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The Diagnosis: Porokeratosis of Mibelli

There are 5 variants of porokeratosis: disseminated superficial actinic porokeratosis (DSAP), linear porokeratosis, porokeratosis of Mibelli, porokeratosis palmaris et plantaris disseminata, and punctate porokeratosis. The most common type is DSAP,¹ which is characterized by multiple lesions on the body, particularly in sun-exposed areas. The distinguishing feature of porokeratosis is the cornoid lamella, which is made up of parakeratotic cells extending through the stratum corneum. There also is a thin or absent granular layer beneath it (Figure).²

Patients generally present in the third and fourth decades of life.¹ Risk factors for porokeratosis include sun exposure, immunosuppression, and genetics.^2-4 Overexpression of the protein p53 in porokeratosis lesions has been demonstrated in studies investigating the genetics of porokeratosis.^5,6 A study of Chinese families with DSAP identified 3 different loci associated with DSAP: DSAP1, DSAP2, and DSAP3.² The progression to cancer has been noted in all types of porokeratosis lesions. Malignancies include squamous cell carcinoma, Bowen disease, and basal cell carcinoma.^7,8

Many treatments have been tried for DSAP including cryotherapy, topical 5-fluorouracil, photodynamic therapy, and topical imiquimod with varying success.¹ Our patient was treated with 
cryotherapy but had side effects from treatment including cellulitis and local infections with ulceration before finally healing.

Interestingly, our patient had a single lesion with pathology findings most consistent with DSAP at a later age. Although the pathology suggested DSAP, the size and solitary lesion was more consistent with porokeratosis of Mibelli. Porokeratosis of Mibelli can occur concurrently with DSAP,⁹ but we have not seen other lesions in this patient. We have educated our patient to be aware of other lesions that may occur in the future. Due to risk for malignant conversion, it is generally viewed as beneficial to treat patients who present with porokeratosis lesions. Our patient’s lesion ultimately cleared and he has not developed new lesions at 1-year follow-up.

Although DSAP generally presents in the third and fourth decades of life and porokeratosis of Mibelli during childhood, it is important to educate both dermatologists and primary care physicians to be aware of the possibility of both diagnoses in the elderly population.

The Diagnosis: Porokeratosis of Mibelli

There are 5 variants of porokeratosis: disseminated superficial actinic porokeratosis (DSAP), linear porokeratosis, porokeratosis of Mibelli, porokeratosis palmaris et plantaris disseminata, and punctate porokeratosis. The most common type is DSAP,¹ which is characterized by multiple lesions on the body, particularly in sun-exposed areas. The distinguishing feature of porokeratosis is the cornoid lamella, which is made up of parakeratotic cells extending through the stratum corneum. There also is a thin or absent granular layer beneath it (Figure).²

Patients generally present in the third and fourth decades of life.¹ Risk factors for porokeratosis include sun exposure, immunosuppression, and genetics.^2-4 Overexpression of the protein p53 in porokeratosis lesions has been demonstrated in studies investigating the genetics of porokeratosis.^5,6 A study of Chinese families with DSAP identified 3 different loci associated with DSAP: DSAP1, DSAP2, and DSAP3.² The progression to cancer has been noted in all types of porokeratosis lesions. Malignancies include squamous cell carcinoma, Bowen disease, and basal cell carcinoma.^7,8

Many treatments have been tried for DSAP including cryotherapy, topical 5-fluorouracil, photodynamic therapy, and topical imiquimod with varying success.¹ Our patient was treated with 
cryotherapy but had side effects from treatment including cellulitis and local infections with ulceration before finally healing.

Interestingly, our patient had a single lesion with pathology findings most consistent with DSAP at a later age. Although the pathology suggested DSAP, the size and solitary lesion was more consistent with porokeratosis of Mibelli. Porokeratosis of Mibelli can occur concurrently with DSAP,⁹ but we have not seen other lesions in this patient. We have educated our patient to be aware of other lesions that may occur in the future. Due to risk for malignant conversion, it is generally viewed as beneficial to treat patients who present with porokeratosis lesions. Our patient’s lesion ultimately cleared and he has not developed new lesions at 1-year follow-up.

Although DSAP generally presents in the third and fourth decades of life and porokeratosis of Mibelli during childhood, it is important to educate both dermatologists and primary care physicians to be aware of the possibility of both diagnoses in the elderly population.

The Diagnosis: Porokeratosis of Mibelli

There are 5 variants of porokeratosis: disseminated superficial actinic porokeratosis (DSAP), linear porokeratosis, porokeratosis of Mibelli, porokeratosis palmaris et plantaris disseminata, and punctate porokeratosis. The most common type is DSAP,¹ which is characterized by multiple lesions on the body, particularly in sun-exposed areas. The distinguishing feature of porokeratosis is the cornoid lamella, which is made up of parakeratotic cells extending through the stratum corneum. There also is a thin or absent granular layer beneath it (Figure).²

Patients generally present in the third and fourth decades of life.¹ Risk factors for porokeratosis include sun exposure, immunosuppression, and genetics.^2-4 Overexpression of the protein p53 in porokeratosis lesions has been demonstrated in studies investigating the genetics of porokeratosis.^5,6 A study of Chinese families with DSAP identified 3 different loci associated with DSAP: DSAP1, DSAP2, and DSAP3.² The progression to cancer has been noted in all types of porokeratosis lesions. Malignancies include squamous cell carcinoma, Bowen disease, and basal cell carcinoma.^7,8

Many treatments have been tried for DSAP including cryotherapy, topical 5-fluorouracil, photodynamic therapy, and topical imiquimod with varying success.¹ Our patient was treated with 
cryotherapy but had side effects from treatment including cellulitis and local infections with ulceration before finally healing.

Interestingly, our patient had a single lesion with pathology findings most consistent with DSAP at a later age. Although the pathology suggested DSAP, the size and solitary lesion was more consistent with porokeratosis of Mibelli. Porokeratosis of Mibelli can occur concurrently with DSAP,⁹ but we have not seen other lesions in this patient. We have educated our patient to be aware of other lesions that may occur in the future. Due to risk for malignant conversion, it is generally viewed as beneficial to treat patients who present with porokeratosis lesions. Our patient’s lesion ultimately cleared and he has not developed new lesions at 1-year follow-up.

Although DSAP generally presents in the third and fourth decades of life and porokeratosis of Mibelli during childhood, it is important to educate both dermatologists and primary care physicians to be aware of the possibility of both diagnoses in the elderly population.

The Diagnosis: Fixed Cutaneous Sporotrichosis

On further questioning at our dermatology clinic, the patient reported having landed face-first into rocks and gravel during the all-terrain vehicle accident. After his medical history was noted and a physical examination was completed, bacterial and fungal cultures of the wound were taken. The fungal culture was positive for Sporothrix schenckii. The patient was prescribed itraconazole 200 mg 3 times daily for 3 days, then 200 mg twice daily for an additional 4 weeks after the lesions completely resolved. An ophthalmologist was immediately consulted to rule out sinus and periorbital involvement. After computed tomography revealed possible preseptal cellulitis with frontal sinus involvement, the patient was admitted and intravenous amphotericin B was administered. Following consultations with infectious disease specialists and radiologists, amphotericin B was discontinued and the patient was discharged on itraconazole 200 mg twice daily with close monitoring. At 3-month follow-up, the sporotrichosis infection had completely cleared (Figure).

Deep fungal infections comprise 2 distinct groups: systemic and subcutaneous mycoses. Individuals with subcutaneous mycoses present with skin involvement as the primary feature. Sporotrichosis is the most common cause of this type of mycosis¹ and is caused by the dimorphic fungus S schenckii, an environmental saprophyte often residing in soil. Sporothrix schenckii exists as mold in a natural environment but exists as yeast in host tissue, thus causing ensuing infection.

Epidemiology

Sporotrichosis occurs worldwide but most frequently in temperate tropical and subtropical regions. The majority of cases are reported in Mexico and Central and South America¹; however, cases have been seen in the southern United States, Japan, and Australia.² In the United States, sporotrichosis is most commonly found in river valleys of the Midwest.

Sporothrix schenckii is most commonly isolated in hay, sphagnum moss, thorny plants, and soil, but it also has been described in other manifold host environments. Unusual origins of inoculation include an old and rust-stained camping tent in Mexico,³ crawl space joists of a house in Indiana,⁴ and hay bales used as props in a haunted house in Oklahoma.⁵

The incidence of infection is primarily sporadic; however, outbreaks among individuals who share a common environment favorable for the growth of S schenckii are at risk. Those identified to be at risk include rose gardeners, berry pickers, those who work in tree nurseries, horticulturists, landscapers, and miners.

Pathogenesis

As a dimorphic fungus, infection occurs when a conidium in the mold phase is introduced into the skin, usually by traumatic skin injury, and is 
converted to the yeast form in vivo. Distribution of infection by this organism is most commonly 
localized to the cutaneous, subcutaneous, and lymphocutaneous regions in healthy hosts but can involve visceral and osteoarticular structures in immunocompromised hosts.^1,6 Pulmonary and disseminated forms are rare but can occur when 
S schenckii conidia are inhaled. Zoonotic transmission of the fungus also can occur with exposure to infected animals. Sporothrix schenckii has been reported to occur in cats, dogs, horses, donkeys, squirrels, armadillos, and dolphins.^7-11

Pathology

Sporothrix schenckii is typically not visualized on microscopic examination due to the small number of microorganisms present; however, cultures grow rapidly 
(3–5 days) on Sabouraud agar. The fungus most commonly develops as white or off-white compact colonies that progressively darken with age, transitioning to gray and then black.¹ Microscopically, the hyphae produce oval or pyriform conidia, which are assembled 
in a typical bouquetlike manner. Conversion of the organism to yeast on enriched medium such as brain-heart infusion agar or blood-cysteine-glucose agar confirms the diagnosis.

Acute lesions typically show a nonspecific mixed infiltrate, but established lesions may reveal granulomatous formation and neutrophilic microabscesses.^1,2 Asteroid bodies, which are cigar-shaped yeasts surrounded by eosinophilic coronae radiata, may be found. Organisms are sparsely distributed within the lesions, necessitating a thorough examination of the culture for identification.

Clinical Features

Sporotrichosis has 3 main classifications: lymphocutaneous, fixed cutaneous, and disseminated. Lymphocutaneous sporotrichosis is the most common form of the infection.² The disease presents with a small indurated papule occurring approximately 7 to 30 days after inoculation into the skin. The papule slowly enlarges, forms a nodule, and then frequently ulcerates. Over time, draining lymphatics become edematous and inflammatory, and a chain of secondary nodules begins to appear proximal to the initial lesion. The primary and secondary nodules may continue to ulcerate; alternately, they may heal or become chronic.

In fixed cutaneous sporotrichosis, the infection remains localized to one region and a granuloma may develop, which also may ulcerate. Satellite nodules may appear along the periphery of the lesion. Lymphatic spread is not observed in this form of 
the disease.

The disseminated form is a result of hematogenous spread from the primary inoculation site and typically occurs in an immunocompromised host. This form can present as pulmonary disease, sinusitis, and meningitis.¹

Differential Diagnosis

The differential diagnosis for sporotrichosis includes atypical mycobacteria, nocardiosis, blastomycosis, pyogenic bacteria, leishmaniasis, tularemia, 
and tuberculosis.

Treatment

Treatment of sporotrichosis is always required. A saturated solution of potassium iodide has classically been used; however, it is frequently associated with side effects and can be problematic to administer.¹² Given its low cost and traditional efficacy, it may still be used in some parts of the world.

Currently, the treatment of choice for fixed cutaneous and lymphocutaneous sporotrichosis is itraconazole 100 to 200 mg once daily for 3 to 6 months.¹ The recommended treatment of osteoarticular sporotrichosis is itraconazole, but prolonged therapy is required.

Heat therapy is an alternative treatment option, as certain strains of S schenckii do not grow at temperatures higher than 35°C. Hot compresses must be used for at least 1 hour a day for several months, which may affect patient compliance.

