Search

Standard treatment for lentigo maligna (LM) is surgical excision, yet insights into the frequency of and risk factors for incomplete excisions remain limited. The primary objectives were to assess the incomplete excision rate (IER) in primary LM and to explore potential risk factors for incomplete excisions. A retrospective analysis was conducted encompassing consecutive histopathologically confirmed LMs from 2014-2020. Descriptive statistics were used for LM characteristics and IER, while uni- and multivariate analyses were used for calculating risk factors. The study included 395 LMs with an IER of 16.7% (n = 66). Risk factors for higher incomplete excision rates included: head and neck lesions (p = 0.0014), clinical excision margins < 5 mm (p = 0.040), and utilization of preoperative partial biopsies (p = 0.023). Plastic surgeons had higher IERs than dermatologists (p = 0.036). Lesion diameter (p = 0.20) and surgeon experience (p = 0.20) showed no associations with incomplete excisions, yet LMs with a diameter ≥ 20 mm exhibited higher incomplete excision rates (23.2%) compared witho those < 10 mm (12.9%). LMs should be excised with at least 5-mm clinical margins, especially in the head and neck area. LMs ≥ 20 mm may be more surgically challenging. High-er incomplete excision rates associated with the use of preoperative biopsies and/or plastic surgeons may reflect challenging anatomical locations, larger lesion diameter, and/or ill-defined borders.

External ear lentigo maligna/lentigo melanoma (LM/LMM) represents approximately 1%-4% of all primary cutaneous melanomas. Over the past 20 years, dermoscopy has proven highly effective in early detection of LM/LMM, with recent studies identifying perifollicular linear projections (PLP) as a specific diagnostic criterion for early LM. However, in clinical practice, LM and LMM turn out to be very difficult to distinguish based on dermoscopic findings. Therefore, our retrospective monocentric study aimed to investigate dermoscopic characteristics, as well as the epidemiological and clinical data of 19 patients diagnosed with the external ear (EE) LM/LMM at the Oncologic Dermatology Unit in Bologna. Dermoscopic images were obtained using the FotoFinder Medicam 800HD, and specific criteria validated by the International Dermoscopy Society (IDS) for atypical pigmented facial lesions were assessed. Fisher's exact test was primarily used for statistical comparisons. As results, most of the patients were male (74%) with an average age (± SD) at diagnosis of 69.8 (± 15.1) years old. LMM appeared more commonly observed in elderly patients as compared to LM (mean 71.6 vs. 66.7, p = 0.514), presenting as pigmented macule (89.5%) of the ear lobule (23.9%). A statistically significant difference (p = 0.01) of tumour' diameter between LMM and LM was reported with the first resulting more than twice the size of the latter. Concerning dermoscopic findings, asymmetric pigmented follicles, obliteration of the follicular openings and grey circles were more frequently observed in LMM compared to LM (63.2% vs. 31.6%; 63.2% vs. 26.3%; 47.4% vs. 15.8%, respectively)., (© 2024 The Author(s). Experimental Dermatology published by John Wiley & Sons Ltd.)

Competing Interests: Conflicts of interest None to declare.

Lentigo maligna (LM) is a subtype of lentiginous melanoma confined to the epidermis, which is associated with chronic sun exposure. Its clinical, dermatoscopic, and histopathological diagnosis can be challenging, particularly in the early and advanced stages, requiring appropriate clinicopathological correlation. This article reviews the clinical presentation, diagnosis through noninvasive methods (dermoscopy and confocal microscopy), and provides insights for diagnosis of extrafacial LM through the presentation of four representative clinical cases from different phases of a theoretical-practical progression model. Recognizing these lesions is crucial, as once they invade the dermis, they can behave like any other type of melanoma., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Surgical excision with clear histopathological margins is the preferred treatment to prevent progression of lentigo maligna (LM) to invasive melanoma. However, the assessment of resection margins on sun-damaged skin is challenging. We developed a deep learning model for detection of melanocytes in resection margins of LM., Methods: In total, 353 whole slide images (WSIs) were included. 295 WSIs were used for training and 58 for validation and testing. The algorithm was trained with 3,973 manual pixel-wise annotations. The AI analyses were compared to those of three blinded dermatopathologists and two pathology residents, who performed their evaluations without AI and AI-assisted. Immunohistochemistry (SOX10) served as the reference standard. We used a dichotomized cutoff for low and high risk of recurrence (≤ 25 melanocytes in an area of 0.5 mm for low risk and > 25 for high risk)., Results: The AI model achieved an area under the receiver operating characteristic curve (AUC) of 0.84 in discriminating margins with low and high recurrence risk. In comparison, the AUC for dermatopathologists ranged from 0.72 to 0.90 and for the residents in pathology, 0.68 to 0.80. Additionally, with aid of the AI model the performance of two pathologists significantly improved., Conclusions: The deep learning showed notable accuracy in detecting resection margins of LM with a high versus low risk of recurrence. Furthermore, the use of AI improved the performance of 2/5 pathologists. This automated tool could aid pathologists in the assessment or pre-screening of LM margins., (© 2024. The Author(s).)

