Quiz

The Diagnosis: Disseminated Superficial Actinic Porokeratosis

Physical examination after 7 years of tanning salon use showed a tanned white man with multiple 4- to 5-mm, discrete, round to oval, reddish brown papules on the chest, back, abdomen, arms, and legs that were rough to palpate (Figure 1), with a peripheral rim of scale seen more prominently on dermoscopy. There were no lesions on the palms or soles. A subsequent 4-mm punch biopsy was done on the right abdomen and right thigh, which showed focal thinning of the epidermis, loss of the granular layer, a discrete column of parakeratosis and a characteristic feature of a coronoid lamella in the epidermis (Figure 2). The patient received 14 narrowband UVB (NB-UVB) treatments; however, he could not continue due to transportation issues. He visited the clinic sporadically for 6 months thereafter and reportedly went to tanning salons daily. The patient was subsequently lost to follow-up.

Figure 1. Multiple 4- to 5-mm, discrete, round to oval, reddish brown papules on the abdomen (A) and leg (B) that were rough to palpate.

Disseminated porokeratosis, or disseminated superficial actinic porokeratosis (DSAP), was first described in 1967 by Chernosky and Freeman.¹ It is the most common variant of porokeratosis. Other variants include Mibelli type, porokeratosis palmaris et plantaris disseminata, punctuate porokeratosis, and linear porokeratosis.^2-4 Porokeratosis is inherited in an autosomal-dominant fashion, presenting in the third or fourth decades of life; however, most cases are sporadic.⁵ Pruritus is a common symptom and can be debilitating.⁵

Disseminated superficial actinic porokeratosis can be precipitated by excessive sun exposure, with a reported increase in lesions during summer months and resolution during the winter months.⁶ The lesions of DSAP can be experimentally induced by exposure to daily use of artificial UV sunlamps.⁷ Patients with psoriasis undergoing psoralen plus UVA and NB-UVB treatments also have been reported to trigger DSAP.⁸ A study by Neumann et al⁶ suggested that a combination of both UVB and UVA wavelengths may be most effective in inducing DSAP. Exposure to UVA and UVB light may explain an increased number of DSAP lesions in patients who excessively visit tanning salons, as the bulbs emit a combination of wavelengths with UVA in much greater amounts than UVB.

Our patient developed DSAP secondary to artificial UV light exposure from excessive tanning salon use. Medications (allopurinol and lisinopril) were initially thought to be etiologic agents for the eruption and also corroborated with histologic findings of a drug eruption on the initial biopsy. However, new lesions continued to develop even after cessation of medications and NB-UVB treatments. A subsequent biopsy and further history of daily tanning salon use confirmed the diagnosis of DSAP.

Figure 2. Biopsy revealed a discrete column of parakeratosis, a characteristic feature of a coronoid lamella in the epidermis, and moderate papillary dermis lymphocytic infiltrate (H&E, original magnification ×10).

Therapies for this condition are limited with variable degrees of success. Cryotherapy, 5-fluorouracil cream, imiquimod cream 5%, Q-switched ruby laser, diclofenac gel 3%, and acitretin for more widespread or refractory lesions have been used with partial to complete resolution of DSAP.⁹

We present this case to highlight the occurrence of DSAP secondary to UV light exposure from excessive tanning salon use.

The Diagnosis: Disseminated Superficial Actinic Porokeratosis

Physical examination after 7 years of tanning salon use showed a tanned white man with multiple 4- to 5-mm, discrete, round to oval, reddish brown papules on the chest, back, abdomen, arms, and legs that were rough to palpate (Figure 1), with a peripheral rim of scale seen more prominently on dermoscopy. There were no lesions on the palms or soles. A subsequent 4-mm punch biopsy was done on the right abdomen and right thigh, which showed focal thinning of the epidermis, loss of the granular layer, a discrete column of parakeratosis and a characteristic feature of a coronoid lamella in the epidermis (Figure 2). The patient received 14 narrowband UVB (NB-UVB) treatments; however, he could not continue due to transportation issues. He visited the clinic sporadically for 6 months thereafter and reportedly went to tanning salons daily. The patient was subsequently lost to follow-up.

Figure 1. Multiple 4- to 5-mm, discrete, round to oval, reddish brown papules on the abdomen (A) and leg (B) that were rough to palpate.

