Nonmelanoma Skin Cancer

Basal cell carcinoma (BCC) is the most common skin cancer in the United States¹ and most commonly occurs in sun-exposed areas. Although BCCs can and do develop on other non–sun-exposed areas of the body, BCCs of the perianal or genital regions are very rare (0.27% of cases). It is estimated that perianal BCCs account for less than 0.08% of all BCCs.²

We present a case of a superficial nodular perianal BCC that was discovered following an annual total-body skin examination and was treated with Mohs micrographic surgery (MMS).

Case Report

A 76-year-old man presented to the dermatology clinic for an annual total-body skin examination as well as evaluation of a new submental skin lesion. The patient’s medical history included successfully treated malignant melanoma in situ, multiple actinic keratoses, and an eccrine carcinoma. His family history was noncontributory. Inspection of the submental lesion revealed a pearly, 1.8-cm, telangiectatic, nodular plaque that was highly suspected to be a BCC. During the examination, a 1-cm pinkish-red plaque was found on the skin in the left perianal region (Figure 1). The patient was unaware of the lesion and did not report any symptoms upon questioning.

A shave biopsy of the submental lesion confirmed a diagnosis of micronodular BCC, and the patient was referred for MMS. It was decided to reevaluate the perianal lesion clinically at a follow-up appointment 2 months later and biopsy if it had not resolved. However, the patient did not attend the 2-month follow-up visit as scheduled, and it was not until the following year at his next annual total-body skin examination that the perianal lesion was rechecked. The lesion was unchanged at the time and was similar to the previous findings in both appearance and size. A punch biopsy was performed, and the pathology showed a superficial nodular perianal BCC (Figure 2). The perianal BCC was excised during a 2-stage MMS procedure with no recurrence at 6-month follow-up (Figure 3).

Comment

At the time of the patient’s initial visit, the differential diagnosis for this perianal lesion included an inflammatory or infectious dermatosis. Its asymptomatic nature made it difficult to determine how long it had been present. The lack of resolution on reevaluation of the lesion 1 year later raised the possibilities of amelanotic melanoma, squamous cell carcinoma, and lichen planus. Basal cell carcinoma was much lower in the differential diagnosis, as BCCs rarely are found in this area of the body; in fact, BCCs account for 0.2% of all anorectal neoplasms,³ and less than 0.08% of BCCs will occur in the perianal region.²

This challenging presentation is common for BCCs found in the perianal and perineal regions, as they are difficult to diagnose and often are overlooked as inflammatory dermatoses.^4,5 The infrequency of perianal BCC reported in the literature as well as the predominance of BCC in sun-exposed areas makes it difficult for dermatologists to diagnose perianal BCC without biopsy. Another feature indicative of this diagnostic difficulty is that the average size of perianal and perineal BCCs has been found to be 1.95 cm.² Without thorough and routine total-body skin examinations, there is no reliable way to catch asymptomatic BCCs in the perianal region until they have progressed far enough to become symptomatic. When possible, we recommend that dermatologists check the genital and anal regions during skin examinations and biopsy any suspicious lesions.

This case also highlights the challenge of missed appointments, which dermatologists also consistently face. Nonattendance rates in US dermatology clinics have been estimated at 17%,⁶ 18.6%,⁷ 19.4%,⁸ and 23.9%⁹ and present a challenge for even the best-run practices. Among patients with missed appointments, the most frequently stated reason in one survey was forgetting, and 24% of those contacted reported that they had not been reminded of their appointment.⁸ Many of the patients surveyed also expressed that they had preferred methods of receiving reminders such as e-mail or text message, which fell outside of traditional contact methods (eg, phone calls, voicemails). Confirming appointments ahead of time can reduce the number of missed appointments due to patient forgetfulness, and incorporating multiple communication modalities may lead to more effective appointment reminders.

Conclusion

Perianal BCC is challenging to diagnose and easy to overlook. Basal cell carcinoma is rarely found in the perianal regions and accounts for a fraction of all anorectal neoplasms. We recommend thorough total-body skin examinations that include the genital region and gluteal cleft when possible and encourage physicians to biopsy suspicious lesions in these regions. Routine, thorough total-body skin examinations can reveal neoplasms when they are smaller and asymptomatic. When surgical excision is indicated, MMS is an effective way to preserve as much tissue as possible and minimize recurrence.

Basal cell carcinoma (BCC) is the most common skin cancer in the United States¹ and most commonly occurs in sun-exposed areas. Although BCCs can and do develop on other non–sun-exposed areas of the body, BCCs of the perianal or genital regions are very rare (0.27% of cases). It is estimated that perianal BCCs account for less than 0.08% of all BCCs.²

We present a case of a superficial nodular perianal BCC that was discovered following an annual total-body skin examination and was treated with Mohs micrographic surgery (MMS).

Case Report

A 76-year-old man presented to the dermatology clinic for an annual total-body skin examination as well as evaluation of a new submental skin lesion. The patient’s medical history included successfully treated malignant melanoma in situ, multiple actinic keratoses, and an eccrine carcinoma. His family history was noncontributory. Inspection of the submental lesion revealed a pearly, 1.8-cm, telangiectatic, nodular plaque that was highly suspected to be a BCC. During the examination, a 1-cm pinkish-red plaque was found on the skin in the left perianal region (Figure 1). The patient was unaware of the lesion and did not report any symptoms upon questioning.

A shave biopsy of the submental lesion confirmed a diagnosis of micronodular BCC, and the patient was referred for MMS. It was decided to reevaluate the perianal lesion clinically at a follow-up appointment 2 months later and biopsy if it had not resolved. However, the patient did not attend the 2-month follow-up visit as scheduled, and it was not until the following year at his next annual total-body skin examination that the perianal lesion was rechecked. The lesion was unchanged at the time and was similar to the previous findings in both appearance and size. A punch biopsy was performed, and the pathology showed a superficial nodular perianal BCC (Figure 2). The perianal BCC was excised during a 2-stage MMS procedure with no recurrence at 6-month follow-up (Figure 3).

Comment

At the time of the patient’s initial visit, the differential diagnosis for this perianal lesion included an inflammatory or infectious dermatosis. Its asymptomatic nature made it difficult to determine how long it had been present. The lack of resolution on reevaluation of the lesion 1 year later raised the possibilities of amelanotic melanoma, squamous cell carcinoma, and lichen planus. Basal cell carcinoma was much lower in the differential diagnosis, as BCCs rarely are found in this area of the body; in fact, BCCs account for 0.2% of all anorectal neoplasms,³ and less than 0.08% of BCCs will occur in the perianal region.²

This challenging presentation is common for BCCs found in the perianal and perineal regions, as they are difficult to diagnose and often are overlooked as inflammatory dermatoses.^4,5 The infrequency of perianal BCC reported in the literature as well as the predominance of BCC in sun-exposed areas makes it difficult for dermatologists to diagnose perianal BCC without biopsy. Another feature indicative of this diagnostic difficulty is that the average size of perianal and perineal BCCs has been found to be 1.95 cm.² Without thorough and routine total-body skin examinations, there is no reliable way to catch asymptomatic BCCs in the perianal region until they have progressed far enough to become symptomatic. When possible, we recommend that dermatologists check the genital and anal regions during skin examinations and biopsy any suspicious lesions.

This case also highlights the challenge of missed appointments, which dermatologists also consistently face. Nonattendance rates in US dermatology clinics have been estimated at 17%,⁶ 18.6%,⁷ 19.4%,⁸ and 23.9%⁹ and present a challenge for even the best-run practices. Among patients with missed appointments, the most frequently stated reason in one survey was forgetting, and 24% of those contacted reported that they had not been reminded of their appointment.⁸ Many of the patients surveyed also expressed that they had preferred methods of receiving reminders such as e-mail or text message, which fell outside of traditional contact methods (eg, phone calls, voicemails). Confirming appointments ahead of time can reduce the number of missed appointments due to patient forgetfulness, and incorporating multiple communication modalities may lead to more effective appointment reminders.

Conclusion

Perianal BCC is challenging to diagnose and easy to overlook. Basal cell carcinoma is rarely found in the perianal regions and accounts for a fraction of all anorectal neoplasms. We recommend thorough total-body skin examinations that include the genital region and gluteal cleft when possible and encourage physicians to biopsy suspicious lesions in these regions. Routine, thorough total-body skin examinations can reveal neoplasms when they are smaller and asymptomatic. When surgical excision is indicated, MMS is an effective way to preserve as much tissue as possible and minimize recurrence.

Basal cell carcinoma (BCC) is the most common skin cancer in the United States¹ and most commonly occurs in sun-exposed areas. Although BCCs can and do develop on other non–sun-exposed areas of the body, BCCs of the perianal or genital regions are very rare (0.27% of cases). It is estimated that perianal BCCs account for less than 0.08% of all BCCs.²

We present a case of a superficial nodular perianal BCC that was discovered following an annual total-body skin examination and was treated with Mohs micrographic surgery (MMS).

