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The Diagnosis: Epidermolysis Bullosa Acquisita  

The diagnosis of epidermolysis bullosa acquisita (EBA) was made based on the clinical and pathologic findings. A blistering disorder that resolves with milia is characteristic of EBA. Hematoxylin and eosin staining demonstrated a pauci-inflammatory separation between the epidermis and dermis (Figure 1). Direct immunofluorescence studies showed linear IgG deposition along the basement membrane zone while C3 was negative (Figure 2). Salt-split skin was essential, as it revealed IgG deposition to the floor of the split (Figure 3), a pattern seen in EBA and not bullous pemphigoid (BP).¹ 

Epidermolysis bullosa acquisita is an acquired autoimmune bullous disorder that results from antibodies to type VII collagen, an anchoring fibril that attaches the lamina densa to the dermis. The epidemiology and etiology of the trigger that leads to antibody production are not well known, but an association between EBA and inflammatory bowel disease has been described.² Although this disease may present in childhood, EBA most commonly is a disorder seen in adults and the elderly. A classic noninflammatory mechanobullous form as well as an inflammatory BP-like form are the most commonly encountered presentations. Light microscopy demonstrates subepidermal cleavage without acantholysis. In the inflammatory BP-like subtype, an inflammatory infiltrate may be present. Direct immunofluorescence is remarkable for a linear band of IgG deposits along the basement membrane zone, with or without C3 deposition in a similar pattern.¹ 

Bullous pemphigoid is within the differential of EBA. It can be difficult to differentiate clinically, especially when a patient has the BP-like variant of EBA because, as the name implies, it mimics BP. Patients with BP often will report a pruritic patch that will then develop into an urticarial plaque. Scarring and milia rarely are seen in BP but can be observed in the multiple presentations of EBA. Hematoxylin and eosin staining and direct immunofluorescence may be almost identical, and differentiating between the 2 disorders can be a challenge. Immunodeposition in EBA occurs in a U-shaped, serrated pattern, while the pattern in BP is N-shaped and serrated.³ Although the U-shaped, serrated pattern is relatively specific, it is not always easy to interpret and requires a high-quality biopsy specimen, which can be difficult to discern with certainty in suboptimal preparations. Another way to differentiate between the 2 entities is to utilize the salt-split skin technique, as performed in our patient. With salt-split skin, the biopsy is placed into a solution of 1 mol/L sodium chloride and incubated at 4 °C (39 °F) for 18 to 24 hours. A blister is then produced at the level of the lamina lucida, which allows for the staining of immunoreactants to occur either above or below that split (commonly referred to as staining on the roof or floor of the blister cavity). With EBA, there is immunoreactant deposition on the floor of the blister, while the opposite occurs in BP.⁴ 

Epidermolysis bullosa simplex is the most common type of epidermolysis bullosa, with keratin genes KRT5 and KRT14 as frequent mutations. Patients develop blisters, vesicles, bullae, and milia on traumatized areas of the body such as the hands, elbows, knees, and feet. This disease presents early in childhood. Histology exhibits a cell-poor subepidermal blister.⁵ With porphyria cutanea tarda, reduced activity of uroporphyrinogen decarboxylase, a major enzyme in the heme synthesis pathway, leads to blisters with erosions and milia on sun-exposed areas of the body. Histologic evaluation reveals a subepidermal pauci-inflammatory vesicle with festooning of the dermal papillae and amphophilic basement membrane within the epidermis. Direct immunofluorescence of porphyria cutanea tarda demonstrates IgM and C3 in the vessels.⁶ Sweet syndrome is a neutrophilic dermatosis that presents as erythematous, edematous, hot, and tender plaques along with fever and leukocytosis. It is associated with myeloproliferative disorders. Biopsy demonstrates papillary dermal edema along with diffuse neutrophilic infiltrate.⁷ 

Numerous medications have been recommended for the treatment of EBA, ranging from steroids to steroid-sparing drugs such as colchicine and dapsone.^8,9 Our patient was educated on physical precautions and was started on dapsone alone due to comorbid diabetes mellitus and renal disease. Within a few weeks of initiating dapsone, he observed a reduction in erythema, and within months he experienced a decrease in blister eruption frequency.  

The Diagnosis: Epidermolysis Bullosa Acquisita  

The diagnosis of epidermolysis bullosa acquisita (EBA) was made based on the clinical and pathologic findings. A blistering disorder that resolves with milia is characteristic of EBA. Hematoxylin and eosin staining demonstrated a pauci-inflammatory separation between the epidermis and dermis (Figure 1). Direct immunofluorescence studies showed linear IgG deposition along the basement membrane zone while C3 was negative (Figure 2). Salt-split skin was essential, as it revealed IgG deposition to the floor of the split (Figure 3), a pattern seen in EBA and not bullous pemphigoid (BP).¹ 

Epidermolysis bullosa acquisita is an acquired autoimmune bullous disorder that results from antibodies to type VII collagen, an anchoring fibril that attaches the lamina densa to the dermis. The epidemiology and etiology of the trigger that leads to antibody production are not well known, but an association between EBA and inflammatory bowel disease has been described.² Although this disease may present in childhood, EBA most commonly is a disorder seen in adults and the elderly. A classic noninflammatory mechanobullous form as well as an inflammatory BP-like form are the most commonly encountered presentations. Light microscopy demonstrates subepidermal cleavage without acantholysis. In the inflammatory BP-like subtype, an inflammatory infiltrate may be present. Direct immunofluorescence is remarkable for a linear band of IgG deposits along the basement membrane zone, with or without C3 deposition in a similar pattern.¹ 

Bullous pemphigoid is within the differential of EBA. It can be difficult to differentiate clinically, especially when a patient has the BP-like variant of EBA because, as the name implies, it mimics BP. Patients with BP often will report a pruritic patch that will then develop into an urticarial plaque. Scarring and milia rarely are seen in BP but can be observed in the multiple presentations of EBA. Hematoxylin and eosin staining and direct immunofluorescence may be almost identical, and differentiating between the 2 disorders can be a challenge. Immunodeposition in EBA occurs in a U-shaped, serrated pattern, while the pattern in BP is N-shaped and serrated.³ Although the U-shaped, serrated pattern is relatively specific, it is not always easy to interpret and requires a high-quality biopsy specimen, which can be difficult to discern with certainty in suboptimal preparations. Another way to differentiate between the 2 entities is to utilize the salt-split skin technique, as performed in our patient. With salt-split skin, the biopsy is placed into a solution of 1 mol/L sodium chloride and incubated at 4 °C (39 °F) for 18 to 24 hours. A blister is then produced at the level of the lamina lucida, which allows for the staining of immunoreactants to occur either above or below that split (commonly referred to as staining on the roof or floor of the blister cavity). With EBA, there is immunoreactant deposition on the floor of the blister, while the opposite occurs in BP.⁴ 

Epidermolysis bullosa simplex is the most common type of epidermolysis bullosa, with keratin genes KRT5 and KRT14 as frequent mutations. Patients develop blisters, vesicles, bullae, and milia on traumatized areas of the body such as the hands, elbows, knees, and feet. This disease presents early in childhood. Histology exhibits a cell-poor subepidermal blister.⁵ With porphyria cutanea tarda, reduced activity of uroporphyrinogen decarboxylase, a major enzyme in the heme synthesis pathway, leads to blisters with erosions and milia on sun-exposed areas of the body. Histologic evaluation reveals a subepidermal pauci-inflammatory vesicle with festooning of the dermal papillae and amphophilic basement membrane within the epidermis. Direct immunofluorescence of porphyria cutanea tarda demonstrates IgM and C3 in the vessels.⁶ Sweet syndrome is a neutrophilic dermatosis that presents as erythematous, edematous, hot, and tender plaques along with fever and leukocytosis. It is associated with myeloproliferative disorders. Biopsy demonstrates papillary dermal edema along with diffuse neutrophilic infiltrate.⁷ 

Numerous medications have been recommended for the treatment of EBA, ranging from steroids to steroid-sparing drugs such as colchicine and dapsone.^8,9 Our patient was educated on physical precautions and was started on dapsone alone due to comorbid diabetes mellitus and renal disease. Within a few weeks of initiating dapsone, he observed a reduction in erythema, and within months he experienced a decrease in blister eruption frequency.  

The Diagnosis: Epidermolysis Bullosa Acquisita  

The diagnosis of epidermolysis bullosa acquisita (EBA) was made based on the clinical and pathologic findings. A blistering disorder that resolves with milia is characteristic of EBA. Hematoxylin and eosin staining demonstrated a pauci-inflammatory separation between the epidermis and dermis (Figure 1). Direct immunofluorescence studies showed linear IgG deposition along the basement membrane zone while C3 was negative (Figure 2). Salt-split skin was essential, as it revealed IgG deposition to the floor of the split (Figure 3), a pattern seen in EBA and not bullous pemphigoid (BP).¹ 

Epidermolysis bullosa acquisita is an acquired autoimmune bullous disorder that results from antibodies to type VII collagen, an anchoring fibril that attaches the lamina densa to the dermis. The epidemiology and etiology of the trigger that leads to antibody production are not well known, but an association between EBA and inflammatory bowel disease has been described.² Although this disease may present in childhood, EBA most commonly is a disorder seen in adults and the elderly. A classic noninflammatory mechanobullous form as well as an inflammatory BP-like form are the most commonly encountered presentations. Light microscopy demonstrates subepidermal cleavage without acantholysis. In the inflammatory BP-like subtype, an inflammatory infiltrate may be present. Direct immunofluorescence is remarkable for a linear band of IgG deposits along the basement membrane zone, with or without C3 deposition in a similar pattern.¹ 

Bullous pemphigoid is within the differential of EBA. It can be difficult to differentiate clinically, especially when a patient has the BP-like variant of EBA because, as the name implies, it mimics BP. Patients with BP often will report a pruritic patch that will then develop into an urticarial plaque. Scarring and milia rarely are seen in BP but can be observed in the multiple presentations of EBA. Hematoxylin and eosin staining and direct immunofluorescence may be almost identical, and differentiating between the 2 disorders can be a challenge. Immunodeposition in EBA occurs in a U-shaped, serrated pattern, while the pattern in BP is N-shaped and serrated.³ Although the U-shaped, serrated pattern is relatively specific, it is not always easy to interpret and requires a high-quality biopsy specimen, which can be difficult to discern with certainty in suboptimal preparations. Another way to differentiate between the 2 entities is to utilize the salt-split skin technique, as performed in our patient. With salt-split skin, the biopsy is placed into a solution of 1 mol/L sodium chloride and incubated at 4 °C (39 °F) for 18 to 24 hours. A blister is then produced at the level of the lamina lucida, which allows for the staining of immunoreactants to occur either above or below that split (commonly referred to as staining on the roof or floor of the blister cavity). With EBA, there is immunoreactant deposition on the floor of the blister, while the opposite occurs in BP.⁴ 

Epidermolysis bullosa simplex is the most common type of epidermolysis bullosa, with keratin genes KRT5 and KRT14 as frequent mutations. Patients develop blisters, vesicles, bullae, and milia on traumatized areas of the body such as the hands, elbows, knees, and feet. This disease presents early in childhood. Histology exhibits a cell-poor subepidermal blister.⁵ With porphyria cutanea tarda, reduced activity of uroporphyrinogen decarboxylase, a major enzyme in the heme synthesis pathway, leads to blisters with erosions and milia on sun-exposed areas of the body. Histologic evaluation reveals a subepidermal pauci-inflammatory vesicle with festooning of the dermal papillae and amphophilic basement membrane within the epidermis. Direct immunofluorescence of porphyria cutanea tarda demonstrates IgM and C3 in the vessels.⁶ Sweet syndrome is a neutrophilic dermatosis that presents as erythematous, edematous, hot, and tender plaques along with fever and leukocytosis. It is associated with myeloproliferative disorders. Biopsy demonstrates papillary dermal edema along with diffuse neutrophilic infiltrate.⁷ 

Numerous medications have been recommended for the treatment of EBA, ranging from steroids to steroid-sparing drugs such as colchicine and dapsone.^8,9 Our patient was educated on physical precautions and was started on dapsone alone due to comorbid diabetes mellitus and renal disease. Within a few weeks of initiating dapsone, he observed a reduction in erythema, and within months he experienced a decrease in blister eruption frequency.  

The Diagnosis: Anetoderma of Prematurity 

Anetoderma is a rare benign cutaneous disorder characterized by atrophic patches of skin due to dermal thinning. The term anetoderma is derived from the Greek words anetos (relaxed) and derma (skin).¹ The physical appearance of the skin is associated with a reduction or loss of elastic tissue in the dermal layer, as seen on histolopathology.²  

Two forms of anetoderma have been described. Primary anetoderma is an idiopathic form with no preceding inflammatory lesions. Secondary anetoderma is a reactive process linked to a known preceding inflammatory, infectious, autoimmune, or drug-induced condition.³ On histopathology, both primary and secondary anetoderma are characterized by a loss of elastic tissue or elastin fibers in the superficial to mid dermis.²  

Anetoderma of prematurity was first described in 1996 by Prizant et al⁴ in 9 extremely premature (24-29 weeks' gestation) infants in neonatal intensive care units (NICUs). Although the exact mechanism behind anetoderma of prematurity is still unknown, Prizant et al⁴ and other investigators⁵ postulated that application of adhesive monitoring leads in the NICU played a role in the development of the lesions. 

