Case Letter

To the Editor:

Tinea incognito occurs when superficial fungal infections fail to demonstrate typical clinical features in the setting of immune suppression caused by topical or systemic steroids.^1,2 A case of tinea corporis obscured by an allergic tattoo reaction is presented.

A 52-year-old man presented for evaluation of a rash overlying a tattoo on the right calf of 3 weeks’ duration (Figure, A). The tattoo was placed 4 years prior to presentation. Within 6 months of the tattoo’s placement, pruritus, scaling, and edema developed in a 2-mm rim around the outer border and in the eyes of the elephant tattoo but not in the lettering portion of the tattoo, which was added by a different tattoo artist with a different red dye. A diagnosis of red dye tattoo allergic reaction was made. Daily treatment with tacrolimus ointment 0.1% and halobetasol propionate cream 0.05% under occlusion for 18 months provided only partial relief of incessant pruritus. Three months prior to presentation the tattoo reaction appeared to become worse with more pruritus and extension outside the bounds of the original tattoo.

Physical examination revealed the red rim of the tattoo was erythematous, edematous, and crusted. In addition, a 5×4-cm well-demarcated, erythematous, scaling patch was present overlying the elephant tattoo on the right calf and extending superiorly and laterally away from the tattoo. Scaling and maceration also were present in the web spaces between the fourth and fifth toes, and the toenails were yellowed, thickened, and dystrophic with signs of distal onycholysis. A potassium hydroxide preparation performed from the plaque on the right calf demonstrated septate fungal hyphae.

The diagnosis of tinea corporis secondary to tinea pedis overlying a red dye tattoo allergic reaction was made. Tacrolimus and halobetasol propionate were discontinued and treatment with ketoconazole cream 2% twice daily and oral terbinafine 250 mg once daily was started. The erythematous patch beyond the borders of the tattoo cleared within weeks, but the patient reported worsening of cracking, itching, and swelling overlying the red dye in the rim of the tattoo following discontinuation of topical anti-inflammatory drugs (Figure, B).

A potassium hydroxide preparation demonstrated that the expansible rash was tinea corporis disguised in its character by the coloration of the tattoo; the erythematous, edematous, pruritic tattoo allergic reaction at its rim; and suppression of the normal inflammatory response by daily use of a topical steroid and a calcineurin inhibitor. The latter effect (an immunocompromised district) impacts the classic exaggerated scaling, inflamed rim, and central clearing of tinea corporis present in individuals with a normal inflammatory response.² Although tinea incognito is classically described on the ankles and lower legs of patients with stasis dermatitis chronically treated with topical steroids, it could occur anywhere in the setting of immunosuppression.³

An analysis of this case using Occam’s razor suggests that the association of this tattoo and tinea was not a coincidence. This guiding principle (heuristic) suggests that economy and succinctness in the logic of science is most likely to produce a correct medical diagnosis (eg, associated findings can be explained by identifying one underlying cause).⁴ The topical anti-inflammatory drugs increase the likelihood that the patient’s interdigital tinea would spread to this precise location symmetrically expanding in the outline of the tattoo.²

To the Editor:

Tinea incognito occurs when superficial fungal infections fail to demonstrate typical clinical features in the setting of immune suppression caused by topical or systemic steroids.^1,2 A case of tinea corporis obscured by an allergic tattoo reaction is presented.

A 52-year-old man presented for evaluation of a rash overlying a tattoo on the right calf of 3 weeks’ duration (Figure, A). The tattoo was placed 4 years prior to presentation. Within 6 months of the tattoo’s placement, pruritus, scaling, and edema developed in a 2-mm rim around the outer border and in the eyes of the elephant tattoo but not in the lettering portion of the tattoo, which was added by a different tattoo artist with a different red dye. A diagnosis of red dye tattoo allergic reaction was made. Daily treatment with tacrolimus ointment 0.1% and halobetasol propionate cream 0.05% under occlusion for 18 months provided only partial relief of incessant pruritus. Three months prior to presentation the tattoo reaction appeared to become worse with more pruritus and extension outside the bounds of the original tattoo.

Physical examination revealed the red rim of the tattoo was erythematous, edematous, and crusted. In addition, a 5×4-cm well-demarcated, erythematous, scaling patch was present overlying the elephant tattoo on the right calf and extending superiorly and laterally away from the tattoo. Scaling and maceration also were present in the web spaces between the fourth and fifth toes, and the toenails were yellowed, thickened, and dystrophic with signs of distal onycholysis. A potassium hydroxide preparation performed from the plaque on the right calf demonstrated septate fungal hyphae.

The diagnosis of tinea corporis secondary to tinea pedis overlying a red dye tattoo allergic reaction was made. Tacrolimus and halobetasol propionate were discontinued and treatment with ketoconazole cream 2% twice daily and oral terbinafine 250 mg once daily was started. The erythematous patch beyond the borders of the tattoo cleared within weeks, but the patient reported worsening of cracking, itching, and swelling overlying the red dye in the rim of the tattoo following discontinuation of topical anti-inflammatory drugs (Figure, B).

A potassium hydroxide preparation demonstrated that the expansible rash was tinea corporis disguised in its character by the coloration of the tattoo; the erythematous, edematous, pruritic tattoo allergic reaction at its rim; and suppression of the normal inflammatory response by daily use of a topical steroid and a calcineurin inhibitor. The latter effect (an immunocompromised district) impacts the classic exaggerated scaling, inflamed rim, and central clearing of tinea corporis present in individuals with a normal inflammatory response.² Although tinea incognito is classically described on the ankles and lower legs of patients with stasis dermatitis chronically treated with topical steroids, it could occur anywhere in the setting of immunosuppression.³

An analysis of this case using Occam’s razor suggests that the association of this tattoo and tinea was not a coincidence. This guiding principle (heuristic) suggests that economy and succinctness in the logic of science is most likely to produce a correct medical diagnosis (eg, associated findings can be explained by identifying one underlying cause).⁴ The topical anti-inflammatory drugs increase the likelihood that the patient’s interdigital tinea would spread to this precise location symmetrically expanding in the outline of the tattoo.²

To the Editor:

Tinea incognito occurs when superficial fungal infections fail to demonstrate typical clinical features in the setting of immune suppression caused by topical or systemic steroids.^1,2 A case of tinea corporis obscured by an allergic tattoo reaction is presented.

A 52-year-old man presented for evaluation of a rash overlying a tattoo on the right calf of 3 weeks’ duration (Figure, A). The tattoo was placed 4 years prior to presentation. Within 6 months of the tattoo’s placement, pruritus, scaling, and edema developed in a 2-mm rim around the outer border and in the eyes of the elephant tattoo but not in the lettering portion of the tattoo, which was added by a different tattoo artist with a different red dye. A diagnosis of red dye tattoo allergic reaction was made. Daily treatment with tacrolimus ointment 0.1% and halobetasol propionate cream 0.05% under occlusion for 18 months provided only partial relief of incessant pruritus. Three months prior to presentation the tattoo reaction appeared to become worse with more pruritus and extension outside the bounds of the original tattoo.

Physical examination revealed the red rim of the tattoo was erythematous, edematous, and crusted. In addition, a 5×4-cm well-demarcated, erythematous, scaling patch was present overlying the elephant tattoo on the right calf and extending superiorly and laterally away from the tattoo. Scaling and maceration also were present in the web spaces between the fourth and fifth toes, and the toenails were yellowed, thickened, and dystrophic with signs of distal onycholysis. A potassium hydroxide preparation performed from the plaque on the right calf demonstrated septate fungal hyphae.

The diagnosis of tinea corporis secondary to tinea pedis overlying a red dye tattoo allergic reaction was made. Tacrolimus and halobetasol propionate were discontinued and treatment with ketoconazole cream 2% twice daily and oral terbinafine 250 mg once daily was started. The erythematous patch beyond the borders of the tattoo cleared within weeks, but the patient reported worsening of cracking, itching, and swelling overlying the red dye in the rim of the tattoo following discontinuation of topical anti-inflammatory drugs (Figure, B).

A potassium hydroxide preparation demonstrated that the expansible rash was tinea corporis disguised in its character by the coloration of the tattoo; the erythematous, edematous, pruritic tattoo allergic reaction at its rim; and suppression of the normal inflammatory response by daily use of a topical steroid and a calcineurin inhibitor. The latter effect (an immunocompromised district) impacts the classic exaggerated scaling, inflamed rim, and central clearing of tinea corporis present in individuals with a normal inflammatory response.² Although tinea incognito is classically described on the ankles and lower legs of patients with stasis dermatitis chronically treated with topical steroids, it could occur anywhere in the setting of immunosuppression.³

An analysis of this case using Occam’s razor suggests that the association of this tattoo and tinea was not a coincidence. This guiding principle (heuristic) suggests that economy and succinctness in the logic of science is most likely to produce a correct medical diagnosis (eg, associated findings can be explained by identifying one underlying cause).⁴ The topical anti-inflammatory drugs increase the likelihood that the patient’s interdigital tinea would spread to this precise location symmetrically expanding in the outline of the tattoo.²

To the Editor:

According to the Centers for Disease Control and Prevention, the number of syphilis cases in the United States decreased 95% from 1945 to 2000.¹ Since 2000, the number of cases of syphilis in the United States has increased from 2.1 cases per 100,000 to 8.7 cases per 100,000.¹ We report the case of an atypical presentation of secondary syphilis with a false negative rapid plasma reagin (RPR) test, which resulted in delayed diagnosis and treatment. The goal of this report is to raise awareness of the increasing prevalence of syphilis in the United States, draw attention to atypical presentations of syphilis, and inform physicians of some of the pitfalls in current syphilis screening and testing modalities.

A 37-year-old man presented with cutaneous ulcers on the forehead, thighs, and forearms of 3 months’ duration. The lesions started as a scarlet fever–like rash consisting of diffuse boils that would burst and become ulcerated. He reported arthralgias and drenching night sweats and had unintentionally lost 20 pounds over the last 3 months. He also had pharyngitis 8 months prior to presentation and sinusitis 4 months prior to presentation. These symptoms were present during his initial evaluation. One month prior to the current presentation, a nurse practitioner from an outside clinic had prescribed sulfamethoxazole/trimethoprim and ordered an RPR test, which was nonreactive. The lesions did not resolve, and the patient was referred to our dermatology department.

On physical examination, multiple 1- to 3-cm erythematous, well-defined papules were noted on the thighs and forearms. Some of the papules were covered with crusts, some were ulcerated with yellow discharge, and all were nontender. The differential diagnoses included dermatomyositis, polyarteritis nodosa, deep fungal infection, mycobacterial infection, leishmaniasis, and cutaneous anthrax. Secondary syphilis was a possible differential but was discounted due to the nonreactive RPR 1 month prior to presentation.

Punch biopsies were collected from lesions on the forehead, forearms, and thighs and sent to multiple institutions for pathology evaluation, which revealed dermal and pannicular necrosis and acute suppurative and granulomatous inflammation focally involving vessels (Figure 1). The biopsies were negative for acid-fast and fungal organisms, Mycobacterium tuberculosis, Leishmania, and anthrax. A work-up for Wegener granulomatosis was recommended by the pathology department.

Three days later, the patient was admitted to the hospital for syncope. The hospitalist noted the cutaneous lesions and reordered the RPR test, which was now reactive. The ulcers had worsened since the original presentation (Figure 2). A fluorescent treponemal antibody absorption (FTA-ABS) test confirmed the reactive RPR, and a diagnosis of secondary syphilis was made. He was allergic to penicillin G, so the patient was prescribed doxycycline 100 mg twice daily for 28 days. His cutaneous ulcers have since healed with no recurrence of symptoms.

Secondary syphilis often is preceded by a prodrome of fever, malaise, sore throat, adenopathy, unintentional weight loss, myalgias, and headaches. It usually presents as a nonpruritic papulosquamous eruption with painless mucosal ulcers but rarely presents as cutaneous ulcers.^2-4 Cutaneous ulcers are typical of lues maligna, which usually occurs in immunosuppressed patients.^5,6 Our patient was human immunodeficiency virus–negative and was not otherwise immunocompromised.

Rapid plasma reagin is a common screening test for syphilis. In this case, it was initially negative, which may be attributed to the prozone phenomenon, a false negative result due to a high antibody titer that prevents the flocculation reaction from occurring. The prozone phenomenon can occur with a titer as low as 1:8.⁷ A 50% dilution of the negative sample should overcome the prozone phenomenon and yield a positive result⁷; unfortunately, this is not standard practice in all hospital laboratories.

The standard method of diagnosing syphilis in the United States is to screen with nontreponemal tests (eg, RPR) followed by treponemal tests (eg, FTA-ABS) to confirm a positive screen. According to the United States Preventive Services Task Force, the sensitivity of the RPR test is approximately 78% to 86%, while FTA-ABS has a sensitivity of 84% for detecting primary syphilis and 100% for secondary and tertiary syphilis.⁸ Seña et al⁴ suggest that FTA-ABS should be used as the screening test for syphilis. Fluorescent treponemal antibody absorption testing more accurately detects syphilis, while RPR testing is more useful in monitoring serum response once treatment has been initiated.

In conclusion, our patient could have benefited from earlier diagnosis and treatment if a treponemal test had been performed earlier or if the initial nonreactive RPR test was diluted and retested.

Acknowledgments
We would like to acknowledge Dr. Timothy Weiland (Pathology Department, Altru Health System, Grand Forks, North Dakota), and Dr. Mark Koponen (University of North Dakota, Grand Forks).

To the Editor:

According to the Centers for Disease Control and Prevention, the number of syphilis cases in the United States decreased 95% from 1945 to 2000.¹ Since 2000, the number of cases of syphilis in the United States has increased from 2.1 cases per 100,000 to 8.7 cases per 100,000.¹ We report the case of an atypical presentation of secondary syphilis with a false negative rapid plasma reagin (RPR) test, which resulted in delayed diagnosis and treatment. The goal of this report is to raise awareness of the increasing prevalence of syphilis in the United States, draw attention to atypical presentations of syphilis, and inform physicians of some of the pitfalls in current syphilis screening and testing modalities.

A 37-year-old man presented with cutaneous ulcers on the forehead, thighs, and forearms of 3 months’ duration. The lesions started as a scarlet fever–like rash consisting of diffuse boils that would burst and become ulcerated. He reported arthralgias and drenching night sweats and had unintentionally lost 20 pounds over the last 3 months. He also had pharyngitis 8 months prior to presentation and sinusitis 4 months prior to presentation. These symptoms were present during his initial evaluation. One month prior to the current presentation, a nurse practitioner from an outside clinic had prescribed sulfamethoxazole/trimethoprim and ordered an RPR test, which was nonreactive. The lesions did not resolve, and the patient was referred to our dermatology department.

On physical examination, multiple 1- to 3-cm erythematous, well-defined papules were noted on the thighs and forearms. Some of the papules were covered with crusts, some were ulcerated with yellow discharge, and all were nontender. The differential diagnoses included dermatomyositis, polyarteritis nodosa, deep fungal infection, mycobacterial infection, leishmaniasis, and cutaneous anthrax. Secondary syphilis was a possible differential but was discounted due to the nonreactive RPR 1 month prior to presentation.

Punch biopsies were collected from lesions on the forehead, forearms, and thighs and sent to multiple institutions for pathology evaluation, which revealed dermal and pannicular necrosis and acute suppurative and granulomatous inflammation focally involving vessels (Figure 1). The biopsies were negative for acid-fast and fungal organisms, Mycobacterium tuberculosis, Leishmania, and anthrax. A work-up for Wegener granulomatosis was recommended by the pathology department.

Three days later, the patient was admitted to the hospital for syncope. The hospitalist noted the cutaneous lesions and reordered the RPR test, which was now reactive. The ulcers had worsened since the original presentation (Figure 2). A fluorescent treponemal antibody absorption (FTA-ABS) test confirmed the reactive RPR, and a diagnosis of secondary syphilis was made. He was allergic to penicillin G, so the patient was prescribed doxycycline 100 mg twice daily for 28 days. His cutaneous ulcers have since healed with no recurrence of symptoms.

Secondary syphilis often is preceded by a prodrome of fever, malaise, sore throat, adenopathy, unintentional weight loss, myalgias, and headaches. It usually presents as a nonpruritic papulosquamous eruption with painless mucosal ulcers but rarely presents as cutaneous ulcers.^2-4 Cutaneous ulcers are typical of lues maligna, which usually occurs in immunosuppressed patients.^5,6 Our patient was human immunodeficiency virus–negative and was not otherwise immunocompromised.

Rapid plasma reagin is a common screening test for syphilis. In this case, it was initially negative, which may be attributed to the prozone phenomenon, a false negative result due to a high antibody titer that prevents the flocculation reaction from occurring. The prozone phenomenon can occur with a titer as low as 1:8.⁷ A 50% dilution of the negative sample should overcome the prozone phenomenon and yield a positive result⁷; unfortunately, this is not standard practice in all hospital laboratories.

