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A 24-year-old man presented with a 5-cm asymptomatic, indurated, well-defined nodule with a violaceous center surrounded by a greenish halo on the lower back of 3 months’ duration, along with lymphadenopathy. There was no history of trauma, weight loss, bleeding, or systemic illness. A biopsy revealed sheets of pleomorphic cells with lobulated nuclei and detectable granular cytoplasm. Immunohistochemistry showed strong myeloperoxidase activity in neoplastic cells that were CD13^- and CD56^-.

The Diagnosis: Granulocytic Sarcoma

Granulocytic sarcoma (GS), sometimes known as leukemia cutis, myeloid sarcoma, or an extramedullary myeloid tumor, is a rare localized collection of immature cells of granulocytic series or the cells of each maturation step in extramedullary sites. Originally described in 1811, the condition was noted after identifying an extramedullary collection of immature granulocytes involving the orbit. Then in 1853 the term chloroma was coined because of the greenish appearance of the tumor when exposed to light due to myeloperoxidase activity in the tumor cells. Finally, in 1967 the term granulocytic sarcoma was introduced because the greenish appearance was not observed in all cases, providing a more correct term.¹

Granulocytic sarcoma often manifests in patients with acute myeloid leukemia, chronic myelogenous leukemia, chronic idiopathic myelofibrosis, eosinophilia, refractory anemia, or polycythemia vera, and as an isolated form in patients without apparent hematologic disorder.²

Cutaneous manifestations of leukemia can be specific (eg, GS) or nonspecific (eg, panniculitis, generalized pruritus).^2,3 The tumor often appears as a solitary mass (Figure 1); however, in rare instances it can be multifocal. It usually presents as a rapidly growing nodular mass with solid consistence, and it is seen in patients of any age but most often those aged 45 to 55 years as well as in patients younger than 15 years.⁴

Figure 1. A 5-cm indurated nodule with a violaceous center surrounded by a greenish halo on the lower back.

Granulocytic sarcoma is most commonly associated with acute myeloid leukemia. However, it is interesting that the chloroma appears before the onset of leukemia. Occasionally GS is associated with acute myeloid leukemia as a presenting symptom or as a manifestation of recurrence of the disease that was usually related to poor prognosis.⁵ In patients with GS that is associated with myeloproliferative neoplasms, the occurrence of GS frequently is associated with acute transformation of the disease and therefore a poor prognosis.⁶

The most common sites of involvement are bone, soft tissue, lymph nodes, and skin. The prognosis does not vary according to location.

Cutaneous B-cell lymphoma should be considered in the differential diagnosis, as it may be clinically observed as single or multiple violaceous nodules involving the head, neck, and/or trunk. Histologically, there generally is a bottom-heavy infiltrate of lymphocytes sparing the epidermis (Figure 2). Immunohistochemistry, flow cytometry, or cytochemical stains often are needed to exclude lymphoma. Pseudochloroma is a rare disease characterized by a collection of normal hematopoietic tissue in locations other than GS. It can be distinguished from GS by its constituent of mature cells.⁷

Figure 2.  A biopsy demonstrated pleomorphic cells with lobulated nuclei and detectable granular cytoplasm (H&E, original magnification ×220), with strong myeloperoxidase activity in neoplastic cells (original magnification ×400 [inset]).

Granulocytic sarcoma implies a therapeutic challenge for the clinician. It should always be considered as part of a systemic disease rather than an isolated skin disorder. In patients with evidence of leukemia and GS, systemic chemotherapy is the first line of treatment. Other effective treatment regimens include radiotherapy (electron beam radiation), either alone or in combination with systemic chemotherapy (eg, hydroxyurea, methotrexate).⁸ If GS persists after chemotherapy, local treatment (eg, radiotherapy, surgery) should be considered with variable results.²


                 

A 24-year-old man presented with a 5-cm asymptomatic, indurated, well-defined nodule with a violaceous center surrounded by a greenish halo on the lower back of 3 months’ duration, along with lymphadenopathy. There was no history of trauma, weight loss, bleeding, or systemic illness. A biopsy revealed sheets of pleomorphic cells with lobulated nuclei and detectable granular cytoplasm. Immunohistochemistry showed strong myeloperoxidase activity in neoplastic cells that were CD13^- and CD56^-.

The Diagnosis: Granulocytic Sarcoma

Granulocytic sarcoma (GS), sometimes known as leukemia cutis, myeloid sarcoma, or an extramedullary myeloid tumor, is a rare localized collection of immature cells of granulocytic series or the cells of each maturation step in extramedullary sites. Originally described in 1811, the condition was noted after identifying an extramedullary collection of immature granulocytes involving the orbit. Then in 1853 the term chloroma was coined because of the greenish appearance of the tumor when exposed to light due to myeloperoxidase activity in the tumor cells. Finally, in 1967 the term granulocytic sarcoma was introduced because the greenish appearance was not observed in all cases, providing a more correct term.¹

Granulocytic sarcoma often manifests in patients with acute myeloid leukemia, chronic myelogenous leukemia, chronic idiopathic myelofibrosis, eosinophilia, refractory anemia, or polycythemia vera, and as an isolated form in patients without apparent hematologic disorder.²

Cutaneous manifestations of leukemia can be specific (eg, GS) or nonspecific (eg, panniculitis, generalized pruritus).^2,3 The tumor often appears as a solitary mass (Figure 1); however, in rare instances it can be multifocal. It usually presents as a rapidly growing nodular mass with solid consistence, and it is seen in patients of any age but most often those aged 45 to 55 years as well as in patients younger than 15 years.⁴

Figure 1. A 5-cm indurated nodule with a violaceous center surrounded by a greenish halo on the lower back.

Granulocytic sarcoma is most commonly associated with acute myeloid leukemia. However, it is interesting that the chloroma appears before the onset of leukemia. Occasionally GS is associated with acute myeloid leukemia as a presenting symptom or as a manifestation of recurrence of the disease that was usually related to poor prognosis.⁵ In patients with GS that is associated with myeloproliferative neoplasms, the occurrence of GS frequently is associated with acute transformation of the disease and therefore a poor prognosis.⁶

The most common sites of involvement are bone, soft tissue, lymph nodes, and skin. The prognosis does not vary according to location.

Cutaneous B-cell lymphoma should be considered in the differential diagnosis, as it may be clinically observed as single or multiple violaceous nodules involving the head, neck, and/or trunk. Histologically, there generally is a bottom-heavy infiltrate of lymphocytes sparing the epidermis (Figure 2). Immunohistochemistry, flow cytometry, or cytochemical stains often are needed to exclude lymphoma. Pseudochloroma is a rare disease characterized by a collection of normal hematopoietic tissue in locations other than GS. It can be distinguished from GS by its constituent of mature cells.⁷

Figure 2.  A biopsy demonstrated pleomorphic cells with lobulated nuclei and detectable granular cytoplasm (H&E, original magnification ×220), with strong myeloperoxidase activity in neoplastic cells (original magnification ×400 [inset]).

