Nonmelanoma Skin Cancer

Mohs micrographic surgery (MMS) is a specialized surgical technique for the treatment of melanoma and nonmelanoma skin cancers (NMSCs).^1-3 The procedure involves surgical excision, histopathologic examination, precise mapping of malignant tissue, and wound management. Indications for MMS in skin cancer patients include recurring lesions, lesions in high-risk anatomic locations, aggressive histologic subtypes (ie, morpheaform, micronodular, infiltrative, high-grade, poorly differentiated), perineural invasion, large lesion size (>2 cm in diameter), poorly defined lateral or vertical clinical borders, rapid growth of the lesion, immunocompromised status, and sites of positive margins on prior excision. The therapeutic advantages of MMS include tissue conservation and optimal margin control in cosmetically or functionally sensitive areas, such as acral sites (eg, hands, feet, digits).^1,3

The intricacies of the nail apparatus complicate diagnostic biopsy and precise delineation of peripheral margins in digital skin cancers; thus, early diagnosis and intraoperative histologic examination of the margins are essential. Traditionally, the surgical approach to subungual cutaneous tumors such as melanoma has included digital amputation⁴; however, a study of the treatment of subungual melanoma revealed no difference in survival based on the level of amputation, therefore advocating for less radical treatment.⁴

Interestingly, MMS for cutaneous tumors localized to the digits is not frequently reviewed in the dermatologic literature. We present a retrospective case series evaluating the clinical outcomes of digital melanoma and NMSCs treated with MMS.

Methods

A retrospective chart review was performed at a private dermatology practice to identify patients who underwent MMS for melanoma or NMSC localized to the digits from January 2009 to December 2014. All patients were treated in the office by 1 Mohs surgeon (A.H.) and were evaluated before and after MMS. Data were collected from the electronic medical record of the practice, including patient demographics, histopathologic diagnosis, tumor status (primary or recurrent lesion), anatomic site of the tumor, preoperative and postoperative size of the lesion, number of MMS stages, surgical repair technique, postoperative complications, and follow-up period.

Results

Twenty-seven patients (13 male, 14 female) with a total of 28 lesions (malignant melanoma or NMSC) localized to the digits were identified (Table). The mean age at the time of MMS was 64.07 years. Twelve (42.86%) patients were 70 years of age or older, 11 (39.29%) were between 50 and 69 years, and 5 (17.85%) were younger than 50 years. Fifteen (53.57%) of the lesions were localized to the fingers, and 13 (46.43%) were localized to the toes; 18 (64.3%) of the lesions were distal and 10 (35.7%) were proximal to the distal interphalangeal joint. The most common pathologic diagnosis was squamous cell carcinoma (SCC) in situ (12/28 [42.86%]), followed by melanoma in situ (6/28 [21.42%]), severely dysplastic nevus (4/28 [14.29%]), SCC (4/28 [14.29%]), acrospiroma (1/28 [3.57%]), and melanoma (1/28 [3.57%]).

Surgical techniques used for repair following MMS included xenograft (10/28 [35.71%]); split-thickness skin graft (7/28 [25.0%]); secondary intention (4/28 [14.29%]); flap (4/28 [14.29%]); full-thickness skin graft (2/28 [7.14%]); and complex closure (1/28 [3.57%]). Clinical preoperative, operative, and postoperative photos from Patient 21 in this series are shown here (Figure). Two patients required bony phalanx resection due to invasion of the tumor into the periosteum: 1 had a malignant melanoma (Breslow depth, 2.52 mm); the other had an SCC. In addition, following removal of a severely dysplastic nevus, debulked tissue revealed melanoma in 1 patient.

Postoperative complications were noted in 4 (14.29%) of 28 MMS procedures, including bacterial wound infection (3.57%), excess granulation tissue that required wound debridement (7.14%), and delay in wound healing (3.57%). Follow-up data were available for 25 of the 28 MMS procedures (mean follow-up, 35.4 months), during which no recurrences were observed.

Comment

Mohs micrographic surgery is a specialized technique used in the treatment of cutaneous tumors, including basal cell carcinoma, SCC, melanoma in situ, atypical fibroxanthoma, dermatofibrosarcoma protuberans, sebaceous carcinoma, microcystic adnexal carcinoma, and Merkel cell carcinoma, among other cutaneous tumors.^1-3 Mohs micrographic surgery provides the advantage of tissue conservation as well as optimal margin control in cosmetically or functionally sensitive areas while providing a higher cure rate than surgical excision. During the procedure, the surgical margin is examined histologically, thus ensuring definitive removal of the tumor but minimal loss of surrounding normal tissue.^1-3 Mohs micrographic surgery is particularly useful for treating lesions on acral sites (eg, hands, feet, and digits).^3-5

The treatment of digital skin cancers has evolved over the past 50 years with advancements resulting in more precise, tissue-sparing methods, in contrast to previous treatments such as amputation and wide local excision.⁶ More specifically, traditional digital amputation for the treatment of subungual melanoma has been reevaluated in multiple studies, which did not demonstrate a statistically significant difference in survival based on the level of amputation, thereby favoring less radical treatment.^4,6 Moehrle et al⁷ found no statistical difference in recurrence rate when comparing patients with digital melanomas treated with partial amputation and those treated with digit-sparing surgery with limited excision and histologic evaluation of margins. Additionally, in a study conducted by Lazar et al,⁸ no recurrence of 13 subungual malignancies treated with MMS that utilized a full-thickness graft was reported at 4-year follow-up. In a large retrospective series of digital melanomas treated with MMS, Terushkin et al⁵ reported that 96.5% (55/57) of patients with primary melanomas that were treated with MMS avoided amputation, and the 5- and 10-year melanoma-specific survival rates for all patients treated with MMS were 95.0% and 82.6%, respectively. Based on a review of PubMed articles indexed for MEDLINE using the search terms surgical treatment of digital melanoma and nonmelanoma skin cancers, Mohs micrographic surgery for melanoma and nonmelanoma skin cancer, and surgical treatment of subungual skin cancer, conservative functional surgical approaches have been found to be cosmetically favorable, whereas local recurrence and survival rates have been shown to be unaffected by the level and degree of amputation.^4,5

In our study, cutaneous malignancies were located most often on the fingers, and the most common skin cancer identified was SCC in situ. The literature has shown that SCC in situ and SCC are the most common cutaneous neoplasms of the digits and nail unit.⁹ The most common specific anatomic site of cutaneous malignancy in our study was the great toe, followed by the fourth finger. A study conducted by Tan et al⁹ revealed that the great toe was the most common location of melanoma of the nail bed and subungual region, followed by the thumb. In contrast, primary subungual SCCs occur most frequently on the finger, with rare cases involving the toes.¹⁰

The etiology of digital SCC may involve extensive sun exposure, chronic trauma and wounds, and viral infection.^9,11 More specifically, the dermatologic literature provides evidence of human papillomavirus (HPV) type 16 involvement in the pathogenesis of digital and periungual SCC. A genital-digital mechanism of spread has been implicated.^11,12 An increased recurrence rate of HPV-associated digital SCCs has been reported following MMS, likely secondary to residual postsurgical HPV infection.^11,12

Maintaining function and cosmesis of the hands, feet, and digits following MMS can be challenging, sometimes requiring skin grafts and flaps to close the defect. In the 28 MMS procedures evaluated in our study, 19 (67.9%) surgical defects were repaired with a graft (ie, split-thickness skin graft, full-thickness skin graft, xenograft), 4 (14.3%) with a flap (advancement and rotation), 4 (14.3%) by secondary intention, and 1 (3.6%) with primary complex closure.

Surgical grafts can be categorized based on the origin of the graft.^2,13 Autografts, derived from the patient’s skin, are the most frequently used dermatologic graft and can be further categorized as full-thickness skin grafts, which include the epidermis and the entire dermis, thus preserving adnexal structures, and split-thickness skin grafts, which include the epidermis and partial dermis.^2,13Xenografts (eg, porcine grafts) can be used to repair defects involving the mucosa and those with a large wound depth, exposed cartilage, and/or bony defects, as well as wounds with indeterminate tumor margins and in patients with medical comorbidities that might prevent or delay plans for immediate wound reconstruction (eg, diabetes, cardiovascular disease, autoimmune connective tissue disease).^13,14

A cross-sectional survey of fellowship-trained Mohs surgeons revealed that more than two-thirds of repairs for cutaneous acral cancers were performed using a primary closure technique, and one-fourth of closures were performed using secondary intention.¹⁵ Of the less frequently utilized skin-graft repairs, more were for acral lesions on the legs than on the arms.¹⁴ The type of procedure and graft used is dependent on multiple variables, including the anatomic location of the lesion and final size of the defect following MMS.² Similarly, the use of specific types of sutures depends on the anatomic location of the lesion, relative thickness of the skin, degree of tension, and desired cosmetic result.¹⁵ The expertise of a hand surgeon may be required, particularly in cases in which the extensor tendon of the distal interphalangeal joint is compromised, manifested by a droopy fingertip when the hand is held horizontally. Additionally, special attention should be paid to removing the entire nail matrix before skin grafting for subungual tumors to avoid nail growth under the skin graft.

Evaluation of debulked tissue from digital skin cancers proved to be important in our study. In Patient 21, debulked tissue revealed melanoma following removal of a severely dysplastic nevus. This finding emphasizes the importance of complete excision of such lesions, as remaining underlying portions of the lesion can reveal residual tumor of the same or different histopathology.

In a prospective study, MMS was shown to have a low rate (0.91%; 95% confidence interval, 0.38%-1.45%) of surgical site infection in the absence of prophylactic antibiotics.¹⁶ The highest rates of surgical site infection were closely associated with flap closure. In our study, most patients had an uncomplicated and successful postoperative recovery. Only 1 (3.57%) of the 28 MMS procedures (Patient 22) was complicated by a bacterial wound infection postoperatively. The lesion removed in this case was a severely dysplastic melanocytic nevus on the toe. Infection resolved after a course of oral antibiotics, but the underlying cause of the wound infection in the patient was unclear. Other postoperative complications in our study included delayed wound healing and excess granulation tissue requiring wound debridement.

There are limited data in the dermatologic literature regarding outcomes following MMS for the treatment of cutaneous malignancies localized to the digits. In our study, patients treated with MMS were evaluated for recurrence of the primary lesion during postoperative follow-up appointments at the office or with the patient’s referring dermatologist. Follow-up data evaluating tumor recurrence were obtained for 25 of the patients, demonstrating no recurrence (mean follow-up, 35.4 months). Longer follow-up data would be more informative, but our findings nonetheless demonstrate that MMS is an effective treatment option for cutaneous malignancies of the digits.

Additional limitations of this case review include its single-center and retrospective design, the small sample size, and 1 Mohs surgeon having performed all surgeries.

Conclusion

This study provides further evidence of the benefit of MMS for the treatment of malignant melanoma and NMSCs of the digits. This procedure provides margin-controlled excision of these malignant neoplasms while preserving maximal normal tissue, thereby providing patients with improved postoperative function and cosmesis. Long-term follow-up data demonstrating a lack of tumor recurrence underscores the assertion that MMS is safe and effective for the treatment of skin cancer of the digits.

Mohs micrographic surgery (MMS) is a specialized surgical technique for the treatment of melanoma and nonmelanoma skin cancers (NMSCs).^1-3 The procedure involves surgical excision, histopathologic examination, precise mapping of malignant tissue, and wound management. Indications for MMS in skin cancer patients include recurring lesions, lesions in high-risk anatomic locations, aggressive histologic subtypes (ie, morpheaform, micronodular, infiltrative, high-grade, poorly differentiated), perineural invasion, large lesion size (>2 cm in diameter), poorly defined lateral or vertical clinical borders, rapid growth of the lesion, immunocompromised status, and sites of positive margins on prior excision. The therapeutic advantages of MMS include tissue conservation and optimal margin control in cosmetically or functionally sensitive areas, such as acral sites (eg, hands, feet, digits).^1,3

The intricacies of the nail apparatus complicate diagnostic biopsy and precise delineation of peripheral margins in digital skin cancers; thus, early diagnosis and intraoperative histologic examination of the margins are essential. Traditionally, the surgical approach to subungual cutaneous tumors such as melanoma has included digital amputation⁴; however, a study of the treatment of subungual melanoma revealed no difference in survival based on the level of amputation, therefore advocating for less radical treatment.⁴

Interestingly, MMS for cutaneous tumors localized to the digits is not frequently reviewed in the dermatologic literature. We present a retrospective case series evaluating the clinical outcomes of digital melanoma and NMSCs treated with MMS.

Methods

A retrospective chart review was performed at a private dermatology practice to identify patients who underwent MMS for melanoma or NMSC localized to the digits from January 2009 to December 2014. All patients were treated in the office by 1 Mohs surgeon (A.H.) and were evaluated before and after MMS. Data were collected from the electronic medical record of the practice, including patient demographics, histopathologic diagnosis, tumor status (primary or recurrent lesion), anatomic site of the tumor, preoperative and postoperative size of the lesion, number of MMS stages, surgical repair technique, postoperative complications, and follow-up period.

Results

Twenty-seven patients (13 male, 14 female) with a total of 28 lesions (malignant melanoma or NMSC) localized to the digits were identified (Table). The mean age at the time of MMS was 64.07 years. Twelve (42.86%) patients were 70 years of age or older, 11 (39.29%) were between 50 and 69 years, and 5 (17.85%) were younger than 50 years. Fifteen (53.57%) of the lesions were localized to the fingers, and 13 (46.43%) were localized to the toes; 18 (64.3%) of the lesions were distal and 10 (35.7%) were proximal to the distal interphalangeal joint. The most common pathologic diagnosis was squamous cell carcinoma (SCC) in situ (12/28 [42.86%]), followed by melanoma in situ (6/28 [21.42%]), severely dysplastic nevus (4/28 [14.29%]), SCC (4/28 [14.29%]), acrospiroma (1/28 [3.57%]), and melanoma (1/28 [3.57%]).

Surgical techniques used for repair following MMS included xenograft (10/28 [35.71%]); split-thickness skin graft (7/28 [25.0%]); secondary intention (4/28 [14.29%]); flap (4/28 [14.29%]); full-thickness skin graft (2/28 [7.14%]); and complex closure (1/28 [3.57%]). Clinical preoperative, operative, and postoperative photos from Patient 21 in this series are shown here (Figure). Two patients required bony phalanx resection due to invasion of the tumor into the periosteum: 1 had a malignant melanoma (Breslow depth, 2.52 mm); the other had an SCC. In addition, following removal of a severely dysplastic nevus, debulked tissue revealed melanoma in 1 patient.

Postoperative complications were noted in 4 (14.29%) of 28 MMS procedures, including bacterial wound infection (3.57%), excess granulation tissue that required wound debridement (7.14%), and delay in wound healing (3.57%). Follow-up data were available for 25 of the 28 MMS procedures (mean follow-up, 35.4 months), during which no recurrences were observed.

