Nonmelanoma Skin Cancer

Kaposi sarcoma (KS) is caused by infection with human herpesvirus 8, a DNA virus and member of the Gammaherpesvirinae subfamily.^1,2 Cutaneous KS lesions generally appear as red to purple macules, plaques, and/or nodules that can become ulcerated, causing pain and bleeding. Lesions often are localized on the feet, which may impede walking and daily activities. Early diagnosis and management are important to avoid or minimize severe symptoms (eg, enlargement of lesions, ulceration with bleeding and pain). Injection therapy is recommended for the management of localized disease, while systemic therapy is appropriate for disseminated malignancy.³ There currently is no curative therapy available for KS; however, palliative therapy can avoid or reduce cosmetically unacceptable lesions and painful edema.

Vinblastine (VNB) is a natural vinca alkaloid whose primary cytotoxic effect is prevention of mitotic activity.⁴ However, antiangiogenetic activity has been demonstrated with low concentrations of VNB.⁵ The use of intralesional VNB injections for the management of oral KS in open-label studies⁴ using different doses and multiple courses has proven to be therapeutic.^6-8 There are limited studies regarding the use of intralesional VNB injections in patients with cutaneous KS, particularly in those with associated type 2 diabetes mellitus.^6-8 Thus, we evaluated the clinical efficacy of intralesional VNB injections in the treatment of KS lesions in diabetic patients with no visceral involvement.

Methods

This study was conducted in the department of dermatology from January 1, 2009, to December 31, 2011, and was approved by the institutional review board of the Fondazione IRCCS Policlinico San Matteo (Pavia, Italy). Six patients with type 2 diabetes mellitus and histologically diagnosed cutaneous KS were enrolled in the study. Inclusion criteria included histological diagnosis of KS, negative human immunodeficiency virus testing, history of type 2 diabetes mellitus, more than 5 cutaneous KS lesions, and no visceral involvement (confirmed by colonoscopy, gastroscopy, lymph node and abdominal echography, and chest radiograph). Informed written consent was obtained from all participants.

Treated plaques and nodules measured more than 1 to 2 cm in diameter. Intralesional vinblastine injections were administered, not perilesional, with a standard concentration of 0.5 mg/mL per 1-cm² lesion (maximum dose, 2 mg daily). All participants received 1 injection per nodule and a maximum of 2 injections per plaque. Monitoring of the target lesions was done via photography and mapping. Clinical evaluation of the treated lesions and assessment of side effects was conducted at 1-week and 1-, 3-, and 6-month follow-up. Complete response was defined as 95% to 100% remission of the target lesions, partial response was defined as 50% to 95% remission, and minimal response was defined as less than 50% remission, all at 3-month follow-up. No response was defined as no change or increase in size of the target lesions. Side effects including pain, hyperpigmentation, and ulcer formation were evaluated.

Results

A total of 6 participants (5 men, 1 woman; age range, 66–82 years) completed the study. Baseline demographics and clinical characteristics of the participants are reported in Table 1. Three participants were currently undergoing diabetic therapy with metformin, 2 were receiving insulin injections, and 1 was following a diabetic diet. None of the participants had internal KS. All 5 participants with nodular KS lesions previously underwent surgical excision. One participant also underwent radiotherapy with a good initial outcome, but lesions recurred at the same site within 1 year.

Complete response of nodular KS lesions and partial response of plaques to intralesional VNB injections was observed at 3-month follow-up in all treated lesions (Table 2). Five participants achieved a greater than 50% reduction (overall decrease in size and flattening of the plaque) of the KS plaque lesions. No participants showed minimal or no response.

At 1-week follow-up, shrinkage of nodular lesions was evident with necrotic crusts. Participant 4 who presented with plaques under the feet developed lymphatic serum exudation in the first 3 days following treatment on the legs. All the treated nodular lesions resolved completely within 3 months after treatment (Figures 1 and 2), though some new lesions appeared in new locations. All the treated plaques showed partial response to treatment after 1- to 3-month follow-up (Figure 3).

Figure 1. An ulcerated bleeding nodular lesion of Kaposi sarcoma localized at the base of the first toe (a possible site of infection) in a diabetic patient (participant 1)(A). Three months after a 0.2-mg/mL intralesional vinblastine injection, the lesion had completely resolved (B).

Figure 2. A 2-cm nodular lesion of Kaposi sarcoma in the malleolar region of a diabetic patient (participant 2), a common site of venous ulceration in this patient population (A). One month after a 0.5 mg/mL intralesional vinblastine injection, complete response was noted without signs of ulceration (B).

Figure 3. A diffuse recurrent plaque of Kaposi sarcoma on the plantar region in participant 4 that had been treated with radiotherapy 2 years prior (A). Three months following a 3-mg/mL intralesional vinblastine injection, partial response was evident (B).

All participants reported pain on the second and third days posttreatment, but analgesics were only prescribed to participants 2 and 4. Hyperpigmentation developed after 3 to 6 months in 3 participants. Two participants developed small ulcers within 2 weeks following treatment that healed within 3 months.

Comment

Classic KS is characterized by a localized onset with slow progression of systemic involvement. Cutaneous lesions progress from mild to severe.⁹ Systemic therapeutic strategies currently employed for the management of KS include single-agent and multiagent cytotoxic chemotherapy.¹⁰ Because these drugs have been associated with remarkable systemic side effects and patients often are elderly individuals, systemic therapy may be unsuitable for long-term use. In an epidemiologic study of 37 patients with KS, 12 patients (32%) were found to have concurrent diabetes mellitus.¹¹ Some authors suggest that KS in diabetic patients is a subtype of KS because of the immunosuppressive state caused by diabetes.^12-15

Some of the reported therapies for lesions of classic KS include cryotherapy, surgical excision, radiation therapy, alitretinoin gel 0.1%, and infrared photocoagulation.^3-16 Cryotherapy of a small papular lesion requires a 30- to 60-second freeze time that usually needs to be followed by further cryotherapy applications and is not known to be effective in lesions larger than 1 cm.¹⁷ Surgical procedures in the management of cutaneous KS may cause discomfort and bleeding and also are expensive.¹⁸ Radiotherapy is an alternative therapy, especially in plaque lesions.¹⁹ Alitretinoin gel 0.1% has been shown to be effective and well tolerated for the treatment of cutaneous lesions in patients with AIDS-related KS. Although Morganroth²⁰ reported alitretinoin gel 0.1% as a promising therapy for control of classic KS cutaneous lesions, Rongioletti et al²¹ described failure of this topical treatment for classic KS. The efficacy of topical alitretinoin in classic KS needs to be confirmed by further studies. Short pulses of the infrared coagulator have been reported for the treatment of 10 cutaneous AIDS-related KS lesions in 7 patients. The infrared coagulator may be a useful addition in the palliative cosmetic treatment of KS, producing acceptable results in small (ie, <2 cm in diameter) lesions of the arms and trunk but not in those situated on the legs, as in our patients.¹⁶

The use of VNB in classic KS was pioneered in 1980 by Klein et al²² who described 14 patients with KS who were systemically treated with VNB sulfate at a low dose with excellent therapeutic results leading to regression of cutaneous lesions. In this study, intravenous VNB therapy was supplemented with intralesional VNB.²² In other reports, intralesional VNB injections have proved to be effective in reducing lesion size and symptoms in oral KS with mild adverse effects.^19-29 For this reason, we decided to employ intralesional VNB injections in nodules and plaques of KS patients with diabetes. After treatment, lesion size was reduced in all 6 participants, with 4 participants achieving more than 50% reduction of the lesion size. In other studies reporting oral lesions,³ the highest proportion of complete responses was achieved with injections done periodically until evidence of clinical resolution was obtained, with a mean number of 2.4 injections per patient. In contrast, another study reported complete response of 48% in patients who received a single dose of VNB,⁷ as in our study.

Minimal complications following intralesional VNB injections have been reported. In our study, moderate pain following VNB injection was common during the first week posttreatment but typically resolved partially or completely during the following weeks. Additionally, pain described as needlelike during the procedure was minimal except for 1 participant who reported severe pain a day after the treatment. Unlike the study by Smith et al,³⁰ lidocaine with epinephrine was not used in our study as a pretreatment.

At 1-month follow-up, clinical evaluation of the injection site revealed ulceration in 2 participants, but no ulcers were noted at 3-month follow-up. To avoid this potentially dangerous complication, which can involve the foot in diabetic patients, further studies of a larger sample of patients using a lower dose of VNB are needed.

In our small group of diabetic patients, intralesional injections of VNB proved to be effective in the management of cutaneous lesions of classic KS with minimal adverse side effects. Even in cases where only one intralesional injection was administered, improvement was observed in all treated lesions. Imiquimod also has been proposed for the treatment of KS. Célestin Schartz et al³¹ conducted a study of 17 patients who were treated with imiquimod cream applied under occlusion 3 times weekly for 24 weeks. Eight patients had an objective clinical response (2 complete and 6 partial responses), and tumor progression was noted in 6 patients.³¹ This treatment appears to be suitable for new small skin lesions in immunocompetent patients; however, no known comparative studies have been conducted, possibly because of the relatively high cost of treatment due to the chronic nature of the disease. Intralesional bleomycin also has been reported as useful in the treatment of cutaneous KS. The best results were obtained with macular lesions.³² However, the risk for necrosis is high. Therefore, bleomycin is not the first choice for diabetics, particularly those who have lesions localized on legs.

Conclusion

Standard treatments of KS lesions such as radiotherapy, surgery, and chemotherapy are associated with more severe adverse events, especially in diabetic patients, as well as higher costs due to the use of more sophisticated techniques and equipment. Because KS is a multicentric disease, local therapy should not be expected to prevent the development of new lesions on other sites of the skin or internal disease. The best candidates for localized therapy are patients affected by nodular classic KS without visceral involvement, with fewer than 10 lesions on acral sites.

Kaposi sarcoma (KS) is caused by infection with human herpesvirus 8, a DNA virus and member of the Gammaherpesvirinae subfamily.^1,2 Cutaneous KS lesions generally appear as red to purple macules, plaques, and/or nodules that can become ulcerated, causing pain and bleeding. Lesions often are localized on the feet, which may impede walking and daily activities. Early diagnosis and management are important to avoid or minimize severe symptoms (eg, enlargement of lesions, ulceration with bleeding and pain). Injection therapy is recommended for the management of localized disease, while systemic therapy is appropriate for disseminated malignancy.³ There currently is no curative therapy available for KS; however, palliative therapy can avoid or reduce cosmetically unacceptable lesions and painful edema.

Vinblastine (VNB) is a natural vinca alkaloid whose primary cytotoxic effect is prevention of mitotic activity.⁴ However, antiangiogenetic activity has been demonstrated with low concentrations of VNB.⁵ The use of intralesional VNB injections for the management of oral KS in open-label studies⁴ using different doses and multiple courses has proven to be therapeutic.^6-8 There are limited studies regarding the use of intralesional VNB injections in patients with cutaneous KS, particularly in those with associated type 2 diabetes mellitus.^6-8 Thus, we evaluated the clinical efficacy of intralesional VNB injections in the treatment of KS lesions in diabetic patients with no visceral involvement.

Methods

This study was conducted in the department of dermatology from January 1, 2009, to December 31, 2011, and was approved by the institutional review board of the Fondazione IRCCS Policlinico San Matteo (Pavia, Italy). Six patients with type 2 diabetes mellitus and histologically diagnosed cutaneous KS were enrolled in the study. Inclusion criteria included histological diagnosis of KS, negative human immunodeficiency virus testing, history of type 2 diabetes mellitus, more than 5 cutaneous KS lesions, and no visceral involvement (confirmed by colonoscopy, gastroscopy, lymph node and abdominal echography, and chest radiograph). Informed written consent was obtained from all participants.