Immunocompromised patients often have disseminated infection and require lifelong suppressive therapy with itraconazole and may require initial treatment with amphotericin B.¹³

Conclusion

Subcutaneous sporotrichosis can develop in patients with a traumatic injury involving vegetation, soil, or animals. Although some patients may develop more invasive disease, most infections in immunocompetent patients will resolve after 3 to 6 months of itraconazole 100 to 200 mg once daily.¹

The Diagnosis: Fixed Cutaneous Sporotrichosis

On further questioning at our dermatology clinic, the patient reported having landed face-first into rocks and gravel during the all-terrain vehicle accident. After his medical history was noted and a physical examination was completed, bacterial and fungal cultures of the wound were taken. The fungal culture was positive for Sporothrix schenckii. The patient was prescribed itraconazole 200 mg 3 times daily for 3 days, then 200 mg twice daily for an additional 4 weeks after the lesions completely resolved. An ophthalmologist was immediately consulted to rule out sinus and periorbital involvement. After computed tomography revealed possible preseptal cellulitis with frontal sinus involvement, the patient was admitted and intravenous amphotericin B was administered. Following consultations with infectious disease specialists and radiologists, amphotericin B was discontinued and the patient was discharged on itraconazole 200 mg twice daily with close monitoring. At 3-month follow-up, the sporotrichosis infection had completely cleared (Figure).

Deep fungal infections comprise 2 distinct groups: systemic and subcutaneous mycoses. Individuals with subcutaneous mycoses present with skin involvement as the primary feature. Sporotrichosis is the most common cause of this type of mycosis¹ and is caused by the dimorphic fungus S schenckii, an environmental saprophyte often residing in soil. Sporothrix schenckii exists as mold in a natural environment but exists as yeast in host tissue, thus causing ensuing infection.

Epidemiology

Sporotrichosis occurs worldwide but most frequently in temperate tropical and subtropical regions. The majority of cases are reported in Mexico and Central and South America¹; however, cases have been seen in the southern United States, Japan, and Australia.² In the United States, sporotrichosis is most commonly found in river valleys of the Midwest.

Sporothrix schenckii is most commonly isolated in hay, sphagnum moss, thorny plants, and soil, but it also has been described in other manifold host environments. Unusual origins of inoculation include an old and rust-stained camping tent in Mexico,³ crawl space joists of a house in Indiana,⁴ and hay bales used as props in a haunted house in Oklahoma.⁵

The incidence of infection is primarily sporadic; however, outbreaks among individuals who share a common environment favorable for the growth of S schenckii are at risk. Those identified to be at risk include rose gardeners, berry pickers, those who work in tree nurseries, horticulturists, landscapers, and miners.

Pathogenesis

As a dimorphic fungus, infection occurs when a conidium in the mold phase is introduced into the skin, usually by traumatic skin injury, and is 
converted to the yeast form in vivo. Distribution of infection by this organism is most commonly 
localized to the cutaneous, subcutaneous, and lymphocutaneous regions in healthy hosts but can involve visceral and osteoarticular structures in immunocompromised hosts.^1,6 Pulmonary and disseminated forms are rare but can occur when 
S schenckii conidia are inhaled. Zoonotic transmission of the fungus also can occur with exposure to infected animals. Sporothrix schenckii has been reported to occur in cats, dogs, horses, donkeys, squirrels, armadillos, and dolphins.^7-11

Pathology

Sporothrix schenckii is typically not visualized on microscopic examination due to the small number of microorganisms present; however, cultures grow rapidly 
(3–5 days) on Sabouraud agar. The fungus most commonly develops as white or off-white compact colonies that progressively darken with age, transitioning to gray and then black.¹ Microscopically, the hyphae produce oval or pyriform conidia, which are assembled 
in a typical bouquetlike manner. Conversion of the organism to yeast on enriched medium such as brain-heart infusion agar or blood-cysteine-glucose agar confirms the diagnosis.

Acute lesions typically show a nonspecific mixed infiltrate, but established lesions may reveal granulomatous formation and neutrophilic microabscesses.^1,2 Asteroid bodies, which are cigar-shaped yeasts surrounded by eosinophilic coronae radiata, may be found. Organisms are sparsely distributed within the lesions, necessitating a thorough examination of the culture for identification.

Clinical Features

Sporotrichosis has 3 main classifications: lymphocutaneous, fixed cutaneous, and disseminated. Lymphocutaneous sporotrichosis is the most common form of the infection.² The disease presents with a small indurated papule occurring approximately 7 to 30 days after inoculation into the skin. The papule slowly enlarges, forms a nodule, and then frequently ulcerates. Over time, draining lymphatics become edematous and inflammatory, and a chain of secondary nodules begins to appear proximal to the initial lesion. The primary and secondary nodules may continue to ulcerate; alternately, they may heal or become chronic.

In fixed cutaneous sporotrichosis, the infection remains localized to one region and a granuloma may develop, which also may ulcerate. Satellite nodules may appear along the periphery of the lesion. Lymphatic spread is not observed in this form of 
the disease.

The disseminated form is a result of hematogenous spread from the primary inoculation site and typically occurs in an immunocompromised host. This form can present as pulmonary disease, sinusitis, and meningitis.¹

Differential Diagnosis

The differential diagnosis for sporotrichosis includes atypical mycobacteria, nocardiosis, blastomycosis, pyogenic bacteria, leishmaniasis, tularemia, 
and tuberculosis.

Treatment

Treatment of sporotrichosis is always required. A saturated solution of potassium iodide has classically been used; however, it is frequently associated with side effects and can be problematic to administer.¹² Given its low cost and traditional efficacy, it may still be used in some parts of the world.

Currently, the treatment of choice for fixed cutaneous and lymphocutaneous sporotrichosis is itraconazole 100 to 200 mg once daily for 3 to 6 months.¹ The recommended treatment of osteoarticular sporotrichosis is itraconazole, but prolonged therapy is required.

Heat therapy is an alternative treatment option, as certain strains of S schenckii do not grow at temperatures higher than 35°C. Hot compresses must be used for at least 1 hour a day for several months, which may affect patient compliance.

Immunocompromised patients often have disseminated infection and require lifelong suppressive therapy with itraconazole and may require initial treatment with amphotericin B.¹³

Conclusion

Subcutaneous sporotrichosis can develop in patients with a traumatic injury involving vegetation, soil, or animals. Although some patients may develop more invasive disease, most infections in immunocompetent patients will resolve after 3 to 6 months of itraconazole 100 to 200 mg once daily.¹

The Diagnosis: Fixed Cutaneous Sporotrichosis

On further questioning at our dermatology clinic, the patient reported having landed face-first into rocks and gravel during the all-terrain vehicle accident. After his medical history was noted and a physical examination was completed, bacterial and fungal cultures of the wound were taken. The fungal culture was positive for Sporothrix schenckii. The patient was prescribed itraconazole 200 mg 3 times daily for 3 days, then 200 mg twice daily for an additional 4 weeks after the lesions completely resolved. An ophthalmologist was immediately consulted to rule out sinus and periorbital involvement. After computed tomography revealed possible preseptal cellulitis with frontal sinus involvement, the patient was admitted and intravenous amphotericin B was administered. Following consultations with infectious disease specialists and radiologists, amphotericin B was discontinued and the patient was discharged on itraconazole 200 mg twice daily with close monitoring. At 3-month follow-up, the sporotrichosis infection had completely cleared (Figure).

Deep fungal infections comprise 2 distinct groups: systemic and subcutaneous mycoses. Individuals with subcutaneous mycoses present with skin involvement as the primary feature. Sporotrichosis is the most common cause of this type of mycosis¹ and is caused by the dimorphic fungus S schenckii, an environmental saprophyte often residing in soil. Sporothrix schenckii exists as mold in a natural environment but exists as yeast in host tissue, thus causing ensuing infection.

Epidemiology

Sporotrichosis occurs worldwide but most frequently in temperate tropical and subtropical regions. The majority of cases are reported in Mexico and Central and South America¹; however, cases have been seen in the southern United States, Japan, and Australia.² In the United States, sporotrichosis is most commonly found in river valleys of the Midwest.

Sporothrix schenckii is most commonly isolated in hay, sphagnum moss, thorny plants, and soil, but it also has been described in other manifold host environments. Unusual origins of inoculation include an old and rust-stained camping tent in Mexico,³ crawl space joists of a house in Indiana,⁴ and hay bales used as props in a haunted house in Oklahoma.⁵

The incidence of infection is primarily sporadic; however, outbreaks among individuals who share a common environment favorable for the growth of S schenckii are at risk. Those identified to be at risk include rose gardeners, berry pickers, those who work in tree nurseries, horticulturists, landscapers, and miners.

Pathogenesis

As a dimorphic fungus, infection occurs when a conidium in the mold phase is introduced into the skin, usually by traumatic skin injury, and is 
converted to the yeast form in vivo. Distribution of infection by this organism is most commonly 
localized to the cutaneous, subcutaneous, and lymphocutaneous regions in healthy hosts but can involve visceral and osteoarticular structures in immunocompromised hosts.^1,6 Pulmonary and disseminated forms are rare but can occur when 
S schenckii conidia are inhaled. Zoonotic transmission of the fungus also can occur with exposure to infected animals. Sporothrix schenckii has been reported to occur in cats, dogs, horses, donkeys, squirrels, armadillos, and dolphins.^7-11

Pathology

Sporothrix schenckii is typically not visualized on microscopic examination due to the small number of microorganisms present; however, cultures grow rapidly 
(3–5 days) on Sabouraud agar. The fungus most commonly develops as white or off-white compact colonies that progressively darken with age, transitioning to gray and then black.¹ Microscopically, the hyphae produce oval or pyriform conidia, which are assembled 
in a typical bouquetlike manner. Conversion of the organism to yeast on enriched medium such as brain-heart infusion agar or blood-cysteine-glucose agar confirms the diagnosis.

Acute lesions typically show a nonspecific mixed infiltrate, but established lesions may reveal granulomatous formation and neutrophilic microabscesses.^1,2 Asteroid bodies, which are cigar-shaped yeasts surrounded by eosinophilic coronae radiata, may be found. Organisms are sparsely distributed within the lesions, necessitating a thorough examination of the culture for identification.

Clinical Features

Sporotrichosis has 3 main classifications: lymphocutaneous, fixed cutaneous, and disseminated. Lymphocutaneous sporotrichosis is the most common form of the infection.² The disease presents with a small indurated papule occurring approximately 7 to 30 days after inoculation into the skin. The papule slowly enlarges, forms a nodule, and then frequently ulcerates. Over time, draining lymphatics become edematous and inflammatory, and a chain of secondary nodules begins to appear proximal to the initial lesion. The primary and secondary nodules may continue to ulcerate; alternately, they may heal or become chronic.

In fixed cutaneous sporotrichosis, the infection remains localized to one region and a granuloma may develop, which also may ulcerate. Satellite nodules may appear along the periphery of the lesion. Lymphatic spread is not observed in this form of 
the disease.

The disseminated form is a result of hematogenous spread from the primary inoculation site and typically occurs in an immunocompromised host. This form can present as pulmonary disease, sinusitis, and meningitis.¹

Differential Diagnosis

The differential diagnosis for sporotrichosis includes atypical mycobacteria, nocardiosis, blastomycosis, pyogenic bacteria, leishmaniasis, tularemia, 
and tuberculosis.

Treatment

Treatment of sporotrichosis is always required. A saturated solution of potassium iodide has classically been used; however, it is frequently associated with side effects and can be problematic to administer.¹² Given its low cost and traditional efficacy, it may still be used in some parts of the world.

Currently, the treatment of choice for fixed cutaneous and lymphocutaneous sporotrichosis is itraconazole 100 to 200 mg once daily for 3 to 6 months.¹ The recommended treatment of osteoarticular sporotrichosis is itraconazole, but prolonged therapy is required.

Heat therapy is an alternative treatment option, as certain strains of S schenckii do not grow at temperatures higher than 35°C. Hot compresses must be used for at least 1 hour a day for several months, which may affect patient compliance.

Immunocompromised patients often have disseminated infection and require lifelong suppressive therapy with itraconazole and may require initial treatment with amphotericin B.¹³

Conclusion

Subcutaneous sporotrichosis can develop in patients with a traumatic injury involving vegetation, soil, or animals. Although some patients may develop more invasive disease, most infections in immunocompetent patients will resolve after 3 to 6 months of itraconazole 100 to 200 mg once daily.¹

The Diagnosis: Amelanotic Melanoma In Situ

Histopathology revealed a broad asymmetric melanocytic proliferation at the dermoepidermal junction, consisting both of singly dispersed cells as well as randomly positioned nests (Figure 1). The single cells demonstrated junctional confluence and extension along adnexal structures highlighted by melan-A stain 
(Figure 2). The melanocytes were markedly atypical with enlarged and hyperchromatic nuclei containing multiple nucleoli. No dermal involvement was seen. There was papillary dermal fibrosis and an active host lymphocytic response. Based on these findings, a diagnosis of amelanotic melanoma in situ was made.

