Nonmelanoma Skin Cancer

NEW YORK – If dermatopathologists had a wish list they could give their dermatologist colleagues, what might it include? High up on the list for many, said Robert Phelps, MD, might be to have them share the clinical picture, treat the specimen gently, and give the best landmarks possible.

Speaking at the summer meeting of the American Academy of Dermatology, Dr. Phelps, director of the dermatopathology service at Mount Sinai Medical Center in New York, led off the dermatopathologist-run session – appropriately titled “Help Me Help You” – by asking, “How can the clinician provide the optimal biopsy?”

It’s always helpful to have as much clinical information as possible, said Dr. Phelps, whose discussion focused on tips for neoplastic lesions. This might include prior history of malignancy, autoimmune disease, pathergy, or other relevant medical history, but clinical pictures can also be a big help, although there can be technical and patient privacy issues to overcome, he noted. If, for example, a larger lesion or rash is being biopsied rather than excised, it can be very helpful to see the larger field and full area of distribution of the lesion in question. Submitting multiple specimens for rashes and larger lesions is always a good idea too, he added.

Although curettage can be a great way to biopsy – and perhaps even definitively treat some lesions – problems can arise on the dermatopathologist’s side when melanocytic lesions are curetted for biopsy, according to Dr. Phelps, a practicing dermatologist and a dermatopathologist. “By virtue of the force of the biopsy, the specimen is often fragmented, and histology can be distorted,” he said. One element of that distortion can be that melanocytes can appear to be free floating, which is a problem. “Dyshesion of melanocytes is usually an indication of atypia … It is an important histologic clue as to the possibility of a malignancy supervening.”

These factors can make it tough for a dermatopathologist to make an accurate call. “If there are free-floating melanocytes from a curetted specimen, I can’t rule out invasive melanoma,” explained Dr. Phelps, since he can’t tell if he is seeing true atypia or disruption that’s an artifact of the collection technique.

In this instance, he said, a dermatopathologist would be “obligated to overcall, because one couldn’t really determine the pathology.” The bottom line? “Don’t curette biopsies of melanocytic lesions.”

Another technique that can interfere with the ability to read a tissue specimen accurately is electrodesiccation. Although it’s often performed in conjunction with curettage, electrodesiccation can cause changes in tissue consistent with thermal injury. “Essentially, the tissue has been burned,” Dr. Phelps pointed out. This can result in a characteristic streaming pattern of nuclei, and the dermis can acquire a “peculiar homogenized appearance,” he said.

Although electrodesiccation can be a useful technique to make sure margins are controlled, “when you do this, just be aware that the interpretation is difficult,” he noted. “It’s difficult to tell where the margins are and if they are the appropriate and correct margins,” he said.

When possible, try to avoid squeezing the tumor, Dr. Phelps advised. Excessive pressure on the specimen can distort cell architecture and make pathological diagnosis really challenging, particularly in lymphoid tumors, he said.

“Often, the tumor is not recognizable,” he added. Crush artifact can result in an appearance of small bluish clumps and smearing of collagen fibers. The effect, he said, can be particularly pronounced with small cell carcinoma and lymphoma, and with rapidly proliferating tumors.

Dr. Phelps said that during his training, he was taught not to use forceps to extract a stubborn punch biopsy specimen; rather, he was trained to use a needle to tease out the specimen. Fear of a self-inflicted needle stick with this technique may be a deterrent, he acknowledged. If forceps are used, he suggested being as gentle as possible and using the finest forceps available.

When pathologists receive an intact excised lesion – one not obtained using a Mohs technique, “delineation of the margin is essential,” Dr. Phelps said. Further, accurate mapping is critical to helping the examiner understand the anatomic orientation of the specimen, a key prerequisite that enables accurate communication from the dermatopathologist back to the clinician if there’s a question regarding the need for retreatment, he added.

For an elliptical excision, ideally, both poles of the ellipse would be suture-tagged, and at least one tag is essential, he said. Then superior and inferior borders can be inked with contrasting colors, and the epidermal borders of the lesion should be marked as well. When the specimen is submitted, it should be accompanied by an accurate map that clearly indicates the coding for medial, lateral, inferior, and superior aspects of the specimen. “Always prepare a specimen diagram for oriented specimens,” Dr. Phelps noted.

Don’t forget to make sure that the left-right orientation on the diagram corresponds to the specimen’s orientation on the patient, he added. Some facilities use a clock face system to indicate orientation and positioning, which may be the clearest method of all.

Sometimes, it’s difficult for the dermatopathologist to visualize whether the specimen is aligned in true medial-lateral fashion, or along skin tension lines, which tend to run diagonally, so “the more clinical information, the better,” he said. “With good mapping, precise retreatment can be optimal,” he said.

Dr. Phelps reported that he had no relevant conflicts of interest.
 

koakes@frontlinemedcom.com

On Twitter @karioakes

NEW YORK – If dermatopathologists had a wish list they could give their dermatologist colleagues, what might it include? High up on the list for many, said Robert Phelps, MD, might be to have them share the clinical picture, treat the specimen gently, and give the best landmarks possible.

Speaking at the summer meeting of the American Academy of Dermatology, Dr. Phelps, director of the dermatopathology service at Mount Sinai Medical Center in New York, led off the dermatopathologist-run session – appropriately titled “Help Me Help You” – by asking, “How can the clinician provide the optimal biopsy?”

It’s always helpful to have as much clinical information as possible, said Dr. Phelps, whose discussion focused on tips for neoplastic lesions. This might include prior history of malignancy, autoimmune disease, pathergy, or other relevant medical history, but clinical pictures can also be a big help, although there can be technical and patient privacy issues to overcome, he noted. If, for example, a larger lesion or rash is being biopsied rather than excised, it can be very helpful to see the larger field and full area of distribution of the lesion in question. Submitting multiple specimens for rashes and larger lesions is always a good idea too, he added.

Although curettage can be a great way to biopsy – and perhaps even definitively treat some lesions – problems can arise on the dermatopathologist’s side when melanocytic lesions are curetted for biopsy, according to Dr. Phelps, a practicing dermatologist and a dermatopathologist. “By virtue of the force of the biopsy, the specimen is often fragmented, and histology can be distorted,” he said. One element of that distortion can be that melanocytes can appear to be free floating, which is a problem. “Dyshesion of melanocytes is usually an indication of atypia … It is an important histologic clue as to the possibility of a malignancy supervening.”

These factors can make it tough for a dermatopathologist to make an accurate call. “If there are free-floating melanocytes from a curetted specimen, I can’t rule out invasive melanoma,” explained Dr. Phelps, since he can’t tell if he is seeing true atypia or disruption that’s an artifact of the collection technique.

In this instance, he said, a dermatopathologist would be “obligated to overcall, because one couldn’t really determine the pathology.” The bottom line? “Don’t curette biopsies of melanocytic lesions.”

Another technique that can interfere with the ability to read a tissue specimen accurately is electrodesiccation. Although it’s often performed in conjunction with curettage, electrodesiccation can cause changes in tissue consistent with thermal injury. “Essentially, the tissue has been burned,” Dr. Phelps pointed out. This can result in a characteristic streaming pattern of nuclei, and the dermis can acquire a “peculiar homogenized appearance,” he said.

Although electrodesiccation can be a useful technique to make sure margins are controlled, “when you do this, just be aware that the interpretation is difficult,” he noted. “It’s difficult to tell where the margins are and if they are the appropriate and correct margins,” he said.

When possible, try to avoid squeezing the tumor, Dr. Phelps advised. Excessive pressure on the specimen can distort cell architecture and make pathological diagnosis really challenging, particularly in lymphoid tumors, he said.

“Often, the tumor is not recognizable,” he added. Crush artifact can result in an appearance of small bluish clumps and smearing of collagen fibers. The effect, he said, can be particularly pronounced with small cell carcinoma and lymphoma, and with rapidly proliferating tumors.

Dr. Phelps said that during his training, he was taught not to use forceps to extract a stubborn punch biopsy specimen; rather, he was trained to use a needle to tease out the specimen. Fear of a self-inflicted needle stick with this technique may be a deterrent, he acknowledged. If forceps are used, he suggested being as gentle as possible and using the finest forceps available.

When pathologists receive an intact excised lesion – one not obtained using a Mohs technique, “delineation of the margin is essential,” Dr. Phelps said. Further, accurate mapping is critical to helping the examiner understand the anatomic orientation of the specimen, a key prerequisite that enables accurate communication from the dermatopathologist back to the clinician if there’s a question regarding the need for retreatment, he added.

For an elliptical excision, ideally, both poles of the ellipse would be suture-tagged, and at least one tag is essential, he said. Then superior and inferior borders can be inked with contrasting colors, and the epidermal borders of the lesion should be marked as well. When the specimen is submitted, it should be accompanied by an accurate map that clearly indicates the coding for medial, lateral, inferior, and superior aspects of the specimen. “Always prepare a specimen diagram for oriented specimens,” Dr. Phelps noted.

Don’t forget to make sure that the left-right orientation on the diagram corresponds to the specimen’s orientation on the patient, he added. Some facilities use a clock face system to indicate orientation and positioning, which may be the clearest method of all.

Sometimes, it’s difficult for the dermatopathologist to visualize whether the specimen is aligned in true medial-lateral fashion, or along skin tension lines, which tend to run diagonally, so “the more clinical information, the better,” he said. “With good mapping, precise retreatment can be optimal,” he said.

Dr. Phelps reported that he had no relevant conflicts of interest.
 

koakes@frontlinemedcom.com

On Twitter @karioakes

NEW YORK – If dermatopathologists had a wish list they could give their dermatologist colleagues, what might it include? High up on the list for many, said Robert Phelps, MD, might be to have them share the clinical picture, treat the specimen gently, and give the best landmarks possible.

Speaking at the summer meeting of the American Academy of Dermatology, Dr. Phelps, director of the dermatopathology service at Mount Sinai Medical Center in New York, led off the dermatopathologist-run session – appropriately titled “Help Me Help You” – by asking, “How can the clinician provide the optimal biopsy?”

It’s always helpful to have as much clinical information as possible, said Dr. Phelps, whose discussion focused on tips for neoplastic lesions. This might include prior history of malignancy, autoimmune disease, pathergy, or other relevant medical history, but clinical pictures can also be a big help, although there can be technical and patient privacy issues to overcome, he noted. If, for example, a larger lesion or rash is being biopsied rather than excised, it can be very helpful to see the larger field and full area of distribution of the lesion in question. Submitting multiple specimens for rashes and larger lesions is always a good idea too, he added.

Although curettage can be a great way to biopsy – and perhaps even definitively treat some lesions – problems can arise on the dermatopathologist’s side when melanocytic lesions are curetted for biopsy, according to Dr. Phelps, a practicing dermatologist and a dermatopathologist. “By virtue of the force of the biopsy, the specimen is often fragmented, and histology can be distorted,” he said. One element of that distortion can be that melanocytes can appear to be free floating, which is a problem. “Dyshesion of melanocytes is usually an indication of atypia … It is an important histologic clue as to the possibility of a malignancy supervening.”

These factors can make it tough for a dermatopathologist to make an accurate call. “If there are free-floating melanocytes from a curetted specimen, I can’t rule out invasive melanoma,” explained Dr. Phelps, since he can’t tell if he is seeing true atypia or disruption that’s an artifact of the collection technique.

In this instance, he said, a dermatopathologist would be “obligated to overcall, because one couldn’t really determine the pathology.” The bottom line? “Don’t curette biopsies of melanocytic lesions.”

Another technique that can interfere with the ability to read a tissue specimen accurately is electrodesiccation. Although it’s often performed in conjunction with curettage, electrodesiccation can cause changes in tissue consistent with thermal injury. “Essentially, the tissue has been burned,” Dr. Phelps pointed out. This can result in a characteristic streaming pattern of nuclei, and the dermis can acquire a “peculiar homogenized appearance,” he said.

Although electrodesiccation can be a useful technique to make sure margins are controlled, “when you do this, just be aware that the interpretation is difficult,” he noted. “It’s difficult to tell where the margins are and if they are the appropriate and correct margins,” he said.

When possible, try to avoid squeezing the tumor, Dr. Phelps advised. Excessive pressure on the specimen can distort cell architecture and make pathological diagnosis really challenging, particularly in lymphoid tumors, he said.

“Often, the tumor is not recognizable,” he added. Crush artifact can result in an appearance of small bluish clumps and smearing of collagen fibers. The effect, he said, can be particularly pronounced with small cell carcinoma and lymphoma, and with rapidly proliferating tumors.

Dr. Phelps said that during his training, he was taught not to use forceps to extract a stubborn punch biopsy specimen; rather, he was trained to use a needle to tease out the specimen. Fear of a self-inflicted needle stick with this technique may be a deterrent, he acknowledged. If forceps are used, he suggested being as gentle as possible and using the finest forceps available.

When pathologists receive an intact excised lesion – one not obtained using a Mohs technique, “delineation of the margin is essential,” Dr. Phelps said. Further, accurate mapping is critical to helping the examiner understand the anatomic orientation of the specimen, a key prerequisite that enables accurate communication from the dermatopathologist back to the clinician if there’s a question regarding the need for retreatment, he added.

For an elliptical excision, ideally, both poles of the ellipse would be suture-tagged, and at least one tag is essential, he said. Then superior and inferior borders can be inked with contrasting colors, and the epidermal borders of the lesion should be marked as well. When the specimen is submitted, it should be accompanied by an accurate map that clearly indicates the coding for medial, lateral, inferior, and superior aspects of the specimen. “Always prepare a specimen diagram for oriented specimens,” Dr. Phelps noted.

Don’t forget to make sure that the left-right orientation on the diagram corresponds to the specimen’s orientation on the patient, he added. Some facilities use a clock face system to indicate orientation and positioning, which may be the clearest method of all.

Sometimes, it’s difficult for the dermatopathologist to visualize whether the specimen is aligned in true medial-lateral fashion, or along skin tension lines, which tend to run diagonally, so “the more clinical information, the better,” he said. “With good mapping, precise retreatment can be optimal,” he said.

Dr. Phelps reported that he had no relevant conflicts of interest.
 

koakes@frontlinemedcom.com

On Twitter @karioakes

Timolol is a nonselective β-adrenergic receptor antagonist indicated for treating glaucoma, heart attacks, hypertension, and migraine headaches. It is made in both an oral and ophthalmic form. In dermatology, the beta-blocker propranolol is approved for the treatment of infantile hemangiomas (IHs). The exact mechanism of action of beta-blockers for the treatment of IHs is not yet completely understood, but it is postulated that they inhibit growth by at least 4 distinct mechanisms: (1) vasoconstriction, (2) inhibition of angiogenesis or vasculogenesis, (3) induction of apoptosis, and (4) recruitment of endothelial progenitor cells to the site of the hemangioma.¹

Scar cosmesis can be calculated using the visual analog scale (VAS), which is a subjective scar assessment scored from poor to excellent. The multidimensional VAS is a photograph-based scale derived from evaluating standardized digital photographs in 4 dimensions—pigmentation, vascularity, acceptability, and observer comfort—plus contour. It uses the sum of the individual scores to obtain a single overall score ranging from excellent to poor.² In this study, we sought to determine if the use of topical timolol after excision or Mohs micrographic surgery (MMS) treatment of nonmelanoma skin cancers improved the overall cosmesis of the scar.

Methods

The study protocol was approved by the institutional review board at Roger Williams Medical Center (Providence, Rhode Island). Eligibility criteria included patients who required excision or MMS for their nonmelanoma skin cancer located below the patella and those who agreed to allow their wounds to heal by secondary intention when given options for closure of their wounds. Patients were randomized to either the timolol (study medication) group or the saline (placebo) group. The initial defects were measured and photographed. Patients were educated on how to apply the study medication. All patients were prescribed 40 mm Hg compression stockings to wear following application of the study medication. Patients were asked to return at 1 and 5 weeks postsurgery and then every 1 to 2 weeks for wound assessment and measurement until their wounds had healed or at 13 weeks, depending on which came first. A healed wound was defined as having no exudate, exhibiting complete reepithelialization, and being stable for 1 week.