Comment

Mohs micrographic surgery is a specialized technique used in the treatment of cutaneous tumors, including basal cell carcinoma, SCC, melanoma in situ, atypical fibroxanthoma, dermatofibrosarcoma protuberans, sebaceous carcinoma, microcystic adnexal carcinoma, and Merkel cell carcinoma, among other cutaneous tumors.^1-3 Mohs micrographic surgery provides the advantage of tissue conservation as well as optimal margin control in cosmetically or functionally sensitive areas while providing a higher cure rate than surgical excision. During the procedure, the surgical margin is examined histologically, thus ensuring definitive removal of the tumor but minimal loss of surrounding normal tissue.^1-3 Mohs micrographic surgery is particularly useful for treating lesions on acral sites (eg, hands, feet, and digits).^3-5

The treatment of digital skin cancers has evolved over the past 50 years with advancements resulting in more precise, tissue-sparing methods, in contrast to previous treatments such as amputation and wide local excision.⁶ More specifically, traditional digital amputation for the treatment of subungual melanoma has been reevaluated in multiple studies, which did not demonstrate a statistically significant difference in survival based on the level of amputation, thereby favoring less radical treatment.^4,6 Moehrle et al⁷ found no statistical difference in recurrence rate when comparing patients with digital melanomas treated with partial amputation and those treated with digit-sparing surgery with limited excision and histologic evaluation of margins. Additionally, in a study conducted by Lazar et al,⁸ no recurrence of 13 subungual malignancies treated with MMS that utilized a full-thickness graft was reported at 4-year follow-up. In a large retrospective series of digital melanomas treated with MMS, Terushkin et al⁵ reported that 96.5% (55/57) of patients with primary melanomas that were treated with MMS avoided amputation, and the 5- and 10-year melanoma-specific survival rates for all patients treated with MMS were 95.0% and 82.6%, respectively. Based on a review of PubMed articles indexed for MEDLINE using the search terms surgical treatment of digital melanoma and nonmelanoma skin cancers, Mohs micrographic surgery for melanoma and nonmelanoma skin cancer, and surgical treatment of subungual skin cancer, conservative functional surgical approaches have been found to be cosmetically favorable, whereas local recurrence and survival rates have been shown to be unaffected by the level and degree of amputation.^4,5

In our study, cutaneous malignancies were located most often on the fingers, and the most common skin cancer identified was SCC in situ. The literature has shown that SCC in situ and SCC are the most common cutaneous neoplasms of the digits and nail unit.⁹ The most common specific anatomic site of cutaneous malignancy in our study was the great toe, followed by the fourth finger. A study conducted by Tan et al⁹ revealed that the great toe was the most common location of melanoma of the nail bed and subungual region, followed by the thumb. In contrast, primary subungual SCCs occur most frequently on the finger, with rare cases involving the toes.¹⁰

The etiology of digital SCC may involve extensive sun exposure, chronic trauma and wounds, and viral infection.^9,11 More specifically, the dermatologic literature provides evidence of human papillomavirus (HPV) type 16 involvement in the pathogenesis of digital and periungual SCC. A genital-digital mechanism of spread has been implicated.^11,12 An increased recurrence rate of HPV-associated digital SCCs has been reported following MMS, likely secondary to residual postsurgical HPV infection.^11,12

Maintaining function and cosmesis of the hands, feet, and digits following MMS can be challenging, sometimes requiring skin grafts and flaps to close the defect. In the 28 MMS procedures evaluated in our study, 19 (67.9%) surgical defects were repaired with a graft (ie, split-thickness skin graft, full-thickness skin graft, xenograft), 4 (14.3%) with a flap (advancement and rotation), 4 (14.3%) by secondary intention, and 1 (3.6%) with primary complex closure.

Surgical grafts can be categorized based on the origin of the graft.^2,13 Autografts, derived from the patient’s skin, are the most frequently used dermatologic graft and can be further categorized as full-thickness skin grafts, which include the epidermis and the entire dermis, thus preserving adnexal structures, and split-thickness skin grafts, which include the epidermis and partial dermis.^2,13Xenografts (eg, porcine grafts) can be used to repair defects involving the mucosa and those with a large wound depth, exposed cartilage, and/or bony defects, as well as wounds with indeterminate tumor margins and in patients with medical comorbidities that might prevent or delay plans for immediate wound reconstruction (eg, diabetes, cardiovascular disease, autoimmune connective tissue disease).^13,14

A cross-sectional survey of fellowship-trained Mohs surgeons revealed that more than two-thirds of repairs for cutaneous acral cancers were performed using a primary closure technique, and one-fourth of closures were performed using secondary intention.¹⁵ Of the less frequently utilized skin-graft repairs, more were for acral lesions on the legs than on the arms.¹⁴ The type of procedure and graft used is dependent on multiple variables, including the anatomic location of the lesion and final size of the defect following MMS.² Similarly, the use of specific types of sutures depends on the anatomic location of the lesion, relative thickness of the skin, degree of tension, and desired cosmetic result.¹⁵ The expertise of a hand surgeon may be required, particularly in cases in which the extensor tendon of the distal interphalangeal joint is compromised, manifested by a droopy fingertip when the hand is held horizontally. Additionally, special attention should be paid to removing the entire nail matrix before skin grafting for subungual tumors to avoid nail growth under the skin graft.

Evaluation of debulked tissue from digital skin cancers proved to be important in our study. In Patient 21, debulked tissue revealed melanoma following removal of a severely dysplastic nevus. This finding emphasizes the importance of complete excision of such lesions, as remaining underlying portions of the lesion can reveal residual tumor of the same or different histopathology.

In a prospective study, MMS was shown to have a low rate (0.91%; 95% confidence interval, 0.38%-1.45%) of surgical site infection in the absence of prophylactic antibiotics.¹⁶ The highest rates of surgical site infection were closely associated with flap closure. In our study, most patients had an uncomplicated and successful postoperative recovery. Only 1 (3.57%) of the 28 MMS procedures (Patient 22) was complicated by a bacterial wound infection postoperatively. The lesion removed in this case was a severely dysplastic melanocytic nevus on the toe. Infection resolved after a course of oral antibiotics, but the underlying cause of the wound infection in the patient was unclear. Other postoperative complications in our study included delayed wound healing and excess granulation tissue requiring wound debridement.

There are limited data in the dermatologic literature regarding outcomes following MMS for the treatment of cutaneous malignancies localized to the digits. In our study, patients treated with MMS were evaluated for recurrence of the primary lesion during postoperative follow-up appointments at the office or with the patient’s referring dermatologist. Follow-up data evaluating tumor recurrence were obtained for 25 of the patients, demonstrating no recurrence (mean follow-up, 35.4 months). Longer follow-up data would be more informative, but our findings nonetheless demonstrate that MMS is an effective treatment option for cutaneous malignancies of the digits.

Additional limitations of this case review include its single-center and retrospective design, the small sample size, and 1 Mohs surgeon having performed all surgeries.

Conclusion

This study provides further evidence of the benefit of MMS for the treatment of malignant melanoma and NMSCs of the digits. This procedure provides margin-controlled excision of these malignant neoplasms while preserving maximal normal tissue, thereby providing patients with improved postoperative function and cosmesis. Long-term follow-up data demonstrating a lack of tumor recurrence underscores the assertion that MMS is safe and effective for the treatment of skin cancer of the digits.

Mohs micrographic surgery (MMS) is a specialized surgical technique for the treatment of melanoma and nonmelanoma skin cancers (NMSCs).^1-3 The procedure involves surgical excision, histopathologic examination, precise mapping of malignant tissue, and wound management. Indications for MMS in skin cancer patients include recurring lesions, lesions in high-risk anatomic locations, aggressive histologic subtypes (ie, morpheaform, micronodular, infiltrative, high-grade, poorly differentiated), perineural invasion, large lesion size (>2 cm in diameter), poorly defined lateral or vertical clinical borders, rapid growth of the lesion, immunocompromised status, and sites of positive margins on prior excision. The therapeutic advantages of MMS include tissue conservation and optimal margin control in cosmetically or functionally sensitive areas, such as acral sites (eg, hands, feet, digits).^1,3

The intricacies of the nail apparatus complicate diagnostic biopsy and precise delineation of peripheral margins in digital skin cancers; thus, early diagnosis and intraoperative histologic examination of the margins are essential. Traditionally, the surgical approach to subungual cutaneous tumors such as melanoma has included digital amputation⁴; however, a study of the treatment of subungual melanoma revealed no difference in survival based on the level of amputation, therefore advocating for less radical treatment.⁴

Interestingly, MMS for cutaneous tumors localized to the digits is not frequently reviewed in the dermatologic literature. We present a retrospective case series evaluating the clinical outcomes of digital melanoma and NMSCs treated with MMS.

Methods

A retrospective chart review was performed at a private dermatology practice to identify patients who underwent MMS for melanoma or NMSC localized to the digits from January 2009 to December 2014. All patients were treated in the office by 1 Mohs surgeon (A.H.) and were evaluated before and after MMS. Data were collected from the electronic medical record of the practice, including patient demographics, histopathologic diagnosis, tumor status (primary or recurrent lesion), anatomic site of the tumor, preoperative and postoperative size of the lesion, number of MMS stages, surgical repair technique, postoperative complications, and follow-up period.

Results

Twenty-seven patients (13 male, 14 female) with a total of 28 lesions (malignant melanoma or NMSC) localized to the digits were identified (Table). The mean age at the time of MMS was 64.07 years. Twelve (42.86%) patients were 70 years of age or older, 11 (39.29%) were between 50 and 69 years, and 5 (17.85%) were younger than 50 years. Fifteen (53.57%) of the lesions were localized to the fingers, and 13 (46.43%) were localized to the toes; 18 (64.3%) of the lesions were distal and 10 (35.7%) were proximal to the distal interphalangeal joint. The most common pathologic diagnosis was squamous cell carcinoma (SCC) in situ (12/28 [42.86%]), followed by melanoma in situ (6/28 [21.42%]), severely dysplastic nevus (4/28 [14.29%]), SCC (4/28 [14.29%]), acrospiroma (1/28 [3.57%]), and melanoma (1/28 [3.57%]).

Surgical techniques used for repair following MMS included xenograft (10/28 [35.71%]); split-thickness skin graft (7/28 [25.0%]); secondary intention (4/28 [14.29%]); flap (4/28 [14.29%]); full-thickness skin graft (2/28 [7.14%]); and complex closure (1/28 [3.57%]). Clinical preoperative, operative, and postoperative photos from Patient 21 in this series are shown here (Figure). Two patients required bony phalanx resection due to invasion of the tumor into the periosteum: 1 had a malignant melanoma (Breslow depth, 2.52 mm); the other had an SCC. In addition, following removal of a severely dysplastic nevus, debulked tissue revealed melanoma in 1 patient.

Postoperative complications were noted in 4 (14.29%) of 28 MMS procedures, including bacterial wound infection (3.57%), excess granulation tissue that required wound debridement (7.14%), and delay in wound healing (3.57%). Follow-up data were available for 25 of the 28 MMS procedures (mean follow-up, 35.4 months), during which no recurrences were observed.

Comment

Mohs micrographic surgery is a specialized technique used in the treatment of cutaneous tumors, including basal cell carcinoma, SCC, melanoma in situ, atypical fibroxanthoma, dermatofibrosarcoma protuberans, sebaceous carcinoma, microcystic adnexal carcinoma, and Merkel cell carcinoma, among other cutaneous tumors.^1-3 Mohs micrographic surgery provides the advantage of tissue conservation as well as optimal margin control in cosmetically or functionally sensitive areas while providing a higher cure rate than surgical excision. During the procedure, the surgical margin is examined histologically, thus ensuring definitive removal of the tumor but minimal loss of surrounding normal tissue.^1-3 Mohs micrographic surgery is particularly useful for treating lesions on acral sites (eg, hands, feet, and digits).^3-5

The treatment of digital skin cancers has evolved over the past 50 years with advancements resulting in more precise, tissue-sparing methods, in contrast to previous treatments such as amputation and wide local excision.⁶ More specifically, traditional digital amputation for the treatment of subungual melanoma has been reevaluated in multiple studies, which did not demonstrate a statistically significant difference in survival based on the level of amputation, thereby favoring less radical treatment.^4,6 Moehrle et al⁷ found no statistical difference in recurrence rate when comparing patients with digital melanomas treated with partial amputation and those treated with digit-sparing surgery with limited excision and histologic evaluation of margins. Additionally, in a study conducted by Lazar et al,⁸ no recurrence of 13 subungual malignancies treated with MMS that utilized a full-thickness graft was reported at 4-year follow-up. In a large retrospective series of digital melanomas treated with MMS, Terushkin et al⁵ reported that 96.5% (55/57) of patients with primary melanomas that were treated with MMS avoided amputation, and the 5- and 10-year melanoma-specific survival rates for all patients treated with MMS were 95.0% and 82.6%, respectively. Based on a review of PubMed articles indexed for MEDLINE using the search terms surgical treatment of digital melanoma and nonmelanoma skin cancers, Mohs micrographic surgery for melanoma and nonmelanoma skin cancer, and surgical treatment of subungual skin cancer, conservative functional surgical approaches have been found to be cosmetically favorable, whereas local recurrence and survival rates have been shown to be unaffected by the level and degree of amputation.^4,5

In our study, cutaneous malignancies were located most often on the fingers, and the most common skin cancer identified was SCC in situ. The literature has shown that SCC in situ and SCC are the most common cutaneous neoplasms of the digits and nail unit.⁹ The most common specific anatomic site of cutaneous malignancy in our study was the great toe, followed by the fourth finger. A study conducted by Tan et al⁹ revealed that the great toe was the most common location of melanoma of the nail bed and subungual region, followed by the thumb. In contrast, primary subungual SCCs occur most frequently on the finger, with rare cases involving the toes.¹⁰

The etiology of digital SCC may involve extensive sun exposure, chronic trauma and wounds, and viral infection.^9,11 More specifically, the dermatologic literature provides evidence of human papillomavirus (HPV) type 16 involvement in the pathogenesis of digital and periungual SCC. A genital-digital mechanism of spread has been implicated.^11,12 An increased recurrence rate of HPV-associated digital SCCs has been reported following MMS, likely secondary to residual postsurgical HPV infection.^11,12

Maintaining function and cosmesis of the hands, feet, and digits following MMS can be challenging, sometimes requiring skin grafts and flaps to close the defect. In the 28 MMS procedures evaluated in our study, 19 (67.9%) surgical defects were repaired with a graft (ie, split-thickness skin graft, full-thickness skin graft, xenograft), 4 (14.3%) with a flap (advancement and rotation), 4 (14.3%) by secondary intention, and 1 (3.6%) with primary complex closure.

Surgical grafts can be categorized based on the origin of the graft.^2,13 Autografts, derived from the patient’s skin, are the most frequently used dermatologic graft and can be further categorized as full-thickness skin grafts, which include the epidermis and the entire dermis, thus preserving adnexal structures, and split-thickness skin grafts, which include the epidermis and partial dermis.^2,13Xenografts (eg, porcine grafts) can be used to repair defects involving the mucosa and those with a large wound depth, exposed cartilage, and/or bony defects, as well as wounds with indeterminate tumor margins and in patients with medical comorbidities that might prevent or delay plans for immediate wound reconstruction (eg, diabetes, cardiovascular disease, autoimmune connective tissue disease).^13,14

A cross-sectional survey of fellowship-trained Mohs surgeons revealed that more than two-thirds of repairs for cutaneous acral cancers were performed using a primary closure technique, and one-fourth of closures were performed using secondary intention.¹⁵ Of the less frequently utilized skin-graft repairs, more were for acral lesions on the legs than on the arms.¹⁴ The type of procedure and graft used is dependent on multiple variables, including the anatomic location of the lesion and final size of the defect following MMS.² Similarly, the use of specific types of sutures depends on the anatomic location of the lesion, relative thickness of the skin, degree of tension, and desired cosmetic result.¹⁵ The expertise of a hand surgeon may be required, particularly in cases in which the extensor tendon of the distal interphalangeal joint is compromised, manifested by a droopy fingertip when the hand is held horizontally. Additionally, special attention should be paid to removing the entire nail matrix before skin grafting for subungual tumors to avoid nail growth under the skin graft.

Evaluation of debulked tissue from digital skin cancers proved to be important in our study. In Patient 21, debulked tissue revealed melanoma following removal of a severely dysplastic nevus. This finding emphasizes the importance of complete excision of such lesions, as remaining underlying portions of the lesion can reveal residual tumor of the same or different histopathology.