Disseminated porokeratosis, or disseminated superficial actinic porokeratosis (DSAP), was first described in 1967 by Chernosky and Freeman.¹ It is the most common variant of porokeratosis. Other variants include Mibelli type, porokeratosis palmaris et plantaris disseminata, punctuate porokeratosis, and linear porokeratosis.^2-4 Porokeratosis is inherited in an autosomal-dominant fashion, presenting in the third or fourth decades of life; however, most cases are sporadic.⁵ Pruritus is a common symptom and can be debilitating.⁵

Disseminated superficial actinic porokeratosis can be precipitated by excessive sun exposure, with a reported increase in lesions during summer months and resolution during the winter months.⁶ The lesions of DSAP can be experimentally induced by exposure to daily use of artificial UV sunlamps.⁷ Patients with psoriasis undergoing psoralen plus UVA and NB-UVB treatments also have been reported to trigger DSAP.⁸ A study by Neumann et al⁶ suggested that a combination of both UVB and UVA wavelengths may be most effective in inducing DSAP. Exposure to UVA and UVB light may explain an increased number of DSAP lesions in patients who excessively visit tanning salons, as the bulbs emit a combination of wavelengths with UVA in much greater amounts than UVB.

Our patient developed DSAP secondary to artificial UV light exposure from excessive tanning salon use. Medications (allopurinol and lisinopril) were initially thought to be etiologic agents for the eruption and also corroborated with histologic findings of a drug eruption on the initial biopsy. However, new lesions continued to develop even after cessation of medications and NB-UVB treatments. A subsequent biopsy and further history of daily tanning salon use confirmed the diagnosis of DSAP.

Figure 2. Biopsy revealed a discrete column of parakeratosis, a characteristic feature of a coronoid lamella in the epidermis, and moderate papillary dermis lymphocytic infiltrate (H&E, original magnification ×10).

Therapies for this condition are limited with variable degrees of success. Cryotherapy, 5-fluorouracil cream, imiquimod cream 5%, Q-switched ruby laser, diclofenac gel 3%, and acitretin for more widespread or refractory lesions have been used with partial to complete resolution of DSAP.⁹

We present this case to highlight the occurrence of DSAP secondary to UV light exposure from excessive tanning salon use.

The Diagnosis: Disseminated Superficial Actinic Porokeratosis

Physical examination after 7 years of tanning salon use showed a tanned white man with multiple 4- to 5-mm, discrete, round to oval, reddish brown papules on the chest, back, abdomen, arms, and legs that were rough to palpate (Figure 1), with a peripheral rim of scale seen more prominently on dermoscopy. There were no lesions on the palms or soles. A subsequent 4-mm punch biopsy was done on the right abdomen and right thigh, which showed focal thinning of the epidermis, loss of the granular layer, a discrete column of parakeratosis and a characteristic feature of a coronoid lamella in the epidermis (Figure 2). The patient received 14 narrowband UVB (NB-UVB) treatments; however, he could not continue due to transportation issues. He visited the clinic sporadically for 6 months thereafter and reportedly went to tanning salons daily. The patient was subsequently lost to follow-up.

Figure 1. Multiple 4- to 5-mm, discrete, round to oval, reddish brown papules on the abdomen (A) and leg (B) that were rough to palpate.

Disseminated porokeratosis, or disseminated superficial actinic porokeratosis (DSAP), was first described in 1967 by Chernosky and Freeman.¹ It is the most common variant of porokeratosis. Other variants include Mibelli type, porokeratosis palmaris et plantaris disseminata, punctuate porokeratosis, and linear porokeratosis.^2-4 Porokeratosis is inherited in an autosomal-dominant fashion, presenting in the third or fourth decades of life; however, most cases are sporadic.⁵ Pruritus is a common symptom and can be debilitating.⁵

Disseminated superficial actinic porokeratosis can be precipitated by excessive sun exposure, with a reported increase in lesions during summer months and resolution during the winter months.⁶ The lesions of DSAP can be experimentally induced by exposure to daily use of artificial UV sunlamps.⁷ Patients with psoriasis undergoing psoralen plus UVA and NB-UVB treatments also have been reported to trigger DSAP.⁸ A study by Neumann et al⁶ suggested that a combination of both UVB and UVA wavelengths may be most effective in inducing DSAP. Exposure to UVA and UVB light may explain an increased number of DSAP lesions in patients who excessively visit tanning salons, as the bulbs emit a combination of wavelengths with UVA in much greater amounts than UVB.

Our patient developed DSAP secondary to artificial UV light exposure from excessive tanning salon use. Medications (allopurinol and lisinopril) were initially thought to be etiologic agents for the eruption and also corroborated with histologic findings of a drug eruption on the initial biopsy. However, new lesions continued to develop even after cessation of medications and NB-UVB treatments. A subsequent biopsy and further history of daily tanning salon use confirmed the diagnosis of DSAP.

