Nonmelanoma Skin Cancer

The Diagnosis: Inflammatory Urothelial Carcinoma 

Microscopic examination revealed metastatic carcinoma with extensive dermal lymphatic invasion (Figure). Immunohistochemical stains were positive for p63 and GATA3, markers for urothelial carcinomas, and negative for S-100 and Melan-A, markers for melanoma. Thus, the biopsy was compatible with a diagnosis of urothelial carcinoma. Gram and Grocott-Gomori methenamine-silver stains were negative for bacterial or fungal organisms. An additional 4-mm punch biopsy was performed of the left thigh at the distal-most aspect of the eruption to determine the extent of cutaneous metastasis. Pathology again showed metastatic urothelial carcinoma with extensive dermal lymphatic involvement and overlying epidermal spongiosis.

The patient had a history of bladder cancer diagnosed 1.5 years prior to presentation. It was a high-grade (World Health Organization) urothelial carcinoma that penetrated the bladder muscular wall, focally infiltrating into pericystic fat with multifocal seeding of pericystic lymphatics. It was unresponsive to bacillus Calmette-Guérin therapy. He underwent a cystoprostatectomy and bilateral staging lymph node dissection with clear surgical margins without adjuvant chemotherapy or radiation. He also reported a history of 2 prior cutaneous melanomas that were excised without sentinel lymph node biopsy. 

Four months prior to presentation, he developed a mildly pruritic cutaneous eruption on the abdomen that was treated with topical miconazole for presumed tinea cruris without improvement. He also was previously diagnosed with candidiasis of his urostomy and was taking oral fluconazole. The patient was admitted for the abdominal pain and distension, and computed tomography of the abdomen and pelvis revealed peritoneal carcinomatosis resulting in mechanical small bowel obstruction as well as enlarged pelvic and retroperitoneal lymph nodes. Confirmation of metastatic disease via skin biopsy avoided an invasive peritoneal biopsy. He was treated with triamcinolone acetonide ointment 0.1% with moderate relief of pruritus, and a palliative percutaneous endoscopic gastrostomy tube was placed for bowel decompression. The patient's hospital course was complicated by Proteus mirabilis bacteremia requiring cefepime. He was transitioned to home hospice and died 1 month after presentation. 

Inflammatory carcinoma, also called carcinoma erysipeloides, is a type of cutaneous metastasis most commonly seen in breast adenocarcinoma. Reported cases secondary to urothelial carcinoma are rare and most often involve the abdomen, groin, and lower extremities.^1-5 Clinically, inflammatory carcinoma presents as erythematous indurated patches or plaques with well-defined borders, often with edema, warmth, and tenderness. Its morphologic appearance is due to the obstruction of lymphatic vessels by tumor cells and the release of inflammatory cytokines. Its presentation can mimic other dermatoses such as cellulitis, erysipelas, fungal infection, radiation dermatitis, Majocchi granuloma, or contact dermatitis.⁶ Cutaneous metastases may be the first clinical manifestations of metastatic disease, and they may occur due to hematogenous and lymphatic spread, direct contiguous tissue invasion, or iatrogenic implantation following surgical excision of the primary tumor. Histologically, nuclear markers GATA3 and p63 stain positively in urothelial carcinomas and are negative in prostatic adenocarcinomas.^7,8 Other markers may be used such as cytokeratins 7 and 20, which are cytoplasmic epithelial markers that both stain positive in urothelial neoplasms.⁹  

Inflammatory carcinoma may be treated with radiation or systemic chemotherapy depending on the extent of systemic involvement in the patient; however, its presence portends a poor prognosis. Less than 1% of genitourinary malignancies have cutaneous involvement, and median disease-specific survival is less than 6 months from presentation of the cutaneous metastasis.¹⁰ Clinicians faced with a recalcitrant inflammatory cutaneous eruption should maintain a high index of suspicion for cutaneous metastases, particularly in patients with a history of cancer. Early dermatology referral may help establish the diagnosis and guide disease-targeted therapy or goals of care discussions. 

The Diagnosis: Inflammatory Urothelial Carcinoma 

Microscopic examination revealed metastatic carcinoma with extensive dermal lymphatic invasion (Figure). Immunohistochemical stains were positive for p63 and GATA3, markers for urothelial carcinomas, and negative for S-100 and Melan-A, markers for melanoma. Thus, the biopsy was compatible with a diagnosis of urothelial carcinoma. Gram and Grocott-Gomori methenamine-silver stains were negative for bacterial or fungal organisms. An additional 4-mm punch biopsy was performed of the left thigh at the distal-most aspect of the eruption to determine the extent of cutaneous metastasis. Pathology again showed metastatic urothelial carcinoma with extensive dermal lymphatic involvement and overlying epidermal spongiosis.

The patient had a history of bladder cancer diagnosed 1.5 years prior to presentation. It was a high-grade (World Health Organization) urothelial carcinoma that penetrated the bladder muscular wall, focally infiltrating into pericystic fat with multifocal seeding of pericystic lymphatics. It was unresponsive to bacillus Calmette-Guérin therapy. He underwent a cystoprostatectomy and bilateral staging lymph node dissection with clear surgical margins without adjuvant chemotherapy or radiation. He also reported a history of 2 prior cutaneous melanomas that were excised without sentinel lymph node biopsy. 

Four months prior to presentation, he developed a mildly pruritic cutaneous eruption on the abdomen that was treated with topical miconazole for presumed tinea cruris without improvement. He also was previously diagnosed with candidiasis of his urostomy and was taking oral fluconazole. The patient was admitted for the abdominal pain and distension, and computed tomography of the abdomen and pelvis revealed peritoneal carcinomatosis resulting in mechanical small bowel obstruction as well as enlarged pelvic and retroperitoneal lymph nodes. Confirmation of metastatic disease via skin biopsy avoided an invasive peritoneal biopsy. He was treated with triamcinolone acetonide ointment 0.1% with moderate relief of pruritus, and a palliative percutaneous endoscopic gastrostomy tube was placed for bowel decompression. The patient's hospital course was complicated by Proteus mirabilis bacteremia requiring cefepime. He was transitioned to home hospice and died 1 month after presentation. 

Inflammatory carcinoma, also called carcinoma erysipeloides, is a type of cutaneous metastasis most commonly seen in breast adenocarcinoma. Reported cases secondary to urothelial carcinoma are rare and most often involve the abdomen, groin, and lower extremities.^1-5 Clinically, inflammatory carcinoma presents as erythematous indurated patches or plaques with well-defined borders, often with edema, warmth, and tenderness. Its morphologic appearance is due to the obstruction of lymphatic vessels by tumor cells and the release of inflammatory cytokines. Its presentation can mimic other dermatoses such as cellulitis, erysipelas, fungal infection, radiation dermatitis, Majocchi granuloma, or contact dermatitis.⁶ Cutaneous metastases may be the first clinical manifestations of metastatic disease, and they may occur due to hematogenous and lymphatic spread, direct contiguous tissue invasion, or iatrogenic implantation following surgical excision of the primary tumor. Histologically, nuclear markers GATA3 and p63 stain positively in urothelial carcinomas and are negative in prostatic adenocarcinomas.^7,8 Other markers may be used such as cytokeratins 7 and 20, which are cytoplasmic epithelial markers that both stain positive in urothelial neoplasms.⁹  

Inflammatory carcinoma may be treated with radiation or systemic chemotherapy depending on the extent of systemic involvement in the patient; however, its presence portends a poor prognosis. Less than 1% of genitourinary malignancies have cutaneous involvement, and median disease-specific survival is less than 6 months from presentation of the cutaneous metastasis.¹⁰ Clinicians faced with a recalcitrant inflammatory cutaneous eruption should maintain a high index of suspicion for cutaneous metastases, particularly in patients with a history of cancer. Early dermatology referral may help establish the diagnosis and guide disease-targeted therapy or goals of care discussions. 

The Diagnosis: Inflammatory Urothelial Carcinoma 

Microscopic examination revealed metastatic carcinoma with extensive dermal lymphatic invasion (Figure). Immunohistochemical stains were positive for p63 and GATA3, markers for urothelial carcinomas, and negative for S-100 and Melan-A, markers for melanoma. Thus, the biopsy was compatible with a diagnosis of urothelial carcinoma. Gram and Grocott-Gomori methenamine-silver stains were negative for bacterial or fungal organisms. An additional 4-mm punch biopsy was performed of the left thigh at the distal-most aspect of the eruption to determine the extent of cutaneous metastasis. Pathology again showed metastatic urothelial carcinoma with extensive dermal lymphatic involvement and overlying epidermal spongiosis.

The patient had a history of bladder cancer diagnosed 1.5 years prior to presentation. It was a high-grade (World Health Organization) urothelial carcinoma that penetrated the bladder muscular wall, focally infiltrating into pericystic fat with multifocal seeding of pericystic lymphatics. It was unresponsive to bacillus Calmette-Guérin therapy. He underwent a cystoprostatectomy and bilateral staging lymph node dissection with clear surgical margins without adjuvant chemotherapy or radiation. He also reported a history of 2 prior cutaneous melanomas that were excised without sentinel lymph node biopsy. 

Four months prior to presentation, he developed a mildly pruritic cutaneous eruption on the abdomen that was treated with topical miconazole for presumed tinea cruris without improvement. He also was previously diagnosed with candidiasis of his urostomy and was taking oral fluconazole. The patient was admitted for the abdominal pain and distension, and computed tomography of the abdomen and pelvis revealed peritoneal carcinomatosis resulting in mechanical small bowel obstruction as well as enlarged pelvic and retroperitoneal lymph nodes. Confirmation of metastatic disease via skin biopsy avoided an invasive peritoneal biopsy. He was treated with triamcinolone acetonide ointment 0.1% with moderate relief of pruritus, and a palliative percutaneous endoscopic gastrostomy tube was placed for bowel decompression. The patient's hospital course was complicated by Proteus mirabilis bacteremia requiring cefepime. He was transitioned to home hospice and died 1 month after presentation. 

Inflammatory carcinoma, also called carcinoma erysipeloides, is a type of cutaneous metastasis most commonly seen in breast adenocarcinoma. Reported cases secondary to urothelial carcinoma are rare and most often involve the abdomen, groin, and lower extremities.^1-5 Clinically, inflammatory carcinoma presents as erythematous indurated patches or plaques with well-defined borders, often with edema, warmth, and tenderness. Its morphologic appearance is due to the obstruction of lymphatic vessels by tumor cells and the release of inflammatory cytokines. Its presentation can mimic other dermatoses such as cellulitis, erysipelas, fungal infection, radiation dermatitis, Majocchi granuloma, or contact dermatitis.⁶ Cutaneous metastases may be the first clinical manifestations of metastatic disease, and they may occur due to hematogenous and lymphatic spread, direct contiguous tissue invasion, or iatrogenic implantation following surgical excision of the primary tumor. Histologically, nuclear markers GATA3 and p63 stain positively in urothelial carcinomas and are negative in prostatic adenocarcinomas.^7,8 Other markers may be used such as cytokeratins 7 and 20, which are cytoplasmic epithelial markers that both stain positive in urothelial neoplasms.⁹  

Inflammatory carcinoma may be treated with radiation or systemic chemotherapy depending on the extent of systemic involvement in the patient; however, its presence portends a poor prognosis. Less than 1% of genitourinary malignancies have cutaneous involvement, and median disease-specific survival is less than 6 months from presentation of the cutaneous metastasis.¹⁰ Clinicians faced with a recalcitrant inflammatory cutaneous eruption should maintain a high index of suspicion for cutaneous metastases, particularly in patients with a history of cancer. Early dermatology referral may help establish the diagnosis and guide disease-targeted therapy or goals of care discussions. 

To the Editor:

Nevus sebaceous of Jadassohn (or nevus sebaceous [NS]) is a congenital hamartomatous disorder initially described by Jadassohn¹ in 1895. Nevus sebaceous occurs in 0.3% of newborns² and is most commonly identified on the face and scalp.^3,4 Mehregan and Pinkus⁵ characterized NS as an organoid tumor containing multiple skin components with 3 life stages. The first stage—occurring during infancy—consists of immature hair follicles and sebaceous glands. The second stage—beginning at puberty—shows development of sebaceous glands, epidermal hyperplasia, and maturation of apocrine glands. The final stage involves formation of secondary benign and malignant neoplasms.

Historically, basal cell carcinoma (BCC) was thought to be the most common neoplasm arising in NS.^5-8 In 1993, Ackerman et al⁹ introduced a new definition of trichoblastoma (TB), expanding the definition to encompass previously excluded benign follicular neoplasms. Large studies conducted after this new definition was proposed suggested that syringocystadenoma papilliferum and TB develop more frequently than does BCC.^3,4,10-15 Furthermore, Cribier et al⁴ and Merrot et al¹⁵ reviewed prior cases of NS using the new definition and asserted that the majority of previously diagnosed cases of BCC were considered to be TB under the new criteria. With the advent of modern diagnostic testing, the rate of secondary benign neoplasm growth is now thought to be between 7% and 19%, with syringocystadenoma papilliferum arising in 2% to 13% of cases and TB in 1.5% to 7%.^3,4,10-14 Malignant neoplasms are observed much less frequently, with BCC arising in 0% to 1% of NS cases.

Nevus sebaceous lesions typically enlarge during puberty, while malignant neoplasms occur almost exclusively in adulthood,^4,10-12 suggesting that hormones contribute to NS stage progression. We present the case of a woman who developed BCC in a previously asymptomatic NS during pregnancy.

A 32-year-old woman who was otherwise healthy presented to our dermatology clinic with a pink-yellow verrucous plaque on the right temporal hairline extending to the preauricular area of the face. The patient had no personal or family history of skin cancer and no history of tanning bed use. She reported that the lesion had been present since birth. A diagnosis of NS was made.

Two years later, she presented with a new bleeding growth atop the previously diagnosed NS that had been present for approximately 4 months (Figure). At this visit she was pregnant (30 weeks’ gestation). Physical examination revealed a 4-mm, brown, pearly papule at the inferior margin of the previously noted pink verrucous plaque on the right temporal hairline. A biopsy was performed and histopathology displayed aggregates of basaloid cells with a high nuclear to cytoplasmic ratio, peripheral palisading, and abundant melanin, consistent with pigmented BCC. The patient was referred for Mohs micrographic surgery; the lesion was removed with clear margins. The patient had no recurrence of BCC at 36-month follow-up.