In a prospective study, MMS was shown to have a low rate (0.91%; 95% confidence interval, 0.38%-1.45%) of surgical site infection in the absence of prophylactic antibiotics.¹⁶ The highest rates of surgical site infection were closely associated with flap closure. In our study, most patients had an uncomplicated and successful postoperative recovery. Only 1 (3.57%) of the 28 MMS procedures (Patient 22) was complicated by a bacterial wound infection postoperatively. The lesion removed in this case was a severely dysplastic melanocytic nevus on the toe. Infection resolved after a course of oral antibiotics, but the underlying cause of the wound infection in the patient was unclear. Other postoperative complications in our study included delayed wound healing and excess granulation tissue requiring wound debridement.

There are limited data in the dermatologic literature regarding outcomes following MMS for the treatment of cutaneous malignancies localized to the digits. In our study, patients treated with MMS were evaluated for recurrence of the primary lesion during postoperative follow-up appointments at the office or with the patient’s referring dermatologist. Follow-up data evaluating tumor recurrence were obtained for 25 of the patients, demonstrating no recurrence (mean follow-up, 35.4 months). Longer follow-up data would be more informative, but our findings nonetheless demonstrate that MMS is an effective treatment option for cutaneous malignancies of the digits.

Additional limitations of this case review include its single-center and retrospective design, the small sample size, and 1 Mohs surgeon having performed all surgeries.

Conclusion

This study provides further evidence of the benefit of MMS for the treatment of malignant melanoma and NMSCs of the digits. This procedure provides margin-controlled excision of these malignant neoplasms while preserving maximal normal tissue, thereby providing patients with improved postoperative function and cosmesis. Long-term follow-up data demonstrating a lack of tumor recurrence underscores the assertion that MMS is safe and effective for the treatment of skin cancer of the digits.

DALLAS – An investigational device that couples laser spectroscopy with a machine-learning algorithm demonstrated a high sensitivity and specificity for discriminating skin cancers from benign lesions in real time, results from a single-center study showed.

“More than 5.4 million cases of nonmelanoma skin cancer were treated in 2012, but the accuracy of skin cancer screening prior to biopsy is pretty low, about 70%, and is individual dependent,” lead study author Sung Hyun Pyun, PhD, said at the annual conference of the American Society for Laser Medicine and Surgery. “There have been several in vivo skin cancer screening devices based on noninvasive techniques such as multispectral imaging, Raman spectroscopy, and electrical impedance spectroscopy, but their diagnostic accuracies were not sufficient for clinical use and could not be applied in real time.”

dbrunk@mdedge.com

DALLAS – An investigational device that couples laser spectroscopy with a machine-learning algorithm demonstrated a high sensitivity and specificity for discriminating skin cancers from benign lesions in real time, results from a single-center study showed.

“More than 5.4 million cases of nonmelanoma skin cancer were treated in 2012, but the accuracy of skin cancer screening prior to biopsy is pretty low, about 70%, and is individual dependent,” lead study author Sung Hyun Pyun, PhD, said at the annual conference of the American Society for Laser Medicine and Surgery. “There have been several in vivo skin cancer screening devices based on noninvasive techniques such as multispectral imaging, Raman spectroscopy, and electrical impedance spectroscopy, but their diagnostic accuracies were not sufficient for clinical use and could not be applied in real time.”

dbrunk@mdedge.com

DALLAS – An investigational device that couples laser spectroscopy with a machine-learning algorithm demonstrated a high sensitivity and specificity for discriminating skin cancers from benign lesions in real time, results from a single-center study showed.

“More than 5.4 million cases of nonmelanoma skin cancer were treated in 2012, but the accuracy of skin cancer screening prior to biopsy is pretty low, about 70%, and is individual dependent,” lead study author Sung Hyun Pyun, PhD, said at the annual conference of the American Society for Laser Medicine and Surgery. “There have been several in vivo skin cancer screening devices based on noninvasive techniques such as multispectral imaging, Raman spectroscopy, and electrical impedance spectroscopy, but their diagnostic accuracies were not sufficient for clinical use and could not be applied in real time.”

dbrunk@mdedge.com

In January 2018, the American Academy of Dermatology (AAD) released its first guidelines of care for the management of nonmelanoma skin cancer (NMSC), which established official recommendations for the treatment of basal cell carcinoma (BCC)¹ and cutaneous squamous cell carcinoma (cSCC).² The guidelines will help dermatologists address the growing health concern of skin cancer, which remains the most common of any type of cancer in the United States.³ Affecting more than 3 million Americans every year, NMSC is the most common type of skin cancer, and its incidence has continued to increase every year over the past few decades.^3,4 During the past 30 years, the incidence of both BCC and cSCC has more than doubled.⁵

Commonly used guidelines for the management of NMSC are available from the National Comprehensive Cancer Network (NCCN).^6,7 Although the NCCN aimed to develop multidisciplinary guidelines, the new AAD guidelines were established primarily by dermatologists for dermatologists. The NCCN guidelines frequently are referenced throughout the new AAD guidelines, which also recognize the importance of multidisciplinary care. The authors of the AAD guidelines noted that, although many of the NCCN recommendations reiterated prevailing knowledge or current practice, some recommendations highlighted alternative tenets that were not as widely considered or were supported by insufficient evidence.

The AAD guidelines address the complete management of NMSC, which includes biopsy technique, staging, treatment, follow-up, metastatic disease, and prevention.^1,2 Also included are evidence tables evaluating the current literature and available recommendations.

BCC Guidelines

For suspected BCCs, the recommended biopsy techniques are punch biopsy, shave biopsy, and excisional biopsy, all of which can detect the most aggressive histology subtypes.¹ Rebiopsy is recommended if the initial specimen is inadequate. The pathology report should include histologic subtype, invasion beyond the reticular dermis, and perineural involvement. The AAD guidelines do not include a formal staging system for risk stratification but rather refer to the NCCN guidelines, which take both clinical and pathologic parameters into account. The AAD treatment recommendations are based on this stratification.¹

Treatment of BCC includes a broad range of therapeutic modalities. Recurrence rate, preservation of function, patient expectations, and potential adverse effects should be considered in the treatment plan.¹ Curettage and electrodessication may be considered for low-risk tumors in nonterminal hair-bearing locations. Surgical excision with 4-mm margins is recommended for low-risk primary tumors. For high-risk BCC, Mohs micrographic surgery is recommended, although standard excision along with attention to margin control may also be considered. Nonsurgical treatments also may be considered when more effective surgical therapies are contraindicated or impractical. If surgical therapy is not feasible or preferred, other treatment options for low-risk BCCs include cryotherapy, topical 5-fluorouracil, topical imiquimod, photodynamic therapy, or radiation therapy; however, the cure rates for these modalities may be lower than with surgical treatment. The AAD guidelines also note that there is insufficient evidence to recommend routine use of laser or electronic surface brachytherapy.¹

Multidisciplinary consultation is recommended in patients with metastatic BCCs along with first-line treatment with a smoothened inhibitor.¹ Alternative treatment options include platinum-based chemotherapy and/or supportive care. For locally advanced disease, surgery and radiation therapy remain the initial treatments, but smoothened inhibitors and supportive care are suitable alternative treatments.¹

The AAD guidelines also offer recommendations for follow-up and reducing future risk of skin cancer. After the first diagnosis of BCC, a skin cancer screening should be performed at least annually, and patients should be counseled about self-examinations and sun protection.¹ Topical and oral retinoids are not recommended for the prevention of additional skin cancers, nor is dietary supplementation with selenium or beta-carotene. There also is insufficient evidence regarding the use of oral nicotinamide, celecoxib, or α-difluoromethylornithine for chemoprevention of disease.¹

cSCC Guidelines

For suspected cSCCs, no single optimal biopsy technique is recommended, but repeat biopsy may be considered if the initial biopsy is insufficient for diagnosis.² The guidelines further recommend an extensive list of elements to be included in the final pathology report (eg, lesion size, immunosuppression, depth of invasion, degree of differentiation). There is no universally recognized stratification for localized cSCC; therefore, the AAD guidelines refer to the framework provided by the NCCN. Also mentioned is the recent release of the American Joint Committee on Cancer’s staging manual,⁸ which includes the management of cSCC in conjunction with all SCCs of the head and neck. The Brigham and Women’s system⁹ was considered as an alternative classification system; however, the NCCN guidelines were chosen because they primarily provide clinical guidance for treatment of cSCC rather than provide accurate prognostication or outcome assessment.

Considerations for surgical treatment of cSCC are similar to those for BCC.² In low-risk tumors, surgical excision with 4- to 6-mm margins to the midsubcutaneous fat or curettage with electrodessication may be considered. Mohs micrographic surgery or standard excision with attention to margin control may be considered for high-risk tumors. Nonsurgical therapies generally are not recommended as a first-line treatment, particularly in cSCC, due to possible recurrence and metastasis. When nonsurgical therapies are preferred, options may include cryosurgery or radiation therapy, with the understanding that cure rates may be lower than with surgical options. Topical therapy with imiquimod or 5-fluorouracil as well as photodynamic or laser therapy are not recommended for cSCCs.²

For patients with metastatic cSCC or locally advanced disease, multidisciplinary consultation is recommended.² In cSCCs with regional lymph node metastases, the recommended approach includes surgical resection with possible adjuvant radiation therapy and/or systemic therapy. For inoperable disease, combination chemoradiation may be considered. Epidermal growth factor inhibitors and cisplatin may be considered in metastatic disease, although there are limited data to support their efficacy. As with BCC, all patients with cSCCs should receive supportive and palliative care to optimize quality of life.²

Recommendations for follow-up after the first diagnosis of cSCC are the same as those for BCC.² Additionally, acitretin is the only therapy that may be beneficial in the reduction of recurrent skin cancer in patients who are solid-organ transplant recipients.

Final Thoughts

A comprehensive understanding of the management of NMSC and the evidence on which recommendations are based is critically important for optimal patient care. These guidelines are an efficient way for dermatologists and their colleagues to understand the latest evidence and recommendations. The AAD guidelines provide support for clinical decision making with standardized approaches to the diagnosis, care, and prevention of NMSC that are consistent with established practice patterns.

With few exceptions, surgical therapy is the most effective approach for the treatment of BCC and cSCC; however, the AAD guidelines include an important review on nonsurgical management options.^1,2 The AAD guidelines help to highlight where data on evidence-based outcomes exist and reveal where data remain insufficient. This is illustrated by the guideline recommendations for providing additional histopathologic characteristics in the pathology reports, which will likely produce future data to enhance the prognosis and eventual treatment of patients with NMSC.^1,2 Future guidelines also may include newer technologies (eg, gene expression profiling).

The guidelines do not cover the management of premalignant and in situ lesions, nor do they provide details on the management of metastatic or locally advanced disease. These topics certainly will require a similar critical review and may be addressed separately. The guidelines are identifying unanswered questions about patient care and are concurrently establishing the collection of appropriate data to answer these questions in the future.

Official guidelines often become the primary source for the measured standard of both treatment and outcomes in patient care; therefore, it is critical that dermatologists and the AAD take the lead in creating these guidelines so that we can provide our patients with the best evidenced-based comprehensive care.

The AAD guidelines emphasize the importance of considering the patient perspective in determining how to treat BCCs and cSCCs.^1,2 It is important for patients to understand the available treatment options and participate in their own medical care. The AAD work group for these guidelines included patient advocates to ensure that the guidelines would promote further dialogue between physicians and their patients.

The AAD guidelines for the management of NMSC were developed by board-certified dermatologists and other experts in the field. They allow dermatologists to work with patients diagnosed with NMSC to determine the treatment option that is best for each individual patient.

In January 2018, the American Academy of Dermatology (AAD) released its first guidelines of care for the management of nonmelanoma skin cancer (NMSC), which established official recommendations for the treatment of basal cell carcinoma (BCC)¹ and cutaneous squamous cell carcinoma (cSCC).² The guidelines will help dermatologists address the growing health concern of skin cancer, which remains the most common of any type of cancer in the United States.³ Affecting more than 3 million Americans every year, NMSC is the most common type of skin cancer, and its incidence has continued to increase every year over the past few decades.^3,4 During the past 30 years, the incidence of both BCC and cSCC has more than doubled.⁵

Commonly used guidelines for the management of NMSC are available from the National Comprehensive Cancer Network (NCCN).^6,7 Although the NCCN aimed to develop multidisciplinary guidelines, the new AAD guidelines were established primarily by dermatologists for dermatologists. The NCCN guidelines frequently are referenced throughout the new AAD guidelines, which also recognize the importance of multidisciplinary care. The authors of the AAD guidelines noted that, although many of the NCCN recommendations reiterated prevailing knowledge or current practice, some recommendations highlighted alternative tenets that were not as widely considered or were supported by insufficient evidence.

The AAD guidelines address the complete management of NMSC, which includes biopsy technique, staging, treatment, follow-up, metastatic disease, and prevention.^1,2 Also included are evidence tables evaluating the current literature and available recommendations.

BCC Guidelines

For suspected BCCs, the recommended biopsy techniques are punch biopsy, shave biopsy, and excisional biopsy, all of which can detect the most aggressive histology subtypes.¹ Rebiopsy is recommended if the initial specimen is inadequate. The pathology report should include histologic subtype, invasion beyond the reticular dermis, and perineural involvement. The AAD guidelines do not include a formal staging system for risk stratification but rather refer to the NCCN guidelines, which take both clinical and pathologic parameters into account. The AAD treatment recommendations are based on this stratification.¹

Treatment of BCC includes a broad range of therapeutic modalities. Recurrence rate, preservation of function, patient expectations, and potential adverse effects should be considered in the treatment plan.¹ Curettage and electrodessication may be considered for low-risk tumors in nonterminal hair-bearing locations. Surgical excision with 4-mm margins is recommended for low-risk primary tumors. For high-risk BCC, Mohs micrographic surgery is recommended, although standard excision along with attention to margin control may also be considered. Nonsurgical treatments also may be considered when more effective surgical therapies are contraindicated or impractical. If surgical therapy is not feasible or preferred, other treatment options for low-risk BCCs include cryotherapy, topical 5-fluorouracil, topical imiquimod, photodynamic therapy, or radiation therapy; however, the cure rates for these modalities may be lower than with surgical treatment. The AAD guidelines also note that there is insufficient evidence to recommend routine use of laser or electronic surface brachytherapy.¹

Multidisciplinary consultation is recommended in patients with metastatic BCCs along with first-line treatment with a smoothened inhibitor.¹ Alternative treatment options include platinum-based chemotherapy and/or supportive care. For locally advanced disease, surgery and radiation therapy remain the initial treatments, but smoothened inhibitors and supportive care are suitable alternative treatments.¹

The AAD guidelines also offer recommendations for follow-up and reducing future risk of skin cancer. After the first diagnosis of BCC, a skin cancer screening should be performed at least annually, and patients should be counseled about self-examinations and sun protection.¹ Topical and oral retinoids are not recommended for the prevention of additional skin cancers, nor is dietary supplementation with selenium or beta-carotene. There also is insufficient evidence regarding the use of oral nicotinamide, celecoxib, or α-difluoromethylornithine for chemoprevention of disease.¹

cSCC Guidelines

For suspected cSCCs, no single optimal biopsy technique is recommended, but repeat biopsy may be considered if the initial biopsy is insufficient for diagnosis.² The guidelines further recommend an extensive list of elements to be included in the final pathology report (eg, lesion size, immunosuppression, depth of invasion, degree of differentiation). There is no universally recognized stratification for localized cSCC; therefore, the AAD guidelines refer to the framework provided by the NCCN. Also mentioned is the recent release of the American Joint Committee on Cancer’s staging manual,⁸ which includes the management of cSCC in conjunction with all SCCs of the head and neck. The Brigham and Women’s system⁹ was considered as an alternative classification system; however, the NCCN guidelines were chosen because they primarily provide clinical guidance for treatment of cSCC rather than provide accurate prognostication or outcome assessment.

