Radhika Srivastava, BA

The Diagnosis: Interstitial Granulomatous Dermatitis 

Interstitial granulomatous dermatitis (IGD) is rare, and the exact incidence is unknown, with only a few cases reported in the literature annually.¹ Although IGD may arise in both children and adults, it occurs more commonly in adults, with an age of onset of 52 to 58.5 years. Interstitial granulomatous dermatitis also shows a female predominance.¹  

Interstitial granulomatous dermatitis may present as annular flesh-colored or erythematous to violaceous papules and plaques, or less commonly erythematous linear cordlike subcutaneous nodules (called the rope sign).¹ Lesions often are asymptomatic but may be pruritic or tender. Interstitial granulomatous dermatitis has been associated with autoimmune conditions such as rheumatoid arthritis, systemic lupus erythematosus, and primary biliary cholangitis, and rarely malignancy.² Interstitial granulomatous drug reactions can occur months to years after initiation of therapy with offending agents, and common causes include calcium channel blockers, statins, and tumor necrosis factor α inhibitors.³  

Interstitial granulomatous dermatitis and palisaded neutrophilic and granulomatous dermatitis (PNGD) demonstrate overlapping clinical features and are thought to be part of the same spectrum of granulomatous dermatitis.⁴ Both IGD and PNGD may present with symmetric flesh-colored to erythematous papules or erythematous annular or linear plaques.⁵ Interstitial granulomatous dermatitis and PNGD may be differentiated through histopathologic examination.  

Histopathology of IGD shows an interstitial infiltrate of epithelioid histiocytes in the dermis, often surrounding foci of degenerated collagen resembling palisading granulomas (quiz images).¹ Perivascular and interstitial lymphocytic infiltrates also are present in most cases. Epidermal changes are minimal in IGD but can be associated with interstitial granulomatous drug reactions.¹ There usually is no vasculitis, and mucin typically is absent, unlike granuloma annulare (GA).^3,6 In comparison, histopathologic examination of PNGD shows basophilic degenerated collagen surrounded by palisades of histiocytes, neutrophils, and nuclear debris with focal areas of leukocytoclastic vasculitis and rare mucin.⁵  

No specific treatment is recommended, and lesions may resolve without any therapy. Reported treatments include topical, intralesional, or systemic steroids; nonsteroidal anti-inflammatory drugs; methotrexate; hydroxychloroquine; and cyclosporine.⁶ Due to the strong association with systemic diseases, it is important to evaluate patients with IGD for autoimmune diseases and conduct age-appropriate cancer screening. Furthermore, a review of medications is warranted to assess the possibility of interstitial granulomatous drug reactions.⁶ In our patient, rheumatologic workup and age-appropriate cancer screenings were negative, and the rash spontaneously resolved without treatment. 

Granuloma annulare presents with asymptomatic flesh-colored to erythematous papules and plaques in an annular configuration. In the localized variant of GA, plaques frequently localize to the distal extremities, especially the dorsal hands, as in our patient. Other variants include generalized GA, subcutaneous GA, and perforating GA. Mucin and a palisading or interstitial pattern of granulomatous inflammation are key features on histopathology in all subtypes of GA (Figure 1).⁷ Patch GA is a rare variant that presents with asymptomatic erythematous to brown patches, is associated with interstitial-type inflammation on histopathology, and can be difficult to distinguish from IGD.⁸ Granuloma annulare with interstitial inflammation on histology can be differentiated from IGD by the comparative lack of mucin in IGD.⁷ 

Sweet syndrome (SS) is characterized by sudden-onset, painful, erythematous plaques and/or nodules, commonly associated with fever and leukocytosis. Clinical variants of SS include pustular and bullous SS; giant cellulitis-like SS; necrotizing SS; and neutrophilic dermatosis of the dorsal hands presenting with hemorrhagic bullae, plaques, and pustules.^7-9 Histopathologic examination shows dense nodular or perivascular neutrophilic infiltrate in the dermis without evidence of vasculitis (Figure 2).¹⁰ Histopathologic variants include histiocytoid, lymphocytic, subcutaneous, and cryptococcoid.⁹ The classic variant of SS has a bandlike, predominantly neutrophilic infiltrate with marked leukocytoclasia, which can be differentiated from the histiocytoid infiltrate of IGD.¹¹ It has been shown that the infiltrate of the histiocytoid variant of SS is composed of myeloperoxidase-positive, immature myeloid cells rather than true histiocytes, and therefore can be differentiated from IGD.¹² Lastly, all variants of SS have dermal edema, which typically is absent in IGD, and SS has no evidence of necrobiosis.  

Erythema elevatum diutinum (EED) is a rare disease that presents with bilateral violaceous or erythematous to brown papules, plaques, or nodules. Lesions frequently localize to extensor surfaces, including the hands and fingers, and may be asymptomatic or associated with pruritus, burning, or tingling.¹³ Early EED lesions are characterized by leukocytoclastic vasculitis of the papillary and mid-dermal vessels with a perivascular neutrophilic infiltrate and perivascular fibrinoid necrosis. With older EED lesions, dermal and perivascular onion skin-like fibrosis become more prominent (Figure 3).¹⁴ The neutrophilic infiltrate, dermal fibrosis, and chronic vasculitic changes distinguish EED from IGD. 

Necrobiosis lipoidica (NL) is a rare disease that presents with well-demarcated, yellow to red-brown papules and nodules most commonly localized to the bilateral lower extremities on the pretibial area. Papules and nodules evolve into plaques over time, and ulceration is common.¹⁵ On histopathology, NL primarily exhibits granulomatous inflammation with parallel palisading (Figure 4). The hallmark feature is necrobiosis--or degeneration--of collagen; the alternation of necrobiotic collagen and inflammatory infiltrate creates a layered cake-like appearance on low power.¹⁶ The clinical presentation as well as the dermal necrobiotic granuloma consisting of a large confluent area of necrobiosis centered in the superficial dermis and subcutaneous tissue of NL distinguishes it from the histiocytic infiltrate of IGD.  

The Diagnosis: Interstitial Granulomatous Dermatitis 

Interstitial granulomatous dermatitis (IGD) is rare, and the exact incidence is unknown, with only a few cases reported in the literature annually.¹ Although IGD may arise in both children and adults, it occurs more commonly in adults, with an age of onset of 52 to 58.5 years. Interstitial granulomatous dermatitis also shows a female predominance.¹  

Interstitial granulomatous dermatitis may present as annular flesh-colored or erythematous to violaceous papules and plaques, or less commonly erythematous linear cordlike subcutaneous nodules (called the rope sign).¹ Lesions often are asymptomatic but may be pruritic or tender. Interstitial granulomatous dermatitis has been associated with autoimmune conditions such as rheumatoid arthritis, systemic lupus erythematosus, and primary biliary cholangitis, and rarely malignancy.² Interstitial granulomatous drug reactions can occur months to years after initiation of therapy with offending agents, and common causes include calcium channel blockers, statins, and tumor necrosis factor α inhibitors.³  

Interstitial granulomatous dermatitis and palisaded neutrophilic and granulomatous dermatitis (PNGD) demonstrate overlapping clinical features and are thought to be part of the same spectrum of granulomatous dermatitis.⁴ Both IGD and PNGD may present with symmetric flesh-colored to erythematous papules or erythematous annular or linear plaques.⁵ Interstitial granulomatous dermatitis and PNGD may be differentiated through histopathologic examination.  

Histopathology of IGD shows an interstitial infiltrate of epithelioid histiocytes in the dermis, often surrounding foci of degenerated collagen resembling palisading granulomas (quiz images).¹ Perivascular and interstitial lymphocytic infiltrates also are present in most cases. Epidermal changes are minimal in IGD but can be associated with interstitial granulomatous drug reactions.¹ There usually is no vasculitis, and mucin typically is absent, unlike granuloma annulare (GA).^3,6 In comparison, histopathologic examination of PNGD shows basophilic degenerated collagen surrounded by palisades of histiocytes, neutrophils, and nuclear debris with focal areas of leukocytoclastic vasculitis and rare mucin.⁵  

No specific treatment is recommended, and lesions may resolve without any therapy. Reported treatments include topical, intralesional, or systemic steroids; nonsteroidal anti-inflammatory drugs; methotrexate; hydroxychloroquine; and cyclosporine.⁶ Due to the strong association with systemic diseases, it is important to evaluate patients with IGD for autoimmune diseases and conduct age-appropriate cancer screening. Furthermore, a review of medications is warranted to assess the possibility of interstitial granulomatous drug reactions.⁶ In our patient, rheumatologic workup and age-appropriate cancer screenings were negative, and the rash spontaneously resolved without treatment. 

