Nonmelanoma Skin Cancer

In 1909, Sabouraud¹ published a report delineating the clinical subsets of a chronic fungal infection of the scalp known as favus. The rarest subset was termed favus papyroide and consisted of a thin, dry, gray, parchmentlike crust up to 5 cm in diameter. Hair shafts were described as piercing the crust, with the underlying skin exhibiting erythema, moisture, and erosions. Children were reported to be affected more often than adults.¹ Subsequent descriptions of patients with similar presentations have not appeared in the medical literature. In this case, an elderly woman with tinea capitis (TC) due to Trichophyton rubrum exhibited features of favus papyroide.

Case Report

An 87-year-old woman with a long history of actinic keratoses and nonmelanoma skin cancers presented to our dermatology clinic with numerous growths on the head, neck, and arms. The patient resided in a nursing home and had a history of hypertension, osteoarthritis, and mild to moderate dementia. Physical examination revealed a frail elderly woman in a wheelchair. Numerous actinic keratoses were noted on the arms and face. Examination of the scalp revealed a large, white-gray, palm-sized plaque on the crown (Figure 1) with 2 yellow, quarter-sized, hyperkeratotic nodules on the left temple and left parietal scalp. The differential diagnosis for the nodules on the temple and scalp included squamous cell carcinoma and hyperkeratotic actinic keratosis, and both lesions were biopsied. Histologically, they demonstrated pronounced hyperkeratosis and parakeratosis with numerous infiltrating neutrophils. The stratum malpighii exhibited focal atypia consistent with an actinic keratosis with areas of spongiosis and pustular folliculitis but no evidence of an invasive cutaneous malignancy. Periodic acid–Schiff stains were performed on both specimens and revealed numerous fungal hyphae within the stratum corneum (Figure 2) as well as evidence of a fungal folliculitis.

At a follow-up visit 2 weeks later, a portion of the hyperkeratotic material on the crown of the scalp was lifted free from the skin surface, removed with scissors, and submitted for histologic analysis and culture. The underlying skin exhibited substantial erythema and diffuse alopecia. The specimen consisted entirely of masses of hyperkeratotic and parakeratotic stratum corneum with numerous infiltrating neutrophils, cellular debris, and focal secondary bacterial colonization (Figure 3). Fungal hyphae and spores were readily demonstrated on Gomori methenamine-silver stain (Figure 4). A fungal culture from this material failed to demonstrate growth at 28 days. The organism was molecularly identified as T rubrum using the Sanger sequencing assay. The patient was treated with fluconazole 150 mg once daily for 3 weeks with eventual resolution of the plaque. The patient died approximately 3 months later (unrelated to her scalp infection).

Comment

Favus, or tinea favosa, is a chronic inflammatory dermatophyte infection of the scalp, less commonly involving the skin and nails.² The classic lesion is termed a scutulum or godet consisting of concave, cup-shaped, yellow crusts typically pierced by a single hair shaft.¹ With an increase in size, the scutula may become confluent. Alopecia commonly results and infected patients may exude a “cheesy” or “mousy” odor from the lesions.³ Sabouraud¹ delineated 3 clinical presentations of favus: (1) favus pityroide, the most common type consisting of a seborrheic dermatitis–like picture and scutula; (2) favus impetigoide, exhibiting honey-colored crusts reminiscent of impetigo but without appreciable scutula; and (3) favus papyroide, the rarest variant, demonstrating a dry, gray, parchmentlike crust pierced by hair shafts overlying an eroded erythematous scalp.

Favus usually is acquired in childhood or adolescence and often persists into adulthood.³ It is transmitted directly by hairs, infected keratinocytes, and fomites. Child-to-child transmission is much less common than other forms of TC.⁴ The responsible organism is almost always Trichophyton schoenleinii, with rare cases of Trichophyton violaceum, Trichophyton verrucosum, Trichophyton mentagrophytes var quinckeanum, Microsporum canis, and Microsporum gypseum having been reported.^2,5,6 This anthropophilic dermatophyte infects only humans, is capable of surviving in the same dwelling space for generations, and is believed to require prolonged exposure for transmission. Trichophyton schoenleinii was the predominant infectious cause of TC in eastern Europe in the 19th and early 20th centuries, but its incidence has dramatically declined in the last 50 years.⁷ A survey conducted in 1997 and published in 2001 of TC that was culture-positive for T schoenleinii in 19 European countries found only 3 cases among 3671 isolates (0.08%).⁸ Between 1980 and 2005, no cases were reported in the British Isles.⁹ Currently, favus generally is found in impoverished geographic regions with poor hygiene, malnutrition, and limited access to health care; however, endemic foci in Kentucky, Quebec, and Montreal have been reported in North America.¹⁰ Although favus rarely resolves spontaneously, T schoenleinii was eradicated in most of the world with the introduction of griseofulvin in 1958.⁷ Terbinafine and itraconazole are currently the drugs of choice for therapy.¹⁰

Tinea capitis is the most common fungal infection in children, with 1 in 20 US children displaying evidence of overt infection.¹¹ Infection in adults is rare and most affected patients typically display serious illnesses with concomitant immune compromise.¹² Only 3% to 5% of cases arise in patients older than 20 years.¹³ Adult hair appears to be relatively resistant to dermatophyte infection, probably from the fungistatic properties of long-chain fatty acids found in sebum.¹³ Tinea capitis in adults usually occurs in postmenopausal women, presumably from involution of sebaceous glands associated with declining estrogen levels. Patients typically exhibit erythematous scaly patches with central clearing, alopecia, varying degrees of inflammation, and few pustules, though exudative and heavily inflammatory lesions also have been described.¹⁴

In the current case, TC was not raised in the differential diagnosis. Regardless, given that scaly red patches and papules of the scalp may represent a dermatophyte infection in this patient population, clinicians are encouraged to consider this possibility. Transmission is by direct human-to-human contact and contact with objects containing fomites including brushes, combs, bedding, clothing, toys, furniture, and telephones.¹⁵ It is frequently spread among family members and classmates.¹⁶

Prior to World War II, most cases of TC in the United States were due to M canis, with Microsporum audouinii becoming more prevalent until the 1960s and 1970s when Trichophyton tonsurans began surging in incidence.^12,17 Currently, the latter organism is responsible for more than 95% of TC cases in the United States.¹⁸Microsporum canis is the main causative species in Europe but varies widely by country. In the Middle East and Africa, T violaceum is responsible for many infections.

Trichophyton rubrum–associated TC appears to be a rare occurrence. A global study in 1995 noted that less than 1% of TC cases were due to T rubrum infection, most having been described in emerging nations.¹² A meta-analysis of 9 studies from developed countries found only 9 of 10,145 cases of TC with a culture positive for T rubrum.¹⁴ In adults, infected patients typically exhibit either evidence of a concomitant fungal infection of the skin and/or nails or health conditions with impaired immunity, whereas in children, interfamilial spread appears more common.¹¹

In 1909, Sabouraud¹ published a report delineating the clinical subsets of a chronic fungal infection of the scalp known as favus. The rarest subset was termed favus papyroide and consisted of a thin, dry, gray, parchmentlike crust up to 5 cm in diameter. Hair shafts were described as piercing the crust, with the underlying skin exhibiting erythema, moisture, and erosions. Children were reported to be affected more often than adults.¹ Subsequent descriptions of patients with similar presentations have not appeared in the medical literature. In this case, an elderly woman with tinea capitis (TC) due to Trichophyton rubrum exhibited features of favus papyroide.

Case Report

An 87-year-old woman with a long history of actinic keratoses and nonmelanoma skin cancers presented to our dermatology clinic with numerous growths on the head, neck, and arms. The patient resided in a nursing home and had a history of hypertension, osteoarthritis, and mild to moderate dementia. Physical examination revealed a frail elderly woman in a wheelchair. Numerous actinic keratoses were noted on the arms and face. Examination of the scalp revealed a large, white-gray, palm-sized plaque on the crown (Figure 1) with 2 yellow, quarter-sized, hyperkeratotic nodules on the left temple and left parietal scalp. The differential diagnosis for the nodules on the temple and scalp included squamous cell carcinoma and hyperkeratotic actinic keratosis, and both lesions were biopsied. Histologically, they demonstrated pronounced hyperkeratosis and parakeratosis with numerous infiltrating neutrophils. The stratum malpighii exhibited focal atypia consistent with an actinic keratosis with areas of spongiosis and pustular folliculitis but no evidence of an invasive cutaneous malignancy. Periodic acid–Schiff stains were performed on both specimens and revealed numerous fungal hyphae within the stratum corneum (Figure 2) as well as evidence of a fungal folliculitis.

At a follow-up visit 2 weeks later, a portion of the hyperkeratotic material on the crown of the scalp was lifted free from the skin surface, removed with scissors, and submitted for histologic analysis and culture. The underlying skin exhibited substantial erythema and diffuse alopecia. The specimen consisted entirely of masses of hyperkeratotic and parakeratotic stratum corneum with numerous infiltrating neutrophils, cellular debris, and focal secondary bacterial colonization (Figure 3). Fungal hyphae and spores were readily demonstrated on Gomori methenamine-silver stain (Figure 4). A fungal culture from this material failed to demonstrate growth at 28 days. The organism was molecularly identified as T rubrum using the Sanger sequencing assay. The patient was treated with fluconazole 150 mg once daily for 3 weeks with eventual resolution of the plaque. The patient died approximately 3 months later (unrelated to her scalp infection).

Comment

Favus, or tinea favosa, is a chronic inflammatory dermatophyte infection of the scalp, less commonly involving the skin and nails.² The classic lesion is termed a scutulum or godet consisting of concave, cup-shaped, yellow crusts typically pierced by a single hair shaft.¹ With an increase in size, the scutula may become confluent. Alopecia commonly results and infected patients may exude a “cheesy” or “mousy” odor from the lesions.³ Sabouraud¹ delineated 3 clinical presentations of favus: (1) favus pityroide, the most common type consisting of a seborrheic dermatitis–like picture and scutula; (2) favus impetigoide, exhibiting honey-colored crusts reminiscent of impetigo but without appreciable scutula; and (3) favus papyroide, the rarest variant, demonstrating a dry, gray, parchmentlike crust pierced by hair shafts overlying an eroded erythematous scalp.

Favus usually is acquired in childhood or adolescence and often persists into adulthood.³ It is transmitted directly by hairs, infected keratinocytes, and fomites. Child-to-child transmission is much less common than other forms of TC.⁴ The responsible organism is almost always Trichophyton schoenleinii, with rare cases of Trichophyton violaceum, Trichophyton verrucosum, Trichophyton mentagrophytes var quinckeanum, Microsporum canis, and Microsporum gypseum having been reported.^2,5,6 This anthropophilic dermatophyte infects only humans, is capable of surviving in the same dwelling space for generations, and is believed to require prolonged exposure for transmission. Trichophyton schoenleinii was the predominant infectious cause of TC in eastern Europe in the 19th and early 20th centuries, but its incidence has dramatically declined in the last 50 years.⁷ A survey conducted in 1997 and published in 2001 of TC that was culture-positive for T schoenleinii in 19 European countries found only 3 cases among 3671 isolates (0.08%).⁸ Between 1980 and 2005, no cases were reported in the British Isles.⁹ Currently, favus generally is found in impoverished geographic regions with poor hygiene, malnutrition, and limited access to health care; however, endemic foci in Kentucky, Quebec, and Montreal have been reported in North America.¹⁰ Although favus rarely resolves spontaneously, T schoenleinii was eradicated in most of the world with the introduction of griseofulvin in 1958.⁷ Terbinafine and itraconazole are currently the drugs of choice for therapy.¹⁰

Tinea capitis is the most common fungal infection in children, with 1 in 20 US children displaying evidence of overt infection.¹¹ Infection in adults is rare and most affected patients typically display serious illnesses with concomitant immune compromise.¹² Only 3% to 5% of cases arise in patients older than 20 years.¹³ Adult hair appears to be relatively resistant to dermatophyte infection, probably from the fungistatic properties of long-chain fatty acids found in sebum.¹³ Tinea capitis in adults usually occurs in postmenopausal women, presumably from involution of sebaceous glands associated with declining estrogen levels. Patients typically exhibit erythematous scaly patches with central clearing, alopecia, varying degrees of inflammation, and few pustules, though exudative and heavily inflammatory lesions also have been described.¹⁴

In the current case, TC was not raised in the differential diagnosis. Regardless, given that scaly red patches and papules of the scalp may represent a dermatophyte infection in this patient population, clinicians are encouraged to consider this possibility. Transmission is by direct human-to-human contact and contact with objects containing fomites including brushes, combs, bedding, clothing, toys, furniture, and telephones.¹⁵ It is frequently spread among family members and classmates.¹⁶

Prior to World War II, most cases of TC in the United States were due to M canis, with Microsporum audouinii becoming more prevalent until the 1960s and 1970s when Trichophyton tonsurans began surging in incidence.^12,17 Currently, the latter organism is responsible for more than 95% of TC cases in the United States.¹⁸Microsporum canis is the main causative species in Europe but varies widely by country. In the Middle East and Africa, T violaceum is responsible for many infections.