Considerations for surgical treatment of cSCC are similar to those for BCC.² In low-risk tumors, surgical excision with 4- to 6-mm margins to the midsubcutaneous fat or curettage with electrodessication may be considered. Mohs micrographic surgery or standard excision with attention to margin control may be considered for high-risk tumors. Nonsurgical therapies generally are not recommended as a first-line treatment, particularly in cSCC, due to possible recurrence and metastasis. When nonsurgical therapies are preferred, options may include cryosurgery or radiation therapy, with the understanding that cure rates may be lower than with surgical options. Topical therapy with imiquimod or 5-fluorouracil as well as photodynamic or laser therapy are not recommended for cSCCs.²

For patients with metastatic cSCC or locally advanced disease, multidisciplinary consultation is recommended.² In cSCCs with regional lymph node metastases, the recommended approach includes surgical resection with possible adjuvant radiation therapy and/or systemic therapy. For inoperable disease, combination chemoradiation may be considered. Epidermal growth factor inhibitors and cisplatin may be considered in metastatic disease, although there are limited data to support their efficacy. As with BCC, all patients with cSCCs should receive supportive and palliative care to optimize quality of life.²

Recommendations for follow-up after the first diagnosis of cSCC are the same as those for BCC.² Additionally, acitretin is the only therapy that may be beneficial in the reduction of recurrent skin cancer in patients who are solid-organ transplant recipients.

Final Thoughts

A comprehensive understanding of the management of NMSC and the evidence on which recommendations are based is critically important for optimal patient care. These guidelines are an efficient way for dermatologists and their colleagues to understand the latest evidence and recommendations. The AAD guidelines provide support for clinical decision making with standardized approaches to the diagnosis, care, and prevention of NMSC that are consistent with established practice patterns.

With few exceptions, surgical therapy is the most effective approach for the treatment of BCC and cSCC; however, the AAD guidelines include an important review on nonsurgical management options.^1,2 The AAD guidelines help to highlight where data on evidence-based outcomes exist and reveal where data remain insufficient. This is illustrated by the guideline recommendations for providing additional histopathologic characteristics in the pathology reports, which will likely produce future data to enhance the prognosis and eventual treatment of patients with NMSC.^1,2 Future guidelines also may include newer technologies (eg, gene expression profiling).

The guidelines do not cover the management of premalignant and in situ lesions, nor do they provide details on the management of metastatic or locally advanced disease. These topics certainly will require a similar critical review and may be addressed separately. The guidelines are identifying unanswered questions about patient care and are concurrently establishing the collection of appropriate data to answer these questions in the future.

Official guidelines often become the primary source for the measured standard of both treatment and outcomes in patient care; therefore, it is critical that dermatologists and the AAD take the lead in creating these guidelines so that we can provide our patients with the best evidenced-based comprehensive care.

The AAD guidelines emphasize the importance of considering the patient perspective in determining how to treat BCCs and cSCCs.^1,2 It is important for patients to understand the available treatment options and participate in their own medical care. The AAD work group for these guidelines included patient advocates to ensure that the guidelines would promote further dialogue between physicians and their patients.

The AAD guidelines for the management of NMSC were developed by board-certified dermatologists and other experts in the field. They allow dermatologists to work with patients diagnosed with NMSC to determine the treatment option that is best for each individual patient.

In January 2018, the American Academy of Dermatology (AAD) released its first guidelines of care for the management of nonmelanoma skin cancer (NMSC), which established official recommendations for the treatment of basal cell carcinoma (BCC)¹ and cutaneous squamous cell carcinoma (cSCC).² The guidelines will help dermatologists address the growing health concern of skin cancer, which remains the most common of any type of cancer in the United States.³ Affecting more than 3 million Americans every year, NMSC is the most common type of skin cancer, and its incidence has continued to increase every year over the past few decades.^3,4 During the past 30 years, the incidence of both BCC and cSCC has more than doubled.⁵

Commonly used guidelines for the management of NMSC are available from the National Comprehensive Cancer Network (NCCN).^6,7 Although the NCCN aimed to develop multidisciplinary guidelines, the new AAD guidelines were established primarily by dermatologists for dermatologists. The NCCN guidelines frequently are referenced throughout the new AAD guidelines, which also recognize the importance of multidisciplinary care. The authors of the AAD guidelines noted that, although many of the NCCN recommendations reiterated prevailing knowledge or current practice, some recommendations highlighted alternative tenets that were not as widely considered or were supported by insufficient evidence.

The AAD guidelines address the complete management of NMSC, which includes biopsy technique, staging, treatment, follow-up, metastatic disease, and prevention.^1,2 Also included are evidence tables evaluating the current literature and available recommendations.

BCC Guidelines

For suspected BCCs, the recommended biopsy techniques are punch biopsy, shave biopsy, and excisional biopsy, all of which can detect the most aggressive histology subtypes.¹ Rebiopsy is recommended if the initial specimen is inadequate. The pathology report should include histologic subtype, invasion beyond the reticular dermis, and perineural involvement. The AAD guidelines do not include a formal staging system for risk stratification but rather refer to the NCCN guidelines, which take both clinical and pathologic parameters into account. The AAD treatment recommendations are based on this stratification.¹

Treatment of BCC includes a broad range of therapeutic modalities. Recurrence rate, preservation of function, patient expectations, and potential adverse effects should be considered in the treatment plan.¹ Curettage and electrodessication may be considered for low-risk tumors in nonterminal hair-bearing locations. Surgical excision with 4-mm margins is recommended for low-risk primary tumors. For high-risk BCC, Mohs micrographic surgery is recommended, although standard excision along with attention to margin control may also be considered. Nonsurgical treatments also may be considered when more effective surgical therapies are contraindicated or impractical. If surgical therapy is not feasible or preferred, other treatment options for low-risk BCCs include cryotherapy, topical 5-fluorouracil, topical imiquimod, photodynamic therapy, or radiation therapy; however, the cure rates for these modalities may be lower than with surgical treatment. The AAD guidelines also note that there is insufficient evidence to recommend routine use of laser or electronic surface brachytherapy.¹

Multidisciplinary consultation is recommended in patients with metastatic BCCs along with first-line treatment with a smoothened inhibitor.¹ Alternative treatment options include platinum-based chemotherapy and/or supportive care. For locally advanced disease, surgery and radiation therapy remain the initial treatments, but smoothened inhibitors and supportive care are suitable alternative treatments.¹

The AAD guidelines also offer recommendations for follow-up and reducing future risk of skin cancer. After the first diagnosis of BCC, a skin cancer screening should be performed at least annually, and patients should be counseled about self-examinations and sun protection.¹ Topical and oral retinoids are not recommended for the prevention of additional skin cancers, nor is dietary supplementation with selenium or beta-carotene. There also is insufficient evidence regarding the use of oral nicotinamide, celecoxib, or α-difluoromethylornithine for chemoprevention of disease.¹

cSCC Guidelines

For suspected cSCCs, no single optimal biopsy technique is recommended, but repeat biopsy may be considered if the initial biopsy is insufficient for diagnosis.² The guidelines further recommend an extensive list of elements to be included in the final pathology report (eg, lesion size, immunosuppression, depth of invasion, degree of differentiation). There is no universally recognized stratification for localized cSCC; therefore, the AAD guidelines refer to the framework provided by the NCCN. Also mentioned is the recent release of the American Joint Committee on Cancer’s staging manual,⁸ which includes the management of cSCC in conjunction with all SCCs of the head and neck. The Brigham and Women’s system⁹ was considered as an alternative classification system; however, the NCCN guidelines were chosen because they primarily provide clinical guidance for treatment of cSCC rather than provide accurate prognostication or outcome assessment.

Considerations for surgical treatment of cSCC are similar to those for BCC.² In low-risk tumors, surgical excision with 4- to 6-mm margins to the midsubcutaneous fat or curettage with electrodessication may be considered. Mohs micrographic surgery or standard excision with attention to margin control may be considered for high-risk tumors. Nonsurgical therapies generally are not recommended as a first-line treatment, particularly in cSCC, due to possible recurrence and metastasis. When nonsurgical therapies are preferred, options may include cryosurgery or radiation therapy, with the understanding that cure rates may be lower than with surgical options. Topical therapy with imiquimod or 5-fluorouracil as well as photodynamic or laser therapy are not recommended for cSCCs.²

For patients with metastatic cSCC or locally advanced disease, multidisciplinary consultation is recommended.² In cSCCs with regional lymph node metastases, the recommended approach includes surgical resection with possible adjuvant radiation therapy and/or systemic therapy. For inoperable disease, combination chemoradiation may be considered. Epidermal growth factor inhibitors and cisplatin may be considered in metastatic disease, although there are limited data to support their efficacy. As with BCC, all patients with cSCCs should receive supportive and palliative care to optimize quality of life.²

Recommendations for follow-up after the first diagnosis of cSCC are the same as those for BCC.² Additionally, acitretin is the only therapy that may be beneficial in the reduction of recurrent skin cancer in patients who are solid-organ transplant recipients.

Final Thoughts

A comprehensive understanding of the management of NMSC and the evidence on which recommendations are based is critically important for optimal patient care. These guidelines are an efficient way for dermatologists and their colleagues to understand the latest evidence and recommendations. The AAD guidelines provide support for clinical decision making with standardized approaches to the diagnosis, care, and prevention of NMSC that are consistent with established practice patterns.

With few exceptions, surgical therapy is the most effective approach for the treatment of BCC and cSCC; however, the AAD guidelines include an important review on nonsurgical management options.^1,2 The AAD guidelines help to highlight where data on evidence-based outcomes exist and reveal where data remain insufficient. This is illustrated by the guideline recommendations for providing additional histopathologic characteristics in the pathology reports, which will likely produce future data to enhance the prognosis and eventual treatment of patients with NMSC.^1,2 Future guidelines also may include newer technologies (eg, gene expression profiling).

The guidelines do not cover the management of premalignant and in situ lesions, nor do they provide details on the management of metastatic or locally advanced disease. These topics certainly will require a similar critical review and may be addressed separately. The guidelines are identifying unanswered questions about patient care and are concurrently establishing the collection of appropriate data to answer these questions in the future.

Official guidelines often become the primary source for the measured standard of both treatment and outcomes in patient care; therefore, it is critical that dermatologists and the AAD take the lead in creating these guidelines so that we can provide our patients with the best evidenced-based comprehensive care.

The AAD guidelines emphasize the importance of considering the patient perspective in determining how to treat BCCs and cSCCs.^1,2 It is important for patients to understand the available treatment options and participate in their own medical care. The AAD work group for these guidelines included patient advocates to ensure that the guidelines would promote further dialogue between physicians and their patients.

The AAD guidelines for the management of NMSC were developed by board-certified dermatologists and other experts in the field. They allow dermatologists to work with patients diagnosed with NMSC to determine the treatment option that is best for each individual patient.

The Food and Drug Administration will conduct a priority review of cemiplimab for the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma (SCC), the companies developing the treatment announced on April 30.

Cemiplimab, a human monoclonal antibody being developed by Regeneron Pharmaceuticals and Sanofi, targets the checkpoint inhibitor programmed cell death protein-1 (PD-1). The drug was previously granted Breakthrough Therapy status by the FDA in September 2017.

lfranki@frontlinemedcom.com

The Food and Drug Administration will conduct a priority review of cemiplimab for the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma (SCC), the companies developing the treatment announced on April 30.

Cemiplimab, a human monoclonal antibody being developed by Regeneron Pharmaceuticals and Sanofi, targets the checkpoint inhibitor programmed cell death protein-1 (PD-1). The drug was previously granted Breakthrough Therapy status by the FDA in September 2017.

lfranki@frontlinemedcom.com

The Food and Drug Administration will conduct a priority review of cemiplimab for the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma (SCC), the companies developing the treatment announced on April 30.

Cemiplimab, a human monoclonal antibody being developed by Regeneron Pharmaceuticals and Sanofi, targets the checkpoint inhibitor programmed cell death protein-1 (PD-1). The drug was previously granted Breakthrough Therapy status by the FDA in September 2017.

lfranki@frontlinemedcom.com

A Danish cohort study provides more evidence of a significant link between HIV infection and two types of skin cancer.

Danish researchers report that HIV-positive patients as a whole faced a higher risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with incidence rate ratios (IRRs) of 1.79 and 5.40, respectively, when compared with a background population, who were HIV-negative.

“The risk of SCC seemed to increase with increasing level of immunosuppression while the increased risk of BCC was restricted to patients reporting MSM [men who have sex with men] as route of infection,” wrote the authors, led by Silje Haukali Omland, MD, PhD, of the department of dermato-venereology, Copenhagen University Hospital.

The Danish nationwide cohort study, which matched each HIV patient with 5 age- and sex-matched individuals from the background population, was published online March 26 in the Journal of the American Academy of Dermatology.

The results are similar to those published elsewhere, as is the finding that HIV-positive patients do not face a higher risk of malignant melanoma. “The results here confirm prior studies and support heightened vigilance for skin conditions, such as SCC and BCC in HIV patients,” said Michael J. Silverberg, PhD, of Kaiser Permanente Division of Research, in an interview after reviewing the study findings. He was not a study author.

Overall, those who were HIV-positive were more likely to develop BCC (IRR, 1.79, 95% CI, 1.43-2.22), and males who reported sex with men had an even higher risk (IRR, 2.30, 95% CI, 1.76-3.02).

As for SCC, the IRR was 5.40 (95% CI, 3.07-9.52) among those who were HIV-positive, compared with the background population, and the researchers found evidence that risk increased with level of immunosuppression. Those who indicated heterosexual and male homosexual transmission had similar rates of SCC.

The rates of BCC or SCC were not higher among siblings of HIV-positive patients.

In addition, the risk of melanoma was not increased among those who were HIV-positive subjects or their siblings, when compared with the background group. However, the researchers noted that the study turned up a low number of HIV-positive subjects with melanoma, potentially throwing off the results.

The researchers noted that the inclusion of siblings in the study suggests that sun exposure in childhood was not a confounding factor. Presumably, they wrote, the siblings had similar levels of exposure as children, although exposure to sun bed tanning could differ between siblings.

“Study methods appear very strong and consistent with other work done in the area,” Dr. Silverberg said in the interview. As for possible causes of the disparities, he noted that exposure to the sun or to tanning beds could explain the greater risk of BCC among men who have sex with men. “For SCC, there may be a biological link, as studies have suggested a link with human papillomavirus for that particular cancer,” he added.

No study funding was reported. The study authors reported disclosures that included grants, research grants, speaker fees, and/or advisory board honoraria from several drug manufacturers. Dr. Silverberg has no relevant disclosures.

SOURCE: Omland S et al. J Am Acad Dermatol. 2018 Mar 24. pii: S0190-9622(18)30475-4. doi: 10.1016/j.jaad.2018.03.024.

A Danish cohort study provides more evidence of a significant link between HIV infection and two types of skin cancer.

Danish researchers report that HIV-positive patients as a whole faced a higher risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with incidence rate ratios (IRRs) of 1.79 and 5.40, respectively, when compared with a background population, who were HIV-negative.

“The risk of SCC seemed to increase with increasing level of immunosuppression while the increased risk of BCC was restricted to patients reporting MSM [men who have sex with men] as route of infection,” wrote the authors, led by Silje Haukali Omland, MD, PhD, of the department of dermato-venereology, Copenhagen University Hospital.

The Danish nationwide cohort study, which matched each HIV patient with 5 age- and sex-matched individuals from the background population, was published online March 26 in the Journal of the American Academy of Dermatology.

The results are similar to those published elsewhere, as is the finding that HIV-positive patients do not face a higher risk of malignant melanoma. “The results here confirm prior studies and support heightened vigilance for skin conditions, such as SCC and BCC in HIV patients,” said Michael J. Silverberg, PhD, of Kaiser Permanente Division of Research, in an interview after reviewing the study findings. He was not a study author.

