Mohs surgery for the treatment of lentigo maligna and lentigo maligna melanoma - a systematic review.

BACKGROUND: The role of Mohs micrographic surgery (MMS) in the treatment of lentigo maligna (LM), and lentigo maligna melanoma (LMM) has been controversial. The use of frozen sections is commonly cited as a suboptimal way to distinguish atypical melanocytes, resulting in traditional wide-local excision techniques as the mainstay of therapy. OBJECTIVE: To compare the success of MMS as a treatment option for LM and LMM with that of traditional surgical and nonsurgical therapies by analyzing the published recurrence rates of these lesions after MMS procedures. METHODS AND MATERIALS: PubMed database was used to find relevant articles with search terms related to MMS, LM, and LMM. RESULTS: The search strategy resulted in 27 articles that fulfilled the inclusion criteria. All studies considered; MMS provided a 1.35% recurrence rate with follow-up times ranging from 1 month to 5 years. Specifically, studies employing classical MMS and MMS with rush sections provided recurrence rates of 1.17% and 2.4%, respectively. CONCLUSION: MMS is one of the most successful treatment options for LM and LMM, with published evidence of improved recurrence rates when compared to other forms of therapy. Additional clinical trials are needed to further delineate the role of MMS in the treatment algorithm for these conditions.

Ten-year Follow-up Study of Grenz Ray Treatment for Lentigo Maligna and Early Lentigo Maligna Melanoma.

Radiotherapy is often used to treat lentigo maligna. However, the long-term efficacy and safety of radiotherapy approaches have not been thoroughly evaluated. We aimed to evaluate the long-term efficacy and safety of ultrasoft X-ray/Grenz ray treatment in those patients. A total of 161 lesions from 159 patients received treatment with Grenz ray between 2005 and 2007. Follow-up of recurrence was performed 10 years after the final treatment. In the study setting, the cure rates were 97% for primary therapy with Grenz ray alone and 100% when Grenz ray was combined with partial or radical excision. The treatment is well tolerated, simple to perform, and has an excellent cosmetic outcome, with 94% of patients pleased with the results. Grenz ray is painless, effective, and safe for use when surgery is not feasible. Thus, Grenz ray can be considered as a standard treatment option for lentigo maligna.

Radiotherapy for lentigo maligna and lentigo maligna melanoma - a systematic review.

Lentigo maligna (LM) is the most common subtype of in situ melanoma und occurs frequently in the sun-exposed head and neck region in elderly patients. The therapeutic "gold standard" is surgical excision, as there is the risk of progression to invasive (lentigo maligna) melanoma (LMM). However, surgery is not feasible in certain patients due to age, comorbidities or patient preference. Radiotherapy using Grenz rays or superficial X-rays has been established as non-invasive alternative for the treatment of LM and LMM. We performed a systematic literature search of MEDLINE and Embase databases in September 2019 and identified 14 patient series using radiotherapy for LM or LMM. No prospective trials were found. The 14 studies reported a total of 1243 lesions (1075 LM and 168 LMM) treated with radiotherapy. Local recurrence rates ranged from 0 to 31% and were comparable to surgical series in most of the reports on radiotherapy. Superficial radiotherapy was prescribed in 5-23 fractions with a total dose of 35-57 Gy. Grenz ray therapy was prescribed in 42-160 Gy in 3-13 fractions with single doses up to 20 Gy. Cosmetic results were reported as "good" to "excellent" for the majority of patients.In conclusion, the available low-level evidence suggests that radiotherapy may be a safe and effective treatment for LM and LMM. Data from prospective trials such as the phase 3 RADICAL trial are needed to confirm these promising findings and to compare radiotherapy to other non-surgical therapies and to surgery.

Evidence-Based Clinical Practice Guidelines for the Management of Patients with Lentigo Maligna.