Healed wounds were assessed by a blinded outside dermatologist who examined photographs of the wounds and then completed the VAS for each participant’s scar.

Results

A total of 9 participants were enrolled in the study. Three participants were lost to follow-up; 6 completed the study (4 females, 2 males). The mean age was 70 years (age range, 46–89 years). The average wound size was 2×2 cm with a depth of 1 mm. Three participants were in the active medication group and 3 were in the control group.

A VAS was completed for each participant’s scar by an outside blinded dermatologist. Based on the VAS, wounds treated with timolol resulted in more cosmetically favorable scars (scored higher on the VAS) compared to control (mean [SD]: 6.5±0.9 vs 2.5±0.7; P<0.05). See Figures 1 and 2 for representative results.

Comment

Dermatologists create acute wounds in patients on a daily basis. Ensuring that patients achieve the most desirable cosmetic outcome is a primary goal for dermatologists and an important component of patient satisfaction. A number of studies have examined patient satisfaction following MMS.^3,4 Patient satisfaction is an especially important outcome measure in dermatology, as dermatologic diseases affect cosmetic appearance and are related to quality of life.^3,4

Timolol is a nonselective β-adrenergic receptor antagonist that is used in dermatology to treat IHs. In this preliminary study, the authors sought to determine if topical timolol applied to acute wounds following surgical removal of nonmelanoma skin cancers could improve the overall cosmetic outcome of acute surgical scars. The results showed that compared to control, topical timolol resulted in a more cosmetically favorable scar. The results are preliminary, and it would be of future interest to further study the effects of topical timolol on acute surgical wounds from a wound-healing standpoint as well as to further test its effects on the cosmesis of these wounds.

Timolol is a nonselective β-adrenergic receptor antagonist indicated for treating glaucoma, heart attacks, hypertension, and migraine headaches. It is made in both an oral and ophthalmic form. In dermatology, the beta-blocker propranolol is approved for the treatment of infantile hemangiomas (IHs). The exact mechanism of action of beta-blockers for the treatment of IHs is not yet completely understood, but it is postulated that they inhibit growth by at least 4 distinct mechanisms: (1) vasoconstriction, (2) inhibition of angiogenesis or vasculogenesis, (3) induction of apoptosis, and (4) recruitment of endothelial progenitor cells to the site of the hemangioma.¹

Scar cosmesis can be calculated using the visual analog scale (VAS), which is a subjective scar assessment scored from poor to excellent. The multidimensional VAS is a photograph-based scale derived from evaluating standardized digital photographs in 4 dimensions—pigmentation, vascularity, acceptability, and observer comfort—plus contour. It uses the sum of the individual scores to obtain a single overall score ranging from excellent to poor.² In this study, we sought to determine if the use of topical timolol after excision or Mohs micrographic surgery (MMS) treatment of nonmelanoma skin cancers improved the overall cosmesis of the scar.

Methods

The study protocol was approved by the institutional review board at Roger Williams Medical Center (Providence, Rhode Island). Eligibility criteria included patients who required excision or MMS for their nonmelanoma skin cancer located below the patella and those who agreed to allow their wounds to heal by secondary intention when given options for closure of their wounds. Patients were randomized to either the timolol (study medication) group or the saline (placebo) group. The initial defects were measured and photographed. Patients were educated on how to apply the study medication. All patients were prescribed 40 mm Hg compression stockings to wear following application of the study medication. Patients were asked to return at 1 and 5 weeks postsurgery and then every 1 to 2 weeks for wound assessment and measurement until their wounds had healed or at 13 weeks, depending on which came first. A healed wound was defined as having no exudate, exhibiting complete reepithelialization, and being stable for 1 week.

Healed wounds were assessed by a blinded outside dermatologist who examined photographs of the wounds and then completed the VAS for each participant’s scar.

Results

A total of 9 participants were enrolled in the study. Three participants were lost to follow-up; 6 completed the study (4 females, 2 males). The mean age was 70 years (age range, 46–89 years). The average wound size was 2×2 cm with a depth of 1 mm. Three participants were in the active medication group and 3 were in the control group.

A VAS was completed for each participant’s scar by an outside blinded dermatologist. Based on the VAS, wounds treated with timolol resulted in more cosmetically favorable scars (scored higher on the VAS) compared to control (mean [SD]: 6.5±0.9 vs 2.5±0.7; P<0.05). See Figures 1 and 2 for representative results.

Comment

Dermatologists create acute wounds in patients on a daily basis. Ensuring that patients achieve the most desirable cosmetic outcome is a primary goal for dermatologists and an important component of patient satisfaction. A number of studies have examined patient satisfaction following MMS.^3,4 Patient satisfaction is an especially important outcome measure in dermatology, as dermatologic diseases affect cosmetic appearance and are related to quality of life.^3,4

Timolol is a nonselective β-adrenergic receptor antagonist that is used in dermatology to treat IHs. In this preliminary study, the authors sought to determine if topical timolol applied to acute wounds following surgical removal of nonmelanoma skin cancers could improve the overall cosmetic outcome of acute surgical scars. The results showed that compared to control, topical timolol resulted in a more cosmetically favorable scar. The results are preliminary, and it would be of future interest to further study the effects of topical timolol on acute surgical wounds from a wound-healing standpoint as well as to further test its effects on the cosmesis of these wounds.

Timolol is a nonselective β-adrenergic receptor antagonist indicated for treating glaucoma, heart attacks, hypertension, and migraine headaches. It is made in both an oral and ophthalmic form. In dermatology, the beta-blocker propranolol is approved for the treatment of infantile hemangiomas (IHs). The exact mechanism of action of beta-blockers for the treatment of IHs is not yet completely understood, but it is postulated that they inhibit growth by at least 4 distinct mechanisms: (1) vasoconstriction, (2) inhibition of angiogenesis or vasculogenesis, (3) induction of apoptosis, and (4) recruitment of endothelial progenitor cells to the site of the hemangioma.¹

Scar cosmesis can be calculated using the visual analog scale (VAS), which is a subjective scar assessment scored from poor to excellent. The multidimensional VAS is a photograph-based scale derived from evaluating standardized digital photographs in 4 dimensions—pigmentation, vascularity, acceptability, and observer comfort—plus contour. It uses the sum of the individual scores to obtain a single overall score ranging from excellent to poor.² In this study, we sought to determine if the use of topical timolol after excision or Mohs micrographic surgery (MMS) treatment of nonmelanoma skin cancers improved the overall cosmesis of the scar.

Methods

The study protocol was approved by the institutional review board at Roger Williams Medical Center (Providence, Rhode Island). Eligibility criteria included patients who required excision or MMS for their nonmelanoma skin cancer located below the patella and those who agreed to allow their wounds to heal by secondary intention when given options for closure of their wounds. Patients were randomized to either the timolol (study medication) group or the saline (placebo) group. The initial defects were measured and photographed. Patients were educated on how to apply the study medication. All patients were prescribed 40 mm Hg compression stockings to wear following application of the study medication. Patients were asked to return at 1 and 5 weeks postsurgery and then every 1 to 2 weeks for wound assessment and measurement until their wounds had healed or at 13 weeks, depending on which came first. A healed wound was defined as having no exudate, exhibiting complete reepithelialization, and being stable for 1 week.

Healed wounds were assessed by a blinded outside dermatologist who examined photographs of the wounds and then completed the VAS for each participant’s scar.

Results

A total of 9 participants were enrolled in the study. Three participants were lost to follow-up; 6 completed the study (4 females, 2 males). The mean age was 70 years (age range, 46–89 years). The average wound size was 2×2 cm with a depth of 1 mm. Three participants were in the active medication group and 3 were in the control group.

A VAS was completed for each participant’s scar by an outside blinded dermatologist. Based on the VAS, wounds treated with timolol resulted in more cosmetically favorable scars (scored higher on the VAS) compared to control (mean [SD]: 6.5±0.9 vs 2.5±0.7; P<0.05). See Figures 1 and 2 for representative results.

Comment

Dermatologists create acute wounds in patients on a daily basis. Ensuring that patients achieve the most desirable cosmetic outcome is a primary goal for dermatologists and an important component of patient satisfaction. A number of studies have examined patient satisfaction following MMS.^3,4 Patient satisfaction is an especially important outcome measure in dermatology, as dermatologic diseases affect cosmetic appearance and are related to quality of life.^3,4

Timolol is a nonselective β-adrenergic receptor antagonist that is used in dermatology to treat IHs. In this preliminary study, the authors sought to determine if topical timolol applied to acute wounds following surgical removal of nonmelanoma skin cancers could improve the overall cosmetic outcome of acute surgical scars. The results showed that compared to control, topical timolol resulted in a more cosmetically favorable scar. The results are preliminary, and it would be of future interest to further study the effects of topical timolol on acute surgical wounds from a wound-healing standpoint as well as to further test its effects on the cosmesis of these wounds.

The Diagnosis: Lymphomatoid Papulosis

A shave biopsy of an established lesion on the volar aspect of the left wrist was performed (Figure 1). The biopsy showed an ulcerated nodular lesion characterized by a dense mixed inflammatory cell infiltrate in the dermis composed of lymphocytes, histiocytes, scattered neutrophils, and numerous eosinophils (Figure 2). Notably there was a minor population of large atypical cells with immunoblastic and anaplastic morphology present individually and in small clusters most prominently within the upper dermis (Figures 3 and 4). Immunohistochemistry of the anaplastic cells revealed a CD30⁺, CD3⁻, CD4⁺, CD5⁻, CD8⁻, CD2⁻, CD7⁻, CD56⁻, ALK1⁻ (anaplastic lymphoma kinase-1), PAX5⁻ (paired box protein-5), CD20⁻, and CD15⁻ phenotype. These morphologic and immunohistochemical features suggested a CD30⁺ cutaneous lymphoproliferative disorder. The clinical history of recurrent self-healing papulonodules in an otherwise-healthy patient established the diagnosis of lymphomatoid papulosis (LyP).

Lymphomatoid papulosis is a lymphoproliferative disorder characterized by recurrent crops of self-resolving eruptive papulonodular skin lesions that may show a variety of histologic features including a CD30⁺ malignant T-cell lymphoma.¹ Lymphomatoid papulosis was first described in 1968¹ but debate continues whether the condition should be considered malignant or benign.² Although the prognosis is excellent, LyP is characterized by a protracted course, often lasting many years. Additionally, these patients have a lifelong increased risk for development of a second cutaneous or systemic lymphoma such as mycosis fungoides (MF), cutaneous or nodal anaplastic large cell lymphoma (ALCL), or Hodgkin lymphoma, among others.

Lymphomatoid papulosis is a rare disease occurring in all ethnic groups and at any age, though most commonly presenting in the fifth decade of life. Finding large atypical T cells expressing CD30 in recurring skin lesions is highly suggestive of LyP; however, large CD30⁺ cells also can be seen in numerous benign reactive processes such as arthropod assault, drug eruption, viral skin infections, and other dermatoses, thus clinical correlation is always paramount. The cause of LyP is largely unknown; however, spontaneous regression may be explained by CD30-CD30 ligand interaction³ as well as an increased proapoptotic milieu.⁴ Specific translocations such as interferon regulatory factor-4 have been hypothesized as a risk factor for malignant progression.^5-7 Additionally, an inactivating gene mutation resulting in loss of transforming growth factor β1 receptor expression and subsequent unresponsiveness to the growth inhibitory effect of transforming growth factor β may play a role in progression of LyP to ALCL.⁸

Clinically, LyP consists of red-brown papules and nodules generally smaller than 2 cm, often with central hemorrhage, necrosis, and crusting. Lesions are at different stages of eruption and resolution. They are often grouped but may be disseminated. Spontaneous regression typically occurs within 3 to 8 weeks. Pruritus or mild tenderness may occur as well as residual hyperpigmentation or scarring. Systemic symptoms are notably absent.

The histologic features of LyP vary according to the age of the lesion and subtype.² Early lesions may only show a few inflammatory cells, but as lesions evolve, larger immunoblastlike CD30⁺ atypical cells accumulate that may resemble the Reed-Sternberg cells of Hodgkin lymphoma. Of the 5 subtypes, the most common is type A. It is characterized by a wedge-shaped infiltrate with a mixed population of scattered or clustered, large, atypical CD30⁺ cells, lymphocytes, neutrophils, eosinophils, and histiocytes.⁹ Frequent mitoses often are seen. Type B appears similar to MF due to a predominantly epidermotropic infiltrate of CD3⁺ and often CD30⁻ atypical cells. Spontaneously regressing papules favor LyP, whereas persistent patches or plaques favor MF. Type C appears identical to ALCL with diffuse sheets of large atypical CD30⁺ cells and relatively few inflammatory cells, but spontaneously regressing lesions again favor LyP, whereas persistent tumors favor ALCL. Type D appears similar to primary cutaneous aggressive epidermotropic CD8⁺ cytotoxic T cell lymphoma due to a markedly epidermotropic infiltrate of small atypical CD8⁺ and CD30⁺ lymphocytes, often TIA-1⁺ (T-cell intracytoplasmic antigen-1) or granzyme B⁺, but CD30 positivity and self-resolving lesions favor LyP. Type E mimics extranodal natural killer/T cell lymphoma (nasal type) due to angioinvasive CD30⁺ and beta F1⁺ T lymphocytes, often CD8⁺ and/or TIA-1⁺, but self-resolving lesions again favor LyP, as well as absence of Epstein-Barr virus and CD56⁻.⁹

The most common therapeutic approaches to LyP include topical steroids, phototherapy, and low-dose methotrexate.¹⁰ However, treatment does not change overall disease course or reduce the future risk for developing an associated lymphoma. Accordingly, abstaining from active therapeutic intervention is reasonable, especially in patients with only a few asymptomatic lesions.

The Diagnosis: Lymphomatoid Papulosis

A shave biopsy of an established lesion on the volar aspect of the left wrist was performed (Figure 1). The biopsy showed an ulcerated nodular lesion characterized by a dense mixed inflammatory cell infiltrate in the dermis composed of lymphocytes, histiocytes, scattered neutrophils, and numerous eosinophils (Figure 2). Notably there was a minor population of large atypical cells with immunoblastic and anaplastic morphology present individually and in small clusters most prominently within the upper dermis (Figures 3 and 4). Immunohistochemistry of the anaplastic cells revealed a CD30⁺, CD3⁻, CD4⁺, CD5⁻, CD8⁻, CD2⁻, CD7⁻, CD56⁻, ALK1⁻ (anaplastic lymphoma kinase-1), PAX5⁻ (paired box protein-5), CD20⁻, and CD15⁻ phenotype. These morphologic and immunohistochemical features suggested a CD30⁺ cutaneous lymphoproliferative disorder. The clinical history of recurrent self-healing papulonodules in an otherwise-healthy patient established the diagnosis of lymphomatoid papulosis (LyP).

Lymphomatoid papulosis is a lymphoproliferative disorder characterized by recurrent crops of self-resolving eruptive papulonodular skin lesions that may show a variety of histologic features including a CD30⁺ malignant T-cell lymphoma.¹ Lymphomatoid papulosis was first described in 1968¹ but debate continues whether the condition should be considered malignant or benign.² Although the prognosis is excellent, LyP is characterized by a protracted course, often lasting many years. Additionally, these patients have a lifelong increased risk for development of a second cutaneous or systemic lymphoma such as mycosis fungoides (MF), cutaneous or nodal anaplastic large cell lymphoma (ALCL), or Hodgkin lymphoma, among others.