Overall, those who were HIV-positive were more likely to develop BCC (IRR, 1.79, 95% CI, 1.43-2.22), and males who reported sex with men had an even higher risk (IRR, 2.30, 95% CI, 1.76-3.02).

As for SCC, the IRR was 5.40 (95% CI, 3.07-9.52) among those who were HIV-positive, compared with the background population, and the researchers found evidence that risk increased with level of immunosuppression. Those who indicated heterosexual and male homosexual transmission had similar rates of SCC.

The rates of BCC or SCC were not higher among siblings of HIV-positive patients.

In addition, the risk of melanoma was not increased among those who were HIV-positive subjects or their siblings, when compared with the background group. However, the researchers noted that the study turned up a low number of HIV-positive subjects with melanoma, potentially throwing off the results.

The researchers noted that the inclusion of siblings in the study suggests that sun exposure in childhood was not a confounding factor. Presumably, they wrote, the siblings had similar levels of exposure as children, although exposure to sun bed tanning could differ between siblings.

“Study methods appear very strong and consistent with other work done in the area,” Dr. Silverberg said in the interview. As for possible causes of the disparities, he noted that exposure to the sun or to tanning beds could explain the greater risk of BCC among men who have sex with men. “For SCC, there may be a biological link, as studies have suggested a link with human papillomavirus for that particular cancer,” he added.

No study funding was reported. The study authors reported disclosures that included grants, research grants, speaker fees, and/or advisory board honoraria from several drug manufacturers. Dr. Silverberg has no relevant disclosures.

SOURCE: Omland S et al. J Am Acad Dermatol. 2018 Mar 24. pii: S0190-9622(18)30475-4. doi: 10.1016/j.jaad.2018.03.024.

A Danish cohort study provides more evidence of a significant link between HIV infection and two types of skin cancer.

Danish researchers report that HIV-positive patients as a whole faced a higher risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with incidence rate ratios (IRRs) of 1.79 and 5.40, respectively, when compared with a background population, who were HIV-negative.

“The risk of SCC seemed to increase with increasing level of immunosuppression while the increased risk of BCC was restricted to patients reporting MSM [men who have sex with men] as route of infection,” wrote the authors, led by Silje Haukali Omland, MD, PhD, of the department of dermato-venereology, Copenhagen University Hospital.

The Danish nationwide cohort study, which matched each HIV patient with 5 age- and sex-matched individuals from the background population, was published online March 26 in the Journal of the American Academy of Dermatology.

The results are similar to those published elsewhere, as is the finding that HIV-positive patients do not face a higher risk of malignant melanoma. “The results here confirm prior studies and support heightened vigilance for skin conditions, such as SCC and BCC in HIV patients,” said Michael J. Silverberg, PhD, of Kaiser Permanente Division of Research, in an interview after reviewing the study findings. He was not a study author.

Overall, those who were HIV-positive were more likely to develop BCC (IRR, 1.79, 95% CI, 1.43-2.22), and males who reported sex with men had an even higher risk (IRR, 2.30, 95% CI, 1.76-3.02).

As for SCC, the IRR was 5.40 (95% CI, 3.07-9.52) among those who were HIV-positive, compared with the background population, and the researchers found evidence that risk increased with level of immunosuppression. Those who indicated heterosexual and male homosexual transmission had similar rates of SCC.

The rates of BCC or SCC were not higher among siblings of HIV-positive patients.

In addition, the risk of melanoma was not increased among those who were HIV-positive subjects or their siblings, when compared with the background group. However, the researchers noted that the study turned up a low number of HIV-positive subjects with melanoma, potentially throwing off the results.

The researchers noted that the inclusion of siblings in the study suggests that sun exposure in childhood was not a confounding factor. Presumably, they wrote, the siblings had similar levels of exposure as children, although exposure to sun bed tanning could differ between siblings.

“Study methods appear very strong and consistent with other work done in the area,” Dr. Silverberg said in the interview. As for possible causes of the disparities, he noted that exposure to the sun or to tanning beds could explain the greater risk of BCC among men who have sex with men. “For SCC, there may be a biological link, as studies have suggested a link with human papillomavirus for that particular cancer,” he added.

No study funding was reported. The study authors reported disclosures that included grants, research grants, speaker fees, and/or advisory board honoraria from several drug manufacturers. Dr. Silverberg has no relevant disclosures.

SOURCE: Omland S et al. J Am Acad Dermatol. 2018 Mar 24. pii: S0190-9622(18)30475-4. doi: 10.1016/j.jaad.2018.03.024.

FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

The number of new cases per year of Merkel cell carcinoma (MCC) increased by 95% during 2000-2013, according to a review of Surveillance, Epidemiology, and End Results (SEER) data.

There were 652 cases of MCC in the SEER-18 registry in 2013, up from the 334 cases captured by the database in 2000.

This increase exceeded the 56.5% increase seen with melanoma over the same time period, the investigators wrote in the Journal of the American Academy of Dermatology.

The total number of incident MCC cases in the United States in 2013 was calculated as 2,488 cases/year by using SEER-derived incidence rates combined with U.S. Census population data. The MCC incidence rate rose precipitously with age, increasing 10-fold between ages 40-44 years (0.1 cases/100,000 person-years) and ages 60-64 years (0.9 cases/100,000 person-years).

Given the aging of the population and an assumption that the incidence rates within any given age group will remain stable, the annual incidence of Merkel cell carcinoma in the United States will increase to 3,284 cases/year in 2025, Kelly G. Paulson, MD, PhD, of the Fred Hutchinson Cancer Research Center, Seattle, and her colleagues projected.

“The incidence of MCC is increasing and will likely continue to rise as the Baby Boomer population enters the higher-risk age groups for MCC,” Dr. Paulson and colleagues said. ”Because of its high propensity for spread, the need for adjuvant radiation in many cases, and the clear role for early immunotherapy in the metastatic setting, both early detection and optimal management will be critical for improved outcomes,” they concluded.

SOURCE: Paulson KG et al. J Am Acad Derm. 2018 Mar;78(3):457-463.

FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

The number of new cases per year of Merkel cell carcinoma (MCC) increased by 95% during 2000-2013, according to a review of Surveillance, Epidemiology, and End Results (SEER) data.

There were 652 cases of MCC in the SEER-18 registry in 2013, up from the 334 cases captured by the database in 2000.

This increase exceeded the 56.5% increase seen with melanoma over the same time period, the investigators wrote in the Journal of the American Academy of Dermatology.

The total number of incident MCC cases in the United States in 2013 was calculated as 2,488 cases/year by using SEER-derived incidence rates combined with U.S. Census population data. The MCC incidence rate rose precipitously with age, increasing 10-fold between ages 40-44 years (0.1 cases/100,000 person-years) and ages 60-64 years (0.9 cases/100,000 person-years).

Given the aging of the population and an assumption that the incidence rates within any given age group will remain stable, the annual incidence of Merkel cell carcinoma in the United States will increase to 3,284 cases/year in 2025, Kelly G. Paulson, MD, PhD, of the Fred Hutchinson Cancer Research Center, Seattle, and her colleagues projected.

“The incidence of MCC is increasing and will likely continue to rise as the Baby Boomer population enters the higher-risk age groups for MCC,” Dr. Paulson and colleagues said. ”Because of its high propensity for spread, the need for adjuvant radiation in many cases, and the clear role for early immunotherapy in the metastatic setting, both early detection and optimal management will be critical for improved outcomes,” they concluded.

SOURCE: Paulson KG et al. J Am Acad Derm. 2018 Mar;78(3):457-463.

FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

The number of new cases per year of Merkel cell carcinoma (MCC) increased by 95% during 2000-2013, according to a review of Surveillance, Epidemiology, and End Results (SEER) data.

There were 652 cases of MCC in the SEER-18 registry in 2013, up from the 334 cases captured by the database in 2000.

This increase exceeded the 56.5% increase seen with melanoma over the same time period, the investigators wrote in the Journal of the American Academy of Dermatology.

The total number of incident MCC cases in the United States in 2013 was calculated as 2,488 cases/year by using SEER-derived incidence rates combined with U.S. Census population data. The MCC incidence rate rose precipitously with age, increasing 10-fold between ages 40-44 years (0.1 cases/100,000 person-years) and ages 60-64 years (0.9 cases/100,000 person-years).

Given the aging of the population and an assumption that the incidence rates within any given age group will remain stable, the annual incidence of Merkel cell carcinoma in the United States will increase to 3,284 cases/year in 2025, Kelly G. Paulson, MD, PhD, of the Fred Hutchinson Cancer Research Center, Seattle, and her colleagues projected.

“The incidence of MCC is increasing and will likely continue to rise as the Baby Boomer population enters the higher-risk age groups for MCC,” Dr. Paulson and colleagues said. ”Because of its high propensity for spread, the need for adjuvant radiation in many cases, and the clear role for early immunotherapy in the metastatic setting, both early detection and optimal management will be critical for improved outcomes,” they concluded.

SOURCE: Paulson KG et al. J Am Acad Derm. 2018 Mar;78(3):457-463.

DALLAS – The use of CO₂ laser ablation guided by reflectance confocal microscopy is an effective, minimally invasive treatment for superficial and early nodular basal cell carcinoma (BCC), according to results from an ongoing study.

“While surgery is the gold standard for many basal cell carcinomas, nonsurgical therapies may be a good option for the superficial and early nodular subtypes,” lead study author Anthony M. Rossi, MD, said at the annual conference of the American Society for Laser Medicine and Surgery. “Laser ablation was used many years ago, so this is not a novel concept, but we’re bringing it back and we’re trying to use confocal microscopy to hone in on the basal cell and selectively target the tumor.”

Courtesy MSKCC

For the current analysis, he and his associates used a 10,600 nm CO₂ laser that selectively targets water to treat 20 BCCs in four males and three females with a mean age of 55 years. Of the 20 lesions, 18 were located on the limbs and trunk, while two were on the head and neck. The median lesion diameter was 7 mm. Prior to laser ablation, the researchers performed reflectance confocal microscopy to define lateral and deep margins and define the laser parameters.

Courtesy Dr. Anthony M. Rossi

The median number of laser passes was three, and ranged from two to eight, delivered at a fluence of 7.5 J/cm². Reflectance confocal microscopy was repeated immediately after the laser treatment to the skin wound margins and deep margins, and it was performed every 3-6 months thereafter. “If you do confocal microscopy too early, you’ll see mainly inflammation and you may see residual tumor that hasn’t been fully resolved yet,” Dr. Rossi said.

Courtesy Dr. Anthony M. Rossi

As for future directions, he and his colleagues are developing contrast agents to enhance the ability to detect BCC tumors in vivo, to highlight tumor islands, and to differentiate sebaceous glands and hair follicles. Dr. Rossi reported having no relevant disclosures.

dbrunk@mdedge.com

DALLAS – The use of CO₂ laser ablation guided by reflectance confocal microscopy is an effective, minimally invasive treatment for superficial and early nodular basal cell carcinoma (BCC), according to results from an ongoing study.

“While surgery is the gold standard for many basal cell carcinomas, nonsurgical therapies may be a good option for the superficial and early nodular subtypes,” lead study author Anthony M. Rossi, MD, said at the annual conference of the American Society for Laser Medicine and Surgery. “Laser ablation was used many years ago, so this is not a novel concept, but we’re bringing it back and we’re trying to use confocal microscopy to hone in on the basal cell and selectively target the tumor.”

Courtesy MSKCC

For the current analysis, he and his associates used a 10,600 nm CO₂ laser that selectively targets water to treat 20 BCCs in four males and three females with a mean age of 55 years. Of the 20 lesions, 18 were located on the limbs and trunk, while two were on the head and neck. The median lesion diameter was 7 mm. Prior to laser ablation, the researchers performed reflectance confocal microscopy to define lateral and deep margins and define the laser parameters.

Courtesy Dr. Anthony M. Rossi

The median number of laser passes was three, and ranged from two to eight, delivered at a fluence of 7.5 J/cm². Reflectance confocal microscopy was repeated immediately after the laser treatment to the skin wound margins and deep margins, and it was performed every 3-6 months thereafter. “If you do confocal microscopy too early, you’ll see mainly inflammation and you may see residual tumor that hasn’t been fully resolved yet,” Dr. Rossi said.

Courtesy Dr. Anthony M. Rossi

As for future directions, he and his colleagues are developing contrast agents to enhance the ability to detect BCC tumors in vivo, to highlight tumor islands, and to differentiate sebaceous glands and hair follicles. Dr. Rossi reported having no relevant disclosures.

dbrunk@mdedge.com

DALLAS – The use of CO₂ laser ablation guided by reflectance confocal microscopy is an effective, minimally invasive treatment for superficial and early nodular basal cell carcinoma (BCC), according to results from an ongoing study.

“While surgery is the gold standard for many basal cell carcinomas, nonsurgical therapies may be a good option for the superficial and early nodular subtypes,” lead study author Anthony M. Rossi, MD, said at the annual conference of the American Society for Laser Medicine and Surgery. “Laser ablation was used many years ago, so this is not a novel concept, but we’re bringing it back and we’re trying to use confocal microscopy to hone in on the basal cell and selectively target the tumor.”

Courtesy MSKCC

For the current analysis, he and his associates used a 10,600 nm CO₂ laser that selectively targets water to treat 20 BCCs in four males and three females with a mean age of 55 years. Of the 20 lesions, 18 were located on the limbs and trunk, while two were on the head and neck. The median lesion diameter was 7 mm. Prior to laser ablation, the researchers performed reflectance confocal microscopy to define lateral and deep margins and define the laser parameters.

Courtesy Dr. Anthony M. Rossi

The median number of laser passes was three, and ranged from two to eight, delivered at a fluence of 7.5 J/cm². Reflectance confocal microscopy was repeated immediately after the laser treatment to the skin wound margins and deep margins, and it was performed every 3-6 months thereafter. “If you do confocal microscopy too early, you’ll see mainly inflammation and you may see residual tumor that hasn’t been fully resolved yet,” Dr. Rossi said.

Courtesy Dr. Anthony M. Rossi

As for future directions, he and his colleagues are developing contrast agents to enhance the ability to detect BCC tumors in vivo, to highlight tumor islands, and to differentiate sebaceous glands and hair follicles. Dr. Rossi reported having no relevant disclosures.

dbrunk@mdedge.com

I was driving to work the other day, perched up in my pickup truck (somehow you knew that) and noticed a fancy race car in front of me with a vanity tag. It read HRTATTK 4. Well, I thought after four heart attacks maybe I would splurge on a special car too (more likely a newer truck). Then I noticed smoke coming out of the driver’s window, and I could see this guy in his side view mirror, presumably Mr. “Heart Attack 4,” puffing away on a cigarette. Wow.

Then I got to work and saw my secretary, who works with her oxygen on, out back puffing a cigarette. Wow.

It turns out that cigarette smoke contains substances that act as a monoamine oxidase (MAO) A inhibitor, prolonging the dopamine high in the brain (Proc Natl Acad Sci U S A. 1996 Nov 26;93[24]:14065-9). Makes sense and may explain the above smoking behavior. I truly believe cigarettes are as or more addictive than any other dopamine enhancing drug.

More than 50 years ago, a national campaign against smoking was launched after the 1964 Surgeon General’s report concluded that smoking was a major health hazard. (Looking back, one of the few losses of not having to pull journal articles from the stacks in the library, is that medical students and residents can’t shake their heads in wonder at the cigarette ads in old medical journals.) The impact of the national antismoking campaign has been dramatic, but smoking remains the leading preventable cause of death in the United States and globally, according to the Centers for Disease Control and Prevention.

karenfoleyphotography/Thinkstock

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at dermnews@mdedge.com.