Figure 1. Histopathology revealed confluence of atypical melanocytes at the dermoepidermal junction and pagetoid scatter of melanocytes to the spinous layer (A)(H&E, original magnification ×4). Higher-power magnification highlighted the atypia of the individual melanocytes (B)(H&E, original magnification ×10).

Subsequent scouting punch biopsies at the superior, anterior, and posterior aspects of the lesion were performed (Figure 3). All 3 revealed a similar nested and single cell proliferation at the dermoepidermal junction, confirming residual amelanotic melanoma in situ. The patient was referred to the otolaryngology department and underwent wide local excision with 5-mm margins and reconstructive repair.

Amelanotic melanoma comprises 2% to 8% of cutaneous melanomas. It is more common in fair-skinned elderly women with an average age of diagnosis of 61.8 years. Because features typically associated with melanoma such as asymmetry, border irregularity, and color variegation often are absent, amelanotic melanoma represents a notable diagnostic challenge for clinicians. Lesions can present nonspecifically as erythematous macules, papules, patches, or plaques and can have associated pruritus and scale.^1,2

Clinical misdiagnoses for amelanotic melanoma include Bowen disease, basal cell carcinoma, actinic keratosis, lichenoid keratosis, intradermal nevus, dermatofibroma, inflamed seborrheic keratosis, nummular dermatitis, pyogenic granuloma, and granuloma annulare.^1-6 There have been few case reports of amelanotic melanoma in situ, with most being the lentigo maligna variant that were initially clinically diagnosed as superficial basal cell carcinoma, 
Bowen disease, or dermatitis.^7,8 In one case report, an amelanotic lentigo maligna was incidentally discovered after performing a mapping shave biopsy on what was normal-appearing skin.⁹

Dermoscopic evidence of vascular structures in lesions, including the presence of dotted vessels, milky red areas, and/or serpentine (linear irregular) vessels, may be the only clues to suggest amelanotic melanoma before biopsy. However, these findings are nonspecific and can be seen in other benign and malignant skin conditions.²

Complete surgical excision is the standard treatment of amelanotic melanoma in situ given its potential for invasion. However, the lack of pigment can make margins difficult to define. Because of its ability to detect disease beyond visual margins, Mohs micrographic surgery may have better cure rates than conventional excision.⁴ Prognosis for amelanotic melanoma is the same as other melanomas of equal thickness and location, though delay in diagnosis can adversely affect outcomes. Furthermore, amelanotic melanoma in situ can rapidly progress to invasive melanoma.^3,5 Thus it is important to maintain clinical suspicion for amelanotic melanoma in fair-skinned elderly women presenting with a persistent or recurring erythematous scaly lesion on sun-exposed skin.

The Diagnosis: Amelanotic Melanoma In Situ

Histopathology revealed a broad asymmetric melanocytic proliferation at the dermoepidermal junction, consisting both of singly dispersed cells as well as randomly positioned nests (Figure 1). The single cells demonstrated junctional confluence and extension along adnexal structures highlighted by melan-A stain 
(Figure 2). The melanocytes were markedly atypical with enlarged and hyperchromatic nuclei containing multiple nucleoli. No dermal involvement was seen. There was papillary dermal fibrosis and an active host lymphocytic response. Based on these findings, a diagnosis of amelanotic melanoma in situ was made.

Figure 1. Histopathology revealed confluence of atypical melanocytes at the dermoepidermal junction and pagetoid scatter of melanocytes to the spinous layer (A)(H&E, original magnification ×4). Higher-power magnification highlighted the atypia of the individual melanocytes (B)(H&E, original magnification ×10).

Subsequent scouting punch biopsies at the superior, anterior, and posterior aspects of the lesion were performed (Figure 3). All 3 revealed a similar nested and single cell proliferation at the dermoepidermal junction, confirming residual amelanotic melanoma in situ. The patient was referred to the otolaryngology department and underwent wide local excision with 5-mm margins and reconstructive repair.

Amelanotic melanoma comprises 2% to 8% of cutaneous melanomas. It is more common in fair-skinned elderly women with an average age of diagnosis of 61.8 years. Because features typically associated with melanoma such as asymmetry, border irregularity, and color variegation often are absent, amelanotic melanoma represents a notable diagnostic challenge for clinicians. Lesions can present nonspecifically as erythematous macules, papules, patches, or plaques and can have associated pruritus and scale.^1,2

Clinical misdiagnoses for amelanotic melanoma include Bowen disease, basal cell carcinoma, actinic keratosis, lichenoid keratosis, intradermal nevus, dermatofibroma, inflamed seborrheic keratosis, nummular dermatitis, pyogenic granuloma, and granuloma annulare.^1-6 There have been few case reports of amelanotic melanoma in situ, with most being the lentigo maligna variant that were initially clinically diagnosed as superficial basal cell carcinoma, 
Bowen disease, or dermatitis.^7,8 In one case report, an amelanotic lentigo maligna was incidentally discovered after performing a mapping shave biopsy on what was normal-appearing skin.⁹

Dermoscopic evidence of vascular structures in lesions, including the presence of dotted vessels, milky red areas, and/or serpentine (linear irregular) vessels, may be the only clues to suggest amelanotic melanoma before biopsy. However, these findings are nonspecific and can be seen in other benign and malignant skin conditions.²

Complete surgical excision is the standard treatment of amelanotic melanoma in situ given its potential for invasion. However, the lack of pigment can make margins difficult to define. Because of its ability to detect disease beyond visual margins, Mohs micrographic surgery may have better cure rates than conventional excision.⁴ Prognosis for amelanotic melanoma is the same as other melanomas of equal thickness and location, though delay in diagnosis can adversely affect outcomes. Furthermore, amelanotic melanoma in situ can rapidly progress to invasive melanoma.^3,5 Thus it is important to maintain clinical suspicion for amelanotic melanoma in fair-skinned elderly women presenting with a persistent or recurring erythematous scaly lesion on sun-exposed skin.

The Diagnosis: Amelanotic Melanoma In Situ

Histopathology revealed a broad asymmetric melanocytic proliferation at the dermoepidermal junction, consisting both of singly dispersed cells as well as randomly positioned nests (Figure 1). The single cells demonstrated junctional confluence and extension along adnexal structures highlighted by melan-A stain 
(Figure 2). The melanocytes were markedly atypical with enlarged and hyperchromatic nuclei containing multiple nucleoli. No dermal involvement was seen. There was papillary dermal fibrosis and an active host lymphocytic response. Based on these findings, a diagnosis of amelanotic melanoma in situ was made.

Figure 1. Histopathology revealed confluence of atypical melanocytes at the dermoepidermal junction and pagetoid scatter of melanocytes to the spinous layer (A)(H&E, original magnification ×4). Higher-power magnification highlighted the atypia of the individual melanocytes (B)(H&E, original magnification ×10).

Subsequent scouting punch biopsies at the superior, anterior, and posterior aspects of the lesion were performed (Figure 3). All 3 revealed a similar nested and single cell proliferation at the dermoepidermal junction, confirming residual amelanotic melanoma in situ. The patient was referred to the otolaryngology department and underwent wide local excision with 5-mm margins and reconstructive repair.

Amelanotic melanoma comprises 2% to 8% of cutaneous melanomas. It is more common in fair-skinned elderly women with an average age of diagnosis of 61.8 years. Because features typically associated with melanoma such as asymmetry, border irregularity, and color variegation often are absent, amelanotic melanoma represents a notable diagnostic challenge for clinicians. Lesions can present nonspecifically as erythematous macules, papules, patches, or plaques and can have associated pruritus and scale.^1,2

Clinical misdiagnoses for amelanotic melanoma include Bowen disease, basal cell carcinoma, actinic keratosis, lichenoid keratosis, intradermal nevus, dermatofibroma, inflamed seborrheic keratosis, nummular dermatitis, pyogenic granuloma, and granuloma annulare.^1-6 There have been few case reports of amelanotic melanoma in situ, with most being the lentigo maligna variant that were initially clinically diagnosed as superficial basal cell carcinoma, 
Bowen disease, or dermatitis.^7,8 In one case report, an amelanotic lentigo maligna was incidentally discovered after performing a mapping shave biopsy on what was normal-appearing skin.⁹

Dermoscopic evidence of vascular structures in lesions, including the presence of dotted vessels, milky red areas, and/or serpentine (linear irregular) vessels, may be the only clues to suggest amelanotic melanoma before biopsy. However, these findings are nonspecific and can be seen in other benign and malignant skin conditions.²

Complete surgical excision is the standard treatment of amelanotic melanoma in situ given its potential for invasion. However, the lack of pigment can make margins difficult to define. Because of its ability to detect disease beyond visual margins, Mohs micrographic surgery may have better cure rates than conventional excision.⁴ Prognosis for amelanotic melanoma is the same as other melanomas of equal thickness and location, though delay in diagnosis can adversely affect outcomes. Furthermore, amelanotic melanoma in situ can rapidly progress to invasive melanoma.^3,5 Thus it is important to maintain clinical suspicion for amelanotic melanoma in fair-skinned elderly women presenting with a persistent or recurring erythematous scaly lesion on sun-exposed skin.

The Diagnosis: Herpes Simplex Vegetans

Histopathologic examination using hematoxylin and eosin stain demonstrated marked pseudoepitheliomatous hyperplasia with granulation tissue, ulceration, and abundant exudate joined by a dense mixed inflammatory cell infiltrate that included a myriad of eosinophils (Figure, A). At higher power (Figure, B), many single and multinucleate acantholytic keratinocytes showed ground-glass nuclei and peripheral margination of chromatin within zones of ulceration and crust. Viral culture and direct fluorescent antibody assay identified herpes simplex virus (HSV) type 2. Based on the clinical and histopathologic findings, the patient was diagnosed with herpes simplex vegetans. He was initially treated with oral acyclovir and then oral famciclovir but showed minimal improvement. Eventually, he was referred to surgery and the mass was totally excised with clear margins and no evidence of underlying malignancy.

Histopathology revealed marked pseudoepitheliomatous hyperplasia, ulceration, and a dense mixed inflammatory cell infiltrate (A)(H&E, original magnification ×20). Many multinucleate acantholytic keratinocytes with ground-glass nuclei and peripheral margination of chromatin were shown (B)(H&E, original magnification ×400).

Herpes simplex virus is one of the most common sexually transmitted infections, with a notably increased incidence and prevalence among individuals with human immunodeficiency virus (HIV) infection.¹ Although typical HSV manifestation in immunocompetent patients includes clustered vesicles and/or ulcerations, immunocompromised patients may have unusual presentations, such as persistent and extensive ulcerations or nodular hyperkeratotic lesions.^2,3 Herpes vegetans, a term used to describe these atypical exophytic lesions, rarely has been reported in literature, but its presence should raise suspicion for possible underlying immunocompromise. The pathogenesis behind the hypertrophic nature of these lesions is not well understood, but it is postulated that the immune dysregulation from concomitant HIV and HSV infection plays a role.² Overproduction of tumor necrosis factor and IL-6 by HIV-infected dermal dendritic cells causes an increase in antiapoptotic factors within the epidermis, resulting in enhanced keratinocyte proliferation and clinical hyperkeratosis.^2,4

The differential diagnosis for herpes vegetans is somewhat broad, owing to the verrucous and often eroded appearance of the lesions. Biopsy and cultures can be obtained to differentiate from condyloma acuminatum, condyloma latum (secondary syphilis), pyoderma vegetans, pemphigus vegetans, granuloma inguinale, extraintestinal Crohn disease, deep fungal infections, cutaneous tuberculosis, and malignancy.^2-4 Histopathology shows epithelial hyperplasia and ulceration with scattered multinucleate keratinocytes, usually at the periphery of the ulcer, and intranuclear inclusions typical of HSV. In addition, a dense dermal infiltrate of lymphocytes, histiocytes, plasma cells, and eosinophils is usually present beneath the base of the ulcer.^2,4

Treatment options for herpes vegetans are limited due to the high prevalence of acyclovir-resistant (ACV-R) HSV-2 strains in HIV patients. Valacyclovir and penciclovir have been largely ineffective against ACV-R HSV due to their dependence on the same enzyme—thymidine kinase—involved in the mechanism of acyclovir resistance. Intravenous foscarnet and cidofovir have shown efficacy against ACV-R virus, but concerns of nephrotoxicity have limited their use over prolonged intervals.⁵ Castelo-Soccio et al⁶ reported promising results with intralesional cidofovir. This route of administration provides the advantage of increased bioavailability with reduced risk for nephrotoxicity.⁶ Finally, surgical resection may be considered for refractory lesions to circumvent the toxicity from systemically administered drugs.³

The Diagnosis: Herpes Simplex Vegetans

Histopathologic examination using hematoxylin and eosin stain demonstrated marked pseudoepitheliomatous hyperplasia with granulation tissue, ulceration, and abundant exudate joined by a dense mixed inflammatory cell infiltrate that included a myriad of eosinophils (Figure, A). At higher power (Figure, B), many single and multinucleate acantholytic keratinocytes showed ground-glass nuclei and peripheral margination of chromatin within zones of ulceration and crust. Viral culture and direct fluorescent antibody assay identified herpes simplex virus (HSV) type 2. Based on the clinical and histopathologic findings, the patient was diagnosed with herpes simplex vegetans. He was initially treated with oral acyclovir and then oral famciclovir but showed minimal improvement. Eventually, he was referred to surgery and the mass was totally excised with clear margins and no evidence of underlying malignancy.

