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The Diagnosis: Cutaneous Deposits Of Myeloma

Cutaneous deposits of myeloma are a rare skin manifestation of multiple myeloma that typically occur in less than 5% of patients.^1,2 The lesions represent monoclonal proliferations of plasma cells and arise from direct extension of a neoplastic mass or less commonly from hematogenous or lymphatic spread. This secondary cutaneous involvement by plasma cell myeloma has been referred to in the literature as metastatic or extramedullary cutaneous plasmacytoma.^1,2 This condition must be distinguished from cutaneous plasma cell infiltrates without underlying bone marrow involvement, classified by the World Health Organization as primary cutaneous marginal zone B-cell lymphoma and previously referred to as primary cutaneous plasmacytoma.³

Clinically, cutaneous deposits of myeloma manifest as erythematous to violaceous papules, plaques, or nodules with a smooth surface and firm consistency.^1,2 The lesions typically occur on the trunk and less commonly on the head, neck, arms, and legs. In a review of  83 cases of metastatic cutaneous plasmacytoma and primary cutaneous plasmacytoma in multiple myeloma, Kato et al⁴ found that 52% (43/83) of cases occurred in IgG myelomas and 23% (19/83) in IgA myelomas.

In our patient, a 4-mm punch biopsy of an umbilical plaque demonstrated a dense infiltrate of atypical plasmacytoid cells through the full thickness of the dermis with nuclear pleomorphism, prominent nucleoli, and frequent mitoses (Figure 1). Immunohistochemical staining was positive for IgA λ light chain (Figure 2A) and CD138 (Figure 2B) and was negative for CD20, which was consistent with the patient's known plasma cell myeloma. Positron emission tomography revealed progression of underlying disease compared to prior studies with hypermetabolic mediastinal, retroperitoneal, and pelvic side wall lymphadenopathy, as well as extensive hypermetabolic soft tissue masses with involvement of the periumbilical region.

The differential diagnosis for violaceous periumbilical plaques includes cutaneous marginal zone B-cell lymphoma (primary or secondary) or T-cell lymphoma (primary or secondary), cutaneous metastases from solid organ or hematologic malignancies (eg, Sister Mary Joseph nodule), AIDS-associated Kaposi sarcoma (plum-colored plaques that may be extensive), and cutaneous endometriosis (umbilical nodules that may develop in women after surgical excision of endometrial tissue).

The mainstay of therapy for secondary cutaneous involvement of plasma cell myeloma includes treatment with chemotherapy and local radiotherapy.^1,2,5 After the diagnosis of cutaneous deposits of myeloma was made in our patient, he was treated with bortezomib, cyclophosphamide with dexamethasone, and local radiotherapy to symptomatic bony lesions; however, he was unresponsive to therapy and the disease progressed with numerous extramedullary lesions of the mediastinum, gastrointestinal tract, and retroperitoneum 2 months later. The patient developed hydronephrosis from external renal compression necessitating nephrostomy tube and malignant pleural effusions requiring intubation. He experienced rapid clinical decline and died 3 months after the initial presentation due to multiorgan failure.

Cutaneous deposits of myeloma are a sign of underlying disease progression in plasma cell myeloma and often herald a fulminant course (eg, death within 12 months of presentation), as seen in our patient.⁵ Clinicians should be aware of this rare manifestation of plasma cell myeloma and pursue aggressive therapy given the poor prognostic nature of these cutaneous findings.

The Diagnosis: Cutaneous Deposits Of Myeloma

Cutaneous deposits of myeloma are a rare skin manifestation of multiple myeloma that typically occur in less than 5% of patients.^1,2 The lesions represent monoclonal proliferations of plasma cells and arise from direct extension of a neoplastic mass or less commonly from hematogenous or lymphatic spread. This secondary cutaneous involvement by plasma cell myeloma has been referred to in the literature as metastatic or extramedullary cutaneous plasmacytoma.^1,2 This condition must be distinguished from cutaneous plasma cell infiltrates without underlying bone marrow involvement, classified by the World Health Organization as primary cutaneous marginal zone B-cell lymphoma and previously referred to as primary cutaneous plasmacytoma.³

Clinically, cutaneous deposits of myeloma manifest as erythematous to violaceous papules, plaques, or nodules with a smooth surface and firm consistency.^1,2 The lesions typically occur on the trunk and less commonly on the head, neck, arms, and legs. In a review of  83 cases of metastatic cutaneous plasmacytoma and primary cutaneous plasmacytoma in multiple myeloma, Kato et al⁴ found that 52% (43/83) of cases occurred in IgG myelomas and 23% (19/83) in IgA myelomas.

In our patient, a 4-mm punch biopsy of an umbilical plaque demonstrated a dense infiltrate of atypical plasmacytoid cells through the full thickness of the dermis with nuclear pleomorphism, prominent nucleoli, and frequent mitoses (Figure 1). Immunohistochemical staining was positive for IgA λ light chain (Figure 2A) and CD138 (Figure 2B) and was negative for CD20, which was consistent with the patient's known plasma cell myeloma. Positron emission tomography revealed progression of underlying disease compared to prior studies with hypermetabolic mediastinal, retroperitoneal, and pelvic side wall lymphadenopathy, as well as extensive hypermetabolic soft tissue masses with involvement of the periumbilical region.

The differential diagnosis for violaceous periumbilical plaques includes cutaneous marginal zone B-cell lymphoma (primary or secondary) or T-cell lymphoma (primary or secondary), cutaneous metastases from solid organ or hematologic malignancies (eg, Sister Mary Joseph nodule), AIDS-associated Kaposi sarcoma (plum-colored plaques that may be extensive), and cutaneous endometriosis (umbilical nodules that may develop in women after surgical excision of endometrial tissue).

The mainstay of therapy for secondary cutaneous involvement of plasma cell myeloma includes treatment with chemotherapy and local radiotherapy.^1,2,5 After the diagnosis of cutaneous deposits of myeloma was made in our patient, he was treated with bortezomib, cyclophosphamide with dexamethasone, and local radiotherapy to symptomatic bony lesions; however, he was unresponsive to therapy and the disease progressed with numerous extramedullary lesions of the mediastinum, gastrointestinal tract, and retroperitoneum 2 months later. The patient developed hydronephrosis from external renal compression necessitating nephrostomy tube and malignant pleural effusions requiring intubation. He experienced rapid clinical decline and died 3 months after the initial presentation due to multiorgan failure.

Cutaneous deposits of myeloma are a sign of underlying disease progression in plasma cell myeloma and often herald a fulminant course (eg, death within 12 months of presentation), as seen in our patient.⁵ Clinicians should be aware of this rare manifestation of plasma cell myeloma and pursue aggressive therapy given the poor prognostic nature of these cutaneous findings.

The Diagnosis: Cutaneous Deposits Of Myeloma

Cutaneous deposits of myeloma are a rare skin manifestation of multiple myeloma that typically occur in less than 5% of patients.^1,2 The lesions represent monoclonal proliferations of plasma cells and arise from direct extension of a neoplastic mass or less commonly from hematogenous or lymphatic spread. This secondary cutaneous involvement by plasma cell myeloma has been referred to in the literature as metastatic or extramedullary cutaneous plasmacytoma.^1,2 This condition must be distinguished from cutaneous plasma cell infiltrates without underlying bone marrow involvement, classified by the World Health Organization as primary cutaneous marginal zone B-cell lymphoma and previously referred to as primary cutaneous plasmacytoma.³

Clinically, cutaneous deposits of myeloma manifest as erythematous to violaceous papules, plaques, or nodules with a smooth surface and firm consistency.^1,2 The lesions typically occur on the trunk and less commonly on the head, neck, arms, and legs. In a review of  83 cases of metastatic cutaneous plasmacytoma and primary cutaneous plasmacytoma in multiple myeloma, Kato et al⁴ found that 52% (43/83) of cases occurred in IgG myelomas and 23% (19/83) in IgA myelomas.

In our patient, a 4-mm punch biopsy of an umbilical plaque demonstrated a dense infiltrate of atypical plasmacytoid cells through the full thickness of the dermis with nuclear pleomorphism, prominent nucleoli, and frequent mitoses (Figure 1). Immunohistochemical staining was positive for IgA λ light chain (Figure 2A) and CD138 (Figure 2B) and was negative for CD20, which was consistent with the patient's known plasma cell myeloma. Positron emission tomography revealed progression of underlying disease compared to prior studies with hypermetabolic mediastinal, retroperitoneal, and pelvic side wall lymphadenopathy, as well as extensive hypermetabolic soft tissue masses with involvement of the periumbilical region.

The differential diagnosis for violaceous periumbilical plaques includes cutaneous marginal zone B-cell lymphoma (primary or secondary) or T-cell lymphoma (primary or secondary), cutaneous metastases from solid organ or hematologic malignancies (eg, Sister Mary Joseph nodule), AIDS-associated Kaposi sarcoma (plum-colored plaques that may be extensive), and cutaneous endometriosis (umbilical nodules that may develop in women after surgical excision of endometrial tissue).

The mainstay of therapy for secondary cutaneous involvement of plasma cell myeloma includes treatment with chemotherapy and local radiotherapy.^1,2,5 After the diagnosis of cutaneous deposits of myeloma was made in our patient, he was treated with bortezomib, cyclophosphamide with dexamethasone, and local radiotherapy to symptomatic bony lesions; however, he was unresponsive to therapy and the disease progressed with numerous extramedullary lesions of the mediastinum, gastrointestinal tract, and retroperitoneum 2 months later. The patient developed hydronephrosis from external renal compression necessitating nephrostomy tube and malignant pleural effusions requiring intubation. He experienced rapid clinical decline and died 3 months after the initial presentation due to multiorgan failure.

Cutaneous deposits of myeloma are a sign of underlying disease progression in plasma cell myeloma and often herald a fulminant course (eg, death within 12 months of presentation), as seen in our patient.⁵ Clinicians should be aware of this rare manifestation of plasma cell myeloma and pursue aggressive therapy given the poor prognostic nature of these cutaneous findings.

The Diagnosis: Glochid Dermatitis

Biopsy of a nodule on the upper right arm showed chronic granulomatous inflammation and polarizable foreign material consistent with plant cellulose (Figure). A diagnosis of glochid dermatitis was made. The treatment plan included follow-up skin evaluation and punch excision of persistent papules 1 month after the initial presentation. The patient reported the rash began after he fell on a cactus plant while chasing his grandson. He was seen by various clinicians and was given hydrocortisone and clobetasol, which helped with pruritis but did not resolve the rash. His grandson developed a similar rash at the site of contact with the cactus plant. The patient and his grandson did not detect the presence of any cactus spines.

