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Background: Lentigo maligna (LM) based on biopsy material might be lentigo maligna melanoma (LMM) after excision. Objectives: Investigate whether clinical and dermoscopic mapping increases the detection rate of LMM when investigating staged excision specimens of biopsy proven LM. Methods: Patients with biopsy-proven LM planned for staged excision were included. Using clinical inspection and dermoscopy, spots suspicious for LMM were marked. After the excision, needles were placed at the marked spots. Histological examination using vertical sections was done at the needles followed by the standard amount of vertical sections. Results: In 28 of the 58 biopsy-proven LM, there was clinical suspicion of LMM, only 3 of these 28 cases were upgraded into LMM. These three cases showed LMM in other sections, whereas only 1 case showed LMM around the needle. Within the group without clinical suspicion of LMM, 2 cases were LMM. Biopsy-proven LM were in fact LMM in 8.6% of the cases and were found without the clinical guidance of the dermatologist. Conclusions: 8.6% of the biopsy-proven LM were LMM after complete histological examination. In this study, the dermatologist was not able to increase the detection rate of LMM by using clinical and dermoscopic mapping.

The incidence of non-melanoma skin cancer is on the rise and melanoma is among the most common cancers in the United States. Establishing an early diagnosis is essential for improving the prognosis of patients with skin cancer. High-resolution non-invasive imaging techniques may represent key tools for helping to identify and monitor early signs of skin cancer in seemingly healthy skin. Cumulative lifetime sun exposure leads to photoaging and photocarcinogenenis and the reaction of the skin to this solar-induced damage is balanced between the DNA repair and photoprotection defence mechanisms of melanocytes and keratinocytes. In the first part of this article we provide an overview of these defence mechanisms and of the photoaging process, and discuss how non-invasive imaging can be used to evaluate these changes. We then propose a model in which skin aging manifestations can be classified according to subject-specific sun-damage reaction profiles observed by reflectance confocal microscopy (RCM) and optical coherence tomography (OCT). These photoaging profiles include an atrophic phenotype characterized by actinic keratosis, and a hypertrophic phenotype characterized by hyperplastic pigmented skin. According to our model, these phenotypes may be predictive of predispositions to different types of skin cancer: squamous cell carcinoma for the atrophic phenotype and lentigo maligna and freckles for the hypertrophic phenotype. In addition to RCM and OCT, dermoscopy is another non-invasive technique that has improved the diagnosis of skin cancer. In the second part of this article, we describe how the YouDermoscopy™ application can improve skills and thus enhance the dermoscopic recognition of sun-induced skin tumours, and then show how this training tool enables its users to collaborate with dermatologists worldwide to obtain second opinions for the diagnosis of ambiguous lesions. Altogether, RCM, OCT and dermoscopy are valuable tools that can contribute significantly to improving the early diagnosis of precancerous and cancerous lesions.

Background Mohs micrographic surgery (MMS) has risen in popularity as a management option for treating lentigo maligna (LM) because of its ability to accurately detect subclinical spread while conserving tissue. The primary concern for opponents of MMS in melanoma remains the difficulty associated with interpretation of frozen sections compared with traditional paraffin sections; this has been made easier with the advent of immunostaining. Objective Our study aims to assess the concordance in clearance reporting of LM in immunostained frozen sections compared with permanent paraffin sections and hematoxylin and eosin staining. Methods We conducted a retrospective analysis of 38 LM cases treated by MMS between 2017 and 2020 in Melbourne, Australia. Immunostained frozen sections were assessed by a Mohs surgeon, whereas permanent paraffin sections were assessed by an external dermatopathologist. Results We report 86% agreement in reporting of LM in immunostained frozen sections compared with permanent paraffin sections. In 5/38 cases, permanent paraffin sections were reported as clear for LM, but the Mohs surgeon had detected positive margins, requiring further excision. Conclusion For LM treated with MMS, there is a high agreement of clearance reporting between immunostained stained frozen sections and permanent paraffin sections without immunostaining; however, immunostained frozen sections may be more sensitive.