The standard method of diagnosing syphilis in the United States is to screen with nontreponemal tests (eg, RPR) followed by treponemal tests (eg, FTA-ABS) to confirm a positive screen. According to the United States Preventive Services Task Force, the sensitivity of the RPR test is approximately 78% to 86%, while FTA-ABS has a sensitivity of 84% for detecting primary syphilis and 100% for secondary and tertiary syphilis.⁸ Seña et al⁴ suggest that FTA-ABS should be used as the screening test for syphilis. Fluorescent treponemal antibody absorption testing more accurately detects syphilis, while RPR testing is more useful in monitoring serum response once treatment has been initiated.

In conclusion, our patient could have benefited from earlier diagnosis and treatment if a treponemal test had been performed earlier or if the initial nonreactive RPR test was diluted and retested.

Acknowledgments
We would like to acknowledge Dr. Timothy Weiland (Pathology Department, Altru Health System, Grand Forks, North Dakota), and Dr. Mark Koponen (University of North Dakota, Grand Forks).

To the Editor:

According to the Centers for Disease Control and Prevention, the number of syphilis cases in the United States decreased 95% from 1945 to 2000.¹ Since 2000, the number of cases of syphilis in the United States has increased from 2.1 cases per 100,000 to 8.7 cases per 100,000.¹ We report the case of an atypical presentation of secondary syphilis with a false negative rapid plasma reagin (RPR) test, which resulted in delayed diagnosis and treatment. The goal of this report is to raise awareness of the increasing prevalence of syphilis in the United States, draw attention to atypical presentations of syphilis, and inform physicians of some of the pitfalls in current syphilis screening and testing modalities.

A 37-year-old man presented with cutaneous ulcers on the forehead, thighs, and forearms of 3 months’ duration. The lesions started as a scarlet fever–like rash consisting of diffuse boils that would burst and become ulcerated. He reported arthralgias and drenching night sweats and had unintentionally lost 20 pounds over the last 3 months. He also had pharyngitis 8 months prior to presentation and sinusitis 4 months prior to presentation. These symptoms were present during his initial evaluation. One month prior to the current presentation, a nurse practitioner from an outside clinic had prescribed sulfamethoxazole/trimethoprim and ordered an RPR test, which was nonreactive. The lesions did not resolve, and the patient was referred to our dermatology department.

On physical examination, multiple 1- to 3-cm erythematous, well-defined papules were noted on the thighs and forearms. Some of the papules were covered with crusts, some were ulcerated with yellow discharge, and all were nontender. The differential diagnoses included dermatomyositis, polyarteritis nodosa, deep fungal infection, mycobacterial infection, leishmaniasis, and cutaneous anthrax. Secondary syphilis was a possible differential but was discounted due to the nonreactive RPR 1 month prior to presentation.

Punch biopsies were collected from lesions on the forehead, forearms, and thighs and sent to multiple institutions for pathology evaluation, which revealed dermal and pannicular necrosis and acute suppurative and granulomatous inflammation focally involving vessels (Figure 1). The biopsies were negative for acid-fast and fungal organisms, Mycobacterium tuberculosis, Leishmania, and anthrax. A work-up for Wegener granulomatosis was recommended by the pathology department.

Three days later, the patient was admitted to the hospital for syncope. The hospitalist noted the cutaneous lesions and reordered the RPR test, which was now reactive. The ulcers had worsened since the original presentation (Figure 2). A fluorescent treponemal antibody absorption (FTA-ABS) test confirmed the reactive RPR, and a diagnosis of secondary syphilis was made. He was allergic to penicillin G, so the patient was prescribed doxycycline 100 mg twice daily for 28 days. His cutaneous ulcers have since healed with no recurrence of symptoms.

Secondary syphilis often is preceded by a prodrome of fever, malaise, sore throat, adenopathy, unintentional weight loss, myalgias, and headaches. It usually presents as a nonpruritic papulosquamous eruption with painless mucosal ulcers but rarely presents as cutaneous ulcers.^2-4 Cutaneous ulcers are typical of lues maligna, which usually occurs in immunosuppressed patients.^5,6 Our patient was human immunodeficiency virus–negative and was not otherwise immunocompromised.

Rapid plasma reagin is a common screening test for syphilis. In this case, it was initially negative, which may be attributed to the prozone phenomenon, a false negative result due to a high antibody titer that prevents the flocculation reaction from occurring. The prozone phenomenon can occur with a titer as low as 1:8.⁷ A 50% dilution of the negative sample should overcome the prozone phenomenon and yield a positive result⁷; unfortunately, this is not standard practice in all hospital laboratories.

The standard method of diagnosing syphilis in the United States is to screen with nontreponemal tests (eg, RPR) followed by treponemal tests (eg, FTA-ABS) to confirm a positive screen. According to the United States Preventive Services Task Force, the sensitivity of the RPR test is approximately 78% to 86%, while FTA-ABS has a sensitivity of 84% for detecting primary syphilis and 100% for secondary and tertiary syphilis.⁸ Seña et al⁴ suggest that FTA-ABS should be used as the screening test for syphilis. Fluorescent treponemal antibody absorption testing more accurately detects syphilis, while RPR testing is more useful in monitoring serum response once treatment has been initiated.

In conclusion, our patient could have benefited from earlier diagnosis and treatment if a treponemal test had been performed earlier or if the initial nonreactive RPR test was diluted and retested.

Acknowledgments
We would like to acknowledge Dr. Timothy Weiland (Pathology Department, Altru Health System, Grand Forks, North Dakota), and Dr. Mark Koponen (University of North Dakota, Grand Forks).

To the Editor:

Angiokeratoma is a benign vascular tumor characterized by several dilated vessels in the superficial dermis accompanied by epidermal hyperplasia and hyperkeratosis.¹ Angiokeratoma of the vulva is a rare clinical finding, usually involving multiple lesions as part of the Fordyce type.² Solitary angiokeratoma occurs predominantly on the lower legs,³ and although other locations have been described, the presence of a solitary angiokeratoma on the vulva is rare.⁴ We report 2 cases of solitary angiokeratoma on the vulva that was misdiagnosed as malignant melanoma. Both patients were referred to our center for evaluation and excision.

A 65-year-old woman (patient 1) and a 67-year-old woman (patient 2) presented with a bluish black, growing, asymptomatic lesion on the right (Figure 1) and left labia majora, respectively. Both patients were referred by outside physicians for excision because of suspected malignant melanoma. Physical examinations revealed bluish black globular nodules that measured 0.5 and 0.3 cm in diameter, respectively. Dermoscopy (patient 1) revealed dark lacunae. Histopathologic examination of the vulvar lesion (patient 2) showed dilated, blood-filled, vascular spaces in the papillary dermis, accompanied by overlying acanthosis, hyperkeratosis, and papillomatosis that was consistent with angiokeratoma (Figure 2).

Angiokeratoma, particularly the solitary type, often is misdiagnosed. Clinical differential diagnoses may include a wide range of pathologic conditions, including condyloma acuminata, basal cell carcinoma, pyogenic granuloma, lymphangioma, nevi, condyloma lata, nodular prurigo, seborrheic keratosis, granuloma inguinale, and deep fungal infection.^2,5 However, due to its quickly growing nature and its dark complexion, malignant melanoma often is initially diagnosed. Because patients affected by angiokeratoma of the vulva usually are aged 20 to 40 years,⁵ and vulvar melanoma is typical for middle-aged women (median age, 68 years),⁶ this misdiagnosis is more likely in older patients. It should be noted that a high index of suspicion for melanoma often is present when examining the vulva, considering that this area is difficult to monitor, and there is an especially poor prognosis of vulvar melanoma due to its late detection.^6,7

In the past, biopsy was considered mandatory for confirming the diagnosis of vulvar angiokeratoma.^5,8,9 However, dermoscopy has emerged as a valuable tool for diagnosis of angiokeratoma¹⁰ and also was helpful as a diagnostic aid in one of our patients (patient 1). Therefore, we believe that dermoscopy should be performed prior to a biopsy of angiokeratomas of the vulva.

To the Editor:

Angiokeratoma is a benign vascular tumor characterized by several dilated vessels in the superficial dermis accompanied by epidermal hyperplasia and hyperkeratosis.¹ Angiokeratoma of the vulva is a rare clinical finding, usually involving multiple lesions as part of the Fordyce type.² Solitary angiokeratoma occurs predominantly on the lower legs,³ and although other locations have been described, the presence of a solitary angiokeratoma on the vulva is rare.⁴ We report 2 cases of solitary angiokeratoma on the vulva that was misdiagnosed as malignant melanoma. Both patients were referred to our center for evaluation and excision.

A 65-year-old woman (patient 1) and a 67-year-old woman (patient 2) presented with a bluish black, growing, asymptomatic lesion on the right (Figure 1) and left labia majora, respectively. Both patients were referred by outside physicians for excision because of suspected malignant melanoma. Physical examinations revealed bluish black globular nodules that measured 0.5 and 0.3 cm in diameter, respectively. Dermoscopy (patient 1) revealed dark lacunae. Histopathologic examination of the vulvar lesion (patient 2) showed dilated, blood-filled, vascular spaces in the papillary dermis, accompanied by overlying acanthosis, hyperkeratosis, and papillomatosis that was consistent with angiokeratoma (Figure 2).

Angiokeratoma, particularly the solitary type, often is misdiagnosed. Clinical differential diagnoses may include a wide range of pathologic conditions, including condyloma acuminata, basal cell carcinoma, pyogenic granuloma, lymphangioma, nevi, condyloma lata, nodular prurigo, seborrheic keratosis, granuloma inguinale, and deep fungal infection.^2,5 However, due to its quickly growing nature and its dark complexion, malignant melanoma often is initially diagnosed. Because patients affected by angiokeratoma of the vulva usually are aged 20 to 40 years,⁵ and vulvar melanoma is typical for middle-aged women (median age, 68 years),⁶ this misdiagnosis is more likely in older patients. It should be noted that a high index of suspicion for melanoma often is present when examining the vulva, considering that this area is difficult to monitor, and there is an especially poor prognosis of vulvar melanoma due to its late detection.^6,7

In the past, biopsy was considered mandatory for confirming the diagnosis of vulvar angiokeratoma.^5,8,9 However, dermoscopy has emerged as a valuable tool for diagnosis of angiokeratoma¹⁰ and also was helpful as a diagnostic aid in one of our patients (patient 1). Therefore, we believe that dermoscopy should be performed prior to a biopsy of angiokeratomas of the vulva.

To the Editor:

Angiokeratoma is a benign vascular tumor characterized by several dilated vessels in the superficial dermis accompanied by epidermal hyperplasia and hyperkeratosis.¹ Angiokeratoma of the vulva is a rare clinical finding, usually involving multiple lesions as part of the Fordyce type.² Solitary angiokeratoma occurs predominantly on the lower legs,³ and although other locations have been described, the presence of a solitary angiokeratoma on the vulva is rare.⁴ We report 2 cases of solitary angiokeratoma on the vulva that was misdiagnosed as malignant melanoma. Both patients were referred to our center for evaluation and excision.

A 65-year-old woman (patient 1) and a 67-year-old woman (patient 2) presented with a bluish black, growing, asymptomatic lesion on the right (Figure 1) and left labia majora, respectively. Both patients were referred by outside physicians for excision because of suspected malignant melanoma. Physical examinations revealed bluish black globular nodules that measured 0.5 and 0.3 cm in diameter, respectively. Dermoscopy (patient 1) revealed dark lacunae. Histopathologic examination of the vulvar lesion (patient 2) showed dilated, blood-filled, vascular spaces in the papillary dermis, accompanied by overlying acanthosis, hyperkeratosis, and papillomatosis that was consistent with angiokeratoma (Figure 2).

Angiokeratoma, particularly the solitary type, often is misdiagnosed. Clinical differential diagnoses may include a wide range of pathologic conditions, including condyloma acuminata, basal cell carcinoma, pyogenic granuloma, lymphangioma, nevi, condyloma lata, nodular prurigo, seborrheic keratosis, granuloma inguinale, and deep fungal infection.^2,5 However, due to its quickly growing nature and its dark complexion, malignant melanoma often is initially diagnosed. Because patients affected by angiokeratoma of the vulva usually are aged 20 to 40 years,⁵ and vulvar melanoma is typical for middle-aged women (median age, 68 years),⁶ this misdiagnosis is more likely in older patients. It should be noted that a high index of suspicion for melanoma often is present when examining the vulva, considering that this area is difficult to monitor, and there is an especially poor prognosis of vulvar melanoma due to its late detection.^6,7

In the past, biopsy was considered mandatory for confirming the diagnosis of vulvar angiokeratoma.^5,8,9 However, dermoscopy has emerged as a valuable tool for diagnosis of angiokeratoma¹⁰ and also was helpful as a diagnostic aid in one of our patients (patient 1). Therefore, we believe that dermoscopy should be performed prior to a biopsy of angiokeratomas of the vulva.

To the Editor:

Carotenoderma is a cutaneous manifestation of elevated serum β-carotene levels and classically localizes to fatty tissues and areas rich in sweat glands. We present a case of carotenoderma associated with a diet rich in red palm oil, a common food additive in parts of the world outside of the United States.

A previously healthy 8-year-old boy who recently immigrated to the United States from Liberia was hospitalized for treatment of a febrile illness that subsequently was attributed to a viral syndrome. On physical examination by the dermatology department, the patient was noted to have marked orange discoloration on the palms and soles (Figure). Laboratory workup revealed elevated serum β-carotene levels of 809 μg/dL (reference range, 10–85 μg/dL). Testing of hemoglobin/hematocrit levels and liver, thyroid, and kidney function was normal, and systemic examination revealed no further abnormalities. Upon further inquiry by the dermatology department, the patient’s family reported frequent addition of red palm oil to all of the child’s meals. The patient subsequently was diagnosed with carotenoderma and was instructed to limit inclusion of red palm oil in his diet.

Red palm oil is a rich source of β-carotene and is commonly used outside the United States as a dietary supplement or food flavoring. Excessive consumption of red palm oil or other sources rich in carotenes can result in elevated serum carotene levels or hypercarotenemia. An elevation in serum β-carotene levels may be recognized from 4 to 7 weeks after starting a β-carotene–rich diet.¹

While dietary consumption of carotenes is the most common cause of carotenoderma, others include kidney or liver disease, hyperlipidemia, porphyria, diabetes mellitus, hypothyroidism, and anorexia nervosa.^2-4 Moreover, since carotenoids are enzymatically converted to vitamin A in the small intestine, a mutation of the gene of the conversion enzyme β-carotene 15,15’-monooxygenase 1 (BCMO1) also can cause be a rare cause of hypercarotenemia.³

Carotenoderma, the clinical cutaneous manifestation of hypercarotenemia, occurs as a result of β-carotene deposits in the skin when serum concentration exceeds 250 μg/dL. More specifically, β-carotene accumulates mainly in the lipid-rich stratum corneum as well as in sweat and sebum, which explains the localized discoloration in fatty tissues and areas rich in sweat glands (eg, nasolabial folds, palms, soles).^3,4 The sclerae of the eyes are not affected by the surplus of β-carotene in carotenoderma, which helps distinguish it from jaundice.⁵

The differential diagnosis of yellow discoloration of the skin includes jaundice, encompassing the prehepatic, hepatocellular, and posthepatic categories.⁴ Also noteworthy in the differential diagnosis is lycopenemia, which occurs as a result of eating lycopene-rich foods (eg, tomatoes), resulting in a deeper orange-yellow pigmentation when compared to the cutaneous manifestation of hypercarotenemia.^2,4,6 Several drugs also have been reported to induce yellow discoloration of the skin, including sunitinib,⁷ sorafenib,⁸ quinacrine, saffron supplements, santonin, fluorescein, 2,4-dinitrophenol, canthaxanthin, tetryl and picric acids, and acriflavine.^2,4

Carotenoderma caused by a diet rich in β-carotene is a benign condition in which a diet low in β-carotene is implicated for treatment. Contrary to popular belief, vitamin A toxicity does not occur in the presence of a surplus of β-carotenes because the enzymatic conversion of β-carotene to vitamin A is strictly regulated.⁹ Although acknowledging the various causes of carotenoderma is important, a simple history and laboratory testing for elevated serum β-carotene levels can eliminate further unnecessary testing and allow for prompt recognition of the condition. Appropriate dietary modifications also may be warranted.

To the Editor:

Carotenoderma is a cutaneous manifestation of elevated serum β-carotene levels and classically localizes to fatty tissues and areas rich in sweat glands. We present a case of carotenoderma associated with a diet rich in red palm oil, a common food additive in parts of the world outside of the United States.

A previously healthy 8-year-old boy who recently immigrated to the United States from Liberia was hospitalized for treatment of a febrile illness that subsequently was attributed to a viral syndrome. On physical examination by the dermatology department, the patient was noted to have marked orange discoloration on the palms and soles (Figure). Laboratory workup revealed elevated serum β-carotene levels of 809 μg/dL (reference range, 10–85 μg/dL). Testing of hemoglobin/hematocrit levels and liver, thyroid, and kidney function was normal, and systemic examination revealed no further abnormalities. Upon further inquiry by the dermatology department, the patient’s family reported frequent addition of red palm oil to all of the child’s meals. The patient subsequently was diagnosed with carotenoderma and was instructed to limit inclusion of red palm oil in his diet.