Similarly, cases of rapid growth of NS lesions during pregnancy, a state of increased testosterone production,²⁷ have been reported.²⁸ We present a case of a BCC arising in a previously asymptomatic NS during pregnancy. To our knowledge, no large studies have assessed the effect of hormone level changes during pregnancy on NS growth and secondary malignant transformation. Prior to the 1990s, prophylactic excision of NS during childhood was recommended to prevent malignant neoplasm formation.^29,30 More recently, a more conservative approach has been advocated because of a lower rate of malignant transformation than previously thought; some dermatologists recommend close monitoring as an alternative to early removal.^{4,13,14,29,31} This case report proposes that pregnancy may be a time of increased risk for malignant transformation and that NS lesions might require close monitoring during pregnancy.

To the Editor:

Nevus sebaceous of Jadassohn (or nevus sebaceous [NS]) is a congenital hamartomatous disorder initially described by Jadassohn¹ in 1895. Nevus sebaceous occurs in 0.3% of newborns² and is most commonly identified on the face and scalp.^3,4 Mehregan and Pinkus⁵ characterized NS as an organoid tumor containing multiple skin components with 3 life stages. The first stage—occurring during infancy—consists of immature hair follicles and sebaceous glands. The second stage—beginning at puberty—shows development of sebaceous glands, epidermal hyperplasia, and maturation of apocrine glands. The final stage involves formation of secondary benign and malignant neoplasms.

Historically, basal cell carcinoma (BCC) was thought to be the most common neoplasm arising in NS.^5-8 In 1993, Ackerman et al⁹ introduced a new definition of trichoblastoma (TB), expanding the definition to encompass previously excluded benign follicular neoplasms. Large studies conducted after this new definition was proposed suggested that syringocystadenoma papilliferum and TB develop more frequently than does BCC.^3,4,10-15 Furthermore, Cribier et al⁴ and Merrot et al¹⁵ reviewed prior cases of NS using the new definition and asserted that the majority of previously diagnosed cases of BCC were considered to be TB under the new criteria. With the advent of modern diagnostic testing, the rate of secondary benign neoplasm growth is now thought to be between 7% and 19%, with syringocystadenoma papilliferum arising in 2% to 13% of cases and TB in 1.5% to 7%.^3,4,10-14 Malignant neoplasms are observed much less frequently, with BCC arising in 0% to 1% of NS cases.

Nevus sebaceous lesions typically enlarge during puberty, while malignant neoplasms occur almost exclusively in adulthood,^4,10-12 suggesting that hormones contribute to NS stage progression. We present the case of a woman who developed BCC in a previously asymptomatic NS during pregnancy.

A 32-year-old woman who was otherwise healthy presented to our dermatology clinic with a pink-yellow verrucous plaque on the right temporal hairline extending to the preauricular area of the face. The patient had no personal or family history of skin cancer and no history of tanning bed use. She reported that the lesion had been present since birth. A diagnosis of NS was made.

Two years later, she presented with a new bleeding growth atop the previously diagnosed NS that had been present for approximately 4 months (Figure). At this visit she was pregnant (30 weeks’ gestation). Physical examination revealed a 4-mm, brown, pearly papule at the inferior margin of the previously noted pink verrucous plaque on the right temporal hairline. A biopsy was performed and histopathology displayed aggregates of basaloid cells with a high nuclear to cytoplasmic ratio, peripheral palisading, and abundant melanin, consistent with pigmented BCC. The patient was referred for Mohs micrographic surgery; the lesion was removed with clear margins. The patient had no recurrence of BCC at 36-month follow-up.

Similarly, cases of rapid growth of NS lesions during pregnancy, a state of increased testosterone production,²⁷ have been reported.²⁸ We present a case of a BCC arising in a previously asymptomatic NS during pregnancy. To our knowledge, no large studies have assessed the effect of hormone level changes during pregnancy on NS growth and secondary malignant transformation. Prior to the 1990s, prophylactic excision of NS during childhood was recommended to prevent malignant neoplasm formation.^29,30 More recently, a more conservative approach has been advocated because of a lower rate of malignant transformation than previously thought; some dermatologists recommend close monitoring as an alternative to early removal.^{4,13,14,29,31} This case report proposes that pregnancy may be a time of increased risk for malignant transformation and that NS lesions might require close monitoring during pregnancy.

To the Editor:

Nevus sebaceous of Jadassohn (or nevus sebaceous [NS]) is a congenital hamartomatous disorder initially described by Jadassohn¹ in 1895. Nevus sebaceous occurs in 0.3% of newborns² and is most commonly identified on the face and scalp.^3,4 Mehregan and Pinkus⁵ characterized NS as an organoid tumor containing multiple skin components with 3 life stages. The first stage—occurring during infancy—consists of immature hair follicles and sebaceous glands. The second stage—beginning at puberty—shows development of sebaceous glands, epidermal hyperplasia, and maturation of apocrine glands. The final stage involves formation of secondary benign and malignant neoplasms.

Historically, basal cell carcinoma (BCC) was thought to be the most common neoplasm arising in NS.^5-8 In 1993, Ackerman et al⁹ introduced a new definition of trichoblastoma (TB), expanding the definition to encompass previously excluded benign follicular neoplasms. Large studies conducted after this new definition was proposed suggested that syringocystadenoma papilliferum and TB develop more frequently than does BCC.^3,4,10-15 Furthermore, Cribier et al⁴ and Merrot et al¹⁵ reviewed prior cases of NS using the new definition and asserted that the majority of previously diagnosed cases of BCC were considered to be TB under the new criteria. With the advent of modern diagnostic testing, the rate of secondary benign neoplasm growth is now thought to be between 7% and 19%, with syringocystadenoma papilliferum arising in 2% to 13% of cases and TB in 1.5% to 7%.^3,4,10-14 Malignant neoplasms are observed much less frequently, with BCC arising in 0% to 1% of NS cases.

Nevus sebaceous lesions typically enlarge during puberty, while malignant neoplasms occur almost exclusively in adulthood,^4,10-12 suggesting that hormones contribute to NS stage progression. We present the case of a woman who developed BCC in a previously asymptomatic NS during pregnancy.

A 32-year-old woman who was otherwise healthy presented to our dermatology clinic with a pink-yellow verrucous plaque on the right temporal hairline extending to the preauricular area of the face. The patient had no personal or family history of skin cancer and no history of tanning bed use. She reported that the lesion had been present since birth. A diagnosis of NS was made.

Two years later, she presented with a new bleeding growth atop the previously diagnosed NS that had been present for approximately 4 months (Figure). At this visit she was pregnant (30 weeks’ gestation). Physical examination revealed a 4-mm, brown, pearly papule at the inferior margin of the previously noted pink verrucous plaque on the right temporal hairline. A biopsy was performed and histopathology displayed aggregates of basaloid cells with a high nuclear to cytoplasmic ratio, peripheral palisading, and abundant melanin, consistent with pigmented BCC. The patient was referred for Mohs micrographic surgery; the lesion was removed with clear margins. The patient had no recurrence of BCC at 36-month follow-up.

Similarly, cases of rapid growth of NS lesions during pregnancy, a state of increased testosterone production,²⁷ have been reported.²⁸ We present a case of a BCC arising in a previously asymptomatic NS during pregnancy. To our knowledge, no large studies have assessed the effect of hormone level changes during pregnancy on NS growth and secondary malignant transformation. Prior to the 1990s, prophylactic excision of NS during childhood was recommended to prevent malignant neoplasm formation.^29,30 More recently, a more conservative approach has been advocated because of a lower rate of malignant transformation than previously thought; some dermatologists recommend close monitoring as an alternative to early removal.^{4,13,14,29,31} This case report proposes that pregnancy may be a time of increased risk for malignant transformation and that NS lesions might require close monitoring during pregnancy.

To the Editor:

Keratoacanthoma (KA)–type squamous cell carcinomas (SCCs) are rapidly evolving neoplasms of the epithelium that often spontaneously regress but rarely metastasize.^1,2 Keratoacanthomas are thought to ascend from the hair follicle,¹ and they clinically present as an enlarging solitary crateriform nodule with a keratin-filled center. Multiple KAs are rare²; histologically, KAs can be difficult to distinguish from conventional SCCs and are frequently treated by standard surgical excision.¹ Reactive KAs are a subtype of KA that are induced by trauma including UV exposure, electromagnetic radiation, surgical procedures, chemical peels, laser treatments, and rarely tattoos.^3-5

A 56-year-old man presented to the clinic with 3 asymptomatic enlarging papulonodules within a multicolored tattoo along the right forearm and elbow of 5 months’ duration (Figure 1). The lesions developed 1 month after the tattoo was placed and were localized to the areas of red pigment. The patient had several other tattoos. Histologic examination of the lesions revealed a well-differentiated squamous neoplasm with a crateriform invagination consistent with the superficial portion of a KA (Figures 2A–C). The specimen also revealed exogenous red pigment that was consistent with the background tattoo (Figure 2D). The patient underwent excisions of all 3 KAs, and free surgical margins were obtained.

Cipollaro¹⁰ reported the first case of a KA in a tattoo in 1973. Although there have been reports of melanoma and basal cell carcinoma occurring within tattoos, KAs and conventional SCCs are the most common cutaneous neoplasms arising in tattoos.

The pathogenesis underlying the development of malignancies in tattoos is unclear. It has been hypothesized that trauma from tattooing may play a role given the temporal relationship between tattoo placement and malignancy development.¹¹ Another theory is that tattoo pigment causes a chronic inflammatory foreign body reaction that triggers carcinogenesis.¹² Lastly, it has been postulated that tattoo pigment may alter UV light absorption in the skin that could potentially impact mutagenesis.¹¹

The most common treatment of KAs is standard surgical excision.⁴ Mohs micrographic surgery is an option if the KA is located in a cosmetically sensitive area. Although there are no reports of recurrence after excision of tattoo-related KAs, new KAs forming adjacent to a previously excised KA have been reported.¹³

Currently, tattoos are not regulated by the US Food and Drug Administration before going to market. Although many states regulate the practice of tattooing, few regulate the contents of tattoo ink, and ink is only investigated when safety issues arise.¹⁴ This case provides further evidence of an association between KAs, tattooing, and potentially carcinogenic pigments, especially in red dye, supporting the need for further research on the safety of pigment components and more regulation of tattoo ink.

To the Editor:

Keratoacanthoma (KA)–type squamous cell carcinomas (SCCs) are rapidly evolving neoplasms of the epithelium that often spontaneously regress but rarely metastasize.^1,2 Keratoacanthomas are thought to ascend from the hair follicle,¹ and they clinically present as an enlarging solitary crateriform nodule with a keratin-filled center. Multiple KAs are rare²; histologically, KAs can be difficult to distinguish from conventional SCCs and are frequently treated by standard surgical excision.¹ Reactive KAs are a subtype of KA that are induced by trauma including UV exposure, electromagnetic radiation, surgical procedures, chemical peels, laser treatments, and rarely tattoos.^3-5

A 56-year-old man presented to the clinic with 3 asymptomatic enlarging papulonodules within a multicolored tattoo along the right forearm and elbow of 5 months’ duration (Figure 1). The lesions developed 1 month after the tattoo was placed and were localized to the areas of red pigment. The patient had several other tattoos. Histologic examination of the lesions revealed a well-differentiated squamous neoplasm with a crateriform invagination consistent with the superficial portion of a KA (Figures 2A–C). The specimen also revealed exogenous red pigment that was consistent with the background tattoo (Figure 2D). The patient underwent excisions of all 3 KAs, and free surgical margins were obtained.

Cipollaro¹⁰ reported the first case of a KA in a tattoo in 1973. Although there have been reports of melanoma and basal cell carcinoma occurring within tattoos, KAs and conventional SCCs are the most common cutaneous neoplasms arising in tattoos.

The pathogenesis underlying the development of malignancies in tattoos is unclear. It has been hypothesized that trauma from tattooing may play a role given the temporal relationship between tattoo placement and malignancy development.¹¹ Another theory is that tattoo pigment causes a chronic inflammatory foreign body reaction that triggers carcinogenesis.¹² Lastly, it has been postulated that tattoo pigment may alter UV light absorption in the skin that could potentially impact mutagenesis.¹¹

The most common treatment of KAs is standard surgical excision.⁴ Mohs micrographic surgery is an option if the KA is located in a cosmetically sensitive area. Although there are no reports of recurrence after excision of tattoo-related KAs, new KAs forming adjacent to a previously excised KA have been reported.¹³

Currently, tattoos are not regulated by the US Food and Drug Administration before going to market. Although many states regulate the practice of tattooing, few regulate the contents of tattoo ink, and ink is only investigated when safety issues arise.¹⁴ This case provides further evidence of an association between KAs, tattooing, and potentially carcinogenic pigments, especially in red dye, supporting the need for further research on the safety of pigment components and more regulation of tattoo ink.

To the Editor:

Keratoacanthoma (KA)–type squamous cell carcinomas (SCCs) are rapidly evolving neoplasms of the epithelium that often spontaneously regress but rarely metastasize.^1,2 Keratoacanthomas are thought to ascend from the hair follicle,¹ and they clinically present as an enlarging solitary crateriform nodule with a keratin-filled center. Multiple KAs are rare²; histologically, KAs can be difficult to distinguish from conventional SCCs and are frequently treated by standard surgical excision.¹ Reactive KAs are a subtype of KA that are induced by trauma including UV exposure, electromagnetic radiation, surgical procedures, chemical peels, laser treatments, and rarely tattoos.^3-5

A 56-year-old man presented to the clinic with 3 asymptomatic enlarging papulonodules within a multicolored tattoo along the right forearm and elbow of 5 months’ duration (Figure 1). The lesions developed 1 month after the tattoo was placed and were localized to the areas of red pigment. The patient had several other tattoos. Histologic examination of the lesions revealed a well-differentiated squamous neoplasm with a crateriform invagination consistent with the superficial portion of a KA (Figures 2A–C). The specimen also revealed exogenous red pigment that was consistent with the background tattoo (Figure 2D). The patient underwent excisions of all 3 KAs, and free surgical margins were obtained.

Cipollaro¹⁰ reported the first case of a KA in a tattoo in 1973. Although there have been reports of melanoma and basal cell carcinoma occurring within tattoos, KAs and conventional SCCs are the most common cutaneous neoplasms arising in tattoos.

