Quiz

Cutaneous Metastasis of Pulmonary Adenocarcinoma

Cutaneous metastasis of pulmonary adenocarcinoma (CMPA) is a rare phenomenon with an overall survival rate of less than 5 months.1,2 Often, CMPA can be the heralding feature of an aggressive systemic malignancy in 2.8% to 22% of reported cases.^2-4 Clinically, CMPAs often present as fixed, violaceous, ulcerated nodules on the chest wall, scalp, or site of a prior procedure.^3,5,6 Other clinical presentations have been described including zosteriform and inflammatory carcinomalike CMPA and CMPA on the tip of the nose.⁷ Histologically, CMPA presents as a subdermal collection of atypical glands arranged as clustered aggregates of infiltrative glands penetrating the dermal stroma (quiz image). The atypical glands have large oval nuclei with high nuclear to cytoplasm ratios with scant pale cytoplasm.

Cutaneous metastasis of pulmonary adenocarcinoma is difficult to distinguish from other metastatic or primary glandular malignancies based on histology alone. Immunohistochemical analysis can aid in the diagnosis of the primary tumor. Pulmonary adenocarcinomas are positive for cytokeratin (CK) 7 and thyroid transcription factor 1 (TTF-1), and they are negative for CK5/6 and CK20.⁷ The differential diagnosis for CMPA includes other internal malignancies such as invasive ductal adenocarcinoma of the breast and gastrointestinal adenocarcinomas (eg, gastric or colorectal carcinoma [CRC]). Additionally, endometriosis and primary sebaceous carcinomas can mimic cutaneous metastatic adenocarcinomas.

Endometriosis can mimic adenocarcinoma, especially when presenting as a subdermal nodule. However, the scattered dermal glands are cytologically banal and are surrounded by uterine-type stroma and extravasated hemorrhage, a classic presentation of endometriosis (Figure 1).

Primary sebaceous carcinoma also can mimic metastatic adenocarcinoma within the skin and is histologically similar to metastatic adenocarcinomas. The most distinguishing feature is sebaceous differentiation characterized by sebocytes, which have a vacuolated cytoplasm giving the nucleus a scalloped appearance, frequently with adjacent ductlike structures (Figure 5). Epidermotropism sometimes is present in sebaceous carcinomas but cannot be relied on as a distinguishing feature. Immunohistochemical analysis also is a helpful tool; these tumors typically are positive for p63 and podoplanin, distinguishing them from negative-staining metastatic adenocarcinomas.^10,11 

Cutaneous Metastasis of Pulmonary Adenocarcinoma

Cutaneous metastasis of pulmonary adenocarcinoma (CMPA) is a rare phenomenon with an overall survival rate of less than 5 months.1,2 Often, CMPA can be the heralding feature of an aggressive systemic malignancy in 2.8% to 22% of reported cases.^2-4 Clinically, CMPAs often present as fixed, violaceous, ulcerated nodules on the chest wall, scalp, or site of a prior procedure.^3,5,6 Other clinical presentations have been described including zosteriform and inflammatory carcinomalike CMPA and CMPA on the tip of the nose.⁷ Histologically, CMPA presents as a subdermal collection of atypical glands arranged as clustered aggregates of infiltrative glands penetrating the dermal stroma (quiz image). The atypical glands have large oval nuclei with high nuclear to cytoplasm ratios with scant pale cytoplasm.

Cutaneous metastasis of pulmonary adenocarcinoma is difficult to distinguish from other metastatic or primary glandular malignancies based on histology alone. Immunohistochemical analysis can aid in the diagnosis of the primary tumor. Pulmonary adenocarcinomas are positive for cytokeratin (CK) 7 and thyroid transcription factor 1 (TTF-1), and they are negative for CK5/6 and CK20.⁷ The differential diagnosis for CMPA includes other internal malignancies such as invasive ductal adenocarcinoma of the breast and gastrointestinal adenocarcinomas (eg, gastric or colorectal carcinoma [CRC]). Additionally, endometriosis and primary sebaceous carcinomas can mimic cutaneous metastatic adenocarcinomas.

Endometriosis can mimic adenocarcinoma, especially when presenting as a subdermal nodule. However, the scattered dermal glands are cytologically banal and are surrounded by uterine-type stroma and extravasated hemorrhage, a classic presentation of endometriosis (Figure 1).

Primary sebaceous carcinoma also can mimic metastatic adenocarcinoma within the skin and is histologically similar to metastatic adenocarcinomas. The most distinguishing feature is sebaceous differentiation characterized by sebocytes, which have a vacuolated cytoplasm giving the nucleus a scalloped appearance, frequently with adjacent ductlike structures (Figure 5). Epidermotropism sometimes is present in sebaceous carcinomas but cannot be relied on as a distinguishing feature. Immunohistochemical analysis also is a helpful tool; these tumors typically are positive for p63 and podoplanin, distinguishing them from negative-staining metastatic adenocarcinomas.^10,11 

Cutaneous Metastasis of Pulmonary Adenocarcinoma

Cutaneous metastasis of pulmonary adenocarcinoma (CMPA) is a rare phenomenon with an overall survival rate of less than 5 months.1,2 Often, CMPA can be the heralding feature of an aggressive systemic malignancy in 2.8% to 22% of reported cases.^2-4 Clinically, CMPAs often present as fixed, violaceous, ulcerated nodules on the chest wall, scalp, or site of a prior procedure.^3,5,6 Other clinical presentations have been described including zosteriform and inflammatory carcinomalike CMPA and CMPA on the tip of the nose.⁷ Histologically, CMPA presents as a subdermal collection of atypical glands arranged as clustered aggregates of infiltrative glands penetrating the dermal stroma (quiz image). The atypical glands have large oval nuclei with high nuclear to cytoplasm ratios with scant pale cytoplasm.

Cutaneous metastasis of pulmonary adenocarcinoma is difficult to distinguish from other metastatic or primary glandular malignancies based on histology alone. Immunohistochemical analysis can aid in the diagnosis of the primary tumor. Pulmonary adenocarcinomas are positive for cytokeratin (CK) 7 and thyroid transcription factor 1 (TTF-1), and they are negative for CK5/6 and CK20.⁷ The differential diagnosis for CMPA includes other internal malignancies such as invasive ductal adenocarcinoma of the breast and gastrointestinal adenocarcinomas (eg, gastric or colorectal carcinoma [CRC]). Additionally, endometriosis and primary sebaceous carcinomas can mimic cutaneous metastatic adenocarcinomas.

Endometriosis can mimic adenocarcinoma, especially when presenting as a subdermal nodule. However, the scattered dermal glands are cytologically banal and are surrounded by uterine-type stroma and extravasated hemorrhage, a classic presentation of endometriosis (Figure 1).

Primary sebaceous carcinoma also can mimic metastatic adenocarcinoma within the skin and is histologically similar to metastatic adenocarcinomas. The most distinguishing feature is sebaceous differentiation characterized by sebocytes, which have a vacuolated cytoplasm giving the nucleus a scalloped appearance, frequently with adjacent ductlike structures (Figure 5). Epidermotropism sometimes is present in sebaceous carcinomas but cannot be relied on as a distinguishing feature. Immunohistochemical analysis also is a helpful tool; these tumors typically are positive for p63 and podoplanin, distinguishing them from negative-staining metastatic adenocarcinomas.^10,11 

The Diagnosis: Blue Toe Syndrome

The clinical manifestation suggested blue toe syndrome. A variety of causes for blue toe syndrome are known such as embolism, thrombosis, vasoconstrictive disorders, infectious and noninfectious inflammation, extensive venous thrombosis, and abnormal circulating blood.¹ Among them, only emboli from atherosclerotic plaques give rise to typical cholesterol clefts on skin biopsy (Figure 1). Such atheroemboli often are an iatrogenic complication, especially those caused by invasive percutaneous procedures or damage to the arterial walls from vascular surgery. However, spontaneous plaque hemorrhage or shearing forces of the circulating blood can disrupt atheromatous plaques and cause embolization of the cholesterol crystals, which was likely to be the case in our patient because no preceding trigger events were noted.

