Cutis

Dupixent

Sanofi and Regeneron Pharmaceuticals, Inc, announce US Food and Drug Administration approval of Dupixent (dupilumab) injection, a biologic for the treatment of adults with moderate to severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Dupixent is a human monoclonal antibody that inhibits overactive signaling of IL-4 and IL-3. It comes in a prefilled syringe and can be self-administered as a subcutaneous injection every other week after an initial loading dose. Dupixent MyWay will help eligible patients who are uninsured, lack coverage, or need assistance with out-of-pocket costs. For more information, visit www.dupixentHCP.com.

Renflexis

Samsung Bioepis Co, Ltd, announces US Food and Drug Administration approval of Renflexis (infliximab-abda) injection 100 mg, a biosimilar referencing infliximab. It is indicated in the United States for reducing signs and symptoms in patients with adult and pediatric Crohn disease, adult ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and adult plaque psoriasis. Renflexis will be marketed and distributed in the United States by Merck. For more information, visit www.samsungbioepis.com.

Replenix RetinolForte Treatment Serum

Topix Pharmaceuticals, Inc, introduces Replenix Retinol Forte Treatment Serum containing all- trans -retinol, which helps increase cell turnover to reduce the appearance of fine lines and wrinkles, im- prove skin texture and tone, and promote a collagen-rich appearance. The micropolymer delivery system stabilizes the retinol to protect and shield it from oxidation while on the skin. Its time-released delivery system creates a reservoir that continuously bathes the skin and minimizes irritation. It also contains green tea polyphenols to soothe and calm the skin, caffeine to diminish the appearance of redness, and hyaluronic acid to help skin retain moisture to replenish and repair skin barrier function. For more information, visit www.topixpharm.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

Dupixent

Sanofi and Regeneron Pharmaceuticals, Inc, announce US Food and Drug Administration approval of Dupixent (dupilumab) injection, a biologic for the treatment of adults with moderate to severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Dupixent is a human monoclonal antibody that inhibits overactive signaling of IL-4 and IL-3. It comes in a prefilled syringe and can be self-administered as a subcutaneous injection every other week after an initial loading dose. Dupixent MyWay will help eligible patients who are uninsured, lack coverage, or need assistance with out-of-pocket costs. For more information, visit www.dupixentHCP.com.

Renflexis

Samsung Bioepis Co, Ltd, announces US Food and Drug Administration approval of Renflexis (infliximab-abda) injection 100 mg, a biosimilar referencing infliximab. It is indicated in the United States for reducing signs and symptoms in patients with adult and pediatric Crohn disease, adult ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and adult plaque psoriasis. Renflexis will be marketed and distributed in the United States by Merck. For more information, visit www.samsungbioepis.com.

Replenix RetinolForte Treatment Serum

Topix Pharmaceuticals, Inc, introduces Replenix Retinol Forte Treatment Serum containing all- trans -retinol, which helps increase cell turnover to reduce the appearance of fine lines and wrinkles, im- prove skin texture and tone, and promote a collagen-rich appearance. The micropolymer delivery system stabilizes the retinol to protect and shield it from oxidation while on the skin. Its time-released delivery system creates a reservoir that continuously bathes the skin and minimizes irritation. It also contains green tea polyphenols to soothe and calm the skin, caffeine to diminish the appearance of redness, and hyaluronic acid to help skin retain moisture to replenish and repair skin barrier function. For more information, visit www.topixpharm.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

Dupixent

Sanofi and Regeneron Pharmaceuticals, Inc, announce US Food and Drug Administration approval of Dupixent (dupilumab) injection, a biologic for the treatment of adults with moderate to severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Dupixent is a human monoclonal antibody that inhibits overactive signaling of IL-4 and IL-3. It comes in a prefilled syringe and can be self-administered as a subcutaneous injection every other week after an initial loading dose. Dupixent MyWay will help eligible patients who are uninsured, lack coverage, or need assistance with out-of-pocket costs. For more information, visit www.dupixentHCP.com.

Renflexis

Samsung Bioepis Co, Ltd, announces US Food and Drug Administration approval of Renflexis (infliximab-abda) injection 100 mg, a biosimilar referencing infliximab. It is indicated in the United States for reducing signs and symptoms in patients with adult and pediatric Crohn disease, adult ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and adult plaque psoriasis. Renflexis will be marketed and distributed in the United States by Merck. For more information, visit www.samsungbioepis.com.

Replenix RetinolForte Treatment Serum

Topix Pharmaceuticals, Inc, introduces Replenix Retinol Forte Treatment Serum containing all- trans -retinol, which helps increase cell turnover to reduce the appearance of fine lines and wrinkles, im- prove skin texture and tone, and promote a collagen-rich appearance. The micropolymer delivery system stabilizes the retinol to protect and shield it from oxidation while on the skin. Its time-released delivery system creates a reservoir that continuously bathes the skin and minimizes irritation. It also contains green tea polyphenols to soothe and calm the skin, caffeine to diminish the appearance of redness, and hyaluronic acid to help skin retain moisture to replenish and repair skin barrier function. For more information, visit www.topixpharm.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

To the Editor:

An 85-year-old woman with a history of hypertension, hyperlipidemia, stroke, hypothyroidism, chronic obstructive pulmonary disease, and chronic myeloproliferative disorder presented to our clinic for evaluation of brown lesions on the hands and discoloration of the fingernails and toenails of 4 months’ duration. Six months prior to visiting our clinic she was admitted to the hospital for a pulmonary embolism. On admission she was noted to have a platelet count of more than 2 million/μL (reference range, 150,000–350,000/μL). She received urgent plasmapheresis and started hydroxyurea 500 mg twice daily, which she continued as an outpatient.

On physical examination at our clinic she had diffusely scattered red and brown macules on the bilateral palms and transverse hyperpigmented bands of various intensities on all fingernails and toenails (Figure). Her platelet count was 372,000/μL, white blood cell count was 5200/μL (reference range, 4500–11,000/μL), hemoglobin was 12.6 g/dL (reference range, 14.0–17.5 g/dL), hematocrit was 39.0% (reference range, 41%–50%), and mean corpuscular volume was 87.5 fL per red cell (reference range, 80–96 fL per red cell).

The patient was diagnosed with hydroxyurea-induced nail hyperpigmentation and was counseled on the benign nature of the condition. Three months later her platelet count decreased to below 100,000/μL, and hydroxyurea was discontinued. She noticed considerable improvement in the lesions on the hands and nails with the cessation of hydroxyurea.

Hydroxyurea is a cytostatic agent that has been used for more than 40 years in the treatment of myeloproliferative disorders including chronic myelogenous leukemia, polycythemia vera, essential thrombocythemia, and sickle cell anemia.¹ It inhibits ribonucleoside diphosphate reductase and promotes cell death in the S phase of the cell cycle.^1-3

Several adverse cutaneous reactions have been associated with hydroxyurea including increased pigmentation, hyperkeratosis, skin atrophy, xerosis, lichenoid eruptions, palmoplantar keratoderma, cutaneous vasculitis, alopecia, chronic leg ulcers, cutaneous carcinomas, and melanonychia.^3,4

Hydroxyurea-induced melanonychia most often occurs after several months of therapy but has been reported to occur as early as 4 months and as late as 5 years after initiating the drug.^1,4-6 The prevalence of melanonychia in the general population has been estimated at 1% and is thought to increase to approximately 4% in patients treated with hydroxyurea.^1,2,6,7 The prevalence of affected individuals increases with age; it is more common in females as well as black and Hispanic patients.²

Multiple patterns of hydroxyurea-induced melanonychia have been described, including longitudinal bands, transverse bands, and diffuse hyperpigmentation.^1-3,6 By far the most common pattern described in the literature is longitudinal banding^1-3,8; transverse bands are more rare. Although there are sporadic case reports linking the transverse bands with hydroxyurea, these bands occur more frequently with systemic chemotherapy such as doxorubicin and cyclosphosphamide.^1,6

The exact pathogenesis of hydroxyurea-induced melanonychia remains unclear, though it is thought to result from focal melanogenesis in the nail bed or matrix followed by deposition of melanin granules on the nail plate.^5,8 When these melanocytes are activated, melanosomes filled with melanin are transferred to differentiating matrix cells, which migrate distally as they become nail plate oncocytes, resulting in a visible band of pigmentation in the nail plate.² There also may be a genetic and photosensitivity component.^1,2

Prior case series have described spontaneous remission of nail hyperpigmentation following discontinuation of hydroxyurea therapy.¹ In many patients, however, the chronic nature of the myeloproliferative disorder and lack of alternative treatments make a therapeutic change difficult. Although the melanonychia itself is benign, it may precede the appearance of more serious mucocutaneous side effects, such as skin ulceration or development of cutaneous carcinomas, so careful monitoring should be performed.²

Our patient presented with melanonychia that was transverse, polydactylic, monochromic, stable in size and shape, and associated with palmar hyperpigmentation. Of note, the pigmentation remitted over time along with discontinuation of the drug. Although this presentation did not warrant a nail matrix biopsy, it should be noted that patients with single nail melanonychia suspicious for melanoma should have a biopsy, even with concomitant use of hydroxyurea.² Although transverse melanonychia most commonly is associated with other systemic chemotherapeutics, in the absence of such medications hydroxyurea was the likely culprit in our patient. The palmar hyperpigmentation, which has previously been reported with hydroxyurea use, further solidifies the diagnosis.

To the Editor:

An 85-year-old woman with a history of hypertension, hyperlipidemia, stroke, hypothyroidism, chronic obstructive pulmonary disease, and chronic myeloproliferative disorder presented to our clinic for evaluation of brown lesions on the hands and discoloration of the fingernails and toenails of 4 months’ duration. Six months prior to visiting our clinic she was admitted to the hospital for a pulmonary embolism. On admission she was noted to have a platelet count of more than 2 million/μL (reference range, 150,000–350,000/μL). She received urgent plasmapheresis and started hydroxyurea 500 mg twice daily, which she continued as an outpatient.

On physical examination at our clinic she had diffusely scattered red and brown macules on the bilateral palms and transverse hyperpigmented bands of various intensities on all fingernails and toenails (Figure). Her platelet count was 372,000/μL, white blood cell count was 5200/μL (reference range, 4500–11,000/μL), hemoglobin was 12.6 g/dL (reference range, 14.0–17.5 g/dL), hematocrit was 39.0% (reference range, 41%–50%), and mean corpuscular volume was 87.5 fL per red cell (reference range, 80–96 fL per red cell).

The patient was diagnosed with hydroxyurea-induced nail hyperpigmentation and was counseled on the benign nature of the condition. Three months later her platelet count decreased to below 100,000/μL, and hydroxyurea was discontinued. She noticed considerable improvement in the lesions on the hands and nails with the cessation of hydroxyurea.