Case Report

A 76-year-old man presented to the dermatology clinic for an annual total-body skin examination as well as evaluation of a new submental skin lesion. The patient’s medical history included successfully treated malignant melanoma in situ, multiple actinic keratoses, and an eccrine carcinoma. His family history was noncontributory. Inspection of the submental lesion revealed a pearly, 1.8-cm, telangiectatic, nodular plaque that was highly suspected to be a BCC. During the examination, a 1-cm pinkish-red plaque was found on the skin in the left perianal region (Figure 1). The patient was unaware of the lesion and did not report any symptoms upon questioning.

A shave biopsy of the submental lesion confirmed a diagnosis of micronodular BCC, and the patient was referred for MMS. It was decided to reevaluate the perianal lesion clinically at a follow-up appointment 2 months later and biopsy if it had not resolved. However, the patient did not attend the 2-month follow-up visit as scheduled, and it was not until the following year at his next annual total-body skin examination that the perianal lesion was rechecked. The lesion was unchanged at the time and was similar to the previous findings in both appearance and size. A punch biopsy was performed, and the pathology showed a superficial nodular perianal BCC (Figure 2). The perianal BCC was excised during a 2-stage MMS procedure with no recurrence at 6-month follow-up (Figure 3).

Comment

At the time of the patient’s initial visit, the differential diagnosis for this perianal lesion included an inflammatory or infectious dermatosis. Its asymptomatic nature made it difficult to determine how long it had been present. The lack of resolution on reevaluation of the lesion 1 year later raised the possibilities of amelanotic melanoma, squamous cell carcinoma, and lichen planus. Basal cell carcinoma was much lower in the differential diagnosis, as BCCs rarely are found in this area of the body; in fact, BCCs account for 0.2% of all anorectal neoplasms,³ and less than 0.08% of BCCs will occur in the perianal region.²

This challenging presentation is common for BCCs found in the perianal and perineal regions, as they are difficult to diagnose and often are overlooked as inflammatory dermatoses.^4,5 The infrequency of perianal BCC reported in the literature as well as the predominance of BCC in sun-exposed areas makes it difficult for dermatologists to diagnose perianal BCC without biopsy. Another feature indicative of this diagnostic difficulty is that the average size of perianal and perineal BCCs has been found to be 1.95 cm.² Without thorough and routine total-body skin examinations, there is no reliable way to catch asymptomatic BCCs in the perianal region until they have progressed far enough to become symptomatic. When possible, we recommend that dermatologists check the genital and anal regions during skin examinations and biopsy any suspicious lesions.

This case also highlights the challenge of missed appointments, which dermatologists also consistently face. Nonattendance rates in US dermatology clinics have been estimated at 17%,⁶ 18.6%,⁷ 19.4%,⁸ and 23.9%⁹ and present a challenge for even the best-run practices. Among patients with missed appointments, the most frequently stated reason in one survey was forgetting, and 24% of those contacted reported that they had not been reminded of their appointment.⁸ Many of the patients surveyed also expressed that they had preferred methods of receiving reminders such as e-mail or text message, which fell outside of traditional contact methods (eg, phone calls, voicemails). Confirming appointments ahead of time can reduce the number of missed appointments due to patient forgetfulness, and incorporating multiple communication modalities may lead to more effective appointment reminders.

Conclusion

Perianal BCC is challenging to diagnose and easy to overlook. Basal cell carcinoma is rarely found in the perianal regions and accounts for a fraction of all anorectal neoplasms. We recommend thorough total-body skin examinations that include the genital region and gluteal cleft when possible and encourage physicians to biopsy suspicious lesions in these regions. Routine, thorough total-body skin examinations can reveal neoplasms when they are smaller and asymptomatic. When surgical excision is indicated, MMS is an effective way to preserve as much tissue as possible and minimize recurrence.

In cutaneous field cancerization, focal treatments such as cryotherapy are impractical, thus necessitating the use of field-directed therapies over the lesion and the surrounding skin field. Although evidence-based guidelines do not exist, field-directed therapy has been proposed in cases of 3 or more actinic keratoses (AKs) in a 25-cm² area or larger.¹ It can be further speculated that patients who are vulnerable to aggressive phenotypes of cutaneous malignancies, such as those with a genodermatosis or who are immunocompromised, necessitate a higher index of suspicion for field effect with even 1 or 2 AKs.

Current field-directed therapies include topical agents (imiquimod, fluorouracil, ingenol mebutate, and diclo-fenac), photodynamic therapy (PDT), and resurfacing procedures (lasers, chemical peels, dermabrasion). Although topical agents and PDT currently are gold standards in field treatment, the use of energy-based devices (ie, ablative and nonablative lasers) are attractive options as monotherapy or as part of a combination therapy. These devices are attractive options for field-directed therapy because they offer defined, customizable control of settings, allowing for optimal cosmesis and precision of therapy.

Principally, lasers function by damaging skin tissue to induce resurfacing, neocollagenesis, and vascular restructuring. Fractional versions of ablative and nonablative systems are available to target a fraction of the treatment area in evenly spaced microthermal zones and to minimize overall thermal damage.²

Given recent advances in laser systems and numerous investigations reported in the literature, a review of ablative and nonablative lasers that have been studied as treatment options for cutaneous field cancerization is provided, with a focus on treatment efficacy.

Ablative Lasers

Ablative lasers operate at higher wavelengths than nonablative lasers to destroy epidermal and dermal tissue. The 10,600-nm carbon dioxide (CO₂) and 2940-nm Er:YAG lasers have been heavily investigated for field therapy for multiple AKs, both as monotherapies (Table 1) and in combination with PDT (Table 2).

Monotherapy
One randomized trial with 5-year follow-up compared the efficacy of full-face pulsed CO₂ laser therapy, full-face trichloroacetic acid (TCA) peel 30%, and fluorouracil cream 5% (twice daily for 3 weeks) on AKs on the face and head.³ Thirty-one participants were randomized to the 3 treatment arms and a negative control arm. The mean AK counts at baseline for the CO₂, TCA, and fluorouracil treatment groups were 78.0, 83.7, and 61.8, respectively. At 3-month follow-up, all treatment groups had significant reductions in the mean AK count from baseline (CO₂ group, 92% [P=.03]; TCA group, 89% [P=.004]; fluorouracil group, 83% [P=.008]). No significant differences in efficacy among the treatment groups were noted. All 3 treatment groups had a demonstrably lower incidence of nonmelanoma skin cancer over 5-year follow-up compared to the control group (P<.001).³

In contrast to these promising results, the pulsed CO₂ laser showed only short-term efficacy in a split-face study of 12 participants with at least 5 facial or scalp AKs on each of 2 symmetric facial sides who were randomized to 1 treatment side.⁴ At 1-month follow-up, the treatment side exhibited significantly fewer AKs compared to the control side (47% vs 71% at baseline; P=.01), but the improvement was not sustained at 3-month follow-up (49% vs 57%; P=.47).⁴

In another study, the CO₂ laser was found to be inferior to 5-aminolevulinic acid PDT.⁵ Twenty-one participants who had at least 4 AKs in each symmetric half of a body region (head, hands, forearms) were randomized to PDT on 1 side and CO₂ laser therapy on the other. Median baseline AK counts for the PDT and CO₂ laser groups were 6 and 8, respectively. Both treatment groups exhibited significant median AK reduction from baseline 4 weeks posttreatment (PDT group, 82.1% [P<.05], CO₂ laser group, 100% [P<.05]); however. at 3 months posttreatment the PDT group had significantly higher absolute (P=.0155) and relative (P=.0362) reductions in AK count compared to the CO₂ laser group. One participant received a topical antibiotic for superficial infection on the PDT treatment side.⁵

Many questions remain regarding the practical application of laser ablation monotherapy for multiple AKs. More studies are needed to determine the practicality and long-term clinical efficacy of these devices.

PDT Combination Therapy
Laser ablation may be combined with PDT to increase efficacy and prolong remission rates. In fact, laser ablation may be thought of as a physical drug-delivery system to boost uptake of topical agents—in this case, aminolevulinic acid and methyl aminolevulinate (MAL)—given that it disrupts the skin barrier.