Iatrogenic anetoderma of prematurity is clinically characterized by circumscribed areas of either wrinkled macular depression or pouchlike herniations, ranging from flesh-colored to violaceous hues. Lesion size varies from a few millimeters to several centimeters in diameter, and they often are oval or round in shape.² Although not common, it is possible for the atrophic patches to be preceded by an area of ecchymosis without necrosis or atrophy and, if present, they usually evolve within a few days to the characteristic appearance of anetoderma.³ They are found at discrete sites where monitoring leads or other medical devices are commonly placed, such as the forehead, abdomen, chest, and proximal limbs. 

Lesions of anetoderma of prematurity are not present at birth, which distinguishes them from congenital anetoderma.⁶ It is unclear if the lesions are associated with the degree of prematurity, extremely low birth weight, or other associated factors of preterm birth. Although often clinically diagnosed, the diagnosis can be confirmed by a loss of elastic fibers on histopathology when stained with Verhoeff-van Gieson stain.¹ Over time, the atrophic patches have the potential to evolve into herniated forms of anetoderma. Self-healing or improvement of the lesions often does not occur. Although the lesion is benign, it often requires surgical correction later in life for cosmesis.  

Infants in the NICU are at risk for iatrogenic cutaneous injuries, which rarely may include anetoderma. Anetoderma of prematurity has been linked to the use of monitoring leads, adhesive tape, and other medical devices placed on the skin. Prizant et al⁴ postulated that the cause of anetoderma in these infants was irritants such as skin cleansers, urine, or sweat that may be trapped under the electrodes. Other hypotheses include local hypoxemia due to prolonged pressure from the electrodes on immature skin or excessive traction used when removing adhesive tape from the skin.^7,8 Premature infants may be more susceptible to these lesions because of the reduced epidermal thickness of premature skin; immaturity of skin structure; or functional immaturity of elastin deposition regulators, such as elastase, lysyl oxidase, the complement system, and decay-accelerating factor.³ The diagnosis should be differentiated from congenital anetoderma, which also has been described in premature neonates but is characterized by lesions that are present at birth. Its origins are still unclear, despite having histopathologic features similar to iatrogenic anetoderma.⁹  

Focal dermal hypoplasia (FDH) is the hallmark cutaneous finding in Goltz syndrome, a rare set of congenital abnormalities of the skin, oral structures, musculoskeletal system, and central nervous system. Similar to congenital anetoderma, FDH also is characterized by atrophic cutaneous lesions; however, the cutaneous lesions in FDH appear as linear, streaky atrophic lesions often with telangiectasias that follow Blaschko lines.¹⁰ The cutaneous lesions in FDH often are associated with other noncutaneous signs such as polydactyly or asymmetric limbs.¹⁰ Cutis laxa is caused by an abnormality in the elastic tissue resulting in a loose sagging appearance of the skin and frequently results in an aged facial appearance. There are both acquired and inherited forms that can be either solely cutaneous or present with extracutaneous features, such as cardiac abnormalities or emphysema.¹¹ 

In contrast to the atrophic appearance of anetodermas, connective tissue nevi and nevus lipomatosus superficialis present as hamartomas that either can be present at birth or arise in infancy. Connective tissue nevi are hamartomas of dermal connective tissue that consist of excessive production of collagen, elastin, or glycosaminoglycans and appear as slightly elevated, flesh-colored to yellow nodules or plaques.¹² Connective tissue nevi often are described in association with other diseases, most commonly tuberous sclerosis (shagreen patches) or familial cutaneous collagenoma. Nevus lipomatosus superficialis is an asymptomatic connective tissue hamartoma composed of mature adipocytes in the dermis. The lesions consist of clusters of flesh-colored to yellow, soft, rubbery papules or nodules with a smooth or verrucoid surface that do not cross the midline and may follow Blaschko lines.¹¹ 

With advances in neonatal infant medical care, survival of extremely premature infants is increasing, and it is possible that this rare cutaneous disorder may become more prevalent. Care should be taken to avoid unnecessary pressure on surfaces where electrodes are placed and tightly applied adhesive tape. When electrodes are placed on the ventral side, the child should be placed supine; similarly, place electrodes on the dorsal side when the child is lying prone.⁵ A diagnosis of anetoderma of prematurity later in childhood may be difficult, so knowledge and awareness can help guide pediatricians and dermatologists to a correct diagnosis and prevent unnecessary evaluations and/or concerns. 

The Diagnosis: Anetoderma of Prematurity 

Anetoderma is a rare benign cutaneous disorder characterized by atrophic patches of skin due to dermal thinning. The term anetoderma is derived from the Greek words anetos (relaxed) and derma (skin).¹ The physical appearance of the skin is associated with a reduction or loss of elastic tissue in the dermal layer, as seen on histolopathology.²  

Two forms of anetoderma have been described. Primary anetoderma is an idiopathic form with no preceding inflammatory lesions. Secondary anetoderma is a reactive process linked to a known preceding inflammatory, infectious, autoimmune, or drug-induced condition.³ On histopathology, both primary and secondary anetoderma are characterized by a loss of elastic tissue or elastin fibers in the superficial to mid dermis.²  

Anetoderma of prematurity was first described in 1996 by Prizant et al⁴ in 9 extremely premature (24-29 weeks' gestation) infants in neonatal intensive care units (NICUs). Although the exact mechanism behind anetoderma of prematurity is still unknown, Prizant et al⁴ and other investigators⁵ postulated that application of adhesive monitoring leads in the NICU played a role in the development of the lesions. 

Iatrogenic anetoderma of prematurity is clinically characterized by circumscribed areas of either wrinkled macular depression or pouchlike herniations, ranging from flesh-colored to violaceous hues. Lesion size varies from a few millimeters to several centimeters in diameter, and they often are oval or round in shape.² Although not common, it is possible for the atrophic patches to be preceded by an area of ecchymosis without necrosis or atrophy and, if present, they usually evolve within a few days to the characteristic appearance of anetoderma.³ They are found at discrete sites where monitoring leads or other medical devices are commonly placed, such as the forehead, abdomen, chest, and proximal limbs. 

Lesions of anetoderma of prematurity are not present at birth, which distinguishes them from congenital anetoderma.⁶ It is unclear if the lesions are associated with the degree of prematurity, extremely low birth weight, or other associated factors of preterm birth. Although often clinically diagnosed, the diagnosis can be confirmed by a loss of elastic fibers on histopathology when stained with Verhoeff-van Gieson stain.¹ Over time, the atrophic patches have the potential to evolve into herniated forms of anetoderma. Self-healing or improvement of the lesions often does not occur. Although the lesion is benign, it often requires surgical correction later in life for cosmesis.  

Infants in the NICU are at risk for iatrogenic cutaneous injuries, which rarely may include anetoderma. Anetoderma of prematurity has been linked to the use of monitoring leads, adhesive tape, and other medical devices placed on the skin. Prizant et al⁴ postulated that the cause of anetoderma in these infants was irritants such as skin cleansers, urine, or sweat that may be trapped under the electrodes. Other hypotheses include local hypoxemia due to prolonged pressure from the electrodes on immature skin or excessive traction used when removing adhesive tape from the skin.^7,8 Premature infants may be more susceptible to these lesions because of the reduced epidermal thickness of premature skin; immaturity of skin structure; or functional immaturity of elastin deposition regulators, such as elastase, lysyl oxidase, the complement system, and decay-accelerating factor.³ The diagnosis should be differentiated from congenital anetoderma, which also has been described in premature neonates but is characterized by lesions that are present at birth. Its origins are still unclear, despite having histopathologic features similar to iatrogenic anetoderma.⁹  

Focal dermal hypoplasia (FDH) is the hallmark cutaneous finding in Goltz syndrome, a rare set of congenital abnormalities of the skin, oral structures, musculoskeletal system, and central nervous system. Similar to congenital anetoderma, FDH also is characterized by atrophic cutaneous lesions; however, the cutaneous lesions in FDH appear as linear, streaky atrophic lesions often with telangiectasias that follow Blaschko lines.¹⁰ The cutaneous lesions in FDH often are associated with other noncutaneous signs such as polydactyly or asymmetric limbs.¹⁰ Cutis laxa is caused by an abnormality in the elastic tissue resulting in a loose sagging appearance of the skin and frequently results in an aged facial appearance. There are both acquired and inherited forms that can be either solely cutaneous or present with extracutaneous features, such as cardiac abnormalities or emphysema.¹¹ 

In contrast to the atrophic appearance of anetodermas, connective tissue nevi and nevus lipomatosus superficialis present as hamartomas that either can be present at birth or arise in infancy. Connective tissue nevi are hamartomas of dermal connective tissue that consist of excessive production of collagen, elastin, or glycosaminoglycans and appear as slightly elevated, flesh-colored to yellow nodules or plaques.¹² Connective tissue nevi often are described in association with other diseases, most commonly tuberous sclerosis (shagreen patches) or familial cutaneous collagenoma. Nevus lipomatosus superficialis is an asymptomatic connective tissue hamartoma composed of mature adipocytes in the dermis. The lesions consist of clusters of flesh-colored to yellow, soft, rubbery papules or nodules with a smooth or verrucoid surface that do not cross the midline and may follow Blaschko lines.¹¹ 

With advances in neonatal infant medical care, survival of extremely premature infants is increasing, and it is possible that this rare cutaneous disorder may become more prevalent. Care should be taken to avoid unnecessary pressure on surfaces where electrodes are placed and tightly applied adhesive tape. When electrodes are placed on the ventral side, the child should be placed supine; similarly, place electrodes on the dorsal side when the child is lying prone.⁵ A diagnosis of anetoderma of prematurity later in childhood may be difficult, so knowledge and awareness can help guide pediatricians and dermatologists to a correct diagnosis and prevent unnecessary evaluations and/or concerns. 

The Diagnosis: Anetoderma of Prematurity 

Anetoderma is a rare benign cutaneous disorder characterized by atrophic patches of skin due to dermal thinning. The term anetoderma is derived from the Greek words anetos (relaxed) and derma (skin).¹ The physical appearance of the skin is associated with a reduction or loss of elastic tissue in the dermal layer, as seen on histolopathology.²  

Two forms of anetoderma have been described. Primary anetoderma is an idiopathic form with no preceding inflammatory lesions. Secondary anetoderma is a reactive process linked to a known preceding inflammatory, infectious, autoimmune, or drug-induced condition.³ On histopathology, both primary and secondary anetoderma are characterized by a loss of elastic tissue or elastin fibers in the superficial to mid dermis.²  

Anetoderma of prematurity was first described in 1996 by Prizant et al⁴ in 9 extremely premature (24-29 weeks' gestation) infants in neonatal intensive care units (NICUs). Although the exact mechanism behind anetoderma of prematurity is still unknown, Prizant et al⁴ and other investigators⁵ postulated that application of adhesive monitoring leads in the NICU played a role in the development of the lesions. 

Iatrogenic anetoderma of prematurity is clinically characterized by circumscribed areas of either wrinkled macular depression or pouchlike herniations, ranging from flesh-colored to violaceous hues. Lesion size varies from a few millimeters to several centimeters in diameter, and they often are oval or round in shape.² Although not common, it is possible for the atrophic patches to be preceded by an area of ecchymosis without necrosis or atrophy and, if present, they usually evolve within a few days to the characteristic appearance of anetoderma.³ They are found at discrete sites where monitoring leads or other medical devices are commonly placed, such as the forehead, abdomen, chest, and proximal limbs. 

Lesions of anetoderma of prematurity are not present at birth, which distinguishes them from congenital anetoderma.⁶ It is unclear if the lesions are associated with the degree of prematurity, extremely low birth weight, or other associated factors of preterm birth. Although often clinically diagnosed, the diagnosis can be confirmed by a loss of elastic fibers on histopathology when stained with Verhoeff-van Gieson stain.¹ Over time, the atrophic patches have the potential to evolve into herniated forms of anetoderma. Self-healing or improvement of the lesions often does not occur. Although the lesion is benign, it often requires surgical correction later in life for cosmesis.  

Infants in the NICU are at risk for iatrogenic cutaneous injuries, which rarely may include anetoderma. Anetoderma of prematurity has been linked to the use of monitoring leads, adhesive tape, and other medical devices placed on the skin. Prizant et al⁴ postulated that the cause of anetoderma in these infants was irritants such as skin cleansers, urine, or sweat that may be trapped under the electrodes. Other hypotheses include local hypoxemia due to prolonged pressure from the electrodes on immature skin or excessive traction used when removing adhesive tape from the skin.^7,8 Premature infants may be more susceptible to these lesions because of the reduced epidermal thickness of premature skin; immaturity of skin structure; or functional immaturity of elastin deposition regulators, such as elastase, lysyl oxidase, the complement system, and decay-accelerating factor.³ The diagnosis should be differentiated from congenital anetoderma, which also has been described in premature neonates but is characterized by lesions that are present at birth. Its origins are still unclear, despite having histopathologic features similar to iatrogenic anetoderma.⁹  

Focal dermal hypoplasia (FDH) is the hallmark cutaneous finding in Goltz syndrome, a rare set of congenital abnormalities of the skin, oral structures, musculoskeletal system, and central nervous system. Similar to congenital anetoderma, FDH also is characterized by atrophic cutaneous lesions; however, the cutaneous lesions in FDH appear as linear, streaky atrophic lesions often with telangiectasias that follow Blaschko lines.¹⁰ The cutaneous lesions in FDH often are associated with other noncutaneous signs such as polydactyly or asymmetric limbs.¹⁰ Cutis laxa is caused by an abnormality in the elastic tissue resulting in a loose sagging appearance of the skin and frequently results in an aged facial appearance. There are both acquired and inherited forms that can be either solely cutaneous or present with extracutaneous features, such as cardiac abnormalities or emphysema.¹¹ 

In contrast to the atrophic appearance of anetodermas, connective tissue nevi and nevus lipomatosus superficialis present as hamartomas that either can be present at birth or arise in infancy. Connective tissue nevi are hamartomas of dermal connective tissue that consist of excessive production of collagen, elastin, or glycosaminoglycans and appear as slightly elevated, flesh-colored to yellow nodules or plaques.¹² Connective tissue nevi often are described in association with other diseases, most commonly tuberous sclerosis (shagreen patches) or familial cutaneous collagenoma. Nevus lipomatosus superficialis is an asymptomatic connective tissue hamartoma composed of mature adipocytes in the dermis. The lesions consist of clusters of flesh-colored to yellow, soft, rubbery papules or nodules with a smooth or verrucoid surface that do not cross the midline and may follow Blaschko lines.¹¹ 

With advances in neonatal infant medical care, survival of extremely premature infants is increasing, and it is possible that this rare cutaneous disorder may become more prevalent. Care should be taken to avoid unnecessary pressure on surfaces where electrodes are placed and tightly applied adhesive tape. When electrodes are placed on the ventral side, the child should be placed supine; similarly, place electrodes on the dorsal side when the child is lying prone.⁵ A diagnosis of anetoderma of prematurity later in childhood may be difficult, so knowledge and awareness can help guide pediatricians and dermatologists to a correct diagnosis and prevent unnecessary evaluations and/or concerns. 