The pathogenesis underlying the development of malignancies in tattoos is unclear. It has been hypothesized that trauma from tattooing may play a role given the temporal relationship between tattoo placement and malignancy development.¹¹ Another theory is that tattoo pigment causes a chronic inflammatory foreign body reaction that triggers carcinogenesis.¹² Lastly, it has been postulated that tattoo pigment may alter UV light absorption in the skin that could potentially impact mutagenesis.¹¹

The most common treatment of KAs is standard surgical excision.⁴ Mohs micrographic surgery is an option if the KA is located in a cosmetically sensitive area. Although there are no reports of recurrence after excision of tattoo-related KAs, new KAs forming adjacent to a previously excised KA have been reported.¹³

Currently, tattoos are not regulated by the US Food and Drug Administration before going to market. Although many states regulate the practice of tattooing, few regulate the contents of tattoo ink, and ink is only investigated when safety issues arise.¹⁴ This case provides further evidence of an association between KAs, tattooing, and potentially carcinogenic pigments, especially in red dye, supporting the need for further research on the safety of pigment components and more regulation of tattoo ink.

The practice of dermatology is rife with bedside tools: swabs, smears, and scoring systems. First popularized in specialties such as emergency medicine and internal medicine, clinical scoring systems are now emerging in dermatology. These evidence-based scores can be calculated quickly at the bedside—often through a free smartphone app—to help guide clinical decision-making regarding diagnosis, prognosis, and management. As with any medical tool, scoring systems have limitations and should be used as a supplement, not substitute, for one’s clinical judgement. This article reviews 4 clinical scoring systems practical for dermatology residents.

SCORTEN Prognosticates Cases of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Perhaps the best-known scoring system in dermatology, the SCORTEN is widely used to predict hospital mortality from Stevens-Johnson syndrome/toxic epidermal necrolysis. The SCORTEN includes 7 variables of equal weight—age of 40 years or older, heart rate of 120 beats per minute or more, cancer/hematologic malignancy, involved body surface area (BSA) greater than 10%, serum urea greater than 10 mmol/L, serum bicarbonate less than 20 mmol/L, and serum glucose greater than 14 mmol/L—each contributing 1 point to the overall score if present.¹ The involved BSA is defined as the sum of detached and detachable epidermis.¹

The SCORTEN was developed and prospectively validated to be calculated at the end of the first 24 hours of admission; for this calculation, use the BSA affected at that time, and use the most abnormal values during the first 24 hours of admission for the other variables.¹ In addition, a follow-up study including some of the original coauthors recommends recalculating the SCORTEN at the end of hospital day 3, having found that the score’s predictive value was better on this day than hospital days 1, 2, 4, or 5.² Based on the original study, a SCORTEN of 0 to 1 corresponds to a mortality rate of 3.2%, 2 to 12.1%, 3 to 35.3%, 4 to 58.3%, and 5 or greater to 90.0%.¹

Limitations of the SCORTEN include its ability to overestimate or underestimate mortality as demonstrated by 2 multi-institutional cohorts.^3,4 Recently, the ABCD-10 score was developed as an alternative to the SCORTEN and was found to predict mortality similarly when validated in an internal cohort.⁵

PEST Screens for Psoriatic Arthritis

Dermatologists play an important role in screening for psoriatic arthritis, as an estimated 1 in 5 patients with psoriasis have psoriatic arthritis.⁶ To this end, several screening tools have been developed to help differentiate psoriatic arthritis from other arthritides. Joint guidelines from the American Academy of Dermatology and the National Psoriasis Foundation acknowledge that “. . . these screening tools have tended to perform less well when tested in groups of people other than those for which they were originally developed. As such, their usefulness in routine clinical practice remains controversial.”⁷ Nevertheless, the guidelines state, “[b]ecause screening and early detection of inflammatory arthritis are essential to optimize patient [quality of life] and reduce morbidity, providers may consider using a formal screening tool of their choice.”⁷

With these limitations in mind, I have found the Psoriasis Epidemiology Screening Tool (PEST) to be the most useful psoriatic arthritis screening tool. One study determined that the PEST has the best trade-off between sensitivity and specificity compared to 2 other psoriatic arthritis screening tools, the Psoriatic Arthritis Screening and Evaluation (PASE) and the Early Arthritis for Psoriatic Patients (EARP).⁸

The PEST is comprised of 5 questions: (1) Have you ever had a swollen joint (or joints)? (2) Has a doctor ever told you that you have arthritis? (3) Do your fingernails or toenails have holes or pits? (4) Have you had pain in your heel? (5) Have you had a finger or toe that was completely swollen and painful for no apparent reason? According to the PEST, a referral to a rheumatologist should be considered for patients answering yes to 3 or more questions, which is 97% sensitive and 79% specific for psoriatic arthritis.⁹ Patients who answer yes to fewer than 3 questions should still be referred to a rheumatologist if there is a strong clinical suspicion of psoriatic arthritis.¹⁰

The PEST can be accessed for free in 13 languages via the GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) app as well as downloaded for free from the National Psoriasis Foundation’s website (https://www.psoriasis.org/psa-screening/providers).

ALT-70 Differentiates Cellulitis From Pseudocellulitis

Overdiagnosing cellulitis in the United States has been estimated to result in up to 130,000 unnecessary hospitalizations and up to $515 million in avoidable health care spending.¹¹ Dermatologists are in a unique position to help fix this issue. In one retrospective study of 1430 inpatient dermatology consultations, 74.32% of inpatients evaluated for presumed cellulitis by a dermatologist were instead diagnosed with a cellulitis mimicker (ie, pseudocellulitis), such as stasis dermatitis or contact dermatitis.¹²

The ALT-70 score was developed and prospectively validated to help differentiate lower extremity cellulitis from pseudocellulitis in adult patients in the emergency department (ED).¹³ In addition, the score has retrospectively been shown to function similarly in the inpatient setting when calculated at 24 and 48 hours after ED presentation.¹⁴ Although the ALT-70 score was designed for use by frontline clinicians prior to dermatology consultation, I also have found it helpful to calculate as a consultant, as it provides an objective measure of risk to communicate to the primary team in support of one diagnosis or another.

ALT-70 is an acronym for the score’s 4 variables: asymmetry, leukocytosis, tachycardia, and age of 70 years or older.¹⁵ If present, each variable confers a certain number of points to the final score: 3 points for asymmetry (defined as unilateral leg involvement), 1 point for leukocytosis (white blood cell count ≥10,000/μL), 1 point for tachycardia (≥90 beats per minute), and 2 points for age of 70 years or older. An ALT-70 score of 0 to 2 corresponds to an 83.3% or greater chance of pseudocellulitis, suggesting that the diagnosis of cellulitis be reconsidered. A score of 3 to 4 is indeterminate, and additional information such as a dermatology consultation should be pursued. A score of 5 to 7 corresponds to an 82.2% or greater chance of cellulitis, signifying that empiric treatment with antibiotics be considered.¹⁵

The ALT-70 score does not apply to cases involving areas other than the lower extremities; intravenous antibiotic use within 48 hours before ED presentation; surgery within the last 30 days; abscess; penetrating trauma; burn; or known history of osteomyelitis, diabetic ulcer, or indwelling hardware at the site of infection.¹⁵ The ALT-70 score is available for free via the MDCalc app and website (https://www.mdcalc.com/alt-70-score-cellulitis).

Mohs AUC Determines the Appropriateness of Mohs Micrographic Surgery

In 2012, the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and American Society for Mohs Surgery published appropriate use criteria (AUC) to guide the decision to pursue Mohs micrographic surgery (MMS) in the United States.¹⁶ Based on various tumor and patient characteristics, the Mohs AUC assign scores to 270 different clinical scenarios. A score of 1 to 3 signifies that MMS is inappropriate and generally not considered acceptable. A score 4 to 6 indicates that the appropriateness of MMS is uncertain. A score 7 to 9 means that MMS is appropriate and generally considered acceptable.¹⁶

Since publication, the Mohs AUC have been criticized for classifying most primary superficial basal cell carcinomas as appropriate for MMS¹⁷ (which an AUC coauthor¹⁸ and others^19,20 have defended), excluding certain reasons for performing MMS (such as operating on multiple tumors on the same day),²¹ including counterintuitive scores,²² and omitting trials from Europe²³ (which AUC coauthors also have defended²⁴). As with any clinical scoring system, the Mohs AUC has limitations; the creators acknowledge that “. . . these criteria should not be interpreted as setting a standard of care, or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results, even for those indications scored as inappropriate.”¹⁶ The Mohs AUC app (https://www.aad.org/members/aad-apps/mohs-auc) is free and allows users to enter tumor and patient characteristics to determine the score for their specific scenario.

Final Thoughts

Scoring systems are emerging in dermatology as evidence-based bedside tools to help guide clinical decision-making. Despite their limitations, these scores have the potential to make a meaningful impact in dermatology as they have in other specialties.

The practice of dermatology is rife with bedside tools: swabs, smears, and scoring systems. First popularized in specialties such as emergency medicine and internal medicine, clinical scoring systems are now emerging in dermatology. These evidence-based scores can be calculated quickly at the bedside—often through a free smartphone app—to help guide clinical decision-making regarding diagnosis, prognosis, and management. As with any medical tool, scoring systems have limitations and should be used as a supplement, not substitute, for one’s clinical judgement. This article reviews 4 clinical scoring systems practical for dermatology residents.

SCORTEN Prognosticates Cases of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Perhaps the best-known scoring system in dermatology, the SCORTEN is widely used to predict hospital mortality from Stevens-Johnson syndrome/toxic epidermal necrolysis. The SCORTEN includes 7 variables of equal weight—age of 40 years or older, heart rate of 120 beats per minute or more, cancer/hematologic malignancy, involved body surface area (BSA) greater than 10%, serum urea greater than 10 mmol/L, serum bicarbonate less than 20 mmol/L, and serum glucose greater than 14 mmol/L—each contributing 1 point to the overall score if present.¹ The involved BSA is defined as the sum of detached and detachable epidermis.¹

The SCORTEN was developed and prospectively validated to be calculated at the end of the first 24 hours of admission; for this calculation, use the BSA affected at that time, and use the most abnormal values during the first 24 hours of admission for the other variables.¹ In addition, a follow-up study including some of the original coauthors recommends recalculating the SCORTEN at the end of hospital day 3, having found that the score’s predictive value was better on this day than hospital days 1, 2, 4, or 5.² Based on the original study, a SCORTEN of 0 to 1 corresponds to a mortality rate of 3.2%, 2 to 12.1%, 3 to 35.3%, 4 to 58.3%, and 5 or greater to 90.0%.¹

Limitations of the SCORTEN include its ability to overestimate or underestimate mortality as demonstrated by 2 multi-institutional cohorts.^3,4 Recently, the ABCD-10 score was developed as an alternative to the SCORTEN and was found to predict mortality similarly when validated in an internal cohort.⁵

PEST Screens for Psoriatic Arthritis

Dermatologists play an important role in screening for psoriatic arthritis, as an estimated 1 in 5 patients with psoriasis have psoriatic arthritis.⁶ To this end, several screening tools have been developed to help differentiate psoriatic arthritis from other arthritides. Joint guidelines from the American Academy of Dermatology and the National Psoriasis Foundation acknowledge that “. . . these screening tools have tended to perform less well when tested in groups of people other than those for which they were originally developed. As such, their usefulness in routine clinical practice remains controversial.”⁷ Nevertheless, the guidelines state, “[b]ecause screening and early detection of inflammatory arthritis are essential to optimize patient [quality of life] and reduce morbidity, providers may consider using a formal screening tool of their choice.”⁷

With these limitations in mind, I have found the Psoriasis Epidemiology Screening Tool (PEST) to be the most useful psoriatic arthritis screening tool. One study determined that the PEST has the best trade-off between sensitivity and specificity compared to 2 other psoriatic arthritis screening tools, the Psoriatic Arthritis Screening and Evaluation (PASE) and the Early Arthritis for Psoriatic Patients (EARP).⁸

The PEST is comprised of 5 questions: (1) Have you ever had a swollen joint (or joints)? (2) Has a doctor ever told you that you have arthritis? (3) Do your fingernails or toenails have holes or pits? (4) Have you had pain in your heel? (5) Have you had a finger or toe that was completely swollen and painful for no apparent reason? According to the PEST, a referral to a rheumatologist should be considered for patients answering yes to 3 or more questions, which is 97% sensitive and 79% specific for psoriatic arthritis.⁹ Patients who answer yes to fewer than 3 questions should still be referred to a rheumatologist if there is a strong clinical suspicion of psoriatic arthritis.¹⁰

The PEST can be accessed for free in 13 languages via the GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) app as well as downloaded for free from the National Psoriasis Foundation’s website (https://www.psoriasis.org/psa-screening/providers).

ALT-70 Differentiates Cellulitis From Pseudocellulitis

Overdiagnosing cellulitis in the United States has been estimated to result in up to 130,000 unnecessary hospitalizations and up to $515 million in avoidable health care spending.¹¹ Dermatologists are in a unique position to help fix this issue. In one retrospective study of 1430 inpatient dermatology consultations, 74.32% of inpatients evaluated for presumed cellulitis by a dermatologist were instead diagnosed with a cellulitis mimicker (ie, pseudocellulitis), such as stasis dermatitis or contact dermatitis.¹²

The ALT-70 score was developed and prospectively validated to help differentiate lower extremity cellulitis from pseudocellulitis in adult patients in the emergency department (ED).¹³ In addition, the score has retrospectively been shown to function similarly in the inpatient setting when calculated at 24 and 48 hours after ED presentation.¹⁴ Although the ALT-70 score was designed for use by frontline clinicians prior to dermatology consultation, I also have found it helpful to calculate as a consultant, as it provides an objective measure of risk to communicate to the primary team in support of one diagnosis or another.

ALT-70 is an acronym for the score’s 4 variables: asymmetry, leukocytosis, tachycardia, and age of 70 years or older.¹⁵ If present, each variable confers a certain number of points to the final score: 3 points for asymmetry (defined as unilateral leg involvement), 1 point for leukocytosis (white blood cell count ≥10,000/μL), 1 point for tachycardia (≥90 beats per minute), and 2 points for age of 70 years or older. An ALT-70 score of 0 to 2 corresponds to an 83.3% or greater chance of pseudocellulitis, suggesting that the diagnosis of cellulitis be reconsidered. A score of 3 to 4 is indeterminate, and additional information such as a dermatology consultation should be pursued. A score of 5 to 7 corresponds to an 82.2% or greater chance of cellulitis, signifying that empiric treatment with antibiotics be considered.¹⁵

The ALT-70 score does not apply to cases involving areas other than the lower extremities; intravenous antibiotic use within 48 hours before ED presentation; surgery within the last 30 days; abscess; penetrating trauma; burn; or known history of osteomyelitis, diabetic ulcer, or indwelling hardware at the site of infection.¹⁵ The ALT-70 score is available for free via the MDCalc app and website (https://www.mdcalc.com/alt-70-score-cellulitis).