Background: Lentigo maligna (LM) exhibits a particular epidemiological profile compared to other histopathologic subtypes of melanoma, with a propensity for the head and neck area and a higher mean age at diagnosis. Few small-scale studies have exclusively evaluated the risk factors for the development of LM., Objective: This study aims to compare LM to other histological subtypes of melanoma for the prevalence of known melanoma risk factors, including pigmentary characteristics, history of occupational sun exposure, nevus count, and familial melanoma history., Patients and Methods: We conducted a case-control study of 152 patients with LM and 784 patients with other melanoma subtypes (OM). The Mann-Whitney t-test and Pearson chi-squared test were used to detect differences between the two groups in continuous and categorical variables, respectively. Univariate and multivariate logistic regression models were then constructed to identify risk factors for developing LM compared to other melanoma subtypes., Results: In multivariate logistic regression analysis, LM was positively associated with a lentigines count >50 and occupational sun exposure compared to OM (OR 2.10, 95% CI 1.35-3.29 and OR 2.18, 95% CI 1.33-3.57, respectively). In contrast, patients with an increased nevus count and fair or medium skin color were less likely to develop LM than OM (OR 0.93, P < 0.001, 95% CI 0.91-0.94, and OR 0.28, P < 0.001, 95% CI 0.17-0.46, respectively). In univariate analysis, LM exhibited a weaker association with all pigmentary traits than OM. No significant associations were found for atypical nevi count and family history., Conclusion: We found significant differences in the prevalence of known melanoma risk factors between LM and other melanoma subtypes, which supports the hypothesis of a distinct pathogenetic pathway of LM., (© 2024 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Purpose of Review: This review summarizes the current role of radiotherapy for the treatment of cutaneous melanoma in the definitive, adjuvant, and palliative settings, and combinations with immunotherapy and targeted therapies., Recent Findings: Definitive radiotherapy may be considered for lentigo maligna if surgery would be disfiguring. High risk, resected melanoma may be treated with adjuvant radiotherapy, but the role is poorly defined since the advent of effective systemic therapies. For patients with metastatic disease, immunotherapy and targeted therapies can be delivered safely in tandem with radiotherapy to improve outcomes. Radiotherapy and modern systemic therapies act in concert to improve outcomes, especially in the metastatic setting. Further prospective data is needed to guide the use of definitive radiotherapy for lentigo maligna and adjuvant radiotherapy for high-risk melanoma in the immunotherapy era. Current evidence does not support an abscopal response or at least identify the conditions necessary to reliably produce one with combinations of radiation and immunotherapy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Paraffin-embedded margin-controlled Mohs micrographic surgery (PMMS) includes various procedures such as slow Mohs or deferred Mohs technique, the Muffin and Tübingen techniques, and staged margin excision, or the spaghetti technique. PMMS is a variation of conventional Mohs micrographic surgery (MMS) that allows histopathological examination with delayed margin control. PMMS requires minimum training and may be adopted by any hospital. The setback is that PMMS can require procedures across multiple days. PMMS lowers the rate of recurrence of basal cell carcinoma vs wide local excision in high-risk basal cell carcinoma, and improves the rates of recurrence and survival in lentigo maligna. PMMS can be very useful in high-risk squamous cell carcinoma treatment. Finally, it is a promising technique to treat infrequent skin neoplasms, such as dermatofibrosarcoma protuberans, or extramammary Paget's disease, among others. In this article, we present a literature narrative review on PMMS, describing techniques and indications, and highlighting long-term outcomes., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Abstract: Histologic differentiation between melanoma in situ in chronically sun-damaged skin (CSDS) [lentigo maligna (LM)] and CSDS without malignancy is difficult because signs of melanocyte activation and proliferation are found in both. A potentially reliable and quantifiable criterion is melanocyte density (MD). Here, we evaluated whether and to what extent MD allows the distinction between LM and CSDS, which is particularly relevant for the evaluation of borderline cases and surgical margins.Articles assessing MD in LM and/or CSDS were evaluated in a systematic review. The results were categorized and compared according to staining. Cutoff values were included whenever stated.Twenty articles matched the selection criteria. Six hundred forty-four samples of CSDS and 227 samples of LM were considered. In each individual study, mean MD scores were higher for LM than for CSDS. However, looking at the overall study situation, it becomes clear that the data are very heterogeneous and show overlaps. Therefore, no reliable orientation value can be derived. Only 1 article defined a cutoff value.The data of MD in LM in contrast to CSDS were sparse, and a defined cutoff value was only mentioned in 1 article for microphthalmia-associated transcription factor, which cannot yet be generalized. Especially regarding the importance for the definition of surgical resection margins, this unsatisfactory data set highlights the need for further studies. More precise diagnostic criteria could spare some patients extensive and possibly disfiguring surgery., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Information on lentigo maligna (LM) and lentigo maligna melanoma (LMM) in the 21st century is scarce. We aimed to elucidate the incidence of LM and LMM using the Surveillance, Epidemiology, and End Results (SEER) 17 Registries., Methods: The data of patients diagnosed between 2000 and 2019 were extracted from the SEER database. The percentage of LM/LMM cases among all melanoma patients, age-standardized incidence rates, estimated annual percentage changes, and the cumulative incidence of LMM after LM were calculated., Results: The SEER data yielded 95,175 patients with LM/LMM between 2000 and 2019. Cases of LM/LMM accounted for 15.7% of all melanomas. The age-standardized incidence per 100,000 person-years for LM increased from 4.16 to 5.61 and for LMM from 1.33 to 2.35 between 2000 and 2019. The annual increase in incidence of LM was 2.42%, and that of LMM was 3.32%. The cumulative incidence of LMM after a primary LM after 10-year follow-up was 0.94%., Conclusions: This study provides the first comprehensive analysis of the epidemiological status of LM/LMM in the United States in the 21st century using the population-based SEER data., (© 2024 the International Society of Dermatology.)

The dermoscopic diagnosis of amelanotic/hypomelanotic lentigo maligna/lentigo maligna melanoma (AHLM/LMM) may be very difficult in its early stages because of lack of pigment. Reflectance confocal microscopy (RCM) is an imaging technique that is especially helpful for the diagnosis of lentigo maligna. To determine the diagnostic performances of dermoscopy and RCM in the diagnosis of AHLM/LMMs we evaluated dermoscopic and RCM images of consecutive cases of histopathologically confirmed AHLM/LMMs, amelanotic/hypomelanotic basal cell carcinoma and squamous cell carcinoma (AHBCCs/AHSCCs), amelanotic/hypomelanotic benign lesions (AHBLs), and actinic keratoses (AKs) from five participating centers. Sensitivity, specificity, accuracy, predictive values, and level of diagnosis confidence were calculated for both diagnostic procedures. Both dermoscopy and RCM showed diagnostic performance >97% in the diagnosis of AHLM/LMMs versus AHBCC/AHSCCs and their combination slightly improved diagnostic performance, with accuracy increasing from 98.0% to 99.1%. Similarly, RCM in combination with dermoscopy showed a tiny increase in the diagnostic performance in the diagnosis of AHLM/LMMs versus AHBLs (accuracy increased from 87.2% to 88.8%) and versus AKs (accuracy increased from 91.4% to 93.4%). Although the increase in diagnostic performance due to RCM was modest, the combination of dermoscopy and RCM greatly increased the level of confidence; high confidence in the diagnosis of AHLM/LMMs versus AHBLs increased from 36.2% with dermoscopy alone to 76.6% with dermoscopy plus RMC. Based on our results, dermoscopy and RCM should be complementary to improve not only diagnostic accuracy but also the level of diagnostic certainty in the diagnosis of AHLM/LMMs., (© 2024 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Introduction: Lentigo maligna (LM) and lentigo maligna melanoma (LMM) predominantly affect the head and neck areas in elderly patients, presenting as challenging ill-defined pigmented lesions with indistinct borders. Surgical margin determination for complete removal remains intricate due to these characteristics. Morphological examination of surgical margins is the key form of determining successful treatment in LM/LMM and underpin the greater margin control provided through the Slow Mohs micrographic surgery (SMMS) approach. Recent assessments have explored the use of immunohistochemistry (IHC) markers, such as Preferentially Expressed Antigen in Melanoma (PRAME), to aid in LM/LMM and margin evaluation, leveraging the selectivity of PRAME labelling in malignant melanocytic neoplasms. Methods: A Novel double-labelling (DL) method incorporating both PRAME and MelanA IHC was employed to further maximise the clinical applicability of PRAME in the assessment of LM/LMM in SMMS biopsies. The evaluation involved 51 samples, comparing the results of the novel DL with respective single-labelling (SL) IHC slides. Results: The findings demonstrated a significant agreement of 96.1% between the DL method and SL slides across the tested samples. The benchmark PRAME SL exhibited a sensitivity of 91.3% in the SMMS specimens and 67.9% in histologically confirmed positive margins. Discussion: This study highlights the utility of PRAME IHC and by extension PRAME DL as an adjunctive tool in the assessment of melanocytic tumours within staged excision margins in SMMS samples., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Salih, Ismail and Orchard.)