Granulocytic sarcoma implies a therapeutic challenge for the clinician. It should always be considered as part of a systemic disease rather than an isolated skin disorder. In patients with evidence of leukemia and GS, systemic chemotherapy is the first line of treatment. Other effective treatment regimens include radiotherapy (electron beam radiation), either alone or in combination with systemic chemotherapy (eg, hydroxyurea, methotrexate).⁸ If GS persists after chemotherapy, local treatment (eg, radiotherapy, surgery) should be considered with variable results.²


                 

A 24-year-old man presented with a 5-cm asymptomatic, indurated, well-defined nodule with a violaceous center surrounded by a greenish halo on the lower back of 3 months’ duration, along with lymphadenopathy. There was no history of trauma, weight loss, bleeding, or systemic illness. A biopsy revealed sheets of pleomorphic cells with lobulated nuclei and detectable granular cytoplasm. Immunohistochemistry showed strong myeloperoxidase activity in neoplastic cells that were CD13^- and CD56^-.

The Diagnosis: Granulocytic Sarcoma

Granulocytic sarcoma (GS), sometimes known as leukemia cutis, myeloid sarcoma, or an extramedullary myeloid tumor, is a rare localized collection of immature cells of granulocytic series or the cells of each maturation step in extramedullary sites. Originally described in 1811, the condition was noted after identifying an extramedullary collection of immature granulocytes involving the orbit. Then in 1853 the term chloroma was coined because of the greenish appearance of the tumor when exposed to light due to myeloperoxidase activity in the tumor cells. Finally, in 1967 the term granulocytic sarcoma was introduced because the greenish appearance was not observed in all cases, providing a more correct term.¹

Granulocytic sarcoma often manifests in patients with acute myeloid leukemia, chronic myelogenous leukemia, chronic idiopathic myelofibrosis, eosinophilia, refractory anemia, or polycythemia vera, and as an isolated form in patients without apparent hematologic disorder.²

Cutaneous manifestations of leukemia can be specific (eg, GS) or nonspecific (eg, panniculitis, generalized pruritus).^2,3 The tumor often appears as a solitary mass (Figure 1); however, in rare instances it can be multifocal. It usually presents as a rapidly growing nodular mass with solid consistence, and it is seen in patients of any age but most often those aged 45 to 55 years as well as in patients younger than 15 years.⁴

Figure 1. A 5-cm indurated nodule with a violaceous center surrounded by a greenish halo on the lower back.

Granulocytic sarcoma is most commonly associated with acute myeloid leukemia. However, it is interesting that the chloroma appears before the onset of leukemia. Occasionally GS is associated with acute myeloid leukemia as a presenting symptom or as a manifestation of recurrence of the disease that was usually related to poor prognosis.⁵ In patients with GS that is associated with myeloproliferative neoplasms, the occurrence of GS frequently is associated with acute transformation of the disease and therefore a poor prognosis.⁶

The most common sites of involvement are bone, soft tissue, lymph nodes, and skin. The prognosis does not vary according to location.

Cutaneous B-cell lymphoma should be considered in the differential diagnosis, as it may be clinically observed as single or multiple violaceous nodules involving the head, neck, and/or trunk. Histologically, there generally is a bottom-heavy infiltrate of lymphocytes sparing the epidermis (Figure 2). Immunohistochemistry, flow cytometry, or cytochemical stains often are needed to exclude lymphoma. Pseudochloroma is a rare disease characterized by a collection of normal hematopoietic tissue in locations other than GS. It can be distinguished from GS by its constituent of mature cells.⁷

Figure 2.  A biopsy demonstrated pleomorphic cells with lobulated nuclei and detectable granular cytoplasm (H&E, original magnification ×220), with strong myeloperoxidase activity in neoplastic cells (original magnification ×400 [inset]).

Granulocytic sarcoma implies a therapeutic challenge for the clinician. It should always be considered as part of a systemic disease rather than an isolated skin disorder. In patients with evidence of leukemia and GS, systemic chemotherapy is the first line of treatment. Other effective treatment regimens include radiotherapy (electron beam radiation), either alone or in combination with systemic chemotherapy (eg, hydroxyurea, methotrexate).⁸ If GS persists after chemotherapy, local treatment (eg, radiotherapy, surgery) should be considered with variable results.²


                 

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.

The Diagnosis: Granulomatous Periorificial Dermatitis

Review of the prior biopsy from the lower cutaneous lip revealed granulomatous perifolliculitis. The patient’s age combined with the morphology, distribution, and histopathologic features (Figure) of his eruption were characteristic of granulomatous periorificial dermatitis (GPD) of childhood. The patient was treated with oral erythromycin and topical metronidazole with immediate improvement, particularly with resolution of the erythema.

Granulomatous periorificial dermatitis is a benign, self-limited eruption in healthy prepubertal children that is characterized by coalescent, asymptomatic, dome-shaped, yellow-brown to erythematous papules.^1,2 The monomorphous lesions are firm, measure 1 to 3 mm in diameter, and are most commonly located around the mouth.^2,3 Other areas of involvement include the nostrils and alar creases as well as the periocular skin.⁴ Less commonly, GPD has been described on the scalp, ears, neck, trunk, extremities, and genital region.⁵ Slight peripheral scaling or erythema and small pitted scarring are variable.^4,5 There may be a history of failed topical corticosteroid treatment that either caused no change or a flare in the rash.^1-5 Patients have no systemic findings.^3,5

Biopsy of GPD shows characteristic noncaseating granulomas in the dermis, typified by perifollicular localization.⁵ The granulomatous infiltrate consists of epithelioid histiocytes and multinucleated giant cells surrounded by lymphocytes, with focal collections of neutrophils and occasionally overlying parakeratosis.^2,3

The nomenclature of GPD has varied since the 1970s and has included Gianotti-type perioral dermatitis,⁶ GPD of childhood,⁷ rosacealike eruption in children,⁸ FACE (facial Afro-Caribbean childhood eruption),⁹ and sarcoidlike granulomatous dermatitis.¹⁰

The etiology of GPD is unknown, though it has been associated with use of topical, inhaled, or systemic steroids; a personal history of skin problems; a family history of atopy; vaccination; and local reactions to allergens such as cosmetic preparations, antiseptic solutions, tartar control toothpaste, and bubble gum.^4,5,11-13 Granulomatous periorificial dermatitis may represent a pediatric variant of granulomatous rosacea or a granulomatous variant of perioral dermatitis, but importantly, it is not related to sarcoidosis.^1,4,5 Granulomatous periorificial dermatitis typically affects children of dark-skinned, African Caribbean ancestry, though it has been described in both white and Asian populations.^1,2,5 Genders are equally affected.

Although generally a benign condition that spontaneously remits within a few months to 3 years,⁵ GPD can be quite disruptive to a patient’s self-image, necessitating therapy to hasten resolution. Prior to initiation of treatment, any topical corticosteroids being applied to the affected region should be discontinued. For children older than 9 years, a suggested regimen is oral tetracycline 250 mg twice daily; for those younger than 9 years, erythromycin 30 to 40 mg/kg daily in 2 divided doses is advised.¹⁴ Metronidazole 0.75% cream and gel also have shown efficacy in GPD and represent a topical adjunct or alternative to oral therapy.^1,14,15

The Diagnosis: Granulomatous Periorificial Dermatitis

Review of the prior biopsy from the lower cutaneous lip revealed granulomatous perifolliculitis. The patient’s age combined with the morphology, distribution, and histopathologic features (Figure) of his eruption were characteristic of granulomatous periorificial dermatitis (GPD) of childhood. The patient was treated with oral erythromycin and topical metronidazole with immediate improvement, particularly with resolution of the erythema.