In a comparative study of ablative fractional laser (AFXL)–assisted PDT and AFXL alone in 10 organ transplant recipients on immunosuppression with at least 5 AKs on each dorsal hand, participants were randomized to AFXL-PDT on one treatment side and PDT on the other side.⁶ Participants received AFXL in an initial lesion-directed pass and then a second field-directed pass of a fractional CO₂ laser. After AFXL exposure, methyl aminolevulinate was applied to the AFXL-PDT treatment side, with 3-hour occlusion. A total of 680 AKs were treated (335 in the AFXL-PDT group, 345 in the PDT group); results were stratified by the clinical grade of the lesion (1, slightly palpable; 2, moderately thick; 3, very thick or obvious). At 4-month follow-up, the AFXL-PDT group had a significantly higher median complete response rate of 73% compared to 31% in the AFXL group (P=.002). Interestingly, AFXL-PDT was also significantly more efficacious compared to AFXL for grades 1 (80% vs 37%; P=.02) and 2 (53% vs 7%, P=.009) AKs but not grade 3 AKs (4% vs 0%, P=.17).⁶

The combination of fractional CO₂ laser and PDT also demonstrated superiority to PDT.⁷ In a split-face investigation, 15 participants with bilateral symmetric areas of 2 to 10 AKs on the face or scalp were randomized to receive fractional CO₂ laser and MAL-PDT combination therapy on 1 treatment side and conventional MAL-PDT on the other side.⁷ The AFXL-PDT treatment side received laser ablation with immediate subsequent application of MAL to both treatment sides under 3-hour occlusion. At baseline, 103 AKs were treated by AFXL-PDT and 109 AKs were treated with conventional PDT. At 3-month follow-up, the AFXL-PDT treatment group exhibited a significantly higher rate of complete response (90%) compared to the conventional PDT group (67%)(P=.0002).⁷

Like the CO₂ laser, the Er:YAG laser has demonstrated superior results when used in combination with PDT to treat field cancerization compared to either treatment alone. In a comparison study, 93 patients with 2 to 10 AK lesions on the face or scalp were randomized to treatment with AFXL (Er:YAG laser) and MAL-PDT with 3-hour occlusion, AFXL (Er:YAG laser) and MAL-PDT with 2-hour occlusion, and MAL-PDT with 3-hour occlusion.⁸ A total of 440 baseline AK lesions on the face or scalp were treated. At 3-month follow-up, the AFXL-PDT (3-hour occlusion) group had the highest rate of complete response (91.7%), compared to 76.8% (P=.001) in the AFXL-PDT (2-hour occlusion) and 65.6% (P=.001) in the PDT groups, regardless of the grade of AK lesion. The AFXL-PDT (2-hour occlusion) treatment was also superior to PDT alone (P=.038). These findings were sustained at 12-month follow-up (84.8% in the AFXL-PDT [3-hour occlusion] group [P<.001, compared to others]; 67.5% in the AFXL-PDT [2-hour occlusion] group [P<.001, compared to 3-hour PDT]; 51.1% in the PDT group). Importantly, the AK lesion recurrence rate was also lowest in the AFL-PDT (3-hour occlusion) group (7.5% vs 12.1% and 22.1% in the AFXL-PDT [2-hour occlusion] and PDT groups, respectively; P=.007).⁸

Combination therapy with AFXL and daylight PDT (dPDT) may improve the tolerability of PDT and the efficacy rate of field therapy in organ transplant recipients. One study demonstrated the superiority of this combination therapy in a population of 16 organ transplant recipients on immunosuppressants with at least 2 moderate to severely thick AKs in each of 4 comparable areas in the same anatomic region.⁹ The 4 areas were randomized to a single session of AFXL-dPDT, dPDT alone, conventional PDT, or AFXL alone. Ablation was performed with a fractional Er:YAG laser. The AFXL-dPDT and dPDT alone groups received MAL for 2.5 hours without occlusion, and the conventional PDT group received MAL for 3 hours with occlusion. Daylight exposure in dPDT groups was initiated 30 minutes after MAL application for 2 hours total. A baseline total of 542 AKs were treated. At 3-month follow-up, the complete response rate was highest for the AFXL-dPDT group (74%) compared to dPDT alone (46%; P=.0262), conventional PDT (50%; P=.042), and AFXL alone (5%; P=.004). Pain scores for AFXL–dPDT and dPDT alone were significantly lower than for conventional PDT and AFXL alone (P<.001).⁹

Nonablative Lasers

By heating the dermis to induce neogenesis without destruction, nonablative lasers offer superior healing times compared to their ablative counterparts. Multiple treatments with nonablative lasers may be necessary for maximal effect. Four nonablative laser devices have demonstrated efficacy in the treatment of multiple AKs^10-14: (1) the Q-switched 1064-nm Nd:YAG laser, with or without a 532-nm potassium titanyl phosphate (KTP) laser; (2) the 1540-nm fractional erbium glass laser; (3) the 1550-nm fractional erbium-doped fiber laser; and (4) the 1927-nm fractional thulium laser (Table 3).

In a proof-of-concept study of the Q-switched Nd:YAG laser with the 532-nm KTP laser, 1 treatment session induced full remission of AKs in 10 patients at follow-up day 20, although the investigator did not grade improvement on a numerical scale.¹⁰ In a study of the fractional Q-switched 1064-nm Nd:YAG laser alone, 6 patients with trace or mild AKs received 4 treatment sessions at approximately 2-week intervals.¹⁴ All but 1 patient (who had trace AKs) had no AKs at 3-month follow-up.

The efficacy of the 1540-nm fractional erbium glass laser was examined in 17 participants with investigator-rated moderate-to-severe AK involvement of the scalp and face.¹² Participants were given 2 or 3 treatment sessions at 3- to 4-week intervals and were graded by blinded dermatologists on a quartile scale of 0 (no improvement), 1 (1%–25% improvement), 2 (26%–50% improvement), 3 (51%–75% improvement), or 4 (76%–100% improvement). At 3 months posttreatment, the average grade of improvement was 3.4.¹²

The 1550-nm fractional erbium-doped fiber laser was tested in 14 men with multiple facial AKs (range, 9–44 AKs [mean, 22.1 AKs]).¹¹ Participants received 5 treatment sessions at 2- to 4-week intervals, with majority energies used at 70 MJ and treatment level 11. The mean AK count was reduced significantly by 73.1%, 66.2%, and 55.6% at 1-, 3-, and 6-month follow-up, respectively (P<.001).¹¹

The 1927-nm fractional thulium laser showed promising results in 24 participants with facial AKs.¹³ Participants received up to 4 treatment sessions at intervals from 2 to 6 weeks at the investigators’ discretion. At baseline, patients had an average of 14.04 facial AKs. At 1-, 3-, and 6-month follow-up, participants exhibited 91.3%, 87.3%, and 86.6% reduction in AK counts, respectively. The mean AK count at 3-month follow-up was 1.88.¹³

Due to limited sample sizes and/or lack of quantifiable results and controls in these studies, more studies are needed to fully elucidate the role of nonablative lasers in the treatment of AK.

Future Directions

Iontophoresis involves the noninvasive induction of an electrical current to facilitate ion movement through the skin and may be a novel method to boost the efficacy of current field therapies. In the first known study of its kisnd, iontophoresis-assisted AFXL-PDT was found to be noninferior to conventional AFXL-PDT¹⁵; however, additional studies demonstrating its superiority are needed before more widespread clinical use is considered.

Pretreatment with AFXL prior to topical field-directed therapies also has been proposed.¹⁶ In a case series of 13 patients, combination therapy with AFXL and ingenol mebutate was shown to be superior to ingenol mebutate alone (AK clearance rate, 89.2% vs 72.1%, respectively; P<.001).¹⁶ Randomized studies with longer follow-up time are needed.

Conclusion

Ablative and nonablative laser systems have yielded limited data about their potential as monotherapies for treatment of multiple AKs and are unlikely to replace topical agents and PDT as a first-line modality in field-directed treatment at this time. More studies with a larger number of participants and long-term follow-up are needed for further clarification of efficacy, safety, and clinical feasibility. Nevertheless, fractional ablative lasers in combination with PDT have shown robust efficacy and a favorable safety profile for treatment of multiple AKs.^6-9 Further, this combination therapy exhibited a superior clearance rate and lower lesion recurrence in organ transplant recipients—a demographic that classically is difficult to treat.^6-9

With continued rapid evolution of laser systems and more widespread use in dermatology, monotherapy and combination therapy may offer a dynamic new option in field cancerization that can decrease disease burden and treatment frequency.

In cutaneous field cancerization, focal treatments such as cryotherapy are impractical, thus necessitating the use of field-directed therapies over the lesion and the surrounding skin field. Although evidence-based guidelines do not exist, field-directed therapy has been proposed in cases of 3 or more actinic keratoses (AKs) in a 25-cm² area or larger.¹ It can be further speculated that patients who are vulnerable to aggressive phenotypes of cutaneous malignancies, such as those with a genodermatosis or who are immunocompromised, necessitate a higher index of suspicion for field effect with even 1 or 2 AKs.

Current field-directed therapies include topical agents (imiquimod, fluorouracil, ingenol mebutate, and diclo-fenac), photodynamic therapy (PDT), and resurfacing procedures (lasers, chemical peels, dermabrasion). Although topical agents and PDT currently are gold standards in field treatment, the use of energy-based devices (ie, ablative and nonablative lasers) are attractive options as monotherapy or as part of a combination therapy. These devices are attractive options for field-directed therapy because they offer defined, customizable control of settings, allowing for optimal cosmesis and precision of therapy.