Injuries from cactus glochids most often occur due to accidental falls on cactus plants, but glochids also may be transferred from clothing to other individuals. The thin, hairlike glochids easily detach from the stem of the cactus and can become deeply embedded with virtually no pressure.¹

Glochid implantation from the prickly pear cactus commonly presents as a pruritic papular eruption known as glochid dermatitis. These penetrating injuries can lead to inoculation of Clostridium tetani and Staphylococcus aureus. Additionally, unrecognized and unremoved cactus spines may be highly inflammatory and may cause chronic granulomatous inflammation.²

Initially, acute glochid dermatitis occurs due to mechanical damage caused by the detatched cactus spine and may not resolve for up to 4 months. Granuloma formation has been reported several weeks after exposure and may persist for more than 8 months.³ Although an immune mechanism has been suggested, the literature has indicated that delayed hypersensitivity reactions are a more probable cause of the granulomatous inflammation after glochid exposure.³ Madkan et al⁴ reported that relatively few patients developed granulomas after implantation of glochids in the skin, thus suggesting that granuloma formation is an allergic response.

With regard to the pathogenesis of glochid dermatitis, the initial response to foreign plant matter in the dermis involves a neutrophilic infiltrate, which later is replaced by histiocytes; however, the foreign material remains undegraded in the macrophage cytoplasm.⁵ Activated macrophages secrete cytokines that intensify the inflammatory response, resulting in formation of a granuloma around the foreign body. The granuloma acts as a wall to isolate the foreign matter from the rest of the body.⁵

Regarding treatment of chronic granulomas, Madkan et al⁴ reported a case that showed some improvement with clobetasol ointment; however, clinical lesions resolved only after punch biopsies were performed to confirm the diagnosis of cactus spine granuloma. In a controlled study in rabbits, glochids were successfully removed by first detaching the larger clumps with tweezers then applying glue and gauze to the affected area.⁶ After the glue dried, the gauze was peeled off, resulting in the removal of 95% of the implanted glochids. Overall, removal of embedded spines is difficult because the glochids typically radiate in several directions.⁷ Treatment of foreign body granulomas caused by cactus spines can be achieved by expulsion of plant matter remnants and symptomatic treatment using midpotency topical steroids twice daily.⁴ Uncovering and performing punch biopsies of papules also can result in rapid healing of the lesions. Without manual removal of the glochid, lesions can persist for 2 to 8 months until gradual resolution with possible postinflammatory hyperpigmentation.⁴

The Diagnosis: Glochid Dermatitis

Biopsy of a nodule on the upper right arm showed chronic granulomatous inflammation and polarizable foreign material consistent with plant cellulose (Figure). A diagnosis of glochid dermatitis was made. The treatment plan included follow-up skin evaluation and punch excision of persistent papules 1 month after the initial presentation. The patient reported the rash began after he fell on a cactus plant while chasing his grandson. He was seen by various clinicians and was given hydrocortisone and clobetasol, which helped with pruritis but did not resolve the rash. His grandson developed a similar rash at the site of contact with the cactus plant. The patient and his grandson did not detect the presence of any cactus spines.

Injuries from cactus glochids most often occur due to accidental falls on cactus plants, but glochids also may be transferred from clothing to other individuals. The thin, hairlike glochids easily detach from the stem of the cactus and can become deeply embedded with virtually no pressure.¹

Glochid implantation from the prickly pear cactus commonly presents as a pruritic papular eruption known as glochid dermatitis. These penetrating injuries can lead to inoculation of Clostridium tetani and Staphylococcus aureus. Additionally, unrecognized and unremoved cactus spines may be highly inflammatory and may cause chronic granulomatous inflammation.²

Initially, acute glochid dermatitis occurs due to mechanical damage caused by the detatched cactus spine and may not resolve for up to 4 months. Granuloma formation has been reported several weeks after exposure and may persist for more than 8 months.³ Although an immune mechanism has been suggested, the literature has indicated that delayed hypersensitivity reactions are a more probable cause of the granulomatous inflammation after glochid exposure.³ Madkan et al⁴ reported that relatively few patients developed granulomas after implantation of glochids in the skin, thus suggesting that granuloma formation is an allergic response.

With regard to the pathogenesis of glochid dermatitis, the initial response to foreign plant matter in the dermis involves a neutrophilic infiltrate, which later is replaced by histiocytes; however, the foreign material remains undegraded in the macrophage cytoplasm.⁵ Activated macrophages secrete cytokines that intensify the inflammatory response, resulting in formation of a granuloma around the foreign body. The granuloma acts as a wall to isolate the foreign matter from the rest of the body.⁵

Regarding treatment of chronic granulomas, Madkan et al⁴ reported a case that showed some improvement with clobetasol ointment; however, clinical lesions resolved only after punch biopsies were performed to confirm the diagnosis of cactus spine granuloma. In a controlled study in rabbits, glochids were successfully removed by first detaching the larger clumps with tweezers then applying glue and gauze to the affected area.⁶ After the glue dried, the gauze was peeled off, resulting in the removal of 95% of the implanted glochids. Overall, removal of embedded spines is difficult because the glochids typically radiate in several directions.⁷ Treatment of foreign body granulomas caused by cactus spines can be achieved by expulsion of plant matter remnants and symptomatic treatment using midpotency topical steroids twice daily.⁴ Uncovering and performing punch biopsies of papules also can result in rapid healing of the lesions. Without manual removal of the glochid, lesions can persist for 2 to 8 months until gradual resolution with possible postinflammatory hyperpigmentation.⁴

The Diagnosis: Glochid Dermatitis

Biopsy of a nodule on the upper right arm showed chronic granulomatous inflammation and polarizable foreign material consistent with plant cellulose (Figure). A diagnosis of glochid dermatitis was made. The treatment plan included follow-up skin evaluation and punch excision of persistent papules 1 month after the initial presentation. The patient reported the rash began after he fell on a cactus plant while chasing his grandson. He was seen by various clinicians and was given hydrocortisone and clobetasol, which helped with pruritis but did not resolve the rash. His grandson developed a similar rash at the site of contact with the cactus plant. The patient and his grandson did not detect the presence of any cactus spines.

Injuries from cactus glochids most often occur due to accidental falls on cactus plants, but glochids also may be transferred from clothing to other individuals. The thin, hairlike glochids easily detach from the stem of the cactus and can become deeply embedded with virtually no pressure.¹

Glochid implantation from the prickly pear cactus commonly presents as a pruritic papular eruption known as glochid dermatitis. These penetrating injuries can lead to inoculation of Clostridium tetani and Staphylococcus aureus. Additionally, unrecognized and unremoved cactus spines may be highly inflammatory and may cause chronic granulomatous inflammation.²

Initially, acute glochid dermatitis occurs due to mechanical damage caused by the detatched cactus spine and may not resolve for up to 4 months. Granuloma formation has been reported several weeks after exposure and may persist for more than 8 months.³ Although an immune mechanism has been suggested, the literature has indicated that delayed hypersensitivity reactions are a more probable cause of the granulomatous inflammation after glochid exposure.³ Madkan et al⁴ reported that relatively few patients developed granulomas after implantation of glochids in the skin, thus suggesting that granuloma formation is an allergic response.

With regard to the pathogenesis of glochid dermatitis, the initial response to foreign plant matter in the dermis involves a neutrophilic infiltrate, which later is replaced by histiocytes; however, the foreign material remains undegraded in the macrophage cytoplasm.⁵ Activated macrophages secrete cytokines that intensify the inflammatory response, resulting in formation of a granuloma around the foreign body. The granuloma acts as a wall to isolate the foreign matter from the rest of the body.⁵

Regarding treatment of chronic granulomas, Madkan et al⁴ reported a case that showed some improvement with clobetasol ointment; however, clinical lesions resolved only after punch biopsies were performed to confirm the diagnosis of cactus spine granuloma. In a controlled study in rabbits, glochids were successfully removed by first detaching the larger clumps with tweezers then applying glue and gauze to the affected area.⁶ After the glue dried, the gauze was peeled off, resulting in the removal of 95% of the implanted glochids. Overall, removal of embedded spines is difficult because the glochids typically radiate in several directions.⁷ Treatment of foreign body granulomas caused by cactus spines can be achieved by expulsion of plant matter remnants and symptomatic treatment using midpotency topical steroids twice daily.⁴ Uncovering and performing punch biopsies of papules also can result in rapid healing of the lesions. Without manual removal of the glochid, lesions can persist for 2 to 8 months until gradual resolution with possible postinflammatory hyperpigmentation.⁴

The Diagnosis: Bullous Scabies

Scabies infection is caused by the mite Sarcoptes scabiei var hominis. It is commonly transmitted via direct skin-to-skin contact.¹ Classic manifestations include pruritus that worsens at night. It commonly presents with burrows and papules in the interdigital web spaces, as well as flexor surfaces of the wrists, elbows, axillae, buttocks, and genitalia. Pruritus occurs from infestation and delayed hypersensitivity reaction to mites. The recommended treatment of classic scabies is permethrin cream 5% for all occupants of the household and a repeat application for just the patients in 1 week. Posttreatment pruritus can last up to 3 weeks.² At-risk populations include school-aged children and patients in long-term care facilities.

In our case, bullous lesions in a classic distribution with potassium hydroxide preparation of a scabietic mite (Figure) confirmed the diagnosis of bullous scabies. Treatment of bullous scabies is the same as classic scabies. Both patients were treated with 1 application of permethrin cream 5% before we evaluated them. We instructed to repeat application in 7 days for both boys and all family members.

Bullae may be secondary to hypersensitivity response³ or superinfection with Staphylococcus aureus causing bullous impetigo.⁴ Bullous scabies may present a diagnostic challenge and requires a high index of suspicion. Although childhood bullous pemphigoid can involve the palms and soles, patients usually present in infancy. Diagnoses such as dyshidrotic eczema and bullous tinea can present with pustules on the hands and feet; however, involvement of the genitalia would be uncommon.

The Diagnosis: Bullous Scabies

Scabies infection is caused by the mite Sarcoptes scabiei var hominis. It is commonly transmitted via direct skin-to-skin contact.¹ Classic manifestations include pruritus that worsens at night. It commonly presents with burrows and papules in the interdigital web spaces, as well as flexor surfaces of the wrists, elbows, axillae, buttocks, and genitalia. Pruritus occurs from infestation and delayed hypersensitivity reaction to mites. The recommended treatment of classic scabies is permethrin cream 5% for all occupants of the household and a repeat application for just the patients in 1 week. Posttreatment pruritus can last up to 3 weeks.² At-risk populations include school-aged children and patients in long-term care facilities.

In our case, bullous lesions in a classic distribution with potassium hydroxide preparation of a scabietic mite (Figure) confirmed the diagnosis of bullous scabies. Treatment of bullous scabies is the same as classic scabies. Both patients were treated with 1 application of permethrin cream 5% before we evaluated them. We instructed to repeat application in 7 days for both boys and all family members.