Granulomatous periorificial dermatitis is a benign, self-limited eruption in healthy prepubertal children that is characterized by coalescent, asymptomatic, dome-shaped, yellow-brown to erythematous papules.^1,2 The monomorphous lesions are firm, measure 1 to 3 mm in diameter, and are most commonly located around the mouth.^2,3 Other areas of involvement include the nostrils and alar creases as well as the periocular skin.⁴ Less commonly, GPD has been described on the scalp, ears, neck, trunk, extremities, and genital region.⁵ Slight peripheral scaling or erythema and small pitted scarring are variable.^4,5 There may be a history of failed topical corticosteroid treatment that either caused no change or a flare in the rash.^1-5 Patients have no systemic findings.^3,5

Biopsy of GPD shows characteristic noncaseating granulomas in the dermis, typified by perifollicular localization.⁵ The granulomatous infiltrate consists of epithelioid histiocytes and multinucleated giant cells surrounded by lymphocytes, with focal collections of neutrophils and occasionally overlying parakeratosis.^2,3

The nomenclature of GPD has varied since the 1970s and has included Gianotti-type perioral dermatitis,⁶ GPD of childhood,⁷ rosacealike eruption in children,⁸ FACE (facial Afro-Caribbean childhood eruption),⁹ and sarcoidlike granulomatous dermatitis.¹⁰

The etiology of GPD is unknown, though it has been associated with use of topical, inhaled, or systemic steroids; a personal history of skin problems; a family history of atopy; vaccination; and local reactions to allergens such as cosmetic preparations, antiseptic solutions, tartar control toothpaste, and bubble gum.^4,5,11-13 Granulomatous periorificial dermatitis may represent a pediatric variant of granulomatous rosacea or a granulomatous variant of perioral dermatitis, but importantly, it is not related to sarcoidosis.^1,4,5 Granulomatous periorificial dermatitis typically affects children of dark-skinned, African Caribbean ancestry, though it has been described in both white and Asian populations.^1,2,5 Genders are equally affected.

Although generally a benign condition that spontaneously remits within a few months to 3 years,⁵ GPD can be quite disruptive to a patient’s self-image, necessitating therapy to hasten resolution. Prior to initiation of treatment, any topical corticosteroids being applied to the affected region should be discontinued. For children older than 9 years, a suggested regimen is oral tetracycline 250 mg twice daily; for those younger than 9 years, erythromycin 30 to 40 mg/kg daily in 2 divided doses is advised.¹⁴ Metronidazole 0.75% cream and gel also have shown efficacy in GPD and represent a topical adjunct or alternative to oral therapy.^1,14,15

The Diagnosis: Granulomatous Periorificial Dermatitis

Review of the prior biopsy from the lower cutaneous lip revealed granulomatous perifolliculitis. The patient’s age combined with the morphology, distribution, and histopathologic features (Figure) of his eruption were characteristic of granulomatous periorificial dermatitis (GPD) of childhood. The patient was treated with oral erythromycin and topical metronidazole with immediate improvement, particularly with resolution of the erythema.

Granulomatous periorificial dermatitis is a benign, self-limited eruption in healthy prepubertal children that is characterized by coalescent, asymptomatic, dome-shaped, yellow-brown to erythematous papules.^1,2 The monomorphous lesions are firm, measure 1 to 3 mm in diameter, and are most commonly located around the mouth.^2,3 Other areas of involvement include the nostrils and alar creases as well as the periocular skin.⁴ Less commonly, GPD has been described on the scalp, ears, neck, trunk, extremities, and genital region.⁵ Slight peripheral scaling or erythema and small pitted scarring are variable.^4,5 There may be a history of failed topical corticosteroid treatment that either caused no change or a flare in the rash.^1-5 Patients have no systemic findings.^3,5

Biopsy of GPD shows characteristic noncaseating granulomas in the dermis, typified by perifollicular localization.⁵ The granulomatous infiltrate consists of epithelioid histiocytes and multinucleated giant cells surrounded by lymphocytes, with focal collections of neutrophils and occasionally overlying parakeratosis.^2,3

The nomenclature of GPD has varied since the 1970s and has included Gianotti-type perioral dermatitis,⁶ GPD of childhood,⁷ rosacealike eruption in children,⁸ FACE (facial Afro-Caribbean childhood eruption),⁹ and sarcoidlike granulomatous dermatitis.¹⁰

The etiology of GPD is unknown, though it has been associated with use of topical, inhaled, or systemic steroids; a personal history of skin problems; a family history of atopy; vaccination; and local reactions to allergens such as cosmetic preparations, antiseptic solutions, tartar control toothpaste, and bubble gum.^4,5,11-13 Granulomatous periorificial dermatitis may represent a pediatric variant of granulomatous rosacea or a granulomatous variant of perioral dermatitis, but importantly, it is not related to sarcoidosis.^1,4,5 Granulomatous periorificial dermatitis typically affects children of dark-skinned, African Caribbean ancestry, though it has been described in both white and Asian populations.^1,2,5 Genders are equally affected.

Although generally a benign condition that spontaneously remits within a few months to 3 years,⁵ GPD can be quite disruptive to a patient’s self-image, necessitating therapy to hasten resolution. Prior to initiation of treatment, any topical corticosteroids being applied to the affected region should be discontinued. For children older than 9 years, a suggested regimen is oral tetracycline 250 mg twice daily; for those younger than 9 years, erythromycin 30 to 40 mg/kg daily in 2 divided doses is advised.¹⁴ Metronidazole 0.75% cream and gel also have shown efficacy in GPD and represent a topical adjunct or alternative to oral therapy.^1,14,15

The Diagnosis: Elephantiasis Nostras Verrucosa

Elephantiasis nostras verrucosa (ENV) is a chronic deforming disorder characterized by hyperkeratosis and papillomatosis of the epidermis with underlying woody fibrosis of the dermis and the subcutaneous tissue in the setting of chronic nonfilarial lymphedema. Mossy papules, plaques, and cobblestonelike nodules are classic clinical features of ENV (Figure). The cobblestone lesion often is foul smelling and may be colonized with multiple bacteria and fungi.¹

The differential diagnosis includes filariasis, chromoblastomycosis, and venous stasis dermatitis. Filariasis is infection with the filarial worms Wuchereria bancrofti, Brugia malayi, or Brugia timori. These parasites are transmitted to humans through the bite of an infected mosquito and develop into adult worms in the lymphatic vessels, causing lymphedema. Elephantiasis, the classic sign of late-stage disease, also causes swelling of the legs and genital organs that can be disfiguring. Thus travel history to Southeast Asia and Africa regions is particularly important.

Chromoblastomycosis is a chronic fungal infection of the skin and subcutaneous tissue caused by traumatic inoculation of a specific group of dematiaceous fungi, usually Fonsecaea pedrosoi, Phialophora verrucosa, Cladosporium carrionii, or Fonsecaea compacta. Chromoblastomycosis-induced lymphedema may mimic elephantiasis. Thus it is important to perform fungal culture and fungal scraping, which will show typical thick-walled, cigar-colored, sclerotic cells (known as Medlar bodies).