Trichophyton rubrum–associated TC appears to be a rare occurrence. A global study in 1995 noted that less than 1% of TC cases were due to T rubrum infection, most having been described in emerging nations.¹² A meta-analysis of 9 studies from developed countries found only 9 of 10,145 cases of TC with a culture positive for T rubrum.¹⁴ In adults, infected patients typically exhibit either evidence of a concomitant fungal infection of the skin and/or nails or health conditions with impaired immunity, whereas in children, interfamilial spread appears more common.¹¹

In 1909, Sabouraud¹ published a report delineating the clinical subsets of a chronic fungal infection of the scalp known as favus. The rarest subset was termed favus papyroide and consisted of a thin, dry, gray, parchmentlike crust up to 5 cm in diameter. Hair shafts were described as piercing the crust, with the underlying skin exhibiting erythema, moisture, and erosions. Children were reported to be affected more often than adults.¹ Subsequent descriptions of patients with similar presentations have not appeared in the medical literature. In this case, an elderly woman with tinea capitis (TC) due to Trichophyton rubrum exhibited features of favus papyroide.

Case Report

An 87-year-old woman with a long history of actinic keratoses and nonmelanoma skin cancers presented to our dermatology clinic with numerous growths on the head, neck, and arms. The patient resided in a nursing home and had a history of hypertension, osteoarthritis, and mild to moderate dementia. Physical examination revealed a frail elderly woman in a wheelchair. Numerous actinic keratoses were noted on the arms and face. Examination of the scalp revealed a large, white-gray, palm-sized plaque on the crown (Figure 1) with 2 yellow, quarter-sized, hyperkeratotic nodules on the left temple and left parietal scalp. The differential diagnosis for the nodules on the temple and scalp included squamous cell carcinoma and hyperkeratotic actinic keratosis, and both lesions were biopsied. Histologically, they demonstrated pronounced hyperkeratosis and parakeratosis with numerous infiltrating neutrophils. The stratum malpighii exhibited focal atypia consistent with an actinic keratosis with areas of spongiosis and pustular folliculitis but no evidence of an invasive cutaneous malignancy. Periodic acid–Schiff stains were performed on both specimens and revealed numerous fungal hyphae within the stratum corneum (Figure 2) as well as evidence of a fungal folliculitis.

At a follow-up visit 2 weeks later, a portion of the hyperkeratotic material on the crown of the scalp was lifted free from the skin surface, removed with scissors, and submitted for histologic analysis and culture. The underlying skin exhibited substantial erythema and diffuse alopecia. The specimen consisted entirely of masses of hyperkeratotic and parakeratotic stratum corneum with numerous infiltrating neutrophils, cellular debris, and focal secondary bacterial colonization (Figure 3). Fungal hyphae and spores were readily demonstrated on Gomori methenamine-silver stain (Figure 4). A fungal culture from this material failed to demonstrate growth at 28 days. The organism was molecularly identified as T rubrum using the Sanger sequencing assay. The patient was treated with fluconazole 150 mg once daily for 3 weeks with eventual resolution of the plaque. The patient died approximately 3 months later (unrelated to her scalp infection).

Comment

Favus, or tinea favosa, is a chronic inflammatory dermatophyte infection of the scalp, less commonly involving the skin and nails.² The classic lesion is termed a scutulum or godet consisting of concave, cup-shaped, yellow crusts typically pierced by a single hair shaft.¹ With an increase in size, the scutula may become confluent. Alopecia commonly results and infected patients may exude a “cheesy” or “mousy” odor from the lesions.³ Sabouraud¹ delineated 3 clinical presentations of favus: (1) favus pityroide, the most common type consisting of a seborrheic dermatitis–like picture and scutula; (2) favus impetigoide, exhibiting honey-colored crusts reminiscent of impetigo but without appreciable scutula; and (3) favus papyroide, the rarest variant, demonstrating a dry, gray, parchmentlike crust pierced by hair shafts overlying an eroded erythematous scalp.

Favus usually is acquired in childhood or adolescence and often persists into adulthood.³ It is transmitted directly by hairs, infected keratinocytes, and fomites. Child-to-child transmission is much less common than other forms of TC.⁴ The responsible organism is almost always Trichophyton schoenleinii, with rare cases of Trichophyton violaceum, Trichophyton verrucosum, Trichophyton mentagrophytes var quinckeanum, Microsporum canis, and Microsporum gypseum having been reported.^2,5,6 This anthropophilic dermatophyte infects only humans, is capable of surviving in the same dwelling space for generations, and is believed to require prolonged exposure for transmission. Trichophyton schoenleinii was the predominant infectious cause of TC in eastern Europe in the 19th and early 20th centuries, but its incidence has dramatically declined in the last 50 years.⁷ A survey conducted in 1997 and published in 2001 of TC that was culture-positive for T schoenleinii in 19 European countries found only 3 cases among 3671 isolates (0.08%).⁸ Between 1980 and 2005, no cases were reported in the British Isles.⁹ Currently, favus generally is found in impoverished geographic regions with poor hygiene, malnutrition, and limited access to health care; however, endemic foci in Kentucky, Quebec, and Montreal have been reported in North America.¹⁰ Although favus rarely resolves spontaneously, T schoenleinii was eradicated in most of the world with the introduction of griseofulvin in 1958.⁷ Terbinafine and itraconazole are currently the drugs of choice for therapy.¹⁰

Tinea capitis is the most common fungal infection in children, with 1 in 20 US children displaying evidence of overt infection.¹¹ Infection in adults is rare and most affected patients typically display serious illnesses with concomitant immune compromise.¹² Only 3% to 5% of cases arise in patients older than 20 years.¹³ Adult hair appears to be relatively resistant to dermatophyte infection, probably from the fungistatic properties of long-chain fatty acids found in sebum.¹³ Tinea capitis in adults usually occurs in postmenopausal women, presumably from involution of sebaceous glands associated with declining estrogen levels. Patients typically exhibit erythematous scaly patches with central clearing, alopecia, varying degrees of inflammation, and few pustules, though exudative and heavily inflammatory lesions also have been described.¹⁴

In the current case, TC was not raised in the differential diagnosis. Regardless, given that scaly red patches and papules of the scalp may represent a dermatophyte infection in this patient population, clinicians are encouraged to consider this possibility. Transmission is by direct human-to-human contact and contact with objects containing fomites including brushes, combs, bedding, clothing, toys, furniture, and telephones.¹⁵ It is frequently spread among family members and classmates.¹⁶

Prior to World War II, most cases of TC in the United States were due to M canis, with Microsporum audouinii becoming more prevalent until the 1960s and 1970s when Trichophyton tonsurans began surging in incidence.^12,17 Currently, the latter organism is responsible for more than 95% of TC cases in the United States.¹⁸Microsporum canis is the main causative species in Europe but varies widely by country. In the Middle East and Africa, T violaceum is responsible for many infections.

Trichophyton rubrum–associated TC appears to be a rare occurrence. A global study in 1995 noted that less than 1% of TC cases were due to T rubrum infection, most having been described in emerging nations.¹² A meta-analysis of 9 studies from developed countries found only 9 of 10,145 cases of TC with a culture positive for T rubrum.¹⁴ In adults, infected patients typically exhibit either evidence of a concomitant fungal infection of the skin and/or nails or health conditions with impaired immunity, whereas in children, interfamilial spread appears more common.¹¹

When you pick up the Current Procedural Terminology (CPT) manual and read it, you may wonder what certain terms mean and how they may be looked at by payers and auditors. As your eyes glaze over from reading mind-numbing descriptions, a few points should be obvious, but conversations with friends, colleagues, and US Office of Inspector General and Centers for Medicare & Medicaid Services forensic investigators have convinced me that it is time for a refresher.

Excisions

For excisions (11400–11646), size is easy to determine. You measure the longest diameter of the lesion and the smallest margin required based on your judgment. The sum of the diameter and twice the margin is your lesion size. For benign lesions, the margin can be as small as 0 to 1 mm. For malignancies, it might be 5 to 9 mm for a melanoma in situ, 1 cm or more for an invasive melanoma with similar margins for squamous cell carcinoma, and somewhat less than 1 cm for basal cell carcinomas and more than 1 cm for Merkel cell carcinomas or spindle cell neoplasms. Unlike the shave removal codes (11300–11313), which do not involve subcutaneous tissue, an excision is at least full thickness through the dermis, which means a clever auditor would expect to see at least some fat on sections in most cases. Assuming you are through to fat, you may or may not close the wound. If you close the wound in a nonlayered manner, the repair is included and is not separately reportable. If you need to perform an intermediate layered closure (12031–12057) to get optimal function and cosmesis, the repair is separately reportable, as is a complex repair (13100–13163), which often includes wide undermining and other factors that differentiate it from an intermediate repair. If a more demanding repair is needed, you might use an adjacent tissue transfer (14000–14061), but the excision is included and not separately reportable. Skin grafts, most commonly split-thickness grafts, do not include the excision, which can be reported separately; direct closure of the graft donor site also is included.

There are times when you may delay a repair for medical reasons, which you would document in the medical record, but if you systematically delay a repair overnight to avoid the multiple procedure payment reduction, you may become “a person of interest,” which is a bad thing.

The shave removal codes (11300–11313) do not require repair and hemostasis is included. The size of the lesion determines the size of the lesion reported, and margins are not included. Hemostasis is included in the value of the CPT code and is not separately reportable.

It is not uncommon for a patient, usually one well known to you, to present with another skin cancer that has classic clinical findings. You review options with your patient and proceed to take one of the following approaches.

Option 1: You can tangentially remove or curette the tumor bulk and send the specimen for pathology review. At the same time, you curette and cauterize the base. In this case, you should hold your bill and await pathology. If the lesion is malignant, you would report the appropriate malignant destruction code (17260–17286) only. If it is benign, you would report a biopsy based on site or a benign destruction (17110) if for some reason the destruction was medically necessary. If it is an actinic keratosis, you could report either a biopsy or a premalignant destruction (17000).

Option 2: You perform a full-thickness excision of the lesion with a margin to remove it and send the specimen for pathology review. You should hold your bill and await pathology. If the lesion is malignant, you would report the appropriate malignant excision (11600–11646) and repair as discussed above. If it is benign, you would report the appropriate benign excision (11400–11446) and repair as discussed above.

If a shave, excision, or destruction is performed, a biopsy of the tissue should never be reported separately simply because the tissue may be sent to the laboratory. In other words, a biopsy is not separately reportable when another procedure was done at the same site on the same day.