Lymphomatoid papulosis is a rare disease occurring in all ethnic groups and at any age, though most commonly presenting in the fifth decade of life. Finding large atypical T cells expressing CD30 in recurring skin lesions is highly suggestive of LyP; however, large CD30⁺ cells also can be seen in numerous benign reactive processes such as arthropod assault, drug eruption, viral skin infections, and other dermatoses, thus clinical correlation is always paramount. The cause of LyP is largely unknown; however, spontaneous regression may be explained by CD30-CD30 ligand interaction³ as well as an increased proapoptotic milieu.⁴ Specific translocations such as interferon regulatory factor-4 have been hypothesized as a risk factor for malignant progression.^5-7 Additionally, an inactivating gene mutation resulting in loss of transforming growth factor β1 receptor expression and subsequent unresponsiveness to the growth inhibitory effect of transforming growth factor β may play a role in progression of LyP to ALCL.⁸

Clinically, LyP consists of red-brown papules and nodules generally smaller than 2 cm, often with central hemorrhage, necrosis, and crusting. Lesions are at different stages of eruption and resolution. They are often grouped but may be disseminated. Spontaneous regression typically occurs within 3 to 8 weeks. Pruritus or mild tenderness may occur as well as residual hyperpigmentation or scarring. Systemic symptoms are notably absent.

The histologic features of LyP vary according to the age of the lesion and subtype.² Early lesions may only show a few inflammatory cells, but as lesions evolve, larger immunoblastlike CD30⁺ atypical cells accumulate that may resemble the Reed-Sternberg cells of Hodgkin lymphoma. Of the 5 subtypes, the most common is type A. It is characterized by a wedge-shaped infiltrate with a mixed population of scattered or clustered, large, atypical CD30⁺ cells, lymphocytes, neutrophils, eosinophils, and histiocytes.⁹ Frequent mitoses often are seen. Type B appears similar to MF due to a predominantly epidermotropic infiltrate of CD3⁺ and often CD30⁻ atypical cells. Spontaneously regressing papules favor LyP, whereas persistent patches or plaques favor MF. Type C appears identical to ALCL with diffuse sheets of large atypical CD30⁺ cells and relatively few inflammatory cells, but spontaneously regressing lesions again favor LyP, whereas persistent tumors favor ALCL. Type D appears similar to primary cutaneous aggressive epidermotropic CD8⁺ cytotoxic T cell lymphoma due to a markedly epidermotropic infiltrate of small atypical CD8⁺ and CD30⁺ lymphocytes, often TIA-1⁺ (T-cell intracytoplasmic antigen-1) or granzyme B⁺, but CD30 positivity and self-resolving lesions favor LyP. Type E mimics extranodal natural killer/T cell lymphoma (nasal type) due to angioinvasive CD30⁺ and beta F1⁺ T lymphocytes, often CD8⁺ and/or TIA-1⁺, but self-resolving lesions again favor LyP, as well as absence of Epstein-Barr virus and CD56⁻.⁹

The most common therapeutic approaches to LyP include topical steroids, phototherapy, and low-dose methotrexate.¹⁰ However, treatment does not change overall disease course or reduce the future risk for developing an associated lymphoma. Accordingly, abstaining from active therapeutic intervention is reasonable, especially in patients with only a few asymptomatic lesions.

The Diagnosis: Lymphomatoid Papulosis

A shave biopsy of an established lesion on the volar aspect of the left wrist was performed (Figure 1). The biopsy showed an ulcerated nodular lesion characterized by a dense mixed inflammatory cell infiltrate in the dermis composed of lymphocytes, histiocytes, scattered neutrophils, and numerous eosinophils (Figure 2). Notably there was a minor population of large atypical cells with immunoblastic and anaplastic morphology present individually and in small clusters most prominently within the upper dermis (Figures 3 and 4). Immunohistochemistry of the anaplastic cells revealed a CD30⁺, CD3⁻, CD4⁺, CD5⁻, CD8⁻, CD2⁻, CD7⁻, CD56⁻, ALK1⁻ (anaplastic lymphoma kinase-1), PAX5⁻ (paired box protein-5), CD20⁻, and CD15⁻ phenotype. These morphologic and immunohistochemical features suggested a CD30⁺ cutaneous lymphoproliferative disorder. The clinical history of recurrent self-healing papulonodules in an otherwise-healthy patient established the diagnosis of lymphomatoid papulosis (LyP).

Lymphomatoid papulosis is a lymphoproliferative disorder characterized by recurrent crops of self-resolving eruptive papulonodular skin lesions that may show a variety of histologic features including a CD30⁺ malignant T-cell lymphoma.¹ Lymphomatoid papulosis was first described in 1968¹ but debate continues whether the condition should be considered malignant or benign.² Although the prognosis is excellent, LyP is characterized by a protracted course, often lasting many years. Additionally, these patients have a lifelong increased risk for development of a second cutaneous or systemic lymphoma such as mycosis fungoides (MF), cutaneous or nodal anaplastic large cell lymphoma (ALCL), or Hodgkin lymphoma, among others.

Lymphomatoid papulosis is a rare disease occurring in all ethnic groups and at any age, though most commonly presenting in the fifth decade of life. Finding large atypical T cells expressing CD30 in recurring skin lesions is highly suggestive of LyP; however, large CD30⁺ cells also can be seen in numerous benign reactive processes such as arthropod assault, drug eruption, viral skin infections, and other dermatoses, thus clinical correlation is always paramount. The cause of LyP is largely unknown; however, spontaneous regression may be explained by CD30-CD30 ligand interaction³ as well as an increased proapoptotic milieu.⁴ Specific translocations such as interferon regulatory factor-4 have been hypothesized as a risk factor for malignant progression.^5-7 Additionally, an inactivating gene mutation resulting in loss of transforming growth factor β1 receptor expression and subsequent unresponsiveness to the growth inhibitory effect of transforming growth factor β may play a role in progression of LyP to ALCL.⁸

Clinically, LyP consists of red-brown papules and nodules generally smaller than 2 cm, often with central hemorrhage, necrosis, and crusting. Lesions are at different stages of eruption and resolution. They are often grouped but may be disseminated. Spontaneous regression typically occurs within 3 to 8 weeks. Pruritus or mild tenderness may occur as well as residual hyperpigmentation or scarring. Systemic symptoms are notably absent.

The histologic features of LyP vary according to the age of the lesion and subtype.² Early lesions may only show a few inflammatory cells, but as lesions evolve, larger immunoblastlike CD30⁺ atypical cells accumulate that may resemble the Reed-Sternberg cells of Hodgkin lymphoma. Of the 5 subtypes, the most common is type A. It is characterized by a wedge-shaped infiltrate with a mixed population of scattered or clustered, large, atypical CD30⁺ cells, lymphocytes, neutrophils, eosinophils, and histiocytes.⁹ Frequent mitoses often are seen. Type B appears similar to MF due to a predominantly epidermotropic infiltrate of CD3⁺ and often CD30⁻ atypical cells. Spontaneously regressing papules favor LyP, whereas persistent patches or plaques favor MF. Type C appears identical to ALCL with diffuse sheets of large atypical CD30⁺ cells and relatively few inflammatory cells, but spontaneously regressing lesions again favor LyP, whereas persistent tumors favor ALCL. Type D appears similar to primary cutaneous aggressive epidermotropic CD8⁺ cytotoxic T cell lymphoma due to a markedly epidermotropic infiltrate of small atypical CD8⁺ and CD30⁺ lymphocytes, often TIA-1⁺ (T-cell intracytoplasmic antigen-1) or granzyme B⁺, but CD30 positivity and self-resolving lesions favor LyP. Type E mimics extranodal natural killer/T cell lymphoma (nasal type) due to angioinvasive CD30⁺ and beta F1⁺ T lymphocytes, often CD8⁺ and/or TIA-1⁺, but self-resolving lesions again favor LyP, as well as absence of Epstein-Barr virus and CD56⁻.⁹

The most common therapeutic approaches to LyP include topical steroids, phototherapy, and low-dose methotrexate.¹⁰ However, treatment does not change overall disease course or reduce the future risk for developing an associated lymphoma. Accordingly, abstaining from active therapeutic intervention is reasonable, especially in patients with only a few asymptomatic lesions.

Clinically significant bleeding events occurred in two elderly men who were taking ibrutinib and underwent Mohs micrographic surgery for squamous cell carcinomas, Cindy E. Parra and her colleagues reported in JAMA Dermatology.

On day 3 after his Mohs procedure, one 73-year-old man taking ibrutinib for Waldenstrom macroglobulinemia developed extensive bilateral periorbital ecchymosis that extended down to his upper chest. The other patient, an 88-year-old man taking ibrutinib for chronic lymphocytic leukemia, developed ecchymosis down to the chin. The first patient discontinued ibrutinib 3 days before his surgery; the second patient was taking ibrutinib at the time of his surgery.

“The increased incidence of nonmelanoma skin cancer and poorer outcomes in patients with non-Hodgkin lymphoma and CLL is well recognized, as is the importance of aggressive dermatologic management,” the researchers wrote (JAMA Dermatol. 2017 Jul 12. doi: 10.1001/jamadermatol.2017.1877). “It may be prudent to withhold ibrutinib treatment prior to dermatologic surgery to avoid potential bleeding complications.”

The findings argue for close collaboration between the dermatologic surgeon and the patient’s hematologist when scheduling extended-duration dermatologic procedures in patients taking ibrutinib.

Find the full summary here.

acruz@frontlinemedcom.com

Clinically significant bleeding events occurred in two elderly men who were taking ibrutinib and underwent Mohs micrographic surgery for squamous cell carcinomas, Cindy E. Parra and her colleagues reported in JAMA Dermatology.

On day 3 after his Mohs procedure, one 73-year-old man taking ibrutinib for Waldenstrom macroglobulinemia developed extensive bilateral periorbital ecchymosis that extended down to his upper chest. The other patient, an 88-year-old man taking ibrutinib for chronic lymphocytic leukemia, developed ecchymosis down to the chin. The first patient discontinued ibrutinib 3 days before his surgery; the second patient was taking ibrutinib at the time of his surgery.

“The increased incidence of nonmelanoma skin cancer and poorer outcomes in patients with non-Hodgkin lymphoma and CLL is well recognized, as is the importance of aggressive dermatologic management,” the researchers wrote (JAMA Dermatol. 2017 Jul 12. doi: 10.1001/jamadermatol.2017.1877). “It may be prudent to withhold ibrutinib treatment prior to dermatologic surgery to avoid potential bleeding complications.”

The findings argue for close collaboration between the dermatologic surgeon and the patient’s hematologist when scheduling extended-duration dermatologic procedures in patients taking ibrutinib.

Find the full summary here.

acruz@frontlinemedcom.com

Clinically significant bleeding events occurred in two elderly men who were taking ibrutinib and underwent Mohs micrographic surgery for squamous cell carcinomas, Cindy E. Parra and her colleagues reported in JAMA Dermatology.

On day 3 after his Mohs procedure, one 73-year-old man taking ibrutinib for Waldenstrom macroglobulinemia developed extensive bilateral periorbital ecchymosis that extended down to his upper chest. The other patient, an 88-year-old man taking ibrutinib for chronic lymphocytic leukemia, developed ecchymosis down to the chin. The first patient discontinued ibrutinib 3 days before his surgery; the second patient was taking ibrutinib at the time of his surgery.

“The increased incidence of nonmelanoma skin cancer and poorer outcomes in patients with non-Hodgkin lymphoma and CLL is well recognized, as is the importance of aggressive dermatologic management,” the researchers wrote (JAMA Dermatol. 2017 Jul 12. doi: 10.1001/jamadermatol.2017.1877). “It may be prudent to withhold ibrutinib treatment prior to dermatologic surgery to avoid potential bleeding complications.”

The findings argue for close collaboration between the dermatologic surgeon and the patient’s hematologist when scheduling extended-duration dermatologic procedures in patients taking ibrutinib.

Find the full summary here.

acruz@frontlinemedcom.com

HIV-infected individuals who have experienced a nonmelanoma skin cancer may be at significantly greater risk of subsequent new squamous cell carcinoma if they have a lower CD4 cell count, a new study suggests.

In a study published online July 12 in JAMA Dermatology, researchers reported the results of a retrospective cohort study using medical record data from 455 HIV-infected and 1,952 HIV-uninfected patients who had previously been diagnosed with at least one nonmelanoma skin cancer.

Patients with CD4 cell counts below 200 cells/mcL had a 44% greater risk of a subsequent nonmelanoma skin cancer, compared with uninfected individuals (95% confidence interval, 1.10-1.88), while those with a viral load greater than 10,000 copies/mL had a 31% greater risk (95% CI, 1.00-1.72), after adjusting for age, sex, smoking status, and obesity.

The increase in nonmelanoma skin cancer risk was largely accounted for by an increased risk of squamous cell carcinoma (SCC). Among patients with lower CD4 cell counts and those with higher viral loads, the risk of SCC was more than twofold greater than among uninfected individuals. In contrast, while there was a trend toward a higher risk of basal cell carcinoma in those two groups, it did not reach significance (JAMA Dermatol. 2017 Jul 12. doi: 10.1001/jamadermatol.2017.1716).

Overall, HIV-infected individuals had a significant 15% increase in the risk of subsequent nonmelanoma skin cancer over an average follow-up period of 5 years, compared with uninfected individuals.

“This study addresses key questions regarding subsequent NMSC [nonmelanoma skin cancer] risk among a high-risk subgroup of HIV-infected population who, by virtue of having had a pathologically validated skin cancer, are at increased risk of subsequent NMSCs,” wrote Maryam M. Asgari, MD, of Massachusetts General Hospital, Boston, and her coauthors. “Specifically, it was previously not known precisely which NMSC subtype is increased in high-risk persons with HIV and whether biomarkers of HIV infections, such as degree of immune dysfunction, are associated with subsequent skin cancer risk.”

While the study wasn’t able to control for known skin cancer risk factors such as skin type, the patients were all non-Hispanic white, which the authors said selected for individuals with fair skin and some sun-exposure history.

The findings could have implications for skin cancer screening among individuals with HIV infection, with the authors suggesting more targeted monitoring for SCC among individuals with low CD4 counts or high viral loads.

“Our findings support immune dysfunction as a risk factor for SCCs and dovetail with SCC risk data from iatrogenic immunodeficiency states, such as organ transplantation and autoimmune diseases.”

The study was partly supported by Kaiser Permanente Northern California, and one author was supported by a grant from the National Cancer Institute. Two authors had previously served as investigators on studies funded by the pharmaceutical industry, one author declared research funding from the pharmaceutical industry, and one declared shares in two medical companies.

HIV-infected individuals who have experienced a nonmelanoma skin cancer may be at significantly greater risk of subsequent new squamous cell carcinoma if they have a lower CD4 cell count, a new study suggests.

In a study published online July 12 in JAMA Dermatology, researchers reported the results of a retrospective cohort study using medical record data from 455 HIV-infected and 1,952 HIV-uninfected patients who had previously been diagnosed with at least one nonmelanoma skin cancer.

Patients with CD4 cell counts below 200 cells/mcL had a 44% greater risk of a subsequent nonmelanoma skin cancer, compared with uninfected individuals (95% confidence interval, 1.10-1.88), while those with a viral load greater than 10,000 copies/mL had a 31% greater risk (95% CI, 1.00-1.72), after adjusting for age, sex, smoking status, and obesity.

The increase in nonmelanoma skin cancer risk was largely accounted for by an increased risk of squamous cell carcinoma (SCC). Among patients with lower CD4 cell counts and those with higher viral loads, the risk of SCC was more than twofold greater than among uninfected individuals. In contrast, while there was a trend toward a higher risk of basal cell carcinoma in those two groups, it did not reach significance (JAMA Dermatol. 2017 Jul 12. doi: 10.1001/jamadermatol.2017.1716).

Overall, HIV-infected individuals had a significant 15% increase in the risk of subsequent nonmelanoma skin cancer over an average follow-up period of 5 years, compared with uninfected individuals.

