Laser thermal therapy of benign skin tumours: Review and update

Abstract

The goal of this review is to provide an overview on laser treatment of benign skin tumours and recent developments in this field. Ablational laser systems are established treatment devices for benign skin tumours. They obtain good cosmetic results with mostly minimal side-effects. Recently, fractional laser devices or combination of laser therapy with photodynamic therapy has gained attention in this field. However, there is a lack of randomised, controlled trials for laser treatment of benign skin tumours.

• ablational/fractional laser device
• hamartoma
• xanthelasma
• cyst

Introduction

Treatment with different laser systems has become an integral part of dermatological therapy. The group of indications regarding benign tumours and organoid nevi is very heterogeneous. For these indications, patients often search help for cosmetic reasons. Therefore, high standards for treatment are required. Ablative and semi-ablative laser devices are mainly used for superficial ablation of tissue without damage of the surrounding structures. The ablation depth of the laser depends on wavelength, fluence rate and spot size. The most common or classic treatment devices include the erbium:yttrium-aluminium-garnet (Er:YAG) and the carbon dioxide (CO₂) laser. Although the argon laser is only of historical importance it is still used for the ablation of benign skin tumours but can frequently be replaced by the potassium titanium oxide phosphate (KTP) laser. Argon lasers are gas ion lasers and emit a continuous-wave blue-green visible light at peak wavelengths of 488 and 514 nm. Pigmented lesions can be damaged selectively with the argon laser with rapid wound healing [1]. The Er:YAG laser with a 2940 nm wavelength is well established for ablation of soft and hard biological tissue because the wavelength is highly absorbed in water. It is capable of ablating thin layers of skin precisely, especially in delicate locations, with minimal collateral damage [2]. The CO₂ laser is widely used for medical surgery. At a wavelength of 10,600 nm the energy is mainly absorbed by the extracellular fluid of biologic structures which leads to a non-specific vaporisation and coagulation of tissue. Ultra-pulsed CO₂ lasers emit short light pulses (600–900 µs) with high peak energies so that tissue can be ablated very precisely layer by layer [3].

Further treatment devices for benign skin tumours include the alexandrite, ruby, neodymium:YAG (Nd:YAG), and the diode laser. Alexandrite lasers emit light at wavelengths ranging from 700 to 830 nm. As these wavelengths are absorbed by melanin and dyes, but not significantly by blood, it can be used for the destruction of melanin-containing structures. The ruby laser has an emission wavelength of 694 nm and the laser light is absorbed by melanin and dark pigments.

The Nd:YAG laser is the most important solid-state laser with a wavelength of 1064 nm. Doubling the frequency of 1064 nm by a potassium titanyl phosphate crystal results in green light-emitting KTP lasers (532 nm) [4]. Quality (Q)-switched lasers have extremely short pulse times of about 10 ns which is much shorter than the relaxation time of the target chromophore. Q-switched Nd:YAG lasers are especially suited for treatment of tattoos, but also other pigmented lesions [4].

In diode lasers electrical energy is transformed directly into laser light. Laser diodes are available from the ultraviolet (UV) spectrum into the visible spectrum until the near-infra red (IR) spectrum for surgical applications. Diode lasers are non-ablative devices but they are capable of inducing thermal damage in the middle to upper dermis without causing scarring or epidermal damage [5].

The 585 nm pulsed dye laser (PDL) is usually no appropriate device for ablational therapy of benign skin tumours. Its main indication is for the treatment of vascular lesions [6]. However, it produces a non-specific thermal effect so that the PDL has proved to be effective for the treatment of xanthelasmas [7]. It has the further advantage of not producing an open wound in contrast to ablative laser systems.

There is a wide range of different laser devices for the treatment of benign skin tumours. Their application depends on the indication as well as the experience of the practioner.

Indications

The group of benign skin tumours that might be treated by laser therapy is rather heterogeneous. These tumours can be roughly classified as epidermal tumours/nevi, adnexal, fibrous, and neural tumours, as well as xanthelasmas and cysts.