I was driving to work the other day, perched up in my pickup truck (somehow you knew that) and noticed a fancy race car in front of me with a vanity tag. It read HRTATTK 4. Well, I thought after four heart attacks maybe I would splurge on a special car too (more likely a newer truck). Then I noticed smoke coming out of the driver’s window, and I could see this guy in his side view mirror, presumably Mr. “Heart Attack 4,” puffing away on a cigarette. Wow.

Then I got to work and saw my secretary, who works with her oxygen on, out back puffing a cigarette. Wow.

It turns out that cigarette smoke contains substances that act as a monoamine oxidase (MAO) A inhibitor, prolonging the dopamine high in the brain (Proc Natl Acad Sci U S A. 1996 Nov 26;93[24]:14065-9). Makes sense and may explain the above smoking behavior. I truly believe cigarettes are as or more addictive than any other dopamine enhancing drug.

More than 50 years ago, a national campaign against smoking was launched after the 1964 Surgeon General’s report concluded that smoking was a major health hazard. (Looking back, one of the few losses of not having to pull journal articles from the stacks in the library, is that medical students and residents can’t shake their heads in wonder at the cigarette ads in old medical journals.) The impact of the national antismoking campaign has been dramatic, but smoking remains the leading preventable cause of death in the United States and globally, according to the Centers for Disease Control and Prevention.

karenfoleyphotography/Thinkstock

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at dermnews@mdedge.com.

I was driving to work the other day, perched up in my pickup truck (somehow you knew that) and noticed a fancy race car in front of me with a vanity tag. It read HRTATTK 4. Well, I thought after four heart attacks maybe I would splurge on a special car too (more likely a newer truck). Then I noticed smoke coming out of the driver’s window, and I could see this guy in his side view mirror, presumably Mr. “Heart Attack 4,” puffing away on a cigarette. Wow.

Then I got to work and saw my secretary, who works with her oxygen on, out back puffing a cigarette. Wow.

It turns out that cigarette smoke contains substances that act as a monoamine oxidase (MAO) A inhibitor, prolonging the dopamine high in the brain (Proc Natl Acad Sci U S A. 1996 Nov 26;93[24]:14065-9). Makes sense and may explain the above smoking behavior. I truly believe cigarettes are as or more addictive than any other dopamine enhancing drug.

More than 50 years ago, a national campaign against smoking was launched after the 1964 Surgeon General’s report concluded that smoking was a major health hazard. (Looking back, one of the few losses of not having to pull journal articles from the stacks in the library, is that medical students and residents can’t shake their heads in wonder at the cigarette ads in old medical journals.) The impact of the national antismoking campaign has been dramatic, but smoking remains the leading preventable cause of death in the United States and globally, according to the Centers for Disease Control and Prevention.

karenfoleyphotography/Thinkstock

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at dermnews@mdedge.com.

KAUAI, HAWAII – Every child diagnosed with medulloblastoma deserves a careful dermatologic evaluation for possible comorbid basal cell nevus syndrome, according to Jennifer Huang, MD, a pediatric dermatologist at Boston Children’s Hospital and Harvard Medical School.

“Medulloblastoma occurs in 10%-20% of patients with basal cell nevus syndrome and can be the presenting sign. So if a patient with basal cell nevus syndrome gets medulloblastoma, it usually occurs within the first year of life – and it can be the first thing you see,” she said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. Huang presented a series of pediatric dermatology clinical pearls focused not only on basal cell nevus syndrome (BCNS) and medulloblastoma, but also on the implications of skin-limited Langerhans cell histiocytosis, how to recognize and treat drug-induced follicular eruptions in pediatric patients on targeted anticancer therapies, and when to suspect Demodex folliculitis in immunosuppressed patients.
 

Skin-limited Langerhans cell histiocytosis

Around 10%-20% of patients with Langerhans cell histiocytosis (LCH) have the skin-limited form of the malignancy. These are patients who, after a thorough workup, have a normal CBC, skeletal survey, and liver function tests; essentially, no evidence of multisystem disease.

Bruce Jancin/MDedge News

Basal cell nevus syndrome and medulloblastoma

“Half of cases of medulloblastoma are associated with mutations in the sonic hedgehog pathway – and a subset of that group has basal cell nevus syndrome,” Dr. Huang said.

BCNS is not a diagnosis frequently made by oncologists, who typically dismiss the multitude of lesions as skin tags, which they often mimic in both appearance and location, particularly on the neck and intertriginous areas. So it’s useful for dermatologists to establish a good referral relationship with their local oncologists.

“As dermatologists it’s really important to recognize not only the major features of basal cell nevus syndrome, but also the associated findings because we can really help in making this diagnosis early,” Dr. Huang stressed.

Early diagnosis of BCNS is a high priority for two reasons: to start treatment aimed at reducing development of basal cell carcinomas, and because radiation therapy for their medulloblastoma is contraindicated in patients with BCNS because it boosts their skin cancer burden.

BCNS is caused by mutations in the PTCH (Patched) gene found on chromosome arm 9q. The major features of BCNS include odontogenic keratocysts, palmoplantar pits, ectopic calcification, and, of course, basal cell carcinomas. The associated findings in BCNS, in addition to medulloblastoma, include macrocephaly and dysmorphic features such as cleft lip or palate, frontal bossing, and hypertelorism.

Follicular eruptions in cancer patients on MAPK inhibitors

Cutaneous reactions to anticancer drugs aimed at inhibiting the key MAPK (mitogen-activated protein kinase) pathway in children are common and diverse. Dr. Huang focused on the most common one: follicular eruptions, which occur in up to 80% of pediatric cancer patients on targeted therapy. These eruptions can express themselves in a variety of ways and are easily mistaken for comedonal acne, varicella zoster infection, herpes simplex, or bacterial folliculitis.

The key clues are highly suggestive that a follicular eruption in a child on targeted anticancer therapy is caused by the drug and not something else are the eruption’s symmetric distribution, that it’s truly follicular upon close inspection, and the timing: The eruption typically begins 2-3 weeks after initiation of therapy or within a week after a dose escalation.

Anti-inflammatory agents are the treatment mainstay. Treatment of the cutaneous eruption often is successful without need to discontinue the patient’s MAPK inhibitor.

“Even though some of these eruptions look comedonal, they’re not. It’s not a follicular plugging disorder, it’s an inflammatory condition. Topical steroids, oral tetracyclines, and dilute bleach baths all work pretty well. I haven’t had good experiences with keratolytics like tretinoin cream and benzoyl peroxide; they’re less effective. Dose reduction is the last resort for these patients. Often they are very sick. They need the drug and I think the last thing we want to do is take them off it,” Dr. Huang said.

She has observed that prepubertal children are more likely to have an eczematous reaction to their targeted anticancer therapy than a follicular eruption.

D. folliculitis in immunocompromised patients

“The clinical pearl here is to strongly consider the diagnosis of Demodex folliculitis in an immunosuppresed patient with an itchy acneiform eruption,” Dr. Huang said.

Demodex is a human mite which is part of the normal skin flora. She called it “a great mimicker”: It can cause dermatoses mistaken for rosacea, acne, seborrheic dermatitis, perioral facial dermatitis, blepharitis, and acute graft-versus-host disease.

In the setting of a young, immunosuppressed patient who develops an acneiform eruption, the differential diagnosis is lengthy and includes steroid-induced acne, a cutaneous reaction to targeted anticancer therapy, gram-negative folliculitis secondary to long-term antibiotic therapy, and Pityrosporum folliculitis, as well as D. folliculitis.

Demodex and P. folliculitis are the two acneiform dermatoses where itch figures prominently. A couple of clues are helpful in differentiating the two conditions: P. folliculitis often involves the chest and back, while D. folliculitis generally spares the trunk and is focused on the face and neck. And D. folliculitis typically arises when immunosuppression is weaned. Overgrowth of the mites occurs during immunosuppression, then as the immunosuppression is lifted a prominent inflammatory response with an acne-like appearance occurs.

Dr. Huang usually sticks with topical therapies for D. folliculitis. These include topical sulfur 5%, permethrin 5%, metronidazole, and/or ivermectin. If a young patient is unresponsive to this panoply of topical agents, she resorts to a single dose of oral ivermectin at 0.2 mg/kg, usually with good effect.

Dr. Huang reported having no financial conflicts of interest regarding her presentation.

The SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

bjancin@mdedge.com

KAUAI, HAWAII – Every child diagnosed with medulloblastoma deserves a careful dermatologic evaluation for possible comorbid basal cell nevus syndrome, according to Jennifer Huang, MD, a pediatric dermatologist at Boston Children’s Hospital and Harvard Medical School.

“Medulloblastoma occurs in 10%-20% of patients with basal cell nevus syndrome and can be the presenting sign. So if a patient with basal cell nevus syndrome gets medulloblastoma, it usually occurs within the first year of life – and it can be the first thing you see,” she said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. Huang presented a series of pediatric dermatology clinical pearls focused not only on basal cell nevus syndrome (BCNS) and medulloblastoma, but also on the implications of skin-limited Langerhans cell histiocytosis, how to recognize and treat drug-induced follicular eruptions in pediatric patients on targeted anticancer therapies, and when to suspect Demodex folliculitis in immunosuppressed patients.
 

Skin-limited Langerhans cell histiocytosis

Around 10%-20% of patients with Langerhans cell histiocytosis (LCH) have the skin-limited form of the malignancy. These are patients who, after a thorough workup, have a normal CBC, skeletal survey, and liver function tests; essentially, no evidence of multisystem disease.

Bruce Jancin/MDedge News

Basal cell nevus syndrome and medulloblastoma

“Half of cases of medulloblastoma are associated with mutations in the sonic hedgehog pathway – and a subset of that group has basal cell nevus syndrome,” Dr. Huang said.

BCNS is not a diagnosis frequently made by oncologists, who typically dismiss the multitude of lesions as skin tags, which they often mimic in both appearance and location, particularly on the neck and intertriginous areas. So it’s useful for dermatologists to establish a good referral relationship with their local oncologists.

“As dermatologists it’s really important to recognize not only the major features of basal cell nevus syndrome, but also the associated findings because we can really help in making this diagnosis early,” Dr. Huang stressed.

Early diagnosis of BCNS is a high priority for two reasons: to start treatment aimed at reducing development of basal cell carcinomas, and because radiation therapy for their medulloblastoma is contraindicated in patients with BCNS because it boosts their skin cancer burden.

BCNS is caused by mutations in the PTCH (Patched) gene found on chromosome arm 9q. The major features of BCNS include odontogenic keratocysts, palmoplantar pits, ectopic calcification, and, of course, basal cell carcinomas. The associated findings in BCNS, in addition to medulloblastoma, include macrocephaly and dysmorphic features such as cleft lip or palate, frontal bossing, and hypertelorism.

Follicular eruptions in cancer patients on MAPK inhibitors

Cutaneous reactions to anticancer drugs aimed at inhibiting the key MAPK (mitogen-activated protein kinase) pathway in children are common and diverse. Dr. Huang focused on the most common one: follicular eruptions, which occur in up to 80% of pediatric cancer patients on targeted therapy. These eruptions can express themselves in a variety of ways and are easily mistaken for comedonal acne, varicella zoster infection, herpes simplex, or bacterial folliculitis.

The key clues are highly suggestive that a follicular eruption in a child on targeted anticancer therapy is caused by the drug and not something else are the eruption’s symmetric distribution, that it’s truly follicular upon close inspection, and the timing: The eruption typically begins 2-3 weeks after initiation of therapy or within a week after a dose escalation.

Anti-inflammatory agents are the treatment mainstay. Treatment of the cutaneous eruption often is successful without need to discontinue the patient’s MAPK inhibitor.

“Even though some of these eruptions look comedonal, they’re not. It’s not a follicular plugging disorder, it’s an inflammatory condition. Topical steroids, oral tetracyclines, and dilute bleach baths all work pretty well. I haven’t had good experiences with keratolytics like tretinoin cream and benzoyl peroxide; they’re less effective. Dose reduction is the last resort for these patients. Often they are very sick. They need the drug and I think the last thing we want to do is take them off it,” Dr. Huang said.

She has observed that prepubertal children are more likely to have an eczematous reaction to their targeted anticancer therapy than a follicular eruption.

D. folliculitis in immunocompromised patients

“The clinical pearl here is to strongly consider the diagnosis of Demodex folliculitis in an immunosuppresed patient with an itchy acneiform eruption,” Dr. Huang said.

Demodex is a human mite which is part of the normal skin flora. She called it “a great mimicker”: It can cause dermatoses mistaken for rosacea, acne, seborrheic dermatitis, perioral facial dermatitis, blepharitis, and acute graft-versus-host disease.

In the setting of a young, immunosuppressed patient who develops an acneiform eruption, the differential diagnosis is lengthy and includes steroid-induced acne, a cutaneous reaction to targeted anticancer therapy, gram-negative folliculitis secondary to long-term antibiotic therapy, and Pityrosporum folliculitis, as well as D. folliculitis.

Demodex and P. folliculitis are the two acneiform dermatoses where itch figures prominently. A couple of clues are helpful in differentiating the two conditions: P. folliculitis often involves the chest and back, while D. folliculitis generally spares the trunk and is focused on the face and neck. And D. folliculitis typically arises when immunosuppression is weaned. Overgrowth of the mites occurs during immunosuppression, then as the immunosuppression is lifted a prominent inflammatory response with an acne-like appearance occurs.

Dr. Huang usually sticks with topical therapies for D. folliculitis. These include topical sulfur 5%, permethrin 5%, metronidazole, and/or ivermectin. If a young patient is unresponsive to this panoply of topical agents, she resorts to a single dose of oral ivermectin at 0.2 mg/kg, usually with good effect.

Dr. Huang reported having no financial conflicts of interest regarding her presentation.

The SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

bjancin@mdedge.com

KAUAI, HAWAII – Every child diagnosed with medulloblastoma deserves a careful dermatologic evaluation for possible comorbid basal cell nevus syndrome, according to Jennifer Huang, MD, a pediatric dermatologist at Boston Children’s Hospital and Harvard Medical School.

“Medulloblastoma occurs in 10%-20% of patients with basal cell nevus syndrome and can be the presenting sign. So if a patient with basal cell nevus syndrome gets medulloblastoma, it usually occurs within the first year of life – and it can be the first thing you see,” she said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. Huang presented a series of pediatric dermatology clinical pearls focused not only on basal cell nevus syndrome (BCNS) and medulloblastoma, but also on the implications of skin-limited Langerhans cell histiocytosis, how to recognize and treat drug-induced follicular eruptions in pediatric patients on targeted anticancer therapies, and when to suspect Demodex folliculitis in immunosuppressed patients.
 

Skin-limited Langerhans cell histiocytosis

Around 10%-20% of patients with Langerhans cell histiocytosis (LCH) have the skin-limited form of the malignancy. These are patients who, after a thorough workup, have a normal CBC, skeletal survey, and liver function tests; essentially, no evidence of multisystem disease.

Bruce Jancin/MDedge News

Basal cell nevus syndrome and medulloblastoma

“Half of cases of medulloblastoma are associated with mutations in the sonic hedgehog pathway – and a subset of that group has basal cell nevus syndrome,” Dr. Huang said.

BCNS is not a diagnosis frequently made by oncologists, who typically dismiss the multitude of lesions as skin tags, which they often mimic in both appearance and location, particularly on the neck and intertriginous areas. So it’s useful for dermatologists to establish a good referral relationship with their local oncologists.

“As dermatologists it’s really important to recognize not only the major features of basal cell nevus syndrome, but also the associated findings because we can really help in making this diagnosis early,” Dr. Huang stressed.

Early diagnosis of BCNS is a high priority for two reasons: to start treatment aimed at reducing development of basal cell carcinomas, and because radiation therapy for their medulloblastoma is contraindicated in patients with BCNS because it boosts their skin cancer burden.