Treated plaques and nodules measured more than 1 to 2 cm in diameter. Intralesional vinblastine injections were administered, not perilesional, with a standard concentration of 0.5 mg/mL per 1-cm² lesion (maximum dose, 2 mg daily). All participants received 1 injection per nodule and a maximum of 2 injections per plaque. Monitoring of the target lesions was done via photography and mapping. Clinical evaluation of the treated lesions and assessment of side effects was conducted at 1-week and 1-, 3-, and 6-month follow-up. Complete response was defined as 95% to 100% remission of the target lesions, partial response was defined as 50% to 95% remission, and minimal response was defined as less than 50% remission, all at 3-month follow-up. No response was defined as no change or increase in size of the target lesions. Side effects including pain, hyperpigmentation, and ulcer formation were evaluated.

Results

A total of 6 participants (5 men, 1 woman; age range, 66–82 years) completed the study. Baseline demographics and clinical characteristics of the participants are reported in Table 1. Three participants were currently undergoing diabetic therapy with metformin, 2 were receiving insulin injections, and 1 was following a diabetic diet. None of the participants had internal KS. All 5 participants with nodular KS lesions previously underwent surgical excision. One participant also underwent radiotherapy with a good initial outcome, but lesions recurred at the same site within 1 year.

Complete response of nodular KS lesions and partial response of plaques to intralesional VNB injections was observed at 3-month follow-up in all treated lesions (Table 2). Five participants achieved a greater than 50% reduction (overall decrease in size and flattening of the plaque) of the KS plaque lesions. No participants showed minimal or no response.

At 1-week follow-up, shrinkage of nodular lesions was evident with necrotic crusts. Participant 4 who presented with plaques under the feet developed lymphatic serum exudation in the first 3 days following treatment on the legs. All the treated nodular lesions resolved completely within 3 months after treatment (Figures 1 and 2), though some new lesions appeared in new locations. All the treated plaques showed partial response to treatment after 1- to 3-month follow-up (Figure 3).

Figure 1. An ulcerated bleeding nodular lesion of Kaposi sarcoma localized at the base of the first toe (a possible site of infection) in a diabetic patient (participant 1)(A). Three months after a 0.2-mg/mL intralesional vinblastine injection, the lesion had completely resolved (B).

Figure 2. A 2-cm nodular lesion of Kaposi sarcoma in the malleolar region of a diabetic patient (participant 2), a common site of venous ulceration in this patient population (A). One month after a 0.5 mg/mL intralesional vinblastine injection, complete response was noted without signs of ulceration (B).

Figure 3. A diffuse recurrent plaque of Kaposi sarcoma on the plantar region in participant 4 that had been treated with radiotherapy 2 years prior (A). Three months following a 3-mg/mL intralesional vinblastine injection, partial response was evident (B).

All participants reported pain on the second and third days posttreatment, but analgesics were only prescribed to participants 2 and 4. Hyperpigmentation developed after 3 to 6 months in 3 participants. Two participants developed small ulcers within 2 weeks following treatment that healed within 3 months.

Comment

Classic KS is characterized by a localized onset with slow progression of systemic involvement. Cutaneous lesions progress from mild to severe.⁹ Systemic therapeutic strategies currently employed for the management of KS include single-agent and multiagent cytotoxic chemotherapy.¹⁰ Because these drugs have been associated with remarkable systemic side effects and patients often are elderly individuals, systemic therapy may be unsuitable for long-term use. In an epidemiologic study of 37 patients with KS, 12 patients (32%) were found to have concurrent diabetes mellitus.¹¹ Some authors suggest that KS in diabetic patients is a subtype of KS because of the immunosuppressive state caused by diabetes.^12-15

Some of the reported therapies for lesions of classic KS include cryotherapy, surgical excision, radiation therapy, alitretinoin gel 0.1%, and infrared photocoagulation.^3-16 Cryotherapy of a small papular lesion requires a 30- to 60-second freeze time that usually needs to be followed by further cryotherapy applications and is not known to be effective in lesions larger than 1 cm.¹⁷ Surgical procedures in the management of cutaneous KS may cause discomfort and bleeding and also are expensive.¹⁸ Radiotherapy is an alternative therapy, especially in plaque lesions.¹⁹ Alitretinoin gel 0.1% has been shown to be effective and well tolerated for the treatment of cutaneous lesions in patients with AIDS-related KS. Although Morganroth²⁰ reported alitretinoin gel 0.1% as a promising therapy for control of classic KS cutaneous lesions, Rongioletti et al²¹ described failure of this topical treatment for classic KS. The efficacy of topical alitretinoin in classic KS needs to be confirmed by further studies. Short pulses of the infrared coagulator have been reported for the treatment of 10 cutaneous AIDS-related KS lesions in 7 patients. The infrared coagulator may be a useful addition in the palliative cosmetic treatment of KS, producing acceptable results in small (ie, <2 cm in diameter) lesions of the arms and trunk but not in those situated on the legs, as in our patients.¹⁶

The use of VNB in classic KS was pioneered in 1980 by Klein et al²² who described 14 patients with KS who were systemically treated with VNB sulfate at a low dose with excellent therapeutic results leading to regression of cutaneous lesions. In this study, intravenous VNB therapy was supplemented with intralesional VNB.²² In other reports, intralesional VNB injections have proved to be effective in reducing lesion size and symptoms in oral KS with mild adverse effects.^19-29 For this reason, we decided to employ intralesional VNB injections in nodules and plaques of KS patients with diabetes. After treatment, lesion size was reduced in all 6 participants, with 4 participants achieving more than 50% reduction of the lesion size. In other studies reporting oral lesions,³ the highest proportion of complete responses was achieved with injections done periodically until evidence of clinical resolution was obtained, with a mean number of 2.4 injections per patient. In contrast, another study reported complete response of 48% in patients who received a single dose of VNB,⁷ as in our study.

Minimal complications following intralesional VNB injections have been reported. In our study, moderate pain following VNB injection was common during the first week posttreatment but typically resolved partially or completely during the following weeks. Additionally, pain described as needlelike during the procedure was minimal except for 1 participant who reported severe pain a day after the treatment. Unlike the study by Smith et al,³⁰ lidocaine with epinephrine was not used in our study as a pretreatment.

At 1-month follow-up, clinical evaluation of the injection site revealed ulceration in 2 participants, but no ulcers were noted at 3-month follow-up. To avoid this potentially dangerous complication, which can involve the foot in diabetic patients, further studies of a larger sample of patients using a lower dose of VNB are needed.

In our small group of diabetic patients, intralesional injections of VNB proved to be effective in the management of cutaneous lesions of classic KS with minimal adverse side effects. Even in cases where only one intralesional injection was administered, improvement was observed in all treated lesions. Imiquimod also has been proposed for the treatment of KS. Célestin Schartz et al³¹ conducted a study of 17 patients who were treated with imiquimod cream applied under occlusion 3 times weekly for 24 weeks. Eight patients had an objective clinical response (2 complete and 6 partial responses), and tumor progression was noted in 6 patients.³¹ This treatment appears to be suitable for new small skin lesions in immunocompetent patients; however, no known comparative studies have been conducted, possibly because of the relatively high cost of treatment due to the chronic nature of the disease. Intralesional bleomycin also has been reported as useful in the treatment of cutaneous KS. The best results were obtained with macular lesions.³² However, the risk for necrosis is high. Therefore, bleomycin is not the first choice for diabetics, particularly those who have lesions localized on legs.

Conclusion

Standard treatments of KS lesions such as radiotherapy, surgery, and chemotherapy are associated with more severe adverse events, especially in diabetic patients, as well as higher costs due to the use of more sophisticated techniques and equipment. Because KS is a multicentric disease, local therapy should not be expected to prevent the development of new lesions on other sites of the skin or internal disease. The best candidates for localized therapy are patients affected by nodular classic KS without visceral involvement, with fewer than 10 lesions on acral sites.

Kaposi sarcoma (KS) is caused by infection with human herpesvirus 8, a DNA virus and member of the Gammaherpesvirinae subfamily.^1,2 Cutaneous KS lesions generally appear as red to purple macules, plaques, and/or nodules that can become ulcerated, causing pain and bleeding. Lesions often are localized on the feet, which may impede walking and daily activities. Early diagnosis and management are important to avoid or minimize severe symptoms (eg, enlargement of lesions, ulceration with bleeding and pain). Injection therapy is recommended for the management of localized disease, while systemic therapy is appropriate for disseminated malignancy.³ There currently is no curative therapy available for KS; however, palliative therapy can avoid or reduce cosmetically unacceptable lesions and painful edema.

Vinblastine (VNB) is a natural vinca alkaloid whose primary cytotoxic effect is prevention of mitotic activity.⁴ However, antiangiogenetic activity has been demonstrated with low concentrations of VNB.⁵ The use of intralesional VNB injections for the management of oral KS in open-label studies⁴ using different doses and multiple courses has proven to be therapeutic.^6-8 There are limited studies regarding the use of intralesional VNB injections in patients with cutaneous KS, particularly in those with associated type 2 diabetes mellitus.^6-8 Thus, we evaluated the clinical efficacy of intralesional VNB injections in the treatment of KS lesions in diabetic patients with no visceral involvement.

Methods

This study was conducted in the department of dermatology from January 1, 2009, to December 31, 2011, and was approved by the institutional review board of the Fondazione IRCCS Policlinico San Matteo (Pavia, Italy). Six patients with type 2 diabetes mellitus and histologically diagnosed cutaneous KS were enrolled in the study. Inclusion criteria included histological diagnosis of KS, negative human immunodeficiency virus testing, history of type 2 diabetes mellitus, more than 5 cutaneous KS lesions, and no visceral involvement (confirmed by colonoscopy, gastroscopy, lymph node and abdominal echography, and chest radiograph). Informed written consent was obtained from all participants.

Treated plaques and nodules measured more than 1 to 2 cm in diameter. Intralesional vinblastine injections were administered, not perilesional, with a standard concentration of 0.5 mg/mL per 1-cm² lesion (maximum dose, 2 mg daily). All participants received 1 injection per nodule and a maximum of 2 injections per plaque. Monitoring of the target lesions was done via photography and mapping. Clinical evaluation of the treated lesions and assessment of side effects was conducted at 1-week and 1-, 3-, and 6-month follow-up. Complete response was defined as 95% to 100% remission of the target lesions, partial response was defined as 50% to 95% remission, and minimal response was defined as less than 50% remission, all at 3-month follow-up. No response was defined as no change or increase in size of the target lesions. Side effects including pain, hyperpigmentation, and ulcer formation were evaluated.

Results

A total of 6 participants (5 men, 1 woman; age range, 66–82 years) completed the study. Baseline demographics and clinical characteristics of the participants are reported in Table 1. Three participants were currently undergoing diabetic therapy with metformin, 2 were receiving insulin injections, and 1 was following a diabetic diet. None of the participants had internal KS. All 5 participants with nodular KS lesions previously underwent surgical excision. One participant also underwent radiotherapy with a good initial outcome, but lesions recurred at the same site within 1 year.

Complete response of nodular KS lesions and partial response of plaques to intralesional VNB injections was observed at 3-month follow-up in all treated lesions (Table 2). Five participants achieved a greater than 50% reduction (overall decrease in size and flattening of the plaque) of the KS plaque lesions. No participants showed minimal or no response.

At 1-week follow-up, shrinkage of nodular lesions was evident with necrotic crusts. Participant 4 who presented with plaques under the feet developed lymphatic serum exudation in the first 3 days following treatment on the legs. All the treated nodular lesions resolved completely within 3 months after treatment (Figures 1 and 2), though some new lesions appeared in new locations. All the treated plaques showed partial response to treatment after 1- to 3-month follow-up (Figure 3).