Other clinical features also are seen in atheroembolism. Approximately half of patients with atheroembolism develop clinical kidney disease.² Almost all iatrogenic cases have acute or subacute reduction in glomerular filtration rate of at least to 50% level, whereas the spontaneous cases present as stable chronic renal failure.³ Approximately 20% of patients with atheroembolism also have involvement of digestive organs.^4,5 Abdominal pain, diarrhea, and gastrointestinal blood loss are common features; bowel infarction and perforation occasionally occur.⁵ Pancreatitis is another common complication, and serum amylase levels are raised in approximately 50% of patients.6 Atheroemboli may reach the eyes and brain. They occasionally can cause loss of vision,⁷ as well as transient ischemic attacks, strokes, and gradual deterioration in cerebral function.³ Blood eosinophilia, which occurs in approximately 60% of patients, is an important finding.^3,8

Although there is no specific therapy for atheroembolism, the use of antiplatelet agents is considered reasonable because they are beneficial in preventing myocardial infarction in patients with atherosclerosis.⁹ In our case, the livedo reticularis cleared, as did the coldness on the affected toes after 2 weeks of sarpogrelate hydrochloride administration; however, development of necrotic change was noted (Figure 2). Necrotic change on the hallux disappeared after 2 weeks.

The Diagnosis: Blue Toe Syndrome

The clinical manifestation suggested blue toe syndrome. A variety of causes for blue toe syndrome are known such as embolism, thrombosis, vasoconstrictive disorders, infectious and noninfectious inflammation, extensive venous thrombosis, and abnormal circulating blood.¹ Among them, only emboli from atherosclerotic plaques give rise to typical cholesterol clefts on skin biopsy (Figure 1). Such atheroemboli often are an iatrogenic complication, especially those caused by invasive percutaneous procedures or damage to the arterial walls from vascular surgery. However, spontaneous plaque hemorrhage or shearing forces of the circulating blood can disrupt atheromatous plaques and cause embolization of the cholesterol crystals, which was likely to be the case in our patient because no preceding trigger events were noted.

Other clinical features also are seen in atheroembolism. Approximately half of patients with atheroembolism develop clinical kidney disease.² Almost all iatrogenic cases have acute or subacute reduction in glomerular filtration rate of at least to 50% level, whereas the spontaneous cases present as stable chronic renal failure.³ Approximately 20% of patients with atheroembolism also have involvement of digestive organs.^4,5 Abdominal pain, diarrhea, and gastrointestinal blood loss are common features; bowel infarction and perforation occasionally occur.⁵ Pancreatitis is another common complication, and serum amylase levels are raised in approximately 50% of patients.6 Atheroemboli may reach the eyes and brain. They occasionally can cause loss of vision,⁷ as well as transient ischemic attacks, strokes, and gradual deterioration in cerebral function.³ Blood eosinophilia, which occurs in approximately 60% of patients, is an important finding.^3,8

Although there is no specific therapy for atheroembolism, the use of antiplatelet agents is considered reasonable because they are beneficial in preventing myocardial infarction in patients with atherosclerosis.⁹ In our case, the livedo reticularis cleared, as did the coldness on the affected toes after 2 weeks of sarpogrelate hydrochloride administration; however, development of necrotic change was noted (Figure 2). Necrotic change on the hallux disappeared after 2 weeks.

The Diagnosis: Blue Toe Syndrome

The clinical manifestation suggested blue toe syndrome. A variety of causes for blue toe syndrome are known such as embolism, thrombosis, vasoconstrictive disorders, infectious and noninfectious inflammation, extensive venous thrombosis, and abnormal circulating blood.¹ Among them, only emboli from atherosclerotic plaques give rise to typical cholesterol clefts on skin biopsy (Figure 1). Such atheroemboli often are an iatrogenic complication, especially those caused by invasive percutaneous procedures or damage to the arterial walls from vascular surgery. However, spontaneous plaque hemorrhage or shearing forces of the circulating blood can disrupt atheromatous plaques and cause embolization of the cholesterol crystals, which was likely to be the case in our patient because no preceding trigger events were noted.

Other clinical features also are seen in atheroembolism. Approximately half of patients with atheroembolism develop clinical kidney disease.² Almost all iatrogenic cases have acute or subacute reduction in glomerular filtration rate of at least to 50% level, whereas the spontaneous cases present as stable chronic renal failure.³ Approximately 20% of patients with atheroembolism also have involvement of digestive organs.^4,5 Abdominal pain, diarrhea, and gastrointestinal blood loss are common features; bowel infarction and perforation occasionally occur.⁵ Pancreatitis is another common complication, and serum amylase levels are raised in approximately 50% of patients.6 Atheroemboli may reach the eyes and brain. They occasionally can cause loss of vision,⁷ as well as transient ischemic attacks, strokes, and gradual deterioration in cerebral function.³ Blood eosinophilia, which occurs in approximately 60% of patients, is an important finding.^3,8

Although there is no specific therapy for atheroembolism, the use of antiplatelet agents is considered reasonable because they are beneficial in preventing myocardial infarction in patients with atherosclerosis.⁹ In our case, the livedo reticularis cleared, as did the coldness on the affected toes after 2 weeks of sarpogrelate hydrochloride administration; however, development of necrotic change was noted (Figure 2). Necrotic change on the hallux disappeared after 2 weeks.

The Diagnosis: Secondary Syphilis

Syphilis, known as the great mimicker, has a wide-ranging clinical and histologic presentation. There can be overlapping features with many of the entities included in the differential diagnoses. As our patient exemplifies, clinicians and pathologists must have a high index of suspicion, and any concerning features should lead to a more in-depth patient history, spirochete stains, and serologic testing.

Our patient was seen by several dermatologists over the course of 2 years and therapy with topical steroids failed. He was eager to pursue more aggressive therapy with methotrexate, and a punch biopsy was performed to confirm the diagnosis of psoriasis prior to initiating treatment. Hematoxylin and eosin staining results on low power can be seen in Figure 1A. Medium-power view demonstrated vacuolar interface dermatitis (Figure 1B) with psoriasiform epidermal hyperplasia with slender elongation of rete ridges; neutrophils in the stratum corneum; endothelial cell swelling (Figure 1C); and mixed infiltrate with high plasma cells (Figure 1D), lymphocytes, and histiocytes. Although the biopsy results were psoriasiform, there was high suspicion for syphilis in this case. Additional staining for spirochetes was performed with syphilis immunohistochemical stain¹ (Figure 2), which revealed spirochetes present on the patient's biopsy, confirming the diagnosis of syphilis. Warthin-Starry stain also can be performed to confirm the diagnosis.