The skin changes of venous stasis dermatitis include edema, varicosities, hyperpigmentation, atrophie blanche, diffuse red-brown discoloration representing deep dermal deposits of hemosiderin, and lipodermatosclerosis. Venous stasis dermatitis is caused by chronic venous insufficiency. It is one of the predispositions to ENV, as it can cause repeated infections and cellulitis leading to blockage of lymphatic drainage and secondary lymphedema. A study of 21 cases highlighted that chronic venous insufficiency may be an underappreciated risk factor in the pathogenesis of ENV.²

The development of verrucous cobblestonelike plaques in ENV occurs with chronic lymphedema. Chronic lymphedema can be caused by a variety of etiologies including infection, chronic venous stasis, congestive heart failure, obesity, trauma, tumor obstruction, and radiation. Our patient was obese with chronic venous stasis, congestive heart failure, and recurrent cellulitis that can lead to secondary lymphatic obstruction and edema, all contributing to the picture of ENV. Because of the unilateral presentation in our patient, we believe that recurrent infections and inflammation are the important risk factors that lead to fibrosis of the dermis and lymph channels, ultimately resulting in ENV.

The diagnosis of ENV is based on the patient’s history and characteristic skin changes. However, a biopsy should be performed if the diagnosis is not clinically apparent, if the lesion looks suspicious for malignancy, or if areas of chronic ulceration exist. Histologic findings include hyperkeratosis as well as a collarette of acanthotic epidermis extending around dilated lymph vessels in the upper dermis. Sometimes a few dilated lymph vessels present in the deeper or subcutaneous tissue. Bacterial and fungal culture should be done to exclude concomitant infection. Ultrasonography can be used to evaluate the lymphatic and venous systems.

Treatment of ENV aims at improving lymphedema and preventing infection. Physical therapy to improve lymphedema includes manual lymphatic drainage, massage, compression stockings, elastic bandages, and leg elevation. In cases associated with obesity, weight loss is recommended. In cases of recurrent cellulitis or lymphangitis, long-term antibiotic therapy with agents such as penicillins or cephalosporins is sometimes used.³ Success has been reported with the use of oral and topical retinoids, such as acitretin and tazarotene, which are thought to decrease epidermal proliferation, fibrogenesis, and inflammation.^4,5 Our patient was started on tretinoin cream. Surgery is reserved for cases of lymphedema resistant to medical therapies, including debridement,⁶ lymphatic and lymphovenous anastomosis,⁷ lymphatic transplantation, and amputation for severe cases.

Malignancies can develop in areas of chronic lymphedema such as lymphangiosarcoma, squamous cell carcinoma, Kaposi sarcoma, B-cell lymphoma, and malignant fibrous histiocytoma. The morbidity and mortality usually are from the underlying medical problems rather than ENV itself. Our patient died 1 month after the diagnosis of ENV from his poorly controlled heart failure.

The Diagnosis: Elephantiasis Nostras Verrucosa

Elephantiasis nostras verrucosa (ENV) is a chronic deforming disorder characterized by hyperkeratosis and papillomatosis of the epidermis with underlying woody fibrosis of the dermis and the subcutaneous tissue in the setting of chronic nonfilarial lymphedema. Mossy papules, plaques, and cobblestonelike nodules are classic clinical features of ENV (Figure). The cobblestone lesion often is foul smelling and may be colonized with multiple bacteria and fungi.¹

The differential diagnosis includes filariasis, chromoblastomycosis, and venous stasis dermatitis. Filariasis is infection with the filarial worms Wuchereria bancrofti, Brugia malayi, or Brugia timori. These parasites are transmitted to humans through the bite of an infected mosquito and develop into adult worms in the lymphatic vessels, causing lymphedema. Elephantiasis, the classic sign of late-stage disease, also causes swelling of the legs and genital organs that can be disfiguring. Thus travel history to Southeast Asia and Africa regions is particularly important.

Chromoblastomycosis is a chronic fungal infection of the skin and subcutaneous tissue caused by traumatic inoculation of a specific group of dematiaceous fungi, usually Fonsecaea pedrosoi, Phialophora verrucosa, Cladosporium carrionii, or Fonsecaea compacta. Chromoblastomycosis-induced lymphedema may mimic elephantiasis. Thus it is important to perform fungal culture and fungal scraping, which will show typical thick-walled, cigar-colored, sclerotic cells (known as Medlar bodies).

The skin changes of venous stasis dermatitis include edema, varicosities, hyperpigmentation, atrophie blanche, diffuse red-brown discoloration representing deep dermal deposits of hemosiderin, and lipodermatosclerosis. Venous stasis dermatitis is caused by chronic venous insufficiency. It is one of the predispositions to ENV, as it can cause repeated infections and cellulitis leading to blockage of lymphatic drainage and secondary lymphedema. A study of 21 cases highlighted that chronic venous insufficiency may be an underappreciated risk factor in the pathogenesis of ENV.²

The development of verrucous cobblestonelike plaques in ENV occurs with chronic lymphedema. Chronic lymphedema can be caused by a variety of etiologies including infection, chronic venous stasis, congestive heart failure, obesity, trauma, tumor obstruction, and radiation. Our patient was obese with chronic venous stasis, congestive heart failure, and recurrent cellulitis that can lead to secondary lymphatic obstruction and edema, all contributing to the picture of ENV. Because of the unilateral presentation in our patient, we believe that recurrent infections and inflammation are the important risk factors that lead to fibrosis of the dermis and lymph channels, ultimately resulting in ENV.

The diagnosis of ENV is based on the patient’s history and characteristic skin changes. However, a biopsy should be performed if the diagnosis is not clinically apparent, if the lesion looks suspicious for malignancy, or if areas of chronic ulceration exist. Histologic findings include hyperkeratosis as well as a collarette of acanthotic epidermis extending around dilated lymph vessels in the upper dermis. Sometimes a few dilated lymph vessels present in the deeper or subcutaneous tissue. Bacterial and fungal culture should be done to exclude concomitant infection. Ultrasonography can be used to evaluate the lymphatic and venous systems.

Treatment of ENV aims at improving lymphedema and preventing infection. Physical therapy to improve lymphedema includes manual lymphatic drainage, massage, compression stockings, elastic bandages, and leg elevation. In cases associated with obesity, weight loss is recommended. In cases of recurrent cellulitis or lymphangitis, long-term antibiotic therapy with agents such as penicillins or cephalosporins is sometimes used.³ Success has been reported with the use of oral and topical retinoids, such as acitretin and tazarotene, which are thought to decrease epidermal proliferation, fibrogenesis, and inflammation.^4,5 Our patient was started on tretinoin cream. Surgery is reserved for cases of lymphedema resistant to medical therapies, including debridement,⁶ lymphatic and lymphovenous anastomosis,⁷ lymphatic transplantation, and amputation for severe cases.

Malignancies can develop in areas of chronic lymphedema such as lymphangiosarcoma, squamous cell carcinoma, Kaposi sarcoma, B-cell lymphoma, and malignant fibrous histiocytoma. The morbidity and mortality usually are from the underlying medical problems rather than ENV itself. Our patient died 1 month after the diagnosis of ENV from his poorly controlled heart failure.

The Diagnosis: Elephantiasis Nostras Verrucosa

Elephantiasis nostras verrucosa (ENV) is a chronic deforming disorder characterized by hyperkeratosis and papillomatosis of the epidermis with underlying woody fibrosis of the dermis and the subcutaneous tissue in the setting of chronic nonfilarial lymphedema. Mossy papules, plaques, and cobblestonelike nodules are classic clinical features of ENV (Figure). The cobblestone lesion often is foul smelling and may be colonized with multiple bacteria and fungi.¹

The differential diagnosis includes filariasis, chromoblastomycosis, and venous stasis dermatitis. Filariasis is infection with the filarial worms Wuchereria bancrofti, Brugia malayi, or Brugia timori. These parasites are transmitted to humans through the bite of an infected mosquito and develop into adult worms in the lymphatic vessels, causing lymphedema. Elephantiasis, the classic sign of late-stage disease, also causes swelling of the legs and genital organs that can be disfiguring. Thus travel history to Southeast Asia and Africa regions is particularly important.