Histopathology revealed marked pseudoepitheliomatous hyperplasia, ulceration, and a dense mixed inflammatory cell infiltrate (A)(H&E, original magnification ×20). Many multinucleate acantholytic keratinocytes with ground-glass nuclei and peripheral margination of chromatin were shown (B)(H&E, original magnification ×400).

Herpes simplex virus is one of the most common sexually transmitted infections, with a notably increased incidence and prevalence among individuals with human immunodeficiency virus (HIV) infection.¹ Although typical HSV manifestation in immunocompetent patients includes clustered vesicles and/or ulcerations, immunocompromised patients may have unusual presentations, such as persistent and extensive ulcerations or nodular hyperkeratotic lesions.^2,3 Herpes vegetans, a term used to describe these atypical exophytic lesions, rarely has been reported in literature, but its presence should raise suspicion for possible underlying immunocompromise. The pathogenesis behind the hypertrophic nature of these lesions is not well understood, but it is postulated that the immune dysregulation from concomitant HIV and HSV infection plays a role.² Overproduction of tumor necrosis factor and IL-6 by HIV-infected dermal dendritic cells causes an increase in antiapoptotic factors within the epidermis, resulting in enhanced keratinocyte proliferation and clinical hyperkeratosis.^2,4

The differential diagnosis for herpes vegetans is somewhat broad, owing to the verrucous and often eroded appearance of the lesions. Biopsy and cultures can be obtained to differentiate from condyloma acuminatum, condyloma latum (secondary syphilis), pyoderma vegetans, pemphigus vegetans, granuloma inguinale, extraintestinal Crohn disease, deep fungal infections, cutaneous tuberculosis, and malignancy.^2-4 Histopathology shows epithelial hyperplasia and ulceration with scattered multinucleate keratinocytes, usually at the periphery of the ulcer, and intranuclear inclusions typical of HSV. In addition, a dense dermal infiltrate of lymphocytes, histiocytes, plasma cells, and eosinophils is usually present beneath the base of the ulcer.^2,4

Treatment options for herpes vegetans are limited due to the high prevalence of acyclovir-resistant (ACV-R) HSV-2 strains in HIV patients. Valacyclovir and penciclovir have been largely ineffective against ACV-R HSV due to their dependence on the same enzyme—thymidine kinase—involved in the mechanism of acyclovir resistance. Intravenous foscarnet and cidofovir have shown efficacy against ACV-R virus, but concerns of nephrotoxicity have limited their use over prolonged intervals.⁵ Castelo-Soccio et al⁶ reported promising results with intralesional cidofovir. This route of administration provides the advantage of increased bioavailability with reduced risk for nephrotoxicity.⁶ Finally, surgical resection may be considered for refractory lesions to circumvent the toxicity from systemically administered drugs.³

The Diagnosis: Herpes Simplex Vegetans

Histopathologic examination using hematoxylin and eosin stain demonstrated marked pseudoepitheliomatous hyperplasia with granulation tissue, ulceration, and abundant exudate joined by a dense mixed inflammatory cell infiltrate that included a myriad of eosinophils (Figure, A). At higher power (Figure, B), many single and multinucleate acantholytic keratinocytes showed ground-glass nuclei and peripheral margination of chromatin within zones of ulceration and crust. Viral culture and direct fluorescent antibody assay identified herpes simplex virus (HSV) type 2. Based on the clinical and histopathologic findings, the patient was diagnosed with herpes simplex vegetans. He was initially treated with oral acyclovir and then oral famciclovir but showed minimal improvement. Eventually, he was referred to surgery and the mass was totally excised with clear margins and no evidence of underlying malignancy.

Histopathology revealed marked pseudoepitheliomatous hyperplasia, ulceration, and a dense mixed inflammatory cell infiltrate (A)(H&E, original magnification ×20). Many multinucleate acantholytic keratinocytes with ground-glass nuclei and peripheral margination of chromatin were shown (B)(H&E, original magnification ×400).

Herpes simplex virus is one of the most common sexually transmitted infections, with a notably increased incidence and prevalence among individuals with human immunodeficiency virus (HIV) infection.¹ Although typical HSV manifestation in immunocompetent patients includes clustered vesicles and/or ulcerations, immunocompromised patients may have unusual presentations, such as persistent and extensive ulcerations or nodular hyperkeratotic lesions.^2,3 Herpes vegetans, a term used to describe these atypical exophytic lesions, rarely has been reported in literature, but its presence should raise suspicion for possible underlying immunocompromise. The pathogenesis behind the hypertrophic nature of these lesions is not well understood, but it is postulated that the immune dysregulation from concomitant HIV and HSV infection plays a role.² Overproduction of tumor necrosis factor and IL-6 by HIV-infected dermal dendritic cells causes an increase in antiapoptotic factors within the epidermis, resulting in enhanced keratinocyte proliferation and clinical hyperkeratosis.^2,4

The differential diagnosis for herpes vegetans is somewhat broad, owing to the verrucous and often eroded appearance of the lesions. Biopsy and cultures can be obtained to differentiate from condyloma acuminatum, condyloma latum (secondary syphilis), pyoderma vegetans, pemphigus vegetans, granuloma inguinale, extraintestinal Crohn disease, deep fungal infections, cutaneous tuberculosis, and malignancy.^2-4 Histopathology shows epithelial hyperplasia and ulceration with scattered multinucleate keratinocytes, usually at the periphery of the ulcer, and intranuclear inclusions typical of HSV. In addition, a dense dermal infiltrate of lymphocytes, histiocytes, plasma cells, and eosinophils is usually present beneath the base of the ulcer.^2,4

Treatment options for herpes vegetans are limited due to the high prevalence of acyclovir-resistant (ACV-R) HSV-2 strains in HIV patients. Valacyclovir and penciclovir have been largely ineffective against ACV-R HSV due to their dependence on the same enzyme—thymidine kinase—involved in the mechanism of acyclovir resistance. Intravenous foscarnet and cidofovir have shown efficacy against ACV-R virus, but concerns of nephrotoxicity have limited their use over prolonged intervals.⁵ Castelo-Soccio et al⁶ reported promising results with intralesional cidofovir. This route of administration provides the advantage of increased bioavailability with reduced risk for nephrotoxicity.⁶ Finally, surgical resection may be considered for refractory lesions to circumvent the toxicity from systemically administered drugs.³

The Diagnosis: Idiopathic Guttate Hypomelanosis

A biopsy of the largest lesion from the left leg 
superior to the lateral malleolus was performed. 
 Histopathologic examination revealed solar elastosis, diminished number of focal melanocytes and pigment within keratinocytes compared to uninvolved skin, and presence of hyperkeratosis with flattening of rete ridges. The clinical presentation along with histopathologic analysis confirmed a diagnosis of idiopathic guttate hypomelanosis (IGH). The lesions were treated with short-exposure cryotherapy, which resulted in partial repigmentation after several treatments.

Idiopathic guttate hypomelanosis is a common but underreported condition in elderly patients that usually presents with small, discrete, asymptomatic, hypopigmented macules. The frequency of IGH increases with age.¹ Frequency of the condition is much lower in patients aged 21 to 30 years and does not exceed 7%. Lesions of IGH have a predilection for sun-exposed areas such as the arms and legs but rarely can be seen on the face and trunk. Facial lesions of IGH are more frequently reported in women.¹ The size of lesions can be up to 1.5 cm in diameter. The condition generally is self-limited, but some patients may express aesthetic concerns. Rare cases of IGH in children have been associated with prolonged sun exposure.²

The etiology of IGH is unknown but an association with sun exposure has been noted. Patients with IGH frequently show other signs of photoaging, such as numerous seborrheic keratoses, solar lentigines, xeroses, freckles, and actinic keratoses.¹ Short-term exposure to UVB radiation and psoralen plus UVA therapy has been shown to cause IGH in patients with chronic diseases such as mycosis fungoides.^3-5 One small study that examined renal transplant recipients determined an association between HLA-DQ3 antigens and IGH, whereas HLA-DR8 antigens were not identified in any patients with IGH, indicating it may have some advantage in preventing the development of IGH.⁶ Shin et al¹ reported that IGH was prevalent among patients who regularly traumatized their skin by scrubbing.

Clinically, IGH should be differentiated from other conditions characterized by hypopigmentation, such as pityriasis alba, pityriasis versicolor, postinflammatory hypopigmentation, progressive macular hypomelanosis, and vitiligo. Aside from clinical examination, histopathologic studies are helpful in making a definitive diagnosis. The differential diagnosis of IGH is presented in the Table.

Histopathology of IGH lesions usually reveals slight atrophy of the epidermis with flattening of rete ridges and concomitant hyperkeratosis. A thickened stratum granulosum also has been noted in lesions of IGH.² The diminished number of melanocytes and melanin pigment granules along with hyperkeratosis both appear to contribute to the hypopigmentation noted in IGH.⁷ Ultrastructural studies of lesions of IGH can confirm melanocytic degeneration and a decreased number of melanosomes in melanocytes and keratinocytes.^2,8

There is no uniformly effective treatment of IGH. Topical application of tacrolimus and tretinoin have shown efficacy in repigmenting IGH lesions.^8,9 Short-exposure cryotherapy with a duration of 3 to 
5 seconds, localized chemical peels, and/or local dermabrasion can be helpful.^10-12 CO₂ lasers also have demonstrated promising results.¹³

The Diagnosis: Idiopathic Guttate Hypomelanosis

A biopsy of the largest lesion from the left leg 
superior to the lateral malleolus was performed. 
 Histopathologic examination revealed solar elastosis, diminished number of focal melanocytes and pigment within keratinocytes compared to uninvolved skin, and presence of hyperkeratosis with flattening of rete ridges. The clinical presentation along with histopathologic analysis confirmed a diagnosis of idiopathic guttate hypomelanosis (IGH). The lesions were treated with short-exposure cryotherapy, which resulted in partial repigmentation after several treatments.

Idiopathic guttate hypomelanosis is a common but underreported condition in elderly patients that usually presents with small, discrete, asymptomatic, hypopigmented macules. The frequency of IGH increases with age.¹ Frequency of the condition is much lower in patients aged 21 to 30 years and does not exceed 7%. Lesions of IGH have a predilection for sun-exposed areas such as the arms and legs but rarely can be seen on the face and trunk. Facial lesions of IGH are more frequently reported in women.¹ The size of lesions can be up to 1.5 cm in diameter. The condition generally is self-limited, but some patients may express aesthetic concerns. Rare cases of IGH in children have been associated with prolonged sun exposure.²

The etiology of IGH is unknown but an association with sun exposure has been noted. Patients with IGH frequently show other signs of photoaging, such as numerous seborrheic keratoses, solar lentigines, xeroses, freckles, and actinic keratoses.¹ Short-term exposure to UVB radiation and psoralen plus UVA therapy has been shown to cause IGH in patients with chronic diseases such as mycosis fungoides.^3-5 One small study that examined renal transplant recipients determined an association between HLA-DQ3 antigens and IGH, whereas HLA-DR8 antigens were not identified in any patients with IGH, indicating it may have some advantage in preventing the development of IGH.⁶ Shin et al¹ reported that IGH was prevalent among patients who regularly traumatized their skin by scrubbing.

Clinically, IGH should be differentiated from other conditions characterized by hypopigmentation, such as pityriasis alba, pityriasis versicolor, postinflammatory hypopigmentation, progressive macular hypomelanosis, and vitiligo. Aside from clinical examination, histopathologic studies are helpful in making a definitive diagnosis. The differential diagnosis of IGH is presented in the Table.