Figure 1. An ulcerated bleeding nodular lesion of Kaposi sarcoma localized at the base of the first toe (a possible site of infection) in a diabetic patient (participant 1)(A). Three months after a 0.2-mg/mL intralesional vinblastine injection, the lesion had completely resolved (B).

Figure 2. A 2-cm nodular lesion of Kaposi sarcoma in the malleolar region of a diabetic patient (participant 2), a common site of venous ulceration in this patient population (A). One month after a 0.5 mg/mL intralesional vinblastine injection, complete response was noted without signs of ulceration (B).

Figure 3. A diffuse recurrent plaque of Kaposi sarcoma on the plantar region in participant 4 that had been treated with radiotherapy 2 years prior (A). Three months following a 3-mg/mL intralesional vinblastine injection, partial response was evident (B).

All participants reported pain on the second and third days posttreatment, but analgesics were only prescribed to participants 2 and 4. Hyperpigmentation developed after 3 to 6 months in 3 participants. Two participants developed small ulcers within 2 weeks following treatment that healed within 3 months.

Comment

Classic KS is characterized by a localized onset with slow progression of systemic involvement. Cutaneous lesions progress from mild to severe.⁹ Systemic therapeutic strategies currently employed for the management of KS include single-agent and multiagent cytotoxic chemotherapy.¹⁰ Because these drugs have been associated with remarkable systemic side effects and patients often are elderly individuals, systemic therapy may be unsuitable for long-term use. In an epidemiologic study of 37 patients with KS, 12 patients (32%) were found to have concurrent diabetes mellitus.¹¹ Some authors suggest that KS in diabetic patients is a subtype of KS because of the immunosuppressive state caused by diabetes.^12-15

Some of the reported therapies for lesions of classic KS include cryotherapy, surgical excision, radiation therapy, alitretinoin gel 0.1%, and infrared photocoagulation.^3-16 Cryotherapy of a small papular lesion requires a 30- to 60-second freeze time that usually needs to be followed by further cryotherapy applications and is not known to be effective in lesions larger than 1 cm.¹⁷ Surgical procedures in the management of cutaneous KS may cause discomfort and bleeding and also are expensive.¹⁸ Radiotherapy is an alternative therapy, especially in plaque lesions.¹⁹ Alitretinoin gel 0.1% has been shown to be effective and well tolerated for the treatment of cutaneous lesions in patients with AIDS-related KS. Although Morganroth²⁰ reported alitretinoin gel 0.1% as a promising therapy for control of classic KS cutaneous lesions, Rongioletti et al²¹ described failure of this topical treatment for classic KS. The efficacy of topical alitretinoin in classic KS needs to be confirmed by further studies. Short pulses of the infrared coagulator have been reported for the treatment of 10 cutaneous AIDS-related KS lesions in 7 patients. The infrared coagulator may be a useful addition in the palliative cosmetic treatment of KS, producing acceptable results in small (ie, <2 cm in diameter) lesions of the arms and trunk but not in those situated on the legs, as in our patients.¹⁶

The use of VNB in classic KS was pioneered in 1980 by Klein et al²² who described 14 patients with KS who were systemically treated with VNB sulfate at a low dose with excellent therapeutic results leading to regression of cutaneous lesions. In this study, intravenous VNB therapy was supplemented with intralesional VNB.²² In other reports, intralesional VNB injections have proved to be effective in reducing lesion size and symptoms in oral KS with mild adverse effects.^19-29 For this reason, we decided to employ intralesional VNB injections in nodules and plaques of KS patients with diabetes. After treatment, lesion size was reduced in all 6 participants, with 4 participants achieving more than 50% reduction of the lesion size. In other studies reporting oral lesions,³ the highest proportion of complete responses was achieved with injections done periodically until evidence of clinical resolution was obtained, with a mean number of 2.4 injections per patient. In contrast, another study reported complete response of 48% in patients who received a single dose of VNB,⁷ as in our study.

Minimal complications following intralesional VNB injections have been reported. In our study, moderate pain following VNB injection was common during the first week posttreatment but typically resolved partially or completely during the following weeks. Additionally, pain described as needlelike during the procedure was minimal except for 1 participant who reported severe pain a day after the treatment. Unlike the study by Smith et al,³⁰ lidocaine with epinephrine was not used in our study as a pretreatment.

At 1-month follow-up, clinical evaluation of the injection site revealed ulceration in 2 participants, but no ulcers were noted at 3-month follow-up. To avoid this potentially dangerous complication, which can involve the foot in diabetic patients, further studies of a larger sample of patients using a lower dose of VNB are needed.

In our small group of diabetic patients, intralesional injections of VNB proved to be effective in the management of cutaneous lesions of classic KS with minimal adverse side effects. Even in cases where only one intralesional injection was administered, improvement was observed in all treated lesions. Imiquimod also has been proposed for the treatment of KS. Célestin Schartz et al³¹ conducted a study of 17 patients who were treated with imiquimod cream applied under occlusion 3 times weekly for 24 weeks. Eight patients had an objective clinical response (2 complete and 6 partial responses), and tumor progression was noted in 6 patients.³¹ This treatment appears to be suitable for new small skin lesions in immunocompetent patients; however, no known comparative studies have been conducted, possibly because of the relatively high cost of treatment due to the chronic nature of the disease. Intralesional bleomycin also has been reported as useful in the treatment of cutaneous KS. The best results were obtained with macular lesions.³² However, the risk for necrosis is high. Therefore, bleomycin is not the first choice for diabetics, particularly those who have lesions localized on legs.

Conclusion

Standard treatments of KS lesions such as radiotherapy, surgery, and chemotherapy are associated with more severe adverse events, especially in diabetic patients, as well as higher costs due to the use of more sophisticated techniques and equipment. Because KS is a multicentric disease, local therapy should not be expected to prevent the development of new lesions on other sites of the skin or internal disease. The best candidates for localized therapy are patients affected by nodular classic KS without visceral involvement, with fewer than 10 lesions on acral sites.

To the Editor:

Marjolin ulcers are malignancies arising in nonhealing cutaneous wounds. Although burn wounds are the most common type of cutaneous trauma associated with this entity, there are a multitude of possible lesions that may initiate this disease process including traumatic wounds, venous stasis ulcers, and vaccination sites.^1,2 The most common type of malignancy reported in a Marjolin ulcer is an aggressive squamous cell carcinoma (SCC).^1-3 Less commonly, basal cell carcinoma (BCC) also has been reported.^1,3,4 However, cases of BCCs developing in surgical scars are exceedingly rare. We describe a case of a morphoeic BCC in a long-standing surgical scar in a 50-year-old woman with Crohn disease.

A 50-year-old woman presented with an intermittent ulceration within a horizontal surgical scar on the right side of the upper abdomen of 2 years’ duration that had not healed over the course of the last 6 months. The scar was present from surgeries conducted while she was a teenager for complications associated with Crohn disease. She underwent her first abdominal surgery for a partial gastric resection at 16 years of age, followed by multiple laparotomies from a perforated bile duct that occurred during the first surgery. The original incision created for the partial gastric resection was used for all subsequent surgeries.

The patient’s medical history was notable for central nervous system vasculitis with vision loss, chronic pancreatitis, Crohn disease, arthritis, multiple superficial BCCs on the back that were successfully treated with imiquimod cream, a nodular BCC on the neck that was surgically removed, and facial actinic keratoses treated with liquid nitrogen. She had Fitzpatrick skin type I. She grew up in a residential area in Southern Ontario and did not have a history of heavy sun exposure. She did not receive notable radiation from treatment of Crohn disease, and she usually wore a 1-piece bathing suit when swimming outdoors. According to the patient, she had never been exposed to arsenic. The patient’s family history was negative for skin cancer and she was a nonsmoker. She was taking methotrexate, prednisone, folic acid, pentazocine, and vitamin B₁₂ injections at the time of presentation for the aforementioned conditions.

On physical examination a 1.5-cm honey-crusted ulcer with surrounding violaceous erythema in a long-standing surgical scar was observed (Figure 1). There was no palpable adenopathy in the inguinal or axillary regions. The suspected diagnosis prebiopsy was an SCC developing within the scar tissue. On histologic examination sections of small nests and strands of basal cell infiltrating thick collagen bundles were visualized. The appearance was consistent with a morphoeic BCC. The pathologist’s interpretation indicated that the lesion appeared to be a morphoeic BCC within the scar as opposed to a BCC that appeared morphoeic because of background scarring. Histologic images stained with hematoxylin and eosin showed small nests and strands of basal cells penetrating thick collagen bundles (Figure 2).

Figure 1. Complete visualization of the surgical scar with the associated ulcer in the epigastric region (A). Magnified view of a honey-crusted ulcer with surrounding violaceous erythema (B).

Figure 2. Histology showed small nests and strands of basal cells penetrating thick collagen bundles (A and B)(both H&E, original magnifications ×40 and ×100).

Marjolin ulcer was first described in 1828 by the French surgeon Jean-Nicolas Marjolin who published 4 cases of ulcers arising from scar tissue but did not appreciate their malignant capacity. However, the term Marjolin ulcer is now widely accepted as meaning any malignant tumor occurring within scar tissue or a chronic nonhealing wound.^1,2

The exact incidence of malignant transformation in cutaneous wounds remains unknown, but this phenomenon can occur in individuals of all races and across all age groups.^1,5-7 The most prevalent malignancy identified on biopsy is SCC, followed by BCC, melanoma, osteosarcoma, fibrosarcoma, and liposarcoma.^1,2,6,7 With this entity infrequently occurring in the clinical setting, it often is overlooked or misdiagnosed.² In addition, malignancies presenting as Marjolin ulcers have a greater tendency to metastasize and are reported to have a higher associated fatality rate.^2,8 Thus, early recognition is essential, as a delay in diagnosis can potentially allow the tumor to progress to a life-threatening stage. In our patient, malignancy was clinically suspected based on the presence of an ulcer that was not healing despite adequate wound care and the location in a scar that was present for more than 30 years. The surgical scar had been a place of repeated trauma given the number of surgical procedures and the perforated bile duct, which can increase the potential for malignant transformation. Furthermore, the patient also was on immunosuppressive therapy for an extended period of time, possibly contributing to the development of this cancerous lesion and prior cutaneous malignancies.

The pathogenesis of a Marjolin ulcer is unclear, though many hypotheses have been suggested.^1,2,6,9 Theories investigating decreased vascularity, lowered immune surveillance, decreased regenerative capacity, genetic mutations, and injury-related release of toxins have all been postulated as possible explanations for the increase in potential of malignant transformation.^1-3,6,9 However, despite the pathogenesis, the mainstay of treatment remains wide local excision with at least 2-cm margins.^1-3,10 Alternatively, Mohs micrographic surgery can be considered for Marjolin ulcers, but it is less frequently conducted in comparison to wide local excision. Radiation therapy often follows excision as adjuvant therapy, depending on the type of tumor.^2,10 Prophylactic lymph node dissection is not indicated in most cases, but regional node dissection is suggested when palpable lymphadenopathy is present.^1,2,10 Moreover, amputation is indicated with deep bone or joint involvement.^1-3,10 Recurrence rates are high, ranging from 20% to 50%, and metastases to the brain, liver, lungs, kidneys, and lymph nodes have been reported.^1,3 The prognosis of the cutaneous malignancy in this setting is not as favorable, and the 5-year survival rate is cited at approximately 60%.³ Overall prognosis depends on several factors including location, type of malignancy, immune status, progression of disease, and lymph node metastasis. Our patient’s presentation with a BCC instead of the more common SCC should carry a good overall prognosis, though she will need to be closely followed for recurrence after wide local excision.

