Lentigo maligna: a comprehensive review on diagnosis and treatment.

Lentigo maligna (LM), a form of melanoma in situ, and LM melanoma (LMM), its invasive counterpart, exhibit distinctive epidemiology, risk factors, and clinical features compared to other melanoma subtypes. Notably, LM occurs on chronically sun-damaged skin presenting as a slow-growing, ill-defined patch which makes it difficult to diagnose and to treat. Additionally, while LM generally presents a favourable prognosis, it can also lead to dermal invasion and behave similarly to other melanomas with the same Breslow thickness. Hence, surgery continues to be the cornerstone treatment. Wide excisions are often necessary, but challenges arise when these lesions manifest in cosmetically sensitive regions, limiting the feasibility and desirability of large excisions. Specialized approaches, including margin-controlled surgery and image-guided treatment with reflectance confocal microscopy, have been developed to address these issues. Other non-surgical treatments such as cryosurgery, imiquimod, radiotherapy, or photodynamic therapy, may also be used but commonly present with recurrent/persistent disease. Herein we comprehensively review the existing literature on the management of LM/LMM, and discus the potential new advances on managing this challenging skin cancer.

Lentigo maligna: a review.

Lentigo maligna (LM) is a melanoma in situ with distinct clinical features and histology. It commonly affects men after the sixth decade of life. Incidence rates of LM have increased based on early 21st century data from different countries; however, data are suboptimal. Data from England show a plateauing crude incidence between 2013 and 2019. By comparison, invasive melanoma and other types of melanoma in situ commonly appears in younger age groups (median age 58 and 67 years old, respectively) and incidence is rising. The most important risk factors for LM include fair skin and cumulative ultraviolet solar radiation exposure. Although LM is limited to the epidermis and connected skin adnexa, it may progress to invasive LM melanoma. The reported rate of malignant progression varies, reflecting a challenge for LM epidemiology research as often lesions are removed on diagnosis. LM poses a challenge in diagnosis and management. Although it can be diagnosed clinically or dermoscopically, histopathological assessment of biopsied skin tissue remains the gold standard. Reflectance confocal microscopy allows for better appreciation of the complexity of LM at a cellular level, often progressing beyond clinical margins. Management of LM may involve Mohs micrographic surgery or excision, although recurrence may occur even with 5 mm clinical margins. Imiquimod cream may be effective, but incomplete treatment and recurrence has been reported. Conservative management with observation or radiotherapy may be used in selected patients' cases. Five-year net survival rates are excellent. This paper reviews the natural history, epidemiology, aetiology, pathogenesis, diagnosis and management of LM.

Clinical Practice Guideline on Melanoma From the Spanish Academy of Dermatology and Venereology (AEDV). / Guía de práctica clínica de melanoma de la Academia Española de Dermatología y Venereología.

Specialist approaches to the diagnosis and treatment of melanoma have undergone many changes. This guideline aims to provide Spanish dermatologists with evidence-based information for resolving the most common doubts that arise in clinical practice. Members of the Spanish Oncologic Dermatology and Surgery Group (GEDOC) with experience treating melanoma were invited to participate in drafting the guideline. The group developed a new guideline on the basis of existing ones, using the ADAPTE collaboration process, first summarizing the care process and posing relevant clinical questions, then selecting guidelines with the best scores according to the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. Finally, the group searched the selected guidelines for answers to the clinical questions, drafted recommendations, and sent them for external review. The guideline is structured around 21 clinical questions chosen for their relevance to issues that make clinical decisions about the management of melanoma difficult. Evidence from existing guidelines was used to answer the questions. A limitation of this guide derives from the scarce evidence available for answering some questions. Moreover, some areas are changing rapidly, so recommendations must be updated often. The present guideline offers answers to clinical questions about the routine management of melanoma in clinical practice and provides dermatologists with a reference to guide decisions, taking into consideration the resources available and patient preferences.

[Facial skin cancers: Comparison of opinions in French multidisciplinary team meetings]. / Cancers cutanés de la face : avis comparés de réunions de concertation pluridisciplinaire françaises.