Background Fluorescence-advanced videodermatoscopy (FAV) is a new non-invasive high-resolution skin imaging technique to assess pigmented lesions in conjunction with the clinical examination and dermatoscopy. Objectives This is the first prospective study to identify morphologic descriptors and standardized terminology to examine facial pigmented lesions using FAV. The objectives were to identify FAV indicators, which can assist physicians in diagnosing suspicious flat facial pigmented lesions. Methods Consecutive equivocal pigmented lesions were retrospective analysed. Histopathological examination was performed for all the lesions. The main cytomorphological and cytoarchitectural FAV features were described and correlated with histopathological characteristics. Results From January to October 2020, 21 consecutive clinically suspected pigmented lesions in 20 patients were analysed using dermatoscopy and FAV and then surgically excised. Histopathological examination identified lentigo maligna (LM), lentigo maligna melanoma (LMM), solar lentigo (SL), flat seborrheic keratosis (SK) and pigmented actinic keratosis (PAK). Thirteen malignant melanocytic lesions were removed (11 LM, 2 LMM), two were diagnosed as PAK, and the remaining six pigmented lesions were SL-SKs. With FAV, large ovoid pleomorphic and dendritic cells arranged in the intrafollicular disposition, are typical of most malignant melanocytic lesions (12/13, 92.3%). No benign lesions displayed these features. In dermatoscopy, this folliculotropism corresponded to the presence of an annular-granular pattern with slate grey dots that were aggregated asymmetrically around follicular openings. Conclusions FAV features can provide an improved diagnostic approach in the differential diagnosis of flat pigmented facial lesions.

BACKGROUND Imiquimod cream may be used as a non-surgical treatment for lentigo maligna or as adjuvant therapy following excision to decrease the risk of recurrence. OBJECTIVES To evaluate histologic and clinical factors associated with clinical clearance of lentigo maligna treated with imiquimod. METHODS We performed a retrospective review of all patients diagnosed with lentigo maligna and treated with imiquimod between 1997 and 2019 at our academic institution. RESULTS We observed clinical clearance in 93% (66/71) of participants who received adjuvant imiquimod following surgery and 79% (19/24) in the primary non-surgical treatment group over a median of 38 months of follow-up. In the adjuvant therapy group, positive surgical margins were associated with a decreased rate of clinical clearance when compared to cases with close (

Background There are no well-defined clinical factors to predict the risk of occult invasion in melanoma of the lentigo maligna type (LM) before complete histopathologic analysis. Objective To evaluate whether clinical size was a predictor of invasion in LM and subclinical extension. Methods Consecutive cases of LM were recorded in a prospectively maintained database from 2006 to 2019. Patient and tumor data were recorded during initial evaluation. The LM clinical area was calculated in square millimeters (length × width). All patients were treated with staged excision. Results We included 600 patients. The mean age was 65.9 years (standard deviation, 12.3; range, 27-95 years); 62.8% (n = 377) were men. The mean LM clinical area was 128.32 mm2 for in situ lesions versus 200.14 mm for invasive lesions (P = .1). Based on quantile regression, the median margin required for complete removal increased with LM clinical area. Limitations The study was performed in a tertiary cancer center with possible referral bias and more complex cases. Conclusions LM can present with variable clinical size, which may correlate with subclinical extension; however, the presence of invasion is not well estimated by LM clinical area.

Background The incidence of xeroderma pigmentosum (XP) in Yemen seems to be quite high but there are no previous reports. Objective To study the clinicoepidemiologic aspect of XP in Yemen. Methods All 40 patients (24 male and 16 female patients from 32 families) treated and followed between 1997 and 2014 were subjected to detailed analysis with the help of a standardized protocol. The diagnosis was based on clinical features and histopathologic data, when needed. The diagnosis of tumors was confirmed by histopathologic examination in all cases. Results The median age of onset of initial manifestations was 9.5 months, and that of malignant lesions was 7 years. Parents of the patients were not affected, but history of consanguinity was recorded in 38. Initial lesions, such as dryness of the skin and freckles on the face, were noticed in all patients. In addition, erythema of the face with photosensitivity was observed in 21 patients. Premalignant and malignant skin lesions observed later were actinic keratosis in 15 patients, lentigo maligna in one, squamous cell carcinoma (SCC) in 10, and basosquamous carcinoma in one. Eyes were affected with SCC in seven and malignant melanoma (MM) in two patients. SCC of the lip developed in two patients and that of the tongue in one patient. Judicious use of acitretin in 12 patients showed good result. Conclusion XP in Yemen is characterized by a relatively high incidence, high percentage of consanguinity in parents of the patients, early onset of initial manifestations, malignant tumors, and severe ocular and oral lesions. Acitretin showed good result.