Hydroxyurea is a cytostatic agent that has been used for more than 40 years in the treatment of myeloproliferative disorders including chronic myelogenous leukemia, polycythemia vera, essential thrombocythemia, and sickle cell anemia.¹ It inhibits ribonucleoside diphosphate reductase and promotes cell death in the S phase of the cell cycle.^1-3

Several adverse cutaneous reactions have been associated with hydroxyurea including increased pigmentation, hyperkeratosis, skin atrophy, xerosis, lichenoid eruptions, palmoplantar keratoderma, cutaneous vasculitis, alopecia, chronic leg ulcers, cutaneous carcinomas, and melanonychia.^3,4

Hydroxyurea-induced melanonychia most often occurs after several months of therapy but has been reported to occur as early as 4 months and as late as 5 years after initiating the drug.^1,4-6 The prevalence of melanonychia in the general population has been estimated at 1% and is thought to increase to approximately 4% in patients treated with hydroxyurea.^1,2,6,7 The prevalence of affected individuals increases with age; it is more common in females as well as black and Hispanic patients.²

Multiple patterns of hydroxyurea-induced melanonychia have been described, including longitudinal bands, transverse bands, and diffuse hyperpigmentation.^1-3,6 By far the most common pattern described in the literature is longitudinal banding^1-3,8; transverse bands are more rare. Although there are sporadic case reports linking the transverse bands with hydroxyurea, these bands occur more frequently with systemic chemotherapy such as doxorubicin and cyclosphosphamide.^1,6

The exact pathogenesis of hydroxyurea-induced melanonychia remains unclear, though it is thought to result from focal melanogenesis in the nail bed or matrix followed by deposition of melanin granules on the nail plate.^5,8 When these melanocytes are activated, melanosomes filled with melanin are transferred to differentiating matrix cells, which migrate distally as they become nail plate oncocytes, resulting in a visible band of pigmentation in the nail plate.² There also may be a genetic and photosensitivity component.^1,2

Prior case series have described spontaneous remission of nail hyperpigmentation following discontinuation of hydroxyurea therapy.¹ In many patients, however, the chronic nature of the myeloproliferative disorder and lack of alternative treatments make a therapeutic change difficult. Although the melanonychia itself is benign, it may precede the appearance of more serious mucocutaneous side effects, such as skin ulceration or development of cutaneous carcinomas, so careful monitoring should be performed.²

Our patient presented with melanonychia that was transverse, polydactylic, monochromic, stable in size and shape, and associated with palmar hyperpigmentation. Of note, the pigmentation remitted over time along with discontinuation of the drug. Although this presentation did not warrant a nail matrix biopsy, it should be noted that patients with single nail melanonychia suspicious for melanoma should have a biopsy, even with concomitant use of hydroxyurea.² Although transverse melanonychia most commonly is associated with other systemic chemotherapeutics, in the absence of such medications hydroxyurea was the likely culprit in our patient. The palmar hyperpigmentation, which has previously been reported with hydroxyurea use, further solidifies the diagnosis.

To the Editor:

An 85-year-old woman with a history of hypertension, hyperlipidemia, stroke, hypothyroidism, chronic obstructive pulmonary disease, and chronic myeloproliferative disorder presented to our clinic for evaluation of brown lesions on the hands and discoloration of the fingernails and toenails of 4 months’ duration. Six months prior to visiting our clinic she was admitted to the hospital for a pulmonary embolism. On admission she was noted to have a platelet count of more than 2 million/μL (reference range, 150,000–350,000/μL). She received urgent plasmapheresis and started hydroxyurea 500 mg twice daily, which she continued as an outpatient.

On physical examination at our clinic she had diffusely scattered red and brown macules on the bilateral palms and transverse hyperpigmented bands of various intensities on all fingernails and toenails (Figure). Her platelet count was 372,000/μL, white blood cell count was 5200/μL (reference range, 4500–11,000/μL), hemoglobin was 12.6 g/dL (reference range, 14.0–17.5 g/dL), hematocrit was 39.0% (reference range, 41%–50%), and mean corpuscular volume was 87.5 fL per red cell (reference range, 80–96 fL per red cell).

The patient was diagnosed with hydroxyurea-induced nail hyperpigmentation and was counseled on the benign nature of the condition. Three months later her platelet count decreased to below 100,000/μL, and hydroxyurea was discontinued. She noticed considerable improvement in the lesions on the hands and nails with the cessation of hydroxyurea.

Hydroxyurea is a cytostatic agent that has been used for more than 40 years in the treatment of myeloproliferative disorders including chronic myelogenous leukemia, polycythemia vera, essential thrombocythemia, and sickle cell anemia.¹ It inhibits ribonucleoside diphosphate reductase and promotes cell death in the S phase of the cell cycle.^1-3

Several adverse cutaneous reactions have been associated with hydroxyurea including increased pigmentation, hyperkeratosis, skin atrophy, xerosis, lichenoid eruptions, palmoplantar keratoderma, cutaneous vasculitis, alopecia, chronic leg ulcers, cutaneous carcinomas, and melanonychia.^3,4

Hydroxyurea-induced melanonychia most often occurs after several months of therapy but has been reported to occur as early as 4 months and as late as 5 years after initiating the drug.^1,4-6 The prevalence of melanonychia in the general population has been estimated at 1% and is thought to increase to approximately 4% in patients treated with hydroxyurea.^1,2,6,7 The prevalence of affected individuals increases with age; it is more common in females as well as black and Hispanic patients.²

Multiple patterns of hydroxyurea-induced melanonychia have been described, including longitudinal bands, transverse bands, and diffuse hyperpigmentation.^1-3,6 By far the most common pattern described in the literature is longitudinal banding^1-3,8; transverse bands are more rare. Although there are sporadic case reports linking the transverse bands with hydroxyurea, these bands occur more frequently with systemic chemotherapy such as doxorubicin and cyclosphosphamide.^1,6

The exact pathogenesis of hydroxyurea-induced melanonychia remains unclear, though it is thought to result from focal melanogenesis in the nail bed or matrix followed by deposition of melanin granules on the nail plate.^5,8 When these melanocytes are activated, melanosomes filled with melanin are transferred to differentiating matrix cells, which migrate distally as they become nail plate oncocytes, resulting in a visible band of pigmentation in the nail plate.² There also may be a genetic and photosensitivity component.^1,2

Prior case series have described spontaneous remission of nail hyperpigmentation following discontinuation of hydroxyurea therapy.¹ In many patients, however, the chronic nature of the myeloproliferative disorder and lack of alternative treatments make a therapeutic change difficult. Although the melanonychia itself is benign, it may precede the appearance of more serious mucocutaneous side effects, such as skin ulceration or development of cutaneous carcinomas, so careful monitoring should be performed.²

Our patient presented with melanonychia that was transverse, polydactylic, monochromic, stable in size and shape, and associated with palmar hyperpigmentation. Of note, the pigmentation remitted over time along with discontinuation of the drug. Although this presentation did not warrant a nail matrix biopsy, it should be noted that patients with single nail melanonychia suspicious for melanoma should have a biopsy, even with concomitant use of hydroxyurea.² Although transverse melanonychia most commonly is associated with other systemic chemotherapeutics, in the absence of such medications hydroxyurea was the likely culprit in our patient. The palmar hyperpigmentation, which has previously been reported with hydroxyurea use, further solidifies the diagnosis.

Branchial Cleft Cyst

Cystic lesions present in a myriad of ways and often require histopathologic examination for definitive diagnosis. Correct identification of the cells comprising the lining of the cyst and the composition of the surrounding tissue are utilized to classify these lesions.

Branchial cleft cysts (quiz image, Figure 1) most commonly present as a soft tissue swelling of the lateral neck anterior to the sternocleidomastoid; they also can present in the preauricular or mandibular region.^1,2 Although the cyst is present at birth, it typically is not clinically apparent until the second or third decades of life. The origin of branchial cleft cysts is subject to some debate; however, the prevailing theory is that they result from failure of obliteration of the second branchial arch during development.¹ Histopathologically, branchial cleft cysts are characterized by a stratified squamous epithelial lining and abundant lymphoid tissue with germinal centers.^3,4 Infection is a common reason for presentation and excision is curative.

Bronchogenic cysts (Figure 2) present as midline lesions in the suprasternal notch and can present clinically due to compression of the airway.⁵ They develop as anomalies of the primitive foregut, budding off of the tracheobronchial tree. Similar to respiratory tissue, they are lined with a ciliated pseudostratified columnar epithelium and contain goblet cells. Concentric smooth muscle often surrounds the cyst and cartilage may be present.⁴ Excision is curative and recommended if the cyst encroaches on vital structures.

Median raphe cysts occur most commonly on the ventral surface of the penis on or near the glans (Figure 3). These cysts are thought to result from anomalous budding from the urethral epithelium, though they do not maintain contact with the urethra.³ The lining varies in thickness from 1 to 4 cell layers and mimics the transitional epithelium of the urethra. Amorphous debris often is seen within the cyst, and surrounding genital tissue can be appreciated by identification of delicate collagen, smooth muscle, and numerous small nerves and vessels.^3,4 Excision is curative and often is sought when the cyst becomes irritated or cosmetically bothersome.

Steatocystomas can present as solitary (steatocystoma simplex) or multiple lesions (steatocystoma multiplex)(Figure 4). They present as small, well-defined, yellow cystic papules most commonly on the chest, axilla, or groin.² Their lining is composed of a stratified squamous epithelium that lacks a granular layer and contains a distinct overlying corrugated "shark tooth" eosinophilic cuticle. Sebaceous lobules are characteristically present along or within the cyst wall.^3,4 Excision is curative and treatment often is sought for cosmetic purposes.

Similar to bronchogenic cysts, thyroglossal duct cysts (Figure 5) present on the midline neck, though they characteristically move with swallowing. The thyroglossal duct develops as the thyroid migrates from the floor of the pharynx to the anterior neck. Remnants of this duct result in the thyroglossal duct cyst.² These cysts contain a respiratory-type epithelial lining and are distinguished by distinct thyroid follicles and lymphoid aggregates surrounding the cyst wall. Unlike bronchogenic cysts, they do not contain smooth muscle.^3,4 Excision is curative.

Branchial Cleft Cyst

Cystic lesions present in a myriad of ways and often require histopathologic examination for definitive diagnosis. Correct identification of the cells comprising the lining of the cyst and the composition of the surrounding tissue are utilized to classify these lesions.

Branchial cleft cysts (quiz image, Figure 1) most commonly present as a soft tissue swelling of the lateral neck anterior to the sternocleidomastoid; they also can present in the preauricular or mandibular region.^1,2 Although the cyst is present at birth, it typically is not clinically apparent until the second or third decades of life. The origin of branchial cleft cysts is subject to some debate; however, the prevailing theory is that they result from failure of obliteration of the second branchial arch during development.¹ Histopathologically, branchial cleft cysts are characterized by a stratified squamous epithelial lining and abundant lymphoid tissue with germinal centers.^3,4 Infection is a common reason for presentation and excision is curative.

Bronchogenic cysts (Figure 2) present as midline lesions in the suprasternal notch and can present clinically due to compression of the airway.⁵ They develop as anomalies of the primitive foregut, budding off of the tracheobronchial tree. Similar to respiratory tissue, they are lined with a ciliated pseudostratified columnar epithelium and contain goblet cells. Concentric smooth muscle often surrounds the cyst and cartilage may be present.⁴ Excision is curative and recommended if the cyst encroaches on vital structures.