Granuloma annulare presents with asymptomatic flesh-colored to erythematous papules and plaques in an annular configuration. In the localized variant of GA, plaques frequently localize to the distal extremities, especially the dorsal hands, as in our patient. Other variants include generalized GA, subcutaneous GA, and perforating GA. Mucin and a palisading or interstitial pattern of granulomatous inflammation are key features on histopathology in all subtypes of GA (Figure 1).⁷ Patch GA is a rare variant that presents with asymptomatic erythematous to brown patches, is associated with interstitial-type inflammation on histopathology, and can be difficult to distinguish from IGD.⁸ Granuloma annulare with interstitial inflammation on histology can be differentiated from IGD by the comparative lack of mucin in IGD.⁷ 

Sweet syndrome (SS) is characterized by sudden-onset, painful, erythematous plaques and/or nodules, commonly associated with fever and leukocytosis. Clinical variants of SS include pustular and bullous SS; giant cellulitis-like SS; necrotizing SS; and neutrophilic dermatosis of the dorsal hands presenting with hemorrhagic bullae, plaques, and pustules.^7-9 Histopathologic examination shows dense nodular or perivascular neutrophilic infiltrate in the dermis without evidence of vasculitis (Figure 2).¹⁰ Histopathologic variants include histiocytoid, lymphocytic, subcutaneous, and cryptococcoid.⁹ The classic variant of SS has a bandlike, predominantly neutrophilic infiltrate with marked leukocytoclasia, which can be differentiated from the histiocytoid infiltrate of IGD.¹¹ It has been shown that the infiltrate of the histiocytoid variant of SS is composed of myeloperoxidase-positive, immature myeloid cells rather than true histiocytes, and therefore can be differentiated from IGD.¹² Lastly, all variants of SS have dermal edema, which typically is absent in IGD, and SS has no evidence of necrobiosis.  

Erythema elevatum diutinum (EED) is a rare disease that presents with bilateral violaceous or erythematous to brown papules, plaques, or nodules. Lesions frequently localize to extensor surfaces, including the hands and fingers, and may be asymptomatic or associated with pruritus, burning, or tingling.¹³ Early EED lesions are characterized by leukocytoclastic vasculitis of the papillary and mid-dermal vessels with a perivascular neutrophilic infiltrate and perivascular fibrinoid necrosis. With older EED lesions, dermal and perivascular onion skin-like fibrosis become more prominent (Figure 3).¹⁴ The neutrophilic infiltrate, dermal fibrosis, and chronic vasculitic changes distinguish EED from IGD. 

Necrobiosis lipoidica (NL) is a rare disease that presents with well-demarcated, yellow to red-brown papules and nodules most commonly localized to the bilateral lower extremities on the pretibial area. Papules and nodules evolve into plaques over time, and ulceration is common.¹⁵ On histopathology, NL primarily exhibits granulomatous inflammation with parallel palisading (Figure 4). The hallmark feature is necrobiosis--or degeneration--of collagen; the alternation of necrobiotic collagen and inflammatory infiltrate creates a layered cake-like appearance on low power.¹⁶ The clinical presentation as well as the dermal necrobiotic granuloma consisting of a large confluent area of necrobiosis centered in the superficial dermis and subcutaneous tissue of NL distinguishes it from the histiocytic infiltrate of IGD.  

The Diagnosis: Interstitial Granulomatous Dermatitis 

Interstitial granulomatous dermatitis (IGD) is rare, and the exact incidence is unknown, with only a few cases reported in the literature annually.¹ Although IGD may arise in both children and adults, it occurs more commonly in adults, with an age of onset of 52 to 58.5 years. Interstitial granulomatous dermatitis also shows a female predominance.¹  

Interstitial granulomatous dermatitis may present as annular flesh-colored or erythematous to violaceous papules and plaques, or less commonly erythematous linear cordlike subcutaneous nodules (called the rope sign).¹ Lesions often are asymptomatic but may be pruritic or tender. Interstitial granulomatous dermatitis has been associated with autoimmune conditions such as rheumatoid arthritis, systemic lupus erythematosus, and primary biliary cholangitis, and rarely malignancy.² Interstitial granulomatous drug reactions can occur months to years after initiation of therapy with offending agents, and common causes include calcium channel blockers, statins, and tumor necrosis factor α inhibitors.³  

Interstitial granulomatous dermatitis and palisaded neutrophilic and granulomatous dermatitis (PNGD) demonstrate overlapping clinical features and are thought to be part of the same spectrum of granulomatous dermatitis.⁴ Both IGD and PNGD may present with symmetric flesh-colored to erythematous papules or erythematous annular or linear plaques.⁵ Interstitial granulomatous dermatitis and PNGD may be differentiated through histopathologic examination.  

Histopathology of IGD shows an interstitial infiltrate of epithelioid histiocytes in the dermis, often surrounding foci of degenerated collagen resembling palisading granulomas (quiz images).¹ Perivascular and interstitial lymphocytic infiltrates also are present in most cases. Epidermal changes are minimal in IGD but can be associated with interstitial granulomatous drug reactions.¹ There usually is no vasculitis, and mucin typically is absent, unlike granuloma annulare (GA).^3,6 In comparison, histopathologic examination of PNGD shows basophilic degenerated collagen surrounded by palisades of histiocytes, neutrophils, and nuclear debris with focal areas of leukocytoclastic vasculitis and rare mucin.⁵  

No specific treatment is recommended, and lesions may resolve without any therapy. Reported treatments include topical, intralesional, or systemic steroids; nonsteroidal anti-inflammatory drugs; methotrexate; hydroxychloroquine; and cyclosporine.⁶ Due to the strong association with systemic diseases, it is important to evaluate patients with IGD for autoimmune diseases and conduct age-appropriate cancer screening. Furthermore, a review of medications is warranted to assess the possibility of interstitial granulomatous drug reactions.⁶ In our patient, rheumatologic workup and age-appropriate cancer screenings were negative, and the rash spontaneously resolved without treatment. 

Granuloma annulare presents with asymptomatic flesh-colored to erythematous papules and plaques in an annular configuration. In the localized variant of GA, plaques frequently localize to the distal extremities, especially the dorsal hands, as in our patient. Other variants include generalized GA, subcutaneous GA, and perforating GA. Mucin and a palisading or interstitial pattern of granulomatous inflammation are key features on histopathology in all subtypes of GA (Figure 1).⁷ Patch GA is a rare variant that presents with asymptomatic erythematous to brown patches, is associated with interstitial-type inflammation on histopathology, and can be difficult to distinguish from IGD.⁸ Granuloma annulare with interstitial inflammation on histology can be differentiated from IGD by the comparative lack of mucin in IGD.⁷ 

Sweet syndrome (SS) is characterized by sudden-onset, painful, erythematous plaques and/or nodules, commonly associated with fever and leukocytosis. Clinical variants of SS include pustular and bullous SS; giant cellulitis-like SS; necrotizing SS; and neutrophilic dermatosis of the dorsal hands presenting with hemorrhagic bullae, plaques, and pustules.^7-9 Histopathologic examination shows dense nodular or perivascular neutrophilic infiltrate in the dermis without evidence of vasculitis (Figure 2).¹⁰ Histopathologic variants include histiocytoid, lymphocytic, subcutaneous, and cryptococcoid.⁹ The classic variant of SS has a bandlike, predominantly neutrophilic infiltrate with marked leukocytoclasia, which can be differentiated from the histiocytoid infiltrate of IGD.¹¹ It has been shown that the infiltrate of the histiocytoid variant of SS is composed of myeloperoxidase-positive, immature myeloid cells rather than true histiocytes, and therefore can be differentiated from IGD.¹² Lastly, all variants of SS have dermal edema, which typically is absent in IGD, and SS has no evidence of necrobiosis.  

Erythema elevatum diutinum (EED) is a rare disease that presents with bilateral violaceous or erythematous to brown papules, plaques, or nodules. Lesions frequently localize to extensor surfaces, including the hands and fingers, and may be asymptomatic or associated with pruritus, burning, or tingling.¹³ Early EED lesions are characterized by leukocytoclastic vasculitis of the papillary and mid-dermal vessels with a perivascular neutrophilic infiltrate and perivascular fibrinoid necrosis. With older EED lesions, dermal and perivascular onion skin-like fibrosis become more prominent (Figure 3).¹⁴ The neutrophilic infiltrate, dermal fibrosis, and chronic vasculitic changes distinguish EED from IGD. 

Necrobiosis lipoidica (NL) is a rare disease that presents with well-demarcated, yellow to red-brown papules and nodules most commonly localized to the bilateral lower extremities on the pretibial area. Papules and nodules evolve into plaques over time, and ulceration is common.¹⁵ On histopathology, NL primarily exhibits granulomatous inflammation with parallel palisading (Figure 4). The hallmark feature is necrobiosis--or degeneration--of collagen; the alternation of necrobiotic collagen and inflammatory infiltrate creates a layered cake-like appearance on low power.¹⁶ The clinical presentation as well as the dermal necrobiotic granuloma consisting of a large confluent area of necrobiosis centered in the superficial dermis and subcutaneous tissue of NL distinguishes it from the histiocytic infiltrate of IGD.  

To the Editor:

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

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

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

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

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

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

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

To the Editor:

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

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

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

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

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

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

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

To the Editor:

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

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

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

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

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

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

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

Traditionally, diagnosis of skin disease relies on clinical inspection, often followed by biopsy and histopathologic examination. In recent years, new noninvasive tools have emerged that can aid in clinical diagnosis and reduce the number of unnecessary benign biopsies. Although there has been a surge in noninvasive diagnostic technologies, many tools are still in research and development phases, with few tools widely adopted and used in regular clinical practice. In this article, we discuss the use of dermoscopy, reflectance confocal microscopy (RCM), and optical coherence tomography (OCT) in the diagnosis and management of skin disease.