Background A recently introduced dermoscopic method for the diagnosis of early lentigo maligna (LM) is based on the absence of prevalent patterns of pigmented actinic keratosis and solar lentigo/flat seborrheic keratosis. We term this the inverse approach. Objective To determine whether training on the inverse approach increases the diagnostic accuracy of readers compared to classic pattern analysis. Methods We used clinical and dermoscopic images of histopathologically diagnosed LMs, pigmented actinic keratoses, and solar lentigo/flat seborrheic keratoses. Participants in a dermoscopy masterclass classified the lesions at baseline and after training on pattern analysis and the inverse approach. We compared their diagnostic performance among the 3 timepoints and to that of a trained convolutional neural network. Results The mean sensitivity for LM without training was 51.5%; after training on pattern analysis, it increased to 56.7%; and after learning the inverse approach, it increased to 83.6%. The mean proportions of correct answers at the 3 timepoints were 62.1%, 65.5, and 78.5%. The percentages of readers outperforming the convolutional neural network were 6.4%, 15.4%, and 53.9%, respectively. Limitations The experimental setting and the inclusion of histopathologically diagnosed lesions only. Conclusions The inverse approach, added to the classic pattern analysis, significantly improves the sensitivity of human readers for early LM diagnosis.

Oral pigmentations are a heterogeneous group and can be the result of physiological activity of oral mucosal melanocytes, secondary to exogenous causes, associated with systemic or local diseases, or due to proliferative activity of melanocytes. Their diagnosis is critical because these lesions can be markers of internal diseases or, in the case of melanocytic proliferative processes, they may represent a malignant neoplasm. In the past decade, the use of reflectance confocal microscopy, a noninvasive imaging tool, has aided the analysis of such lesions, but the establishment of firm criteria in their evaluation is still lacking. This study evaluated a series of 19 cases of pigmented oral lesions and correlated the reflectance confocal microscopy findings with histopathological classical criteria. We found 13 cases of melanotic macule, 1 of them associated with Peutz-Jeghers syndrome and 2 with Laugier-Hunzinker syndrome; 1 melanocytic nevus; 2 lentigo maligna; 2 pigmented actinic cheilitis; and 1 case of postinflammatory pigmentation secondary to a lupus erythematosus oral discoid lesion. The main difference between benign and malignant lesions was the presence of atypical proliferation in lentigo maligna. Langerhans cells with thick dendritic processes, which may be present in other benign and inflammatory pigmentations is one of the main reasons for diagnostic pitfalls.

Background Treatment practices vary for lentigo maligna (LM). Staged excision with circumferential margin control (SECMC) has the potential to achieve low recurrence rates. Objectives To evaluate the clinical outcomes of SECMC using permanent, paraffin-embedded sections and delayed reconstruction. Methods We conducted a retrospective, uncontrolled, observational cohort study involving patients who underwent staged excision for LM of the head and neck at Women’s College Hospital in Toronto, Canada, from September 2010 to March 2013. Recurrence and infection rates were ascertained from patient charts and postal surveys. Results One hundred and two patients (45 female, 57 male) were included with a median follow-up time of 1410.5 (IQR 260-1756) days. The median age was 69 (IQR 61-79) years. Approximately one-fifth (21%, 21/102) of patients required greater than 0.5 cm margins to achieve histological clearance. One patient (1/102) upstaged to invasive melanoma based on the initial stage of excision. The infection rate was 6% (6/102) and the 5-year cumulative recurrence rate was 1.4% (95% CI 0.2-9.6%). Conclusion SECMC using permanent sections and delayed reconstruction appears to be a safe and effective treatment method for LM on the head and neck. Randomized trials are needed to help define the optimal treatment.

Aim: The evaluation of the trend in the occurrence of melanoma nodulare, melanoma superficiale, lentigo maligna and melanoma in situ in the period of 2002–2017 in East Bohemia region in the Czech Republic. We examine if the annual numbers of hours of sunshine could affect the number of patients with melanoma. Method: In the peridod of 2002–2017, altogether 2230 patients with new diagnosis of melanoma were examined. We studied 1) If there is some trend in the occurrence of lentigo maligna and melanoma in situ, melanoma superficiale, and melanoma nodulare and if there is a difference in the age of patients with this diagnosis (adjusted calculation of specific kind of melanomas and adjusted calculation of age). 2) If the annual numbers of hours of sunshine affect the trend in the occurrence of melanoma and if the annual numbers of hours of sunshine affect the body site of melanoma. Results and conclusion: Our study confirmed that the number of patients with lentigo maligna and melanoma in situ had increased in East Bohemia region in the period of 2002–2017. The number of melanomas of nodular and superficial type does not increase. The total number of melanomas in this period does not increase either. No difference of the age of patients with melanoma nodulare, superficiale, lentigo maligna and melanoma in situ was confirmed. We confirmed no relation of the annual numbers of hours of sunshine to the number of melanoma and to the body site of melanoma.