Epidermal, dermal and organoid nevi/tumours

Epidermal nevi are the most common manifestation of cutaneous mosaicism (Figure 1A). They are present at birth and affect only the epidermis, whereas organoid nevi involve adnexal structures. A distinction must be made between papillomatous soft and hard verrucous lesions. Inflammatory linear verrucous epidermal nevus (ILVEN) is an unusual form of epidermal nevus marked by an additional inflammatory component. Complete removal of epidermal nevi remains difficult. Whereas aggressive approaches like surgical excision result in scar formation, superficial means of removal often result in recurrence [8].

Figure 1. (A) Epidermal nevus in the cervical region of an 11-year-old boy. (B) Result after three sessions of CO₂ laser (cw mode), 10 W of power, 2 mm spot size.

Different types of lasers have been reported to be effective in the treatment of epidermal nevi. The first report on the successful laser treatment of verrucous, epidermal nevi was published in 1984 [9]. In two patients, localised verrucous nevi were removed completely and in another patient with a systemic verrucous nevus, a marked improvement was obtained after several argon laser sessions. Paradela et al. [10] treated a total of 25 patients with epidermal nevi with the CO₂ laser in the super-pulsed mode (2 W/cm²). The mean number of treatment sessions was four (range: 1 to 28). Good results were achieved in 92% of soft, flattened nevi and in only 33% of patients with verrucous lesions. These authors believe that the thickness of the nevus is the most determining factor for the cosmetic result. Hohenleutner et al. [8] found the argon laser and the continuous-wave (cw) carbon dioxide laser able to remove epidermal nevi of various types and textures in 43 patients. Papillomatous, soft variants could be treated successfully with the argon laser without scarring whereas hard, keratotic lesions responded to CO₂ laser therapy but with a tendency to scar formation (Figure 1B). The CO₂ laser offers the advantage of intraoperative haemostasis whereas bleeding might complicate treatment with the Er:YAG laser [11]. Various case reports have proved the efficacy of the CO₂ laser [11], [12]. Park et al. [13] treated 20 patients with verrucous epidermal nevi either with the variable pulsed or the dual-mode Er:YAG laser. In 15 out of 20 patients, successful removal of the verrucous epidermal nevus could be obtained after one treatment session. All patients showed post-operative erythema and 15% had pigmentary changes. Five patients showed a relapse within one year.

Further treatment devices for epidermal nevi include the long-pulsed ruby laser [14] and the pulsed dye laser for treating itch in ILVEN [15]. In conclusion, the CO₂ laser (cw/pulsed) has proved to be a good therapy option, especially for treating large areas with limited bleeding. The Er:YAG laser offers a good alternative for smaller lesions with comparable results although bleeding might hamper the visibility and thus exact ablation. Alternative treatment strategies for ILVEN include trichloroacetic acid peeling [16], topical calcipotriol [17] and cryosurgery. Photodynamic therapy (PDT) has been reported to be successful in the treatment of a verrucous epidermal nevus [18].

Nevus sebaceous usually presents at birth as a yellow patch and tends to thicken during puberty, so that patients then often request their removal for cosmetic reasons. As in epidermal nevi, the CO₂ laser offers a good therapy modality to ablate such lesions [19]. Recently, the combination of CO₂ laser treatment followed by photodynamic therapy has proved to be effective for ablation of nevus sebaceous on the face in 12 patients [20]. However, several treatment sessions (2–9) were necessary and two patients showed partial recurrences shortly after completion of treatment.