Figure 2. Biopsy revealed a discrete column of parakeratosis, a characteristic feature of a coronoid lamella in the epidermis, and moderate papillary dermis lymphocytic infiltrate (H&E, original magnification ×10).

Therapies for this condition are limited with variable degrees of success. Cryotherapy, 5-fluorouracil cream, imiquimod cream 5%, Q-switched ruby laser, diclofenac gel 3%, and acitretin for more widespread or refractory lesions have been used with partial to complete resolution of DSAP.⁹

We present this case to highlight the occurrence of DSAP secondary to UV light exposure from excessive tanning salon use.

The Diagnosis: Primary Systemic Amyloidosis

Our patient presented with multiple firm waxy nodules on the mucosal surface of the lower lip. Excision biopsy showed thickening of blood vessel walls with abundant amorphous material that was consistent with amyloid. Further staining with Congo red demonstrated brick red amorphous material within the vessel walls on routine light microscopy (Figure 1), and crystal violet stain showed metachromasia (Figure 2). Fine needle aspiration of the abdominal fat-pad showed amyloid. The final diagnosis was primary systemic amyloidosis (PSA).

Figure 1. Congo red staining showed a brick red appearance of amyloid within the vessel walls on routine light microscopy (original magnification ×200).

Figure 2. Crystal violet staining around the blood vessels showed metachromasia (original magnification ×100).

Amyloid is an ubiquitous fibrillar protein arranged in a cross-beta-pleated sheet that is confirmed with x-ray crystallography.^1,2 More than 25 variants of amyloid have been identified.³ Pathologic deposition of amyloid-derived material results in a variable spectrum of clinical findings, collectively known as amyloidosis, with presentations ranging from nonspecific fever or fatigue to frank organ failure, depending on the organ involved. In PSA, immunoglobulin light chains are deposited throughout the body. Associated conditions include malignant or benign monoclonal gammopathy, multiple myeloma, Waldenström macroglobulinemia, malignant lymphoma, heavy chain disease, and chronic lymphocytic leukemia.^2,4 The most commonly involved organ systems are the heart, lungs, liver, and kidneys. When patients present with unexplained heart failure, orthostatic hypotension, hepatomegaly, peripheral neuropathy, carpal tunnel syndrome, or renal insufficiency, amyloidosis should always be considered in the differential diagnosis.³

Cutaneous lesions of PSA tend to be vascular due to amyloid infiltration of blood vessel walls, manifesting as petechiae, purpura, ecchymoses, or nonhealing ulcers. Pinch purpura frequently are seen in the periorbital region after minor trauma and are recognized as a clinical indicator of PSA.^2,4 Xerostomia from amyloid infiltrates in salivary glands is extremely common, and cases of amyloid in the eyes, bones, and thyroid gland have been reported.² Macroglossia is seen in 12% to 40% of cases; coupled with xerostomia, it can lead to oropharyngeal dysphagia.^2,5

Systemic amyloidosis can be further divided into primary (idiopathic or multiple myeloma associated) or secondary to chronic inflammatory conditions or infections; the key difference is the protein from which the abnormal amyloid is derived.^1,4 The presence of cutaneous amyloidosis renders the need to rule out systemic disease because amyloidosis may be a purely localized or systemic process.⁴ Nodular amyloidosis is a localized form of amyloid that also has immunoglobulin light chain deposits and clinically appears exactly the same as PSA; however, the deposits are restricted to the skin.^1,2,4,5

Characteristic biopsy findings in cutaneous amyloidosis include amorphous orange-red amyloid deposits on hematoxylin and eosin–stained sections. The gold standard for amyloid detection is apple green birefringence under polarized light with Congo red stain or electron microscopy.^6,7 Other stains used to identify amyloid include crystal violet, methyl violet, periodic acid–Schiff, Sirius red, pagoda red, Dylon stain, and thioflavine T.^1,2 Confirmation of systemic disease can be accomplished by fine needle aspiration of abdominal fat-pads or rectal mucosal biopsies.^1,3,4 Biopsy of accessory salivary glands also has been reported to be very sensitive and specific.²

Treatment options remain limited; localized cutaneous disease may respond to topical corticosteroids, calcineurin inhibitors, or phototherapy. Primary systemic amyloidosis can be treated with a combination of steroids, melphalan, or colchicine often followed by autologous stem cell transplantation⁸; however, these regimens are not always curative and patients often have a poor prognosis.¹

The Diagnosis: Primary Systemic Amyloidosis

Our patient presented with multiple firm waxy nodules on the mucosal surface of the lower lip. Excision biopsy showed thickening of blood vessel walls with abundant amorphous material that was consistent with amyloid. Further staining with Congo red demonstrated brick red amorphous material within the vessel walls on routine light microscopy (Figure 1), and crystal violet stain showed metachromasia (Figure 2). Fine needle aspiration of the abdominal fat-pad showed amyloid. The final diagnosis was primary systemic amyloidosis (PSA).