Skin cancer is a broad term used to describe a number of different malignant indications of the skin. Skin cancers mostly comprise of the keratinocyte cancers [Basal Cell Carcinoma (BCC) and cutaneous Squamous Cell Carcinoma (SCC)], and melanoma. Surgical excision of these malignancies has been the preferred treatment of patients for decades. However, the decision to perform surgery can be affected by various considerations, including co-morbidities of the patient, the anatomical site of the lesion and potential intolerance for repeated excisions. Topical treatment of skin cancer may therefore be more appropriate in certain instances. Topical treatment potentially allows for higher drug levels at the tumor site, and may result in less overall toxicity than systemic agents. This review will specifically address the current agents used in topical treatment of skin cancers, and introduce emerging treatments from the natural product field that may also find utility in these indications.

Lentigo maligna (LM) can be difficult to diagnose and recurrence is not uncommon. In vivo reflectance confocal microscopy (RCM) improves diagnostic accuracy of LM. LM can be difficult to discern from coexistent metal-induced cutaneous hyperpigmentation (MICH). We are the first to describe three cases of LM associated with gold, silver, and metal oxide (from tattoos) and the RCM findings, respectively. The images obtained via RCM were analyzed by two RCM experts, and histopathology reviewed by a dermatopathologist. MICH under RCM appeared as intensely hyperreflective dots (when found freely) or clusters of variable sizes (when engulfed by macrophages) limited to the dermis. Dermal dendritic cells and melanophages were also found in association but distinct from the confluence of dendritic cells at the dermoepidermal junction observed in LM. We showed longitudinal changes within the dermis in MICH, not previously reported, where these hyperreflective dots congregate into clusters. RCM was able to distinguish the features of LM from MICH, delineate treatment margins, and monitor for recurrence.

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Background CONCORD-3 highlighted wide disparities in population-based 5-year net survival for cutaneous melanoma during 2000–2014. Clinical evidence suggests marked international differences in the proportion of lethal acral and nodular subtypes of cutaneous melanoma. Objectives We aimed to assess whether the differences in morphology may explain global variation in survival. Methods Patients with melanoma were grouped into the following seven morphological categories: malignant melanoma, not otherwise specified (International Classification of Diseases for Oncology, third revision morphology code 8720), superficial spreading melanoma (8743), lentigo maligna melanoma (8742), nodular melanoma (8721), acral lentiginous melanoma (8744), desmoplastic melanoma (8745) and other morphologies (8722–8723, 8726–8727, 8730, 8740–8741, 8746, 8761, 8770–8774, 8780). We estimated net survival using the nonparametric Pohar Perme estimator, correcting for background mortality by single year of age, sex and calendar year in each country or region. All-ages survival estimates were standardized using the International Cancer Survival Standard weights. We fitted a flexible parametric model to estimate the effect of morphology on the hazard of death. Results Worldwide, the proportion of nodular melanoma ranged between 7% and 13%. Acral lentiginous melanoma accounted for less than 2% of all registrations but was more common in Asia (6%) and Central and South America (7%). Overall, 36% of tumours were classified as superficial spreading melanoma. During 2010–2014, age-standardized 5-year net survival for superficial spreading melanoma was 95% or higher in Oceania, North America and most European countries, but was only 71% in Taiwan. Survival for acral lentiginous melanoma ranged between 66% and 95%. Nodular melanoma had the poorest prognosis in all countries. The multivariable analysis of data from registries with complete information on stage and morphology found that sex, age and stage at diagnosis only partially explain the higher risk of death for nodular and acral lentiginous subtypes. Conclusions This study provides the broadest picture of distribution and population-based survival trends for the main morphological subtypes of cutaneous melanoma in 59 countries. The poorer prognosis for nodular and acral lentiginous melanomas, more frequent in Asia and Latin America, suggests the need for health policies aimed at specific populations to improve awareness, early diagnosis and access to treatment. What is already known about this topic? The histopathological features of cutaneous melanoma vary markedly worldwide. The proportion of melanomas with the more aggressive acral lentiginous or nodular histological subtypes is higher in populations with predominantly dark skin than in populations with predominantly fair skin. What does this study add? We aimed to assess the extent to which these differences in morphology may explain international variation in survival when all histological subtypes are combined. This study provides, for the first time, international comparisons of population-based survival at 5 years for the main histological subtypes of melanoma for over 1.5 million adults diagnosed during 2000–2014. This study highlights the less favourable distribution of histological subtypes in Asia and Central and South America, and the poorer prognosis for nodular and acral lentiginous melanomas. We found that later stage at diagnosis does not fully explain the higher excess risk of death for nodular and acral lentiginous melanoma compared with superficial spreading melanoma.