Red palm oil is a rich source of β-carotene and is commonly used outside the United States as a dietary supplement or food flavoring. Excessive consumption of red palm oil or other sources rich in carotenes can result in elevated serum carotene levels or hypercarotenemia. An elevation in serum β-carotene levels may be recognized from 4 to 7 weeks after starting a β-carotene–rich diet.¹

While dietary consumption of carotenes is the most common cause of carotenoderma, others include kidney or liver disease, hyperlipidemia, porphyria, diabetes mellitus, hypothyroidism, and anorexia nervosa.^2-4 Moreover, since carotenoids are enzymatically converted to vitamin A in the small intestine, a mutation of the gene of the conversion enzyme β-carotene 15,15’-monooxygenase 1 (BCMO1) also can cause be a rare cause of hypercarotenemia.³

Carotenoderma, the clinical cutaneous manifestation of hypercarotenemia, occurs as a result of β-carotene deposits in the skin when serum concentration exceeds 250 μg/dL. More specifically, β-carotene accumulates mainly in the lipid-rich stratum corneum as well as in sweat and sebum, which explains the localized discoloration in fatty tissues and areas rich in sweat glands (eg, nasolabial folds, palms, soles).^3,4 The sclerae of the eyes are not affected by the surplus of β-carotene in carotenoderma, which helps distinguish it from jaundice.⁵

The differential diagnosis of yellow discoloration of the skin includes jaundice, encompassing the prehepatic, hepatocellular, and posthepatic categories.⁴ Also noteworthy in the differential diagnosis is lycopenemia, which occurs as a result of eating lycopene-rich foods (eg, tomatoes), resulting in a deeper orange-yellow pigmentation when compared to the cutaneous manifestation of hypercarotenemia.^2,4,6 Several drugs also have been reported to induce yellow discoloration of the skin, including sunitinib,⁷ sorafenib,⁸ quinacrine, saffron supplements, santonin, fluorescein, 2,4-dinitrophenol, canthaxanthin, tetryl and picric acids, and acriflavine.^2,4

Carotenoderma caused by a diet rich in β-carotene is a benign condition in which a diet low in β-carotene is implicated for treatment. Contrary to popular belief, vitamin A toxicity does not occur in the presence of a surplus of β-carotenes because the enzymatic conversion of β-carotene to vitamin A is strictly regulated.⁹ Although acknowledging the various causes of carotenoderma is important, a simple history and laboratory testing for elevated serum β-carotene levels can eliminate further unnecessary testing and allow for prompt recognition of the condition. Appropriate dietary modifications also may be warranted.

To the Editor:

Carotenoderma is a cutaneous manifestation of elevated serum β-carotene levels and classically localizes to fatty tissues and areas rich in sweat glands. We present a case of carotenoderma associated with a diet rich in red palm oil, a common food additive in parts of the world outside of the United States.

A previously healthy 8-year-old boy who recently immigrated to the United States from Liberia was hospitalized for treatment of a febrile illness that subsequently was attributed to a viral syndrome. On physical examination by the dermatology department, the patient was noted to have marked orange discoloration on the palms and soles (Figure). Laboratory workup revealed elevated serum β-carotene levels of 809 μg/dL (reference range, 10–85 μg/dL). Testing of hemoglobin/hematocrit levels and liver, thyroid, and kidney function was normal, and systemic examination revealed no further abnormalities. Upon further inquiry by the dermatology department, the patient’s family reported frequent addition of red palm oil to all of the child’s meals. The patient subsequently was diagnosed with carotenoderma and was instructed to limit inclusion of red palm oil in his diet.

Red palm oil is a rich source of β-carotene and is commonly used outside the United States as a dietary supplement or food flavoring. Excessive consumption of red palm oil or other sources rich in carotenes can result in elevated serum carotene levels or hypercarotenemia. An elevation in serum β-carotene levels may be recognized from 4 to 7 weeks after starting a β-carotene–rich diet.¹

While dietary consumption of carotenes is the most common cause of carotenoderma, others include kidney or liver disease, hyperlipidemia, porphyria, diabetes mellitus, hypothyroidism, and anorexia nervosa.^2-4 Moreover, since carotenoids are enzymatically converted to vitamin A in the small intestine, a mutation of the gene of the conversion enzyme β-carotene 15,15’-monooxygenase 1 (BCMO1) also can cause be a rare cause of hypercarotenemia.³

Carotenoderma, the clinical cutaneous manifestation of hypercarotenemia, occurs as a result of β-carotene deposits in the skin when serum concentration exceeds 250 μg/dL. More specifically, β-carotene accumulates mainly in the lipid-rich stratum corneum as well as in sweat and sebum, which explains the localized discoloration in fatty tissues and areas rich in sweat glands (eg, nasolabial folds, palms, soles).^3,4 The sclerae of the eyes are not affected by the surplus of β-carotene in carotenoderma, which helps distinguish it from jaundice.⁵

The differential diagnosis of yellow discoloration of the skin includes jaundice, encompassing the prehepatic, hepatocellular, and posthepatic categories.⁴ Also noteworthy in the differential diagnosis is lycopenemia, which occurs as a result of eating lycopene-rich foods (eg, tomatoes), resulting in a deeper orange-yellow pigmentation when compared to the cutaneous manifestation of hypercarotenemia.^2,4,6 Several drugs also have been reported to induce yellow discoloration of the skin, including sunitinib,⁷ sorafenib,⁸ quinacrine, saffron supplements, santonin, fluorescein, 2,4-dinitrophenol, canthaxanthin, tetryl and picric acids, and acriflavine.^2,4

Carotenoderma caused by a diet rich in β-carotene is a benign condition in which a diet low in β-carotene is implicated for treatment. Contrary to popular belief, vitamin A toxicity does not occur in the presence of a surplus of β-carotenes because the enzymatic conversion of β-carotene to vitamin A is strictly regulated.⁹ Although acknowledging the various causes of carotenoderma is important, a simple history and laboratory testing for elevated serum β-carotene levels can eliminate further unnecessary testing and allow for prompt recognition of the condition. Appropriate dietary modifications also may be warranted.

To the Editor:

A 65-year-old woman with B-cell marginal zone lymphoma presented with asymptomatic swelling and redness of the upper and lower eyelids of 1 week’s duration that was unresponsive to topical corticosteroids for presumptive allergic contact dermatitis. She denied any lip or tongue swelling, abdominal pain, or difficulty breathing or swallowing. Diagnosis of acquired angioedema (AAE) was confirmed on laboratory analysis, which showed C1q levels less than 3.6 mg/dL (reference range, 5.0–8.6 mg/dL), complement component 4 levels less than 8 mg/dL (reference range, 14–44 mg/dL), and C1 esterase inhibitor (C1-INH) levels of 3 mg/dL (reference range, 12–30 mg/dL).

A review of the patient’s medical record showed chronic thrombocytopenia secondary to previous chemotherapy. It was determined that the patient’s ecchymosis and purpura of the eyelids was secondary to a low platelet count resulting in bleeding into the area of angioedema (Figure). Serum protein electrophoresis did not demonstrate a monoclonal spike, and flow cytometry showed persistent B-cell leukemia without evidence of an aberrant T-cell antigenic profile. The edema and purpura of the eyelids spontaneously resolved over days, and the patient has had no recurrences to date. She was prescribed icatibant for treatment of future acute AAE attacks.

The common pathway of AAE involves the inability of C1-INH to stop activation of the complement, fibrinolytic, and contact systems. Failure to control the contact system leads to increased bradykinin production resulting in vasodilation and edema. Diagnosis of hereditary angioedema (HAE) types 1 and 2 can be confirmed in the setting of low complement component 4 and C1-INH functional levels and normal C1q levels; in AAE, C1q levels also are low.^1,2

The malignancies most frequently associated with AAE are non-Hodgkin lymphomas (eg, nodal marginal zone lymphoma, splenic marginal zone lymphoma), such as in our patient, as well as monoclonal gammopathies.² Triggers of AAE include trauma (eg, surgery, strenuous exercise), infection, and use of certain medications such as angiotensin-converting enzyme inhibitors and estrogen, but most episodes are spontaneous. Swelling of any cutaneous surface can occur in the setting of AAE. Mucosal involvement appears to be limited to the upper airway and gastrointestinal tract. Edema of the upper airway mucosa can lead to asphyxiation. In these cases, asphyxia can occur rapidly, and therefore all patients with upper airway involvement should present to the emergency room or call 911. Pain from swelling in the gastrointestinal tract can mimic an acute abdomen.³

Newly developed targeted therapies for HAE also appear to be effective in treating AAE. A summary of available treatments for angioedema is provided in the Table. Human plasma C1-INH can be used intravenously to treat acute attacks or can be given prophylactically to prevent attacks, but large doses may be necessary due to consumption of the protein.^1,3 The risk of bloodborne disease as a result of treatment exists, but screening and processing during production of the plasma makes this unlikely. Ecallantide is a reversible inhibitor of plasma kallikrein.^1,3 Rapid onset and subcutaneous dosing make it useful for treatment of acute AAE attacks. Because anaphylaxis has been reported in up to 3% of patients, ecallantide includes a boxed warning indicating that it must be administered by a health care professional with appropriate medical support to manage anaphylaxis and HAE.⁴ Icatibant is a selective competitive antagonist of bradykinin receptor B2. It can be administered subcutaneously by the patient, making it ideal for rapid treatment of angioedema.^1,3 Adverse events include pain and irritation at the injection site.

The most appropriate therapy for AAE is treatment of the underlying malignancy. Recognition and proper treatment of AAE is essential, as bradykinin-induced angioedema (AAE, HAE and angiotensin-converting enzyme inhibitor induced angioedema) does not respond to antihistamines and corticosteroids and instead requires therapy as discussed above.

To the Editor:

A 65-year-old woman with B-cell marginal zone lymphoma presented with asymptomatic swelling and redness of the upper and lower eyelids of 1 week’s duration that was unresponsive to topical corticosteroids for presumptive allergic contact dermatitis. She denied any lip or tongue swelling, abdominal pain, or difficulty breathing or swallowing. Diagnosis of acquired angioedema (AAE) was confirmed on laboratory analysis, which showed C1q levels less than 3.6 mg/dL (reference range, 5.0–8.6 mg/dL), complement component 4 levels less than 8 mg/dL (reference range, 14–44 mg/dL), and C1 esterase inhibitor (C1-INH) levels of 3 mg/dL (reference range, 12–30 mg/dL).

A review of the patient’s medical record showed chronic thrombocytopenia secondary to previous chemotherapy. It was determined that the patient’s ecchymosis and purpura of the eyelids was secondary to a low platelet count resulting in bleeding into the area of angioedema (Figure). Serum protein electrophoresis did not demonstrate a monoclonal spike, and flow cytometry showed persistent B-cell leukemia without evidence of an aberrant T-cell antigenic profile. The edema and purpura of the eyelids spontaneously resolved over days, and the patient has had no recurrences to date. She was prescribed icatibant for treatment of future acute AAE attacks.

The common pathway of AAE involves the inability of C1-INH to stop activation of the complement, fibrinolytic, and contact systems. Failure to control the contact system leads to increased bradykinin production resulting in vasodilation and edema. Diagnosis of hereditary angioedema (HAE) types 1 and 2 can be confirmed in the setting of low complement component 4 and C1-INH functional levels and normal C1q levels; in AAE, C1q levels also are low.^1,2

The malignancies most frequently associated with AAE are non-Hodgkin lymphomas (eg, nodal marginal zone lymphoma, splenic marginal zone lymphoma), such as in our patient, as well as monoclonal gammopathies.² Triggers of AAE include trauma (eg, surgery, strenuous exercise), infection, and use of certain medications such as angiotensin-converting enzyme inhibitors and estrogen, but most episodes are spontaneous. Swelling of any cutaneous surface can occur in the setting of AAE. Mucosal involvement appears to be limited to the upper airway and gastrointestinal tract. Edema of the upper airway mucosa can lead to asphyxiation. In these cases, asphyxia can occur rapidly, and therefore all patients with upper airway involvement should present to the emergency room or call 911. Pain from swelling in the gastrointestinal tract can mimic an acute abdomen.³

Newly developed targeted therapies for HAE also appear to be effective in treating AAE. A summary of available treatments for angioedema is provided in the Table. Human plasma C1-INH can be used intravenously to treat acute attacks or can be given prophylactically to prevent attacks, but large doses may be necessary due to consumption of the protein.^1,3 The risk of bloodborne disease as a result of treatment exists, but screening and processing during production of the plasma makes this unlikely. Ecallantide is a reversible inhibitor of plasma kallikrein.^1,3 Rapid onset and subcutaneous dosing make it useful for treatment of acute AAE attacks. Because anaphylaxis has been reported in up to 3% of patients, ecallantide includes a boxed warning indicating that it must be administered by a health care professional with appropriate medical support to manage anaphylaxis and HAE.⁴ Icatibant is a selective competitive antagonist of bradykinin receptor B2. It can be administered subcutaneously by the patient, making it ideal for rapid treatment of angioedema.^1,3 Adverse events include pain and irritation at the injection site.

The most appropriate therapy for AAE is treatment of the underlying malignancy. Recognition and proper treatment of AAE is essential, as bradykinin-induced angioedema (AAE, HAE and angiotensin-converting enzyme inhibitor induced angioedema) does not respond to antihistamines and corticosteroids and instead requires therapy as discussed above.

To the Editor:

A 65-year-old woman with B-cell marginal zone lymphoma presented with asymptomatic swelling and redness of the upper and lower eyelids of 1 week’s duration that was unresponsive to topical corticosteroids for presumptive allergic contact dermatitis. She denied any lip or tongue swelling, abdominal pain, or difficulty breathing or swallowing. Diagnosis of acquired angioedema (AAE) was confirmed on laboratory analysis, which showed C1q levels less than 3.6 mg/dL (reference range, 5.0–8.6 mg/dL), complement component 4 levels less than 8 mg/dL (reference range, 14–44 mg/dL), and C1 esterase inhibitor (C1-INH) levels of 3 mg/dL (reference range, 12–30 mg/dL).

A review of the patient’s medical record showed chronic thrombocytopenia secondary to previous chemotherapy. It was determined that the patient’s ecchymosis and purpura of the eyelids was secondary to a low platelet count resulting in bleeding into the area of angioedema (Figure). Serum protein electrophoresis did not demonstrate a monoclonal spike, and flow cytometry showed persistent B-cell leukemia without evidence of an aberrant T-cell antigenic profile. The edema and purpura of the eyelids spontaneously resolved over days, and the patient has had no recurrences to date. She was prescribed icatibant for treatment of future acute AAE attacks.

The common pathway of AAE involves the inability of C1-INH to stop activation of the complement, fibrinolytic, and contact systems. Failure to control the contact system leads to increased bradykinin production resulting in vasodilation and edema. Diagnosis of hereditary angioedema (HAE) types 1 and 2 can be confirmed in the setting of low complement component 4 and C1-INH functional levels and normal C1q levels; in AAE, C1q levels also are low.^1,2

The malignancies most frequently associated with AAE are non-Hodgkin lymphomas (eg, nodal marginal zone lymphoma, splenic marginal zone lymphoma), such as in our patient, as well as monoclonal gammopathies.² Triggers of AAE include trauma (eg, surgery, strenuous exercise), infection, and use of certain medications such as angiotensin-converting enzyme inhibitors and estrogen, but most episodes are spontaneous. Swelling of any cutaneous surface can occur in the setting of AAE. Mucosal involvement appears to be limited to the upper airway and gastrointestinal tract. Edema of the upper airway mucosa can lead to asphyxiation. In these cases, asphyxia can occur rapidly, and therefore all patients with upper airway involvement should present to the emergency room or call 911. Pain from swelling in the gastrointestinal tract can mimic an acute abdomen.³

Newly developed targeted therapies for HAE also appear to be effective in treating AAE. A summary of available treatments for angioedema is provided in the Table. Human plasma C1-INH can be used intravenously to treat acute attacks or can be given prophylactically to prevent attacks, but large doses may be necessary due to consumption of the protein.^1,3 The risk of bloodborne disease as a result of treatment exists, but screening and processing during production of the plasma makes this unlikely. Ecallantide is a reversible inhibitor of plasma kallikrein.^1,3 Rapid onset and subcutaneous dosing make it useful for treatment of acute AAE attacks. Because anaphylaxis has been reported in up to 3% of patients, ecallantide includes a boxed warning indicating that it must be administered by a health care professional with appropriate medical support to manage anaphylaxis and HAE.⁴ Icatibant is a selective competitive antagonist of bradykinin receptor B2. It can be administered subcutaneously by the patient, making it ideal for rapid treatment of angioedema.^1,3 Adverse events include pain and irritation at the injection site.

The most appropriate therapy for AAE is treatment of the underlying malignancy. Recognition and proper treatment of AAE is essential, as bradykinin-induced angioedema (AAE, HAE and angiotensin-converting enzyme inhibitor induced angioedema) does not respond to antihistamines and corticosteroids and instead requires therapy as discussed above.

To the Editor:

A 40-year-old woman with a history of stage IIIC ovarian cancer presented with progressing abdominal erythema and pain of 1 month’s duration. She had been diagnosed 4 years prior with grade 3, poorly differentiated papillary serous carcinoma involving the bilateral ovaries, uterine tubes, uterus, and omentum with lymphovascular invasion. She underwent tumor resection and debulking followed by paclitaxel plus platinum-based chemotherapy. The cancer recurred 2 years later with carcinomatous ascites. She declined chemotherapy but underwent therapeutic paracentesis.