Chromoblastomycosis is a chronic fungal infection of the skin and subcutaneous tissue caused by traumatic inoculation of a specific group of dematiaceous fungi, usually Fonsecaea pedrosoi, Phialophora verrucosa, Cladosporium carrionii, or Fonsecaea compacta. Chromoblastomycosis-induced lymphedema may mimic elephantiasis. Thus it is important to perform fungal culture and fungal scraping, which will show typical thick-walled, cigar-colored, sclerotic cells (known as Medlar bodies).

The skin changes of venous stasis dermatitis include edema, varicosities, hyperpigmentation, atrophie blanche, diffuse red-brown discoloration representing deep dermal deposits of hemosiderin, and lipodermatosclerosis. Venous stasis dermatitis is caused by chronic venous insufficiency. It is one of the predispositions to ENV, as it can cause repeated infections and cellulitis leading to blockage of lymphatic drainage and secondary lymphedema. A study of 21 cases highlighted that chronic venous insufficiency may be an underappreciated risk factor in the pathogenesis of ENV.²

The development of verrucous cobblestonelike plaques in ENV occurs with chronic lymphedema. Chronic lymphedema can be caused by a variety of etiologies including infection, chronic venous stasis, congestive heart failure, obesity, trauma, tumor obstruction, and radiation. Our patient was obese with chronic venous stasis, congestive heart failure, and recurrent cellulitis that can lead to secondary lymphatic obstruction and edema, all contributing to the picture of ENV. Because of the unilateral presentation in our patient, we believe that recurrent infections and inflammation are the important risk factors that lead to fibrosis of the dermis and lymph channels, ultimately resulting in ENV.

The diagnosis of ENV is based on the patient’s history and characteristic skin changes. However, a biopsy should be performed if the diagnosis is not clinically apparent, if the lesion looks suspicious for malignancy, or if areas of chronic ulceration exist. Histologic findings include hyperkeratosis as well as a collarette of acanthotic epidermis extending around dilated lymph vessels in the upper dermis. Sometimes a few dilated lymph vessels present in the deeper or subcutaneous tissue. Bacterial and fungal culture should be done to exclude concomitant infection. Ultrasonography can be used to evaluate the lymphatic and venous systems.

Treatment of ENV aims at improving lymphedema and preventing infection. Physical therapy to improve lymphedema includes manual lymphatic drainage, massage, compression stockings, elastic bandages, and leg elevation. In cases associated with obesity, weight loss is recommended. In cases of recurrent cellulitis or lymphangitis, long-term antibiotic therapy with agents such as penicillins or cephalosporins is sometimes used.³ Success has been reported with the use of oral and topical retinoids, such as acitretin and tazarotene, which are thought to decrease epidermal proliferation, fibrogenesis, and inflammation.^4,5 Our patient was started on tretinoin cream. Surgery is reserved for cases of lymphedema resistant to medical therapies, including debridement,⁶ lymphatic and lymphovenous anastomosis,⁷ lymphatic transplantation, and amputation for severe cases.

Malignancies can develop in areas of chronic lymphedema such as lymphangiosarcoma, squamous cell carcinoma, Kaposi sarcoma, B-cell lymphoma, and malignant fibrous histiocytoma. The morbidity and mortality usually are from the underlying medical problems rather than ENV itself. Our patient died 1 month after the diagnosis of ENV from his poorly controlled heart failure.

A 62-year-old woman who was obese with idiopathic thrombocytopenic purpura; a history of diabetes mellitus, hypertension, and acute renal insufficiency; recent treatment with high-dose (2 mg/kg) glucocorticosteroids; and sepsis presented with ulcers on the thighs and buttocks after being transferred in a patient lift. The ulcers had developed in areas of pressure corresponding to placement in the patient lift.

The Diagnosis: Calciphylaxis

Calciphylaxis is a rare disorder that most commonly affects patients with impaired renal failure. Calciphylaxis, known as calcific uremic arteriolopathy,^1,2 involves calcification of small- and medium-sized blood vessels,³ which may lead to necrosis of the dermis, subcutaneous tissue, muscles, fascia, and internal organs.^4-6 Calciphylaxis usually occurs in fatty areas such as the calves, thighs (Figure 1), abdomen, and buttocks.^3,7,8 Although calciphylaxis most commonly is associated with severe renal disease,^1,3 pharmacologic agents such as glucocorticoids, high-dose vitamin D, warfarin, iron salts, insulin injections, calcium-based phosphate binders, and chemotherapeutic agents also may precipitate this condition.^9,10 Diagnostic biopsies typically reveal fat necrosis, inflammation, and associated small vessel calcification (Figures 2 and 3).

Our patient may have been predisposed to calciphylaxis due to her history of obesity, diabetes mellitus, and hypertension, and recent high-dose (2 mg/kg) glucocorticosteroid treatment. Five months prior to the current presentation, the patient was admitted to the hospital for treatment of sepsis with high-dose glucocorticoids for presumed idiopathic thrombocytopenic purpura. She also developed several ecchymotic regions on her skin at that time. Additionally, she developed acute renal insufficiency resulting from septic shock that improved over several weeks. Interestingly, 2 months after full recovery of her renal function, which was marked by normal creatinine levels and glomerular filtration rate, she developed a violaceous rash over the thighs and buttocks in the distribution of the straps from a patient lift that was used to transfer her from a bed into a wheelchair while residing at a physical rehabilitation facility. In the time after recovery of renal function, the eruption progressed to necrosis over 2 weeks in the areas of skin that came into contact with the lift’s straps. The patient’s renal function and parathyroid hormone, ionized calcium, phosphate, and vitamin D levels were all within reference range at the time of diagnosis.

On biopsy, characteristic findings established the diagnosis of calciphylaxis. Furthermore, the pattern of ulceration in pressure areas associated with the patient lift indicated that infection was not the precipitating event. A von Kossa stain highlighted the calcium deposition in small blood vessels in areas of panniculitis (Figure 4). Atherosclerosis may be associated with vascular calcification but does not involve acute small blood vessel calcification, and other ulcerative disorders in the differential diagnosis (eg, pyoderma gangrenosum) would not be associated with small vessel vasculitis.

Treatment of calciphylaxis must be individualized. It is important to treat any underlying disease and remove any precipitating factors. In the case of severe renal disease, a multidisciplinary approach typically is necessary.³ Correction of serum calcium and phosphate levels, rapid and safe rehydration, dialysis, and intravenous bisphosphonates all may be needed in patients with chronic kidney disease.¹¹ Surgical management of the nonhealing necrotic skin lesions via surgical debridement and skin grafting has been reported to improve overall morbidity and survival rates.¹² For patients with calciphylaxis from hyperparathyroidism, parathyroidectomy has been used but has demonstrated minimal effects on survival rates.⁹ Currently, there is no standard therapy in place for treatment of calciphylaxis but several are under investigation. Most notably, sodium thiosulfate, an inorganic salt that promotes dissolution of calcium deposits by chelating calcium, has shown rapid improvement when other treatments have failed.^13-16 In patients with marginal decreases in blood flow and ischemia of skin, hyperbaric oxygen therapy has been found to resolve cutaneous ulcers of calciphylaxis.^17,18 Patients with renal disease who develop calciphylaxis have benefited from treatment with cinacalcet, a calcimemetic that lowers parathyroid hormone levels and improves calcium phosphorus metabolism in patients undergoing dialysis.^13,14

Our patient was treated with 2 weeks of broad-spectrum antibiotics along with extensive wound care and vacuum-assisted closure of surgically debrided tissue on her thighs and buttocks. Glucocorticoid therapy was rapidly tapered. Three months after the initial presentation, the patient was placed in outpatient wound care with evaluation for hyperbaric oxygen therapy.