Mohs micrographic surgery (MMS) is a precise and effective method commonly used to treat high-risk basal cell carcinoma and squamous cell carcinoma on the head and neck. Although the majority of evidence for MMS relates to keratinocyte cancers, there is published evidence for other types of skin cancer. This review aims to discuss the evidence for using MMS to treat six different types of skin cancer [malignant melanoma, lentigo maligna, dermatofibrosarcoma protuberans, atypical fibroxanthoma (AFX), microcystic adnexal carcinoma and pleomorphic dermal sarcoma (PDS)] particularly in the context of survival rates and cancer recurrence. These cancers were chosen because there was sufficient literature for inclusion and because MMS is most useful when cancers are contiguous, rather than for cancers with marked metastatic potential such as angiosarcoma or Merkel cell carcinoma. We searched MEDLINE, PubMed and Embase using the keywords: 'melanoma', 'mohs micrographic surgery', 'lentigo maligna', 'dermatofibrosarcoma protuberans', 'atypical fibroxanthoma', 'microcystic adnexal carcinoma' and 'pleomorphic dermal sarcoma' along with their appropriate synonyms, to identify the relevant English-language articles from 2000 onwards, given that literature for MMS on nonkeratinocyte cancers is sparse prior to this year. AMSTAR (A MeaSurement Tool to Assess systematic Review) was used to assess the validity of systematic reviews. Further high-quality, multicentre randomized trials are necessary to establish the indications and efficacy of MMS for rarer cancers, particularly for AFX and PDS, for which only limited studies were identified.

Lentigo maligna (LM) can develop into lentigo maligna melanoma (LMM) with risk of metastatic dissemination. LMM may be underestimated on the basis of the initial biopsy. The invasion may affect both the therapeutic options and the prognosis.To identify the clinical features associated with invasive forms of LM and factors associated with its recurrence.A retrospective, single-centre study of consecutive LM and LMM histologically confirmed and treated by surgery between 2009 and 2014.In total, 175 patients with LM/LMM were surgically treated in our establishment. In men, lesions were more likely to be in the "peripheral zone" (41.8%), while in women they were seen more often in the "central zone" (P=0.001). In multivariate analysis, only the peripheral zone was found to be associated with a risk of invasion (P=0.008). The rate of recurrence was 9% and lesions were more likely to be primary LMM (P=0.0006) excised with clear margins.The treatment of choice in LM with non-clear margins must be re-excision, especially for lesions situated in the peripheral zone. Close follow-up is recommended due to risk of recurrence, even in the case of clear margins.

Topical imiquimod 5% cream has been investigated as off-label primary or adjuvant treatment for melanoma in situ, lentigo maligna type (LM). Herein, we present the largest known case series of lentigo maligna treated with topical imiquimod, with up to 17 years of follow-up, and include a recurrence-free survival analysis. In this case series, 103 lesions were retrospectively evaluated for treatment response and recurrence following a course of topical imiquimod with or without tazarotene gel 0.1% pretreatment between January 1, 2002 and March 31, 2019, and prospectively followed through November 15, 2019. Over median follow-up of 5.1 years (mean = 6.2 years, S = 5.2 years, range, 0.08ndash;17.1 years), including 29.1% LM withgt;10 years follow-up, we observed a response rate of 97.1% (100/103), with 8 local recurrences (8/100, 8.0%) developing at mean 2.9 years (SD: 2.7 years). Local recurrence was significantly associated with a history of failed excision (P= 0.001),lt;60 applications of imiquimod (P= 0.04) and partial clinical clearance (P= 0.0003). Recurrence-free survival analysis demonstrated significant risk-stratification for low and high-risk groups (P= 0.0001). Long term risk for recurrence showed significant differences among low- and high-risk cases, with low-risk cases demonstrating favorable long-term outcomes, comparable to conventional and staged surgery. Our observed low recurrence in a large case series with long-term follow-up suggests the efficacy of topical 5% imiquimod for LM and emphasizes the need for randomized control trials comparing imiquimod with, or as an adjunct to, surgical treatment. J Drugs Dermatol. 2021;20(3):346-348. doi:10.36849/JDD.5660.