Bullae may be secondary to hypersensitivity response³ or superinfection with Staphylococcus aureus causing bullous impetigo.⁴ Bullous scabies may present a diagnostic challenge and requires a high index of suspicion. Although childhood bullous pemphigoid can involve the palms and soles, patients usually present in infancy. Diagnoses such as dyshidrotic eczema and bullous tinea can present with pustules on the hands and feet; however, involvement of the genitalia would be uncommon.

The Diagnosis: Bullous Scabies

Scabies infection is caused by the mite Sarcoptes scabiei var hominis. It is commonly transmitted via direct skin-to-skin contact.¹ Classic manifestations include pruritus that worsens at night. It commonly presents with burrows and papules in the interdigital web spaces, as well as flexor surfaces of the wrists, elbows, axillae, buttocks, and genitalia. Pruritus occurs from infestation and delayed hypersensitivity reaction to mites. The recommended treatment of classic scabies is permethrin cream 5% for all occupants of the household and a repeat application for just the patients in 1 week. Posttreatment pruritus can last up to 3 weeks.² At-risk populations include school-aged children and patients in long-term care facilities.

In our case, bullous lesions in a classic distribution with potassium hydroxide preparation of a scabietic mite (Figure) confirmed the diagnosis of bullous scabies. Treatment of bullous scabies is the same as classic scabies. Both patients were treated with 1 application of permethrin cream 5% before we evaluated them. We instructed to repeat application in 7 days for both boys and all family members.

Bullae may be secondary to hypersensitivity response³ or superinfection with Staphylococcus aureus causing bullous impetigo.⁴ Bullous scabies may present a diagnostic challenge and requires a high index of suspicion. Although childhood bullous pemphigoid can involve the palms and soles, patients usually present in infancy. Diagnoses such as dyshidrotic eczema and bullous tinea can present with pustules on the hands and feet; however, involvement of the genitalia would be uncommon.

The Diagnosis: Granuloma Faciale

A biopsy from a scalp lesion showed an intense mixed inflammatory infiltrate mainly consisting of eosinophils, but lymphocytes, histiocytes, neutrophils, and plasma cells also were present. A grenz zone was observed between the dermal infiltrate and epidermis. Perivascular infiltrates were penetrating vessel walls, and hyalinization of the vessel walls also was seen (Figure 1). Direct immunofluorescence demonstrated IgG positivity on vessel walls (Figure 2). A diagnosis of granuloma faciale with extrafacial lesions was made. Twice daily application of tacrolimus ointment 0.1% was started, but after a 10-month course of treatment, there was no notable difference in the lesions.

Granuloma faciale (GF) is an uncommon benign dermatosis of unknown pathogenesis characterized by erythematous, brown, or violaceous papules, plaques, or nodules. Granuloma faciale lesions can be solitary or multiple as well as disseminated and most often occur on the face. Predilection sites include the nose, periauricular area, cheeks, forehead, eyelids, and ears; however, lesions also have been reported to occur in extrafacial areas such as the trunk, arms, and legs.^1-4 In our patient, multiple plaques were seen on the scalp. Facial lesions usually precede extrafacial lesions, which may present months to several years after the appearance of facial disease; however, according to our patient's history his scalp lesions appeared before the facial lesions.

The differential diagnoses for GF mainly include erythema elevatum diutinum, cutaneous sarcoidosis, cutaneous lymphoma, lupus, basal cell carcinoma, and cutaneous pseudolymphoma.⁵ Diagnosis may be established based on a combination of clinical features and skin biopsy results. On histopathologic examination, small-vessel vasculitis usually is present with an infiltrate predominantly consisting of neutrophils and eosinophils.⁶

It has been suggested that actinic damage plays a role in the etiology of GF.⁷ The pathogenesis is uncertain, but it is thought that immunophenotypic and molecular analysis of the dermal infiltrate in GF reveals that most lymphocytes are clonally expanded and the process is mediated by interferon gamma.⁷ Tacrolimus acts by binding and inactivating calcineurin and thus blocking T-cell activation and proliferation, so it is not surprising that topical tacrolimus has been shown to be useful in the management of this condition.⁸

The Diagnosis: Granuloma Faciale

A biopsy from a scalp lesion showed an intense mixed inflammatory infiltrate mainly consisting of eosinophils, but lymphocytes, histiocytes, neutrophils, and plasma cells also were present. A grenz zone was observed between the dermal infiltrate and epidermis. Perivascular infiltrates were penetrating vessel walls, and hyalinization of the vessel walls also was seen (Figure 1). Direct immunofluorescence demonstrated IgG positivity on vessel walls (Figure 2). A diagnosis of granuloma faciale with extrafacial lesions was made. Twice daily application of tacrolimus ointment 0.1% was started, but after a 10-month course of treatment, there was no notable difference in the lesions.

Granuloma faciale (GF) is an uncommon benign dermatosis of unknown pathogenesis characterized by erythematous, brown, or violaceous papules, plaques, or nodules. Granuloma faciale lesions can be solitary or multiple as well as disseminated and most often occur on the face. Predilection sites include the nose, periauricular area, cheeks, forehead, eyelids, and ears; however, lesions also have been reported to occur in extrafacial areas such as the trunk, arms, and legs.^1-4 In our patient, multiple plaques were seen on the scalp. Facial lesions usually precede extrafacial lesions, which may present months to several years after the appearance of facial disease; however, according to our patient's history his scalp lesions appeared before the facial lesions.

The differential diagnoses for GF mainly include erythema elevatum diutinum, cutaneous sarcoidosis, cutaneous lymphoma, lupus, basal cell carcinoma, and cutaneous pseudolymphoma.⁵ Diagnosis may be established based on a combination of clinical features and skin biopsy results. On histopathologic examination, small-vessel vasculitis usually is present with an infiltrate predominantly consisting of neutrophils and eosinophils.⁶

It has been suggested that actinic damage plays a role in the etiology of GF.⁷ The pathogenesis is uncertain, but it is thought that immunophenotypic and molecular analysis of the dermal infiltrate in GF reveals that most lymphocytes are clonally expanded and the process is mediated by interferon gamma.⁷ Tacrolimus acts by binding and inactivating calcineurin and thus blocking T-cell activation and proliferation, so it is not surprising that topical tacrolimus has been shown to be useful in the management of this condition.⁸

The Diagnosis: Granuloma Faciale

A biopsy from a scalp lesion showed an intense mixed inflammatory infiltrate mainly consisting of eosinophils, but lymphocytes, histiocytes, neutrophils, and plasma cells also were present. A grenz zone was observed between the dermal infiltrate and epidermis. Perivascular infiltrates were penetrating vessel walls, and hyalinization of the vessel walls also was seen (Figure 1). Direct immunofluorescence demonstrated IgG positivity on vessel walls (Figure 2). A diagnosis of granuloma faciale with extrafacial lesions was made. Twice daily application of tacrolimus ointment 0.1% was started, but after a 10-month course of treatment, there was no notable difference in the lesions.

Granuloma faciale (GF) is an uncommon benign dermatosis of unknown pathogenesis characterized by erythematous, brown, or violaceous papules, plaques, or nodules. Granuloma faciale lesions can be solitary or multiple as well as disseminated and most often occur on the face. Predilection sites include the nose, periauricular area, cheeks, forehead, eyelids, and ears; however, lesions also have been reported to occur in extrafacial areas such as the trunk, arms, and legs.^1-4 In our patient, multiple plaques were seen on the scalp. Facial lesions usually precede extrafacial lesions, which may present months to several years after the appearance of facial disease; however, according to our patient's history his scalp lesions appeared before the facial lesions.

The differential diagnoses for GF mainly include erythema elevatum diutinum, cutaneous sarcoidosis, cutaneous lymphoma, lupus, basal cell carcinoma, and cutaneous pseudolymphoma.⁵ Diagnosis may be established based on a combination of clinical features and skin biopsy results. On histopathologic examination, small-vessel vasculitis usually is present with an infiltrate predominantly consisting of neutrophils and eosinophils.⁶

It has been suggested that actinic damage plays a role in the etiology of GF.⁷ The pathogenesis is uncertain, but it is thought that immunophenotypic and molecular analysis of the dermal infiltrate in GF reveals that most lymphocytes are clonally expanded and the process is mediated by interferon gamma.⁷ Tacrolimus acts by binding and inactivating calcineurin and thus blocking T-cell activation and proliferation, so it is not surprising that topical tacrolimus has been shown to be useful in the management of this condition.⁸

The Diagnosis: Hypopigmented Mycosis Fungoides

The patient was started on clobetasol dipropionate cream 0.05% twice daily, which she did not tolerate due to a burning sensation on application. She then was started on narrowband UVB phototherapy 2 to 3 times weekly, and the hypopigmented areas began to improve. Narrowband UVB phototherapy was discontinued after 7 weeks due to the high cost to the patient, but the hypopigmented patches on the left thigh appeared to remit, and the patient did not return to the clinic for 6 months. She returned when the areas on the left thigh reappeared, along with new areas on the right buttock and right medial upper arm. Serial biopsies of the new patches also revealed a CD8⁺ atypical lymphocytic infiltrate consistent with hypopigmented patch-stage mycosis fungoides (MF). She was started on halobetasol ointment 0.05% twice daily to affected areas, which she tolerated well. Complete blood count and peripheral blood smear were unremarkable, and the patient continued to deny systemic symptoms. Over the next year, the patient's cutaneous findings continued to wax and wane with topical treatment, and she was referred to a regional cancer treatment center for a second opinion from a hematopathologist. Hematopathologic and dermatopathologic review of the case, including hematoxylin and eosin and immunohistochemical staining, was highly consistent with hypopigmented MF (Figures 1-3).

Mycosis fungoides is an uncommon disease characterized by atypical clonal T cells exhibiting epidermotropism. Most commonly, MF is characterized by a CD4⁺ lymphocytic infiltrate. Mycosis fungoides can be difficult to diagnose in its early stages, as it may resemble benign inflammatory conditions (eg, chronic atopic dermatitis, nummular eczema) and often requires biopsy and additional studies, such as immunohistochemistry, to secure a diagnosis. Hypopigmented MF is regarded as a subtype of MF, as it can exhibit different clinical and pathologic characteristics from classical MF. In particular, the lymphocytic phenotype in hypopigmented MF is more likely to be CD8⁺. 

