermoscopy or dermatoscopy or epiluminescence microscopy. Only English-language articles published between 1996 and 2016 were included in the search. Articles that focused solely on confocal microscopy were excluded. Article titles and abstracts were evaluated and articles that omitted mention of dermoscopy and psoriasis were excluded, yielding a total of 31 articles. Of these articles, only 2 discussed the specificity or sensitivity of the dermoscopic findings of psoriasis.^4,5 Most of the articles were case reports and descriptive cross-sectional studies. The reports addressed multiple subtypes of psoriasis, but reports on psoriasis vulgaris and scalp psoriasis were most common (Table). Lallas et al⁶ provided a comprehensive descriptive review of the main findings on dermoscopy for psoriasis and other inflammatory skin conditions, but it lacked a comparison between psoriasis and BCC or data on the sensitivity and specificity of the findings. Two studies reported sensitivity and specificity values for the dermoscopic findings of psoriasis.^4,5 Pan et al⁵ reported a 98% diagnostic probability of psoriasis if red dots, homogeneous vascular pattern, and a light red background are all present. Additionally, they reported that the presence of 4 of 6 criteria for BCC—scattered vascular pattern, arborizing microvessels, telangiectatic or atypical vessels, milky-pink background, and brown dots⁄globules—yielded a diagnostic probability of 99%.⁵ Similarly, Lallas et al⁶ demonstrated that the presence of dotted vessels alone is not sufficient to presume a diagnosis of psoriasis, as this finding can be seen in other inflammatory skin conditions. However, “the combination of regularly distributed dotted vessels over a light red background associated with diffuse white scales was highly predictive of [plaque psoriasis] and allowed a correct diagnosis with 88.0% specificity and 84.9% sensitivity.”⁴ Figure 3 shows a dermoscopic image of plaque psoriasis that demonstrates these findings. The remaining literature corroborated this evidence, with the most commonly reported dermoscopic findings of psoriasis being red dots, red globules, glomerular vessels (also known as twisted capillary loops), red globular rings, and white scale.^7-12

Dermoscopy and BCC
Much has been published on the dermoscopic findings of BCC.^5,13-15 The dermoscopic findings of BCC include large blue-gray ovoid nests, leaflike areas, spoke-wheel–like areas, arborizing vessels (telangiectasia), and ulceration.¹⁵ Superficial BCC is characterized by short fine or arborizing telangiectasia, shallow erosions, and shiny white areas.¹⁵ The positive predictive value of dermoscopy in BCC is as high as 97%.¹⁶ Additionally, multiple studies report a sensitivity of 95% to 99%^5,13,14 and a specificity of 79% to 99% in the use of dermoscopy for identifying BCC. According to Pan et al,⁵ the most sensitive finding for BCC is a scattered vascular pattern (97%), while the most specific finding is arborizing microvessels (99%).

Utility of Dermoscopy
Our case of a 63-year-old man with a history of psoriasis and BCC highlights the usefulness of dermoscopy in accurately determining the features of each condition. Additionally, dermoscopy aids in differentiating between psoriasis and squamous cell carcinoma. In contrast to the dotted vessels seen in psoriasis, squamous cell carcinomas often have peripheral hairpin (glomerular) vessels.¹⁷

If future reports confirm dermoscopy’s utility in accurately diagnosing psoriasis, fewer biopsies may be needed when evaluating patients with new rashes. Furthermore, dermoscopy may expedite treatment of psoriasis (as it can for malignant conditions) by obviating the wait for pathology results currently needed to initiate systemic treatment. For patients with psoriasis who also have sun-damaged skin, dermoscopy may assist in differentiating pink patches and plaques of psoriasis from skin cancer, such as superficial BCCs, which often have shiny white lines not seen in psoriasis.¹⁵

Dermoscopy increases diagnostic accuracy in the analysis of skin growths.^1,2 Recently the use of dermoscopy has broadened to include inflammatory dermatoses and skin infections.³ To substantiate the value of dermoscopy in assessing psoriasis, we performed a systematic review of the literature and briefly reviewed 31 articles. We also report a case that highlights the differences between psoriasis and basal cell carcinoma (BCC) under dermoscopic examination, and we discuss the literature on the dermoscopic findings of psoriasis with an emphasis on the relative sensitivities and specificities of dermoscopic findings for psoriasis and for BCC.

Case Report

A 63-year-old man with psoriasis and a history of BCC presented for follow-up of psoriasis, which was well-controlled on etanercept. The physical examination was remarkable for scaly pink papules scattered on the trunk and extremities. A new larger red-pink patch was located on the left lower back (Figure 1). Dermoscopic evaluation of the new patch revealed shiny white lines and branching blood vessels (Figure 2). Pathology results of a shave biopsy revealed superficial BCC. The skin cancer was treated with electrodesiccation and curettage.

Comment

The clinical morphology of psoriasis and BCC can be similar, and dermoscopy can help in differentiating between the 2 conditions.

Literature Search on Dermoscopy and Psoriasis
We performed a PubMed search of articles indexed for MEDLINE to review the published literature on dermoscopy and psoriasis. Two reviewers (C.H. and L.C.) searched for psoriasis paired with the terms dermoscopy or dermatoscopy or epiluminescence microscopy. Only English-language articles published between 1996 and 2016 were included in the search. Articles that focused solely on confocal microscopy were excluded. Article titles and abstracts were evaluated and articles that omitted mention of dermoscopy and psoriasis were excluded, yielding a total of 31 articles. Of these articles, only 2 discussed the specificity or sensitivity of the dermoscopic findings of psoriasis.^4,5 Most of the articles were case reports and descriptive cross-sectional studies. The reports addressed multiple subtypes of psoriasis, but reports on psoriasis vulgaris and scalp psoriasis were most common (Table). Lallas et al⁶ provided a comprehensive descriptive review of the main findings on dermoscopy for psoriasis and other inflammatory skin conditions, but it lacked a comparison between psoriasis and BCC or data on the sensitivity and specificity of the findings. Two studies reported sensitivity and specificity values for the dermoscopic findings of psoriasis.^4,5 Pan et al⁵ reported a 98% diagnostic probability of psoriasis if red dots, homogeneous vascular pattern, and a light red background are all present. Additionally, they reported that the presence of 4 of 6 criteria for BCC—scattered vascular pattern, arborizing microvessels, telangiectatic or atypical vessels, milky-pink background, and brown dots⁄globules—yielded a diagnostic probability of 99%.⁵ Similarly, Lallas et al⁶ demonstrated that the presence of dotted vessels alone is not sufficient to presume a diagnosis of psoriasis, as this finding can be seen in other inflammatory skin conditions. However, “the combination of regularly distributed dotted vessels over a light red background associated with diffuse white scales was highly predictive of [plaque psoriasis] and allowed a correct diagnosis with 88.0% specificity and 84.9% sensitivity.”⁴ Figure 3 shows a dermoscopic image of plaque psoriasis that demonstrates these findings. The remaining literature corroborated this evidence, with the most commonly reported dermoscopic findings of psoriasis being red dots, red globules, glomerular vessels (also known as twisted capillary loops), red globular rings, and white scale.^7-12

Dermoscopy and BCC
Much has been published on the dermoscopic findings of BCC.^5,13-15 The dermoscopic findings of BCC include large blue-gray ovoid nests, leaflike areas, spoke-wheel–like areas, arborizing vessels (telangiectasia), and ulceration.¹⁵ Superficial BCC is characterized by short fine or arborizing telangiectasia, shallow erosions, and shiny white areas.¹⁵ The positive predictive value of dermoscopy in BCC is as high as 97%.¹⁶ Additionally, multiple studies report a sensitivity of 95% to 99%^5,13,14 and a specificity of 79% to 99% in the use of dermoscopy for identifying BCC. According to Pan et al,⁵ the most sensitive finding for BCC is a scattered vascular pattern (97%), while the most specific finding is arborizing microvessels (99%).

Utility of Dermoscopy
Our case of a 63-year-old man with a history of psoriasis and BCC highlights the usefulness of dermoscopy in accurately determining the features of each condition. Additionally, dermoscopy aids in differentiating between psoriasis and squamous cell carcinoma. In contrast to the dotted vessels seen in psoriasis, squamous cell carcinomas often have peripheral hairpin (glomerular) vessels.¹⁷

If future reports confirm dermoscopy’s utility in accurately diagnosing psoriasis, fewer biopsies may be needed when evaluating patients with new rashes. Furthermore, dermoscopy may expedite treatment of psoriasis (as it can for malignant conditions) by obviating the wait for pathology results currently needed to initiate systemic treatment. For patients with psoriasis who also have sun-damaged skin, dermoscopy may assist in differentiating pink patches and plaques of psoriasis from skin cancer, such as superficial BCCs, which often have shiny white lines not seen in psoriasis.¹⁵

The incidence of melanoma is increasing at a rate greater than any other cancer,¹ possibly due to the increasing use of indoor tanning devices. These devices emit unnaturally high levels of UVA and low levels of UVA and UVB rays.² The risks of using these devices include increased incidence of melanoma (3438 cases attributed to indoor tanning in 2008) and keratinocytes cancer (increased risk of squamous cell carcinoma by 67% and basal cell carcinoma by 29%), severe sunburns (61.1% of female users and 44.6% of male users have reported sunburns), and aggravation of underlying disorders such as systemic lupus erythematosus.^3-5

The literature varies in its explanation of how indoor tanning increases the risk of developing melanoma. Some authors suggest it is due to increased frequency of use, duration of sessions, and years of using tanning devices.^1,6 Others suggest the increased cancer risk is the result of starting to tan at an earlier age.^2,3,6-10 There is conflicting literature on the level of increased risk of melanoma in those who tan indoors at a young age (<35 years). Although the estimated rate of increased skin cancer risk varies, with rates up to 75% compared to nonusers, nearly all sources support an increased rate.⁶ Despite the growing body of knowledge that indoor tanning is dangerous, as well as the academic publication of these risks (eg, carcinogenesis, short-term and long-term eye injury, burns, UV sensitivity when combined with certain medications), teenagers in the United States and affluent countries appear to disregard the risks of tanning.¹¹

Tanning companies have promoted the misconception that only UVB rays cause cell damage and UVA rays, which the devices emit, result in “damage-free” or “safe” tans.^2,3 Until 2013, indoor tanning devices were classified by the US Food and Drug Administration (FDA) as class I, indicating that they are safe in terms of electrical shock. Many indoor tanning facilities have promoted the FDA “safe” label without clarifying that the safety indications only referred to electrical-shock potential. Nonetheless, it is known now that these devices, which emit high UVA and low UVB rays, promote melanoma, nonmelanoma skin cancers, and severe sunburns, as well as aggravate existing conditions (eg, systemic lupus erythematosus).⁴ As a result of an unacceptably high incidence of these disease complications, a 2014 FDA regulation categorized tanning beds as class II, requiring that tanning bed users be informed of the risk of skin cancer in an effort to reverse the growing trend of indoor tanning.¹² Despite these regulatory interventions, it is not clear if this knowledge of cancer risk deters patients from indoor tanning.

The purpose of this study was to investigate the patients’ perspective on indoor tanning behaviors as associated with the severity of their melanoma and the time frame in which they were diagnosed as well as their perceived views on the safety of indoor tanning and the frequency in which they continue to tan indoors. This information is highly relevant in helping to determine if requiring a warning of the risk of skin cancer will deter patients from this unhealthy habit, especially given recent reclassification of sunbeds as class II by the FDA. Additional insights from these data may clarify if indoor tanning decreases the time frame in which melanoma is diagnosed or increases the severity of the resulting melanoma. Moreover, it will help elucidate whether or not the age at which indoor tanning is initiated affects the time frame to melanoma onset and corresponding severity.