Mohs AUC Determines the Appropriateness of Mohs Micrographic Surgery

In 2012, the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and American Society for Mohs Surgery published appropriate use criteria (AUC) to guide the decision to pursue Mohs micrographic surgery (MMS) in the United States.¹⁶ Based on various tumor and patient characteristics, the Mohs AUC assign scores to 270 different clinical scenarios. A score of 1 to 3 signifies that MMS is inappropriate and generally not considered acceptable. A score 4 to 6 indicates that the appropriateness of MMS is uncertain. A score 7 to 9 means that MMS is appropriate and generally considered acceptable.¹⁶

Since publication, the Mohs AUC have been criticized for classifying most primary superficial basal cell carcinomas as appropriate for MMS¹⁷ (which an AUC coauthor¹⁸ and others^19,20 have defended), excluding certain reasons for performing MMS (such as operating on multiple tumors on the same day),²¹ including counterintuitive scores,²² and omitting trials from Europe²³ (which AUC coauthors also have defended²⁴). As with any clinical scoring system, the Mohs AUC has limitations; the creators acknowledge that “. . . these criteria should not be interpreted as setting a standard of care, or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results, even for those indications scored as inappropriate.”¹⁶ The Mohs AUC app (https://www.aad.org/members/aad-apps/mohs-auc) is free and allows users to enter tumor and patient characteristics to determine the score for their specific scenario.

Final Thoughts

Scoring systems are emerging in dermatology as evidence-based bedside tools to help guide clinical decision-making. Despite their limitations, these scores have the potential to make a meaningful impact in dermatology as they have in other specialties.

The practice of dermatology is rife with bedside tools: swabs, smears, and scoring systems. First popularized in specialties such as emergency medicine and internal medicine, clinical scoring systems are now emerging in dermatology. These evidence-based scores can be calculated quickly at the bedside—often through a free smartphone app—to help guide clinical decision-making regarding diagnosis, prognosis, and management. As with any medical tool, scoring systems have limitations and should be used as a supplement, not substitute, for one’s clinical judgement. This article reviews 4 clinical scoring systems practical for dermatology residents.

SCORTEN Prognosticates Cases of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Perhaps the best-known scoring system in dermatology, the SCORTEN is widely used to predict hospital mortality from Stevens-Johnson syndrome/toxic epidermal necrolysis. The SCORTEN includes 7 variables of equal weight—age of 40 years or older, heart rate of 120 beats per minute or more, cancer/hematologic malignancy, involved body surface area (BSA) greater than 10%, serum urea greater than 10 mmol/L, serum bicarbonate less than 20 mmol/L, and serum glucose greater than 14 mmol/L—each contributing 1 point to the overall score if present.¹ The involved BSA is defined as the sum of detached and detachable epidermis.¹

The SCORTEN was developed and prospectively validated to be calculated at the end of the first 24 hours of admission; for this calculation, use the BSA affected at that time, and use the most abnormal values during the first 24 hours of admission for the other variables.¹ In addition, a follow-up study including some of the original coauthors recommends recalculating the SCORTEN at the end of hospital day 3, having found that the score’s predictive value was better on this day than hospital days 1, 2, 4, or 5.² Based on the original study, a SCORTEN of 0 to 1 corresponds to a mortality rate of 3.2%, 2 to 12.1%, 3 to 35.3%, 4 to 58.3%, and 5 or greater to 90.0%.¹

Limitations of the SCORTEN include its ability to overestimate or underestimate mortality as demonstrated by 2 multi-institutional cohorts.^3,4 Recently, the ABCD-10 score was developed as an alternative to the SCORTEN and was found to predict mortality similarly when validated in an internal cohort.⁵

PEST Screens for Psoriatic Arthritis

Dermatologists play an important role in screening for psoriatic arthritis, as an estimated 1 in 5 patients with psoriasis have psoriatic arthritis.⁶ To this end, several screening tools have been developed to help differentiate psoriatic arthritis from other arthritides. Joint guidelines from the American Academy of Dermatology and the National Psoriasis Foundation acknowledge that “. . . these screening tools have tended to perform less well when tested in groups of people other than those for which they were originally developed. As such, their usefulness in routine clinical practice remains controversial.”⁷ Nevertheless, the guidelines state, “[b]ecause screening and early detection of inflammatory arthritis are essential to optimize patient [quality of life] and reduce morbidity, providers may consider using a formal screening tool of their choice.”⁷

With these limitations in mind, I have found the Psoriasis Epidemiology Screening Tool (PEST) to be the most useful psoriatic arthritis screening tool. One study determined that the PEST has the best trade-off between sensitivity and specificity compared to 2 other psoriatic arthritis screening tools, the Psoriatic Arthritis Screening and Evaluation (PASE) and the Early Arthritis for Psoriatic Patients (EARP).⁸

The PEST is comprised of 5 questions: (1) Have you ever had a swollen joint (or joints)? (2) Has a doctor ever told you that you have arthritis? (3) Do your fingernails or toenails have holes or pits? (4) Have you had pain in your heel? (5) Have you had a finger or toe that was completely swollen and painful for no apparent reason? According to the PEST, a referral to a rheumatologist should be considered for patients answering yes to 3 or more questions, which is 97% sensitive and 79% specific for psoriatic arthritis.⁹ Patients who answer yes to fewer than 3 questions should still be referred to a rheumatologist if there is a strong clinical suspicion of psoriatic arthritis.¹⁰

The PEST can be accessed for free in 13 languages via the GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) app as well as downloaded for free from the National Psoriasis Foundation’s website (https://www.psoriasis.org/psa-screening/providers).

ALT-70 Differentiates Cellulitis From Pseudocellulitis

Overdiagnosing cellulitis in the United States has been estimated to result in up to 130,000 unnecessary hospitalizations and up to $515 million in avoidable health care spending.¹¹ Dermatologists are in a unique position to help fix this issue. In one retrospective study of 1430 inpatient dermatology consultations, 74.32% of inpatients evaluated for presumed cellulitis by a dermatologist were instead diagnosed with a cellulitis mimicker (ie, pseudocellulitis), such as stasis dermatitis or contact dermatitis.¹²

The ALT-70 score was developed and prospectively validated to help differentiate lower extremity cellulitis from pseudocellulitis in adult patients in the emergency department (ED).¹³ In addition, the score has retrospectively been shown to function similarly in the inpatient setting when calculated at 24 and 48 hours after ED presentation.¹⁴ Although the ALT-70 score was designed for use by frontline clinicians prior to dermatology consultation, I also have found it helpful to calculate as a consultant, as it provides an objective measure of risk to communicate to the primary team in support of one diagnosis or another.

ALT-70 is an acronym for the score’s 4 variables: asymmetry, leukocytosis, tachycardia, and age of 70 years or older.¹⁵ If present, each variable confers a certain number of points to the final score: 3 points for asymmetry (defined as unilateral leg involvement), 1 point for leukocytosis (white blood cell count ≥10,000/μL), 1 point for tachycardia (≥90 beats per minute), and 2 points for age of 70 years or older. An ALT-70 score of 0 to 2 corresponds to an 83.3% or greater chance of pseudocellulitis, suggesting that the diagnosis of cellulitis be reconsidered. A score of 3 to 4 is indeterminate, and additional information such as a dermatology consultation should be pursued. A score of 5 to 7 corresponds to an 82.2% or greater chance of cellulitis, signifying that empiric treatment with antibiotics be considered.¹⁵

The ALT-70 score does not apply to cases involving areas other than the lower extremities; intravenous antibiotic use within 48 hours before ED presentation; surgery within the last 30 days; abscess; penetrating trauma; burn; or known history of osteomyelitis, diabetic ulcer, or indwelling hardware at the site of infection.¹⁵ The ALT-70 score is available for free via the MDCalc app and website (https://www.mdcalc.com/alt-70-score-cellulitis).

Mohs AUC Determines the Appropriateness of Mohs Micrographic Surgery

In 2012, the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and American Society for Mohs Surgery published appropriate use criteria (AUC) to guide the decision to pursue Mohs micrographic surgery (MMS) in the United States.¹⁶ Based on various tumor and patient characteristics, the Mohs AUC assign scores to 270 different clinical scenarios. A score of 1 to 3 signifies that MMS is inappropriate and generally not considered acceptable. A score 4 to 6 indicates that the appropriateness of MMS is uncertain. A score 7 to 9 means that MMS is appropriate and generally considered acceptable.¹⁶

Since publication, the Mohs AUC have been criticized for classifying most primary superficial basal cell carcinomas as appropriate for MMS¹⁷ (which an AUC coauthor¹⁸ and others^19,20 have defended), excluding certain reasons for performing MMS (such as operating on multiple tumors on the same day),²¹ including counterintuitive scores,²² and omitting trials from Europe²³ (which AUC coauthors also have defended²⁴). As with any clinical scoring system, the Mohs AUC has limitations; the creators acknowledge that “. . . these criteria should not be interpreted as setting a standard of care, or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results, even for those indications scored as inappropriate.”¹⁶ The Mohs AUC app (https://www.aad.org/members/aad-apps/mohs-auc) is free and allows users to enter tumor and patient characteristics to determine the score for their specific scenario.

Final Thoughts

Scoring systems are emerging in dermatology as evidence-based bedside tools to help guide clinical decision-making. Despite their limitations, these scores have the potential to make a meaningful impact in dermatology as they have in other specialties.

Women who accumulated more indoor tanning sessions over time significantly increased their risk for squamous cell cancer over women who never engaged in indoor tanning, based on data from 159,419 women.

Previous research has examined associations between indoor tanning and cutaneous melanoma, but an association between indoor tanning and squamous cell carcinoma (SCC) has not been well studied, wrote Simon Lergenmuller, MSc, of the University of Oslo, and colleagues.

In a prospective cohort study published in JAMA Dermatology, the researchers surveyed 159,419 women from the Norwegian Women and Cancer study. Of these, 95,552 women (69%) reported ever use of indoor tanning. The average age at study inclusion was 50 years. During an average of 17 years’ follow-up, 597 women developed SCC.

Overall, the risk of SCC increased with increasing numbers of indoor tanning sessions. The adjusted hazard ratio for most tanning sessions versus no tanning sessions was 1.83. “The association between cumulative exposure to indoor tanning and SCC risk was the same regardless of duration of use and age at initiation,” the researchers wrote.

The risk of SCC was significantly higher both among women with 10 years or less of tanning bed use and among those with more than 10 years of use, compared with never users (HRs, 1.41 and 1.43, respectively). Similarly, researchers found a significantly higher risk of SCC among women who started indoor tanning at age 30 years or older and those who started younger than 30 years, compared with never users (HRs, 1.36 and HR, 1.51, respectively).

No significant association appeared between age at initiation of indoor tanning and age at the time of SCC diagnosis.

The study findings were limited by several factors including the variation in UV radiation among tanning devices, the lack of data on men, and the retrospective collection of UV exposure data that likely led to some misclassification, the researchers noted.

However, the results were strengthened by the large sample size and support the association between increased exposure to indoor tanning and increased risk of SCC, they wrote. “Avoidance of indoor tanning may help prevent not only melanoma but also SCC, and our results support the development of policies that regulate indoor tanning.”

The study was supported by the Institute of Basic Medical Sciences, University of Oslo, and the Norwegian Cancer Society. The researchers had no financial conflicts to disclose.

SOURCE: Lergenmuller S et al. JAMA Dermatol. 2019 Oct 2. doi: 10.1001/jamadermatol.2019.2681.

Women who accumulated more indoor tanning sessions over time significantly increased their risk for squamous cell cancer over women who never engaged in indoor tanning, based on data from 159,419 women.

Previous research has examined associations between indoor tanning and cutaneous melanoma, but an association between indoor tanning and squamous cell carcinoma (SCC) has not been well studied, wrote Simon Lergenmuller, MSc, of the University of Oslo, and colleagues.

In a prospective cohort study published in JAMA Dermatology, the researchers surveyed 159,419 women from the Norwegian Women and Cancer study. Of these, 95,552 women (69%) reported ever use of indoor tanning. The average age at study inclusion was 50 years. During an average of 17 years’ follow-up, 597 women developed SCC.

Overall, the risk of SCC increased with increasing numbers of indoor tanning sessions. The adjusted hazard ratio for most tanning sessions versus no tanning sessions was 1.83. “The association between cumulative exposure to indoor tanning and SCC risk was the same regardless of duration of use and age at initiation,” the researchers wrote.

The risk of SCC was significantly higher both among women with 10 years or less of tanning bed use and among those with more than 10 years of use, compared with never users (HRs, 1.41 and 1.43, respectively). Similarly, researchers found a significantly higher risk of SCC among women who started indoor tanning at age 30 years or older and those who started younger than 30 years, compared with never users (HRs, 1.36 and HR, 1.51, respectively).

No significant association appeared between age at initiation of indoor tanning and age at the time of SCC diagnosis.

The study findings were limited by several factors including the variation in UV radiation among tanning devices, the lack of data on men, and the retrospective collection of UV exposure data that likely led to some misclassification, the researchers noted.

However, the results were strengthened by the large sample size and support the association between increased exposure to indoor tanning and increased risk of SCC, they wrote. “Avoidance of indoor tanning may help prevent not only melanoma but also SCC, and our results support the development of policies that regulate indoor tanning.”

The study was supported by the Institute of Basic Medical Sciences, University of Oslo, and the Norwegian Cancer Society. The researchers had no financial conflicts to disclose.

SOURCE: Lergenmuller S et al. JAMA Dermatol. 2019 Oct 2. doi: 10.1001/jamadermatol.2019.2681.

Women who accumulated more indoor tanning sessions over time significantly increased their risk for squamous cell cancer over women who never engaged in indoor tanning, based on data from 159,419 women.

Previous research has examined associations between indoor tanning and cutaneous melanoma, but an association between indoor tanning and squamous cell carcinoma (SCC) has not been well studied, wrote Simon Lergenmuller, MSc, of the University of Oslo, and colleagues.

In a prospective cohort study published in JAMA Dermatology, the researchers surveyed 159,419 women from the Norwegian Women and Cancer study. Of these, 95,552 women (69%) reported ever use of indoor tanning. The average age at study inclusion was 50 years. During an average of 17 years’ follow-up, 597 women developed SCC.

Overall, the risk of SCC increased with increasing numbers of indoor tanning sessions. The adjusted hazard ratio for most tanning sessions versus no tanning sessions was 1.83. “The association between cumulative exposure to indoor tanning and SCC risk was the same regardless of duration of use and age at initiation,” the researchers wrote.