Median raphe cysts occur most commonly on the ventral surface of the penis on or near the glans (Figure 3). These cysts are thought to result from anomalous budding from the urethral epithelium, though they do not maintain contact with the urethra.³ The lining varies in thickness from 1 to 4 cell layers and mimics the transitional epithelium of the urethra. Amorphous debris often is seen within the cyst, and surrounding genital tissue can be appreciated by identification of delicate collagen, smooth muscle, and numerous small nerves and vessels.^3,4 Excision is curative and often is sought when the cyst becomes irritated or cosmetically bothersome.

Steatocystomas can present as solitary (steatocystoma simplex) or multiple lesions (steatocystoma multiplex)(Figure 4). They present as small, well-defined, yellow cystic papules most commonly on the chest, axilla, or groin.² Their lining is composed of a stratified squamous epithelium that lacks a granular layer and contains a distinct overlying corrugated "shark tooth" eosinophilic cuticle. Sebaceous lobules are characteristically present along or within the cyst wall.^3,4 Excision is curative and treatment often is sought for cosmetic purposes.

Similar to bronchogenic cysts, thyroglossal duct cysts (Figure 5) present on the midline neck, though they characteristically move with swallowing. The thyroglossal duct develops as the thyroid migrates from the floor of the pharynx to the anterior neck. Remnants of this duct result in the thyroglossal duct cyst.² These cysts contain a respiratory-type epithelial lining and are distinguished by distinct thyroid follicles and lymphoid aggregates surrounding the cyst wall. Unlike bronchogenic cysts, they do not contain smooth muscle.^3,4 Excision is curative.

Branchial Cleft Cyst

Cystic lesions present in a myriad of ways and often require histopathologic examination for definitive diagnosis. Correct identification of the cells comprising the lining of the cyst and the composition of the surrounding tissue are utilized to classify these lesions.

Branchial cleft cysts (quiz image, Figure 1) most commonly present as a soft tissue swelling of the lateral neck anterior to the sternocleidomastoid; they also can present in the preauricular or mandibular region.^1,2 Although the cyst is present at birth, it typically is not clinically apparent until the second or third decades of life. The origin of branchial cleft cysts is subject to some debate; however, the prevailing theory is that they result from failure of obliteration of the second branchial arch during development.¹ Histopathologically, branchial cleft cysts are characterized by a stratified squamous epithelial lining and abundant lymphoid tissue with germinal centers.^3,4 Infection is a common reason for presentation and excision is curative.

Bronchogenic cysts (Figure 2) present as midline lesions in the suprasternal notch and can present clinically due to compression of the airway.⁵ They develop as anomalies of the primitive foregut, budding off of the tracheobronchial tree. Similar to respiratory tissue, they are lined with a ciliated pseudostratified columnar epithelium and contain goblet cells. Concentric smooth muscle often surrounds the cyst and cartilage may be present.⁴ Excision is curative and recommended if the cyst encroaches on vital structures.

Median raphe cysts occur most commonly on the ventral surface of the penis on or near the glans (Figure 3). These cysts are thought to result from anomalous budding from the urethral epithelium, though they do not maintain contact with the urethra.³ The lining varies in thickness from 1 to 4 cell layers and mimics the transitional epithelium of the urethra. Amorphous debris often is seen within the cyst, and surrounding genital tissue can be appreciated by identification of delicate collagen, smooth muscle, and numerous small nerves and vessels.^3,4 Excision is curative and often is sought when the cyst becomes irritated or cosmetically bothersome.

Steatocystomas can present as solitary (steatocystoma simplex) or multiple lesions (steatocystoma multiplex)(Figure 4). They present as small, well-defined, yellow cystic papules most commonly on the chest, axilla, or groin.² Their lining is composed of a stratified squamous epithelium that lacks a granular layer and contains a distinct overlying corrugated "shark tooth" eosinophilic cuticle. Sebaceous lobules are characteristically present along or within the cyst wall.^3,4 Excision is curative and treatment often is sought for cosmetic purposes.

Similar to bronchogenic cysts, thyroglossal duct cysts (Figure 5) present on the midline neck, though they characteristically move with swallowing. The thyroglossal duct develops as the thyroid migrates from the floor of the pharynx to the anterior neck. Remnants of this duct result in the thyroglossal duct cyst.² These cysts contain a respiratory-type epithelial lining and are distinguished by distinct thyroid follicles and lymphoid aggregates surrounding the cyst wall. Unlike bronchogenic cysts, they do not contain smooth muscle.^3,4 Excision is curative.

The US Census Bureau predicts that more than half of the country’s population will identify as a race other than non-Hispanic white by the year 2044.In 2014, the US population was 62.2% non-Hispanic white, and the projected figure for 2060 is 43.6%.¹ However, most physicians currently are informed by research that is generalized from a study population of primarily white males.² Disparities also exist among the physician population where black individuals and Latinos are underrepresented.³ These differences have inspired dermatologists to develop methods to address the need for parity among patients with skin of color. Both ethnic skin centers and the Skin of Color Society (SOCS) have been established since the turn of the millennium to improve disparities and prepare for the future. The efforts and impact of SOCS are widening since its inception and chronicle one approach to broadening the scope of the specialty of dermatology.

Established in 2004 by dermatologist Susan C. Taylor, MD (Philadelphia, Pennsylvania), SOCS provides educational support to health care providers, the media, the legislature, third parties (eg, insurance organizations), and the general public on dermatologic health for patients with skin of color. The society is organized into committees that represent the multifaceted aspects of the organization. It also stimulates and endorses an increase in scientific knowledge through basic science and clinical, surgical, and cosmetic research.⁴

Scientific, research, mentorship, professional development, national and international outreach, patient education, and technology and media committees within SOCS, as well as a newly formed diversity in action task force, uphold the mission of the society. The scientific committee, one of the organization’s major committees, plans the annual symposium. The annual symposium, which immediately precedes the Annual Meeting of the American Academy of Dermatology, acts as a central educational symposium for dermatologists (both domestic and international), residents, students, and other scientists to present data on unique properties, statistics, and diseases associated with individuals with ethnic skin. New research, perspectives, and interests are shared with an audience of physicians, research fellows, residents, and students who are also the presenters of topics relevant to skin of color such as cutaneous T-cell lymphomas/mycosis fungoides in black individuals, central centrifugal cicatricial alopecia (CCCA), pigmentary disorders in Brazilians, and many others. There is an emphasis on allowing learners to present their research in a comfortable and constructive setting, and these shorter talks are interspersed with experts who deliver cutting-edge lectures in their specialty area.⁴

Each year during the SOCS symposium, the SOCS Research Award is endowed to a dermatology resident, fellow, or young dermatologist within the first 8 years of postgraduate training. The research committee oversees the selection of the SOCS Research Award. Prior recipients of the award have explored topics such as genetic causes of keloid formation or CCCA, epigenetic changes in ethnic skin during skin aging, and development of a vitiligo-specific quality-of-life scale.⁴

Another key mission of SOCS is to foster the growth of younger dermatologists interested in skin of color via mentorships; SOCS has a mentorship committee dedicated to engaging in this effort. Dermatology residents or young dermatologists who are within 3 years of finishing residency can work with a SOCS-approved mentor to develop knowledge, skills, and networking in the skin of color realm. Research is encouraged, and 3 to 4 professional development meetings (both in person or online) help set objectives. The professional development committee also coordinates efforts to offer young dermatologists opportunities to work with experienced mentors and further partnerships with existing members.⁴

The national and international outreach committee acts as a liaison between organizations abroad and those based in the United States. The patient education committee strives to improve public knowledge about dermatologic diseases that affect individuals with skin of color. Ethnic patients often have poor access to medical information, and sometimes adequate medical information does not exist in the current searchable medical literature. The SOCS website (http://skinofcolorsociety.org/) offers an entire section on dermatology education with succinct, patient-friendly prose on diseases such as acne in skin of color, CCCA, eczema, melanoma, melasma, sun protection, tinea capitis, and more; the website also includes educational videos, blogs, and a central location for useful links to other dermatology organizations that may be of interest to both members and patients who use the site. Maintenance of the website and the SOCS media day fall under the purview of the technology and media committee. There have been 2 media days thus far that have given voice to sun safety and skin cancer in individuals with skin of color as well as hair health and cosmetic treatments for patients with pigmented skin. The content for the media days is provided by SOCS experts to national magazine editors and beauty bloggers to raise awareness about these issues and get the message to the public.⁴

The diversity in action task force is a new committee that is tasked with addressing training for individuals of diverse ethnicities and backgrounds for health care careers at every level, ranging from middle school to dermatology residency. Resources to help those applying to medical school and current medical students interested in dermatology as well as those applying for dermatology residency are being developed for students at all stages of their academic careers. The middle school to undergraduate educational levels will encompass general guidelines for success; the medical school level will focus on students taking the appropriate steps to enter dermatology residency. The task force also will act as a liaison through existing student groups, such as the Student National Medical Association, Minority Association of Premedical Students, Latino Medical Student Association, Dermatology Interest Group Association, and more to reach learners at critical stages in their academic development.⁴The society plays an important role in the educational process for dermatologists at all levels. Although this organization is critical in increasing knowledge of treatment of individuals with skin of color in research, clinical practice, and the public domain, the hope is that SOCS will continue to reach new members of the dermatology community. As a group that embraces the onus to improve skin of color education, the members of SOCS know that there is still much to do to increase awareness among the public as well as dermatology residents and dermatologists practicing in geographical regions that are not ethnically diverse. There are many reasons that both cultural competence and knowledge of skin of color in dermatology will be important as the United States becomes increasingly diverse, and SOCS is at the forefront of this effort. Looking to the future, the goals of SOCS really are the goals of dermatology, which are to continue to deliver the best care to all patients and to continue to improve our specialty with new techniques and medications for all patients who need care.

The US Census Bureau predicts that more than half of the country’s population will identify as a race other than non-Hispanic white by the year 2044.In 2014, the US population was 62.2% non-Hispanic white, and the projected figure for 2060 is 43.6%.¹ However, most physicians currently are informed by research that is generalized from a study population of primarily white males.² Disparities also exist among the physician population where black individuals and Latinos are underrepresented.³ These differences have inspired dermatologists to develop methods to address the need for parity among patients with skin of color. Both ethnic skin centers and the Skin of Color Society (SOCS) have been established since the turn of the millennium to improve disparities and prepare for the future. The efforts and impact of SOCS are widening since its inception and chronicle one approach to broadening the scope of the specialty of dermatology.