Based on histologic features, the differential diagnosis includes psoriasis vulgaris, eczema, lichen planus, or lichenoid drug eruption. Psoriasis vulgaris displays regular psoriasiform epidermal hyperplasia with hypergranulosis and confluent parakeratosis. The elongated rete pegs are broad rather than slender.² Neutrophils are present in the stratum corneum. In contrast, eczematous dermatitis is characterized by epidermal hyperplasia, spongiosis, parakeratosis, and eosinophils. Lichen planus classically displays a brisk bandlike lymphocytic infiltrate that closely abuts or obscures the dermoepidermal junction. Parakeratosis, neutrophils, and eosinophils should be absent. The rete pegs taper to a point, similar to a sawtooth, while they are long and slender with syphilis, similar to an ice pick. Although lichenoid drug eruption presents with interface dermatitis, parakeratosis, and eosinophils, the epidermis is hyperplastic without the slender elongation of rete pegs seen in syphilis.

Further workup with serologic testing demonstrated that the patient had a syphilis IgG titer of greater than 8.0 (reactive, >6.0), indicating the patient had been infected.³ Reactive syphilis IgG, a specific treponemal test, should be followed with a nontreponemal assay of either rapid plasma reagin (RPR) or VDRL test to confirm disease activity, according to recommendations from the Centers for Disease Control and Prevention,4 which represents a change to the traditional algorithm that called for screening with a nontreponemal test and confirming with a specific treponemal test. The patient had a positive RPR and quantitative RPR titer was found as 1:2048, indicating that syphilis was active or recently treated. Testing for human immunodeficiency virus (HIV) revealed a quantitative RNA polymerase chain reaction of 145,000 copies/mL and a CD4 count of 18 cells/µL (reference range, 533-1674 cells/µL).

The patient initially was treated for latent syphilis with 3 doses of intramuscular penicillin G benzathine 2.4 million U once weekly for 3 weeks. Due to his high RPR titers and low CD4 count, a lumbar puncture was later pursued, which revealed positive results from a cerebrospinal fluid (CSF)-VDRL test, confirming a diagnosis of neurosyphilis. Although a positive CSF-VDRL test is specific for the diagnosis of neurosyphilis, the sensitivity of the CSF-VDRL test against clinical diagnosis is only 30% to 70%.⁵ Intravenous aqueous penicillin G 4 million U every 4 hours was started for 14 days for neurosyphilis. One month following the completion of the intravenous penicillin, the rash completely resolved. The patient was in a 10-year monogamous relationship with a man and did not use condoms. Typically, signs and symptoms of secondary syphilis begin 4 to 10 weeks after the appearance of a chancre. However, the classic chancre of primary syphilis among men who have sex with men may go unnoticed in those who may not be able to see anal lesions.⁶ Also, infection with syphilis increases the likelihood of acquiring and transmitting HIV. All patients diagnosed with syphilis should have additional testing for HIV and other sexually transmitted diseases. 

For patients with a history of thick scaly plaques on the wrists, knees, and feet resistant to topical steroid therapy, dermatologists should maintain a high index of clinical suspicion for syphilis. 

The Diagnosis: Secondary Syphilis

Syphilis, known as the great mimicker, has a wide-ranging clinical and histologic presentation. There can be overlapping features with many of the entities included in the differential diagnoses. As our patient exemplifies, clinicians and pathologists must have a high index of suspicion, and any concerning features should lead to a more in-depth patient history, spirochete stains, and serologic testing.

Our patient was seen by several dermatologists over the course of 2 years and therapy with topical steroids failed. He was eager to pursue more aggressive therapy with methotrexate, and a punch biopsy was performed to confirm the diagnosis of psoriasis prior to initiating treatment. Hematoxylin and eosin staining results on low power can be seen in Figure 1A. Medium-power view demonstrated vacuolar interface dermatitis (Figure 1B) with psoriasiform epidermal hyperplasia with slender elongation of rete ridges; neutrophils in the stratum corneum; endothelial cell swelling (Figure 1C); and mixed infiltrate with high plasma cells (Figure 1D), lymphocytes, and histiocytes. Although the biopsy results were psoriasiform, there was high suspicion for syphilis in this case. Additional staining for spirochetes was performed with syphilis immunohistochemical stain¹ (Figure 2), which revealed spirochetes present on the patient's biopsy, confirming the diagnosis of syphilis. Warthin-Starry stain also can be performed to confirm the diagnosis.

Based on histologic features, the differential diagnosis includes psoriasis vulgaris, eczema, lichen planus, or lichenoid drug eruption. Psoriasis vulgaris displays regular psoriasiform epidermal hyperplasia with hypergranulosis and confluent parakeratosis. The elongated rete pegs are broad rather than slender.² Neutrophils are present in the stratum corneum. In contrast, eczematous dermatitis is characterized by epidermal hyperplasia, spongiosis, parakeratosis, and eosinophils. Lichen planus classically displays a brisk bandlike lymphocytic infiltrate that closely abuts or obscures the dermoepidermal junction. Parakeratosis, neutrophils, and eosinophils should be absent. The rete pegs taper to a point, similar to a sawtooth, while they are long and slender with syphilis, similar to an ice pick. Although lichenoid drug eruption presents with interface dermatitis, parakeratosis, and eosinophils, the epidermis is hyperplastic without the slender elongation of rete pegs seen in syphilis.

Further workup with serologic testing demonstrated that the patient had a syphilis IgG titer of greater than 8.0 (reactive, >6.0), indicating the patient had been infected.³ Reactive syphilis IgG, a specific treponemal test, should be followed with a nontreponemal assay of either rapid plasma reagin (RPR) or VDRL test to confirm disease activity, according to recommendations from the Centers for Disease Control and Prevention,4 which represents a change to the traditional algorithm that called for screening with a nontreponemal test and confirming with a specific treponemal test. The patient had a positive RPR and quantitative RPR titer was found as 1:2048, indicating that syphilis was active or recently treated. Testing for human immunodeficiency virus (HIV) revealed a quantitative RNA polymerase chain reaction of 145,000 copies/mL and a CD4 count of 18 cells/µL (reference range, 533-1674 cells/µL).

The patient initially was treated for latent syphilis with 3 doses of intramuscular penicillin G benzathine 2.4 million U once weekly for 3 weeks. Due to his high RPR titers and low CD4 count, a lumbar puncture was later pursued, which revealed positive results from a cerebrospinal fluid (CSF)-VDRL test, confirming a diagnosis of neurosyphilis. Although a positive CSF-VDRL test is specific for the diagnosis of neurosyphilis, the sensitivity of the CSF-VDRL test against clinical diagnosis is only 30% to 70%.⁵ Intravenous aqueous penicillin G 4 million U every 4 hours was started for 14 days for neurosyphilis. One month following the completion of the intravenous penicillin, the rash completely resolved. The patient was in a 10-year monogamous relationship with a man and did not use condoms. Typically, signs and symptoms of secondary syphilis begin 4 to 10 weeks after the appearance of a chancre. However, the classic chancre of primary syphilis among men who have sex with men may go unnoticed in those who may not be able to see anal lesions.⁶ Also, infection with syphilis increases the likelihood of acquiring and transmitting HIV. All patients diagnosed with syphilis should have additional testing for HIV and other sexually transmitted diseases. 

For patients with a history of thick scaly plaques on the wrists, knees, and feet resistant to topical steroid therapy, dermatologists should maintain a high index of clinical suspicion for syphilis. 

The Diagnosis: Secondary Syphilis

Syphilis, known as the great mimicker, has a wide-ranging clinical and histologic presentation. There can be overlapping features with many of the entities included in the differential diagnoses. As our patient exemplifies, clinicians and pathologists must have a high index of suspicion, and any concerning features should lead to a more in-depth patient history, spirochete stains, and serologic testing.