Biopsy

Biopsies come in 2 varieties: general and site specific. All dermatologists are familiar with the basic skin biopsy codes 11110 and 11101 (biopsy of skin, subcutaneous tissue and/or mucous membrane [including simple closure], unless otherwise listed). Many are not aware of site-specific biopsy codes that often are more appropriate and should be used when their localization is more precise than the general skin biopsy.

Biopsies of the nail unit (eg, plate, bed, matrix, hyponychium, proximal and lateral nail folds) are reported using CPT code 11755. A simple nail clipping for culture or periodic acid–Schiff stain is not a nail biopsy and should not be separately reported from the evaluation and management component of the visit.

The lip biopsy code (40490) is used appropriately when the vermilion is sampled, not the skin around it. If the skin and vermilion are contiguously sampled, only report 40490. Specific codes exist for the vestibule of the mouth (40808), the anterior two-thirds (41100) and posterior one-third (41105) of the tongue, the floor (41108) and roof (42100) of the mouth, and the salivary glands by needle (42400) or by incision (42405).

The penis can be biopsied on the surface (54100) or deep structures can be sampled (54105), though the latter is uncommon in dermatology practices. The vulva can be sampled with codes comparable to general biopsy, with 54605 for the first biopsy and 54606 used for each additional one.

An incisional biopsy of the eyelid margin is reported with 67810, while conjunctival biopsy is reported with 68100; 68510 describes a lacrimal gland biopsy. The ear, not to be left out, has its own biopsy codes, with 69100 for the external ear and 69105 for the auditory canal.

Clipping of hair or tape stripping of skin (similar to nail clipping described above) are not biopsies and are not separately reportable, as the work involved is considered incident to the cognitive visit taking place.

Final Thoughts

These points should all be fairly straightforward—yes, the skin biopsy includes mucosa, but if a mucosal site such as the mouth has a more specific code, then that code is correct—and the simplest test for the clinician is to ask yourself, “If I were reviewing the claim, what would I expect to see?” As always, document what you do, do what you document, and report that which is medically necessary.

When you pick up the Current Procedural Terminology (CPT) manual and read it, you may wonder what certain terms mean and how they may be looked at by payers and auditors. As your eyes glaze over from reading mind-numbing descriptions, a few points should be obvious, but conversations with friends, colleagues, and US Office of Inspector General and Centers for Medicare & Medicaid Services forensic investigators have convinced me that it is time for a refresher.

Excisions

For excisions (11400–11646), size is easy to determine. You measure the longest diameter of the lesion and the smallest margin required based on your judgment. The sum of the diameter and twice the margin is your lesion size. For benign lesions, the margin can be as small as 0 to 1 mm. For malignancies, it might be 5 to 9 mm for a melanoma in situ, 1 cm or more for an invasive melanoma with similar margins for squamous cell carcinoma, and somewhat less than 1 cm for basal cell carcinomas and more than 1 cm for Merkel cell carcinomas or spindle cell neoplasms. Unlike the shave removal codes (11300–11313), which do not involve subcutaneous tissue, an excision is at least full thickness through the dermis, which means a clever auditor would expect to see at least some fat on sections in most cases. Assuming you are through to fat, you may or may not close the wound. If you close the wound in a nonlayered manner, the repair is included and is not separately reportable. If you need to perform an intermediate layered closure (12031–12057) to get optimal function and cosmesis, the repair is separately reportable, as is a complex repair (13100–13163), which often includes wide undermining and other factors that differentiate it from an intermediate repair. If a more demanding repair is needed, you might use an adjacent tissue transfer (14000–14061), but the excision is included and not separately reportable. Skin grafts, most commonly split-thickness grafts, do not include the excision, which can be reported separately; direct closure of the graft donor site also is included.

There are times when you may delay a repair for medical reasons, which you would document in the medical record, but if you systematically delay a repair overnight to avoid the multiple procedure payment reduction, you may become “a person of interest,” which is a bad thing.

The shave removal codes (11300–11313) do not require repair and hemostasis is included. The size of the lesion determines the size of the lesion reported, and margins are not included. Hemostasis is included in the value of the CPT code and is not separately reportable.

It is not uncommon for a patient, usually one well known to you, to present with another skin cancer that has classic clinical findings. You review options with your patient and proceed to take one of the following approaches.

Option 1: You can tangentially remove or curette the tumor bulk and send the specimen for pathology review. At the same time, you curette and cauterize the base. In this case, you should hold your bill and await pathology. If the lesion is malignant, you would report the appropriate malignant destruction code (17260–17286) only. If it is benign, you would report a biopsy based on site or a benign destruction (17110) if for some reason the destruction was medically necessary. If it is an actinic keratosis, you could report either a biopsy or a premalignant destruction (17000).

Option 2: You perform a full-thickness excision of the lesion with a margin to remove it and send the specimen for pathology review. You should hold your bill and await pathology. If the lesion is malignant, you would report the appropriate malignant excision (11600–11646) and repair as discussed above. If it is benign, you would report the appropriate benign excision (11400–11446) and repair as discussed above.

If a shave, excision, or destruction is performed, a biopsy of the tissue should never be reported separately simply because the tissue may be sent to the laboratory. In other words, a biopsy is not separately reportable when another procedure was done at the same site on the same day.

Biopsy

Biopsies come in 2 varieties: general and site specific. All dermatologists are familiar with the basic skin biopsy codes 11110 and 11101 (biopsy of skin, subcutaneous tissue and/or mucous membrane [including simple closure], unless otherwise listed). Many are not aware of site-specific biopsy codes that often are more appropriate and should be used when their localization is more precise than the general skin biopsy.

Biopsies of the nail unit (eg, plate, bed, matrix, hyponychium, proximal and lateral nail folds) are reported using CPT code 11755. A simple nail clipping for culture or periodic acid–Schiff stain is not a nail biopsy and should not be separately reported from the evaluation and management component of the visit.

The lip biopsy code (40490) is used appropriately when the vermilion is sampled, not the skin around it. If the skin and vermilion are contiguously sampled, only report 40490. Specific codes exist for the vestibule of the mouth (40808), the anterior two-thirds (41100) and posterior one-third (41105) of the tongue, the floor (41108) and roof (42100) of the mouth, and the salivary glands by needle (42400) or by incision (42405).

The penis can be biopsied on the surface (54100) or deep structures can be sampled (54105), though the latter is uncommon in dermatology practices. The vulva can be sampled with codes comparable to general biopsy, with 54605 for the first biopsy and 54606 used for each additional one.

An incisional biopsy of the eyelid margin is reported with 67810, while conjunctival biopsy is reported with 68100; 68510 describes a lacrimal gland biopsy. The ear, not to be left out, has its own biopsy codes, with 69100 for the external ear and 69105 for the auditory canal.

Clipping of hair or tape stripping of skin (similar to nail clipping described above) are not biopsies and are not separately reportable, as the work involved is considered incident to the cognitive visit taking place.

Final Thoughts

These points should all be fairly straightforward—yes, the skin biopsy includes mucosa, but if a mucosal site such as the mouth has a more specific code, then that code is correct—and the simplest test for the clinician is to ask yourself, “If I were reviewing the claim, what would I expect to see?” As always, document what you do, do what you document, and report that which is medically necessary.

When you pick up the Current Procedural Terminology (CPT) manual and read it, you may wonder what certain terms mean and how they may be looked at by payers and auditors. As your eyes glaze over from reading mind-numbing descriptions, a few points should be obvious, but conversations with friends, colleagues, and US Office of Inspector General and Centers for Medicare & Medicaid Services forensic investigators have convinced me that it is time for a refresher.

Excisions

For excisions (11400–11646), size is easy to determine. You measure the longest diameter of the lesion and the smallest margin required based on your judgment. The sum of the diameter and twice the margin is your lesion size. For benign lesions, the margin can be as small as 0 to 1 mm. For malignancies, it might be 5 to 9 mm for a melanoma in situ, 1 cm or more for an invasive melanoma with similar margins for squamous cell carcinoma, and somewhat less than 1 cm for basal cell carcinomas and more than 1 cm for Merkel cell carcinomas or spindle cell neoplasms. Unlike the shave removal codes (11300–11313), which do not involve subcutaneous tissue, an excision is at least full thickness through the dermis, which means a clever auditor would expect to see at least some fat on sections in most cases. Assuming you are through to fat, you may or may not close the wound. If you close the wound in a nonlayered manner, the repair is included and is not separately reportable. If you need to perform an intermediate layered closure (12031–12057) to get optimal function and cosmesis, the repair is separately reportable, as is a complex repair (13100–13163), which often includes wide undermining and other factors that differentiate it from an intermediate repair. If a more demanding repair is needed, you might use an adjacent tissue transfer (14000–14061), but the excision is included and not separately reportable. Skin grafts, most commonly split-thickness grafts, do not include the excision, which can be reported separately; direct closure of the graft donor site also is included.

There are times when you may delay a repair for medical reasons, which you would document in the medical record, but if you systematically delay a repair overnight to avoid the multiple procedure payment reduction, you may become “a person of interest,” which is a bad thing.

The shave removal codes (11300–11313) do not require repair and hemostasis is included. The size of the lesion determines the size of the lesion reported, and margins are not included. Hemostasis is included in the value of the CPT code and is not separately reportable.

It is not uncommon for a patient, usually one well known to you, to present with another skin cancer that has classic clinical findings. You review options with your patient and proceed to take one of the following approaches.

Option 1: You can tangentially remove or curette the tumor bulk and send the specimen for pathology review. At the same time, you curette and cauterize the base. In this case, you should hold your bill and await pathology. If the lesion is malignant, you would report the appropriate malignant destruction code (17260–17286) only. If it is benign, you would report a biopsy based on site or a benign destruction (17110) if for some reason the destruction was medically necessary. If it is an actinic keratosis, you could report either a biopsy or a premalignant destruction (17000).

Option 2: You perform a full-thickness excision of the lesion with a margin to remove it and send the specimen for pathology review. You should hold your bill and await pathology. If the lesion is malignant, you would report the appropriate malignant excision (11600–11646) and repair as discussed above. If it is benign, you would report the appropriate benign excision (11400–11446) and repair as discussed above.

If a shave, excision, or destruction is performed, a biopsy of the tissue should never be reported separately simply because the tissue may be sent to the laboratory. In other words, a biopsy is not separately reportable when another procedure was done at the same site on the same day.

Biopsy

Biopsies come in 2 varieties: general and site specific. All dermatologists are familiar with the basic skin biopsy codes 11110 and 11101 (biopsy of skin, subcutaneous tissue and/or mucous membrane [including simple closure], unless otherwise listed). Many are not aware of site-specific biopsy codes that often are more appropriate and should be used when their localization is more precise than the general skin biopsy.

Biopsies of the nail unit (eg, plate, bed, matrix, hyponychium, proximal and lateral nail folds) are reported using CPT code 11755. A simple nail clipping for culture or periodic acid–Schiff stain is not a nail biopsy and should not be separately reported from the evaluation and management component of the visit.

The lip biopsy code (40490) is used appropriately when the vermilion is sampled, not the skin around it. If the skin and vermilion are contiguously sampled, only report 40490. Specific codes exist for the vestibule of the mouth (40808), the anterior two-thirds (41100) and posterior one-third (41105) of the tongue, the floor (41108) and roof (42100) of the mouth, and the salivary glands by needle (42400) or by incision (42405).

The penis can be biopsied on the surface (54100) or deep structures can be sampled (54105), though the latter is uncommon in dermatology practices. The vulva can be sampled with codes comparable to general biopsy, with 54605 for the first biopsy and 54606 used for each additional one.