In general, the progression of MF is characterized as stage IA (patches or plaques involving less than 10% body surface area [BSA]), IB (patches or plaques involving ≥10% BSA without lymph node or visceral involvement), IIA (patches or plaques of any percentage of BSA with lymph node involvement), IIB (cutaneous tumors with or without lymph node involvement), III (erythroderma with low blood tumor burden), or IV (erythroderma with high blood tumor burden with or without visceral involvement). Hypopigmented MF generally presents in early patch stage and rarely progresses past stage IB, and thus generally has a favorable prognosis.^1,2 Kim et al³ demonstrated that evolution from patch to plaque stage MF is accompanied by a shift in lymphocytes from the T helper 1 (Th1) to T helper 2 phenotype; therefore the Th1 phenotype, CD8⁺ T cells are associated with lower risk for disease progression. Other investigators also have hypothesized that predominance of Th1 phenotype, CD8⁺ T cells may have an immunoregulatory effect, thus preventing evolution of disease from patch to plaque stage and explaining why hypopigmented MF, with a predominantly CD8⁺ phenotype, confers better prognosis with less chance for disease progression than classical MF.^4,5 The patch- or plaque-stage lesions of classical MF have a predilection for non-sun exposed areas (eg, buttocks, medial thighs, breasts),² whereas hypopigmented MF tends to present with hypopigmented or depigmented lesions mainly distributed on the trunk, arms, and legs. These lesions may become more visible following sun exposure.¹ The size of the hypopigmented lesions can vary, and patients may complain of pruritus with variable intensity.

Hypopigmented MF presents more commonly in younger populations, in contrast to classical MF.^6-8 However, like classical MF, hypopigmented MF appears to more frequently affect individuals with darker Fitzpatrick skin types.^1,9,10 Although it generally is accepted that hypopigmented MF does not favor either sex, some studies suggest that hypopigmented MF has a female predominance.^6,10

Classical MF is characterized by an epidermotropic infiltrate of CD4⁺ T helper cells,¹⁰ whereas CD8⁺ epidermotropism is considered hallmark in hypopigmented MF.^10-12 The other typical histopathologic features of hypopigmented MF generally are identical to those of classical MF, with solitary or small groups of atypical haloed lymphocytes within the basal layer, exocytosis of lymphocytes out of proportion to spongiosis, and papillary dermal fibrosis. Immunohistochemistry generally is helpful in distinguishing between classical MF and hypopigmented MF.

The clinical differential diagnosis for hypopigmented MF includes the early (inflammatory) stage of vitiligo, postinflammatory hypopigmentation, lichen sclerosus, pityriasis alba, and leprosy.

First-line treatment for hypopigmented MF consists of phototherapy/photochemotherapy and topical steroids.^9,13 Narrowband UVB phototherapy has been used with good success in pediatric patients.¹⁴ However, narrowband UVB may not be as effective in darker-skinned individuals; it has been hypothesized that this lack of efficacy could be due to the protective effects of increased melanin in the skin.¹ Other topical therapies may include topical carmustine and topical nitrogen mustard.

The Diagnosis: Hypopigmented Mycosis Fungoides

The patient was started on clobetasol dipropionate cream 0.05% twice daily, which she did not tolerate due to a burning sensation on application. She then was started on narrowband UVB phototherapy 2 to 3 times weekly, and the hypopigmented areas began to improve. Narrowband UVB phototherapy was discontinued after 7 weeks due to the high cost to the patient, but the hypopigmented patches on the left thigh appeared to remit, and the patient did not return to the clinic for 6 months. She returned when the areas on the left thigh reappeared, along with new areas on the right buttock and right medial upper arm. Serial biopsies of the new patches also revealed a CD8⁺ atypical lymphocytic infiltrate consistent with hypopigmented patch-stage mycosis fungoides (MF). She was started on halobetasol ointment 0.05% twice daily to affected areas, which she tolerated well. Complete blood count and peripheral blood smear were unremarkable, and the patient continued to deny systemic symptoms. Over the next year, the patient's cutaneous findings continued to wax and wane with topical treatment, and she was referred to a regional cancer treatment center for a second opinion from a hematopathologist. Hematopathologic and dermatopathologic review of the case, including hematoxylin and eosin and immunohistochemical staining, was highly consistent with hypopigmented MF (Figures 1-3).

Mycosis fungoides is an uncommon disease characterized by atypical clonal T cells exhibiting epidermotropism. Most commonly, MF is characterized by a CD4⁺ lymphocytic infiltrate. Mycosis fungoides can be difficult to diagnose in its early stages, as it may resemble benign inflammatory conditions (eg, chronic atopic dermatitis, nummular eczema) and often requires biopsy and additional studies, such as immunohistochemistry, to secure a diagnosis. Hypopigmented MF is regarded as a subtype of MF, as it can exhibit different clinical and pathologic characteristics from classical MF. In particular, the lymphocytic phenotype in hypopigmented MF is more likely to be CD8⁺. 

In general, the progression of MF is characterized as stage IA (patches or plaques involving less than 10% body surface area [BSA]), IB (patches or plaques involving ≥10% BSA without lymph node or visceral involvement), IIA (patches or plaques of any percentage of BSA with lymph node involvement), IIB (cutaneous tumors with or without lymph node involvement), III (erythroderma with low blood tumor burden), or IV (erythroderma with high blood tumor burden with or without visceral involvement). Hypopigmented MF generally presents in early patch stage and rarely progresses past stage IB, and thus generally has a favorable prognosis.^1,2 Kim et al³ demonstrated that evolution from patch to plaque stage MF is accompanied by a shift in lymphocytes from the T helper 1 (Th1) to T helper 2 phenotype; therefore the Th1 phenotype, CD8⁺ T cells are associated with lower risk for disease progression. Other investigators also have hypothesized that predominance of Th1 phenotype, CD8⁺ T cells may have an immunoregulatory effect, thus preventing evolution of disease from patch to plaque stage and explaining why hypopigmented MF, with a predominantly CD8⁺ phenotype, confers better prognosis with less chance for disease progression than classical MF.^4,5 The patch- or plaque-stage lesions of classical MF have a predilection for non-sun exposed areas (eg, buttocks, medial thighs, breasts),² whereas hypopigmented MF tends to present with hypopigmented or depigmented lesions mainly distributed on the trunk, arms, and legs. These lesions may become more visible following sun exposure.¹ The size of the hypopigmented lesions can vary, and patients may complain of pruritus with variable intensity.

Hypopigmented MF presents more commonly in younger populations, in contrast to classical MF.^6-8 However, like classical MF, hypopigmented MF appears to more frequently affect individuals with darker Fitzpatrick skin types.^1,9,10 Although it generally is accepted that hypopigmented MF does not favor either sex, some studies suggest that hypopigmented MF has a female predominance.^6,10

Classical MF is characterized by an epidermotropic infiltrate of CD4⁺ T helper cells,¹⁰ whereas CD8⁺ epidermotropism is considered hallmark in hypopigmented MF.^10-12 The other typical histopathologic features of hypopigmented MF generally are identical to those of classical MF, with solitary or small groups of atypical haloed lymphocytes within the basal layer, exocytosis of lymphocytes out of proportion to spongiosis, and papillary dermal fibrosis. Immunohistochemistry generally is helpful in distinguishing between classical MF and hypopigmented MF.

The clinical differential diagnosis for hypopigmented MF includes the early (inflammatory) stage of vitiligo, postinflammatory hypopigmentation, lichen sclerosus, pityriasis alba, and leprosy.

First-line treatment for hypopigmented MF consists of phototherapy/photochemotherapy and topical steroids.^9,13 Narrowband UVB phototherapy has been used with good success in pediatric patients.¹⁴ However, narrowband UVB may not be as effective in darker-skinned individuals; it has been hypothesized that this lack of efficacy could be due to the protective effects of increased melanin in the skin.¹ Other topical therapies may include topical carmustine and topical nitrogen mustard.

The Diagnosis: Hypopigmented Mycosis Fungoides

The patient was started on clobetasol dipropionate cream 0.05% twice daily, which she did not tolerate due to a burning sensation on application. She then was started on narrowband UVB phototherapy 2 to 3 times weekly, and the hypopigmented areas began to improve. Narrowband UVB phototherapy was discontinued after 7 weeks due to the high cost to the patient, but the hypopigmented patches on the left thigh appeared to remit, and the patient did not return to the clinic for 6 months. She returned when the areas on the left thigh reappeared, along with new areas on the right buttock and right medial upper arm. Serial biopsies of the new patches also revealed a CD8⁺ atypical lymphocytic infiltrate consistent with hypopigmented patch-stage mycosis fungoides (MF). She was started on halobetasol ointment 0.05% twice daily to affected areas, which she tolerated well. Complete blood count and peripheral blood smear were unremarkable, and the patient continued to deny systemic symptoms. Over the next year, the patient's cutaneous findings continued to wax and wane with topical treatment, and she was referred to a regional cancer treatment center for a second opinion from a hematopathologist. Hematopathologic and dermatopathologic review of the case, including hematoxylin and eosin and immunohistochemical staining, was highly consistent with hypopigmented MF (Figures 1-3).

Mycosis fungoides is an uncommon disease characterized by atypical clonal T cells exhibiting epidermotropism. Most commonly, MF is characterized by a CD4⁺ lymphocytic infiltrate. Mycosis fungoides can be difficult to diagnose in its early stages, as it may resemble benign inflammatory conditions (eg, chronic atopic dermatitis, nummular eczema) and often requires biopsy and additional studies, such as immunohistochemistry, to secure a diagnosis. Hypopigmented MF is regarded as a subtype of MF, as it can exhibit different clinical and pathologic characteristics from classical MF. In particular, the lymphocytic phenotype in hypopigmented MF is more likely to be CD8⁺. 

In general, the progression of MF is characterized as stage IA (patches or plaques involving less than 10% body surface area [BSA]), IB (patches or plaques involving ≥10% BSA without lymph node or visceral involvement), IIA (patches or plaques of any percentage of BSA with lymph node involvement), IIB (cutaneous tumors with or without lymph node involvement), III (erythroderma with low blood tumor burden), or IV (erythroderma with high blood tumor burden with or without visceral involvement). Hypopigmented MF generally presents in early patch stage and rarely progresses past stage IB, and thus generally has a favorable prognosis.^1,2 Kim et al³ demonstrated that evolution from patch to plaque stage MF is accompanied by a shift in lymphocytes from the T helper 1 (Th1) to T helper 2 phenotype; therefore the Th1 phenotype, CD8⁺ T cells are associated with lower risk for disease progression. Other investigators also have hypothesized that predominance of Th1 phenotype, CD8⁺ T cells may have an immunoregulatory effect, thus preventing evolution of disease from patch to plaque stage and explaining why hypopigmented MF, with a predominantly CD8⁺ phenotype, confers better prognosis with less chance for disease progression than classical MF.^4,5 The patch- or plaque-stage lesions of classical MF have a predilection for non-sun exposed areas (eg, buttocks, medial thighs, breasts),² whereas hypopigmented MF tends to present with hypopigmented or depigmented lesions mainly distributed on the trunk, arms, and legs. These lesions may become more visible following sun exposure.¹ The size of the hypopigmented lesions can vary, and patients may complain of pruritus with variable intensity.