Background and Objectives: Sentinel lymph node biopsy (SLNB) is an area of debate in the management of lentigo maligna melanoma (LMM). The utility of SLNB and its prognostic value in LMM have not yet been studied with large databases., Methods: We performed a retrospective review of the National Cancer Database (2012-2020) and the Surveillance, Epidemiology, and End Results (2010-2019) database for patients with cutaneous nonmetastatic LMM with Breslow thickness >1.0 mm. Multivariable logistic regression identified factors associated with SLNB performance and sentinel lymph node (SLN) positivity. Univariable and multivariable analyses assessed overall survival (OS) and melanoma-specific survival (MSS) based on SLNB performance and SLN status., Results: Compared to other melanoma subtypes, LMM had lower rates of SLNB (66.6% vs. 80.0%-84.0%) and SLN positivity (11.3% vs. 18.6%-34.2%). Compared to patients who did not undergo SLNB, SLN status was significantly associated with improved OS in patients with SLN positive (HR = 0.64 [0.55-0.76]) and SLN negative (HR = 0.68 [0.49-0.94]), and worse MSS only in patients with positive SLN (HR = 3.93, p < 0.05)., Conclusion: The improved OS associated with SLNB likely implies surgical selection bias. Analysis of MSS confirms appropriate patient selection and suggests important prognostic value associated with SLN status. These results support continued SLNB for LMM patients according to standard guidelines., (© 2023 Wiley Periodicals LLC.)

Background: Dermoscopic and reflectance confocal microscopy (RCM) correlations between morphologic groups of melanoma have not yet been described., Objective: Describe and compare dermoscopic and RCM features of cutaneous melanomas with histopathological confirmation., Methods: Single center, retrospective analysis of consecutive melanomas evaluated with RCM (2015-2019). Lesions were clinically classified as typical, nevus-like, amelanotic/nonmelanoma skin cancer (NMSC)-like, seborrheic keratosis (SK)-like and lentigo/lentigo maligna (LM)-like. Presence or absence of common facial and nonfacial melanoma dermoscopic and RCM patterns were recorded. Clusters were compared with typical lesions by multivariate logistic regression., Results: Among 583 melanoma lesions, significant differences between clusters were evident (compared to typical lesions). Observation of dermoscopic features (>50% of lesions) in amelanotic/NMSC-like lesions consistently displayed 3 patterns (atypical network, atypical vascular pattern + regression structures), and nevus-like and SK-like lesions and lentigo/LM-like lesions consistently displayed 2 patterns (atypical network + regression structures, and nonevident follicles + heavy pigmentation intensity). Differences were less evident with RCM, as almost all lesions were consistent with melanoma diagnosis., Limitations: Small SK-like lesions sample, single RCM analyses (no reproduction of outcome)., Conclusion: RCM has the potential to augment our ability to consistently and accurately diagnose melanoma independently of clinical and dermoscopic features., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2023 American Academy of Dermatology, Inc. All rights reserved.)

Background: Lentigo maligna/lentigo maligna melanoma (LM/LMM) is usually diagnosed in older patients, when lesions are larger. However, it is important to detect it at an earlier stage to minimize the area for surgical procedure., Objectives: To determine and define clinical, dermoscopic and reflectance confocal microscopy (RCM) features of LM/LMM in patients < 50 years old., Methods: This was a multicentre study involving tertiary referral centres for skin cancer management. The study included cases of consecutively excised LM/LMM arising in patients < 50 years of age with a histopathological diagnosis of LM/LMM and a complete set of clinical and dermoscopic images; RCM images were considered when present., Results: In total, 85 LM/LMM of the face from 85 patients < 50 years were included in the study. A regression model showed a direct association with the size of the lesion (R2 = 0.08; P = 0.01) and with the number of dermoscopic features at diagnosis (R2 = 0.12; P < 0.01). In a multivariable analysis, an increasing number of dermoscopic features correlated with increased patient age (P < 0.01), while the presence of grey colour was a predictor of younger age at diagnosis (P = 0.03). RCM revealed the presence of melanoma diagnostic features in all cases (pagetoid cells and atypical nesting)., Conclusions: LM is not a disease limited to older people as previously thought. LM presenting in young adults tends to be smaller and with fewer dermoscopic features, making its diagnosis challenging. Careful evaluation of facial pigmented lesions prior to cosmetic procedures is imperative to avoid incorrectly treating early LM as a benign lesion., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Although the dermoscopic features of facial lentiginous melanomas (LM), including lentigo maligna and lentigo maligna melanoma, have been extensively studied, the literature about those located on the scalp is scarce. This study aims to describe the dermoscopic features of scalp LM and assess the diagnostic accuracy of dermoscopy to discriminate them from equivocal benign pigmented macules., Methods: Consecutive cases of scalp LM and histopathology-proven benign but clinically equivocal pigmented macules (actinic keratoses, solar lentigos, seborrhoeic keratoses, and lichen planus-like keratoses) from four referral centres were included. Dermoscopic features were analysed by two blinded experts. The diagnostic performance of a predictive model was assessed., Results: 56 LM and 44 controls were included. Multiple features previously described for facial and extrafacial LM were frequently identified in both groups. Expert's sensitivity to diagnose scalp LM was 76.8% (63.6-87.0) and 78.6% (65.6-88.4), with specificity of 54.5% (38.9-69.6) and 56.8% (41.0-71.7), and fair agreement (kappa coefficient 0.248). The strongest independent predictors of malignancy were (OR, 95% CI) chaos of colour (15.43, 1.48-160.3), pigmented reticular lines (14.96, 1.68-132.9), increased density of vascular network (3.45, 1.09-10.92), and perifollicular grey circles (2.89, 0.96-8.67). The predictive model achieved 85.7% (73.8-93.6) sensitivity, 61.4% (45.5-75.6) specificity, and 81.5 (73.0-90.0) area under curve to discriminate benign and malignant lesions. A diagnostic flowchart was proposed, which should improve the diagnostic performance of dermoscopy., Conclusion: Both facial and extrafacial dermoscopic patterns can be identified in scalp LM, with considerable overlap with benign pigmented macules, leading to low specificity and interobserver agreement on dermoscopy., (© 2023 S. Karger AG, Basel.)