Seborrhoeic keratoses are very frequent benign epithelial tumours that are especially annoying when situated on the head and neck area or in case of extensive occurrence. Recurrence after curettage, shave excision, cryoablation, or chemical peelings can be observed. As these lesions might be confused with malignant tumours such as melanoma or basal cell carcinoma, laser therapy should be performed only by experienced dermatologists or after histological examination of the lesion. A recent study [21] investigated the efficacy of the 532-nm diode laser to remove 1567 seborrhoeic keratoses in 326 patients. The lesions were coloured with a red marker or ferric subsulphate to enhance the ablative effects of laser treatment. Complete resolution occurred in 93% of lesions after one single treatment, whereas 7% of lesions required a second laser treatment. Other suitable laser devices include the CO₂, erbium, argon, and alexandrite laser [1], [22–24]. Dermatosis papulosa nigra is very common among people with skin type V and VI and is considered a variant of seborrhoeic keratoses. In 2008, Schweiger and colleagues reported the use of a long-pulsed Nd:YAG laser for dermatosis papulosa nigra in two patients who achieved 70 to 90% clearance of the treated lesions [25]. Kundu et al. [26] reported the efficacy of a KTP laser for dermatosis papulosa nigra in 14 patients, with 96% of patients achieving greater than 50% improvement. A case report describes the successful treatment of dermatosis papulosa nigra with a 1.550 nm fractionated erbium-doped fibre laser resulting in greater than 75% improvement [27].

Er:YAG and CO₂ lasers can be used for ablation of benign, papillomatous dermal nevi [28]. However, a number of case reports have been published wherein melanoma has been diagnosed after laser ablation of presumed benign skin lesions [29], [30]. In patients with a history of melanoma or evolution of a pigmented lesion, laser therapy should be avoided or a biopsy should be performed before laser treatment. Alternative treatment options for benign epidermal/dermal tumours include surgical excision, cryotherapy and chemical peelings with a risk of scar formation and hypopigmentation. Surgical excision is especially difficult in extensive lesions.

Adnexal tumours

Therapy options for adnexal tumours are limited and include chemical peelings, surgical excision, electrocauterisation and laser therapy. Hair follicle tumours occur most often on the face and scalp. Trichoblastomas are the most common secondary tumours in nevus sebaceous. They are often difficult to distinguish from basal cell carcinoma, both clinically and histologically. Therefore, surgical excision and histological examination is mandatory in these cases. Multiple trichoblastomas might occur in a context of Brooke-Spiegler syndrome along with trichoepitheliomas, spiradenomas and cylindromas [31]. In the case of multiple tumours, non-surgical treatments are favoured. Lopiccolo et al. [32] treated a patient with Brooke-Spiegler syndrome after histological examination of facial trichoepitheliomas either with Er:YAG fractionated ablative laser resurfacing and photodynamic therapy (PDT), resurfacing combined with imiquimod, resurfacing alone, or PDT alone. Ablative laser resurfacing in combination with PDT was rated best by the patient. Treatment with CO₂ laser alone, argon laser or the combination of Er:YAG and CO₂ laser has also been reported for this indication [33–36]. Multiple trichodiscomas and fibrofolliculomas, or so-called mantleomas, are typical for Birt-Hogg-Dubé syndrome. They present as flat white papules, most commonly on the face and chest, and might be treated successfully with the CO₂ or Er:YAG laser [37], [38].

Syringomas are probably the most common adnexal tumours arising from sweat glands. They typically appear in the periorbital or perinasal region of young women and are almost always multiple (Figure 2A). Recently it has been shown that familial syringoma is an autosomal dominant disorder and the syringoma gene has been mapped to chromosome 16q22 [39]. Several studies and case reports have proved the effectiveness of the CO₂ laser in the treatment of syringomas [40–42]. Park et al. [41] treated 11 patients with syringomas with the CO₂ laser using a multiple-drilling method. In small lesions, a single hole was made in the centre of the lesion, whereas for conglomerate lesions, multiple holes were made within the lesions at distinct distances. Patients received 1 to 4 treatment sessions at 4- to 6-week intervals. Clinical response was excellent in seven patients and good in four patients without occurrence of any serious side effect. Fractional laser devices are widely used for skin rejuvenation but they might also be beneficial for the treatment of syringomas. Cho et al. [42] treated 35 patients with periorbital syringomas with an ablative 10,600 nm fractional CO₂ laser. After two treatment sessions at 1-month interval, 8.6% showed ≥75% improvement, 42.9% had marked improvement and 34.3% had moderate improvement. Five patients (14.3%) had transitory hyperpigmentation after the treatment. Fractional CO₂ laser treatment seems to be a promising new method for the treatment of syringomas with minimal side-effects.