One month prior to presentation, the patient developed a small, tender, erythematous patch on the abdomen. Her primary physician started her on cephalexin for presumed cellulitis without improvement. The erythema continued to spread on the abdomen with worsening pain, which prompted her presentation to the emergency department. She was admitted and started on intravenous vancomycin.

On admission to the hospital, the patient was cachexic and afebrile with a white blood cell count of 10,400/µL (reference range, 4500–11,000/µL). Physical examination revealed a well-demarcated, 15×20-cm, erythematous, blanchable, indurated plaque in the periumbilical region (Figure 1). The plaque was tender to palpation with guarding but no increased warmth. Punch biopsies of the abdominal skin revealed carcinoma within the lymphatic channels in the deep dermis and dilated lymphatics throughout the overlying dermis (Figure 2). These findings were diagnostic for carcinoma erysipeloides. Tissue and blood cultures were negative for bacterial, fungal, or mycobacterial growth. Vancomycin was discontinued, and she was discharged with pain medication. She declined chemotherapy due to the potential side effects and elected to continue symptomatic management with palliative paracentesis. After she was discharged, she underwent a tunneled pleural catheterization for recurrent malignant pleural effusions.

Carcinoma erysipeloides is a rare cutaneous metastasis secondary to internal malignancy that presents as well-demarcated areas of erythema and is sometimes misdiagnosed as cellulitis or erysipelas. Histology is notable for lymphovascular congestion without inflammation. Carcinoma erysipeloides most commonly is associated with breast cancer, but it also has been described in cancers of the prostate, larynx, stomach, lungs, thyroid, parotid gland, fallopian tubes, cervix, pancreas, and metastatic melanoma.^1-5 While the pathogenesis of carcinoma erysipeloides is poorly understood, it is thought to occur by direct spread of tumor cells from the lymph nodes to the cutaneous lymphatics, causing obstruction and edema.

Ovarian cancer has the highest mortality of all gynecologic cancers and often is associated with delayed diagnosis. Cutaneous metastasis is a late manifestation often presenting as subcutaneous nodules.^6,7 Carcinoma erysipeloides is an even rarer presentation of ovarian cancer, with a poor prognosis and a median survival of 18 months.⁸ A PubMed search of articles indexed for MEDLINE using the term carcinoma erysipeloides revealed 9 cases of carcinoma erysipeloides from ovarian cancer: 1 describing erythematous papules, plaques, and zosteriform vesicles on the upper thighs to the lower abdomen,⁹ and 8 describing erythematous plaques on the breasts.^8,10 We report a case of carcinoma erysipeloides associated with stage IIIc ovarian cancer localized to the abdominal wall mimicking cellulitis. Our report reminds clinicians of this important diagnosis in ovarian cancer and of the importance of a skin biopsy to expedite a definitive diagnosis. Immunohistochemistry using ovarian tumor markers (eg, paired-box gene 8, cancer antigen 125) is an additional tool to accurately identify malignant cells in skin biopsy.^8,10 Once diagnosed, primary treatment for carcinoma erysipeloides is treatment of the underlying malignancy.

To the Editor:

A 40-year-old woman with a history of stage IIIC ovarian cancer presented with progressing abdominal erythema and pain of 1 month’s duration. She had been diagnosed 4 years prior with grade 3, poorly differentiated papillary serous carcinoma involving the bilateral ovaries, uterine tubes, uterus, and omentum with lymphovascular invasion. She underwent tumor resection and debulking followed by paclitaxel plus platinum-based chemotherapy. The cancer recurred 2 years later with carcinomatous ascites. She declined chemotherapy but underwent therapeutic paracentesis.

One month prior to presentation, the patient developed a small, tender, erythematous patch on the abdomen. Her primary physician started her on cephalexin for presumed cellulitis without improvement. The erythema continued to spread on the abdomen with worsening pain, which prompted her presentation to the emergency department. She was admitted and started on intravenous vancomycin.

On admission to the hospital, the patient was cachexic and afebrile with a white blood cell count of 10,400/µL (reference range, 4500–11,000/µL). Physical examination revealed a well-demarcated, 15×20-cm, erythematous, blanchable, indurated plaque in the periumbilical region (Figure 1). The plaque was tender to palpation with guarding but no increased warmth. Punch biopsies of the abdominal skin revealed carcinoma within the lymphatic channels in the deep dermis and dilated lymphatics throughout the overlying dermis (Figure 2). These findings were diagnostic for carcinoma erysipeloides. Tissue and blood cultures were negative for bacterial, fungal, or mycobacterial growth. Vancomycin was discontinued, and she was discharged with pain medication. She declined chemotherapy due to the potential side effects and elected to continue symptomatic management with palliative paracentesis. After she was discharged, she underwent a tunneled pleural catheterization for recurrent malignant pleural effusions.

Carcinoma erysipeloides is a rare cutaneous metastasis secondary to internal malignancy that presents as well-demarcated areas of erythema and is sometimes misdiagnosed as cellulitis or erysipelas. Histology is notable for lymphovascular congestion without inflammation. Carcinoma erysipeloides most commonly is associated with breast cancer, but it also has been described in cancers of the prostate, larynx, stomach, lungs, thyroid, parotid gland, fallopian tubes, cervix, pancreas, and metastatic melanoma.^1-5 While the pathogenesis of carcinoma erysipeloides is poorly understood, it is thought to occur by direct spread of tumor cells from the lymph nodes to the cutaneous lymphatics, causing obstruction and edema.

Ovarian cancer has the highest mortality of all gynecologic cancers and often is associated with delayed diagnosis. Cutaneous metastasis is a late manifestation often presenting as subcutaneous nodules.^6,7 Carcinoma erysipeloides is an even rarer presentation of ovarian cancer, with a poor prognosis and a median survival of 18 months.⁸ A PubMed search of articles indexed for MEDLINE using the term carcinoma erysipeloides revealed 9 cases of carcinoma erysipeloides from ovarian cancer: 1 describing erythematous papules, plaques, and zosteriform vesicles on the upper thighs to the lower abdomen,⁹ and 8 describing erythematous plaques on the breasts.^8,10 We report a case of carcinoma erysipeloides associated with stage IIIc ovarian cancer localized to the abdominal wall mimicking cellulitis. Our report reminds clinicians of this important diagnosis in ovarian cancer and of the importance of a skin biopsy to expedite a definitive diagnosis. Immunohistochemistry using ovarian tumor markers (eg, paired-box gene 8, cancer antigen 125) is an additional tool to accurately identify malignant cells in skin biopsy.^8,10 Once diagnosed, primary treatment for carcinoma erysipeloides is treatment of the underlying malignancy.

To the Editor:

A 40-year-old woman with a history of stage IIIC ovarian cancer presented with progressing abdominal erythema and pain of 1 month’s duration. She had been diagnosed 4 years prior with grade 3, poorly differentiated papillary serous carcinoma involving the bilateral ovaries, uterine tubes, uterus, and omentum with lymphovascular invasion. She underwent tumor resection and debulking followed by paclitaxel plus platinum-based chemotherapy. The cancer recurred 2 years later with carcinomatous ascites. She declined chemotherapy but underwent therapeutic paracentesis.

One month prior to presentation, the patient developed a small, tender, erythematous patch on the abdomen. Her primary physician started her on cephalexin for presumed cellulitis without improvement. The erythema continued to spread on the abdomen with worsening pain, which prompted her presentation to the emergency department. She was admitted and started on intravenous vancomycin.

On admission to the hospital, the patient was cachexic and afebrile with a white blood cell count of 10,400/µL (reference range, 4500–11,000/µL). Physical examination revealed a well-demarcated, 15×20-cm, erythematous, blanchable, indurated plaque in the periumbilical region (Figure 1). The plaque was tender to palpation with guarding but no increased warmth. Punch biopsies of the abdominal skin revealed carcinoma within the lymphatic channels in the deep dermis and dilated lymphatics throughout the overlying dermis (Figure 2). These findings were diagnostic for carcinoma erysipeloides. Tissue and blood cultures were negative for bacterial, fungal, or mycobacterial growth. Vancomycin was discontinued, and she was discharged with pain medication. She declined chemotherapy due to the potential side effects and elected to continue symptomatic management with palliative paracentesis. After she was discharged, she underwent a tunneled pleural catheterization for recurrent malignant pleural effusions.

Carcinoma erysipeloides is a rare cutaneous metastasis secondary to internal malignancy that presents as well-demarcated areas of erythema and is sometimes misdiagnosed as cellulitis or erysipelas. Histology is notable for lymphovascular congestion without inflammation. Carcinoma erysipeloides most commonly is associated with breast cancer, but it also has been described in cancers of the prostate, larynx, stomach, lungs, thyroid, parotid gland, fallopian tubes, cervix, pancreas, and metastatic melanoma.^1-5 While the pathogenesis of carcinoma erysipeloides is poorly understood, it is thought to occur by direct spread of tumor cells from the lymph nodes to the cutaneous lymphatics, causing obstruction and edema.

Ovarian cancer has the highest mortality of all gynecologic cancers and often is associated with delayed diagnosis. Cutaneous metastasis is a late manifestation often presenting as subcutaneous nodules.^6,7 Carcinoma erysipeloides is an even rarer presentation of ovarian cancer, with a poor prognosis and a median survival of 18 months.⁸ A PubMed search of articles indexed for MEDLINE using the term carcinoma erysipeloides revealed 9 cases of carcinoma erysipeloides from ovarian cancer: 1 describing erythematous papules, plaques, and zosteriform vesicles on the upper thighs to the lower abdomen,⁹ and 8 describing erythematous plaques on the breasts.^8,10 We report a case of carcinoma erysipeloides associated with stage IIIc ovarian cancer localized to the abdominal wall mimicking cellulitis. Our report reminds clinicians of this important diagnosis in ovarian cancer and of the importance of a skin biopsy to expedite a definitive diagnosis. Immunohistochemistry using ovarian tumor markers (eg, paired-box gene 8, cancer antigen 125) is an additional tool to accurately identify malignant cells in skin biopsy.^8,10 Once diagnosed, primary treatment for carcinoma erysipeloides is treatment of the underlying malignancy.

To the Editor:

Sentinel lymph node (SLN) biopsies routinely are performed to detect regional metastases in a variety of malignancies, including breast cancer, squamous cell carcinoma, Merkel cell carcinoma, and melanoma. Histologic examination of an SLN occasionally enables detection of other unsuspected underlying diseases that typically are inflammatory in nature. Although concomitant hematolymphoid malignancy, particularly chronic lymphocytic leukemia, has been reported in SLNs, collision of 2 different solid tumors in the same SLN is rare.^1,2 We report a unique case documenting collision of both metastatic melanoma and prostatic adenocarcinoma detected in an SLN to raise awareness of the diagnostic challenges occurring in patients with coexisting malignancies.

A 71-year-old man with a history of metastatic prostatic adenocarcinoma to the bone presented for treatment of a melanoma that was newly diagnosed by an outside dermatologist. The patient’s medical history was notable for radical prostatectomy performed 15 years prior for treatment of a prostatic adenocarcinoma (Gleason score unknown) followed by bilateral orchiectomy performed 7 years later after his serum prostate-specific antigen (PSA) level began to rise, with no response to goserelin (a gonadotropin-releasing hormone agonist) therapy. Two years prior to the diagnosis of metastatic disease, his PSA level started to rise again and the patient received bicalutamide with little improvement, followed by 8 cycles of docetaxel. His PSA level improved and he most recently was being treated with abiraterone acetate. The patient’s latest computed tomography scan showed that the bony metastases secondary to prostatic adenocarcinoma had progressed. His serum PSA level was 105 ng/mL (reference range, <4.0 ng/mL) at the current presentation, elevated from 64 ng/mL one year prior.

Recently, the patient had noted a changing pigmented skin lesion on the left side of the flank. The patient described the lesion as a “black mole” first appearing 2 years prior, which had begun to ooze, change shape, and become darker and more nodular. A shave biopsy revealed a primary cutaneous malignant melanoma at least 3.4 mm in depth with ulceration and a mitotic rate of 15/mm². No molecular studies were performed on the melanoma. Standard treatment via wide local excision and sentinel lymphadenectomy was planned.

Lymphoscintigraphy revealed 3 left draining axillary lymph nodes. The patient was treated with wide local excision and left axillary SLN biopsy. Five SLNs and 3 non-SLNs were excised. Per protocol, all SLNs were examined pathologically with serial sections: 2 hematoxylin and eosin–stained levels, S-100, and melan-A immunohistochemical stains. No residual melanoma was identified in the wide-excision specimen. Examination of the left axillary SLNs revealed metastatic melanoma in 3 of 5 SLNs. Two SLNs demonstrated total replacement by metastatic melanoma. A third SLN revealed a metastatic malignant neoplasm occupying 75% of the nodal area (Figure, A). S-100 and melan-A immunohistochemical staining were negative in this nodule but revealed small aggregates and isolated tumor cells distinct from this nodule that were diagnostic of micrometastatic melanoma (Figures, B and C). The tumor cells in the large nodule were histologically distinct from the melanoma and were instead composed of nests of epithelioid cells with clear cytoplasm (Figure, D). Upon further immunohistochemical staining, this tumor was strongly positive for AE1/AE3 keratin and PIN4 cocktail (cytokeratin 5, cytokeratin 15, p63, and p504s/alpha-methylacyl-CoA-racemase)(Figure, E) with focal positivity for PSA and prostatic acid phosphatase, diagnostic of metastatic adenocarcinoma of prostate origin.

A positron emission tomography scan performed a few days after the discovery of metastatic prostatic adenocarcinoma in the SLNs showed expected postoperative changes (eg, increased activity from procedure-related inflammation) in the left side of the flank and axilla as well as moderately hypermetabolic left supraclavicular lymph nodes suspicious for viable metastatic disease. Subsequent fine-needle aspiration of the aforementioned lymph nodes revealed metastatic prostatic adenocarcinoma. The preoperative lymphoscintigraphy at the time of SLN biopsy did not show drainage to the left supraclavicular nodal basin.

Based on a discussion of the patient’s case during a multidisciplinary tumor board consultation, the benefit of performing completion lymph node dissection for melanoma management did not outweigh the risks. Accordingly, the patient received adjuvant radiation therapy to the axillary nodal basin. He was started on ketoconazole and zoledronic acid therapy for metastatic prostate adenocarcinoma and was alive with disease at 6-month follow-up. The finding of both metastatic melanoma and prostate adenocarcinoma detected in an SLN after wide excision and SLN biopsy for cutaneous melanoma is a unique report of collision of these 2 tumors. Rare cases of collision between 2 solid tumors occurring in the same lymph node have involved prostate adenocarcinoma as one of the solid tumor components.^1,3 Detection of tumor collision on lymph node biopsy between prostatic adenocarcinoma and urothelial carcinoma has been documented in 2 separate cases.¹ Three additional cases of concurrent prostatic adenocarcinoma and colorectal adenocarcinoma identified on lymph node biopsy have been reported.^1,3 Although never proven statistically, it is likely that these concurrent diagnoses are due to the high incidences of prostate and colorectal adenocarcinomas in the general US population; they are ranked first and third, respectively, for cancer incidence in US males.⁴

As demonstrated in the current case and the available literature, immunohistochemical stains play a vital role in the detection of tumor collision phenomena as well as identification of histologic source of the metastases. Furthermore, thorough histopathologic examination of biopsy specimens in the context of a patient’s clinical history remains paramount in obtaining an accurate diagnosis. Earlier identification of second malignancies in SLNs can alert the clinician to the presence of relapse of a known concurrent malignancy before it is clinically apparent, enhancing the possibility of more effective treatment of earlier disease. As has been demonstrated for lymphoma and melanoma, in rare cases awareness of the possibility of a second malignancy in the SLN can result in earlier initial diagnosis of undiscovered malignancy.²

To the Editor:

Sentinel lymph node (SLN) biopsies routinely are performed to detect regional metastases in a variety of malignancies, including breast cancer, squamous cell carcinoma, Merkel cell carcinoma, and melanoma. Histologic examination of an SLN occasionally enables detection of other unsuspected underlying diseases that typically are inflammatory in nature. Although concomitant hematolymphoid malignancy, particularly chronic lymphocytic leukemia, has been reported in SLNs, collision of 2 different solid tumors in the same SLN is rare.^1,2 We report a unique case documenting collision of both metastatic melanoma and prostatic adenocarcinoma detected in an SLN to raise awareness of the diagnostic challenges occurring in patients with coexisting malignancies.

A 71-year-old man with a history of metastatic prostatic adenocarcinoma to the bone presented for treatment of a melanoma that was newly diagnosed by an outside dermatologist. The patient’s medical history was notable for radical prostatectomy performed 15 years prior for treatment of a prostatic adenocarcinoma (Gleason score unknown) followed by bilateral orchiectomy performed 7 years later after his serum prostate-specific antigen (PSA) level began to rise, with no response to goserelin (a gonadotropin-releasing hormone agonist) therapy. Two years prior to the diagnosis of metastatic disease, his PSA level started to rise again and the patient received bicalutamide with little improvement, followed by 8 cycles of docetaxel. His PSA level improved and he most recently was being treated with abiraterone acetate. The patient’s latest computed tomography scan showed that the bony metastases secondary to prostatic adenocarcinoma had progressed. His serum PSA level was 105 ng/mL (reference range, <4.0 ng/mL) at the current presentation, elevated from 64 ng/mL one year prior.