Background: Lentigo maligna melanoma is mainly localized in the head and neck region in elderly patients. Due to its slow horizontal growth, it has a good prognosis compared to other melanoma subtypes, but specific data are rare., Objectives: The aim of this study was to investigate sentinel lymph node biopsy in lentigo maligna melanoma under local anaesthesia and to discuss the benefit., Methods: Investigation of patients with lentigo maligna melanoma and tumour thickness ≥1 mm treated at the Department of Dermatology, University Medical Centre Tuebingen, between January 2008 and October 2019., Results: In total, 204 patients (126 SLNB, 78 non-SLNB) with a median age of 75.7 years (SLNB: 73.3 years, non-SLNB: 79.7 years) could be included. Sixteen of 126 (12.7%) sentinel lymph nodes were positive. Five-year overall survival was 87.9% (88.5% SLNB; 87.4% non-SLNB) and 5-year distant metastasis-free survival was 85.8% (85.4% SLNB; 86.7% non-SLNB). There was no significant difference for distant metastasis-free survival (p = 0.861) and overall survival (p = 0.247) between patients with and without sentinel lymph node biopsy., Conclusions: Sentinel lymph node biopsy in lentigo maligna melanoma under local anaesthesia is a safe and simple method, even in very old patients. However, LMM has a very good 5-year overall survival. In high-risk patients with high tumour thickness and/or ulceration, adjuvant immunotherapy can now be offered without the need to perform this procedure., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Lentigo maligna (LM) can mimic benign, flat, pigmented lesions and can be challenging to diagnose., Objective: To describe a new dermatoscopic feature termed "perifollicular linear projections (PLP)" as a diagnostic criterion for LM on the face., Methods: Retrospective study on reflectance confocal microscopy and dermatoscopy images of flat facial pigmented lesions originating from 2 databases. PLP were defined as short, linear, pigmented projections emanating from hair follicles. Dermatoscopy readers were blinded to the final histopathologic diagnosis., Results: From 83 consecutive LMs, 21/83 (25.3%) displayed "bulging of hair follicles" on reflectance confocal microscopy and 18 of these 21 (85.7%), displayed PLP on dermatoscopy. From a database of 2873 consecutively imaged and biopsied lesions, 252 flat-pigmented facial lesions were included. PLP was seen in 47/76 melanomas (61.8%), compared with 7/176 lesions (3.9%) with other diagnosis (P < .001). The sensitivity was 61.8% (95% CI, 49.9%-72.7%), specificity 96.0% (95% CI, 92.9%-98.4%). PLP was independently associated with LM diagnosis on multivariate analysis (OR 26.1 [95% CI, 9.6%-71.0])., Limitations: Retrospective study., Conclusion: PLP is a newly described dermatoscopic criterion that may add specificity and sensitivity to the early diagnosis of LM located on the face. We postulate that PLP constitutes an intermediary step in the LM progression model., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Atypical pigmented facial lesions (aPFLs)-including lentigo maligna (LM) and lentigo maligna melanoma (LMM), solar lentigo (SL), pigmented actinic keratosis (PAK), atypical nevi (AN), seborrheic keratosis (SK) and lichen planus-like keratosis (LPLK)-can exhibit clinical and dermoscopic overlapping features. We aimed to investigate if and how 14 dermoscopic features suggestive for the aforementioned aPFLs vary according to six facial sites among 1197 aPFLs cases (excised to rule out malignancy) along with lesion and patients' metadata. According to distribution and association analysis, aPFLs on the forehead of a male patient aged > 69 years displaying the obliterated follicular openings pattern, appear to be more at risk of malignancy. Of converse, aPFLs of the orbital/cheek/nose area with evident and regular follicular openings with diameter < 10 mm in a female aged below 68 are probably benign. The obliterated follicular openings, keratin plugs, evident and regular follicular openings and target-like pattern features differed significantly among six facial areas in all aPFLs cases. Lesion of the nose may show both features suggestive of malignancy and benignity (e.g. many SL and PAK may display target-like pattern and some LM/LMM cases display keratin plugs and evident and follicular openings), making these features less specific., (© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Background: Extra facial lentigo maligna (EF-LM) arises outside the head and neck area. EF-LM presents the classic histological features of lentigo maligna. The dermoscopic aspects of EF-LM have been poorly studied., Objective: The primary aims of our study were to analyse and describe the clinical, dermoscopic and confocal microscopy features of a series of histologically confirmed EF-LM., Method: We conducted a retrospective and multicentric study. From our database, we selected 48 cases of thin melanomas on photodamaged skin with histological features of EF-LM of which clinical, dermoscopic and confocal microscopy images were available, and a control group of 45 lesions, that can be subjected to differential diagnosis such as solar lentigo, lichenoid keratosis, seborrheic keratosis and melanocytic nevi, of which dermoscopic and confocal microscope images were available., Results: Extra facial lentigo maligna had a higher prevalence of lentigo-like pigment patterns, angulated lines and zigzag structures. At confocal microscopy, LM-EF cases showed a higher prevalence of pagetoid spreading, round cells, dendritic cells in the epidermis, atypical cells at the dermo-epidermal junction, dendritic cells at the junction, meshwork pattern and elastosis. Our study shows that reflectance confocal microscopy (RCM) has a sensitivity of 90% and a specificity of 97% for the differential diagnosis of this type of melanoma., Conclusions: Extra facial lentigo maligna does not have the classic dermoscopic features of superficial spreading melanoma, the most observed dermoscopic criteria are angulated lines and lentigo-like pigment patterns without lentigo-like border. RCM can be a valuable imaging tool for the evaluation of all those suspicion skin lesions at dermoscopy highlighting cellular atypia suggestive for melanoma., (© 2023 European Academy of Dermatology and Venereology.)

Background: Due to progressive ageing of the population, the incidence of facial lentigo maligna (LM) of the face is increasing. Many benign simulators of LM and LMM, known as atypical pigmented facial lesions (aPFLs-pigmented actinic keratosis, solar lentigo, seborrheic keratosis, seborrheic-lichenoid keratosis, atypical nevus) may be found on photodamaged skin. This generates many diagnostic issues and increases the number of biopsies, with a subsequent impact on aesthetic outcome and health insurance costs., Objectives: Our aim was to develop a risk-scoring classifier-based algorithm to estimate the probability of an aPFL being malignant. A second aim was to compare its diagnostic accuracy with that of dermoscopists so as to define the advantages of using the model in patient management., Materials and Methods: A total of 154 dermatologists analysed 1111 aPFLs and their management in a teledermatology setting: They performed pattern analysis, gave an intuitive clinical diagnosis and proposed lesion management options (follow-up/reflectance confocal microscopy/biopsy). Each case was composed of a dermoscopic and/or clinical picture plus metadata (histology, age, sex, location, diameter). The risk-scoring classifier was developed and tested on this dataset and then validated on 86 additional aPFLs., Results: The facial Integrated Dermoscopic Score (iDScore) model consisted of seven dermoscopic variables and three objective parameters (diameter ≥ 8 mm, age ≥ 70 years, male sex); the score ranged from 0 to 16. In the testing set, the facial iDScore-aided diagnosis was more accurate (AUC = 0.79 [IC 95% 0.757-0.843]) than the intuitive diagnosis proposed by dermatologists (average of 43.5%). In the management study, the score model reduced the number of benign lesions sent for biopsies by 41.5% and increased the number of LM/LMM cases sent for reflectance confocal microscopy or biopsy instead of follow-up by 66%., Conclusions: The facial iDScore can be proposed as a feasible tool for managing patients with aPFLs., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Malignant melanoma in-situ, lentigo maligna (MMIS-LM) can be successfully treated with several different surgical techniques; however, the literature is inconsistent in defining them., Objective: To comprehensively define and describe the national guideline recommended surgical techniques used to treat MMIS-LM to help clarify and standardize this terminology to ensure compliance with the guidelines., Methods: A targeted literature review was performed from 1990 to 2022 focusing on articles that discussed the national guideline recommended surgical techniques of wide local excision, Mohs micrographic surgery (MMS), modified Mohs surgery, and staged excision/Slow-Mohs for MMIS-LM, as well as the related methods of tissue processing. National Comprehensive Cancer Network and American Academy of Dermatology guidelines were reviewed to identify how the techniques need to be employed to be compliant with guideline recommendations., Results: We describe the various surgical and tissue processing techniques and discuss advantages and disadvantages of each., Limitations: This paper was styled as a narrative review defining and clarifying terminology and technique and does not investigate these topics more broadly., Conclusion: Understanding the methodology and terminology for these surgical procedures and tissue processing methods is critical so that both general dermatologists and surgeons can employ these techniques effectively for optimal patient care., Competing Interests: Conflicts of interest None disclosed., (Published by Elsevier Inc.)