Despite the rapid recent advances in molecular analysis of tumors, which allow large-scale and high-resolution genomics, the "gold standard" for melanoma diagnosis continues to be histopathology, in conjunction with clinical characteristics and sometimes with important support of immunohistochemistry. Observations, where postulated that cutaneous melanomas may arise through two distinct pathways, discoveries such as that BRAFV600E mutations were mostly common in melanomas on sun-exposed skin with little solar elastosis and seminal works for melanoma progression and evolution set the groundwork for the new WHO Classification of Melanoma: a classification of melanoma that not only encompasses histologic but also clinical, epidemiologic, and genetic characteristics. The melanomas were divided into those etiologically related to sun exposure and those that are not, based on their mutational signatures, anatomic site, and epidemiology. On the basis of degree of associated solar elastosis melanomas on the sun exposed skin were further divided by the histopathologic degree of cumulative solar damage (CSD) of the surrounding skin, into low and high CSD. On the low-CSD group of melanomas are included superficial spreading melanomas, while the high-CSD melanomas encompasses lentigo maligna and desmoplastic melanomas. The "non-CSD" classification includes acral melanomas, some melanomas in congenital nevi, melanomas in blue nevi, Spitz melanomas, mucosal melanomas, and uveal melanomas. Nodular and nevoid melanoma may occur in any pathway. A group of intermediate tumors termed melanocytoma is proposed for tumors that in addition to mutations that activate the MAPK pathway, harbor multiple driver mutations, and they are either low-grade or high-grade, to indicate that they may carry a higher risk of malignant transformation. In this review a summary of the most recent WHO classification of melanoma is provided. A short analysis of essential histopathologic prognostic parameters is also provided. The new classification of melanoma discriminates distinct types of melanoma based on their clinicopathologic, and genomic characteristics. Undoubtedly, melanoma research will continue to evolve as new clinical, pathological, molecular data accumulates. The challenge of the forthcoming years is to better characterize the intermediate category of melanocytic lesions.

Lentigo maligna/lentigo maligna melanoma (LM/LMM) affects chronically sun-damaged skin of the head and neck with a slow radial growth phase. It is characterised by predominantly lentiginous proliferation of small, but atypical melanocytes with occasional upward scatter in an atrophic epidermis. It is not uncommon for pathologists to receive partial or scouting biopsies to assess for LM. This makes the interpretation of symmetry and circumscription of the lesions challenging. Therefore, both cytologic and architectural criteria should be taken into consideration to render an accurate diagnosis of melanoma. Moreover, pathologists should be vigilant to avoid missing invasion, as this can change the treatment plan and prognosis. Herein, we aim to discuss important pitfalls in the diagnosis of LMM and its invasive component. Some of these caveats are differentiating between true invasion versus adnexal involvement by the in situ component or an incidental intradermal nevus, detection of microinvasion and multifocal invasion, and recognition of desmoplastic/spindle cell melanoma component.

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.

In vivo reflectance confocal microscopy (RCM) is a noninvasive high-resolution skin imaging tool that has become an important adjunct to clinical exam, dermoscopy and histopathology assessment, in the diagnosis and management of pigmented macules of the face. The diagnosis of early stage lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging and RCM improves the diagnostic accuracy in the differential diagnosis of LM with other macules of the face such as solar lentigo (SL), pigmented actinic keratosis (PAK), seborrheic keratosis (SK) and lichen planus-like keratosis (LPLK). Here we review the state-of-the-art of RCM morphologic descriptors, standardized terminology, and diagnostic algorithms for the RCM assessment of pigmented macules of the face including melanocytic, and nonmelanocytic lesions. Clinical applications of RCM are broad and include diagnosis, assessment of large lesions on cosmetically sensitive areas, directing areas to biopsy, delineating margins prior to surgery, detecting response to treatment and assessing recurrence. The present review is intended to summarize the application of RCM for the correct diagnosis of challenging pigmented facial macules and to evaluate its application in LM margin mapping during the pre surgical phase.