Hypopigmented MF presents more commonly in younger populations, in contrast to classical MF.^6-8 However, like classical MF, hypopigmented MF appears to more frequently affect individuals with darker Fitzpatrick skin types.^1,9,10 Although it generally is accepted that hypopigmented MF does not favor either sex, some studies suggest that hypopigmented MF has a female predominance.^6,10

Classical MF is characterized by an epidermotropic infiltrate of CD4⁺ T helper cells,¹⁰ whereas CD8⁺ epidermotropism is considered hallmark in hypopigmented MF.^10-12 The other typical histopathologic features of hypopigmented MF generally are identical to those of classical MF, with solitary or small groups of atypical haloed lymphocytes within the basal layer, exocytosis of lymphocytes out of proportion to spongiosis, and papillary dermal fibrosis. Immunohistochemistry generally is helpful in distinguishing between classical MF and hypopigmented MF.

The clinical differential diagnosis for hypopigmented MF includes the early (inflammatory) stage of vitiligo, postinflammatory hypopigmentation, lichen sclerosus, pityriasis alba, and leprosy.

First-line treatment for hypopigmented MF consists of phototherapy/photochemotherapy and topical steroids.^9,13 Narrowband UVB phototherapy has been used with good success in pediatric patients.¹⁴ However, narrowband UVB may not be as effective in darker-skinned individuals; it has been hypothesized that this lack of efficacy could be due to the protective effects of increased melanin in the skin.¹ Other topical therapies may include topical carmustine and topical nitrogen mustard.

The Diagnosis: Metastatic Renal Cell Carcinoma

Histopathologic examination of the punch biopsy demonstrated epithelioid cells with abundant clear cytoplasm and numerous chicken wire-like vascular channels consistent with a diagnosis of cutaneous metastasis of renal cell carcinoma (RCC)(Figure). Collateral history revealed that 8 years prior, the patient had been diagnosed with clear cell RCC, stage III (T3aN0M0). At that time, he was treated with radical nephrectomy, which was considered curative. He remained disease free until several months prior to the development of the cutaneous lesion when he was found to have pulmonary and cerebral metastases with biopsies showing metastatic RCC. He was treated with lobectomy and Gamma Knife radiation for the lung and cerebral metastases, respectively. His oncologist planned to initiate therapy with the multikinase inhibitor sunitinib, which inhibits vascular endothelial growth factor (VEGF) signaling. Unfortunately, the patient died prior to treatment due to overwhelming tumor burden.

Clear cell RCC, the most common renal malignancy, presents with metastatic disease at the time of diagnosis in 21% of patients.¹ An additional 20% of patients with localized disease develop metastases within several years of receiving a nephrectomy without adjuvant therapy, which is standard treatment for stage I to stage III disease.^1,2 Metastatic RCC most frequently targets the lungs, bone, liver, and brain, though virtually any organ can be involved. Cutaneous involvement is estimated to occur in 3.3% of RCC cases,³ accounting for only 1.4% of cutaneous metastases overall.⁴ The risk for developing cutaneous metastases is greatest within 3 years following nephrectomy.³ However, our patient demonstrates that metastasis of RCC to skin can be long delayed (>5 years) despite an initial diagnosis of localized disease.

Cutaneous RCC classically presents as a painless firm papulonodule with a deep red or purple color due to its high vascularity.⁴ Several retrospective studies have identified the scalp as the most frequent site of cutaneous involvement, followed by the chest, abdomen, and nephrectomy scar.^3,4 The differential diagnosis includes other vascular lesions such as pyogenic granuloma, hemangioma, angiosarcoma, bacillary angiomatosis, and Kaposi sarcoma. Diagnosis usually is easily confirmed histologically. Proliferative nests of epithelioid cells with clear cell morphology are surrounded by delicately branching vessels referred to as chicken wire-like vasculature. Immunohistochemical studies demonstrate positivity for pan-cytokeratin, vimentin, and CD-10, and negativity for p63 and cytokeratins 5 and 6, helping to confirm the diagnosis in more challenging cases, especially when there is no known history of primary RCC.⁵

If cutaneous metastasis of RCC is diagnosed, a chest and abdominal computed tomography scan as well as serum alkaline phosphatase test are warranted, as up to 90% of patients with RCC in the skin have additional lesions in at least 1 other site such as the lungs, bones, or liver.³ Management of metastatic RCC includes surgical excision if a single metastasis is found and either immunotherapy with high-dose IL-2 or an anti-programmed cell death inhibitor. Patients with progressive disease also may receive targeted anti-VEGF inhibitors (eg, axitinib, pazopanib, sunitinib), which have been shown to increase progression-free survival in metastatic RCC.^6-8 Interestingly, some evidence suggests severely delayed recurrence of RCC (>5 years following nephrectomy) may predict better response to systemic therapy.⁹

This case of severely delayed metastasis of RCC 8 years after nephrectomy raises the question of whether routine surveillance for RCC recurrence should continue beyond 5 years. It also underscores the need for further studies to determine the utility of postsurgical adjuvant therapy for localized disease (stages I-III). A randomized clinical trial showed no significant difference in disease-free survival when the multikinase inhibitors sunitinib and sorafenib were used as adjuvant therapy.¹⁰ The randomized, placebo-controlled PROTECT trial showed no significant difference in disease-free survival between the VEGF inhibitor pazopanib and placebo when used as adjuvant therapy.¹¹ However, trials are ongoing to investigate a potential survival advantage of adjuvant therapy with the VEGF receptor inhibitor axitinib and the mammalian target of rapamycin inhibitor everolimus.

The Diagnosis: Metastatic Renal Cell Carcinoma

Histopathologic examination of the punch biopsy demonstrated epithelioid cells with abundant clear cytoplasm and numerous chicken wire-like vascular channels consistent with a diagnosis of cutaneous metastasis of renal cell carcinoma (RCC)(Figure). Collateral history revealed that 8 years prior, the patient had been diagnosed with clear cell RCC, stage III (T3aN0M0). At that time, he was treated with radical nephrectomy, which was considered curative. He remained disease free until several months prior to the development of the cutaneous lesion when he was found to have pulmonary and cerebral metastases with biopsies showing metastatic RCC. He was treated with lobectomy and Gamma Knife radiation for the lung and cerebral metastases, respectively. His oncologist planned to initiate therapy with the multikinase inhibitor sunitinib, which inhibits vascular endothelial growth factor (VEGF) signaling. Unfortunately, the patient died prior to treatment due to overwhelming tumor burden.

Clear cell RCC, the most common renal malignancy, presents with metastatic disease at the time of diagnosis in 21% of patients.¹ An additional 20% of patients with localized disease develop metastases within several years of receiving a nephrectomy without adjuvant therapy, which is standard treatment for stage I to stage III disease.^1,2 Metastatic RCC most frequently targets the lungs, bone, liver, and brain, though virtually any organ can be involved. Cutaneous involvement is estimated to occur in 3.3% of RCC cases,³ accounting for only 1.4% of cutaneous metastases overall.⁴ The risk for developing cutaneous metastases is greatest within 3 years following nephrectomy.³ However, our patient demonstrates that metastasis of RCC to skin can be long delayed (>5 years) despite an initial diagnosis of localized disease.

Cutaneous RCC classically presents as a painless firm papulonodule with a deep red or purple color due to its high vascularity.⁴ Several retrospective studies have identified the scalp as the most frequent site of cutaneous involvement, followed by the chest, abdomen, and nephrectomy scar.^3,4 The differential diagnosis includes other vascular lesions such as pyogenic granuloma, hemangioma, angiosarcoma, bacillary angiomatosis, and Kaposi sarcoma. Diagnosis usually is easily confirmed histologically. Proliferative nests of epithelioid cells with clear cell morphology are surrounded by delicately branching vessels referred to as chicken wire-like vasculature. Immunohistochemical studies demonstrate positivity for pan-cytokeratin, vimentin, and CD-10, and negativity for p63 and cytokeratins 5 and 6, helping to confirm the diagnosis in more challenging cases, especially when there is no known history of primary RCC.⁵

If cutaneous metastasis of RCC is diagnosed, a chest and abdominal computed tomography scan as well as serum alkaline phosphatase test are warranted, as up to 90% of patients with RCC in the skin have additional lesions in at least 1 other site such as the lungs, bones, or liver.³ Management of metastatic RCC includes surgical excision if a single metastasis is found and either immunotherapy with high-dose IL-2 or an anti-programmed cell death inhibitor. Patients with progressive disease also may receive targeted anti-VEGF inhibitors (eg, axitinib, pazopanib, sunitinib), which have been shown to increase progression-free survival in metastatic RCC.^6-8 Interestingly, some evidence suggests severely delayed recurrence of RCC (>5 years following nephrectomy) may predict better response to systemic therapy.⁹

This case of severely delayed metastasis of RCC 8 years after nephrectomy raises the question of whether routine surveillance for RCC recurrence should continue beyond 5 years. It also underscores the need for further studies to determine the utility of postsurgical adjuvant therapy for localized disease (stages I-III). A randomized clinical trial showed no significant difference in disease-free survival when the multikinase inhibitors sunitinib and sorafenib were used as adjuvant therapy.¹⁰ The randomized, placebo-controlled PROTECT trial showed no significant difference in disease-free survival between the VEGF inhibitor pazopanib and placebo when used as adjuvant therapy.¹¹ However, trials are ongoing to investigate a potential survival advantage of adjuvant therapy with the VEGF receptor inhibitor axitinib and the mammalian target of rapamycin inhibitor everolimus.

The Diagnosis: Metastatic Renal Cell Carcinoma

Histopathologic examination of the punch biopsy demonstrated epithelioid cells with abundant clear cytoplasm and numerous chicken wire-like vascular channels consistent with a diagnosis of cutaneous metastasis of renal cell carcinoma (RCC)(Figure). Collateral history revealed that 8 years prior, the patient had been diagnosed with clear cell RCC, stage III (T3aN0M0). At that time, he was treated with radical nephrectomy, which was considered curative. He remained disease free until several months prior to the development of the cutaneous lesion when he was found to have pulmonary and cerebral metastases with biopsies showing metastatic RCC. He was treated with lobectomy and Gamma Knife radiation for the lung and cerebral metastases, respectively. His oncologist planned to initiate therapy with the multikinase inhibitor sunitinib, which inhibits vascular endothelial growth factor (VEGF) signaling. Unfortunately, the patient died prior to treatment due to overwhelming tumor burden.

Clear cell RCC, the most common renal malignancy, presents with metastatic disease at the time of diagnosis in 21% of patients.¹ An additional 20% of patients with localized disease develop metastases within several years of receiving a nephrectomy without adjuvant therapy, which is standard treatment for stage I to stage III disease.^1,2 Metastatic RCC most frequently targets the lungs, bone, liver, and brain, though virtually any organ can be involved. Cutaneous involvement is estimated to occur in 3.3% of RCC cases,³ accounting for only 1.4% of cutaneous metastases overall.⁴ The risk for developing cutaneous metastases is greatest within 3 years following nephrectomy.³ However, our patient demonstrates that metastasis of RCC to skin can be long delayed (>5 years) despite an initial diagnosis of localized disease.