Histopathology of IGH lesions usually reveals slight atrophy of the epidermis with flattening of rete ridges and concomitant hyperkeratosis. A thickened stratum granulosum also has been noted in lesions of IGH.² The diminished number of melanocytes and melanin pigment granules along with hyperkeratosis both appear to contribute to the hypopigmentation noted in IGH.⁷ Ultrastructural studies of lesions of IGH can confirm melanocytic degeneration and a decreased number of melanosomes in melanocytes and keratinocytes.^2,8

There is no uniformly effective treatment of IGH. Topical application of tacrolimus and tretinoin have shown efficacy in repigmenting IGH lesions.^8,9 Short-exposure cryotherapy with a duration of 3 to 
5 seconds, localized chemical peels, and/or local dermabrasion can be helpful.^10-12 CO₂ lasers also have demonstrated promising results.¹³

The Diagnosis: Idiopathic Guttate Hypomelanosis

A biopsy of the largest lesion from the left leg 
superior to the lateral malleolus was performed. 
 Histopathologic examination revealed solar elastosis, diminished number of focal melanocytes and pigment within keratinocytes compared to uninvolved skin, and presence of hyperkeratosis with flattening of rete ridges. The clinical presentation along with histopathologic analysis confirmed a diagnosis of idiopathic guttate hypomelanosis (IGH). The lesions were treated with short-exposure cryotherapy, which resulted in partial repigmentation after several treatments.

Idiopathic guttate hypomelanosis is a common but underreported condition in elderly patients that usually presents with small, discrete, asymptomatic, hypopigmented macules. The frequency of IGH increases with age.¹ Frequency of the condition is much lower in patients aged 21 to 30 years and does not exceed 7%. Lesions of IGH have a predilection for sun-exposed areas such as the arms and legs but rarely can be seen on the face and trunk. Facial lesions of IGH are more frequently reported in women.¹ The size of lesions can be up to 1.5 cm in diameter. The condition generally is self-limited, but some patients may express aesthetic concerns. Rare cases of IGH in children have been associated with prolonged sun exposure.²

The etiology of IGH is unknown but an association with sun exposure has been noted. Patients with IGH frequently show other signs of photoaging, such as numerous seborrheic keratoses, solar lentigines, xeroses, freckles, and actinic keratoses.¹ Short-term exposure to UVB radiation and psoralen plus UVA therapy has been shown to cause IGH in patients with chronic diseases such as mycosis fungoides.^3-5 One small study that examined renal transplant recipients determined an association between HLA-DQ3 antigens and IGH, whereas HLA-DR8 antigens were not identified in any patients with IGH, indicating it may have some advantage in preventing the development of IGH.⁶ Shin et al¹ reported that IGH was prevalent among patients who regularly traumatized their skin by scrubbing.

Clinically, IGH should be differentiated from other conditions characterized by hypopigmentation, such as pityriasis alba, pityriasis versicolor, postinflammatory hypopigmentation, progressive macular hypomelanosis, and vitiligo. Aside from clinical examination, histopathologic studies are helpful in making a definitive diagnosis. The differential diagnosis of IGH is presented in the Table.

Histopathology of IGH lesions usually reveals slight atrophy of the epidermis with flattening of rete ridges and concomitant hyperkeratosis. A thickened stratum granulosum also has been noted in lesions of IGH.² The diminished number of melanocytes and melanin pigment granules along with hyperkeratosis both appear to contribute to the hypopigmentation noted in IGH.⁷ Ultrastructural studies of lesions of IGH can confirm melanocytic degeneration and a decreased number of melanosomes in melanocytes and keratinocytes.^2,8

There is no uniformly effective treatment of IGH. Topical application of tacrolimus and tretinoin have shown efficacy in repigmenting IGH lesions.^8,9 Short-exposure cryotherapy with a duration of 3 to 
5 seconds, localized chemical peels, and/or local dermabrasion can be helpful.^10-12 CO₂ lasers also have demonstrated promising results.¹³

The Diagnosis: Allergic Contact Dermatitis to 
Para-phenylenediamine

To darken the color of henna and increase penetrance and staining, para-phenylenediamine (PPD) is added.¹ Allergic contact dermatitis is the most common type of hypersensitivity to PPD.² A retrospective study that examined severe adverse events from applying henna dyes in children found that angioedema of mucosal tissues was the most common severe adverse event; others included renal failure and shock.³

Black henna is associated with multiple cultural practices. For example, Indian weddings contain a henna decoration ceremony for the bride based on the belief that the longer the henna lasts, the longer the marriage lasts. Black henna is favored for this practice, as it lasts longer than red henna.

Henna (Lawsonia inermis) is a plant that contains the molecule lawsone (naphthoquinone). Lawsone has an intense affinity for keratin; as a result, lawsone is frequently added to temporary body tattoos and hair dyes to create a relatively permanent change in skin or hair color.⁴ Henna is mixed with hennotannic acid to release the lawsone from the plant. Lawsone and hennotannic acid rarely cause allergic reactions.^1,5-7 Once applied to skin, henna takes a few hours to dry, and the resulting color is orange to red.⁸ Often, PPD is added to henna paste to create a black color, to speed up the drying process, and to increase its longevity.

Para-phenylenediamine has been repeatedly reported to cause allergic contact dermatitis. We describe a case of allergic contact dermatitis secondary to PPD in black henna. Our patient is a clear example that PPD is the allergen in black henna given that there was no reaction to the natural red henna tattoo that was applied at the same time to the palmar surfaces of the hands (Figure). Aside from the bullous reaction to black henna dye described here, other reported presentations include erythema multiforme–like and exudative erythema reactions.^9,10

Contact dermatitis lesions from black henna dye can be treated with topical corticosteroids. Patients may develop residual postinflammatory hyperpigmentation or hypopigmentation, leukoderma, keloids, or scars.^1,11,12

The Diagnosis: Allergic Contact Dermatitis to 
Para-phenylenediamine

To darken the color of henna and increase penetrance and staining, para-phenylenediamine (PPD) is added.¹ Allergic contact dermatitis is the most common type of hypersensitivity to PPD.² A retrospective study that examined severe adverse events from applying henna dyes in children found that angioedema of mucosal tissues was the most common severe adverse event; others included renal failure and shock.³

Black henna is associated with multiple cultural practices. For example, Indian weddings contain a henna decoration ceremony for the bride based on the belief that the longer the henna lasts, the longer the marriage lasts. Black henna is favored for this practice, as it lasts longer than red henna.

Henna (Lawsonia inermis) is a plant that contains the molecule lawsone (naphthoquinone). Lawsone has an intense affinity for keratin; as a result, lawsone is frequently added to temporary body tattoos and hair dyes to create a relatively permanent change in skin or hair color.⁴ Henna is mixed with hennotannic acid to release the lawsone from the plant. Lawsone and hennotannic acid rarely cause allergic reactions.^1,5-7 Once applied to skin, henna takes a few hours to dry, and the resulting color is orange to red.⁸ Often, PPD is added to henna paste to create a black color, to speed up the drying process, and to increase its longevity.

Para-phenylenediamine has been repeatedly reported to cause allergic contact dermatitis. We describe a case of allergic contact dermatitis secondary to PPD in black henna. Our patient is a clear example that PPD is the allergen in black henna given that there was no reaction to the natural red henna tattoo that was applied at the same time to the palmar surfaces of the hands (Figure). Aside from the bullous reaction to black henna dye described here, other reported presentations include erythema multiforme–like and exudative erythema reactions.^9,10

Contact dermatitis lesions from black henna dye can be treated with topical corticosteroids. Patients may develop residual postinflammatory hyperpigmentation or hypopigmentation, leukoderma, keloids, or scars.^1,11,12

The Diagnosis: Allergic Contact Dermatitis to 
Para-phenylenediamine

To darken the color of henna and increase penetrance and staining, para-phenylenediamine (PPD) is added.¹ Allergic contact dermatitis is the most common type of hypersensitivity to PPD.² A retrospective study that examined severe adverse events from applying henna dyes in children found that angioedema of mucosal tissues was the most common severe adverse event; others included renal failure and shock.³

Black henna is associated with multiple cultural practices. For example, Indian weddings contain a henna decoration ceremony for the bride based on the belief that the longer the henna lasts, the longer the marriage lasts. Black henna is favored for this practice, as it lasts longer than red henna.

Henna (Lawsonia inermis) is a plant that contains the molecule lawsone (naphthoquinone). Lawsone has an intense affinity for keratin; as a result, lawsone is frequently added to temporary body tattoos and hair dyes to create a relatively permanent change in skin or hair color.⁴ Henna is mixed with hennotannic acid to release the lawsone from the plant. Lawsone and hennotannic acid rarely cause allergic reactions.^1,5-7 Once applied to skin, henna takes a few hours to dry, and the resulting color is orange to red.⁸ Often, PPD is added to henna paste to create a black color, to speed up the drying process, and to increase its longevity.

Para-phenylenediamine has been repeatedly reported to cause allergic contact dermatitis. We describe a case of allergic contact dermatitis secondary to PPD in black henna. Our patient is a clear example that PPD is the allergen in black henna given that there was no reaction to the natural red henna tattoo that was applied at the same time to the palmar surfaces of the hands (Figure). Aside from the bullous reaction to black henna dye described here, other reported presentations include erythema multiforme–like and exudative erythema reactions.^9,10

Contact dermatitis lesions from black henna dye can be treated with topical corticosteroids. Patients may develop residual postinflammatory hyperpigmentation or hypopigmentation, leukoderma, keloids, or scars.^1,11,12

The Diagnosis: Phrynoderma

Phrynoderma, meaning “toad skin,” was first described by Nicholls¹ in 1933 as a condition due to vitamin A deficiency and characterized by follicular hyperkeratosis. Since then, there has been debate in the literature over the etiology of phrynoderma, as studies have demonstrated different causes for this condition,^2-5 which suggests that it is prudent to check several markers of nutritional status including vitamin A, vitamin B, vitamin E, and essential fatty acid studies.

Phrynoderma is most commonly seen in South and East Asia with relatively rare occurrences in the United States. Although it characteristically occurs in children and adolescents aged 5 to 15 years, almost all of the cases reported in the United States have occurred in adults.^6,7 A clear gender predilection has not been established.⁷

Phrynoderma tends to favor the extensor surfaces. In particular, the elbows, thighs, and buttocks are the most commonly affected locations. The face is typically the last site to become involved. On physical examination of a patient with phrynoderma, there are various-sized, discrete, red-brown to flesh-colored papules with a conical keratotic follicular plug (Figure).³ The eruption is often asymptomatic, but mild pruritus may be reported.⁷ Additional signs of vitamin A deficiency may be present, including night blindness, hyperpigmentation, or xerosis. Patients with phrynoderma also may have evidence of other nutritional deficiencies, such as angular stomatitis, cheilitis, or glossitis. The differential diagnosis for a patient with this type of papular eruption may include pityriasis rubra pilaris, keratosis pilaris, lichen spinulosus, crusted scabies, and follicular lichen planus.⁷ History and clinical presentation can generally help to distinguish these diagnoses.

Generalized follicular, erythematous, and scaly papular eruption on the chest (A) and abdomen (B).

Histopathology typically shows moderate hyperkeratosis with distension of the upper portion of the follicle by large keratotic plugs. Sebaceous glands are greatly reduced in size and may exhibit epithelial atrophy.^8,9

A reduced serum vitamin A level can confirm the diagnosis of phrynoderma. Our patient’s laboratory results revealed a vitamin A value of 26 mg/100 dL (reference range, 38–106 mg/100 dL), consistent with his clinical presentation of phrynoderma. Other markers of nutritional status, including vitamins D, E, and K₁, were all within reference range. Treatment consists of replacing the nutritional deficit. High doses of vitamin A, such as 200,000 to 500,000 IU daily for 3 to 5 days or daily doses of 2000 to 50,000 IU, can lead to resolution of the rash in 1 to 4 months.^8,9 Our patient was started on 10,000 IU of oral vitamin A daily at discharge but unfortunately died a few months later.

Vitamin A has been shown to promote maturation and differentiation of the basal keratinocytes as they move up through the epidermis, which may in part explain why this treatment is effective.¹⁰ It is important to be aware of this condition when seeing a patient with follicular hyperkeratosis because even patients in developed countries with malnutrition due to diet or gastrointestinal disease may develop phrynoderma.

The Diagnosis: Phrynoderma

Phrynoderma, meaning “toad skin,” was first described by Nicholls¹ in 1933 as a condition due to vitamin A deficiency and characterized by follicular hyperkeratosis. Since then, there has been debate in the literature over the etiology of phrynoderma, as studies have demonstrated different causes for this condition,^2-5 which suggests that it is prudent to check several markers of nutritional status including vitamin A, vitamin B, vitamin E, and essential fatty acid studies.