Our patient was seen by several dermatologists over the course of 2 years and therapy with topical steroids failed. He was eager to pursue more aggressive therapy with methotrexate, and a punch biopsy was performed to confirm the diagnosis of psoriasis prior to initiating treatment. Hematoxylin and eosin staining results on low power can be seen in Figure 1A. Medium-power view demonstrated vacuolar interface dermatitis (Figure 1B) with psoriasiform epidermal hyperplasia with slender elongation of rete ridges; neutrophils in the stratum corneum; endothelial cell swelling (Figure 1C); and mixed infiltrate with high plasma cells (Figure 1D), lymphocytes, and histiocytes. Although the biopsy results were psoriasiform, there was high suspicion for syphilis in this case. Additional staining for spirochetes was performed with syphilis immunohistochemical stain¹ (Figure 2), which revealed spirochetes present on the patient's biopsy, confirming the diagnosis of syphilis. Warthin-Starry stain also can be performed to confirm the diagnosis.

Based on histologic features, the differential diagnosis includes psoriasis vulgaris, eczema, lichen planus, or lichenoid drug eruption. Psoriasis vulgaris displays regular psoriasiform epidermal hyperplasia with hypergranulosis and confluent parakeratosis. The elongated rete pegs are broad rather than slender.² Neutrophils are present in the stratum corneum. In contrast, eczematous dermatitis is characterized by epidermal hyperplasia, spongiosis, parakeratosis, and eosinophils. Lichen planus classically displays a brisk bandlike lymphocytic infiltrate that closely abuts or obscures the dermoepidermal junction. Parakeratosis, neutrophils, and eosinophils should be absent. The rete pegs taper to a point, similar to a sawtooth, while they are long and slender with syphilis, similar to an ice pick. Although lichenoid drug eruption presents with interface dermatitis, parakeratosis, and eosinophils, the epidermis is hyperplastic without the slender elongation of rete pegs seen in syphilis.

Further workup with serologic testing demonstrated that the patient had a syphilis IgG titer of greater than 8.0 (reactive, >6.0), indicating the patient had been infected.³ Reactive syphilis IgG, a specific treponemal test, should be followed with a nontreponemal assay of either rapid plasma reagin (RPR) or VDRL test to confirm disease activity, according to recommendations from the Centers for Disease Control and Prevention,4 which represents a change to the traditional algorithm that called for screening with a nontreponemal test and confirming with a specific treponemal test. The patient had a positive RPR and quantitative RPR titer was found as 1:2048, indicating that syphilis was active or recently treated. Testing for human immunodeficiency virus (HIV) revealed a quantitative RNA polymerase chain reaction of 145,000 copies/mL and a CD4 count of 18 cells/µL (reference range, 533-1674 cells/µL).

The patient initially was treated for latent syphilis with 3 doses of intramuscular penicillin G benzathine 2.4 million U once weekly for 3 weeks. Due to his high RPR titers and low CD4 count, a lumbar puncture was later pursued, which revealed positive results from a cerebrospinal fluid (CSF)-VDRL test, confirming a diagnosis of neurosyphilis. Although a positive CSF-VDRL test is specific for the diagnosis of neurosyphilis, the sensitivity of the CSF-VDRL test against clinical diagnosis is only 30% to 70%.⁵ Intravenous aqueous penicillin G 4 million U every 4 hours was started for 14 days for neurosyphilis. One month following the completion of the intravenous penicillin, the rash completely resolved. The patient was in a 10-year monogamous relationship with a man and did not use condoms. Typically, signs and symptoms of secondary syphilis begin 4 to 10 weeks after the appearance of a chancre. However, the classic chancre of primary syphilis among men who have sex with men may go unnoticed in those who may not be able to see anal lesions.⁶ Also, infection with syphilis increases the likelihood of acquiring and transmitting HIV. All patients diagnosed with syphilis should have additional testing for HIV and other sexually transmitted diseases. 

For patients with a history of thick scaly plaques on the wrists, knees, and feet resistant to topical steroid therapy, dermatologists should maintain a high index of clinical suspicion for syphilis. 

ANSWER

There are degenerative changes present. Bilateral hip prostheses are noted. Within the coccyx, there is bone remodeling and angulation that are likely chronic and related to remote trauma or injury (arrow). Below this, some cortical lucency (circled) is noted, most likely consistent with an acute fracture. The patient was prescribed a nonsteroidal medication and a mild narcotic pain medication.

ANSWER

There are degenerative changes present. Bilateral hip prostheses are noted. Within the coccyx, there is bone remodeling and angulation that are likely chronic and related to remote trauma or injury (arrow). Below this, some cortical lucency (circled) is noted, most likely consistent with an acute fracture. The patient was prescribed a nonsteroidal medication and a mild narcotic pain medication.

ANSWER

There are degenerative changes present. Bilateral hip prostheses are noted. Within the coccyx, there is bone remodeling and angulation that are likely chronic and related to remote trauma or injury (arrow). Below this, some cortical lucency (circled) is noted, most likely consistent with an acute fracture. The patient was prescribed a nonsteroidal medication and a mild narcotic pain medication.

The Diagnosis: Livedoid Vasculopathy

Livedoid vasculopathy (LV) is a rare cutaneous disorder that most commonly affects the lower legs. It has an estimated incidence of 1 case per 100,000 per year and predominantly affects women.¹ The disease pathogenesis is not fully understood but is thought to involve thrombosis and occlusion of dermal vessels resulting in tissue hypoxia.² Both inherited and acquired thrombophilic conditions frequently are seen in patients with LV.^3,4 Livedoid vasculopathy also has been described as idiopathic⁵ and is associated with immune complex deposition.⁶ However, the number of cases of idiopathic LV may be overestimated; as technological advancements to detect coagulation abnormalities improve, it is hypothesized that this entity will be identified less often.^2,4

Livedoid vasculopathy has been described in the literature using the term PPURPLE (painful purpuric ulcers with reticular pattern of lower extremities).⁷ The triad of livedo racemosa, recurrent painful ulcerations, and residual healing with atrophie blanche characterizes the clinical manifestations of LV; however, all 3 characteristics do not need to appear simultaneously for a diagnosis to be made. The condition has a chronic course with spontaneous remissions and exacerbations. Episodic ulcerations occur, especially in the summertime, and heal slowly, leaving behind atrophic, porcelain white, stellate-shaped scars called atrophie blanche. Livedo racemosa also may be seen in Sneddon syndrome; however, these patients experience neurologic symptoms secondary to cerebrovascular occlusion. In contrast to livedo racemosa, acquired livedo reticularis represents a physiologic hypoperfusion pattern that occurs in response to cold exposure.⁸ A localized sharp pain, known as angina cutis, typically precedes the clinical symptom of painful ulcerations.⁹ Atrophie blanche once was thought to be specific to LV but has been seen in other diseases such as systemic lupus erythematosus and chronic venous insufficiency.²

The diagnosis of LV is based on identification of characteristic clinical features and skin biopsy. In almost all biopsy specimens, histopathology reveals fibrinoid occlusion of vessels in the superficial and mid dermis.⁴ Other findings may include epidermal necrosis and vessel wall hyalinization and infarction² (Figure). Because LV is commonly misdiagnosed as vasculitis, the absence of hallmark features of vasculitis such as neutrophilic infiltrate of blood vessel walls and fibrinoid necrosis suggest the diagnosis. Extensive laboratory evaluation for inherited and acquired coagulation abnormalities should be performed.