This novel presentation of a morpheaform BCC in a surgical scar may serve as a reminder to consider this diagnosis and biopsy nonhealing ulcers within any type of chronic wound or scar.

To the Editor:

Marjolin ulcers are malignancies arising in nonhealing cutaneous wounds. Although burn wounds are the most common type of cutaneous trauma associated with this entity, there are a multitude of possible lesions that may initiate this disease process including traumatic wounds, venous stasis ulcers, and vaccination sites.^1,2 The most common type of malignancy reported in a Marjolin ulcer is an aggressive squamous cell carcinoma (SCC).^1-3 Less commonly, basal cell carcinoma (BCC) also has been reported.^1,3,4 However, cases of BCCs developing in surgical scars are exceedingly rare. We describe a case of a morphoeic BCC in a long-standing surgical scar in a 50-year-old woman with Crohn disease.

A 50-year-old woman presented with an intermittent ulceration within a horizontal surgical scar on the right side of the upper abdomen of 2 years’ duration that had not healed over the course of the last 6 months. The scar was present from surgeries conducted while she was a teenager for complications associated with Crohn disease. She underwent her first abdominal surgery for a partial gastric resection at 16 years of age, followed by multiple laparotomies from a perforated bile duct that occurred during the first surgery. The original incision created for the partial gastric resection was used for all subsequent surgeries.

The patient’s medical history was notable for central nervous system vasculitis with vision loss, chronic pancreatitis, Crohn disease, arthritis, multiple superficial BCCs on the back that were successfully treated with imiquimod cream, a nodular BCC on the neck that was surgically removed, and facial actinic keratoses treated with liquid nitrogen. She had Fitzpatrick skin type I. She grew up in a residential area in Southern Ontario and did not have a history of heavy sun exposure. She did not receive notable radiation from treatment of Crohn disease, and she usually wore a 1-piece bathing suit when swimming outdoors. According to the patient, she had never been exposed to arsenic. The patient’s family history was negative for skin cancer and she was a nonsmoker. She was taking methotrexate, prednisone, folic acid, pentazocine, and vitamin B₁₂ injections at the time of presentation for the aforementioned conditions.

On physical examination a 1.5-cm honey-crusted ulcer with surrounding violaceous erythema in a long-standing surgical scar was observed (Figure 1). There was no palpable adenopathy in the inguinal or axillary regions. The suspected diagnosis prebiopsy was an SCC developing within the scar tissue. On histologic examination sections of small nests and strands of basal cell infiltrating thick collagen bundles were visualized. The appearance was consistent with a morphoeic BCC. The pathologist’s interpretation indicated that the lesion appeared to be a morphoeic BCC within the scar as opposed to a BCC that appeared morphoeic because of background scarring. Histologic images stained with hematoxylin and eosin showed small nests and strands of basal cells penetrating thick collagen bundles (Figure 2).

Figure 1. Complete visualization of the surgical scar with the associated ulcer in the epigastric region (A). Magnified view of a honey-crusted ulcer with surrounding violaceous erythema (B).

Figure 2. Histology showed small nests and strands of basal cells penetrating thick collagen bundles (A and B)(both H&E, original magnifications ×40 and ×100).

Marjolin ulcer was first described in 1828 by the French surgeon Jean-Nicolas Marjolin who published 4 cases of ulcers arising from scar tissue but did not appreciate their malignant capacity. However, the term Marjolin ulcer is now widely accepted as meaning any malignant tumor occurring within scar tissue or a chronic nonhealing wound.^1,2

The exact incidence of malignant transformation in cutaneous wounds remains unknown, but this phenomenon can occur in individuals of all races and across all age groups.^1,5-7 The most prevalent malignancy identified on biopsy is SCC, followed by BCC, melanoma, osteosarcoma, fibrosarcoma, and liposarcoma.^1,2,6,7 With this entity infrequently occurring in the clinical setting, it often is overlooked or misdiagnosed.² In addition, malignancies presenting as Marjolin ulcers have a greater tendency to metastasize and are reported to have a higher associated fatality rate.^2,8 Thus, early recognition is essential, as a delay in diagnosis can potentially allow the tumor to progress to a life-threatening stage. In our patient, malignancy was clinically suspected based on the presence of an ulcer that was not healing despite adequate wound care and the location in a scar that was present for more than 30 years. The surgical scar had been a place of repeated trauma given the number of surgical procedures and the perforated bile duct, which can increase the potential for malignant transformation. Furthermore, the patient also was on immunosuppressive therapy for an extended period of time, possibly contributing to the development of this cancerous lesion and prior cutaneous malignancies.

The pathogenesis of a Marjolin ulcer is unclear, though many hypotheses have been suggested.^1,2,6,9 Theories investigating decreased vascularity, lowered immune surveillance, decreased regenerative capacity, genetic mutations, and injury-related release of toxins have all been postulated as possible explanations for the increase in potential of malignant transformation.^1-3,6,9 However, despite the pathogenesis, the mainstay of treatment remains wide local excision with at least 2-cm margins.^1-3,10 Alternatively, Mohs micrographic surgery can be considered for Marjolin ulcers, but it is less frequently conducted in comparison to wide local excision. Radiation therapy often follows excision as adjuvant therapy, depending on the type of tumor.^2,10 Prophylactic lymph node dissection is not indicated in most cases, but regional node dissection is suggested when palpable lymphadenopathy is present.^1,2,10 Moreover, amputation is indicated with deep bone or joint involvement.^1-3,10 Recurrence rates are high, ranging from 20% to 50%, and metastases to the brain, liver, lungs, kidneys, and lymph nodes have been reported.^1,3 The prognosis of the cutaneous malignancy in this setting is not as favorable, and the 5-year survival rate is cited at approximately 60%.³ Overall prognosis depends on several factors including location, type of malignancy, immune status, progression of disease, and lymph node metastasis. Our patient’s presentation with a BCC instead of the more common SCC should carry a good overall prognosis, though she will need to be closely followed for recurrence after wide local excision.

This novel presentation of a morpheaform BCC in a surgical scar may serve as a reminder to consider this diagnosis and biopsy nonhealing ulcers within any type of chronic wound or scar.

To the Editor:

Marjolin ulcers are malignancies arising in nonhealing cutaneous wounds. Although burn wounds are the most common type of cutaneous trauma associated with this entity, there are a multitude of possible lesions that may initiate this disease process including traumatic wounds, venous stasis ulcers, and vaccination sites.^1,2 The most common type of malignancy reported in a Marjolin ulcer is an aggressive squamous cell carcinoma (SCC).^1-3 Less commonly, basal cell carcinoma (BCC) also has been reported.^1,3,4 However, cases of BCCs developing in surgical scars are exceedingly rare. We describe a case of a morphoeic BCC in a long-standing surgical scar in a 50-year-old woman with Crohn disease.

A 50-year-old woman presented with an intermittent ulceration within a horizontal surgical scar on the right side of the upper abdomen of 2 years’ duration that had not healed over the course of the last 6 months. The scar was present from surgeries conducted while she was a teenager for complications associated with Crohn disease. She underwent her first abdominal surgery for a partial gastric resection at 16 years of age, followed by multiple laparotomies from a perforated bile duct that occurred during the first surgery. The original incision created for the partial gastric resection was used for all subsequent surgeries.

The patient’s medical history was notable for central nervous system vasculitis with vision loss, chronic pancreatitis, Crohn disease, arthritis, multiple superficial BCCs on the back that were successfully treated with imiquimod cream, a nodular BCC on the neck that was surgically removed, and facial actinic keratoses treated with liquid nitrogen. She had Fitzpatrick skin type I. She grew up in a residential area in Southern Ontario and did not have a history of heavy sun exposure. She did not receive notable radiation from treatment of Crohn disease, and she usually wore a 1-piece bathing suit when swimming outdoors. According to the patient, she had never been exposed to arsenic. The patient’s family history was negative for skin cancer and she was a nonsmoker. She was taking methotrexate, prednisone, folic acid, pentazocine, and vitamin B₁₂ injections at the time of presentation for the aforementioned conditions.

On physical examination a 1.5-cm honey-crusted ulcer with surrounding violaceous erythema in a long-standing surgical scar was observed (Figure 1). There was no palpable adenopathy in the inguinal or axillary regions. The suspected diagnosis prebiopsy was an SCC developing within the scar tissue. On histologic examination sections of small nests and strands of basal cell infiltrating thick collagen bundles were visualized. The appearance was consistent with a morphoeic BCC. The pathologist’s interpretation indicated that the lesion appeared to be a morphoeic BCC within the scar as opposed to a BCC that appeared morphoeic because of background scarring. Histologic images stained with hematoxylin and eosin showed small nests and strands of basal cells penetrating thick collagen bundles (Figure 2).

Figure 1. Complete visualization of the surgical scar with the associated ulcer in the epigastric region (A). Magnified view of a honey-crusted ulcer with surrounding violaceous erythema (B).

Figure 2. Histology showed small nests and strands of basal cells penetrating thick collagen bundles (A and B)(both H&E, original magnifications ×40 and ×100).

Marjolin ulcer was first described in 1828 by the French surgeon Jean-Nicolas Marjolin who published 4 cases of ulcers arising from scar tissue but did not appreciate their malignant capacity. However, the term Marjolin ulcer is now widely accepted as meaning any malignant tumor occurring within scar tissue or a chronic nonhealing wound.^1,2

The exact incidence of malignant transformation in cutaneous wounds remains unknown, but this phenomenon can occur in individuals of all races and across all age groups.^1,5-7 The most prevalent malignancy identified on biopsy is SCC, followed by BCC, melanoma, osteosarcoma, fibrosarcoma, and liposarcoma.^1,2,6,7 With this entity infrequently occurring in the clinical setting, it often is overlooked or misdiagnosed.² In addition, malignancies presenting as Marjolin ulcers have a greater tendency to metastasize and are reported to have a higher associated fatality rate.^2,8 Thus, early recognition is essential, as a delay in diagnosis can potentially allow the tumor to progress to a life-threatening stage. In our patient, malignancy was clinically suspected based on the presence of an ulcer that was not healing despite adequate wound care and the location in a scar that was present for more than 30 years. The surgical scar had been a place of repeated trauma given the number of surgical procedures and the perforated bile duct, which can increase the potential for malignant transformation. Furthermore, the patient also was on immunosuppressive therapy for an extended period of time, possibly contributing to the development of this cancerous lesion and prior cutaneous malignancies.

The pathogenesis of a Marjolin ulcer is unclear, though many hypotheses have been suggested.^1,2,6,9 Theories investigating decreased vascularity, lowered immune surveillance, decreased regenerative capacity, genetic mutations, and injury-related release of toxins have all been postulated as possible explanations for the increase in potential of malignant transformation.^1-3,6,9 However, despite the pathogenesis, the mainstay of treatment remains wide local excision with at least 2-cm margins.^1-3,10 Alternatively, Mohs micrographic surgery can be considered for Marjolin ulcers, but it is less frequently conducted in comparison to wide local excision. Radiation therapy often follows excision as adjuvant therapy, depending on the type of tumor.^2,10 Prophylactic lymph node dissection is not indicated in most cases, but regional node dissection is suggested when palpable lymphadenopathy is present.^1,2,10 Moreover, amputation is indicated with deep bone or joint involvement.^1-3,10 Recurrence rates are high, ranging from 20% to 50%, and metastases to the brain, liver, lungs, kidneys, and lymph nodes have been reported.^1,3 The prognosis of the cutaneous malignancy in this setting is not as favorable, and the 5-year survival rate is cited at approximately 60%.³ Overall prognosis depends on several factors including location, type of malignancy, immune status, progression of disease, and lymph node metastasis. Our patient’s presentation with a BCC instead of the more common SCC should carry a good overall prognosis, though she will need to be closely followed for recurrence after wide local excision.

