Lentigo Maligna Melanoma Research Articles

Six-Year Outcome of Lentigo Maligna Treated with "Spaghetti" Technique and Margin Identification by Reflectance Confocal Microscopy.

Lentigo maligna (LM) and LM melanoma (LMM) present surgical challenges due to their poorly defined boundaries, making it difficult to determine precise peripheral margins. In addition, their preferential localization on the face increases the need to minimize the amount of tissue excised. Striking a balance between reducing the excision size and maintaining oncologic effectiveness is critical in managing LM/LMM. Reflectance Confocal Microscopy (RCM), a noninvasive imaging method that provides cellular-level visualization, could be an ideal tool to define the peripheral margins in the "spaghetti" surgical technique. This study aimed to evaluate the long-term outcomes of using RCM combined with the "spaghetti" technique for LM/LMM excisions. Seventy patients with LM/LMM on the face underwent RCM-guided margin definition followed by the "spaghetti" technique. The sample of patients was the same group of patients included in the authors' 2017 study. The authors subsequently evaluated the effectiveness of the authors' protocol via regular follow-up of the cohort. A total of 59 LMs and 11 LMMs were included. The mean follow-up time was 6.3 years. The recurrence rate was 5.7%. The authors identified 4 recurrences: 3 of which occurred more than 5 years after the procedure. The recorded mortality was 20%, no deaths were attributed to LM/LMM. The mean margin from lesion to clearance was 2.7 mm. If the authors cluster the 3 principal studies in terms of cohort and follow-up time for LM/LMM treated by Wide local Excision, the recurrence rate is from 5.3% to 5.9%, which is equivalent to the authors'. However, the mean margin excision from lesion is more than 2 times inferior in the authors' protocol (2.7 mm vs 6.7 mm). Therefore, the spaghetti technique with RCM margin identification seems to be an effective method for LM/LMM management.

Mohs Micrographic Surgery for the Treatment of Lentigo Maligna and Lentigo Maligna Melanoma: An Outcomes Study.

Lentigo maligna (LM), a type of melanoma in situ (MIS), usually develops on sun-damaged skin in the elderly. If left untreated, it may advance to the point of dermal invasion, developing into lentigo maligna melanoma (LMM). While surgeons have achieved robust clinical outcomes for LM treated with Mohs micrographic surgery (MMS), performing this treatment for LMM remains controversial and is not standard amongst all Mohs surgeons. We examined survival outcomes in LM/LMM cases treated with MMS and wide local excision (WLE). Data from the National Cancer Institute Surveillance, Epidemiology, and End Results (NCI SEER) program, collected from 2000-2019, was retrospectively analyzed. Patients with microscopically confirmed diagnosis of LM/LMM who received surgical treatment with MMS or WLE were included. The effect of different surgery types on melanoma survival was evaluated. A total of 22,852 LM/LMM cases performed during the years 2000-2019 were considered for analysis. There were no significant differences in disease-specific survival comparing WLE to MMS. Our research hints at the utility of MMS for LM/LMM. We encourage practitioners to consider MMS for the management LM/LMM when appropriate. J Drugs Dermatol. 2024;23(12):1094-1099.  doi:10.36849/JDD.7898.

A delayed Tenzel flap

A 71-year-old man presented with a lentigo maligna melanoma (Breslow 0.25 mm) of the left lower eyelid. Complete excision was achieved after 3 Slow Mohs stages, resulting in a quadrangular 1.8x1.2 cm full-thickness defect. After the first stage, upper and lateral margins resulted as histologically infiltrated. Therefore, an additional lateral strip was taken after 3 days, resulting in a tumor-free result. Radicalization was completed after another 8 days on the posterior lamella and rim with immediate reconstruction.

Dermoscopy Training Course Improves Ophthalmologists' Accuracy in Diagnosing Atypical Pigmented Periorbital Skin Lesions.