Recently, the patient had noted a changing pigmented skin lesion on the left side of the flank. The patient described the lesion as a “black mole” first appearing 2 years prior, which had begun to ooze, change shape, and become darker and more nodular. A shave biopsy revealed a primary cutaneous malignant melanoma at least 3.4 mm in depth with ulceration and a mitotic rate of 15/mm². No molecular studies were performed on the melanoma. Standard treatment via wide local excision and sentinel lymphadenectomy was planned.

Lymphoscintigraphy revealed 3 left draining axillary lymph nodes. The patient was treated with wide local excision and left axillary SLN biopsy. Five SLNs and 3 non-SLNs were excised. Per protocol, all SLNs were examined pathologically with serial sections: 2 hematoxylin and eosin–stained levels, S-100, and melan-A immunohistochemical stains. No residual melanoma was identified in the wide-excision specimen. Examination of the left axillary SLNs revealed metastatic melanoma in 3 of 5 SLNs. Two SLNs demonstrated total replacement by metastatic melanoma. A third SLN revealed a metastatic malignant neoplasm occupying 75% of the nodal area (Figure, A). S-100 and melan-A immunohistochemical staining were negative in this nodule but revealed small aggregates and isolated tumor cells distinct from this nodule that were diagnostic of micrometastatic melanoma (Figures, B and C). The tumor cells in the large nodule were histologically distinct from the melanoma and were instead composed of nests of epithelioid cells with clear cytoplasm (Figure, D). Upon further immunohistochemical staining, this tumor was strongly positive for AE1/AE3 keratin and PIN4 cocktail (cytokeratin 5, cytokeratin 15, p63, and p504s/alpha-methylacyl-CoA-racemase)(Figure, E) with focal positivity for PSA and prostatic acid phosphatase, diagnostic of metastatic adenocarcinoma of prostate origin.

A positron emission tomography scan performed a few days after the discovery of metastatic prostatic adenocarcinoma in the SLNs showed expected postoperative changes (eg, increased activity from procedure-related inflammation) in the left side of the flank and axilla as well as moderately hypermetabolic left supraclavicular lymph nodes suspicious for viable metastatic disease. Subsequent fine-needle aspiration of the aforementioned lymph nodes revealed metastatic prostatic adenocarcinoma. The preoperative lymphoscintigraphy at the time of SLN biopsy did not show drainage to the left supraclavicular nodal basin.

Based on a discussion of the patient’s case during a multidisciplinary tumor board consultation, the benefit of performing completion lymph node dissection for melanoma management did not outweigh the risks. Accordingly, the patient received adjuvant radiation therapy to the axillary nodal basin. He was started on ketoconazole and zoledronic acid therapy for metastatic prostate adenocarcinoma and was alive with disease at 6-month follow-up. The finding of both metastatic melanoma and prostate adenocarcinoma detected in an SLN after wide excision and SLN biopsy for cutaneous melanoma is a unique report of collision of these 2 tumors. Rare cases of collision between 2 solid tumors occurring in the same lymph node have involved prostate adenocarcinoma as one of the solid tumor components.^1,3 Detection of tumor collision on lymph node biopsy between prostatic adenocarcinoma and urothelial carcinoma has been documented in 2 separate cases.¹ Three additional cases of concurrent prostatic adenocarcinoma and colorectal adenocarcinoma identified on lymph node biopsy have been reported.^1,3 Although never proven statistically, it is likely that these concurrent diagnoses are due to the high incidences of prostate and colorectal adenocarcinomas in the general US population; they are ranked first and third, respectively, for cancer incidence in US males.⁴

As demonstrated in the current case and the available literature, immunohistochemical stains play a vital role in the detection of tumor collision phenomena as well as identification of histologic source of the metastases. Furthermore, thorough histopathologic examination of biopsy specimens in the context of a patient’s clinical history remains paramount in obtaining an accurate diagnosis. Earlier identification of second malignancies in SLNs can alert the clinician to the presence of relapse of a known concurrent malignancy before it is clinically apparent, enhancing the possibility of more effective treatment of earlier disease. As has been demonstrated for lymphoma and melanoma, in rare cases awareness of the possibility of a second malignancy in the SLN can result in earlier initial diagnosis of undiscovered malignancy.²

To the Editor:

Sentinel lymph node (SLN) biopsies routinely are performed to detect regional metastases in a variety of malignancies, including breast cancer, squamous cell carcinoma, Merkel cell carcinoma, and melanoma. Histologic examination of an SLN occasionally enables detection of other unsuspected underlying diseases that typically are inflammatory in nature. Although concomitant hematolymphoid malignancy, particularly chronic lymphocytic leukemia, has been reported in SLNs, collision of 2 different solid tumors in the same SLN is rare.^1,2 We report a unique case documenting collision of both metastatic melanoma and prostatic adenocarcinoma detected in an SLN to raise awareness of the diagnostic challenges occurring in patients with coexisting malignancies.

A 71-year-old man with a history of metastatic prostatic adenocarcinoma to the bone presented for treatment of a melanoma that was newly diagnosed by an outside dermatologist. The patient’s medical history was notable for radical prostatectomy performed 15 years prior for treatment of a prostatic adenocarcinoma (Gleason score unknown) followed by bilateral orchiectomy performed 7 years later after his serum prostate-specific antigen (PSA) level began to rise, with no response to goserelin (a gonadotropin-releasing hormone agonist) therapy. Two years prior to the diagnosis of metastatic disease, his PSA level started to rise again and the patient received bicalutamide with little improvement, followed by 8 cycles of docetaxel. His PSA level improved and he most recently was being treated with abiraterone acetate. The patient’s latest computed tomography scan showed that the bony metastases secondary to prostatic adenocarcinoma had progressed. His serum PSA level was 105 ng/mL (reference range, <4.0 ng/mL) at the current presentation, elevated from 64 ng/mL one year prior.

Recently, the patient had noted a changing pigmented skin lesion on the left side of the flank. The patient described the lesion as a “black mole” first appearing 2 years prior, which had begun to ooze, change shape, and become darker and more nodular. A shave biopsy revealed a primary cutaneous malignant melanoma at least 3.4 mm in depth with ulceration and a mitotic rate of 15/mm². No molecular studies were performed on the melanoma. Standard treatment via wide local excision and sentinel lymphadenectomy was planned.

Lymphoscintigraphy revealed 3 left draining axillary lymph nodes. The patient was treated with wide local excision and left axillary SLN biopsy. Five SLNs and 3 non-SLNs were excised. Per protocol, all SLNs were examined pathologically with serial sections: 2 hematoxylin and eosin–stained levels, S-100, and melan-A immunohistochemical stains. No residual melanoma was identified in the wide-excision specimen. Examination of the left axillary SLNs revealed metastatic melanoma in 3 of 5 SLNs. Two SLNs demonstrated total replacement by metastatic melanoma. A third SLN revealed a metastatic malignant neoplasm occupying 75% of the nodal area (Figure, A). S-100 and melan-A immunohistochemical staining were negative in this nodule but revealed small aggregates and isolated tumor cells distinct from this nodule that were diagnostic of micrometastatic melanoma (Figures, B and C). The tumor cells in the large nodule were histologically distinct from the melanoma and were instead composed of nests of epithelioid cells with clear cytoplasm (Figure, D). Upon further immunohistochemical staining, this tumor was strongly positive for AE1/AE3 keratin and PIN4 cocktail (cytokeratin 5, cytokeratin 15, p63, and p504s/alpha-methylacyl-CoA-racemase)(Figure, E) with focal positivity for PSA and prostatic acid phosphatase, diagnostic of metastatic adenocarcinoma of prostate origin.

A positron emission tomography scan performed a few days after the discovery of metastatic prostatic adenocarcinoma in the SLNs showed expected postoperative changes (eg, increased activity from procedure-related inflammation) in the left side of the flank and axilla as well as moderately hypermetabolic left supraclavicular lymph nodes suspicious for viable metastatic disease. Subsequent fine-needle aspiration of the aforementioned lymph nodes revealed metastatic prostatic adenocarcinoma. The preoperative lymphoscintigraphy at the time of SLN biopsy did not show drainage to the left supraclavicular nodal basin.

Based on a discussion of the patient’s case during a multidisciplinary tumor board consultation, the benefit of performing completion lymph node dissection for melanoma management did not outweigh the risks. Accordingly, the patient received adjuvant radiation therapy to the axillary nodal basin. He was started on ketoconazole and zoledronic acid therapy for metastatic prostate adenocarcinoma and was alive with disease at 6-month follow-up. The finding of both metastatic melanoma and prostate adenocarcinoma detected in an SLN after wide excision and SLN biopsy for cutaneous melanoma is a unique report of collision of these 2 tumors. Rare cases of collision between 2 solid tumors occurring in the same lymph node have involved prostate adenocarcinoma as one of the solid tumor components.^1,3 Detection of tumor collision on lymph node biopsy between prostatic adenocarcinoma and urothelial carcinoma has been documented in 2 separate cases.¹ Three additional cases of concurrent prostatic adenocarcinoma and colorectal adenocarcinoma identified on lymph node biopsy have been reported.^1,3 Although never proven statistically, it is likely that these concurrent diagnoses are due to the high incidences of prostate and colorectal adenocarcinomas in the general US population; they are ranked first and third, respectively, for cancer incidence in US males.⁴

As demonstrated in the current case and the available literature, immunohistochemical stains play a vital role in the detection of tumor collision phenomena as well as identification of histologic source of the metastases. Furthermore, thorough histopathologic examination of biopsy specimens in the context of a patient’s clinical history remains paramount in obtaining an accurate diagnosis. Earlier identification of second malignancies in SLNs can alert the clinician to the presence of relapse of a known concurrent malignancy before it is clinically apparent, enhancing the possibility of more effective treatment of earlier disease. As has been demonstrated for lymphoma and melanoma, in rare cases awareness of the possibility of a second malignancy in the SLN can result in earlier initial diagnosis of undiscovered malignancy.²

To the Editor:

A 79-year-old man presented with a scaling eruption in the periorbital area, on the bilateral forearms, and on the chest of 4 weeks’ duration. The patient denied systemic symptoms including lethargy, muscle weakness, and fevers. His medical history was notable for blastic plasmacytoid dendritic cell neoplasm, a form of acute myeloid leukemia, diagnosed 3 years prior to presentation. The patient received an allogeneic hematopoietic stem cell transplant 8 months later. His posttransplant course was complicated by gastrointestinal graft-versus-host disease (GVHD); progressive graft loss requiring a donor lymphocyte infusion after 1 month; and leukemia cutis, which spontaneously resolved after 1 month. The patient was taken off all immunosuppressive therapy 5 months after the transplant and had been doing well for 2 years with only mild mucosal GVHD affecting the oral mucosa and the head of the penis.

Physical examination at the current presentation revealed linear, atrophic, scaling, purplish plaques with adherent white scale on the upper and lower eyelids (Figure 1). The patient also had scattered purple scaling patches on the bilateral forearms and chest. Laboratory tests including complete blood cell count, comprehensive metabolic panel, and lactate dehydrogenase demonstrated no gross abnormalities. Two shave biopsies of the right lower eyelid (Figure 2) and left arm (Figure 3) were performed for histologic examination and revealed basket weave hyperkeratosis, irregular acanthosis, sawtooth rete ridges, and scattered dyskeratotic cells. Vacuolar changes and smudging of the basement membrane zone along with a bandlike lymphocytic infiltrate in the upper dermis also were noted in both biopsies. A diagnosis of lupuslike grade 1 GVHD was made.

Graft-versus-host disease remains a notable cause of morbidity and mortality in allogenic hematopoietic stem cell transplant patients.¹ Skin manifestations represent the most common manifestation of GVHD and have been reclassified as acute or chronic disease based on clinical and histologic findings rather than time of onset. Although acute GVHD classically presents as diffuse morbilliform papules and macules, chronic GVHD has a large range of clinical presentations most commonly mimicking the skin findings of lichen planus, morphea, scleroderma, or lichen sclerosus.¹

Lupuslike GVHD is a rarely reported manifestation of chronic GVHD that predominantly affects the lower eyelids and malar regions.^2,3 Our case documents extensive involvement of both the upper and lower eyelids. A lupuslike manifestation of GVHD may portend a poor prognosis. In a case series of 5 patients with chronic GVHD presenting as facial lupuslike plaques, 1 patient died from a relapse of leukemia and 3 patients developed sclerodermatous GVHD. The fifth patient was lost to follow-up.² In another case series, a retrospective analysis discovered that 3 of 7 patients with sclerodermatous GVHD initially presented with hyperpigmented periorbital plaques.⁴ Resolution of skin findings with topical steroids and oral tacrolimus was reported in a case of GVHD presenting with periorbital lupuslike plaques.³ Although further reports are needed to validate the relationship, a lupuslike presentation of chronic GVHD may be an important harbinger for the development of extensive sclerodermatous GVHD.

A diagnosis of lupuslike GVHD is made based on the correlation of a comprehensive medical history, clinical examination, and histopathologic findings. Although other cases of chronic GVHD resembling dermatomyositis presented with purple periorbital plaques, these patients demonstrated dermatomyositislike systemic symptoms including muscle weakness and fatigue, which were not present in our patient.^5,6 Antinuclear antibody (ANA) testing is unlikely to be helpful in the diagnosis of this uncommon presentation, as 65% (41/63) of chronic GVHD patients developed ANA antibodies in one study.⁷ Also, other patients with lupuslike GVHD who progressed to sclerodermatous GVHD have had both positive and negative ANA serology.² The histopathology of GVHD and lupus erythematosus can exhibit overlapping features, such as lymphocytic infiltrate with interface changes; however, in lupus erythematosus, mucin usually is present, the infiltrate usually is denser and deeper, and a thickened basement membrane zone may be present. Necrotic keratinocytes also usually are not seen in lupus erythematosus unless the patient’s photosensitivity has led to a sunburn reaction.

After his initial presentation, our patient’s mucosal GVHD flared in the mouth and on the penis, and he was started on prednisone 50 mg once daily and mycophenolate mofetil 1 g twice daily. With this treatment, our patient’s periorbital scaling plaques resolved to residual hyperpigmentation along with remarkable improvement of the mucosal GVHD. He has not manifested any signs of leukemia relapse or sclerodermatous GVHD; however, he remains under close clinical evaluation.

This case highlights an unusual presentation of GVHD with periorbital plaques mimicking hypertrophic lupus erythematous. A greater recognition of this rare entity is essential to further elucidate its prognosis and its relationship with sclerodermatous GVHD.

To the Editor:

A 79-year-old man presented with a scaling eruption in the periorbital area, on the bilateral forearms, and on the chest of 4 weeks’ duration. The patient denied systemic symptoms including lethargy, muscle weakness, and fevers. His medical history was notable for blastic plasmacytoid dendritic cell neoplasm, a form of acute myeloid leukemia, diagnosed 3 years prior to presentation. The patient received an allogeneic hematopoietic stem cell transplant 8 months later. His posttransplant course was complicated by gastrointestinal graft-versus-host disease (GVHD); progressive graft loss requiring a donor lymphocyte infusion after 1 month; and leukemia cutis, which spontaneously resolved after 1 month. The patient was taken off all immunosuppressive therapy 5 months after the transplant and had been doing well for 2 years with only mild mucosal GVHD affecting the oral mucosa and the head of the penis.

Physical examination at the current presentation revealed linear, atrophic, scaling, purplish plaques with adherent white scale on the upper and lower eyelids (Figure 1). The patient also had scattered purple scaling patches on the bilateral forearms and chest. Laboratory tests including complete blood cell count, comprehensive metabolic panel, and lactate dehydrogenase demonstrated no gross abnormalities. Two shave biopsies of the right lower eyelid (Figure 2) and left arm (Figure 3) were performed for histologic examination and revealed basket weave hyperkeratosis, irregular acanthosis, sawtooth rete ridges, and scattered dyskeratotic cells. Vacuolar changes and smudging of the basement membrane zone along with a bandlike lymphocytic infiltrate in the upper dermis also were noted in both biopsies. A diagnosis of lupuslike grade 1 GVHD was made.