Figure 1. Congo red staining showed a brick red appearance of amyloid within the vessel walls on routine light microscopy (original magnification ×200).

Figure 2. Crystal violet staining around the blood vessels showed metachromasia (original magnification ×100).

Amyloid is an ubiquitous fibrillar protein arranged in a cross-beta-pleated sheet that is confirmed with x-ray crystallography.^1,2 More than 25 variants of amyloid have been identified.³ Pathologic deposition of amyloid-derived material results in a variable spectrum of clinical findings, collectively known as amyloidosis, with presentations ranging from nonspecific fever or fatigue to frank organ failure, depending on the organ involved. In PSA, immunoglobulin light chains are deposited throughout the body. Associated conditions include malignant or benign monoclonal gammopathy, multiple myeloma, Waldenström macroglobulinemia, malignant lymphoma, heavy chain disease, and chronic lymphocytic leukemia.^2,4 The most commonly involved organ systems are the heart, lungs, liver, and kidneys. When patients present with unexplained heart failure, orthostatic hypotension, hepatomegaly, peripheral neuropathy, carpal tunnel syndrome, or renal insufficiency, amyloidosis should always be considered in the differential diagnosis.³

Cutaneous lesions of PSA tend to be vascular due to amyloid infiltration of blood vessel walls, manifesting as petechiae, purpura, ecchymoses, or nonhealing ulcers. Pinch purpura frequently are seen in the periorbital region after minor trauma and are recognized as a clinical indicator of PSA.^2,4 Xerostomia from amyloid infiltrates in salivary glands is extremely common, and cases of amyloid in the eyes, bones, and thyroid gland have been reported.² Macroglossia is seen in 12% to 40% of cases; coupled with xerostomia, it can lead to oropharyngeal dysphagia.^2,5

Systemic amyloidosis can be further divided into primary (idiopathic or multiple myeloma associated) or secondary to chronic inflammatory conditions or infections; the key difference is the protein from which the abnormal amyloid is derived.^1,4 The presence of cutaneous amyloidosis renders the need to rule out systemic disease because amyloidosis may be a purely localized or systemic process.⁴ Nodular amyloidosis is a localized form of amyloid that also has immunoglobulin light chain deposits and clinically appears exactly the same as PSA; however, the deposits are restricted to the skin.^1,2,4,5

Characteristic biopsy findings in cutaneous amyloidosis include amorphous orange-red amyloid deposits on hematoxylin and eosin–stained sections. The gold standard for amyloid detection is apple green birefringence under polarized light with Congo red stain or electron microscopy.^6,7 Other stains used to identify amyloid include crystal violet, methyl violet, periodic acid–Schiff, Sirius red, pagoda red, Dylon stain, and thioflavine T.^1,2 Confirmation of systemic disease can be accomplished by fine needle aspiration of abdominal fat-pads or rectal mucosal biopsies.^1,3,4 Biopsy of accessory salivary glands also has been reported to be very sensitive and specific.²

Treatment options remain limited; localized cutaneous disease may respond to topical corticosteroids, calcineurin inhibitors, or phototherapy. Primary systemic amyloidosis can be treated with a combination of steroids, melphalan, or colchicine often followed by autologous stem cell transplantation⁸; however, these regimens are not always curative and patients often have a poor prognosis.¹

The Diagnosis: Primary Systemic Amyloidosis

Our patient presented with multiple firm waxy nodules on the mucosal surface of the lower lip. Excision biopsy showed thickening of blood vessel walls with abundant amorphous material that was consistent with amyloid. Further staining with Congo red demonstrated brick red amorphous material within the vessel walls on routine light microscopy (Figure 1), and crystal violet stain showed metachromasia (Figure 2). Fine needle aspiration of the abdominal fat-pad showed amyloid. The final diagnosis was primary systemic amyloidosis (PSA).

Figure 1. Congo red staining showed a brick red appearance of amyloid within the vessel walls on routine light microscopy (original magnification ×200).

Figure 2. Crystal violet staining around the blood vessels showed metachromasia (original magnification ×100).