Phrynoderma is most commonly seen in South and East Asia with relatively rare occurrences in the United States. Although it characteristically occurs in children and adolescents aged 5 to 15 years, almost all of the cases reported in the United States have occurred in adults.^6,7 A clear gender predilection has not been established.⁷

Phrynoderma tends to favor the extensor surfaces. In particular, the elbows, thighs, and buttocks are the most commonly affected locations. The face is typically the last site to become involved. On physical examination of a patient with phrynoderma, there are various-sized, discrete, red-brown to flesh-colored papules with a conical keratotic follicular plug (Figure).³ The eruption is often asymptomatic, but mild pruritus may be reported.⁷ Additional signs of vitamin A deficiency may be present, including night blindness, hyperpigmentation, or xerosis. Patients with phrynoderma also may have evidence of other nutritional deficiencies, such as angular stomatitis, cheilitis, or glossitis. The differential diagnosis for a patient with this type of papular eruption may include pityriasis rubra pilaris, keratosis pilaris, lichen spinulosus, crusted scabies, and follicular lichen planus.⁷ History and clinical presentation can generally help to distinguish these diagnoses.

Generalized follicular, erythematous, and scaly papular eruption on the chest (A) and abdomen (B).

Histopathology typically shows moderate hyperkeratosis with distension of the upper portion of the follicle by large keratotic plugs. Sebaceous glands are greatly reduced in size and may exhibit epithelial atrophy.^8,9

A reduced serum vitamin A level can confirm the diagnosis of phrynoderma. Our patient’s laboratory results revealed a vitamin A value of 26 mg/100 dL (reference range, 38–106 mg/100 dL), consistent with his clinical presentation of phrynoderma. Other markers of nutritional status, including vitamins D, E, and K₁, were all within reference range. Treatment consists of replacing the nutritional deficit. High doses of vitamin A, such as 200,000 to 500,000 IU daily for 3 to 5 days or daily doses of 2000 to 50,000 IU, can lead to resolution of the rash in 1 to 4 months.^8,9 Our patient was started on 10,000 IU of oral vitamin A daily at discharge but unfortunately died a few months later.

Vitamin A has been shown to promote maturation and differentiation of the basal keratinocytes as they move up through the epidermis, which may in part explain why this treatment is effective.¹⁰ It is important to be aware of this condition when seeing a patient with follicular hyperkeratosis because even patients in developed countries with malnutrition due to diet or gastrointestinal disease may develop phrynoderma.

The Diagnosis: Phrynoderma

Phrynoderma, meaning “toad skin,” was first described by Nicholls¹ in 1933 as a condition due to vitamin A deficiency and characterized by follicular hyperkeratosis. Since then, there has been debate in the literature over the etiology of phrynoderma, as studies have demonstrated different causes for this condition,^2-5 which suggests that it is prudent to check several markers of nutritional status including vitamin A, vitamin B, vitamin E, and essential fatty acid studies.

Phrynoderma is most commonly seen in South and East Asia with relatively rare occurrences in the United States. Although it characteristically occurs in children and adolescents aged 5 to 15 years, almost all of the cases reported in the United States have occurred in adults.^6,7 A clear gender predilection has not been established.⁷

Phrynoderma tends to favor the extensor surfaces. In particular, the elbows, thighs, and buttocks are the most commonly affected locations. The face is typically the last site to become involved. On physical examination of a patient with phrynoderma, there are various-sized, discrete, red-brown to flesh-colored papules with a conical keratotic follicular plug (Figure).³ The eruption is often asymptomatic, but mild pruritus may be reported.⁷ Additional signs of vitamin A deficiency may be present, including night blindness, hyperpigmentation, or xerosis. Patients with phrynoderma also may have evidence of other nutritional deficiencies, such as angular stomatitis, cheilitis, or glossitis. The differential diagnosis for a patient with this type of papular eruption may include pityriasis rubra pilaris, keratosis pilaris, lichen spinulosus, crusted scabies, and follicular lichen planus.⁷ History and clinical presentation can generally help to distinguish these diagnoses.

Generalized follicular, erythematous, and scaly papular eruption on the chest (A) and abdomen (B).

Histopathology typically shows moderate hyperkeratosis with distension of the upper portion of the follicle by large keratotic plugs. Sebaceous glands are greatly reduced in size and may exhibit epithelial atrophy.^8,9

A reduced serum vitamin A level can confirm the diagnosis of phrynoderma. Our patient’s laboratory results revealed a vitamin A value of 26 mg/100 dL (reference range, 38–106 mg/100 dL), consistent with his clinical presentation of phrynoderma. Other markers of nutritional status, including vitamins D, E, and K₁, were all within reference range. Treatment consists of replacing the nutritional deficit. High doses of vitamin A, such as 200,000 to 500,000 IU daily for 3 to 5 days or daily doses of 2000 to 50,000 IU, can lead to resolution of the rash in 1 to 4 months.^8,9 Our patient was started on 10,000 IU of oral vitamin A daily at discharge but unfortunately died a few months later.

Vitamin A has been shown to promote maturation and differentiation of the basal keratinocytes as they move up through the epidermis, which may in part explain why this treatment is effective.¹⁰ It is important to be aware of this condition when seeing a patient with follicular hyperkeratosis because even patients in developed countries with malnutrition due to diet or gastrointestinal disease may develop phrynoderma.

The Diagnosis: Crusted Scabies

Approximately 1 year prior to presentation the patient completed a course of therapy comprised of repeat doses of ivermectin and permethrin for crusted scabies. He stated that the crusts had recurred shortly after treatment (Figure 1). The initial differential diagnosis included crusted scabies, pityriasis rubra pilaris, and psoriasis. Scraping from the interdigital web space (Figure 2) revealed multiple scabies mites, scabella, and ova (Figure 3). The patient was diagnosed with crusted scabies. Laboratory test results revealed a normal white blood cell count of 7300/μL, with an elevated eosinophil count of 1900/μL (reference range, <500/μL). Human T-lymphotropic virus 1 (HTLV-1) was found to be positive. Serum protein electrophoresis showed a moderate polyclonal increase in gamma globulins. Treatment was promptly initiated with permethrin cream 5% applied to the whole body for a total of 2 treatments that were administered 7 days apart. Ivermectin also was started at 200 μg/kg and was given on days 1, 7, 14, and 29. Salicylic acid cream 25% was applied daily to help hasten resolution of the crusts.

Human T-lymphotropic virus 1 is endemic to Japan, Central and South America, the Middle East, and regions of Africa and the Caribbean.¹ Multiple cases of HTLV-1 associated with crusted scabies have been reported in endemic areas.^2-6 In the present case, we encountered a patient with crusted scabies and HTLV-1 in a nonendemic area.

Cases of HTLV-1 and crusted scabies have been reported in Brazil, Peru, and Central Australia.^3,4,7 A retrospective study in Brazil showed a notable association between HTLV-1 infection and crusted scabies; of 23 patients with crusted scabies, 21 were HTLV-1 positive.³ In another small study from Peru, 23 patients with crusted scabies were tested for HTLV-1 and 16 (70%) were seropositive.⁴ Neither study had a control group for comparison; however, interestingly, the estimated seroprevalence in the general population (based on blood donors) is only 0.04% to 1% and 1.2% to 1.7% in Brazil and Peru, respectively, thus reinforcing the association between HTLV-1 and crusted scabies.¹ Crusted scabies and HTLV-1 seropositivity acting as a predictor for adult T-cell leukemia/lymphoma (ATL) has been reported⁸ but not consistently.³ Our patient had abnormal serum protein electrophoresis findings. Although the results were not diagnostic of ATL, patients with HTLV-1 are at increased risk for ATL and the pres-ence of this virus is important to document when there is a high index of suspicion for ATL, as with crusted scabies.

Our patient resided in the northeastern United States and there was no evidence in support of underlying immunosuppression. This case of crusted scabies is unique because the patient was HTLV-1 positive without other underlying immunocompromise and he resided in a region where HTLV-1 is nonendemic. In light of these findings, the present case serves as a reminder to check for HTLV-1 infection in those patients with severe or crusted scabies and without an identifiable reason for immunosuppression, even if the patient resides in an area that is nonendemic for HTLV-1.

The Diagnosis: Crusted Scabies

Approximately 1 year prior to presentation the patient completed a course of therapy comprised of repeat doses of ivermectin and permethrin for crusted scabies. He stated that the crusts had recurred shortly after treatment (Figure 1). The initial differential diagnosis included crusted scabies, pityriasis rubra pilaris, and psoriasis. Scraping from the interdigital web space (Figure 2) revealed multiple scabies mites, scabella, and ova (Figure 3). The patient was diagnosed with crusted scabies. Laboratory test results revealed a normal white blood cell count of 7300/μL, with an elevated eosinophil count of 1900/μL (reference range, <500/μL). Human T-lymphotropic virus 1 (HTLV-1) was found to be positive. Serum protein electrophoresis showed a moderate polyclonal increase in gamma globulins. Treatment was promptly initiated with permethrin cream 5% applied to the whole body for a total of 2 treatments that were administered 7 days apart. Ivermectin also was started at 200 μg/kg and was given on days 1, 7, 14, and 29. Salicylic acid cream 25% was applied daily to help hasten resolution of the crusts.

Human T-lymphotropic virus 1 is endemic to Japan, Central and South America, the Middle East, and regions of Africa and the Caribbean.¹ Multiple cases of HTLV-1 associated with crusted scabies have been reported in endemic areas.^2-6 In the present case, we encountered a patient with crusted scabies and HTLV-1 in a nonendemic area.

Cases of HTLV-1 and crusted scabies have been reported in Brazil, Peru, and Central Australia.^3,4,7 A retrospective study in Brazil showed a notable association between HTLV-1 infection and crusted scabies; of 23 patients with crusted scabies, 21 were HTLV-1 positive.³ In another small study from Peru, 23 patients with crusted scabies were tested for HTLV-1 and 16 (70%) were seropositive.⁴ Neither study had a control group for comparison; however, interestingly, the estimated seroprevalence in the general population (based on blood donors) is only 0.04% to 1% and 1.2% to 1.7% in Brazil and Peru, respectively, thus reinforcing the association between HTLV-1 and crusted scabies.¹ Crusted scabies and HTLV-1 seropositivity acting as a predictor for adult T-cell leukemia/lymphoma (ATL) has been reported⁸ but not consistently.³ Our patient had abnormal serum protein electrophoresis findings. Although the results were not diagnostic of ATL, patients with HTLV-1 are at increased risk for ATL and the pres-ence of this virus is important to document when there is a high index of suspicion for ATL, as with crusted scabies.

Our patient resided in the northeastern United States and there was no evidence in support of underlying immunosuppression. This case of crusted scabies is unique because the patient was HTLV-1 positive without other underlying immunocompromise and he resided in a region where HTLV-1 is nonendemic. In light of these findings, the present case serves as a reminder to check for HTLV-1 infection in those patients with severe or crusted scabies and without an identifiable reason for immunosuppression, even if the patient resides in an area that is nonendemic for HTLV-1.

The Diagnosis: Crusted Scabies

Approximately 1 year prior to presentation the patient completed a course of therapy comprised of repeat doses of ivermectin and permethrin for crusted scabies. He stated that the crusts had recurred shortly after treatment (Figure 1). The initial differential diagnosis included crusted scabies, pityriasis rubra pilaris, and psoriasis. Scraping from the interdigital web space (Figure 2) revealed multiple scabies mites, scabella, and ova (Figure 3). The patient was diagnosed with crusted scabies. Laboratory test results revealed a normal white blood cell count of 7300/μL, with an elevated eosinophil count of 1900/μL (reference range, <500/μL). Human T-lymphotropic virus 1 (HTLV-1) was found to be positive. Serum protein electrophoresis showed a moderate polyclonal increase in gamma globulins. Treatment was promptly initiated with permethrin cream 5% applied to the whole body for a total of 2 treatments that were administered 7 days apart. Ivermectin also was started at 200 μg/kg and was given on days 1, 7, 14, and 29. Salicylic acid cream 25% was applied daily to help hasten resolution of the crusts.

Human T-lymphotropic virus 1 is endemic to Japan, Central and South America, the Middle East, and regions of Africa and the Caribbean.¹ Multiple cases of HTLV-1 associated with crusted scabies have been reported in endemic areas.^2-6 In the present case, we encountered a patient with crusted scabies and HTLV-1 in a nonendemic area.