Figure 2. (A) Syringomas in the periorbital region of a 41-year-old woman. (B) Result after four treatment sessions with the argon laser, 1.3 W of power, 2 mm spot size, 300 ms pulse duration.

Sebaceous gland hyperplasia is an extremely common finding in seborrhoeic sun-damaged skin. Besides cryotherapy and chemical peelings, ablational laser devices (argon (Figure 2B), CO₂ laser, Er:YAG laser), the PDL and 1450 nm diode laser lead to good cosmetic results [43–46]. A rather new therapy option is the combination of PDT with CO₂ laser treatment that was tested in four patients. CO₂ laser therapy was performed before PDT to reduce lesion size and facilitate penetration of the photosensitiser. Three of four patients showed marked improvement without any side-effects [47].

In conclusion, there is a wide range of possible laser devices for ablation of adnexal tumours with good cosmetic results and a low incidence of side-effects.

Fibrous tumours

Angiofibromas can occur as solitary lesions or aggregated in a context of tuberous sclerosis, then often misnamed as adenoma sebaceum (Figure 3A). Further typical lesions of tuberous sclerosis include fibromas appearing in the sub- or periungual region, so-called Koenen tumours. Fibrous papules of the nose occur mostly isolated as small, red papules on the tip of the nose.

Figure 3. (A) Angiofibromas in the facial region of a 41-year-old man with tuberous sclerosis. (B) Results after five treatment sessions with the argon laser, 1.3 W of power, 2 mm spot size, 300 ms pulse duration.

Boixeda et al. [48] treated 10 patients with facial angiofibromas with CO₂, argon (Figure 3B) or PDL. Excellent results were obtained in seven patients and good in three patients, with CO₂ laser treatment being superior to argon laser therapy. Other authors described successful treatment of angiofibromas with argon laser surgery [49–51]. Song et al. [52] tried CO₂ laser resurfacing in two Asian patients with angiofibromas with a flash scanner because it produces less thermal damage than the CO₂ laser defocused mode. Furthermore, it enables controlled depth vaporisation for more precise ablation of lesions. Both patients showed remarkable cosmetic improvement, but post-treatment erythema persisted about 2 months.

The treatment of Koenen tumours is difficult due to their location next to the nail plate. There is a great risk of injury of the nail plate and consecutive disturbed nail growth. Therapeutic options include surgical excision, electrodessication, shave excision and phenolisation [53], as well as CO₂ laser treatment [54]. CO₂ laser therapy of Koenen tumours proved to be similar to conventional surgical resection in terms of cosmetic outcome. However, bleeding was negligible and operating time was considerably shorter for laser treatment compared to surgical excision [54].

Fibrous papules of the nose are common benign lesions that might be treated by tangential excision or laser ablation. There are no studies comparing different laser devices for this indication. In our experience, the argon laser is a very suitable device for ablation of those small papules. Ablation with the pulsed CO₂ laser or the Er:YAG laser might be a treatment alternative.

Ablative laser devices like the CO₂ or the argon laser are the most suitable devices for ablation of benign fibrous tumours. Surgical excision is only an alternative treatment in cases of solitary lesions.

Neural tumours

Neurofibromas may occur as solitary molluscoid nodules that can be pushed back into the skin like a bell button. When multiple, they are an important marker for neurofibromatosis and a condition of cosmetic concern. In contrast to surgical treatment, the CO₂ laser can rapidly remove large numbers of lesions with high patient satisfaction [55], [56]. After opening the epidermis, the lesion can be squeezed out and ablated. A complete removal down to the base should be done to prevent recurrences. However, the risk of scar formation after CO₂ laser therapy has been reported in the literature [57], [58]. Elwakil et al. [59] treated 12 patients with multiple neurofibromas either with a long-pulsed Nd:YAG laser (74% of lesions, thickness ≤ 5 mm) or bulkier lesions (26%, thickness ≥ 5 mm) with a cw Nd:YAG laser. Patients received 1 to 2 treatment sessions. Regarding flat lesions, a regression of 76% to 100% could be obtained in 43% of lesions, and 34% of lesions showed a regression of 51% to 75%. Hyperpigmentation occurred in 4.8% of lesions. Regarding bulkier lesions, 68% of lesions had a regression between 51% and 100%. In this group, wound infection and ulceration occurred in 1.5% and 3%, respectively, whereas hyperpigmentation occurred in 4.5% of lesions. There were no recurrences during a follow-up of 14 months.