Graft-versus-host disease remains a notable cause of morbidity and mortality in allogenic hematopoietic stem cell transplant patients.¹ Skin manifestations represent the most common manifestation of GVHD and have been reclassified as acute or chronic disease based on clinical and histologic findings rather than time of onset. Although acute GVHD classically presents as diffuse morbilliform papules and macules, chronic GVHD has a large range of clinical presentations most commonly mimicking the skin findings of lichen planus, morphea, scleroderma, or lichen sclerosus.¹

Lupuslike GVHD is a rarely reported manifestation of chronic GVHD that predominantly affects the lower eyelids and malar regions.^2,3 Our case documents extensive involvement of both the upper and lower eyelids. A lupuslike manifestation of GVHD may portend a poor prognosis. In a case series of 5 patients with chronic GVHD presenting as facial lupuslike plaques, 1 patient died from a relapse of leukemia and 3 patients developed sclerodermatous GVHD. The fifth patient was lost to follow-up.² In another case series, a retrospective analysis discovered that 3 of 7 patients with sclerodermatous GVHD initially presented with hyperpigmented periorbital plaques.⁴ Resolution of skin findings with topical steroids and oral tacrolimus was reported in a case of GVHD presenting with periorbital lupuslike plaques.³ Although further reports are needed to validate the relationship, a lupuslike presentation of chronic GVHD may be an important harbinger for the development of extensive sclerodermatous GVHD.

A diagnosis of lupuslike GVHD is made based on the correlation of a comprehensive medical history, clinical examination, and histopathologic findings. Although other cases of chronic GVHD resembling dermatomyositis presented with purple periorbital plaques, these patients demonstrated dermatomyositislike systemic symptoms including muscle weakness and fatigue, which were not present in our patient.^5,6 Antinuclear antibody (ANA) testing is unlikely to be helpful in the diagnosis of this uncommon presentation, as 65% (41/63) of chronic GVHD patients developed ANA antibodies in one study.⁷ Also, other patients with lupuslike GVHD who progressed to sclerodermatous GVHD have had both positive and negative ANA serology.² The histopathology of GVHD and lupus erythematosus can exhibit overlapping features, such as lymphocytic infiltrate with interface changes; however, in lupus erythematosus, mucin usually is present, the infiltrate usually is denser and deeper, and a thickened basement membrane zone may be present. Necrotic keratinocytes also usually are not seen in lupus erythematosus unless the patient’s photosensitivity has led to a sunburn reaction.

After his initial presentation, our patient’s mucosal GVHD flared in the mouth and on the penis, and he was started on prednisone 50 mg once daily and mycophenolate mofetil 1 g twice daily. With this treatment, our patient’s periorbital scaling plaques resolved to residual hyperpigmentation along with remarkable improvement of the mucosal GVHD. He has not manifested any signs of leukemia relapse or sclerodermatous GVHD; however, he remains under close clinical evaluation.

This case highlights an unusual presentation of GVHD with periorbital plaques mimicking hypertrophic lupus erythematous. A greater recognition of this rare entity is essential to further elucidate its prognosis and its relationship with sclerodermatous GVHD.

To the Editor:

A 79-year-old man presented with a scaling eruption in the periorbital area, on the bilateral forearms, and on the chest of 4 weeks’ duration. The patient denied systemic symptoms including lethargy, muscle weakness, and fevers. His medical history was notable for blastic plasmacytoid dendritic cell neoplasm, a form of acute myeloid leukemia, diagnosed 3 years prior to presentation. The patient received an allogeneic hematopoietic stem cell transplant 8 months later. His posttransplant course was complicated by gastrointestinal graft-versus-host disease (GVHD); progressive graft loss requiring a donor lymphocyte infusion after 1 month; and leukemia cutis, which spontaneously resolved after 1 month. The patient was taken off all immunosuppressive therapy 5 months after the transplant and had been doing well for 2 years with only mild mucosal GVHD affecting the oral mucosa and the head of the penis.

Physical examination at the current presentation revealed linear, atrophic, scaling, purplish plaques with adherent white scale on the upper and lower eyelids (Figure 1). The patient also had scattered purple scaling patches on the bilateral forearms and chest. Laboratory tests including complete blood cell count, comprehensive metabolic panel, and lactate dehydrogenase demonstrated no gross abnormalities. Two shave biopsies of the right lower eyelid (Figure 2) and left arm (Figure 3) were performed for histologic examination and revealed basket weave hyperkeratosis, irregular acanthosis, sawtooth rete ridges, and scattered dyskeratotic cells. Vacuolar changes and smudging of the basement membrane zone along with a bandlike lymphocytic infiltrate in the upper dermis also were noted in both biopsies. A diagnosis of lupuslike grade 1 GVHD was made.

Graft-versus-host disease remains a notable cause of morbidity and mortality in allogenic hematopoietic stem cell transplant patients.¹ Skin manifestations represent the most common manifestation of GVHD and have been reclassified as acute or chronic disease based on clinical and histologic findings rather than time of onset. Although acute GVHD classically presents as diffuse morbilliform papules and macules, chronic GVHD has a large range of clinical presentations most commonly mimicking the skin findings of lichen planus, morphea, scleroderma, or lichen sclerosus.¹

Lupuslike GVHD is a rarely reported manifestation of chronic GVHD that predominantly affects the lower eyelids and malar regions.^2,3 Our case documents extensive involvement of both the upper and lower eyelids. A lupuslike manifestation of GVHD may portend a poor prognosis. In a case series of 5 patients with chronic GVHD presenting as facial lupuslike plaques, 1 patient died from a relapse of leukemia and 3 patients developed sclerodermatous GVHD. The fifth patient was lost to follow-up.² In another case series, a retrospective analysis discovered that 3 of 7 patients with sclerodermatous GVHD initially presented with hyperpigmented periorbital plaques.⁴ Resolution of skin findings with topical steroids and oral tacrolimus was reported in a case of GVHD presenting with periorbital lupuslike plaques.³ Although further reports are needed to validate the relationship, a lupuslike presentation of chronic GVHD may be an important harbinger for the development of extensive sclerodermatous GVHD.

A diagnosis of lupuslike GVHD is made based on the correlation of a comprehensive medical history, clinical examination, and histopathologic findings. Although other cases of chronic GVHD resembling dermatomyositis presented with purple periorbital plaques, these patients demonstrated dermatomyositislike systemic symptoms including muscle weakness and fatigue, which were not present in our patient.^5,6 Antinuclear antibody (ANA) testing is unlikely to be helpful in the diagnosis of this uncommon presentation, as 65% (41/63) of chronic GVHD patients developed ANA antibodies in one study.⁷ Also, other patients with lupuslike GVHD who progressed to sclerodermatous GVHD have had both positive and negative ANA serology.² The histopathology of GVHD and lupus erythematosus can exhibit overlapping features, such as lymphocytic infiltrate with interface changes; however, in lupus erythematosus, mucin usually is present, the infiltrate usually is denser and deeper, and a thickened basement membrane zone may be present. Necrotic keratinocytes also usually are not seen in lupus erythematosus unless the patient’s photosensitivity has led to a sunburn reaction.

After his initial presentation, our patient’s mucosal GVHD flared in the mouth and on the penis, and he was started on prednisone 50 mg once daily and mycophenolate mofetil 1 g twice daily. With this treatment, our patient’s periorbital scaling plaques resolved to residual hyperpigmentation along with remarkable improvement of the mucosal GVHD. He has not manifested any signs of leukemia relapse or sclerodermatous GVHD; however, he remains under close clinical evaluation.

This case highlights an unusual presentation of GVHD with periorbital plaques mimicking hypertrophic lupus erythematous. A greater recognition of this rare entity is essential to further elucidate its prognosis and its relationship with sclerodermatous GVHD.

To the Editor:

A 69-year-old white man presented with a skin lesion on the back of 1 to 2 weeks’ duration. The patient stated he was unaware of it, but his wife had recently noticed the new spot. He denied any bleeding, pain, pruritus, or other associated symptoms with the lesion. He also denied any prior treatment to the area. The patient’s medical history was remarkable for severe psoriasis involving more than 80% body surface area, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, coronary artery disease, squamous cell carcinoma, and actinic keratoses. He had been on multiple treatment regimens over the last 20 years for control of psoriasis including topical corticosteroids, psoralen plus UVA and UVB phototherapy, gold injections, acitretin, prednisone, efalizumab, ustekinumab, and alefacept upon evaluation of this new skin lesion. Utilization of immunosuppressive agents also provided an additional benefit of controlling the patient’s inflammatory arthritic disease.

On physical examination a 0.6×0.7-cm, pink to erythematous, pearly papule with superficial telangiectases was noted on the right side of the dorsal thorax (Figure 1). Multiple well-demarcated erythematous plaques with silvery scale and areas of secondary excoriation were noted on the trunk and both legs consistent with the patient’s history of psoriasis.

A shave biopsy was performed on the skin lesion on the right side of the dorsal thorax with a suspected clinical diagnosis of basal cell carcinoma. Two weeks later the patient returned for a discussion of the pathology report, which revealed nodules of basaloid cells with tightly packed vesicular nuclei and scant cytoplasm in sheets within the superficial dermis, as well as areas of nuclear molding, numerous mitotic figures, and areas of focal necrosis (Figure 2). In addition, immunostaining was positive for cytokeratin (CK) 20 antibodies with a characteristic paranuclear dot uptake of the antibody. These findings were consistent with a diagnosis of Merkel cell carcinoma (MCC). At that time, alefacept was discontinued and he was referred to a tertiary referral center for further evaluation and treatment.

The patient subsequently underwent wide excision with 1-cm margins of the MCC, with intraoperative lymphatic mapping/sentinel lymph node biopsy (SLNB) of the right axillary nodal basin 1 month later, which he tolerated well without any associated complications. Further histopathologic examination revealed the deep, medial, and lateral surgical margins to be negative of residual neoplasm. However, one sentinel lymph node indicated positivity for micrometastatic MCC, consistent with stage IIIA disease progression.

He underwent a second procedure the following month for complete right axillary lymph node dissection. Histopathologic examination of the right axillary contents included 28 lymph nodes, which were negative for carcinoma. He continued to do well without any signs of clinical recurrence or distant metastasis at subsequent follow-up visits.

Approximately 2.5 years after the second procedure, the patient began to develop right upper quadrant abdominal pain of an unclear etiology. Computed tomography of the abdomen and pelvis was performed, revealing areas of calcification and findings consistent with malignant lymphadenopathy. Multiple hepatic lesions also were noted including a 9-cm lesion in the posterior right hepatic lobe. Computed tomography–guided biopsy of the liver lesion was performed and the findings were consistent with metastatic MCC, indicating progression to stage IV disease.

The patient was subsequently started on combination chemotherapeutic treatment with carboplatin and VP-16, with a planned treatment course of 4 to 6 cycles. He was able to complete a total of 6 cycles over a 4-month period, tolerating the treatment regimen fairly well. Follow-up positron emission tomography–computed tomography was within normal limits with no evidence of any hypermetabolic activity noted, indicating a complete radiographic remission of MCC. He was seen approximately 1 month after completion of treatment for clinical follow-up and monthly thereafter.

While on chemotherapy, the patient experienced a notable improvement in the psoriasis and psoriatic joint disease. Upon completion of chemotherapy, he was restarted on the same treatment plan that was utilized prior to surgery including topical corticosteroids, calcitriol, intramuscular steroid injections, and UVB phototherapy, which provided substantial control of psoriasis and arthritic joint disease. The patient later died, likely due to his multiple comorbidities.

Merkel cells are slow-responding mechanoreceptors located within the basal layer of the epidermis and are the source of a rare aggressive cutaneous malignancy.¹ Merkel cell carcinoma was first noted in 1972 and termed trabecular carcinoma of the skin, and it accounts for less than 1% of all nonmelanoma skin cancer.^2,3 This primary neuroendocrine carcinoma has remarkable metastatic potential (34%–75%) and can invade regional lymph nodes, as well as distant metastasis most commonly to the liver, lungs, bones, and brain.² Approximately 25% of patients present with palpable lymphadenopathy and 5% with distant metastasis at the time of diagnosis. This frequency of metastasis at diagnosis as well as the recurrence after treatment contributes to the poor prognosis of MCC. Local recurrence rates have been reported at 25% with lymph node involvement in 52% and metastasis in 34%, with most recurrences occurring within 2 years of diagnosis. Patient mortality is dependent on the aggressiveness of the tumor, with 5-year survival rates of 83.3% without lymph node involvement, 58.3% with lymph node involvement, and 31.3% in those with metastatic disease.⁴

The tumor classically presents as a red to violaceous, painless nodule with a smooth shiny surface most often on the head and neck region.^4-6 Approximately 50% of MCC cases present in the head and neck region, 32% to 38% on the extremities, and 12% to 14% on the trunk.¹ This nonspecific presentation may lead to diagnostic uncertainty and a consequent delay in treatment. Definitive diagnosis of MCC is achieved with a skin biopsy and allows for distinction from other clinically similar–appearing neoplasms. Merkel cell carcinoma presents histologically as small round basophilic cells penetrating through the dermis in 3 histologic patterns: the trabecular, intermediate (80% of cases), and small cell type.⁵ It may be differentiated immunohistochemically from other neoplasms, as it displays CK20 positivity (showing paranuclear dotlike depositions in the cytoplasm or cell membrane) and is negative for CK7. Chromagranin and synaptophysin positivity also may provide further histologic confirmation. In addition, absence of peripheral palisading, retraction artifact, and a fibromyxoid stroma allow for distinction from cutaneous basal cell carcinoma, which may display these features histologically. Other immunohistochemical markers that may be of value include thyroid transcription factor 1, which is typically positive in cutaneous metastasis of neuroendocrine carcinoma of the lung; S-100 and human melanoma black 45, which are positive in melanoma; and leukocyte common antigen (CD45), which can be positive in lymphoma. These stains are classically negative in MCC.³

Merkel cell carcinoma is commonly associated with the presence of Merkel cell polyomavirus (MCPyV) in tumor specimens, with a prevalence of 70% to 80% in all cases. Merkel cell polyomavirus is a class 2A carcinogen (ie, a probable carcinogen to humans) and is classified among a group of viruses that encode T antigens (ie, an antigen coded by a viral genome associated with transformation of infected cells by tumor viruses), which can lead to initiation of tumorigenesis through interference with cellular tumor suppressing proteins such as p53.⁵ In addition, several risk factors have been associated with the development of MCC including immunosuppression, older age (>50 years), and UV-exposed fair skin.⁷ One explanation for this phenomenon is the increase in MCPyV small T antigen transcripts induced by UV irradiation.⁵ In addition, as with other cancers induced by viruses, host immunity can impede tumor progression and development. Therefore, impairment of normal immune function likely creates a higher risk for MCC development and potential for a worse prognosis.³Although the exact incidence of MCC in immunosuppressed patients appears unclear, chronic immunosuppressive therapy may play a notable role in the pathogenesis of the tumor.³

Although each of these factors was observed in our patient, it also was possible that his associated comorbidities further contributed to disease presentation. In particular, rheumatoid arthritis has been shown to carry an increased risk for the development of MCC.⁸ In addition, inflammatory monocytes infected with MCPyV, as evidenced in a patient with a history of chronic psoriasis prior to diagnosis of MCC, also may contribute to the pathogenesis of MCC by traveling to inflammatory skin lesions, such as those seen in psoriasis, releasing MCPyV locally and infecting Merkel cells.⁹ Although MCPyV testing was never performed in our patient, it certainly would be prudent as well as further studies determining the correlation of MCC to these disease processes.

Although regression is rare, multiple cases have documented spontaneous regression of MCC after biopsy of these lesions.^4,6,10 The exact mechanism is unclear, but apoptosis induced by T-cell immunity is suspected to play a role. Programmed cell death 1 protein (PD-1)–positive cells play a role. The PD-1 receptor is an inhibitory receptor expressed by T cells and in approximately half of tumor-infiltrating cells in MCC. It was found that in a regressed case of MCC there was a notably lower percentage of PD-1 positivity compared to cases with no apparent regression, suggesting that PD-1–positive cells suppress tumor immunity to MCC and that significant reduction in these cells may induce clinical regression.¹⁰ Additional investigation would be beneficial to examine the relationship of this phenomenon to tumor regression.

Initial evaluation of these patients should include a meticulous clinical examination with an emphasis on detection of cutaneous, lymph node, and distant metastasis. Due to the risk of metastatic potential, regional lymph node ultrasonography and computed tomography of the chest, abdomen, and pelvis typically are recommended at baseline. Other imaging modalities may be warranted based on clinical findings.³ Treatment modalities include various approaches, with surgical excision of the primary tumor with more than 1-cm margin to the fascial plane being the primary modality for uncomplicated cases.^1,3,7 In addition, SLNB also should be performed at the time of the procedure. In the case of a positive SLNB or suspected regional lymph node involvement upon initial examination, radical regional lymph node dissection also is recommended.³ Although some authorities advocate postsurgical radiation therapy to minimize the risk of local recurrence, there does not appear to be a clear benefit in survival rate.^3,5 However, radiation treatment as monotherapy has been advocated in certain instances, particularly in cases of unresectable tumors or patients who are poor surgical candidates.^5,7 Cases of distant metastasis (stage IV disease) may include management with surgery, radiation, and/or chemotherapy. Although none of these modalities have consistently shown to improve survival, there appears to be up to a 60% response with chemotherapy in these patients.³

Because MCC tends to affect an older population, often with other notable comorbidities, important considerations involving a treatment plan include the cost, side effects, and convenience for patients. The combination of carboplatin and VP-16 (etoposide) was utilized and tolerated well in our patient, and it has been successful in achieving complete radiologic and clinical remission of his metastatic disease. This combination appears to prolong survival in patients with distant metastasis, as compared to those patients not receiving chemotherapy.¹ Our patient has since died, but in these high-risk patients, close clinical monitoring is essential to help optimize their prognosis.