Cases of HTLV-1 and crusted scabies have been reported in Brazil, Peru, and Central Australia.^3,4,7 A retrospective study in Brazil showed a notable association between HTLV-1 infection and crusted scabies; of 23 patients with crusted scabies, 21 were HTLV-1 positive.³ In another small study from Peru, 23 patients with crusted scabies were tested for HTLV-1 and 16 (70%) were seropositive.⁴ Neither study had a control group for comparison; however, interestingly, the estimated seroprevalence in the general population (based on blood donors) is only 0.04% to 1% and 1.2% to 1.7% in Brazil and Peru, respectively, thus reinforcing the association between HTLV-1 and crusted scabies.¹ Crusted scabies and HTLV-1 seropositivity acting as a predictor for adult T-cell leukemia/lymphoma (ATL) has been reported⁸ but not consistently.³ Our patient had abnormal serum protein electrophoresis findings. Although the results were not diagnostic of ATL, patients with HTLV-1 are at increased risk for ATL and the pres-ence of this virus is important to document when there is a high index of suspicion for ATL, as with crusted scabies.

Our patient resided in the northeastern United States and there was no evidence in support of underlying immunosuppression. This case of crusted scabies is unique because the patient was HTLV-1 positive without other underlying immunocompromise and he resided in a region where HTLV-1 is nonendemic. In light of these findings, the present case serves as a reminder to check for HTLV-1 infection in those patients with severe or crusted scabies and without an identifiable reason for immunosuppression, even if the patient resides in an area that is nonendemic for HTLV-1.

An 81-year-old woman presented for evaluation of a nodule on the right labia majora that had been present for 1 year. She had a history of intertriginous psoriasis, and several biopsies were performed at an outside facility over the last 5 years that revealed psoriasis but were otherwise noncontributory. Physical examination revealed erythema and scaling on the buttocks with maceration in the intertriginous area (top) and the perineum associated with a verrucous nodule (bottom).

The Diagnosis: Verrucous Carcinoma

Biopsies of early lesions often may be difficult to interpret without clinicopathological correlation. Our patient’s tumor was associated with intertriginous psoriasis, which was the only abnormality previously noted on superficial biopsies performed at an outside facility. The patient was scheduled for an excisional biopsy due to the large tumor size and clinical suspicion that the prior biopsies were inadequate and failed to demonstrate the primary underlying pathology. Excisional biopsy of the verrucous tumor revealed epithelium composed of keratinocytes with glassy cytoplasm. Papillomatosis was noted along with an endophytic component of well-differentiated epithelial cells extending into the dermis in a bulbous pattern consistent with the verrucous carcinoma variant of squamous cell carcinoma (SCC)(Figure). Verrucous carcinoma often requires correlation with both the clinical and histopathologic findings for definitive diagnosis, as keratinocytes often appear to be well differentiated.¹

Excisional biopsy of the verrucous nodule revealed marked acanthosis of the epidermis and bulbous projections of epithelium extending into the dermis. The endophytic “pushing border” supported a diagnosis of verrucous carcinoma (H&amp;E, original magnification ×100).

Verrucous carcinoma may begin as an innocuous papule that slowly grows into a large fungating tumor. Verrucous carcinomas typically are slow growing, exophytic, and low grade. The etiology of verrucous carcinoma is not clear, and the role of human papillomavirus (HPV) infection is controversial.² Best classified as a well-differentiated SCC, verrucous carcinoma rarely metastasizes but may invade adjacent tissues.

Differential diagnoses include a giant inflamed seborrheic keratosis, condyloma acuminatum, rupioid psoriasis, and inflammatory linear verrucous epidermal nevus (ILVEN). Although large and inflamed seborrheic keratoses may have squamous eddies that mimic SCC, seborrheic keratoses do not invade the dermis and typically have a well-circumscribed stuck-on appearance. Abnormal mitotic figures are not identified. Condylomas are genital warts caused by HPV infection that often are clustered, well circumscribed, and exophytic. Large lesions can be difficult to distinguish from verrucous carcinomas, and biopsy generally reveals koilocytes identified by perinuclear clearing and raisinlike nuclei. Immunohistochemical staining and in situ hybridization studies can be of value in diagnosis and in identifying those lesions that are at high risk for malignant transformation. High-risk condylomas are associated with HPV-16, HPV-18, HPV-31, HPV-33, HPV-35, and HPV-39, as well as other types, whereas low-risk condylomas are associated with HPV-6, HPV-11, HPV-42, and others.² Differentiating squamous cell hyperplasia from squamous cell carcinoma in situ also can be aided by immunohistochemistry. Squamous cell hyperplasia is usually negative for INK4 p16^Ink4A and p53 and exhibits variable Ki-67 staining. Differentiated squamous cell carcinoma in situ exhibits a profile that is p16^Ink4A negative, Ki-67 positive, and exhibits variable p53 staining.³ Basaloid and warty intraepithelial neoplasia is consistently p16^Ink4A positive, Ki-67 positive, and variably positive for p53.³ Therefore, p16 staining of high-grade areas is a useful biomarker that can help establish diagnosis of associated squamous cell carcinoma.⁴ The role of papillomaviruses in the development of nonmelanoma skin cancer is an area of active study, and research suggests that papillomaviruses may have a much greater role than previously suspected.⁵

At times, psoriasis may be markedly hyperkeratotic, clinically mimicking a verrucous neoplasm. This hyperkeratotic type of psoriasis is known as rupioid psoriasis. However, these psoriatic lesions are exophytic, are associated with spongiform pustules, and lack the atypia and endophytic pattern typically seen with verrucous carcinoma. An ILVEN also lacks atypia and an endophytic pattern and usually presents in childhood as a persistent linear plaque, rather than the verrucous plaque noted in our patient. Squamous cell carcinoma has been reported to arise in the setting of verrucoid ILVEN but is exceptionally uncommon.⁶

Successful treatment of verrucous carcinoma is best achieved by complete excision. Oral retinoids and immunomodulators such as imiquimod also may be of value.⁷ Our patient’s tumor qualifies as T2N0M0 because it was greater than 2 cm in size.⁸ A Breslow thickness of 2 mm or greater and Clark level IV are high-risk features associated with a worse prognosis, but clinical evaluation of our patient’s lymph nodes was unremarkable and no distant metastases were identified. Our patient continues to do well with no evidence of recurrence.

An 81-year-old woman presented for evaluation of a nodule on the right labia majora that had been present for 1 year. She had a history of intertriginous psoriasis, and several biopsies were performed at an outside facility over the last 5 years that revealed psoriasis but were otherwise noncontributory. Physical examination revealed erythema and scaling on the buttocks with maceration in the intertriginous area (top) and the perineum associated with a verrucous nodule (bottom).

The Diagnosis: Verrucous Carcinoma

Biopsies of early lesions often may be difficult to interpret without clinicopathological correlation. Our patient’s tumor was associated with intertriginous psoriasis, which was the only abnormality previously noted on superficial biopsies performed at an outside facility. The patient was scheduled for an excisional biopsy due to the large tumor size and clinical suspicion that the prior biopsies were inadequate and failed to demonstrate the primary underlying pathology. Excisional biopsy of the verrucous tumor revealed epithelium composed of keratinocytes with glassy cytoplasm. Papillomatosis was noted along with an endophytic component of well-differentiated epithelial cells extending into the dermis in a bulbous pattern consistent with the verrucous carcinoma variant of squamous cell carcinoma (SCC)(Figure). Verrucous carcinoma often requires correlation with both the clinical and histopathologic findings for definitive diagnosis, as keratinocytes often appear to be well differentiated.¹

Excisional biopsy of the verrucous nodule revealed marked acanthosis of the epidermis and bulbous projections of epithelium extending into the dermis. The endophytic “pushing border” supported a diagnosis of verrucous carcinoma (H&amp;E, original magnification ×100).

Verrucous carcinoma may begin as an innocuous papule that slowly grows into a large fungating tumor. Verrucous carcinomas typically are slow growing, exophytic, and low grade. The etiology of verrucous carcinoma is not clear, and the role of human papillomavirus (HPV) infection is controversial.² Best classified as a well-differentiated SCC, verrucous carcinoma rarely metastasizes but may invade adjacent tissues.

Differential diagnoses include a giant inflamed seborrheic keratosis, condyloma acuminatum, rupioid psoriasis, and inflammatory linear verrucous epidermal nevus (ILVEN). Although large and inflamed seborrheic keratoses may have squamous eddies that mimic SCC, seborrheic keratoses do not invade the dermis and typically have a well-circumscribed stuck-on appearance. Abnormal mitotic figures are not identified. Condylomas are genital warts caused by HPV infection that often are clustered, well circumscribed, and exophytic. Large lesions can be difficult to distinguish from verrucous carcinomas, and biopsy generally reveals koilocytes identified by perinuclear clearing and raisinlike nuclei. Immunohistochemical staining and in situ hybridization studies can be of value in diagnosis and in identifying those lesions that are at high risk for malignant transformation. High-risk condylomas are associated with HPV-16, HPV-18, HPV-31, HPV-33, HPV-35, and HPV-39, as well as other types, whereas low-risk condylomas are associated with HPV-6, HPV-11, HPV-42, and others.² Differentiating squamous cell hyperplasia from squamous cell carcinoma in situ also can be aided by immunohistochemistry. Squamous cell hyperplasia is usually negative for INK4 p16^Ink4A and p53 and exhibits variable Ki-67 staining. Differentiated squamous cell carcinoma in situ exhibits a profile that is p16^Ink4A negative, Ki-67 positive, and exhibits variable p53 staining.³ Basaloid and warty intraepithelial neoplasia is consistently p16^Ink4A positive, Ki-67 positive, and variably positive for p53.³ Therefore, p16 staining of high-grade areas is a useful biomarker that can help establish diagnosis of associated squamous cell carcinoma.⁴ The role of papillomaviruses in the development of nonmelanoma skin cancer is an area of active study, and research suggests that papillomaviruses may have a much greater role than previously suspected.⁵

At times, psoriasis may be markedly hyperkeratotic, clinically mimicking a verrucous neoplasm. This hyperkeratotic type of psoriasis is known as rupioid psoriasis. However, these psoriatic lesions are exophytic, are associated with spongiform pustules, and lack the atypia and endophytic pattern typically seen with verrucous carcinoma. An ILVEN also lacks atypia and an endophytic pattern and usually presents in childhood as a persistent linear plaque, rather than the verrucous plaque noted in our patient. Squamous cell carcinoma has been reported to arise in the setting of verrucoid ILVEN but is exceptionally uncommon.⁶

Successful treatment of verrucous carcinoma is best achieved by complete excision. Oral retinoids and immunomodulators such as imiquimod also may be of value.⁷ Our patient’s tumor qualifies as T2N0M0 because it was greater than 2 cm in size.⁸ A Breslow thickness of 2 mm or greater and Clark level IV are high-risk features associated with a worse prognosis, but clinical evaluation of our patient’s lymph nodes was unremarkable and no distant metastases were identified. Our patient continues to do well with no evidence of recurrence.

An 81-year-old woman presented for evaluation of a nodule on the right labia majora that had been present for 1 year. She had a history of intertriginous psoriasis, and several biopsies were performed at an outside facility over the last 5 years that revealed psoriasis but were otherwise noncontributory. Physical examination revealed erythema and scaling on the buttocks with maceration in the intertriginous area (top) and the perineum associated with a verrucous nodule (bottom).

The Diagnosis: Verrucous Carcinoma

Biopsies of early lesions often may be difficult to interpret without clinicopathological correlation. Our patient’s tumor was associated with intertriginous psoriasis, which was the only abnormality previously noted on superficial biopsies performed at an outside facility. The patient was scheduled for an excisional biopsy due to the large tumor size and clinical suspicion that the prior biopsies were inadequate and failed to demonstrate the primary underlying pathology. Excisional biopsy of the verrucous tumor revealed epithelium composed of keratinocytes with glassy cytoplasm. Papillomatosis was noted along with an endophytic component of well-differentiated epithelial cells extending into the dermis in a bulbous pattern consistent with the verrucous carcinoma variant of squamous cell carcinoma (SCC)(Figure). Verrucous carcinoma often requires correlation with both the clinical and histopathologic findings for definitive diagnosis, as keratinocytes often appear to be well differentiated.¹

Excisional biopsy of the verrucous nodule revealed marked acanthosis of the epidermis and bulbous projections of epithelium extending into the dermis. The endophytic “pushing border” supported a diagnosis of verrucous carcinoma (H&amp;E, original magnification ×100).