INTRODUCTION: Lentigo maligna (LM) is a subtype of melanoma in situ that usually occurs in sun-damaged skin and is characterised by an atypical proliferation of melanocytes within the basal epidermis. If left untreated, LM can develop into invasive melanoma, termed lentigo maligna melanoma, which shares the same prognosis as other types of invasive melanoma. The incidence rates of LM are steadily increasing worldwide, in parallel with increases in the incidence rates of invasive melanoma, and establishing appropriate guidelines for the management of LM is therefore of great importance. METHODS: A multidisciplinary working party established by Cancer Council Australia has recently produced up-to-date, evidence-based clinical practice guidelines for the management of melanoma and LM. Following selection of the most relevant clinical questions, a comprehensive literature search for relevant studies was conducted, followed by systematic review of these studies. Data were summarised and the evidence was assessed, leading to the development of recommendations. After public consultation and approval by the full guidelines working party, these recommendations were published on the Cancer Council Australia wiki platform (https://wiki.cancer.org.au/australia/Clinical_question:Effective_interventions_to_improve_outcomes_in_lentigo_maligna%3F). Main Recommendations: Surgical removal of LM remains the standard treatment, with 5- to 10-mm clinical margins when possible. While yet to be fully validated, the use of peri-operative reflectance confocal microscopy to assess margins should be considered where available. There is a lack of high-quality evidence to infer the most effective non-surgical treatment. When surgical removal of LM is not possible or refused, radiotherapy is recommended. When both surgery and radiotherapy are not appropriate or refused, topical imiquimod is the recommended treatment. Cryotherapy and laser therapy are not recommended for the treatment of LM.

Radiotherapy in Periocular Cutaneous Malignancies: A Retrospective Study.

BACKGROUND: Due to the importance of function and cosmetics, periocular skin malignancies represent a therapeutic challenge. OBJECTIVE: To evaluate the safety and efficacy of radiotherapy (RT) treating periocular skin tumors. METHODS: Data of patients with periocular tumors treated with grenz or soft X-rays at the University Hospital Zurich, Switzerland, between 2009 and 2014 were reviewed. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with associated in situ lesions, cutaneous melanoma, lentigo maligna (LM), cutaneous lymphoma and Kaposi's sarcoma were included in the analysis. RESULTS: We found 159 periocular lesions in 145 patients. Overall recurrence was highest for actinic keratosis and Bowen's disease (27%), melanoma (17%) and LM (15%), whereas SCC and BCC showed recurrence in 11 and 10%, respectively. 45% of all recurrences occurred within 12 months after treatment, with a median time to recurrence of 13 months (range 3-73). CONCLUSION: RT, which provides a good therapeutic response with minimal adverse events, is a therapy option for periocular cutaneous malignancies.

The use of 2940-nm ER:YAG laser for the treatment of lentigo maligna.

OBJECTIVES: Lentigo maligna is a common in situ malignancy in elderly patients, with a low risk of progression to an invasive tumor. Surgical treatment may be complicated or refused. Non-surgical treatment options (such as lasers) may therefore be needed. PATIENTS AND METHODS: We report on 17 patients treated with a 2940-nm Er:YAG (erbium-doped yttrium aluminum) laser for histopathologically confirmed lentigo maligna. The lesions were ablated with a 5 mm margin of adjacent skin under local anesthesia with a 3.5 mm overlapping spot, energy density of 6.5 J/cm2 and a repetition rate of 5 Hz. If clinically visible pigmentation was seen in the ablated area during the following three months, the lesion was re-treated. All patients were followed up for residual or recurrent tumors. RESULTS: We achieved clinical clearance in all 17 patients. There were three recurrences during the follow-up period (9, 30 and 36 months after laser therapy). All patients were satisfied with the treatment course and cosmetic outcome. The mean follow-up duration was 28 months. CONCLUSIONS: Laser ablation is an interesting alternative method for treatment of lentigo maligna. It can be used for selected cases where surgery is contraindicated, complicated or declined by the patient.

A systematic review of non-surgical treatments for lentigo maligna.