BACKGROUND: The aim of our study was to evaluate the diversity, or homogeneity, of recommendations made in multidisciplinary team meetings (MTM) concerning the management of facial skin cancers in France, and to analyze the determinants thereof. PATIENTS AND METHODS: We contacted a panel of dermatology and ENT multidisciplinary teams (MDT) and collected their recommendations made at meetings regarding 3 clinical cases: squamous cell carcinoma in a renal transplant patient with an incomplete excision margin (case 1), locally advanced basal cell carcinoma (case 2), and lentigo maligna (case 3). The responses were analyzed globally and then based on 2 subgroups defined by the presence or absence of a dermatologist in the MTM. The effect of the makeup of the MTM (based on the presence of a dermatologist, a plastic surgeon, an oncologist and an ENT specialist) was evaluated for the main therapeutic proposals. RESULTS: The opinions of the 45 MDMs that responded to the survey were mixed for the three cases as regards important elements such as the indication of surgical revision for case 1, the proposal of an alternative treatment to surgery for case 2, and monitoring arrangements for case 3. Certain proposals were associated with the presence of a dermatologist in the MTM, such as discussion of adaptation of immunosuppressive treatment and details of the surgical margins to be applied for case 1, as well as simple monitoring and details of monitoring arrangements in case 3. CONCLUSION: It is important to maintain dermatologists in MTMs on account of their expertise in all therapeutic areas concerning skin cancers.

Strategies for Reducing Final Surgical Defect Sizes in the Treatment of Lentigo Maligna.

BACKGROUND: Lentigo maligna (LM) is associated with disproportionately high surgical morbidity. OBJECTIVE: The authors report on 2 strategies to reduce the surgical morbidity associated with LM. METHODS: Forty LM lesions were removed with excisional biopsies without margins and closed with purse-string sutures. Invasive cases underwent staged excisions with 10-mm margins. Cases without invasion were treated with neoadjuvant topical imiquimod 5% cream (5 d/wk × 8 weeks) followed by conservative staged excisions with 2-mm margins using radial sections stained with hematoxylin and eosin and immunostaining with Mart-1, with or without SOX10. RESULTS: Invasion was detected in 12/40 (30%) of the excisional biopsy specimens (average depth 0.45 mm). No invasion was detected in 28/40 (70%). All 24 patients who completed neoadjuvant topical imiquimod 5% cream before staged excisions had negative first-stage margins at 2 mm. Compared with average published margins for LM, this represents a 71.4% reduction in the required margin and an average reduction in the final surgical defect by 74%. CONCLUSION: LM treatment by excisional biopsies with a purse-string closure enables accurate tumor staging and contracts the tumor footprint to its minimal size. Subsequent neoadjuvant imiquimod followed by a conservative staged excision with 2-mm margins allows for removal of LM with decreased surgical morbidity.

Ablative fractional laser-assisted photodynamic therapy for lentigo maligna: a prospective pilot study.

BACKGROUND: Lentigo maligna (LM) is an in situ form of melanoma carrying a risk of progression to invasive lentigo maligna melanoma (LMM). LM poses a clinical challenge, with subclinical extension and high recurrence rates after incomplete surgery. Alternative treatment methods have been investigated with varying results. Photodynamic therapy (PDT) with methylaminolaevulinate (MAL) has already proved promising in this respect. OBJECTIVES: To investigate the efficacy of ablative fractional laser (AFL)-assisted PDT with 5-aminolaevulinic acid nanoemulsion (BF-200 ALA) for treating LM. METHODS: In this non-sponsored prospective pilot study, ten histologically verified LMs were treated with AFL-assisted PDT three times at 2-week intervals using a light dose of 90 J/cm2 per treatment session. Local anaesthesia with ropivacaine was used. Four weeks after the last PDT treatment the lesions were treated surgically with a wide excision and sent for histopathological examination. The primary outcome was complete histopathological clearance of the LM from the surgical specimen. Patient-reported pain during illumination and the severity of the skin reaction after the PDT treatments were monitored as secondary outcomes. RESULTS: The complete histopathological clearance rate was 7 out of 10 LMs (70%). The pain during illumination was tolerable, with the mean pain scores for the PDT sessions on a visual assessment scale ranging from 2.9 to 3.8. Some severe skin reactions occurred during the treatment period, however. CONCLUSIONS: Ablative fractional laser-assisted PDT showed moderate efficacy in terms of histological clearance. It could constitute an alternative treatment for LM but due to the side effects it should only be considered in inoperable cases.