The risk of SCC was significantly higher both among women with 10 years or less of tanning bed use and among those with more than 10 years of use, compared with never users (HRs, 1.41 and 1.43, respectively). Similarly, researchers found a significantly higher risk of SCC among women who started indoor tanning at age 30 years or older and those who started younger than 30 years, compared with never users (HRs, 1.36 and HR, 1.51, respectively).

No significant association appeared between age at initiation of indoor tanning and age at the time of SCC diagnosis.

The study findings were limited by several factors including the variation in UV radiation among tanning devices, the lack of data on men, and the retrospective collection of UV exposure data that likely led to some misclassification, the researchers noted.

However, the results were strengthened by the large sample size and support the association between increased exposure to indoor tanning and increased risk of SCC, they wrote. “Avoidance of indoor tanning may help prevent not only melanoma but also SCC, and our results support the development of policies that regulate indoor tanning.”

The study was supported by the Institute of Basic Medical Sciences, University of Oslo, and the Norwegian Cancer Society. The researchers had no financial conflicts to disclose.

SOURCE: Lergenmuller S et al. JAMA Dermatol. 2019 Oct 2. doi: 10.1001/jamadermatol.2019.2681.

Join us on Tuesday, October 8, 2019, at 8:00 pm EST on Twitter at #MDedgeChats as we discuss skin cancer, and what’s new in sunscreen, skin of color, and melanoma. 

Special guests include physicians with expertise in dermatology and skin cancer, Anthony Rossi, MD (@DrAnthonyRossi), Julie Amthor Croley, MD, 15k followers on IG (@Drskinandsmiles), and Candrice Heath, MD (@DrCandriceHeath). Background information about the chat can be found below.

What will the conversation cover?

Q1: What are the most common types of skin cancer? 
Q2: What recent research findings can better inform patients about skin cancer risks?
Q3: What’s the difference between melanoma in fair skin vs. darker skin?
Q4: How does the risk of skin cancer differ in people with darker skin?
Q5: Why should sunscreen be used even in the fall and winter?

About Dr. Rossi: 

Dr. Anthony Rossi (@DrAnthonyRossi) is a board-certified dermatologist with fellowship training in Mohs micrographic surgery, cosmetic and laser surgery, and advanced cutaneous oncology at the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College program, both in New York.  He specializes in skin cancer surgery, cosmetic dermatologic surgery, and laser surgery.  

His research includes quality of life in cancer survivors, the use of noninvasive imaging of the skin, and nonsurgical treatments of skin cancer. Additionally, Dr. Rossi is active in dermatologic organizations and advocacy for medicine.

Research and Publications by Dr. Rossi 

About Dr. Heath:
 

Dr. Candrice Heath (@DrCandriceHeath) is Assistant Professor of Dermatology at the Lewis Katz School of Medicine at Temple University in Philadelphia, Pennsylvania with fellowship training in pediatric dermatology at Johns Hopkins University in Baltimore, Maryland. Dr. Heath is triple board certified in pediatrics, dermatology, and pediatric dermatology. She specializes in adult and pediatric dermatology, skin of color, acne, and eczema. Dr. Heath also enjoys educating primary care physicians on the front lines of health care and delivering easy to understand information to consumers. 

Research and publications by Dr. Heath 
Guest host of MDedge podcast: A sunscreen update with Dr. Vincent DeLeo. 
 

About Dr. Croley:  

Dr. Julie Amthor Croley (@Drskinandsmiles) also known as “Dr. Skin and Smiles” has 15,000 followers on Instagram, and is a Chief Dermatology Resident at the University of Texas Medical Branch in Galveston, Texas. She has a special interest in skin cancer and dermatological surgery and hopes to complete a fellowship in Mohs micrographic surgery after residency. In her free time, Dr. Croley enjoys spending time with her husband (an orthopedic surgeon), running and competing in marathons, and spending time on the beach. 

Media coverage by Dr. Croley

Cutaneous melanoma is the most fatal form of skin cancer and is a considerable public health concern in the United States. Early detection and management of skin cancer can lead to decreased morbidity and mortality from skin cancer. As a result, the American Academy of Dermatology Association supports safe sun-protective practices and diligent self-screening for changing lesions.

Sunscreen use is an essential component of sun protection. New regulations from the US Food and Drug Administration (FDA) have left consumers concerned about the safety of sunscreens. According to a recent Cutis editorial from Vincent A. DeLeo, MD, “There is no question that, as physicians, we want to ‘first, do no harm,’ so we should all be interested in assuring our patients that our sunscreen recommendations are safe and we support the FDA proposal for additional data.”

Patients with skin of color experience disproportionately higher morbidity and mortality when diagnosed with melanoma. “Poor prognosis in patients with skin of color is multifactorial and may be due to poor use of sun protection, misconceptions about melanoma risk, atypical clinical presentation, impaired access to care, and delay in diagnosis,” according to a recent Cutis article. 

Population-based skin cancer screening performed exclusively by dermatologists is not practical. Primary care physicians and other experts in melanoma and public health need to be involved in reducing melanoma mortality. 

In this chat, we will provide expert recommendations on the diagnosis of skin cancer, preventive measures, and the latest research discussed among physicians.

Research & Resources

• “Doctor, Do I Need a Skin Check?”
• Assessing the effectiveness of knowledge-based interventions in skin of color populations.
• Melanoma in US Hispanics
• Podcast: Sunscreen update from Dr. Vincent DeLeo
• Windshield and UV exposure  
• Racial, ethnic minorities often don’t practice sun-protective behaviors.
• Sunscreen regulations and advice for your patients.

Join us on Tuesday, October 8, 2019, at 8:00 pm EST on Twitter at #MDedgeChats as we discuss skin cancer, and what’s new in sunscreen, skin of color, and melanoma. 

Special guests include physicians with expertise in dermatology and skin cancer, Anthony Rossi, MD (@DrAnthonyRossi), Julie Amthor Croley, MD, 15k followers on IG (@Drskinandsmiles), and Candrice Heath, MD (@DrCandriceHeath). Background information about the chat can be found below.

What will the conversation cover?

Q1: What are the most common types of skin cancer? 
Q2: What recent research findings can better inform patients about skin cancer risks?
Q3: What’s the difference between melanoma in fair skin vs. darker skin?
Q4: How does the risk of skin cancer differ in people with darker skin?
Q5: Why should sunscreen be used even in the fall and winter?

About Dr. Rossi: 

Dr. Anthony Rossi (@DrAnthonyRossi) is a board-certified dermatologist with fellowship training in Mohs micrographic surgery, cosmetic and laser surgery, and advanced cutaneous oncology at the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College program, both in New York.  He specializes in skin cancer surgery, cosmetic dermatologic surgery, and laser surgery.  

His research includes quality of life in cancer survivors, the use of noninvasive imaging of the skin, and nonsurgical treatments of skin cancer. Additionally, Dr. Rossi is active in dermatologic organizations and advocacy for medicine.

Research and Publications by Dr. Rossi 

About Dr. Heath:
 

Dr. Candrice Heath (@DrCandriceHeath) is Assistant Professor of Dermatology at the Lewis Katz School of Medicine at Temple University in Philadelphia, Pennsylvania with fellowship training in pediatric dermatology at Johns Hopkins University in Baltimore, Maryland. Dr. Heath is triple board certified in pediatrics, dermatology, and pediatric dermatology. She specializes in adult and pediatric dermatology, skin of color, acne, and eczema. Dr. Heath also enjoys educating primary care physicians on the front lines of health care and delivering easy to understand information to consumers. 

Research and publications by Dr. Heath 
Guest host of MDedge podcast: A sunscreen update with Dr. Vincent DeLeo. 
 

About Dr. Croley:  

Dr. Julie Amthor Croley (@Drskinandsmiles) also known as “Dr. Skin and Smiles” has 15,000 followers on Instagram, and is a Chief Dermatology Resident at the University of Texas Medical Branch in Galveston, Texas. She has a special interest in skin cancer and dermatological surgery and hopes to complete a fellowship in Mohs micrographic surgery after residency. In her free time, Dr. Croley enjoys spending time with her husband (an orthopedic surgeon), running and competing in marathons, and spending time on the beach. 

Media coverage by Dr. Croley

Cutaneous melanoma is the most fatal form of skin cancer and is a considerable public health concern in the United States. Early detection and management of skin cancer can lead to decreased morbidity and mortality from skin cancer. As a result, the American Academy of Dermatology Association supports safe sun-protective practices and diligent self-screening for changing lesions.

Sunscreen use is an essential component of sun protection. New regulations from the US Food and Drug Administration (FDA) have left consumers concerned about the safety of sunscreens. According to a recent Cutis editorial from Vincent A. DeLeo, MD, “There is no question that, as physicians, we want to ‘first, do no harm,’ so we should all be interested in assuring our patients that our sunscreen recommendations are safe and we support the FDA proposal for additional data.”

Patients with skin of color experience disproportionately higher morbidity and mortality when diagnosed with melanoma. “Poor prognosis in patients with skin of color is multifactorial and may be due to poor use of sun protection, misconceptions about melanoma risk, atypical clinical presentation, impaired access to care, and delay in diagnosis,” according to a recent Cutis article. 

Population-based skin cancer screening performed exclusively by dermatologists is not practical. Primary care physicians and other experts in melanoma and public health need to be involved in reducing melanoma mortality. 

In this chat, we will provide expert recommendations on the diagnosis of skin cancer, preventive measures, and the latest research discussed among physicians.

Research & Resources

• “Doctor, Do I Need a Skin Check?”
• Assessing the effectiveness of knowledge-based interventions in skin of color populations.
• Melanoma in US Hispanics
• Podcast: Sunscreen update from Dr. Vincent DeLeo
• Windshield and UV exposure  
• Racial, ethnic minorities often don’t practice sun-protective behaviors.
• Sunscreen regulations and advice for your patients.

Join us on Tuesday, October 8, 2019, at 8:00 pm EST on Twitter at #MDedgeChats as we discuss skin cancer, and what’s new in sunscreen, skin of color, and melanoma. 

Special guests include physicians with expertise in dermatology and skin cancer, Anthony Rossi, MD (@DrAnthonyRossi), Julie Amthor Croley, MD, 15k followers on IG (@Drskinandsmiles), and Candrice Heath, MD (@DrCandriceHeath). Background information about the chat can be found below.

What will the conversation cover?

Q1: What are the most common types of skin cancer? 
Q2: What recent research findings can better inform patients about skin cancer risks?
Q3: What’s the difference between melanoma in fair skin vs. darker skin?
Q4: How does the risk of skin cancer differ in people with darker skin?
Q5: Why should sunscreen be used even in the fall and winter?

About Dr. Rossi: 

Dr. Anthony Rossi (@DrAnthonyRossi) is a board-certified dermatologist with fellowship training in Mohs micrographic surgery, cosmetic and laser surgery, and advanced cutaneous oncology at the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College program, both in New York.  He specializes in skin cancer surgery, cosmetic dermatologic surgery, and laser surgery.  

His research includes quality of life in cancer survivors, the use of noninvasive imaging of the skin, and nonsurgical treatments of skin cancer. Additionally, Dr. Rossi is active in dermatologic organizations and advocacy for medicine.

Research and Publications by Dr. Rossi 

About Dr. Heath:
 

Dr. Candrice Heath (@DrCandriceHeath) is Assistant Professor of Dermatology at the Lewis Katz School of Medicine at Temple University in Philadelphia, Pennsylvania with fellowship training in pediatric dermatology at Johns Hopkins University in Baltimore, Maryland. Dr. Heath is triple board certified in pediatrics, dermatology, and pediatric dermatology. She specializes in adult and pediatric dermatology, skin of color, acne, and eczema. Dr. Heath also enjoys educating primary care physicians on the front lines of health care and delivering easy to understand information to consumers. 

Research and publications by Dr. Heath 
Guest host of MDedge podcast: A sunscreen update with Dr. Vincent DeLeo. 
 

About Dr. Croley:  

Dr. Julie Amthor Croley (@Drskinandsmiles) also known as “Dr. Skin and Smiles” has 15,000 followers on Instagram, and is a Chief Dermatology Resident at the University of Texas Medical Branch in Galveston, Texas. She has a special interest in skin cancer and dermatological surgery and hopes to complete a fellowship in Mohs micrographic surgery after residency. In her free time, Dr. Croley enjoys spending time with her husband (an orthopedic surgeon), running and competing in marathons, and spending time on the beach. 

Media coverage by Dr. Croley

Cutaneous melanoma is the most fatal form of skin cancer and is a considerable public health concern in the United States. Early detection and management of skin cancer can lead to decreased morbidity and mortality from skin cancer. As a result, the American Academy of Dermatology Association supports safe sun-protective practices and diligent self-screening for changing lesions.

Sunscreen use is an essential component of sun protection. New regulations from the US Food and Drug Administration (FDA) have left consumers concerned about the safety of sunscreens. According to a recent Cutis editorial from Vincent A. DeLeo, MD, “There is no question that, as physicians, we want to ‘first, do no harm,’ so we should all be interested in assuring our patients that our sunscreen recommendations are safe and we support the FDA proposal for additional data.”

Patients with skin of color experience disproportionately higher morbidity and mortality when diagnosed with melanoma. “Poor prognosis in patients with skin of color is multifactorial and may be due to poor use of sun protection, misconceptions about melanoma risk, atypical clinical presentation, impaired access to care, and delay in diagnosis,” according to a recent Cutis article. 

Population-based skin cancer screening performed exclusively by dermatologists is not practical. Primary care physicians and other experts in melanoma and public health need to be involved in reducing melanoma mortality. 

In this chat, we will provide expert recommendations on the diagnosis of skin cancer, preventive measures, and the latest research discussed among physicians.

Research & Resources

• “Doctor, Do I Need a Skin Check?”
• Assessing the effectiveness of knowledge-based interventions in skin of color populations.
• Melanoma in US Hispanics
• Podcast: Sunscreen update from Dr. Vincent DeLeo
• Windshield and UV exposure  
• Racial, ethnic minorities often don’t practice sun-protective behaviors.
• Sunscreen regulations and advice for your patients.

Practice Gap

Management of nonmelanoma skin cancer (NMSC) in elderly patients can cause morbidity because these patients frequently struggle to care for their biopsy sites and experience biopsy- and surgery-related complications. To minimize this treatment-related morbidity, we designed a knifeless treatment approach that employs reflectance confocal microscopy (RCM) in lieu of skin biopsy to establish the diagnosis of NMSC, then uses either intralesional or topical chemotherapy or immunotherapy (as appropriate, depending on depth of invasion) to cure the NMSC. With this approach, the patient is spared both biopsy- and surgery-related difficulties, though both intralesional and topical chemotherapy are accompanied by their own risks for adverse effects.