Background and Objectives: The melanoma guideline is mainly based on the AJCC stage. There is no difference according to histological subtypes such as superficial spreading melanoma (SSM), lentigo maligna melanoma (LMM) or nodular malignant melanoma (NM). We aimed to evaluate whether patients with LMM have a different clinical course from patients with SSM/NM. This is particularly important as adjuvant anti-PD-1 therapy is approved for stage IIB and IIC melanoma., Patients and Methods: Data were extracted from the Central Registry of Malignant Melanoma. Only patients with LMM, SSM, and NM of the head and neck with primary diagnosis between 01/01/2000 and 12/31/2019 were included. Progression-free survival (PFS), melanoma-specific survival (MSS), and pattern of metastases were analyzed for the LMM group compared to SSM/NM., Results: The LMM cohort (n = 902) had significantly better MSS than the SSM/NM cohort (n = 604). There was no difference in PFS. The 5-year MSS of the stage II LMM cohort was 88.5% (95% CI 81.4-95.6) compared to 79.7% (95% CI 72.8-86.6) in the stage II SSM/NM cohort., Conclusion: It does not appear appropriate to use adjuvant therapy in stage II LMM patients to the same extent as in patients with SSM/NM., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

External ear melanoma (EEM) belongs to extremely rare melanoma locations. So far, only single cases of EEM have been described in terms of dermoscopic presentations. This case study report presents dermoscopic patterns of EEM in six patients. The retrospective case study was based on medical documentation (epidemiological, anamnestic, clinical, videodermoscopic, and histopathologic) of consecutive patients who were diagnosed with melanoma located on the external ear between January 2013 and May 2021 in three diagnostic dermatologic centers. In four of six cases, the melanoma was placed on the helix. The histopathological diagnoses included 1/6 lentigo maligna and 5/6 invasive melanomas. The dermoscopic pattern of facial melanoma (FM) was present in 3/6 cases, 1/6 exhibited the typical superficial spreading pattern (one with nodular invasion), 1/6 the multicomponent asymmetric pattern, and 1/6 the hypomelanotic type. Five melanomas presented numerous (3-6) dermoscopic structures characteristic for each dermoscopic subtype. In conclusion, dermoscopy has proved effective for detection of both difficult and easy-to-diagnose EEM, but also in differentiating their dermoscopic subtypes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Because of an increased risk of local recurrence following surgical treatment of lentigo maligna (melanoma) (LM/LMM), the optimal surgical technique is still a matter of debate. We aimed to evaluate the effect of different surgical techniques and reflectance confocal microscopy (RCM) on local recurrence and survival outcomes. We searched MEDLINE, Embase and PubMed databases through 20 May 2022. Randomized and observational studies with ≥10 lesions were eligible for inclusion. Bias assessment was performed using the Methodological Index for Non-Randomized Studies instrument. Meta-analysis was performed for local recurrence, as there were insufficient events for the other clinical outcomes. We included 41 studies with 5059 LM and 1271 LMM. Surgical techniques included wide local excision (WLE) (n = 1355), staged excision (n = 2442) and Mohs' micrographic surgery (MMS) (n = 2909). Six studies included RCM. The guideline-recommended margin was insufficient in 21.6%-44.6% of LM/LMM. Local recurrence rate was lowest for patients treated by MMS combined with immunohistochemistry (<1%; 95% CI, 0.3%-1.9%), and highest for WLE (13%; 95% CI, 7.2%-21.6%). The mean follow-up varied from 27 to 63 months depending on surgical technique with moderate to high heterogeneity for MMS and WLE. Handheld-RCM decreased both the rate of positive histological margins (p < 0.0001) and necessary surgical stages (p < 0.0001). The majority of regional (17/25) and distant (34/43) recurrences occurred in patients treated by WLE. Melanoma-associated mortality was low (1.5%; 32/2107), and more patients died due to unrelated causes (6.7%; 107/1608). This systematic review shows a clear reduction in local recurrences using microscopically controlled surgical techniques over WLE. The use of HH-RCM showed a trend in the reduction in incomplete resections and local recurrences even when used with WLE. Due to selection bias, heterogeneity, low prevalence of stage III/IV disease and limited survival data, it was not possible to determine the effect of the different surgical techniques on survival outcomes., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background/objective: Photographic aides are increasingly used in melanoma surveillance. We report melanoma characteristics detected using traditional surveillance without photographic technologies., Methods: Retrospective study of melanomas diagnosed by three dermatologists at a private dermatology practice over 7 years. Patients underwent full skin examinations with dermoscopy and suspect lesions were excised or biopsied. Total body photography (TBP) and serial digital dermoscopic imaging (SDDI) were not used. Patient demographics, melanoma subtype and thickness, location, biopsy technique and keratinocyte cancers diagnosed at the same visit were recorded. Ratio of in situ to invasive melanomas was calculated. Melanoma risk factors were recorded for 69 randomly-selected patients., Results: 492 patients were diagnosed with 615 melanomas during 579 visits. 505 (82%) were in situ (in situ to invasive ratio of 4.6:1). Of the invasive melanomas, 85.5% had a Breslow thickness <0.8 mm, 10 (9.1%) 0.8-1 mm and 6 (5.5%) >1 mm. 43.3% of in situ melanomas were lentiginous or lentigo maligna and 41.6% were superficial spreading melanomas (SSM). Of invasive melanomas, 24.3% were lentigo maligna melanoma and 59.5% were SSM. 48.4% of melanomas were diagnosed by shave procedures. Where risk factors were known, 25% were very-high-risk and 43% had a history of melanoma. Keratinocyte carcinoma was diagnosed by biopsy at 26.1% of visits. Studies using TBP and/or SDDI report in situ to invasive ratios of 0.59:1 to 2.17:1., Conclusion: Tradiational melanoma surveillance with immediate biopsy of suspect lesions results in high in situ to invasive ratios. Studies using photographic surveillance show lower ratios of in situ to invasive disease., (© 2023 The Authors. Australasian Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Australasian College of Dermatologists.)