Both Nd:YAG and CO₂ lasers are useful devices for ablation of neurofibromas. However, there is a risk of scar formation so that patients have to be informed about these possible side-effects. Test spots are mandatory before treatment of larger areas.

Xanthelasmas

Xanthelasmas represent lipid deposits in the skin and are sometimes the first clinical marker of hypercholesterolemia. They present as flat, yellow plaques and are most often found in the periorbital region. When performing laser therapy, protection of the eyes is mandatory, for example by insertion of steel eye shields or sterile rubberised contact lenses. The classic laser devices for treatment of xanthelasmas include CO₂, argon, and Er:YAG lasers [2], [3], [60]. Furthermore, KTP, Nd:YAG, PDL, and diode lasers have been applied successfully [7], [61–63]. Fractional photothermolysis has recently been reported as a new therapy strategy in a case report [64].

Raulin et al. [3] treated 23 patients with 52 periorbital xanthelasmas with an ultra-pulsed CO₂ laser and could remove all lesions by a single treatment (4 to 7 passes). Three patients developed a recurrence during a follow-up of 10 months. No side-effects occurred besides transient pigmentary changes. The cw CO₂ laser has a higher risk of scar formation and should be used only cautiously [65]. Basar et al. [60] treated 24 patients in one to four sessions with an argon laser and obtained good cosmetic results in 85% of patients. The Er:YAG laser also represents an effective and safe therapy option for this indication [2]. The Q-switched Nd:YAG laser as well as the KTP laser have obtained good results after one to three treatment sessions with minimal side-effects in two studies [61], [62]. Another study could not reproduce the good effects of the Q-switched Nd:YAG laser in 37 patients and these authors do not recommend it for the treatment of xanthelasmas [66].

In contrast to ablative laser systems, PDL treatment does not produce an open wound. In the treatment of xanthelasmas it causes an unspecific thermal effect. A recently published study [7] has investigated the efficacy of PDL treatment for xanthelasma palpebrarum. Twenty patients received five treatment sessions (two passes per session) with a short-pulsed PDL. About 90% of patients had good or excellent clearance of their lesions and patient satisfaction was high. Hyperpigmentation occurred in 7.9% of lesions and was still present at the end of the final 4-week follow-up. Park et al. [63] investigated the safety and efficacy of a 1450 nm diode laser in 16 patients with xanthelasmas. A moderate or marked improvement was seen in 75% of patients, whereas mild focal transient hyperpigmentation occurred in five patients.

Besides laser ablation, xanthelasmas might be treated by surgical excision, with a risk of scar formation or ectropion, or by the use of trichloroacetic acid [67]. Recurrence of xanthelasmas is common, regardless of the mode of treatment. Most often several treatment sessions are necessary. New treatment options like diode laser therapy or fractional photothermolysis have to be investigated in larger controlled, randomised studies.

Cysts

Cysts are well-circumscribed tumours that can be divided into true cysts (epithelial, glandular and developmental cysts) and pseudocysts. Eruptive vellus hair cysts are epithelial cysts that are closely related to steatocystoma multiplex. CO₂ and Er:YAG lasers have been used with variable success to treat this entity [68–71]. Coras et al. [70] treated a patient with dense facial eruptive vellus hair cysts with the pulsed Er:YAG laser. The lesions recurred shortly after therapy and the authors concluded that the therapy is not successful in regions where the depth of ablation is limited, owing to the risk of atrophy and scarring. Kageyama et al. [72] treated two patients with truncal eruptive vellus hair cysts successfully with the Er:YAG laser. After penetration of the cyst wall and digital expression of the cyst content, three additional passes were performed to ablate the posterior cyst wall. There was no recurrence during a 13-month follow-up. Individual cases report good results with the Er:YAG and CO₂ laser for the treatment of steatocystoma multiplex [68], [69].