Amyloid is an ubiquitous fibrillar protein arranged in a cross-beta-pleated sheet that is confirmed with x-ray crystallography.^1,2 More than 25 variants of amyloid have been identified.³ Pathologic deposition of amyloid-derived material results in a variable spectrum of clinical findings, collectively known as amyloidosis, with presentations ranging from nonspecific fever or fatigue to frank organ failure, depending on the organ involved. In PSA, immunoglobulin light chains are deposited throughout the body. Associated conditions include malignant or benign monoclonal gammopathy, multiple myeloma, Waldenström macroglobulinemia, malignant lymphoma, heavy chain disease, and chronic lymphocytic leukemia.^2,4 The most commonly involved organ systems are the heart, lungs, liver, and kidneys. When patients present with unexplained heart failure, orthostatic hypotension, hepatomegaly, peripheral neuropathy, carpal tunnel syndrome, or renal insufficiency, amyloidosis should always be considered in the differential diagnosis.³

Cutaneous lesions of PSA tend to be vascular due to amyloid infiltration of blood vessel walls, manifesting as petechiae, purpura, ecchymoses, or nonhealing ulcers. Pinch purpura frequently are seen in the periorbital region after minor trauma and are recognized as a clinical indicator of PSA.^2,4 Xerostomia from amyloid infiltrates in salivary glands is extremely common, and cases of amyloid in the eyes, bones, and thyroid gland have been reported.² Macroglossia is seen in 12% to 40% of cases; coupled with xerostomia, it can lead to oropharyngeal dysphagia.^2,5

Systemic amyloidosis can be further divided into primary (idiopathic or multiple myeloma associated) or secondary to chronic inflammatory conditions or infections; the key difference is the protein from which the abnormal amyloid is derived.^1,4 The presence of cutaneous amyloidosis renders the need to rule out systemic disease because amyloidosis may be a purely localized or systemic process.⁴ Nodular amyloidosis is a localized form of amyloid that also has immunoglobulin light chain deposits and clinically appears exactly the same as PSA; however, the deposits are restricted to the skin.^1,2,4,5

Characteristic biopsy findings in cutaneous amyloidosis include amorphous orange-red amyloid deposits on hematoxylin and eosin–stained sections. The gold standard for amyloid detection is apple green birefringence under polarized light with Congo red stain or electron microscopy.^6,7 Other stains used to identify amyloid include crystal violet, methyl violet, periodic acid–Schiff, Sirius red, pagoda red, Dylon stain, and thioflavine T.^1,2 Confirmation of systemic disease can be accomplished by fine needle aspiration of abdominal fat-pads or rectal mucosal biopsies.^1,3,4 Biopsy of accessory salivary glands also has been reported to be very sensitive and specific.²

Treatment options remain limited; localized cutaneous disease may respond to topical corticosteroids, calcineurin inhibitors, or phototherapy. Primary systemic amyloidosis can be treated with a combination of steroids, melphalan, or colchicine often followed by autologous stem cell transplantation⁸; however, these regimens are not always curative and patients often have a poor prognosis.¹

The Diagnosis: Prostate Cancer Metastases

Cutaneous involvement of visceral tumors can occur indirectly, with the tumor causing changes in the skin without the presence of tumor cells (ie, paraneoplastic processes), or directly, with the presence of tumor cells in the skin (ie, metastasis).¹ Cutaneous metastases from solid primary tumors are uncommon. The incidence of metastasis to the skin from visceral malignancies ranges from 0.3% to 9.0%.² The most common primary internal tumors to metastasize to the skin are those arising from the breasts, lungs, colon, ovaries, and head and neck.³ Although prostate cancer is the most common cancer in males (making up 28% of new cancer diagnoses), excluding basal and squamous cell skin cancers, it rarely metastasizes to the skin, representing less than 1% of all cutaneous metastasis.^4,5

There are 4 proposed mechanisms for metastatic dissemination to the skin: (1) direct invasion from underlying neoplasm; (2) implantation from a surgical scar; (3) spread through the lymphatics; and/or (4) hematogenous spread. The most common sites of prostate cancer cutaneous metastasis are the inguinal area, penis, and lower abdomen,² which is likely due to spread via the lymphatic drainage. Cutaneous metastasis to distant sites such as the scalp or chest, as in our patient, may be secondary to hematogenous spread.

Generally, cutaneous metastases from visceral malignancies manifest as urticaria or a nonspecific macular rash.² However, prostate cancer cutaneous metastases commonly present as papules or subcutaneous nodules but also can have inflammatory, cicatricial, sclerodermoid, telangiectatic, or zosteriform morphologies.^2,5,6 The lesions of prostate cancer cutaneous metastases are typically well-circumscribed, flesh-colored or pink to red, oval plaques or nodules ranging in size from several millimeters to a few centimeters.² The cutaneous lesions generally are multiple and can be localized or diffuse in distribution. The clinical differential diagnosis is broad in patients undergoing systemic treatment of prostate cancer and often includes drug reaction, cutaneous lymphoma, atypical mycobacterial or deep fungal infection, or paraneoplastic dermatosis.