Facial pigmented skin lesions are extremely common, starting from the fourth to fifth decades, especially in South-European countries, often located in the periorbital region. These include malignant forms, Lentigo maligna (LM) and lentigo maligna melanoma (LMM), characterized by growing incidence, and a series of benign simulators, including solar lentigo (SL), pigmented actinic keratosis (PAK), seborrheic keratosis (SK) and lichen planus-like keratosis (LPK). The clinical differential diagnosis of atypical pigmented skin lesions (aPFLs) can be difficult, even for dermatologists, leading to inappropriate skin biopsies with consequent aesthetic impacts. Dermoscopy of the facial area is a specific dermoscopic field that requires dedicated training and proved to increase diagnostic accuracy in dermatologists. Since these lesions are often seen by ophthalmologists at first, we aimed to evaluate the effect of a focused dermoscopy training course on a group of ophthalmologists naïve to the use of a dermatoscope. A set of 80 periorbital pigmented skin lesions with both clinical and dermoscopic images was selected and evaluated by six ophthalmologists before and after a one-day intensive dermoscopic training course. They were required to evaluate 80 periorbital lesions one month before and after a one-day intensive dermoscopic training course, illustrating second-level diagnostic options such as reflectance confocal microscopy (RCM), obtaining a total of 480 evaluations. Specifically, they had to provide, for each case, a punctual diagnosis and a management option among dermoscopic follow-up/skin biopsy/RCM/LC-OCT. Descriptive statistics were carried out, and the accuracy (ACC), sensitivity (SE), and specificity (SP), with their 95% confidence interval (95% CI), were estimated. In the pre-course test, ophthalmologists achieved 84.0% SP, 33.3% SE and 63.7% ACC, while after the course, SE increased by +9% (i.e., 41.7%), SP decreased by 4%, and ACC remained comparable, i.e., 64.6%. In the management study, the percentage of benign lesions for which a close dermoscopic follow-up was suggested significantly decreased (51.6% versus 22.2%), in parallel with an increase in the number of lesions referred for RCM. As for malignant cases, the reduction in responses "close dermoscopic follow-up" decreased from 37.0% to 9.9%, (-27%), in favor of RCM (+15%) and skin biopsy (+12%). The ophthalmologists proved to be very receptive in quickly metabolizing and putting into practice the concepts learned during the one-day intensive dermoscopy training course. Indeed, after only a one-day lesson, they were able to increase their SE by 9% and to improve their management strategy. The present findings highlight the importance of providing training ophthalmologists in dermoscopy during residency programs, in terms of benefits for the correct patient care.

Reflectance confocal microscopy for margin mapping of melanoma of the lentigo maligna type: A systematic review and meta-analysis.

Melanoma of the lentigo maligna (LM) type and its invasive counterpart, lentigo maligna melanoma (LMM), occur in chronically sun-damaged skin and tend to have subclinical extension that makes presurgical margin mapping challenging. Reflectance confocal microscopy (RCM) is a non-invasive imaging modality that enables invivo visualization of the skin at the cellular level, allowing for adequate estimation of LM/LMM margins. We aimed to perform a systematic review and meta-analysis evaluating RCM's performance compared with histopathology in margin mapping of LM/LMM. We searched MEDLINE, Embase, Cochrane, and Clinicaltrials.gov for studies published until July 2023, assessing RCM diagnostic accuracy for presurgical LM/LMM margin delineation. Negative predictive value (NPV; number of true negatives confirmed by histopathology out of all negatives found on RCM) was our primary outcome. Secondary outcomes were proportion of agreement between RCM and histopathology, mean number of stages to clear lesion, sensitivity, and specificity. Of the 955 search results, nine studies (329 participants) were included. Pooled NPV for RCM detection of LM/LMM clear margins was 89.15% (95% CI 80.95-95.46; I2 = 80%). The RCM and histopathology agreement rate was 92.09% (95% CI 84.71-96.07; I2 = 57%). Mean number of stages needed to clear the lesion using RCM was 1.16 (95% CI 1.08-1.23; I2 = 0). Compared with histopathology, RCM sensitivity and specificity were 91.4% (95% CI 82.2-96.1; I2 = 0%) and 95.7% (95% CI 90.7-98; I2 = 68%), respectively. These results support that RCM has a high concordance rate with the gold standard histopathology for presurgical LM/LMM margin mapping, constituting a valuable tool for its management.