Methods

An original unvalidated online survey was conducted worldwide via a link distributed to the following supporting institutions: Advanced Dermatology & Cosmetic Surgery, Ameriderm Research, Melanoma Research Foundation (a melanoma patient advocacy group), Florida State University Department of Dermatology, Moffitt Cancer Center Cutaneous Oncology Program, Cleveland Clinic, Ohio State University Division of Medical Oncology, Harvard Medical School Department of Dermatology, The University of Texas MD Anderson Cancer Center Department of Dermatology, University of Colorado Department of Dermatology, and Northwestern University Department of Dermatology. However, there was not confirmation that all of these institutions promoted the survey. Additionally, respondents were recruited through patient advocacy groups and social media sites including Facebook, Twitter, LinkedIn, Tumblr, and Instagram. The patient advocacy groups and social media sites invited participation through recruitment announcements, including DermNetNZ (a global dermatology patient information site), with additional help from the International Federation of Dermatology Clinical Trial Network.

The survey was restricted to those who were self-identified as 18 years or older and who self-reported a diagnosis of melanoma following the use of indoor tanning devices. The survey was hosted by SurveyMonkey, which allowed consent to be obtained and responses to remain anonymous. Access to the survey was sponsored by the Basal Cell Carcinoma Nevus Syndrome Life Support Network. The University of Central Florida (Orlando, Florida) institutional review board reviewed and approved this study as exempt human research.

Survey responses collected from January 2014 to June 2015 were analyzed herein. The survey contained 58 questions and was divided into different topics including indoor tanning background (eg, states/countries in which participants tanned indoors, age when they first tanned, frequency of tanning), consenting process (eg, length, did someone review the consent with participants, what was contained in the consent), indoor tanning and melanoma (eg, how long after tanning did melanoma develop, age at development, location of melanoma), indoor tanning postmelanoma (eg, did participants tan after diagnosis and why), and other risk factors (eg, did participants smoke or drink pre- or postmelanoma).

Statistical Analysis
The data consist of both categorical and continuous variables. The categorical variables included age (<35 years or ≥35 years), frequency of indoor tanning (≤1 time weekly or >1 time weekly), and onset of melanoma diagnosis (within or after 5 years of indoor tanning). The continuous variables consisted of current age, age at start of indoor tanning, age at melanoma diagnosis, Breslow depth, and Clark level. Frequency of indoor tanning and warning of the risk of skin cancer were converted to be used as both categorical and continuous variables. For frequency of indoor tanning, the variables less than or equal to once weekly and more than once weekly were used as categorical variables, whereas less than monthly, 1 time monthly, 4 times monthly, 2 times weekly, and more than 2 times weekly were used as continuous variables. For warning of the risk of skin cancer, no and yes were converted to 0 and 1 for use in the Spearman correlations, which allowed for greater analyses among other variables. Spearman correlation was used to determine if a significant relationship existed among the age at melanoma diagnosis, age at start of indoor tanning, Breslow depth, Clark level, frequency of indoor and outdoor tanning, and knowledge and warning of the risk of skin cancer. All data were analyzed by use of IBM SPSS Statistics (version 21.0).

Difference in proportions among groups, age, frequency of tanning, onset of melanoma diagnosis within or after 5 years of starting indoor tanning, and knowledge of cancer risks was tested for significance using the χ² test. Reported P values were 2-tailed, corresponding with a significance level of P<.05. All data were analyzed using SPSS (version 21.0). All statistical analyses were conducted independent of the participants’ sex.

Results

Of the 454 participants who accessed the survey, 448 were analyzed in this study; 6 participants did not complete the questionnaire. Both males and females were analyzed: 289 females, 12 males, and 153 who did not report gender. The age range of participants was 18 to 69 years. The age at start of indoor tanning ranged from 8 to 54 years, with a mean of 22 years. Additional participant characteristics are described in Table 1. The mean frequency of indoor tanning was reported as 2 times weekly. When participants were asked if they were warned of the risk of skin cancer, 21.5% reported yes while 78.4% reported not being told of the risk. This knowledge was compared to their frequency of indoor tanning. Having the knowledge of the risk of skin cancer had no influence on their frequency of indoor tanning (Table 2).

Among responders, those who perceived indoor tanning as safer than outdoor tanning tanned indoors more frequently than those who do not (Spearman r=−0.224; P<.05)(Table 3). The frequency of indoor tanning was divided into those who tanned indoors more than once weekly and those who tanned indoors once a week or less. This study showed that the frequency of indoor tanning had no effect on the latency time between the commencement of indoor tanning and diagnosis of melanoma (Table 4). The time frame from the onset of melanoma diagnosis also was compared to the age at which the participants started to tan indoors. Age was divided into those younger than 35 years and those 35 years and older. There was no correlation between the age when indoor tanning began and the time frame in which the melanoma was diagnosed (eTable).

Comment

Thirty million Americans utilize indoor tanning devices at least once a year.¹³ UVA light comprises the majority of the spectrum used by indoor tanning devices, with a fraction (<5%) being UVB light. Until recently, UVB light was the only solar spectrum considered carcinogenic. In 2009, the International Agency for Research on Cancer classified the whole spectrum as carcinogenic to humans.^5,11 Despite this evidence, indoor tanning facilities have promoted indoor tanning as damage free.³ The goal of this study was to collect the patient perspective on the safety of indoor tanning, indoor tanning behaviors, time frame of onset of melanoma, and the severity (ie, Breslow depth) of those melanomas.

Melanoma is the most prevalent cancer in females aged 25 to 29 years.³ The median age of diagnosis of melanoma (with and without the use of indoor tanning devices) is approximately 60 years¹⁴ versus our study, which found the average age at diagnosis was 37.6 years. Our findings are consistent with other literature in that those who start indoor tanning earlier (<35 years of age) develop melanoma at an earlier age.^14,15 Cust et al¹⁴ also promoted the idea that patients develop melanoma earlier because younger individuals are more biologically susceptible to the carcinogenic effects of artificial UV light. However, our study found that those who started indoor tanning at an older age reported being diagnosed with a melanoma of greater Breslow depth, seemingly incongruent with the aforementioned hypothesis. One limitation is the age range for this research sample (18–69 years). The young age range may be attributable to the recruitment through social media, which is geared toward a younger population. Additionally, indoor tanning is a relatively new phenomenon practiced since the 1980s,² which may contribute to the younger sample size. However, 2.7 billion individuals use social media worldwide with 40% of those older than 65 years on social media.¹⁶

Prior research has shown that those who start indoor tanning before the age of 35 years have a 75% increased risk of developing melanoma.¹⁴ Another study also has suggested that UVA-rich sunlamps may shorten the latency period for induction of melanoma and nonmelanoma skin cancers.³ Our study used similar age cutoffs in concluding that there was no earlier onset of melanoma diagnosis between those who started indoor tanning before the age of 35 years and those who started at the age of 35 years or older. Limitations include that our study is cross-sectional, and therefore time course cannot be established. Also, survey responses were self-reported, allowing the possibility of recall bias.

A plethora of research has been conducted to determine if there is a connection between the use of indoor tanning devices and developing melanoma. Cust et al¹⁴ suggested the risk of melanoma was 41% higher for those who had ever used a sunbed in comparison to those who had not. Other studies describe the difficulty in making the connection between indoor tanning and melanoma, as those who more frequently tan indoors also more frequently tan outdoors,¹¹ as suggested by this study. However, there is a paucity of literature on the patients’ perspectives on the safety of indoor tanning. This study determined that those who more frequently tan indoors believed that indoor tanning is safer than outdoor tanning. With this altered perception promoted by the indoor tanning industry, the FDA has added a warning label to all indoor tanning devices about the risk of skin cancer. Our study revealed that having the knowledge of the risk of skin cancer had no influence on the frequency of indoor tanning. This concerning finding highlights a pressing need for an alternative approach to increase awareness of the harmful consequences that accompany indoor tanning. Further studies may elaborate on potential effective methods and messages to relate to an indoor tanning population comprised mostly of young females.

Acknowledgments
Supported and funded by the Basal Cell Carcinoma Nevus Syndrome Life Support Network. This research project was completed as part of the FIRE Module at the University of Central Florida, College of Medicine. We thank the FIRE Module faculty and staff for their assistance with this project.

The incidence of melanoma is increasing at a rate greater than any other cancer,¹ possibly due to the increasing use of indoor tanning devices. These devices emit unnaturally high levels of UVA and low levels of UVA and UVB rays.² The risks of using these devices include increased incidence of melanoma (3438 cases attributed to indoor tanning in 2008) and keratinocytes cancer (increased risk of squamous cell carcinoma by 67% and basal cell carcinoma by 29%), severe sunburns (61.1% of female users and 44.6% of male users have reported sunburns), and aggravation of underlying disorders such as systemic lupus erythematosus.^3-5

The literature varies in its explanation of how indoor tanning increases the risk of developing melanoma. Some authors suggest it is due to increased frequency of use, duration of sessions, and years of using tanning devices.^1,6 Others suggest the increased cancer risk is the result of starting to tan at an earlier age.^2,3,6-10 There is conflicting literature on the level of increased risk of melanoma in those who tan indoors at a young age (<35 years). Although the estimated rate of increased skin cancer risk varies, with rates up to 75% compared to nonusers, nearly all sources support an increased rate.⁶ Despite the growing body of knowledge that indoor tanning is dangerous, as well as the academic publication of these risks (eg, carcinogenesis, short-term and long-term eye injury, burns, UV sensitivity when combined with certain medications), teenagers in the United States and affluent countries appear to disregard the risks of tanning.¹¹

Tanning companies have promoted the misconception that only UVB rays cause cell damage and UVA rays, which the devices emit, result in “damage-free” or “safe” tans.^2,3 Until 2013, indoor tanning devices were classified by the US Food and Drug Administration (FDA) as class I, indicating that they are safe in terms of electrical shock. Many indoor tanning facilities have promoted the FDA “safe” label without clarifying that the safety indications only referred to electrical-shock potential. Nonetheless, it is known now that these devices, which emit high UVA and low UVB rays, promote melanoma, nonmelanoma skin cancers, and severe sunburns, as well as aggravate existing conditions (eg, systemic lupus erythematosus).⁴ As a result of an unacceptably high incidence of these disease complications, a 2014 FDA regulation categorized tanning beds as class II, requiring that tanning bed users be informed of the risk of skin cancer in an effort to reverse the growing trend of indoor tanning.¹² Despite these regulatory interventions, it is not clear if this knowledge of cancer risk deters patients from indoor tanning.

The purpose of this study was to investigate the patients’ perspective on indoor tanning behaviors as associated with the severity of their melanoma and the time frame in which they were diagnosed as well as their perceived views on the safety of indoor tanning and the frequency in which they continue to tan indoors. This information is highly relevant in helping to determine if requiring a warning of the risk of skin cancer will deter patients from this unhealthy habit, especially given recent reclassification of sunbeds as class II by the FDA. Additional insights from these data may clarify if indoor tanning decreases the time frame in which melanoma is diagnosed or increases the severity of the resulting melanoma. Moreover, it will help elucidate whether or not the age at which indoor tanning is initiated affects the time frame to melanoma onset and corresponding severity.