Treatment of LV is difficult, as there is currently no consensus on optimal therapy. The mainstay of therapy is to reduce pain, prevent infection, and reduce ulceration and development of atrophie blanche. Underlying causes should be identified and appropriately treated. Because the primary pathogenesis of LV is considered to be a hypercoagulable state, first-line treatment often includes therapies to enhance blood flow and prevent thrombosis such as smoking cessation, antiplatelet therapy, and pentoxifylline. Vasodilating agents, anti-inflammatory agents, anticoagulation, and fibrinolytic therapy also have been used with varying degrees of success.⁷

The Diagnosis: Livedoid Vasculopathy

Livedoid vasculopathy (LV) is a rare cutaneous disorder that most commonly affects the lower legs. It has an estimated incidence of 1 case per 100,000 per year and predominantly affects women.¹ The disease pathogenesis is not fully understood but is thought to involve thrombosis and occlusion of dermal vessels resulting in tissue hypoxia.² Both inherited and acquired thrombophilic conditions frequently are seen in patients with LV.^3,4 Livedoid vasculopathy also has been described as idiopathic⁵ and is associated with immune complex deposition.⁶ However, the number of cases of idiopathic LV may be overestimated; as technological advancements to detect coagulation abnormalities improve, it is hypothesized that this entity will be identified less often.^2,4

Livedoid vasculopathy has been described in the literature using the term PPURPLE (painful purpuric ulcers with reticular pattern of lower extremities).⁷ The triad of livedo racemosa, recurrent painful ulcerations, and residual healing with atrophie blanche characterizes the clinical manifestations of LV; however, all 3 characteristics do not need to appear simultaneously for a diagnosis to be made. The condition has a chronic course with spontaneous remissions and exacerbations. Episodic ulcerations occur, especially in the summertime, and heal slowly, leaving behind atrophic, porcelain white, stellate-shaped scars called atrophie blanche. Livedo racemosa also may be seen in Sneddon syndrome; however, these patients experience neurologic symptoms secondary to cerebrovascular occlusion. In contrast to livedo racemosa, acquired livedo reticularis represents a physiologic hypoperfusion pattern that occurs in response to cold exposure.⁸ A localized sharp pain, known as angina cutis, typically precedes the clinical symptom of painful ulcerations.⁹ Atrophie blanche once was thought to be specific to LV but has been seen in other diseases such as systemic lupus erythematosus and chronic venous insufficiency.²

The diagnosis of LV is based on identification of characteristic clinical features and skin biopsy. In almost all biopsy specimens, histopathology reveals fibrinoid occlusion of vessels in the superficial and mid dermis.⁴ Other findings may include epidermal necrosis and vessel wall hyalinization and infarction² (Figure). Because LV is commonly misdiagnosed as vasculitis, the absence of hallmark features of vasculitis such as neutrophilic infiltrate of blood vessel walls and fibrinoid necrosis suggest the diagnosis. Extensive laboratory evaluation for inherited and acquired coagulation abnormalities should be performed.

Treatment of LV is difficult, as there is currently no consensus on optimal therapy. The mainstay of therapy is to reduce pain, prevent infection, and reduce ulceration and development of atrophie blanche. Underlying causes should be identified and appropriately treated. Because the primary pathogenesis of LV is considered to be a hypercoagulable state, first-line treatment often includes therapies to enhance blood flow and prevent thrombosis such as smoking cessation, antiplatelet therapy, and pentoxifylline. Vasodilating agents, anti-inflammatory agents, anticoagulation, and fibrinolytic therapy also have been used with varying degrees of success.⁷

The Diagnosis: Livedoid Vasculopathy

Livedoid vasculopathy (LV) is a rare cutaneous disorder that most commonly affects the lower legs. It has an estimated incidence of 1 case per 100,000 per year and predominantly affects women.¹ The disease pathogenesis is not fully understood but is thought to involve thrombosis and occlusion of dermal vessels resulting in tissue hypoxia.² Both inherited and acquired thrombophilic conditions frequently are seen in patients with LV.^3,4 Livedoid vasculopathy also has been described as idiopathic⁵ and is associated with immune complex deposition.⁶ However, the number of cases of idiopathic LV may be overestimated; as technological advancements to detect coagulation abnormalities improve, it is hypothesized that this entity will be identified less often.^2,4

Livedoid vasculopathy has been described in the literature using the term PPURPLE (painful purpuric ulcers with reticular pattern of lower extremities).⁷ The triad of livedo racemosa, recurrent painful ulcerations, and residual healing with atrophie blanche characterizes the clinical manifestations of LV; however, all 3 characteristics do not need to appear simultaneously for a diagnosis to be made. The condition has a chronic course with spontaneous remissions and exacerbations. Episodic ulcerations occur, especially in the summertime, and heal slowly, leaving behind atrophic, porcelain white, stellate-shaped scars called atrophie blanche. Livedo racemosa also may be seen in Sneddon syndrome; however, these patients experience neurologic symptoms secondary to cerebrovascular occlusion. In contrast to livedo racemosa, acquired livedo reticularis represents a physiologic hypoperfusion pattern that occurs in response to cold exposure.⁸ A localized sharp pain, known as angina cutis, typically precedes the clinical symptom of painful ulcerations.⁹ Atrophie blanche once was thought to be specific to LV but has been seen in other diseases such as systemic lupus erythematosus and chronic venous insufficiency.²

The diagnosis of LV is based on identification of characteristic clinical features and skin biopsy. In almost all biopsy specimens, histopathology reveals fibrinoid occlusion of vessels in the superficial and mid dermis.⁴ Other findings may include epidermal necrosis and vessel wall hyalinization and infarction² (Figure). Because LV is commonly misdiagnosed as vasculitis, the absence of hallmark features of vasculitis such as neutrophilic infiltrate of blood vessel walls and fibrinoid necrosis suggest the diagnosis. Extensive laboratory evaluation for inherited and acquired coagulation abnormalities should be performed.

Treatment of LV is difficult, as there is currently no consensus on optimal therapy. The mainstay of therapy is to reduce pain, prevent infection, and reduce ulceration and development of atrophie blanche. Underlying causes should be identified and appropriately treated. Because the primary pathogenesis of LV is considered to be a hypercoagulable state, first-line treatment often includes therapies to enhance blood flow and prevent thrombosis such as smoking cessation, antiplatelet therapy, and pentoxifylline. Vasodilating agents, anti-inflammatory agents, anticoagulation, and fibrinolytic therapy also have been used with varying degrees of success.⁷

The Diagnosis: Radiation-Associated Angiosarcoma

At the time of presentation, a 4-mm lesional punch biopsy was obtained (Figure), which revealed an epithelioid neoplasm within the dermis expressing CD31 and CD34, and staining negatively for S-100, CD45, and estrogen and progesterone receptors. The histologic and immunophenotypic findings were compatible with the diagnosis of angiosarcoma. Given the patient’s history of radiation for breast carcinoma several years ago, this tumor was consistent with radiation-associated angiosarcoma (RAAS).

Development of secondary angiosarcoma has been linked to both prior radiation (RAAS) and chronic lymphedema (Stewart-Treves syndrome).¹ Radiation-associated angiosarcoma is defined as a “pathologically confirmed breast or chest wall angiosarcoma arising within a previously irradiated field.”² The incidence of RAAS is estimated to be 0.9 per 1000 individuals following radiation treatment of breast cancer over the subsequent 15 years and a mean time from radiation to development of 7 years.¹ Incidence is expected to increase in the future due to improved likelihood of surviving early-stage breast carcinoma and the increased use of external beam radiation therapy for management of breast cancer.