Principally, lasers function by damaging skin tissue to induce resurfacing, neocollagenesis, and vascular restructuring. Fractional versions of ablative and nonablative systems are available to target a fraction of the treatment area in evenly spaced microthermal zones and to minimize overall thermal damage.²

Given recent advances in laser systems and numerous investigations reported in the literature, a review of ablative and nonablative lasers that have been studied as treatment options for cutaneous field cancerization is provided, with a focus on treatment efficacy.

Ablative Lasers

Ablative lasers operate at higher wavelengths than nonablative lasers to destroy epidermal and dermal tissue. The 10,600-nm carbon dioxide (CO₂) and 2940-nm Er:YAG lasers have been heavily investigated for field therapy for multiple AKs, both as monotherapies (Table 1) and in combination with PDT (Table 2).

Monotherapy
One randomized trial with 5-year follow-up compared the efficacy of full-face pulsed CO₂ laser therapy, full-face trichloroacetic acid (TCA) peel 30%, and fluorouracil cream 5% (twice daily for 3 weeks) on AKs on the face and head.³ Thirty-one participants were randomized to the 3 treatment arms and a negative control arm. The mean AK counts at baseline for the CO₂, TCA, and fluorouracil treatment groups were 78.0, 83.7, and 61.8, respectively. At 3-month follow-up, all treatment groups had significant reductions in the mean AK count from baseline (CO₂ group, 92% [P=.03]; TCA group, 89% [P=.004]; fluorouracil group, 83% [P=.008]). No significant differences in efficacy among the treatment groups were noted. All 3 treatment groups had a demonstrably lower incidence of nonmelanoma skin cancer over 5-year follow-up compared to the control group (P<.001).³

In contrast to these promising results, the pulsed CO₂ laser showed only short-term efficacy in a split-face study of 12 participants with at least 5 facial or scalp AKs on each of 2 symmetric facial sides who were randomized to 1 treatment side.⁴ At 1-month follow-up, the treatment side exhibited significantly fewer AKs compared to the control side (47% vs 71% at baseline; P=.01), but the improvement was not sustained at 3-month follow-up (49% vs 57%; P=.47).⁴

In another study, the CO₂ laser was found to be inferior to 5-aminolevulinic acid PDT.⁵ Twenty-one participants who had at least 4 AKs in each symmetric half of a body region (head, hands, forearms) were randomized to PDT on 1 side and CO₂ laser therapy on the other. Median baseline AK counts for the PDT and CO₂ laser groups were 6 and 8, respectively. Both treatment groups exhibited significant median AK reduction from baseline 4 weeks posttreatment (PDT group, 82.1% [P<.05], CO₂ laser group, 100% [P<.05]); however. at 3 months posttreatment the PDT group had significantly higher absolute (P=.0155) and relative (P=.0362) reductions in AK count compared to the CO₂ laser group. One participant received a topical antibiotic for superficial infection on the PDT treatment side.⁵

Many questions remain regarding the practical application of laser ablation monotherapy for multiple AKs. More studies are needed to determine the practicality and long-term clinical efficacy of these devices.

PDT Combination Therapy
Laser ablation may be combined with PDT to increase efficacy and prolong remission rates. In fact, laser ablation may be thought of as a physical drug-delivery system to boost uptake of topical agents—in this case, aminolevulinic acid and methyl aminolevulinate (MAL)—given that it disrupts the skin barrier.

In a comparative study of ablative fractional laser (AFXL)–assisted PDT and AFXL alone in 10 organ transplant recipients on immunosuppression with at least 5 AKs on each dorsal hand, participants were randomized to AFXL-PDT on one treatment side and PDT on the other side.⁶ Participants received AFXL in an initial lesion-directed pass and then a second field-directed pass of a fractional CO₂ laser. After AFXL exposure, methyl aminolevulinate was applied to the AFXL-PDT treatment side, with 3-hour occlusion. A total of 680 AKs were treated (335 in the AFXL-PDT group, 345 in the PDT group); results were stratified by the clinical grade of the lesion (1, slightly palpable; 2, moderately thick; 3, very thick or obvious). At 4-month follow-up, the AFXL-PDT group had a significantly higher median complete response rate of 73% compared to 31% in the AFXL group (P=.002). Interestingly, AFXL-PDT was also significantly more efficacious compared to AFXL for grades 1 (80% vs 37%; P=.02) and 2 (53% vs 7%, P=.009) AKs but not grade 3 AKs (4% vs 0%, P=.17).⁶

The combination of fractional CO₂ laser and PDT also demonstrated superiority to PDT.⁷ In a split-face investigation, 15 participants with bilateral symmetric areas of 2 to 10 AKs on the face or scalp were randomized to receive fractional CO₂ laser and MAL-PDT combination therapy on 1 treatment side and conventional MAL-PDT on the other side.⁷ The AFXL-PDT treatment side received laser ablation with immediate subsequent application of MAL to both treatment sides under 3-hour occlusion. At baseline, 103 AKs were treated by AFXL-PDT and 109 AKs were treated with conventional PDT. At 3-month follow-up, the AFXL-PDT treatment group exhibited a significantly higher rate of complete response (90%) compared to the conventional PDT group (67%)(P=.0002).⁷

Like the CO₂ laser, the Er:YAG laser has demonstrated superior results when used in combination with PDT to treat field cancerization compared to either treatment alone. In a comparison study, 93 patients with 2 to 10 AK lesions on the face or scalp were randomized to treatment with AFXL (Er:YAG laser) and MAL-PDT with 3-hour occlusion, AFXL (Er:YAG laser) and MAL-PDT with 2-hour occlusion, and MAL-PDT with 3-hour occlusion.⁸ A total of 440 baseline AK lesions on the face or scalp were treated. At 3-month follow-up, the AFXL-PDT (3-hour occlusion) group had the highest rate of complete response (91.7%), compared to 76.8% (P=.001) in the AFXL-PDT (2-hour occlusion) and 65.6% (P=.001) in the PDT groups, regardless of the grade of AK lesion. The AFXL-PDT (2-hour occlusion) treatment was also superior to PDT alone (P=.038). These findings were sustained at 12-month follow-up (84.8% in the AFXL-PDT [3-hour occlusion] group [P<.001, compared to others]; 67.5% in the AFXL-PDT [2-hour occlusion] group [P<.001, compared to 3-hour PDT]; 51.1% in the PDT group). Importantly, the AK lesion recurrence rate was also lowest in the AFL-PDT (3-hour occlusion) group (7.5% vs 12.1% and 22.1% in the AFXL-PDT [2-hour occlusion] and PDT groups, respectively; P=.007).⁸

Combination therapy with AFXL and daylight PDT (dPDT) may improve the tolerability of PDT and the efficacy rate of field therapy in organ transplant recipients. One study demonstrated the superiority of this combination therapy in a population of 16 organ transplant recipients on immunosuppressants with at least 2 moderate to severely thick AKs in each of 4 comparable areas in the same anatomic region.⁹ The 4 areas were randomized to a single session of AFXL-dPDT, dPDT alone, conventional PDT, or AFXL alone. Ablation was performed with a fractional Er:YAG laser. The AFXL-dPDT and dPDT alone groups received MAL for 2.5 hours without occlusion, and the conventional PDT group received MAL for 3 hours with occlusion. Daylight exposure in dPDT groups was initiated 30 minutes after MAL application for 2 hours total. A baseline total of 542 AKs were treated. At 3-month follow-up, the complete response rate was highest for the AFXL-dPDT group (74%) compared to dPDT alone (46%; P=.0262), conventional PDT (50%; P=.042), and AFXL alone (5%; P=.004). Pain scores for AFXL–dPDT and dPDT alone were significantly lower than for conventional PDT and AFXL alone (P<.001).⁹

Nonablative Lasers

By heating the dermis to induce neogenesis without destruction, nonablative lasers offer superior healing times compared to their ablative counterparts. Multiple treatments with nonablative lasers may be necessary for maximal effect. Four nonablative laser devices have demonstrated efficacy in the treatment of multiple AKs^10-14: (1) the Q-switched 1064-nm Nd:YAG laser, with or without a 532-nm potassium titanyl phosphate (KTP) laser; (2) the 1540-nm fractional erbium glass laser; (3) the 1550-nm fractional erbium-doped fiber laser; and (4) the 1927-nm fractional thulium laser (Table 3).

In a proof-of-concept study of the Q-switched Nd:YAG laser with the 532-nm KTP laser, 1 treatment session induced full remission of AKs in 10 patients at follow-up day 20, although the investigator did not grade improvement on a numerical scale.¹⁰ In a study of the fractional Q-switched 1064-nm Nd:YAG laser alone, 6 patients with trace or mild AKs received 4 treatment sessions at approximately 2-week intervals.¹⁴ All but 1 patient (who had trace AKs) had no AKs at 3-month follow-up.