An incisional biopsy of the eyelid margin is reported with 67810, while conjunctival biopsy is reported with 68100; 68510 describes a lacrimal gland biopsy. The ear, not to be left out, has its own biopsy codes, with 69100 for the external ear and 69105 for the auditory canal.

Clipping of hair or tape stripping of skin (similar to nail clipping described above) are not biopsies and are not separately reportable, as the work involved is considered incident to the cognitive visit taking place.

Final Thoughts

These points should all be fairly straightforward—yes, the skin biopsy includes mucosa, but if a mucosal site such as the mouth has a more specific code, then that code is correct—and the simplest test for the clinician is to ask yourself, “If I were reviewing the claim, what would I expect to see?” As always, document what you do, do what you document, and report that which is medically necessary.

CenterWatch (http://www.centerwatch.com/) is an online resource that provides directories, analysis, and market research of medications that are either under clinical evaluation or available for use in patients. A list of currently approved drugs by the US Food and Drug Administration (FDA) also is available by specialty. It is important for dermatologists in-training to know about recently approved drugs and those that are in the pipeline, as these treatments may benefit patients who are unresponsive to other previously used medications. New drugs also may be useful for physicians who have a difficult time getting insurance to cover prescriptions for their patients, as most new medications have built-in patient assistance.

New Drugs in Dermatology

Actinic Keratosis

Ameluz (aminolevulinic acid hydrochloride)(Biofrontera AG) is a new drug that was approved in May 2016 for treatment of mild to moderate actinic keratosis on the face and scalp.¹ It is only intended for in-office use on patients who may not be candidates for other treatment options for actinic keratosis. The product is a gel formulation that should be applied to cover the lesions and approximately 5 mm of the surrounding area with a film of approximately 1-mm thickness. The entire treatment area is then illuminated with a red light source, either with a narrow spectrum around 630 nm with a light dose of approximately 37 J/cm² or a broader and continuous spectrum in the range of 570 to 670 nm with a light dose between 75 and 200 J/cm².¹ Similar to the previously used aminolevulinic acid treatment method for actinic keratosis, the patient may experience a burning stinging sensation throughout the treatment and the skin will then proceed to peel.

Psoriasis and Psoriatic Arthritis

Taltz (ixekizumab)(Eli Lilly and Company) was approved by the FDA in March 2016 for the treatment of moderate to severe plaque psoriasis.² It is a humanized IL-17A antagonist that works when IgG4 monoclonal antibodies selectively bind with IL-17A cytokines and inhibit their interaction with the IL-17 receptor. Although this injectable medication is approved for the treatment of psoriasis, it also can potentially be used off label for the treatment of psoriatic arthritis and rheumatoid arthritis. The approved dosage is 160 mg (two 80-mg injections) at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.² Injectable immunomodulatory medications such as ixekizumab are ideal for patients in whom topical treatments and light therapy failed and they continue to have serious psoriatic discomfort as well as for those who have substantial body surface area coverage.

Melanoma

Cotellic (cobimetinib)(Genentech USA, Inc) was FDA approved in November 2015.⁴ Cobimetinib is a reversible inhibitor of mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase 1. Mitogen-activated protein kinase MEK1 and MEK2 are regulators of the extracellular signal-­related kinase pathway, which promotes cellular proliferation. This pathway is key, as melanomas that have a BRAF V600E and kinase mutation continue to proliferate due to the constitutive activation of MEK1 and MEK2, further promoting cellular proliferation. Cobimetinib is approved for the treatment of melanoma in patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in conjunction with vemurafenib. Zelboraf (vemurafenib)(Genentech USA, Inc), another inhibitor of BRAF V600E, also is used for the treatment of unresectable melanomas and was initially approved in 2011.⁵

BRAF is a serine/threonine protein kinase. When unregulated, it results in the deregulation of cell proliferation. According to Ascierto et al,⁶ 50% of melanomas have a BRAF mutation, with nearly 90% of them with a V600E mutation. Hence, since the advent of direct chemotherapeutic agents such as BRAF inhibitors, clinical trials have shown notable reduction in mortality and morbidity of melanoma patients with BRAF mutations.⁶

Imlygic (talimogene laherparepvec)(Amgen, Inc) is a modified oncolytic viral therapy.⁷ This treatment was approved by the FDA in 2015 and replicates within tumors to produce granulocyte-macrophage colony-stimulating factor protein, which promotes an antitumor immune response within unresectable cutaneous, subcutaneous, and nodal melanoma lesions. Although it is not a gene-directed therapy, the melanoma does not require a specific mutation for treatment. Again, this medication is better served in conjunction with other melanoma chemotherapeutic and surgical interventions.

Submental Fat

Kybella (deoxycholic acid)(Allergan) is a nonhuman, nonanimal, synthetically created compound that is naturally found within the human body for the breakdown and absorption of dietary fat.⁸ This drug was FDA approved in 2015 for the improvement of the appearance of moderate subcutaneous fat under the chin. Patients are evaluated in clinic to determine if the submental fat would be responsive to an injectable or require more radical surgical intervention based on desired outcomes. The treatment is administered as 0.2-mL injections (up to a total of 10 mL) spaced 1-cm apart and ideally is repeated at regular intervals to evaluate for efficacy.

Basal Cell Carcinoma

Odomzo (sonidegib)(Novartis Corporation) was FDA approved in 2015 for locally advanced basal cell carcinoma.⁹ Odomzo is a smoothened antagonist that inhibits the hedgehog signaling pathway. Smoothened is a transmembrane protein that allows for signal transduction of hedgehog proteins.¹⁰ Protein patched homolog 1 binds to smoothened protein and prevents the signal transduction through the cell for Gli family zinc factor 1 to continue protein translation; however, when PTCH is mutated and can no longer bind to smoothened, tumor formation results, specifically basal cell carcinoma. Hence, sonidegib is for the treatment of basal cell carcinomas that have persisted despite radiation treatment and/or surgery as well as for patients who have multiple basal cell carcinomas that can no longer be treated with surgery or radiation.

Final Thoughts

Overall, although there are several medications that can be used in conjunction for treatment of dermatological conditions, it always is recommended to know what is in the pipeline as FDA-approved medications for dermatology.

CenterWatch (http://www.centerwatch.com/) is an online resource that provides directories, analysis, and market research of medications that are either under clinical evaluation or available for use in patients. A list of currently approved drugs by the US Food and Drug Administration (FDA) also is available by specialty. It is important for dermatologists in-training to know about recently approved drugs and those that are in the pipeline, as these treatments may benefit patients who are unresponsive to other previously used medications. New drugs also may be useful for physicians who have a difficult time getting insurance to cover prescriptions for their patients, as most new medications have built-in patient assistance.

New Drugs in Dermatology

Actinic Keratosis

Ameluz (aminolevulinic acid hydrochloride)(Biofrontera AG) is a new drug that was approved in May 2016 for treatment of mild to moderate actinic keratosis on the face and scalp.¹ It is only intended for in-office use on patients who may not be candidates for other treatment options for actinic keratosis. The product is a gel formulation that should be applied to cover the lesions and approximately 5 mm of the surrounding area with a film of approximately 1-mm thickness. The entire treatment area is then illuminated with a red light source, either with a narrow spectrum around 630 nm with a light dose of approximately 37 J/cm² or a broader and continuous spectrum in the range of 570 to 670 nm with a light dose between 75 and 200 J/cm².¹ Similar to the previously used aminolevulinic acid treatment method for actinic keratosis, the patient may experience a burning stinging sensation throughout the treatment and the skin will then proceed to peel.

Psoriasis and Psoriatic Arthritis

Taltz (ixekizumab)(Eli Lilly and Company) was approved by the FDA in March 2016 for the treatment of moderate to severe plaque psoriasis.² It is a humanized IL-17A antagonist that works when IgG4 monoclonal antibodies selectively bind with IL-17A cytokines and inhibit their interaction with the IL-17 receptor. Although this injectable medication is approved for the treatment of psoriasis, it also can potentially be used off label for the treatment of psoriatic arthritis and rheumatoid arthritis. The approved dosage is 160 mg (two 80-mg injections) at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.² Injectable immunomodulatory medications such as ixekizumab are ideal for patients in whom topical treatments and light therapy failed and they continue to have serious psoriatic discomfort as well as for those who have substantial body surface area coverage.

Melanoma

Cotellic (cobimetinib)(Genentech USA, Inc) was FDA approved in November 2015.⁴ Cobimetinib is a reversible inhibitor of mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase 1. Mitogen-activated protein kinase MEK1 and MEK2 are regulators of the extracellular signal-­related kinase pathway, which promotes cellular proliferation. This pathway is key, as melanomas that have a BRAF V600E and kinase mutation continue to proliferate due to the constitutive activation of MEK1 and MEK2, further promoting cellular proliferation. Cobimetinib is approved for the treatment of melanoma in patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in conjunction with vemurafenib. Zelboraf (vemurafenib)(Genentech USA, Inc), another inhibitor of BRAF V600E, also is used for the treatment of unresectable melanomas and was initially approved in 2011.⁵

BRAF is a serine/threonine protein kinase. When unregulated, it results in the deregulation of cell proliferation. According to Ascierto et al,⁶ 50% of melanomas have a BRAF mutation, with nearly 90% of them with a V600E mutation. Hence, since the advent of direct chemotherapeutic agents such as BRAF inhibitors, clinical trials have shown notable reduction in mortality and morbidity of melanoma patients with BRAF mutations.⁶

Imlygic (talimogene laherparepvec)(Amgen, Inc) is a modified oncolytic viral therapy.⁷ This treatment was approved by the FDA in 2015 and replicates within tumors to produce granulocyte-macrophage colony-stimulating factor protein, which promotes an antitumor immune response within unresectable cutaneous, subcutaneous, and nodal melanoma lesions. Although it is not a gene-directed therapy, the melanoma does not require a specific mutation for treatment. Again, this medication is better served in conjunction with other melanoma chemotherapeutic and surgical interventions.

Submental Fat

Kybella (deoxycholic acid)(Allergan) is a nonhuman, nonanimal, synthetically created compound that is naturally found within the human body for the breakdown and absorption of dietary fat.⁸ This drug was FDA approved in 2015 for the improvement of the appearance of moderate subcutaneous fat under the chin. Patients are evaluated in clinic to determine if the submental fat would be responsive to an injectable or require more radical surgical intervention based on desired outcomes. The treatment is administered as 0.2-mL injections (up to a total of 10 mL) spaced 1-cm apart and ideally is repeated at regular intervals to evaluate for efficacy.

Basal Cell Carcinoma

Odomzo (sonidegib)(Novartis Corporation) was FDA approved in 2015 for locally advanced basal cell carcinoma.⁹ Odomzo is a smoothened antagonist that inhibits the hedgehog signaling pathway. Smoothened is a transmembrane protein that allows for signal transduction of hedgehog proteins.¹⁰ Protein patched homolog 1 binds to smoothened protein and prevents the signal transduction through the cell for Gli family zinc factor 1 to continue protein translation; however, when PTCH is mutated and can no longer bind to smoothened, tumor formation results, specifically basal cell carcinoma. Hence, sonidegib is for the treatment of basal cell carcinomas that have persisted despite radiation treatment and/or surgery as well as for patients who have multiple basal cell carcinomas that can no longer be treated with surgery or radiation.

Final Thoughts

Overall, although there are several medications that can be used in conjunction for treatment of dermatological conditions, it always is recommended to know what is in the pipeline as FDA-approved medications for dermatology.

CenterWatch (http://www.centerwatch.com/) is an online resource that provides directories, analysis, and market research of medications that are either under clinical evaluation or available for use in patients. A list of currently approved drugs by the US Food and Drug Administration (FDA) also is available by specialty. It is important for dermatologists in-training to know about recently approved drugs and those that are in the pipeline, as these treatments may benefit patients who are unresponsive to other previously used medications. New drugs also may be useful for physicians who have a difficult time getting insurance to cover prescriptions for their patients, as most new medications have built-in patient assistance.