Methods

An original unvalidated online survey was conducted worldwide via a link distributed to the following supporting institutions: Advanced Dermatology & Cosmetic Surgery, Ameriderm Research, Melanoma Research Foundation (a melanoma patient advocacy group), Florida State University Department of Dermatology, Moffitt Cancer Center Cutaneous Oncology Program, Cleveland Clinic, Ohio State University Division of Medical Oncology, Harvard Medical School Department of Dermatology, The University of Texas MD Anderson Cancer Center Department of Dermatology, University of Colorado Department of Dermatology, and Northwestern University Department of Dermatology. However, there was not confirmation that all of these institutions promoted the survey. Additionally, respondents were recruited through patient advocacy groups and social media sites including Facebook, Twitter, LinkedIn, Tumblr, and Instagram. The patient advocacy groups and social media sites invited participation through recruitment announcements, including DermNetNZ (a global dermatology patient information site), with additional help from the International Federation of Dermatology Clinical Trial Network.

The survey was restricted to those who were self-identified as 18 years or older and who self-reported a diagnosis of melanoma following the use of indoor tanning devices. The survey was hosted by SurveyMonkey, which allowed consent to be obtained and responses to remain anonymous. Access to the survey was sponsored by the Basal Cell Carcinoma Nevus Syndrome Life Support Network. The University of Central Florida (Orlando, Florida) institutional review board reviewed and approved this study as exempt human research.

Survey responses collected from January 2014 to June 2015 were analyzed herein. The survey contained 58 questions and was divided into different topics including indoor tanning background (eg, states/countries in which participants tanned indoors, age when they first tanned, frequency of tanning), consenting process (eg, length, did someone review the consent with participants, what was contained in the consent), indoor tanning and melanoma (eg, how long after tanning did melanoma develop, age at development, location of melanoma), indoor tanning postmelanoma (eg, did participants tan after diagnosis and why), and other risk factors (eg, did participants smoke or drink pre- or postmelanoma).

Statistical Analysis
The data consist of both categorical and continuous variables. The categorical variables included age (<35 years or ≥35 years), frequency of indoor tanning (≤1 time weekly or >1 time weekly), and onset of melanoma diagnosis (within or after 5 years of indoor tanning). The continuous variables consisted of current age, age at start of indoor tanning, age at melanoma diagnosis, Breslow depth, and Clark level. Frequency of indoor tanning and warning of the risk of skin cancer were converted to be used as both categorical and continuous variables. For frequency of indoor tanning, the variables less than or equal to once weekly and more than once weekly were used as categorical variables, whereas less than monthly, 1 time monthly, 4 times monthly, 2 times weekly, and more than 2 times weekly were used as continuous variables. For warning of the risk of skin cancer, no and yes were converted to 0 and 1 for use in the Spearman correlations, which allowed for greater analyses among other variables. Spearman correlation was used to determine if a significant relationship existed among the age at melanoma diagnosis, age at start of indoor tanning, Breslow depth, Clark level, frequency of indoor and outdoor tanning, and knowledge and warning of the risk of skin cancer. All data were analyzed by use of IBM SPSS Statistics (version 21.0).

Difference in proportions among groups, age, frequency of tanning, onset of melanoma diagnosis within or after 5 years of starting indoor tanning, and knowledge of cancer risks was tested for significance using the χ² test. Reported P values were 2-tailed, corresponding with a significance level of P<.05. All data were analyzed using SPSS (version 21.0). All statistical analyses were conducted independent of the participants’ sex.

Results

Of the 454 participants who accessed the survey, 448 were analyzed in this study; 6 participants did not complete the questionnaire. Both males and females were analyzed: 289 females, 12 males, and 153 who did not report gender. The age range of participants was 18 to 69 years. The age at start of indoor tanning ranged from 8 to 54 years, with a mean of 22 years. Additional participant characteristics are described in Table 1. The mean frequency of indoor tanning was reported as 2 times weekly. When participants were asked if they were warned of the risk of skin cancer, 21.5% reported yes while 78.4% reported not being told of the risk. This knowledge was compared to their frequency of indoor tanning. Having the knowledge of the risk of skin cancer had no influence on their frequency of indoor tanning (Table 2).

Among responders, those who perceived indoor tanning as safer than outdoor tanning tanned indoors more frequently than those who do not (Spearman r=−0.224; P<.05)(Table 3). The frequency of indoor tanning was divided into those who tanned indoors more than once weekly and those who tanned indoors once a week or less. This study showed that the frequency of indoor tanning had no effect on the latency time between the commencement of indoor tanning and diagnosis of melanoma (Table 4). The time frame from the onset of melanoma diagnosis also was compared to the age at which the participants started to tan indoors. Age was divided into those younger than 35 years and those 35 years and older. There was no correlation between the age when indoor tanning began and the time frame in which the melanoma was diagnosed (eTable).

Comment

Thirty million Americans utilize indoor tanning devices at least once a year.¹³ UVA light comprises the majority of the spectrum used by indoor tanning devices, with a fraction (<5%) being UVB light. Until recently, UVB light was the only solar spectrum considered carcinogenic. In 2009, the International Agency for Research on Cancer classified the whole spectrum as carcinogenic to humans.^5,11 Despite this evidence, indoor tanning facilities have promoted indoor tanning as damage free.³ The goal of this study was to collect the patient perspective on the safety of indoor tanning, indoor tanning behaviors, time frame of onset of melanoma, and the severity (ie, Breslow depth) of those melanomas.

Melanoma is the most prevalent cancer in females aged 25 to 29 years.³ The median age of diagnosis of melanoma (with and without the use of indoor tanning devices) is approximately 60 years¹⁴ versus our study, which found the average age at diagnosis was 37.6 years. Our findings are consistent with other literature in that those who start indoor tanning earlier (<35 years of age) develop melanoma at an earlier age.^14,15 Cust et al¹⁴ also promoted the idea that patients develop melanoma earlier because younger individuals are more biologically susceptible to the carcinogenic effects of artificial UV light. However, our study found that those who started indoor tanning at an older age reported being diagnosed with a melanoma of greater Breslow depth, seemingly incongruent with the aforementioned hypothesis. One limitation is the age range for this research sample (18–69 years). The young age range may be attributable to the recruitment through social media, which is geared toward a younger population. Additionally, indoor tanning is a relatively new phenomenon practiced since the 1980s,² which may contribute to the younger sample size. However, 2.7 billion individuals use social media worldwide with 40% of those older than 65 years on social media.¹⁶

Prior research has shown that those who start indoor tanning before the age of 35 years have a 75% increased risk of developing melanoma.¹⁴ Another study also has suggested that UVA-rich sunlamps may shorten the latency period for induction of melanoma and nonmelanoma skin cancers.³ Our study used similar age cutoffs in concluding that there was no earlier onset of melanoma diagnosis between those who started indoor tanning before the age of 35 years and those who started at the age of 35 years or older. Limitations include that our study is cross-sectional, and therefore time course cannot be established. Also, survey responses were self-reported, allowing the possibility of recall bias.

A plethora of research has been conducted to determine if there is a connection between the use of indoor tanning devices and developing melanoma. Cust et al¹⁴ suggested the risk of melanoma was 41% higher for those who had ever used a sunbed in comparison to those who had not. Other studies describe the difficulty in making the connection between indoor tanning and melanoma, as those who more frequently tan indoors also more frequently tan outdoors,¹¹ as suggested by this study. However, there is a paucity of literature on the patients’ perspectives on the safety of indoor tanning. This study determined that those who more frequently tan indoors believed that indoor tanning is safer than outdoor tanning. With this altered perception promoted by the indoor tanning industry, the FDA has added a warning label to all indoor tanning devices about the risk of skin cancer. Our study revealed that having the knowledge of the risk of skin cancer had no influence on the frequency of indoor tanning. This concerning finding highlights a pressing need for an alternative approach to increase awareness of the harmful consequences that accompany indoor tanning. Further studies may elaborate on potential effective methods and messages to relate to an indoor tanning population comprised mostly of young females.

Acknowledgments
Supported and funded by the Basal Cell Carcinoma Nevus Syndrome Life Support Network. This research project was completed as part of the FIRE Module at the University of Central Florida, College of Medicine. We thank the FIRE Module faculty and staff for their assistance with this project.

The incidence of melanoma is increasing at a rate greater than any other cancer,¹ possibly due to the increasing use of indoor tanning devices. These devices emit unnaturally high levels of UVA and low levels of UVA and UVB rays.² The risks of using these devices include increased incidence of melanoma (3438 cases attributed to indoor tanning in 2008) and keratinocytes cancer (increased risk of squamous cell carcinoma by 67% and basal cell carcinoma by 29%), severe sunburns (61.1% of female users and 44.6% of male users have reported sunburns), and aggravation of underlying disorders such as systemic lupus erythematosus.^3-5

The literature varies in its explanation of how indoor tanning increases the risk of developing melanoma. Some authors suggest it is due to increased frequency of use, duration of sessions, and years of using tanning devices.^1,6 Others suggest the increased cancer risk is the result of starting to tan at an earlier age.^2,3,6-10 There is conflicting literature on the level of increased risk of melanoma in those who tan indoors at a young age (<35 years). Although the estimated rate of increased skin cancer risk varies, with rates up to 75% compared to nonusers, nearly all sources support an increased rate.⁶ Despite the growing body of knowledge that indoor tanning is dangerous, as well as the academic publication of these risks (eg, carcinogenesis, short-term and long-term eye injury, burns, UV sensitivity when combined with certain medications), teenagers in the United States and affluent countries appear to disregard the risks of tanning.¹¹

Tanning companies have promoted the misconception that only UVB rays cause cell damage and UVA rays, which the devices emit, result in “damage-free” or “safe” tans.^2,3 Until 2013, indoor tanning devices were classified by the US Food and Drug Administration (FDA) as class I, indicating that they are safe in terms of electrical shock. Many indoor tanning facilities have promoted the FDA “safe” label without clarifying that the safety indications only referred to electrical-shock potential. Nonetheless, it is known now that these devices, which emit high UVA and low UVB rays, promote melanoma, nonmelanoma skin cancers, and severe sunburns, as well as aggravate existing conditions (eg, systemic lupus erythematosus).⁴ As a result of an unacceptably high incidence of these disease complications, a 2014 FDA regulation categorized tanning beds as class II, requiring that tanning bed users be informed of the risk of skin cancer in an effort to reverse the growing trend of indoor tanning.¹² Despite these regulatory interventions, it is not clear if this knowledge of cancer risk deters patients from indoor tanning.

The purpose of this study was to investigate the patients’ perspective on indoor tanning behaviors as associated with the severity of their melanoma and the time frame in which they were diagnosed as well as their perceived views on the safety of indoor tanning and the frequency in which they continue to tan indoors. This information is highly relevant in helping to determine if requiring a warning of the risk of skin cancer will deter patients from this unhealthy habit, especially given recent reclassification of sunbeds as class II by the FDA. Additional insights from these data may clarify if indoor tanning decreases the time frame in which melanoma is diagnosed or increases the severity of the resulting melanoma. Moreover, it will help elucidate whether or not the age at which indoor tanning is initiated affects the time frame to melanoma onset and corresponding severity.

Methods

An original unvalidated online survey was conducted worldwide via a link distributed to the following supporting institutions: Advanced Dermatology & Cosmetic Surgery, Ameriderm Research, Melanoma Research Foundation (a melanoma patient advocacy group), Florida State University Department of Dermatology, Moffitt Cancer Center Cutaneous Oncology Program, Cleveland Clinic, Ohio State University Division of Medical Oncology, Harvard Medical School Department of Dermatology, The University of Texas MD Anderson Cancer Center Department of Dermatology, University of Colorado Department of Dermatology, and Northwestern University Department of Dermatology. However, there was not confirmation that all of these institutions promoted the survey. Additionally, respondents were recruited through patient advocacy groups and social media sites including Facebook, Twitter, LinkedIn, Tumblr, and Instagram. The patient advocacy groups and social media sites invited participation through recruitment announcements, including DermNetNZ (a global dermatology patient information site), with additional help from the International Federation of Dermatology Clinical Trial Network.