The efficacy of the 1540-nm fractional erbium glass laser was examined in 17 participants with investigator-rated moderate-to-severe AK involvement of the scalp and face.¹² Participants were given 2 or 3 treatment sessions at 3- to 4-week intervals and were graded by blinded dermatologists on a quartile scale of 0 (no improvement), 1 (1%–25% improvement), 2 (26%–50% improvement), 3 (51%–75% improvement), or 4 (76%–100% improvement). At 3 months posttreatment, the average grade of improvement was 3.4.¹²

The 1550-nm fractional erbium-doped fiber laser was tested in 14 men with multiple facial AKs (range, 9–44 AKs [mean, 22.1 AKs]).¹¹ Participants received 5 treatment sessions at 2- to 4-week intervals, with majority energies used at 70 MJ and treatment level 11. The mean AK count was reduced significantly by 73.1%, 66.2%, and 55.6% at 1-, 3-, and 6-month follow-up, respectively (P<.001).¹¹

The 1927-nm fractional thulium laser showed promising results in 24 participants with facial AKs.¹³ Participants received up to 4 treatment sessions at intervals from 2 to 6 weeks at the investigators’ discretion. At baseline, patients had an average of 14.04 facial AKs. At 1-, 3-, and 6-month follow-up, participants exhibited 91.3%, 87.3%, and 86.6% reduction in AK counts, respectively. The mean AK count at 3-month follow-up was 1.88.¹³

Due to limited sample sizes and/or lack of quantifiable results and controls in these studies, more studies are needed to fully elucidate the role of nonablative lasers in the treatment of AK.

Future Directions

Iontophoresis involves the noninvasive induction of an electrical current to facilitate ion movement through the skin and may be a novel method to boost the efficacy of current field therapies. In the first known study of its kisnd, iontophoresis-assisted AFXL-PDT was found to be noninferior to conventional AFXL-PDT¹⁵; however, additional studies demonstrating its superiority are needed before more widespread clinical use is considered.

Pretreatment with AFXL prior to topical field-directed therapies also has been proposed.¹⁶ In a case series of 13 patients, combination therapy with AFXL and ingenol mebutate was shown to be superior to ingenol mebutate alone (AK clearance rate, 89.2% vs 72.1%, respectively; P<.001).¹⁶ Randomized studies with longer follow-up time are needed.

Conclusion

Ablative and nonablative laser systems have yielded limited data about their potential as monotherapies for treatment of multiple AKs and are unlikely to replace topical agents and PDT as a first-line modality in field-directed treatment at this time. More studies with a larger number of participants and long-term follow-up are needed for further clarification of efficacy, safety, and clinical feasibility. Nevertheless, fractional ablative lasers in combination with PDT have shown robust efficacy and a favorable safety profile for treatment of multiple AKs.^6-9 Further, this combination therapy exhibited a superior clearance rate and lower lesion recurrence in organ transplant recipients—a demographic that classically is difficult to treat.^6-9

With continued rapid evolution of laser systems and more widespread use in dermatology, monotherapy and combination therapy may offer a dynamic new option in field cancerization that can decrease disease burden and treatment frequency.

In cutaneous field cancerization, focal treatments such as cryotherapy are impractical, thus necessitating the use of field-directed therapies over the lesion and the surrounding skin field. Although evidence-based guidelines do not exist, field-directed therapy has been proposed in cases of 3 or more actinic keratoses (AKs) in a 25-cm² area or larger.¹ It can be further speculated that patients who are vulnerable to aggressive phenotypes of cutaneous malignancies, such as those with a genodermatosis or who are immunocompromised, necessitate a higher index of suspicion for field effect with even 1 or 2 AKs.

Current field-directed therapies include topical agents (imiquimod, fluorouracil, ingenol mebutate, and diclo-fenac), photodynamic therapy (PDT), and resurfacing procedures (lasers, chemical peels, dermabrasion). Although topical agents and PDT currently are gold standards in field treatment, the use of energy-based devices (ie, ablative and nonablative lasers) are attractive options as monotherapy or as part of a combination therapy. These devices are attractive options for field-directed therapy because they offer defined, customizable control of settings, allowing for optimal cosmesis and precision of therapy.

Principally, lasers function by damaging skin tissue to induce resurfacing, neocollagenesis, and vascular restructuring. Fractional versions of ablative and nonablative systems are available to target a fraction of the treatment area in evenly spaced microthermal zones and to minimize overall thermal damage.²

Given recent advances in laser systems and numerous investigations reported in the literature, a review of ablative and nonablative lasers that have been studied as treatment options for cutaneous field cancerization is provided, with a focus on treatment efficacy.

Ablative Lasers

Ablative lasers operate at higher wavelengths than nonablative lasers to destroy epidermal and dermal tissue. The 10,600-nm carbon dioxide (CO₂) and 2940-nm Er:YAG lasers have been heavily investigated for field therapy for multiple AKs, both as monotherapies (Table 1) and in combination with PDT (Table 2).

Monotherapy
One randomized trial with 5-year follow-up compared the efficacy of full-face pulsed CO₂ laser therapy, full-face trichloroacetic acid (TCA) peel 30%, and fluorouracil cream 5% (twice daily for 3 weeks) on AKs on the face and head.³ Thirty-one participants were randomized to the 3 treatment arms and a negative control arm. The mean AK counts at baseline for the CO₂, TCA, and fluorouracil treatment groups were 78.0, 83.7, and 61.8, respectively. At 3-month follow-up, all treatment groups had significant reductions in the mean AK count from baseline (CO₂ group, 92% [P=.03]; TCA group, 89% [P=.004]; fluorouracil group, 83% [P=.008]). No significant differences in efficacy among the treatment groups were noted. All 3 treatment groups had a demonstrably lower incidence of nonmelanoma skin cancer over 5-year follow-up compared to the control group (P<.001).³

In contrast to these promising results, the pulsed CO₂ laser showed only short-term efficacy in a split-face study of 12 participants with at least 5 facial or scalp AKs on each of 2 symmetric facial sides who were randomized to 1 treatment side.⁴ At 1-month follow-up, the treatment side exhibited significantly fewer AKs compared to the control side (47% vs 71% at baseline; P=.01), but the improvement was not sustained at 3-month follow-up (49% vs 57%; P=.47).⁴

In another study, the CO₂ laser was found to be inferior to 5-aminolevulinic acid PDT.⁵ Twenty-one participants who had at least 4 AKs in each symmetric half of a body region (head, hands, forearms) were randomized to PDT on 1 side and CO₂ laser therapy on the other. Median baseline AK counts for the PDT and CO₂ laser groups were 6 and 8, respectively. Both treatment groups exhibited significant median AK reduction from baseline 4 weeks posttreatment (PDT group, 82.1% [P<.05], CO₂ laser group, 100% [P<.05]); however. at 3 months posttreatment the PDT group had significantly higher absolute (P=.0155) and relative (P=.0362) reductions in AK count compared to the CO₂ laser group. One participant received a topical antibiotic for superficial infection on the PDT treatment side.⁵

Many questions remain regarding the practical application of laser ablation monotherapy for multiple AKs. More studies are needed to determine the practicality and long-term clinical efficacy of these devices.

PDT Combination Therapy
Laser ablation may be combined with PDT to increase efficacy and prolong remission rates. In fact, laser ablation may be thought of as a physical drug-delivery system to boost uptake of topical agents—in this case, aminolevulinic acid and methyl aminolevulinate (MAL)—given that it disrupts the skin barrier.

In a comparative study of ablative fractional laser (AFXL)–assisted PDT and AFXL alone in 10 organ transplant recipients on immunosuppression with at least 5 AKs on each dorsal hand, participants were randomized to AFXL-PDT on one treatment side and PDT on the other side.⁶ Participants received AFXL in an initial lesion-directed pass and then a second field-directed pass of a fractional CO₂ laser. After AFXL exposure, methyl aminolevulinate was applied to the AFXL-PDT treatment side, with 3-hour occlusion. A total of 680 AKs were treated (335 in the AFXL-PDT group, 345 in the PDT group); results were stratified by the clinical grade of the lesion (1, slightly palpable; 2, moderately thick; 3, very thick or obvious). At 4-month follow-up, the AFXL-PDT group had a significantly higher median complete response rate of 73% compared to 31% in the AFXL group (P=.002). Interestingly, AFXL-PDT was also significantly more efficacious compared to AFXL for grades 1 (80% vs 37%; P=.02) and 2 (53% vs 7%, P=.009) AKs but not grade 3 AKs (4% vs 0%, P=.17).⁶

The combination of fractional CO₂ laser and PDT also demonstrated superiority to PDT.⁷ In a split-face investigation, 15 participants with bilateral symmetric areas of 2 to 10 AKs on the face or scalp were randomized to receive fractional CO₂ laser and MAL-PDT combination therapy on 1 treatment side and conventional MAL-PDT on the other side.⁷ The AFXL-PDT treatment side received laser ablation with immediate subsequent application of MAL to both treatment sides under 3-hour occlusion. At baseline, 103 AKs were treated by AFXL-PDT and 109 AKs were treated with conventional PDT. At 3-month follow-up, the AFXL-PDT treatment group exhibited a significantly higher rate of complete response (90%) compared to the conventional PDT group (67%)(P=.0002).⁷