New Drugs in Dermatology

Actinic Keratosis

Ameluz (aminolevulinic acid hydrochloride)(Biofrontera AG) is a new drug that was approved in May 2016 for treatment of mild to moderate actinic keratosis on the face and scalp.¹ It is only intended for in-office use on patients who may not be candidates for other treatment options for actinic keratosis. The product is a gel formulation that should be applied to cover the lesions and approximately 5 mm of the surrounding area with a film of approximately 1-mm thickness. The entire treatment area is then illuminated with a red light source, either with a narrow spectrum around 630 nm with a light dose of approximately 37 J/cm² or a broader and continuous spectrum in the range of 570 to 670 nm with a light dose between 75 and 200 J/cm².¹ Similar to the previously used aminolevulinic acid treatment method for actinic keratosis, the patient may experience a burning stinging sensation throughout the treatment and the skin will then proceed to peel.

Psoriasis and Psoriatic Arthritis

Taltz (ixekizumab)(Eli Lilly and Company) was approved by the FDA in March 2016 for the treatment of moderate to severe plaque psoriasis.² It is a humanized IL-17A antagonist that works when IgG4 monoclonal antibodies selectively bind with IL-17A cytokines and inhibit their interaction with the IL-17 receptor. Although this injectable medication is approved for the treatment of psoriasis, it also can potentially be used off label for the treatment of psoriatic arthritis and rheumatoid arthritis. The approved dosage is 160 mg (two 80-mg injections) at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.² Injectable immunomodulatory medications such as ixekizumab are ideal for patients in whom topical treatments and light therapy failed and they continue to have serious psoriatic discomfort as well as for those who have substantial body surface area coverage.

Melanoma

Cotellic (cobimetinib)(Genentech USA, Inc) was FDA approved in November 2015.⁴ Cobimetinib is a reversible inhibitor of mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase 1. Mitogen-activated protein kinase MEK1 and MEK2 are regulators of the extracellular signal-­related kinase pathway, which promotes cellular proliferation. This pathway is key, as melanomas that have a BRAF V600E and kinase mutation continue to proliferate due to the constitutive activation of MEK1 and MEK2, further promoting cellular proliferation. Cobimetinib is approved for the treatment of melanoma in patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in conjunction with vemurafenib. Zelboraf (vemurafenib)(Genentech USA, Inc), another inhibitor of BRAF V600E, also is used for the treatment of unresectable melanomas and was initially approved in 2011.⁵

BRAF is a serine/threonine protein kinase. When unregulated, it results in the deregulation of cell proliferation. According to Ascierto et al,⁶ 50% of melanomas have a BRAF mutation, with nearly 90% of them with a V600E mutation. Hence, since the advent of direct chemotherapeutic agents such as BRAF inhibitors, clinical trials have shown notable reduction in mortality and morbidity of melanoma patients with BRAF mutations.⁶

Imlygic (talimogene laherparepvec)(Amgen, Inc) is a modified oncolytic viral therapy.⁷ This treatment was approved by the FDA in 2015 and replicates within tumors to produce granulocyte-macrophage colony-stimulating factor protein, which promotes an antitumor immune response within unresectable cutaneous, subcutaneous, and nodal melanoma lesions. Although it is not a gene-directed therapy, the melanoma does not require a specific mutation for treatment. Again, this medication is better served in conjunction with other melanoma chemotherapeutic and surgical interventions.

Submental Fat

Kybella (deoxycholic acid)(Allergan) is a nonhuman, nonanimal, synthetically created compound that is naturally found within the human body for the breakdown and absorption of dietary fat.⁸ This drug was FDA approved in 2015 for the improvement of the appearance of moderate subcutaneous fat under the chin. Patients are evaluated in clinic to determine if the submental fat would be responsive to an injectable or require more radical surgical intervention based on desired outcomes. The treatment is administered as 0.2-mL injections (up to a total of 10 mL) spaced 1-cm apart and ideally is repeated at regular intervals to evaluate for efficacy.

Basal Cell Carcinoma

Odomzo (sonidegib)(Novartis Corporation) was FDA approved in 2015 for locally advanced basal cell carcinoma.⁹ Odomzo is a smoothened antagonist that inhibits the hedgehog signaling pathway. Smoothened is a transmembrane protein that allows for signal transduction of hedgehog proteins.¹⁰ Protein patched homolog 1 binds to smoothened protein and prevents the signal transduction through the cell for Gli family zinc factor 1 to continue protein translation; however, when PTCH is mutated and can no longer bind to smoothened, tumor formation results, specifically basal cell carcinoma. Hence, sonidegib is for the treatment of basal cell carcinomas that have persisted despite radiation treatment and/or surgery as well as for patients who have multiple basal cell carcinomas that can no longer be treated with surgery or radiation.

Final Thoughts

Overall, although there are several medications that can be used in conjunction for treatment of dermatological conditions, it always is recommended to know what is in the pipeline as FDA-approved medications for dermatology.

The Diagnosis: Epidermotropic CD8⁺ T-Cell Lymphoma

Epidermotropic CD8⁺ T-cell lymphoma is a rare aggressive form of cutaneous T-cell lymphoma (CTCL), accounting for less than 1% of all cases.¹ Since this subtype of CTCL was first described in 1999 by Berti et al,² approximately 45 cases have been reported in the literature.¹ It typically is found in elderly men and presents as disseminated or localized papules, patches, plaques, nodules, and tumors, often with central necrosis, ulceration, crusting, and hemorrhage (Figure 1).^1,3 These lesions rapidly progress and can affect any skin site, but acral accentuation and mucosal involvement are common.⁴ Due to the rapidly progressive nature of this disease, patients typically present with widespread plaque- and tumor-stage disease.³ Frequency of systemic spread is high, with metastasis to the central nervous system, lungs, and testes being most common. Lymph nodes typically are spared, helping to differentiate this form of CTCL from classic mycosis fungoides.

Diagnosis of epidermotropic CD8⁺ T-cell lymphoma is based on a combination of clinical, histopathologic, and immunohistochemical features. Histopathologic components include epidermotropism, particularly in the basal cell layer, in a pagetoid or linear pattern. A second feature is a dermal infiltrate consisting of a nodular or diffuse pattern of atypical lymphocytes that extend to the subcutaneous fat (Figure 2). All cases of epidermotropic CD8⁺ T-cell lymphoma express the CD8⁺ phenotype and most have a high Ki-67 proliferation index and are CD3, CD45RA, and/or T-cell intracellular antigen 1 positive.¹

Due to its aggressive nature, epidermotropic CD8⁺ T-cell lymphoma has a poor prognosis, with an average 5-year survival rate of 18% and median survival of 22.5 months.³ Treatment proves difficult as conventional therapies for CD4⁺ CTCL have proven ineffective for epidermotropic CD8⁺ T-cell lymphoma. Partial response has been seen with bexarotene alone and with total skin electron beam therapy combined with oral retinoids.¹

The Diagnosis: Epidermotropic CD8⁺ T-Cell Lymphoma

Epidermotropic CD8⁺ T-cell lymphoma is a rare aggressive form of cutaneous T-cell lymphoma (CTCL), accounting for less than 1% of all cases.¹ Since this subtype of CTCL was first described in 1999 by Berti et al,² approximately 45 cases have been reported in the literature.¹ It typically is found in elderly men and presents as disseminated or localized papules, patches, plaques, nodules, and tumors, often with central necrosis, ulceration, crusting, and hemorrhage (Figure 1).^1,3 These lesions rapidly progress and can affect any skin site, but acral accentuation and mucosal involvement are common.⁴ Due to the rapidly progressive nature of this disease, patients typically present with widespread plaque- and tumor-stage disease.³ Frequency of systemic spread is high, with metastasis to the central nervous system, lungs, and testes being most common. Lymph nodes typically are spared, helping to differentiate this form of CTCL from classic mycosis fungoides.

Diagnosis of epidermotropic CD8⁺ T-cell lymphoma is based on a combination of clinical, histopathologic, and immunohistochemical features. Histopathologic components include epidermotropism, particularly in the basal cell layer, in a pagetoid or linear pattern. A second feature is a dermal infiltrate consisting of a nodular or diffuse pattern of atypical lymphocytes that extend to the subcutaneous fat (Figure 2). All cases of epidermotropic CD8⁺ T-cell lymphoma express the CD8⁺ phenotype and most have a high Ki-67 proliferation index and are CD3, CD45RA, and/or T-cell intracellular antigen 1 positive.¹

Due to its aggressive nature, epidermotropic CD8⁺ T-cell lymphoma has a poor prognosis, with an average 5-year survival rate of 18% and median survival of 22.5 months.³ Treatment proves difficult as conventional therapies for CD4⁺ CTCL have proven ineffective for epidermotropic CD8⁺ T-cell lymphoma. Partial response has been seen with bexarotene alone and with total skin electron beam therapy combined with oral retinoids.¹

The Diagnosis: Epidermotropic CD8⁺ T-Cell Lymphoma

Epidermotropic CD8⁺ T-cell lymphoma is a rare aggressive form of cutaneous T-cell lymphoma (CTCL), accounting for less than 1% of all cases.¹ Since this subtype of CTCL was first described in 1999 by Berti et al,² approximately 45 cases have been reported in the literature.¹ It typically is found in elderly men and presents as disseminated or localized papules, patches, plaques, nodules, and tumors, often with central necrosis, ulceration, crusting, and hemorrhage (Figure 1).^1,3 These lesions rapidly progress and can affect any skin site, but acral accentuation and mucosal involvement are common.⁴ Due to the rapidly progressive nature of this disease, patients typically present with widespread plaque- and tumor-stage disease.³ Frequency of systemic spread is high, with metastasis to the central nervous system, lungs, and testes being most common. Lymph nodes typically are spared, helping to differentiate this form of CTCL from classic mycosis fungoides.

Diagnosis of epidermotropic CD8⁺ T-cell lymphoma is based on a combination of clinical, histopathologic, and immunohistochemical features. Histopathologic components include epidermotropism, particularly in the basal cell layer, in a pagetoid or linear pattern. A second feature is a dermal infiltrate consisting of a nodular or diffuse pattern of atypical lymphocytes that extend to the subcutaneous fat (Figure 2). All cases of epidermotropic CD8⁺ T-cell lymphoma express the CD8⁺ phenotype and most have a high Ki-67 proliferation index and are CD3, CD45RA, and/or T-cell intracellular antigen 1 positive.¹

Due to its aggressive nature, epidermotropic CD8⁺ T-cell lymphoma has a poor prognosis, with an average 5-year survival rate of 18% and median survival of 22.5 months.³ Treatment proves difficult as conventional therapies for CD4⁺ CTCL have proven ineffective for epidermotropic CD8⁺ T-cell lymphoma. Partial response has been seen with bexarotene alone and with total skin electron beam therapy combined with oral retinoids.¹

I heard Marty Makary, MD, speak at the annual meeting of the American College of Mohs Surgery (ACMS) a few months ago, and got to meet with him there. He is the author of the book “Unaccountable: What Hospitals Won’t Tell You and How Transparency Can Revolutionize Health Care,” published in 2013, and is a potent advocate for physicians, patients, and effective, safe, and efficient medical care.

His personal epiphany centered around the stubborn, continued use of open colonic resection of polyps by one of his professors, despite the availability of much safer and less expensive endoscopic removal. He is a powerful advocate for abandoning obsolete treatment techniques for safer and more effective ones. He insists on transparency in selecting the best treatments for patients.

Dr. Coldiron is past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics.