Established in 2004 by dermatologist Susan C. Taylor, MD (Philadelphia, Pennsylvania), SOCS provides educational support to health care providers, the media, the legislature, third parties (eg, insurance organizations), and the general public on dermatologic health for patients with skin of color. The society is organized into committees that represent the multifaceted aspects of the organization. It also stimulates and endorses an increase in scientific knowledge through basic science and clinical, surgical, and cosmetic research.⁴

Scientific, research, mentorship, professional development, national and international outreach, patient education, and technology and media committees within SOCS, as well as a newly formed diversity in action task force, uphold the mission of the society. The scientific committee, one of the organization’s major committees, plans the annual symposium. The annual symposium, which immediately precedes the Annual Meeting of the American Academy of Dermatology, acts as a central educational symposium for dermatologists (both domestic and international), residents, students, and other scientists to present data on unique properties, statistics, and diseases associated with individuals with ethnic skin. New research, perspectives, and interests are shared with an audience of physicians, research fellows, residents, and students who are also the presenters of topics relevant to skin of color such as cutaneous T-cell lymphomas/mycosis fungoides in black individuals, central centrifugal cicatricial alopecia (CCCA), pigmentary disorders in Brazilians, and many others. There is an emphasis on allowing learners to present their research in a comfortable and constructive setting, and these shorter talks are interspersed with experts who deliver cutting-edge lectures in their specialty area.⁴

Each year during the SOCS symposium, the SOCS Research Award is endowed to a dermatology resident, fellow, or young dermatologist within the first 8 years of postgraduate training. The research committee oversees the selection of the SOCS Research Award. Prior recipients of the award have explored topics such as genetic causes of keloid formation or CCCA, epigenetic changes in ethnic skin during skin aging, and development of a vitiligo-specific quality-of-life scale.⁴

Another key mission of SOCS is to foster the growth of younger dermatologists interested in skin of color via mentorships; SOCS has a mentorship committee dedicated to engaging in this effort. Dermatology residents or young dermatologists who are within 3 years of finishing residency can work with a SOCS-approved mentor to develop knowledge, skills, and networking in the skin of color realm. Research is encouraged, and 3 to 4 professional development meetings (both in person or online) help set objectives. The professional development committee also coordinates efforts to offer young dermatologists opportunities to work with experienced mentors and further partnerships with existing members.⁴

The national and international outreach committee acts as a liaison between organizations abroad and those based in the United States. The patient education committee strives to improve public knowledge about dermatologic diseases that affect individuals with skin of color. Ethnic patients often have poor access to medical information, and sometimes adequate medical information does not exist in the current searchable medical literature. The SOCS website (http://skinofcolorsociety.org/) offers an entire section on dermatology education with succinct, patient-friendly prose on diseases such as acne in skin of color, CCCA, eczema, melanoma, melasma, sun protection, tinea capitis, and more; the website also includes educational videos, blogs, and a central location for useful links to other dermatology organizations that may be of interest to both members and patients who use the site. Maintenance of the website and the SOCS media day fall under the purview of the technology and media committee. There have been 2 media days thus far that have given voice to sun safety and skin cancer in individuals with skin of color as well as hair health and cosmetic treatments for patients with pigmented skin. The content for the media days is provided by SOCS experts to national magazine editors and beauty bloggers to raise awareness about these issues and get the message to the public.⁴

The diversity in action task force is a new committee that is tasked with addressing training for individuals of diverse ethnicities and backgrounds for health care careers at every level, ranging from middle school to dermatology residency. Resources to help those applying to medical school and current medical students interested in dermatology as well as those applying for dermatology residency are being developed for students at all stages of their academic careers. The middle school to undergraduate educational levels will encompass general guidelines for success; the medical school level will focus on students taking the appropriate steps to enter dermatology residency. The task force also will act as a liaison through existing student groups, such as the Student National Medical Association, Minority Association of Premedical Students, Latino Medical Student Association, Dermatology Interest Group Association, and more to reach learners at critical stages in their academic development.⁴The society plays an important role in the educational process for dermatologists at all levels. Although this organization is critical in increasing knowledge of treatment of individuals with skin of color in research, clinical practice, and the public domain, the hope is that SOCS will continue to reach new members of the dermatology community. As a group that embraces the onus to improve skin of color education, the members of SOCS know that there is still much to do to increase awareness among the public as well as dermatology residents and dermatologists practicing in geographical regions that are not ethnically diverse. There are many reasons that both cultural competence and knowledge of skin of color in dermatology will be important as the United States becomes increasingly diverse, and SOCS is at the forefront of this effort. Looking to the future, the goals of SOCS really are the goals of dermatology, which are to continue to deliver the best care to all patients and to continue to improve our specialty with new techniques and medications for all patients who need care.

The US Census Bureau predicts that more than half of the country’s population will identify as a race other than non-Hispanic white by the year 2044.In 2014, the US population was 62.2% non-Hispanic white, and the projected figure for 2060 is 43.6%.¹ However, most physicians currently are informed by research that is generalized from a study population of primarily white males.² Disparities also exist among the physician population where black individuals and Latinos are underrepresented.³ These differences have inspired dermatologists to develop methods to address the need for parity among patients with skin of color. Both ethnic skin centers and the Skin of Color Society (SOCS) have been established since the turn of the millennium to improve disparities and prepare for the future. The efforts and impact of SOCS are widening since its inception and chronicle one approach to broadening the scope of the specialty of dermatology.

Established in 2004 by dermatologist Susan C. Taylor, MD (Philadelphia, Pennsylvania), SOCS provides educational support to health care providers, the media, the legislature, third parties (eg, insurance organizations), and the general public on dermatologic health for patients with skin of color. The society is organized into committees that represent the multifaceted aspects of the organization. It also stimulates and endorses an increase in scientific knowledge through basic science and clinical, surgical, and cosmetic research.⁴

Scientific, research, mentorship, professional development, national and international outreach, patient education, and technology and media committees within SOCS, as well as a newly formed diversity in action task force, uphold the mission of the society. The scientific committee, one of the organization’s major committees, plans the annual symposium. The annual symposium, which immediately precedes the Annual Meeting of the American Academy of Dermatology, acts as a central educational symposium for dermatologists (both domestic and international), residents, students, and other scientists to present data on unique properties, statistics, and diseases associated with individuals with ethnic skin. New research, perspectives, and interests are shared with an audience of physicians, research fellows, residents, and students who are also the presenters of topics relevant to skin of color such as cutaneous T-cell lymphomas/mycosis fungoides in black individuals, central centrifugal cicatricial alopecia (CCCA), pigmentary disorders in Brazilians, and many others. There is an emphasis on allowing learners to present their research in a comfortable and constructive setting, and these shorter talks are interspersed with experts who deliver cutting-edge lectures in their specialty area.⁴

Each year during the SOCS symposium, the SOCS Research Award is endowed to a dermatology resident, fellow, or young dermatologist within the first 8 years of postgraduate training. The research committee oversees the selection of the SOCS Research Award. Prior recipients of the award have explored topics such as genetic causes of keloid formation or CCCA, epigenetic changes in ethnic skin during skin aging, and development of a vitiligo-specific quality-of-life scale.⁴

Another key mission of SOCS is to foster the growth of younger dermatologists interested in skin of color via mentorships; SOCS has a mentorship committee dedicated to engaging in this effort. Dermatology residents or young dermatologists who are within 3 years of finishing residency can work with a SOCS-approved mentor to develop knowledge, skills, and networking in the skin of color realm. Research is encouraged, and 3 to 4 professional development meetings (both in person or online) help set objectives. The professional development committee also coordinates efforts to offer young dermatologists opportunities to work with experienced mentors and further partnerships with existing members.⁴

The national and international outreach committee acts as a liaison between organizations abroad and those based in the United States. The patient education committee strives to improve public knowledge about dermatologic diseases that affect individuals with skin of color. Ethnic patients often have poor access to medical information, and sometimes adequate medical information does not exist in the current searchable medical literature. The SOCS website (http://skinofcolorsociety.org/) offers an entire section on dermatology education with succinct, patient-friendly prose on diseases such as acne in skin of color, CCCA, eczema, melanoma, melasma, sun protection, tinea capitis, and more; the website also includes educational videos, blogs, and a central location for useful links to other dermatology organizations that may be of interest to both members and patients who use the site. Maintenance of the website and the SOCS media day fall under the purview of the technology and media committee. There have been 2 media days thus far that have given voice to sun safety and skin cancer in individuals with skin of color as well as hair health and cosmetic treatments for patients with pigmented skin. The content for the media days is provided by SOCS experts to national magazine editors and beauty bloggers to raise awareness about these issues and get the message to the public.⁴

The diversity in action task force is a new committee that is tasked with addressing training for individuals of diverse ethnicities and backgrounds for health care careers at every level, ranging from middle school to dermatology residency. Resources to help those applying to medical school and current medical students interested in dermatology as well as those applying for dermatology residency are being developed for students at all stages of their academic careers. The middle school to undergraduate educational levels will encompass general guidelines for success; the medical school level will focus on students taking the appropriate steps to enter dermatology residency. The task force also will act as a liaison through existing student groups, such as the Student National Medical Association, Minority Association of Premedical Students, Latino Medical Student Association, Dermatology Interest Group Association, and more to reach learners at critical stages in their academic development.⁴The society plays an important role in the educational process for dermatologists at all levels. Although this organization is critical in increasing knowledge of treatment of individuals with skin of color in research, clinical practice, and the public domain, the hope is that SOCS will continue to reach new members of the dermatology community. As a group that embraces the onus to improve skin of color education, the members of SOCS know that there is still much to do to increase awareness among the public as well as dermatology residents and dermatologists practicing in geographical regions that are not ethnically diverse. There are many reasons that both cultural competence and knowledge of skin of color in dermatology will be important as the United States becomes increasingly diverse, and SOCS is at the forefront of this effort. Looking to the future, the goals of SOCS really are the goals of dermatology, which are to continue to deliver the best care to all patients and to continue to improve our specialty with new techniques and medications for all patients who need care.

The Diagnosis: Pagetoid Reticulosis

Histopathologic examination demonstrated a dense infiltrate and psoriasiform pattern epidermal hyperplasia (Figure, A). There was conspicuous epidermotropism of moderately enlarged, hyperchromatic lymphocytes. Intraepidermal lymphocytes were slightly larger, darker, and more convoluted than those in the subjacent dermis (Figure, B). These cells exhibited CD3⁺ T-cell differentiation with an abnormal CD4-CD7-CD8- phenotype (Figure, C). The histopathologic finding of atypical epidermotropic T-cell infiltrate was compatible with a rare variant of mycosis fungoides known as pagetoid reticulosis (PR). After discussing the diagnosis and treatment options, the patient elected to begin with a conservative approach to therapy. We prescribed fluocinonide ointment 0.05% twice daily under occlusion. At 1 month follow-up, the patient experienced marked improvement of the erythema and scaling of the lesion.

Pagetoid reticulosis is a primary cutaneous T-cell lymphoma that has been categorized as an indolent localized variant of mycosis fungoides. This rare skin disorder was originally described by Woringer and Kolopp in 1939¹ and was further renamed in 1973 by Braun-Falco et al.² At that time the term pagetoid reticulosis was introduced due to similarities in histopathologic findings seen in Paget disease of the nipple. Two variants of the disease have been described since then: the localized type and the disseminated type. The localized type, also known as Woringer-Kolopp disease (WKD), typically presents as a persistent, sharply localized, scaly patch that slowly expands over several years. The lesion is classically located on the extensor surface of the hand or foot and often is asymptomatic. Due to the benign presentation, WKD can easily be confused with much more common diseases, such as psoriasis or fungal infections, resulting in a substantial delay in the diagnosis. The patient will often report a medical history notable for frequent office visits and numerous failed therapies. Even though it is exceedingly uncommon, these findings should prompt the practitioner to add WKD to their differential. The disseminated type of PR (also known as Ketron-Goodman disease) is characterized by diffuse cutaneous involvement, carries a much more progressive course, and often leads to a poor outcome.³ The histopathologic features of WKD and Ketron-Goodman disease are identical, and the 2 types are distinguished on clinical grounds alone.