“This study addresses key questions regarding subsequent NMSC [nonmelanoma skin cancer] risk among a high-risk subgroup of HIV-infected population who, by virtue of having had a pathologically validated skin cancer, are at increased risk of subsequent NMSCs,” wrote Maryam M. Asgari, MD, of Massachusetts General Hospital, Boston, and her coauthors. “Specifically, it was previously not known precisely which NMSC subtype is increased in high-risk persons with HIV and whether biomarkers of HIV infections, such as degree of immune dysfunction, are associated with subsequent skin cancer risk.”

While the study wasn’t able to control for known skin cancer risk factors such as skin type, the patients were all non-Hispanic white, which the authors said selected for individuals with fair skin and some sun-exposure history.

The findings could have implications for skin cancer screening among individuals with HIV infection, with the authors suggesting more targeted monitoring for SCC among individuals with low CD4 counts or high viral loads.

“Our findings support immune dysfunction as a risk factor for SCCs and dovetail with SCC risk data from iatrogenic immunodeficiency states, such as organ transplantation and autoimmune diseases.”

The study was partly supported by Kaiser Permanente Northern California, and one author was supported by a grant from the National Cancer Institute. Two authors had previously served as investigators on studies funded by the pharmaceutical industry, one author declared research funding from the pharmaceutical industry, and one declared shares in two medical companies.

HIV-infected individuals who have experienced a nonmelanoma skin cancer may be at significantly greater risk of subsequent new squamous cell carcinoma if they have a lower CD4 cell count, a new study suggests.

In a study published online July 12 in JAMA Dermatology, researchers reported the results of a retrospective cohort study using medical record data from 455 HIV-infected and 1,952 HIV-uninfected patients who had previously been diagnosed with at least one nonmelanoma skin cancer.

Patients with CD4 cell counts below 200 cells/mcL had a 44% greater risk of a subsequent nonmelanoma skin cancer, compared with uninfected individuals (95% confidence interval, 1.10-1.88), while those with a viral load greater than 10,000 copies/mL had a 31% greater risk (95% CI, 1.00-1.72), after adjusting for age, sex, smoking status, and obesity.

The increase in nonmelanoma skin cancer risk was largely accounted for by an increased risk of squamous cell carcinoma (SCC). Among patients with lower CD4 cell counts and those with higher viral loads, the risk of SCC was more than twofold greater than among uninfected individuals. In contrast, while there was a trend toward a higher risk of basal cell carcinoma in those two groups, it did not reach significance (JAMA Dermatol. 2017 Jul 12. doi: 10.1001/jamadermatol.2017.1716).

Overall, HIV-infected individuals had a significant 15% increase in the risk of subsequent nonmelanoma skin cancer over an average follow-up period of 5 years, compared with uninfected individuals.

“This study addresses key questions regarding subsequent NMSC [nonmelanoma skin cancer] risk among a high-risk subgroup of HIV-infected population who, by virtue of having had a pathologically validated skin cancer, are at increased risk of subsequent NMSCs,” wrote Maryam M. Asgari, MD, of Massachusetts General Hospital, Boston, and her coauthors. “Specifically, it was previously not known precisely which NMSC subtype is increased in high-risk persons with HIV and whether biomarkers of HIV infections, such as degree of immune dysfunction, are associated with subsequent skin cancer risk.”

While the study wasn’t able to control for known skin cancer risk factors such as skin type, the patients were all non-Hispanic white, which the authors said selected for individuals with fair skin and some sun-exposure history.

The findings could have implications for skin cancer screening among individuals with HIV infection, with the authors suggesting more targeted monitoring for SCC among individuals with low CD4 counts or high viral loads.

“Our findings support immune dysfunction as a risk factor for SCCs and dovetail with SCC risk data from iatrogenic immunodeficiency states, such as organ transplantation and autoimmune diseases.”

The study was partly supported by Kaiser Permanente Northern California, and one author was supported by a grant from the National Cancer Institute. Two authors had previously served as investigators on studies funded by the pharmaceutical industry, one author declared research funding from the pharmaceutical industry, and one declared shares in two medical companies.

To the Editor:

A 41-year-old man presented with a slowly enlarging, tender, firm lesion on the left hallux of approximately 5 months' duration that initially appeared to be a blister. He reported no history of keloids or trauma to the left foot. On examination, a 3.5-cm, flesh-colored, pedunculated, firm nodule was present on the lateral aspect of the left great hallux (Figure 1). No lymphadenopathy was found. The lesion was diagnosed at that time as a keloid and treated with intralesional steroids without response. The patient was lost to follow-up, and after 5 months he presented again with pain and drainage from the lesion. Acute drainage resolved after antibiotic therapy. A shave biopsy was performed, which revealed findings consistent with a dermatofibrosarcoma protuberans (DFSP). A chest radiograph was unremarkable. Re-excision was performed with negative margins on frozen section but with positive peripheral and deep margins on permanent sections. The patient subsequently underwent amputation of the left great toe and was lost to follow-up after the initial postoperative period.

Histopathologic examination demonstrated a polypoid spindle cell tumor that filled the dermis and invaded into the subcutaneous adipose tissue (Figure 2). The spindle cells had tapered nuclei in a honeycomb arrangement with only mild nuclear pleomorphism arranged in fascicles with a herringbone formation. Areas showed a myxoid stroma with abundant mucin (Figure 3). Immunostaining demonstrated cells strongly positive for CD34 and negative for MART (melanoma-associated antigen recognized by T cells), S-100, and smooth muscle actin immunostains.

Dermatofibrosarcoma protuberans is a sarcoma that is locally aggressive and tends to recur after surgical excision, though rare cases of metastasis involving the lungs have been reported.¹² Dermatofibrosarcoma protuberans usually affects young to middle-aged adults. Acral DFSP is rare in adults, with tumors most commonly occurring on the trunk (50%-60%), proximal extremities (20%-30%), or the head and neck (10%-15%).^1,2 A higher rate of acral DFSP has been found in children, which may be due to the increased rate of extremity trauma. Dermatofibrosarcoma protuberans commonly presents as an asymptomatic, slowly growing, indurated plaque that may be flesh colored or hyperpigmented, followed by development of erythematous firm nodules of up to several centimeters.^1,3 Dermatofibrosarcoma protuberans may be associated with a purulent exudate or ulceration, and pain may develop as the lesion grows.

Histopathologic evaluation shows an early plaque stage characterized by low cellularity, minimal nuclear atypia, and rare mitotic figures.⁴ In the nodular stage, the spindle cells are arranged as short fascicles in a storiform arrangement and infiltrate the subcutaneous tissue in a honeycomb pattern with hyperchromatic nuclei and mitotic figures. The nodules may develop myxomatous areas as well as less-differentiated foci with intersecting fascicles in a herringbone pattern. Anti-CD34 antibody immunostaining demonstrates strongly positive spindle cells, while DFSP is negative for stromelysin 3, factor XIIIa, and D2-40, which can help to differentiate DFSP from dermatofibroma.⁵ The myxoid subtype of DFSP does not differ clinically or prognostically from conventional DFSP, though its recognition can be of use in differentiating other myxoid tumors. Myxoid DFSP is nearly always positive for CD34 and negative for the neural marker S-100 protein.⁶

Some reports have demonstrated that Mohs micrographic surgery is superior to wide local excision in treatment of DFSP, as it results in fewer local recurrences and metastases.^7,8 Because of cytogenic abnormalities such as a reciprocal chromosomal (17;22) translocation or supernumerary ring chromosome derived from t(17;22) that place the PDGFB gene under the control of COL1A1 promoter, imatinib mesylate has been tested in DFSP and resulted in dramatic responses in both adults and children.^9,10 Suggested uses of imatinib include metastatic disease and locally invasive disease not suitable for surgical excision as well as a method to debulk tumors prior to resection.¹¹

To the Editor:

A 41-year-old man presented with a slowly enlarging, tender, firm lesion on the left hallux of approximately 5 months' duration that initially appeared to be a blister. He reported no history of keloids or trauma to the left foot. On examination, a 3.5-cm, flesh-colored, pedunculated, firm nodule was present on the lateral aspect of the left great hallux (Figure 1). No lymphadenopathy was found. The lesion was diagnosed at that time as a keloid and treated with intralesional steroids without response. The patient was lost to follow-up, and after 5 months he presented again with pain and drainage from the lesion. Acute drainage resolved after antibiotic therapy. A shave biopsy was performed, which revealed findings consistent with a dermatofibrosarcoma protuberans (DFSP). A chest radiograph was unremarkable. Re-excision was performed with negative margins on frozen section but with positive peripheral and deep margins on permanent sections. The patient subsequently underwent amputation of the left great toe and was lost to follow-up after the initial postoperative period.

Histopathologic examination demonstrated a polypoid spindle cell tumor that filled the dermis and invaded into the subcutaneous adipose tissue (Figure 2). The spindle cells had tapered nuclei in a honeycomb arrangement with only mild nuclear pleomorphism arranged in fascicles with a herringbone formation. Areas showed a myxoid stroma with abundant mucin (Figure 3). Immunostaining demonstrated cells strongly positive for CD34 and negative for MART (melanoma-associated antigen recognized by T cells), S-100, and smooth muscle actin immunostains.

Dermatofibrosarcoma protuberans is a sarcoma that is locally aggressive and tends to recur after surgical excision, though rare cases of metastasis involving the lungs have been reported.¹² Dermatofibrosarcoma protuberans usually affects young to middle-aged adults. Acral DFSP is rare in adults, with tumors most commonly occurring on the trunk (50%-60%), proximal extremities (20%-30%), or the head and neck (10%-15%).^1,2 A higher rate of acral DFSP has been found in children, which may be due to the increased rate of extremity trauma. Dermatofibrosarcoma protuberans commonly presents as an asymptomatic, slowly growing, indurated plaque that may be flesh colored or hyperpigmented, followed by development of erythematous firm nodules of up to several centimeters.^1,3 Dermatofibrosarcoma protuberans may be associated with a purulent exudate or ulceration, and pain may develop as the lesion grows.

Histopathologic evaluation shows an early plaque stage characterized by low cellularity, minimal nuclear atypia, and rare mitotic figures.⁴ In the nodular stage, the spindle cells are arranged as short fascicles in a storiform arrangement and infiltrate the subcutaneous tissue in a honeycomb pattern with hyperchromatic nuclei and mitotic figures. The nodules may develop myxomatous areas as well as less-differentiated foci with intersecting fascicles in a herringbone pattern. Anti-CD34 antibody immunostaining demonstrates strongly positive spindle cells, while DFSP is negative for stromelysin 3, factor XIIIa, and D2-40, which can help to differentiate DFSP from dermatofibroma.⁵ The myxoid subtype of DFSP does not differ clinically or prognostically from conventional DFSP, though its recognition can be of use in differentiating other myxoid tumors. Myxoid DFSP is nearly always positive for CD34 and negative for the neural marker S-100 protein.⁶

Some reports have demonstrated that Mohs micrographic surgery is superior to wide local excision in treatment of DFSP, as it results in fewer local recurrences and metastases.^7,8 Because of cytogenic abnormalities such as a reciprocal chromosomal (17;22) translocation or supernumerary ring chromosome derived from t(17;22) that place the PDGFB gene under the control of COL1A1 promoter, imatinib mesylate has been tested in DFSP and resulted in dramatic responses in both adults and children.^9,10 Suggested uses of imatinib include metastatic disease and locally invasive disease not suitable for surgical excision as well as a method to debulk tumors prior to resection.¹¹

To the Editor:

A 41-year-old man presented with a slowly enlarging, tender, firm lesion on the left hallux of approximately 5 months' duration that initially appeared to be a blister. He reported no history of keloids or trauma to the left foot. On examination, a 3.5-cm, flesh-colored, pedunculated, firm nodule was present on the lateral aspect of the left great hallux (Figure 1). No lymphadenopathy was found. The lesion was diagnosed at that time as a keloid and treated with intralesional steroids without response. The patient was lost to follow-up, and after 5 months he presented again with pain and drainage from the lesion. Acute drainage resolved after antibiotic therapy. A shave biopsy was performed, which revealed findings consistent with a dermatofibrosarcoma protuberans (DFSP). A chest radiograph was unremarkable. Re-excision was performed with negative margins on frozen section but with positive peripheral and deep margins on permanent sections. The patient subsequently underwent amputation of the left great toe and was lost to follow-up after the initial postoperative period.

Histopathologic examination demonstrated a polypoid spindle cell tumor that filled the dermis and invaded into the subcutaneous adipose tissue (Figure 2). The spindle cells had tapered nuclei in a honeycomb arrangement with only mild nuclear pleomorphism arranged in fascicles with a herringbone formation. Areas showed a myxoid stroma with abundant mucin (Figure 3). Immunostaining demonstrated cells strongly positive for CD34 and negative for MART (melanoma-associated antigen recognized by T cells), S-100, and smooth muscle actin immunostains.

Dermatofibrosarcoma protuberans is a sarcoma that is locally aggressive and tends to recur after surgical excision, though rare cases of metastasis involving the lungs have been reported.¹² Dermatofibrosarcoma protuberans usually affects young to middle-aged adults. Acral DFSP is rare in adults, with tumors most commonly occurring on the trunk (50%-60%), proximal extremities (20%-30%), or the head and neck (10%-15%).^1,2 A higher rate of acral DFSP has been found in children, which may be due to the increased rate of extremity trauma. Dermatofibrosarcoma protuberans commonly presents as an asymptomatic, slowly growing, indurated plaque that may be flesh colored or hyperpigmented, followed by development of erythematous firm nodules of up to several centimeters.^1,3 Dermatofibrosarcoma protuberans may be associated with a purulent exudate or ulceration, and pain may develop as the lesion grows.

Histopathologic evaluation shows an early plaque stage characterized by low cellularity, minimal nuclear atypia, and rare mitotic figures.⁴ In the nodular stage, the spindle cells are arranged as short fascicles in a storiform arrangement and infiltrate the subcutaneous tissue in a honeycomb pattern with hyperchromatic nuclei and mitotic figures. The nodules may develop myxomatous areas as well as less-differentiated foci with intersecting fascicles in a herringbone pattern. Anti-CD34 antibody immunostaining demonstrates strongly positive spindle cells, while DFSP is negative for stromelysin 3, factor XIIIa, and D2-40, which can help to differentiate DFSP from dermatofibroma.⁵ The myxoid subtype of DFSP does not differ clinically or prognostically from conventional DFSP, though its recognition can be of use in differentiating other myxoid tumors. Myxoid DFSP is nearly always positive for CD34 and negative for the neural marker S-100 protein.⁶

Some reports have demonstrated that Mohs micrographic surgery is superior to wide local excision in treatment of DFSP, as it results in fewer local recurrences and metastases.^7,8 Because of cytogenic abnormalities such as a reciprocal chromosomal (17;22) translocation or supernumerary ring chromosome derived from t(17;22) that place the PDGFB gene under the control of COL1A1 promoter, imatinib mesylate has been tested in DFSP and resulted in dramatic responses in both adults and children.^9,10 Suggested uses of imatinib include metastatic disease and locally invasive disease not suitable for surgical excision as well as a method to debulk tumors prior to resection.¹¹

The Diagnosis: Squamous Cell Carcinoma

The initial clinical presentation suggested a diagnosis of herpes simplex labialis. The patient reported no response to topical acyclovir, and because the plaque persisted, a biopsy was performed. Pathology demonstrated squamous cell carcinoma (SCC) that was moderately well differentiated and invasive (Figure). 