I heard Marty Makary, MD, speak at the annual meeting of the American College of Mohs Surgery (ACMS) a few months ago, and got to meet with him there. He is the author of the book “Unaccountable: What Hospitals Won’t Tell You and How Transparency Can Revolutionize Health Care,” published in 2013, and is a potent advocate for physicians, patients, and effective, safe, and efficient medical care.

His personal epiphany centered around the stubborn, continued use of open colonic resection of polyps by one of his professors, despite the availability of much safer and less expensive endoscopic removal. He is a powerful advocate for abandoning obsolete treatment techniques for safer and more effective ones. He insists on transparency in selecting the best treatments for patients.

Dr. Coldiron is past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics.

I heard Marty Makary, MD, speak at the annual meeting of the American College of Mohs Surgery (ACMS) a few months ago, and got to meet with him there. He is the author of the book “Unaccountable: What Hospitals Won’t Tell You and How Transparency Can Revolutionize Health Care,” published in 2013, and is a potent advocate for physicians, patients, and effective, safe, and efficient medical care.

His personal epiphany centered around the stubborn, continued use of open colonic resection of polyps by one of his professors, despite the availability of much safer and less expensive endoscopic removal. He is a powerful advocate for abandoning obsolete treatment techniques for safer and more effective ones. He insists on transparency in selecting the best treatments for patients.

Dr. Coldiron is past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics.

Nineteen percent of Merkel cell carcinomas are not driven by the Merkel cell polyomavirus and are substantially more aggressive than those that are virus positive, according to a report published online in the Journal of Investigative Dermatology.

This and other findings from a retrospective analysis of samples from 282 Merkel cell carcinomas in a Seattle repository “suggest that it may be clinically indicated to determine tumor viral status at the time of diagnosis, as the results may affect prognosis as well as optimal clinical management,” wrote Ata Moshiri, MD, who was with the University of Washington, Seattle, at the time of the study, and his associates.

Wikimedia Commons/Ed Uthman/CC BY-SA 2.0

The National Institutes of Health, the Colin Johnston Fund, and the Janet Canning Fund supported the study. Dr. Moshiri reported having no relevant financial disclosures; one of his associates reported that her institute received research funding from Valeant and Pfizer unrelated to this work.

Nineteen percent of Merkel cell carcinomas are not driven by the Merkel cell polyomavirus and are substantially more aggressive than those that are virus positive, according to a report published online in the Journal of Investigative Dermatology.

This and other findings from a retrospective analysis of samples from 282 Merkel cell carcinomas in a Seattle repository “suggest that it may be clinically indicated to determine tumor viral status at the time of diagnosis, as the results may affect prognosis as well as optimal clinical management,” wrote Ata Moshiri, MD, who was with the University of Washington, Seattle, at the time of the study, and his associates.

Wikimedia Commons/Ed Uthman/CC BY-SA 2.0

The National Institutes of Health, the Colin Johnston Fund, and the Janet Canning Fund supported the study. Dr. Moshiri reported having no relevant financial disclosures; one of his associates reported that her institute received research funding from Valeant and Pfizer unrelated to this work.

Nineteen percent of Merkel cell carcinomas are not driven by the Merkel cell polyomavirus and are substantially more aggressive than those that are virus positive, according to a report published online in the Journal of Investigative Dermatology.

This and other findings from a retrospective analysis of samples from 282 Merkel cell carcinomas in a Seattle repository “suggest that it may be clinically indicated to determine tumor viral status at the time of diagnosis, as the results may affect prognosis as well as optimal clinical management,” wrote Ata Moshiri, MD, who was with the University of Washington, Seattle, at the time of the study, and his associates.

Wikimedia Commons/Ed Uthman/CC BY-SA 2.0

The National Institutes of Health, the Colin Johnston Fund, and the Janet Canning Fund supported the study. Dr. Moshiri reported having no relevant financial disclosures; one of his associates reported that her institute received research funding from Valeant and Pfizer unrelated to this work.

To the Editor:

Prior studies have assessed the quality of text-based dermatology information on the Internet using traditional search engine queries.¹ However, little is understood about the sources, accuracy, and quality of online dermatology images derived from direct image searches. Previous work has shown that direct search engine image queries were largely accurate for 3 pediatric dermatology diagnosis searches: atopic dermatitis, lichen striatus, and subcutaneous fat necrosis.² We assessed images obtained for common dermatologic conditions from a Google image search (GIS) compared to a traditional text-based Google web search (GWS).

Image results for 32 unique dermatologic search terms were analyzed (Table 1). These search terms were selected using the results of a prior study that identified the most common dermatologic diagnoses that led users to the 2 most popular dermatology-specific websites worldwide: the American Academy of Dermatology (www.aad.org) and DermNet New Zealand (www.dermnetnz.org).³ The Alexa directory (www.alexa.com), a large publicly available Internet analytics resource, was used to determine the most common dermatology search terms that led a user to either www.dermnetnz.org or www.aad.org. In addition, searches for the 3 most common types of skin cancer—melanoma, squamous cell carcinoma, and basal cell carcinoma—were included. Each term was entered into a GIS and a GWS. The first 10 results, which represent 92% of the websites ultimately visited by users,⁴ were analyzed. The source, diagnostic accuracy, and Fitzpatrick skin type of the images was determined. Website sources were organized into 11 categories. All data collection occurred within a 1-week period in August 2015.

A total of 320 images were analyzed. In the GIS, private websites (36%), dermatology association websites (28%), and general health information websites (10%) were the 3 most common sources. In the GWS, health information websites (35%), private websites (21%), and dermatology association websites (20%) accounted for the most common sources (Table 2). The majority of images were of Fitzpatrick skin types I and II (89%) and nearly all images were diagnostically accurate (98%). There was no statistically significant difference in accuracy of diagnosis between physician-associated websites (100% accuracy) versus nonphysician-associated sites (98% accuracy, P=.25).

Our results showed high diagnostic accuracy among the top GIS results for common dermatology search terms. Diagnostic accuracy did not vary between websites that were physician associated versus those that were not. Our results are comparable to the reported accuracy of online dermatologic health information.¹ In GIS results, the majority of images were provided by private websites, whereas the top websites in GWS results were health information websites.

Only 1% of images were of Fitzpatrick skin types VI and VII. Presentation of skin diseases is remarkably different based on the patient’s skin type.⁵ The shortage of readily accessible images of skin of color is in line with the lack of familiarity physicians and trainees have with dermatologic conditions in ethnic skin.⁶

Based on the results from this analysis, providers and patients searching for dermatologic conditions via a direct GIS should be cognizant of several considerations. Although our results showed that GIS was accurate, the searcher should note that image-based searches are not accompanied by relevant text that can help confirm relevancy and accuracy. Image searches depend on textual tags added by the source website. Websites that represent dermatological associations and academic centers can add an additional layer of confidence for users. Patients and clinicians also should be aware that the consideration of a patient’s Fitzpatrick skin type is critical when assessing the relevancy of a GIS result. In conclusion, search results via GIS queries are accurate for the dermatological diagnoses tested but may be lacking in skin of color variations, suggesting a potential unmet need based on our growing ethnic skin population.

To the Editor:

Prior studies have assessed the quality of text-based dermatology information on the Internet using traditional search engine queries.¹ However, little is understood about the sources, accuracy, and quality of online dermatology images derived from direct image searches. Previous work has shown that direct search engine image queries were largely accurate for 3 pediatric dermatology diagnosis searches: atopic dermatitis, lichen striatus, and subcutaneous fat necrosis.² We assessed images obtained for common dermatologic conditions from a Google image search (GIS) compared to a traditional text-based Google web search (GWS).

Image results for 32 unique dermatologic search terms were analyzed (Table 1). These search terms were selected using the results of a prior study that identified the most common dermatologic diagnoses that led users to the 2 most popular dermatology-specific websites worldwide: the American Academy of Dermatology (www.aad.org) and DermNet New Zealand (www.dermnetnz.org).³ The Alexa directory (www.alexa.com), a large publicly available Internet analytics resource, was used to determine the most common dermatology search terms that led a user to either www.dermnetnz.org or www.aad.org. In addition, searches for the 3 most common types of skin cancer—melanoma, squamous cell carcinoma, and basal cell carcinoma—were included. Each term was entered into a GIS and a GWS. The first 10 results, which represent 92% of the websites ultimately visited by users,⁴ were analyzed. The source, diagnostic accuracy, and Fitzpatrick skin type of the images was determined. Website sources were organized into 11 categories. All data collection occurred within a 1-week period in August 2015.

A total of 320 images were analyzed. In the GIS, private websites (36%), dermatology association websites (28%), and general health information websites (10%) were the 3 most common sources. In the GWS, health information websites (35%), private websites (21%), and dermatology association websites (20%) accounted for the most common sources (Table 2). The majority of images were of Fitzpatrick skin types I and II (89%) and nearly all images were diagnostically accurate (98%). There was no statistically significant difference in accuracy of diagnosis between physician-associated websites (100% accuracy) versus nonphysician-associated sites (98% accuracy, P=.25).

Our results showed high diagnostic accuracy among the top GIS results for common dermatology search terms. Diagnostic accuracy did not vary between websites that were physician associated versus those that were not. Our results are comparable to the reported accuracy of online dermatologic health information.¹ In GIS results, the majority of images were provided by private websites, whereas the top websites in GWS results were health information websites.

Only 1% of images were of Fitzpatrick skin types VI and VII. Presentation of skin diseases is remarkably different based on the patient’s skin type.⁵ The shortage of readily accessible images of skin of color is in line with the lack of familiarity physicians and trainees have with dermatologic conditions in ethnic skin.⁶

Based on the results from this analysis, providers and patients searching for dermatologic conditions via a direct GIS should be cognizant of several considerations. Although our results showed that GIS was accurate, the searcher should note that image-based searches are not accompanied by relevant text that can help confirm relevancy and accuracy. Image searches depend on textual tags added by the source website. Websites that represent dermatological associations and academic centers can add an additional layer of confidence for users. Patients and clinicians also should be aware that the consideration of a patient’s Fitzpatrick skin type is critical when assessing the relevancy of a GIS result. In conclusion, search results via GIS queries are accurate for the dermatological diagnoses tested but may be lacking in skin of color variations, suggesting a potential unmet need based on our growing ethnic skin population.

To the Editor:

Prior studies have assessed the quality of text-based dermatology information on the Internet using traditional search engine queries.¹ However, little is understood about the sources, accuracy, and quality of online dermatology images derived from direct image searches. Previous work has shown that direct search engine image queries were largely accurate for 3 pediatric dermatology diagnosis searches: atopic dermatitis, lichen striatus, and subcutaneous fat necrosis.² We assessed images obtained for common dermatologic conditions from a Google image search (GIS) compared to a traditional text-based Google web search (GWS).

Image results for 32 unique dermatologic search terms were analyzed (Table 1). These search terms were selected using the results of a prior study that identified the most common dermatologic diagnoses that led users to the 2 most popular dermatology-specific websites worldwide: the American Academy of Dermatology (www.aad.org) and DermNet New Zealand (www.dermnetnz.org).³ The Alexa directory (www.alexa.com), a large publicly available Internet analytics resource, was used to determine the most common dermatology search terms that led a user to either www.dermnetnz.org or www.aad.org. In addition, searches for the 3 most common types of skin cancer—melanoma, squamous cell carcinoma, and basal cell carcinoma—were included. Each term was entered into a GIS and a GWS. The first 10 results, which represent 92% of the websites ultimately visited by users,⁴ were analyzed. The source, diagnostic accuracy, and Fitzpatrick skin type of the images was determined. Website sources were organized into 11 categories. All data collection occurred within a 1-week period in August 2015.

A total of 320 images were analyzed. In the GIS, private websites (36%), dermatology association websites (28%), and general health information websites (10%) were the 3 most common sources. In the GWS, health information websites (35%), private websites (21%), and dermatology association websites (20%) accounted for the most common sources (Table 2). The majority of images were of Fitzpatrick skin types I and II (89%) and nearly all images were diagnostically accurate (98%). There was no statistically significant difference in accuracy of diagnosis between physician-associated websites (100% accuracy) versus nonphysician-associated sites (98% accuracy, P=.25).