In vivo reflectance confocal microscopy role for early to advanced lentigo maligna melanoma spectrum: A systematic review and pooled analysis.

Lentigo maligna (LM) is a growing problem worldwide and the main type of melanoma insitu in some Caucasian populations. It presents as a spectrum from atypical intraepidermal melanocytic proliferation (AIMP) to invasive lentigo maligna melanoma (LMM). Accurate diagnosis and staging are crucial for determining appropriate management strategies. To assess the role of invivo reflectance confocal microscopy (RCM) in differentiating early and advanced stages of lentigo maligna. A systematic search was conducted on Medline, PubMed, Scopus, Web of Science, Proquest Central, Embase, Cochrane and Google Scholar. References of included and excluded studies were reviewed for additional sources. Studies involving RCM for AIMP, LM and LMM diagnosis published until 1 December 2023, were selected for analysis. Publications on other non-invasive imaging techniques, other skin diseases or those addressing only RCM surgical margins and therapeutic response without reporting RCM features were excluded. Each article was reviewed by two experts, with disagreements resolved by a third expert. Data for each RCM feature were pooled, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Features were stratified for architecture, cellular morphology and distribution. Twenty-seven articles involving 303 lesions were included. Features favouring LM over AIMP included (1) Architecture: the presence of non-edged papillae (OR 4.50, 95% CI 1.92-10.52) and (2) Cellular distribution: widespread pagetoid cells and junctional atypical cells (OR 25.06, 95% CI 4.19-148.45) and junctional nests (OR 18.06, 95% CI 3.04-106.32). Features favouring LMM over LM included (1) Architecture: epidermal disarray (OR 5.03, 95% CI 1.90-13.22), junctional disarray (OR 4.19, 95% CI 1.54-11.33) and destroyed collagen fibres (OR 3.91, 95% CI 1.80-8.44) and (2) cellular distribution: widespread pagetoid and junctional atypical cells (OR 2.71, 95% CI 1.27-5.75) and junctional nests (OR 4.48, 95% CI 2.12-9.43). This study identifies the RCM features associated with the LM/LMM spectrum.

Epidemiological, clinical and histological characteristics of melanoma in young adults: a 30-year retrospective study (1993-2022).

Melanoma in young adults significantly impacts the survival of this age group. There are limited studies that analyze melanoma characteristics in young patients. We aimed to describe the epidemiological, clinical, and histological characteristics of melanoma in young adults and their temporal trends over the last decades. A retrospective observational study was conducted, involving 399 melanoma patients aged 18-44, over a 30-year period (1993-2022). Patients were divided into two groups based on their date of diagnosis (period 1, 1993-2007, and period 2, 2008-2022). Age at diagnosis was higher in the most recent period (34.3 vs 37; p=0.001). Over time, there was a reduction in thickness (1 vs 0.68 mm; p=0.01), a rise in melanomas located on the head and neck (6.5% vs 14.8%) and extremities (42.2% vs 45%), along with a decrease on the trunk (51.3% vs 40.2%) (p=0.009); and an increase in lentigo maligna (2.3% vs 5.3%) and superficial spreading melanomas (76.5% vs 84%), along with reduction in nodular types (16.1% vs 5.9%) (p=0.012). Women had, compared to men, higher limb melanoma prevalence (56.3% vs 27.1%; p<0.001), family history (11.7% vs 5.1%; p=0.020), lower thickness (0.69 vs 1.10; p= 0.001) and better prognosis (14.4% vs 20.9% deaths; p=0.012). Melanoma diagnoses in young adults occur at progressively advanced ages, with a rise in melanomas situated on the head and extremities and in histological types linked to prolonged sun exposure. Strategies like minimizing sun exposure from a young age and encouraging self-examination could lead to improved survival rates.

Parallel pigmented network in lentigo maligna: a case series and correlation with in vivo reflectance confocal microscopy.