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.

Background Lentigo maligna (LM) may be disfiguring and can progress to LM melanoma. Surgical excision remains the mainstay of treatment, but may result in disfigurement when used for large facial lesions. Topical imiquimod is a nonsurgical alternative although data on its long-term efficacy remain limited. Aim To assess long-term outcomes of LM treated with imiquimod cream. Methods We collected data retrospectively for 33 patients treated with imiquimod cream for biopsy-proven LM from 2001 to 2016. Patients initially applied imiquimod once daily, 5 days/week for 6 weeks, aiming to produce a brisk local inflammatory response. If there was no response, the dose was increased to twice daily 7 days/week for 6 weeks and if again there was no response, to twice daily for 10 weeks. Results An inflammatory response developed in 29 (88%) of the 33 patients, and of these, 4 patients stopped treatment earlier than planned because they could not tolerate the inflammatory reaction, while 3 patients reported systemic side effects. There was lesion clearance in 21 (72%) of the 29 patients, and they remained clear after a mean follow-up of 4.1 years. Eight failed to clear; in five the lesion was excised, while the remaining three were managed expectantly. Conclusions Our results support the use of imiquimod as an alternative to surgery for the treatment of LM in selected cases. With adequate patient preparation, imiquimod is generally tolerated and can achieve excellent cosmetic results. A clinical response is more likely if there is a brisk inflammatory response, and LM will not resolve if there is no inflammatory response.

Background: More epidemiological data about lentigo maligna melanoma (LMM) are required to define follow-up guidelines. The study focused on recurrence, progression, and overall survival of LMM managed with primary wide local excision. Methods: In a 23-year retrospective study (1994 to 2016), a cohort of patients with LMM was evaluated by collecting data about the tumor location, the Breslow depth, the presence of ulceration, and patients’ age and sex. Local recurrences, locoregional and distant metastases, and disease-free and overall survival were additionally assessed. Results: Overall, 150 cases (84 male, 66 female, mean age 71.3 ± 11.3 years) of single, localized, primary LMM with a mean follow-up of 6.6 ± 4.4 years were included. A total of 33 (22.2%) patients underwent sentinel lymph node biopsy (SLNB) during surgical excision. However, positive SLNB was detected in none of them. The multivariable Cox analysis indicated that age of diagnosis and male gender significantly influenced the overall survival, while a shorter disease-free survival could be correlated with a greater Breslow thickness. The metastatic potential turned out to be low, entailing 7 deaths in the context of the LMM. Conclusion: Male gender, age over 70 at diagnosis, and a Breslow thickness greater than 0.75 mm were associated with a statistically significant decrease in overall disease-free survival in the current study. The results of the study confirm the favorable outcome of LMM. However, diagnosed patients should undertake regular follow-ups. The intensity of follow-up in these patients can be individualized based on the probability of recurrence/metastasis and overall survival. Furthermore, the study showed that SLNB might not be a necessary staging procedure in patients with LMM.

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.

Background Recent epidemiological studies suggest that past data where superficial spreading melanoma was by far the most common subtype of melanoma may not reflect current patterns of sun exposure or other risk factors more involved in other subtypes of melanoma as lentigo maligna (LM) or lentigo maligna melanoma (LMM). Methods In order to measure the current situation in our country, all cases of LM and LMM diagnosed in 23 hospitals in Catalonia, from 2000 to 2007, were recorded. Results Although for the global period LM/LMM represented only 8.4% of cases, an increasing trend in this percentage was observed throughout the study period (from 6.9% [27 cases] in 2000 to 13.1% [94 cases] in 2007). Also, an increasing incidence of LM/LMM was observed, especially in chronically sun-exposed areas (85.5% involving the head and neck region). During the 8 years of the registry, the mean Breslow thickness of LMM remained stable. However, the increase in the number of LM (in situ) cases was significantly higher than the increase of the invasive ones. Conclusions An important observation from this data is that aging of population and current sun exposure patterns could keep increasing the incidence of LM/LMM, which may become an important public healthcare problem, over the other histological subtypes. In order to establish primary or secondary preventive measures to the LM/LMM risk-population, it is imperative to highlight the importance of chronic sun damage as a melanoma risk factor, and not only sunburn, most commonly addressed in melanoma prevention campaigns.