The survey was restricted to those who were self-identified as 18 years or older and who self-reported a diagnosis of melanoma following the use of indoor tanning devices. The survey was hosted by SurveyMonkey, which allowed consent to be obtained and responses to remain anonymous. Access to the survey was sponsored by the Basal Cell Carcinoma Nevus Syndrome Life Support Network. The University of Central Florida (Orlando, Florida) institutional review board reviewed and approved this study as exempt human research.

Survey responses collected from January 2014 to June 2015 were analyzed herein. The survey contained 58 questions and was divided into different topics including indoor tanning background (eg, states/countries in which participants tanned indoors, age when they first tanned, frequency of tanning), consenting process (eg, length, did someone review the consent with participants, what was contained in the consent), indoor tanning and melanoma (eg, how long after tanning did melanoma develop, age at development, location of melanoma), indoor tanning postmelanoma (eg, did participants tan after diagnosis and why), and other risk factors (eg, did participants smoke or drink pre- or postmelanoma).

Statistical Analysis
The data consist of both categorical and continuous variables. The categorical variables included age (<35 years or ≥35 years), frequency of indoor tanning (≤1 time weekly or >1 time weekly), and onset of melanoma diagnosis (within or after 5 years of indoor tanning). The continuous variables consisted of current age, age at start of indoor tanning, age at melanoma diagnosis, Breslow depth, and Clark level. Frequency of indoor tanning and warning of the risk of skin cancer were converted to be used as both categorical and continuous variables. For frequency of indoor tanning, the variables less than or equal to once weekly and more than once weekly were used as categorical variables, whereas less than monthly, 1 time monthly, 4 times monthly, 2 times weekly, and more than 2 times weekly were used as continuous variables. For warning of the risk of skin cancer, no and yes were converted to 0 and 1 for use in the Spearman correlations, which allowed for greater analyses among other variables. Spearman correlation was used to determine if a significant relationship existed among the age at melanoma diagnosis, age at start of indoor tanning, Breslow depth, Clark level, frequency of indoor and outdoor tanning, and knowledge and warning of the risk of skin cancer. All data were analyzed by use of IBM SPSS Statistics (version 21.0).

Difference in proportions among groups, age, frequency of tanning, onset of melanoma diagnosis within or after 5 years of starting indoor tanning, and knowledge of cancer risks was tested for significance using the χ² test. Reported P values were 2-tailed, corresponding with a significance level of P<.05. All data were analyzed using SPSS (version 21.0). All statistical analyses were conducted independent of the participants’ sex.

Results

Of the 454 participants who accessed the survey, 448 were analyzed in this study; 6 participants did not complete the questionnaire. Both males and females were analyzed: 289 females, 12 males, and 153 who did not report gender. The age range of participants was 18 to 69 years. The age at start of indoor tanning ranged from 8 to 54 years, with a mean of 22 years. Additional participant characteristics are described in Table 1. The mean frequency of indoor tanning was reported as 2 times weekly. When participants were asked if they were warned of the risk of skin cancer, 21.5% reported yes while 78.4% reported not being told of the risk. This knowledge was compared to their frequency of indoor tanning. Having the knowledge of the risk of skin cancer had no influence on their frequency of indoor tanning (Table 2).

Among responders, those who perceived indoor tanning as safer than outdoor tanning tanned indoors more frequently than those who do not (Spearman r=−0.224; P<.05)(Table 3). The frequency of indoor tanning was divided into those who tanned indoors more than once weekly and those who tanned indoors once a week or less. This study showed that the frequency of indoor tanning had no effect on the latency time between the commencement of indoor tanning and diagnosis of melanoma (Table 4). The time frame from the onset of melanoma diagnosis also was compared to the age at which the participants started to tan indoors. Age was divided into those younger than 35 years and those 35 years and older. There was no correlation between the age when indoor tanning began and the time frame in which the melanoma was diagnosed (eTable).

Comment

Thirty million Americans utilize indoor tanning devices at least once a year.¹³ UVA light comprises the majority of the spectrum used by indoor tanning devices, with a fraction (<5%) being UVB light. Until recently, UVB light was the only solar spectrum considered carcinogenic. In 2009, the International Agency for Research on Cancer classified the whole spectrum as carcinogenic to humans.^5,11 Despite this evidence, indoor tanning facilities have promoted indoor tanning as damage free.³ The goal of this study was to collect the patient perspective on the safety of indoor tanning, indoor tanning behaviors, time frame of onset of melanoma, and the severity (ie, Breslow depth) of those melanomas.

Melanoma is the most prevalent cancer in females aged 25 to 29 years.³ The median age of diagnosis of melanoma (with and without the use of indoor tanning devices) is approximately 60 years¹⁴ versus our study, which found the average age at diagnosis was 37.6 years. Our findings are consistent with other literature in that those who start indoor tanning earlier (<35 years of age) develop melanoma at an earlier age.^14,15 Cust et al¹⁴ also promoted the idea that patients develop melanoma earlier because younger individuals are more biologically susceptible to the carcinogenic effects of artificial UV light. However, our study found that those who started indoor tanning at an older age reported being diagnosed with a melanoma of greater Breslow depth, seemingly incongruent with the aforementioned hypothesis. One limitation is the age range for this research sample (18–69 years). The young age range may be attributable to the recruitment through social media, which is geared toward a younger population. Additionally, indoor tanning is a relatively new phenomenon practiced since the 1980s,² which may contribute to the younger sample size. However, 2.7 billion individuals use social media worldwide with 40% of those older than 65 years on social media.¹⁶

Prior research has shown that those who start indoor tanning before the age of 35 years have a 75% increased risk of developing melanoma.¹⁴ Another study also has suggested that UVA-rich sunlamps may shorten the latency period for induction of melanoma and nonmelanoma skin cancers.³ Our study used similar age cutoffs in concluding that there was no earlier onset of melanoma diagnosis between those who started indoor tanning before the age of 35 years and those who started at the age of 35 years or older. Limitations include that our study is cross-sectional, and therefore time course cannot be established. Also, survey responses were self-reported, allowing the possibility of recall bias.

A plethora of research has been conducted to determine if there is a connection between the use of indoor tanning devices and developing melanoma. Cust et al¹⁴ suggested the risk of melanoma was 41% higher for those who had ever used a sunbed in comparison to those who had not. Other studies describe the difficulty in making the connection between indoor tanning and melanoma, as those who more frequently tan indoors also more frequently tan outdoors,¹¹ as suggested by this study. However, there is a paucity of literature on the patients’ perspectives on the safety of indoor tanning. This study determined that those who more frequently tan indoors believed that indoor tanning is safer than outdoor tanning. With this altered perception promoted by the indoor tanning industry, the FDA has added a warning label to all indoor tanning devices about the risk of skin cancer. Our study revealed that having the knowledge of the risk of skin cancer had no influence on the frequency of indoor tanning. This concerning finding highlights a pressing need for an alternative approach to increase awareness of the harmful consequences that accompany indoor tanning. Further studies may elaborate on potential effective methods and messages to relate to an indoor tanning population comprised mostly of young females.

Acknowledgments
Supported and funded by the Basal Cell Carcinoma Nevus Syndrome Life Support Network. This research project was completed as part of the FIRE Module at the University of Central Florida, College of Medicine. We thank the FIRE Module faculty and staff for their assistance with this project.

Daily application of topical fluorouracil for 4 weeks reduced the risk of developing squamous cell cancer (SCC) requiring surgery by 75% in a population of high-risk older adults.

The findings were published online Jan. 3 in JAMA Dermatology.

Although topical fluorouracil can help reduce actinic keratoses and cure some superficial basal cell and squamous cell carcinomas, it has not been studied as a strategy to prevent the development of lesions that might require surgery, wrote Martin A. Weinstock, MD, PhD, of Providence (R.I.) Veterans Affairs Medical Center, and his colleagues (JAMA Dermatol. 2017 Jan 3. doi: 10.1001/jamadermatol.2017.3631).

SOURCE: Weinstock, M et al. JAMA Dermatol. 2017 Jan 3. doi: 10.1001/jamadermatol.2017.3631.

Daily application of topical fluorouracil for 4 weeks reduced the risk of developing squamous cell cancer (SCC) requiring surgery by 75% in a population of high-risk older adults.

The findings were published online Jan. 3 in JAMA Dermatology.

Although topical fluorouracil can help reduce actinic keratoses and cure some superficial basal cell and squamous cell carcinomas, it has not been studied as a strategy to prevent the development of lesions that might require surgery, wrote Martin A. Weinstock, MD, PhD, of Providence (R.I.) Veterans Affairs Medical Center, and his colleagues (JAMA Dermatol. 2017 Jan 3. doi: 10.1001/jamadermatol.2017.3631).

SOURCE: Weinstock, M et al. JAMA Dermatol. 2017 Jan 3. doi: 10.1001/jamadermatol.2017.3631.

Daily application of topical fluorouracil for 4 weeks reduced the risk of developing squamous cell cancer (SCC) requiring surgery by 75% in a population of high-risk older adults.

The findings were published online Jan. 3 in JAMA Dermatology.

Although topical fluorouracil can help reduce actinic keratoses and cure some superficial basal cell and squamous cell carcinomas, it has not been studied as a strategy to prevent the development of lesions that might require surgery, wrote Martin A. Weinstock, MD, PhD, of Providence (R.I.) Veterans Affairs Medical Center, and his colleagues (JAMA Dermatol. 2017 Jan 3. doi: 10.1001/jamadermatol.2017.3631).

SOURCE: Weinstock, M et al. JAMA Dermatol. 2017 Jan 3. doi: 10.1001/jamadermatol.2017.3631.

The common diuretic hydrochlorothiazide is linked to a dose-dependent increased risk of nonmelanoma skin cancer, in particular, squamous cell carcinoma, a case-controlled registry study showed.

This nationwide, case-matched control study examined patients’ cumulative hydrochlorothiazide use between 1995 and 2012 and found a clear dose-response patterns for both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with a more than sevenfold increased risk of SCC for a cumulative use of greater than or equal to 200,000 mg of hydrochlorothiazide (HCTZ).

“Assuming causality, the present results suggest that 1 in 10 SCC cases diagnosed during the study period can be attributed to HCTZ use,” wrote the study authors, who were led by Sidsel Arnspang, MD, of the department of neurology at Odense (Denmark) University Hospital, which is affiliated with the University of Southern Denmark.

The authors noted that they previously had reported a sevenfold increased risk of lip squamous cell carcinoma with hydrochlorothiazide. Furthermore, the International Agency for Research on Cancer recently classified the diuretic and antihypertensive as “possibly carcinogenic to humans.”

“As HCTZ is among the most widely used drugs in the U.S. and Western Europe, a carcinogenic effect of HCTZ would have a considerable impact on public health,” they wrote in their paper, published in the Journal of American Academy of Dermatology.

According to the study authors, the few studies that have investigated a potential link between thiazide use and nonmelanoma skin cancer (NMSC) have reported inconsistent results.

They speculated that this could be because HCTZ often is prescribed in combination with other diuretics, and there may have been difficulties with disentangling its effect from those of the other drugs.