This novel presentation of a morpheaform BCC in a surgical scar may serve as a reminder to consider this diagnosis and biopsy nonhealing ulcers within any type of chronic wound or scar.

KISSIMMEE, FLA. – Using a needle-free device to inject nodular basal cell carcinomas with intralesional 5-aminolevulinic acid before photodynamic therapy led to complete, years-long remissions and few side effects in a small case series.

“This approach represents an interesting alternative to Mohs, for sure,” Dr. Daniel Barolet said at the annual meeting of the American Society for Laser Medicine and Surgery. “The secret is in the injector nozzle, which lets you inject with multiple openings to get the best uniformity around the tumor.”

Mohs micrographic surgery remains the standard for basal cell carcinoma (BCC) in high-risk sites, and the number of Mohs surgeries has approximately doubled since 2001, said Dr. Barolet, adjunct professor of dermatology at McGill University in Montreal.

Mohs, however, can cause scarring, and BCCs recur in about 4% of patients. In contrast, photodynamic therapy (PDT) is associated with less scarring and pain, fewer complications, shorter recovery times, and lower costs, although the recurrence rate is about 14%, he noted.

Since PDT alone does not efficiently penetrate thick tumor volumes, it works best with pretreatment using agents such as aminolevulinic acid (ALA).

Using needles to inject the tumor, however, can cause pain, vascular damage, vasoconstriction, deep purpura, necrosis, and infection. “Because of this, no-needle injection is an interesting avenue for PDT,” he noted. Needle-free devices currently are used to inject insulin and to administer some vaccines. They are “virtually painless,” noninvasive, and tissue sparing, he said.

To explore the potential role for needle-free injection in ALA-PDT, Dr. Barolot used a prototype high-speed jet to deliver intralesional 5-ALA in the nodular facial BCCs of four patients. He then performed photoactivation with a red light–emitting diode, with continuous wave at 630 nm, irradiance at 50 mW/cm², and total fluence 50-100 J/cm².

Patients had no evidence of clinical or histopathologic recurrence for up to 7 years after treatment, Dr. Barolet reported. They experienced mild crusting at treated sites for up to a week after treatment, but no other adverse effects. Two patients needed a second treatment 2 months after the initial treatment to achieve complete remission. “Excellent cosmesis was obtained,” he added, pointing to before and after photos that showed no evidence of lesions several months after treatment.

Multicenter clinical trials are needed to further evaluate the modality, but the preliminary data suggest that intralesional PDT is a reasonable alternative to Mohs for BCCs in high-risk body sites, as long as lesions are few in number and do not affect large areas of the body, Dr. Barolet said.

The modality is especially well suited to “tricky” areas of the body that are difficult to treat with Mohs, he said.

“Developing a user-friendly, disposable no-needle injector will make it much easier for users,” he added. For low-risk BCCs in low-risk sites, conventional treatments such as surgical excision remain the best option, he said.

Dr. Barolet reported no funding sources for the study and said he had no relevant financial disclosures.

KISSIMMEE, FLA. – Using a needle-free device to inject nodular basal cell carcinomas with intralesional 5-aminolevulinic acid before photodynamic therapy led to complete, years-long remissions and few side effects in a small case series.

“This approach represents an interesting alternative to Mohs, for sure,” Dr. Daniel Barolet said at the annual meeting of the American Society for Laser Medicine and Surgery. “The secret is in the injector nozzle, which lets you inject with multiple openings to get the best uniformity around the tumor.”

Mohs micrographic surgery remains the standard for basal cell carcinoma (BCC) in high-risk sites, and the number of Mohs surgeries has approximately doubled since 2001, said Dr. Barolet, adjunct professor of dermatology at McGill University in Montreal.

Mohs, however, can cause scarring, and BCCs recur in about 4% of patients. In contrast, photodynamic therapy (PDT) is associated with less scarring and pain, fewer complications, shorter recovery times, and lower costs, although the recurrence rate is about 14%, he noted.

Since PDT alone does not efficiently penetrate thick tumor volumes, it works best with pretreatment using agents such as aminolevulinic acid (ALA).

Using needles to inject the tumor, however, can cause pain, vascular damage, vasoconstriction, deep purpura, necrosis, and infection. “Because of this, no-needle injection is an interesting avenue for PDT,” he noted. Needle-free devices currently are used to inject insulin and to administer some vaccines. They are “virtually painless,” noninvasive, and tissue sparing, he said.

To explore the potential role for needle-free injection in ALA-PDT, Dr. Barolot used a prototype high-speed jet to deliver intralesional 5-ALA in the nodular facial BCCs of four patients. He then performed photoactivation with a red light–emitting diode, with continuous wave at 630 nm, irradiance at 50 mW/cm², and total fluence 50-100 J/cm².

Patients had no evidence of clinical or histopathologic recurrence for up to 7 years after treatment, Dr. Barolet reported. They experienced mild crusting at treated sites for up to a week after treatment, but no other adverse effects. Two patients needed a second treatment 2 months after the initial treatment to achieve complete remission. “Excellent cosmesis was obtained,” he added, pointing to before and after photos that showed no evidence of lesions several months after treatment.

Multicenter clinical trials are needed to further evaluate the modality, but the preliminary data suggest that intralesional PDT is a reasonable alternative to Mohs for BCCs in high-risk body sites, as long as lesions are few in number and do not affect large areas of the body, Dr. Barolet said.

The modality is especially well suited to “tricky” areas of the body that are difficult to treat with Mohs, he said.

“Developing a user-friendly, disposable no-needle injector will make it much easier for users,” he added. For low-risk BCCs in low-risk sites, conventional treatments such as surgical excision remain the best option, he said.

Dr. Barolet reported no funding sources for the study and said he had no relevant financial disclosures.

KISSIMMEE, FLA. – Using a needle-free device to inject nodular basal cell carcinomas with intralesional 5-aminolevulinic acid before photodynamic therapy led to complete, years-long remissions and few side effects in a small case series.

“This approach represents an interesting alternative to Mohs, for sure,” Dr. Daniel Barolet said at the annual meeting of the American Society for Laser Medicine and Surgery. “The secret is in the injector nozzle, which lets you inject with multiple openings to get the best uniformity around the tumor.”

Mohs micrographic surgery remains the standard for basal cell carcinoma (BCC) in high-risk sites, and the number of Mohs surgeries has approximately doubled since 2001, said Dr. Barolet, adjunct professor of dermatology at McGill University in Montreal.

Mohs, however, can cause scarring, and BCCs recur in about 4% of patients. In contrast, photodynamic therapy (PDT) is associated with less scarring and pain, fewer complications, shorter recovery times, and lower costs, although the recurrence rate is about 14%, he noted.

Since PDT alone does not efficiently penetrate thick tumor volumes, it works best with pretreatment using agents such as aminolevulinic acid (ALA).

Using needles to inject the tumor, however, can cause pain, vascular damage, vasoconstriction, deep purpura, necrosis, and infection. “Because of this, no-needle injection is an interesting avenue for PDT,” he noted. Needle-free devices currently are used to inject insulin and to administer some vaccines. They are “virtually painless,” noninvasive, and tissue sparing, he said.

To explore the potential role for needle-free injection in ALA-PDT, Dr. Barolot used a prototype high-speed jet to deliver intralesional 5-ALA in the nodular facial BCCs of four patients. He then performed photoactivation with a red light–emitting diode, with continuous wave at 630 nm, irradiance at 50 mW/cm², and total fluence 50-100 J/cm².

Patients had no evidence of clinical or histopathologic recurrence for up to 7 years after treatment, Dr. Barolet reported. They experienced mild crusting at treated sites for up to a week after treatment, but no other adverse effects. Two patients needed a second treatment 2 months after the initial treatment to achieve complete remission. “Excellent cosmesis was obtained,” he added, pointing to before and after photos that showed no evidence of lesions several months after treatment.

Multicenter clinical trials are needed to further evaluate the modality, but the preliminary data suggest that intralesional PDT is a reasonable alternative to Mohs for BCCs in high-risk body sites, as long as lesions are few in number and do not affect large areas of the body, Dr. Barolet said.

The modality is especially well suited to “tricky” areas of the body that are difficult to treat with Mohs, he said.

“Developing a user-friendly, disposable no-needle injector will make it much easier for users,” he added. For low-risk BCCs in low-risk sites, conventional treatments such as surgical excision remain the best option, he said.

Dr. Barolet reported no funding sources for the study and said he had no relevant financial disclosures.

Case Report

A 45-year-old man presented with persistent swelling and “black-and-blue” lesions on the legs, feet, and toes of 6 months’ duration. The painless lesions first appeared on the left lower leg and then began to appear on the right leg in recent months. Three weeks prior to presentation, he developed swelling of the left lower leg during hospitalization for a lumbar laminectomy. A venous ultrasound was negative for a deep vein thrombosis. He denied trauma or history of bleeding diathesis. He did not report symptoms of dyspnea, angina, or claudication, and a review of systems was unremarkable.

The patient’s medical history included spinal stenosis, chronic back pain, osteoarthritis, and anxiety. His medications included oxycodone, zolpidem, and alprazolam. In addition to a recent lumbar laminectomy, he had undergone extensive dental work in the last 6 months. The patient denied the use of cigarettes, alcohol, or intravenous drugs.

Physical examination revealed scattered, purple, segmented patches on the dorsal and plantar aspects of the feet, both calves, both heels, and toes (Figure 1). Mild nonpitting edema was present below the left knee along with edema on the dorsum of the left foot. The distribution of the lesions was initially suggestive of cholesterol embolization syndrome; however, both the femoral and posterior tibial pulses were symmetric and palpable (+2). Well-demarcated violaceous plaques with central clearing and a rustlike discoloration were noted on the hard and soft palates. Cervical lymphadenopathy was not present.

Figure 1. Scattered, purple, segmented patches along the dorsal surface of the toes. Figure 2. Punch biopsy specimen of the right fourth toe showed an acanthotic epidermis and focally lobulated proliferation of cells and small caliber vessels, representing the plaque stage of Kaposi sarcoma (H&E, original magnification ×40). Figure 3. Red blood cells were evident in the holes and in between the tumor cells. The promontory sign was present and the native vessels were seen protruding into the lumens of newly formed tumoral vessels (H&E, original magnification ×400).

Laboratory tests including a repeat venous ultrasound of the left lower leg revealed no evidence of deep vein thrombosis. Ankle brachial index revealed no abnormalities and blood flow to the lower legs was adequate. Computed tomography scans of the chest, abdomen, and pelvis were unremarkable except for mild splenomegaly and moderate cardiomegaly. Lastly, human immunodeficiency virus (HIV) 1 and HIV-2 enzyme immunoassay was reactive.

Histopathologic examination of a punch biopsy from the right fourth toe was representative of the plaque stage of Kaposi sarcoma (KS) with a diffuse collection of extravasated erythrocytes and neoplastic vascular proliferation among a background of numerous plasma cells and hemosiderophages (Figure 2). Higher magnification illustrated the promontory sign, whereby native vessels encroach on neoplastic slitlike vascular spaces (Figure 3). A final diagnosis of AIDS-related KS was made. The patient was referred to an infectious disease specialist for evaluation of his CD4 levels and HIV management.