Cutaneous RCC classically presents as a painless firm papulonodule with a deep red or purple color due to its high vascularity.⁴ Several retrospective studies have identified the scalp as the most frequent site of cutaneous involvement, followed by the chest, abdomen, and nephrectomy scar.^3,4 The differential diagnosis includes other vascular lesions such as pyogenic granuloma, hemangioma, angiosarcoma, bacillary angiomatosis, and Kaposi sarcoma. Diagnosis usually is easily confirmed histologically. Proliferative nests of epithelioid cells with clear cell morphology are surrounded by delicately branching vessels referred to as chicken wire-like vasculature. Immunohistochemical studies demonstrate positivity for pan-cytokeratin, vimentin, and CD-10, and negativity for p63 and cytokeratins 5 and 6, helping to confirm the diagnosis in more challenging cases, especially when there is no known history of primary RCC.⁵

If cutaneous metastasis of RCC is diagnosed, a chest and abdominal computed tomography scan as well as serum alkaline phosphatase test are warranted, as up to 90% of patients with RCC in the skin have additional lesions in at least 1 other site such as the lungs, bones, or liver.³ Management of metastatic RCC includes surgical excision if a single metastasis is found and either immunotherapy with high-dose IL-2 or an anti-programmed cell death inhibitor. Patients with progressive disease also may receive targeted anti-VEGF inhibitors (eg, axitinib, pazopanib, sunitinib), which have been shown to increase progression-free survival in metastatic RCC.^6-8 Interestingly, some evidence suggests severely delayed recurrence of RCC (>5 years following nephrectomy) may predict better response to systemic therapy.⁹

This case of severely delayed metastasis of RCC 8 years after nephrectomy raises the question of whether routine surveillance for RCC recurrence should continue beyond 5 years. It also underscores the need for further studies to determine the utility of postsurgical adjuvant therapy for localized disease (stages I-III). A randomized clinical trial showed no significant difference in disease-free survival when the multikinase inhibitors sunitinib and sorafenib were used as adjuvant therapy.¹⁰ The randomized, placebo-controlled PROTECT trial showed no significant difference in disease-free survival between the VEGF inhibitor pazopanib and placebo when used as adjuvant therapy.¹¹ However, trials are ongoing to investigate a potential survival advantage of adjuvant therapy with the VEGF receptor inhibitor axitinib and the mammalian target of rapamycin inhibitor everolimus.

The Diagnosis: Nevus Sebaceous

The patient presented with a typical solitary scalp lesion characteristic of nevus sebaceous (NS). The lesion was present at birth as a flat and smooth hairless plaque; however, over time it became more thickened and noticeable, which prompted the parents to seek medical advice.

Nevus sebaceous, also known as NS of Jadassohn, is a benign congenital hamartoma of the sebaceous gland that usually is present at birth and frequently involves the scalp and/or the face. The classic NS lesion is solitary and appears as a well-circumscribed, waxy, yellow-orange or tan, hairless plaque. Despite the presence of these lesions at birth, they may not be noted until early childhood or rarely until adulthood. Generally, the lesion tends to thicken and become more verrucous and velvety over time, particularly around the time of reaching puberty.¹ Clinically, NS lesions vary in size from 1 cm to several centimeters. Lesions initially tend to grow proportionately with the child until puberty when they become notably thicker, greasier, and verrucous or nodular under hormonal influences. The yellow discoloration of the lesion is due to sebaceous gland secretion, and the characteristic color usually becomes less evident with age.

Nevus sebaceous occurs in approximately 0.3% of newborns and tends to be sporadic in nature; however, rare familial forms have been reported.^2,3 Nevus sebaceous can present as multiple nevi that tend to be extensive and distributed along the Blaschko lines, and they usually are associated with neurologic, ocular, or skeletal defects. Involvement of the central nervous system frequently is associated with large sebaceous nevi located on the face or scalp. This association has been termed NS syndrome.⁴ Neurologic abnormalities associated with NS syndrome include seizures, mental retardation, and hemimegalencephaly.⁵ Ocular findings most communally associated with the syndrome are choristomas and colobomas.^6-8

There are several benign and malignant epithelial neoplasms that may develop within sebaceous nevi. Benign tumors include trichoblastoma, syringocystadenoma papilliferum, trichilemmoma, sebaceoma, nodular hidradenoma, and hidrocystoma.^1,8,9 Malignant neoplasms include basal cell carcinoma (BCC), apocrine carcinoma, sebaceous carcinoma, and squamous cell carcinoma. The lifetime risk of malignancy in NS is unknown. In an extensive literature review by Moody et al¹⁰ of 4923 cases of NS for the development of secondary benign and malignant neoplasms, 16% developed benign tumors while 8% developed malignant tumors such as BCC. However, subsequent studies suggested that the incidence of BCC may have been overestimated due to misinterpretation of trichoblastoma and may be less than 1%.^11-13

Usually the diagnosis of NS is made clinically and rarely a biopsy for histopathologic confirmation may be needed when the diagnosis is uncertain. Typically, these histopathologic findings include immature hair follicles, hyperplastic immature sebaceous glands, dilated apocrine glands, and epidermal hyperplasia.⁹ For patients with suspected NS syndrome, additional neurologic and ophthalmologic evaluations should be performed including neuroimaging studies, skeletal radiography, and analysis of liver and renal function.¹⁴

The current standard of care in treating NS is full-thickness excision. However, the decision should be individualized based on patient age, extension and location of the lesion, concerns about the cosmetic appearance, and the risk for malignancy. 

The 2 main reasons to excise NS include concern about malignancy and undesirable cosmetic appearance. Once a malignant lesion develops within NS, it generally is agreed that the tumor and the entire nevus should be removed; however, recommendations vary for excising NS prophylactically to decrease the risk for malignant growths. Because the risk for malignant transformation seems to be lower than previously thought, observation can be a reasonable choice for lesions that are not associated with cosmetic concern.^12,13

Photodynamic therapy, CO2 laser resurfacing, and dermabrasion have been reported as alternative therapeutic approaches. However, there is a growing concern on how effective these treatment modalities are in completely removing the lesion and whether the risk for recurrence and potential for neoplasm development remains.^1,9

This patient was healthy with normal development and growth and no signs of neurologic or ocular involvement. The parents were counseled about the risk for malignancy and the long-term cosmetic appearance of the lesion. They opted for surgical excision of the lesion at 18 months of age.

The Diagnosis: Nevus Sebaceous

The patient presented with a typical solitary scalp lesion characteristic of nevus sebaceous (NS). The lesion was present at birth as a flat and smooth hairless plaque; however, over time it became more thickened and noticeable, which prompted the parents to seek medical advice.

Nevus sebaceous, also known as NS of Jadassohn, is a benign congenital hamartoma of the sebaceous gland that usually is present at birth and frequently involves the scalp and/or the face. The classic NS lesion is solitary and appears as a well-circumscribed, waxy, yellow-orange or tan, hairless plaque. Despite the presence of these lesions at birth, they may not be noted until early childhood or rarely until adulthood. Generally, the lesion tends to thicken and become more verrucous and velvety over time, particularly around the time of reaching puberty.¹ Clinically, NS lesions vary in size from 1 cm to several centimeters. Lesions initially tend to grow proportionately with the child until puberty when they become notably thicker, greasier, and verrucous or nodular under hormonal influences. The yellow discoloration of the lesion is due to sebaceous gland secretion, and the characteristic color usually becomes less evident with age.

Nevus sebaceous occurs in approximately 0.3% of newborns and tends to be sporadic in nature; however, rare familial forms have been reported.^2,3 Nevus sebaceous can present as multiple nevi that tend to be extensive and distributed along the Blaschko lines, and they usually are associated with neurologic, ocular, or skeletal defects. Involvement of the central nervous system frequently is associated with large sebaceous nevi located on the face or scalp. This association has been termed NS syndrome.⁴ Neurologic abnormalities associated with NS syndrome include seizures, mental retardation, and hemimegalencephaly.⁵ Ocular findings most communally associated with the syndrome are choristomas and colobomas.^6-8

There are several benign and malignant epithelial neoplasms that may develop within sebaceous nevi. Benign tumors include trichoblastoma, syringocystadenoma papilliferum, trichilemmoma, sebaceoma, nodular hidradenoma, and hidrocystoma.^1,8,9 Malignant neoplasms include basal cell carcinoma (BCC), apocrine carcinoma, sebaceous carcinoma, and squamous cell carcinoma. The lifetime risk of malignancy in NS is unknown. In an extensive literature review by Moody et al¹⁰ of 4923 cases of NS for the development of secondary benign and malignant neoplasms, 16% developed benign tumors while 8% developed malignant tumors such as BCC. However, subsequent studies suggested that the incidence of BCC may have been overestimated due to misinterpretation of trichoblastoma and may be less than 1%.^11-13

Usually the diagnosis of NS is made clinically and rarely a biopsy for histopathologic confirmation may be needed when the diagnosis is uncertain. Typically, these histopathologic findings include immature hair follicles, hyperplastic immature sebaceous glands, dilated apocrine glands, and epidermal hyperplasia.⁹ For patients with suspected NS syndrome, additional neurologic and ophthalmologic evaluations should be performed including neuroimaging studies, skeletal radiography, and analysis of liver and renal function.¹⁴

The current standard of care in treating NS is full-thickness excision. However, the decision should be individualized based on patient age, extension and location of the lesion, concerns about the cosmetic appearance, and the risk for malignancy. 

The 2 main reasons to excise NS include concern about malignancy and undesirable cosmetic appearance. Once a malignant lesion develops within NS, it generally is agreed that the tumor and the entire nevus should be removed; however, recommendations vary for excising NS prophylactically to decrease the risk for malignant growths. Because the risk for malignant transformation seems to be lower than previously thought, observation can be a reasonable choice for lesions that are not associated with cosmetic concern.^12,13

Photodynamic therapy, CO2 laser resurfacing, and dermabrasion have been reported as alternative therapeutic approaches. However, there is a growing concern on how effective these treatment modalities are in completely removing the lesion and whether the risk for recurrence and potential for neoplasm development remains.^1,9

This patient was healthy with normal development and growth and no signs of neurologic or ocular involvement. The parents were counseled about the risk for malignancy and the long-term cosmetic appearance of the lesion. They opted for surgical excision of the lesion at 18 months of age.

The Diagnosis: Nevus Sebaceous

The patient presented with a typical solitary scalp lesion characteristic of nevus sebaceous (NS). The lesion was present at birth as a flat and smooth hairless plaque; however, over time it became more thickened and noticeable, which prompted the parents to seek medical advice.