The Diagnosis: Blastomycosis 

Histopathologic examination of 3 punch biopsies from the left side of the upper lip showed pseudoepitheliomatous hyperplasia with intraepidermal microabscesses and dermal suppurative granulomatous inflammation (Figure 1A). Stains were negative for periodic acid-Schiff, herpes simplex virus, and varicella-zoster virus. Direct and indirect immunofluorescence for skin autoantibodies were negative. Two separate tissue culture specimens showed no bacterial, fungal, or mycobacterial growth. Leishmania polymerase chain reaction and DNA sequencing were negative. An additional punch biopsy revealed yeast forms with broad-based budding and refractile walls (Figures 1B and 1C) that were highlighted with Grocott-Gomori methenamine-silver stain of the tissue (Figure 2). Chest radiography demonstrated no pulmonary involvement. In collaboration with an infectious disease specialist, the patient was started on itraconazole 200 mg twice daily for a total of 6 months.  

Blastomycosis is a fungal infection caused by Blastomyces dermatitidis, a thermally dimorphic fungus endemic in the soils of the Ohio and Mississippi River valleys and southeastern United States.¹ It most commonly manifests as a pulmonary infection following inhalation of spores that are transformed into thick-walled yeasts capable of evading the host's immune system. Unlike other deep fungal infections, blastomycosis occurs in both immunocompetent and immunocompromised hosts. Extrapulmonary disease after hematogenous dissemination from the lungs occurs in approximately 25% to 30% of patients, with the skin as the most common site of dissemination.² Clinically, cutaneous blastomycosis typically starts as papules that evolve into crusted vegetative plaques, often with central clearing or ulceration. Primary cutaneous blastomycosis is rare and occurs due to direct inoculation after trauma to the skin via an infected animal bite, direct inoculation in laboratory settings, or due to injury during outdoor activities involving contact with soil.³ Given our patient's horticultural hobbies, lack of pulmonary symptoms, and negative radiologic examination, primary cutaneous blastomycosis infection due to direct inoculation from contaminated soil was a possibility; however, definite confirmation was difficult, as the primary pulmonary infection of blastomycosis can be asymptomatic and therefore often goes undetected. 

Cutaneous blastomycosis can be mistaken for pemphigus vegetans, leishmaniasis, herpes vegetans, bacterial pyoderma, and other deep fungal infections that also display pseudoepitheliomatous hyperplasia with pyogranulomatous inflammation on histopathology. Direct visualization of the characteristic yeast forms in a histologic specimen or the growth of fungus in culture is essential for a definitive diagnosis. The yeasts are 8 to 15 µm in diameter with thick, double-contoured walls and characteristically display broad-based budding.⁴ This budding pattern aids in differentiating blastomycosis from other entities with a similar histopathologic appearance. Chromoblastomycosis would show brown, thick-walled fungal cells inside giant cells, while coccidioidomycosis displays large spherules containing endospores, and leishmaniasis demonstrates amastigotes (small oval organisms with a bar-shaped kinetoplast) highlighted with Giemsa staining. Pemphigus vegetans would show intercellular deposition of IgG on direct immunofluorescence. Blastomyces dermatitidis can be difficult to visualize with routine hematoxylin and eosin stains, and it is important to note that a negative result does not exclude the possibility of blastomycosis, as demonstrated in our case.⁴ Special stains including Grocott-Gomori methenamine-silver and periodic acid-Schiff can aid in examining tissue for the presence of fungal elements, which typically can be found within histiocytes or abscesses in the dermis. Culture is the most sensitive method for detecting and diagnosing blastomycosis. Growth typically is detected in 5 to 10 days but can take up to 30 days if few organisms are present in the specimen.¹  

Although spontaneous remission can occur, it is recommended that all patients with cutaneous blastomycosis be treated to avoid dissemination and recurrence. Itraconazole currently is the treatment of choice.⁵ Doses typically are 200 to 400 mg/d for 8 to 12 months.⁶ Itraconazole-related side effects experienced by our patient during his 6-month treatment course included leg edema, 20-lb weight gain, gastrointestinal upset, blurred vision, and a transient increase in blood pressure, all resolving once the medication was discontinued. Complete resolution of the lesion was noted at the completion of the treatment course. At a 6-month posttreatment follow-up, residual scarring and alopecia were noted in parts of the previously affected areas of the upper cutaneous lip and nasolabial fold. 

The Diagnosis: Blastomycosis 

Histopathologic examination of 3 punch biopsies from the left side of the upper lip showed pseudoepitheliomatous hyperplasia with intraepidermal microabscesses and dermal suppurative granulomatous inflammation (Figure 1A). Stains were negative for periodic acid-Schiff, herpes simplex virus, and varicella-zoster virus. Direct and indirect immunofluorescence for skin autoantibodies were negative. Two separate tissue culture specimens showed no bacterial, fungal, or mycobacterial growth. Leishmania polymerase chain reaction and DNA sequencing were negative. An additional punch biopsy revealed yeast forms with broad-based budding and refractile walls (Figures 1B and 1C) that were highlighted with Grocott-Gomori methenamine-silver stain of the tissue (Figure 2). Chest radiography demonstrated no pulmonary involvement. In collaboration with an infectious disease specialist, the patient was started on itraconazole 200 mg twice daily for a total of 6 months.  

Blastomycosis is a fungal infection caused by Blastomyces dermatitidis, a thermally dimorphic fungus endemic in the soils of the Ohio and Mississippi River valleys and southeastern United States.¹ It most commonly manifests as a pulmonary infection following inhalation of spores that are transformed into thick-walled yeasts capable of evading the host's immune system. Unlike other deep fungal infections, blastomycosis occurs in both immunocompetent and immunocompromised hosts. Extrapulmonary disease after hematogenous dissemination from the lungs occurs in approximately 25% to 30% of patients, with the skin as the most common site of dissemination.² Clinically, cutaneous blastomycosis typically starts as papules that evolve into crusted vegetative plaques, often with central clearing or ulceration. Primary cutaneous blastomycosis is rare and occurs due to direct inoculation after trauma to the skin via an infected animal bite, direct inoculation in laboratory settings, or due to injury during outdoor activities involving contact with soil.³ Given our patient's horticultural hobbies, lack of pulmonary symptoms, and negative radiologic examination, primary cutaneous blastomycosis infection due to direct inoculation from contaminated soil was a possibility; however, definite confirmation was difficult, as the primary pulmonary infection of blastomycosis can be asymptomatic and therefore often goes undetected. 

Cutaneous blastomycosis can be mistaken for pemphigus vegetans, leishmaniasis, herpes vegetans, bacterial pyoderma, and other deep fungal infections that also display pseudoepitheliomatous hyperplasia with pyogranulomatous inflammation on histopathology. Direct visualization of the characteristic yeast forms in a histologic specimen or the growth of fungus in culture is essential for a definitive diagnosis. The yeasts are 8 to 15 µm in diameter with thick, double-contoured walls and characteristically display broad-based budding.⁴ This budding pattern aids in differentiating blastomycosis from other entities with a similar histopathologic appearance. Chromoblastomycosis would show brown, thick-walled fungal cells inside giant cells, while coccidioidomycosis displays large spherules containing endospores, and leishmaniasis demonstrates amastigotes (small oval organisms with a bar-shaped kinetoplast) highlighted with Giemsa staining. Pemphigus vegetans would show intercellular deposition of IgG on direct immunofluorescence. Blastomyces dermatitidis can be difficult to visualize with routine hematoxylin and eosin stains, and it is important to note that a negative result does not exclude the possibility of blastomycosis, as demonstrated in our case.⁴ Special stains including Grocott-Gomori methenamine-silver and periodic acid-Schiff can aid in examining tissue for the presence of fungal elements, which typically can be found within histiocytes or abscesses in the dermis. Culture is the most sensitive method for detecting and diagnosing blastomycosis. Growth typically is detected in 5 to 10 days but can take up to 30 days if few organisms are present in the specimen.¹  

Although spontaneous remission can occur, it is recommended that all patients with cutaneous blastomycosis be treated to avoid dissemination and recurrence. Itraconazole currently is the treatment of choice.⁵ Doses typically are 200 to 400 mg/d for 8 to 12 months.⁶ Itraconazole-related side effects experienced by our patient during his 6-month treatment course included leg edema, 20-lb weight gain, gastrointestinal upset, blurred vision, and a transient increase in blood pressure, all resolving once the medication was discontinued. Complete resolution of the lesion was noted at the completion of the treatment course. At a 6-month posttreatment follow-up, residual scarring and alopecia were noted in parts of the previously affected areas of the upper cutaneous lip and nasolabial fold. 

The Diagnosis: Blastomycosis 

Histopathologic examination of 3 punch biopsies from the left side of the upper lip showed pseudoepitheliomatous hyperplasia with intraepidermal microabscesses and dermal suppurative granulomatous inflammation (Figure 1A). Stains were negative for periodic acid-Schiff, herpes simplex virus, and varicella-zoster virus. Direct and indirect immunofluorescence for skin autoantibodies were negative. Two separate tissue culture specimens showed no bacterial, fungal, or mycobacterial growth. Leishmania polymerase chain reaction and DNA sequencing were negative. An additional punch biopsy revealed yeast forms with broad-based budding and refractile walls (Figures 1B and 1C) that were highlighted with Grocott-Gomori methenamine-silver stain of the tissue (Figure 2). Chest radiography demonstrated no pulmonary involvement. In collaboration with an infectious disease specialist, the patient was started on itraconazole 200 mg twice daily for a total of 6 months.  

Blastomycosis is a fungal infection caused by Blastomyces dermatitidis, a thermally dimorphic fungus endemic in the soils of the Ohio and Mississippi River valleys and southeastern United States.¹ It most commonly manifests as a pulmonary infection following inhalation of spores that are transformed into thick-walled yeasts capable of evading the host's immune system. Unlike other deep fungal infections, blastomycosis occurs in both immunocompetent and immunocompromised hosts. Extrapulmonary disease after hematogenous dissemination from the lungs occurs in approximately 25% to 30% of patients, with the skin as the most common site of dissemination.² Clinically, cutaneous blastomycosis typically starts as papules that evolve into crusted vegetative plaques, often with central clearing or ulceration. Primary cutaneous blastomycosis is rare and occurs due to direct inoculation after trauma to the skin via an infected animal bite, direct inoculation in laboratory settings, or due to injury during outdoor activities involving contact with soil.³ Given our patient's horticultural hobbies, lack of pulmonary symptoms, and negative radiologic examination, primary cutaneous blastomycosis infection due to direct inoculation from contaminated soil was a possibility; however, definite confirmation was difficult, as the primary pulmonary infection of blastomycosis can be asymptomatic and therefore often goes undetected. 

Cutaneous blastomycosis can be mistaken for pemphigus vegetans, leishmaniasis, herpes vegetans, bacterial pyoderma, and other deep fungal infections that also display pseudoepitheliomatous hyperplasia with pyogranulomatous inflammation on histopathology. Direct visualization of the characteristic yeast forms in a histologic specimen or the growth of fungus in culture is essential for a definitive diagnosis. The yeasts are 8 to 15 µm in diameter with thick, double-contoured walls and characteristically display broad-based budding.⁴ This budding pattern aids in differentiating blastomycosis from other entities with a similar histopathologic appearance. Chromoblastomycosis would show brown, thick-walled fungal cells inside giant cells, while coccidioidomycosis displays large spherules containing endospores, and leishmaniasis demonstrates amastigotes (small oval organisms with a bar-shaped kinetoplast) highlighted with Giemsa staining. Pemphigus vegetans would show intercellular deposition of IgG on direct immunofluorescence. Blastomyces dermatitidis can be difficult to visualize with routine hematoxylin and eosin stains, and it is important to note that a negative result does not exclude the possibility of blastomycosis, as demonstrated in our case.⁴ Special stains including Grocott-Gomori methenamine-silver and periodic acid-Schiff can aid in examining tissue for the presence of fungal elements, which typically can be found within histiocytes or abscesses in the dermis. Culture is the most sensitive method for detecting and diagnosing blastomycosis. Growth typically is detected in 5 to 10 days but can take up to 30 days if few organisms are present in the specimen.¹  

Although spontaneous remission can occur, it is recommended that all patients with cutaneous blastomycosis be treated to avoid dissemination and recurrence. Itraconazole currently is the treatment of choice.⁵ Doses typically are 200 to 400 mg/d for 8 to 12 months.⁶ Itraconazole-related side effects experienced by our patient during his 6-month treatment course included leg edema, 20-lb weight gain, gastrointestinal upset, blurred vision, and a transient increase in blood pressure, all resolving once the medication was discontinued. Complete resolution of the lesion was noted at the completion of the treatment course. At a 6-month posttreatment follow-up, residual scarring and alopecia were noted in parts of the previously affected areas of the upper cutaneous lip and nasolabial fold. 