Differentiating between primary and secondary angiosarcoma of the breast is important. Although primary breast angiosarcoma usually arises in women aged 30 to 40 years, RAAS tends to arise in older women (mean age, 68 years) and is seen only in those women with prior radiation.² Additionally, high-level amplification of MYC, a known photo-oncogene, on chromosome 8 is a key genetic alteration of RAAS that helps to distinguish it from primary angiosarcoma, though this variance may be present in only half of RAAS cases.³ Immunohistochemical analysis of tumor cells for MYC expression correlates well with this amplification and also is helpful in distinguishing atypical vascular lesions from RAAS.⁴ Atypical vascular lesions, similar to RAAS, occur years after radiation exposure and may have a similar clinical presentation. Atypical vascular lesions do not progress to angiosarcoma in reported cases, but clinical and histologic overlap with RAAS make the diagnosis difficult.⁵ In these cases, analysis with fluorescence in situ hybridization or immunohistochemistry for the MYC amplification is important to differentiate these tumors.⁶

At the time of presentation, the majority of patients with RAAS of the breast have localized disease, often with a variable presentation. In all known cases, there have been skin changes present, emphasizing the importance of both patient and clinician vigilance on a regular basis in at-risk individuals. In one study, the most common presentation was breast ecchymosis, which was observed in 55% of patients.⁷ These lesions involve the dermis and are commonly mistaken for benign conditions such as infection or hemorrhage.² In 2 other studies, RAAS most often manifested as a skin nodule or apparent tumor, closely followed by either a rash or bruiselike presentation.^1,2

The overall recommendation for management of patients with ecchymotic skin lesions in previously irradiated regions is to obtain a biopsy specimen for tissue diagnosis. Although there is no standard of care for the management of RAAS, a multidisciplinary approach involving specialists from oncology, surgical oncology, and radiation oncology is recommended. Most often, radical surgery encompassing both the breast parenchyma and the at-risk radiated skin is performed. Extensive surgery has demonstrated the best survival benefits compared to mastectomy alone.⁷ Chemotherapeutics also may be used as adjuncts to surgery, which have been determined to decrease local recurrence rates but have no proven survival benefits.² Adverse prognostic factors for survival are tumor size greater than 10 cm and development of local and/or distant metastases.² Following the diagnosis of RAAS, our patient underwent radical mastectomy with adjuvant chemotherapy and remained disease free 6 months after surgery.

In summary, RAAS is a well-known, albeit relatively uncommon, consequence of radiation therapy. Dermatologists, oncologists, and primary care providers play an important role in recognizing this entity when evaluating patients with ecchymotic lesions as well as nodules or tumors within an irradiated field. Biopsy should be obtained promptly to prevent delay in diagnosis and to expedite referral to appropriate specialists for further evaluation and treatment.

The Diagnosis: Radiation-Associated Angiosarcoma

At the time of presentation, a 4-mm lesional punch biopsy was obtained (Figure), which revealed an epithelioid neoplasm within the dermis expressing CD31 and CD34, and staining negatively for S-100, CD45, and estrogen and progesterone receptors. The histologic and immunophenotypic findings were compatible with the diagnosis of angiosarcoma. Given the patient’s history of radiation for breast carcinoma several years ago, this tumor was consistent with radiation-associated angiosarcoma (RAAS).

Development of secondary angiosarcoma has been linked to both prior radiation (RAAS) and chronic lymphedema (Stewart-Treves syndrome).¹ Radiation-associated angiosarcoma is defined as a “pathologically confirmed breast or chest wall angiosarcoma arising within a previously irradiated field.”² The incidence of RAAS is estimated to be 0.9 per 1000 individuals following radiation treatment of breast cancer over the subsequent 15 years and a mean time from radiation to development of 7 years.¹ Incidence is expected to increase in the future due to improved likelihood of surviving early-stage breast carcinoma and the increased use of external beam radiation therapy for management of breast cancer.

Differentiating between primary and secondary angiosarcoma of the breast is important. Although primary breast angiosarcoma usually arises in women aged 30 to 40 years, RAAS tends to arise in older women (mean age, 68 years) and is seen only in those women with prior radiation.² Additionally, high-level amplification of MYC, a known photo-oncogene, on chromosome 8 is a key genetic alteration of RAAS that helps to distinguish it from primary angiosarcoma, though this variance may be present in only half of RAAS cases.³ Immunohistochemical analysis of tumor cells for MYC expression correlates well with this amplification and also is helpful in distinguishing atypical vascular lesions from RAAS.⁴ Atypical vascular lesions, similar to RAAS, occur years after radiation exposure and may have a similar clinical presentation. Atypical vascular lesions do not progress to angiosarcoma in reported cases, but clinical and histologic overlap with RAAS make the diagnosis difficult.⁵ In these cases, analysis with fluorescence in situ hybridization or immunohistochemistry for the MYC amplification is important to differentiate these tumors.⁶

At the time of presentation, the majority of patients with RAAS of the breast have localized disease, often with a variable presentation. In all known cases, there have been skin changes present, emphasizing the importance of both patient and clinician vigilance on a regular basis in at-risk individuals. In one study, the most common presentation was breast ecchymosis, which was observed in 55% of patients.⁷ These lesions involve the dermis and are commonly mistaken for benign conditions such as infection or hemorrhage.² In 2 other studies, RAAS most often manifested as a skin nodule or apparent tumor, closely followed by either a rash or bruiselike presentation.^1,2

The overall recommendation for management of patients with ecchymotic skin lesions in previously irradiated regions is to obtain a biopsy specimen for tissue diagnosis. Although there is no standard of care for the management of RAAS, a multidisciplinary approach involving specialists from oncology, surgical oncology, and radiation oncology is recommended. Most often, radical surgery encompassing both the breast parenchyma and the at-risk radiated skin is performed. Extensive surgery has demonstrated the best survival benefits compared to mastectomy alone.⁷ Chemotherapeutics also may be used as adjuncts to surgery, which have been determined to decrease local recurrence rates but have no proven survival benefits.² Adverse prognostic factors for survival are tumor size greater than 10 cm and development of local and/or distant metastases.² Following the diagnosis of RAAS, our patient underwent radical mastectomy with adjuvant chemotherapy and remained disease free 6 months after surgery.

In summary, RAAS is a well-known, albeit relatively uncommon, consequence of radiation therapy. Dermatologists, oncologists, and primary care providers play an important role in recognizing this entity when evaluating patients with ecchymotic lesions as well as nodules or tumors within an irradiated field. Biopsy should be obtained promptly to prevent delay in diagnosis and to expedite referral to appropriate specialists for further evaluation and treatment.

The Diagnosis: Radiation-Associated Angiosarcoma

At the time of presentation, a 4-mm lesional punch biopsy was obtained (Figure), which revealed an epithelioid neoplasm within the dermis expressing CD31 and CD34, and staining negatively for S-100, CD45, and estrogen and progesterone receptors. The histologic and immunophenotypic findings were compatible with the diagnosis of angiosarcoma. Given the patient’s history of radiation for breast carcinoma several years ago, this tumor was consistent with radiation-associated angiosarcoma (RAAS).

Development of secondary angiosarcoma has been linked to both prior radiation (RAAS) and chronic lymphedema (Stewart-Treves syndrome).¹ Radiation-associated angiosarcoma is defined as a “pathologically confirmed breast or chest wall angiosarcoma arising within a previously irradiated field.”² The incidence of RAAS is estimated to be 0.9 per 1000 individuals following radiation treatment of breast cancer over the subsequent 15 years and a mean time from radiation to development of 7 years.¹ Incidence is expected to increase in the future due to improved likelihood of surviving early-stage breast carcinoma and the increased use of external beam radiation therapy for management of breast cancer.