BCNS is caused by mutations in the PTCH (Patched) gene found on chromosome arm 9q. The major features of BCNS include odontogenic keratocysts, palmoplantar pits, ectopic calcification, and, of course, basal cell carcinomas. The associated findings in BCNS, in addition to medulloblastoma, include macrocephaly and dysmorphic features such as cleft lip or palate, frontal bossing, and hypertelorism.

Follicular eruptions in cancer patients on MAPK inhibitors

Cutaneous reactions to anticancer drugs aimed at inhibiting the key MAPK (mitogen-activated protein kinase) pathway in children are common and diverse. Dr. Huang focused on the most common one: follicular eruptions, which occur in up to 80% of pediatric cancer patients on targeted therapy. These eruptions can express themselves in a variety of ways and are easily mistaken for comedonal acne, varicella zoster infection, herpes simplex, or bacterial folliculitis.

The key clues are highly suggestive that a follicular eruption in a child on targeted anticancer therapy is caused by the drug and not something else are the eruption’s symmetric distribution, that it’s truly follicular upon close inspection, and the timing: The eruption typically begins 2-3 weeks after initiation of therapy or within a week after a dose escalation.

Anti-inflammatory agents are the treatment mainstay. Treatment of the cutaneous eruption often is successful without need to discontinue the patient’s MAPK inhibitor.

“Even though some of these eruptions look comedonal, they’re not. It’s not a follicular plugging disorder, it’s an inflammatory condition. Topical steroids, oral tetracyclines, and dilute bleach baths all work pretty well. I haven’t had good experiences with keratolytics like tretinoin cream and benzoyl peroxide; they’re less effective. Dose reduction is the last resort for these patients. Often they are very sick. They need the drug and I think the last thing we want to do is take them off it,” Dr. Huang said.

She has observed that prepubertal children are more likely to have an eczematous reaction to their targeted anticancer therapy than a follicular eruption.

D. folliculitis in immunocompromised patients

“The clinical pearl here is to strongly consider the diagnosis of Demodex folliculitis in an immunosuppresed patient with an itchy acneiform eruption,” Dr. Huang said.

Demodex is a human mite which is part of the normal skin flora. She called it “a great mimicker”: It can cause dermatoses mistaken for rosacea, acne, seborrheic dermatitis, perioral facial dermatitis, blepharitis, and acute graft-versus-host disease.

In the setting of a young, immunosuppressed patient who develops an acneiform eruption, the differential diagnosis is lengthy and includes steroid-induced acne, a cutaneous reaction to targeted anticancer therapy, gram-negative folliculitis secondary to long-term antibiotic therapy, and Pityrosporum folliculitis, as well as D. folliculitis.

Demodex and P. folliculitis are the two acneiform dermatoses where itch figures prominently. A couple of clues are helpful in differentiating the two conditions: P. folliculitis often involves the chest and back, while D. folliculitis generally spares the trunk and is focused on the face and neck. And D. folliculitis typically arises when immunosuppression is weaned. Overgrowth of the mites occurs during immunosuppression, then as the immunosuppression is lifted a prominent inflammatory response with an acne-like appearance occurs.

Dr. Huang usually sticks with topical therapies for D. folliculitis. These include topical sulfur 5%, permethrin 5%, metronidazole, and/or ivermectin. If a young patient is unresponsive to this panoply of topical agents, she resorts to a single dose of oral ivermectin at 0.2 mg/kg, usually with good effect.

Dr. Huang reported having no financial conflicts of interest regarding her presentation.

The SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

bjancin@mdedge.com

Merkel cell carcinoma (MCC) is a rare, rapidly growing, aggressive neoplasm with a generally poor prognosis. The cells of origin are highly anaplastic and share structural and immunohistochemical features with various neuroectodermally derived cells. Although Merkel cells, which are slow-acting cutaneous mechanoreceptors located in the basal layer of the epidermis, and MCC share immunohistochemical and ultrastructural features, there is limited evidence of a direct histogenetic relationship between the two.^1,2 Additionally, some extracutaneous neuroendocrine tumors have features similar to MCC; therefore, although it may be more accurate and perhaps more practical to describe these lesions as primary neuroendocrine carcinomas of the skin, the term MCC is more commonly used both in the literature and in clinical practice.^1,2

Merkel cell carcinoma typically presents in the head and neck region in white patients older than 70 years of age and in the immunocompromised population.^3-6 The mean age of diagnosis is 76 years for women and 74 years for men.⁷ The incidence of MCC in the United States tripled over a 15-year period, and there are approximately 1500 new cases of MCC diagnosed each year, making it about 40 times less common than melanoma.⁸ The 5-year survival rate for patients without lymph node involvement is 75%, whereas the 5-year survival rate for patients with distant metastases is 25%.⁹

Merkel cell carcinoma is thought to develop through 1 of 2 distinct pathways. In a virally mediated pathway, which represents at least 80% of cases, the Merkel cell polyomavirus (MCV) monoclonally integrates into the host genome and promotes oncogenesis via altered p53 and retinoblastoma protein expression.^10-12 The remainder of cases are believed to develop via a nonvirally mediated pathway in which genetic anomalies, immune status, and environmental factors influence oncogenesis.^10-13

Due to the similarity between MCC and metastatic neuroendocrine neoplasms, especially small-cell lung carcinomas, immunohistochemistry is important in making the diagnosis. Cytokeratin 20 and neuron-specific enolase positivity and thyroid transcription factor 1 negativity are the most useful markers in identifying MCC.

Regression of MCC is a very rare and poorly understood event. A 2010 review of the literature described 22 cases of spontaneous regression.¹⁴ We report a rare case of rapid and complete regression of MCC following punch biopsy in a 96-year-old woman.

Case Report

A 96-year-old woman presented with a rapidly enlarging lesion overlying the suprasternal notch of 8 weeks’ duration (Figure 1). The lesion consisted of a 5.0×4.5-cm, friable, erythematous, flesh-colored nodule with ulceration and heavy crusting. Surrounding the nodule was an erythematous to violaceous patch extending to the anterior chest and bilateral supraclavicular area. No cervical or clavicular lymphadenopathy was observed. According to the patient’s caregiver, the lesion originated as a small, erythematous, scaly macule that rapidly increased in size over an 8-week period to a maximum of 5.0×4.5 cm at presentation. The lesion bled on 2 or 3 occasions during the 8-week period and was controlled with a warm compress. The patient’s caregiver had treated the lesion with topical tea tree oil (for malodor) and antibiotic ointment as needed. The clinical differential diagnosis included squamous cell carcinoma, keratoacanthoma, amelanotic melanoma, cutaneous metastasis of a primary visceral malignancy, basal cell carcinoma, and MCC. Biopsy of the lesion was recommended at this time but the patient’s family declined.

A 4-mm punch biopsy was obtained at a follow-up visit 4 weeks later (12 weeks after the reported onset of the lesion). Hematoxylin and eosin staining showed a small-cell neoplasm with stippled nuclei and scant cytoplasm forming a nested and somewhat trabecular pattern. Mitotic activity, apoptosis, and nuclear molding also were present (Figure 2). The tumor cells were positive for cytokeratin 20 with a dotlike, paranuclear pattern (Figure 3). Staining for CAM 5.2 also was positive. Cytokeratin 5/6, human melanoma black 45, and leukocyte common antigen were negative. The immunophenotyping of the lymphocytic response to the tumor showed that the majority of intratumoral lymphocytes were CD8 positive (Figure 4). CD4-positive lymphocytes were predominantly seen at the periphery of the tumor nests without tumor infiltration (Figure 5). Based on these findings, a diagnosis of MCC was made. The patient’s family declined treatment based on her advanced age and current health status, which included advanced dementia.

Two weeks after the punch biopsy, the lesion had noticeably decreased in size and lost its dome-shaped appearance. Within 8 weeks after biopsy (20 weeks since the lesion first appeared), the lesion had completely resolved (Figure 6). The patient was lost to follow-up months later, but no recurrence of the lesion was reported.

Comment

Spontaneous regression is not unique to MCC, as this phenomenon also has been reported in keratoacanthoma, lymphoma, basal cell carcinoma, and melanoma.¹⁵ Complete spontaneous regression is defined as occurring in the absence of therapy that is intended to have a treatment effect.^15,16 Spontaneous regression is estimated to occur in malignant neoplasms at a rate of 1 case per 60,000 to 100,000 (approximately 0.0013% of all malignant neoplasms).¹⁷ Considering the reported prevalence of MCC and the number of cases that have been known to regress, the estimated incidence of complete spontaneous regression may be as high as 1.5%.¹⁴ Though spontaneous regression of MCC is more prevalent than expected, it still is considered a rare phenomenon. A 2010 review of the literature yielded 22 cases of complete spontaneous regression of MCC.¹⁴ No recurrences have been observed; however, follow-up was relatively short in some cases.

In a unique report by Bertolotti et al,¹⁸ a patient with MCC on the nasal tip presented 4 weeks after biopsy with complete spontaneous regression of the tumor, which was associated with bilateral cervical lymph node involvement as noted by hypermetabolic uptake on positron emission tomography scanning. The patient underwent radiation therapy and was disease free at 12 months’ follow-up.¹⁸

Complete spontaneous regression has been described in MCC patients with local disease, regional recurrences, and metastatic disease.¹⁹ In all reviewed cases, the regression is a fairly quick phenomenon occurring over the course of 1 to 5 months.^16,19,20,21 Our patient presented with advanced age and a tumor location characteristic of MCC. In our search of PubMed articles indexed for MEDLINE using the terms MCC, Merkel cell carcinoma, regression, and spontaneous regression, all but 1 case of MCC regression involved tumors that were located on the head.¹⁴

The histopathologic features observed in our case, specifically intratumoral CD8-positive cytotoxic lymphocytes and peritumoral CD4-positive cells, were similar to the findings in other reported cases. In one series of 2 cases, the one case showed scar tissue with a moderate, predominantly T-lymphocytic infiltrate and no tumor cells, and the second showed cellular proliferation in the deep dermis with dense lymphocytic infiltrates primarily composed of CD3-positive T cells.¹⁴ Other studies of regression of both localized and metastatic MCC demonstrated infiltration by CD4-positive, CD8-positive, and CD3-positive lymphocytes and foamy macrophages.^21-23

The discovery of the MCV was one of the most important advances in elucidating the pathogenesis of MCC.^10,24-26 Merkel cell polyomavirus DNA has been detected in a majority of MCC cases.^25,27 Viral integration has been shown to take place early, prior to tumor clonal expansion.¹⁰ Importantly, not all cases of MCC show MCV infection, and MCV infection is not exclusive to MCC.²⁸ Merkel cell polyomavirus is considered to be part of the normal human flora, and asymptomatic infection is quite common.²⁹ It has been identified in 80% of adults older than 50 years of age and, interestingly, in 35% of children by 13 years of age or younger.^30,31 It remains unclear what role the presence of MCV plays in determining MCC prognosis. Several reports have demonstrated lower disease-specific mortality associated with MCV-positive MCC.^32-35 In contrast, Schrama et al³⁶ correlated the MCV status of 174 MCC tumors and found no difference in clinical behavior or prognosis between MCV-positive and MCV-negative MCCs.

Immunosuppression also may play a role in the development of MCC.^5,25 There is increased prevalence of MCC in the human immunodeficiency virus–positive population, as well as in organ-transplant recipients and patients with leukemia. Chronic lymphocytic leukemia seems to be the most frequent neoplasia associated with development of MCC.³⁷

The mechanism of MCC regression remains unclear, but many investigators emphasize the importance of T-cell–mediated immunity.^{16,21-23,38,39} Apoptosis also has been shown to play an important role.⁴⁰ Our case showed tumor-infiltrating CD8-positive lymphocytes and CD4-positive lymphocytes present predominantly at the periphery of the tumor, with close proximity to the tumor nests but with no tumor infiltration (Figure 3). This distribution was consistently present in multiple sections of the tumor. These findings are consistent with prior reports of both CD4-positive and CD8-positive T lymphocytes associated with MCC regression. Our findings confirm that immune response may play an important role in spontaneous regression of MCC.

There is much speculation regarding the initial biopsy of an MCC lesion (or other traumatic event) and its role in tumor regression. Koba et al⁴¹ examined the effect of biopsy on CD8-positive lymphocytic infiltration of MCC tumor cells and found that biopsy does not commonly alter intratumoral CD8-positive infiltration. These findings suggest trauma does not directly induce immunologic recognition of this cancer.

Conclusion

We report a case of complete spontaneous regression of a localized MCC following a punch biopsy. The histopathology showed a brisk T-lymphocyte response with intratumoral CD8-positive cytotoxic lymphocytes and peritumoral CD4-positive cells. The age and clinical profile of our patient as well as the clinicopathologic characteristics of the tumor regression are similar to other reported cases. Further research is needed to elucidate the mechanism of MCC regression, and a better understanding of this fascinating phenomenon could help in development of new immunotherapeutic approaches.

Merkel cell carcinoma (MCC) is a rare, rapidly growing, aggressive neoplasm with a generally poor prognosis. The cells of origin are highly anaplastic and share structural and immunohistochemical features with various neuroectodermally derived cells. Although Merkel cells, which are slow-acting cutaneous mechanoreceptors located in the basal layer of the epidermis, and MCC share immunohistochemical and ultrastructural features, there is limited evidence of a direct histogenetic relationship between the two.^1,2 Additionally, some extracutaneous neuroendocrine tumors have features similar to MCC; therefore, although it may be more accurate and perhaps more practical to describe these lesions as primary neuroendocrine carcinomas of the skin, the term MCC is more commonly used both in the literature and in clinical practice.^1,2

Merkel cell carcinoma typically presents in the head and neck region in white patients older than 70 years of age and in the immunocompromised population.^3-6 The mean age of diagnosis is 76 years for women and 74 years for men.⁷ The incidence of MCC in the United States tripled over a 15-year period, and there are approximately 1500 new cases of MCC diagnosed each year, making it about 40 times less common than melanoma.⁸ The 5-year survival rate for patients without lymph node involvement is 75%, whereas the 5-year survival rate for patients with distant metastases is 25%.⁹

Merkel cell carcinoma is thought to develop through 1 of 2 distinct pathways. In a virally mediated pathway, which represents at least 80% of cases, the Merkel cell polyomavirus (MCV) monoclonally integrates into the host genome and promotes oncogenesis via altered p53 and retinoblastoma protein expression.^10-12 The remainder of cases are believed to develop via a nonvirally mediated pathway in which genetic anomalies, immune status, and environmental factors influence oncogenesis.^10-13

Due to the similarity between MCC and metastatic neuroendocrine neoplasms, especially small-cell lung carcinomas, immunohistochemistry is important in making the diagnosis. Cytokeratin 20 and neuron-specific enolase positivity and thyroid transcription factor 1 negativity are the most useful markers in identifying MCC.

Regression of MCC is a very rare and poorly understood event. A 2010 review of the literature described 22 cases of spontaneous regression.¹⁴ We report a rare case of rapid and complete regression of MCC following punch biopsy in a 96-year-old woman.

Case Report

A 96-year-old woman presented with a rapidly enlarging lesion overlying the suprasternal notch of 8 weeks’ duration (Figure 1). The lesion consisted of a 5.0×4.5-cm, friable, erythematous, flesh-colored nodule with ulceration and heavy crusting. Surrounding the nodule was an erythematous to violaceous patch extending to the anterior chest and bilateral supraclavicular area. No cervical or clavicular lymphadenopathy was observed. According to the patient’s caregiver, the lesion originated as a small, erythematous, scaly macule that rapidly increased in size over an 8-week period to a maximum of 5.0×4.5 cm at presentation. The lesion bled on 2 or 3 occasions during the 8-week period and was controlled with a warm compress. The patient’s caregiver had treated the lesion with topical tea tree oil (for malodor) and antibiotic ointment as needed. The clinical differential diagnosis included squamous cell carcinoma, keratoacanthoma, amelanotic melanoma, cutaneous metastasis of a primary visceral malignancy, basal cell carcinoma, and MCC. Biopsy of the lesion was recommended at this time but the patient’s family declined.