Using data from five nationwide data sources, the research team compared HCTZ use among people diagnosed with SCC or BCC of the skin to use among a matched control group without such cancers. People were excluded from the analysis if they had SCC of the lip because they had been evaluated in the research team’s previous study.

SOURCE: Arnspang S et al. JAAD. 2017. doi: 10.1016/j.jaad.2017.11.042.

The common diuretic hydrochlorothiazide is linked to a dose-dependent increased risk of nonmelanoma skin cancer, in particular, squamous cell carcinoma, a case-controlled registry study showed.

This nationwide, case-matched control study examined patients’ cumulative hydrochlorothiazide use between 1995 and 2012 and found a clear dose-response patterns for both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with a more than sevenfold increased risk of SCC for a cumulative use of greater than or equal to 200,000 mg of hydrochlorothiazide (HCTZ).

“Assuming causality, the present results suggest that 1 in 10 SCC cases diagnosed during the study period can be attributed to HCTZ use,” wrote the study authors, who were led by Sidsel Arnspang, MD, of the department of neurology at Odense (Denmark) University Hospital, which is affiliated with the University of Southern Denmark.

The authors noted that they previously had reported a sevenfold increased risk of lip squamous cell carcinoma with hydrochlorothiazide. Furthermore, the International Agency for Research on Cancer recently classified the diuretic and antihypertensive as “possibly carcinogenic to humans.”

“As HCTZ is among the most widely used drugs in the U.S. and Western Europe, a carcinogenic effect of HCTZ would have a considerable impact on public health,” they wrote in their paper, published in the Journal of American Academy of Dermatology.

According to the study authors, the few studies that have investigated a potential link between thiazide use and nonmelanoma skin cancer (NMSC) have reported inconsistent results.

They speculated that this could be because HCTZ often is prescribed in combination with other diuretics, and there may have been difficulties with disentangling its effect from those of the other drugs.

Using data from five nationwide data sources, the research team compared HCTZ use among people diagnosed with SCC or BCC of the skin to use among a matched control group without such cancers. People were excluded from the analysis if they had SCC of the lip because they had been evaluated in the research team’s previous study.

SOURCE: Arnspang S et al. JAAD. 2017. doi: 10.1016/j.jaad.2017.11.042.

The common diuretic hydrochlorothiazide is linked to a dose-dependent increased risk of nonmelanoma skin cancer, in particular, squamous cell carcinoma, a case-controlled registry study showed.

This nationwide, case-matched control study examined patients’ cumulative hydrochlorothiazide use between 1995 and 2012 and found a clear dose-response patterns for both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with a more than sevenfold increased risk of SCC for a cumulative use of greater than or equal to 200,000 mg of hydrochlorothiazide (HCTZ).

“Assuming causality, the present results suggest that 1 in 10 SCC cases diagnosed during the study period can be attributed to HCTZ use,” wrote the study authors, who were led by Sidsel Arnspang, MD, of the department of neurology at Odense (Denmark) University Hospital, which is affiliated with the University of Southern Denmark.

The authors noted that they previously had reported a sevenfold increased risk of lip squamous cell carcinoma with hydrochlorothiazide. Furthermore, the International Agency for Research on Cancer recently classified the diuretic and antihypertensive as “possibly carcinogenic to humans.”

“As HCTZ is among the most widely used drugs in the U.S. and Western Europe, a carcinogenic effect of HCTZ would have a considerable impact on public health,” they wrote in their paper, published in the Journal of American Academy of Dermatology.

According to the study authors, the few studies that have investigated a potential link between thiazide use and nonmelanoma skin cancer (NMSC) have reported inconsistent results.

They speculated that this could be because HCTZ often is prescribed in combination with other diuretics, and there may have been difficulties with disentangling its effect from those of the other drugs.

Using data from five nationwide data sources, the research team compared HCTZ use among people diagnosed with SCC or BCC of the skin to use among a matched control group without such cancers. People were excluded from the analysis if they had SCC of the lip because they had been evaluated in the research team’s previous study.

SOURCE: Arnspang S et al. JAAD. 2017. doi: 10.1016/j.jaad.2017.11.042.

Pseudomyogenic hemangioendothelioma (PMHE), also referred to as epithelioid sarcoma–like hemangioendothelioma,¹ is a rare soft tissue tumor that was described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. It predominantly affects males between the second and fifth decades of life and most commonly presents as multiple nodules that may involve either the superficial or deep soft tissues of the legs and less often the arms. It also can arise on the trunk. We present a case of PMHE occurring in a young man and briefly review the literature on clinical presentation and histologic differentiation of this unique tumor, comparing these findings to its mimickers.

Case Report

A 20-year-old man presented with skin lesions on the left leg that had been present for 1 year. The patient described the lesions as tender pimples that would drain yellow discharge on occasion but had now transformed into large brown plaques. Physical examination showed 4 verrucous plaques ranging in size from 1 to 3 cm with hyperpigmentation and a central crust (Figure 1). Initially, the patient thought the lesions appeared due to shaving his legs for sports. He presented to the emergency department multiple times over the past year; pain control was provided and local skin care was recommended. Culture of the discharge had been performed 6 months prior to biopsy with negative results. No biopsy was performed on initial presentation and the lesions were diagnosed in the emergency department clinically as boils.

After failing to improve, the patient was seen by an outside dermatologist and the clinical differential diagnosis included deep fungal infection, atypical mycobacterial infection, and keloids. A 4-mm punch biopsy was taken from the periphery of one of the lesions and demonstrated hyperkeratosis, papillomatosis, and acanthosis (Figure 2). Within the superficial and deep dermis and focally extending into the subcutaneous tissue, there were sheets of spindled to epithelioid-appearing cells with moderate cytologic atypia (Figure 3). The tumor showed infiltrative margins. There was moderate cellularity. The individual cells had a rhabdoid appearance with large eccentric vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm (Figure 4). No definitive evidence of glandular, squamous, or vascular differentiation was present. There was an associated moderate inflammatory host response composed of neutrophils and lymphocytes. Occasional extravasated red blood cells were present. Immunohistochemistry staining was performed and the atypical cells demonstrated diffuse positive staining for friend leukemia integration 1 transcription factor (FLI-1), erythroblastosis virus E26 transforming sequence-related gene (ERG)(Figure 5), CD31, and CD68. There was patchy positive staining for cytokeratin AE1/AE3, CD10, and factor VIII. There was no remarkable staining for human herpesvirus 8, epithelial membrane antigen, S-100, CD34, cytokeratin 903, and desmin. Overall, the histologic features in conjunction with the immunohistochemistry staining were consistent with a diagnosis of PMHE.

Magnetic resonance imaging was then performed to evaluate the depth and extent of the lesions for surgical excision planning (Figure 6), which showed 5 nodular lesions within the dermis and subcutis adjacent to the proximal aspect of the left tibia and medial aspect of the left knee. An additional lesion was noted between the sartorius and semimembranosus muscles, which was thought to represent either a lymph node or an additional neoplastic lesion. Chest computed tomography also displayed indeterminate lesions in the lungs.

Excision of the superficial lesions was performed. All of the lesions demonstrated similar histologic changes to the previously described biopsy specimen. The tumor was limited to the dermis and subcutaneous tissue. The patient was lost to follow-up and the etiology of the lung lesions was unknown.

Comment

Nomenclature
Pseudomyogenic hemangioendothelioma is a relatively new type of vascular tumor that has been included in the updated 2013 edition of the World Health Organization classification as an intermediate malignant tumor that rarely metastasizes.³ It typically involves multiple tissue planes, most notably the dermis and subcutaneous layers but also muscle and bone.⁴ The term pseudomyogenic refers to the histologic resemblance of some of the cells to rhabdomyoblasts; however, these tumors are negative for all immunohistochemical muscle markers, most notably myogenin, desmin, and α-smooth muscle actin.⁵

Clinical Presentation
Gross features of PMHE typically include multiple firm nodules with ill-defined margins. The tumor was initially described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. In 2003, a series of 7 cases of PMHE was reported by Billings et al⁶ under the term epithelioid sarcomalike hemangioendothelioma. Other than the predominance of an epithelioid morphology, the cases reported as epithelioid sarcomalike hemangioendothelioma had similar clinical features and immunophenotype to what has been reported as PMHE.

Based on a PubMed search of articles indexed for MEDLINE using the term pseudomyogenic hemangioendothelioma, the 2 largest case series were reported by Pradhan et al⁷ (N=8) in 2017 and Hornick and Fletcher⁴ (N=50) in 2011. Hornick and Fletcher⁴ reported a male (41/50 [82.0%]) to female (9/50 [18.0%]) ratio of 4.6 to 1, and an average age at presentation of 31 years with 82% (41/50) of patients 40 years or younger. Pradhan et al⁷ also reported a male predominance (7/8 [87.5%]) with a similar average age at presentation of 29 years (age range, 9–62 years). The size of individual tumors ranged from 0.3 to 5.5 cm (mean size, 1.9 cm) in the series by Hornick and Fletcher⁴ and 0.3 to 6.0 com in the series by Pradhan et al.⁷ Hornick and Fletcher⁴ reported the most common site of involvement was the leg (27/50 [54.0%]), followed by the arm (12/50 [24.0%]), trunk (9/50 [18.0%]), and head and neck (2/50 [4.0%]). The leg (6/8 [75.0%]) also was the most common site of involvement in the series by Pradhan et al,⁷ with 2 cases occurring on the arm. In the series by Hornick and Fletcher,⁴ the tumors typically involved the dermis and subcutaneous tissue (26/50 [52%]) with a smaller number involving skeletal muscle (17/50 [34%]) and bone (7/50 [14%]). They reported 66% of their patients (33/50) had multifocal disease at presentation.⁴ Pradhan et al⁷ also reported 2 (25.0%) cases being limited to the superficial soft tissue, 2 (25.0%) being limited to the deep soft tissue, and 4 (50.0%) involving the bone; 5 (62.5%) patients had multifocal disease at presentation. The presentation of our patient in regards to gender, age, and tumor characteristics is consistent with other published cases.^5-10

Histopathology
Microscopic features of PMHE include sheets of spindled to epithelioid-appearing cells with mild to moderate nuclear atypia and eosinophilic cytoplasm. The tumor has an infiltrative growth pattern. Some of the cells may resemble rhabdomyoblastlike cells, hence the moniker pseudomyogenic. There is no recapitulation of vascular structures or remarkable cytoplasmic vacuolization. Mitotic rate is low and there is no tumor necrosis.⁴ The tumor cells do not appear to arise from a vessel or display an angiocentric growth pattern. Many cases report the presence of an inflammatory infiltrate containing neutrophils interspersed within the tumor.^4,5,7 The overlying epidermis will commonly show hyperkeratosis, epidermal hyperplasia, and acanthosis.^4,11

Differential Diagnosis
The histopathologic differential diagnosis would include epithelioid sarcoma, epithelioid hemangioendothelioma, and to a lesser extent dermatofibrosarcoma protuberans (DFSP) and rhabdomyosarcoma. Dermatofibrosarcoma protuberans is the most commonly encountered of these tumors. Histologically, DFSP is characterized by a cellular proliferation of small spindle cells with plump nuclei arranged in a storiform or cartwheel pattern. Dermatofibrosarcoma protuberans tends to be limited to the dermis and subcutaneous tissue and only rarely involves underlying skeletal muscle. The presence of the storiform growth pattern in conjunction with the lack of rhabdoid changes would favor a diagnosis of DFSP. Another characteristic histologic finding typically only associated with DFSP is the interdigitating growth pattern of the spindle cells within the lobules of the subcutaneous tissue, creating a lacelike or honeycomb appearance.