Differentiating between primary and secondary angiosarcoma of the breast is important. Although primary breast angiosarcoma usually arises in women aged 30 to 40 years, RAAS tends to arise in older women (mean age, 68 years) and is seen only in those women with prior radiation.² Additionally, high-level amplification of MYC, a known photo-oncogene, on chromosome 8 is a key genetic alteration of RAAS that helps to distinguish it from primary angiosarcoma, though this variance may be present in only half of RAAS cases.³ Immunohistochemical analysis of tumor cells for MYC expression correlates well with this amplification and also is helpful in distinguishing atypical vascular lesions from RAAS.⁴ Atypical vascular lesions, similar to RAAS, occur years after radiation exposure and may have a similar clinical presentation. Atypical vascular lesions do not progress to angiosarcoma in reported cases, but clinical and histologic overlap with RAAS make the diagnosis difficult.⁵ In these cases, analysis with fluorescence in situ hybridization or immunohistochemistry for the MYC amplification is important to differentiate these tumors.⁶

At the time of presentation, the majority of patients with RAAS of the breast have localized disease, often with a variable presentation. In all known cases, there have been skin changes present, emphasizing the importance of both patient and clinician vigilance on a regular basis in at-risk individuals. In one study, the most common presentation was breast ecchymosis, which was observed in 55% of patients.⁷ These lesions involve the dermis and are commonly mistaken for benign conditions such as infection or hemorrhage.² In 2 other studies, RAAS most often manifested as a skin nodule or apparent tumor, closely followed by either a rash or bruiselike presentation.^1,2

The overall recommendation for management of patients with ecchymotic skin lesions in previously irradiated regions is to obtain a biopsy specimen for tissue diagnosis. Although there is no standard of care for the management of RAAS, a multidisciplinary approach involving specialists from oncology, surgical oncology, and radiation oncology is recommended. Most often, radical surgery encompassing both the breast parenchyma and the at-risk radiated skin is performed. Extensive surgery has demonstrated the best survival benefits compared to mastectomy alone.⁷ Chemotherapeutics also may be used as adjuncts to surgery, which have been determined to decrease local recurrence rates but have no proven survival benefits.² Adverse prognostic factors for survival are tumor size greater than 10 cm and development of local and/or distant metastases.² Following the diagnosis of RAAS, our patient underwent radical mastectomy with adjuvant chemotherapy and remained disease free 6 months after surgery.

In summary, RAAS is a well-known, albeit relatively uncommon, consequence of radiation therapy. Dermatologists, oncologists, and primary care providers play an important role in recognizing this entity when evaluating patients with ecchymotic lesions as well as nodules or tumors within an irradiated field. Biopsy should be obtained promptly to prevent delay in diagnosis and to expedite referral to appropriate specialists for further evaluation and treatment.

ANSWERThe correct interpretation includes sinus rhythm with blocked premature atrial complexes, left-axis deviation, and serial changes of an evolving anterior MI.

The presence of a P wave without a QRS between the third and fourth QRS complex represents a blocked premature atrial complex. The fifth QRS complex also indicates a premature atrial complex; however, it is not blocked.

Left-axis deviation is evidenced by the R axis of –82°. The loss of an R wave in V₁, the poor R-wave progression in V₂ and V₃, and the ST-T wave changes are all consistent with an evolving anterior MI.

ANSWERThe correct interpretation includes sinus rhythm with blocked premature atrial complexes, left-axis deviation, and serial changes of an evolving anterior MI.

The presence of a P wave without a QRS between the third and fourth QRS complex represents a blocked premature atrial complex. The fifth QRS complex also indicates a premature atrial complex; however, it is not blocked.

Left-axis deviation is evidenced by the R axis of –82°. The loss of an R wave in V₁, the poor R-wave progression in V₂ and V₃, and the ST-T wave changes are all consistent with an evolving anterior MI.

ANSWERThe correct interpretation includes sinus rhythm with blocked premature atrial complexes, left-axis deviation, and serial changes of an evolving anterior MI.

The presence of a P wave without a QRS between the third and fourth QRS complex represents a blocked premature atrial complex. The fifth QRS complex also indicates a premature atrial complex; however, it is not blocked.

Left-axis deviation is evidenced by the R axis of –82°. The loss of an R wave in V₁, the poor R-wave progression in V₂ and V₃, and the ST-T wave changes are all consistent with an evolving anterior MI.

ANSWER
The correct answer is impetigo (choice “a”). Impetigo is almost always secondary to another condition, such as contact or irritant dermatitis, eczema, or dry skin.

DISCUSSION
Impetigo is a superficial bacterial infection usually caused by a combination of strep and staph organisms. It requires a break in the skin to provide a point of entry for the organisms. In young children, scratching and picking at eczema, along with lip licking, exacerbate the barrier-breaching process.

The organisms that cause impetigo are typically benign, but this was not always the case. Prior to WWI, certain strains of strep were capable of triggering an immune response that resulted in kidney damage. These “nephritogenic” strains of the Streptococcus family caused acute post-streptococcal glomerulonephritis (Bright disease), which, at that time, killed thousands each year. Fortunately, these strains are rare now.

In the pre-antibiotic days, when the average person bathed once a week, impetigo was highly contagious and serious enough that whole households were quarantined because of it.

Today, impetigo, once diagnosed, is relatively simple to manage. Mild cases can be treated with application of mupirocin ointment or cream three times a day. In this particular case, a 10-day course of an oral antibiotic (trimethoprim sulfa) was added, and the rash rapidly cleared.

ANSWER
The correct answer is impetigo (choice “a”). Impetigo is almost always secondary to another condition, such as contact or irritant dermatitis, eczema, or dry skin.

DISCUSSION
Impetigo is a superficial bacterial infection usually caused by a combination of strep and staph organisms. It requires a break in the skin to provide a point of entry for the organisms. In young children, scratching and picking at eczema, along with lip licking, exacerbate the barrier-breaching process.

The organisms that cause impetigo are typically benign, but this was not always the case. Prior to WWI, certain strains of strep were capable of triggering an immune response that resulted in kidney damage. These “nephritogenic” strains of the Streptococcus family caused acute post-streptococcal glomerulonephritis (Bright disease), which, at that time, killed thousands each year. Fortunately, these strains are rare now.

In the pre-antibiotic days, when the average person bathed once a week, impetigo was highly contagious and serious enough that whole households were quarantined because of it.

Today, impetigo, once diagnosed, is relatively simple to manage. Mild cases can be treated with application of mupirocin ointment or cream three times a day. In this particular case, a 10-day course of an oral antibiotic (trimethoprim sulfa) was added, and the rash rapidly cleared.

ANSWER
The correct answer is impetigo (choice “a”). Impetigo is almost always secondary to another condition, such as contact or irritant dermatitis, eczema, or dry skin.

DISCUSSION
Impetigo is a superficial bacterial infection usually caused by a combination of strep and staph organisms. It requires a break in the skin to provide a point of entry for the organisms. In young children, scratching and picking at eczema, along with lip licking, exacerbate the barrier-breaching process.

The organisms that cause impetigo are typically benign, but this was not always the case. Prior to WWI, certain strains of strep were capable of triggering an immune response that resulted in kidney damage. These “nephritogenic” strains of the Streptococcus family caused acute post-streptococcal glomerulonephritis (Bright disease), which, at that time, killed thousands each year. Fortunately, these strains are rare now.