Laboratory studies often reveal an elevated serum prostate-specific antigen (PSA) level, a glycoprotein that functions in the liquefaction of seminal fluid made primarily by the prostate, often in benign hypertrophic and malignant prostatic processes.⁷ Definitive diagnosis of prostate cancer cutaneous metastasis can be established by histologic examination. Excisional or punch biopsy is preferred over superficial shave biopsy. Metastasis from prostate adenocarcinoma often reveals infiltrative growth of disorganized atypical epithelial cells along collagen bundles in the dermis and subcutis (Figure 1).^2,8 The presence of lymphovascular invasion further increases the suspicion of metastasis. Metastatic lesions may resemble the primary lesion; however, they are often poorly differentiated, making histologic comparison difficult.

Figure 1. Biopsy revealed cords of atypical epithelioid cells dissecting through dermal collagen bundles, accompanied by abundant mucin. Atypical cells displayed nuclear pleomorphism, and multiple mitotic figures were present (H&E, original magnification ×100).

Figure 2. Immunohistochemistry was strongly positive for prostate-specific antigen and focally positive for prostate-specific acid phosphatase (original magnification ×100).

The diagnosis is confirmed immunohistochemically with PSA and/or prostate-specific acid phosphatase immunostaining (Figure 2), which together have nearly 100% specificity for prostate adenocarcinomas.⁹ Although rare, PSA and or prostate-specific acid phosphatase may be weakly positive in nephrogenic adenoma.¹⁰ Another biomarker, urinary prostate cancer antigen 3, is being evaluated to identify men with indolent prostate cancer.¹¹ It is unknown how useful this marker will be in the immunohistochemical identification of prostate cancer cutaneous metastases.

A large review of reported cases of cutaneous metastases from internal malignancies revealed that the majority of patients had known systemic disease but enjoyed a good performance status at the time of diagnosis.² As such, skin metastases may serve as the initial indicator of visceral recurrence. Prostate cancer is second only to lung cancer as the deadliest cancer in males,⁴ and cutaneous metastasis garners a particularly poor prognosis. The mean survival time after diagnosis of cutaneous metastasis is 7 months.⁸ Therefore, treatment of cutaneous metastases is largely palliative, including local excision and intralesional chemotherapy.

The Diagnosis: Prostate Cancer Metastases

Cutaneous involvement of visceral tumors can occur indirectly, with the tumor causing changes in the skin without the presence of tumor cells (ie, paraneoplastic processes), or directly, with the presence of tumor cells in the skin (ie, metastasis).¹ Cutaneous metastases from solid primary tumors are uncommon. The incidence of metastasis to the skin from visceral malignancies ranges from 0.3% to 9.0%.² The most common primary internal tumors to metastasize to the skin are those arising from the breasts, lungs, colon, ovaries, and head and neck.³ Although prostate cancer is the most common cancer in males (making up 28% of new cancer diagnoses), excluding basal and squamous cell skin cancers, it rarely metastasizes to the skin, representing less than 1% of all cutaneous metastasis.^4,5

There are 4 proposed mechanisms for metastatic dissemination to the skin: (1) direct invasion from underlying neoplasm; (2) implantation from a surgical scar; (3) spread through the lymphatics; and/or (4) hematogenous spread. The most common sites of prostate cancer cutaneous metastasis are the inguinal area, penis, and lower abdomen,² which is likely due to spread via the lymphatic drainage. Cutaneous metastasis to distant sites such as the scalp or chest, as in our patient, may be secondary to hematogenous spread.

Generally, cutaneous metastases from visceral malignancies manifest as urticaria or a nonspecific macular rash.² However, prostate cancer cutaneous metastases commonly present as papules or subcutaneous nodules but also can have inflammatory, cicatricial, sclerodermoid, telangiectatic, or zosteriform morphologies.^2,5,6 The lesions of prostate cancer cutaneous metastases are typically well-circumscribed, flesh-colored or pink to red, oval plaques or nodules ranging in size from several millimeters to a few centimeters.² The cutaneous lesions generally are multiple and can be localized or diffuse in distribution. The clinical differential diagnosis is broad in patients undergoing systemic treatment of prostate cancer and often includes drug reaction, cutaneous lymphoma, atypical mycobacterial or deep fungal infection, or paraneoplastic dermatosis.