Merkel cell carcinoma is a rare aggressive cutaneous neoplasm that most commonly affects the elderly, immunosuppressed, and those with chronic UV sun damage. An association between the oncogenesis of MCC and infection with MCPyV has been documented, but other underlying diseases also may play a role in this process including rheumatoid arthritis and psoriasis. Although these risk factors were associated with our patient, his history of chronic immunosuppressive therapy for treatment of his psoriasis and inflammatory joint disease likely played a role in the pathogenesis of the tumor and should be an important point of discussion with any patient requiring this type of long-term management for disease control. Our unique clinical case highlights a patient with substantial comorbidities who developed metastatic MCC and achieved complete clinical and radiologic remission after treatment with surgery and chemotherapy.

To the Editor:

A 69-year-old white man presented with a skin lesion on the back of 1 to 2 weeks’ duration. The patient stated he was unaware of it, but his wife had recently noticed the new spot. He denied any bleeding, pain, pruritus, or other associated symptoms with the lesion. He also denied any prior treatment to the area. The patient’s medical history was remarkable for severe psoriasis involving more than 80% body surface area, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, coronary artery disease, squamous cell carcinoma, and actinic keratoses. He had been on multiple treatment regimens over the last 20 years for control of psoriasis including topical corticosteroids, psoralen plus UVA and UVB phototherapy, gold injections, acitretin, prednisone, efalizumab, ustekinumab, and alefacept upon evaluation of this new skin lesion. Utilization of immunosuppressive agents also provided an additional benefit of controlling the patient’s inflammatory arthritic disease.

On physical examination a 0.6×0.7-cm, pink to erythematous, pearly papule with superficial telangiectases was noted on the right side of the dorsal thorax (Figure 1). Multiple well-demarcated erythematous plaques with silvery scale and areas of secondary excoriation were noted on the trunk and both legs consistent with the patient’s history of psoriasis.

A shave biopsy was performed on the skin lesion on the right side of the dorsal thorax with a suspected clinical diagnosis of basal cell carcinoma. Two weeks later the patient returned for a discussion of the pathology report, which revealed nodules of basaloid cells with tightly packed vesicular nuclei and scant cytoplasm in sheets within the superficial dermis, as well as areas of nuclear molding, numerous mitotic figures, and areas of focal necrosis (Figure 2). In addition, immunostaining was positive for cytokeratin (CK) 20 antibodies with a characteristic paranuclear dot uptake of the antibody. These findings were consistent with a diagnosis of Merkel cell carcinoma (MCC). At that time, alefacept was discontinued and he was referred to a tertiary referral center for further evaluation and treatment.

The patient subsequently underwent wide excision with 1-cm margins of the MCC, with intraoperative lymphatic mapping/sentinel lymph node biopsy (SLNB) of the right axillary nodal basin 1 month later, which he tolerated well without any associated complications. Further histopathologic examination revealed the deep, medial, and lateral surgical margins to be negative of residual neoplasm. However, one sentinel lymph node indicated positivity for micrometastatic MCC, consistent with stage IIIA disease progression.

He underwent a second procedure the following month for complete right axillary lymph node dissection. Histopathologic examination of the right axillary contents included 28 lymph nodes, which were negative for carcinoma. He continued to do well without any signs of clinical recurrence or distant metastasis at subsequent follow-up visits.

Approximately 2.5 years after the second procedure, the patient began to develop right upper quadrant abdominal pain of an unclear etiology. Computed tomography of the abdomen and pelvis was performed, revealing areas of calcification and findings consistent with malignant lymphadenopathy. Multiple hepatic lesions also were noted including a 9-cm lesion in the posterior right hepatic lobe. Computed tomography–guided biopsy of the liver lesion was performed and the findings were consistent with metastatic MCC, indicating progression to stage IV disease.

The patient was subsequently started on combination chemotherapeutic treatment with carboplatin and VP-16, with a planned treatment course of 4 to 6 cycles. He was able to complete a total of 6 cycles over a 4-month period, tolerating the treatment regimen fairly well. Follow-up positron emission tomography–computed tomography was within normal limits with no evidence of any hypermetabolic activity noted, indicating a complete radiographic remission of MCC. He was seen approximately 1 month after completion of treatment for clinical follow-up and monthly thereafter.

While on chemotherapy, the patient experienced a notable improvement in the psoriasis and psoriatic joint disease. Upon completion of chemotherapy, he was restarted on the same treatment plan that was utilized prior to surgery including topical corticosteroids, calcitriol, intramuscular steroid injections, and UVB phototherapy, which provided substantial control of psoriasis and arthritic joint disease. The patient later died, likely due to his multiple comorbidities.

Merkel cells are slow-responding mechanoreceptors located within the basal layer of the epidermis and are the source of a rare aggressive cutaneous malignancy.¹ Merkel cell carcinoma was first noted in 1972 and termed trabecular carcinoma of the skin, and it accounts for less than 1% of all nonmelanoma skin cancer.^2,3 This primary neuroendocrine carcinoma has remarkable metastatic potential (34%–75%) and can invade regional lymph nodes, as well as distant metastasis most commonly to the liver, lungs, bones, and brain.² Approximately 25% of patients present with palpable lymphadenopathy and 5% with distant metastasis at the time of diagnosis. This frequency of metastasis at diagnosis as well as the recurrence after treatment contributes to the poor prognosis of MCC. Local recurrence rates have been reported at 25% with lymph node involvement in 52% and metastasis in 34%, with most recurrences occurring within 2 years of diagnosis. Patient mortality is dependent on the aggressiveness of the tumor, with 5-year survival rates of 83.3% without lymph node involvement, 58.3% with lymph node involvement, and 31.3% in those with metastatic disease.⁴

The tumor classically presents as a red to violaceous, painless nodule with a smooth shiny surface most often on the head and neck region.^4-6 Approximately 50% of MCC cases present in the head and neck region, 32% to 38% on the extremities, and 12% to 14% on the trunk.¹ This nonspecific presentation may lead to diagnostic uncertainty and a consequent delay in treatment. Definitive diagnosis of MCC is achieved with a skin biopsy and allows for distinction from other clinically similar–appearing neoplasms. Merkel cell carcinoma presents histologically as small round basophilic cells penetrating through the dermis in 3 histologic patterns: the trabecular, intermediate (80% of cases), and small cell type.⁵ It may be differentiated immunohistochemically from other neoplasms, as it displays CK20 positivity (showing paranuclear dotlike depositions in the cytoplasm or cell membrane) and is negative for CK7. Chromagranin and synaptophysin positivity also may provide further histologic confirmation. In addition, absence of peripheral palisading, retraction artifact, and a fibromyxoid stroma allow for distinction from cutaneous basal cell carcinoma, which may display these features histologically. Other immunohistochemical markers that may be of value include thyroid transcription factor 1, which is typically positive in cutaneous metastasis of neuroendocrine carcinoma of the lung; S-100 and human melanoma black 45, which are positive in melanoma; and leukocyte common antigen (CD45), which can be positive in lymphoma. These stains are classically negative in MCC.³

Merkel cell carcinoma is commonly associated with the presence of Merkel cell polyomavirus (MCPyV) in tumor specimens, with a prevalence of 70% to 80% in all cases. Merkel cell polyomavirus is a class 2A carcinogen (ie, a probable carcinogen to humans) and is classified among a group of viruses that encode T antigens (ie, an antigen coded by a viral genome associated with transformation of infected cells by tumor viruses), which can lead to initiation of tumorigenesis through interference with cellular tumor suppressing proteins such as p53.⁵ In addition, several risk factors have been associated with the development of MCC including immunosuppression, older age (>50 years), and UV-exposed fair skin.⁷ One explanation for this phenomenon is the increase in MCPyV small T antigen transcripts induced by UV irradiation.⁵ In addition, as with other cancers induced by viruses, host immunity can impede tumor progression and development. Therefore, impairment of normal immune function likely creates a higher risk for MCC development and potential for a worse prognosis.³Although the exact incidence of MCC in immunosuppressed patients appears unclear, chronic immunosuppressive therapy may play a notable role in the pathogenesis of the tumor.³

Although each of these factors was observed in our patient, it also was possible that his associated comorbidities further contributed to disease presentation. In particular, rheumatoid arthritis has been shown to carry an increased risk for the development of MCC.⁸ In addition, inflammatory monocytes infected with MCPyV, as evidenced in a patient with a history of chronic psoriasis prior to diagnosis of MCC, also may contribute to the pathogenesis of MCC by traveling to inflammatory skin lesions, such as those seen in psoriasis, releasing MCPyV locally and infecting Merkel cells.⁹ Although MCPyV testing was never performed in our patient, it certainly would be prudent as well as further studies determining the correlation of MCC to these disease processes.

Although regression is rare, multiple cases have documented spontaneous regression of MCC after biopsy of these lesions.^4,6,10 The exact mechanism is unclear, but apoptosis induced by T-cell immunity is suspected to play a role. Programmed cell death 1 protein (PD-1)–positive cells play a role. The PD-1 receptor is an inhibitory receptor expressed by T cells and in approximately half of tumor-infiltrating cells in MCC. It was found that in a regressed case of MCC there was a notably lower percentage of PD-1 positivity compared to cases with no apparent regression, suggesting that PD-1–positive cells suppress tumor immunity to MCC and that significant reduction in these cells may induce clinical regression.¹⁰ Additional investigation would be beneficial to examine the relationship of this phenomenon to tumor regression.

Initial evaluation of these patients should include a meticulous clinical examination with an emphasis on detection of cutaneous, lymph node, and distant metastasis. Due to the risk of metastatic potential, regional lymph node ultrasonography and computed tomography of the chest, abdomen, and pelvis typically are recommended at baseline. Other imaging modalities may be warranted based on clinical findings.³ Treatment modalities include various approaches, with surgical excision of the primary tumor with more than 1-cm margin to the fascial plane being the primary modality for uncomplicated cases.^1,3,7 In addition, SLNB also should be performed at the time of the procedure. In the case of a positive SLNB or suspected regional lymph node involvement upon initial examination, radical regional lymph node dissection also is recommended.³ Although some authorities advocate postsurgical radiation therapy to minimize the risk of local recurrence, there does not appear to be a clear benefit in survival rate.^3,5 However, radiation treatment as monotherapy has been advocated in certain instances, particularly in cases of unresectable tumors or patients who are poor surgical candidates.^5,7 Cases of distant metastasis (stage IV disease) may include management with surgery, radiation, and/or chemotherapy. Although none of these modalities have consistently shown to improve survival, there appears to be up to a 60% response with chemotherapy in these patients.³

Because MCC tends to affect an older population, often with other notable comorbidities, important considerations involving a treatment plan include the cost, side effects, and convenience for patients. The combination of carboplatin and VP-16 (etoposide) was utilized and tolerated well in our patient, and it has been successful in achieving complete radiologic and clinical remission of his metastatic disease. This combination appears to prolong survival in patients with distant metastasis, as compared to those patients not receiving chemotherapy.¹ Our patient has since died, but in these high-risk patients, close clinical monitoring is essential to help optimize their prognosis.

Merkel cell carcinoma is a rare aggressive cutaneous neoplasm that most commonly affects the elderly, immunosuppressed, and those with chronic UV sun damage. An association between the oncogenesis of MCC and infection with MCPyV has been documented, but other underlying diseases also may play a role in this process including rheumatoid arthritis and psoriasis. Although these risk factors were associated with our patient, his history of chronic immunosuppressive therapy for treatment of his psoriasis and inflammatory joint disease likely played a role in the pathogenesis of the tumor and should be an important point of discussion with any patient requiring this type of long-term management for disease control. Our unique clinical case highlights a patient with substantial comorbidities who developed metastatic MCC and achieved complete clinical and radiologic remission after treatment with surgery and chemotherapy.

To the Editor:

A 69-year-old white man presented with a skin lesion on the back of 1 to 2 weeks’ duration. The patient stated he was unaware of it, but his wife had recently noticed the new spot. He denied any bleeding, pain, pruritus, or other associated symptoms with the lesion. He also denied any prior treatment to the area. The patient’s medical history was remarkable for severe psoriasis involving more than 80% body surface area, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, coronary artery disease, squamous cell carcinoma, and actinic keratoses. He had been on multiple treatment regimens over the last 20 years for control of psoriasis including topical corticosteroids, psoralen plus UVA and UVB phototherapy, gold injections, acitretin, prednisone, efalizumab, ustekinumab, and alefacept upon evaluation of this new skin lesion. Utilization of immunosuppressive agents also provided an additional benefit of controlling the patient’s inflammatory arthritic disease.

On physical examination a 0.6×0.7-cm, pink to erythematous, pearly papule with superficial telangiectases was noted on the right side of the dorsal thorax (Figure 1). Multiple well-demarcated erythematous plaques with silvery scale and areas of secondary excoriation were noted on the trunk and both legs consistent with the patient’s history of psoriasis.

A shave biopsy was performed on the skin lesion on the right side of the dorsal thorax with a suspected clinical diagnosis of basal cell carcinoma. Two weeks later the patient returned for a discussion of the pathology report, which revealed nodules of basaloid cells with tightly packed vesicular nuclei and scant cytoplasm in sheets within the superficial dermis, as well as areas of nuclear molding, numerous mitotic figures, and areas of focal necrosis (Figure 2). In addition, immunostaining was positive for cytokeratin (CK) 20 antibodies with a characteristic paranuclear dot uptake of the antibody. These findings were consistent with a diagnosis of Merkel cell carcinoma (MCC). At that time, alefacept was discontinued and he was referred to a tertiary referral center for further evaluation and treatment.

The patient subsequently underwent wide excision with 1-cm margins of the MCC, with intraoperative lymphatic mapping/sentinel lymph node biopsy (SLNB) of the right axillary nodal basin 1 month later, which he tolerated well without any associated complications. Further histopathologic examination revealed the deep, medial, and lateral surgical margins to be negative of residual neoplasm. However, one sentinel lymph node indicated positivity for micrometastatic MCC, consistent with stage IIIA disease progression.

He underwent a second procedure the following month for complete right axillary lymph node dissection. Histopathologic examination of the right axillary contents included 28 lymph nodes, which were negative for carcinoma. He continued to do well without any signs of clinical recurrence or distant metastasis at subsequent follow-up visits.

Approximately 2.5 years after the second procedure, the patient began to develop right upper quadrant abdominal pain of an unclear etiology. Computed tomography of the abdomen and pelvis was performed, revealing areas of calcification and findings consistent with malignant lymphadenopathy. Multiple hepatic lesions also were noted including a 9-cm lesion in the posterior right hepatic lobe. Computed tomography–guided biopsy of the liver lesion was performed and the findings were consistent with metastatic MCC, indicating progression to stage IV disease.

The patient was subsequently started on combination chemotherapeutic treatment with carboplatin and VP-16, with a planned treatment course of 4 to 6 cycles. He was able to complete a total of 6 cycles over a 4-month period, tolerating the treatment regimen fairly well. Follow-up positron emission tomography–computed tomography was within normal limits with no evidence of any hypermetabolic activity noted, indicating a complete radiographic remission of MCC. He was seen approximately 1 month after completion of treatment for clinical follow-up and monthly thereafter.

While on chemotherapy, the patient experienced a notable improvement in the psoriasis and psoriatic joint disease. Upon completion of chemotherapy, he was restarted on the same treatment plan that was utilized prior to surgery including topical corticosteroids, calcitriol, intramuscular steroid injections, and UVB phototherapy, which provided substantial control of psoriasis and arthritic joint disease. The patient later died, likely due to his multiple comorbidities.