Like the CO₂ laser, the Er:YAG laser has demonstrated superior results when used in combination with PDT to treat field cancerization compared to either treatment alone. In a comparison study, 93 patients with 2 to 10 AK lesions on the face or scalp were randomized to treatment with AFXL (Er:YAG laser) and MAL-PDT with 3-hour occlusion, AFXL (Er:YAG laser) and MAL-PDT with 2-hour occlusion, and MAL-PDT with 3-hour occlusion.⁸ A total of 440 baseline AK lesions on the face or scalp were treated. At 3-month follow-up, the AFXL-PDT (3-hour occlusion) group had the highest rate of complete response (91.7%), compared to 76.8% (P=.001) in the AFXL-PDT (2-hour occlusion) and 65.6% (P=.001) in the PDT groups, regardless of the grade of AK lesion. The AFXL-PDT (2-hour occlusion) treatment was also superior to PDT alone (P=.038). These findings were sustained at 12-month follow-up (84.8% in the AFXL-PDT [3-hour occlusion] group [P<.001, compared to others]; 67.5% in the AFXL-PDT [2-hour occlusion] group [P<.001, compared to 3-hour PDT]; 51.1% in the PDT group). Importantly, the AK lesion recurrence rate was also lowest in the AFL-PDT (3-hour occlusion) group (7.5% vs 12.1% and 22.1% in the AFXL-PDT [2-hour occlusion] and PDT groups, respectively; P=.007).⁸

Combination therapy with AFXL and daylight PDT (dPDT) may improve the tolerability of PDT and the efficacy rate of field therapy in organ transplant recipients. One study demonstrated the superiority of this combination therapy in a population of 16 organ transplant recipients on immunosuppressants with at least 2 moderate to severely thick AKs in each of 4 comparable areas in the same anatomic region.⁹ The 4 areas were randomized to a single session of AFXL-dPDT, dPDT alone, conventional PDT, or AFXL alone. Ablation was performed with a fractional Er:YAG laser. The AFXL-dPDT and dPDT alone groups received MAL for 2.5 hours without occlusion, and the conventional PDT group received MAL for 3 hours with occlusion. Daylight exposure in dPDT groups was initiated 30 minutes after MAL application for 2 hours total. A baseline total of 542 AKs were treated. At 3-month follow-up, the complete response rate was highest for the AFXL-dPDT group (74%) compared to dPDT alone (46%; P=.0262), conventional PDT (50%; P=.042), and AFXL alone (5%; P=.004). Pain scores for AFXL–dPDT and dPDT alone were significantly lower than for conventional PDT and AFXL alone (P<.001).⁹

Nonablative Lasers

By heating the dermis to induce neogenesis without destruction, nonablative lasers offer superior healing times compared to their ablative counterparts. Multiple treatments with nonablative lasers may be necessary for maximal effect. Four nonablative laser devices have demonstrated efficacy in the treatment of multiple AKs^10-14: (1) the Q-switched 1064-nm Nd:YAG laser, with or without a 532-nm potassium titanyl phosphate (KTP) laser; (2) the 1540-nm fractional erbium glass laser; (3) the 1550-nm fractional erbium-doped fiber laser; and (4) the 1927-nm fractional thulium laser (Table 3).

In a proof-of-concept study of the Q-switched Nd:YAG laser with the 532-nm KTP laser, 1 treatment session induced full remission of AKs in 10 patients at follow-up day 20, although the investigator did not grade improvement on a numerical scale.¹⁰ In a study of the fractional Q-switched 1064-nm Nd:YAG laser alone, 6 patients with trace or mild AKs received 4 treatment sessions at approximately 2-week intervals.¹⁴ All but 1 patient (who had trace AKs) had no AKs at 3-month follow-up.

The efficacy of the 1540-nm fractional erbium glass laser was examined in 17 participants with investigator-rated moderate-to-severe AK involvement of the scalp and face.¹² Participants were given 2 or 3 treatment sessions at 3- to 4-week intervals and were graded by blinded dermatologists on a quartile scale of 0 (no improvement), 1 (1%–25% improvement), 2 (26%–50% improvement), 3 (51%–75% improvement), or 4 (76%–100% improvement). At 3 months posttreatment, the average grade of improvement was 3.4.¹²

The 1550-nm fractional erbium-doped fiber laser was tested in 14 men with multiple facial AKs (range, 9–44 AKs [mean, 22.1 AKs]).¹¹ Participants received 5 treatment sessions at 2- to 4-week intervals, with majority energies used at 70 MJ and treatment level 11. The mean AK count was reduced significantly by 73.1%, 66.2%, and 55.6% at 1-, 3-, and 6-month follow-up, respectively (P<.001).¹¹

The 1927-nm fractional thulium laser showed promising results in 24 participants with facial AKs.¹³ Participants received up to 4 treatment sessions at intervals from 2 to 6 weeks at the investigators’ discretion. At baseline, patients had an average of 14.04 facial AKs. At 1-, 3-, and 6-month follow-up, participants exhibited 91.3%, 87.3%, and 86.6% reduction in AK counts, respectively. The mean AK count at 3-month follow-up was 1.88.¹³

Due to limited sample sizes and/or lack of quantifiable results and controls in these studies, more studies are needed to fully elucidate the role of nonablative lasers in the treatment of AK.

Future Directions

Iontophoresis involves the noninvasive induction of an electrical current to facilitate ion movement through the skin and may be a novel method to boost the efficacy of current field therapies. In the first known study of its kisnd, iontophoresis-assisted AFXL-PDT was found to be noninferior to conventional AFXL-PDT¹⁵; however, additional studies demonstrating its superiority are needed before more widespread clinical use is considered.

Pretreatment with AFXL prior to topical field-directed therapies also has been proposed.¹⁶ In a case series of 13 patients, combination therapy with AFXL and ingenol mebutate was shown to be superior to ingenol mebutate alone (AK clearance rate, 89.2% vs 72.1%, respectively; P<.001).¹⁶ Randomized studies with longer follow-up time are needed.

Conclusion

Ablative and nonablative laser systems have yielded limited data about their potential as monotherapies for treatment of multiple AKs and are unlikely to replace topical agents and PDT as a first-line modality in field-directed treatment at this time. More studies with a larger number of participants and long-term follow-up are needed for further clarification of efficacy, safety, and clinical feasibility. Nevertheless, fractional ablative lasers in combination with PDT have shown robust efficacy and a favorable safety profile for treatment of multiple AKs.^6-9 Further, this combination therapy exhibited a superior clearance rate and lower lesion recurrence in organ transplant recipients—a demographic that classically is difficult to treat.^6-9

With continued rapid evolution of laser systems and more widespread use in dermatology, monotherapy and combination therapy may offer a dynamic new option in field cancerization that can decrease disease burden and treatment frequency.

DALLAS – One year after patients underwent treatment of basal cell carcinoma (BCC) with the 1064-nm Nd:YAG laser, no recurrences have occurred, according to early results from a study being conducted at two centers.

“The 1064-nm Nd:YAG laser is a promising noninvasive treatment approach for treating basal cell carcinoma,” Arisa E. Ortiz, MD, said at the annual conference of the American Society for Laser Medicine and Surgery. “Clearance rates are comparable to or better than other topical modalities such as electrodesiccation and curettage and topical imiquimod. It’s a reasonable alternative for treatment patients with multiple tumors or those who are poor surgical candidates.”

“Laser surgery also provides precision that ordinary surgical techniques cannot match. Despite the obvious obstacles, there is no reason such surgical techniques cannot be expanded someday to other internal cutaneous tumors, including GI tumors. To some extent this is happening already. Vascular lasers are being used to treat a bleeding disorder of the colon known as angiodysplasia. Cautious exploration of laser- and light-based treatments should be further explored as a means of sparing tissue and surgical morbidity.”

Dr. Ortiz disclosed that she has received grant funding from Sienna and Revance, as well as equipment from BTL, Invasix, and Sciton. She has received consulting fees from Alastin, Merz, and Sciton; honoraria from Alastin, Cutera, Invasix, and Sciton; and she holds ownership interest with Allergan. She also has served on the advisory boards for Alastin, Allergan, Invasix, Rodan + Fields, Sciton, Sienna, and Merz.

Dr. Avram disclosed that he serves on the medical advisory board of Sciton and on the scientific advisory boards of Sienna Biopharmaceuticals, Cytrellis, and Allergan. He is also a consultant for Merz Aesthetics, Allergan, Soliton, Invasix, and Revance and has intellectual property with Cytrellis. He also holds stock options with Cytrellis, Invasix, and Zalea.

dbrunk@mdedge.com

DALLAS – One year after patients underwent treatment of basal cell carcinoma (BCC) with the 1064-nm Nd:YAG laser, no recurrences have occurred, according to early results from a study being conducted at two centers.

“The 1064-nm Nd:YAG laser is a promising noninvasive treatment approach for treating basal cell carcinoma,” Arisa E. Ortiz, MD, said at the annual conference of the American Society for Laser Medicine and Surgery. “Clearance rates are comparable to or better than other topical modalities such as electrodesiccation and curettage and topical imiquimod. It’s a reasonable alternative for treatment patients with multiple tumors or those who are poor surgical candidates.”