Histopathologic features of PR are unique and often distinct in comparison to mycosis fungoides. Pagetoid reticulosis often is described as epidermal hyperplasia with parakeratosis, prominent acanthosis, and excessive epidermotropism of atypical lymphocytes scattered throughout the epidermis.³ The distinct pattern of epidermotropism seen in PR is the characteristic finding. Review of immunocytochemistry from reported cases has shown that CD marker expression of neoplastic T cells in PR can be variable in nature.⁴ Although it is known that immunophenotyping can be useful in diagnosing and distinguishing PR from other types of primary cutaneous T-cell lymphoma, the clinical significance of the observed phenotypic variation remains a mystery. As of now, it appears to be prognostically irrelevant.⁵

There are numerous therapeutic options available for PR. Depending on the size and extent of the disease, surgical excision and radiotherapy may be an option and are the most effective.⁶ For patients who are not good candidates or opt out of these options, there are various pharmacotherapies that also have proven to work. Traditional therapies include topical corticosteroids, corticosteroid injections, and phototherapy. However, more recent trials with retinoids, such as alitretinoin or bexarotene, appear to offer a promising therapeutic approach.⁷

Pagetoid reticulosis is a true malignant lymphoma of T-cell lineage, but it typically carries an excellent prognosis. Rare cases have been reported to progress to disseminated lymphoma.⁸ Therefore, long-term follow-up for a patient diagnosed with PR is recommended.

The Diagnosis: Pagetoid Reticulosis

Histopathologic examination demonstrated a dense infiltrate and psoriasiform pattern epidermal hyperplasia (Figure, A). There was conspicuous epidermotropism of moderately enlarged, hyperchromatic lymphocytes. Intraepidermal lymphocytes were slightly larger, darker, and more convoluted than those in the subjacent dermis (Figure, B). These cells exhibited CD3⁺ T-cell differentiation with an abnormal CD4-CD7-CD8- phenotype (Figure, C). The histopathologic finding of atypical epidermotropic T-cell infiltrate was compatible with a rare variant of mycosis fungoides known as pagetoid reticulosis (PR). After discussing the diagnosis and treatment options, the patient elected to begin with a conservative approach to therapy. We prescribed fluocinonide ointment 0.05% twice daily under occlusion. At 1 month follow-up, the patient experienced marked improvement of the erythema and scaling of the lesion.

Pagetoid reticulosis is a primary cutaneous T-cell lymphoma that has been categorized as an indolent localized variant of mycosis fungoides. This rare skin disorder was originally described by Woringer and Kolopp in 1939¹ and was further renamed in 1973 by Braun-Falco et al.² At that time the term pagetoid reticulosis was introduced due to similarities in histopathologic findings seen in Paget disease of the nipple. Two variants of the disease have been described since then: the localized type and the disseminated type. The localized type, also known as Woringer-Kolopp disease (WKD), typically presents as a persistent, sharply localized, scaly patch that slowly expands over several years. The lesion is classically located on the extensor surface of the hand or foot and often is asymptomatic. Due to the benign presentation, WKD can easily be confused with much more common diseases, such as psoriasis or fungal infections, resulting in a substantial delay in the diagnosis. The patient will often report a medical history notable for frequent office visits and numerous failed therapies. Even though it is exceedingly uncommon, these findings should prompt the practitioner to add WKD to their differential. The disseminated type of PR (also known as Ketron-Goodman disease) is characterized by diffuse cutaneous involvement, carries a much more progressive course, and often leads to a poor outcome.³ The histopathologic features of WKD and Ketron-Goodman disease are identical, and the 2 types are distinguished on clinical grounds alone.

Histopathologic features of PR are unique and often distinct in comparison to mycosis fungoides. Pagetoid reticulosis often is described as epidermal hyperplasia with parakeratosis, prominent acanthosis, and excessive epidermotropism of atypical lymphocytes scattered throughout the epidermis.³ The distinct pattern of epidermotropism seen in PR is the characteristic finding. Review of immunocytochemistry from reported cases has shown that CD marker expression of neoplastic T cells in PR can be variable in nature.⁴ Although it is known that immunophenotyping can be useful in diagnosing and distinguishing PR from other types of primary cutaneous T-cell lymphoma, the clinical significance of the observed phenotypic variation remains a mystery. As of now, it appears to be prognostically irrelevant.⁵

There are numerous therapeutic options available for PR. Depending on the size and extent of the disease, surgical excision and radiotherapy may be an option and are the most effective.⁶ For patients who are not good candidates or opt out of these options, there are various pharmacotherapies that also have proven to work. Traditional therapies include topical corticosteroids, corticosteroid injections, and phototherapy. However, more recent trials with retinoids, such as alitretinoin or bexarotene, appear to offer a promising therapeutic approach.⁷

Pagetoid reticulosis is a true malignant lymphoma of T-cell lineage, but it typically carries an excellent prognosis. Rare cases have been reported to progress to disseminated lymphoma.⁸ Therefore, long-term follow-up for a patient diagnosed with PR is recommended.

The Diagnosis: Pagetoid Reticulosis

Histopathologic examination demonstrated a dense infiltrate and psoriasiform pattern epidermal hyperplasia (Figure, A). There was conspicuous epidermotropism of moderately enlarged, hyperchromatic lymphocytes. Intraepidermal lymphocytes were slightly larger, darker, and more convoluted than those in the subjacent dermis (Figure, B). These cells exhibited CD3⁺ T-cell differentiation with an abnormal CD4-CD7-CD8- phenotype (Figure, C). The histopathologic finding of atypical epidermotropic T-cell infiltrate was compatible with a rare variant of mycosis fungoides known as pagetoid reticulosis (PR). After discussing the diagnosis and treatment options, the patient elected to begin with a conservative approach to therapy. We prescribed fluocinonide ointment 0.05% twice daily under occlusion. At 1 month follow-up, the patient experienced marked improvement of the erythema and scaling of the lesion.

Pagetoid reticulosis is a primary cutaneous T-cell lymphoma that has been categorized as an indolent localized variant of mycosis fungoides. This rare skin disorder was originally described by Woringer and Kolopp in 1939¹ and was further renamed in 1973 by Braun-Falco et al.² At that time the term pagetoid reticulosis was introduced due to similarities in histopathologic findings seen in Paget disease of the nipple. Two variants of the disease have been described since then: the localized type and the disseminated type. The localized type, also known as Woringer-Kolopp disease (WKD), typically presents as a persistent, sharply localized, scaly patch that slowly expands over several years. The lesion is classically located on the extensor surface of the hand or foot and often is asymptomatic. Due to the benign presentation, WKD can easily be confused with much more common diseases, such as psoriasis or fungal infections, resulting in a substantial delay in the diagnosis. The patient will often report a medical history notable for frequent office visits and numerous failed therapies. Even though it is exceedingly uncommon, these findings should prompt the practitioner to add WKD to their differential. The disseminated type of PR (also known as Ketron-Goodman disease) is characterized by diffuse cutaneous involvement, carries a much more progressive course, and often leads to a poor outcome.³ The histopathologic features of WKD and Ketron-Goodman disease are identical, and the 2 types are distinguished on clinical grounds alone.

Histopathologic features of PR are unique and often distinct in comparison to mycosis fungoides. Pagetoid reticulosis often is described as epidermal hyperplasia with parakeratosis, prominent acanthosis, and excessive epidermotropism of atypical lymphocytes scattered throughout the epidermis.³ The distinct pattern of epidermotropism seen in PR is the characteristic finding. Review of immunocytochemistry from reported cases has shown that CD marker expression of neoplastic T cells in PR can be variable in nature.⁴ Although it is known that immunophenotyping can be useful in diagnosing and distinguishing PR from other types of primary cutaneous T-cell lymphoma, the clinical significance of the observed phenotypic variation remains a mystery. As of now, it appears to be prognostically irrelevant.⁵

There are numerous therapeutic options available for PR. Depending on the size and extent of the disease, surgical excision and radiotherapy may be an option and are the most effective.⁶ For patients who are not good candidates or opt out of these options, there are various pharmacotherapies that also have proven to work. Traditional therapies include topical corticosteroids, corticosteroid injections, and phototherapy. However, more recent trials with retinoids, such as alitretinoin or bexarotene, appear to offer a promising therapeutic approach.⁷

Pagetoid reticulosis is a true malignant lymphoma of T-cell lineage, but it typically carries an excellent prognosis. Rare cases have been reported to progress to disseminated lymphoma.⁸ Therefore, long-term follow-up for a patient diagnosed with PR is recommended.

Skin cancer is an important public health issue in the United States, as 1 in 5 Americans are projected to develop a cutaneous malignancy during their lifetime. Currently, 75% of all skin cancer–related deaths are due to malignant melanomas (MMs), though melanomas account for less than 5% of all skin cancers.¹ Early detection of MM is essential, as prognosis depends on tumor stage, particularly the depth of the melanoma.^2-4 In general, patients with thin, early-stage melanomas have a more than 96% survival rate, which drops to 14% in late-stage disease.^5,6 Five percent to 30% of all melanomas are identified incidentally on total-body skin examinations (TBSEs) performed by a trained provider and thus would not have been caught with only a focused skin examination or patient self-examination.^7,8 Nonetheless, the clinical utility of skin cancer screening with TBSEs remains controversial, largely due to the poor quality of data available to establish a notable mortality benefit from skin cancer screening. As a result, obtaining endorsement from the larger medical community, federal government, and health insurance industry to include routine TBSEs as part of a preventive care health care strategy has not occurred. The absence of definitive clinical care guidelines mandating routine TBSEs is one of the greatest barriers preventing access to appropriate dermatologic screening along with the paucity of trained providers; however, standardized total-body photography (TBP) promises to provide a way forward by lowering the costs of dermatologic screening while simultaneously leveraging technology to increase availability.