Immunohistochemistry staining is necessary to help differentiate PMHE from other tumors in the differential diagnosis. Pseudomyogenic hemangioendothelioma stains positive for cytokeratin AE1/AE3; integrase interactor 1; and vascular markers FLI-1, CD31, and ERG, and negative for CD34.^4,6,12-15 In contrast to epithelioid hemangioendothelioma, DFSP, and to a lesser extent epithelioid sarcoma, all of which are positive for CD34, epithelioid sarcoma is negative for both CD31 and integrase interactor 1. Dermatofibrosarcoma protuberans is negative for cytokeratin AE1/AE3. Rhabdomyosarcomas are positive for myogenic markers such as MyoD1 and myogenin, unlike any of the other tumors mentioned. Histologically, epithelioid sarcomas will tend to have a granulomalike growth pattern with central necrosis, unlike PMHE.¹² Epithelioid hemangioendothelioma often will have a cordlike growth pattern in a myxochondroid background. Unlike PMHE, these tumors often will appear to be arising from vessels, and intracytoplasmic vacuoles are common. Three cases of PMHE have been reported to have a t(7;19)(q22;q13) chromosomal anomaly, which is not consistent with every case.¹⁶

Treatment Options
Standard treatment typically includes wide excision of the lesions, as was done in our case. Because of the substantial risk of local recurrence, which was up to 58% in the series by Hornick and Fletcher,⁴ adjuvant therapy may be considered if positive margins are found on excision. Metastasis to lymph nodes and the lungs has been reported but is rare.^2,4 Most cases have been shown to have a favorable prognosis; however, local recurrence seems to be common. Rarely, amputation of the limb may be required.⁵ In contrast, epithelioid sarcomas have been found to spread to lymph nodes and the lungs in up to 50% of cases with a 5-year survival rate of 10% to 30%.¹³

Conclusion

In summary, we describe a case of PMHE involving the lower leg in a 20-year-old man. These tumors often are multinodular and multiplanar, with the dermis and subcutaneous tissues being the most common areas affected. It has a high rate of local recurrence but rarely has distant metastasis. Pseudomyogenic hemangioendothelioma, similar to other soft tissue tumors, can be difficult to diagnose on shave biopsy or superficial punch biopsy not extending into subcutaneous tissue. Deep incisional or punch biopsies are required to more definitively diagnose these types of tumors. The diagnosis of PMHE versus other soft tissue tumors requires correlation of histology and immunohistochemistry staining with clinical information and radiographic findings.

Pseudomyogenic hemangioendothelioma (PMHE), also referred to as epithelioid sarcoma–like hemangioendothelioma,¹ is a rare soft tissue tumor that was described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. It predominantly affects males between the second and fifth decades of life and most commonly presents as multiple nodules that may involve either the superficial or deep soft tissues of the legs and less often the arms. It also can arise on the trunk. We present a case of PMHE occurring in a young man and briefly review the literature on clinical presentation and histologic differentiation of this unique tumor, comparing these findings to its mimickers.

Case Report

A 20-year-old man presented with skin lesions on the left leg that had been present for 1 year. The patient described the lesions as tender pimples that would drain yellow discharge on occasion but had now transformed into large brown plaques. Physical examination showed 4 verrucous plaques ranging in size from 1 to 3 cm with hyperpigmentation and a central crust (Figure 1). Initially, the patient thought the lesions appeared due to shaving his legs for sports. He presented to the emergency department multiple times over the past year; pain control was provided and local skin care was recommended. Culture of the discharge had been performed 6 months prior to biopsy with negative results. No biopsy was performed on initial presentation and the lesions were diagnosed in the emergency department clinically as boils.

After failing to improve, the patient was seen by an outside dermatologist and the clinical differential diagnosis included deep fungal infection, atypical mycobacterial infection, and keloids. A 4-mm punch biopsy was taken from the periphery of one of the lesions and demonstrated hyperkeratosis, papillomatosis, and acanthosis (Figure 2). Within the superficial and deep dermis and focally extending into the subcutaneous tissue, there were sheets of spindled to epithelioid-appearing cells with moderate cytologic atypia (Figure 3). The tumor showed infiltrative margins. There was moderate cellularity. The individual cells had a rhabdoid appearance with large eccentric vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm (Figure 4). No definitive evidence of glandular, squamous, or vascular differentiation was present. There was an associated moderate inflammatory host response composed of neutrophils and lymphocytes. Occasional extravasated red blood cells were present. Immunohistochemistry staining was performed and the atypical cells demonstrated diffuse positive staining for friend leukemia integration 1 transcription factor (FLI-1), erythroblastosis virus E26 transforming sequence-related gene (ERG)(Figure 5), CD31, and CD68. There was patchy positive staining for cytokeratin AE1/AE3, CD10, and factor VIII. There was no remarkable staining for human herpesvirus 8, epithelial membrane antigen, S-100, CD34, cytokeratin 903, and desmin. Overall, the histologic features in conjunction with the immunohistochemistry staining were consistent with a diagnosis of PMHE.

Magnetic resonance imaging was then performed to evaluate the depth and extent of the lesions for surgical excision planning (Figure 6), which showed 5 nodular lesions within the dermis and subcutis adjacent to the proximal aspect of the left tibia and medial aspect of the left knee. An additional lesion was noted between the sartorius and semimembranosus muscles, which was thought to represent either a lymph node or an additional neoplastic lesion. Chest computed tomography also displayed indeterminate lesions in the lungs.

Excision of the superficial lesions was performed. All of the lesions demonstrated similar histologic changes to the previously described biopsy specimen. The tumor was limited to the dermis and subcutaneous tissue. The patient was lost to follow-up and the etiology of the lung lesions was unknown.

Comment

Nomenclature
Pseudomyogenic hemangioendothelioma is a relatively new type of vascular tumor that has been included in the updated 2013 edition of the World Health Organization classification as an intermediate malignant tumor that rarely metastasizes.³ It typically involves multiple tissue planes, most notably the dermis and subcutaneous layers but also muscle and bone.⁴ The term pseudomyogenic refers to the histologic resemblance of some of the cells to rhabdomyoblasts; however, these tumors are negative for all immunohistochemical muscle markers, most notably myogenin, desmin, and α-smooth muscle actin.⁵

Clinical Presentation
Gross features of PMHE typically include multiple firm nodules with ill-defined margins. The tumor was initially described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. In 2003, a series of 7 cases of PMHE was reported by Billings et al⁶ under the term epithelioid sarcomalike hemangioendothelioma. Other than the predominance of an epithelioid morphology, the cases reported as epithelioid sarcomalike hemangioendothelioma had similar clinical features and immunophenotype to what has been reported as PMHE.

Based on a PubMed search of articles indexed for MEDLINE using the term pseudomyogenic hemangioendothelioma, the 2 largest case series were reported by Pradhan et al⁷ (N=8) in 2017 and Hornick and Fletcher⁴ (N=50) in 2011. Hornick and Fletcher⁴ reported a male (41/50 [82.0%]) to female (9/50 [18.0%]) ratio of 4.6 to 1, and an average age at presentation of 31 years with 82% (41/50) of patients 40 years or younger. Pradhan et al⁷ also reported a male predominance (7/8 [87.5%]) with a similar average age at presentation of 29 years (age range, 9–62 years). The size of individual tumors ranged from 0.3 to 5.5 cm (mean size, 1.9 cm) in the series by Hornick and Fletcher⁴ and 0.3 to 6.0 com in the series by Pradhan et al.⁷ Hornick and Fletcher⁴ reported the most common site of involvement was the leg (27/50 [54.0%]), followed by the arm (12/50 [24.0%]), trunk (9/50 [18.0%]), and head and neck (2/50 [4.0%]). The leg (6/8 [75.0%]) also was the most common site of involvement in the series by Pradhan et al,⁷ with 2 cases occurring on the arm. In the series by Hornick and Fletcher,⁴ the tumors typically involved the dermis and subcutaneous tissue (26/50 [52%]) with a smaller number involving skeletal muscle (17/50 [34%]) and bone (7/50 [14%]). They reported 66% of their patients (33/50) had multifocal disease at presentation.⁴ Pradhan et al⁷ also reported 2 (25.0%) cases being limited to the superficial soft tissue, 2 (25.0%) being limited to the deep soft tissue, and 4 (50.0%) involving the bone; 5 (62.5%) patients had multifocal disease at presentation. The presentation of our patient in regards to gender, age, and tumor characteristics is consistent with other published cases.^5-10

Histopathology
Microscopic features of PMHE include sheets of spindled to epithelioid-appearing cells with mild to moderate nuclear atypia and eosinophilic cytoplasm. The tumor has an infiltrative growth pattern. Some of the cells may resemble rhabdomyoblastlike cells, hence the moniker pseudomyogenic. There is no recapitulation of vascular structures or remarkable cytoplasmic vacuolization. Mitotic rate is low and there is no tumor necrosis.⁴ The tumor cells do not appear to arise from a vessel or display an angiocentric growth pattern. Many cases report the presence of an inflammatory infiltrate containing neutrophils interspersed within the tumor.^4,5,7 The overlying epidermis will commonly show hyperkeratosis, epidermal hyperplasia, and acanthosis.^4,11

Differential Diagnosis
The histopathologic differential diagnosis would include epithelioid sarcoma, epithelioid hemangioendothelioma, and to a lesser extent dermatofibrosarcoma protuberans (DFSP) and rhabdomyosarcoma. Dermatofibrosarcoma protuberans is the most commonly encountered of these tumors. Histologically, DFSP is characterized by a cellular proliferation of small spindle cells with plump nuclei arranged in a storiform or cartwheel pattern. Dermatofibrosarcoma protuberans tends to be limited to the dermis and subcutaneous tissue and only rarely involves underlying skeletal muscle. The presence of the storiform growth pattern in conjunction with the lack of rhabdoid changes would favor a diagnosis of DFSP. Another characteristic histologic finding typically only associated with DFSP is the interdigitating growth pattern of the spindle cells within the lobules of the subcutaneous tissue, creating a lacelike or honeycomb appearance.

Immunohistochemistry staining is necessary to help differentiate PMHE from other tumors in the differential diagnosis. Pseudomyogenic hemangioendothelioma stains positive for cytokeratin AE1/AE3; integrase interactor 1; and vascular markers FLI-1, CD31, and ERG, and negative for CD34.^4,6,12-15 In contrast to epithelioid hemangioendothelioma, DFSP, and to a lesser extent epithelioid sarcoma, all of which are positive for CD34, epithelioid sarcoma is negative for both CD31 and integrase interactor 1. Dermatofibrosarcoma protuberans is negative for cytokeratin AE1/AE3. Rhabdomyosarcomas are positive for myogenic markers such as MyoD1 and myogenin, unlike any of the other tumors mentioned. Histologically, epithelioid sarcomas will tend to have a granulomalike growth pattern with central necrosis, unlike PMHE.¹² Epithelioid hemangioendothelioma often will have a cordlike growth pattern in a myxochondroid background. Unlike PMHE, these tumors often will appear to be arising from vessels, and intracytoplasmic vacuoles are common. Three cases of PMHE have been reported to have a t(7;19)(q22;q13) chromosomal anomaly, which is not consistent with every case.¹⁶

Treatment Options
Standard treatment typically includes wide excision of the lesions, as was done in our case. Because of the substantial risk of local recurrence, which was up to 58% in the series by Hornick and Fletcher,⁴ adjuvant therapy may be considered if positive margins are found on excision. Metastasis to lymph nodes and the lungs has been reported but is rare.^2,4 Most cases have been shown to have a favorable prognosis; however, local recurrence seems to be common. Rarely, amputation of the limb may be required.⁵ In contrast, epithelioid sarcomas have been found to spread to lymph nodes and the lungs in up to 50% of cases with a 5-year survival rate of 10% to 30%.¹³

Conclusion

In summary, we describe a case of PMHE involving the lower leg in a 20-year-old man. These tumors often are multinodular and multiplanar, with the dermis and subcutaneous tissues being the most common areas affected. It has a high rate of local recurrence but rarely has distant metastasis. Pseudomyogenic hemangioendothelioma, similar to other soft tissue tumors, can be difficult to diagnose on shave biopsy or superficial punch biopsy not extending into subcutaneous tissue. Deep incisional or punch biopsies are required to more definitively diagnose these types of tumors. The diagnosis of PMHE versus other soft tissue tumors requires correlation of histology and immunohistochemistry staining with clinical information and radiographic findings.