Background: Time trend analysis of cutaneous melanoma (CM) mortality in fair skin populations shows both a gradual decrease and/or an increase. To explain these differences, we analyzed long-term time trends in the incidence of the most common histological subtypes of CM: superficial spreading melanoma (SSM), lentigo maligna melanoma (LMM), and nodular melanoma (NM)., Methods: Using data from the Netherlands Cancer Registry and Statistics Netherlands, the number and rates of cases diagnosed with SSM, LLM, and NM from 1989 to 2016 were analyzed by age, calendar period, and birth cohort of people born in successive periods from 1925 to 1973., Results: Primary CM was diagnosed in 52,000 men and 66,588 women in the study period. The annual age-standardized incidence rate increased three-fold from 14 to 42 per 100,000 person-years. The most common subtype was SSM (50%), followed by LMM (23%) and NM (14%). Age-specific subtype rates showed an upward trend over time for both men and women. Younger birth cohorts had higher rates of SSM and LMM diagnosis than older birth cohorts. This birth cohort pattern was not observed for NM., Conclusions: We observed a strong increase in the melanoma epidemic curves in the light-skinned Dutch population over the last three decades. This increase is explained by younger generations having higher rates of SSM and LMM than older generations., (© 2022 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Background: Knowledge about lentigo maligna (melanoma) (LM/LMM) and its associated prognostic clinicopathological characteristics are limited compared to that of non-LM/LMM subtypes. The current study aimed to determine the clinical relevance of the LM/LMM subtype and its influence on recurrence and survival outcomes., Methods: All consecutive cases of primary cutaneous head and neck LM/LMM treated by wide local excision over a ten-year period were retrospectively reviewed and compared to non-LM/LMM. Clinical outcome and prognostic factors were assessed by cumulative incidence and competing risk analyses., Results: A total of 345 patients were identified. Specific clinicopathological characteristics such as lower median Breslow thickness (1.6 mm versus 2.1 mm; P = 0.013), association with diagnostic sampling errors (17.3% versus 5.2%; P = 0.01), and increased risk of local recurrences due to incomplete resection (18.7% versus 2.3%; P < 0.001), were significantly associated with LM/LMM. Guideline adherence was similar between the two study groups. The positive nodal status at baseline for LMM was low compared to non-LM/LMM (4.2% vs 17.9%; P = 0.037). The LMM subtype, facial localization, and reduced surgical margins (i.e., guideline non-adherence) were not shown to be independent prognostic factors for disease-free, melanoma-specific, or overall survival after correction for competing risks such as patient age and Breslow thickness., Conclusions: The LMM subtype was not shown to be prognostically different from non-LM/LMM when corrected for other variables of influence such as patient age and Breslow thickness. Reduced resection margins did not seem to affect disease-free, and melanoma-specific survival and warrant LM/LMM-specific guidelines. Further research is needed to evaluate the value of SLNB in LMM patients., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Objectives: To provide evidence for long-term outcomes for margin-controlled excision of eyelid melanoma., Methods: Retrospective single-centre observational case series of patients treated for eyelid melanoma between 2007 and 2016, with a minimum of 5-year follow-up. Tumour excision involved rush-paraffin en face horizontal sections and delayed repair (Slow Mohs; SM)., Results: Twenty-two cases were seen with a survival of 91% (two deaths from nodular and lentigo maligna melanoma) and seven with melanoma in situ (MIS). Invasive melanoma includes eight lentigo maligna melanoma, four nodular, two amelanotic and one desmoplastic. Mean Breslow thickness was 6 mm for invasive (range 0.5-26). Mean excision margin for MIS was 3 mm (range 2-5 mm) and for invasive was 5 mm (range 2-10). Further excisions were performed in nine (41%); two went on to recur. Local recurrence was 36%; six invasive (27%) at a mean of 24 months (range 1.5-5 years) and two for MIS at a mean of 15 months (range 1-1.5 years). Imaging occurred for suspected advanced disease. Sentinel node biopsy was not performed. Advanced melanoma therapy was performed in two cases. No vitamin D testing occurred., Conclusions: Survival rates are in line with 90% overall survival in the UK. Prescriptive excision margins are not applicable in the periocular region and margin-controlled excision with a delayed repair is recommended, but patients need to know further excision may be needed to obtain clearance. Evidence recommending vitamin D therapy needs to be put into clinical practice. In addition, upstaging of MIS occurred advocating excision rather than observation of MIS. More studies are needed to determine the best management of eyelid melanoma., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: Staged excision has emerged as a superior treatment option for lentigo maligna (LM) of the head and neck when compared with conventional wide local excision. Assessing surgical excision margins for remaining LM poses a diagnostic challenge., Objectives: To determine whether immunohistochemical (IHC) staining with SOX10 and preferentially expressed antigen in melanoma (PRAME) aids in diagnosing LM on excision margins compared with conventional hematoxylin and eosin and Melan A IHC staining., Methods: This study included cases of LM of the head and neck treated with staged excision. Histological findings were reviewed according to standard criteria for the diagnosis of LM and compared with the results after IHC staining for Melan A, SOX10, and PRAME., Results: The cohort consisted of 35 sections. Based on hematoxylin and eosin and Melan A IHC staining, 23 sections were diagnosed as LM by the initial pathologist. Further staining with SOX10 IHC showed only 8 to be consistent with a diagnosis of LM and 9 revealing features of actinic melanocyte hyperplasia. PRAME was positive in 5 of the 8 cases of LM and negative in all 9 cases of actinic melanocyte hyperplasia (P = 0.009). The presence of melanocyte nests (P = 0.29) and pagetoid spread (P = 0.003) was the most reliable histological findings distinguishing LM from its mimics., Conclusion: SOX10 is a more specific and sensitive marker for melanocytes when assessing for LM on excision margins compared with Melan A. The addition of PRAME can be useful to confirm or exclude the diagnosis in challenging cases., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Prostaglandin F 2a analogs (PGAs) are considered efficacious in the first-line treatment of glaucoma. They have however been associated with a number of periocular side effects. We present a case of periocular hyperpigmentation and progression to lentigo maligna melanoma (LMM) in a patient using bimatoprost eye drops. We conducted a literature review regarding the etiology and pathophysiology of periocular pigmentation in this setting.A 71-year-old female Caucasian patient with open-angle glaucoma using bimatoprost exclusively in her right eye noticed an ipsilateral lower eyelid/upper cheek area dark lesion after commencing treatment. Examination demonstrated a heterogeneously pigmented lesion. Excisional biopsy demonstrated extensive lentigo maligna (melanoma in situ) with superficially invasive malignant melanoma in the lesion center. The patient underwent successful staged excision and reconstruction. Literature review has demonstrated case reports supporting periocular hyperpigmentation; however, there has been no description of progression to periocular lentigo maligna and melanoma in a patient using bimatoprost.

Competing Interests: Conflicts of interest None disclosed.