Lentigo maligna: diagnosis and treatment.

Lentigo maligna (LM) is an in situ subtype of melanoma, clinically presenting as a pigmented, asymmetric macule that originates mostly on the head and neck and spreads slowly. The diagnosis may be challenging both for clinicians and pathologists. Dermatoscopy and reflectance confocal microscopy represent a useful tool in the differentiation of LM from other pigmented lesions, such as pigmented actinic keratosis, solar lentigines, seborrheic keratosis and lichen planus-like keratosis. Moreover, those non-invasive diagnostic technique may be crucial in the selection of optimal biopsy sites in equivocal lesions, in pre-surgical mapping and in evaluating and monitoring response to non-surgical treatments. Histologic examination remains the gold standard for the diagnosis of LM, showing a lentiginous proliferation of basal atypical melanocytes on a severe sun-damaged skin. The management of LM is constantly evolving. Treatments include surgery (the first choice, when available), radiotherapy and imiquimod cream (in patients not candidates to surgery). Many other possible treatments for LM have been tested, but they are not yet supported by strong evidences. We collected current guidelines and PubMed available reviews, studies and case-reports in order to make an overview on diagnosis and treatment of LM.

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.

Clinical usefulness of dermoscopy in the management of lentigo maligna melanoma treated with topical imiquimod: A case report.

The importance of dermoscopy for diagnosing lentigo maligna melanoma (LMM) is well known. More recently, dermoscopy has been proposed as a useful tool also for the treatment choice and monitoring. Herein, we present an 87-year-old woman, who was successfully treated with imiquimod 5% cream after surgical persistence of residual LMM and for whom dermoscopy was helpful to assist diagnosis and assess tumor persistence after surgery and its response to topical treatment with imiquimod.

Melanoma on chronically sun-damaged skin: Lentigo maligna and desmoplastic melanoma.

There are multiple, genetically distinct pathways that give rise to melanoma. Melanomas on sun-damaged skin (MSDS), including lentigo maligna and desmoplastic melanoma, have distinct genetic profiles and are uniquely linked to chronic ultraviolet exposure. In this article, we discuss the etiologies of lentigo maligna and desmoplastic melanoma, emerging diagnostic adjuncts that might be helpful for accurately identifying these lesions, and the clinical relevance of their frequent co-occurrence. We present unique and overlapping features of these entities and discuss challenges in MSDS management, including margin assessment, excision, and the potential role of nonsurgical therapy. Last, we address the role of immunotherapy in invasive disease. Understanding MSDS as distinct from melanoma arising on intermittently sun-exposed or sun-protected skin will ultimately help optimize patient outcomes.

Rate of Recurrence of Lentigo Maligna Treated With Off-Label Neoadjuvant Topical Imiquimod, 5%, Cream Prior to Conservatively Staged Excision.

Importance: Staged excision of lentigo maligna (LM) often requires multiple stages and can result in significant cosmetic morbidity. Imiquimod cream has been used off-label as monotherapy in the treatment of LM and may be used in the neoadjuvant setting prior to staged excision as a strategy to reduce the size of the surgical margins required to confirm negative histologic margins. Objective: To examine the rate of recurrence of LM in patients treated with neoadjuvant topical imiquimod, 5%, cream prior to conservatively staged excisions. Design, Setting, and Participants: This was a retrospective medical record review of 334 patients with 345 biopsy-confirmed LM tumors from June 2004 to January 2012 who were treated with imiquimod prior to undergoing staged excisions at the University of Utah Medical Center and Huntsman Cancer Institute, large academic hospitals in Salt Lake City. Interventions: Patients were treated with off-label imiquimod, 5%, cream 5 nights per week for 2 to 3 months. Those deemed to have an inadequate inflammatory response were also treated with tazarotene, 0.1%, gel twice weekly. Conservatively staged excisions, beginning with 2-mm margins, were then performed. Main Outcomes and Measures: The rate of recurrence of LM after long-term follow-up. Results: Patients included 235 men (70%) and 99 women (30%) with a mean (SD) age of 67 (13) years. Patients were treated with imiquimod cream for a mean of 2.5 months prior to undergoing conservatively staged excisions. There were 12 local recurrences (a rate of 3.9%) with a mean time to recurrence of 4.3 years and a mean length of follow-up of 5.5 years. Conclusions and Relevance: Neoadjuvant topical imiquimod, 5%, cream prior to conservatively staged excisions for LM allowed for negative histologic margins with a median final margin of 2 mm and a rate of recurrence similar to reported recurrence rates with standard staged excisions by either Mohs surgery or en face permanent sections.