Lentigo maligna (LM) is the most common melanocytic malignancy of the head and neck. If left untreated, LM can progress to lentigo maligna melanoma (LMM). Complete surgical excision is the gold standard for treatment, however, due to the location, size, and advanced age of patients, surgery is not always acceptable. As a result, there is ongoing interest in alternative, less invasive treatment modalities. The objective was to provide a structured review of key literature reporting the use of radiotherapy, imiquimod and laser therapy for the management of LM in patients where surgical resection is prohibited. An independent review was conducted following a comprehensive search of the National Library of Medicine using MEDLINE and PubMed, Embase, Scopus, ScienceDirect and Cochrane Library databases. Data were presented in tabular format, and crude data pooled to calculate mean recurrence rates for each therapy. 29 studies met the inclusion criteria: radiotherapy 10; topical imiquimod 10; laser therapies 9. Radiotherapy demostrated recurrence rates of up to 31% (mean 11.5%), with follow-up durations of 1-96 months. Topical imiquimod recurrence rates were up to 50% (mean 24.5%), with follow-up durations of 2-49 months. Laser therapy yielded recurrence rates of up to 100% (mean 34.4%), and follow-up durations of 8-78 months. in each of the treatment series the I(2) value measuring statistical heterogeneity exceeded the accepted threshold of 50% and as such a meta-analysis of included data were inappropriate. For non-surgical patients with LM, radiotherapy and topical imiquimod were efficacious treatments. Radiotherapy produced superior complete response rates and fewer recurrences than imiquimod although both are promising non-invasive modalities. There was no consistent body of evidence regarding laser therapy although response rates of up to 100% were reported in low quality studies. A prospective comparative trial is indicated and would provide accurate data on the long-term efficacy and overall utility of these treatments.

Assessment of changes in lentigo maligna during radiotherapy by in-vivo reflectance confocal microscopy: a pilot study.

BACKGROUND: Radiotherapy is an effective treatment for therapy of lentigo maligna (LM). OBJECTIVES: To investigate the usefulness of in-vivo reflectance confocal microscopy (RCM) in radiotherapy of LM and document the changes within the lesions during treatment. METHODS: A total of six lesions in six patients were investigated by RCM before, during and after radiotherapy. For diagnostic assessment three observers with experience in RCM diagnosis, blinded as to the stage of treatment, assessed the RCM images of each lesion and documented the findings by consensus. RESULTS: Epidermal disarray worsened in three patients during radiotherapy and superficial necrosis was observed in four patients. Large pagetoid round/dendritic cells decreased or even vanished during or after radiotherapy. Dilated vessels and apoptotic cells were seen in all patients during radiotherapy as well as an increase of inflammatory cells in the epidermis and dermis in most of the patients. Dendritic cells with small dendrites were observed during radiotherapy in all patients with an increase in number in three patients. Melanophages appeared in five patients at least once during the examination period. All RCM images were assessed correctly by the three observers. CONCLUSIONS: Reflectance confocal microscopy is a useful method to visualize changes during and after radiotherapy and might also be used for early detection of potential treatment failures. In addition, it might be helpful in planning radiotherapy.

Surveillance for treatment failure of lentigo maligna with dermoscopy and in vivo confocal microscopy: new descriptors.