Comment

Kaposi sarcoma is a neoplastic proliferation of the blood vessels in the skin characterized by the formation of violaceous macules and papules that often appear on a single distal extremity, such as the foot. Over time the lesions can develop on the opposite extremity and coalesce into poorly demarcated plaques and nodules with accompanying stasis and lymphedema of the involved extremities.¹ Evolution of the lesions depends on the KS subtype. The most common clinical variant of KS is the classic form, which primarily is seen in those of Mediterranean, Eastern European, or Ashkenazi Jewish descent, with a predilection for men and older adults.^1,2 The endemic form of KS, or African KS, is more aggressive with rapid visceral involvement and rare skin lesions; it is common among prepubertal children in sub-Saharan Africa with no predilection for either sex.² In the setting of severe immune suppression, organ transplantation, or chemotherapy, a third KS subtype known as iatrogenic KS can occur. The clinical course of iatrogenic KS may range from scattered cutaneous lesions to diffuse involvement secondary to increased dosages and long-term use of immunosuppressive agents.²

Our patient had AIDS-related or epidemic KS. AIDS-related KS is largely predominant among homosexual men, but due to the awareness of safe sexual practices and the introduction of highly active antiretroviral therapy (HAART), KS incidence in the United States has declined.^1,2 However, despite recent advances in HIV therapy, AIDS-related KS is still the most common neoplasm seen in AIDS patients and is the presenting manifestation of AIDS in up to 30% of cases.³ Up to 22% of cases first appear on the gingiva, hard palate, and tongue, with concomitant dysphagia and airway obstruction in severe cases.^4,5 More advanced cases of AIDS-related KS can present with initial symptoms such as abdominal pain, melena, dyspnea, lymphadenopathy, and weight loss, which suggests involvement of the gastrointestinal tract, lungs, and other organ systems.

Regardless of the subtype, the etiology of KS currently is thought to be secondary to infection with human herpesvirus 8 (HHV-8), also known as Kaposi sarcoma–associated herpesvirus (KSHV).¹ Human immunodeficiency virus infection can enhance KSHV expression through the HIV transactivator protein, which activates KSHV oncogenes and angiogenic growth factors to promote the development of KS lesions.^2,6Likewise, KSHV enhances HIV upregulation through latency-associated nuclear antigen, a protein that interacts with HIV Tat protein to further activate long terminal repeats of HIV-1.²

The differential diagnosis of KS is broad. The slightly elevated, pinkish reddish discolorations of KS may resemble verruca plana and/or squamous cell carcinoma on visual observation, whereas nodular KS may resemble giant cell granuloma, pyogenic granuloma, or hemangiopericytoma.^4,7 Cases of KS with lymph node involvement may include a differential diagnosis of lymphoma, angiosarcoma, and bacillary angiomatosis.⁷ Other vascular pathologies that may be considered in the differential diagnosis include vascular tumors (eg, spindle cell hemangioma), fibrohistiocytic tumors (eg, dermatofibrosarcoma protuberans), and a collection of spindle cell mesenchymal tumors.⁸

Kaposi sarcoma progresses through several histologic stages beginning with the patch stage, then progressing to the plaque stage, and finally culminating in the nodular stage. The patch stage is the first stage in KS progression and a crowded dermis can be seen with the formation of slitlike vascular spaces lined by endothelial cells with red blood cell extravasation into the lumens of newly formed vascular channels, hence demonstrating the promontory sign.⁸ In the plaque stage, the promontory sign still is present and there is a greater presence of slitlike spaces, giving the micrograph an overall sievelike appearance. Erythrocytes can be found residing within the clear cytoplasm of spindled endothelial cells, leading to the development of autolumination. Finally, the nodular stage is characterized by a neoplastic proliferation of monomorphic spindle cells that form fasciclelike nests in the dermis.⁸ To distinguish KS from other angioproliferative tumors, one can stain for HHV-8 latent nuclear antigen-1, which is found in the nuclei of infected endothelial cells.^1,8,9

Kaposi sarcoma is treated through a variety of mechanisms depending on the subtype. Classic KS lesions often can be observed as they a follow a benign and nonaggressive course.¹ Highly active antiretroviral therapy is the mainstay of care in AIDS-related KS and has led to regression of lesions and a remarkable decline in the incidence of KS.³ The HAART regimen consists of a protease inhibitor or nonnucleoside reverse-transcriptase inhibitor with the addition of 2 nucleoside reverse-transcriptase inhibitors. More advanced or refractory cases of KS often require dual treatment with HAART and a chemotherapy agent such as pegylated liposomal doxorubicin. Combination therapy has been shown to result in stronger therapeutic responses and lower relapse rates in contrast to HAART alone.⁷ Patients also may consider other treatment modalities to manage KS lesions such as surgical removal of lesions, laser therapy, paclitaxel, interferon alfa, oral etoposide, thalidomide, and topical therapies such as imiquimod cream 5% and alitretinoin.^1,7

Conclusion

Kaposi sarcoma is a rare but concerning dermatologic condition that signals the need for further diagnostic evaluation. Coexpression of viruses such as HIV and HHV-8 can result in a more virulent and rapid progression of KS to encompass both mucous membrane and systemic involvement. Our patient’s lesions were the first presenting sign of HIV infection despite being asymptomatic at the time of diagnosis, which is alarming in the sense that more than 21% of HIV-infected individuals in the United States have not been clinically diagnosed.¹⁰ Inquiry of HIV risk factors and routine screening for HIV should be performed in refractory cases of skin disease as an underlying clue to further investigate the immune system. We present our unique case of mucocutaneous development of KS in an asymptomatic HIV-positive man to stress the importance of KS recognition and management.

Case Report

A 45-year-old man presented with persistent swelling and “black-and-blue” lesions on the legs, feet, and toes of 6 months’ duration. The painless lesions first appeared on the left lower leg and then began to appear on the right leg in recent months. Three weeks prior to presentation, he developed swelling of the left lower leg during hospitalization for a lumbar laminectomy. A venous ultrasound was negative for a deep vein thrombosis. He denied trauma or history of bleeding diathesis. He did not report symptoms of dyspnea, angina, or claudication, and a review of systems was unremarkable.

The patient’s medical history included spinal stenosis, chronic back pain, osteoarthritis, and anxiety. His medications included oxycodone, zolpidem, and alprazolam. In addition to a recent lumbar laminectomy, he had undergone extensive dental work in the last 6 months. The patient denied the use of cigarettes, alcohol, or intravenous drugs.

Physical examination revealed scattered, purple, segmented patches on the dorsal and plantar aspects of the feet, both calves, both heels, and toes (Figure 1). Mild nonpitting edema was present below the left knee along with edema on the dorsum of the left foot. The distribution of the lesions was initially suggestive of cholesterol embolization syndrome; however, both the femoral and posterior tibial pulses were symmetric and palpable (+2). Well-demarcated violaceous plaques with central clearing and a rustlike discoloration were noted on the hard and soft palates. Cervical lymphadenopathy was not present.

Figure 1. Scattered, purple, segmented patches along the dorsal surface of the toes. Figure 2. Punch biopsy specimen of the right fourth toe showed an acanthotic epidermis and focally lobulated proliferation of cells and small caliber vessels, representing the plaque stage of Kaposi sarcoma (H&E, original magnification ×40). Figure 3. Red blood cells were evident in the holes and in between the tumor cells. The promontory sign was present and the native vessels were seen protruding into the lumens of newly formed tumoral vessels (H&E, original magnification ×400).

Laboratory tests including a repeat venous ultrasound of the left lower leg revealed no evidence of deep vein thrombosis. Ankle brachial index revealed no abnormalities and blood flow to the lower legs was adequate. Computed tomography scans of the chest, abdomen, and pelvis were unremarkable except for mild splenomegaly and moderate cardiomegaly. Lastly, human immunodeficiency virus (HIV) 1 and HIV-2 enzyme immunoassay was reactive.

Histopathologic examination of a punch biopsy from the right fourth toe was representative of the plaque stage of Kaposi sarcoma (KS) with a diffuse collection of extravasated erythrocytes and neoplastic vascular proliferation among a background of numerous plasma cells and hemosiderophages (Figure 2). Higher magnification illustrated the promontory sign, whereby native vessels encroach on neoplastic slitlike vascular spaces (Figure 3). A final diagnosis of AIDS-related KS was made. The patient was referred to an infectious disease specialist for evaluation of his CD4 levels and HIV management.

Comment

Kaposi sarcoma is a neoplastic proliferation of the blood vessels in the skin characterized by the formation of violaceous macules and papules that often appear on a single distal extremity, such as the foot. Over time the lesions can develop on the opposite extremity and coalesce into poorly demarcated plaques and nodules with accompanying stasis and lymphedema of the involved extremities.¹ Evolution of the lesions depends on the KS subtype. The most common clinical variant of KS is the classic form, which primarily is seen in those of Mediterranean, Eastern European, or Ashkenazi Jewish descent, with a predilection for men and older adults.^1,2 The endemic form of KS, or African KS, is more aggressive with rapid visceral involvement and rare skin lesions; it is common among prepubertal children in sub-Saharan Africa with no predilection for either sex.² In the setting of severe immune suppression, organ transplantation, or chemotherapy, a third KS subtype known as iatrogenic KS can occur. The clinical course of iatrogenic KS may range from scattered cutaneous lesions to diffuse involvement secondary to increased dosages and long-term use of immunosuppressive agents.²

Our patient had AIDS-related or epidemic KS. AIDS-related KS is largely predominant among homosexual men, but due to the awareness of safe sexual practices and the introduction of highly active antiretroviral therapy (HAART), KS incidence in the United States has declined.^1,2 However, despite recent advances in HIV therapy, AIDS-related KS is still the most common neoplasm seen in AIDS patients and is the presenting manifestation of AIDS in up to 30% of cases.³ Up to 22% of cases first appear on the gingiva, hard palate, and tongue, with concomitant dysphagia and airway obstruction in severe cases.^4,5 More advanced cases of AIDS-related KS can present with initial symptoms such as abdominal pain, melena, dyspnea, lymphadenopathy, and weight loss, which suggests involvement of the gastrointestinal tract, lungs, and other organ systems.

Regardless of the subtype, the etiology of KS currently is thought to be secondary to infection with human herpesvirus 8 (HHV-8), also known as Kaposi sarcoma–associated herpesvirus (KSHV).¹ Human immunodeficiency virus infection can enhance KSHV expression through the HIV transactivator protein, which activates KSHV oncogenes and angiogenic growth factors to promote the development of KS lesions.^2,6Likewise, KSHV enhances HIV upregulation through latency-associated nuclear antigen, a protein that interacts with HIV Tat protein to further activate long terminal repeats of HIV-1.²

The differential diagnosis of KS is broad. The slightly elevated, pinkish reddish discolorations of KS may resemble verruca plana and/or squamous cell carcinoma on visual observation, whereas nodular KS may resemble giant cell granuloma, pyogenic granuloma, or hemangiopericytoma.^4,7 Cases of KS with lymph node involvement may include a differential diagnosis of lymphoma, angiosarcoma, and bacillary angiomatosis.⁷ Other vascular pathologies that may be considered in the differential diagnosis include vascular tumors (eg, spindle cell hemangioma), fibrohistiocytic tumors (eg, dermatofibrosarcoma protuberans), and a collection of spindle cell mesenchymal tumors.⁸

Kaposi sarcoma progresses through several histologic stages beginning with the patch stage, then progressing to the plaque stage, and finally culminating in the nodular stage. The patch stage is the first stage in KS progression and a crowded dermis can be seen with the formation of slitlike vascular spaces lined by endothelial cells with red blood cell extravasation into the lumens of newly formed vascular channels, hence demonstrating the promontory sign.⁸ In the plaque stage, the promontory sign still is present and there is a greater presence of slitlike spaces, giving the micrograph an overall sievelike appearance. Erythrocytes can be found residing within the clear cytoplasm of spindled endothelial cells, leading to the development of autolumination. Finally, the nodular stage is characterized by a neoplastic proliferation of monomorphic spindle cells that form fasciclelike nests in the dermis.⁸ To distinguish KS from other angioproliferative tumors, one can stain for HHV-8 latent nuclear antigen-1, which is found in the nuclei of infected endothelial cells.^1,8,9