The Diagnosis: Trigeminal Trophic Syndrome (Self-induced Trauma) 

The patient admitted to manipulation of the ala in response to persistent pain despite resolution of the herpes zoster, for which he recently had completed a course of oral acyclovir. A preliminary diagnosis of trigeminal trophic syndrome (TTS) was made, and a subsequent punch biopsy revealed no evidence of malignancy. Topical antibiotic prophylaxis was prescribed, and he was instructed to avoid manipulation of the affected area. Treatment was initiated in consultation with pain specialists, and over the following 3 years our patient experienced a waxing and waning course of persistent pain complicated by new scalp and oral ulcers as well as alar impetigo. His condition eventually stabilized with tolerable pain on oral gabapentin and doxepin cream 5% applied up to 4 times daily. The alar lesion healed following sufficient abstinence from manipulation, leaving a crescent-shaped rim defect.  

Trigeminal trophic syndrome classically is characterized by a triad of cutaneous anesthesia, paresthesia and/or pain, and ulceration secondary to pathology of trigeminal nerve sensory branches. Ulceration arises primarily through excoriation in response to paresthetic pruritus or pain. The differential diagnosis for TTS includes ulcerating cutaneous neoplasms (eg, basal cell carcinoma); mycobacterial, fungal, and viral infections (especially herpetic lesions); and cutaneous involvement of systemic vasculitides (eg, granulomatosis with polyangiitis).¹ Biopsy is necessary to exclude malignancy, and ulcers may be scraped for viral diagnosis. Complete blood cell count and serologic testing also may help to exclude immunodeficiencies or disorders. Apart from viral neuropathy, common etiologies of TTS include iatrogenic trigeminal injury (eg, in ablation treatment for trigeminal neuralgia) and stroke (eg, lateral medullary syndrome).  

The Diagnosis: Trigeminal Trophic Syndrome (Self-induced Trauma) 

The patient admitted to manipulation of the ala in response to persistent pain despite resolution of the herpes zoster, for which he recently had completed a course of oral acyclovir. A preliminary diagnosis of trigeminal trophic syndrome (TTS) was made, and a subsequent punch biopsy revealed no evidence of malignancy. Topical antibiotic prophylaxis was prescribed, and he was instructed to avoid manipulation of the affected area. Treatment was initiated in consultation with pain specialists, and over the following 3 years our patient experienced a waxing and waning course of persistent pain complicated by new scalp and oral ulcers as well as alar impetigo. His condition eventually stabilized with tolerable pain on oral gabapentin and doxepin cream 5% applied up to 4 times daily. The alar lesion healed following sufficient abstinence from manipulation, leaving a crescent-shaped rim defect.  

Trigeminal trophic syndrome classically is characterized by a triad of cutaneous anesthesia, paresthesia and/or pain, and ulceration secondary to pathology of trigeminal nerve sensory branches. Ulceration arises primarily through excoriation in response to paresthetic pruritus or pain. The differential diagnosis for TTS includes ulcerating cutaneous neoplasms (eg, basal cell carcinoma); mycobacterial, fungal, and viral infections (especially herpetic lesions); and cutaneous involvement of systemic vasculitides (eg, granulomatosis with polyangiitis).¹ Biopsy is necessary to exclude malignancy, and ulcers may be scraped for viral diagnosis. Complete blood cell count and serologic testing also may help to exclude immunodeficiencies or disorders. Apart from viral neuropathy, common etiologies of TTS include iatrogenic trigeminal injury (eg, in ablation treatment for trigeminal neuralgia) and stroke (eg, lateral medullary syndrome).  

The Diagnosis: Trigeminal Trophic Syndrome (Self-induced Trauma) 

The patient admitted to manipulation of the ala in response to persistent pain despite resolution of the herpes zoster, for which he recently had completed a course of oral acyclovir. A preliminary diagnosis of trigeminal trophic syndrome (TTS) was made, and a subsequent punch biopsy revealed no evidence of malignancy. Topical antibiotic prophylaxis was prescribed, and he was instructed to avoid manipulation of the affected area. Treatment was initiated in consultation with pain specialists, and over the following 3 years our patient experienced a waxing and waning course of persistent pain complicated by new scalp and oral ulcers as well as alar impetigo. His condition eventually stabilized with tolerable pain on oral gabapentin and doxepin cream 5% applied up to 4 times daily. The alar lesion healed following sufficient abstinence from manipulation, leaving a crescent-shaped rim defect.  

Trigeminal trophic syndrome classically is characterized by a triad of cutaneous anesthesia, paresthesia and/or pain, and ulceration secondary to pathology of trigeminal nerve sensory branches. Ulceration arises primarily through excoriation in response to paresthetic pruritus or pain. The differential diagnosis for TTS includes ulcerating cutaneous neoplasms (eg, basal cell carcinoma); mycobacterial, fungal, and viral infections (especially herpetic lesions); and cutaneous involvement of systemic vasculitides (eg, granulomatosis with polyangiitis).¹ Biopsy is necessary to exclude malignancy, and ulcers may be scraped for viral diagnosis. Complete blood cell count and serologic testing also may help to exclude immunodeficiencies or disorders. Apart from viral neuropathy, common etiologies of TTS include iatrogenic trigeminal injury (eg, in ablation treatment for trigeminal neuralgia) and stroke (eg, lateral medullary syndrome).  

The Diagnosis: Cutaneous B-cell Lymphoma  

Histopathology was suggestive of cutaneous B-cell lymphoma (Figure). Further immunohistochemical studies including Bcl-6 positivity and Bcl-2 negativity in the large atypical cells supported a diagnosis of primary cutaneous follicle center lymphoma (PCFCL). The designation of primary cutaneous B-cell lymphoma includes several different types of lymphoma, including marginal zone lymphoma, diffuse large B-cell lymphoma, and intravascular lymphoma. To be considered a primary cutaneous lymphoma, there must be evidence of the lymphoma in the skin without concomitant evidence of systemic involvement, as determined through a full staging workup. Primary cutaneous follicle center lymphoma is an indolent lymphoma that most commonly presents as solitary or grouped, pink to plum-colored papules, plaques, nodules, and tumors on the scalp, forehead, or back.¹ The lesions often are biopsied as suspected basal cell carcinomas or Merkel cell carcinomas (MCCs). Lesions on the face or scalp may easily evade diagnosis, as they initially may mimic rosacea or insect bites. Less common presentations include infiltrative lesions that cause rhinophymatous changes or scarring alopecia. Multifocal or disseminated lesions rarely can be observed. This case presentation is unique in its patchy appearance that clinically resembled angiosarcoma.² When identified and treated, the disease-specific 5-year survival rate for PCFCL is greater than 95%.³  

Merkel cell carcinoma was first described in 1972 and has been diagnosed with increasing frequency each year.⁴ It generally presents as an erythematous or violaceous, tender, indurated nodule on sun-exposed skin of the head or neck in elderly White men. However, other presentations have been reported, including papules, plaques, cystlike structures, pruritic tumors, pedunculated lesions, subcutaneous masses, and telangiectatic papules.⁵ Histopathologically, MCC is characterized by dermal nests and sheets of basaloid cells with finely granular salt and pepper-like chromatin. The histologic features can resemble other small blue cell tumors; therefore, the differential diagnosis can be broad.⁵ Immunohistochemistry that can confirm the diagnosis of MCC generally will be positive for cytokeratin 20 and neuroendocrine markers but negative for cytokeratin ⁷ and thyroid transcription factor ¹. Merkel cell carcinoma is an aggressive tumor with a high risk for local recurrence and distant metastasis that carries a generally poor prognosis, especially when there is evidence of metastatic disease at presentation.^5,6  

Rosacea can appear as telangiectatic patches, though generally not as one discrete patch limited to the forehead, as in our patient. Histologic features vary based on the age of the lesion and clinical variant. In early lesions there is a mild perivascular lymphoplasmacytic infiltrate within the dermis, while older lesions can have a mixed infiltrate crowded around vessels and adnexal structures. Granulomas often are seen near hair follicles and interspersed throughout the dermis with ectatic vessels and dermal edema.⁷  

Angiosarcoma is divided into 3 clinicopathological subtypes: idiopathic angiosarcoma of the head and neck, angiosarcoma in the setting of lymphedema, and postirradiation angiosarcoma.⁷ Idiopathic angiosarcoma most closely mimics PCFCL, as it can present as single or multifocal nodules, plaques, or patches. Histologically, the 3 groups appear similar with poorly circumscribed, infiltrative, dermal tumors. The neoplastic endothelial cells have large hyperchromatic nuclei that protrude into vascular lumens. The prognosis for idiopathic angiosarcoma of the head and neck is poor, with a 5-year survival rate of 15% to 34%, which often is due to delayed diagnosis.⁷ 

Pigmented purpuric dermatoses (PPDs) are chronic skin disorders characterized by purpura due to extravasation of blood from capillaries; the resulting hemosiderin deposition leads to pigmentation.⁷ There are various forms of PPD, which are classified into groups based on clinical appearance including Schamberg disease, purpura annularis telangiectodes of Majocchi, pigmented purpuric lichenoid dermatosis of Gougerot and Blum, lichen aureus, and others including eczematid and itching variants, which some consider to be distinct entities. Purpura annularis telangiectodes of Majocchi is the specific PPD that should be included in the clinical differential for PCFCL because it presents as annular patches with telangiectasias. Histologically, PPDs are characterized by a CD4⁺ lymphocytic infiltrate in the upper dermis with extravasated red blood cells and the presence of hemosiderin mostly within macrophages and a lack of true vasculitis. Clonality of the T cells has been shown, and there is some evidence that PPD may overlap with mycosis fungoides. However, this overlap mainly has been seen in patients with widespread lesions and would not apply to this case. In general, patients with PPD can be reassured of the benign process. In cases of widespread PPD, patients should be followed clinically to assess for progression to mycosis fungoides, though the likelihood is low.⁷  

Our patient underwent a full staging workup, which confirmed the diagnosis of PCFCL. He was treated with radiation to the forehead that resulted in clearance of the lesion. Approximately 2 years after the initial diagnosis, the patient was alive and well with no evidence of recurrence of PCFCL. 

In conclusion, it is imperative to identify unusual, macular, vascular-appearing patches, especially on the head and neck in older individuals. Because the clinical presentations of PCFCL, angiosarcoma, rosacea, MCC, and PPD can overlap with one another as well as with other entities, it is necessary to have a high level of suspicion and low threshold to biopsy these types of lesions, as outcomes can be drastically different. 

The Diagnosis: Cutaneous B-cell Lymphoma  

Histopathology was suggestive of cutaneous B-cell lymphoma (Figure). Further immunohistochemical studies including Bcl-6 positivity and Bcl-2 negativity in the large atypical cells supported a diagnosis of primary cutaneous follicle center lymphoma (PCFCL). The designation of primary cutaneous B-cell lymphoma includes several different types of lymphoma, including marginal zone lymphoma, diffuse large B-cell lymphoma, and intravascular lymphoma. To be considered a primary cutaneous lymphoma, there must be evidence of the lymphoma in the skin without concomitant evidence of systemic involvement, as determined through a full staging workup. Primary cutaneous follicle center lymphoma is an indolent lymphoma that most commonly presents as solitary or grouped, pink to plum-colored papules, plaques, nodules, and tumors on the scalp, forehead, or back.¹ The lesions often are biopsied as suspected basal cell carcinomas or Merkel cell carcinomas (MCCs). Lesions on the face or scalp may easily evade diagnosis, as they initially may mimic rosacea or insect bites. Less common presentations include infiltrative lesions that cause rhinophymatous changes or scarring alopecia. Multifocal or disseminated lesions rarely can be observed. This case presentation is unique in its patchy appearance that clinically resembled angiosarcoma.² When identified and treated, the disease-specific 5-year survival rate for PCFCL is greater than 95%.³  

Merkel cell carcinoma was first described in 1972 and has been diagnosed with increasing frequency each year.⁴ It generally presents as an erythematous or violaceous, tender, indurated nodule on sun-exposed skin of the head or neck in elderly White men. However, other presentations have been reported, including papules, plaques, cystlike structures, pruritic tumors, pedunculated lesions, subcutaneous masses, and telangiectatic papules.⁵ Histopathologically, MCC is characterized by dermal nests and sheets of basaloid cells with finely granular salt and pepper-like chromatin. The histologic features can resemble other small blue cell tumors; therefore, the differential diagnosis can be broad.⁵ Immunohistochemistry that can confirm the diagnosis of MCC generally will be positive for cytokeratin 20 and neuroendocrine markers but negative for cytokeratin ⁷ and thyroid transcription factor ¹. Merkel cell carcinoma is an aggressive tumor with a high risk for local recurrence and distant metastasis that carries a generally poor prognosis, especially when there is evidence of metastatic disease at presentation.^5,6  

Rosacea can appear as telangiectatic patches, though generally not as one discrete patch limited to the forehead, as in our patient. Histologic features vary based on the age of the lesion and clinical variant. In early lesions there is a mild perivascular lymphoplasmacytic infiltrate within the dermis, while older lesions can have a mixed infiltrate crowded around vessels and adnexal structures. Granulomas often are seen near hair follicles and interspersed throughout the dermis with ectatic vessels and dermal edema.⁷  