The Technique

Elderly patients, diabetic patients, and patients with lesions suspicious for NMSC on areas prone to poor wound healing or to notable treatment-related morbidity (eg, lower legs, genitals, the face of younger patients) are offered skin biopsy or RCM; the latter is performed during the appointment by an RCM-trained medical assistant. Patients who elect to undergo RCM and who have a diagnosis of superficial basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) in situ are then treated with topical imiquimod or 5-fluorouracil. Patients with an invasive subtype of either BCC, SCC, or keratoacanthoma receive intralesional 5-fluorouracil injected at a concentration of 50 mg/cc at weekly intervals until the lesion blanches, with ongoing follow-up until the lesion is observed to have resolved under dermoscopic inspection.

When resolution is uncertain, RCM is repeated to assess for tumor clearance. Repeat RCM is performed at least 4 weeks after termination of treatment to avoid misinterpretation caused by treatment-related tissue inflammation. Patients who are not cured using this management approach are offered appropriate surgical management.

Practice Implications

Reflectance confocal microscopy has emerged as an effective modality for confirming the diagnosis of NMSC with high sensitivity and specificity.^1,2 Emergence of this technology presents an opportunity for improving the way the NMSC is managed because RCM allows dermatologists to confirm the diagnosis of BCC and SCC by interpretation of RCM mosaics rather than by histopathologic examination of biopsied tissue. Our knifeless approach to skin cancer management is especially beneficial when biopsy and dermatologic surgery are likely to confer notable morbidity, such as managing NMSC on the face of a young adult, in the frail elderly population, or in diabetic patients, and when treating sites on the lower extremity prone to poor wound healing.

Practice Gap

Management of nonmelanoma skin cancer (NMSC) in elderly patients can cause morbidity because these patients frequently struggle to care for their biopsy sites and experience biopsy- and surgery-related complications. To minimize this treatment-related morbidity, we designed a knifeless treatment approach that employs reflectance confocal microscopy (RCM) in lieu of skin biopsy to establish the diagnosis of NMSC, then uses either intralesional or topical chemotherapy or immunotherapy (as appropriate, depending on depth of invasion) to cure the NMSC. With this approach, the patient is spared both biopsy- and surgery-related difficulties, though both intralesional and topical chemotherapy are accompanied by their own risks for adverse effects.

The Technique

Elderly patients, diabetic patients, and patients with lesions suspicious for NMSC on areas prone to poor wound healing or to notable treatment-related morbidity (eg, lower legs, genitals, the face of younger patients) are offered skin biopsy or RCM; the latter is performed during the appointment by an RCM-trained medical assistant. Patients who elect to undergo RCM and who have a diagnosis of superficial basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) in situ are then treated with topical imiquimod or 5-fluorouracil. Patients with an invasive subtype of either BCC, SCC, or keratoacanthoma receive intralesional 5-fluorouracil injected at a concentration of 50 mg/cc at weekly intervals until the lesion blanches, with ongoing follow-up until the lesion is observed to have resolved under dermoscopic inspection.

When resolution is uncertain, RCM is repeated to assess for tumor clearance. Repeat RCM is performed at least 4 weeks after termination of treatment to avoid misinterpretation caused by treatment-related tissue inflammation. Patients who are not cured using this management approach are offered appropriate surgical management.

Practice Implications

Reflectance confocal microscopy has emerged as an effective modality for confirming the diagnosis of NMSC with high sensitivity and specificity.^1,2 Emergence of this technology presents an opportunity for improving the way the NMSC is managed because RCM allows dermatologists to confirm the diagnosis of BCC and SCC by interpretation of RCM mosaics rather than by histopathologic examination of biopsied tissue. Our knifeless approach to skin cancer management is especially beneficial when biopsy and dermatologic surgery are likely to confer notable morbidity, such as managing NMSC on the face of a young adult, in the frail elderly population, or in diabetic patients, and when treating sites on the lower extremity prone to poor wound healing.

Practice Gap

Management of nonmelanoma skin cancer (NMSC) in elderly patients can cause morbidity because these patients frequently struggle to care for their biopsy sites and experience biopsy- and surgery-related complications. To minimize this treatment-related morbidity, we designed a knifeless treatment approach that employs reflectance confocal microscopy (RCM) in lieu of skin biopsy to establish the diagnosis of NMSC, then uses either intralesional or topical chemotherapy or immunotherapy (as appropriate, depending on depth of invasion) to cure the NMSC. With this approach, the patient is spared both biopsy- and surgery-related difficulties, though both intralesional and topical chemotherapy are accompanied by their own risks for adverse effects.

The Technique

Elderly patients, diabetic patients, and patients with lesions suspicious for NMSC on areas prone to poor wound healing or to notable treatment-related morbidity (eg, lower legs, genitals, the face of younger patients) are offered skin biopsy or RCM; the latter is performed during the appointment by an RCM-trained medical assistant. Patients who elect to undergo RCM and who have a diagnosis of superficial basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) in situ are then treated with topical imiquimod or 5-fluorouracil. Patients with an invasive subtype of either BCC, SCC, or keratoacanthoma receive intralesional 5-fluorouracil injected at a concentration of 50 mg/cc at weekly intervals until the lesion blanches, with ongoing follow-up until the lesion is observed to have resolved under dermoscopic inspection.

When resolution is uncertain, RCM is repeated to assess for tumor clearance. Repeat RCM is performed at least 4 weeks after termination of treatment to avoid misinterpretation caused by treatment-related tissue inflammation. Patients who are not cured using this management approach are offered appropriate surgical management.

Practice Implications

Reflectance confocal microscopy has emerged as an effective modality for confirming the diagnosis of NMSC with high sensitivity and specificity.^1,2 Emergence of this technology presents an opportunity for improving the way the NMSC is managed because RCM allows dermatologists to confirm the diagnosis of BCC and SCC by interpretation of RCM mosaics rather than by histopathologic examination of biopsied tissue. Our knifeless approach to skin cancer management is especially beneficial when biopsy and dermatologic surgery are likely to confer notable morbidity, such as managing NMSC on the face of a young adult, in the frail elderly population, or in diabetic patients, and when treating sites on the lower extremity prone to poor wound healing.

SAN DIEGO – Using laser and light sources to treat nonaggressive basal cell carcinoma (BCC) is emerging as a promising treatment option, especially for those with multiple tumors and those who are poor surgical candidates, Arisa E. Ortiz, MD, said at the annual Masters of Aesthetics Symposium.

“Topical therapies often result in recurrence, so there really is a need for an alternative [to surgery] that’s effective, efficient, and carries a low risk of side effects,” said Dr. Ortiz, who is director of laser and cosmetic dermatology at the University of California, San Diego,

“The prototypic feature of BCC is the presence of telangiectatic vessels,” she explained, and the postulated mechanism of action is selective photothermolysis of the tumor vasculature. “These vessels are slightly larger in caliber, compared with normal skin – 40 micrometers versus 15 micrometers – and more fragile. You can tailor your pulse duration to the size of the vessels. Theoretically, by targeting the vasculature then you get tumor regression with sparing of normal tissue.”

Initial studies of this approach have used the 595-nm pulsed-dye laser, which is well absorbed by oxyhemoglobin, but more recent studies have used the 1064-nm Nd:YAG to reach deep arterial vessels. In a prospective, open-label study, 10 patients with 13 BCCs less than 1.5 cm in diameter received one treatment with a 10-ms pulsed 1064-nm Nd:YAG laser delivered on the trunk or extremities at a fluence of 80-120 J/cm² (Lasers Surg Med. 2015;47[2]:106-10). Dr. Ortiz and her colleagues observed a 92% clearance rate overall.

She described other earlier studies of the approach as flawed, because they relied on confirmation of clearance rates with clinical exam or biopsy rather than with surgical excision. “Also, some of the protocols weren’t standardized, multiple treatments were required, and subjects with suboptimal response were currently on anticoagulation,” she said. “Intravascular coagulation is important for effective treatment with vascular lasers, so anticoagulation may interfere with efficacy.”

In a more recent multicenter study, Dr. Ortiz and her colleagues treated 33 BCCs once with the long-pulsed 1064-nm Nd:YAG laser delivered with a 5-6 mm spot size at a fluence of 125-140 J/cm² and a 7-10 ms pulse duration (Laser Surgery Med. Feb 13 2018. doi: 10.1002/lsm.22803). Standard surgical excision with 5-mm margins was performed 4 weeks after laser treatment. Among 31 subjects who completed the study, 28 of 31 BCC tumors (90%) cleared after one treatment.

“The treatments were performed without anesthesia, because we didn’t want the vasculature to be affected, but in clinical practice I am now using lidocaine with no epinephrine,” Dr. Ortiz said. She characterized the results as “at least comparable to, if not superior to” common modalities including methyl aminolevulinate–PDT (72.8%), imiquimod cream (83.4%), and fluorouracil cream (80.1%). “One criticism I hear is that with such high fluences, you’re probably getting some bulk heating,” she said. “Maybe so, but it seems to work and there’s no scarring, which suggests otherwise.”

Advantages of using a 1064-nm Nd:YAG for treating nonaggressive BCCs are that it requires just one treatment, it takes about 5 minutes, and there is no significant downtime, with no limitations in posttreatment activity. “Potentially there is a relatively decreased risk for complications, including infection and bleeding,” she added. “It’s a good alternative for treating patients with multiple tumors or those who are poor surgical candidates.”

She and her colleagues are currently performing a long-term follow-up study of 35 BCC lesions. Only one has potentially recurred, but that recurrence has not yet been confirmed.

Dr. Ortiz treats BCCs with a standard 5-mm margin and uses lidocaine without epinephrine to avoid vasoconstriction. She typically uses a 1064-nm Cutera excel V laser delivered at a pulse duration of 8 ms and a fluence of 140 J/cm^2, with no cooling. “Theoretically, any 1064-nm pulsed-dye laser could work, but the way the pulse is delivered is different, depending on which device” is used, she said.

“I always like waiting between passes to avoid any bulk heating. The immediate endpoint to strive for is slight graying and slight contraction,” she said. Billing codes for malignant destruction/electrodesiccation and curettage can be used (codes 17260-17266 for the trunk and 17280-17283 for the face).

In order to determine the mechanism of cell death and to optimize results, Dr. Ortiz said that further studies need to be conducted in vitro and in vivo. In order to determine treatment efficacy, clinical studies involving various heat sources and low concentrations of lidocaine are also required.

Dr. Ortiz disclosed having financial relationships with numerous pharmaceutical and device companies. She is also cochair of the MOAS.

dbrunk@mdedge.com

SAN DIEGO – Using laser and light sources to treat nonaggressive basal cell carcinoma (BCC) is emerging as a promising treatment option, especially for those with multiple tumors and those who are poor surgical candidates, Arisa E. Ortiz, MD, said at the annual Masters of Aesthetics Symposium.

“Topical therapies often result in recurrence, so there really is a need for an alternative [to surgery] that’s effective, efficient, and carries a low risk of side effects,” said Dr. Ortiz, who is director of laser and cosmetic dermatology at the University of California, San Diego,

“The prototypic feature of BCC is the presence of telangiectatic vessels,” she explained, and the postulated mechanism of action is selective photothermolysis of the tumor vasculature. “These vessels are slightly larger in caliber, compared with normal skin – 40 micrometers versus 15 micrometers – and more fragile. You can tailor your pulse duration to the size of the vessels. Theoretically, by targeting the vasculature then you get tumor regression with sparing of normal tissue.”

Initial studies of this approach have used the 595-nm pulsed-dye laser, which is well absorbed by oxyhemoglobin, but more recent studies have used the 1064-nm Nd:YAG to reach deep arterial vessels. In a prospective, open-label study, 10 patients with 13 BCCs less than 1.5 cm in diameter received one treatment with a 10-ms pulsed 1064-nm Nd:YAG laser delivered on the trunk or extremities at a fluence of 80-120 J/cm² (Lasers Surg Med. 2015;47[2]:106-10). Dr. Ortiz and her colleagues observed a 92% clearance rate overall.

She described other earlier studies of the approach as flawed, because they relied on confirmation of clearance rates with clinical exam or biopsy rather than with surgical excision. “Also, some of the protocols weren’t standardized, multiple treatments were required, and subjects with suboptimal response were currently on anticoagulation,” she said. “Intravascular coagulation is important for effective treatment with vascular lasers, so anticoagulation may interfere with efficacy.”

In a more recent multicenter study, Dr. Ortiz and her colleagues treated 33 BCCs once with the long-pulsed 1064-nm Nd:YAG laser delivered with a 5-6 mm spot size at a fluence of 125-140 J/cm² and a 7-10 ms pulse duration (Laser Surgery Med. Feb 13 2018. doi: 10.1002/lsm.22803). Standard surgical excision with 5-mm margins was performed 4 weeks after laser treatment. Among 31 subjects who completed the study, 28 of 31 BCC tumors (90%) cleared after one treatment.

“The treatments were performed without anesthesia, because we didn’t want the vasculature to be affected, but in clinical practice I am now using lidocaine with no epinephrine,” Dr. Ortiz said. She characterized the results as “at least comparable to, if not superior to” common modalities including methyl aminolevulinate–PDT (72.8%), imiquimod cream (83.4%), and fluorouracil cream (80.1%). “One criticism I hear is that with such high fluences, you’re probably getting some bulk heating,” she said. “Maybe so, but it seems to work and there’s no scarring, which suggests otherwise.”

Advantages of using a 1064-nm Nd:YAG for treating nonaggressive BCCs are that it requires just one treatment, it takes about 5 minutes, and there is no significant downtime, with no limitations in posttreatment activity. “Potentially there is a relatively decreased risk for complications, including infection and bleeding,” she added. “It’s a good alternative for treating patients with multiple tumors or those who are poor surgical candidates.”

She and her colleagues are currently performing a long-term follow-up study of 35 BCC lesions. Only one has potentially recurred, but that recurrence has not yet been confirmed.

Dr. Ortiz treats BCCs with a standard 5-mm margin and uses lidocaine without epinephrine to avoid vasoconstriction. She typically uses a 1064-nm Cutera excel V laser delivered at a pulse duration of 8 ms and a fluence of 140 J/cm^2, with no cooling. “Theoretically, any 1064-nm pulsed-dye laser could work, but the way the pulse is delivered is different, depending on which device” is used, she said.

“I always like waiting between passes to avoid any bulk heating. The immediate endpoint to strive for is slight graying and slight contraction,” she said. Billing codes for malignant destruction/electrodesiccation and curettage can be used (codes 17260-17266 for the trunk and 17280-17283 for the face).