Approximately 38% of all oral SCCs in the United States occur on the lower lip and typically are solar-related cancers developing within the epidermis.¹ Oral lesions initially may be asymptomatic and may not be of concern to the patient; however, it is important to recognize SCC early, as invasive lesions have the potential to metastasize. Some factors that increase the chance for the development of metastases include tumor size larger than 2 cm; location on the ear, lip, or other sites on the head and neck; and history of prior unsuccessful treatment.² Any solitary ulcer, lump, wound, or lesion that will not heal and persists for more than 3 weeks should be regarded as cancer until proven otherwise. Although few oral SCCs are detected by clinicians at an early stage, diagnostic aids such as vital staining and molecular markers in tissues and saliva may be implemented.³ Toluidine blue is a simple, fast, and inexpensive technique that stains the nuclear material of malignant lesions, but not normal mucosa, and may be a worthwhile diagnostic adjunct to clinical inspection.⁴

Our patient presented with a lesion that clinically looked herpetic, though he reported no prodromal signs of tingling, burning, or pain before the occurrence of the lesion. Due to the persistence of the lesion and lack of response to treatment, a biopsy was indicated. The differential diagnoses include aphthous ulcers, which may occasionally extend on to the vermilion border of the lip and exhibit nondiagnostic histology.⁵ Bullous oral lichen planus is the least common variant of oral lichen planus, is unlikely to present as a solitary lesion, and is rarely seen on the lips. Histologically, the lesion demonstrated lichenoid inflammation.⁶ Solitary keratoacanthoma, though histologically similar to SCC, typically presents as a rapidly growing crateriform nodule without erosion or ulceration.⁷ The differential diagnoses are summarized in the Table.

The patient underwent wide excision with repair by mucosal advancement flap. He continues to be regularly seen in the clinic for monitoring of other skin cancers and is doing well. Clinicians encountering any wound or ulcer that does not show signs of healing should be wary of underlying malignancy and be prompted to perform a biopsy.

The Diagnosis: Squamous Cell Carcinoma

The initial clinical presentation suggested a diagnosis of herpes simplex labialis. The patient reported no response to topical acyclovir, and because the plaque persisted, a biopsy was performed. Pathology demonstrated squamous cell carcinoma (SCC) that was moderately well differentiated and invasive (Figure). 

Approximately 38% of all oral SCCs in the United States occur on the lower lip and typically are solar-related cancers developing within the epidermis.¹ Oral lesions initially may be asymptomatic and may not be of concern to the patient; however, it is important to recognize SCC early, as invasive lesions have the potential to metastasize. Some factors that increase the chance for the development of metastases include tumor size larger than 2 cm; location on the ear, lip, or other sites on the head and neck; and history of prior unsuccessful treatment.² Any solitary ulcer, lump, wound, or lesion that will not heal and persists for more than 3 weeks should be regarded as cancer until proven otherwise. Although few oral SCCs are detected by clinicians at an early stage, diagnostic aids such as vital staining and molecular markers in tissues and saliva may be implemented.³ Toluidine blue is a simple, fast, and inexpensive technique that stains the nuclear material of malignant lesions, but not normal mucosa, and may be a worthwhile diagnostic adjunct to clinical inspection.⁴

Our patient presented with a lesion that clinically looked herpetic, though he reported no prodromal signs of tingling, burning, or pain before the occurrence of the lesion. Due to the persistence of the lesion and lack of response to treatment, a biopsy was indicated. The differential diagnoses include aphthous ulcers, which may occasionally extend on to the vermilion border of the lip and exhibit nondiagnostic histology.⁵ Bullous oral lichen planus is the least common variant of oral lichen planus, is unlikely to present as a solitary lesion, and is rarely seen on the lips. Histologically, the lesion demonstrated lichenoid inflammation.⁶ Solitary keratoacanthoma, though histologically similar to SCC, typically presents as a rapidly growing crateriform nodule without erosion or ulceration.⁷ The differential diagnoses are summarized in the Table.

The patient underwent wide excision with repair by mucosal advancement flap. He continues to be regularly seen in the clinic for monitoring of other skin cancers and is doing well. Clinicians encountering any wound or ulcer that does not show signs of healing should be wary of underlying malignancy and be prompted to perform a biopsy.

The Diagnosis: Squamous Cell Carcinoma

The initial clinical presentation suggested a diagnosis of herpes simplex labialis. The patient reported no response to topical acyclovir, and because the plaque persisted, a biopsy was performed. Pathology demonstrated squamous cell carcinoma (SCC) that was moderately well differentiated and invasive (Figure). 

Approximately 38% of all oral SCCs in the United States occur on the lower lip and typically are solar-related cancers developing within the epidermis.¹ Oral lesions initially may be asymptomatic and may not be of concern to the patient; however, it is important to recognize SCC early, as invasive lesions have the potential to metastasize. Some factors that increase the chance for the development of metastases include tumor size larger than 2 cm; location on the ear, lip, or other sites on the head and neck; and history of prior unsuccessful treatment.² Any solitary ulcer, lump, wound, or lesion that will not heal and persists for more than 3 weeks should be regarded as cancer until proven otherwise. Although few oral SCCs are detected by clinicians at an early stage, diagnostic aids such as vital staining and molecular markers in tissues and saliva may be implemented.³ Toluidine blue is a simple, fast, and inexpensive technique that stains the nuclear material of malignant lesions, but not normal mucosa, and may be a worthwhile diagnostic adjunct to clinical inspection.⁴

Our patient presented with a lesion that clinically looked herpetic, though he reported no prodromal signs of tingling, burning, or pain before the occurrence of the lesion. Due to the persistence of the lesion and lack of response to treatment, a biopsy was indicated. The differential diagnoses include aphthous ulcers, which may occasionally extend on to the vermilion border of the lip and exhibit nondiagnostic histology.⁵ Bullous oral lichen planus is the least common variant of oral lichen planus, is unlikely to present as a solitary lesion, and is rarely seen on the lips. Histologically, the lesion demonstrated lichenoid inflammation.⁶ Solitary keratoacanthoma, though histologically similar to SCC, typically presents as a rapidly growing crateriform nodule without erosion or ulceration.⁷ The differential diagnoses are summarized in the Table.

The patient underwent wide excision with repair by mucosal advancement flap. He continues to be regularly seen in the clinic for monitoring of other skin cancers and is doing well. Clinicians encountering any wound or ulcer that does not show signs of healing should be wary of underlying malignancy and be prompted to perform a biopsy.

Cutaneous myoepithelial tumors are rare neoplasms but are being increasingly recognized and reported in the literature.^1-7 Myoepithelial tumors are related to benign mixed tumors of the skin but lack the epithelial ductules that are present in mixed tumors. Cutaneous myoepithelial tumors may show a variety of architectural, cytological, and stromal features. Their immunophenotype usually is characterized by coexpression of an epithelial marker (eg, keratin, epithelial membrane antigen [EMA]) and S-100 protein; they also may express a variety of other myoepithelial markers, including keratins, smooth muscle actin, calponin, glial fibrillary acidic protein, p63, and desmin.⁷ EWS RNA binding protein 1 (EWSR1) and pleomorphic adenoma gene 1 (PLAG1) gene rearrangement has been detected in subsets of these tumors on in situ hybridization.^8-10

Malignant myoepithelial tumors of the skin, also referred to as cutaneous myoepithelial carcinomas, are exceedingly rare. Including the current case, a search of PubMed articles indexed for MEDLINE and Google Scholar using the terms myoepithelial carcinoma and cutaneous revealed 12 cases that have been reported in the literature (Table).^1-7,11-13 These tumors often occur in the head and neck areas and the lower extremities and display a bimodal age distribution, generally occurring in patients younger than 21 years and older than 50 years of age; they also show a slight female predominance. Available follow-up data from the literature have shown local recurrence or metastasis in 3 cases^3,4,6; however, in one case the metastatic focus was not histologically identified.⁴ Cutaneous myoepithelial carcinoma presenting with metastatic disease further limits treatment options. Here, we describe a case of metastatic cutaneous myoepithelial carcinoma in a 47-year-old man, a rare example of cutaneous myoepithelial carcinoma with histologically documented metastatic disease at the initial presentation.

Case Report

A 47-year-old man who underwent a renal transplant 19 years prior presented with a weeping, ulcerated, mildly tender lesion on the scalp of 4 months’ duration with neck and back pain of 3 months’ duration. Physical examination demonstrated a 6-cm area of ulceration on the anterior crown of the scalp with adjacent enlarged keratoacanthomalike craters and satellite nodules (Figure 1). He was previously diagnosed with basal cell carcinoma (BCC) of the scalp at an outside institution 4 years prior and was treated with radiation therapy. The prior scalp biopsy for BCC diagnosis was unavailable for review. The patient had a history of chronic eczematous dermatitis in the waistband area that had been present for 19 years and another BCC with nodular and infiltrative patterns on the left helix. Of note, he also had been taking long-term immunosuppressant medications (ie, cyclosporine, azathioprine) for maintenance following the renal transplant.

Because of the extensive ulceration of the primary lesion, a shave biopsy of the scalp was performed on an adjacent satellite nodule. Histopathologic findings showed an intradermal neoplasm characterized by poorly cohesive cells exhibiting epithelioid to plasmacytoid morphologic features surrounded by abundant chondromyxoid stroma. Ductular differentiation was not identified (Figure 2A). The neoplastic cells displayed hyperchromatic nuclei with marked nuclear pleomorphism and atypical mitotic figures (Figure 2B). On immunohistochemistry the tumor cells stained positive for cytokeratin AE1/AE3 (Figure 3), S-100 protein (Figure 4), and p63, and were negative for calponin, desmin, melan-A, cytokeratin 7, and brachyury (Figure 5).

Radiographic imaging was performed due to the patient’s history of neck and back pain. Magnetic resonance imaging showed innumerable slightly expansile, T1-hypointense, T2-hyperintense, and robustly enhancing lesions involving the cervical, thoracic, lumbar, and sacral spine, as well as the thoracic ribs and bilateral iliac bones. There was no evidence of soft tissue tumor around the bone lesions. Ventral cervical spinal cord compression was detected at the C4 vertebra, causing a symptomatic radiculopathy; however, due to widely metastatic disease, the patient was not considered appropriate for neurosurgical intervention of the compression. Computerized tomography of the chest, abdomen, and pelvis did not identify any visceral source of malignancy, though multiple bilaterally enlarged cervical lymph nodes were identified on magnetic resonance imaging.

Fine needle aspiration of a left iliac bone lesion demonstrated neoplastic cells and chondromyxoid stroma essentially identical to the features shown in the skin biopsy (Figure 6). Given the morphologic features of the tumor and coexpression of cytokeratin and S-100 protein, the findings were interpreted as primary cutaneous myoepithelial carcinoma with disseminated metastatic lesions. The patient began treatment with carboplatin and paclitaxel chemotherapy. To combat the symptomatic bone pain and upper extremity radiculopathy, palliative radiation was administered to the cervical spine, lumbar spine, and right sacrum (30 Gy to each site in 10 fractions at 3 Gy per fraction). Despite the attempted chemotherapy and radiation, the patient continued to decline, and after 2 months, he elected to pursue palliative care. The patient died after 3 months in palliative care (5 months after the initial presentation).

Comment

Myoepithelial cells normally surround ducts in secretory organs, such as the breasts, salivary glands, and cutaneous sweat glands. Myoepithelial neoplasms are well recognized in the salivary glands^14,15; however, myoepithelial neoplasms also can arise in other sites, including the soft tissue^4,5,16-18 and skin.^{1-3,7,11,19,20} Myoepithelioma of soft tissue was first described by Burke et al²¹ in 1995 and later described in the skin by Fernandez-Figueras et al²² in 1998. Since then, diagnostic criteria for cutaneous myoepithelial neoplasms have evolved, suggesting a spectrum of disease rather than a single distinct entity.¹¹ Most often, cutaneous myoepithelial carcinomas arise as soft nodular lesions in the head and neck areas or extremities of adults. The nodules typically are nontender and range in size from 0.5 to 18.0 cm. Our review of the literature revealed 11 additional cases of cutaneous myoepithelial carcinomas have been reported, ranging in size from 0.7 to 7.0 cm (Table). In our case, the main lesion was 6 cm, mildly tender, ulcerated, and accompanied by satellite nodules.

Histologically, cutaneous myoepithelial tumors typically are well-defined, dermal-based nodules with no connection to the overlying epidermis. Similar to myoepithelial tumors of other sites, they can be diagnostically challenging due to the heterogeneity of both their architectural and cytological features. The presence of a chondromyxoid or hyalinized stroma is common but not always present. Neoplastic myoepithelial cells can exhibit spindled, epithelioid, plasmacytoid, or clear cell morphologic features and show growth patterns in clusters, cords, glands, or sheets. Focal epithelial cells can be present. Although benign myoepithelial neoplasms with overt ductal differentiation are consistent with cutaneous mixed tumors (chondroid syringomas), those without ducts are characterized as myoepitheliomas. It is uncertain if cases with only focal ductal differentiation should be classified as mixed tumors or as myoepitheliomas. Malignant myoepithelial tumors show infiltrative borders, nuclear pleomorphism, coarse nuclear chromatin, prominent nucleoli, and increased mitotic activity. A 2003 study by Hornick and Fletcher¹⁶ found that cytologic atypia was the primary predictor of malignant behavior for myoepithelial neoplasms of the soft tissue.

Despite a wide variety of expression patterns, immunohistochemistry is critical in demonstrating myoepithelial differentiation and establishing a diagnosis of a myoepithelial neoplasm. Most cases display coexpression of epithelial markers, including keratins and/or EMA as well as S-100 protein. Myogenic markers also may be variably expressed; however, the absence of myogenic markers does not exclude the diagnosis of a myoepithelial tumor. Commonly expressed epithelial markers are cytokeratin AE1/AE3, cytokeratin 8/18, and EMA, while commonly expressed myogenic markers include muscle specific actin and smooth muscle actin.^5,7,11,19 Myoepithelial tumors also may express calponin, p63, and glial fibrillary acidic protein.¹⁶

Molecular studies also can aid in the diagnosis of myoepithelial tumors. A study by Antonescu et al⁸ demonstrated EWSR1 gene rearrangement in 45% (30/66) of extrasalivary myoepithelial tumors and the absence of EWSR1 gene rearrangement in salivary gland myoepithelial tumors. The authors also showed that EWSR1-negative tumors were more likely to be superficially located, display ductal differentiation, and possess a benign clinical course.⁸ In another study, Bahrami et al²³ suggested that a subset of mixed tumors, specifically those with tubuloductal differentiation, are genetically linked to salivary gland pleomorphic adenomas, which was achieved by the coexpression of the PLAG1 protein and PLAG1 gene rearrangement on immunohistochemistry and fluorescence in situ hybridization (FISH), respectively. Of the 19 cases evaluated, 11 (58%) expressed nuclear staining for PLAG1 immunohistochemistry; 8 of those 11 showed positive gene rearrangement for PLAG1 using FISH. These findings raise the possibility that cutaneous mixed tumors may be more closely related to those of the salivary glands, while deep myoepithelial tumors that lack ductal differentiation may represent a distinct group. Similar to the study by Antonescu et al,⁸ Flucke et al¹⁰ investigated EWSR1 gene rearrangement but limited their sample to cutaneous tumors, including myoepitheliomas, mixed tumors, and myoepithelial carcinoma. The authors found that 44% of cases (7/16) expressed EWSR1; this expression suggests that cutaneous myoepithelial tumors may have a genetic relationship to their soft tissue, bone, and visceral counterparts.¹⁰

Myoepithelial tumors display a broad spectrum of morphologic features; however, one of the most common growth patterns is that of oval to round cells forming cords and chains in a chondromyxoid stroma. As such, the histopathologic differential diagnosis for myoepithelial tumors includes other epithelioid or round-cell neoplasms with similar growth patterns including extraskeletal myxoid chondrosarcoma (EMC), ossifying fibromyxoid tumor of soft parts, and extra-axial soft tissue chordoma. Extraskeletal myxoid chondrosarcoma bears the closest similarity to myoepithelial tumors both histologically and by ancillary studies. It typically possesses cords or chains of small round tumor cells set in a chondromyxoid or myxoid background. In contrast to myoepithelial tumors, which typically have more abundant cytoplasm and can show at least focal areas of spindle cell growth, the cells of EMC are more uniform, small, round cells with relatively scant cytoplasm. Extraskeletal myxoid chondrosarcomas lack the typical myoepithelial coexpression of cytokeratin and S-100 protein, with a minority of EMCs expressing S-100 protein but rarely cytokeratin. Most cases of EMC possess a balanced t(9;22) translocation involving the EWSR1 gene,²⁴ a finding that could lead to confusion with soft tissue myoepithelial tumors, which also may show EWSR1 rearrangement on FISH. Ossifying fibromyxoid tumor of soft parts is also composed of round cells arranged in cords in a myxoid or fibrous stroma; the majority of cases also display a peripheral rim of mature bone, a feature that is not typically seen in myoepithelial tumors. Similar to myoepithelial tumors, ossifying fibromyxoid tumor of soft parts often is positive for S-100 protein; however, it rarely is positive for cytokeratins. Ossifying fibromyxoid tumor of soft parts has been shown to have a rearrangement of the PHD finger protein 1 (PHF1) gene in approximately half of cases, a molecular finding that has not been reported for myoepithelial tumors.²⁵ Finally, extra-axial soft tissue chordomas, though quite rare, may possess striking similarities to myoepithelial tumors both histopathologically and immunohistochemically. Chordomas are composed of epithelioid cells arranged in nests, nodules, and chains with a variably myxoid background. A variable amount of cells with bubbly cytoplasm (known as physaliphorous cells) can be seen. High mitotic activity is not a characteristic feature in chordomas. They classically coexpress cytokeratins and S-100 protein, similar to myoepithelial tumors. A subset of myoepitheliomas with similar histologic features to chordoma was historically referred to as parachordoma.^26,27 The distinction between these 2 entities was challenging until the relatively recent advent of brachyury, a sensitive and specific nuclear marker of chordoma; extra-axial soft tissue chordomas and their central counterparts both express nuclear brachyury, while myoepitheliomas (including those with a parachordoma histologic pattern) do not.²⁸ Our case did not display physaliphorous cells but did demonstrate abundant nuclear pleomorphism and high mitotic activity. In addition, immunohistochemical staining was negative for brachyury.