Angiosarcoma is divided into 3 clinicopathological subtypes: idiopathic angiosarcoma of the head and neck, angiosarcoma in the setting of lymphedema, and postirradiation angiosarcoma.⁷ Idiopathic angiosarcoma most closely mimics PCFCL, as it can present as single or multifocal nodules, plaques, or patches. Histologically, the 3 groups appear similar with poorly circumscribed, infiltrative, dermal tumors. The neoplastic endothelial cells have large hyperchromatic nuclei that protrude into vascular lumens. The prognosis for idiopathic angiosarcoma of the head and neck is poor, with a 5-year survival rate of 15% to 34%, which often is due to delayed diagnosis.⁷ 

Pigmented purpuric dermatoses (PPDs) are chronic skin disorders characterized by purpura due to extravasation of blood from capillaries; the resulting hemosiderin deposition leads to pigmentation.⁷ There are various forms of PPD, which are classified into groups based on clinical appearance including Schamberg disease, purpura annularis telangiectodes of Majocchi, pigmented purpuric lichenoid dermatosis of Gougerot and Blum, lichen aureus, and others including eczematid and itching variants, which some consider to be distinct entities. Purpura annularis telangiectodes of Majocchi is the specific PPD that should be included in the clinical differential for PCFCL because it presents as annular patches with telangiectasias. Histologically, PPDs are characterized by a CD4⁺ lymphocytic infiltrate in the upper dermis with extravasated red blood cells and the presence of hemosiderin mostly within macrophages and a lack of true vasculitis. Clonality of the T cells has been shown, and there is some evidence that PPD may overlap with mycosis fungoides. However, this overlap mainly has been seen in patients with widespread lesions and would not apply to this case. In general, patients with PPD can be reassured of the benign process. In cases of widespread PPD, patients should be followed clinically to assess for progression to mycosis fungoides, though the likelihood is low.⁷  

Our patient underwent a full staging workup, which confirmed the diagnosis of PCFCL. He was treated with radiation to the forehead that resulted in clearance of the lesion. Approximately 2 years after the initial diagnosis, the patient was alive and well with no evidence of recurrence of PCFCL. 

In conclusion, it is imperative to identify unusual, macular, vascular-appearing patches, especially on the head and neck in older individuals. Because the clinical presentations of PCFCL, angiosarcoma, rosacea, MCC, and PPD can overlap with one another as well as with other entities, it is necessary to have a high level of suspicion and low threshold to biopsy these types of lesions, as outcomes can be drastically different. 

The Diagnosis: Cutaneous B-cell Lymphoma  

Histopathology was suggestive of cutaneous B-cell lymphoma (Figure). Further immunohistochemical studies including Bcl-6 positivity and Bcl-2 negativity in the large atypical cells supported a diagnosis of primary cutaneous follicle center lymphoma (PCFCL). The designation of primary cutaneous B-cell lymphoma includes several different types of lymphoma, including marginal zone lymphoma, diffuse large B-cell lymphoma, and intravascular lymphoma. To be considered a primary cutaneous lymphoma, there must be evidence of the lymphoma in the skin without concomitant evidence of systemic involvement, as determined through a full staging workup. Primary cutaneous follicle center lymphoma is an indolent lymphoma that most commonly presents as solitary or grouped, pink to plum-colored papules, plaques, nodules, and tumors on the scalp, forehead, or back.¹ The lesions often are biopsied as suspected basal cell carcinomas or Merkel cell carcinomas (MCCs). Lesions on the face or scalp may easily evade diagnosis, as they initially may mimic rosacea or insect bites. Less common presentations include infiltrative lesions that cause rhinophymatous changes or scarring alopecia. Multifocal or disseminated lesions rarely can be observed. This case presentation is unique in its patchy appearance that clinically resembled angiosarcoma.² When identified and treated, the disease-specific 5-year survival rate for PCFCL is greater than 95%.³  

Merkel cell carcinoma was first described in 1972 and has been diagnosed with increasing frequency each year.⁴ It generally presents as an erythematous or violaceous, tender, indurated nodule on sun-exposed skin of the head or neck in elderly White men. However, other presentations have been reported, including papules, plaques, cystlike structures, pruritic tumors, pedunculated lesions, subcutaneous masses, and telangiectatic papules.⁵ Histopathologically, MCC is characterized by dermal nests and sheets of basaloid cells with finely granular salt and pepper-like chromatin. The histologic features can resemble other small blue cell tumors; therefore, the differential diagnosis can be broad.⁵ Immunohistochemistry that can confirm the diagnosis of MCC generally will be positive for cytokeratin 20 and neuroendocrine markers but negative for cytokeratin ⁷ and thyroid transcription factor ¹. Merkel cell carcinoma is an aggressive tumor with a high risk for local recurrence and distant metastasis that carries a generally poor prognosis, especially when there is evidence of metastatic disease at presentation.^5,6  

Rosacea can appear as telangiectatic patches, though generally not as one discrete patch limited to the forehead, as in our patient. Histologic features vary based on the age of the lesion and clinical variant. In early lesions there is a mild perivascular lymphoplasmacytic infiltrate within the dermis, while older lesions can have a mixed infiltrate crowded around vessels and adnexal structures. Granulomas often are seen near hair follicles and interspersed throughout the dermis with ectatic vessels and dermal edema.⁷  

Angiosarcoma is divided into 3 clinicopathological subtypes: idiopathic angiosarcoma of the head and neck, angiosarcoma in the setting of lymphedema, and postirradiation angiosarcoma.⁷ Idiopathic angiosarcoma most closely mimics PCFCL, as it can present as single or multifocal nodules, plaques, or patches. Histologically, the 3 groups appear similar with poorly circumscribed, infiltrative, dermal tumors. The neoplastic endothelial cells have large hyperchromatic nuclei that protrude into vascular lumens. The prognosis for idiopathic angiosarcoma of the head and neck is poor, with a 5-year survival rate of 15% to 34%, which often is due to delayed diagnosis.⁷ 

Pigmented purpuric dermatoses (PPDs) are chronic skin disorders characterized by purpura due to extravasation of blood from capillaries; the resulting hemosiderin deposition leads to pigmentation.⁷ There are various forms of PPD, which are classified into groups based on clinical appearance including Schamberg disease, purpura annularis telangiectodes of Majocchi, pigmented purpuric lichenoid dermatosis of Gougerot and Blum, lichen aureus, and others including eczematid and itching variants, which some consider to be distinct entities. Purpura annularis telangiectodes of Majocchi is the specific PPD that should be included in the clinical differential for PCFCL because it presents as annular patches with telangiectasias. Histologically, PPDs are characterized by a CD4⁺ lymphocytic infiltrate in the upper dermis with extravasated red blood cells and the presence of hemosiderin mostly within macrophages and a lack of true vasculitis. Clonality of the T cells has been shown, and there is some evidence that PPD may overlap with mycosis fungoides. However, this overlap mainly has been seen in patients with widespread lesions and would not apply to this case. In general, patients with PPD can be reassured of the benign process. In cases of widespread PPD, patients should be followed clinically to assess for progression to mycosis fungoides, though the likelihood is low.⁷  

Our patient underwent a full staging workup, which confirmed the diagnosis of PCFCL. He was treated with radiation to the forehead that resulted in clearance of the lesion. Approximately 2 years after the initial diagnosis, the patient was alive and well with no evidence of recurrence of PCFCL. 

In conclusion, it is imperative to identify unusual, macular, vascular-appearing patches, especially on the head and neck in older individuals. Because the clinical presentations of PCFCL, angiosarcoma, rosacea, MCC, and PPD can overlap with one another as well as with other entities, it is necessary to have a high level of suspicion and low threshold to biopsy these types of lesions, as outcomes can be drastically different. 

The Diagnosis: Kaposi Sarcoma 

On initial presentation, the differential diagnosis included secondary syphilis, Kaposi sarcoma (KS), lichen planus pigmentosus, sarcoidosis, and psoriasis. A laboratory workup was ordered, which included complete blood cell count, comprehensive metabolic panel, antinuclear antibodies, anti-Ro/Sjögren syndrome antigen A and anti-La/Sjögren syndrome antigen B autoantibodies, angiotensin-converting enzyme, rapid plasma reagin, and human immunodeficiency virus (HIV) antibodies. A 4-mm punch biopsy of the rash also was performed from the right upper back. Histology revealed a vascular proliferation that was diffusely positive for human herpesvirus 8 (HHV-8)(Figure 1). The patient was informed of the diagnosis, at which time he revealed he had a history of homosexual relationships, with his last sexual contact being more than 1 year prior to presentation. The laboratory workup confirmed a diagnosis of HIV, and the remainder of the tests were unremarkable. 

He was referred to our university's HIV clinic where he was started on highly active antiretroviral therapy (HAART). His facial swelling worsened, leading to hospital admission. Computed tomography (CT) of the chest, abdomen, and pelvis showed diffuse lymphadenopathy and lung nodules concerning for visceral involvement of KS. Hematology and oncology was consulted for further evaluation, and he was treated with 6 cycles of doxorubicin 20 mg/m², which led to resolution of the lung nodules on CT and improvement of the rash burden. He was then started on alitretinoin gel 0.1% twice daily, which led to continued slow improvement (Figure 2). 

Kaposi sarcoma is a vascular neoplasm that occurs from infection with HHV-8. It typically presents as painless, reddish to violaceous macules or patches involving the skin and mucosa that often progress to plaques or nodules with possible visceral involvement. Kaposi sarcoma is classified into 4 subtypes based on epidemiology and clinical presentation: classic, endemic, iatrogenic, and AIDS associated.^1,2  

Classic KS primarily affects elderly males of Mediterranean or Eastern European descent, with a mean age of 64.¹ years and a male to female ratio of 3 to 1. It has an indolent course and a strong predilection for the skin of the lower extremities. The endemic form occurs mainly in Africa and has a more aggressive course, especially the lymphadenopathic type that affects children younger than 10 years.³ Iatrogenic KS develops in immunosuppressed patients, such as transplant recipients, and may regress if the immunosuppressive agent is stopped.¹ Kaposi sarcoma is an AIDS-defining illness and is the most common malignancy in AIDS patients. It is strongly associated with a low CD4 count, which accounts for the notable decline in its incidence after the widespread introduction of HAART.¹ Among HIV patients, KS has the highest incidence in men who have sex with men. This population has a higher seroprevalence of HHV-8, which suggests possible sexual transmission of HHV-8. AIDS-associated KS most commonly involves the lower extremities, face, and oral mucosa. It may have visceral involvement, particularly of the gastrointestinal and respiratory systems, which carries a poor prognosis.^4,5 

Approximately 40% of patients presenting with KS have gastrointestinal tract involvement.⁶ Of these patients, up to 80% are asymptomatic, with diagnosis usually being made on endoscopy.⁷ In contrast, pulmonary KS is less common and typically is symptomatic. It can involve the lung parenchyma, airways, or pleura and is diagnosed by chest radiography or CT scans. Glucocorticoid therapy is a known trigger for pulmonary KS exacerbation.⁸  

All 4 subtypes share the same histopathologic findings consisting of spindled endothelial cell proliferation, inflammation, and angiogenesis. Immunohistochemistry reveals tumor cells that are CD34 and CD31 positive but are factor VIII negative. Staining for HHV-8 antigen is used to confirm the diagnosis. The inflammatory infiltrate predominantly is lymphocytic with scattered plasma cells.⁹  

The laboratory results and histopathologic findings clearly indicated a diagnosis of KS in our patient. Other entities in the clinical differential would have shown notably different histopathologic findings and laboratory results. Lichen planus pigmentosus displays a lichenoid infiltrate and pigment dropout on histology. Histologic findings of psoriasis include psoriasiform acanthosis, dilated vessels in the dermal papillae, thinning of suprapapillary plates, and neutrophilic microabscesses. Sarcoidosis would demonstrate naked granulomas on histopathology. Syphilis displays variable but often psoriasiform or lichenoid findings on histology, and a positive rapid plasma reagin also would be noted.  

First-line treatment of AIDS-related KS is HAART. For patients with severe and rapidly progressive KS or with visceral involvement, cytotoxic chemotherapy with doxorubicin or taxanes often is required. Additional therapies include radiotherapy, topical alitretinoin, and cryotherapy.^1,10 

The Diagnosis: Kaposi Sarcoma 

On initial presentation, the differential diagnosis included secondary syphilis, Kaposi sarcoma (KS), lichen planus pigmentosus, sarcoidosis, and psoriasis. A laboratory workup was ordered, which included complete blood cell count, comprehensive metabolic panel, antinuclear antibodies, anti-Ro/Sjögren syndrome antigen A and anti-La/Sjögren syndrome antigen B autoantibodies, angiotensin-converting enzyme, rapid plasma reagin, and human immunodeficiency virus (HIV) antibodies. A 4-mm punch biopsy of the rash also was performed from the right upper back. Histology revealed a vascular proliferation that was diffusely positive for human herpesvirus 8 (HHV-8)(Figure 1). The patient was informed of the diagnosis, at which time he revealed he had a history of homosexual relationships, with his last sexual contact being more than 1 year prior to presentation. The laboratory workup confirmed a diagnosis of HIV, and the remainder of the tests were unremarkable. 

He was referred to our university's HIV clinic where he was started on highly active antiretroviral therapy (HAART). His facial swelling worsened, leading to hospital admission. Computed tomography (CT) of the chest, abdomen, and pelvis showed diffuse lymphadenopathy and lung nodules concerning for visceral involvement of KS. Hematology and oncology was consulted for further evaluation, and he was treated with 6 cycles of doxorubicin 20 mg/m², which led to resolution of the lung nodules on CT and improvement of the rash burden. He was then started on alitretinoin gel 0.1% twice daily, which led to continued slow improvement (Figure 2). 