Kaposi sarcoma is treated through a variety of mechanisms depending on the subtype. Classic KS lesions often can be observed as they a follow a benign and nonaggressive course.¹ Highly active antiretroviral therapy is the mainstay of care in AIDS-related KS and has led to regression of lesions and a remarkable decline in the incidence of KS.³ The HAART regimen consists of a protease inhibitor or nonnucleoside reverse-transcriptase inhibitor with the addition of 2 nucleoside reverse-transcriptase inhibitors. More advanced or refractory cases of KS often require dual treatment with HAART and a chemotherapy agent such as pegylated liposomal doxorubicin. Combination therapy has been shown to result in stronger therapeutic responses and lower relapse rates in contrast to HAART alone.⁷ Patients also may consider other treatment modalities to manage KS lesions such as surgical removal of lesions, laser therapy, paclitaxel, interferon alfa, oral etoposide, thalidomide, and topical therapies such as imiquimod cream 5% and alitretinoin.^1,7

Conclusion

Kaposi sarcoma is a rare but concerning dermatologic condition that signals the need for further diagnostic evaluation. Coexpression of viruses such as HIV and HHV-8 can result in a more virulent and rapid progression of KS to encompass both mucous membrane and systemic involvement. Our patient’s lesions were the first presenting sign of HIV infection despite being asymptomatic at the time of diagnosis, which is alarming in the sense that more than 21% of HIV-infected individuals in the United States have not been clinically diagnosed.¹⁰ Inquiry of HIV risk factors and routine screening for HIV should be performed in refractory cases of skin disease as an underlying clue to further investigate the immune system. We present our unique case of mucocutaneous development of KS in an asymptomatic HIV-positive man to stress the importance of KS recognition and management.

Case Report

A 45-year-old man presented with persistent swelling and “black-and-blue” lesions on the legs, feet, and toes of 6 months’ duration. The painless lesions first appeared on the left lower leg and then began to appear on the right leg in recent months. Three weeks prior to presentation, he developed swelling of the left lower leg during hospitalization for a lumbar laminectomy. A venous ultrasound was negative for a deep vein thrombosis. He denied trauma or history of bleeding diathesis. He did not report symptoms of dyspnea, angina, or claudication, and a review of systems was unremarkable.

The patient’s medical history included spinal stenosis, chronic back pain, osteoarthritis, and anxiety. His medications included oxycodone, zolpidem, and alprazolam. In addition to a recent lumbar laminectomy, he had undergone extensive dental work in the last 6 months. The patient denied the use of cigarettes, alcohol, or intravenous drugs.

Physical examination revealed scattered, purple, segmented patches on the dorsal and plantar aspects of the feet, both calves, both heels, and toes (Figure 1). Mild nonpitting edema was present below the left knee along with edema on the dorsum of the left foot. The distribution of the lesions was initially suggestive of cholesterol embolization syndrome; however, both the femoral and posterior tibial pulses were symmetric and palpable (+2). Well-demarcated violaceous plaques with central clearing and a rustlike discoloration were noted on the hard and soft palates. Cervical lymphadenopathy was not present.

Figure 1. Scattered, purple, segmented patches along the dorsal surface of the toes. Figure 2. Punch biopsy specimen of the right fourth toe showed an acanthotic epidermis and focally lobulated proliferation of cells and small caliber vessels, representing the plaque stage of Kaposi sarcoma (H&E, original magnification ×40). Figure 3. Red blood cells were evident in the holes and in between the tumor cells. The promontory sign was present and the native vessels were seen protruding into the lumens of newly formed tumoral vessels (H&E, original magnification ×400).

Laboratory tests including a repeat venous ultrasound of the left lower leg revealed no evidence of deep vein thrombosis. Ankle brachial index revealed no abnormalities and blood flow to the lower legs was adequate. Computed tomography scans of the chest, abdomen, and pelvis were unremarkable except for mild splenomegaly and moderate cardiomegaly. Lastly, human immunodeficiency virus (HIV) 1 and HIV-2 enzyme immunoassay was reactive.

Histopathologic examination of a punch biopsy from the right fourth toe was representative of the plaque stage of Kaposi sarcoma (KS) with a diffuse collection of extravasated erythrocytes and neoplastic vascular proliferation among a background of numerous plasma cells and hemosiderophages (Figure 2). Higher magnification illustrated the promontory sign, whereby native vessels encroach on neoplastic slitlike vascular spaces (Figure 3). A final diagnosis of AIDS-related KS was made. The patient was referred to an infectious disease specialist for evaluation of his CD4 levels and HIV management.

Comment

Kaposi sarcoma is a neoplastic proliferation of the blood vessels in the skin characterized by the formation of violaceous macules and papules that often appear on a single distal extremity, such as the foot. Over time the lesions can develop on the opposite extremity and coalesce into poorly demarcated plaques and nodules with accompanying stasis and lymphedema of the involved extremities.¹ Evolution of the lesions depends on the KS subtype. The most common clinical variant of KS is the classic form, which primarily is seen in those of Mediterranean, Eastern European, or Ashkenazi Jewish descent, with a predilection for men and older adults.^1,2 The endemic form of KS, or African KS, is more aggressive with rapid visceral involvement and rare skin lesions; it is common among prepubertal children in sub-Saharan Africa with no predilection for either sex.² In the setting of severe immune suppression, organ transplantation, or chemotherapy, a third KS subtype known as iatrogenic KS can occur. The clinical course of iatrogenic KS may range from scattered cutaneous lesions to diffuse involvement secondary to increased dosages and long-term use of immunosuppressive agents.²

Our patient had AIDS-related or epidemic KS. AIDS-related KS is largely predominant among homosexual men, but due to the awareness of safe sexual practices and the introduction of highly active antiretroviral therapy (HAART), KS incidence in the United States has declined.^1,2 However, despite recent advances in HIV therapy, AIDS-related KS is still the most common neoplasm seen in AIDS patients and is the presenting manifestation of AIDS in up to 30% of cases.³ Up to 22% of cases first appear on the gingiva, hard palate, and tongue, with concomitant dysphagia and airway obstruction in severe cases.^4,5 More advanced cases of AIDS-related KS can present with initial symptoms such as abdominal pain, melena, dyspnea, lymphadenopathy, and weight loss, which suggests involvement of the gastrointestinal tract, lungs, and other organ systems.

Regardless of the subtype, the etiology of KS currently is thought to be secondary to infection with human herpesvirus 8 (HHV-8), also known as Kaposi sarcoma–associated herpesvirus (KSHV).¹ Human immunodeficiency virus infection can enhance KSHV expression through the HIV transactivator protein, which activates KSHV oncogenes and angiogenic growth factors to promote the development of KS lesions.^2,6Likewise, KSHV enhances HIV upregulation through latency-associated nuclear antigen, a protein that interacts with HIV Tat protein to further activate long terminal repeats of HIV-1.²

The differential diagnosis of KS is broad. The slightly elevated, pinkish reddish discolorations of KS may resemble verruca plana and/or squamous cell carcinoma on visual observation, whereas nodular KS may resemble giant cell granuloma, pyogenic granuloma, or hemangiopericytoma.^4,7 Cases of KS with lymph node involvement may include a differential diagnosis of lymphoma, angiosarcoma, and bacillary angiomatosis.⁷ Other vascular pathologies that may be considered in the differential diagnosis include vascular tumors (eg, spindle cell hemangioma), fibrohistiocytic tumors (eg, dermatofibrosarcoma protuberans), and a collection of spindle cell mesenchymal tumors.⁸

Kaposi sarcoma progresses through several histologic stages beginning with the patch stage, then progressing to the plaque stage, and finally culminating in the nodular stage. The patch stage is the first stage in KS progression and a crowded dermis can be seen with the formation of slitlike vascular spaces lined by endothelial cells with red blood cell extravasation into the lumens of newly formed vascular channels, hence demonstrating the promontory sign.⁸ In the plaque stage, the promontory sign still is present and there is a greater presence of slitlike spaces, giving the micrograph an overall sievelike appearance. Erythrocytes can be found residing within the clear cytoplasm of spindled endothelial cells, leading to the development of autolumination. Finally, the nodular stage is characterized by a neoplastic proliferation of monomorphic spindle cells that form fasciclelike nests in the dermis.⁸ To distinguish KS from other angioproliferative tumors, one can stain for HHV-8 latent nuclear antigen-1, which is found in the nuclei of infected endothelial cells.^1,8,9

Kaposi sarcoma is treated through a variety of mechanisms depending on the subtype. Classic KS lesions often can be observed as they a follow a benign and nonaggressive course.¹ Highly active antiretroviral therapy is the mainstay of care in AIDS-related KS and has led to regression of lesions and a remarkable decline in the incidence of KS.³ The HAART regimen consists of a protease inhibitor or nonnucleoside reverse-transcriptase inhibitor with the addition of 2 nucleoside reverse-transcriptase inhibitors. More advanced or refractory cases of KS often require dual treatment with HAART and a chemotherapy agent such as pegylated liposomal doxorubicin. Combination therapy has been shown to result in stronger therapeutic responses and lower relapse rates in contrast to HAART alone.⁷ Patients also may consider other treatment modalities to manage KS lesions such as surgical removal of lesions, laser therapy, paclitaxel, interferon alfa, oral etoposide, thalidomide, and topical therapies such as imiquimod cream 5% and alitretinoin.^1,7

Conclusion

Kaposi sarcoma is a rare but concerning dermatologic condition that signals the need for further diagnostic evaluation. Coexpression of viruses such as HIV and HHV-8 can result in a more virulent and rapid progression of KS to encompass both mucous membrane and systemic involvement. Our patient’s lesions were the first presenting sign of HIV infection despite being asymptomatic at the time of diagnosis, which is alarming in the sense that more than 21% of HIV-infected individuals in the United States have not been clinically diagnosed.¹⁰ Inquiry of HIV risk factors and routine screening for HIV should be performed in refractory cases of skin disease as an underlying clue to further investigate the immune system. We present our unique case of mucocutaneous development of KS in an asymptomatic HIV-positive man to stress the importance of KS recognition and management.

To the Editor:

A 61-year-old man with a medical history of type 2 diabetes mellitus presented to us with a 2.5×3.0-cm erythematous, ulcerated, and exophytic tumor on the right dorsal forearm that had rapidly developed over 2 weeks. A tangential biopsy was performed followed by treatment with electrodesiccation and curettage (ED&C). Histology revealed a squamous cell carcinoma (SCC), keratoacanthoma (KA) type. Over the next 11 days the lesion rapidly recurred and the patient returned with his own daily photodocumentation of the KA’s progression (Figure). The lesion was re-excised with 5-mm margins; histology again revealed SCC, KA type, with deep margin involvement. Chest radiograph revealed findings suspicious for metastatic lesions in the right lung. He was referred to oncology for metastatic workup; positron emission tomography was negative and ultimately the lung lesion was found to be benign. The patient underwent adjuvant radia-tion to the KA resection bed and lymph nodes with minimal side effects. The patient has remained cancer free to date.