Laboratory studies often reveal an elevated serum prostate-specific antigen (PSA) level, a glycoprotein that functions in the liquefaction of seminal fluid made primarily by the prostate, often in benign hypertrophic and malignant prostatic processes.⁷ Definitive diagnosis of prostate cancer cutaneous metastasis can be established by histologic examination. Excisional or punch biopsy is preferred over superficial shave biopsy. Metastasis from prostate adenocarcinoma often reveals infiltrative growth of disorganized atypical epithelial cells along collagen bundles in the dermis and subcutis (Figure 1).^2,8 The presence of lymphovascular invasion further increases the suspicion of metastasis. Metastatic lesions may resemble the primary lesion; however, they are often poorly differentiated, making histologic comparison difficult.

Figure 1. Biopsy revealed cords of atypical epithelioid cells dissecting through dermal collagen bundles, accompanied by abundant mucin. Atypical cells displayed nuclear pleomorphism, and multiple mitotic figures were present (H&E, original magnification ×100).

Figure 2. Immunohistochemistry was strongly positive for prostate-specific antigen and focally positive for prostate-specific acid phosphatase (original magnification ×100).

The diagnosis is confirmed immunohistochemically with PSA and/or prostate-specific acid phosphatase immunostaining (Figure 2), which together have nearly 100% specificity for prostate adenocarcinomas.⁹ Although rare, PSA and or prostate-specific acid phosphatase may be weakly positive in nephrogenic adenoma.¹⁰ Another biomarker, urinary prostate cancer antigen 3, is being evaluated to identify men with indolent prostate cancer.¹¹ It is unknown how useful this marker will be in the immunohistochemical identification of prostate cancer cutaneous metastases.

A large review of reported cases of cutaneous metastases from internal malignancies revealed that the majority of patients had known systemic disease but enjoyed a good performance status at the time of diagnosis.² As such, skin metastases may serve as the initial indicator of visceral recurrence. Prostate cancer is second only to lung cancer as the deadliest cancer in males,⁴ and cutaneous metastasis garners a particularly poor prognosis. The mean survival time after diagnosis of cutaneous metastasis is 7 months.⁸ Therefore, treatment of cutaneous metastases is largely palliative, including local excision and intralesional chemotherapy.

The Diagnosis: Prostate Cancer Metastases

Cutaneous involvement of visceral tumors can occur indirectly, with the tumor causing changes in the skin without the presence of tumor cells (ie, paraneoplastic processes), or directly, with the presence of tumor cells in the skin (ie, metastasis).¹ Cutaneous metastases from solid primary tumors are uncommon. The incidence of metastasis to the skin from visceral malignancies ranges from 0.3% to 9.0%.² The most common primary internal tumors to metastasize to the skin are those arising from the breasts, lungs, colon, ovaries, and head and neck.³ Although prostate cancer is the most common cancer in males (making up 28% of new cancer diagnoses), excluding basal and squamous cell skin cancers, it rarely metastasizes to the skin, representing less than 1% of all cutaneous metastasis.^4,5

There are 4 proposed mechanisms for metastatic dissemination to the skin: (1) direct invasion from underlying neoplasm; (2) implantation from a surgical scar; (3) spread through the lymphatics; and/or (4) hematogenous spread. The most common sites of prostate cancer cutaneous metastasis are the inguinal area, penis, and lower abdomen,² which is likely due to spread via the lymphatic drainage. Cutaneous metastasis to distant sites such as the scalp or chest, as in our patient, may be secondary to hematogenous spread.

Generally, cutaneous metastases from visceral malignancies manifest as urticaria or a nonspecific macular rash.² However, prostate cancer cutaneous metastases commonly present as papules or subcutaneous nodules but also can have inflammatory, cicatricial, sclerodermoid, telangiectatic, or zosteriform morphologies.^2,5,6 The lesions of prostate cancer cutaneous metastases are typically well-circumscribed, flesh-colored or pink to red, oval plaques or nodules ranging in size from several millimeters to a few centimeters.² The cutaneous lesions generally are multiple and can be localized or diffuse in distribution. The clinical differential diagnosis is broad in patients undergoing systemic treatment of prostate cancer and often includes drug reaction, cutaneous lymphoma, atypical mycobacterial or deep fungal infection, or paraneoplastic dermatosis.

Laboratory studies often reveal an elevated serum prostate-specific antigen (PSA) level, a glycoprotein that functions in the liquefaction of seminal fluid made primarily by the prostate, often in benign hypertrophic and malignant prostatic processes.⁷ Definitive diagnosis of prostate cancer cutaneous metastasis can be established by histologic examination. Excisional or punch biopsy is preferred over superficial shave biopsy. Metastasis from prostate adenocarcinoma often reveals infiltrative growth of disorganized atypical epithelial cells along collagen bundles in the dermis and subcutis (Figure 1).^2,8 The presence of lymphovascular invasion further increases the suspicion of metastasis. Metastatic lesions may resemble the primary lesion; however, they are often poorly differentiated, making histologic comparison difficult.