Kaposi sarcoma is a vascular neoplasm that occurs from infection with HHV-8. It typically presents as painless, reddish to violaceous macules or patches involving the skin and mucosa that often progress to plaques or nodules with possible visceral involvement. Kaposi sarcoma is classified into 4 subtypes based on epidemiology and clinical presentation: classic, endemic, iatrogenic, and AIDS associated.^1,2  

Classic KS primarily affects elderly males of Mediterranean or Eastern European descent, with a mean age of 64.¹ years and a male to female ratio of 3 to 1. It has an indolent course and a strong predilection for the skin of the lower extremities. The endemic form occurs mainly in Africa and has a more aggressive course, especially the lymphadenopathic type that affects children younger than 10 years.³ Iatrogenic KS develops in immunosuppressed patients, such as transplant recipients, and may regress if the immunosuppressive agent is stopped.¹ Kaposi sarcoma is an AIDS-defining illness and is the most common malignancy in AIDS patients. It is strongly associated with a low CD4 count, which accounts for the notable decline in its incidence after the widespread introduction of HAART.¹ Among HIV patients, KS has the highest incidence in men who have sex with men. This population has a higher seroprevalence of HHV-8, which suggests possible sexual transmission of HHV-8. AIDS-associated KS most commonly involves the lower extremities, face, and oral mucosa. It may have visceral involvement, particularly of the gastrointestinal and respiratory systems, which carries a poor prognosis.^4,5 

Approximately 40% of patients presenting with KS have gastrointestinal tract involvement.⁶ Of these patients, up to 80% are asymptomatic, with diagnosis usually being made on endoscopy.⁷ In contrast, pulmonary KS is less common and typically is symptomatic. It can involve the lung parenchyma, airways, or pleura and is diagnosed by chest radiography or CT scans. Glucocorticoid therapy is a known trigger for pulmonary KS exacerbation.⁸  

All 4 subtypes share the same histopathologic findings consisting of spindled endothelial cell proliferation, inflammation, and angiogenesis. Immunohistochemistry reveals tumor cells that are CD34 and CD31 positive but are factor VIII negative. Staining for HHV-8 antigen is used to confirm the diagnosis. The inflammatory infiltrate predominantly is lymphocytic with scattered plasma cells.⁹  

The laboratory results and histopathologic findings clearly indicated a diagnosis of KS in our patient. Other entities in the clinical differential would have shown notably different histopathologic findings and laboratory results. Lichen planus pigmentosus displays a lichenoid infiltrate and pigment dropout on histology. Histologic findings of psoriasis include psoriasiform acanthosis, dilated vessels in the dermal papillae, thinning of suprapapillary plates, and neutrophilic microabscesses. Sarcoidosis would demonstrate naked granulomas on histopathology. Syphilis displays variable but often psoriasiform or lichenoid findings on histology, and a positive rapid plasma reagin also would be noted.  

First-line treatment of AIDS-related KS is HAART. For patients with severe and rapidly progressive KS or with visceral involvement, cytotoxic chemotherapy with doxorubicin or taxanes often is required. Additional therapies include radiotherapy, topical alitretinoin, and cryotherapy.^1,10 

The Diagnosis: Kaposi Sarcoma 

On initial presentation, the differential diagnosis included secondary syphilis, Kaposi sarcoma (KS), lichen planus pigmentosus, sarcoidosis, and psoriasis. A laboratory workup was ordered, which included complete blood cell count, comprehensive metabolic panel, antinuclear antibodies, anti-Ro/Sjögren syndrome antigen A and anti-La/Sjögren syndrome antigen B autoantibodies, angiotensin-converting enzyme, rapid plasma reagin, and human immunodeficiency virus (HIV) antibodies. A 4-mm punch biopsy of the rash also was performed from the right upper back. Histology revealed a vascular proliferation that was diffusely positive for human herpesvirus 8 (HHV-8)(Figure 1). The patient was informed of the diagnosis, at which time he revealed he had a history of homosexual relationships, with his last sexual contact being more than 1 year prior to presentation. The laboratory workup confirmed a diagnosis of HIV, and the remainder of the tests were unremarkable. 

He was referred to our university's HIV clinic where he was started on highly active antiretroviral therapy (HAART). His facial swelling worsened, leading to hospital admission. Computed tomography (CT) of the chest, abdomen, and pelvis showed diffuse lymphadenopathy and lung nodules concerning for visceral involvement of KS. Hematology and oncology was consulted for further evaluation, and he was treated with 6 cycles of doxorubicin 20 mg/m², which led to resolution of the lung nodules on CT and improvement of the rash burden. He was then started on alitretinoin gel 0.1% twice daily, which led to continued slow improvement (Figure 2). 

Kaposi sarcoma is a vascular neoplasm that occurs from infection with HHV-8. It typically presents as painless, reddish to violaceous macules or patches involving the skin and mucosa that often progress to plaques or nodules with possible visceral involvement. Kaposi sarcoma is classified into 4 subtypes based on epidemiology and clinical presentation: classic, endemic, iatrogenic, and AIDS associated.^1,2  

Classic KS primarily affects elderly males of Mediterranean or Eastern European descent, with a mean age of 64.¹ years and a male to female ratio of 3 to 1. It has an indolent course and a strong predilection for the skin of the lower extremities. The endemic form occurs mainly in Africa and has a more aggressive course, especially the lymphadenopathic type that affects children younger than 10 years.³ Iatrogenic KS develops in immunosuppressed patients, such as transplant recipients, and may regress if the immunosuppressive agent is stopped.¹ Kaposi sarcoma is an AIDS-defining illness and is the most common malignancy in AIDS patients. It is strongly associated with a low CD4 count, which accounts for the notable decline in its incidence after the widespread introduction of HAART.¹ Among HIV patients, KS has the highest incidence in men who have sex with men. This population has a higher seroprevalence of HHV-8, which suggests possible sexual transmission of HHV-8. AIDS-associated KS most commonly involves the lower extremities, face, and oral mucosa. It may have visceral involvement, particularly of the gastrointestinal and respiratory systems, which carries a poor prognosis.^4,5 

Approximately 40% of patients presenting with KS have gastrointestinal tract involvement.⁶ Of these patients, up to 80% are asymptomatic, with diagnosis usually being made on endoscopy.⁷ In contrast, pulmonary KS is less common and typically is symptomatic. It can involve the lung parenchyma, airways, or pleura and is diagnosed by chest radiography or CT scans. Glucocorticoid therapy is a known trigger for pulmonary KS exacerbation.⁸  

All 4 subtypes share the same histopathologic findings consisting of spindled endothelial cell proliferation, inflammation, and angiogenesis. Immunohistochemistry reveals tumor cells that are CD34 and CD31 positive but are factor VIII negative. Staining for HHV-8 antigen is used to confirm the diagnosis. The inflammatory infiltrate predominantly is lymphocytic with scattered plasma cells.⁹  

The laboratory results and histopathologic findings clearly indicated a diagnosis of KS in our patient. Other entities in the clinical differential would have shown notably different histopathologic findings and laboratory results. Lichen planus pigmentosus displays a lichenoid infiltrate and pigment dropout on histology. Histologic findings of psoriasis include psoriasiform acanthosis, dilated vessels in the dermal papillae, thinning of suprapapillary plates, and neutrophilic microabscesses. Sarcoidosis would demonstrate naked granulomas on histopathology. Syphilis displays variable but often psoriasiform or lichenoid findings on histology, and a positive rapid plasma reagin also would be noted.  

First-line treatment of AIDS-related KS is HAART. For patients with severe and rapidly progressive KS or with visceral involvement, cytotoxic chemotherapy with doxorubicin or taxanes often is required. Additional therapies include radiotherapy, topical alitretinoin, and cryotherapy.^1,10 

The Diagnosis: Warty Dyskeratoma 

Warty dyskeratoma (WD) is a benign cutaneous tumor that was first described in 1954 as isolated Darier disease (DD). In 1957, Szymanski¹ renamed it warty dyskeratoma as a distinct condition from DD. Warty dyskeratoma typically presents as a flesh-colored to brownish, round, well-demarcated, and slightly elevated papule or nodule accompanied by an umbilical invagination at the center. It most commonly arises on the scalp, face, or neck.² In contrast to DD, familial occurrence is uncommon. It usually is difficult to distinguish WD from other conditions such as seborrheic keratosis, verruca vulgaris, or keratoacanthoma due to its macroscopic features. Therefore, histopathologic investigation is necessary for a precise diagnosis. 

In our case, histologic investigation revealed a symmetric cup-shaped invagination filled with acantholytic and dyskeratotic keratinocytes with no atypia or mitotic figures (Figure, A). The bottom of the invagination was occupied with numerous villi covered by a single layer of basal cells (Figure, B). At the edge of the invagination, corps ronds and grains were observed in the granular and cornified layers, respectively (Figure, C).

The hallmark histopathologic findings are acantholysis and dyskeratosis just above the basal cell layer, called focal acantholytic dyskeratosis. The differential diagnosis includes other disorders associated with focal acantholytic dyskeratosis, such as DD and acantholytic squamous cell carcinoma.³ Distinguishing WD from DD may be difficult in rare cases with multiple lesions.⁴ In such cases, an autosomal-dominant inheritance pattern and younger age of onset should prompt clinicians to seek for mutations in the ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 gene, ATP2A2, for the diagnosis of DD.⁵ Additionally, the presence of atypia or mitotic figures will rule out malignant disorders such as squamous cell carcinoma.  

Although the pathogenesis of WD is not fully understood, most clinicians consider it a follicular adnexal neoplasm because the lesions often are connected to the pilosebaceous unit on microscopic observation.⁶ Although WD-like lesions arising from the oral mucosa have been reported,⁷ their etiology may be different from WD because the oral mucosa lacks hair follicles.⁸ The term warty leads to speculation of the contribution of human papillomavirus to the pathogenesis of WD, but this has been questioned due to the negative result of viral DNA detection from WD lesions by polymerase chain reaction analysis.² Therefore, the term follicular dyskeratoma has been suggested as a novel denomination that reflects its etiology more precisely.²  

The efficacy of topical treatment has not yet been established. Cryosurgery is another therapeutic option, but it sometimes fails.⁹ As performed in our patient, excisional biopsy is the most reasonable treatment option to obtain both complete removal and precise diagnosis.  
 

The Diagnosis: Warty Dyskeratoma 

Warty dyskeratoma (WD) is a benign cutaneous tumor that was first described in 1954 as isolated Darier disease (DD). In 1957, Szymanski¹ renamed it warty dyskeratoma as a distinct condition from DD. Warty dyskeratoma typically presents as a flesh-colored to brownish, round, well-demarcated, and slightly elevated papule or nodule accompanied by an umbilical invagination at the center. It most commonly arises on the scalp, face, or neck.² In contrast to DD, familial occurrence is uncommon. It usually is difficult to distinguish WD from other conditions such as seborrheic keratosis, verruca vulgaris, or keratoacanthoma due to its macroscopic features. Therefore, histopathologic investigation is necessary for a precise diagnosis. 

In our case, histologic investigation revealed a symmetric cup-shaped invagination filled with acantholytic and dyskeratotic keratinocytes with no atypia or mitotic figures (Figure, A). The bottom of the invagination was occupied with numerous villi covered by a single layer of basal cells (Figure, B). At the edge of the invagination, corps ronds and grains were observed in the granular and cornified layers, respectively (Figure, C).

The hallmark histopathologic findings are acantholysis and dyskeratosis just above the basal cell layer, called focal acantholytic dyskeratosis. The differential diagnosis includes other disorders associated with focal acantholytic dyskeratosis, such as DD and acantholytic squamous cell carcinoma.³ Distinguishing WD from DD may be difficult in rare cases with multiple lesions.⁴ In such cases, an autosomal-dominant inheritance pattern and younger age of onset should prompt clinicians to seek for mutations in the ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 gene, ATP2A2, for the diagnosis of DD.⁵ Additionally, the presence of atypia or mitotic figures will rule out malignant disorders such as squamous cell carcinoma.  

Although the pathogenesis of WD is not fully understood, most clinicians consider it a follicular adnexal neoplasm because the lesions often are connected to the pilosebaceous unit on microscopic observation.⁶ Although WD-like lesions arising from the oral mucosa have been reported,⁷ their etiology may be different from WD because the oral mucosa lacks hair follicles.⁸ The term warty leads to speculation of the contribution of human papillomavirus to the pathogenesis of WD, but this has been questioned due to the negative result of viral DNA detection from WD lesions by polymerase chain reaction analysis.² Therefore, the term follicular dyskeratoma has been suggested as a novel denomination that reflects its etiology more precisely.²  

The efficacy of topical treatment has not yet been established. Cryosurgery is another therapeutic option, but it sometimes fails.⁹ As performed in our patient, excisional biopsy is the most reasonable treatment option to obtain both complete removal and precise diagnosis.  
 

The Diagnosis: Warty Dyskeratoma 

Warty dyskeratoma (WD) is a benign cutaneous tumor that was first described in 1954 as isolated Darier disease (DD). In 1957, Szymanski¹ renamed it warty dyskeratoma as a distinct condition from DD. Warty dyskeratoma typically presents as a flesh-colored to brownish, round, well-demarcated, and slightly elevated papule or nodule accompanied by an umbilical invagination at the center. It most commonly arises on the scalp, face, or neck.² In contrast to DD, familial occurrence is uncommon. It usually is difficult to distinguish WD from other conditions such as seborrheic keratosis, verruca vulgaris, or keratoacanthoma due to its macroscopic features. Therefore, histopathologic investigation is necessary for a precise diagnosis. 