Dermoscopy

Dermoscopy, also known as epiluminescence light microscopy and previously known as dermatoscopy, utilizes a ×10 to ×100 microscope objective with a light source to magnify and visualize structures present below the skin’s surface, such as melanin and blood vessels. There are 3 types of dermoscopy: conventional nonpolarized dermoscopy, polarized contact dermoscopy, and nonpolarized contact dermoscopy (Figure 1). Traditional nonpolarized dermoscopy requires a liquid medium and direct contact with the skin, and it relies on light reflection and refraction properties.¹ Cross-polarized light sources allow visualization of deeper structures, either with or without a liquid medium and contact with the skin surface. Although there is overall concurrence among the different types of dermoscopy, subtle differences in the appearance of color, features, and structure are present.¹

Dermoscopy offers many benefits for dermatologists and other providers. It can be used to aid in the diagnosis of cutaneous neoplasms and other skin diseases. Numerous low-cost dermatoscopes currently are commercially available. The handheld, easily transportable nature of dermatoscopes have resulted in widespread practice integration. Approximately 84% of attending dermatologists in US academic settings reported using dermoscopy, and many refer to the dermatoscope as “the dermatologist’s stethoscope.”² In addition, 6% to 15% of other US providers, including family physicians, internal medicine physicians, and plastic surgeons, have reported using dermoscopy in their clinical practices. Limitations of dermoscopy include visualization of the skin surface only and not deeper structures within the tissue, the need for training for adequate interpretation of dermoscopic images, and lack of reimbursement for dermoscopic examination.³

Many dermoscopic structures that correspond well with histopathology have been described. Dermoscopy has a sensitivity of 79% to 96% and specificity of 69% to 99% in the diagnosis of melanoma.⁴ There is variable data on the specificity of dermoscopy in the diagnosis of melanoma, with one meta-analysis finding no statistically significant difference in specificity compared to naked eye examination,⁵ while other studies report increased specificity and subsequent reduction in biopsy of benign lesions.^6,7 Dermoscopy also can aid in the diagnosis of keratinocytic neoplasms, and dermoscopy also results in a sensitivity of 78.6% to 100% and a specificity of 53.8% to 100% in the diagnosis of basal cell carcinoma (BCC).⁸ Limitations of dermoscopy include false-positive diagnoses, commonly seborrheic keratoses and nevi, resulting in unnecessary biopsies, as well as false-negative diagnoses, commonly amelanotic and nevoid melanoma, resulting in delays in skin cancer diagnosis and resultant poor outcomes.⁹ Dermoscopy also is used to aid in the diagnosis of inflammatory and infectious skin diseases, as well as scalp, hair, and nail disorders.¹⁰

Reflectance Confocal Microscopy

Reflectance confocal microscopy utilizes an 830-nm laser to capture horizontal en face images of the skin with high resolution. Different structures of the skin have varying indices of refraction: keratin, melanin, and collagen appear bright white, while other components appear dark, generating black-and-white RCM images.¹¹ Currently, there are 2 reflectance confocal microscopes that are commercially available in the United States. The Vivascope 1500 (Caliber ID) is the traditional model that captures 8×8-mm images, and the Vivascope 3000 (Caliber ID) is a smaller handheld model that captures 0.5×0.5-mm images. The traditional model provides the advantages of higher-resolution images and the ability to capture larger surface areas but is best suited to image flat areas of skin to which a square window can be adhered. The handheld model allows improved contact with the varying topography of skin; does not require an adhesive window; and can be used to image cartilaginous, mucosal, and sensitive surfaces. However, it can be difficult to correlate individual images captured by the handheld RCM with the location relative to the lesion, as it is exquisitely sensitive to motion and also is operator dependent. Although complex algorithms are under development to stitch individual images to provide better correlation with the geography of the lesion, such programs are not yet widely available.¹²

Reflectance confocal microscopy affords many benefits for patients and providers. It is noninvasive and painless and is capable of imaging in vivo live skin as compared to clinical examination and dermoscopy, which only allow for visualization of the skin’s surface. Reflectance confocal microscopy also is time efficient, as imaging of a single lesion can be completed in 10 to 15 minutes. This technology generates high-resolution images, and RCM diagnosis has consistently demonstrated high sensitivity and specificity when compared to histopathology.¹³ Additionally, RCM imaging can spare biopsy and resultant scarring on cosmetically sensitive areas. Recently, RCM imaging of the skin has been granted Category I Current Procedural Terminology reimbursement codes that allow provider reimbursement and integration of RCM into daily practice¹⁴; however, private insurance coverage in the United States is variable. Limitations of RCM include a maximum depth of 200 to 300 µm, high cost to procure a reflectance confocal microscope, and the need for considerable training and practice to accurately interpret grayscale en face images.¹⁵

There has been extensive research regarding the use of RCM in the evaluation of cutaneous neoplasms and other skin diseases. Numerous features and patterns have been identified and described that correspond with different skin diseases and correspond well with histopathology (Figure 2).^13,16,17 Reflectance confocal microscopy has demonstrated consistently high accuracy in the diagnosis of melanocytic lesions, with a sensitivity of 93% to 100% and a specificity of 75% to 99%.^18-21 Reflectance confocal microscopy is especially useful in the evaluation of clinically or dermoscopically equivocal pigmented lesions due to greater specificity, resulting in a reduction of unnecessary biopsies.^22,23 It also has high accuracy in the diagnosis of keratinocytic neoplasms, with a sensitivity of 82% to 100% and a specificity of 78% to 97% in the diagnosis of BCC,²⁴ and a sensitivity of 74% to 100% and specificity of 78% to 100% in the diagnosis of squamous cell carcinoma (SCC).^25,26 Evaluation of SCC and actinic keratosis (AK) using RCM may be limited by considerable hyperkeratosis and ulceration. In addition, it can be challenging to differentiate AK and SCC on RCM, and considerable expertise is required to accurately grade cytologic and architectural atypia.²⁷ However, RCM has been used to discriminate between in situ and invasive proliferations.²⁸ Reflectance confocal microscopy has wide applications in the diagnosis and management of cutaneous infections^29,30 and inflammatory skin diseases.^29,31-33 Recent RCM research explored the use of RCM to identify biopsy sites,³⁴ delineate presurgical tumor margins,^35,36 and monitor response to noninvasive treatments.^37,38

Optical Coherence Tomography

Optical coherence tomography is an imaging modality that utilizes light backscatter from infrared light to produce grayscale cross-sectional or vertical images and horizontal en face images.³⁹ Optical coherence tomography can visualize structures in the epidermis, dermoepidermal junction, and upper dermis.⁴⁰ It can image boundaries of structures but cannot visualize individual cells.

There are different types of OCT devices available, including frequency-domain OCT (FD-OCT), or conventional OCT, and high-definition OCT (HD-OCT). With FD-OCT, images are captured at a maximum depth of 1 to 2 mm but with limited resolution. High-definition OCT has superior resolution compared to FD-OCT but is restricted to a shallower depth of 750 μm.³⁹ The main advantage of OCT is the ability to noninvasively image live tissue and visualize 2- to 5-times greater depth as compared to RCM. Several OCT devices have obtained US Food and Drug Administration approval; however, OCT has not been widely adopted into clinical practice and is available only in tertiary academic centers. Additionally, OCT imaging in dermatology is rarely reimbursed. Other limitations of OCT include poor resolution of images, high cost to procure an OCT device, and the need for advanced training and experience to accurately interpret images.^40,41

Optical coherence tomography primarily is used to diagnose cutaneous neoplasms. The best evidence of the diagnostic accuracy of OCT is in the setting of BCC, with a recent systematic review reporting a sensitivity of 66% to 96% and a specificity of 75% to 86% for conventional FD-OCT.⁴² The use of FD-OCT results in an increase in specificity without a significant change in sensitivity when compared to dermoscopy in the diagnosis of BCC.⁴³ Melanoma is difficult to diagnose via FD-OCT, as the visualization of architectural features often is limited by poor resolution.⁴⁴ A study of HD-OCT in the diagnosis of melanoma with a limited sample size reported a sensitivity of 74% to 80% and a specificity of 92% to 93%.⁴⁵ Similarly, a study of HD-OCT used in the diagnosis of AK and SCC revealed a sensitivity and specificity of 81.6% and 92.6%, respectively, for AK and 93.8% and 98.9%, respectively, for SCC.⁴⁶

Numerous algorithms and scoring systems have been developed to further explore the utility of OCT in the diagnosis of cutaneous neoplasms.^47,48 Recent research investigated the utility of dynamic OCT, which can evaluate microvasculature in the diagnosis of cutaneous neoplasms (Figure 3)⁴⁹; the combination of OCT with other imaging modalities^50,51; the use of OCT to delineate presurgical margins^52,53; and the role of OCT in the diagnosis and monitoring of inflammatory and infectious skin diseases.^54,55

Final Thoughts

In recent years, there has been a surge of interest in noninvasive techniques for diagnosis and management of skin diseases; however, noninvasive tools exist on a spectrum in dermatology. Dermoscopy provides low-cost imaging of the skin’s surface and has been widely adopted by dermatologists and other providers to aid in clinical diagnosis. Reflectance confocal microscopy provides reimbursable in vivo imaging of live tissue with cellular-level resolution but is limited by depth, cost, and need for advanced training; thus, RCM has only been adopted in some clinical practices. Optical coherence tomography offers in vivo imaging of live tissue with substantial depth but poor resolution, high cost, need for advanced training, and rare reimbursement for providers. Future directions include combination of complementary imaging modalities, increased clinical practice integration, and education and reimbursement for providers.