Our results showed high diagnostic accuracy among the top GIS results for common dermatology search terms. Diagnostic accuracy did not vary between websites that were physician associated versus those that were not. Our results are comparable to the reported accuracy of online dermatologic health information.¹ In GIS results, the majority of images were provided by private websites, whereas the top websites in GWS results were health information websites.

Only 1% of images were of Fitzpatrick skin types VI and VII. Presentation of skin diseases is remarkably different based on the patient’s skin type.⁵ The shortage of readily accessible images of skin of color is in line with the lack of familiarity physicians and trainees have with dermatologic conditions in ethnic skin.⁶

Based on the results from this analysis, providers and patients searching for dermatologic conditions via a direct GIS should be cognizant of several considerations. Although our results showed that GIS was accurate, the searcher should note that image-based searches are not accompanied by relevant text that can help confirm relevancy and accuracy. Image searches depend on textual tags added by the source website. Websites that represent dermatological associations and academic centers can add an additional layer of confidence for users. Patients and clinicians also should be aware that the consideration of a patient’s Fitzpatrick skin type is critical when assessing the relevancy of a GIS result. In conclusion, search results via GIS queries are accurate for the dermatological diagnoses tested but may be lacking in skin of color variations, suggesting a potential unmet need based on our growing ethnic skin population.

To the Editor:

A recent Cutis article, “Merkel Cell Carcinoma in a Vein Graft Donor Site” (Cutis. 2016;97:364-367), highlighted the localization of a Merkel cell carcinoma (MCC) within a well-healed scar resulting from a vein harvesting procedure performed 18 years prior to presentation. Their discussion focused on factors that may have contributed to the development of the MCC at that specific location. As noted by the authors, this case does not classically fit under the umbrella of a Marjolin ulcer given the stable, well-healed clinical appearance of the scar. We agree and believe it is not secondary to chance either but consistent with Wolf isotopic response.

This concept was originally described by Wyburn-Mason in 1955¹ and later revived by Wolf et al.² Wolf isotopic response describes the development of dermatologic disorders that localize to a site of another distinct and clinically healed skin disorder. Originally, it was reserved for infections, malignancies, and immune conditions restricted to a site of a prior herpetic infection but recently has been expanded to encompass other primary nonherpesvirus-related skin disorders. The pathophysiology behind this phenomenon is unknown but thought to be the interplay of several key elements including immune dysregulation, neural, vascular, and locus minoris resistentiae (ie, a site of lessened resistance).³ Immunosuppression is a known risk factor in the development of MCCs,⁴ thus the proposed local immune dysregulation within a scar may alter the virus-host balance and foster the oncogenic nature of the MCC polyomavirus. A recent article describes another case of an MCC arising within a sternotomy scar,⁵ lending further credibility to a skin vulnerability philosophy. These cases provide further insight into the pathomechanisms involved in the development of this rare and aggressive neoplasm and sheds light on an intriguing dermatologic phenomenon.

To the Editor:

A recent Cutis article, “Merkel Cell Carcinoma in a Vein Graft Donor Site” (Cutis. 2016;97:364-367), highlighted the localization of a Merkel cell carcinoma (MCC) within a well-healed scar resulting from a vein harvesting procedure performed 18 years prior to presentation. Their discussion focused on factors that may have contributed to the development of the MCC at that specific location. As noted by the authors, this case does not classically fit under the umbrella of a Marjolin ulcer given the stable, well-healed clinical appearance of the scar. We agree and believe it is not secondary to chance either but consistent with Wolf isotopic response.

This concept was originally described by Wyburn-Mason in 1955¹ and later revived by Wolf et al.² Wolf isotopic response describes the development of dermatologic disorders that localize to a site of another distinct and clinically healed skin disorder. Originally, it was reserved for infections, malignancies, and immune conditions restricted to a site of a prior herpetic infection but recently has been expanded to encompass other primary nonherpesvirus-related skin disorders. The pathophysiology behind this phenomenon is unknown but thought to be the interplay of several key elements including immune dysregulation, neural, vascular, and locus minoris resistentiae (ie, a site of lessened resistance).³ Immunosuppression is a known risk factor in the development of MCCs,⁴ thus the proposed local immune dysregulation within a scar may alter the virus-host balance and foster the oncogenic nature of the MCC polyomavirus. A recent article describes another case of an MCC arising within a sternotomy scar,⁵ lending further credibility to a skin vulnerability philosophy. These cases provide further insight into the pathomechanisms involved in the development of this rare and aggressive neoplasm and sheds light on an intriguing dermatologic phenomenon.

To the Editor:

A recent Cutis article, “Merkel Cell Carcinoma in a Vein Graft Donor Site” (Cutis. 2016;97:364-367), highlighted the localization of a Merkel cell carcinoma (MCC) within a well-healed scar resulting from a vein harvesting procedure performed 18 years prior to presentation. Their discussion focused on factors that may have contributed to the development of the MCC at that specific location. As noted by the authors, this case does not classically fit under the umbrella of a Marjolin ulcer given the stable, well-healed clinical appearance of the scar. We agree and believe it is not secondary to chance either but consistent with Wolf isotopic response.

This concept was originally described by Wyburn-Mason in 1955¹ and later revived by Wolf et al.² Wolf isotopic response describes the development of dermatologic disorders that localize to a site of another distinct and clinically healed skin disorder. Originally, it was reserved for infections, malignancies, and immune conditions restricted to a site of a prior herpetic infection but recently has been expanded to encompass other primary nonherpesvirus-related skin disorders. The pathophysiology behind this phenomenon is unknown but thought to be the interplay of several key elements including immune dysregulation, neural, vascular, and locus minoris resistentiae (ie, a site of lessened resistance).³ Immunosuppression is a known risk factor in the development of MCCs,⁴ thus the proposed local immune dysregulation within a scar may alter the virus-host balance and foster the oncogenic nature of the MCC polyomavirus. A recent article describes another case of an MCC arising within a sternotomy scar,⁵ lending further credibility to a skin vulnerability philosophy. These cases provide further insight into the pathomechanisms involved in the development of this rare and aggressive neoplasm and sheds light on an intriguing dermatologic phenomenon.

To the Editor:

A 34-year-old man presented with fever, easy bruising, and pancytopenia with increased peripheral blasts of 77%. Bone marrow biopsy showed hypercellular marrow with 80% to 90% involvement by acute promyelocytic leukemia (APL) with complex cytogenetics: 47,XY,t(4;17;18)(p16;q21,q25;q21.1),+8, ins(15;17)(q22;q21q25). He underwent induction chemotherapy with all-trans retinoic acid (ATRA) and idarubicin, which was complicated by differentiation syndrome that presented with fever and fluid retention. Discontinuation of ATRA and initiation of dexamethasone led to resolution of the symptoms. Complete hematologic and molecular remission was achieved after the induction chemotherapy.

Following a risk-adapted treatment protocol for consolidation therapy,¹ he underwent an uneventful first cycle of consolidation therapy. On day 15 of the second cycle of consolidation therapy with ATRA and mitoxantrone he was hospitalized with a fever (temperature, 38°C) in a setting of neutropenia (absolute neutrophil count [ANC], 0/µL [reference range, 1500–7200/µL]). He was empirically treated with ceftazidime and vancomycin and maintained on prophylactic acyclovir and fluconazole. Routine workup was negative for infection. He became afebrile within 24 hours. With negative infectious workup, vancomycin was discontinued on day 17. On day 33 he again developed a fever (temperature, 38.8°C) when the ANC started to recover (570/µL). A new skin rash was noted at this time. Physical examination revealed generalized, nonpruritic, tender, pink papules and plaques with dusky centers and central pustules on the trunk as well as the upper and lower extremities. The palms and soles were spared. The rash was somewhat reminiscent of Sweet syndrome (SS). No vesicles, bullae, or erosions were seen (Figure 1). Repeat blood and urine cultures and chest radiograph were unremarkable. Ceftazidime was discontinued due to concern of drug-associated rash. Within the next 48 hours, the patient developed rigors and a worsening rash that led to reinitiation of broad-spectrum antibiotic coverage with meropenem and vancomycin. Computed tomography of the chest, abdomen, and pelvis did not show any evidence of infection or other abnormalities. Skin biopsy showed an acute folliculitis and multiple foci of mixed granulomatous inflammation consisting of histiocytes, lymphocytes, and neutrophils with focal necrosis present in the dermis, dermis-subcutis junction, and subcutis (Figure 2). Diagnostic features of vasculitis were not seen. Viral cytopathic features were not identified. Tissue culture and special stains including Gram, acid-fast bacteria, and Grocott methenamine silver stains were negative for infectious organisms in the biopsy. Both direct fluorescent antibody study and cell cultures for varicella-zoster virus, cytomegalovirus, and herpes simplex virus also were negative.

In the absence of microorganisms on skin biopsy and low clinical suspicion of infection, vancomycin and meropenem were discontinued on day 35 and empiric treatment with oral prednisone 40 mg daily was initiated on day 38, which resulted in a rapid improvement of the patient’s rash within 24 hours with complete resolution after a 7-day course of prednisone. Notably, the patient manifested concomitant recovery of the ANC. The patient completed his last cycle of consolidation therapy with ATRA and idarubicin without further complications and remains in molecular remission.

Neutrophilic dermatoses (NDs) are a group of disorders characterized by neutrophilic cutaneous infiltration without evidence of infection. These entities include SS, pyoderma gangrenosum, subcorneal pustular dermatosis, erythema elevatum diutinum, and neutrophilic eccrine hidradenitis.² Neutrophilic dermatoses commonly present with acute onset of skin lesions and fever. Underlying systemic disease such as malignancy, inflammatory disease, autoimmune disease, pregnancy, and medications are known to be associated with ND. Although the rash clinically was reminiscent of SS, the histopathologic features were inconsistent with SS. Sweet syndrome typically presents with extensive monotonous neutrophilic infiltrates in the dermis. In this case, the neutrophilic infiltrates were localized and associated with the hair follicle, in the dermis and subcutis, and were accompanied by a granulomatous inflammation. Neutrophilic eccrine hidradenitis clinically is similar to SS and the distinction usually is made on the basis of histopathologic examination. Lack of the neutrophilic infiltrates within the eccrine secretary coils in our case did not support the diagnosis of neutrophilic eccrine hidradenitis.

Although the histopathologic features of the presented case were inconsistent with a particular subtype of ND, the clinical presentation and response to corticosteroids suggested that this unusual mixed inflammatory skin reaction might share a similar pathophysiologic mechanism.

A review of 20 patients with sterile neutrophilic folliculitis demonstrated an association with systemic diseases including cutaneous T-cell lymphoma, monoclonal gammopathy, Crohn disease, and autoimmune disorders.³ In acute myeloid leukemia, sterile neutrophilic folliculitis may be part of the initial presentation and responds to induction chemotherapy.⁴ An extensive search of PubMed articles indexed for MEDLINE using the search terms folliculitis, APL, and neutrophilic dermatoses did not reveal any prior reports of isolated neutrophilic folliculitis or mixed granulomatous reaction in patients with APL in molecular remission.

Although rare, cases of ATRA-induced SS have been reported. Some authors believe that SS in APL may represent a partial form of differentiation syndrome.⁵ Those cases usually occur during first induction. However, a recurrent episode of differentiation syndrome cannot be excluded in this patient.

A cutaneous reaction to chemotherapy with mitoxantrone as a cause also should be considered, given that the rash occurred only during the second cycle of consolidation therapy when mitoxantrone was used. However, this rash is rare in patients receiving mitoxantrone. The late onset of the rash from the time of last mitoxantrone administration argues against this diagnosis.