Keratoacanthomas are rapidly growing, typically painless, cutaneous neoplasms that often develop on sun-exposed areas. They can occur spontaneously or following trauma and have the propensity to regress with time.^1-3 They are described as progressing through 3 clinical stages: rapid proliferation, mature/stable, and involution. However, KAs can be aggressive, becoming locally destructive; therefore, KAs are typically treated to avoid further morbidity. Keratoacanthomas may be considered a subtype of SCC, as some have the potential to become locally destructive and metastasize.^3-5 There are reports of spontaneous resolution of KAs over weeks to months, though surgical excision is the gold standard of treatment.^3,5

Reactive KA is a subtype that is thought to develop at the site of prior trauma, representing a sort of Köbner phenomenon.^3,4 We demonstrated a case of a recurrent KA in the setting of recent ED&C. Several reports describe KAs developing after dermatologic surgery, including Mohs micrographic surgery, laser resurfacing, radiation therapy, and after skin grafting.^3,4,6 Trauma-induced epidermal injury and dermal inflammation may play a role in postoperative KA formation or recurrence.⁶

Keratoacanthoma recurrence has been reported in 3% to 8% of cases within a few weeks after treatment, as seen in our current patient.^3,5 In our case, the patient photodocumented the regrowth of his lesion (Figure). Treatment of reactive KAs may be therapeutically challenging, as they can form or worsen with repeated surgeries and may require several treatment modalities to eradicate them.⁴ Treatment options include observation, ED&C, excision, Mohs micrographic surgery, radiation, cryosurgery, laser, isotretinoin, acitretin, imiquimod, 5-fluorouracil, methotrexate, interferon alfa-2b, or bleomycin, to name a few.^3,4,7

Keratoacanthoma recurrence at day 1 (A), day 3 (B), day 5 (C),day 6 (D), day 7 (E), and day 9 (F) following electrodesiccation and curettage.

Combination therapy should be considered in the presence of recurrent and/or aggressive KAs, such as in our case. Our patient has remained disease free after a combination of surgical excision with radiation therapy.

To the Editor:

A 61-year-old man with a medical history of type 2 diabetes mellitus presented to us with a 2.5×3.0-cm erythematous, ulcerated, and exophytic tumor on the right dorsal forearm that had rapidly developed over 2 weeks. A tangential biopsy was performed followed by treatment with electrodesiccation and curettage (ED&C). Histology revealed a squamous cell carcinoma (SCC), keratoacanthoma (KA) type. Over the next 11 days the lesion rapidly recurred and the patient returned with his own daily photodocumentation of the KA’s progression (Figure). The lesion was re-excised with 5-mm margins; histology again revealed SCC, KA type, with deep margin involvement. Chest radiograph revealed findings suspicious for metastatic lesions in the right lung. He was referred to oncology for metastatic workup; positron emission tomography was negative and ultimately the lung lesion was found to be benign. The patient underwent adjuvant radia-tion to the KA resection bed and lymph nodes with minimal side effects. The patient has remained cancer free to date.

Keratoacanthomas are rapidly growing, typically painless, cutaneous neoplasms that often develop on sun-exposed areas. They can occur spontaneously or following trauma and have the propensity to regress with time.^1-3 They are described as progressing through 3 clinical stages: rapid proliferation, mature/stable, and involution. However, KAs can be aggressive, becoming locally destructive; therefore, KAs are typically treated to avoid further morbidity. Keratoacanthomas may be considered a subtype of SCC, as some have the potential to become locally destructive and metastasize.^3-5 There are reports of spontaneous resolution of KAs over weeks to months, though surgical excision is the gold standard of treatment.^3,5

Reactive KA is a subtype that is thought to develop at the site of prior trauma, representing a sort of Köbner phenomenon.^3,4 We demonstrated a case of a recurrent KA in the setting of recent ED&C. Several reports describe KAs developing after dermatologic surgery, including Mohs micrographic surgery, laser resurfacing, radiation therapy, and after skin grafting.^3,4,6 Trauma-induced epidermal injury and dermal inflammation may play a role in postoperative KA formation or recurrence.⁶

Keratoacanthoma recurrence has been reported in 3% to 8% of cases within a few weeks after treatment, as seen in our current patient.^3,5 In our case, the patient photodocumented the regrowth of his lesion (Figure). Treatment of reactive KAs may be therapeutically challenging, as they can form or worsen with repeated surgeries and may require several treatment modalities to eradicate them.⁴ Treatment options include observation, ED&C, excision, Mohs micrographic surgery, radiation, cryosurgery, laser, isotretinoin, acitretin, imiquimod, 5-fluorouracil, methotrexate, interferon alfa-2b, or bleomycin, to name a few.^3,4,7

Keratoacanthoma recurrence at day 1 (A), day 3 (B), day 5 (C),day 6 (D), day 7 (E), and day 9 (F) following electrodesiccation and curettage.

Combination therapy should be considered in the presence of recurrent and/or aggressive KAs, such as in our case. Our patient has remained disease free after a combination of surgical excision with radiation therapy.

To the Editor:

A 61-year-old man with a medical history of type 2 diabetes mellitus presented to us with a 2.5×3.0-cm erythematous, ulcerated, and exophytic tumor on the right dorsal forearm that had rapidly developed over 2 weeks. A tangential biopsy was performed followed by treatment with electrodesiccation and curettage (ED&C). Histology revealed a squamous cell carcinoma (SCC), keratoacanthoma (KA) type. Over the next 11 days the lesion rapidly recurred and the patient returned with his own daily photodocumentation of the KA’s progression (Figure). The lesion was re-excised with 5-mm margins; histology again revealed SCC, KA type, with deep margin involvement. Chest radiograph revealed findings suspicious for metastatic lesions in the right lung. He was referred to oncology for metastatic workup; positron emission tomography was negative and ultimately the lung lesion was found to be benign. The patient underwent adjuvant radia-tion to the KA resection bed and lymph nodes with minimal side effects. The patient has remained cancer free to date.

Keratoacanthomas are rapidly growing, typically painless, cutaneous neoplasms that often develop on sun-exposed areas. They can occur spontaneously or following trauma and have the propensity to regress with time.^1-3 They are described as progressing through 3 clinical stages: rapid proliferation, mature/stable, and involution. However, KAs can be aggressive, becoming locally destructive; therefore, KAs are typically treated to avoid further morbidity. Keratoacanthomas may be considered a subtype of SCC, as some have the potential to become locally destructive and metastasize.^3-5 There are reports of spontaneous resolution of KAs over weeks to months, though surgical excision is the gold standard of treatment.^3,5

Reactive KA is a subtype that is thought to develop at the site of prior trauma, representing a sort of Köbner phenomenon.^3,4 We demonstrated a case of a recurrent KA in the setting of recent ED&C. Several reports describe KAs developing after dermatologic surgery, including Mohs micrographic surgery, laser resurfacing, radiation therapy, and after skin grafting.^3,4,6 Trauma-induced epidermal injury and dermal inflammation may play a role in postoperative KA formation or recurrence.⁶

Keratoacanthoma recurrence has been reported in 3% to 8% of cases within a few weeks after treatment, as seen in our current patient.^3,5 In our case, the patient photodocumented the regrowth of his lesion (Figure). Treatment of reactive KAs may be therapeutically challenging, as they can form or worsen with repeated surgeries and may require several treatment modalities to eradicate them.⁴ Treatment options include observation, ED&C, excision, Mohs micrographic surgery, radiation, cryosurgery, laser, isotretinoin, acitretin, imiquimod, 5-fluorouracil, methotrexate, interferon alfa-2b, or bleomycin, to name a few.^3,4,7

Keratoacanthoma recurrence at day 1 (A), day 3 (B), day 5 (C),day 6 (D), day 7 (E), and day 9 (F) following electrodesiccation and curettage.

Combination therapy should be considered in the presence of recurrent and/or aggressive KAs, such as in our case. Our patient has remained disease free after a combination of surgical excision with radiation therapy.

Nail matrix biopsies are performed to confirm a diagnosis or surgically remove a skin lesion that is affecting the growth of the nail plate. The procedure may be used to identify:

Nail biopsy can lead to complications such as bleeding, infection, or scarring. Postoperative scarring can cause permanent nail splitting, dystrophy, or both.

In a Cosmetic Dermatology article, “Matrix Biopsy of Longitudinal Melanonychia and Longitudinal Erythronychia: A Step-by-Step Approach,” Drs. Siobhan C. Collins and Nathaniel J. Jellinek review 6 techniques used to biopsy the nail matrix.

Techniques used to biopsy the nail matrix. From Cosmet Dermatol. 2009;22:130-136.

In the setting of longitudinal melanonychia (to diagnose nail melanoma or SCC) and longitudinal erythronychia (to diagnose SCC and rarely amelanotic melanoma or basal cell carcinoma), the techniques they describe accomplish 3 fundamental goals of nail surgery:

Dermatologists must be confident when performing nail biopsies and the techniques discussed by the authors will help approach nail surgery with more certainty.

At the 73rd Annual Meeting of the American Academy of Dermatology, Dr. Jellinek provides a hands-on approach to nail surgery. On Saturday, March 21, he will provide tips for nail surgeries at the “Medical and Surgical Management of Nail Disorders” lecture.

For more information, read the Collins and Jellinek article from Cosmetic Dermatology.

Nail matrix biopsies are performed to confirm a diagnosis or surgically remove a skin lesion that is affecting the growth of the nail plate. The procedure may be used to identify:

Nail biopsy can lead to complications such as bleeding, infection, or scarring. Postoperative scarring can cause permanent nail splitting, dystrophy, or both.

In a Cosmetic Dermatology article, “Matrix Biopsy of Longitudinal Melanonychia and Longitudinal Erythronychia: A Step-by-Step Approach,” Drs. Siobhan C. Collins and Nathaniel J. Jellinek review 6 techniques used to biopsy the nail matrix.

Techniques used to biopsy the nail matrix. From Cosmet Dermatol. 2009;22:130-136.

In the setting of longitudinal melanonychia (to diagnose nail melanoma or SCC) and longitudinal erythronychia (to diagnose SCC and rarely amelanotic melanoma or basal cell carcinoma), the techniques they describe accomplish 3 fundamental goals of nail surgery:

Dermatologists must be confident when performing nail biopsies and the techniques discussed by the authors will help approach nail surgery with more certainty.

At the 73rd Annual Meeting of the American Academy of Dermatology, Dr. Jellinek provides a hands-on approach to nail surgery. On Saturday, March 21, he will provide tips for nail surgeries at the “Medical and Surgical Management of Nail Disorders” lecture.

For more information, read the Collins and Jellinek article from Cosmetic Dermatology.

Nail matrix biopsies are performed to confirm a diagnosis or surgically remove a skin lesion that is affecting the growth of the nail plate. The procedure may be used to identify:

Nail biopsy can lead to complications such as bleeding, infection, or scarring. Postoperative scarring can cause permanent nail splitting, dystrophy, or both.

In a Cosmetic Dermatology article, “Matrix Biopsy of Longitudinal Melanonychia and Longitudinal Erythronychia: A Step-by-Step Approach,” Drs. Siobhan C. Collins and Nathaniel J. Jellinek review 6 techniques used to biopsy the nail matrix.

Techniques used to biopsy the nail matrix. From Cosmet Dermatol. 2009;22:130-136.

In the setting of longitudinal melanonychia (to diagnose nail melanoma or SCC) and longitudinal erythronychia (to diagnose SCC and rarely amelanotic melanoma or basal cell carcinoma), the techniques they describe accomplish 3 fundamental goals of nail surgery:

Dermatologists must be confident when performing nail biopsies and the techniques discussed by the authors will help approach nail surgery with more certainty.

At the 73rd Annual Meeting of the American Academy of Dermatology, Dr. Jellinek provides a hands-on approach to nail surgery. On Saturday, March 21, he will provide tips for nail surgeries at the “Medical and Surgical Management of Nail Disorders” lecture.

For more information, read the Collins and Jellinek article from Cosmetic Dermatology.