In our case, histologic investigation revealed a symmetric cup-shaped invagination filled with acantholytic and dyskeratotic keratinocytes with no atypia or mitotic figures (Figure, A). The bottom of the invagination was occupied with numerous villi covered by a single layer of basal cells (Figure, B). At the edge of the invagination, corps ronds and grains were observed in the granular and cornified layers, respectively (Figure, C).

The hallmark histopathologic findings are acantholysis and dyskeratosis just above the basal cell layer, called focal acantholytic dyskeratosis. The differential diagnosis includes other disorders associated with focal acantholytic dyskeratosis, such as DD and acantholytic squamous cell carcinoma.³ Distinguishing WD from DD may be difficult in rare cases with multiple lesions.⁴ In such cases, an autosomal-dominant inheritance pattern and younger age of onset should prompt clinicians to seek for mutations in the ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 gene, ATP2A2, for the diagnosis of DD.⁵ Additionally, the presence of atypia or mitotic figures will rule out malignant disorders such as squamous cell carcinoma.  

Although the pathogenesis of WD is not fully understood, most clinicians consider it a follicular adnexal neoplasm because the lesions often are connected to the pilosebaceous unit on microscopic observation.⁶ Although WD-like lesions arising from the oral mucosa have been reported,⁷ their etiology may be different from WD because the oral mucosa lacks hair follicles.⁸ The term warty leads to speculation of the contribution of human papillomavirus to the pathogenesis of WD, but this has been questioned due to the negative result of viral DNA detection from WD lesions by polymerase chain reaction analysis.² Therefore, the term follicular dyskeratoma has been suggested as a novel denomination that reflects its etiology more precisely.²  

The efficacy of topical treatment has not yet been established. Cryosurgery is another therapeutic option, but it sometimes fails.⁹ As performed in our patient, excisional biopsy is the most reasonable treatment option to obtain both complete removal and precise diagnosis.  
 

Punch biopsies from the right axilla (Figure) and right abdomen as well as a tangential biopsy from the left volar wrist papule showed an interstitial histiocytic infiltrate with focal palisading of histiocytes around central regions with collagen alteration and increased mucin. Grocott-Gomori methenamine-silver stain and acid-fast bacilli smear both were negative for organisms; these findings were consistent with a diagnosis of granuloma annulare (GA).

Granuloma annulare is a noninfectious granulomatous disease of unknown etiology. It most commonly appears as asymptomatic, flesh-colored, pink or violaceous annular patches or thin plaques favoring the trunk and extremities. Granuloma annulare has many documented presentations including generalized, patch, subcutaneous, and perforating forms. It can present as macules, papules, nodules, patches, or plaques. Reported associations include diabetes mellitus, hyperlipidemia, solid organ tumors, systemic infection, and thyroid disease.¹ Granuloma annulare can occur in any age group but is most common between the ages of 20 and 40 years.²

Diagnosis most often is made clinically and can be confirmed by histopathology. Histologic examination most commonly shows histiocytes within the dermis that palisade around a central area of mucin deposition between degenerating collagen fibers. The histiocytes of GA stain positive with vimentin, lysozyme, and CD68. The increased mucin stains with colloidal iron and Alcian blue. Multinucleated giant cells and perivascular lymphocytic infiltrate also are commonly seen.³

Cutaneous B-cell lymphoma has a wide range of presentations but usually occurs as hyperpigmented plaques and patches with dermal atrophy. Psoriasis can present in an inverse distribution but will show epidermal changes including scale. Sarcoidosis presents as multiple erythematous plaques and papules and also can be accompanied by erythema nodosum. Tinea corporis likely would have resolved with antifungal treatment.

Many different treatments have been described as effective, including cryosurgery, topical and intralesional corticosteroids, antibiotics, immune modulators, phototherapy, and oral corticosteroids.¹ We started our patient on triple-antibiotic therapy with rifampin 600 mg, minocycline 100 mg, and ofloxacin 400 mg all once monthly for 6 months, which has been shown to be efficacious in treating GA.⁴ The patient returned for follow-up 1 year after the initial presentation. At that time, she had faint pink patches on the waist and medial upper thighs, and the axillary lesions had cleared. In the interim, she developed more classic GA lesions—pink to violaceous smooth papules with no overlying epidermal changes—on the volar wrists and dorsal feet. These lesions were asymptomatic, and she currently is not undergoing any further treatment.

Punch biopsies from the right axilla (Figure) and right abdomen as well as a tangential biopsy from the left volar wrist papule showed an interstitial histiocytic infiltrate with focal palisading of histiocytes around central regions with collagen alteration and increased mucin. Grocott-Gomori methenamine-silver stain and acid-fast bacilli smear both were negative for organisms; these findings were consistent with a diagnosis of granuloma annulare (GA).

Granuloma annulare is a noninfectious granulomatous disease of unknown etiology. It most commonly appears as asymptomatic, flesh-colored, pink or violaceous annular patches or thin plaques favoring the trunk and extremities. Granuloma annulare has many documented presentations including generalized, patch, subcutaneous, and perforating forms. It can present as macules, papules, nodules, patches, or plaques. Reported associations include diabetes mellitus, hyperlipidemia, solid organ tumors, systemic infection, and thyroid disease.¹ Granuloma annulare can occur in any age group but is most common between the ages of 20 and 40 years.²

Diagnosis most often is made clinically and can be confirmed by histopathology. Histologic examination most commonly shows histiocytes within the dermis that palisade around a central area of mucin deposition between degenerating collagen fibers. The histiocytes of GA stain positive with vimentin, lysozyme, and CD68. The increased mucin stains with colloidal iron and Alcian blue. Multinucleated giant cells and perivascular lymphocytic infiltrate also are commonly seen.³

Cutaneous B-cell lymphoma has a wide range of presentations but usually occurs as hyperpigmented plaques and patches with dermal atrophy. Psoriasis can present in an inverse distribution but will show epidermal changes including scale. Sarcoidosis presents as multiple erythematous plaques and papules and also can be accompanied by erythema nodosum. Tinea corporis likely would have resolved with antifungal treatment.

Many different treatments have been described as effective, including cryosurgery, topical and intralesional corticosteroids, antibiotics, immune modulators, phototherapy, and oral corticosteroids.¹ We started our patient on triple-antibiotic therapy with rifampin 600 mg, minocycline 100 mg, and ofloxacin 400 mg all once monthly for 6 months, which has been shown to be efficacious in treating GA.⁴ The patient returned for follow-up 1 year after the initial presentation. At that time, she had faint pink patches on the waist and medial upper thighs, and the axillary lesions had cleared. In the interim, she developed more classic GA lesions—pink to violaceous smooth papules with no overlying epidermal changes—on the volar wrists and dorsal feet. These lesions were asymptomatic, and she currently is not undergoing any further treatment.

Punch biopsies from the right axilla (Figure) and right abdomen as well as a tangential biopsy from the left volar wrist papule showed an interstitial histiocytic infiltrate with focal palisading of histiocytes around central regions with collagen alteration and increased mucin. Grocott-Gomori methenamine-silver stain and acid-fast bacilli smear both were negative for organisms; these findings were consistent with a diagnosis of granuloma annulare (GA).

Granuloma annulare is a noninfectious granulomatous disease of unknown etiology. It most commonly appears as asymptomatic, flesh-colored, pink or violaceous annular patches or thin plaques favoring the trunk and extremities. Granuloma annulare has many documented presentations including generalized, patch, subcutaneous, and perforating forms. It can present as macules, papules, nodules, patches, or plaques. Reported associations include diabetes mellitus, hyperlipidemia, solid organ tumors, systemic infection, and thyroid disease.¹ Granuloma annulare can occur in any age group but is most common between the ages of 20 and 40 years.²

Diagnosis most often is made clinically and can be confirmed by histopathology. Histologic examination most commonly shows histiocytes within the dermis that palisade around a central area of mucin deposition between degenerating collagen fibers. The histiocytes of GA stain positive with vimentin, lysozyme, and CD68. The increased mucin stains with colloidal iron and Alcian blue. Multinucleated giant cells and perivascular lymphocytic infiltrate also are commonly seen.³

Cutaneous B-cell lymphoma has a wide range of presentations but usually occurs as hyperpigmented plaques and patches with dermal atrophy. Psoriasis can present in an inverse distribution but will show epidermal changes including scale. Sarcoidosis presents as multiple erythematous plaques and papules and also can be accompanied by erythema nodosum. Tinea corporis likely would have resolved with antifungal treatment.

Many different treatments have been described as effective, including cryosurgery, topical and intralesional corticosteroids, antibiotics, immune modulators, phototherapy, and oral corticosteroids.¹ We started our patient on triple-antibiotic therapy with rifampin 600 mg, minocycline 100 mg, and ofloxacin 400 mg all once monthly for 6 months, which has been shown to be efficacious in treating GA.⁴ The patient returned for follow-up 1 year after the initial presentation. At that time, she had faint pink patches on the waist and medial upper thighs, and the axillary lesions had cleared. In the interim, she developed more classic GA lesions—pink to violaceous smooth papules with no overlying epidermal changes—on the volar wrists and dorsal feet. These lesions were asymptomatic, and she currently is not undergoing any further treatment.

Dermoscopy showed polylobular, whitish yellow, amorphous structures at the center of the lesion surrounded by a crown of vessels (Figure 1). Histopathology revealed hyperplastic crateriform lesions containing large eosinophilic intracytoplasmic inclusion bodies within keratinocytes (Figure 2). At follow-up 2 weeks after the biopsy, the patient presented with approximately 20 more reddish papules of varying sizes on the abdomen and back that presented as dome-shaped papules and had a typical umbilicated center. The clinical manifestations, dermoscopy, and pathology findings were consistent with molluscum contagiosum (MC).

Molluscum contagiosum was first described in 1814. It is a benign cutaneous infectious disease caused by a double-stranded DNA virus of the poxvirus family. Molluscum contagiosum lesions usually manifest clinically as dome-shaped, flesh-colored or translucent, umbilicated papules measuring 1 to 5 mm in diameter that are commonly distributed over the face, trunk, and extremities and usually are self-limiting.¹

Giant MC is rare and can be seen either in patients on immunosuppressive therapy or in those with diseases that can cause immunosuppression, such as human immunodeficiency virus, leukemia, atopic dermatitis, Wiskott-Aldrich syndrome, and sarcoidosis. In these instances, MC often is greater than 1 cm in diameter. Atypical variants may have an eczematous presentation or a lesion with secondary abscess formation and also can be spread widely over the body.² Due to these atypical appearances and large dimensions in immunocompromised patients, other dermatologic diseases should be considered in the differential diagnosis, such as basal cell carcinoma, keratoacanthoma, squamous cell carcinoma, cutaneous horn, cutaneous cryptococcosis, histoplasmosis, and xanthomatosis.³

In our patient, the differential diagnosis included keratoacanthoma, which may present as a solitary, discrete, round to oval, flesh-colored, umbilicated nodule with a central keratin-filled crater and has a rapid clinical evolution, usually regressing within 4 to 6 months.

Squamous cell carcinoma may appear as scaly red patches, open sores, warts, or elevated growths with a central depression and may crust or bleed. Basal cell carcinoma typically may appear as a dome-shaped skin nodule with visible blood vessels or sometimes presents as a red patch similar to eczema. Xanthomatosis often appears as yellow to orange, mostly asymptomatic, supple patches or plaques, usually with sharp and distinctive edges.

Ancillary diagnostic modalities such as dermoscopy may be used to improve diagnostic accuracy. The best known capillaroscopic feature of MC is the peripheral crown of vessels in a radial distribution. A study of 258 MC lesions highlighted that crown and crown plus radial arrangements are the most common vascular structure patterns under dermoscopy. In addition, polylobular amorphous white structures in the center of the lesions tend to be a feature of larger MC papules.⁴ Histologically, MC shows lobulated crateriform lesions, thickening of the epidermis into the dermis, and the typical appearance of large eosinophilic intracytoplasmic inclusion bodies within keratinocytes.⁵

There are several treatment options available for MC. Common modalities include liquid nitrogen cryospray, curettage, and electrocauterization. In immunocompromised patients, MC lesions usually are resistant to ordinary therapy. The efficacy of topical agents such as imiquimod, which can induce high levels of IFN-α and other cytokines, has been demonstrated in these patients.⁶ Cidofovir, a nucleoside analog that has potent antiviral properties, also can be included as a therapeutic option.³ Our patient’s largest MC lesion was treated with surgical excision, the 2 large lesions on the left side of the chest with cryotherapy, and the other small lesions with curettage.

Dermoscopy showed polylobular, whitish yellow, amorphous structures at the center of the lesion surrounded by a crown of vessels (Figure 1). Histopathology revealed hyperplastic crateriform lesions containing large eosinophilic intracytoplasmic inclusion bodies within keratinocytes (Figure 2). At follow-up 2 weeks after the biopsy, the patient presented with approximately 20 more reddish papules of varying sizes on the abdomen and back that presented as dome-shaped papules and had a typical umbilicated center. The clinical manifestations, dermoscopy, and pathology findings were consistent with molluscum contagiosum (MC).