In summary, we describe an unusual presentation of a sterile mixed inflammatory skin reaction that occurred in a setting of neutrophil recovery following a second cycle of induction chemotherapy with ATRA and mitoxantrone for APL.

To the Editor:

A 34-year-old man presented with fever, easy bruising, and pancytopenia with increased peripheral blasts of 77%. Bone marrow biopsy showed hypercellular marrow with 80% to 90% involvement by acute promyelocytic leukemia (APL) with complex cytogenetics: 47,XY,t(4;17;18)(p16;q21,q25;q21.1),+8, ins(15;17)(q22;q21q25). He underwent induction chemotherapy with all-trans retinoic acid (ATRA) and idarubicin, which was complicated by differentiation syndrome that presented with fever and fluid retention. Discontinuation of ATRA and initiation of dexamethasone led to resolution of the symptoms. Complete hematologic and molecular remission was achieved after the induction chemotherapy.

Following a risk-adapted treatment protocol for consolidation therapy,¹ he underwent an uneventful first cycle of consolidation therapy. On day 15 of the second cycle of consolidation therapy with ATRA and mitoxantrone he was hospitalized with a fever (temperature, 38°C) in a setting of neutropenia (absolute neutrophil count [ANC], 0/µL [reference range, 1500–7200/µL]). He was empirically treated with ceftazidime and vancomycin and maintained on prophylactic acyclovir and fluconazole. Routine workup was negative for infection. He became afebrile within 24 hours. With negative infectious workup, vancomycin was discontinued on day 17. On day 33 he again developed a fever (temperature, 38.8°C) when the ANC started to recover (570/µL). A new skin rash was noted at this time. Physical examination revealed generalized, nonpruritic, tender, pink papules and plaques with dusky centers and central pustules on the trunk as well as the upper and lower extremities. The palms and soles were spared. The rash was somewhat reminiscent of Sweet syndrome (SS). No vesicles, bullae, or erosions were seen (Figure 1). Repeat blood and urine cultures and chest radiograph were unremarkable. Ceftazidime was discontinued due to concern of drug-associated rash. Within the next 48 hours, the patient developed rigors and a worsening rash that led to reinitiation of broad-spectrum antibiotic coverage with meropenem and vancomycin. Computed tomography of the chest, abdomen, and pelvis did not show any evidence of infection or other abnormalities. Skin biopsy showed an acute folliculitis and multiple foci of mixed granulomatous inflammation consisting of histiocytes, lymphocytes, and neutrophils with focal necrosis present in the dermis, dermis-subcutis junction, and subcutis (Figure 2). Diagnostic features of vasculitis were not seen. Viral cytopathic features were not identified. Tissue culture and special stains including Gram, acid-fast bacteria, and Grocott methenamine silver stains were negative for infectious organisms in the biopsy. Both direct fluorescent antibody study and cell cultures for varicella-zoster virus, cytomegalovirus, and herpes simplex virus also were negative.

In the absence of microorganisms on skin biopsy and low clinical suspicion of infection, vancomycin and meropenem were discontinued on day 35 and empiric treatment with oral prednisone 40 mg daily was initiated on day 38, which resulted in a rapid improvement of the patient’s rash within 24 hours with complete resolution after a 7-day course of prednisone. Notably, the patient manifested concomitant recovery of the ANC. The patient completed his last cycle of consolidation therapy with ATRA and idarubicin without further complications and remains in molecular remission.

Neutrophilic dermatoses (NDs) are a group of disorders characterized by neutrophilic cutaneous infiltration without evidence of infection. These entities include SS, pyoderma gangrenosum, subcorneal pustular dermatosis, erythema elevatum diutinum, and neutrophilic eccrine hidradenitis.² Neutrophilic dermatoses commonly present with acute onset of skin lesions and fever. Underlying systemic disease such as malignancy, inflammatory disease, autoimmune disease, pregnancy, and medications are known to be associated with ND. Although the rash clinically was reminiscent of SS, the histopathologic features were inconsistent with SS. Sweet syndrome typically presents with extensive monotonous neutrophilic infiltrates in the dermis. In this case, the neutrophilic infiltrates were localized and associated with the hair follicle, in the dermis and subcutis, and were accompanied by a granulomatous inflammation. Neutrophilic eccrine hidradenitis clinically is similar to SS and the distinction usually is made on the basis of histopathologic examination. Lack of the neutrophilic infiltrates within the eccrine secretary coils in our case did not support the diagnosis of neutrophilic eccrine hidradenitis.

Although the histopathologic features of the presented case were inconsistent with a particular subtype of ND, the clinical presentation and response to corticosteroids suggested that this unusual mixed inflammatory skin reaction might share a similar pathophysiologic mechanism.

A review of 20 patients with sterile neutrophilic folliculitis demonstrated an association with systemic diseases including cutaneous T-cell lymphoma, monoclonal gammopathy, Crohn disease, and autoimmune disorders.³ In acute myeloid leukemia, sterile neutrophilic folliculitis may be part of the initial presentation and responds to induction chemotherapy.⁴ An extensive search of PubMed articles indexed for MEDLINE using the search terms folliculitis, APL, and neutrophilic dermatoses did not reveal any prior reports of isolated neutrophilic folliculitis or mixed granulomatous reaction in patients with APL in molecular remission.

Although rare, cases of ATRA-induced SS have been reported. Some authors believe that SS in APL may represent a partial form of differentiation syndrome.⁵ Those cases usually occur during first induction. However, a recurrent episode of differentiation syndrome cannot be excluded in this patient.

A cutaneous reaction to chemotherapy with mitoxantrone as a cause also should be considered, given that the rash occurred only during the second cycle of consolidation therapy when mitoxantrone was used. However, this rash is rare in patients receiving mitoxantrone. The late onset of the rash from the time of last mitoxantrone administration argues against this diagnosis.

In summary, we describe an unusual presentation of a sterile mixed inflammatory skin reaction that occurred in a setting of neutrophil recovery following a second cycle of induction chemotherapy with ATRA and mitoxantrone for APL.

To the Editor:

A 34-year-old man presented with fever, easy bruising, and pancytopenia with increased peripheral blasts of 77%. Bone marrow biopsy showed hypercellular marrow with 80% to 90% involvement by acute promyelocytic leukemia (APL) with complex cytogenetics: 47,XY,t(4;17;18)(p16;q21,q25;q21.1),+8, ins(15;17)(q22;q21q25). He underwent induction chemotherapy with all-trans retinoic acid (ATRA) and idarubicin, which was complicated by differentiation syndrome that presented with fever and fluid retention. Discontinuation of ATRA and initiation of dexamethasone led to resolution of the symptoms. Complete hematologic and molecular remission was achieved after the induction chemotherapy.

Following a risk-adapted treatment protocol for consolidation therapy,¹ he underwent an uneventful first cycle of consolidation therapy. On day 15 of the second cycle of consolidation therapy with ATRA and mitoxantrone he was hospitalized with a fever (temperature, 38°C) in a setting of neutropenia (absolute neutrophil count [ANC], 0/µL [reference range, 1500–7200/µL]). He was empirically treated with ceftazidime and vancomycin and maintained on prophylactic acyclovir and fluconazole. Routine workup was negative for infection. He became afebrile within 24 hours. With negative infectious workup, vancomycin was discontinued on day 17. On day 33 he again developed a fever (temperature, 38.8°C) when the ANC started to recover (570/µL). A new skin rash was noted at this time. Physical examination revealed generalized, nonpruritic, tender, pink papules and plaques with dusky centers and central pustules on the trunk as well as the upper and lower extremities. The palms and soles were spared. The rash was somewhat reminiscent of Sweet syndrome (SS). No vesicles, bullae, or erosions were seen (Figure 1). Repeat blood and urine cultures and chest radiograph were unremarkable. Ceftazidime was discontinued due to concern of drug-associated rash. Within the next 48 hours, the patient developed rigors and a worsening rash that led to reinitiation of broad-spectrum antibiotic coverage with meropenem and vancomycin. Computed tomography of the chest, abdomen, and pelvis did not show any evidence of infection or other abnormalities. Skin biopsy showed an acute folliculitis and multiple foci of mixed granulomatous inflammation consisting of histiocytes, lymphocytes, and neutrophils with focal necrosis present in the dermis, dermis-subcutis junction, and subcutis (Figure 2). Diagnostic features of vasculitis were not seen. Viral cytopathic features were not identified. Tissue culture and special stains including Gram, acid-fast bacteria, and Grocott methenamine silver stains were negative for infectious organisms in the biopsy. Both direct fluorescent antibody study and cell cultures for varicella-zoster virus, cytomegalovirus, and herpes simplex virus also were negative.

In the absence of microorganisms on skin biopsy and low clinical suspicion of infection, vancomycin and meropenem were discontinued on day 35 and empiric treatment with oral prednisone 40 mg daily was initiated on day 38, which resulted in a rapid improvement of the patient’s rash within 24 hours with complete resolution after a 7-day course of prednisone. Notably, the patient manifested concomitant recovery of the ANC. The patient completed his last cycle of consolidation therapy with ATRA and idarubicin without further complications and remains in molecular remission.

Neutrophilic dermatoses (NDs) are a group of disorders characterized by neutrophilic cutaneous infiltration without evidence of infection. These entities include SS, pyoderma gangrenosum, subcorneal pustular dermatosis, erythema elevatum diutinum, and neutrophilic eccrine hidradenitis.² Neutrophilic dermatoses commonly present with acute onset of skin lesions and fever. Underlying systemic disease such as malignancy, inflammatory disease, autoimmune disease, pregnancy, and medications are known to be associated with ND. Although the rash clinically was reminiscent of SS, the histopathologic features were inconsistent with SS. Sweet syndrome typically presents with extensive monotonous neutrophilic infiltrates in the dermis. In this case, the neutrophilic infiltrates were localized and associated with the hair follicle, in the dermis and subcutis, and were accompanied by a granulomatous inflammation. Neutrophilic eccrine hidradenitis clinically is similar to SS and the distinction usually is made on the basis of histopathologic examination. Lack of the neutrophilic infiltrates within the eccrine secretary coils in our case did not support the diagnosis of neutrophilic eccrine hidradenitis.

Although the histopathologic features of the presented case were inconsistent with a particular subtype of ND, the clinical presentation and response to corticosteroids suggested that this unusual mixed inflammatory skin reaction might share a similar pathophysiologic mechanism.

A review of 20 patients with sterile neutrophilic folliculitis demonstrated an association with systemic diseases including cutaneous T-cell lymphoma, monoclonal gammopathy, Crohn disease, and autoimmune disorders.³ In acute myeloid leukemia, sterile neutrophilic folliculitis may be part of the initial presentation and responds to induction chemotherapy.⁴ An extensive search of PubMed articles indexed for MEDLINE using the search terms folliculitis, APL, and neutrophilic dermatoses did not reveal any prior reports of isolated neutrophilic folliculitis or mixed granulomatous reaction in patients with APL in molecular remission.

Although rare, cases of ATRA-induced SS have been reported. Some authors believe that SS in APL may represent a partial form of differentiation syndrome.⁵ Those cases usually occur during first induction. However, a recurrent episode of differentiation syndrome cannot be excluded in this patient.

A cutaneous reaction to chemotherapy with mitoxantrone as a cause also should be considered, given that the rash occurred only during the second cycle of consolidation therapy when mitoxantrone was used. However, this rash is rare in patients receiving mitoxantrone. The late onset of the rash from the time of last mitoxantrone administration argues against this diagnosis.

In summary, we describe an unusual presentation of a sterile mixed inflammatory skin reaction that occurred in a setting of neutrophil recovery following a second cycle of induction chemotherapy with ATRA and mitoxantrone for APL.