Lentigo maligna (LM) often poses a diagnostic challenge due to its clinical and dermoscopic mimicry of benign lesions, leading to delayed diagnosis. Focal areas of reticular disruption have been described as one of the earliest dermoscopic signs observed. To describe a novel dermoscopic sign in LM, namely the presence of a parallel pigmented network. Case series of 22 histopathologically-proven LM and lentigo maligna melanoma (LMM), diagnosed between 2018 and 2023, at a tertiary centre. All lesions showed a parallel network upon dermoscopy, in the form of parallel reticular lines, light or dark brown in colour, not emanating from the follicle, with an asymmetrical distribution. Reflectance confocal microscopy (RCM) images were reviewed to correlate these areas. The median age of patients was 73 years old. The majority of lesions were in situ (91%) and extrafacial (82%). Lesions showed minimal signs of atypia other than a parallel network and mostly focal erased areas (100%), followed by perifollicular linear projections (18%) and asymmetrical follicular pigmentation (18%). On RCM, focally areas correlated with atypical junctional thickenings distributed in a parallel fashion (100%) and mitochondria-like structures (23%). Most cases (88%) showed atypical cells in the epidermis, mostly in the form of isolated dendritic cells (41%). Parallel network emerges as a potential dermoscopic sign associated with LM. We hypothesize that in early stages of LM transformation, disruption of the reticular network manifests as parallel lines and/or radial perifollicular lines. Validation with larger studies is warranted.

Lentigo Maligna and Lentigo Maligna Melanoma of the External Ear: Clinical and Dermoscopic Features of 19 Patients.

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).

Comparison of Ophthalmologists versus Dermatologists for the Diagnosis and Management of Periorbital Atypical Pigmented Skin Lesions.

Background/Objectives: Lentigo maligna (LM) and lentigo maligna melanoma (LMM) are significant subtypes of melanoma, with an annual incidence of 1.37 per 100,000 people in the U.S. These skin tumors, often found in photo-exposed areas such as the face, are frequently misdiagnosed, leading to delayed treatment or unnecessary excisions, especially in the elderly. Facial melanocytic skin tumors (lentigo maligna-LM/lentigo maligna melanoma-LMM) and their simulators (solar lentigo, pigmented actinic keratosis, seborrheic keratosis and lichen planus-like keratosis) often affect the periocular region. Thus, their diagnosis and management can involve different medical figures, mainly dermatologists and ophthalmologists. This study aimed to evaluate the ability of ophthalmologists to diagnose and manage pigmented skin lesions of the periorbital area. Methods: A multicentric, retrospective, cross-sectional study on a dataset of 79 periorbital pigmented skin lesions with both clinical and dermoscopic images was selected. The images were reviewed by six ophthalmologists and two dermatologists. Descriptive statistics were carried out, and the accuracy, sensitivity, and specificity, with their 95% confidence interval (95% CI), were estimated. Results: Ophthalmologists achieved a diagnostic accuracy of 63.50% (95% CI: 58.99-67.85%), while dermatologists achieved 66.50% (95% CI: 58.5-73.8). The sensitivity was lower for ophthalmologists in respect to dermatologists, 33.3% vs. 46.9%, respectively. Concerning the case difficulty rating, ophthalmologists rated as "difficult" 84% of cases, while for dermatologists, it was about 30%. Management was also consistently different, with a "biopsy" decision being suggested in 25.5% of malignant lesions by ophthalmologists compared with 50% of dermatologists. Conclusions: Ophthalmologists revealed a good diagnostic potential in the identification of periorbital LMs/LMMs. Given progressive population ageing and the parallel increase in facial/periorbital skin tumors, the opportunity to train new generations of ophthalmologists in the early diagnosis of these neoformations should be considered in the next future, also taking into account the surgical difficulty/complexity of this peculiar facial area.

Lentigo maligna: a comprehensive review on diagnosis and treatment.

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

Enhanced disease-specific survival in lentigo maligna melanoma patients treated with Mohs surgery over wide local excision: A retrospective cohort analysis of the Surveillance, Epidemiology, and End Results database

Enhanced disease-specific survival in lentigo maligna melanoma patients treated with Mohs surgery over wide local excision: A retrospective cohort analysis of the Surveillance, Epidemiology, and End Results database

Successful implementation of handheld reflectance confocal microscopy as the standard of care in the (surgical) management of lentigo maligna (melanoma).