Because cutaneous myoepithelial tumors are relatively rare, a well-defined standard of care for treatment is lacking. Surgical excision is the primary treatment method in most reported cases in the literature.^17,19 Miller et al²⁹ reported the successful treatment of recurrent cutaneous myoepitheliomas with Mohs micrographic surgery. Chemotherapy may be useful in the setting of metastatic myoepithelial carcinomas in adults, but reported results are inconsistent.^30,31 Radiation treatment of recurrent or metastatic disease has not been shown to be effective. A study of children treated with surgical resection and chemotherapy using ifosfamide, cisplatin, and etoposide followed by radiation therapy showed positive results.³²

Our case highlights several challenges that may arise in establishing a diagnosis of cutaneous myoepithelial carcinoma with disseminated metastases. The diagnostic difficulty in our case was compounded by the advanced nature of the lesion at the time of presentation. Given the rarity of metastatic cutaneous myoepithelial carcinomas and the lack of a prior primary diagnosis of a malignant myoepithelioma, the index of suspicion for this entity was not high. A report of myoepithelial carcinoma of the parotid gland metastatic to the skin has been reported,³³ but in the absence of salivary gland involvement or other visceral lesions, metastasis from any source other than our patient’s cutaneous scalp lesion is unlikely. The histopathologic features in combination with the characteristic immunophenotype, unique clinical setting, and radiographic findings were essential to arriving at the correct diagnosis. Unlike previously reported metastatic lesions, our case is unique in that metastatic lesions were identified at the time of initial clinical presentation.

Conclusion

Cutaneous myoepithelial carcinomas are exceedingly rare tumors with a wide range of histopathologic and immunohistochemical findings. In challenging cases, studies for EWSR1 or PLAG1 gene rearrangement can be helpful. Furthermore, this case illustrates the potential for widespread dissemination of myoepithelial carcinomas requiring clinical evaluation and imaging studies to exclude metastatic lesions.

Cutaneous myoepithelial tumors are rare neoplasms but are being increasingly recognized and reported in the literature.^1-7 Myoepithelial tumors are related to benign mixed tumors of the skin but lack the epithelial ductules that are present in mixed tumors. Cutaneous myoepithelial tumors may show a variety of architectural, cytological, and stromal features. Their immunophenotype usually is characterized by coexpression of an epithelial marker (eg, keratin, epithelial membrane antigen [EMA]) and S-100 protein; they also may express a variety of other myoepithelial markers, including keratins, smooth muscle actin, calponin, glial fibrillary acidic protein, p63, and desmin.⁷ EWS RNA binding protein 1 (EWSR1) and pleomorphic adenoma gene 1 (PLAG1) gene rearrangement has been detected in subsets of these tumors on in situ hybridization.^8-10

Malignant myoepithelial tumors of the skin, also referred to as cutaneous myoepithelial carcinomas, are exceedingly rare. Including the current case, a search of PubMed articles indexed for MEDLINE and Google Scholar using the terms myoepithelial carcinoma and cutaneous revealed 12 cases that have been reported in the literature (Table).^1-7,11-13 These tumors often occur in the head and neck areas and the lower extremities and display a bimodal age distribution, generally occurring in patients younger than 21 years and older than 50 years of age; they also show a slight female predominance. Available follow-up data from the literature have shown local recurrence or metastasis in 3 cases^3,4,6; however, in one case the metastatic focus was not histologically identified.⁴ Cutaneous myoepithelial carcinoma presenting with metastatic disease further limits treatment options. Here, we describe a case of metastatic cutaneous myoepithelial carcinoma in a 47-year-old man, a rare example of cutaneous myoepithelial carcinoma with histologically documented metastatic disease at the initial presentation.

Case Report

A 47-year-old man who underwent a renal transplant 19 years prior presented with a weeping, ulcerated, mildly tender lesion on the scalp of 4 months’ duration with neck and back pain of 3 months’ duration. Physical examination demonstrated a 6-cm area of ulceration on the anterior crown of the scalp with adjacent enlarged keratoacanthomalike craters and satellite nodules (Figure 1). He was previously diagnosed with basal cell carcinoma (BCC) of the scalp at an outside institution 4 years prior and was treated with radiation therapy. The prior scalp biopsy for BCC diagnosis was unavailable for review. The patient had a history of chronic eczematous dermatitis in the waistband area that had been present for 19 years and another BCC with nodular and infiltrative patterns on the left helix. Of note, he also had been taking long-term immunosuppressant medications (ie, cyclosporine, azathioprine) for maintenance following the renal transplant.

Because of the extensive ulceration of the primary lesion, a shave biopsy of the scalp was performed on an adjacent satellite nodule. Histopathologic findings showed an intradermal neoplasm characterized by poorly cohesive cells exhibiting epithelioid to plasmacytoid morphologic features surrounded by abundant chondromyxoid stroma. Ductular differentiation was not identified (Figure 2A). The neoplastic cells displayed hyperchromatic nuclei with marked nuclear pleomorphism and atypical mitotic figures (Figure 2B). On immunohistochemistry the tumor cells stained positive for cytokeratin AE1/AE3 (Figure 3), S-100 protein (Figure 4), and p63, and were negative for calponin, desmin, melan-A, cytokeratin 7, and brachyury (Figure 5).

Radiographic imaging was performed due to the patient’s history of neck and back pain. Magnetic resonance imaging showed innumerable slightly expansile, T1-hypointense, T2-hyperintense, and robustly enhancing lesions involving the cervical, thoracic, lumbar, and sacral spine, as well as the thoracic ribs and bilateral iliac bones. There was no evidence of soft tissue tumor around the bone lesions. Ventral cervical spinal cord compression was detected at the C4 vertebra, causing a symptomatic radiculopathy; however, due to widely metastatic disease, the patient was not considered appropriate for neurosurgical intervention of the compression. Computerized tomography of the chest, abdomen, and pelvis did not identify any visceral source of malignancy, though multiple bilaterally enlarged cervical lymph nodes were identified on magnetic resonance imaging.

Fine needle aspiration of a left iliac bone lesion demonstrated neoplastic cells and chondromyxoid stroma essentially identical to the features shown in the skin biopsy (Figure 6). Given the morphologic features of the tumor and coexpression of cytokeratin and S-100 protein, the findings were interpreted as primary cutaneous myoepithelial carcinoma with disseminated metastatic lesions. The patient began treatment with carboplatin and paclitaxel chemotherapy. To combat the symptomatic bone pain and upper extremity radiculopathy, palliative radiation was administered to the cervical spine, lumbar spine, and right sacrum (30 Gy to each site in 10 fractions at 3 Gy per fraction). Despite the attempted chemotherapy and radiation, the patient continued to decline, and after 2 months, he elected to pursue palliative care. The patient died after 3 months in palliative care (5 months after the initial presentation).

Comment

Myoepithelial cells normally surround ducts in secretory organs, such as the breasts, salivary glands, and cutaneous sweat glands. Myoepithelial neoplasms are well recognized in the salivary glands^14,15; however, myoepithelial neoplasms also can arise in other sites, including the soft tissue^4,5,16-18 and skin.^{1-3,7,11,19,20} Myoepithelioma of soft tissue was first described by Burke et al²¹ in 1995 and later described in the skin by Fernandez-Figueras et al²² in 1998. Since then, diagnostic criteria for cutaneous myoepithelial neoplasms have evolved, suggesting a spectrum of disease rather than a single distinct entity.¹¹ Most often, cutaneous myoepithelial carcinomas arise as soft nodular lesions in the head and neck areas or extremities of adults. The nodules typically are nontender and range in size from 0.5 to 18.0 cm. Our review of the literature revealed 11 additional cases of cutaneous myoepithelial carcinomas have been reported, ranging in size from 0.7 to 7.0 cm (Table). In our case, the main lesion was 6 cm, mildly tender, ulcerated, and accompanied by satellite nodules.

Histologically, cutaneous myoepithelial tumors typically are well-defined, dermal-based nodules with no connection to the overlying epidermis. Similar to myoepithelial tumors of other sites, they can be diagnostically challenging due to the heterogeneity of both their architectural and cytological features. The presence of a chondromyxoid or hyalinized stroma is common but not always present. Neoplastic myoepithelial cells can exhibit spindled, epithelioid, plasmacytoid, or clear cell morphologic features and show growth patterns in clusters, cords, glands, or sheets. Focal epithelial cells can be present. Although benign myoepithelial neoplasms with overt ductal differentiation are consistent with cutaneous mixed tumors (chondroid syringomas), those without ducts are characterized as myoepitheliomas. It is uncertain if cases with only focal ductal differentiation should be classified as mixed tumors or as myoepitheliomas. Malignant myoepithelial tumors show infiltrative borders, nuclear pleomorphism, coarse nuclear chromatin, prominent nucleoli, and increased mitotic activity. A 2003 study by Hornick and Fletcher¹⁶ found that cytologic atypia was the primary predictor of malignant behavior for myoepithelial neoplasms of the soft tissue.

Despite a wide variety of expression patterns, immunohistochemistry is critical in demonstrating myoepithelial differentiation and establishing a diagnosis of a myoepithelial neoplasm. Most cases display coexpression of epithelial markers, including keratins and/or EMA as well as S-100 protein. Myogenic markers also may be variably expressed; however, the absence of myogenic markers does not exclude the diagnosis of a myoepithelial tumor. Commonly expressed epithelial markers are cytokeratin AE1/AE3, cytokeratin 8/18, and EMA, while commonly expressed myogenic markers include muscle specific actin and smooth muscle actin.^5,7,11,19 Myoepithelial tumors also may express calponin, p63, and glial fibrillary acidic protein.¹⁶

Molecular studies also can aid in the diagnosis of myoepithelial tumors. A study by Antonescu et al⁸ demonstrated EWSR1 gene rearrangement in 45% (30/66) of extrasalivary myoepithelial tumors and the absence of EWSR1 gene rearrangement in salivary gland myoepithelial tumors. The authors also showed that EWSR1-negative tumors were more likely to be superficially located, display ductal differentiation, and possess a benign clinical course.⁸ In another study, Bahrami et al²³ suggested that a subset of mixed tumors, specifically those with tubuloductal differentiation, are genetically linked to salivary gland pleomorphic adenomas, which was achieved by the coexpression of the PLAG1 protein and PLAG1 gene rearrangement on immunohistochemistry and fluorescence in situ hybridization (FISH), respectively. Of the 19 cases evaluated, 11 (58%) expressed nuclear staining for PLAG1 immunohistochemistry; 8 of those 11 showed positive gene rearrangement for PLAG1 using FISH. These findings raise the possibility that cutaneous mixed tumors may be more closely related to those of the salivary glands, while deep myoepithelial tumors that lack ductal differentiation may represent a distinct group. Similar to the study by Antonescu et al,⁸ Flucke et al¹⁰ investigated EWSR1 gene rearrangement but limited their sample to cutaneous tumors, including myoepitheliomas, mixed tumors, and myoepithelial carcinoma. The authors found that 44% of cases (7/16) expressed EWSR1; this expression suggests that cutaneous myoepithelial tumors may have a genetic relationship to their soft tissue, bone, and visceral counterparts.¹⁰

Myoepithelial tumors display a broad spectrum of morphologic features; however, one of the most common growth patterns is that of oval to round cells forming cords and chains in a chondromyxoid stroma. As such, the histopathologic differential diagnosis for myoepithelial tumors includes other epithelioid or round-cell neoplasms with similar growth patterns including extraskeletal myxoid chondrosarcoma (EMC), ossifying fibromyxoid tumor of soft parts, and extra-axial soft tissue chordoma. Extraskeletal myxoid chondrosarcoma bears the closest similarity to myoepithelial tumors both histologically and by ancillary studies. It typically possesses cords or chains of small round tumor cells set in a chondromyxoid or myxoid background. In contrast to myoepithelial tumors, which typically have more abundant cytoplasm and can show at least focal areas of spindle cell growth, the cells of EMC are more uniform, small, round cells with relatively scant cytoplasm. Extraskeletal myxoid chondrosarcomas lack the typical myoepithelial coexpression of cytokeratin and S-100 protein, with a minority of EMCs expressing S-100 protein but rarely cytokeratin. Most cases of EMC possess a balanced t(9;22) translocation involving the EWSR1 gene,²⁴ a finding that could lead to confusion with soft tissue myoepithelial tumors, which also may show EWSR1 rearrangement on FISH. Ossifying fibromyxoid tumor of soft parts is also composed of round cells arranged in cords in a myxoid or fibrous stroma; the majority of cases also display a peripheral rim of mature bone, a feature that is not typically seen in myoepithelial tumors. Similar to myoepithelial tumors, ossifying fibromyxoid tumor of soft parts often is positive for S-100 protein; however, it rarely is positive for cytokeratins. Ossifying fibromyxoid tumor of soft parts has been shown to have a rearrangement of the PHD finger protein 1 (PHF1) gene in approximately half of cases, a molecular finding that has not been reported for myoepithelial tumors.²⁵ Finally, extra-axial soft tissue chordomas, though quite rare, may possess striking similarities to myoepithelial tumors both histopathologically and immunohistochemically. Chordomas are composed of epithelioid cells arranged in nests, nodules, and chains with a variably myxoid background. A variable amount of cells with bubbly cytoplasm (known as physaliphorous cells) can be seen. High mitotic activity is not a characteristic feature in chordomas. They classically coexpress cytokeratins and S-100 protein, similar to myoepithelial tumors. A subset of myoepitheliomas with similar histologic features to chordoma was historically referred to as parachordoma.^26,27 The distinction between these 2 entities was challenging until the relatively recent advent of brachyury, a sensitive and specific nuclear marker of chordoma; extra-axial soft tissue chordomas and their central counterparts both express nuclear brachyury, while myoepitheliomas (including those with a parachordoma histologic pattern) do not.²⁸ Our case did not display physaliphorous cells but did demonstrate abundant nuclear pleomorphism and high mitotic activity. In addition, immunohistochemical staining was negative for brachyury.