“Laser surgery also provides precision that ordinary surgical techniques cannot match. Despite the obvious obstacles, there is no reason such surgical techniques cannot be expanded someday to other internal cutaneous tumors, including GI tumors. To some extent this is happening already. Vascular lasers are being used to treat a bleeding disorder of the colon known as angiodysplasia. Cautious exploration of laser- and light-based treatments should be further explored as a means of sparing tissue and surgical morbidity.”

Dr. Ortiz disclosed that she has received grant funding from Sienna and Revance, as well as equipment from BTL, Invasix, and Sciton. She has received consulting fees from Alastin, Merz, and Sciton; honoraria from Alastin, Cutera, Invasix, and Sciton; and she holds ownership interest with Allergan. She also has served on the advisory boards for Alastin, Allergan, Invasix, Rodan + Fields, Sciton, Sienna, and Merz.

Dr. Avram disclosed that he serves on the medical advisory board of Sciton and on the scientific advisory boards of Sienna Biopharmaceuticals, Cytrellis, and Allergan. He is also a consultant for Merz Aesthetics, Allergan, Soliton, Invasix, and Revance and has intellectual property with Cytrellis. He also holds stock options with Cytrellis, Invasix, and Zalea.

dbrunk@mdedge.com

DALLAS – One year after patients underwent treatment of basal cell carcinoma (BCC) with the 1064-nm Nd:YAG laser, no recurrences have occurred, according to early results from a study being conducted at two centers.

“The 1064-nm Nd:YAG laser is a promising noninvasive treatment approach for treating basal cell carcinoma,” Arisa E. Ortiz, MD, said at the annual conference of the American Society for Laser Medicine and Surgery. “Clearance rates are comparable to or better than other topical modalities such as electrodesiccation and curettage and topical imiquimod. It’s a reasonable alternative for treatment patients with multiple tumors or those who are poor surgical candidates.”

“Laser surgery also provides precision that ordinary surgical techniques cannot match. Despite the obvious obstacles, there is no reason such surgical techniques cannot be expanded someday to other internal cutaneous tumors, including GI tumors. To some extent this is happening already. Vascular lasers are being used to treat a bleeding disorder of the colon known as angiodysplasia. Cautious exploration of laser- and light-based treatments should be further explored as a means of sparing tissue and surgical morbidity.”

Dr. Ortiz disclosed that she has received grant funding from Sienna and Revance, as well as equipment from BTL, Invasix, and Sciton. She has received consulting fees from Alastin, Merz, and Sciton; honoraria from Alastin, Cutera, Invasix, and Sciton; and she holds ownership interest with Allergan. She also has served on the advisory boards for Alastin, Allergan, Invasix, Rodan + Fields, Sciton, Sienna, and Merz.

Dr. Avram disclosed that he serves on the medical advisory board of Sciton and on the scientific advisory boards of Sienna Biopharmaceuticals, Cytrellis, and Allergan. He is also a consultant for Merz Aesthetics, Allergan, Soliton, Invasix, and Revance and has intellectual property with Cytrellis. He also holds stock options with Cytrellis, Invasix, and Zalea.

dbrunk@mdedge.com

Early detection of melanoma, which is known to improve survival rates, remains a challenge for dermatologists. Suspicious pigmented lesions typically are evaluated via clinical examination and dermoscopy; however, new technologies are being developed to provide additional objective information for clinicians to incorporate into their biopsy decisions.

Multispectral digital skin lesion analysis (MSDSLA) uses 10 bands of visible and near-infrared light (430–950 nm) to image and analyze pigmented skin lesions (PSLs) down to 2.5 mm below the skin surface and measures the distribution of melanin using 75 unique algorithms to determine the degree of the morphologic disorder. Using a logical regression model previously validated on a set of 1632 PSLs, the probability of melanoma and probability of being a melanoma/PSL of high-risk malignant potential are then provided to the clinician.¹

In this study, we analyzed aggregate data from 7 prior studies^2-8 to better determine how MSDSLA impacts the biopsy decisions of dermatologists and nondermatologists following clinical examination and dermoscopic evaluation of PSLs.

Methods

A total of 855 practitioners (657 dermatologists, 126 dermatology residents, 72 nondermatologists [ie, primary care physicians, physician assistants, nurse practitioners]) in 7 prior reader studies (Table)^2-8 were shown a total of 62 clinical (distant and close-up) and dermoscopic images of PSLs (13 invasive melanomas, 10 melanomas in situ, 7 high-grade dysplastic nevi, 32 benign skin lesions including low-grade dysplastic nevi) previously analyzed by MSDSLA.^2-8 For each lesion evaluated, the practitioners were first asked if they would biopsy based on their review of the clinical and dermoscopic images and were asked again when given the associated MSDSLA information. Data were aggregated across all participants for the individual lesions presented in each reader study. Biopsy decisions were compared overall after evaluation of clinical and dermoscopic findings and then after evaluation of MSDSLA findings. Statistical analyses were performed using t-test and χ² analysis for proportions where appropriate.

Results

Overall sensitivity for the detection of melanoma or other high-grade PSLs improved from 70% on clinical and dermoscopic evaluation to 88% after MSDSLA information was provided (P<.0001), and specificity increased from 52% to 58% (P<.001). Diagnostic accuracy also improved from 59% on clinical evaluation to 69% after review of MSDSLA findings (P<.0001). The positive predictive value of biopsy decisions was 47% following clinical evaluation, which improved to 56% after evaluation of MSDSLA findings (P<.001), and the negative predictive value increased from 74% to 89% (P<.0001). The overall percentage of lesions selected for biopsy did not significantly change following MSDSLA data integration (57% vs 60%)(Figure). Given that similar numbers of lesions were biopsied with improved sensitivity and specificity, the integration of MSDSLA data into the biopsy decision led to an improved biopsy ratio (ratio of melanomas biopsied to total biopsies) and fewer unnecessary biopsies.

Comment

Our broad analysis further supported the findings of prior studies that decisions to biopsy clinically suspicious PSLs are more sensitive, specific, and accurate when practitioners are provided MSDSLA information following clinical examination.^2-8With no significant increase in the number of biopsies performed, the fact that all 5 of the standard diagnostic evaluation metrics (sensitivity, specificity, diagnostic accuracy, positive predictive value, negative predictive value) were improved after MSDSLA information was provided additionally supported this conclusion.

Given the evolution in health care economics, it is clear that greater emphasis will continue to be placed on superior, evidence-based, effective care. The reported diagnostic sensitivities and specificities of clinical evaluation and dermoscopy for melanoma detection vary widely throughout the literature, with sensitivities ranging from 58% to over 90% and specificities ranging from 77% to 99%.^9-11Diagnostic performance generally has been found to be higher among dermatologists than nondermatologists and is highest in specialized pigmented lesion clinics.¹²

Our study had several limitations. For this analysis to be more representative of lesion biopsy selection in the clinical setting, biopsy sensitivity (correctly identifying lesions appropriate for biopsy) vs melanoma sensitivity (identifying a lesion as melanoma) was used.¹³ The overall sensitivity found was within the range of prior studies,^2-8 but this approach may have potentially led to a lower specificity due to an increased number of lesions biopsied. Additionally, the melanomas selected for these studies were early (malignant melanoma in situ or mean thickness of invasive malignant melanoma of 0.3 mm), and the nonmelanomas (including low-grade dysplastic nevi) were not necessarily diagnostically straightforward. This may have led to the clinical and dermoscopic sensitivity and specificity noted being lower than in some prior studies.^9-11

The risk of missing a melanoma with MSDSLA devices has led manufacturers to strive for a high sensitivity for their devices, leading to lower specificity as a consequence. For this reason and other ambiguous practical considerations (eg, device and patient costs, difficulty with insurance reimbursement), the adoption of this technology into routine clinical practice has remained relatively static; however, using enhanced diagnostic technologies such as MSDSLA may help with more accurate identification of high-risk PSLs, thereby leading to earlier detection and overall less expensive, more cost-effective treatment of melanoma.

Early detection of melanoma, which is known to improve survival rates, remains a challenge for dermatologists. Suspicious pigmented lesions typically are evaluated via clinical examination and dermoscopy; however, new technologies are being developed to provide additional objective information for clinicians to incorporate into their biopsy decisions.

Multispectral digital skin lesion analysis (MSDSLA) uses 10 bands of visible and near-infrared light (430–950 nm) to image and analyze pigmented skin lesions (PSLs) down to 2.5 mm below the skin surface and measures the distribution of melanin using 75 unique algorithms to determine the degree of the morphologic disorder. Using a logical regression model previously validated on a set of 1632 PSLs, the probability of melanoma and probability of being a melanoma/PSL of high-risk malignant potential are then provided to the clinician.¹

In this study, we analyzed aggregate data from 7 prior studies^2-8 to better determine how MSDSLA impacts the biopsy decisions of dermatologists and nondermatologists following clinical examination and dermoscopic evaluation of PSLs.