Traditionally, diagnosis of skin disease relies on clinical inspection, often followed by biopsy and histopathologic examination. In recent years, new noninvasive tools have emerged that can aid in clinical diagnosis and reduce the number of unnecessary benign biopsies. Although there has been a surge in noninvasive diagnostic technologies, many tools are still in research and development phases, with few tools widely adopted and used in regular clinical practice. In this article, we discuss the use of dermoscopy, reflectance confocal microscopy (RCM), and optical coherence tomography (OCT) in the diagnosis and management of skin disease.

Dermoscopy

Dermoscopy, also known as epiluminescence light microscopy and previously known as dermatoscopy, utilizes a ×10 to ×100 microscope objective with a light source to magnify and visualize structures present below the skin’s surface, such as melanin and blood vessels. There are 3 types of dermoscopy: conventional nonpolarized dermoscopy, polarized contact dermoscopy, and nonpolarized contact dermoscopy (Figure 1). Traditional nonpolarized dermoscopy requires a liquid medium and direct contact with the skin, and it relies on light reflection and refraction properties.¹ Cross-polarized light sources allow visualization of deeper structures, either with or without a liquid medium and contact with the skin surface. Although there is overall concurrence among the different types of dermoscopy, subtle differences in the appearance of color, features, and structure are present.¹

Dermoscopy offers many benefits for dermatologists and other providers. It can be used to aid in the diagnosis of cutaneous neoplasms and other skin diseases. Numerous low-cost dermatoscopes currently are commercially available. The handheld, easily transportable nature of dermatoscopes have resulted in widespread practice integration. Approximately 84% of attending dermatologists in US academic settings reported using dermoscopy, and many refer to the dermatoscope as “the dermatologist’s stethoscope.”² In addition, 6% to 15% of other US providers, including family physicians, internal medicine physicians, and plastic surgeons, have reported using dermoscopy in their clinical practices. Limitations of dermoscopy include visualization of the skin surface only and not deeper structures within the tissue, the need for training for adequate interpretation of dermoscopic images, and lack of reimbursement for dermoscopic examination.³

Many dermoscopic structures that correspond well with histopathology have been described. Dermoscopy has a sensitivity of 79% to 96% and specificity of 69% to 99% in the diagnosis of melanoma.⁴ There is variable data on the specificity of dermoscopy in the diagnosis of melanoma, with one meta-analysis finding no statistically significant difference in specificity compared to naked eye examination,⁵ while other studies report increased specificity and subsequent reduction in biopsy of benign lesions.^6,7 Dermoscopy also can aid in the diagnosis of keratinocytic neoplasms, and dermoscopy also results in a sensitivity of 78.6% to 100% and a specificity of 53.8% to 100% in the diagnosis of basal cell carcinoma (BCC).⁸ Limitations of dermoscopy include false-positive diagnoses, commonly seborrheic keratoses and nevi, resulting in unnecessary biopsies, as well as false-negative diagnoses, commonly amelanotic and nevoid melanoma, resulting in delays in skin cancer diagnosis and resultant poor outcomes.⁹ Dermoscopy also is used to aid in the diagnosis of inflammatory and infectious skin diseases, as well as scalp, hair, and nail disorders.¹⁰

Reflectance Confocal Microscopy

Reflectance confocal microscopy utilizes an 830-nm laser to capture horizontal en face images of the skin with high resolution. Different structures of the skin have varying indices of refraction: keratin, melanin, and collagen appear bright white, while other components appear dark, generating black-and-white RCM images.¹¹ Currently, there are 2 reflectance confocal microscopes that are commercially available in the United States. The Vivascope 1500 (Caliber ID) is the traditional model that captures 8×8-mm images, and the Vivascope 3000 (Caliber ID) is a smaller handheld model that captures 0.5×0.5-mm images. The traditional model provides the advantages of higher-resolution images and the ability to capture larger surface areas but is best suited to image flat areas of skin to which a square window can be adhered. The handheld model allows improved contact with the varying topography of skin; does not require an adhesive window; and can be used to image cartilaginous, mucosal, and sensitive surfaces. However, it can be difficult to correlate individual images captured by the handheld RCM with the location relative to the lesion, as it is exquisitely sensitive to motion and also is operator dependent. Although complex algorithms are under development to stitch individual images to provide better correlation with the geography of the lesion, such programs are not yet widely available.¹²

Reflectance confocal microscopy affords many benefits for patients and providers. It is noninvasive and painless and is capable of imaging in vivo live skin as compared to clinical examination and dermoscopy, which only allow for visualization of the skin’s surface. Reflectance confocal microscopy also is time efficient, as imaging of a single lesion can be completed in 10 to 15 minutes. This technology generates high-resolution images, and RCM diagnosis has consistently demonstrated high sensitivity and specificity when compared to histopathology.¹³ Additionally, RCM imaging can spare biopsy and resultant scarring on cosmetically sensitive areas. Recently, RCM imaging of the skin has been granted Category I Current Procedural Terminology reimbursement codes that allow provider reimbursement and integration of RCM into daily practice¹⁴; however, private insurance coverage in the United States is variable. Limitations of RCM include a maximum depth of 200 to 300 µm, high cost to procure a reflectance confocal microscope, and the need for considerable training and practice to accurately interpret grayscale en face images.¹⁵

There has been extensive research regarding the use of RCM in the evaluation of cutaneous neoplasms and other skin diseases. Numerous features and patterns have been identified and described that correspond with different skin diseases and correspond well with histopathology (Figure 2).^13,16,17 Reflectance confocal microscopy has demonstrated consistently high accuracy in the diagnosis of melanocytic lesions, with a sensitivity of 93% to 100% and a specificity of 75% to 99%.^18-21 Reflectance confocal microscopy is especially useful in the evaluation of clinically or dermoscopically equivocal pigmented lesions due to greater specificity, resulting in a reduction of unnecessary biopsies.^22,23 It also has high accuracy in the diagnosis of keratinocytic neoplasms, with a sensitivity of 82% to 100% and a specificity of 78% to 97% in the diagnosis of BCC,²⁴ and a sensitivity of 74% to 100% and specificity of 78% to 100% in the diagnosis of squamous cell carcinoma (SCC).^25,26 Evaluation of SCC and actinic keratosis (AK) using RCM may be limited by considerable hyperkeratosis and ulceration. In addition, it can be challenging to differentiate AK and SCC on RCM, and considerable expertise is required to accurately grade cytologic and architectural atypia.²⁷ However, RCM has been used to discriminate between in situ and invasive proliferations.²⁸ Reflectance confocal microscopy has wide applications in the diagnosis and management of cutaneous infections^29,30 and inflammatory skin diseases.^29,31-33 Recent RCM research explored the use of RCM to identify biopsy sites,³⁴ delineate presurgical tumor margins,^35,36 and monitor response to noninvasive treatments.^37,38

Optical Coherence Tomography

Optical coherence tomography is an imaging modality that utilizes light backscatter from infrared light to produce grayscale cross-sectional or vertical images and horizontal en face images.³⁹ Optical coherence tomography can visualize structures in the epidermis, dermoepidermal junction, and upper dermis.⁴⁰ It can image boundaries of structures but cannot visualize individual cells.

There are different types of OCT devices available, including frequency-domain OCT (FD-OCT), or conventional OCT, and high-definition OCT (HD-OCT). With FD-OCT, images are captured at a maximum depth of 1 to 2 mm but with limited resolution. High-definition OCT has superior resolution compared to FD-OCT but is restricted to a shallower depth of 750 μm.³⁹ The main advantage of OCT is the ability to noninvasively image live tissue and visualize 2- to 5-times greater depth as compared to RCM. Several OCT devices have obtained US Food and Drug Administration approval; however, OCT has not been widely adopted into clinical practice and is available only in tertiary academic centers. Additionally, OCT imaging in dermatology is rarely reimbursed. Other limitations of OCT include poor resolution of images, high cost to procure an OCT device, and the need for advanced training and experience to accurately interpret images.^40,41

Optical coherence tomography primarily is used to diagnose cutaneous neoplasms. The best evidence of the diagnostic accuracy of OCT is in the setting of BCC, with a recent systematic review reporting a sensitivity of 66% to 96% and a specificity of 75% to 86% for conventional FD-OCT.⁴² The use of FD-OCT results in an increase in specificity without a significant change in sensitivity when compared to dermoscopy in the diagnosis of BCC.⁴³ Melanoma is difficult to diagnose via FD-OCT, as the visualization of architectural features often is limited by poor resolution.⁴⁴ A study of HD-OCT in the diagnosis of melanoma with a limited sample size reported a sensitivity of 74% to 80% and a specificity of 92% to 93%.⁴⁵ Similarly, a study of HD-OCT used in the diagnosis of AK and SCC revealed a sensitivity and specificity of 81.6% and 92.6%, respectively, for AK and 93.8% and 98.9%, respectively, for SCC.⁴⁶

Numerous algorithms and scoring systems have been developed to further explore the utility of OCT in the diagnosis of cutaneous neoplasms.^47,48 Recent research investigated the utility of dynamic OCT, which can evaluate microvasculature in the diagnosis of cutaneous neoplasms (Figure 3)⁴⁹; the combination of OCT with other imaging modalities^50,51; the use of OCT to delineate presurgical margins^52,53; and the role of OCT in the diagnosis and monitoring of inflammatory and infectious skin diseases.^54,55

Final Thoughts

In recent years, there has been a surge of interest in noninvasive techniques for diagnosis and management of skin diseases; however, noninvasive tools exist on a spectrum in dermatology. Dermoscopy provides low-cost imaging of the skin’s surface and has been widely adopted by dermatologists and other providers to aid in clinical diagnosis. Reflectance confocal microscopy provides reimbursable in vivo imaging of live tissue with cellular-level resolution but is limited by depth, cost, and need for advanced training; thus, RCM has only been adopted in some clinical practices. Optical coherence tomography offers in vivo imaging of live tissue with substantial depth but poor resolution, high cost, need for advanced training, and rare reimbursement for providers. Future directions include combination of complementary imaging modalities, increased clinical practice integration, and education and reimbursement for providers.