Background: Amelanotic/hypomelanotic lentigo maligna and lentigo maligna melanoma (AHLM/LMM) may be very difficult to diagnose at an early stage., Objectives: To quantify the predictive value of dermoscopic and reflectance confocal microscopy (RCM) features for AHLM/LMM., Methods: Dermoscopic and RCM images of histopathologically diagnosed AHLM/LMM, amelanotic/hypomelanotic benign lesions (AHBL), and amelanotic/hypomelanotic basal and squamous cell carcinomas (AHBCC/AHSCC) of the head and neck from consecutive patients were retrospectively collected and blindly evaluated by three observers to assess presence or absence of dermoscopic and RCM criteria., Results: Overall, 224 lesions in 216 patients including LM/LMM (n = 55, 24.6%), AHBL (n = 107, 47.8%) and AHBCC/AHSCC (n = 62, 27.7%) were analysed. Multivariable analysis showed that milky-red areas (OR = 5.46; 95% CI: 1.51-19.75), peripheral light brown structureless areas (OR = 19.10; 4.45-81.96), linear irregular vessels (OR = 5.44; 1.45-20.40), and asymmetric pigmented follicles (OR = 14.45; 2.77-75.44) at dermoscopy, and ≥3 atypical cells in five fields (OR = 10.12; 3.00-34.12) and focal follicular localization of atypical cells at dermo-epidermal junction (DEJ) (OR = 10.48; 1.10-99.81) at RCM were significantly independent diagnostic factors for AHLM/LMM vs. AHBL. In comparison with AHBCC/AHSCC, peripheral light brown structureless area (OR = 7.11; 1.53-32.96), pseudonetwork around hair follicles (OR = 16.69; 2.73-102.07), and annular granular structures (OR = 42.36; 3.51-511.16) at dermoscopy and large dendritic (OR = 6.86; 3.15-38.28) and round pagetoid cells (OR = 26.78; 3.15-227.98) at RCM led to a significantly increased risk of diagnosing AHLM/LMM., Conclusions: Amelanotic/hypomelanotic lentigo maligna and lentigo maligna melanoma may have the same dermoscopic features of AHM on other body sites, such as milky red areas, peripheral light brown structureless areas and linear irregular vessels. These features, asymmetric pigmented follicles and at RCM ≥ 3 atypical cells in five fields and focal follicular extension of atypical cells at DEJ may help in recognizing AHLM/LMM even when LM conventional features (e.g., obliteration of hair follicles under dermoscopy and large pagetoid cells under RCM) are absent or present only in very small areas of the lesion., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Lentigo Maligna is a benign subtype of melanoma in situ and can progress to lentigo maligna melanoma, which is invasive. Complete surgical excision is the gold standard of treatment but requires large margins. If affecting the peri-ocular region, surgical excision leads to extensive defects, complex reconstructions, and functional impairment of the protection of the ocular surface. Here we review the reported literature about the use of Imiquimod 5% topical cream for lentigo maligna of the eyelid, the treatment outcomes, side effects and tolerance. In addition, the side effects of imiquimod treatment of non-LM lesions are described to help better inform the decision-making process. Treatment for peri-ocular Lentigo maligna showed a 56-86% complete treatment response and a 90% tolerability rate. However, reported treatment protocols vary and histopathological confirmation of clearance was only obtained in 56%. Further studies are required to determine the optimal treatment protocol to maximise clearance rates. Overall, Imiquimod was well tolerated in the peri-ocular area., (© 2022. Crown.)

Background: Lentigo maligna/lentigo maligna melanoma (LM/LMM) can present with subclinical extension that may be difficult to define preoperatively and lead to incomplete excision and potential recurrence. Preliminarily studies have used reflectance confocal microscopy (RCM) to assess LM/LMM margins., Objective: To evaluate the correlation of LM/LMM subclinical extension defined by RCM compared with the gold standard histopathology., Methods: Prospective study of LM/LMM patients referred for dermatologic surgery. RCM was performed at the clinically defined initial surgical margin followed by margin-controlled staged excision with paraffin-embedded tissue, and histopathology was correlated with RCM results., Results: Seventy-two patients were included. Mean age was 66.8 years (standard deviation, 11.1; range, 38-89); 69.4% were men. Seventy of 72 lesions (97.2%) were located on the head and neck with mean largest clinical diameter of 1.3 cm (range, 0.3-5). Diagnostic accuracy for detection of residual melanoma in the tumor debulk (after biopsy) had a sensitivity of 96.7% and a specificity of 66.7% when compared with histopathology. RCM margin assessment revealed an overall agreement with final histopathology of 85.9% (κ = 0.71; P < .001)., Limitations: No RCM imaging beyond initial planned margins was performed., Conclusion: RCM showed moderate to excellent overall agreement between RCM imaging of LM/LMM and histopathology of staged excision margins., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Facial skin is characterized by high density of follicles. Facial neoplasms may present overlapping clinical and dermoscopic findings. Our goal was to evaluate and compare, via reflectance confocal microscopy (RCM), follicular involvement in facial neoplasms., Methods: We retrospectively searched our image database, between January 2008 and December 2020, for all facial lesions with (1) a standardized set of clinical, dermoscopic, and RCM images, and (2) a biopsy-proven diagnosis of lentigo maligna/lentigo maligna melanoma (LM/LMM, n = 39), basal cell carcinoma (BCC, n = 51), squamous cell carcinoma in situ (SCCIS, n = 5), actinic keratosis (AK, n = 11), and lichen-planus-like keratosis (LPLK, n = 18). Two readers jointly evaluated the RCM images for a set of predefined features of follicular involvement., Results: Diffuse obliteration of follicles was frequent in BCC (88%), while follicular infiltration by refractile dendritic cells and/or by bright round nucleated cells was common in melanoma (90% and 44%, respectively). Extension of atypical keratinocytes down follicles was more prominent among SCCIS than AK (80% vs. 45%, p = 0.01). In most LPLK (89%), there was follicular sparing., Conclusions: Evaluation of RCM criteria centering on the follicles can be useful in the differential diagnosis between common facial neoplasms., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Melanomas developing on anatomic sites other than the trunk and extremities have a special pathogenetic and mutational profile, morphologic characteristics and biologic behaviour., Objective: By retrospectively screening the databases of our centres, we aimed to investigate the dermatoscopic morphology of early scalp melanoma, including in situ and invasive tumours with a Breslow thickness up to 1 mm., Methods: The databases of three specialized centres for skin cancer diagnosis and management in Greece were retrospectively evaluated to retrieve dermatoscopic images of scalp melanomas. Patients' age and sex were recorded, as well as the precise location of the tumour, using 6 possible sub-locations: frontal, parietal, occipital, temporal, nuchal scalp and vertex. The dermatoscopic images were evaluated by 3 independent investigators for the presence of pre-defined criteria. The dermatoscopic criteria included in the evaluation were selected based on available literature and were categorized in 2 groups: 'classic melanoma criteria' and 'lentigo maligna (LM) criteria'., Results: Of 38 melanomas, 37 (97.4%) displayed brown colour and 23 (60.5%) displayed additional grey or blue colour. The most frequent dermatoscopic criteria were regression (18/38, 47.4%), grey dots/globules (17/38, 44.7%), atypical network (16/38, 42.1%), obliterated follicles (16/38, 42.1%) and angulated lines (15/38, 39.5%). Of 38 melanomas, 28 (73.7%) displayed at least 1 classic melanoma criterion plus at least 1 LM criterion. Of the remaining melanomas, 8 (21.1%) displayed only classic melanoma criteria, 1 (2.6%) only LM criteria and 1 (2.6%) did not exhibit any of the evaluated criteria., Conclusions: This study demonstrates that early scalp melanoma combines classic with LM criteria in terms of colours and structures., (© 2022 European Academy of Dermatology and Venereology.)