Eccrine hidrocystomas are benign, solitary glandular cystic tumours that can be treated by surgical measures or laser therapy. Case reports have described the successful treatment of hidrocystomas with diode lasers, CO₂ and PDL [5], [73], [74]. The PDL targets vascular structures and is mainly used for the treatment of port wine stains and haemangiomas [6]. Lee et al. [73] postulated that PDL therapy for eccrine hidrocystomas leads to destruction of dermal cystic structures by non-selective heating energy diffused out from the selectively photothermolysed adjacent microvasculatures. However, the pulse duration seems to play an important role. Tanzi and Alster [75] used a PDL with a pulse duration of 1.5 ms and needed four treatment sessions at 6- to 8-week intervals to obtain good cosmetic results. Lee et al. [73] used a PDL with a pulse duration of 6 ms and obtained clearing after a single treatment session during a follow-up period of 11 months. Other authors could not reproduce the good results with the PDL using a pulse duration of 3 ms in two Asian women [76]. Therefore, further controlled studies are needed to investigate the efficacy of different laser systems in the treatment of hidrocystomas.

Mucoid dorsal cysts are pseudocysts because they lack an epithelial lining. They may be painful and cause a longitudinal furrow in the nail when arising on the nail fold. In the literature there are only two reports on the successful treatment of mucoid dorsal cysts with the CO₂ laser [77], [78]. Karrer et al. [77] treated four out of six patients successfully with the CO₂ laser without any complications or side-effects. The cyst was penetrated, the content squeezed out and the cyst completely vaporised under protection of the underlying nail matrix. As a consequence of surgical excision, scar formation and deformation of the nail might occur. Thus, CO₂ laser therapy might be used as first line therapy. Oral mucous cysts might be treated by the CO₂ laser, as well [79].

In conclusion, the CO₂ laser is the most common laser for the treatment of cysts. However, non-ablative lasers like PDL or diode lasers might be an alternative for this indication.

Contraindications for laser therapy of benign skin tumours and alternative treatment options

Accurate diagnosis of benign skin tumours is necessary before initiating laser therapy, as this treatment cannot be monitored by histology. In case of the slightest doubt on the benign nature of the lesion, a biopsy must be performed for histopathological examination. Otherwise serious medical complications and legal impacts for the practitioner may arise. Pigmented lesions in patients with a history of melanoma or dysplastic nevi should not be treated by laser therapy. The use of dermatoscopy contributes to the exact clinical classification of pigmented lesions, but even experienced dermatologists are at risk of clinical misdiagnosis. Therefore, laser treatment of pigmented skin lesions is discussed controversially. Furthermore, it is currently not known whether removal or treatment of nevi with laser devices will affect the risk of malignant transformation of these lesions. However, laser treatment to remove or lighten nevi has been used successfully. In the literature, there are several reports of pseudomelanoma following laser treatment of melanocytic nevi [30], [80–82].

Surgical excision, shaving, electrocautery, cryotherapy or dermabrasion are sometimes good alternatives for removal of benign skin tumours. Especially surgical treatments have the advantage of a histopathological confirmation of the suspected diagnosis. However, scar formation and the risk of keloid formation in special localisations limit patients’ acceptance.

Conclusions

Many different laser systems have shown to be effective in the treatment of benign skin tumours. Often, multiple treatment sessions are necessary and recurrences are possible. Patients must be informed about possible side-effects as they are mainly treated for cosmetic reasons.

There must be no doubt about the benign nature of a tumour before performing a laser treatment. If there is any doubt, histological evaluation to clarify the benign or malignant nature of the lesion must be done first.

An optimal treatment of benign skin tumours combines complete destruction of lesions with minimal side-effects. Ablative laser systems are usually used for this indication. Recently, non-ablative laser systems such as the PDL and diode lasers have been used for the treatment of benign skin tumours as well [7], [73]. Fractional laser devices represent a promising addition to the dermatologist's armamentarium. Furthermore, combinational approaches such as laser treatment and PDT are new therapeutic options.

However, there is a lack of randomised, controlled trials in the treatment of benign skin tumours comparing laser therapy with conventional therapy options.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.