Figure 1. Biopsy revealed cords of atypical epithelioid cells dissecting through dermal collagen bundles, accompanied by abundant mucin. Atypical cells displayed nuclear pleomorphism, and multiple mitotic figures were present (H&E, original magnification ×100).

Figure 2. Immunohistochemistry was strongly positive for prostate-specific antigen and focally positive for prostate-specific acid phosphatase (original magnification ×100).

The diagnosis is confirmed immunohistochemically with PSA and/or prostate-specific acid phosphatase immunostaining (Figure 2), which together have nearly 100% specificity for prostate adenocarcinomas.⁹ Although rare, PSA and or prostate-specific acid phosphatase may be weakly positive in nephrogenic adenoma.¹⁰ Another biomarker, urinary prostate cancer antigen 3, is being evaluated to identify men with indolent prostate cancer.¹¹ It is unknown how useful this marker will be in the immunohistochemical identification of prostate cancer cutaneous metastases.

A large review of reported cases of cutaneous metastases from internal malignancies revealed that the majority of patients had known systemic disease but enjoyed a good performance status at the time of diagnosis.² As such, skin metastases may serve as the initial indicator of visceral recurrence. Prostate cancer is second only to lung cancer as the deadliest cancer in males,⁴ and cutaneous metastasis garners a particularly poor prognosis. The mean survival time after diagnosis of cutaneous metastasis is 7 months.⁸ Therefore, treatment of cutaneous metastases is largely palliative, including local excision and intralesional chemotherapy.

The Diagnosis: Onychomadesis

The nail changes were characteristic of onychomadesis. Systemic illness in this patient most likely resulted in temporary arrest of nail matrix activity, leading to separation of the proximal nail plate from the proximal nail fold, which gave rise to a deep transverse sulcus.¹ Conversely, Beau lines are characterized by transverse grooves that move distally as the nail grows. Onychomadesis also is seen in pemphigus vulgaris, which could be due to an autoimmune disease inhibiting normal nail plate growth and development of blisters beneath the nail causing detachment of the nail plate.² Drug-induced Beau lines or onychomadesis are most frequently caused by chemotherapeutic agents (taxanes) and retinoids, which reflect an arrest in epithelial proliferation.³ Familial cases also have been described.⁴ Management of the nail abnormality should focus on the underlying medical problem or triggering factor. In our patient, hypertension and kidney disease were managed by a low-salt diet, oral antihypertensives, and iron replacement.

The Diagnosis: Onychomadesis

The nail changes were characteristic of onychomadesis. Systemic illness in this patient most likely resulted in temporary arrest of nail matrix activity, leading to separation of the proximal nail plate from the proximal nail fold, which gave rise to a deep transverse sulcus.¹ Conversely, Beau lines are characterized by transverse grooves that move distally as the nail grows. Onychomadesis also is seen in pemphigus vulgaris, which could be due to an autoimmune disease inhibiting normal nail plate growth and development of blisters beneath the nail causing detachment of the nail plate.² Drug-induced Beau lines or onychomadesis are most frequently caused by chemotherapeutic agents (taxanes) and retinoids, which reflect an arrest in epithelial proliferation.³ Familial cases also have been described.⁴ Management of the nail abnormality should focus on the underlying medical problem or triggering factor. In our patient, hypertension and kidney disease were managed by a low-salt diet, oral antihypertensives, and iron replacement.

The Diagnosis: Onychomadesis

The nail changes were characteristic of onychomadesis. Systemic illness in this patient most likely resulted in temporary arrest of nail matrix activity, leading to separation of the proximal nail plate from the proximal nail fold, which gave rise to a deep transverse sulcus.¹ Conversely, Beau lines are characterized by transverse grooves that move distally as the nail grows. Onychomadesis also is seen in pemphigus vulgaris, which could be due to an autoimmune disease inhibiting normal nail plate growth and development of blisters beneath the nail causing detachment of the nail plate.² Drug-induced Beau lines or onychomadesis are most frequently caused by chemotherapeutic agents (taxanes) and retinoids, which reflect an arrest in epithelial proliferation.³ Familial cases also have been described.⁴ Management of the nail abnormality should focus on the underlying medical problem or triggering factor. In our patient, hypertension and kidney disease were managed by a low-salt diet, oral antihypertensives, and iron replacement.