Abstract: 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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Diagnosis of non-facial melanomas on sun-damaged skin or extrafacial lentigo maligna is challenging., Objectives: To identify the evolutionary dermoscopic signs, characteristic of this type of non-facial melanoma on sun-damaged skin., Materials & Methods: This retrospective descriptive observational study included 90 dermoscopic follow-up images of 22 non-facial melanomas on sun-damaged skin from 17 high-risk melanoma patients, followed with digital dermoscopy and diagnosed between January 2016 and October 2020. We recorded dermoscopic changes by comparing each dermoscopic image with the previous one (mean dermoscopic follow-up of the excised lesions was 3.6 years). Confocal microscopy images were taken at diagnosis., Results: In total, 51.5% (95% CI: 39-64) showed an appearance or increase in featureless areas with surrounding small round or triangular dark brown-blue structures, 23% (95% CI: 23-46) showed an increase in other geometric structures (angulated lines, zig-zag lines and polycyclic structures), 5.9% (95% CI: 2-14) showed an appearance or increase in bright white lines and atypical vascularization, 26.5% (95% CI: 17-39) showed an appearance or increase in follicular pigmentation structures or follicular radial lines, and 39.7% (95% CI: 28-52) showed focal islands of pigmentation in these areas. Of the changes, 54% occurred at the last and diagnostic visit. There was an increase in size in only 20.6% (95% CI: 12-32). Also, 81.8% showed pagetoid cells in the epidermis, 95.5% atypical cells at the dermoepidermal junction by reflectance confocal microscopy, and 95.5% showed non-edged or edged and non-edged papillae., Conclusion: This study identifies the dermoscopic evolutionary changes associated with extrafacial lentigo maligna.

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., (© 2022 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

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., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

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., (Copyright © 2021 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Conventional tissue sampling can lead to misdiagnoses and repeated biopsies. Additionally, tissue processed for histopathology suffers from poor nucleic acid quality and/or quantity for downstream molecular profiling. Targeted micro-sampling of tissue can ensure accurate diagnosis and molecular profiling in the presence of spatial heterogeneity, especially in tumors, and facilitate acquisition of fresh tissue for molecular analysis. In this study, we explored the feasibility of performing 1-2 mm precision biopsies guided by high-resolution reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), and reflective metallic grids for accurate spatial targeting. Accurate sampling was confirmed with either histopathology or molecular profiling through next generation sequencing (NGS) in 9 skin cancers in 7 patients. Imaging-guided 1-2 mm biopsies enabled spatial targeting for in vivo diagnosis, feature correlation and depth assessment, which were confirmed with histopathology. In vivo 1-mm targeted biopsies achieved adequate quantity and high quality of DNA for next-generation sequencing. Subsequent mutational profiling was confirmed on 1 melanoma in situ and 2 invasive melanomas, using a 505-gene mutational panel called Memorial Sloan Kettering-Integrated mutational profiling of actionable cancer targets (MSK-IMPACT). Differential mutational landscapes, in terms of number and types of mutations, were found between invasive and in situ melanomas in a single patient. Our findings demonstrate feasibility of accurate sampling of regions of interest for downstream histopathological diagnoses and molecular pathology in both in vivo and ex vivo settings with broad diagnostic, therapeutic and research potential in cutaneous diseases accessible by RCM-OCT imaging., (© 2021. The Author(s).)

Lentigo maligna (LM) is a common in situ melanoma subtype arising on chronically sun-damaged skin and mostly affects the head and neck region. Localisation in cosmetically sensitive areas, difficulty to obtain wide resection margins and advanced patient age/comorbidities have encouraged investigation of less invasive therapeutic strategies than surgery in managing complex cases of LM. Radiotherapy and imiquimod have emerged as alternative treatment options in this context. The treatment of LM with imiquimod cream can be challenging due to the nature of the disease including its often large size, variegated appearance, involvement of adnexal structures, poorly defined peripheral edge and frequent localisation close to sensitive structures such as the eyes and lips, and elderly patients with multiple comorbidities. Prolonged and unpredictable inflammatory reaction and side effects and compliance with a patient-delivered therapy can also be challenging. In the literature to date, studies evaluating the use of imiquimod to treat LM have utilised varying methodologies and provided short follow-up and these limitations have impaired the development of clear guidelines for dosage and management of side effects. Based on our multidisciplinary experience and review of the literature, we propose practical clinical strategies for the use of imiquimod for treating LM, detailing optimal administration procedures in various clinical scenarios and long-term management, with the aim of facilitating optimal patient outcomes., (© 2021 The Australasian College of Dermatologists.)

Background: A regional skin cancer prevention program in Eastern Finland revealed a relatively high age-standardized mortality due to malignant melanoma during 2013-2017. An explanation for this is needed., Purpose: To analyse the 543 melanoma samples in 524 subjects collected during 2000-2013 at Kuopio University Hospital and reposited in the Biobank of Eastern Finland. A focus was directed to factors related to metastasis., Methods: The samples were analysed anonymously by examining the histopathological report, referral text and the list of diagnoses. A possible state of immunosuppression was evaluated., Results: The mean age at the diagnosis of malignant melanoma (MM), lentigo maligna (LM) and melanoma in situ was relatively high, i.e., 66.2, 72.1 and 63.3, respectively. Especially the MM type increased markedly during 2000-2013. In further analyses of a representative cohort of 337 samples, the proportion of nodular melanoma and LM/LMM melanoma was relatively high, 35.6 and 22.0%, respectively, but that from superficial spreading melanoma relatively low (33.8%). Metastasis correlated with immunosuppression, male gender, Clark level, Breslow thickness, ulceration, mitosis count, invasion into vessels and/or perineural area, microsatellites, melanoma subtype, body site, recidivism, and the absence of dysplastic nevus cells., Conclusion: The marked increase in aggressive melanomas with associated metastasis, and the relatively high age at diagnosis, can partially explain the mortality., (© 2021. The Author(s).)

Objective: Primary bladder melanomas are rare and aggressive neoplasms. We herein described a new case and performed a review of the literature., Patients and Methods: We present the case of a 81-year-old woman with a primary mucosal melanoma of the bladder after a history of acral melanoma (KRAS mutated) and lentigo maligna of the forehead. Using PubMed, we found that in literature 38 cases were described., Results: In our patients, during a transurethral resection (TURBT), two bladder lesions were detected. The histologic exam revealed a malignant melanoma, Mib1/ki67: 10-12%, PDL1 <1%. No BRAF, NRAS or KRAS mutations were detected. She subsequently underwent a transurethral revision of the trigone and a partial cystectomy of the dome with bilateral pelvic lymph node dissection. Microscopical findings showed a residual 5 mm non-muscle-invasive melanoma of the bladder, with negativity of the surgical margins and of the 17 pelvic lymph nodes. No adjuvant treatment was proposed. To date the patient is disease-free., Conclusions: Primary bladder melanoma carries a poor prognosis and poses a therapeutic challenge to clinicians who manage patients with this rare condition. In our experience the multidisciplinary approach for the diagnosis and management of this rare cancer is mandatory.