Background Our understanding of the relationship between ultraviolet (UV) radiation exposure and lentigo maligna (LM) has been largely derived from epidemiologic/clinical studies based on invasive melanoma. Recent studies have shown gender differences in melanocytic tumours incidence. Objective To examine the association of UV light with LM by gender remains unclear. Methods Two prospective cohort study [Nurses' Health Study (1980-2012)] and [Health Professionals Follow-up Study (1986-2010)] were analysed. All participants with LM or MIS, non-LM type were included in analysis. UV index at birth, age 15, and age 30 were calculated by gender. Lifetime UV flux was calculated. Hazard ratios (HRs) were calculated. Results A total of 110 485 women from NHS and 41 015 men from HPFS were examined. A total of 281 LM and 776 melanoma in situ (MIS), non-LM cases were reported. Risk of LM increased with increasing UV flux exposure in multivariate-adjusted models for men (P for trend = 0.04), but not for women (P for trend = 0.91). Conclusions UV flux may be associated with LM in men but not in women.

Because of the tendency of lentigo maligna (LM) for subclinical extension, staged excisions with margin control achieve lower recurrence rates than conventional wide local excision (0-9.5% vs 8-20%). However, these surgical techniques are limited by their requirement in time, costs and training.

Lentigo maligna (LM) is usually diagnosed in sun-damaged skin of elderly patients and a correct excision of the lesion determines a complete healing from the disease. LM is very rare in young patients and, for this reason, it can be commonly misdiagnosed. We describe the case of a locally recurrent LM in a 19-year-old male patient, which initially arose at the age of 17 years. In order to avoid diagnostic pitfalls, clinicians have to put more emphasis on diseases which previously were prerogative only of elderly patients and that now could begin to engage a younger age, according to climate and behavior changes.

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Treatment of lentigo maligna (LM) is challenging because of the potential functional and esthetic surgical sequelae. Imiquimod has been proposed as a treatment for LM. Reflectance confocal microscopy (RCM) is a noninvasive method for the diagnosis of LM and margin assessment.To compare the overall LM score (LMS) assessed by RCM before and 1 month after the start of imiquimod treatment compared to placebo and to define the immunohistochemical (IHC) profile of responders to imiquimod.A controlled randomized study was conducted. Forty patients underwent RCM examination with calculation of the LMS at baseline and after 1 month of treatment. An IHC analysis of excised tissues was performed.The 1-month LMS was significantly lower in patients treated with imiquimod compared to those treated with placebo (P .001). The criteria in the imiquimod-treated patients that demonstrated significant decrease were nonedged papillae; large, round pagetoid cells; atypical cells at the dermoepidermal junction; and follicular location of atypical cells. IHC analysis showed a higher level of interferon gamma in the resected specimens of patients responding to imiquimod (P = .04).Sample size was small.Assessing the LMS by RCM was useful to monitor LM response to imiquimod accurately.

Introduction Many concerns were raised about the sensitivity and specificity outcome of reflectance confocal microscopy compared to dermoscopy for the diagnosis of lentigo maligna. However, the reported relationships between their sensitivity and specificity were variable. Our meta-analysis was performed to clarify this relationship. Methods A systematic literature search up to July 2020 was performed and 6 included studies had 479 subjects at the baseline with 294 undergoing lentigo maligna diagnoses. They were reporting relationships between sensitivity and specificity outcome of reflectance confocal microscopy compared to dermoscopy for the diagnosis of lentigo maligna. Mean difference (MD) with 95% confidence intervals (CIs) was calculated to evaluate the prognostic role of the sensitivity and specificity of reflectance confocal microscopy compared to dermoscopy for the diagnosis of lentigo maligna using the continuous method with a random or fixed-effect model. Results Reflectance confocal microscopy was significantly related to higher specificity (MD, 19.10; 95% CI, 0.93-37.28, p=0.04) compared to dermoscopy in lentigo maligna diagnosis. However, reflectance confocal microscopy was only relatively but not significantly related to higher sensitivity (MD, 14.56; 95% CI, 0.29-28.83, p=0.05) compared to dermoscopy in lentigo maligna diagnosis. Conclusions Based on this meta-analysis, the reflectance confocal microscopy compared to dermoscopy in lentigo maligna diagnosis had a significantly higher specificity and relatively higher sensitivity. This relationship forces us to recommend reflectance confocal microscopy in lentigo maligna diagnosis for better outcomes and to avoid any possible false-negative results. Further studies are required.