Impact on Biopsy Efficiency

Current US Preventive Services Task Force (USPSTF) guidelines state that evidence is insufficient to assess the balance of benefits and harms of visual skin examination by a clinician to screen for skin cancer in adults. The USPSTF noted that “[d]irect evidence on the effectiveness of screening in reducing melanoma morbidity and mortality is limited to a single fair-quality ecologic study with important methodological limitations” (ie, the Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany [SCREEN] study), and although information on harm is similarly sparse, “[t]he potential for harm clearly exists, including a high rate of unnecessary biopsies, possibly resulting in cosmetic or, more rarely, functional adverse effects, and the risk of overdiagnosis and overtreatment.”⁹ The majority of suspicious skin lesions excised during screenings are not cancerous. For example, the SCREEN study found that 20 to 55 excisions were performed to detect 1 case of melanoma.¹⁰ At that rate, the USPSTF also noted that approximately 4000 excisions would be required to prevent a single death from melanoma.⁹ Following the lead of the USPSTF, the Patient Protection and Affordable Care Act did not mandate that skin examinations be included as essential preventive coverage in its requirements for insurance coverage of primary care prevention. As such, dermatologists face financial pressure to avoid performing time-consuming TBSEs, regardless of their perceived utility.¹¹

As the USPSTF points out, the value of TBSEs relies on the examiner’s ability to correctly identify malignant lesions and minimize biopsies of benign lesions, a concept known as biopsy efficiency.⁹ Secondarily, a TBSE is time consuming, and the time required for a dermatologist to complete a TBSE given the high rate of benign findings may not be financially viable. We argue that the routine use of total-body skin imaging may offer a way forward in addressing these issues. Total-body photography involves a photographic system that can allow dermatologists to acquire standardized images that can be used for primary diagnosis and to track individual lesions over time. Nonmedical personnel and medical assistants can be easily trained to use standardized photography devices to quickly obtain high-quality clinical images, thereby greatly reducing the time and cost of obtaining these images. Studies have found that the use of photographic monitoring may improve biopsy efficiency.^12-15 A recent study by Truong et al¹⁶ found that TBP used to monitor all existing melanocytic lesions on patients substantially reduced the number of biopsies that patients required. These results reflect that most nevi, including clinically atypical nevi, are usually stable and unlikely to exhibit suspicious changes over time.^17,18 For this reason, the use of TBP could minimize unnecessary biopsies because clinically suspicious but stable nevi can be objectively documented and followed over time.

Standardized TBP also offers the ability for dermatologists to work synergistically with modern computer technology involving algorithms capable of analyzing high-quality images to autodiagnose or flag concerning lesions that may require biopsy. Esteva et al¹⁹ described their development of a deep learning algorithm that relies on a convolutional neural network (CNN). This CNN was trained to identify melanomas using a large data set of clinical dermatologic images and subsequently was able to distinguish MMs from benign nevi at a rate on par with a board-certified dermatologist.¹⁹ Widespread use of total-body imaging would create an enormous database of high-resolution images that would be ideally suited to the development of such computerized algorithms, which could then be applied to future images by way of artificial intelligence. Convolutional neural networks that use a single patient’s imaging over time could be developed to assess the change in number or size of benign nevi and identify lesions that are concerning for MM while simultaneously comparing them to a population-based data set.

On a large scale, such a capability would minimize the inefficiency and subjectivity of TBSEs as a tool for identifying malignancy. Currently, dermatologists are only able to track and document a few concerning lesions on a patient’s body, rendering the choice of which lesions require biopsy more subjective. Total-body photography, particularly if used with an algorithm capable of quickly analyzing all the nevi on a person’s body, largely eliminates such subjectivity by creating a standardized set of images that can be tracked over time and flagging concerning lesions prior to the dermatologist examining the patient. In this way, the specialty of dermatology could achieve the same model of objective evaluation of standardized clinical images as those employed in radiology, cardiology, and other clinical disciplines. The additional benefit of such a system would be lower costs, as the images could be acquired by nonmedical personnel and then undergo initial assessment by an algorithm, which would flag concerning lesions, similar to a modern electrocardiogram machine, allowing the dermatologist to use his/her time more efficiently by only focusing on concerning lesions with the confidence that the patient’s entire body has already been rigorously screened.

By using TBP to improve biopsy efficiency and the objectivity of the TBSE as a tool to detect skin cancer, we propose that the benefit-to-harm ratio of the TBSE would remarkably improve. Ultimately, this type of screening would meet the strict requirements to be included in preventive health care strategies and thereby improve access to dermatologic care.

The Use of TBP in the Military

Total-body photography has several specific applications in the military. Standardized imaging has the potential to improve dermatologic care for active-duty soldiers across space and time. First, a large percentage of deployment medical care is devoted to dermatologic issues. From 2008 to 2015, 5% of all medical encounters in the combat theaters of Iraq and Afghanistan involved dermatologic concerns.²⁰ Access to appropriate dermatologic care in a combat theater is important, as poorly controlled dermatologic conditions (eg, psoriasis, eczema) often require evacuation when left untreated. Although current TBP systems may not be portable or durable enough to survive in an austere deployment environment, we propose it would be feasible to have skin imaging booths at larger forward operating bases. The images could then be transported to a remote dermatologist to assess and recommend treatment. The expense of transporting and maintaining the imaging system in country would be offset by the expenses spared by not requiring a dermatologist in country and the reductions in costly medical evacuations from theater.

Although the US military population is younger and generally healthier than the general adult population due to extensive medical screening on admission, age limitations for active-duty service, a mandated active lifestyle, and access to good health care, there are still a substantial number of service members diagnosed with skin cancer each year.²¹ From 2005 through 2014, MM was the most common non–gender-specific cancer (n=1571); in men, only testicular cancer was more prevalent (1591 vs 1298 cases), and in women, only breast cancer was more prevalent (773 vs 273 cases). Furthermore, from 2004 to 2013, the incidence rates of melanoma have increased by 1.4%, while with other cancer rates have declined during the same time period.²¹ Thus, TBP as a screening modality across the military population is a promising method for improving detection of skin cancer and reducing morbidity and mortality.

Military medicine often is on the forefront of medical advances in technology, disease understanding, and clinical care due to the unique resources available in the military health care system, which allow investigators the ability to obtain vast amounts of epidemiologic data.²² The military health care system also is unique in its ability to mandate that its members obtain preventive health services. Thus, it would be possible for the military to mandate TBP at accession and retirement, for instance, or more frequently for annual screening. The implementation of such a program would improve the health of the military population and be a public health service by pioneering the use of a standardized TBP system across a large health care system to improve skin cancer detection.

Current Studies in the Military

The Dermatology Service at the Walter Reed National Military Medical Center (WRNMMC)(Bethesda, Maryland) is evaluating the use of a total-body digital skin imaging system under a grant from the Telemedicine and Advanced Technology Research Center of the US Army. The system in use was found to be particularly well suited for military dermatology because it offers standardized TBP processing, produces a report that can be uploaded to the US Department of Defense (DoD) electronic medical record system, and requires relatively brief training for ancillary personnel to operate. Regardless of the platform the DoD ultimately finds most suitable, it is critical that a standard exist for TBP to ensure that uniform data sets are generated to allow military and other DoD dermatologists as well as civilian health care providers to share clinical information. The goal of the current study at WRNMMC is to vet TBP platforms at WRNMMC so the military can then develop standards to procure additional platforms for placement throughout the Military Health System, Military Entrance Processing Stations, operational environments, and collaborating health care systems (eg, the Veterans Health Administration).

Once deployed broadly across the Military Health System, these TBP platforms would be part of a network of telehealth care. For acute dermatologic issues, diagnoses provided via teledermatology platforms can then be managed by health care providers utilizing appropriate clinical practice guidelines or by non–health care providers utilizing general medical knowledge databases. Such a system with TBP information collected at multiple access points across a service member’s career would build a repository of data that would be immensely useful to patients and to clinical research. Of particular interest to military researchers is that TBP data could be used to study which patients require in-person examinations or more careful monitoring; the proper intervals for skin cancer screening; and the assessment of the benefits of TBP in improving morbidity, mortality, and biopsy efficiency in the detection of MM as well as nonmelanoma skin cancers.

Limitations to Progress

Currently, there are multiple limitations to the implementation of TBP as a part of TBSE screening. First, the potential improvement in biopsy efficiency using TBP is predicated on its ability to prove nevi stability over time, but in younger populations, benign nevi are more likely to change or increase in number, which may reduce the biopsy efficiency of screening in a younger population, thereby negating some of the benefit of imaging and CNN assessment. For instance, Truong et al¹⁶ found that younger age (<30 years) did not show the same improvement in biopsy efficiency with the use of TBP, which the authors theorized may reflect “the dynamic nature of nevi in younger patients” that has been documented in other studies.^23,24 Approximately 65% of the active-duty military population is aged 18 to 30 years, and 98% of accessions to active duty occur in individuals aged 17 to 30 years.²⁵ As such, TBP may not improve biopsy efficiency in the active-duty military population as dramatically as it would across the general population.

A second limitation of the use of TBP in the active-duty military population is the ethics of implementing DoD-wide mandatory TBP. Although the TBP platform will be compliant with the Health Insurance Portability and Accountability Act, mandating that soldiers contribute their TBP to a repository of data that will then be used for research without explicitly requesting their consent is ethically problematic; however, since the 1950s, the DoD has collected serum samples from its service members for force protection and operations reasons as well as for the purpose of research.^22,26 Currently, the DoD Serum Repository collects serum samples as part of a mandatory human immunodeficiency virus screening program that evaluates service members every 2 years; this repository of human serum samples is accessible for research purposes without the consent of the individuals being studied.²⁷ These individuals are not informed of potential use of their serum specimens for research purposes and no consent forms or opt-out options are provided. Thus, although there is precedent in the DoD for such mass data collection, it is an ongoing ethical consideration.²⁸

RELATED ARTICLE: Gigapixel Photography for Skin Cancer Surveillance

Finally, although the potential use of TBP and computer algorithms to improve the efficiency and affordability of TBSEs is exciting, there are no existing computer algorithms that we are aware of that can be used with existing TBP platforms in the manner we proposed. However, we feel that computer algorithms, such as the one created by Esteva et al,¹⁹ are just the beginning and that the use of artificial intelligence is not far off. Even after the creation of a TBP-compatible algorithm adept at analyzing malignant lesions, however, this technology would need to be further evaluated in the clinical setting to determine its capability and practicality. Current TBP platforms also are limited by their large size, cost, and complexity. As TBP platforms improve, it is likely that more streamlined and less expensive versions of current models will greatly enhance the field of teledermatology, particularly in the military setting.

Skin cancer is an important public health issue in the United States, as 1 in 5 Americans are projected to develop a cutaneous malignancy during their lifetime. Currently, 75% of all skin cancer–related deaths are due to malignant melanomas (MMs), though melanomas account for less than 5% of all skin cancers.¹ Early detection of MM is essential, as prognosis depends on tumor stage, particularly the depth of the melanoma.^2-4 In general, patients with thin, early-stage melanomas have a more than 96% survival rate, which drops to 14% in late-stage disease.^5,6 Five percent to 30% of all melanomas are identified incidentally on total-body skin examinations (TBSEs) performed by a trained provider and thus would not have been caught with only a focused skin examination or patient self-examination.^7,8 Nonetheless, the clinical utility of skin cancer screening with TBSEs remains controversial, largely due to the poor quality of data available to establish a notable mortality benefit from skin cancer screening. As a result, obtaining endorsement from the larger medical community, federal government, and health insurance industry to include routine TBSEs as part of a preventive care health care strategy has not occurred. The absence of definitive clinical care guidelines mandating routine TBSEs is one of the greatest barriers preventing access to appropriate dermatologic screening along with the paucity of trained providers; however, standardized total-body photography (TBP) promises to provide a way forward by lowering the costs of dermatologic screening while simultaneously leveraging technology to increase availability.