Pseudomyogenic hemangioendothelioma (PMHE), also referred to as epithelioid sarcoma–like hemangioendothelioma,¹ is a rare soft tissue tumor that was described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. It predominantly affects males between the second and fifth decades of life and most commonly presents as multiple nodules that may involve either the superficial or deep soft tissues of the legs and less often the arms. It also can arise on the trunk. We present a case of PMHE occurring in a young man and briefly review the literature on clinical presentation and histologic differentiation of this unique tumor, comparing these findings to its mimickers.

Case Report

A 20-year-old man presented with skin lesions on the left leg that had been present for 1 year. The patient described the lesions as tender pimples that would drain yellow discharge on occasion but had now transformed into large brown plaques. Physical examination showed 4 verrucous plaques ranging in size from 1 to 3 cm with hyperpigmentation and a central crust (Figure 1). Initially, the patient thought the lesions appeared due to shaving his legs for sports. He presented to the emergency department multiple times over the past year; pain control was provided and local skin care was recommended. Culture of the discharge had been performed 6 months prior to biopsy with negative results. No biopsy was performed on initial presentation and the lesions were diagnosed in the emergency department clinically as boils.

After failing to improve, the patient was seen by an outside dermatologist and the clinical differential diagnosis included deep fungal infection, atypical mycobacterial infection, and keloids. A 4-mm punch biopsy was taken from the periphery of one of the lesions and demonstrated hyperkeratosis, papillomatosis, and acanthosis (Figure 2). Within the superficial and deep dermis and focally extending into the subcutaneous tissue, there were sheets of spindled to epithelioid-appearing cells with moderate cytologic atypia (Figure 3). The tumor showed infiltrative margins. There was moderate cellularity. The individual cells had a rhabdoid appearance with large eccentric vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm (Figure 4). No definitive evidence of glandular, squamous, or vascular differentiation was present. There was an associated moderate inflammatory host response composed of neutrophils and lymphocytes. Occasional extravasated red blood cells were present. Immunohistochemistry staining was performed and the atypical cells demonstrated diffuse positive staining for friend leukemia integration 1 transcription factor (FLI-1), erythroblastosis virus E26 transforming sequence-related gene (ERG)(Figure 5), CD31, and CD68. There was patchy positive staining for cytokeratin AE1/AE3, CD10, and factor VIII. There was no remarkable staining for human herpesvirus 8, epithelial membrane antigen, S-100, CD34, cytokeratin 903, and desmin. Overall, the histologic features in conjunction with the immunohistochemistry staining were consistent with a diagnosis of PMHE.

Magnetic resonance imaging was then performed to evaluate the depth and extent of the lesions for surgical excision planning (Figure 6), which showed 5 nodular lesions within the dermis and subcutis adjacent to the proximal aspect of the left tibia and medial aspect of the left knee. An additional lesion was noted between the sartorius and semimembranosus muscles, which was thought to represent either a lymph node or an additional neoplastic lesion. Chest computed tomography also displayed indeterminate lesions in the lungs.

Excision of the superficial lesions was performed. All of the lesions demonstrated similar histologic changes to the previously described biopsy specimen. The tumor was limited to the dermis and subcutaneous tissue. The patient was lost to follow-up and the etiology of the lung lesions was unknown.

Comment

Nomenclature
Pseudomyogenic hemangioendothelioma is a relatively new type of vascular tumor that has been included in the updated 2013 edition of the World Health Organization classification as an intermediate malignant tumor that rarely metastasizes.³ It typically involves multiple tissue planes, most notably the dermis and subcutaneous layers but also muscle and bone.⁴ The term pseudomyogenic refers to the histologic resemblance of some of the cells to rhabdomyoblasts; however, these tumors are negative for all immunohistochemical muscle markers, most notably myogenin, desmin, and α-smooth muscle actin.⁵

Clinical Presentation
Gross features of PMHE typically include multiple firm nodules with ill-defined margins. The tumor was initially described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. In 2003, a series of 7 cases of PMHE was reported by Billings et al⁶ under the term epithelioid sarcomalike hemangioendothelioma. Other than the predominance of an epithelioid morphology, the cases reported as epithelioid sarcomalike hemangioendothelioma had similar clinical features and immunophenotype to what has been reported as PMHE.

Based on a PubMed search of articles indexed for MEDLINE using the term pseudomyogenic hemangioendothelioma, the 2 largest case series were reported by Pradhan et al⁷ (N=8) in 2017 and Hornick and Fletcher⁴ (N=50) in 2011. Hornick and Fletcher⁴ reported a male (41/50 [82.0%]) to female (9/50 [18.0%]) ratio of 4.6 to 1, and an average age at presentation of 31 years with 82% (41/50) of patients 40 years or younger. Pradhan et al⁷ also reported a male predominance (7/8 [87.5%]) with a similar average age at presentation of 29 years (age range, 9–62 years). The size of individual tumors ranged from 0.3 to 5.5 cm (mean size, 1.9 cm) in the series by Hornick and Fletcher⁴ and 0.3 to 6.0 com in the series by Pradhan et al.⁷ Hornick and Fletcher⁴ reported the most common site of involvement was the leg (27/50 [54.0%]), followed by the arm (12/50 [24.0%]), trunk (9/50 [18.0%]), and head and neck (2/50 [4.0%]). The leg (6/8 [75.0%]) also was the most common site of involvement in the series by Pradhan et al,⁷ with 2 cases occurring on the arm. In the series by Hornick and Fletcher,⁴ the tumors typically involved the dermis and subcutaneous tissue (26/50 [52%]) with a smaller number involving skeletal muscle (17/50 [34%]) and bone (7/50 [14%]). They reported 66% of their patients (33/50) had multifocal disease at presentation.⁴ Pradhan et al⁷ also reported 2 (25.0%) cases being limited to the superficial soft tissue, 2 (25.0%) being limited to the deep soft tissue, and 4 (50.0%) involving the bone; 5 (62.5%) patients had multifocal disease at presentation. The presentation of our patient in regards to gender, age, and tumor characteristics is consistent with other published cases.^5-10

Histopathology
Microscopic features of PMHE include sheets of spindled to epithelioid-appearing cells with mild to moderate nuclear atypia and eosinophilic cytoplasm. The tumor has an infiltrative growth pattern. Some of the cells may resemble rhabdomyoblastlike cells, hence the moniker pseudomyogenic. There is no recapitulation of vascular structures or remarkable cytoplasmic vacuolization. Mitotic rate is low and there is no tumor necrosis.⁴ The tumor cells do not appear to arise from a vessel or display an angiocentric growth pattern. Many cases report the presence of an inflammatory infiltrate containing neutrophils interspersed within the tumor.^4,5,7 The overlying epidermis will commonly show hyperkeratosis, epidermal hyperplasia, and acanthosis.^4,11

Differential Diagnosis
The histopathologic differential diagnosis would include epithelioid sarcoma, epithelioid hemangioendothelioma, and to a lesser extent dermatofibrosarcoma protuberans (DFSP) and rhabdomyosarcoma. Dermatofibrosarcoma protuberans is the most commonly encountered of these tumors. Histologically, DFSP is characterized by a cellular proliferation of small spindle cells with plump nuclei arranged in a storiform or cartwheel pattern. Dermatofibrosarcoma protuberans tends to be limited to the dermis and subcutaneous tissue and only rarely involves underlying skeletal muscle. The presence of the storiform growth pattern in conjunction with the lack of rhabdoid changes would favor a diagnosis of DFSP. Another characteristic histologic finding typically only associated with DFSP is the interdigitating growth pattern of the spindle cells within the lobules of the subcutaneous tissue, creating a lacelike or honeycomb appearance.

Immunohistochemistry staining is necessary to help differentiate PMHE from other tumors in the differential diagnosis. Pseudomyogenic hemangioendothelioma stains positive for cytokeratin AE1/AE3; integrase interactor 1; and vascular markers FLI-1, CD31, and ERG, and negative for CD34.^4,6,12-15 In contrast to epithelioid hemangioendothelioma, DFSP, and to a lesser extent epithelioid sarcoma, all of which are positive for CD34, epithelioid sarcoma is negative for both CD31 and integrase interactor 1. Dermatofibrosarcoma protuberans is negative for cytokeratin AE1/AE3. Rhabdomyosarcomas are positive for myogenic markers such as MyoD1 and myogenin, unlike any of the other tumors mentioned. Histologically, epithelioid sarcomas will tend to have a granulomalike growth pattern with central necrosis, unlike PMHE.¹² Epithelioid hemangioendothelioma often will have a cordlike growth pattern in a myxochondroid background. Unlike PMHE, these tumors often will appear to be arising from vessels, and intracytoplasmic vacuoles are common. Three cases of PMHE have been reported to have a t(7;19)(q22;q13) chromosomal anomaly, which is not consistent with every case.¹⁶

Treatment Options
Standard treatment typically includes wide excision of the lesions, as was done in our case. Because of the substantial risk of local recurrence, which was up to 58% in the series by Hornick and Fletcher,⁴ adjuvant therapy may be considered if positive margins are found on excision. Metastasis to lymph nodes and the lungs has been reported but is rare.^2,4 Most cases have been shown to have a favorable prognosis; however, local recurrence seems to be common. Rarely, amputation of the limb may be required.⁵ In contrast, epithelioid sarcomas have been found to spread to lymph nodes and the lungs in up to 50% of cases with a 5-year survival rate of 10% to 30%.¹³

Conclusion

In summary, we describe a case of PMHE involving the lower leg in a 20-year-old man. These tumors often are multinodular and multiplanar, with the dermis and subcutaneous tissues being the most common areas affected. It has a high rate of local recurrence but rarely has distant metastasis. Pseudomyogenic hemangioendothelioma, similar to other soft tissue tumors, can be difficult to diagnose on shave biopsy or superficial punch biopsy not extending into subcutaneous tissue. Deep incisional or punch biopsies are required to more definitively diagnose these types of tumors. The diagnosis of PMHE versus other soft tissue tumors requires correlation of histology and immunohistochemistry staining with clinical information and radiographic findings.