Calciphylaxis is a rare condition with a high mortality rate, most often due to septicemia from secondary infection of skin lesions.¹⁹ The exact pathogenic mechanisms are vague but may be the result of several precipitating factors.¹⁰ Local wound care and therapeutics should be used synergistically and individualized for each patient with calciphylaxis.

A 62-year-old woman who was obese with idiopathic thrombocytopenic purpura; a history of diabetes mellitus, hypertension, and acute renal insufficiency; recent treatment with high-dose (2 mg/kg) glucocorticosteroids; and sepsis presented with ulcers on the thighs and buttocks after being transferred in a patient lift. The ulcers had developed in areas of pressure corresponding to placement in the patient lift.

The Diagnosis: Calciphylaxis

Calciphylaxis is a rare disorder that most commonly affects patients with impaired renal failure. Calciphylaxis, known as calcific uremic arteriolopathy,^1,2 involves calcification of small- and medium-sized blood vessels,³ which may lead to necrosis of the dermis, subcutaneous tissue, muscles, fascia, and internal organs.^4-6 Calciphylaxis usually occurs in fatty areas such as the calves, thighs (Figure 1), abdomen, and buttocks.^3,7,8 Although calciphylaxis most commonly is associated with severe renal disease,^1,3 pharmacologic agents such as glucocorticoids, high-dose vitamin D, warfarin, iron salts, insulin injections, calcium-based phosphate binders, and chemotherapeutic agents also may precipitate this condition.^9,10 Diagnostic biopsies typically reveal fat necrosis, inflammation, and associated small vessel calcification (Figures 2 and 3).

Our patient may have been predisposed to calciphylaxis due to her history of obesity, diabetes mellitus, and hypertension, and recent high-dose (2 mg/kg) glucocorticosteroid treatment. Five months prior to the current presentation, the patient was admitted to the hospital for treatment of sepsis with high-dose glucocorticoids for presumed idiopathic thrombocytopenic purpura. She also developed several ecchymotic regions on her skin at that time. Additionally, she developed acute renal insufficiency resulting from septic shock that improved over several weeks. Interestingly, 2 months after full recovery of her renal function, which was marked by normal creatinine levels and glomerular filtration rate, she developed a violaceous rash over the thighs and buttocks in the distribution of the straps from a patient lift that was used to transfer her from a bed into a wheelchair while residing at a physical rehabilitation facility. In the time after recovery of renal function, the eruption progressed to necrosis over 2 weeks in the areas of skin that came into contact with the lift’s straps. The patient’s renal function and parathyroid hormone, ionized calcium, phosphate, and vitamin D levels were all within reference range at the time of diagnosis.

On biopsy, characteristic findings established the diagnosis of calciphylaxis. Furthermore, the pattern of ulceration in pressure areas associated with the patient lift indicated that infection was not the precipitating event. A von Kossa stain highlighted the calcium deposition in small blood vessels in areas of panniculitis (Figure 4). Atherosclerosis may be associated with vascular calcification but does not involve acute small blood vessel calcification, and other ulcerative disorders in the differential diagnosis (eg, pyoderma gangrenosum) would not be associated with small vessel vasculitis.

Treatment of calciphylaxis must be individualized. It is important to treat any underlying disease and remove any precipitating factors. In the case of severe renal disease, a multidisciplinary approach typically is necessary.³ Correction of serum calcium and phosphate levels, rapid and safe rehydration, dialysis, and intravenous bisphosphonates all may be needed in patients with chronic kidney disease.¹¹ Surgical management of the nonhealing necrotic skin lesions via surgical debridement and skin grafting has been reported to improve overall morbidity and survival rates.¹² For patients with calciphylaxis from hyperparathyroidism, parathyroidectomy has been used but has demonstrated minimal effects on survival rates.⁹ Currently, there is no standard therapy in place for treatment of calciphylaxis but several are under investigation. Most notably, sodium thiosulfate, an inorganic salt that promotes dissolution of calcium deposits by chelating calcium, has shown rapid improvement when other treatments have failed.^13-16 In patients with marginal decreases in blood flow and ischemia of skin, hyperbaric oxygen therapy has been found to resolve cutaneous ulcers of calciphylaxis.^17,18 Patients with renal disease who develop calciphylaxis have benefited from treatment with cinacalcet, a calcimemetic that lowers parathyroid hormone levels and improves calcium phosphorus metabolism in patients undergoing dialysis.^13,14

Our patient was treated with 2 weeks of broad-spectrum antibiotics along with extensive wound care and vacuum-assisted closure of surgically debrided tissue on her thighs and buttocks. Glucocorticoid therapy was rapidly tapered. Three months after the initial presentation, the patient was placed in outpatient wound care with evaluation for hyperbaric oxygen therapy.

Calciphylaxis is a rare condition with a high mortality rate, most often due to septicemia from secondary infection of skin lesions.¹⁹ The exact pathogenic mechanisms are vague but may be the result of several precipitating factors.¹⁰ Local wound care and therapeutics should be used synergistically and individualized for each patient with calciphylaxis.

A 62-year-old woman who was obese with idiopathic thrombocytopenic purpura; a history of diabetes mellitus, hypertension, and acute renal insufficiency; recent treatment with high-dose (2 mg/kg) glucocorticosteroids; and sepsis presented with ulcers on the thighs and buttocks after being transferred in a patient lift. The ulcers had developed in areas of pressure corresponding to placement in the patient lift.

The Diagnosis: Calciphylaxis

Calciphylaxis is a rare disorder that most commonly affects patients with impaired renal failure. Calciphylaxis, known as calcific uremic arteriolopathy,^1,2 involves calcification of small- and medium-sized blood vessels,³ which may lead to necrosis of the dermis, subcutaneous tissue, muscles, fascia, and internal organs.^4-6 Calciphylaxis usually occurs in fatty areas such as the calves, thighs (Figure 1), abdomen, and buttocks.^3,7,8 Although calciphylaxis most commonly is associated with severe renal disease,^1,3 pharmacologic agents such as glucocorticoids, high-dose vitamin D, warfarin, iron salts, insulin injections, calcium-based phosphate binders, and chemotherapeutic agents also may precipitate this condition.^9,10 Diagnostic biopsies typically reveal fat necrosis, inflammation, and associated small vessel calcification (Figures 2 and 3).