Because cutaneous myoepithelial tumors are relatively rare, a well-defined standard of care for treatment is lacking. Surgical excision is the primary treatment method in most reported cases in the literature.^17,19 Miller et al²⁹ reported the successful treatment of recurrent cutaneous myoepitheliomas with Mohs micrographic surgery. Chemotherapy may be useful in the setting of metastatic myoepithelial carcinomas in adults, but reported results are inconsistent.^30,31 Radiation treatment of recurrent or metastatic disease has not been shown to be effective. A study of children treated with surgical resection and chemotherapy using ifosfamide, cisplatin, and etoposide followed by radiation therapy showed positive results.³²

Our case highlights several challenges that may arise in establishing a diagnosis of cutaneous myoepithelial carcinoma with disseminated metastases. The diagnostic difficulty in our case was compounded by the advanced nature of the lesion at the time of presentation. Given the rarity of metastatic cutaneous myoepithelial carcinomas and the lack of a prior primary diagnosis of a malignant myoepithelioma, the index of suspicion for this entity was not high. A report of myoepithelial carcinoma of the parotid gland metastatic to the skin has been reported,³³ but in the absence of salivary gland involvement or other visceral lesions, metastasis from any source other than our patient’s cutaneous scalp lesion is unlikely. The histopathologic features in combination with the characteristic immunophenotype, unique clinical setting, and radiographic findings were essential to arriving at the correct diagnosis. Unlike previously reported metastatic lesions, our case is unique in that metastatic lesions were identified at the time of initial clinical presentation.

Conclusion

Cutaneous myoepithelial carcinomas are exceedingly rare tumors with a wide range of histopathologic and immunohistochemical findings. In challenging cases, studies for EWSR1 or PLAG1 gene rearrangement can be helpful. Furthermore, this case illustrates the potential for widespread dissemination of myoepithelial carcinomas requiring clinical evaluation and imaging studies to exclude metastatic lesions.

Cutaneous myoepithelial tumors are rare neoplasms but are being increasingly recognized and reported in the literature.^1-7 Myoepithelial tumors are related to benign mixed tumors of the skin but lack the epithelial ductules that are present in mixed tumors. Cutaneous myoepithelial tumors may show a variety of architectural, cytological, and stromal features. Their immunophenotype usually is characterized by coexpression of an epithelial marker (eg, keratin, epithelial membrane antigen [EMA]) and S-100 protein; they also may express a variety of other myoepithelial markers, including keratins, smooth muscle actin, calponin, glial fibrillary acidic protein, p63, and desmin.⁷ EWS RNA binding protein 1 (EWSR1) and pleomorphic adenoma gene 1 (PLAG1) gene rearrangement has been detected in subsets of these tumors on in situ hybridization.^8-10

Malignant myoepithelial tumors of the skin, also referred to as cutaneous myoepithelial carcinomas, are exceedingly rare. Including the current case, a search of PubMed articles indexed for MEDLINE and Google Scholar using the terms myoepithelial carcinoma and cutaneous revealed 12 cases that have been reported in the literature (Table).^1-7,11-13 These tumors often occur in the head and neck areas and the lower extremities and display a bimodal age distribution, generally occurring in patients younger than 21 years and older than 50 years of age; they also show a slight female predominance. Available follow-up data from the literature have shown local recurrence or metastasis in 3 cases^3,4,6; however, in one case the metastatic focus was not histologically identified.⁴ Cutaneous myoepithelial carcinoma presenting with metastatic disease further limits treatment options. Here, we describe a case of metastatic cutaneous myoepithelial carcinoma in a 47-year-old man, a rare example of cutaneous myoepithelial carcinoma with histologically documented metastatic disease at the initial presentation.

Case Report

A 47-year-old man who underwent a renal transplant 19 years prior presented with a weeping, ulcerated, mildly tender lesion on the scalp of 4 months’ duration with neck and back pain of 3 months’ duration. Physical examination demonstrated a 6-cm area of ulceration on the anterior crown of the scalp with adjacent enlarged keratoacanthomalike craters and satellite nodules (Figure 1). He was previously diagnosed with basal cell carcinoma (BCC) of the scalp at an outside institution 4 years prior and was treated with radiation therapy. The prior scalp biopsy for BCC diagnosis was unavailable for review. The patient had a history of chronic eczematous dermatitis in the waistband area that had been present for 19 years and another BCC with nodular and infiltrative patterns on the left helix. Of note, he also had been taking long-term immunosuppressant medications (ie, cyclosporine, azathioprine) for maintenance following the renal transplant.

Because of the extensive ulceration of the primary lesion, a shave biopsy of the scalp was performed on an adjacent satellite nodule. Histopathologic findings showed an intradermal neoplasm characterized by poorly cohesive cells exhibiting epithelioid to plasmacytoid morphologic features surrounded by abundant chondromyxoid stroma. Ductular differentiation was not identified (Figure 2A). The neoplastic cells displayed hyperchromatic nuclei with marked nuclear pleomorphism and atypical mitotic figures (Figure 2B). On immunohistochemistry the tumor cells stained positive for cytokeratin AE1/AE3 (Figure 3), S-100 protein (Figure 4), and p63, and were negative for calponin, desmin, melan-A, cytokeratin 7, and brachyury (Figure 5).

Radiographic imaging was performed due to the patient’s history of neck and back pain. Magnetic resonance imaging showed innumerable slightly expansile, T1-hypointense, T2-hyperintense, and robustly enhancing lesions involving the cervical, thoracic, lumbar, and sacral spine, as well as the thoracic ribs and bilateral iliac bones. There was no evidence of soft tissue tumor around the bone lesions. Ventral cervical spinal cord compression was detected at the C4 vertebra, causing a symptomatic radiculopathy; however, due to widely metastatic disease, the patient was not considered appropriate for neurosurgical intervention of the compression. Computerized tomography of the chest, abdomen, and pelvis did not identify any visceral source of malignancy, though multiple bilaterally enlarged cervical lymph nodes were identified on magnetic resonance imaging.

Fine needle aspiration of a left iliac bone lesion demonstrated neoplastic cells and chondromyxoid stroma essentially identical to the features shown in the skin biopsy (Figure 6). Given the morphologic features of the tumor and coexpression of cytokeratin and S-100 protein, the findings were interpreted as primary cutaneous myoepithelial carcinoma with disseminated metastatic lesions. The patient began treatment with carboplatin and paclitaxel chemotherapy. To combat the symptomatic bone pain and upper extremity radiculopathy, palliative radiation was administered to the cervical spine, lumbar spine, and right sacrum (30 Gy to each site in 10 fractions at 3 Gy per fraction). Despite the attempted chemotherapy and radiation, the patient continued to decline, and after 2 months, he elected to pursue palliative care. The patient died after 3 months in palliative care (5 months after the initial presentation).

Comment

Myoepithelial cells normally surround ducts in secretory organs, such as the breasts, salivary glands, and cutaneous sweat glands. Myoepithelial neoplasms are well recognized in the salivary glands^14,15; however, myoepithelial neoplasms also can arise in other sites, including the soft tissue^4,5,16-18 and skin.^{1-3,7,11,19,20} Myoepithelioma of soft tissue was first described by Burke et al²¹ in 1995 and later described in the skin by Fernandez-Figueras et al²² in 1998. Since then, diagnostic criteria for cutaneous myoepithelial neoplasms have evolved, suggesting a spectrum of disease rather than a single distinct entity.¹¹ Most often, cutaneous myoepithelial carcinomas arise as soft nodular lesions in the head and neck areas or extremities of adults. The nodules typically are nontender and range in size from 0.5 to 18.0 cm. Our review of the literature revealed 11 additional cases of cutaneous myoepithelial carcinomas have been reported, ranging in size from 0.7 to 7.0 cm (Table). In our case, the main lesion was 6 cm, mildly tender, ulcerated, and accompanied by satellite nodules.

Histologically, cutaneous myoepithelial tumors typically are well-defined, dermal-based nodules with no connection to the overlying epidermis. Similar to myoepithelial tumors of other sites, they can be diagnostically challenging due to the heterogeneity of both their architectural and cytological features. The presence of a chondromyxoid or hyalinized stroma is common but not always present. Neoplastic myoepithelial cells can exhibit spindled, epithelioid, plasmacytoid, or clear cell morphologic features and show growth patterns in clusters, cords, glands, or sheets. Focal epithelial cells can be present. Although benign myoepithelial neoplasms with overt ductal differentiation are consistent with cutaneous mixed tumors (chondroid syringomas), those without ducts are characterized as myoepitheliomas. It is uncertain if cases with only focal ductal differentiation should be classified as mixed tumors or as myoepitheliomas. Malignant myoepithelial tumors show infiltrative borders, nuclear pleomorphism, coarse nuclear chromatin, prominent nucleoli, and increased mitotic activity. A 2003 study by Hornick and Fletcher¹⁶ found that cytologic atypia was the primary predictor of malignant behavior for myoepithelial neoplasms of the soft tissue.

Despite a wide variety of expression patterns, immunohistochemistry is critical in demonstrating myoepithelial differentiation and establishing a diagnosis of a myoepithelial neoplasm. Most cases display coexpression of epithelial markers, including keratins and/or EMA as well as S-100 protein. Myogenic markers also may be variably expressed; however, the absence of myogenic markers does not exclude the diagnosis of a myoepithelial tumor. Commonly expressed epithelial markers are cytokeratin AE1/AE3, cytokeratin 8/18, and EMA, while commonly expressed myogenic markers include muscle specific actin and smooth muscle actin.^5,7,11,19 Myoepithelial tumors also may express calponin, p63, and glial fibrillary acidic protein.¹⁶

Molecular studies also can aid in the diagnosis of myoepithelial tumors. A study by Antonescu et al⁸ demonstrated EWSR1 gene rearrangement in 45% (30/66) of extrasalivary myoepithelial tumors and the absence of EWSR1 gene rearrangement in salivary gland myoepithelial tumors. The authors also showed that EWSR1-negative tumors were more likely to be superficially located, display ductal differentiation, and possess a benign clinical course.⁸ In another study, Bahrami et al²³ suggested that a subset of mixed tumors, specifically those with tubuloductal differentiation, are genetically linked to salivary gland pleomorphic adenomas, which was achieved by the coexpression of the PLAG1 protein and PLAG1 gene rearrangement on immunohistochemistry and fluorescence in situ hybridization (FISH), respectively. Of the 19 cases evaluated, 11 (58%) expressed nuclear staining for PLAG1 immunohistochemistry; 8 of those 11 showed positive gene rearrangement for PLAG1 using FISH. These findings raise the possibility that cutaneous mixed tumors may be more closely related to those of the salivary glands, while deep myoepithelial tumors that lack ductal differentiation may represent a distinct group. Similar to the study by Antonescu et al,⁸ Flucke et al¹⁰ investigated EWSR1 gene rearrangement but limited their sample to cutaneous tumors, including myoepitheliomas, mixed tumors, and myoepithelial carcinoma. The authors found that 44% of cases (7/16) expressed EWSR1; this expression suggests that cutaneous myoepithelial tumors may have a genetic relationship to their soft tissue, bone, and visceral counterparts.¹⁰

Myoepithelial tumors display a broad spectrum of morphologic features; however, one of the most common growth patterns is that of oval to round cells forming cords and chains in a chondromyxoid stroma. As such, the histopathologic differential diagnosis for myoepithelial tumors includes other epithelioid or round-cell neoplasms with similar growth patterns including extraskeletal myxoid chondrosarcoma (EMC), ossifying fibromyxoid tumor of soft parts, and extra-axial soft tissue chordoma. Extraskeletal myxoid chondrosarcoma bears the closest similarity to myoepithelial tumors both histologically and by ancillary studies. It typically possesses cords or chains of small round tumor cells set in a chondromyxoid or myxoid background. In contrast to myoepithelial tumors, which typically have more abundant cytoplasm and can show at least focal areas of spindle cell growth, the cells of EMC are more uniform, small, round cells with relatively scant cytoplasm. Extraskeletal myxoid chondrosarcomas lack the typical myoepithelial coexpression of cytokeratin and S-100 protein, with a minority of EMCs expressing S-100 protein but rarely cytokeratin. Most cases of EMC possess a balanced t(9;22) translocation involving the EWSR1 gene,²⁴ a finding that could lead to confusion with soft tissue myoepithelial tumors, which also may show EWSR1 rearrangement on FISH. Ossifying fibromyxoid tumor of soft parts is also composed of round cells arranged in cords in a myxoid or fibrous stroma; the majority of cases also display a peripheral rim of mature bone, a feature that is not typically seen in myoepithelial tumors. Similar to myoepithelial tumors, ossifying fibromyxoid tumor of soft parts often is positive for S-100 protein; however, it rarely is positive for cytokeratins. Ossifying fibromyxoid tumor of soft parts has been shown to have a rearrangement of the PHD finger protein 1 (PHF1) gene in approximately half of cases, a molecular finding that has not been reported for myoepithelial tumors.²⁵ Finally, extra-axial soft tissue chordomas, though quite rare, may possess striking similarities to myoepithelial tumors both histopathologically and immunohistochemically. Chordomas are composed of epithelioid cells arranged in nests, nodules, and chains with a variably myxoid background. A variable amount of cells with bubbly cytoplasm (known as physaliphorous cells) can be seen. High mitotic activity is not a characteristic feature in chordomas. They classically coexpress cytokeratins and S-100 protein, similar to myoepithelial tumors. A subset of myoepitheliomas with similar histologic features to chordoma was historically referred to as parachordoma.^26,27 The distinction between these 2 entities was challenging until the relatively recent advent of brachyury, a sensitive and specific nuclear marker of chordoma; extra-axial soft tissue chordomas and their central counterparts both express nuclear brachyury, while myoepitheliomas (including those with a parachordoma histologic pattern) do not.²⁸ Our case did not display physaliphorous cells but did demonstrate abundant nuclear pleomorphism and high mitotic activity. In addition, immunohistochemical staining was negative for brachyury.

Because cutaneous myoepithelial tumors are relatively rare, a well-defined standard of care for treatment is lacking. Surgical excision is the primary treatment method in most reported cases in the literature.^17,19 Miller et al²⁹ reported the successful treatment of recurrent cutaneous myoepitheliomas with Mohs micrographic surgery. Chemotherapy may be useful in the setting of metastatic myoepithelial carcinomas in adults, but reported results are inconsistent.^30,31 Radiation treatment of recurrent or metastatic disease has not been shown to be effective. A study of children treated with surgical resection and chemotherapy using ifosfamide, cisplatin, and etoposide followed by radiation therapy showed positive results.³²

Our case highlights several challenges that may arise in establishing a diagnosis of cutaneous myoepithelial carcinoma with disseminated metastases. The diagnostic difficulty in our case was compounded by the advanced nature of the lesion at the time of presentation. Given the rarity of metastatic cutaneous myoepithelial carcinomas and the lack of a prior primary diagnosis of a malignant myoepithelioma, the index of suspicion for this entity was not high. A report of myoepithelial carcinoma of the parotid gland metastatic to the skin has been reported,³³ but in the absence of salivary gland involvement or other visceral lesions, metastasis from any source other than our patient’s cutaneous scalp lesion is unlikely. The histopathologic features in combination with the characteristic immunophenotype, unique clinical setting, and radiographic findings were essential to arriving at the correct diagnosis. Unlike previously reported metastatic lesions, our case is unique in that metastatic lesions were identified at the time of initial clinical presentation.

Conclusion

Cutaneous myoepithelial carcinomas are exceedingly rare tumors with a wide range of histopathologic and immunohistochemical findings. In challenging cases, studies for EWSR1 or PLAG1 gene rearrangement can be helpful. Furthermore, this case illustrates the potential for widespread dissemination of myoepithelial carcinomas requiring clinical evaluation and imaging studies to exclude metastatic lesions.