Traditionally, diagnosis of skin disease relies on clinical inspection, often followed by biopsy and histopathologic examination. In recent years, new noninvasive tools have emerged that can aid in clinical diagnosis and reduce the number of unnecessary benign biopsies. Although there has been a surge in noninvasive diagnostic technologies, many tools are still in research and development phases, with few tools widely adopted and used in regular clinical practice. In this article, we discuss the use of dermoscopy, reflectance confocal microscopy (RCM), and optical coherence tomography (OCT) in the diagnosis and management of skin disease.

Dermoscopy

Dermoscopy, also known as epiluminescence light microscopy and previously known as dermatoscopy, utilizes a ×10 to ×100 microscope objective with a light source to magnify and visualize structures present below the skin’s surface, such as melanin and blood vessels. There are 3 types of dermoscopy: conventional nonpolarized dermoscopy, polarized contact dermoscopy, and nonpolarized contact dermoscopy (Figure 1). Traditional nonpolarized dermoscopy requires a liquid medium and direct contact with the skin, and it relies on light reflection and refraction properties.¹ Cross-polarized light sources allow visualization of deeper structures, either with or without a liquid medium and contact with the skin surface. Although there is overall concurrence among the different types of dermoscopy, subtle differences in the appearance of color, features, and structure are present.¹

Dermoscopy offers many benefits for dermatologists and other providers. It can be used to aid in the diagnosis of cutaneous neoplasms and other skin diseases. Numerous low-cost dermatoscopes currently are commercially available. The handheld, easily transportable nature of dermatoscopes have resulted in widespread practice integration. Approximately 84% of attending dermatologists in US academic settings reported using dermoscopy, and many refer to the dermatoscope as “the dermatologist’s stethoscope.”² In addition, 6% to 15% of other US providers, including family physicians, internal medicine physicians, and plastic surgeons, have reported using dermoscopy in their clinical practices. Limitations of dermoscopy include visualization of the skin surface only and not deeper structures within the tissue, the need for training for adequate interpretation of dermoscopic images, and lack of reimbursement for dermoscopic examination.³

Many dermoscopic structures that correspond well with histopathology have been described. Dermoscopy has a sensitivity of 79% to 96% and specificity of 69% to 99% in the diagnosis of melanoma.⁴ There is variable data on the specificity of dermoscopy in the diagnosis of melanoma, with one meta-analysis finding no statistically significant difference in specificity compared to naked eye examination,⁵ while other studies report increased specificity and subsequent reduction in biopsy of benign lesions.^6,7 Dermoscopy also can aid in the diagnosis of keratinocytic neoplasms, and dermoscopy also results in a sensitivity of 78.6% to 100% and a specificity of 53.8% to 100% in the diagnosis of basal cell carcinoma (BCC).⁸ Limitations of dermoscopy include false-positive diagnoses, commonly seborrheic keratoses and nevi, resulting in unnecessary biopsies, as well as false-negative diagnoses, commonly amelanotic and nevoid melanoma, resulting in delays in skin cancer diagnosis and resultant poor outcomes.⁹ Dermoscopy also is used to aid in the diagnosis of inflammatory and infectious skin diseases, as well as scalp, hair, and nail disorders.¹⁰

Reflectance Confocal Microscopy

Reflectance confocal microscopy utilizes an 830-nm laser to capture horizontal en face images of the skin with high resolution. Different structures of the skin have varying indices of refraction: keratin, melanin, and collagen appear bright white, while other components appear dark, generating black-and-white RCM images.¹¹ Currently, there are 2 reflectance confocal microscopes that are commercially available in the United States. The Vivascope 1500 (Caliber ID) is the traditional model that captures 8×8-mm images, and the Vivascope 3000 (Caliber ID) is a smaller handheld model that captures 0.5×0.5-mm images. The traditional model provides the advantages of higher-resolution images and the ability to capture larger surface areas but is best suited to image flat areas of skin to which a square window can be adhered. The handheld model allows improved contact with the varying topography of skin; does not require an adhesive window; and can be used to image cartilaginous, mucosal, and sensitive surfaces. However, it can be difficult to correlate individual images captured by the handheld RCM with the location relative to the lesion, as it is exquisitely sensitive to motion and also is operator dependent. Although complex algorithms are under development to stitch individual images to provide better correlation with the geography of the lesion, such programs are not yet widely available.¹²

Reflectance confocal microscopy affords many benefits for patients and providers. It is noninvasive and painless and is capable of imaging in vivo live skin as compared to clinical examination and dermoscopy, which only allow for visualization of the skin’s surface. Reflectance confocal microscopy also is time efficient, as imaging of a single lesion can be completed in 10 to 15 minutes. This technology generates high-resolution images, and RCM diagnosis has consistently demonstrated high sensitivity and specificity when compared to histopathology.¹³ Additionally, RCM imaging can spare biopsy and resultant scarring on cosmetically sensitive areas. Recently, RCM imaging of the skin has been granted Category I Current Procedural Terminology reimbursement codes that allow provider reimbursement and integration of RCM into daily practice¹⁴; however, private insurance coverage in the United States is variable. Limitations of RCM include a maximum depth of 200 to 300 µm, high cost to procure a reflectance confocal microscope, and the need for considerable training and practice to accurately interpret grayscale en face images.¹⁵

There has been extensive research regarding the use of RCM in the evaluation of cutaneous neoplasms and other skin diseases. Numerous features and patterns have been identified and described that correspond with different skin diseases and correspond well with histopathology (Figure 2).^13,16,17 Reflectance confocal microscopy has demonstrated consistently high accuracy in the diagnosis of melanocytic lesions, with a sensitivity of 93% to 100% and a specificity of 75% to 99%.^18-21 Reflectance confocal microscopy is especially useful in the evaluation of clinically or dermoscopically equivocal pigmented lesions due to greater specificity, resulting in a reduction of unnecessary biopsies.^22,23 It also has high accuracy in the diagnosis of keratinocytic neoplasms, with a sensitivity of 82% to 100% and a specificity of 78% to 97% in the diagnosis of BCC,²⁴ and a sensitivity of 74% to 100% and specificity of 78% to 100% in the diagnosis of squamous cell carcinoma (SCC).^25,26 Evaluation of SCC and actinic keratosis (AK) using RCM may be limited by considerable hyperkeratosis and ulceration. In addition, it can be challenging to differentiate AK and SCC on RCM, and considerable expertise is required to accurately grade cytologic and architectural atypia.²⁷ However, RCM has been used to discriminate between in situ and invasive proliferations.²⁸ Reflectance confocal microscopy has wide applications in the diagnosis and management of cutaneous infections^29,30 and inflammatory skin diseases.^29,31-33 Recent RCM research explored the use of RCM to identify biopsy sites,³⁴ delineate presurgical tumor margins,^35,36 and monitor response to noninvasive treatments.^37,38

Optical Coherence Tomography

Optical coherence tomography is an imaging modality that utilizes light backscatter from infrared light to produce grayscale cross-sectional or vertical images and horizontal en face images.³⁹ Optical coherence tomography can visualize structures in the epidermis, dermoepidermal junction, and upper dermis.⁴⁰ It can image boundaries of structures but cannot visualize individual cells.