In the pre-antibiotic days, when the average person bathed once a week, impetigo was highly contagious and serious enough that whole households were quarantined because of it.

Today, impetigo, once diagnosed, is relatively simple to manage. Mild cases can be treated with application of mupirocin ointment or cream three times a day. In this particular case, a 10-day course of an oral antibiotic (trimethoprim sulfa) was added, and the rash rapidly cleared.

The Diagnosis: Atypical Mycobacterial Infection

Punch biopsy specimens demonstrated necrotizing granulomatous inflammation in the dermis and subcutis (Figure). Special staining for microorganisms was negative. Tissue culture grew Mycobacterium avium-intracellulare (MAI). The patient began treatment with azithromycin, ethambutol, and rifabutin. Tissue susceptibilities later showed resistance to rifabutin and sensitivity to clarithromycin, moxifloxacin, and clofazimine. She subsequently was switched to azithromycin, clofazimine, and moxifloxacin with good response.

Mycobacterium avium-intracellulare is a slow-growing, nonchromogenic, atypical mycobacteria. Although ubiquitous, it tends to only cause serious infection in the setting of immunosuppression. Transmission usually is through the respiratory or gastrointestinal tract.¹ Skin infections with MAI are uncommon and usually are secondary to seeding from disseminated infection or from direct inoculation.²

The clinical presentations of primary cutaneous MAI are myriad, including an isolated red nodule, multiple ulcers, abscesses, draining sinuses, facial nodules, granulomatous plaques, and panniculitis.^2,3 Of 3 reported cases of primary cutaneous MAI in the form of sporotrichoid lesions, 2 involved patients with AIDS² and 1 involved a cardiac transplant recipient.⁴

Cutaneous MAI is typically diagnosed with skin biopsy and tissue culture. Tissue culture is critical for determining the specific mycobacterial species and antibiotic susceptibilities. Polymerase chain reaction has been utilized to rapidly diagnose cutaneous MAI infection from an acid-fast bacilli–positive tissue sample in which the tissue culture was negative.⁵

Recommended treatment protocols for MAI involve multidrug regimens because of the intrinsic resistance of MAI and the concern for development of resistance with monotherapy.² No definitive guidelines exist for treatment of primary cutaneous MAI infections. However, regimens for the treatment of pulmonary infection that also have been successfully utilized for cutaneous infection include a macrolide, ethambutol, and a rifamycin.⁶ Clinicians should be aware of MAI as a cause of primary cutaneous infections presenting as lymphocutaneous suppurative nodules and ulcerations.

The Diagnosis: Atypical Mycobacterial Infection

Punch biopsy specimens demonstrated necrotizing granulomatous inflammation in the dermis and subcutis (Figure). Special staining for microorganisms was negative. Tissue culture grew Mycobacterium avium-intracellulare (MAI). The patient began treatment with azithromycin, ethambutol, and rifabutin. Tissue susceptibilities later showed resistance to rifabutin and sensitivity to clarithromycin, moxifloxacin, and clofazimine. She subsequently was switched to azithromycin, clofazimine, and moxifloxacin with good response.

Mycobacterium avium-intracellulare is a slow-growing, nonchromogenic, atypical mycobacteria. Although ubiquitous, it tends to only cause serious infection in the setting of immunosuppression. Transmission usually is through the respiratory or gastrointestinal tract.¹ Skin infections with MAI are uncommon and usually are secondary to seeding from disseminated infection or from direct inoculation.²

The clinical presentations of primary cutaneous MAI are myriad, including an isolated red nodule, multiple ulcers, abscesses, draining sinuses, facial nodules, granulomatous plaques, and panniculitis.^2,3 Of 3 reported cases of primary cutaneous MAI in the form of sporotrichoid lesions, 2 involved patients with AIDS² and 1 involved a cardiac transplant recipient.⁴

Cutaneous MAI is typically diagnosed with skin biopsy and tissue culture. Tissue culture is critical for determining the specific mycobacterial species and antibiotic susceptibilities. Polymerase chain reaction has been utilized to rapidly diagnose cutaneous MAI infection from an acid-fast bacilli–positive tissue sample in which the tissue culture was negative.⁵

Recommended treatment protocols for MAI involve multidrug regimens because of the intrinsic resistance of MAI and the concern for development of resistance with monotherapy.² No definitive guidelines exist for treatment of primary cutaneous MAI infections. However, regimens for the treatment of pulmonary infection that also have been successfully utilized for cutaneous infection include a macrolide, ethambutol, and a rifamycin.⁶ Clinicians should be aware of MAI as a cause of primary cutaneous infections presenting as lymphocutaneous suppurative nodules and ulcerations.

The Diagnosis: Atypical Mycobacterial Infection

Punch biopsy specimens demonstrated necrotizing granulomatous inflammation in the dermis and subcutis (Figure). Special staining for microorganisms was negative. Tissue culture grew Mycobacterium avium-intracellulare (MAI). The patient began treatment with azithromycin, ethambutol, and rifabutin. Tissue susceptibilities later showed resistance to rifabutin and sensitivity to clarithromycin, moxifloxacin, and clofazimine. She subsequently was switched to azithromycin, clofazimine, and moxifloxacin with good response.

Mycobacterium avium-intracellulare is a slow-growing, nonchromogenic, atypical mycobacteria. Although ubiquitous, it tends to only cause serious infection in the setting of immunosuppression. Transmission usually is through the respiratory or gastrointestinal tract.¹ Skin infections with MAI are uncommon and usually are secondary to seeding from disseminated infection or from direct inoculation.²

The clinical presentations of primary cutaneous MAI are myriad, including an isolated red nodule, multiple ulcers, abscesses, draining sinuses, facial nodules, granulomatous plaques, and panniculitis.^2,3 Of 3 reported cases of primary cutaneous MAI in the form of sporotrichoid lesions, 2 involved patients with AIDS² and 1 involved a cardiac transplant recipient.⁴

Cutaneous MAI is typically diagnosed with skin biopsy and tissue culture. Tissue culture is critical for determining the specific mycobacterial species and antibiotic susceptibilities. Polymerase chain reaction has been utilized to rapidly diagnose cutaneous MAI infection from an acid-fast bacilli–positive tissue sample in which the tissue culture was negative.⁵

Recommended treatment protocols for MAI involve multidrug regimens because of the intrinsic resistance of MAI and the concern for development of resistance with monotherapy.² No definitive guidelines exist for treatment of primary cutaneous MAI infections. However, regimens for the treatment of pulmonary infection that also have been successfully utilized for cutaneous infection include a macrolide, ethambutol, and a rifamycin.⁶ Clinicians should be aware of MAI as a cause of primary cutaneous infections presenting as lymphocutaneous suppurative nodules and ulcerations.

Answer
The radiograph shows no acute fracture or subluxation. Diffuse osteopenia is present. Increased density is noted within the soft tissue lateral to the trochanteric portion of the right femur; this likely represents a contusion or hematoma. 

Answer
The radiograph shows no acute fracture or subluxation. Diffuse osteopenia is present. Increased density is noted within the soft tissue lateral to the trochanteric portion of the right femur; this likely represents a contusion or hematoma. 

Answer
The radiograph shows no acute fracture or subluxation. Diffuse osteopenia is present. Increased density is noted within the soft tissue lateral to the trochanteric portion of the right femur; this likely represents a contusion or hematoma.