UV radiation from sun exposure is a risk factor for most types of skin cancer.¹ Despite comprising only 1% of the body's surface area, the periocular region is the location of approximately 5% to 10% of skin cancers described in one US study.² The efficacy of sunscreen in preventing skin cancer is widely accepted, and the American Academy of Dermatology recommends application of broad-spectrum UVA/UVB sunscreen with a sun protection factor of 30 or higher to help prevent skin cancer.^3-5

RELATED ARTICLE: Sun Protection for Infants: Parent Behaviors and Beliefs

Reducing the risk of skin cancer from sun exposure relies on many factors, including completeness of application. A number of studies have demonstrated incomplete sunscreen application on the hairline, ears, neck, and dorsal feet.^6-8 The purpose of this study was to assess the completeness of facial sunscreen self-application in oculofacial surgery patients using UV photography.

Methods

This single-site, cross-sectional, qualitative study assessed the completeness of facial sunscreen self-application among patients from a single surgeon's (J.A.W.) cosmetic and tertiary-care oculofacial surgery practice at the Duke Eye Center (Durham, North Carolina) between March 2016 and May 2016. Approval from the Duke University institutional review board was obtained, and the research adhered to the tenets of the Declaration of Helsinki and complied with the Health Insurance Portability and Accountability Act. Informed consent was obtained from all patients, and patients could elect to provide specific written consent for publication of photographs in scientific presentations and publications. Patients younger than 18 years of age; those with known sensitivity to sunscreen or its ingredients; and those with an active lesion, rash, or open wound were excluded from the study.

After obtaining informed consent, patients were photographed using a camera with a UV lens in natural outdoor lighting, first without sunscreen and again after self-application of a sunscreen of their choosing using their routine application technique. Completeness of sunscreen application was graded independently by 3 oculofacial surgeons (N.A.L., J.L., J.A.W.) as complete, partial, none, or cannot determine for 15 facial regions. The majority response was used for analysis.

Results

Forty-four patients were enrolled in the study. Six patients were disqualified due to use of mineral-based formulations (zinc oxide and/or titanium dioxide), as these sunscreens could not be visualized using UV photography. The age range of the remaining 38 patients was 28 to 74 years; 26% (10/38) were men and 74% (28/38) were women.

Complete sunscreen application was most frequently performed on the cheeks (97% [37/38]), chin (95% [36/38]), forehead (92% [35/38]), and temples (92% [35/38]). Complete absence of sunscreen coverage was most common on the lower eyelid margin (84% [32/38]), upper eyelid margin (82% [31/38]), medial canthus (71% 27/38]), and upper eyelid (66% [25/38])(Table)(Figure).

Comment

UV radiation-related skin cancers frequently occur in the periocular area, presumably because it is a frequent site of UV exposure. Clothing, sunglasses, and hats can be used to aid in protection from UV radiation, but these products are only regulated by the US Food and Drug Administration if the product claims to prevent skin cancer. Sunscreen is a proven method of protection from UV radiation and the prevention of skin cancer but must be properly applied for it to be effective.^1,2,5,6 Incomplete sunscreen application has been demonstrated in numerous studies. Lademann et al7 studied sunscreen application among 60 beachgoers in Germany and found they typically missed the hairline, ears, and dorsal feet. In a study of 10 women with photosensitivity in England who were asked to apply sunscreen in their routine manner, Azurdia et al⁶ found the posterior neck, lateral neck, temples, and ears, respectively, were the most frequently missed sites. Yang et al⁸ assessed sunscreen application in 39 dermatologists and 41 photosensitive patients in China and found the neck, ears, dorsal hands, hairline, temples, and perioral region, respectively, were most commonly left unprotected.

Our study investigated detailed facial self-application of sunscreen and found excellent coverage of the larger facial units such as the forehead, cheeks, chin, and temples. The brow, medial canthus, lateral canthus, and upper and lower eyelids and eyelid margins were infrequently protected with sunscreen during routine application. Our opinion is that patients are unaware that eyelid sunscreen application is important. They may be afraid that the products will sting or cause damage if they get in the eyes. Although some products do sting if they get into the eyes, there is no evidence that sunscreens cause injury to the eyes. The US Food and Drug Administration does not have clear guidelines about applying sunscreens in the periocular area, but in general, mineral blocks are recommended because they have less chance of irritation. Several companies make such products that are designed to be applied to the eyelids.

Limitations of our study included a small sample size and a majority female demographic, which may have affected the results, as women generally are more familiar with the application of lotions to the face. Additionally, the patients were recruited from a tertiary-care clinic and may have had periocular malignancy or may have previously received counseling on the importance of sunscreen use.

Conclusion

Cancer reconstruction of the periocular area is challenging, and even in the best of hands, a patient's quality of life may be negatively affected by postreconstructive appearance or suboptimal function, resulting in ocular exposure. The authors recommend counseling patients on the importance of good sun protection habits, including daily application of sunscreen to the face and periocular region to prevent malignancy in these delicate areas.

UV radiation from sun exposure is a risk factor for most types of skin cancer.¹ Despite comprising only 1% of the body's surface area, the periocular region is the location of approximately 5% to 10% of skin cancers described in one US study.² The efficacy of sunscreen in preventing skin cancer is widely accepted, and the American Academy of Dermatology recommends application of broad-spectrum UVA/UVB sunscreen with a sun protection factor of 30 or higher to help prevent skin cancer.^3-5

RELATED ARTICLE: Sun Protection for Infants: Parent Behaviors and Beliefs

Reducing the risk of skin cancer from sun exposure relies on many factors, including completeness of application. A number of studies have demonstrated incomplete sunscreen application on the hairline, ears, neck, and dorsal feet.^6-8 The purpose of this study was to assess the completeness of facial sunscreen self-application in oculofacial surgery patients using UV photography.

Methods

This single-site, cross-sectional, qualitative study assessed the completeness of facial sunscreen self-application among patients from a single surgeon's (J.A.W.) cosmetic and tertiary-care oculofacial surgery practice at the Duke Eye Center (Durham, North Carolina) between March 2016 and May 2016. Approval from the Duke University institutional review board was obtained, and the research adhered to the tenets of the Declaration of Helsinki and complied with the Health Insurance Portability and Accountability Act. Informed consent was obtained from all patients, and patients could elect to provide specific written consent for publication of photographs in scientific presentations and publications. Patients younger than 18 years of age; those with known sensitivity to sunscreen or its ingredients; and those with an active lesion, rash, or open wound were excluded from the study.

After obtaining informed consent, patients were photographed using a camera with a UV lens in natural outdoor lighting, first without sunscreen and again after self-application of a sunscreen of their choosing using their routine application technique. Completeness of sunscreen application was graded independently by 3 oculofacial surgeons (N.A.L., J.L., J.A.W.) as complete, partial, none, or cannot determine for 15 facial regions. The majority response was used for analysis.

Results

Forty-four patients were enrolled in the study. Six patients were disqualified due to use of mineral-based formulations (zinc oxide and/or titanium dioxide), as these sunscreens could not be visualized using UV photography. The age range of the remaining 38 patients was 28 to 74 years; 26% (10/38) were men and 74% (28/38) were women.

Complete sunscreen application was most frequently performed on the cheeks (97% [37/38]), chin (95% [36/38]), forehead (92% [35/38]), and temples (92% [35/38]). Complete absence of sunscreen coverage was most common on the lower eyelid margin (84% [32/38]), upper eyelid margin (82% [31/38]), medial canthus (71% 27/38]), and upper eyelid (66% [25/38])(Table)(Figure).

Comment

UV radiation-related skin cancers frequently occur in the periocular area, presumably because it is a frequent site of UV exposure. Clothing, sunglasses, and hats can be used to aid in protection from UV radiation, but these products are only regulated by the US Food and Drug Administration if the product claims to prevent skin cancer. Sunscreen is a proven method of protection from UV radiation and the prevention of skin cancer but must be properly applied for it to be effective.^1,2,5,6 Incomplete sunscreen application has been demonstrated in numerous studies. Lademann et al7 studied sunscreen application among 60 beachgoers in Germany and found they typically missed the hairline, ears, and dorsal feet. In a study of 10 women with photosensitivity in England who were asked to apply sunscreen in their routine manner, Azurdia et al⁶ found the posterior neck, lateral neck, temples, and ears, respectively, were the most frequently missed sites. Yang et al⁸ assessed sunscreen application in 39 dermatologists and 41 photosensitive patients in China and found the neck, ears, dorsal hands, hairline, temples, and perioral region, respectively, were most commonly left unprotected.

Our study investigated detailed facial self-application of sunscreen and found excellent coverage of the larger facial units such as the forehead, cheeks, chin, and temples. The brow, medial canthus, lateral canthus, and upper and lower eyelids and eyelid margins were infrequently protected with sunscreen during routine application. Our opinion is that patients are unaware that eyelid sunscreen application is important. They may be afraid that the products will sting or cause damage if they get in the eyes. Although some products do sting if they get into the eyes, there is no evidence that sunscreens cause injury to the eyes. The US Food and Drug Administration does not have clear guidelines about applying sunscreens in the periocular area, but in general, mineral blocks are recommended because they have less chance of irritation. Several companies make such products that are designed to be applied to the eyelids.

Limitations of our study included a small sample size and a majority female demographic, which may have affected the results, as women generally are more familiar with the application of lotions to the face. Additionally, the patients were recruited from a tertiary-care clinic and may have had periocular malignancy or may have previously received counseling on the importance of sunscreen use.

Conclusion

Cancer reconstruction of the periocular area is challenging, and even in the best of hands, a patient's quality of life may be negatively affected by postreconstructive appearance or suboptimal function, resulting in ocular exposure. The authors recommend counseling patients on the importance of good sun protection habits, including daily application of sunscreen to the face and periocular region to prevent malignancy in these delicate areas.

UV radiation from sun exposure is a risk factor for most types of skin cancer.¹ Despite comprising only 1% of the body's surface area, the periocular region is the location of approximately 5% to 10% of skin cancers described in one US study.² The efficacy of sunscreen in preventing skin cancer is widely accepted, and the American Academy of Dermatology recommends application of broad-spectrum UVA/UVB sunscreen with a sun protection factor of 30 or higher to help prevent skin cancer.^3-5

RELATED ARTICLE: Sun Protection for Infants: Parent Behaviors and Beliefs

Reducing the risk of skin cancer from sun exposure relies on many factors, including completeness of application. A number of studies have demonstrated incomplete sunscreen application on the hairline, ears, neck, and dorsal feet.^6-8 The purpose of this study was to assess the completeness of facial sunscreen self-application in oculofacial surgery patients using UV photography.

Methods

This single-site, cross-sectional, qualitative study assessed the completeness of facial sunscreen self-application among patients from a single surgeon's (J.A.W.) cosmetic and tertiary-care oculofacial surgery practice at the Duke Eye Center (Durham, North Carolina) between March 2016 and May 2016. Approval from the Duke University institutional review board was obtained, and the research adhered to the tenets of the Declaration of Helsinki and complied with the Health Insurance Portability and Accountability Act. Informed consent was obtained from all patients, and patients could elect to provide specific written consent for publication of photographs in scientific presentations and publications. Patients younger than 18 years of age; those with known sensitivity to sunscreen or its ingredients; and those with an active lesion, rash, or open wound were excluded from the study.

After obtaining informed consent, patients were photographed using a camera with a UV lens in natural outdoor lighting, first without sunscreen and again after self-application of a sunscreen of their choosing using their routine application technique. Completeness of sunscreen application was graded independently by 3 oculofacial surgeons (N.A.L., J.L., J.A.W.) as complete, partial, none, or cannot determine for 15 facial regions. The majority response was used for analysis.

Results

Forty-four patients were enrolled in the study. Six patients were disqualified due to use of mineral-based formulations (zinc oxide and/or titanium dioxide), as these sunscreens could not be visualized using UV photography. The age range of the remaining 38 patients was 28 to 74 years; 26% (10/38) were men and 74% (28/38) were women.

Complete sunscreen application was most frequently performed on the cheeks (97% [37/38]), chin (95% [36/38]), forehead (92% [35/38]), and temples (92% [35/38]). Complete absence of sunscreen coverage was most common on the lower eyelid margin (84% [32/38]), upper eyelid margin (82% [31/38]), medial canthus (71% 27/38]), and upper eyelid (66% [25/38])(Table)(Figure).

Comment

UV radiation-related skin cancers frequently occur in the periocular area, presumably because it is a frequent site of UV exposure. Clothing, sunglasses, and hats can be used to aid in protection from UV radiation, but these products are only regulated by the US Food and Drug Administration if the product claims to prevent skin cancer. Sunscreen is a proven method of protection from UV radiation and the prevention of skin cancer but must be properly applied for it to be effective.^1,2,5,6 Incomplete sunscreen application has been demonstrated in numerous studies. Lademann et al7 studied sunscreen application among 60 beachgoers in Germany and found they typically missed the hairline, ears, and dorsal feet. In a study of 10 women with photosensitivity in England who were asked to apply sunscreen in their routine manner, Azurdia et al⁶ found the posterior neck, lateral neck, temples, and ears, respectively, were the most frequently missed sites. Yang et al⁸ assessed sunscreen application in 39 dermatologists and 41 photosensitive patients in China and found the neck, ears, dorsal hands, hairline, temples, and perioral region, respectively, were most commonly left unprotected.

Our study investigated detailed facial self-application of sunscreen and found excellent coverage of the larger facial units such as the forehead, cheeks, chin, and temples. The brow, medial canthus, lateral canthus, and upper and lower eyelids and eyelid margins were infrequently protected with sunscreen during routine application. Our opinion is that patients are unaware that eyelid sunscreen application is important. They may be afraid that the products will sting or cause damage if they get in the eyes. Although some products do sting if they get into the eyes, there is no evidence that sunscreens cause injury to the eyes. The US Food and Drug Administration does not have clear guidelines about applying sunscreens in the periocular area, but in general, mineral blocks are recommended because they have less chance of irritation. Several companies make such products that are designed to be applied to the eyelids.

Limitations of our study included a small sample size and a majority female demographic, which may have affected the results, as women generally are more familiar with the application of lotions to the face. Additionally, the patients were recruited from a tertiary-care clinic and may have had periocular malignancy or may have previously received counseling on the importance of sunscreen use.

Conclusion

Cancer reconstruction of the periocular area is challenging, and even in the best of hands, a patient's quality of life may be negatively affected by postreconstructive appearance or suboptimal function, resulting in ocular exposure. The authors recommend counseling patients on the importance of good sun protection habits, including daily application of sunscreen to the face and periocular region to prevent malignancy in these delicate areas.

I had just done an ED&C, scraping the friable tumor gently from her tissue paper–thin skin. “Yes,” I replied more loudly than our close proximity would warrant. “This is probably another basal cell carcinoma. When I get the pathology back, I’ll call you.” As my medical assistant was putting on the Band-Aid, my patient exclaimed, “Oh, no! “Don’t call me! Just send me an email, honey.”

At the time of the biopsy, she was 84 years old. My 84-year-old patient just chastised me for not using her preferred method of communication. She didn’t want a follow-up visit or a phone call. She wanted an email.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@frontlinemedcom.com.

I had just done an ED&C, scraping the friable tumor gently from her tissue paper–thin skin. “Yes,” I replied more loudly than our close proximity would warrant. “This is probably another basal cell carcinoma. When I get the pathology back, I’ll call you.” As my medical assistant was putting on the Band-Aid, my patient exclaimed, “Oh, no! “Don’t call me! Just send me an email, honey.”

At the time of the biopsy, she was 84 years old. My 84-year-old patient just chastised me for not using her preferred method of communication. She didn’t want a follow-up visit or a phone call. She wanted an email.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@frontlinemedcom.com.

I had just done an ED&C, scraping the friable tumor gently from her tissue paper–thin skin. “Yes,” I replied more loudly than our close proximity would warrant. “This is probably another basal cell carcinoma. When I get the pathology back, I’ll call you.” As my medical assistant was putting on the Band-Aid, my patient exclaimed, “Oh, no! “Don’t call me! Just send me an email, honey.”

At the time of the biopsy, she was 84 years old. My 84-year-old patient just chastised me for not using her preferred method of communication. She didn’t want a follow-up visit or a phone call. She wanted an email.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@frontlinemedcom.com.