Immunocryosurgery as monotherapy for lentigo maligna or combined with surgical excision for lentigo maligna melanoma.

The incidence of lentigo maligna (LM), in situ (LM) or invasive (lentigo maligna melanoma, LMM), has increased during the last decades. Due to functional or cosmetic outcomes, optimal treatment with surgical excision may not be appropriate in some cases. We tried less invasive therapy, immunocryosurgery, as a single treatment for LM or combined with surgery for LMM, with better aesthetic results. Three patients with LM or LMM not amenable to complete surgical excision were selected. LMM patients underwent limited surgical resection of the invasive area. Subsequently, a combined treatment with topical imiquimod and cryosurgery was performed. The LM patient received immunocryosurgery directly. All of them were free of local and systemic disease at 48, 42 and 41 months after discontinuation of therapy. We consider that immunocryosurgery is an alternative option for LM or even for LMM (after removal of the invasive tissue with narrow margins) in poor surgical candidates, with good therapeutic, functional and cosmetic results.

Variation in the diagnosis and clinical management of lentigo maligna across Europe: a survey study among European Association of Dermatologists and Venereologists members.

BACKGROUND: Lentigo maligna (LM), a form of melanoma in situ, is treated to prevent progression to lentigo maligna melanoma (LMM). Surgical treatment is the gold standard. However, treatment guidelines are based on expert opinion, and comparative studies are lacking. OBJECTIVE: The objective of this study was to assess the diagnostic methods and clinical management of LM patients among European dermatologists and residents. METHODS: A survey consisting of 29 questions about diagnostic methods and treatment options used for LM patients was sent to 3308 members of the European Association of Dermatologists and Venereologists (EADV). RESULTS: Most questions were multiple choice, and multiple answers could be ticked per question. A total of N = 415 (12.5%) completed surveys were included in the analyses. A combination of clinical diagnosis (65.7%), dermatoscopy (83.4%) and histopathology (88.2%) is used by most respondents to diagnose LM. Tissue for histopathological evaluation was collected most often using a single punch biopsy in 61.0%. The most common treatment for LM patients <60 years of age is surgery (97.6%). For LM patients >70 years of age, 66.8% of the respondents preferred surgical treatment. Non-surgical options such as radiotherapy (17.0%), topical imiquimod (30.6%), watchful waiting (19.6%) or cryotherapy (20.4%) were used in this elderly group. Subanalysis showed that respondents who take into account patient preference used topical imiquimod, radiotherapy and watchful waiting more often. CONCLUSION: In conclusion, the results of this survey show that there is a variance in the diagnostic methods and treatment modalities used for LM across Europe. Surgery remains the most utilized option. However, non-surgical options, such as topical imiquimod and radiotherapy, are most often used for elderly patients. We recommend that future studies focus on patient preference and compare surgical to non-surgical therapy.

Diagnosis and management of lentigo maligna: an observational study comparing 2005 with 2014 data in one institution.

The incidence, clinical characteristics and management of lentigo maligna (LM) were assessed in a university hospital setting in 2005 and 2014. Multiple clinical variables were compared, and 28 and 43 cases, respectively were identified during the two time periods. The most common site of presentation was the cheek (50% vs. 44%), and an accurate clinical diagnosis of LM was made in 60% vs. 72%) of cases. Most of the patients received surgical treatment (75% in 2005 vs. 97% in 2014), with 47% and 33% of excisions, respectively, remaining involved at the peripheral surgical margin. During the 10-year follow-up for the 2005 cohort, 7 of the 28 patients had recurrence (3 of whom already had previously involved margins following surgery). This study shows that making an accurate clinical diagnosis of LM remains a significant challenge. Although surgery has become the preferred management option, achieving clear excision remains difficult, with involved margins increasing the risk of local recurrence and need for further intervention.

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.