In order to determine the mechanism of cell death and to optimize results, Dr. Ortiz said that further studies need to be conducted in vitro and in vivo. In order to determine treatment efficacy, clinical studies involving various heat sources and low concentrations of lidocaine are also required.

Dr. Ortiz disclosed having financial relationships with numerous pharmaceutical and device companies. She is also cochair of the MOAS.

dbrunk@mdedge.com

SAN DIEGO – Using laser and light sources to treat nonaggressive basal cell carcinoma (BCC) is emerging as a promising treatment option, especially for those with multiple tumors and those who are poor surgical candidates, Arisa E. Ortiz, MD, said at the annual Masters of Aesthetics Symposium.

“Topical therapies often result in recurrence, so there really is a need for an alternative [to surgery] that’s effective, efficient, and carries a low risk of side effects,” said Dr. Ortiz, who is director of laser and cosmetic dermatology at the University of California, San Diego,

“The prototypic feature of BCC is the presence of telangiectatic vessels,” she explained, and the postulated mechanism of action is selective photothermolysis of the tumor vasculature. “These vessels are slightly larger in caliber, compared with normal skin – 40 micrometers versus 15 micrometers – and more fragile. You can tailor your pulse duration to the size of the vessels. Theoretically, by targeting the vasculature then you get tumor regression with sparing of normal tissue.”

Initial studies of this approach have used the 595-nm pulsed-dye laser, which is well absorbed by oxyhemoglobin, but more recent studies have used the 1064-nm Nd:YAG to reach deep arterial vessels. In a prospective, open-label study, 10 patients with 13 BCCs less than 1.5 cm in diameter received one treatment with a 10-ms pulsed 1064-nm Nd:YAG laser delivered on the trunk or extremities at a fluence of 80-120 J/cm² (Lasers Surg Med. 2015;47[2]:106-10). Dr. Ortiz and her colleagues observed a 92% clearance rate overall.

She described other earlier studies of the approach as flawed, because they relied on confirmation of clearance rates with clinical exam or biopsy rather than with surgical excision. “Also, some of the protocols weren’t standardized, multiple treatments were required, and subjects with suboptimal response were currently on anticoagulation,” she said. “Intravascular coagulation is important for effective treatment with vascular lasers, so anticoagulation may interfere with efficacy.”

In a more recent multicenter study, Dr. Ortiz and her colleagues treated 33 BCCs once with the long-pulsed 1064-nm Nd:YAG laser delivered with a 5-6 mm spot size at a fluence of 125-140 J/cm² and a 7-10 ms pulse duration (Laser Surgery Med. Feb 13 2018. doi: 10.1002/lsm.22803). Standard surgical excision with 5-mm margins was performed 4 weeks after laser treatment. Among 31 subjects who completed the study, 28 of 31 BCC tumors (90%) cleared after one treatment.

“The treatments were performed without anesthesia, because we didn’t want the vasculature to be affected, but in clinical practice I am now using lidocaine with no epinephrine,” Dr. Ortiz said. She characterized the results as “at least comparable to, if not superior to” common modalities including methyl aminolevulinate–PDT (72.8%), imiquimod cream (83.4%), and fluorouracil cream (80.1%). “One criticism I hear is that with such high fluences, you’re probably getting some bulk heating,” she said. “Maybe so, but it seems to work and there’s no scarring, which suggests otherwise.”

Advantages of using a 1064-nm Nd:YAG for treating nonaggressive BCCs are that it requires just one treatment, it takes about 5 minutes, and there is no significant downtime, with no limitations in posttreatment activity. “Potentially there is a relatively decreased risk for complications, including infection and bleeding,” she added. “It’s a good alternative for treating patients with multiple tumors or those who are poor surgical candidates.”

She and her colleagues are currently performing a long-term follow-up study of 35 BCC lesions. Only one has potentially recurred, but that recurrence has not yet been confirmed.

Dr. Ortiz treats BCCs with a standard 5-mm margin and uses lidocaine without epinephrine to avoid vasoconstriction. She typically uses a 1064-nm Cutera excel V laser delivered at a pulse duration of 8 ms and a fluence of 140 J/cm^2, with no cooling. “Theoretically, any 1064-nm pulsed-dye laser could work, but the way the pulse is delivered is different, depending on which device” is used, she said.

“I always like waiting between passes to avoid any bulk heating. The immediate endpoint to strive for is slight graying and slight contraction,” she said. Billing codes for malignant destruction/electrodesiccation and curettage can be used (codes 17260-17266 for the trunk and 17280-17283 for the face).

In order to determine the mechanism of cell death and to optimize results, Dr. Ortiz said that further studies need to be conducted in vitro and in vivo. In order to determine treatment efficacy, clinical studies involving various heat sources and low concentrations of lidocaine are also required.

Dr. Ortiz disclosed having financial relationships with numerous pharmaceutical and device companies. She is also cochair of the MOAS.

dbrunk@mdedge.com

To the Editor:

A 43-year-old woman presented with a mole on the central back that had been present since childhood and had changed and grown over the last few years. The patient reported that her 2-year-old rescue dog frequently sniffed the mole and would subsequently get agitated and try to scratch and bite the lesion. This behavior prompted the patient to visit a dermatologist.

She reported no personal history of melanoma or nonmelanoma skin cancer, tanning booth exposure, blistering sunburns, or use of immunosuppressant medications. Her family history was remarkable for basal cell carcinoma in her father but no family history of melanoma. Physical examination revealed a 1.2×1.5-cm brown patch along with a 1×1-cm ulcerated nodule on the lower aspect of the lesion (Figure 1). Dermoscopy showed a blue-white veil and an irregular vascular pattern (Figure 2). No cervical, axillary, or inguinal lymphadenopathy was appreciated on physical examination. Reflectance confocal microscopy showed pagetoid spread of atypical round melanocytes as well as melanocytes in the stratum corneum (Figure 3).

The patient was referred to a surgical oncologist for wide local excision and sentinel lymph node biopsy. Pathology showed a 4-mm-thick melanoma with numerous positive lymph nodes (Figure 4). The patient subsequently underwent a right axillary lymphadenectomy and was diagnosed with stage IIIB malignant melanoma. After surgery, the patient reported that her dog would now sniff her back and calmly rest his head in her lap.

Both anecdotal and systematic evidence have emerged on the role of canine olfaction in the detection of lung, breast, colorectal, ovarian, prostate, and skin cancers, including malignant melanoma.^1-6 A 1989 case report described a woman who was prompted to seek dermatologic evaluation of a pigmented lesion because her dog consistently targeted the lesion. Excision and subsequent histopathologic examination of the lesion revealed that it was malignant melanoma.⁵ Another case report described a patient whose dog, which was not trained to detect cancers in humans, persistently licked a lesion behind the patient’s ear that eventually was found to be malignant melanoma.⁶ These reports have inspired considerable research interest regarding canine olfaction as a potential method to noninvasively screen for and even diagnose malignant melanomas in humans.

Both physiologic and pathologic metabolic processes result in the production of volatile organic compounds (VOCs), or small odorant molecules that evaporate at normal temperatures and pressures.¹ Individual cells release VOCs in extremely low concentrations into the blood, urine, feces, and breath, as well as onto the skin’s surface, but there are methods for detecting these VOCs, including gas chromatography–mass spectrometry and canine olfaction.^7,8 Pathologic processes, such as infection and malignancy, result in irregular protein synthesis and metabolism, producing new VOCs or differing concentrations of VOCs as compared to normal processes.¹

Dimethyl disulfide and dimethyl trisulfide compounds have been identified in malignant melanoma, and these compounds are not produced by normal melanocytes.⁷ Furthermore, malignant melanoma produces differing quantities of these compounds as compared to normal melanocytes, including isovaleric acid, 2-methylbutyric acid, isoamyl alcohol (3-methyl-1-butanol), and 2-methyl-1-butanol, resulting in a distinct odorant profile that previously has been detected via canine olfaction.⁷ Canine olfaction can identify odorant molecules at up to 1 part per trillion (a magnitude more sensitive than the currently available gas chromatography–mass spectrometry technologies) and can detect the production of new VOCs or altered VOC ratios due to pathologic processes.¹ Systematic studies with dogs that are trained to detect cancers in humans have shown that canine olfaction correctly identified malignant melanomas against healthy skin, benign nevi, and even basal cell carcinomas at higher rates than what would have been expected by chance alone.^2,3

Canine olfaction can identify new or altered ratios of odorant VOCs associated with pathologic metabolic processes, and canines can be trained to target odor profiles associated with specific diseases.¹ Canine olfaction for melanoma screening and diagnosis may seem appealing, as it provides an easily transportable, real-time, low-cost method compared to other techniques such as gas chromatography–mass spectrometry.¹ Although preliminary results have shown that canine olfaction detects melanoma at higher rates than would be expected by chance alone, these findings have not approached clinical utility for the widespread use of canine olfaction as a screening method for melanoma.^2,3,9 Further studies are needed to understand the role of canine olfaction in melanoma screening and diagnosis as well as to explore methods to optimize sensitivity and specificity. Until then, patients and dermatologists should not ignore the behavior of dogs toward skin lesions. Dogs may be beneficial in the detection of melanoma and help save lives, as was seen in our case.

To the Editor:

A 43-year-old woman presented with a mole on the central back that had been present since childhood and had changed and grown over the last few years. The patient reported that her 2-year-old rescue dog frequently sniffed the mole and would subsequently get agitated and try to scratch and bite the lesion. This behavior prompted the patient to visit a dermatologist.

She reported no personal history of melanoma or nonmelanoma skin cancer, tanning booth exposure, blistering sunburns, or use of immunosuppressant medications. Her family history was remarkable for basal cell carcinoma in her father but no family history of melanoma. Physical examination revealed a 1.2×1.5-cm brown patch along with a 1×1-cm ulcerated nodule on the lower aspect of the lesion (Figure 1). Dermoscopy showed a blue-white veil and an irregular vascular pattern (Figure 2). No cervical, axillary, or inguinal lymphadenopathy was appreciated on physical examination. Reflectance confocal microscopy showed pagetoid spread of atypical round melanocytes as well as melanocytes in the stratum corneum (Figure 3).

The patient was referred to a surgical oncologist for wide local excision and sentinel lymph node biopsy. Pathology showed a 4-mm-thick melanoma with numerous positive lymph nodes (Figure 4). The patient subsequently underwent a right axillary lymphadenectomy and was diagnosed with stage IIIB malignant melanoma. After surgery, the patient reported that her dog would now sniff her back and calmly rest his head in her lap.

Both anecdotal and systematic evidence have emerged on the role of canine olfaction in the detection of lung, breast, colorectal, ovarian, prostate, and skin cancers, including malignant melanoma.^1-6 A 1989 case report described a woman who was prompted to seek dermatologic evaluation of a pigmented lesion because her dog consistently targeted the lesion. Excision and subsequent histopathologic examination of the lesion revealed that it was malignant melanoma.⁵ Another case report described a patient whose dog, which was not trained to detect cancers in humans, persistently licked a lesion behind the patient’s ear that eventually was found to be malignant melanoma.⁶ These reports have inspired considerable research interest regarding canine olfaction as a potential method to noninvasively screen for and even diagnose malignant melanomas in humans.

Both physiologic and pathologic metabolic processes result in the production of volatile organic compounds (VOCs), or small odorant molecules that evaporate at normal temperatures and pressures.¹ Individual cells release VOCs in extremely low concentrations into the blood, urine, feces, and breath, as well as onto the skin’s surface, but there are methods for detecting these VOCs, including gas chromatography–mass spectrometry and canine olfaction.^7,8 Pathologic processes, such as infection and malignancy, result in irregular protein synthesis and metabolism, producing new VOCs or differing concentrations of VOCs as compared to normal processes.¹

Dimethyl disulfide and dimethyl trisulfide compounds have been identified in malignant melanoma, and these compounds are not produced by normal melanocytes.⁷ Furthermore, malignant melanoma produces differing quantities of these compounds as compared to normal melanocytes, including isovaleric acid, 2-methylbutyric acid, isoamyl alcohol (3-methyl-1-butanol), and 2-methyl-1-butanol, resulting in a distinct odorant profile that previously has been detected via canine olfaction.⁷ Canine olfaction can identify odorant molecules at up to 1 part per trillion (a magnitude more sensitive than the currently available gas chromatography–mass spectrometry technologies) and can detect the production of new VOCs or altered VOC ratios due to pathologic processes.¹ Systematic studies with dogs that are trained to detect cancers in humans have shown that canine olfaction correctly identified malignant melanomas against healthy skin, benign nevi, and even basal cell carcinomas at higher rates than what would have been expected by chance alone.^2,3

Canine olfaction can identify new or altered ratios of odorant VOCs associated with pathologic metabolic processes, and canines can be trained to target odor profiles associated with specific diseases.¹ Canine olfaction for melanoma screening and diagnosis may seem appealing, as it provides an easily transportable, real-time, low-cost method compared to other techniques such as gas chromatography–mass spectrometry.¹ Although preliminary results have shown that canine olfaction detects melanoma at higher rates than would be expected by chance alone, these findings have not approached clinical utility for the widespread use of canine olfaction as a screening method for melanoma.^2,3,9 Further studies are needed to understand the role of canine olfaction in melanoma screening and diagnosis as well as to explore methods to optimize sensitivity and specificity. Until then, patients and dermatologists should not ignore the behavior of dogs toward skin lesions. Dogs may be beneficial in the detection of melanoma and help save lives, as was seen in our case.

To the Editor:

A 43-year-old woman presented with a mole on the central back that had been present since childhood and had changed and grown over the last few years. The patient reported that her 2-year-old rescue dog frequently sniffed the mole and would subsequently get agitated and try to scratch and bite the lesion. This behavior prompted the patient to visit a dermatologist.

She reported no personal history of melanoma or nonmelanoma skin cancer, tanning booth exposure, blistering sunburns, or use of immunosuppressant medications. Her family history was remarkable for basal cell carcinoma in her father but no family history of melanoma. Physical examination revealed a 1.2×1.5-cm brown patch along with a 1×1-cm ulcerated nodule on the lower aspect of the lesion (Figure 1). Dermoscopy showed a blue-white veil and an irregular vascular pattern (Figure 2). No cervical, axillary, or inguinal lymphadenopathy was appreciated on physical examination. Reflectance confocal microscopy showed pagetoid spread of atypical round melanocytes as well as melanocytes in the stratum corneum (Figure 3).