Verrucous carcinoma may begin as an innocuous papule that slowly grows into a large fungating tumor. Verrucous carcinomas typically are slow growing, exophytic, and low grade. The etiology of verrucous carcinoma is not clear, and the role of human papillomavirus (HPV) infection is controversial.² Best classified as a well-differentiated SCC, verrucous carcinoma rarely metastasizes but may invade adjacent tissues.

Differential diagnoses include a giant inflamed seborrheic keratosis, condyloma acuminatum, rupioid psoriasis, and inflammatory linear verrucous epidermal nevus (ILVEN). Although large and inflamed seborrheic keratoses may have squamous eddies that mimic SCC, seborrheic keratoses do not invade the dermis and typically have a well-circumscribed stuck-on appearance. Abnormal mitotic figures are not identified. Condylomas are genital warts caused by HPV infection that often are clustered, well circumscribed, and exophytic. Large lesions can be difficult to distinguish from verrucous carcinomas, and biopsy generally reveals koilocytes identified by perinuclear clearing and raisinlike nuclei. Immunohistochemical staining and in situ hybridization studies can be of value in diagnosis and in identifying those lesions that are at high risk for malignant transformation. High-risk condylomas are associated with HPV-16, HPV-18, HPV-31, HPV-33, HPV-35, and HPV-39, as well as other types, whereas low-risk condylomas are associated with HPV-6, HPV-11, HPV-42, and others.² Differentiating squamous cell hyperplasia from squamous cell carcinoma in situ also can be aided by immunohistochemistry. Squamous cell hyperplasia is usually negative for INK4 p16^Ink4A and p53 and exhibits variable Ki-67 staining. Differentiated squamous cell carcinoma in situ exhibits a profile that is p16^Ink4A negative, Ki-67 positive, and exhibits variable p53 staining.³ Basaloid and warty intraepithelial neoplasia is consistently p16^Ink4A positive, Ki-67 positive, and variably positive for p53.³ Therefore, p16 staining of high-grade areas is a useful biomarker that can help establish diagnosis of associated squamous cell carcinoma.⁴ The role of papillomaviruses in the development of nonmelanoma skin cancer is an area of active study, and research suggests that papillomaviruses may have a much greater role than previously suspected.⁵

At times, psoriasis may be markedly hyperkeratotic, clinically mimicking a verrucous neoplasm. This hyperkeratotic type of psoriasis is known as rupioid psoriasis. However, these psoriatic lesions are exophytic, are associated with spongiform pustules, and lack the atypia and endophytic pattern typically seen with verrucous carcinoma. An ILVEN also lacks atypia and an endophytic pattern and usually presents in childhood as a persistent linear plaque, rather than the verrucous plaque noted in our patient. Squamous cell carcinoma has been reported to arise in the setting of verrucoid ILVEN but is exceptionally uncommon.⁶

Successful treatment of verrucous carcinoma is best achieved by complete excision. Oral retinoids and immunomodulators such as imiquimod also may be of value.⁷ Our patient’s tumor qualifies as T2N0M0 because it was greater than 2 cm in size.⁸ A Breslow thickness of 2 mm or greater and Clark level IV are high-risk features associated with a worse prognosis, but clinical evaluation of our patient’s lymph nodes was unremarkable and no distant metastases were identified. Our patient continues to do well with no evidence of recurrence.

The Diagnosis: Skin Metastases of Vulvar Carcinoma

A Tzanck cytodiagnosis was performed and a punch biopsy specimen was obtained for histologic examination. The patient’s Tzanck cytodiagnosis was initially interpreted as a viral cytopathic effect due to the presence of multinucleated atypical cells; hence, she was treated with intravenous acyclovir. The biopsy specimen showed a preserved epidermis and a dense infiltrate in the mid and deep dermis (Figure 1) formed by atypical squamous cells with enlarged nuclei and anisokaryosis, evident nucleoli, atypical mitoses, and multinucleated cells (Figure 2). The histopathologic diagnosis was skin metastases of moderately differentiated squamous cell carcinoma. The subsequent clinical course was unfavorableand the patient died during hospitalization from septic shock.

Figure 1. Histology revealed a preserved epidermis with a dense infiltrate in the mid and deep dermis (H&E, original magnification ×40).

Figure 2. Atypical squamous cells with enlarged nuclei and anisokaryosis, evident nucleoli, atypical mitoses, and multinucleated cells were evident (H&E, original magnification ×400).

Cutaneous metastases occur in 0.7% to 9% of solid tumors in advanced stages of disease progression or occasionally as an initial manifestation; they are a predictor of poor prognosis and breast cancer is the most frequent cause in women.¹ Vulvar carcinoma comprises 5% of all malignant neoplasms of the female genital tract and 95% are squamous cell carcinoma; metastases appear most frequently in the inguinal and pelvic lymph nodes, followed by the lungs, liver, and bones.² Skin metastases are extremely rare, with few cases documented.^2,3

Clinically, skin metastases present most frequently as nodules, either solitary or multiple, that are sometimes ulcerated. However, a wide spectrum of metastases has been described, including erysipeloid, sclerodermiform (en cuirasse), telangiectatic papulovesicles, purpuric plaques mimicking vasculitis, alopecia areata–like scalp lesions, and others. The zosteriform pattern has been described in few cases, including vesiculobullous herpetiform lesions or nodular metastases with metameric distribution.⁴ In more than half of cases, the lesions were initially interpreted as herpes zoster and hence treated with acyclovir.⁵

Regarding cutaneous metastases of vulvar carcinoma, a case of metastases mimicking primary varicella-zoster virus infection has been reported,³ but our case represents a zosteriform pattern, which is unique.

Multiple theories have been proposed to explain the pathogenic mechanism of zosteriform spread, though none have been adequately proven.^4-7 Some of the patients described in the literature had a history of viral infection by serology or polymerase chain reaction for herpes simplex virus types 1 and 2 and varicella-zoster virus in the same dermatome where metastases were observed. It has been suggested that neural damage caused by the herpesvirus results in an immune function impairment of the overlying skin, which consequently may be more receptive to the inflow of metastatic cells. In such cases, the zosteriform pattern could be due to a Wolf or Köbner phenomenon in an area of vulnerable skin.^4-9

Other possible explanations for the zosteriform spread are the invasion of perineural lymphatic vessels or of the dorsal root ganglion, direct invasion from deeper structures, or the surgical implantation of neoplastic cells,^4-7 though the latter 2 mechanisms do not correspond to true metastases.

The Diagnosis: Skin Metastases of Vulvar Carcinoma

A Tzanck cytodiagnosis was performed and a punch biopsy specimen was obtained for histologic examination. The patient’s Tzanck cytodiagnosis was initially interpreted as a viral cytopathic effect due to the presence of multinucleated atypical cells; hence, she was treated with intravenous acyclovir. The biopsy specimen showed a preserved epidermis and a dense infiltrate in the mid and deep dermis (Figure 1) formed by atypical squamous cells with enlarged nuclei and anisokaryosis, evident nucleoli, atypical mitoses, and multinucleated cells (Figure 2). The histopathologic diagnosis was skin metastases of moderately differentiated squamous cell carcinoma. The subsequent clinical course was unfavorableand the patient died during hospitalization from septic shock.

Figure 1. Histology revealed a preserved epidermis with a dense infiltrate in the mid and deep dermis (H&E, original magnification ×40).

Figure 2. Atypical squamous cells with enlarged nuclei and anisokaryosis, evident nucleoli, atypical mitoses, and multinucleated cells were evident (H&E, original magnification ×400).

Cutaneous metastases occur in 0.7% to 9% of solid tumors in advanced stages of disease progression or occasionally as an initial manifestation; they are a predictor of poor prognosis and breast cancer is the most frequent cause in women.¹ Vulvar carcinoma comprises 5% of all malignant neoplasms of the female genital tract and 95% are squamous cell carcinoma; metastases appear most frequently in the inguinal and pelvic lymph nodes, followed by the lungs, liver, and bones.² Skin metastases are extremely rare, with few cases documented.^2,3

Clinically, skin metastases present most frequently as nodules, either solitary or multiple, that are sometimes ulcerated. However, a wide spectrum of metastases has been described, including erysipeloid, sclerodermiform (en cuirasse), telangiectatic papulovesicles, purpuric plaques mimicking vasculitis, alopecia areata–like scalp lesions, and others. The zosteriform pattern has been described in few cases, including vesiculobullous herpetiform lesions or nodular metastases with metameric distribution.⁴ In more than half of cases, the lesions were initially interpreted as herpes zoster and hence treated with acyclovir.⁵

Regarding cutaneous metastases of vulvar carcinoma, a case of metastases mimicking primary varicella-zoster virus infection has been reported,³ but our case represents a zosteriform pattern, which is unique.

Multiple theories have been proposed to explain the pathogenic mechanism of zosteriform spread, though none have been adequately proven.^4-7 Some of the patients described in the literature had a history of viral infection by serology or polymerase chain reaction for herpes simplex virus types 1 and 2 and varicella-zoster virus in the same dermatome where metastases were observed. It has been suggested that neural damage caused by the herpesvirus results in an immune function impairment of the overlying skin, which consequently may be more receptive to the inflow of metastatic cells. In such cases, the zosteriform pattern could be due to a Wolf or Köbner phenomenon in an area of vulnerable skin.^4-9

Other possible explanations for the zosteriform spread are the invasion of perineural lymphatic vessels or of the dorsal root ganglion, direct invasion from deeper structures, or the surgical implantation of neoplastic cells,^4-7 though the latter 2 mechanisms do not correspond to true metastases.

The Diagnosis: Skin Metastases of Vulvar Carcinoma

A Tzanck cytodiagnosis was performed and a punch biopsy specimen was obtained for histologic examination. The patient’s Tzanck cytodiagnosis was initially interpreted as a viral cytopathic effect due to the presence of multinucleated atypical cells; hence, she was treated with intravenous acyclovir. The biopsy specimen showed a preserved epidermis and a dense infiltrate in the mid and deep dermis (Figure 1) formed by atypical squamous cells with enlarged nuclei and anisokaryosis, evident nucleoli, atypical mitoses, and multinucleated cells (Figure 2). The histopathologic diagnosis was skin metastases of moderately differentiated squamous cell carcinoma. The subsequent clinical course was unfavorableand the patient died during hospitalization from septic shock.

Figure 1. Histology revealed a preserved epidermis with a dense infiltrate in the mid and deep dermis (H&E, original magnification ×40).

Figure 2. Atypical squamous cells with enlarged nuclei and anisokaryosis, evident nucleoli, atypical mitoses, and multinucleated cells were evident (H&E, original magnification ×400).

Cutaneous metastases occur in 0.7% to 9% of solid tumors in advanced stages of disease progression or occasionally as an initial manifestation; they are a predictor of poor prognosis and breast cancer is the most frequent cause in women.¹ Vulvar carcinoma comprises 5% of all malignant neoplasms of the female genital tract and 95% are squamous cell carcinoma; metastases appear most frequently in the inguinal and pelvic lymph nodes, followed by the lungs, liver, and bones.² Skin metastases are extremely rare, with few cases documented.^2,3

Clinically, skin metastases present most frequently as nodules, either solitary or multiple, that are sometimes ulcerated. However, a wide spectrum of metastases has been described, including erysipeloid, sclerodermiform (en cuirasse), telangiectatic papulovesicles, purpuric plaques mimicking vasculitis, alopecia areata–like scalp lesions, and others. The zosteriform pattern has been described in few cases, including vesiculobullous herpetiform lesions or nodular metastases with metameric distribution.⁴ In more than half of cases, the lesions were initially interpreted as herpes zoster and hence treated with acyclovir.⁵

Regarding cutaneous metastases of vulvar carcinoma, a case of metastases mimicking primary varicella-zoster virus infection has been reported,³ but our case represents a zosteriform pattern, which is unique.

Multiple theories have been proposed to explain the pathogenic mechanism of zosteriform spread, though none have been adequately proven.^4-7 Some of the patients described in the literature had a history of viral infection by serology or polymerase chain reaction for herpes simplex virus types 1 and 2 and varicella-zoster virus in the same dermatome where metastases were observed. It has been suggested that neural damage caused by the herpesvirus results in an immune function impairment of the overlying skin, which consequently may be more receptive to the inflow of metastatic cells. In such cases, the zosteriform pattern could be due to a Wolf or Köbner phenomenon in an area of vulnerable skin.^4-9

Other possible explanations for the zosteriform spread are the invasion of perineural lymphatic vessels or of the dorsal root ganglion, direct invasion from deeper structures, or the surgical implantation of neoplastic cells,^4-7 though the latter 2 mechanisms do not correspond to true metastases.