Among rural adults, multiple chronic health conditions are most common in non-Hispanic blacks and American Indians/Alaska Natives (AI/ANs) and least common among Asians and Native Hawaiians/other Pacific Islanders (NHOPIs), according to the Centers for Disease Control and Prevention.

rfranki@frontlinemedcom.com

Among rural adults, multiple chronic health conditions are most common in non-Hispanic blacks and American Indians/Alaska Natives (AI/ANs) and least common among Asians and Native Hawaiians/other Pacific Islanders (NHOPIs), according to the Centers for Disease Control and Prevention.

rfranki@frontlinemedcom.com

Among rural adults, multiple chronic health conditions are most common in non-Hispanic blacks and American Indians/Alaska Natives (AI/ANs) and least common among Asians and Native Hawaiians/other Pacific Islanders (NHOPIs), according to the Centers for Disease Control and Prevention.

rfranki@frontlinemedcom.com

Parents generally can take photographs of good enough quality to allow accurate teledermatology diagnoses to be made of many pediatric skin conditions, said Daniel M. O’Connor, MD, of the Children’s Hospital of Philadelphia, and his associates.

Skin conditions make up 10%-30% of the approximately 200 million pediatric outpatient visits each year, Dr. O’Connor and his colleagues said. But there are fewer than 300 board-certified U.S. pediatric dermatologists for the nation’s nearly 75 million children. So, the possibility of using photos taken by parents for distant pediatric dermatologists to assess is an attractive one.

copyright/Thinkstock.com

Parents generally can take photographs of good enough quality to allow accurate teledermatology diagnoses to be made of many pediatric skin conditions, said Daniel M. O’Connor, MD, of the Children’s Hospital of Philadelphia, and his associates.

Skin conditions make up 10%-30% of the approximately 200 million pediatric outpatient visits each year, Dr. O’Connor and his colleagues said. But there are fewer than 300 board-certified U.S. pediatric dermatologists for the nation’s nearly 75 million children. So, the possibility of using photos taken by parents for distant pediatric dermatologists to assess is an attractive one.

copyright/Thinkstock.com

Parents generally can take photographs of good enough quality to allow accurate teledermatology diagnoses to be made of many pediatric skin conditions, said Daniel M. O’Connor, MD, of the Children’s Hospital of Philadelphia, and his associates.

Skin conditions make up 10%-30% of the approximately 200 million pediatric outpatient visits each year, Dr. O’Connor and his colleagues said. But there are fewer than 300 board-certified U.S. pediatric dermatologists for the nation’s nearly 75 million children. So, the possibility of using photos taken by parents for distant pediatric dermatologists to assess is an attractive one.

copyright/Thinkstock.com

What is the recent research behind 5-fluorouracil cream 5% combined with calcipotriol ointment 0.005% for actinic keratoses?

Cunningham et al published a randomized double-blind study in which 131 patients with actinic keratoses (AKs) were assigned to either 5-fluorouracil (5-FU) cream 5% combined with calcipotriol (calcipotriene) ointment 0.005% twice daily to the face, scalp, and arms for 4 days, or 5-FU 5% combined with petrolatum applied in the same fashion. There was an 87.8% versus 26.3% mean reduction in the number of AKs and less severe pain, crusting, and ulceration in the study cohort compared to the 5-FU plus petrolatum group.

The same study also investigated immune parameters in these patients and found that the study group preferentially displayed activated thymic stromal lymphopoietin and a CD4 T cell-mediated reaction, among other effects. In prior studies, thymic stromal lymphopoietin has been shown to be upregulated in barrier-defective skin, displays antitumor activity, and is enhanced by topical calcipotriol application based on its original indication for psoriasis.

How do these study results impact patient care?

In a perfect world, every patient could tolerate and afford chemopreventative measures such as 5-FU cream, apply it diffusely to sun-exposed skin, and experience no severe irritant reactions and/or social pariah status. We all know that this product is effective, and we all overprepare patients to use it, knowing that they will call our offices panicked and fearful that they are allergic to or are becoming infected by this cream.

Although further study clearly is needed to determine the optimal application amount, duration of use, and vehicle mix, this new compound utilizing 2 topicals that are familiar to us--5-FU cream approved for AKs and early squamous cell skin cancers and calcipotriol ointment (though available only in cream in the United States currently) for psoriasis--is an encouraging step. Home therapy for AKs and possibly early nonmelanoma skin cancers that is more tolerable, of shorter duration, and in turn more effective than the current options would lessen the burden of treating these lesions surgically or rescheduling 5-FU patients often for irritation reaction education.

How do patients respond to this regimen?

In my own anecdotal experience, this regimen has been well received by patients and often is covered by most insurances when written as 2 separate prescriptions (both in cream vehicle).  They still report some irritation, but I prefer to utilize it segmentally instead of treating all sun-exposed areas at once (ie, treat one side of the face/scalp twice daily for 4 days, then the other, or even divide it into smaller segments once the prior segment has healed). This combination, in addition to, for example, adding nicotinamide 500 mg twice daily to a patient's skin cancer chemopreventative sequence, is in my opinion a novel but safe, effective, and well-tolerated field therapy recommendation.

Suggested Readings

• Cunningham TJ, Tabacchi M, Eliane JP, et al. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017;127:106-116.
• Demehri S, Turkoz A, Manivasagam S, et al. Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin. Cancer Cell. 2012;22:494-505.
• Rosamilia LL. Three Cheers for B₃? Cutis. July 7, 2015. http://www.mdedge.com/cutis/article/101102/nonmelanoma-skin-cancer/three-cheers-b3. Accessed November 20, 2017.
• Sato-Deguchi E, Imafuku S, Chou B, et al. Topical vitamin D(3) analogues induce thymic stromal lymphopoietin and cathelicidin in psoriatic skin lesions. Br J Dermatol. 2012;167:77-84.

What is the recent research behind 5-fluorouracil cream 5% combined with calcipotriol ointment 0.005% for actinic keratoses?

Cunningham et al published a randomized double-blind study in which 131 patients with actinic keratoses (AKs) were assigned to either 5-fluorouracil (5-FU) cream 5% combined with calcipotriol (calcipotriene) ointment 0.005% twice daily to the face, scalp, and arms for 4 days, or 5-FU 5% combined with petrolatum applied in the same fashion. There was an 87.8% versus 26.3% mean reduction in the number of AKs and less severe pain, crusting, and ulceration in the study cohort compared to the 5-FU plus petrolatum group.

The same study also investigated immune parameters in these patients and found that the study group preferentially displayed activated thymic stromal lymphopoietin and a CD4 T cell-mediated reaction, among other effects. In prior studies, thymic stromal lymphopoietin has been shown to be upregulated in barrier-defective skin, displays antitumor activity, and is enhanced by topical calcipotriol application based on its original indication for psoriasis.

How do these study results impact patient care?

In a perfect world, every patient could tolerate and afford chemopreventative measures such as 5-FU cream, apply it diffusely to sun-exposed skin, and experience no severe irritant reactions and/or social pariah status. We all know that this product is effective, and we all overprepare patients to use it, knowing that they will call our offices panicked and fearful that they are allergic to or are becoming infected by this cream.

Although further study clearly is needed to determine the optimal application amount, duration of use, and vehicle mix, this new compound utilizing 2 topicals that are familiar to us--5-FU cream approved for AKs and early squamous cell skin cancers and calcipotriol ointment (though available only in cream in the United States currently) for psoriasis--is an encouraging step. Home therapy for AKs and possibly early nonmelanoma skin cancers that is more tolerable, of shorter duration, and in turn more effective than the current options would lessen the burden of treating these lesions surgically or rescheduling 5-FU patients often for irritation reaction education.

How do patients respond to this regimen?

In my own anecdotal experience, this regimen has been well received by patients and often is covered by most insurances when written as 2 separate prescriptions (both in cream vehicle).  They still report some irritation, but I prefer to utilize it segmentally instead of treating all sun-exposed areas at once (ie, treat one side of the face/scalp twice daily for 4 days, then the other, or even divide it into smaller segments once the prior segment has healed). This combination, in addition to, for example, adding nicotinamide 500 mg twice daily to a patient's skin cancer chemopreventative sequence, is in my opinion a novel but safe, effective, and well-tolerated field therapy recommendation.

Suggested Readings

• Cunningham TJ, Tabacchi M, Eliane JP, et al. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017;127:106-116.
• Demehri S, Turkoz A, Manivasagam S, et al. Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin. Cancer Cell. 2012;22:494-505.
• Rosamilia LL. Three Cheers for B₃? Cutis. July 7, 2015. http://www.mdedge.com/cutis/article/101102/nonmelanoma-skin-cancer/three-cheers-b3. Accessed November 20, 2017.
• Sato-Deguchi E, Imafuku S, Chou B, et al. Topical vitamin D(3) analogues induce thymic stromal lymphopoietin and cathelicidin in psoriatic skin lesions. Br J Dermatol. 2012;167:77-84.

What is the recent research behind 5-fluorouracil cream 5% combined with calcipotriol ointment 0.005% for actinic keratoses?

Cunningham et al published a randomized double-blind study in which 131 patients with actinic keratoses (AKs) were assigned to either 5-fluorouracil (5-FU) cream 5% combined with calcipotriol (calcipotriene) ointment 0.005% twice daily to the face, scalp, and arms for 4 days, or 5-FU 5% combined with petrolatum applied in the same fashion. There was an 87.8% versus 26.3% mean reduction in the number of AKs and less severe pain, crusting, and ulceration in the study cohort compared to the 5-FU plus petrolatum group.

The same study also investigated immune parameters in these patients and found that the study group preferentially displayed activated thymic stromal lymphopoietin and a CD4 T cell-mediated reaction, among other effects. In prior studies, thymic stromal lymphopoietin has been shown to be upregulated in barrier-defective skin, displays antitumor activity, and is enhanced by topical calcipotriol application based on its original indication for psoriasis.

How do these study results impact patient care?

In a perfect world, every patient could tolerate and afford chemopreventative measures such as 5-FU cream, apply it diffusely to sun-exposed skin, and experience no severe irritant reactions and/or social pariah status. We all know that this product is effective, and we all overprepare patients to use it, knowing that they will call our offices panicked and fearful that they are allergic to or are becoming infected by this cream.

Although further study clearly is needed to determine the optimal application amount, duration of use, and vehicle mix, this new compound utilizing 2 topicals that are familiar to us--5-FU cream approved for AKs and early squamous cell skin cancers and calcipotriol ointment (though available only in cream in the United States currently) for psoriasis--is an encouraging step. Home therapy for AKs and possibly early nonmelanoma skin cancers that is more tolerable, of shorter duration, and in turn more effective than the current options would lessen the burden of treating these lesions surgically or rescheduling 5-FU patients often for irritation reaction education.

How do patients respond to this regimen?

In my own anecdotal experience, this regimen has been well received by patients and often is covered by most insurances when written as 2 separate prescriptions (both in cream vehicle).  They still report some irritation, but I prefer to utilize it segmentally instead of treating all sun-exposed areas at once (ie, treat one side of the face/scalp twice daily for 4 days, then the other, or even divide it into smaller segments once the prior segment has healed). This combination, in addition to, for example, adding nicotinamide 500 mg twice daily to a patient's skin cancer chemopreventative sequence, is in my opinion a novel but safe, effective, and well-tolerated field therapy recommendation.

Suggested Readings

• Cunningham TJ, Tabacchi M, Eliane JP, et al. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017;127:106-116.
• Demehri S, Turkoz A, Manivasagam S, et al. Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin. Cancer Cell. 2012;22:494-505.
• Rosamilia LL. Three Cheers for B₃? Cutis. July 7, 2015. http://www.mdedge.com/cutis/article/101102/nonmelanoma-skin-cancer/three-cheers-b3. Accessed November 20, 2017.
• Sato-Deguchi E, Imafuku S, Chou B, et al. Topical vitamin D(3) analogues induce thymic stromal lymphopoietin and cathelicidin in psoriatic skin lesions. Br J Dermatol. 2012;167:77-84.