The patient was referred to a surgical oncologist for wide local excision and sentinel lymph node biopsy. Pathology showed a 4-mm-thick melanoma with numerous positive lymph nodes (Figure 4). The patient subsequently underwent a right axillary lymphadenectomy and was diagnosed with stage IIIB malignant melanoma. After surgery, the patient reported that her dog would now sniff her back and calmly rest his head in her lap.

Both anecdotal and systematic evidence have emerged on the role of canine olfaction in the detection of lung, breast, colorectal, ovarian, prostate, and skin cancers, including malignant melanoma.^1-6 A 1989 case report described a woman who was prompted to seek dermatologic evaluation of a pigmented lesion because her dog consistently targeted the lesion. Excision and subsequent histopathologic examination of the lesion revealed that it was malignant melanoma.⁵ Another case report described a patient whose dog, which was not trained to detect cancers in humans, persistently licked a lesion behind the patient’s ear that eventually was found to be malignant melanoma.⁶ These reports have inspired considerable research interest regarding canine olfaction as a potential method to noninvasively screen for and even diagnose malignant melanomas in humans.

Both physiologic and pathologic metabolic processes result in the production of volatile organic compounds (VOCs), or small odorant molecules that evaporate at normal temperatures and pressures.¹ Individual cells release VOCs in extremely low concentrations into the blood, urine, feces, and breath, as well as onto the skin’s surface, but there are methods for detecting these VOCs, including gas chromatography–mass spectrometry and canine olfaction.^7,8 Pathologic processes, such as infection and malignancy, result in irregular protein synthesis and metabolism, producing new VOCs or differing concentrations of VOCs as compared to normal processes.¹

Dimethyl disulfide and dimethyl trisulfide compounds have been identified in malignant melanoma, and these compounds are not produced by normal melanocytes.⁷ Furthermore, malignant melanoma produces differing quantities of these compounds as compared to normal melanocytes, including isovaleric acid, 2-methylbutyric acid, isoamyl alcohol (3-methyl-1-butanol), and 2-methyl-1-butanol, resulting in a distinct odorant profile that previously has been detected via canine olfaction.⁷ Canine olfaction can identify odorant molecules at up to 1 part per trillion (a magnitude more sensitive than the currently available gas chromatography–mass spectrometry technologies) and can detect the production of new VOCs or altered VOC ratios due to pathologic processes.¹ Systematic studies with dogs that are trained to detect cancers in humans have shown that canine olfaction correctly identified malignant melanomas against healthy skin, benign nevi, and even basal cell carcinomas at higher rates than what would have been expected by chance alone.^2,3

Canine olfaction can identify new or altered ratios of odorant VOCs associated with pathologic metabolic processes, and canines can be trained to target odor profiles associated with specific diseases.¹ Canine olfaction for melanoma screening and diagnosis may seem appealing, as it provides an easily transportable, real-time, low-cost method compared to other techniques such as gas chromatography–mass spectrometry.¹ Although preliminary results have shown that canine olfaction detects melanoma at higher rates than would be expected by chance alone, these findings have not approached clinical utility for the widespread use of canine olfaction as a screening method for melanoma.^2,3,9 Further studies are needed to understand the role of canine olfaction in melanoma screening and diagnosis as well as to explore methods to optimize sensitivity and specificity. Until then, patients and dermatologists should not ignore the behavior of dogs toward skin lesions. Dogs may be beneficial in the detection of melanoma and help save lives, as was seen in our case.

To the Editor:

Verrucous carcinoma (VC) is a rare type of squamous cell carcinoma characterized by a well-differentiated low-grade tumor with a high degree of keratinization. First described by Ackerman¹ in 1948, VC presents on the skin or oral and genital mucosae with minimal atypical cytologic findings.^1-3 It most commonly is seen in late middle-aged men (85% of cases) and presents as a slow-growing mass, often of more than 10 years’ duration.^2,3 Verrucous carcinoma frequently is observed at 3 particular anatomic sites: the oral cavity, known as oral florid papillomatosis; the anogenital area, known as Buschke-Löwenstein tumor; and on the plantar surface, known as epithelioma cuniculatum.^2-13

A 19-year-old man presented with an ulcerous lesion on the right big toe of 2 years’ duration. He reported that the lesion had gradually increased in size and was painful when walking. Physical examination revealed an ulcerated lesion on the right big toe with purulent inflammation and necrosis, unclear edges, and border nodules containing a fatty, yellowish, foul-smelling material (Figure 1). Histologic examination of purulent material from deep within the primary lesion revealed gram-negative rods and gram-positive diplococci. Erlich-Ziehl-Neelsen staining and culture in Lowenstein-Jensen medium were negative for mycobacteria. Histologic examination and fungal culture were not diagnostic for fungal infection.

At the initial presentation, radiography of the right big toe revealed porotic signs and cortical irregularity of the distal phalanx. A deep incisional biopsy of the lesion was performed for pathologic and microbiologic analysis. Erlich-Ziehl-Neelsen staining was negative, fungal elements could not be observed, and there was no growth in Lowenstein-Jensen medium or Sabouraud dextrose agar. Polymerase chain reaction for human papillomavirus, M tuberculosis, and atypical mycobacterium was negative. Periodic acid–Schiff staining was negative for fungal elements. Histopathologic examination revealed an exophytic as well as endophytic squamous cell proliferation infiltrating deeper layers of the dermis with a desmoplastic stroma (Figure 2). Slight cytologic atypia was noted. A diagnosis of VC was made based on the clinical and histopathologic findings. The patient’s right big toe was amputated by plastic surgery 6 months after the initial presentation.

Histopathologic examination, especially of superficial biopsies, generally reveals squamous cell proliferation demonstrating minimal pleomorphism and cytologic atypia with sparse mitotic figures.^4-6 Diagnosis of VC can be challenging if the endophytic proliferation, which characteristically pushes into the dermis and even deeper tissues at the base of the lesion, is not seen. This feature is uncommon in squamous cell carcinomas.^3,4,6 Histopathologic detection of koilocytes can lead to difficulty in distinguishing VC from warts.⁵ The growth of lesions is exophytic in plantar verrucae, whereas in VC it may be either exophytic or endophytic.⁴ At early stages, it is too difficult to distinguish VC from pseudoepitheliomatous hyperplasia caused by chronic inflammation, as well as from tuberculosis and subcutaneous mycoses.^3,6 In these situations, possible responsible microorganisms must be sought out. Amelanotic malignant melanoma and eccrine poroma also should be considered in the differential diagnosis.^3,5 If the biopsy specimen is obtained superficially and is fragmented, the diagnosis is more difficult, making deep biopsies essential in suspicious cases.⁴ Excision is the best treatment, and Mohs micrographic surgery may be required in some cases.^2,3,11 It is important to consider that radiotherapy may lead to anaplastic transformation and metastasis.² Metastasis to lymph nodes is very rare, and the prognosis is excellent when complete excision is performed.² Recurrence may be observed.⁴

Our case of plantar VC is notable because of the patient’s young age, which is uncommon, as the typical age for developing VC is late middle age (ie, fifth and sixth decades of life). A long-standing lesion that is therapy resistant and without a detectable microorganism should be investigated for malignancy by repetitive deep biopsy regardless of the patient’s age, as demonstrated in our case.

To the Editor:

Verrucous carcinoma (VC) is a rare type of squamous cell carcinoma characterized by a well-differentiated low-grade tumor with a high degree of keratinization. First described by Ackerman¹ in 1948, VC presents on the skin or oral and genital mucosae with minimal atypical cytologic findings.^1-3 It most commonly is seen in late middle-aged men (85% of cases) and presents as a slow-growing mass, often of more than 10 years’ duration.^2,3 Verrucous carcinoma frequently is observed at 3 particular anatomic sites: the oral cavity, known as oral florid papillomatosis; the anogenital area, known as Buschke-Löwenstein tumor; and on the plantar surface, known as epithelioma cuniculatum.^2-13

A 19-year-old man presented with an ulcerous lesion on the right big toe of 2 years’ duration. He reported that the lesion had gradually increased in size and was painful when walking. Physical examination revealed an ulcerated lesion on the right big toe with purulent inflammation and necrosis, unclear edges, and border nodules containing a fatty, yellowish, foul-smelling material (Figure 1). Histologic examination of purulent material from deep within the primary lesion revealed gram-negative rods and gram-positive diplococci. Erlich-Ziehl-Neelsen staining and culture in Lowenstein-Jensen medium were negative for mycobacteria. Histologic examination and fungal culture were not diagnostic for fungal infection.

At the initial presentation, radiography of the right big toe revealed porotic signs and cortical irregularity of the distal phalanx. A deep incisional biopsy of the lesion was performed for pathologic and microbiologic analysis. Erlich-Ziehl-Neelsen staining was negative, fungal elements could not be observed, and there was no growth in Lowenstein-Jensen medium or Sabouraud dextrose agar. Polymerase chain reaction for human papillomavirus, M tuberculosis, and atypical mycobacterium was negative. Periodic acid–Schiff staining was negative for fungal elements. Histopathologic examination revealed an exophytic as well as endophytic squamous cell proliferation infiltrating deeper layers of the dermis with a desmoplastic stroma (Figure 2). Slight cytologic atypia was noted. A diagnosis of VC was made based on the clinical and histopathologic findings. The patient’s right big toe was amputated by plastic surgery 6 months after the initial presentation.

Histopathologic examination, especially of superficial biopsies, generally reveals squamous cell proliferation demonstrating minimal pleomorphism and cytologic atypia with sparse mitotic figures.^4-6 Diagnosis of VC can be challenging if the endophytic proliferation, which characteristically pushes into the dermis and even deeper tissues at the base of the lesion, is not seen. This feature is uncommon in squamous cell carcinomas.^3,4,6 Histopathologic detection of koilocytes can lead to difficulty in distinguishing VC from warts.⁵ The growth of lesions is exophytic in plantar verrucae, whereas in VC it may be either exophytic or endophytic.⁴ At early stages, it is too difficult to distinguish VC from pseudoepitheliomatous hyperplasia caused by chronic inflammation, as well as from tuberculosis and subcutaneous mycoses.^3,6 In these situations, possible responsible microorganisms must be sought out. Amelanotic malignant melanoma and eccrine poroma also should be considered in the differential diagnosis.^3,5 If the biopsy specimen is obtained superficially and is fragmented, the diagnosis is more difficult, making deep biopsies essential in suspicious cases.⁴ Excision is the best treatment, and Mohs micrographic surgery may be required in some cases.^2,3,11 It is important to consider that radiotherapy may lead to anaplastic transformation and metastasis.² Metastasis to lymph nodes is very rare, and the prognosis is excellent when complete excision is performed.² Recurrence may be observed.⁴

Our case of plantar VC is notable because of the patient’s young age, which is uncommon, as the typical age for developing VC is late middle age (ie, fifth and sixth decades of life). A long-standing lesion that is therapy resistant and without a detectable microorganism should be investigated for malignancy by repetitive deep biopsy regardless of the patient’s age, as demonstrated in our case.

To the Editor:

Verrucous carcinoma (VC) is a rare type of squamous cell carcinoma characterized by a well-differentiated low-grade tumor with a high degree of keratinization. First described by Ackerman¹ in 1948, VC presents on the skin or oral and genital mucosae with minimal atypical cytologic findings.^1-3 It most commonly is seen in late middle-aged men (85% of cases) and presents as a slow-growing mass, often of more than 10 years’ duration.^2,3 Verrucous carcinoma frequently is observed at 3 particular anatomic sites: the oral cavity, known as oral florid papillomatosis; the anogenital area, known as Buschke-Löwenstein tumor; and on the plantar surface, known as epithelioma cuniculatum.^2-13

A 19-year-old man presented with an ulcerous lesion on the right big toe of 2 years’ duration. He reported that the lesion had gradually increased in size and was painful when walking. Physical examination revealed an ulcerated lesion on the right big toe with purulent inflammation and necrosis, unclear edges, and border nodules containing a fatty, yellowish, foul-smelling material (Figure 1). Histologic examination of purulent material from deep within the primary lesion revealed gram-negative rods and gram-positive diplococci. Erlich-Ziehl-Neelsen staining and culture in Lowenstein-Jensen medium were negative for mycobacteria. Histologic examination and fungal culture were not diagnostic for fungal infection.

At the initial presentation, radiography of the right big toe revealed porotic signs and cortical irregularity of the distal phalanx. A deep incisional biopsy of the lesion was performed for pathologic and microbiologic analysis. Erlich-Ziehl-Neelsen staining was negative, fungal elements could not be observed, and there was no growth in Lowenstein-Jensen medium or Sabouraud dextrose agar. Polymerase chain reaction for human papillomavirus, M tuberculosis, and atypical mycobacterium was negative. Periodic acid–Schiff staining was negative for fungal elements. Histopathologic examination revealed an exophytic as well as endophytic squamous cell proliferation infiltrating deeper layers of the dermis with a desmoplastic stroma (Figure 2). Slight cytologic atypia was noted. A diagnosis of VC was made based on the clinical and histopathologic findings. The patient’s right big toe was amputated by plastic surgery 6 months after the initial presentation.

Histopathologic examination, especially of superficial biopsies, generally reveals squamous cell proliferation demonstrating minimal pleomorphism and cytologic atypia with sparse mitotic figures.^4-6 Diagnosis of VC can be challenging if the endophytic proliferation, which characteristically pushes into the dermis and even deeper tissues at the base of the lesion, is not seen. This feature is uncommon in squamous cell carcinomas.^3,4,6 Histopathologic detection of koilocytes can lead to difficulty in distinguishing VC from warts.⁵ The growth of lesions is exophytic in plantar verrucae, whereas in VC it may be either exophytic or endophytic.⁴ At early stages, it is too difficult to distinguish VC from pseudoepitheliomatous hyperplasia caused by chronic inflammation, as well as from tuberculosis and subcutaneous mycoses.^3,6 In these situations, possible responsible microorganisms must be sought out. Amelanotic malignant melanoma and eccrine poroma also should be considered in the differential diagnosis.^3,5 If the biopsy specimen is obtained superficially and is fragmented, the diagnosis is more difficult, making deep biopsies essential in suspicious cases.⁴ Excision is the best treatment, and Mohs micrographic surgery may be required in some cases.^2,3,11 It is important to consider that radiotherapy may lead to anaplastic transformation and metastasis.² Metastasis to lymph nodes is very rare, and the prognosis is excellent when complete excision is performed.² Recurrence may be observed.⁴

Our case of plantar VC is notable because of the patient’s young age, which is uncommon, as the typical age for developing VC is late middle age (ie, fifth and sixth decades of life). A long-standing lesion that is therapy resistant and without a detectable microorganism should be investigated for malignancy by repetitive deep biopsy regardless of the patient’s age, as demonstrated in our case.