There are different types of OCT devices available, including frequency-domain OCT (FD-OCT), or conventional OCT, and high-definition OCT (HD-OCT). With FD-OCT, images are captured at a maximum depth of 1 to 2 mm but with limited resolution. High-definition OCT has superior resolution compared to FD-OCT but is restricted to a shallower depth of 750 μm.³⁹ The main advantage of OCT is the ability to noninvasively image live tissue and visualize 2- to 5-times greater depth as compared to RCM. Several OCT devices have obtained US Food and Drug Administration approval; however, OCT has not been widely adopted into clinical practice and is available only in tertiary academic centers. Additionally, OCT imaging in dermatology is rarely reimbursed. Other limitations of OCT include poor resolution of images, high cost to procure an OCT device, and the need for advanced training and experience to accurately interpret images.^40,41

Optical coherence tomography primarily is used to diagnose cutaneous neoplasms. The best evidence of the diagnostic accuracy of OCT is in the setting of BCC, with a recent systematic review reporting a sensitivity of 66% to 96% and a specificity of 75% to 86% for conventional FD-OCT.⁴² The use of FD-OCT results in an increase in specificity without a significant change in sensitivity when compared to dermoscopy in the diagnosis of BCC.⁴³ Melanoma is difficult to diagnose via FD-OCT, as the visualization of architectural features often is limited by poor resolution.⁴⁴ A study of HD-OCT in the diagnosis of melanoma with a limited sample size reported a sensitivity of 74% to 80% and a specificity of 92% to 93%.⁴⁵ Similarly, a study of HD-OCT used in the diagnosis of AK and SCC revealed a sensitivity and specificity of 81.6% and 92.6%, respectively, for AK and 93.8% and 98.9%, respectively, for SCC.⁴⁶

Numerous algorithms and scoring systems have been developed to further explore the utility of OCT in the diagnosis of cutaneous neoplasms.^47,48 Recent research investigated the utility of dynamic OCT, which can evaluate microvasculature in the diagnosis of cutaneous neoplasms (Figure 3)⁴⁹; the combination of OCT with other imaging modalities^50,51; the use of OCT to delineate presurgical margins^52,53; and the role of OCT in the diagnosis and monitoring of inflammatory and infectious skin diseases.^54,55

Final Thoughts

In recent years, there has been a surge of interest in noninvasive techniques for diagnosis and management of skin diseases; however, noninvasive tools exist on a spectrum in dermatology. Dermoscopy provides low-cost imaging of the skin’s surface and has been widely adopted by dermatologists and other providers to aid in clinical diagnosis. Reflectance confocal microscopy provides reimbursable in vivo imaging of live tissue with cellular-level resolution but is limited by depth, cost, and need for advanced training; thus, RCM has only been adopted in some clinical practices. Optical coherence tomography offers in vivo imaging of live tissue with substantial depth but poor resolution, high cost, need for advanced training, and rare reimbursement for providers. Future directions include combination of complementary imaging modalities, increased clinical practice integration, and education and reimbursement for providers.

The advent of electronic medical records (EMRs) is arguably the most important technological revolution in modern medicine. The transition from paper documentation to EMRs has improved organization of medical records, consolidating all physician notes, orders, consultations, laboratory test results, and radiologic studies into a single accessible location.¹ However, this revolution has led to mixed consequences for patients, especially in the outpatient setting. The use of EMRs can facilitate questions, clarification, and discussion between patients and health care providers, prompted by the sections of the EMR. Unfortunately, patients too often encounter pressed-for-time, documentation-focused providers who may not even look up from the computer. Provider behaviors such as making eye contact, stopping typing during discussion of sensitive topics, and allowing patients to view the computer screen and using it as an educational tool are important for patients to have a positive care experience.² We envision further integration of current and future technology to overcome the challenges of outpatient care. We use a hypothetical patient encounter to illustrate what the future may hold.

Hypothetical Patient Encounter

An established patient, Ms. PS, comes to the dermatology clinic for a follow-up appointment and walks into an examination room (Figure). Prior to entering the room, the provider, Dr. FT, reviews Ms. PS’s history via a dermatology-specific EMR and reads that Ms. PS has a 1.5-year history of psoriasis and is considering other therapeutic options.

Upon entering the room, Dr. FT tells Ms. PS that the visit is being recorded and transcribed. A large interactive screen is a key component of the examination room. A remote medical assistant is virtually present via video to transcribe and document the patient-provider interaction. There is potential for artificial intelligence to replace the remote medical assistant in the future. Wearable technology, including a smartwatch and Bluetooth headphones, allow the provider to record audio of the visit as well as through microphones on the interactive screen.

As the interaction begins, Ms. PS reports that her psoriasis is poorly controlled with her current regimen of topical steroids. Dr. FT inquires about Ms. PS’s current symptoms and psychosocial well-being. Dr. FT then performs a skin examination and is easily able to evaluate her skin vs prior visits, as clinical images from prior visits are automatically displayed on the interactive screen. Dr. FT also closely examines Ms. PS’s nails and conducts a joint examination, reminded by a notification on his wearable technology. After capturing clinical images of Ms. PS’s skin and nails with a secure EMR-connected tablet, Dr. FT briefly steps out of the room to allow Ms. PS to get dressed and feel more comfortable in the discussion to follow.

Once he reenters the examination room, Dr. FT initiates a discussion on next steps. Ms. PS’s pathology report and clinical images are displayed on the interactive screen, along with her most recent laboratory test results, which were completed prior to the visit in anticipation of changing therapies. Dr. FT presents Ms. PS with several evidence-based therapeutic options for psoriasis, and she expresses interest in methotrexate. Following the discussion, the remote medical assistant displays information about methotrexate on the interactive screen, including evidence for treatment of psoriasis, contraindications, laboratory monitoring requirements, and possible adverse effects for both the patient and provider to review together. Dr. FT reviews the laboratory test results displayed on the screen, specifically her transaminase levels, and confirms that methotrexate is an appropriate therapeutic option. After a full discussion of risks and benefits, Ms. PS chooses to initiate methotrexate treatment. Reminded by a notification on his wearable technology, Dr. FT follows evidence-based dosing guidelines and sends the prescription electronically to Ms. PS’s pharmacy, which concludes Ms. PS’s visit.

Analysis of the Patient Encounter

In this interaction, Dr. FT was able to fully engage with the patient, unencumbered by the demands of documentation. There were only a few instances when the provider looked at or touched the interactive screen. Furthermore, joint decision-making was optimized by allowing both the patient and provider to review diagnostic test results and current evidence-based therapeutic guidelines together through the interactive screen. Ms. PS goes home feeling satisfied that she received her provider’s complete attention and that they selected a therapeutic option supported by evidence. After the visit, the remote medial assistant’s transcript populates a patient note template, which Dr. FT reviews and amends to create the final note. Reducing the time required to write patient notes increases the speed at which Dr. FT can complete patient encounters and may improve clinic flow and productivity. In addition, a patient summary is generated from Dr. FT’s final note, with an emphasis on patient instructions, and is sent to Ms. PS.

Final Thoughts

Our proposed integration of currently available and future technology can help minimize documentation burdens on providers and improve patient-provider communication in the age of the EMR, thus optimizing patient satisfaction and outcomes.

The advent of electronic medical records (EMRs) is arguably the most important technological revolution in modern medicine. The transition from paper documentation to EMRs has improved organization of medical records, consolidating all physician notes, orders, consultations, laboratory test results, and radiologic studies into a single accessible location.¹ However, this revolution has led to mixed consequences for patients, especially in the outpatient setting. The use of EMRs can facilitate questions, clarification, and discussion between patients and health care providers, prompted by the sections of the EMR. Unfortunately, patients too often encounter pressed-for-time, documentation-focused providers who may not even look up from the computer. Provider behaviors such as making eye contact, stopping typing during discussion of sensitive topics, and allowing patients to view the computer screen and using it as an educational tool are important for patients to have a positive care experience.² We envision further integration of current and future technology to overcome the challenges of outpatient care. We use a hypothetical patient encounter to illustrate what the future may hold.

Hypothetical Patient Encounter

An established patient, Ms. PS, comes to the dermatology clinic for a follow-up appointment and walks into an examination room (Figure). Prior to entering the room, the provider, Dr. FT, reviews Ms. PS’s history via a dermatology-specific EMR and reads that Ms. PS has a 1.5-year history of psoriasis and is considering other therapeutic options.

Upon entering the room, Dr. FT tells Ms. PS that the visit is being recorded and transcribed. A large interactive screen is a key component of the examination room. A remote medical assistant is virtually present via video to transcribe and document the patient-provider interaction. There is potential for artificial intelligence to replace the remote medical assistant in the future. Wearable technology, including a smartwatch and Bluetooth headphones, allow the provider to record audio of the visit as well as through microphones on the interactive screen.

As the interaction begins, Ms. PS reports that her psoriasis is poorly controlled with her current regimen of topical steroids. Dr. FT inquires about Ms. PS’s current symptoms and psychosocial well-being. Dr. FT then performs a skin examination and is easily able to evaluate her skin vs prior visits, as clinical images from prior visits are automatically displayed on the interactive screen. Dr. FT also closely examines Ms. PS’s nails and conducts a joint examination, reminded by a notification on his wearable technology. After capturing clinical images of Ms. PS’s skin and nails with a secure EMR-connected tablet, Dr. FT briefly steps out of the room to allow Ms. PS to get dressed and feel more comfortable in the discussion to follow.

Once he reenters the examination room, Dr. FT initiates a discussion on next steps. Ms. PS’s pathology report and clinical images are displayed on the interactive screen, along with her most recent laboratory test results, which were completed prior to the visit in anticipation of changing therapies. Dr. FT presents Ms. PS with several evidence-based therapeutic options for psoriasis, and she expresses interest in methotrexate. Following the discussion, the remote medical assistant displays information about methotrexate on the interactive screen, including evidence for treatment of psoriasis, contraindications, laboratory monitoring requirements, and possible adverse effects for both the patient and provider to review together. Dr. FT reviews the laboratory test results displayed on the screen, specifically her transaminase levels, and confirms that methotrexate is an appropriate therapeutic option. After a full discussion of risks and benefits, Ms. PS chooses to initiate methotrexate treatment. Reminded by a notification on his wearable technology, Dr. FT follows evidence-based dosing guidelines and sends the prescription electronically to Ms. PS’s pharmacy, which concludes Ms. PS’s visit.