BACKGROUND: Nonsurgical treatment (radiotherapy, imiquimod) is increasingly employed for the management of lentigo maligna (LM). While the diagnosis of LM remains difficult, the detection of treatment failure is even more challenging. OBJECTIVES: To describe the sensitivity and specificity for the diagnosis of LM of individual features and methods using dermoscopy and in vivo reflectance confocal microscopy (RCM) to aid in the detection of treatment failure of LM following nonsurgical treatment. METHODS: A retrospective study of dermoscopy and RCM images (blinded to the correlation with pathology) in patients with biopsy-confirmed LM who were undergoing nonsurgical treatment in two referral institutions - one in Sydney, Australia, and the other in Barcelona, Spain. Ninety-eight patients were treated nonsurgically for LM during the period 2006-2012. Thirty-one patients had abnormal dermoscopy or RCM evaluation, and had a biopsy that identified LM recurrence in 15 patients and nonmelanoma diagnoses in 16 patients (one Bowen disease, 15 solar changes). RESULTS: The diagnosis of treatment failure was difficult with dermoscopy, with a sensitivity of 80% and specificity of 56%, even with the interpretation of an expert. The best criterion was asymmetric hyperpigmented follicular openings, but this was present in only 47% of treatment failure LM. Isolated, very fine brown dots ('dust' appearance) correlated highly with the diagnosis of treatment failure LM (73% sensitivity and 88% specificity) and with pagetoid cells seen with RCM. The LM score, comprising six criteria, had a specificity of 94% and sensitivity of 100%. CONCLUSIONS: These methods and descriptors should help to manage the diagnosis of treatment failure.

Radiotherapy for lentigo maligna: a literature review and recommendations for treatment.

Lentigo maligna (LM) incidence is increasing. LM frequently involves the face near critical anatomical structures and as a consequence clinical management is challenging. Nonsurgical therapies, including radiotherapy (RT), are increasingly used. Evidenced-based treatment guidelines are lacking. We conducted a review of previously published data analysing RT treatment of LM. A search of PubMed, Embase and Medline databases to June 2012 identified nine clinical studies that examined the use of RT for LM treatment in at least five patients. Nine studies described 537 patients with LM treated with definitive primary RT, between 1941 and 2009, with a median reported follow-up time of 3 years. Eight articles could be reviewed for oncological outcome data. There were 18 recurrences documented in a total of 349 assessable patients (5%). Salvage was successful in the majority of recurrent LM cases by using further RT, surgery or other therapies. Progression to LM melanoma (LMM) occurred in five patients (five out of 349, 1.4%) who all had poor outcomes. There were five marginal recurrences documented out of 123 assessable patients (4%). There were eight in-field recurrences documented with either LM (five) or LMM (three) out of 171 assessable patients (5%). A series of recommendations were then developed for RT parameters for treatment of LM. These parameters include treatment volume, dose, dose per fraction and outcome measures. These may be of use in prospective data collection.

Radiation therapy for cutaneous melanoma.

Radiation therapy is used infrequently for cutaneous melanoma, despite research suggesting benefit in certain clinical scenarios. This review presents data forming the highest level of evidence supporting the use of radiation therapy. Retrospective and prospective studies demonstrate radiation therapy for primary tumors is associated with high control rates. Two randomized trials have found improvements in regional control with adjuvant radiotherapy to regional lymphatics. Retrospective and prospective studies demonstrate radiation therapy is associated with palliative response and metastatic tumor control. Optimal care of melanoma patients involves radiation therapy; awareness of this is incumbent of clinicians caring for patients with this disease.

Grenz ray treatment of lentigo maligna and early lentigo maligna melanoma.

BACKGROUND: Lentigo maligna (LM) is the in situ phase of lentigo maligna melanoma (LMM). A wide variety of modalities has been used to manage LM, including conventional surgery, staged excision, Mohs micrographic surgery, cryotherapy, radiotherapy, laser therapy, and, recently, imiquimod. OBJECTIVES: Soft x-radiation is an accepted treatment for LM/LMM. The aim of the present study was to evaluate the efficacy and safety of ultra-soft x-ray/grenz-ray (GR) treatment in patients with LM and early LMM. METHODS: Five hundred ninety-three patients were treated with GR (primary therapy, n = 350; partial excision followed by GR, n = 71; radical excision followed by GR as recurrence-prophylactic treatment, n = 172) at the Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden between 1990 and 2009. The treatment was given twice a week over 3 consecutive weeks in total doses of 100 to 160 Gy. Dosage depended on the stage of LM and the depth of periadnexal atypical melanocytic extension in histologically examined materials before treatment. Four hundred twenty-five patients have been followed up for at least 2 years; of these, 241 for 5 years. RESULTS: Overall, 520 of 593 patients (88%) showed complete clearance after one fractionated treatment. Residual lesions were seen in 15 patients, and 58 relapsed, 53 of whom (72%) within 2 years. LIMITATION: Woods light examination was not used in the clinical diagnosis of lentigo maligna. CONCLUSIONS: GR is an efficient and safe treatment in LM and early LMM when administered according to the recommendations presented herein. Moreover, GR offers an excellent cosmetic result.