Merkel cells are slow-responding mechanoreceptors located within the basal layer of the epidermis and are the source of a rare aggressive cutaneous malignancy.¹ Merkel cell carcinoma was first noted in 1972 and termed trabecular carcinoma of the skin, and it accounts for less than 1% of all nonmelanoma skin cancer.^2,3 This primary neuroendocrine carcinoma has remarkable metastatic potential (34%–75%) and can invade regional lymph nodes, as well as distant metastasis most commonly to the liver, lungs, bones, and brain.² Approximately 25% of patients present with palpable lymphadenopathy and 5% with distant metastasis at the time of diagnosis. This frequency of metastasis at diagnosis as well as the recurrence after treatment contributes to the poor prognosis of MCC. Local recurrence rates have been reported at 25% with lymph node involvement in 52% and metastasis in 34%, with most recurrences occurring within 2 years of diagnosis. Patient mortality is dependent on the aggressiveness of the tumor, with 5-year survival rates of 83.3% without lymph node involvement, 58.3% with lymph node involvement, and 31.3% in those with metastatic disease.⁴

The tumor classically presents as a red to violaceous, painless nodule with a smooth shiny surface most often on the head and neck region.^4-6 Approximately 50% of MCC cases present in the head and neck region, 32% to 38% on the extremities, and 12% to 14% on the trunk.¹ This nonspecific presentation may lead to diagnostic uncertainty and a consequent delay in treatment. Definitive diagnosis of MCC is achieved with a skin biopsy and allows for distinction from other clinically similar–appearing neoplasms. Merkel cell carcinoma presents histologically as small round basophilic cells penetrating through the dermis in 3 histologic patterns: the trabecular, intermediate (80% of cases), and small cell type.⁵ It may be differentiated immunohistochemically from other neoplasms, as it displays CK20 positivity (showing paranuclear dotlike depositions in the cytoplasm or cell membrane) and is negative for CK7. Chromagranin and synaptophysin positivity also may provide further histologic confirmation. In addition, absence of peripheral palisading, retraction artifact, and a fibromyxoid stroma allow for distinction from cutaneous basal cell carcinoma, which may display these features histologically. Other immunohistochemical markers that may be of value include thyroid transcription factor 1, which is typically positive in cutaneous metastasis of neuroendocrine carcinoma of the lung; S-100 and human melanoma black 45, which are positive in melanoma; and leukocyte common antigen (CD45), which can be positive in lymphoma. These stains are classically negative in MCC.³

Merkel cell carcinoma is commonly associated with the presence of Merkel cell polyomavirus (MCPyV) in tumor specimens, with a prevalence of 70% to 80% in all cases. Merkel cell polyomavirus is a class 2A carcinogen (ie, a probable carcinogen to humans) and is classified among a group of viruses that encode T antigens (ie, an antigen coded by a viral genome associated with transformation of infected cells by tumor viruses), which can lead to initiation of tumorigenesis through interference with cellular tumor suppressing proteins such as p53.⁵ In addition, several risk factors have been associated with the development of MCC including immunosuppression, older age (>50 years), and UV-exposed fair skin.⁷ One explanation for this phenomenon is the increase in MCPyV small T antigen transcripts induced by UV irradiation.⁵ In addition, as with other cancers induced by viruses, host immunity can impede tumor progression and development. Therefore, impairment of normal immune function likely creates a higher risk for MCC development and potential for a worse prognosis.³Although the exact incidence of MCC in immunosuppressed patients appears unclear, chronic immunosuppressive therapy may play a notable role in the pathogenesis of the tumor.³

Although each of these factors was observed in our patient, it also was possible that his associated comorbidities further contributed to disease presentation. In particular, rheumatoid arthritis has been shown to carry an increased risk for the development of MCC.⁸ In addition, inflammatory monocytes infected with MCPyV, as evidenced in a patient with a history of chronic psoriasis prior to diagnosis of MCC, also may contribute to the pathogenesis of MCC by traveling to inflammatory skin lesions, such as those seen in psoriasis, releasing MCPyV locally and infecting Merkel cells.⁹ Although MCPyV testing was never performed in our patient, it certainly would be prudent as well as further studies determining the correlation of MCC to these disease processes.

Although regression is rare, multiple cases have documented spontaneous regression of MCC after biopsy of these lesions.^4,6,10 The exact mechanism is unclear, but apoptosis induced by T-cell immunity is suspected to play a role. Programmed cell death 1 protein (PD-1)–positive cells play a role. The PD-1 receptor is an inhibitory receptor expressed by T cells and in approximately half of tumor-infiltrating cells in MCC. It was found that in a regressed case of MCC there was a notably lower percentage of PD-1 positivity compared to cases with no apparent regression, suggesting that PD-1–positive cells suppress tumor immunity to MCC and that significant reduction in these cells may induce clinical regression.¹⁰ Additional investigation would be beneficial to examine the relationship of this phenomenon to tumor regression.

Initial evaluation of these patients should include a meticulous clinical examination with an emphasis on detection of cutaneous, lymph node, and distant metastasis. Due to the risk of metastatic potential, regional lymph node ultrasonography and computed tomography of the chest, abdomen, and pelvis typically are recommended at baseline. Other imaging modalities may be warranted based on clinical findings.³ Treatment modalities include various approaches, with surgical excision of the primary tumor with more than 1-cm margin to the fascial plane being the primary modality for uncomplicated cases.^1,3,7 In addition, SLNB also should be performed at the time of the procedure. In the case of a positive SLNB or suspected regional lymph node involvement upon initial examination, radical regional lymph node dissection also is recommended.³ Although some authorities advocate postsurgical radiation therapy to minimize the risk of local recurrence, there does not appear to be a clear benefit in survival rate.^3,5 However, radiation treatment as monotherapy has been advocated in certain instances, particularly in cases of unresectable tumors or patients who are poor surgical candidates.^5,7 Cases of distant metastasis (stage IV disease) may include management with surgery, radiation, and/or chemotherapy. Although none of these modalities have consistently shown to improve survival, there appears to be up to a 60% response with chemotherapy in these patients.³

Because MCC tends to affect an older population, often with other notable comorbidities, important considerations involving a treatment plan include the cost, side effects, and convenience for patients. The combination of carboplatin and VP-16 (etoposide) was utilized and tolerated well in our patient, and it has been successful in achieving complete radiologic and clinical remission of his metastatic disease. This combination appears to prolong survival in patients with distant metastasis, as compared to those patients not receiving chemotherapy.¹ Our patient has since died, but in these high-risk patients, close clinical monitoring is essential to help optimize their prognosis.

Merkel cell carcinoma is a rare aggressive cutaneous neoplasm that most commonly affects the elderly, immunosuppressed, and those with chronic UV sun damage. An association between the oncogenesis of MCC and infection with MCPyV has been documented, but other underlying diseases also may play a role in this process including rheumatoid arthritis and psoriasis. Although these risk factors were associated with our patient, his history of chronic immunosuppressive therapy for treatment of his psoriasis and inflammatory joint disease likely played a role in the pathogenesis of the tumor and should be an important point of discussion with any patient requiring this type of long-term management for disease control. Our unique clinical case highlights a patient with substantial comorbidities who developed metastatic MCC and achieved complete clinical and radiologic remission after treatment with surgery and chemotherapy.

To the Editor:

Trigeminal motor neuropathy is a rare condition presenting with muscle weakness and atrophy in the distribution of the trigeminal nerve without sensory changes. We present a challenging case with clinical features that mimic progressive hemifacial atrophy (PHA), a disease characterized by slowly progressive, unilateral facial atrophy that can be accompanied by inflammation and sclerosis as early features.

A 55-year-old man presented with right-sided ptosis and progressive right-sided facial atrophy of 4 years’ duration. A clinical diagnosis of PHA was made by the rheumatology department, and the patient was referred to the dermatology department for further evaluation. Examination at presentation revealed right-sided subcutaneous atrophy of the cheek, temple, and forehead extending to the scalp with absence of sclerosis, pigmentary alteration, or typical linear morphea lesions (Figures 1 and 2). The patient had no sensory changes in the affected area.

Workup by the dermatology department included magnetic resonance imaging (MRI) of the face and scalp, which demonstrated denervation muscle atrophy exclusively in the distribution of the third branch of the right trigeminal nerve, including severe atrophy of the right temporalis and masseter muscles and moderate atrophy of the pterygoid muscles. No signs of inflammation, fibrosis, or atrophy of the skin or subcutaneous fat were found, ruling out a diagnosis of PHA.

The patient was referred to the neurology department where he was found to have a normal neurologic examination with the exception of right-sided ptosis and temporalis and masseter muscle atrophy. Notably, the patient had normal sensation in the distribution of the trigeminal nerve and normal strength of the masseter and temporalis muscles.

An extensive workup by the neurology department was completed, including magnetic resonance angiography, eyeblink testing, and testing for causes of neuropathies (eg, infectious, autoimmune, vitamin deficiencies, toxin related). Of note, magnetic resonance angiography showed no abnormalities within the cavernous sinus or trigeminal cave but showed potential vascular compression of the trigeminal nerve, which was believed to be an incidental finding. The remainder of the workup was unremarkable. Based on muscle denervation atrophy in the distribution of the third branch of the trigeminal nerve in the absence of sensory symptoms or deficits, the patient’s presentation was consistent with trigeminal motor neuropathy.

In reported cases, the pathogenesis of trigeminal motor neuropathy is attributed to tumors, trauma, stroke, viral infection, and autoimmune reaction.^1-6 In other reported cases the cause is unknown,^6-8 as was the case in our patient. Magnetic resonance angiography revealed potential vascular compression of the trigeminal nerve, which has been previously reported to cause trigeminal neuropathy.⁹ However, patients with trigeminal neuropathy presented with sensory changes in the distribution of the trigeminal nerve as opposed to motor symptoms and muscle atrophy.

We present a case of trigeminal motor neuropathy presenting as PHA. Progressive hemifacial atrophy is a rare, slowly progressive disease characterized by unilateral atrophy of the skin, subcutis, muscle, and bony structures of the face. Onset usually is during childhood, though later onset has been reported.¹⁰ The pathogenesis of PHA is not well understood, though trauma, infection, immune-mediated causes, sympathetic dysfunction, and metabolic dysfunction have been proposed.¹¹ Diagnosis of PHA typically is based on clinical presentation, but histology and imaging are useful. In contrast to trigeminal motor neuropathy, MRI findings in PHA demonstrate involvement of the skin.¹²

Differentiation between PHA and trigeminal motor neuropathy is important because treatment differs. Treatment of trigeminal motor neuropathy depends on the etiology and may include removal of underlying neoplasms, while treatment of PHA depends on disease activity. The initial goal when treating PHA is to improve symptoms and slow disease progression; immunosuppressants may be considered. Facial reconstruction is an option when PHA is stable.

In this case, the features differentiating trigeminal motor neuropathy from PHA include age of onset and MRI as well as clinical findings of muscle atrophy limited to the distribution of the third branch of the trigeminal nerve. Although PHA is a rare disorder, this case demonstrates the importance of including trigeminal motor neuropathy in the differential diagnosis.

To the Editor:

Trigeminal motor neuropathy is a rare condition presenting with muscle weakness and atrophy in the distribution of the trigeminal nerve without sensory changes. We present a challenging case with clinical features that mimic progressive hemifacial atrophy (PHA), a disease characterized by slowly progressive, unilateral facial atrophy that can be accompanied by inflammation and sclerosis as early features.

A 55-year-old man presented with right-sided ptosis and progressive right-sided facial atrophy of 4 years’ duration. A clinical diagnosis of PHA was made by the rheumatology department, and the patient was referred to the dermatology department for further evaluation. Examination at presentation revealed right-sided subcutaneous atrophy of the cheek, temple, and forehead extending to the scalp with absence of sclerosis, pigmentary alteration, or typical linear morphea lesions (Figures 1 and 2). The patient had no sensory changes in the affected area.

Workup by the dermatology department included magnetic resonance imaging (MRI) of the face and scalp, which demonstrated denervation muscle atrophy exclusively in the distribution of the third branch of the right trigeminal nerve, including severe atrophy of the right temporalis and masseter muscles and moderate atrophy of the pterygoid muscles. No signs of inflammation, fibrosis, or atrophy of the skin or subcutaneous fat were found, ruling out a diagnosis of PHA.

The patient was referred to the neurology department where he was found to have a normal neurologic examination with the exception of right-sided ptosis and temporalis and masseter muscle atrophy. Notably, the patient had normal sensation in the distribution of the trigeminal nerve and normal strength of the masseter and temporalis muscles.

An extensive workup by the neurology department was completed, including magnetic resonance angiography, eyeblink testing, and testing for causes of neuropathies (eg, infectious, autoimmune, vitamin deficiencies, toxin related). Of note, magnetic resonance angiography showed no abnormalities within the cavernous sinus or trigeminal cave but showed potential vascular compression of the trigeminal nerve, which was believed to be an incidental finding. The remainder of the workup was unremarkable. Based on muscle denervation atrophy in the distribution of the third branch of the trigeminal nerve in the absence of sensory symptoms or deficits, the patient’s presentation was consistent with trigeminal motor neuropathy.

In reported cases, the pathogenesis of trigeminal motor neuropathy is attributed to tumors, trauma, stroke, viral infection, and autoimmune reaction.^1-6 In other reported cases the cause is unknown,^6-8 as was the case in our patient. Magnetic resonance angiography revealed potential vascular compression of the trigeminal nerve, which has been previously reported to cause trigeminal neuropathy.⁹ However, patients with trigeminal neuropathy presented with sensory changes in the distribution of the trigeminal nerve as opposed to motor symptoms and muscle atrophy.

We present a case of trigeminal motor neuropathy presenting as PHA. Progressive hemifacial atrophy is a rare, slowly progressive disease characterized by unilateral atrophy of the skin, subcutis, muscle, and bony structures of the face. Onset usually is during childhood, though later onset has been reported.¹⁰ The pathogenesis of PHA is not well understood, though trauma, infection, immune-mediated causes, sympathetic dysfunction, and metabolic dysfunction have been proposed.¹¹ Diagnosis of PHA typically is based on clinical presentation, but histology and imaging are useful. In contrast to trigeminal motor neuropathy, MRI findings in PHA demonstrate involvement of the skin.¹²

Differentiation between PHA and trigeminal motor neuropathy is important because treatment differs. Treatment of trigeminal motor neuropathy depends on the etiology and may include removal of underlying neoplasms, while treatment of PHA depends on disease activity. The initial goal when treating PHA is to improve symptoms and slow disease progression; immunosuppressants may be considered. Facial reconstruction is an option when PHA is stable.

In this case, the features differentiating trigeminal motor neuropathy from PHA include age of onset and MRI as well as clinical findings of muscle atrophy limited to the distribution of the third branch of the trigeminal nerve. Although PHA is a rare disorder, this case demonstrates the importance of including trigeminal motor neuropathy in the differential diagnosis.

To the Editor:

Trigeminal motor neuropathy is a rare condition presenting with muscle weakness and atrophy in the distribution of the trigeminal nerve without sensory changes. We present a challenging case with clinical features that mimic progressive hemifacial atrophy (PHA), a disease characterized by slowly progressive, unilateral facial atrophy that can be accompanied by inflammation and sclerosis as early features.

A 55-year-old man presented with right-sided ptosis and progressive right-sided facial atrophy of 4 years’ duration. A clinical diagnosis of PHA was made by the rheumatology department, and the patient was referred to the dermatology department for further evaluation. Examination at presentation revealed right-sided subcutaneous atrophy of the cheek, temple, and forehead extending to the scalp with absence of sclerosis, pigmentary alteration, or typical linear morphea lesions (Figures 1 and 2). The patient had no sensory changes in the affected area.

Workup by the dermatology department included magnetic resonance imaging (MRI) of the face and scalp, which demonstrated denervation muscle atrophy exclusively in the distribution of the third branch of the right trigeminal nerve, including severe atrophy of the right temporalis and masseter muscles and moderate atrophy of the pterygoid muscles. No signs of inflammation, fibrosis, or atrophy of the skin or subcutaneous fat were found, ruling out a diagnosis of PHA.

The patient was referred to the neurology department where he was found to have a normal neurologic examination with the exception of right-sided ptosis and temporalis and masseter muscle atrophy. Notably, the patient had normal sensation in the distribution of the trigeminal nerve and normal strength of the masseter and temporalis muscles.

An extensive workup by the neurology department was completed, including magnetic resonance angiography, eyeblink testing, and testing for causes of neuropathies (eg, infectious, autoimmune, vitamin deficiencies, toxin related). Of note, magnetic resonance angiography showed no abnormalities within the cavernous sinus or trigeminal cave but showed potential vascular compression of the trigeminal nerve, which was believed to be an incidental finding. The remainder of the workup was unremarkable. Based on muscle denervation atrophy in the distribution of the third branch of the trigeminal nerve in the absence of sensory symptoms or deficits, the patient’s presentation was consistent with trigeminal motor neuropathy.

In reported cases, the pathogenesis of trigeminal motor neuropathy is attributed to tumors, trauma, stroke, viral infection, and autoimmune reaction.^1-6 In other reported cases the cause is unknown,^6-8 as was the case in our patient. Magnetic resonance angiography revealed potential vascular compression of the trigeminal nerve, which has been previously reported to cause trigeminal neuropathy.⁹ However, patients with trigeminal neuropathy presented with sensory changes in the distribution of the trigeminal nerve as opposed to motor symptoms and muscle atrophy.

We present a case of trigeminal motor neuropathy presenting as PHA. Progressive hemifacial atrophy is a rare, slowly progressive disease characterized by unilateral atrophy of the skin, subcutis, muscle, and bony structures of the face. Onset usually is during childhood, though later onset has been reported.¹⁰ The pathogenesis of PHA is not well understood, though trauma, infection, immune-mediated causes, sympathetic dysfunction, and metabolic dysfunction have been proposed.¹¹ Diagnosis of PHA typically is based on clinical presentation, but histology and imaging are useful. In contrast to trigeminal motor neuropathy, MRI findings in PHA demonstrate involvement of the skin.¹²

Differentiation between PHA and trigeminal motor neuropathy is important because treatment differs. Treatment of trigeminal motor neuropathy depends on the etiology and may include removal of underlying neoplasms, while treatment of PHA depends on disease activity. The initial goal when treating PHA is to improve symptoms and slow disease progression; immunosuppressants may be considered. Facial reconstruction is an option when PHA is stable.

In this case, the features differentiating trigeminal motor neuropathy from PHA include age of onset and MRI as well as clinical findings of muscle atrophy limited to the distribution of the third branch of the trigeminal nerve. Although PHA is a rare disorder, this case demonstrates the importance of including trigeminal motor neuropathy in the differential diagnosis.