A 4-mm punch biopsy was obtained at a follow-up visit 4 weeks later (12 weeks after the reported onset of the lesion). Hematoxylin and eosin staining showed a small-cell neoplasm with stippled nuclei and scant cytoplasm forming a nested and somewhat trabecular pattern. Mitotic activity, apoptosis, and nuclear molding also were present (Figure 2). The tumor cells were positive for cytokeratin 20 with a dotlike, paranuclear pattern (Figure 3). Staining for CAM 5.2 also was positive. Cytokeratin 5/6, human melanoma black 45, and leukocyte common antigen were negative. The immunophenotyping of the lymphocytic response to the tumor showed that the majority of intratumoral lymphocytes were CD8 positive (Figure 4). CD4-positive lymphocytes were predominantly seen at the periphery of the tumor nests without tumor infiltration (Figure 5). Based on these findings, a diagnosis of MCC was made. The patient’s family declined treatment based on her advanced age and current health status, which included advanced dementia.

Two weeks after the punch biopsy, the lesion had noticeably decreased in size and lost its dome-shaped appearance. Within 8 weeks after biopsy (20 weeks since the lesion first appeared), the lesion had completely resolved (Figure 6). The patient was lost to follow-up months later, but no recurrence of the lesion was reported.

Comment

Spontaneous regression is not unique to MCC, as this phenomenon also has been reported in keratoacanthoma, lymphoma, basal cell carcinoma, and melanoma.¹⁵ Complete spontaneous regression is defined as occurring in the absence of therapy that is intended to have a treatment effect.^15,16 Spontaneous regression is estimated to occur in malignant neoplasms at a rate of 1 case per 60,000 to 100,000 (approximately 0.0013% of all malignant neoplasms).¹⁷ Considering the reported prevalence of MCC and the number of cases that have been known to regress, the estimated incidence of complete spontaneous regression may be as high as 1.5%.¹⁴ Though spontaneous regression of MCC is more prevalent than expected, it still is considered a rare phenomenon. A 2010 review of the literature yielded 22 cases of complete spontaneous regression of MCC.¹⁴ No recurrences have been observed; however, follow-up was relatively short in some cases.

In a unique report by Bertolotti et al,¹⁸ a patient with MCC on the nasal tip presented 4 weeks after biopsy with complete spontaneous regression of the tumor, which was associated with bilateral cervical lymph node involvement as noted by hypermetabolic uptake on positron emission tomography scanning. The patient underwent radiation therapy and was disease free at 12 months’ follow-up.¹⁸

Complete spontaneous regression has been described in MCC patients with local disease, regional recurrences, and metastatic disease.¹⁹ In all reviewed cases, the regression is a fairly quick phenomenon occurring over the course of 1 to 5 months.^16,19,20,21 Our patient presented with advanced age and a tumor location characteristic of MCC. In our search of PubMed articles indexed for MEDLINE using the terms MCC, Merkel cell carcinoma, regression, and spontaneous regression, all but 1 case of MCC regression involved tumors that were located on the head.¹⁴

The histopathologic features observed in our case, specifically intratumoral CD8-positive cytotoxic lymphocytes and peritumoral CD4-positive cells, were similar to the findings in other reported cases. In one series of 2 cases, the one case showed scar tissue with a moderate, predominantly T-lymphocytic infiltrate and no tumor cells, and the second showed cellular proliferation in the deep dermis with dense lymphocytic infiltrates primarily composed of CD3-positive T cells.¹⁴ Other studies of regression of both localized and metastatic MCC demonstrated infiltration by CD4-positive, CD8-positive, and CD3-positive lymphocytes and foamy macrophages.^21-23

The discovery of the MCV was one of the most important advances in elucidating the pathogenesis of MCC.^10,24-26 Merkel cell polyomavirus DNA has been detected in a majority of MCC cases.^25,27 Viral integration has been shown to take place early, prior to tumor clonal expansion.¹⁰ Importantly, not all cases of MCC show MCV infection, and MCV infection is not exclusive to MCC.²⁸ Merkel cell polyomavirus is considered to be part of the normal human flora, and asymptomatic infection is quite common.²⁹ It has been identified in 80% of adults older than 50 years of age and, interestingly, in 35% of children by 13 years of age or younger.^30,31 It remains unclear what role the presence of MCV plays in determining MCC prognosis. Several reports have demonstrated lower disease-specific mortality associated with MCV-positive MCC.^32-35 In contrast, Schrama et al³⁶ correlated the MCV status of 174 MCC tumors and found no difference in clinical behavior or prognosis between MCV-positive and MCV-negative MCCs.

Immunosuppression also may play a role in the development of MCC.^5,25 There is increased prevalence of MCC in the human immunodeficiency virus–positive population, as well as in organ-transplant recipients and patients with leukemia. Chronic lymphocytic leukemia seems to be the most frequent neoplasia associated with development of MCC.³⁷

The mechanism of MCC regression remains unclear, but many investigators emphasize the importance of T-cell–mediated immunity.^{16,21-23,38,39} Apoptosis also has been shown to play an important role.⁴⁰ Our case showed tumor-infiltrating CD8-positive lymphocytes and CD4-positive lymphocytes present predominantly at the periphery of the tumor, with close proximity to the tumor nests but with no tumor infiltration (Figure 3). This distribution was consistently present in multiple sections of the tumor. These findings are consistent with prior reports of both CD4-positive and CD8-positive T lymphocytes associated with MCC regression. Our findings confirm that immune response may play an important role in spontaneous regression of MCC.

There is much speculation regarding the initial biopsy of an MCC lesion (or other traumatic event) and its role in tumor regression. Koba et al⁴¹ examined the effect of biopsy on CD8-positive lymphocytic infiltration of MCC tumor cells and found that biopsy does not commonly alter intratumoral CD8-positive infiltration. These findings suggest trauma does not directly induce immunologic recognition of this cancer.

Conclusion

We report a case of complete spontaneous regression of a localized MCC following a punch biopsy. The histopathology showed a brisk T-lymphocyte response with intratumoral CD8-positive cytotoxic lymphocytes and peritumoral CD4-positive cells. The age and clinical profile of our patient as well as the clinicopathologic characteristics of the tumor regression are similar to other reported cases. Further research is needed to elucidate the mechanism of MCC regression, and a better understanding of this fascinating phenomenon could help in development of new immunotherapeutic approaches.

Merkel cell carcinoma (MCC) is a rare, rapidly growing, aggressive neoplasm with a generally poor prognosis. The cells of origin are highly anaplastic and share structural and immunohistochemical features with various neuroectodermally derived cells. Although Merkel cells, which are slow-acting cutaneous mechanoreceptors located in the basal layer of the epidermis, and MCC share immunohistochemical and ultrastructural features, there is limited evidence of a direct histogenetic relationship between the two.^1,2 Additionally, some extracutaneous neuroendocrine tumors have features similar to MCC; therefore, although it may be more accurate and perhaps more practical to describe these lesions as primary neuroendocrine carcinomas of the skin, the term MCC is more commonly used both in the literature and in clinical practice.^1,2

Merkel cell carcinoma typically presents in the head and neck region in white patients older than 70 years of age and in the immunocompromised population.^3-6 The mean age of diagnosis is 76 years for women and 74 years for men.⁷ The incidence of MCC in the United States tripled over a 15-year period, and there are approximately 1500 new cases of MCC diagnosed each year, making it about 40 times less common than melanoma.⁸ The 5-year survival rate for patients without lymph node involvement is 75%, whereas the 5-year survival rate for patients with distant metastases is 25%.⁹

Merkel cell carcinoma is thought to develop through 1 of 2 distinct pathways. In a virally mediated pathway, which represents at least 80% of cases, the Merkel cell polyomavirus (MCV) monoclonally integrates into the host genome and promotes oncogenesis via altered p53 and retinoblastoma protein expression.^10-12 The remainder of cases are believed to develop via a nonvirally mediated pathway in which genetic anomalies, immune status, and environmental factors influence oncogenesis.^10-13

Due to the similarity between MCC and metastatic neuroendocrine neoplasms, especially small-cell lung carcinomas, immunohistochemistry is important in making the diagnosis. Cytokeratin 20 and neuron-specific enolase positivity and thyroid transcription factor 1 negativity are the most useful markers in identifying MCC.

Regression of MCC is a very rare and poorly understood event. A 2010 review of the literature described 22 cases of spontaneous regression.¹⁴ We report a rare case of rapid and complete regression of MCC following punch biopsy in a 96-year-old woman.

Case Report

A 96-year-old woman presented with a rapidly enlarging lesion overlying the suprasternal notch of 8 weeks’ duration (Figure 1). The lesion consisted of a 5.0×4.5-cm, friable, erythematous, flesh-colored nodule with ulceration and heavy crusting. Surrounding the nodule was an erythematous to violaceous patch extending to the anterior chest and bilateral supraclavicular area. No cervical or clavicular lymphadenopathy was observed. According to the patient’s caregiver, the lesion originated as a small, erythematous, scaly macule that rapidly increased in size over an 8-week period to a maximum of 5.0×4.5 cm at presentation. The lesion bled on 2 or 3 occasions during the 8-week period and was controlled with a warm compress. The patient’s caregiver had treated the lesion with topical tea tree oil (for malodor) and antibiotic ointment as needed. The clinical differential diagnosis included squamous cell carcinoma, keratoacanthoma, amelanotic melanoma, cutaneous metastasis of a primary visceral malignancy, basal cell carcinoma, and MCC. Biopsy of the lesion was recommended at this time but the patient’s family declined.

A 4-mm punch biopsy was obtained at a follow-up visit 4 weeks later (12 weeks after the reported onset of the lesion). Hematoxylin and eosin staining showed a small-cell neoplasm with stippled nuclei and scant cytoplasm forming a nested and somewhat trabecular pattern. Mitotic activity, apoptosis, and nuclear molding also were present (Figure 2). The tumor cells were positive for cytokeratin 20 with a dotlike, paranuclear pattern (Figure 3). Staining for CAM 5.2 also was positive. Cytokeratin 5/6, human melanoma black 45, and leukocyte common antigen were negative. The immunophenotyping of the lymphocytic response to the tumor showed that the majority of intratumoral lymphocytes were CD8 positive (Figure 4). CD4-positive lymphocytes were predominantly seen at the periphery of the tumor nests without tumor infiltration (Figure 5). Based on these findings, a diagnosis of MCC was made. The patient’s family declined treatment based on her advanced age and current health status, which included advanced dementia.

Two weeks after the punch biopsy, the lesion had noticeably decreased in size and lost its dome-shaped appearance. Within 8 weeks after biopsy (20 weeks since the lesion first appeared), the lesion had completely resolved (Figure 6). The patient was lost to follow-up months later, but no recurrence of the lesion was reported.

Comment

Spontaneous regression is not unique to MCC, as this phenomenon also has been reported in keratoacanthoma, lymphoma, basal cell carcinoma, and melanoma.¹⁵ Complete spontaneous regression is defined as occurring in the absence of therapy that is intended to have a treatment effect.^15,16 Spontaneous regression is estimated to occur in malignant neoplasms at a rate of 1 case per 60,000 to 100,000 (approximately 0.0013% of all malignant neoplasms).¹⁷ Considering the reported prevalence of MCC and the number of cases that have been known to regress, the estimated incidence of complete spontaneous regression may be as high as 1.5%.¹⁴ Though spontaneous regression of MCC is more prevalent than expected, it still is considered a rare phenomenon. A 2010 review of the literature yielded 22 cases of complete spontaneous regression of MCC.¹⁴ No recurrences have been observed; however, follow-up was relatively short in some cases.

In a unique report by Bertolotti et al,¹⁸ a patient with MCC on the nasal tip presented 4 weeks after biopsy with complete spontaneous regression of the tumor, which was associated with bilateral cervical lymph node involvement as noted by hypermetabolic uptake on positron emission tomography scanning. The patient underwent radiation therapy and was disease free at 12 months’ follow-up.¹⁸

Complete spontaneous regression has been described in MCC patients with local disease, regional recurrences, and metastatic disease.¹⁹ In all reviewed cases, the regression is a fairly quick phenomenon occurring over the course of 1 to 5 months.^16,19,20,21 Our patient presented with advanced age and a tumor location characteristic of MCC. In our search of PubMed articles indexed for MEDLINE using the terms MCC, Merkel cell carcinoma, regression, and spontaneous regression, all but 1 case of MCC regression involved tumors that were located on the head.¹⁴

The histopathologic features observed in our case, specifically intratumoral CD8-positive cytotoxic lymphocytes and peritumoral CD4-positive cells, were similar to the findings in other reported cases. In one series of 2 cases, the one case showed scar tissue with a moderate, predominantly T-lymphocytic infiltrate and no tumor cells, and the second showed cellular proliferation in the deep dermis with dense lymphocytic infiltrates primarily composed of CD3-positive T cells.¹⁴ Other studies of regression of both localized and metastatic MCC demonstrated infiltration by CD4-positive, CD8-positive, and CD3-positive lymphocytes and foamy macrophages.^21-23

The discovery of the MCV was one of the most important advances in elucidating the pathogenesis of MCC.^10,24-26 Merkel cell polyomavirus DNA has been detected in a majority of MCC cases.^25,27 Viral integration has been shown to take place early, prior to tumor clonal expansion.¹⁰ Importantly, not all cases of MCC show MCV infection, and MCV infection is not exclusive to MCC.²⁸ Merkel cell polyomavirus is considered to be part of the normal human flora, and asymptomatic infection is quite common.²⁹ It has been identified in 80% of adults older than 50 years of age and, interestingly, in 35% of children by 13 years of age or younger.^30,31 It remains unclear what role the presence of MCV plays in determining MCC prognosis. Several reports have demonstrated lower disease-specific mortality associated with MCV-positive MCC.^32-35 In contrast, Schrama et al³⁶ correlated the MCV status of 174 MCC tumors and found no difference in clinical behavior or prognosis between MCV-positive and MCV-negative MCCs.

Immunosuppression also may play a role in the development of MCC.^5,25 There is increased prevalence of MCC in the human immunodeficiency virus–positive population, as well as in organ-transplant recipients and patients with leukemia. Chronic lymphocytic leukemia seems to be the most frequent neoplasia associated with development of MCC.³⁷

The mechanism of MCC regression remains unclear, but many investigators emphasize the importance of T-cell–mediated immunity.^{16,21-23,38,39} Apoptosis also has been shown to play an important role.⁴⁰ Our case showed tumor-infiltrating CD8-positive lymphocytes and CD4-positive lymphocytes present predominantly at the periphery of the tumor, with close proximity to the tumor nests but with no tumor infiltration (Figure 3). This distribution was consistently present in multiple sections of the tumor. These findings are consistent with prior reports of both CD4-positive and CD8-positive T lymphocytes associated with MCC regression. Our findings confirm that immune response may play an important role in spontaneous regression of MCC.

There is much speculation regarding the initial biopsy of an MCC lesion (or other traumatic event) and its role in tumor regression. Koba et al⁴¹ examined the effect of biopsy on CD8-positive lymphocytic infiltration of MCC tumor cells and found that biopsy does not commonly alter intratumoral CD8-positive infiltration. These findings suggest trauma does not directly induce immunologic recognition of this cancer.

Conclusion

We report a case of complete spontaneous regression of a localized MCC following a punch biopsy. The histopathology showed a brisk T-lymphocyte response with intratumoral CD8-positive cytotoxic lymphocytes and peritumoral CD4-positive cells. The age and clinical profile of our patient as well as the clinicopathologic characteristics of the tumor regression are similar to other reported cases. Further research is needed to elucidate the mechanism of MCC regression, and a better understanding of this fascinating phenomenon could help in development of new immunotherapeutic approaches.