Reflectance confocal microscopy (RCM) has shown promise in predicting surgical outcomes by non-invasively detecting subclinical lentigo maligna (melanoma) (LM/LMM). To assess the effects of presurgical mapping using handheld RCM (HH-RCM) on surgical treatment, follow-up outcomes and management decisions. A total of 117 consecutive LM/LMM cases (2015-2023) were included. The diagnostic accuracy of HH-RCM in detecting subclinical LM and invasive components was evaluated. The primary endpoints included histological margin status and changes in management based on the outcomes of the HH-RCM mapping procedure. Margin and follow-up outcomes were compared to a historical cohort before HH-RCM was introduced in our center (n = 94) (2003-2014). HH-RCM detected subclinical LM in 60% (n = 60) of cases. The median mapping duration was 14 min (range 4-50). In 27% (n = 33), the mapping procedure resulted in modified management, the majority consisting of limited surgery with adjuvant imiquimod (n = 15) or imiquimod monotherapy (n = 14). The remaining cases (n = 84) underwent HH-RCM-assisted surgery. Histological margins were cleared in 96.5% of the patients with a median histological margin of 3.0 mm, significantly higher than 81% in the historical cohort (median 2.0 mm) (p = 0.001). The sensitivity and specificity for detecting the extent of subclinical LM were 94% (95% CI 80.4-99.3) and 84% (95% CI 70.3-92.7), respectively. The negative predictive value for the detection of LMM was 94% (95% CI 84.4-97.7), and 75% of the initially missed LMM (n = 12) were identified during the HH-RCM mapping procedure. The study cohort had a 1.6% local recurrence rate compared with 25% in the historical cohort. Integrating HH-RCM as the standard of care could lead to more personalized treatment strategies for LM/LMM and allows for the selection of patients suitable for nonsurgical treatment.

Persistent poverty impacts survival and National Comprehensive Cancer Network guideline-concordant care for patients with melanoma.

1598 Background: Based on guidelines from the National Comprehensive Cancer Network (NCCN), sentinel lymph node biopsy (SLNB) should be offered to patients with high-risk stage IB or stage II melanoma and adjuvant systemic therapy is recommended for patients with stage III disease. Persistent poverty census tracts are defined as areas where at least20% of residents were poor as measured by each of the 1980, 1990, 2000 censuses and 2007 American Community Survey 5-year average. The aim of this study was to describe the association between persistent poverty and adherence to NCCN guidelines and cancer-specific survival in patients with cutaneous melanoma. Methods: Patients diagnosed with melanoma from 2006-2018 were identified in Survival, Epidemiology, and End Results (SEER) Program registries. The analytic cohort was restricted to patients with superficial spreading melanoma, nodular melanoma, malignant melanoma with regression, lentigo malignant melanoma, and acral lentiginous melanoma. Patient demographics such as age, race, and ethnicity and tumor characteristics associated with stage at diagnosis were analyzed using adjusted regression analyses for patients of all melanoma stages. Demographics and tumor characteristics associated with receipt of SLNB were analyzed amongst pathologic stage IB and II cases, and demographics and tumor characteristics associated with receipt of adjuvant systemic therapy were analyzed amongst stage III cases. Kaplan-Meier curves and adjusted accelerated failure time models were used to examine disparities in cancer-specific survival. Results: Of 127,308 total patients, 3.13% (n=3994) lived in census tracts with persistent poverty. In adjusted analyses, persistent poverty was an independent predictor of later pathologic stage at diagnosis (OR 1.32 [95% CI 1.21-1.44] p&lt;0.001). Persistent poverty was also associated with lower likelihood of receiving SLNB according to NCCN guidelines (OR 0.717 [SE 0.072] p&lt;0.01) and with worse cancer-specific survival (HR 1.25 [1.06-1.47], p=0.008) when controlling for age, race, ethnicity, pathologic stage at diagnosis, and histology. In univariable models persistent poverty was associated with increased odds of receiving systemic therapy, but this relationship was not significant on multivariable analysis. Conclusions: Patients from areas with persistent poverty had a later pathologic stage at diagnosis, were less likely to receive a SLNB according to NCCN guidelines, and had worse cancer-specific survival. Efforts to better define and resolve disparities in the treatment and survival of patients with melanoma are warranted.