Analysis of the Patient Encounter

In this interaction, Dr. FT was able to fully engage with the patient, unencumbered by the demands of documentation. There were only a few instances when the provider looked at or touched the interactive screen. Furthermore, joint decision-making was optimized by allowing both the patient and provider to review diagnostic test results and current evidence-based therapeutic guidelines together through the interactive screen. Ms. PS goes home feeling satisfied that she received her provider’s complete attention and that they selected a therapeutic option supported by evidence. After the visit, the remote medial assistant’s transcript populates a patient note template, which Dr. FT reviews and amends to create the final note. Reducing the time required to write patient notes increases the speed at which Dr. FT can complete patient encounters and may improve clinic flow and productivity. In addition, a patient summary is generated from Dr. FT’s final note, with an emphasis on patient instructions, and is sent to Ms. PS.

Final Thoughts

Our proposed integration of currently available and future technology can help minimize documentation burdens on providers and improve patient-provider communication in the age of the EMR, thus optimizing patient satisfaction and outcomes.

The advent of electronic medical records (EMRs) is arguably the most important technological revolution in modern medicine. The transition from paper documentation to EMRs has improved organization of medical records, consolidating all physician notes, orders, consultations, laboratory test results, and radiologic studies into a single accessible location.¹ However, this revolution has led to mixed consequences for patients, especially in the outpatient setting. The use of EMRs can facilitate questions, clarification, and discussion between patients and health care providers, prompted by the sections of the EMR. Unfortunately, patients too often encounter pressed-for-time, documentation-focused providers who may not even look up from the computer. Provider behaviors such as making eye contact, stopping typing during discussion of sensitive topics, and allowing patients to view the computer screen and using it as an educational tool are important for patients to have a positive care experience.² We envision further integration of current and future technology to overcome the challenges of outpatient care. We use a hypothetical patient encounter to illustrate what the future may hold.

Hypothetical Patient Encounter

An established patient, Ms. PS, comes to the dermatology clinic for a follow-up appointment and walks into an examination room (Figure). Prior to entering the room, the provider, Dr. FT, reviews Ms. PS’s history via a dermatology-specific EMR and reads that Ms. PS has a 1.5-year history of psoriasis and is considering other therapeutic options.

Upon entering the room, Dr. FT tells Ms. PS that the visit is being recorded and transcribed. A large interactive screen is a key component of the examination room. A remote medical assistant is virtually present via video to transcribe and document the patient-provider interaction. There is potential for artificial intelligence to replace the remote medical assistant in the future. Wearable technology, including a smartwatch and Bluetooth headphones, allow the provider to record audio of the visit as well as through microphones on the interactive screen.

As the interaction begins, Ms. PS reports that her psoriasis is poorly controlled with her current regimen of topical steroids. Dr. FT inquires about Ms. PS’s current symptoms and psychosocial well-being. Dr. FT then performs a skin examination and is easily able to evaluate her skin vs prior visits, as clinical images from prior visits are automatically displayed on the interactive screen. Dr. FT also closely examines Ms. PS’s nails and conducts a joint examination, reminded by a notification on his wearable technology. After capturing clinical images of Ms. PS’s skin and nails with a secure EMR-connected tablet, Dr. FT briefly steps out of the room to allow Ms. PS to get dressed and feel more comfortable in the discussion to follow.

Once he reenters the examination room, Dr. FT initiates a discussion on next steps. Ms. PS’s pathology report and clinical images are displayed on the interactive screen, along with her most recent laboratory test results, which were completed prior to the visit in anticipation of changing therapies. Dr. FT presents Ms. PS with several evidence-based therapeutic options for psoriasis, and she expresses interest in methotrexate. Following the discussion, the remote medical assistant displays information about methotrexate on the interactive screen, including evidence for treatment of psoriasis, contraindications, laboratory monitoring requirements, and possible adverse effects for both the patient and provider to review together. Dr. FT reviews the laboratory test results displayed on the screen, specifically her transaminase levels, and confirms that methotrexate is an appropriate therapeutic option. After a full discussion of risks and benefits, Ms. PS chooses to initiate methotrexate treatment. Reminded by a notification on his wearable technology, Dr. FT follows evidence-based dosing guidelines and sends the prescription electronically to Ms. PS’s pharmacy, which concludes Ms. PS’s visit.

Analysis of the Patient Encounter

In this interaction, Dr. FT was able to fully engage with the patient, unencumbered by the demands of documentation. There were only a few instances when the provider looked at or touched the interactive screen. Furthermore, joint decision-making was optimized by allowing both the patient and provider to review diagnostic test results and current evidence-based therapeutic guidelines together through the interactive screen. Ms. PS goes home feeling satisfied that she received her provider’s complete attention and that they selected a therapeutic option supported by evidence. After the visit, the remote medial assistant’s transcript populates a patient note template, which Dr. FT reviews and amends to create the final note. Reducing the time required to write patient notes increases the speed at which Dr. FT can complete patient encounters and may improve clinic flow and productivity. In addition, a patient summary is generated from Dr. FT’s final note, with an emphasis on patient instructions, and is sent to Ms. PS.

Final Thoughts

Our proposed integration of currently available and future technology can help minimize documentation burdens on providers and improve patient-provider communication in the age of the EMR, thus optimizing patient satisfaction and outcomes.

In February 2019, Dayanara Torres announced that she had been diagnosed with metastatic melanoma. Ms. Torres, a Puerto Rican–born former Miss Universe who has more than 1 million followers on Instagram (@dayanarapr), seemed an unlikely candidate for skin cancer, which often is associated with fair-skinned and light-eyed individuals. She shared the news of her diagnosis in an Instagram video that has now received more than 850,000 views. In the video, Ms. Torres described a new mole with uneven surface that had developed on her leg and noted that she had ignored it, even though it had been growing for years. Ultimately, she was diagnosed with melanoma that had already metastasized to regional lymph nodes in her leg. Ms. Torres concluded the video by urging fans and viewers to be mindful of new or changing skin lesions and to be aware of the seriousness of skin cancer. In March 2019, Ms. Torres posted a follow-up educational video on Instagram highlighting the features of melanoma that has now received more than 300,000 views.

Since her announcement, we have noticed that more Hispanic patients with concerns about skin cancer are presenting to our dermatology clinic, which is located in a highly diverse city (New Brunswick, New Jersey) with approximately 50% of residents identifying as Hispanic.¹ Most Hispanic patients typically present to our dermatology clinic for non–skin cancer–related concerns, such as acne, rash, and dyschromia; however, following Ms. Torres’ announcement, many have cited her diagnosis of metastatic melanoma as a cause for concern and a motivating factor in having their skin examined. The diagnosis in a prominent celebrity and Hispanic woman has given a new face to metastatic melanoma.

Although melanoma most commonly occurs in white patients, Hispanic patients experience disproportionately greater morbidity and mortality when diagnosed with melanoma.² Poor prognosis in patients with skin of color is multifactorial and may be due to poor use of sun protection, misconceptions about melanoma risk, atypical clinical presentation, impaired access to care, and delay in diagnosis. The Hispanic community encompasses a wide variety of individuals with varying levels of skin pigmentation and sun sensitivity.³ However, Hispanics report low levels of sun-protective behaviors. They also may have misconceptions that sunscreen is ineffective in preventing skin cancer and that little can be done to decrease the risk for developing skin cancer.^4,5 Additionally, Hispanic patients often have lower perceptions of their personal risk for melanoma and report low rates of clinical and self-examinations compared to non-Hispanic white patients.^6-8 Many Hispanic patients have reported that they were not instructed to perform self-examinations of their skin regularly by dermatologists or other providers and did not know the signs of skin cancer.⁷ Furthermore, a language barrier also may impede communication and education regarding melanoma risk.⁹

Similar to white patients, superficial spreading melanoma is the most common histologic subtype in Hispanic patients, followed by acral lentiginous melanoma, which is the most common subtype in black and Asian patients.^2,4 Compared to non-Hispanic white patients, who most commonly present with truncal melanomas, Hispanic patients (particularly those from Puerto Rico, such as Ms. Torres) are more likely to present with melanoma on the lower extremities.^4,10 Additionally, Hispanic patients have high rates of head, neck, and mucosal melanomas compared to all other racial and ethnic groups.²

Hispanic patients diagnosed with melanoma are more likely to present with thicker primary tumors, later stages of disease, and distant metastases compared to non-Hispanic white patients, all of which are associated with poor prognosis.^2,4,11 Five-year survival rates for melanoma are lower in Hispanic patients compared to non-Hispanic white patients.¹² Although the Hispanic community is diverse in socioeconomic and immigration status as well as occupation, lack of insurance also may contribute to decreased access to care, delayed diagnosis, and ultimately worse survival.