Impact on Biopsy Efficiency

Current US Preventive Services Task Force (USPSTF) guidelines state that evidence is insufficient to assess the balance of benefits and harms of visual skin examination by a clinician to screen for skin cancer in adults. The USPSTF noted that “[d]irect evidence on the effectiveness of screening in reducing melanoma morbidity and mortality is limited to a single fair-quality ecologic study with important methodological limitations” (ie, the Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany [SCREEN] study), and although information on harm is similarly sparse, “[t]he potential for harm clearly exists, including a high rate of unnecessary biopsies, possibly resulting in cosmetic or, more rarely, functional adverse effects, and the risk of overdiagnosis and overtreatment.”⁹ The majority of suspicious skin lesions excised during screenings are not cancerous. For example, the SCREEN study found that 20 to 55 excisions were performed to detect 1 case of melanoma.¹⁰ At that rate, the USPSTF also noted that approximately 4000 excisions would be required to prevent a single death from melanoma.⁹ Following the lead of the USPSTF, the Patient Protection and Affordable Care Act did not mandate that skin examinations be included as essential preventive coverage in its requirements for insurance coverage of primary care prevention. As such, dermatologists face financial pressure to avoid performing time-consuming TBSEs, regardless of their perceived utility.¹¹

As the USPSTF points out, the value of TBSEs relies on the examiner’s ability to correctly identify malignant lesions and minimize biopsies of benign lesions, a concept known as biopsy efficiency.⁹ Secondarily, a TBSE is time consuming, and the time required for a dermatologist to complete a TBSE given the high rate of benign findings may not be financially viable. We argue that the routine use of total-body skin imaging may offer a way forward in addressing these issues. Total-body photography involves a photographic system that can allow dermatologists to acquire standardized images that can be used for primary diagnosis and to track individual lesions over time. Nonmedical personnel and medical assistants can be easily trained to use standardized photography devices to quickly obtain high-quality clinical images, thereby greatly reducing the time and cost of obtaining these images. Studies have found that the use of photographic monitoring may improve biopsy efficiency.^12-15 A recent study by Truong et al¹⁶ found that TBP used to monitor all existing melanocytic lesions on patients substantially reduced the number of biopsies that patients required. These results reflect that most nevi, including clinically atypical nevi, are usually stable and unlikely to exhibit suspicious changes over time.^17,18 For this reason, the use of TBP could minimize unnecessary biopsies because clinically suspicious but stable nevi can be objectively documented and followed over time.

Standardized TBP also offers the ability for dermatologists to work synergistically with modern computer technology involving algorithms capable of analyzing high-quality images to autodiagnose or flag concerning lesions that may require biopsy. Esteva et al¹⁹ described their development of a deep learning algorithm that relies on a convolutional neural network (CNN). This CNN was trained to identify melanomas using a large data set of clinical dermatologic images and subsequently was able to distinguish MMs from benign nevi at a rate on par with a board-certified dermatologist.¹⁹ Widespread use of total-body imaging would create an enormous database of high-resolution images that would be ideally suited to the development of such computerized algorithms, which could then be applied to future images by way of artificial intelligence. Convolutional neural networks that use a single patient’s imaging over time could be developed to assess the change in number or size of benign nevi and identify lesions that are concerning for MM while simultaneously comparing them to a population-based data set.

On a large scale, such a capability would minimize the inefficiency and subjectivity of TBSEs as a tool for identifying malignancy. Currently, dermatologists are only able to track and document a few concerning lesions on a patient’s body, rendering the choice of which lesions require biopsy more subjective. Total-body photography, particularly if used with an algorithm capable of quickly analyzing all the nevi on a person’s body, largely eliminates such subjectivity by creating a standardized set of images that can be tracked over time and flagging concerning lesions prior to the dermatologist examining the patient. In this way, the specialty of dermatology could achieve the same model of objective evaluation of standardized clinical images as those employed in radiology, cardiology, and other clinical disciplines. The additional benefit of such a system would be lower costs, as the images could be acquired by nonmedical personnel and then undergo initial assessment by an algorithm, which would flag concerning lesions, similar to a modern electrocardiogram machine, allowing the dermatologist to use his/her time more efficiently by only focusing on concerning lesions with the confidence that the patient’s entire body has already been rigorously screened.

By using TBP to improve biopsy efficiency and the objectivity of the TBSE as a tool to detect skin cancer, we propose that the benefit-to-harm ratio of the TBSE would remarkably improve. Ultimately, this type of screening would meet the strict requirements to be included in preventive health care strategies and thereby improve access to dermatologic care.

The Use of TBP in the Military

Total-body photography has several specific applications in the military. Standardized imaging has the potential to improve dermatologic care for active-duty soldiers across space and time. First, a large percentage of deployment medical care is devoted to dermatologic issues. From 2008 to 2015, 5% of all medical encounters in the combat theaters of Iraq and Afghanistan involved dermatologic concerns.²⁰ Access to appropriate dermatologic care in a combat theater is important, as poorly controlled dermatologic conditions (eg, psoriasis, eczema) often require evacuation when left untreated. Although current TBP systems may not be portable or durable enough to survive in an austere deployment environment, we propose it would be feasible to have skin imaging booths at larger forward operating bases. The images could then be transported to a remote dermatologist to assess and recommend treatment. The expense of transporting and maintaining the imaging system in country would be offset by the expenses spared by not requiring a dermatologist in country and the reductions in costly medical evacuations from theater.

Although the US military population is younger and generally healthier than the general adult population due to extensive medical screening on admission, age limitations for active-duty service, a mandated active lifestyle, and access to good health care, there are still a substantial number of service members diagnosed with skin cancer each year.²¹ From 2005 through 2014, MM was the most common non–gender-specific cancer (n=1571); in men, only testicular cancer was more prevalent (1591 vs 1298 cases), and in women, only breast cancer was more prevalent (773 vs 273 cases). Furthermore, from 2004 to 2013, the incidence rates of melanoma have increased by 1.4%, while with other cancer rates have declined during the same time period.²¹ Thus, TBP as a screening modality across the military population is a promising method for improving detection of skin cancer and reducing morbidity and mortality.

Military medicine often is on the forefront of medical advances in technology, disease understanding, and clinical care due to the unique resources available in the military health care system, which allow investigators the ability to obtain vast amounts of epidemiologic data.²² The military health care system also is unique in its ability to mandate that its members obtain preventive health services. Thus, it would be possible for the military to mandate TBP at accession and retirement, for instance, or more frequently for annual screening. The implementation of such a program would improve the health of the military population and be a public health service by pioneering the use of a standardized TBP system across a large health care system to improve skin cancer detection.

Current Studies in the Military

The Dermatology Service at the Walter Reed National Military Medical Center (WRNMMC)(Bethesda, Maryland) is evaluating the use of a total-body digital skin imaging system under a grant from the Telemedicine and Advanced Technology Research Center of the US Army. The system in use was found to be particularly well suited for military dermatology because it offers standardized TBP processing, produces a report that can be uploaded to the US Department of Defense (DoD) electronic medical record system, and requires relatively brief training for ancillary personnel to operate. Regardless of the platform the DoD ultimately finds most suitable, it is critical that a standard exist for TBP to ensure that uniform data sets are generated to allow military and other DoD dermatologists as well as civilian health care providers to share clinical information. The goal of the current study at WRNMMC is to vet TBP platforms at WRNMMC so the military can then develop standards to procure additional platforms for placement throughout the Military Health System, Military Entrance Processing Stations, operational environments, and collaborating health care systems (eg, the Veterans Health Administration).

Once deployed broadly across the Military Health System, these TBP platforms would be part of a network of telehealth care. For acute dermatologic issues, diagnoses provided via teledermatology platforms can then be managed by health care providers utilizing appropriate clinical practice guidelines or by non–health care providers utilizing general medical knowledge databases. Such a system with TBP information collected at multiple access points across a service member’s career would build a repository of data that would be immensely useful to patients and to clinical research. Of particular interest to military researchers is that TBP data could be used to study which patients require in-person examinations or more careful monitoring; the proper intervals for skin cancer screening; and the assessment of the benefits of TBP in improving morbidity, mortality, and biopsy efficiency in the detection of MM as well as nonmelanoma skin cancers.

Limitations to Progress

Currently, there are multiple limitations to the implementation of TBP as a part of TBSE screening. First, the potential improvement in biopsy efficiency using TBP is predicated on its ability to prove nevi stability over time, but in younger populations, benign nevi are more likely to change or increase in number, which may reduce the biopsy efficiency of screening in a younger population, thereby negating some of the benefit of imaging and CNN assessment. For instance, Truong et al¹⁶ found that younger age (<30 years) did not show the same improvement in biopsy efficiency with the use of TBP, which the authors theorized may reflect “the dynamic nature of nevi in younger patients” that has been documented in other studies.^23,24 Approximately 65% of the active-duty military population is aged 18 to 30 years, and 98% of accessions to active duty occur in individuals aged 17 to 30 years.²⁵ As such, TBP may not improve biopsy efficiency in the active-duty military population as dramatically as it would across the general population.

A second limitation of the use of TBP in the active-duty military population is the ethics of implementing DoD-wide mandatory TBP. Although the TBP platform will be compliant with the Health Insurance Portability and Accountability Act, mandating that soldiers contribute their TBP to a repository of data that will then be used for research without explicitly requesting their consent is ethically problematic; however, since the 1950s, the DoD has collected serum samples from its service members for force protection and operations reasons as well as for the purpose of research.^22,26 Currently, the DoD Serum Repository collects serum samples as part of a mandatory human immunodeficiency virus screening program that evaluates service members every 2 years; this repository of human serum samples is accessible for research purposes without the consent of the individuals being studied.²⁷ These individuals are not informed of potential use of their serum specimens for research purposes and no consent forms or opt-out options are provided. Thus, although there is precedent in the DoD for such mass data collection, it is an ongoing ethical consideration.²⁸

RELATED ARTICLE: Gigapixel Photography for Skin Cancer Surveillance

Finally, although the potential use of TBP and computer algorithms to improve the efficiency and affordability of TBSEs is exciting, there are no existing computer algorithms that we are aware of that can be used with existing TBP platforms in the manner we proposed. However, we feel that computer algorithms, such as the one created by Esteva et al,¹⁹ are just the beginning and that the use of artificial intelligence is not far off. Even after the creation of a TBP-compatible algorithm adept at analyzing malignant lesions, however, this technology would need to be further evaluated in the clinical setting to determine its capability and practicality. Current TBP platforms also are limited by their large size, cost, and complexity. As TBP platforms improve, it is likely that more streamlined and less expensive versions of current models will greatly enhance the field of teledermatology, particularly in the military setting.

Skin cancer is an important public health issue in the United States, as 1 in 5 Americans are projected to develop a cutaneous malignancy during their lifetime. Currently, 75% of all skin cancer–related deaths are due to malignant melanomas (MMs), though melanomas account for less than 5% of all skin cancers.¹ Early detection of MM is essential, as prognosis depends on tumor stage, particularly the depth of the melanoma.^2-4 In general, patients with thin, early-stage melanomas have a more than 96% survival rate, which drops to 14% in late-stage disease.^5,6 Five percent to 30% of all melanomas are identified incidentally on total-body skin examinations (TBSEs) performed by a trained provider and thus would not have been caught with only a focused skin examination or patient self-examination.^7,8 Nonetheless, the clinical utility of skin cancer screening with TBSEs remains controversial, largely due to the poor quality of data available to establish a notable mortality benefit from skin cancer screening. As a result, obtaining endorsement from the larger medical community, federal government, and health insurance industry to include routine TBSEs as part of a preventive care health care strategy has not occurred. The absence of definitive clinical care guidelines mandating routine TBSEs is one of the greatest barriers preventing access to appropriate dermatologic screening along with the paucity of trained providers; however, standardized total-body photography (TBP) promises to provide a way forward by lowering the costs of dermatologic screening while simultaneously leveraging technology to increase availability.