Our patient may have been predisposed to calciphylaxis due to her history of obesity, diabetes mellitus, and hypertension, and recent high-dose (2 mg/kg) glucocorticosteroid treatment. Five months prior to the current presentation, the patient was admitted to the hospital for treatment of sepsis with high-dose glucocorticoids for presumed idiopathic thrombocytopenic purpura. She also developed several ecchymotic regions on her skin at that time. Additionally, she developed acute renal insufficiency resulting from septic shock that improved over several weeks. Interestingly, 2 months after full recovery of her renal function, which was marked by normal creatinine levels and glomerular filtration rate, she developed a violaceous rash over the thighs and buttocks in the distribution of the straps from a patient lift that was used to transfer her from a bed into a wheelchair while residing at a physical rehabilitation facility. In the time after recovery of renal function, the eruption progressed to necrosis over 2 weeks in the areas of skin that came into contact with the lift’s straps. The patient’s renal function and parathyroid hormone, ionized calcium, phosphate, and vitamin D levels were all within reference range at the time of diagnosis.

On biopsy, characteristic findings established the diagnosis of calciphylaxis. Furthermore, the pattern of ulceration in pressure areas associated with the patient lift indicated that infection was not the precipitating event. A von Kossa stain highlighted the calcium deposition in small blood vessels in areas of panniculitis (Figure 4). Atherosclerosis may be associated with vascular calcification but does not involve acute small blood vessel calcification, and other ulcerative disorders in the differential diagnosis (eg, pyoderma gangrenosum) would not be associated with small vessel vasculitis.

Treatment of calciphylaxis must be individualized. It is important to treat any underlying disease and remove any precipitating factors. In the case of severe renal disease, a multidisciplinary approach typically is necessary.³ Correction of serum calcium and phosphate levels, rapid and safe rehydration, dialysis, and intravenous bisphosphonates all may be needed in patients with chronic kidney disease.¹¹ Surgical management of the nonhealing necrotic skin lesions via surgical debridement and skin grafting has been reported to improve overall morbidity and survival rates.¹² For patients with calciphylaxis from hyperparathyroidism, parathyroidectomy has been used but has demonstrated minimal effects on survival rates.⁹ Currently, there is no standard therapy in place for treatment of calciphylaxis but several are under investigation. Most notably, sodium thiosulfate, an inorganic salt that promotes dissolution of calcium deposits by chelating calcium, has shown rapid improvement when other treatments have failed.^13-16 In patients with marginal decreases in blood flow and ischemia of skin, hyperbaric oxygen therapy has been found to resolve cutaneous ulcers of calciphylaxis.^17,18 Patients with renal disease who develop calciphylaxis have benefited from treatment with cinacalcet, a calcimemetic that lowers parathyroid hormone levels and improves calcium phosphorus metabolism in patients undergoing dialysis.^13,14

Our patient was treated with 2 weeks of broad-spectrum antibiotics along with extensive wound care and vacuum-assisted closure of surgically debrided tissue on her thighs and buttocks. Glucocorticoid therapy was rapidly tapered. Three months after the initial presentation, the patient was placed in outpatient wound care with evaluation for hyperbaric oxygen therapy.

Calciphylaxis is a rare condition with a high mortality rate, most often due to septicemia from secondary infection of skin lesions.¹⁹ The exact pathogenic mechanisms are vague but may be the result of several precipitating factors.¹⁰ Local wound care and therapeutics should be used synergistically and individualized for each patient with calciphylaxis.

The Diagnosis: Eruptive Disseminated Kaposi Sarcoma

There are 5 types of Kaposi sarcoma (KS): classic KS, African cutaneous KS, African lymphadenopathic KS, AIDS-related KS, and immunosuppression-associated KS. Immunosuppression-associated KS can occur in the setting of lymphoma or in conjunction with immunosuppressive therapy related to organ transplants and long-term corticosteroid treatment.^1,2 Kaposi sarcoma associated with highly active antiretroviral therapy–induced immune reconstitution inflammatory syndrome also may occur.³

The possible causes of the manifestation of KS in our patient were 2-fold: (1) AIDS associated given the patient’s CD4 lymphocyte count of 7 cells/mm³, and (2) iatrogenic secondary to drug-induced immunosuppression that was temporally induced by 2 sustained periods of intravenous dexamethasone for cerebral edema in the setting of primary central nervous system lymphoma. It is unlikely that our patient experienced immune reconstitution inflammatory syndrome–induced KS, as the dysphagia interfered with the ability to take antiretroviral therapy during hospitalization. In patients who have experienced KS in the setting of steroid use or organ transplantation, KS lesions spontaneously improved or completely regressed several months after immunosuppression reduction or removal.^1,2,4

Clinically and morphologically, our patient also clearly demonstrated the occasionally seen striking manifestation of perilesional, ecchymotic-appearing or bruiselike halos surrounding the KS lesions (Figure).

The initial differential diagnosis included hemorrhagic diathesis but later included KS in the setting of AIDS and immunosuppressive therapy with dexamethasone, bacillary angiomatosis, and cutaneous lymphoma. A biopsy of one of the cutaneous lesions confirmed the diagnosis of KS.

Three standard treatments of primary central nervous system lymphoma currently exist: radiation therapy, intrathecal and/or intraventricular chemotherapy, and steroid therapy.⁵ Given the patient’s risk for opportunistic infections and immunodeficient state, the medical team was constrained in its treatment options, as all of the therapies would further weaken the patient’s immune system.

Treatment of KS can be local and/or systemic based on disease stage, progression, distribution, clinical type, and immune status.^6,7 Our patient had generalized cutaneous KS covering more than 50% of the body, thus making local treatments such as radiation therapy, cryotherapy, intralesional chemotherapy with vincristine or vinblastine, excision, laser therapy, or alitretinoin gel impractical. Single- or multiple-agent systemic treatment options for disseminated cutaneous disease with or without internal organ involvement may include liposomal anthracyclines, paclitaxel, gemcitabine, vinblastine, vincristine, bleomycin, etoposide, and interferon-alfa.^6,7 Potent combination antiretroviral therapy is the mainstay for treatment of AIDS-associated KS.⁸

The Diagnosis: Eruptive Disseminated Kaposi Sarcoma

There are 5 types of Kaposi sarcoma (KS): classic KS, African cutaneous KS, African lymphadenopathic KS, AIDS-related KS, and immunosuppression-associated KS. Immunosuppression-associated KS can occur in the setting of lymphoma or in conjunction with immunosuppressive therapy related to organ transplants and long-term corticosteroid treatment.^1,2 Kaposi sarcoma associated with highly active antiretroviral therapy–induced immune reconstitution inflammatory syndrome also may occur.³

The possible causes of the manifestation of KS in our patient were 2-fold: (1) AIDS associated given the patient’s CD4 lymphocyte count of 7 cells/mm³, and (2) iatrogenic secondary to drug-induced immunosuppression that was temporally induced by 2 sustained periods of intravenous dexamethasone for cerebral edema in the setting of primary central nervous system lymphoma. It is unlikely that our patient experienced immune reconstitution inflammatory syndrome–induced KS, as the dysphagia interfered with the ability to take antiretroviral therapy during hospitalization. In patients who have experienced KS in the setting of steroid use or organ transplantation, KS lesions spontaneously improved or completely regressed several months after immunosuppression reduction or removal.^1,2,4

Clinically and morphologically, our patient also clearly demonstrated the occasionally seen striking manifestation of perilesional, ecchymotic-appearing or bruiselike halos surrounding the KS lesions (Figure).

The initial differential diagnosis included hemorrhagic diathesis but later included KS in the setting of AIDS and immunosuppressive therapy with dexamethasone, bacillary angiomatosis, and cutaneous lymphoma. A biopsy of one of the cutaneous lesions confirmed the diagnosis of KS.