Nevus sebaceous, also known as NS of Jadassohn, is a benign congenital hamartoma of the sebaceous gland that usually is present at birth and frequently involves the scalp and/or the face. The classic NS lesion is solitary and appears as a well-circumscribed, waxy, yellow-orange or tan, hairless plaque. Despite the presence of these lesions at birth, they may not be noted until early childhood or rarely until adulthood. Generally, the lesion tends to thicken and become more verrucous and velvety over time, particularly around the time of reaching puberty.¹ Clinically, NS lesions vary in size from 1 cm to several centimeters. Lesions initially tend to grow proportionately with the child until puberty when they become notably thicker, greasier, and verrucous or nodular under hormonal influences. The yellow discoloration of the lesion is due to sebaceous gland secretion, and the characteristic color usually becomes less evident with age.

Nevus sebaceous occurs in approximately 0.3% of newborns and tends to be sporadic in nature; however, rare familial forms have been reported.^2,3 Nevus sebaceous can present as multiple nevi that tend to be extensive and distributed along the Blaschko lines, and they usually are associated with neurologic, ocular, or skeletal defects. Involvement of the central nervous system frequently is associated with large sebaceous nevi located on the face or scalp. This association has been termed NS syndrome.⁴ Neurologic abnormalities associated with NS syndrome include seizures, mental retardation, and hemimegalencephaly.⁵ Ocular findings most communally associated with the syndrome are choristomas and colobomas.^6-8

There are several benign and malignant epithelial neoplasms that may develop within sebaceous nevi. Benign tumors include trichoblastoma, syringocystadenoma papilliferum, trichilemmoma, sebaceoma, nodular hidradenoma, and hidrocystoma.^1,8,9 Malignant neoplasms include basal cell carcinoma (BCC), apocrine carcinoma, sebaceous carcinoma, and squamous cell carcinoma. The lifetime risk of malignancy in NS is unknown. In an extensive literature review by Moody et al¹⁰ of 4923 cases of NS for the development of secondary benign and malignant neoplasms, 16% developed benign tumors while 8% developed malignant tumors such as BCC. However, subsequent studies suggested that the incidence of BCC may have been overestimated due to misinterpretation of trichoblastoma and may be less than 1%.^11-13

Usually the diagnosis of NS is made clinically and rarely a biopsy for histopathologic confirmation may be needed when the diagnosis is uncertain. Typically, these histopathologic findings include immature hair follicles, hyperplastic immature sebaceous glands, dilated apocrine glands, and epidermal hyperplasia.⁹ For patients with suspected NS syndrome, additional neurologic and ophthalmologic evaluations should be performed including neuroimaging studies, skeletal radiography, and analysis of liver and renal function.¹⁴

The current standard of care in treating NS is full-thickness excision. However, the decision should be individualized based on patient age, extension and location of the lesion, concerns about the cosmetic appearance, and the risk for malignancy. 

The 2 main reasons to excise NS include concern about malignancy and undesirable cosmetic appearance. Once a malignant lesion develops within NS, it generally is agreed that the tumor and the entire nevus should be removed; however, recommendations vary for excising NS prophylactically to decrease the risk for malignant growths. Because the risk for malignant transformation seems to be lower than previously thought, observation can be a reasonable choice for lesions that are not associated with cosmetic concern.^12,13

Photodynamic therapy, CO2 laser resurfacing, and dermabrasion have been reported as alternative therapeutic approaches. However, there is a growing concern on how effective these treatment modalities are in completely removing the lesion and whether the risk for recurrence and potential for neoplasm development remains.^1,9

This patient was healthy with normal development and growth and no signs of neurologic or ocular involvement. The parents were counseled about the risk for malignancy and the long-term cosmetic appearance of the lesion. They opted for surgical excision of the lesion at 18 months of age.

The Diagnosis: Dermatofibroma

On dermoscopy, a central stellate, white, scarlike patch was seen (Figure). On both legs the patient had several additional brown 5- to 7-mm papules with similar dermoscopic features.

Dermatofibromas are common benign fibrosing tumors that appear as firm papules or plaques with variable color, commonly on the legs. Typically, lateral compression of a dermatofibroma causes downward displacement, called a positive dimple sign. On histology, fibroblasts and myofibroblasts can be seen as short intersecting fascicles with variable inflammatory cells and induction of adjacent structure hyperplasia. The etiology of dermatofibromas is unclear, though some are thought to be secondary to trauma or arthropod bites.¹ Because these tumors are benign, the correct diagnosis can avoid unnecessary biopsies or other procedures.

The dermoscopic features of dermatofibromas have been well established.² As perhaps the most easily identified structure, scarlike patches were seen in as many as 92% (22/24) of dermatofibromas in one study by Ferarri et al,³ while pigment networks also are commonly seen.² In our case, given the surrounding dense tattoo deposition, it was difficult to ascertain any pigment network. However, the scarlike central patch was clearly apparent by dermoscopy.

Because dermatofibromas are hypothesized to be secondary to trauma, presumably applying tattoos also may cause dermatofibromas. Limited cases have described dermatofibromas arising in tattoos applied several months to years prior.^4-6 No prior cases utilized dermoscopy. In our case, clinical examination and dermoscopy clearly demonstrated features consistent with a dermatofibroma, and the patient had more characteristic dermatofibromas scattered elsewhere on both legs. The patient was reassured that the lesions were benign and that the depigmentation was likely secondary to the process of dermatofibroma growth. She declined any treatment.

The Diagnosis: Dermatofibroma

On dermoscopy, a central stellate, white, scarlike patch was seen (Figure). On both legs the patient had several additional brown 5- to 7-mm papules with similar dermoscopic features.

Dermatofibromas are common benign fibrosing tumors that appear as firm papules or plaques with variable color, commonly on the legs. Typically, lateral compression of a dermatofibroma causes downward displacement, called a positive dimple sign. On histology, fibroblasts and myofibroblasts can be seen as short intersecting fascicles with variable inflammatory cells and induction of adjacent structure hyperplasia. The etiology of dermatofibromas is unclear, though some are thought to be secondary to trauma or arthropod bites.¹ Because these tumors are benign, the correct diagnosis can avoid unnecessary biopsies or other procedures.

The dermoscopic features of dermatofibromas have been well established.² As perhaps the most easily identified structure, scarlike patches were seen in as many as 92% (22/24) of dermatofibromas in one study by Ferarri et al,³ while pigment networks also are commonly seen.² In our case, given the surrounding dense tattoo deposition, it was difficult to ascertain any pigment network. However, the scarlike central patch was clearly apparent by dermoscopy.

Because dermatofibromas are hypothesized to be secondary to trauma, presumably applying tattoos also may cause dermatofibromas. Limited cases have described dermatofibromas arising in tattoos applied several months to years prior.^4-6 No prior cases utilized dermoscopy. In our case, clinical examination and dermoscopy clearly demonstrated features consistent with a dermatofibroma, and the patient had more characteristic dermatofibromas scattered elsewhere on both legs. The patient was reassured that the lesions were benign and that the depigmentation was likely secondary to the process of dermatofibroma growth. She declined any treatment.

The Diagnosis: Dermatofibroma

On dermoscopy, a central stellate, white, scarlike patch was seen (Figure). On both legs the patient had several additional brown 5- to 7-mm papules with similar dermoscopic features.

Dermatofibromas are common benign fibrosing tumors that appear as firm papules or plaques with variable color, commonly on the legs. Typically, lateral compression of a dermatofibroma causes downward displacement, called a positive dimple sign. On histology, fibroblasts and myofibroblasts can be seen as short intersecting fascicles with variable inflammatory cells and induction of adjacent structure hyperplasia. The etiology of dermatofibromas is unclear, though some are thought to be secondary to trauma or arthropod bites.¹ Because these tumors are benign, the correct diagnosis can avoid unnecessary biopsies or other procedures.

The dermoscopic features of dermatofibromas have been well established.² As perhaps the most easily identified structure, scarlike patches were seen in as many as 92% (22/24) of dermatofibromas in one study by Ferarri et al,³ while pigment networks also are commonly seen.² In our case, given the surrounding dense tattoo deposition, it was difficult to ascertain any pigment network. However, the scarlike central patch was clearly apparent by dermoscopy.

Because dermatofibromas are hypothesized to be secondary to trauma, presumably applying tattoos also may cause dermatofibromas. Limited cases have described dermatofibromas arising in tattoos applied several months to years prior.^4-6 No prior cases utilized dermoscopy. In our case, clinical examination and dermoscopy clearly demonstrated features consistent with a dermatofibroma, and the patient had more characteristic dermatofibromas scattered elsewhere on both legs. The patient was reassured that the lesions were benign and that the depigmentation was likely secondary to the process of dermatofibroma growth. She declined any treatment.

The Diagnosis: Necrobiotic Xanthogranuloma

A 4-mm punch biopsy was performed for routine stain with hematoxylin and eosin. The differential diagnosis included sarcoidosis, necrobiosis lipoidica, xanthoma disseminatum, and multicentric reticulohistiocytosis. Histopathologic examination demonstrated a dermal infiltrate of foamy histiocytes and neutrophils (Figure). There were surrounding areas of degenerated collagen containing numerous cholesterol clefts. After clinical pathologic correlation, a diagnosis of necrobiotic xanthogranuloma (NXG) was elucidated.

The patient was referred to general surgery for elective excision of 1 or more of the lesions. Excision of an abdominal lesion was performed without complication. After several months, a new lesion reformed within the excisional scar that also was consistent with NXG. At further dermatologic visits, a trial of intralesional corticosteroids was attempted to the largest lesions with modest improvement. In addition, follow-up with hematology and oncology was recommended for routine surveillance of the known blood dyscrasia.

Necrobiotic xanthogranuloma is a multisystem non-Langerhans cell histiocytic disease. Clinically, NXG is characterized by infiltrative plaques and ulcerative nodules. Lesions may appear red, brown, or yellow with associated atrophy and telangiectasia.¹ Koch et al² described a predilection for granuloma formation within preexisting scars. Periorbital location is the most common cutaneous site of involvement of NXG, seen in 80% of cases, but the trunk and extremities also may be involved.^1,3 Approximately half of those with periocular involvement experience ocular symptoms including prop- tosis, blepharoptosis, and restricted eye movements.⁴ The onset of NXG most commonly is seen in middle age.