Molluscum contagiosum was first described in 1814. It is a benign cutaneous infectious disease caused by a double-stranded DNA virus of the poxvirus family. Molluscum contagiosum lesions usually manifest clinically as dome-shaped, flesh-colored or translucent, umbilicated papules measuring 1 to 5 mm in diameter that are commonly distributed over the face, trunk, and extremities and usually are self-limiting.¹

Giant MC is rare and can be seen either in patients on immunosuppressive therapy or in those with diseases that can cause immunosuppression, such as human immunodeficiency virus, leukemia, atopic dermatitis, Wiskott-Aldrich syndrome, and sarcoidosis. In these instances, MC often is greater than 1 cm in diameter. Atypical variants may have an eczematous presentation or a lesion with secondary abscess formation and also can be spread widely over the body.² Due to these atypical appearances and large dimensions in immunocompromised patients, other dermatologic diseases should be considered in the differential diagnosis, such as basal cell carcinoma, keratoacanthoma, squamous cell carcinoma, cutaneous horn, cutaneous cryptococcosis, histoplasmosis, and xanthomatosis.³

In our patient, the differential diagnosis included keratoacanthoma, which may present as a solitary, discrete, round to oval, flesh-colored, umbilicated nodule with a central keratin-filled crater and has a rapid clinical evolution, usually regressing within 4 to 6 months.

Squamous cell carcinoma may appear as scaly red patches, open sores, warts, or elevated growths with a central depression and may crust or bleed. Basal cell carcinoma typically may appear as a dome-shaped skin nodule with visible blood vessels or sometimes presents as a red patch similar to eczema. Xanthomatosis often appears as yellow to orange, mostly asymptomatic, supple patches or plaques, usually with sharp and distinctive edges.

Ancillary diagnostic modalities such as dermoscopy may be used to improve diagnostic accuracy. The best known capillaroscopic feature of MC is the peripheral crown of vessels in a radial distribution. A study of 258 MC lesions highlighted that crown and crown plus radial arrangements are the most common vascular structure patterns under dermoscopy. In addition, polylobular amorphous white structures in the center of the lesions tend to be a feature of larger MC papules.⁴ Histologically, MC shows lobulated crateriform lesions, thickening of the epidermis into the dermis, and the typical appearance of large eosinophilic intracytoplasmic inclusion bodies within keratinocytes.⁵

There are several treatment options available for MC. Common modalities include liquid nitrogen cryospray, curettage, and electrocauterization. In immunocompromised patients, MC lesions usually are resistant to ordinary therapy. The efficacy of topical agents such as imiquimod, which can induce high levels of IFN-α and other cytokines, has been demonstrated in these patients.⁶ Cidofovir, a nucleoside analog that has potent antiviral properties, also can be included as a therapeutic option.³ Our patient’s largest MC lesion was treated with surgical excision, the 2 large lesions on the left side of the chest with cryotherapy, and the other small lesions with curettage.

Dermoscopy showed polylobular, whitish yellow, amorphous structures at the center of the lesion surrounded by a crown of vessels (Figure 1). Histopathology revealed hyperplastic crateriform lesions containing large eosinophilic intracytoplasmic inclusion bodies within keratinocytes (Figure 2). At follow-up 2 weeks after the biopsy, the patient presented with approximately 20 more reddish papules of varying sizes on the abdomen and back that presented as dome-shaped papules and had a typical umbilicated center. The clinical manifestations, dermoscopy, and pathology findings were consistent with molluscum contagiosum (MC).

Molluscum contagiosum was first described in 1814. It is a benign cutaneous infectious disease caused by a double-stranded DNA virus of the poxvirus family. Molluscum contagiosum lesions usually manifest clinically as dome-shaped, flesh-colored or translucent, umbilicated papules measuring 1 to 5 mm in diameter that are commonly distributed over the face, trunk, and extremities and usually are self-limiting.¹

Giant MC is rare and can be seen either in patients on immunosuppressive therapy or in those with diseases that can cause immunosuppression, such as human immunodeficiency virus, leukemia, atopic dermatitis, Wiskott-Aldrich syndrome, and sarcoidosis. In these instances, MC often is greater than 1 cm in diameter. Atypical variants may have an eczematous presentation or a lesion with secondary abscess formation and also can be spread widely over the body.² Due to these atypical appearances and large dimensions in immunocompromised patients, other dermatologic diseases should be considered in the differential diagnosis, such as basal cell carcinoma, keratoacanthoma, squamous cell carcinoma, cutaneous horn, cutaneous cryptococcosis, histoplasmosis, and xanthomatosis.³

In our patient, the differential diagnosis included keratoacanthoma, which may present as a solitary, discrete, round to oval, flesh-colored, umbilicated nodule with a central keratin-filled crater and has a rapid clinical evolution, usually regressing within 4 to 6 months.

Squamous cell carcinoma may appear as scaly red patches, open sores, warts, or elevated growths with a central depression and may crust or bleed. Basal cell carcinoma typically may appear as a dome-shaped skin nodule with visible blood vessels or sometimes presents as a red patch similar to eczema. Xanthomatosis often appears as yellow to orange, mostly asymptomatic, supple patches or plaques, usually with sharp and distinctive edges.

Ancillary diagnostic modalities such as dermoscopy may be used to improve diagnostic accuracy. The best known capillaroscopic feature of MC is the peripheral crown of vessels in a radial distribution. A study of 258 MC lesions highlighted that crown and crown plus radial arrangements are the most common vascular structure patterns under dermoscopy. In addition, polylobular amorphous white structures in the center of the lesions tend to be a feature of larger MC papules.⁴ Histologically, MC shows lobulated crateriform lesions, thickening of the epidermis into the dermis, and the typical appearance of large eosinophilic intracytoplasmic inclusion bodies within keratinocytes.⁵

There are several treatment options available for MC. Common modalities include liquid nitrogen cryospray, curettage, and electrocauterization. In immunocompromised patients, MC lesions usually are resistant to ordinary therapy. The efficacy of topical agents such as imiquimod, which can induce high levels of IFN-α and other cytokines, has been demonstrated in these patients.⁶ Cidofovir, a nucleoside analog that has potent antiviral properties, also can be included as a therapeutic option.³ Our patient’s largest MC lesion was treated with surgical excision, the 2 large lesions on the left side of the chest with cryotherapy, and the other small lesions with curettage.

The Diagnosis: Monilethrix

Trichoscopy showed a beaded appearance of the hair shafts (Figure, A). Light microscopy demonstrated normal medullated nodes of hair coupled with internodal, thin, nonmedullated hair at regular intervals (Figure, B). Clinical and trichoscopic findings led to a diagnosis of monilethrix.

Monilethrix is a genetic hair disorder characterized by regular periodic thinning of the hair shafts, giving the strands a beaded appearance. The hair tends to break at these constricted parts, resulting in short hairs. Nodosities represent the normal hair shaft, whereas the constricted points are the site of the defect. The hair tends to be normal at birth and then becomes short, fragile, and brittle within months, leading to hypotrichosis, particularly on the occipital scalp.¹ Monilethrix also may involve the eyebrows and eyelashes in addition to scalp hair. Follicular hyperkeratotic papules with perifollicular erythema frequently are noted on the occipital area. Monilethrix can be inherited in an autosomal-dominant fashion with mutations involving KRT81, KRT83, and KRT86, which code for the type II hair keratins Hb1, Hb3, and Hb6, respectively. The autosomal-recessive form is caused by mutations in the DSG4 gene, coding for the desmoglein 4 protein.2 Trichoscopy or light microscopy is essential to establish a diagnosis of monilethrix. Trichoscopy is an easy and rapid tool that is utilized to illustrate the beaded appearance of the hair shafts.³ Light microscopy shows the distinctive nodes that are medullated, with a normal hair diameter alternating with the internodes, or constrictions, that are nonmedullated and represent the sites of fracture.¹ Monilethrix can improve by puberty. There is no definitive treatment; however, some patients show considerable improvement on minoxidil.⁴ Treatment with minoxidil was initiated in this patient; however, she was lost to follow-up.

Genetic hair disorders are rare and can be an isolated phenomenon or part of concurrent genetic syndromes. Therefore, thorough clinical examination of other ectodermal structures such as the nails and teeth is crucial as well as obtaining a detailed family history and review of systems to exclude other syndromes.² Hypotrichosis simplex is characterized by hair loss exclusively on the scalp, sparing other ectodermal structures and with no systemic abnormalities. Ectodermal dysplasia is a heterogeneous group of disorders affecting not only the hair but also the teeth, nails, and sweat glands.² Pili torti is another rare genetic hair disorder that is characterized by twisting of the hair fiber on its own axis. It presents clinically as sparse, depigmented, lusterless hair that is easily broken. Light microscopy demonstrates twists of hair at irregular intervals. Pili annulati is characterized by bright and dark bands when viewed with reflected light. Unlike monilethrix, there is no fragility, and the hair can grow long.⁵

The Diagnosis: Monilethrix

Trichoscopy showed a beaded appearance of the hair shafts (Figure, A). Light microscopy demonstrated normal medullated nodes of hair coupled with internodal, thin, nonmedullated hair at regular intervals (Figure, B). Clinical and trichoscopic findings led to a diagnosis of monilethrix.

Monilethrix is a genetic hair disorder characterized by regular periodic thinning of the hair shafts, giving the strands a beaded appearance. The hair tends to break at these constricted parts, resulting in short hairs. Nodosities represent the normal hair shaft, whereas the constricted points are the site of the defect. The hair tends to be normal at birth and then becomes short, fragile, and brittle within months, leading to hypotrichosis, particularly on the occipital scalp.¹ Monilethrix also may involve the eyebrows and eyelashes in addition to scalp hair. Follicular hyperkeratotic papules with perifollicular erythema frequently are noted on the occipital area. Monilethrix can be inherited in an autosomal-dominant fashion with mutations involving KRT81, KRT83, and KRT86, which code for the type II hair keratins Hb1, Hb3, and Hb6, respectively. The autosomal-recessive form is caused by mutations in the DSG4 gene, coding for the desmoglein 4 protein.2 Trichoscopy or light microscopy is essential to establish a diagnosis of monilethrix. Trichoscopy is an easy and rapid tool that is utilized to illustrate the beaded appearance of the hair shafts.³ Light microscopy shows the distinctive nodes that are medullated, with a normal hair diameter alternating with the internodes, or constrictions, that are nonmedullated and represent the sites of fracture.¹ Monilethrix can improve by puberty. There is no definitive treatment; however, some patients show considerable improvement on minoxidil.⁴ Treatment with minoxidil was initiated in this patient; however, she was lost to follow-up.

Genetic hair disorders are rare and can be an isolated phenomenon or part of concurrent genetic syndromes. Therefore, thorough clinical examination of other ectodermal structures such as the nails and teeth is crucial as well as obtaining a detailed family history and review of systems to exclude other syndromes.² Hypotrichosis simplex is characterized by hair loss exclusively on the scalp, sparing other ectodermal structures and with no systemic abnormalities. Ectodermal dysplasia is a heterogeneous group of disorders affecting not only the hair but also the teeth, nails, and sweat glands.² Pili torti is another rare genetic hair disorder that is characterized by twisting of the hair fiber on its own axis. It presents clinically as sparse, depigmented, lusterless hair that is easily broken. Light microscopy demonstrates twists of hair at irregular intervals. Pili annulati is characterized by bright and dark bands when viewed with reflected light. Unlike monilethrix, there is no fragility, and the hair can grow long.⁵

The Diagnosis: Monilethrix

Trichoscopy showed a beaded appearance of the hair shafts (Figure, A). Light microscopy demonstrated normal medullated nodes of hair coupled with internodal, thin, nonmedullated hair at regular intervals (Figure, B). Clinical and trichoscopic findings led to a diagnosis of monilethrix.

Monilethrix is a genetic hair disorder characterized by regular periodic thinning of the hair shafts, giving the strands a beaded appearance. The hair tends to break at these constricted parts, resulting in short hairs. Nodosities represent the normal hair shaft, whereas the constricted points are the site of the defect. The hair tends to be normal at birth and then becomes short, fragile, and brittle within months, leading to hypotrichosis, particularly on the occipital scalp.¹ Monilethrix also may involve the eyebrows and eyelashes in addition to scalp hair. Follicular hyperkeratotic papules with perifollicular erythema frequently are noted on the occipital area. Monilethrix can be inherited in an autosomal-dominant fashion with mutations involving KRT81, KRT83, and KRT86, which code for the type II hair keratins Hb1, Hb3, and Hb6, respectively. The autosomal-recessive form is caused by mutations in the DSG4 gene, coding for the desmoglein 4 protein.2 Trichoscopy or light microscopy is essential to establish a diagnosis of monilethrix. Trichoscopy is an easy and rapid tool that is utilized to illustrate the beaded appearance of the hair shafts.³ Light microscopy shows the distinctive nodes that are medullated, with a normal hair diameter alternating with the internodes, or constrictions, that are nonmedullated and represent the sites of fracture.¹ Monilethrix can improve by puberty. There is no definitive treatment; however, some patients show considerable improvement on minoxidil.⁴ Treatment with minoxidil was initiated in this patient; however, she was lost to follow-up.

Genetic hair disorders are rare and can be an isolated phenomenon or part of concurrent genetic syndromes. Therefore, thorough clinical examination of other ectodermal structures such as the nails and teeth is crucial as well as obtaining a detailed family history and review of systems to exclude other syndromes.² Hypotrichosis simplex is characterized by hair loss exclusively on the scalp, sparing other ectodermal structures and with no systemic abnormalities. Ectodermal dysplasia is a heterogeneous group of disorders affecting not only the hair but also the teeth, nails, and sweat glands.² Pili torti is another rare genetic hair disorder that is characterized by twisting of the hair fiber on its own axis. It presents clinically as sparse, depigmented, lusterless hair that is easily broken. Light microscopy demonstrates twists of hair at irregular intervals. Pili annulati is characterized by bright and dark bands when viewed with reflected light. Unlike monilethrix, there is no fragility, and the hair can grow long.⁵