Carbon dioxide laser treatment for lentigo maligna: a retrospective review comparing 3 different treatment modalities.

OBJECTIVE: To assess outcomes in managing primary lentigo maligna through surgical excision, radiation therapy, and carbon dioxide laser ablation. METHODS: Retrospective case series review of all patients with primary lentigo maligna diagnosed and treated in London, Ontario, Canada, between July 2, 1991, and June 29, 2010. RESULTS: Seventy-five patients aged 39 to 93 years (mean age, 64.8 years) were included in the study; 73 patients chose treatment. Twenty-seven patients were treated with surgical excision, 31 patients with radiation therapy, and 15 patients with carbon dioxide laser ablation. The median follow-up times were 16.6 months for surgical excision, 46.3 months for radiation therapy, and 77.8 months for carbon dioxide laser ablation (P < .001). Recurrence rates by treatment modality were 4.2% (1 of 27) for surgical excision, 29.0% (9 of 31) for radiation therapy, and 6.7% (1 of 15) for carbon dioxide laser ablation. CONCLUSIONS: A trend toward lower recurrence rates with surgical excision and carbon dioxide laser ablation was identified, but the results were not statistically significant. Carbon dioxide laser ablation may have a role as an alternative treatment for lentigo maligna among patients in whom standard treatments, such as surgical excision and radiation therapy, are declined or carry significant morbidity.

Guidelines of care for the management of primary cutaneous melanoma. American Academy of Dermatology.

The incidence of primary cutaneous melanoma has been increasing dramatically for several decades. Melanoma accounts for the majority of skin cancer-related deaths, but treatment is nearly always curative with early detection of disease. In this update of the guidelines of care, we will discuss the treatment of patients with primary cutaneous melanoma. We will discuss biopsy techniques of a lesion clinically suspicious for melanoma and offer recommendations for the histopathologic interpretation of cutaneous melanoma. We will offer recommendations for the use of laboratory and imaging tests in the initial workup of patients with newly diagnosed melanoma and for follow-up of asymptomatic patients. With regard to treatment of primary cutaneous melanoma, we will provide recommendations for surgical margins and briefly discuss nonsurgical treatments. Finally, we will discuss the value and limitations of sentinel lymph node biopsy and offer recommendations for its use in patients with primary cutaneous melanoma.

Surgical treatments for lentigo maligna: a review.

BACKGROUND: Since its initial description by Jonathan Hutchinson 120 years ago, a substantial amount of research has occurred to determine the optimum surgical therapy for lentigo maligna (LM). OBJECTIVE: To summarize the literature regarding the surgical treatment of LM. METHODS: We searched the National Library of Medicine using Pubmed Central and MEDLINE and included as many investigational reports regarding LM therapy that were available in an attempt to form a comprehensive review of surgical modalities. The key words "lentigo maligna,""lentigo maligna treatment,""lentigo maligna therapy," and "lentigo maligna therapeutic modalities" were used. RESULTS: We included 12 studies examining staged surgical excision (SSE), nine using Mohs micrographic surgery (MMS), six investigating cryosurgery, 22 investigating imiquimod, seven using lasers, nine investigating radiation therapy, and two investigating electrosurgery and curettage. CONCLUSIONS: SSE and MMS are associated with the lowest recurrence rates for LM. Cryotherapy and radiation therapy may be considered the options for treatment of LM in patients who cannot tolerate surgery. Imiquimod, although not currently approved by the FDA, has shown some efficacy in limited experimental studies and may play a future role in the treatment of LM.