Three standard treatments of primary central nervous system lymphoma currently exist: radiation therapy, intrathecal and/or intraventricular chemotherapy, and steroid therapy.⁵ Given the patient’s risk for opportunistic infections and immunodeficient state, the medical team was constrained in its treatment options, as all of the therapies would further weaken the patient’s immune system.

Treatment of KS can be local and/or systemic based on disease stage, progression, distribution, clinical type, and immune status.^6,7 Our patient had generalized cutaneous KS covering more than 50% of the body, thus making local treatments such as radiation therapy, cryotherapy, intralesional chemotherapy with vincristine or vinblastine, excision, laser therapy, or alitretinoin gel impractical. Single- or multiple-agent systemic treatment options for disseminated cutaneous disease with or without internal organ involvement may include liposomal anthracyclines, paclitaxel, gemcitabine, vinblastine, vincristine, bleomycin, etoposide, and interferon-alfa.^6,7 Potent combination antiretroviral therapy is the mainstay for treatment of AIDS-associated KS.⁸

The Diagnosis: Eruptive Disseminated Kaposi Sarcoma

There are 5 types of Kaposi sarcoma (KS): classic KS, African cutaneous KS, African lymphadenopathic KS, AIDS-related KS, and immunosuppression-associated KS. Immunosuppression-associated KS can occur in the setting of lymphoma or in conjunction with immunosuppressive therapy related to organ transplants and long-term corticosteroid treatment.^1,2 Kaposi sarcoma associated with highly active antiretroviral therapy–induced immune reconstitution inflammatory syndrome also may occur.³

The possible causes of the manifestation of KS in our patient were 2-fold: (1) AIDS associated given the patient’s CD4 lymphocyte count of 7 cells/mm³, and (2) iatrogenic secondary to drug-induced immunosuppression that was temporally induced by 2 sustained periods of intravenous dexamethasone for cerebral edema in the setting of primary central nervous system lymphoma. It is unlikely that our patient experienced immune reconstitution inflammatory syndrome–induced KS, as the dysphagia interfered with the ability to take antiretroviral therapy during hospitalization. In patients who have experienced KS in the setting of steroid use or organ transplantation, KS lesions spontaneously improved or completely regressed several months after immunosuppression reduction or removal.^1,2,4

Clinically and morphologically, our patient also clearly demonstrated the occasionally seen striking manifestation of perilesional, ecchymotic-appearing or bruiselike halos surrounding the KS lesions (Figure).

The initial differential diagnosis included hemorrhagic diathesis but later included KS in the setting of AIDS and immunosuppressive therapy with dexamethasone, bacillary angiomatosis, and cutaneous lymphoma. A biopsy of one of the cutaneous lesions confirmed the diagnosis of KS.

Three standard treatments of primary central nervous system lymphoma currently exist: radiation therapy, intrathecal and/or intraventricular chemotherapy, and steroid therapy.⁵ Given the patient’s risk for opportunistic infections and immunodeficient state, the medical team was constrained in its treatment options, as all of the therapies would further weaken the patient’s immune system.

Treatment of KS can be local and/or systemic based on disease stage, progression, distribution, clinical type, and immune status.^6,7 Our patient had generalized cutaneous KS covering more than 50% of the body, thus making local treatments such as radiation therapy, cryotherapy, intralesional chemotherapy with vincristine or vinblastine, excision, laser therapy, or alitretinoin gel impractical. Single- or multiple-agent systemic treatment options for disseminated cutaneous disease with or without internal organ involvement may include liposomal anthracyclines, paclitaxel, gemcitabine, vinblastine, vincristine, bleomycin, etoposide, and interferon-alfa.^6,7 Potent combination antiretroviral therapy is the mainstay for treatment of AIDS-associated KS.⁸

The Diagnosis: Myxoid Cyst

Myxoid cysts, often called ganglion cysts or mucous cysts, are smooth translucent nodules that arise between the dorsal aspect of the distal interphalangeal joint and proximal nail fold.¹ Lesions often have an associated distal depression or groove on the affected fingernail and typically appear on the middle and index fingers between the fourth and seventh decades of life.^2,3 Acute lesions may present as tender nodules, whereas gradually developing lesions tend to be painless.³ Trauma to the distal interphalangeal joint, degenerative processes, and osteoarthritis may increase hyaluronic acid production and allow synovial fluid to escape the joint space, accumulating in the surrounding tissue. Subungual localization of a mucous cyst is rare and may be difficult to diagnose.⁴ The differential diagnosis includes benign and malignant tumors such as periungual fibroma, glomus tumor, basal cell carcinoma, squamous cell carcinoma, and amelanotic melanoma.⁵ Our patient declined treatment with cryotherapy or intralesional steroid injection and drainage. He was referred to the orthopedic surgery department for surgical removal of the cyst and imaging studies. Radiographs of the right thumb revealed severe osteoarthritis of the distal interphalangeal joint, demonstrating the association of digital mucous cysts.

The Diagnosis: Myxoid Cyst

Myxoid cysts, often called ganglion cysts or mucous cysts, are smooth translucent nodules that arise between the dorsal aspect of the distal interphalangeal joint and proximal nail fold.¹ Lesions often have an associated distal depression or groove on the affected fingernail and typically appear on the middle and index fingers between the fourth and seventh decades of life.^2,3 Acute lesions may present as tender nodules, whereas gradually developing lesions tend to be painless.³ Trauma to the distal interphalangeal joint, degenerative processes, and osteoarthritis may increase hyaluronic acid production and allow synovial fluid to escape the joint space, accumulating in the surrounding tissue. Subungual localization of a mucous cyst is rare and may be difficult to diagnose.⁴ The differential diagnosis includes benign and malignant tumors such as periungual fibroma, glomus tumor, basal cell carcinoma, squamous cell carcinoma, and amelanotic melanoma.⁵ Our patient declined treatment with cryotherapy or intralesional steroid injection and drainage. He was referred to the orthopedic surgery department for surgical removal of the cyst and imaging studies. Radiographs of the right thumb revealed severe osteoarthritis of the distal interphalangeal joint, demonstrating the association of digital mucous cysts.

The Diagnosis: Myxoid Cyst

Myxoid cysts, often called ganglion cysts or mucous cysts, are smooth translucent nodules that arise between the dorsal aspect of the distal interphalangeal joint and proximal nail fold.¹ Lesions often have an associated distal depression or groove on the affected fingernail and typically appear on the middle and index fingers between the fourth and seventh decades of life.^2,3 Acute lesions may present as tender nodules, whereas gradually developing lesions tend to be painless.³ Trauma to the distal interphalangeal joint, degenerative processes, and osteoarthritis may increase hyaluronic acid production and allow synovial fluid to escape the joint space, accumulating in the surrounding tissue. Subungual localization of a mucous cyst is rare and may be difficult to diagnose.⁴ The differential diagnosis includes benign and malignant tumors such as periungual fibroma, glomus tumor, basal cell carcinoma, squamous cell carcinoma, and amelanotic melanoma.⁵ Our patient declined treatment with cryotherapy or intralesional steroid injection and drainage. He was referred to the orthopedic surgery department for surgical removal of the cyst and imaging studies. Radiographs of the right thumb revealed severe osteoarthritis of the distal interphalangeal joint, demonstrating the association of digital mucous cysts.