Characteristic systemic associations have been reported in the setting of NXG. More than 20% of patients may exhibit hepatomegaly. Hematologic abnormalities, hyperlipidemia, and cryoglobulinemia also may be seen.¹ In addition, a monoclonal gammopathy of uncertain significance is found in more than 80% of NXG cases. The IgG κ light chain is most commonly identified.² A foreign body reaction is incited by the immunoglobulin-lipid complex, which is thought to contribute to the formation of cutaneous lesions. There may be associated plasma cell dyscrasia such as multiple myeloma or B-cell lymphoma in approximately 13% of cases.² Evaluation for underlying plasma cell dyscrasia or lymphoproliferative disorder should be performed regularly with serum protein electrophoresis or immunofixation electrophoresis, and in some cases full-body imaging with computed tomography or magnetic resonance imaging may be warranted.¹

Treatment of NXG often is unsuccessful. Surgical excision, systemic immunosuppressive agents, electron beam radiation, and destructive therapies such as cryotherapy may be trialed, often with little success.¹ Cutaneous regression has been reported with combination treatment of high-dose dexamethasone and high-dose lenalidomide.⁵

The Diagnosis: Necrobiotic Xanthogranuloma

A 4-mm punch biopsy was performed for routine stain with hematoxylin and eosin. The differential diagnosis included sarcoidosis, necrobiosis lipoidica, xanthoma disseminatum, and multicentric reticulohistiocytosis. Histopathologic examination demonstrated a dermal infiltrate of foamy histiocytes and neutrophils (Figure). There were surrounding areas of degenerated collagen containing numerous cholesterol clefts. After clinical pathologic correlation, a diagnosis of necrobiotic xanthogranuloma (NXG) was elucidated.

The patient was referred to general surgery for elective excision of 1 or more of the lesions. Excision of an abdominal lesion was performed without complication. After several months, a new lesion reformed within the excisional scar that also was consistent with NXG. At further dermatologic visits, a trial of intralesional corticosteroids was attempted to the largest lesions with modest improvement. In addition, follow-up with hematology and oncology was recommended for routine surveillance of the known blood dyscrasia.

Necrobiotic xanthogranuloma is a multisystem non-Langerhans cell histiocytic disease. Clinically, NXG is characterized by infiltrative plaques and ulcerative nodules. Lesions may appear red, brown, or yellow with associated atrophy and telangiectasia.¹ Koch et al² described a predilection for granuloma formation within preexisting scars. Periorbital location is the most common cutaneous site of involvement of NXG, seen in 80% of cases, but the trunk and extremities also may be involved.^1,3 Approximately half of those with periocular involvement experience ocular symptoms including prop- tosis, blepharoptosis, and restricted eye movements.⁴ The onset of NXG most commonly is seen in middle age.

Characteristic systemic associations have been reported in the setting of NXG. More than 20% of patients may exhibit hepatomegaly. Hematologic abnormalities, hyperlipidemia, and cryoglobulinemia also may be seen.¹ In addition, a monoclonal gammopathy of uncertain significance is found in more than 80% of NXG cases. The IgG κ light chain is most commonly identified.² A foreign body reaction is incited by the immunoglobulin-lipid complex, which is thought to contribute to the formation of cutaneous lesions. There may be associated plasma cell dyscrasia such as multiple myeloma or B-cell lymphoma in approximately 13% of cases.² Evaluation for underlying plasma cell dyscrasia or lymphoproliferative disorder should be performed regularly with serum protein electrophoresis or immunofixation electrophoresis, and in some cases full-body imaging with computed tomography or magnetic resonance imaging may be warranted.¹

Treatment of NXG often is unsuccessful. Surgical excision, systemic immunosuppressive agents, electron beam radiation, and destructive therapies such as cryotherapy may be trialed, often with little success.¹ Cutaneous regression has been reported with combination treatment of high-dose dexamethasone and high-dose lenalidomide.⁵

The Diagnosis: Necrobiotic Xanthogranuloma

A 4-mm punch biopsy was performed for routine stain with hematoxylin and eosin. The differential diagnosis included sarcoidosis, necrobiosis lipoidica, xanthoma disseminatum, and multicentric reticulohistiocytosis. Histopathologic examination demonstrated a dermal infiltrate of foamy histiocytes and neutrophils (Figure). There were surrounding areas of degenerated collagen containing numerous cholesterol clefts. After clinical pathologic correlation, a diagnosis of necrobiotic xanthogranuloma (NXG) was elucidated.

The patient was referred to general surgery for elective excision of 1 or more of the lesions. Excision of an abdominal lesion was performed without complication. After several months, a new lesion reformed within the excisional scar that also was consistent with NXG. At further dermatologic visits, a trial of intralesional corticosteroids was attempted to the largest lesions with modest improvement. In addition, follow-up with hematology and oncology was recommended for routine surveillance of the known blood dyscrasia.

Necrobiotic xanthogranuloma is a multisystem non-Langerhans cell histiocytic disease. Clinically, NXG is characterized by infiltrative plaques and ulcerative nodules. Lesions may appear red, brown, or yellow with associated atrophy and telangiectasia.¹ Koch et al² described a predilection for granuloma formation within preexisting scars. Periorbital location is the most common cutaneous site of involvement of NXG, seen in 80% of cases, but the trunk and extremities also may be involved.^1,3 Approximately half of those with periocular involvement experience ocular symptoms including prop- tosis, blepharoptosis, and restricted eye movements.⁴ The onset of NXG most commonly is seen in middle age.

Characteristic systemic associations have been reported in the setting of NXG. More than 20% of patients may exhibit hepatomegaly. Hematologic abnormalities, hyperlipidemia, and cryoglobulinemia also may be seen.¹ In addition, a monoclonal gammopathy of uncertain significance is found in more than 80% of NXG cases. The IgG κ light chain is most commonly identified.² A foreign body reaction is incited by the immunoglobulin-lipid complex, which is thought to contribute to the formation of cutaneous lesions. There may be associated plasma cell dyscrasia such as multiple myeloma or B-cell lymphoma in approximately 13% of cases.² Evaluation for underlying plasma cell dyscrasia or lymphoproliferative disorder should be performed regularly with serum protein electrophoresis or immunofixation electrophoresis, and in some cases full-body imaging with computed tomography or magnetic resonance imaging may be warranted.¹

Treatment of NXG often is unsuccessful. Surgical excision, systemic immunosuppressive agents, electron beam radiation, and destructive therapies such as cryotherapy may be trialed, often with little success.¹ Cutaneous regression has been reported with combination treatment of high-dose dexamethasone and high-dose lenalidomide.⁵

The Diagnosis: Congenital Unilateral Nevoid Telangiectasia

Two weeks later the patches were noticeably lighter (Figures 1A and 1B). She continued to be in good health, but gynecomastia was notably present on examination (Figure 1C). At 3 months of age, all patches on the right arm, superior aspect of the chest, and superior aspect of the back had resolved, along with the gynecomastia (Figure 2).

This case describes the rare condition of congenital unilateral nevoid telangiectasia (UNT). Unilateral nevoid telangiectasia is a rare cutaneous vascular condition first described by Blaschko¹ in 1899. It is characterized by the presence of unilateral superficial telangiectases occurring most often in the cervical and upper thoracic dermatomes in a linear pattern.² Females are more often affected than males (2:1 ratio), and cases of UNT are either congenital or acquired.³ Although most UNT cases are acquired and often found in females, approximately 15% of cases are congenital and are comprised largely by males. Acquired cases have been hypothesized to occur in association with hyperestrogenemic states such as pregnancy, puberty, oral contraceptive use and hormonal therapy, alcoholism, and liver disease including hepatitis B and C infections.^4,5 There is conflicting evidence as to whether there is an absolute increase in the presence of estrogen and progesterone receptors in the skin, as many case reports show no increase. Instead, others hypothesize that the condition is actually a result of somatic mosaicism and that the cutaneous lesions are genetically predisposed to becoming visibly evident under conditions of elevated estrogen.²

In our case, we hypothesize that the cause was elevated maternal estrogen levels present at higher than normal levels in the fetal circulation. The presence of gynecomastia seen in our patient supports the hypothesis that increased circulating estrogen may be present in infants with UNT.

The Diagnosis: Congenital Unilateral Nevoid Telangiectasia

Two weeks later the patches were noticeably lighter (Figures 1A and 1B). She continued to be in good health, but gynecomastia was notably present on examination (Figure 1C). At 3 months of age, all patches on the right arm, superior aspect of the chest, and superior aspect of the back had resolved, along with the gynecomastia (Figure 2).

This case describes the rare condition of congenital unilateral nevoid telangiectasia (UNT). Unilateral nevoid telangiectasia is a rare cutaneous vascular condition first described by Blaschko¹ in 1899. It is characterized by the presence of unilateral superficial telangiectases occurring most often in the cervical and upper thoracic dermatomes in a linear pattern.² Females are more often affected than males (2:1 ratio), and cases of UNT are either congenital or acquired.³ Although most UNT cases are acquired and often found in females, approximately 15% of cases are congenital and are comprised largely by males. Acquired cases have been hypothesized to occur in association with hyperestrogenemic states such as pregnancy, puberty, oral contraceptive use and hormonal therapy, alcoholism, and liver disease including hepatitis B and C infections.^4,5 There is conflicting evidence as to whether there is an absolute increase in the presence of estrogen and progesterone receptors in the skin, as many case reports show no increase. Instead, others hypothesize that the condition is actually a result of somatic mosaicism and that the cutaneous lesions are genetically predisposed to becoming visibly evident under conditions of elevated estrogen.²

In our case, we hypothesize that the cause was elevated maternal estrogen levels present at higher than normal levels in the fetal circulation. The presence of gynecomastia seen in our patient supports the hypothesis that increased circulating estrogen may be present in infants with UNT.

The Diagnosis: Congenital Unilateral Nevoid Telangiectasia

Two weeks later the patches were noticeably lighter (Figures 1A and 1B). She continued to be in good health, but gynecomastia was notably present on examination (Figure 1C). At 3 months of age, all patches on the right arm, superior aspect of the chest, and superior aspect of the back had resolved, along with the gynecomastia (Figure 2).

This case describes the rare condition of congenital unilateral nevoid telangiectasia (UNT). Unilateral nevoid telangiectasia is a rare cutaneous vascular condition first described by Blaschko¹ in 1899. It is characterized by the presence of unilateral superficial telangiectases occurring most often in the cervical and upper thoracic dermatomes in a linear pattern.² Females are more often affected than males (2:1 ratio), and cases of UNT are either congenital or acquired.³ Although most UNT cases are acquired and often found in females, approximately 15% of cases are congenital and are comprised largely by males. Acquired cases have been hypothesized to occur in association with hyperestrogenemic states such as pregnancy, puberty, oral contraceptive use and hormonal therapy, alcoholism, and liver disease including hepatitis B and C infections.^4,5 There is conflicting evidence as to whether there is an absolute increase in the presence of estrogen and progesterone receptors in the skin, as many case reports show no increase. Instead, others hypothesize that the condition is actually a result of somatic mosaicism and that the cutaneous lesions are genetically predisposed to becoming visibly evident under conditions of elevated estrogen.²

In our case, we hypothesize that the cause was elevated maternal estrogen levels present at higher than normal levels in the fetal circulation. The presence of gynecomastia seen in our patient supports the hypothesis that increased circulating estrogen may be present in infants with UNT.