Impact on Biopsy Efficiency

Current US Preventive Services Task Force (USPSTF) guidelines state that evidence is insufficient to assess the balance of benefits and harms of visual skin examination by a clinician to screen for skin cancer in adults. The USPSTF noted that “[d]irect evidence on the effectiveness of screening in reducing melanoma morbidity and mortality is limited to a single fair-quality ecologic study with important methodological limitations” (ie, the Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany [SCREEN] study), and although information on harm is similarly sparse, “[t]he potential for harm clearly exists, including a high rate of unnecessary biopsies, possibly resulting in cosmetic or, more rarely, functional adverse effects, and the risk of overdiagnosis and overtreatment.”⁹ The majority of suspicious skin lesions excised during screenings are not cancerous. For example, the SCREEN study found that 20 to 55 excisions were performed to detect 1 case of melanoma.¹⁰ At that rate, the USPSTF also noted that approximately 4000 excisions would be required to prevent a single death from melanoma.⁹ Following the lead of the USPSTF, the Patient Protection and Affordable Care Act did not mandate that skin examinations be included as essential preventive coverage in its requirements for insurance coverage of primary care prevention. As such, dermatologists face financial pressure to avoid performing time-consuming TBSEs, regardless of their perceived utility.¹¹

As the USPSTF points out, the value of TBSEs relies on the examiner’s ability to correctly identify malignant lesions and minimize biopsies of benign lesions, a concept known as biopsy efficiency.⁹ Secondarily, a TBSE is time consuming, and the time required for a dermatologist to complete a TBSE given the high rate of benign findings may not be financially viable. We argue that the routine use of total-body skin imaging may offer a way forward in addressing these issues. Total-body photography involves a photographic system that can allow dermatologists to acquire standardized images that can be used for primary diagnosis and to track individual lesions over time. Nonmedical personnel and medical assistants can be easily trained to use standardized photography devices to quickly obtain high-quality clinical images, thereby greatly reducing the time and cost of obtaining these images. Studies have found that the use of photographic monitoring may improve biopsy efficiency.^12-15 A recent study by Truong et al¹⁶ found that TBP used to monitor all existing melanocytic lesions on patients substantially reduced the number of biopsies that patients required. These results reflect that most nevi, including clinically atypical nevi, are usually stable and unlikely to exhibit suspicious changes over time.^17,18 For this reason, the use of TBP could minimize unnecessary biopsies because clinically suspicious but stable nevi can be objectively documented and followed over time.

Standardized TBP also offers the ability for dermatologists to work synergistically with modern computer technology involving algorithms capable of analyzing high-quality images to autodiagnose or flag concerning lesions that may require biopsy. Esteva et al¹⁹ described their development of a deep learning algorithm that relies on a convolutional neural network (CNN). This CNN was trained to identify melanomas using a large data set of clinical dermatologic images and subsequently was able to distinguish MMs from benign nevi at a rate on par with a board-certified dermatologist.¹⁹ Widespread use of total-body imaging would create an enormous database of high-resolution images that would be ideally suited to the development of such computerized algorithms, which could then be applied to future images by way of artificial intelligence. Convolutional neural networks that use a single patient’s imaging over time could be developed to assess the change in number or size of benign nevi and identify lesions that are concerning for MM while simultaneously comparing them to a population-based data set.

On a large scale, such a capability would minimize the inefficiency and subjectivity of TBSEs as a tool for identifying malignancy. Currently, dermatologists are only able to track and document a few concerning lesions on a patient’s body, rendering the choice of which lesions require biopsy more subjective. Total-body photography, particularly if used with an algorithm capable of quickly analyzing all the nevi on a person’s body, largely eliminates such subjectivity by creating a standardized set of images that can be tracked over time and flagging concerning lesions prior to the dermatologist examining the patient. In this way, the specialty of dermatology could achieve the same model of objective evaluation of standardized clinical images as those employed in radiology, cardiology, and other clinical disciplines. The additional benefit of such a system would be lower costs, as the images could be acquired by nonmedical personnel and then undergo initial assessment by an algorithm, which would flag concerning lesions, similar to a modern electrocardiogram machine, allowing the dermatologist to use his/her time more efficiently by only focusing on concerning lesions with the confidence that the patient’s entire body has already been rigorously screened.

By using TBP to improve biopsy efficiency and the objectivity of the TBSE as a tool to detect skin cancer, we propose that the benefit-to-harm ratio of the TBSE would remarkably improve. Ultimately, this type of screening would meet the strict requirements to be included in preventive health care strategies and thereby improve access to dermatologic care.

The Use of TBP in the Military

Total-body photography has several specific applications in the military. Standardized imaging has the potential to improve dermatologic care for active-duty soldiers across space and time. First, a large percentage of deployment medical care is devoted to dermatologic issues. From 2008 to 2015, 5% of all medical encounters in the combat theaters of Iraq and Afghanistan involved dermatologic concerns.²⁰ Access to appropriate dermatologic care in a combat theater is important, as poorly controlled dermatologic conditions (eg, psoriasis, eczema) often require evacuation when left untreated. Although current TBP systems may not be portable or durable enough to survive in an austere deployment environment, we propose it would be feasible to have skin imaging booths at larger forward operating bases. The images could then be transported to a remote dermatologist to assess and recommend treatment. The expense of transporting and maintaining the imaging system in country would be offset by the expenses spared by not requiring a dermatologist in country and the reductions in costly medical evacuations from theater.

Although the US military population is younger and generally healthier than the general adult population due to extensive medical screening on admission, age limitations for active-duty service, a mandated active lifestyle, and access to good health care, there are still a substantial number of service members diagnosed with skin cancer each year.²¹ From 2005 through 2014, MM was the most common non–gender-specific cancer (n=1571); in men, only testicular cancer was more prevalent (1591 vs 1298 cases), and in women, only breast cancer was more prevalent (773 vs 273 cases). Furthermore, from 2004 to 2013, the incidence rates of melanoma have increased by 1.4%, while with other cancer rates have declined during the same time period.²¹ Thus, TBP as a screening modality across the military population is a promising method for improving detection of skin cancer and reducing morbidity and mortality.

Military medicine often is on the forefront of medical advances in technology, disease understanding, and clinical care due to the unique resources available in the military health care system, which allow investigators the ability to obtain vast amounts of epidemiologic data.²² The military health care system also is unique in its ability to mandate that its members obtain preventive health services. Thus, it would be possible for the military to mandate TBP at accession and retirement, for instance, or more frequently for annual screening. The implementation of such a program would improve the health of the military population and be a public health service by pioneering the use of a standardized TBP system across a large health care system to improve skin cancer detection.

Current Studies in the Military

The Dermatology Service at the Walter Reed National Military Medical Center (WRNMMC)(Bethesda, Maryland) is evaluating the use of a total-body digital skin imaging system under a grant from the Telemedicine and Advanced Technology Research Center of the US Army. The system in use was found to be particularly well suited for military dermatology because it offers standardized TBP processing, produces a report that can be uploaded to the US Department of Defense (DoD) electronic medical record system, and requires relatively brief training for ancillary personnel to operate. Regardless of the platform the DoD ultimately finds most suitable, it is critical that a standard exist for TBP to ensure that uniform data sets are generated to allow military and other DoD dermatologists as well as civilian health care providers to share clinical information. The goal of the current study at WRNMMC is to vet TBP platforms at WRNMMC so the military can then develop standards to procure additional platforms for placement throughout the Military Health System, Military Entrance Processing Stations, operational environments, and collaborating health care systems (eg, the Veterans Health Administration).

Once deployed broadly across the Military Health System, these TBP platforms would be part of a network of telehealth care. For acute dermatologic issues, diagnoses provided via teledermatology platforms can then be managed by health care providers utilizing appropriate clinical practice guidelines or by non–health care providers utilizing general medical knowledge databases. Such a system with TBP information collected at multiple access points across a service member’s career would build a repository of data that would be immensely useful to patients and to clinical research. Of particular interest to military researchers is that TBP data could be used to study which patients require in-person examinations or more careful monitoring; the proper intervals for skin cancer screening; and the assessment of the benefits of TBP in improving morbidity, mortality, and biopsy efficiency in the detection of MM as well as nonmelanoma skin cancers.

Limitations to Progress

Currently, there are multiple limitations to the implementation of TBP as a part of TBSE screening. First, the potential improvement in biopsy efficiency using TBP is predicated on its ability to prove nevi stability over time, but in younger populations, benign nevi are more likely to change or increase in number, which may reduce the biopsy efficiency of screening in a younger population, thereby negating some of the benefit of imaging and CNN assessment. For instance, Truong et al¹⁶ found that younger age (<30 years) did not show the same improvement in biopsy efficiency with the use of TBP, which the authors theorized may reflect “the dynamic nature of nevi in younger patients” that has been documented in other studies.^23,24 Approximately 65% of the active-duty military population is aged 18 to 30 years, and 98% of accessions to active duty occur in individuals aged 17 to 30 years.²⁵ As such, TBP may not improve biopsy efficiency in the active-duty military population as dramatically as it would across the general population.

A second limitation of the use of TBP in the active-duty military population is the ethics of implementing DoD-wide mandatory TBP. Although the TBP platform will be compliant with the Health Insurance Portability and Accountability Act, mandating that soldiers contribute their TBP to a repository of data that will then be used for research without explicitly requesting their consent is ethically problematic; however, since the 1950s, the DoD has collected serum samples from its service members for force protection and operations reasons as well as for the purpose of research.^22,26 Currently, the DoD Serum Repository collects serum samples as part of a mandatory human immunodeficiency virus screening program that evaluates service members every 2 years; this repository of human serum samples is accessible for research purposes without the consent of the individuals being studied.²⁷ These individuals are not informed of potential use of their serum specimens for research purposes and no consent forms or opt-out options are provided. Thus, although there is precedent in the DoD for such mass data collection, it is an ongoing ethical consideration.²⁸

RELATED ARTICLE: Gigapixel Photography for Skin Cancer Surveillance

Finally, although the potential use of TBP and computer algorithms to improve the efficiency and affordability of TBSEs is exciting, there are no existing computer algorithms that we are aware of that can be used with existing TBP platforms in the manner we proposed. However, we feel that computer algorithms, such as the one created by Esteva et al,¹⁹ are just the beginning and that the use of artificial intelligence is not far off. Even after the creation of a TBP-compatible algorithm adept at analyzing malignant lesions, however, this technology would need to be further evaluated in the clinical setting to determine its capability and practicality. Current TBP platforms also are limited by their large size, cost, and complexity. As TBP platforms improve, it is likely that more streamlined and less expensive versions of current models will greatly enhance the field of teledermatology, particularly in the military setting.