These disparities have spurred suggestions for increased education about skin cancer and the signs and symptoms of melanoma, encouragement of self-examinations, and routine clinical skin examinations for Hispanic patients by dermatologists and other providers.⁸ There is evidence that knowledge-based interventions, especially when presented in Spanish, produce statistically significant improvements in knowledge of skin cancer risk and sun-protective behavior among Hispanic patients.¹² Similarly, we have observed that the videos shared by Ms. Torres regarding her melanoma diagnosis and the features of melanoma, in which she spoke in Spanish, have compelled many Hispanic patients to examine their own skin and have led to increased concern for skin cancer in this patient population. In our practice, we refer to the increase in spot checks and skin examinations requested by Hispanic patients as “The Dayanara Effect,” and we hypothesize that this same effect may be taking place throughout the dermatology community.

In February 2019, Dayanara Torres announced that she had been diagnosed with metastatic melanoma. Ms. Torres, a Puerto Rican–born former Miss Universe who has more than 1 million followers on Instagram (@dayanarapr), seemed an unlikely candidate for skin cancer, which often is associated with fair-skinned and light-eyed individuals. She shared the news of her diagnosis in an Instagram video that has now received more than 850,000 views. In the video, Ms. Torres described a new mole with uneven surface that had developed on her leg and noted that she had ignored it, even though it had been growing for years. Ultimately, she was diagnosed with melanoma that had already metastasized to regional lymph nodes in her leg. Ms. Torres concluded the video by urging fans and viewers to be mindful of new or changing skin lesions and to be aware of the seriousness of skin cancer. In March 2019, Ms. Torres posted a follow-up educational video on Instagram highlighting the features of melanoma that has now received more than 300,000 views.

Since her announcement, we have noticed that more Hispanic patients with concerns about skin cancer are presenting to our dermatology clinic, which is located in a highly diverse city (New Brunswick, New Jersey) with approximately 50% of residents identifying as Hispanic.¹ Most Hispanic patients typically present to our dermatology clinic for non–skin cancer–related concerns, such as acne, rash, and dyschromia; however, following Ms. Torres’ announcement, many have cited her diagnosis of metastatic melanoma as a cause for concern and a motivating factor in having their skin examined. The diagnosis in a prominent celebrity and Hispanic woman has given a new face to metastatic melanoma.

Although melanoma most commonly occurs in white patients, Hispanic patients experience disproportionately greater morbidity and mortality when diagnosed with melanoma.² Poor prognosis in patients with skin of color is multifactorial and may be due to poor use of sun protection, misconceptions about melanoma risk, atypical clinical presentation, impaired access to care, and delay in diagnosis. The Hispanic community encompasses a wide variety of individuals with varying levels of skin pigmentation and sun sensitivity.³ However, Hispanics report low levels of sun-protective behaviors. They also may have misconceptions that sunscreen is ineffective in preventing skin cancer and that little can be done to decrease the risk for developing skin cancer.^4,5 Additionally, Hispanic patients often have lower perceptions of their personal risk for melanoma and report low rates of clinical and self-examinations compared to non-Hispanic white patients.^6-8 Many Hispanic patients have reported that they were not instructed to perform self-examinations of their skin regularly by dermatologists or other providers and did not know the signs of skin cancer.⁷ Furthermore, a language barrier also may impede communication and education regarding melanoma risk.⁹

Similar to white patients, superficial spreading melanoma is the most common histologic subtype in Hispanic patients, followed by acral lentiginous melanoma, which is the most common subtype in black and Asian patients.^2,4 Compared to non-Hispanic white patients, who most commonly present with truncal melanomas, Hispanic patients (particularly those from Puerto Rico, such as Ms. Torres) are more likely to present with melanoma on the lower extremities.^4,10 Additionally, Hispanic patients have high rates of head, neck, and mucosal melanomas compared to all other racial and ethnic groups.²

Hispanic patients diagnosed with melanoma are more likely to present with thicker primary tumors, later stages of disease, and distant metastases compared to non-Hispanic white patients, all of which are associated with poor prognosis.^2,4,11 Five-year survival rates for melanoma are lower in Hispanic patients compared to non-Hispanic white patients.¹² Although the Hispanic community is diverse in socioeconomic and immigration status as well as occupation, lack of insurance also may contribute to decreased access to care, delayed diagnosis, and ultimately worse survival.

These disparities have spurred suggestions for increased education about skin cancer and the signs and symptoms of melanoma, encouragement of self-examinations, and routine clinical skin examinations for Hispanic patients by dermatologists and other providers.⁸ There is evidence that knowledge-based interventions, especially when presented in Spanish, produce statistically significant improvements in knowledge of skin cancer risk and sun-protective behavior among Hispanic patients.¹² Similarly, we have observed that the videos shared by Ms. Torres regarding her melanoma diagnosis and the features of melanoma, in which she spoke in Spanish, have compelled many Hispanic patients to examine their own skin and have led to increased concern for skin cancer in this patient population. In our practice, we refer to the increase in spot checks and skin examinations requested by Hispanic patients as “The Dayanara Effect,” and we hypothesize that this same effect may be taking place throughout the dermatology community.

In February 2019, Dayanara Torres announced that she had been diagnosed with metastatic melanoma. Ms. Torres, a Puerto Rican–born former Miss Universe who has more than 1 million followers on Instagram (@dayanarapr), seemed an unlikely candidate for skin cancer, which often is associated with fair-skinned and light-eyed individuals. She shared the news of her diagnosis in an Instagram video that has now received more than 850,000 views. In the video, Ms. Torres described a new mole with uneven surface that had developed on her leg and noted that she had ignored it, even though it had been growing for years. Ultimately, she was diagnosed with melanoma that had already metastasized to regional lymph nodes in her leg. Ms. Torres concluded the video by urging fans and viewers to be mindful of new or changing skin lesions and to be aware of the seriousness of skin cancer. In March 2019, Ms. Torres posted a follow-up educational video on Instagram highlighting the features of melanoma that has now received more than 300,000 views.

Since her announcement, we have noticed that more Hispanic patients with concerns about skin cancer are presenting to our dermatology clinic, which is located in a highly diverse city (New Brunswick, New Jersey) with approximately 50% of residents identifying as Hispanic.¹ Most Hispanic patients typically present to our dermatology clinic for non–skin cancer–related concerns, such as acne, rash, and dyschromia; however, following Ms. Torres’ announcement, many have cited her diagnosis of metastatic melanoma as a cause for concern and a motivating factor in having their skin examined. The diagnosis in a prominent celebrity and Hispanic woman has given a new face to metastatic melanoma.

Although melanoma most commonly occurs in white patients, Hispanic patients experience disproportionately greater morbidity and mortality when diagnosed with melanoma.² Poor prognosis in patients with skin of color is multifactorial and may be due to poor use of sun protection, misconceptions about melanoma risk, atypical clinical presentation, impaired access to care, and delay in diagnosis. The Hispanic community encompasses a wide variety of individuals with varying levels of skin pigmentation and sun sensitivity.³ However, Hispanics report low levels of sun-protective behaviors. They also may have misconceptions that sunscreen is ineffective in preventing skin cancer and that little can be done to decrease the risk for developing skin cancer.^4,5 Additionally, Hispanic patients often have lower perceptions of their personal risk for melanoma and report low rates of clinical and self-examinations compared to non-Hispanic white patients.^6-8 Many Hispanic patients have reported that they were not instructed to perform self-examinations of their skin regularly by dermatologists or other providers and did not know the signs of skin cancer.⁷ Furthermore, a language barrier also may impede communication and education regarding melanoma risk.⁹

Similar to white patients, superficial spreading melanoma is the most common histologic subtype in Hispanic patients, followed by acral lentiginous melanoma, which is the most common subtype in black and Asian patients.^2,4 Compared to non-Hispanic white patients, who most commonly present with truncal melanomas, Hispanic patients (particularly those from Puerto Rico, such as Ms. Torres) are more likely to present with melanoma on the lower extremities.^4,10 Additionally, Hispanic patients have high rates of head, neck, and mucosal melanomas compared to all other racial and ethnic groups.²

Hispanic patients diagnosed with melanoma are more likely to present with thicker primary tumors, later stages of disease, and distant metastases compared to non-Hispanic white patients, all of which are associated with poor prognosis.^2,4,11 Five-year survival rates for melanoma are lower in Hispanic patients compared to non-Hispanic white patients.¹² Although the Hispanic community is diverse in socioeconomic and immigration status as well as occupation, lack of insurance also may contribute to decreased access to care, delayed diagnosis, and ultimately worse survival.

These disparities have spurred suggestions for increased education about skin cancer and the signs and symptoms of melanoma, encouragement of self-examinations, and routine clinical skin examinations for Hispanic patients by dermatologists and other providers.⁸ There is evidence that knowledge-based interventions, especially when presented in Spanish, produce statistically significant improvements in knowledge of skin cancer risk and sun-protective behavior among Hispanic patients.¹² Similarly, we have observed that the videos shared by Ms. Torres regarding her melanoma diagnosis and the features of melanoma, in which she spoke in Spanish, have compelled many Hispanic patients to examine their own skin and have led to increased concern for skin cancer in this patient population. In our practice, we refer to the increase in spot checks and skin examinations requested by Hispanic patients as “The Dayanara Effect,” and we hypothesize that this same effect may be taking place throughout the dermatology community.