Methods

A total of 855 practitioners (657 dermatologists, 126 dermatology residents, 72 nondermatologists [ie, primary care physicians, physician assistants, nurse practitioners]) in 7 prior reader studies (Table)^2-8 were shown a total of 62 clinical (distant and close-up) and dermoscopic images of PSLs (13 invasive melanomas, 10 melanomas in situ, 7 high-grade dysplastic nevi, 32 benign skin lesions including low-grade dysplastic nevi) previously analyzed by MSDSLA.^2-8 For each lesion evaluated, the practitioners were first asked if they would biopsy based on their review of the clinical and dermoscopic images and were asked again when given the associated MSDSLA information. Data were aggregated across all participants for the individual lesions presented in each reader study. Biopsy decisions were compared overall after evaluation of clinical and dermoscopic findings and then after evaluation of MSDSLA findings. Statistical analyses were performed using t-test and χ² analysis for proportions where appropriate.

Results

Overall sensitivity for the detection of melanoma or other high-grade PSLs improved from 70% on clinical and dermoscopic evaluation to 88% after MSDSLA information was provided (P<.0001), and specificity increased from 52% to 58% (P<.001). Diagnostic accuracy also improved from 59% on clinical evaluation to 69% after review of MSDSLA findings (P<.0001). The positive predictive value of biopsy decisions was 47% following clinical evaluation, which improved to 56% after evaluation of MSDSLA findings (P<.001), and the negative predictive value increased from 74% to 89% (P<.0001). The overall percentage of lesions selected for biopsy did not significantly change following MSDSLA data integration (57% vs 60%)(Figure). Given that similar numbers of lesions were biopsied with improved sensitivity and specificity, the integration of MSDSLA data into the biopsy decision led to an improved biopsy ratio (ratio of melanomas biopsied to total biopsies) and fewer unnecessary biopsies.

Comment

Our broad analysis further supported the findings of prior studies that decisions to biopsy clinically suspicious PSLs are more sensitive, specific, and accurate when practitioners are provided MSDSLA information following clinical examination.^2-8With no significant increase in the number of biopsies performed, the fact that all 5 of the standard diagnostic evaluation metrics (sensitivity, specificity, diagnostic accuracy, positive predictive value, negative predictive value) were improved after MSDSLA information was provided additionally supported this conclusion.

Given the evolution in health care economics, it is clear that greater emphasis will continue to be placed on superior, evidence-based, effective care. The reported diagnostic sensitivities and specificities of clinical evaluation and dermoscopy for melanoma detection vary widely throughout the literature, with sensitivities ranging from 58% to over 90% and specificities ranging from 77% to 99%.^9-11Diagnostic performance generally has been found to be higher among dermatologists than nondermatologists and is highest in specialized pigmented lesion clinics.¹²

Our study had several limitations. For this analysis to be more representative of lesion biopsy selection in the clinical setting, biopsy sensitivity (correctly identifying lesions appropriate for biopsy) vs melanoma sensitivity (identifying a lesion as melanoma) was used.¹³ The overall sensitivity found was within the range of prior studies,^2-8 but this approach may have potentially led to a lower specificity due to an increased number of lesions biopsied. Additionally, the melanomas selected for these studies were early (malignant melanoma in situ or mean thickness of invasive malignant melanoma of 0.3 mm), and the nonmelanomas (including low-grade dysplastic nevi) were not necessarily diagnostically straightforward. This may have led to the clinical and dermoscopic sensitivity and specificity noted being lower than in some prior studies.^9-11

The risk of missing a melanoma with MSDSLA devices has led manufacturers to strive for a high sensitivity for their devices, leading to lower specificity as a consequence. For this reason and other ambiguous practical considerations (eg, device and patient costs, difficulty with insurance reimbursement), the adoption of this technology into routine clinical practice has remained relatively static; however, using enhanced diagnostic technologies such as MSDSLA may help with more accurate identification of high-risk PSLs, thereby leading to earlier detection and overall less expensive, more cost-effective treatment of melanoma.

Early detection of melanoma, which is known to improve survival rates, remains a challenge for dermatologists. Suspicious pigmented lesions typically are evaluated via clinical examination and dermoscopy; however, new technologies are being developed to provide additional objective information for clinicians to incorporate into their biopsy decisions.

Multispectral digital skin lesion analysis (MSDSLA) uses 10 bands of visible and near-infrared light (430–950 nm) to image and analyze pigmented skin lesions (PSLs) down to 2.5 mm below the skin surface and measures the distribution of melanin using 75 unique algorithms to determine the degree of the morphologic disorder. Using a logical regression model previously validated on a set of 1632 PSLs, the probability of melanoma and probability of being a melanoma/PSL of high-risk malignant potential are then provided to the clinician.¹

In this study, we analyzed aggregate data from 7 prior studies^2-8 to better determine how MSDSLA impacts the biopsy decisions of dermatologists and nondermatologists following clinical examination and dermoscopic evaluation of PSLs.

Methods

A total of 855 practitioners (657 dermatologists, 126 dermatology residents, 72 nondermatologists [ie, primary care physicians, physician assistants, nurse practitioners]) in 7 prior reader studies (Table)^2-8 were shown a total of 62 clinical (distant and close-up) and dermoscopic images of PSLs (13 invasive melanomas, 10 melanomas in situ, 7 high-grade dysplastic nevi, 32 benign skin lesions including low-grade dysplastic nevi) previously analyzed by MSDSLA.^2-8 For each lesion evaluated, the practitioners were first asked if they would biopsy based on their review of the clinical and dermoscopic images and were asked again when given the associated MSDSLA information. Data were aggregated across all participants for the individual lesions presented in each reader study. Biopsy decisions were compared overall after evaluation of clinical and dermoscopic findings and then after evaluation of MSDSLA findings. Statistical analyses were performed using t-test and χ² analysis for proportions where appropriate.

Results

Overall sensitivity for the detection of melanoma or other high-grade PSLs improved from 70% on clinical and dermoscopic evaluation to 88% after MSDSLA information was provided (P<.0001), and specificity increased from 52% to 58% (P<.001). Diagnostic accuracy also improved from 59% on clinical evaluation to 69% after review of MSDSLA findings (P<.0001). The positive predictive value of biopsy decisions was 47% following clinical evaluation, which improved to 56% after evaluation of MSDSLA findings (P<.001), and the negative predictive value increased from 74% to 89% (P<.0001). The overall percentage of lesions selected for biopsy did not significantly change following MSDSLA data integration (57% vs 60%)(Figure). Given that similar numbers of lesions were biopsied with improved sensitivity and specificity, the integration of MSDSLA data into the biopsy decision led to an improved biopsy ratio (ratio of melanomas biopsied to total biopsies) and fewer unnecessary biopsies.

Comment

Our broad analysis further supported the findings of prior studies that decisions to biopsy clinically suspicious PSLs are more sensitive, specific, and accurate when practitioners are provided MSDSLA information following clinical examination.^2-8With no significant increase in the number of biopsies performed, the fact that all 5 of the standard diagnostic evaluation metrics (sensitivity, specificity, diagnostic accuracy, positive predictive value, negative predictive value) were improved after MSDSLA information was provided additionally supported this conclusion.

Given the evolution in health care economics, it is clear that greater emphasis will continue to be placed on superior, evidence-based, effective care. The reported diagnostic sensitivities and specificities of clinical evaluation and dermoscopy for melanoma detection vary widely throughout the literature, with sensitivities ranging from 58% to over 90% and specificities ranging from 77% to 99%.^9-11Diagnostic performance generally has been found to be higher among dermatologists than nondermatologists and is highest in specialized pigmented lesion clinics.¹²

Our study had several limitations. For this analysis to be more representative of lesion biopsy selection in the clinical setting, biopsy sensitivity (correctly identifying lesions appropriate for biopsy) vs melanoma sensitivity (identifying a lesion as melanoma) was used.¹³ The overall sensitivity found was within the range of prior studies,^2-8 but this approach may have potentially led to a lower specificity due to an increased number of lesions biopsied. Additionally, the melanomas selected for these studies were early (malignant melanoma in situ or mean thickness of invasive malignant melanoma of 0.3 mm), and the nonmelanomas (including low-grade dysplastic nevi) were not necessarily diagnostically straightforward. This may have led to the clinical and dermoscopic sensitivity and specificity noted being lower than in some prior studies.^9-11

The risk of missing a melanoma with MSDSLA devices has led manufacturers to strive for a high sensitivity for their devices, leading to lower specificity as a consequence. For this reason and other ambiguous practical considerations (eg, device and patient costs, difficulty with insurance reimbursement), the adoption of this technology into routine clinical practice has remained relatively static; however, using enhanced diagnostic technologies such as MSDSLA may help with more accurate identification of high-risk PSLs, thereby leading to earlier detection and overall less expensive, more cost-effective treatment of melanoma.

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.