Association of miR-146a-5p and miR-21-5p with Prognostic Features in Melanomas.

Cutaneous melanoma (CM) is one of the most lethal tumors among skin cancers and its incidence is rising worldwide. Recent data support the role of microRNAs (miRNAs) in melanoma carcinogenesis and their potential use as disease biomarkers. We quantified the expression of miR-146a-5p and miR-21-5p in 170 formalin-fixed paraffin embedded (FFPE) samples of CM, namely 116 superficial spreading melanoma (SSM), 26 nodular melanoma (NM), and 28 lentigo maligna melanoma (LMM). We correlated miRNA expression with specific histopathologic features including Breslow thickness (BT), histological subtype, ulceration and regression status, and mitotic index. miR-146a-5p and miR-21-5p were significantly higher in NM compared to SSM and LMM. The positive correlation between miR-146a-5p and miR-21-5p expression and BT was confirmed for both miRNAs in SSM. Considering the ulceration status, we assessed that individual miR-21-5p expression was significantly higher in ulcerated CMs. The increased combined expression of the two miRNAs was strongly associated with ulceration (p = 0.0093) and higher mitotic rate (≥1/mm2) (p = 0.0005). We demonstrated that the combination of two-miRNA expression and prognostic features (BT and ulceration) can better differentiate cutaneous melanoma prognostic groups, considering overall survival and time-to-relapse clinical outcomes. Specifically, miRNA expression can further stratify prognostic groups among patients with BT ≥ 0.8 mm but without ulceration. Our findings provide further insights into the characterization of CM with specific prognostic features. The graphical abstract was created with BioRender.com.

Lentigo Maligna Treatment-An Update.

Lentigo maligna (LM) is a melanoma in situ that is prevalent in chronically sun-damaged skin. Characterized by a slow growth pattern and high mutation rates due to chronic UV exposure, LM poses diagnostic and therapeutic challenges, particularly given its tendency to mimic other skin lesions and its occurrence in cosmetically sensitive areas. Its diagnosis is based on an integrated approach using dermoscopy and reflectance confocal microscopy (RCM). Despite its slow progression, LM can evolve into lentigo maligna melanoma (LMM), making its treatment necessary. Treatment modalities encompass both surgical and non-surgical methods. Surgical treatments like Wide Local Excision (WLE) and Mohs Micrographic Surgery (MMS) aim for clear histological margins. WLE, a standard melanoma surgery, faces challenges from LM's subclinical extensions, which increase the recurrence risk. MMS, effective for large or poorly defined lesions, is defined by precise margin control while considering cosmetic outcomes. Non-surgical options, including radiotherapy and imiquimod, are alternatives for non-surgical candidates. Radiotherapy has been effective since the 1950s, offering good control and cosmetic results, especially for older patients. Imiquimod, an immunomodulator, shows promise in treating LM, though its application remains off-label. The increasing incidence of LM/LMM necessitates a balance in treatment choices to minimize recurrence and maintain cosmetic integrity. A multidisciplinary approach, integrating clinical examination with dermoscopy and RCM and histological assessment, is essential for accurate diagnosis and effective LM management.

Nevus-associated Lentigo Maligna and Lentigo Maligna Melanoma, Clinicopathological Features.

Nevus-associated lentigo maligna and lentigo maligna melanoma (NALMM) are rarely described in the literature and are considered an incidental finding. This study aimed to evaluate the frequency of NALMM and its clinicopathological features. A total of 201 histopathology reports were reviewed and among them 20% of the samples corresponded to NALMM, with females overrepresented in this group (p = 0.02). A significant association was also observed between NALMM with the presence of multiple nevi (p = 0.01), and dysplastic nevi (p = 0.04). Moreover, the risk of developing a second melanoma of nevus-associated type was 4.3 times higher in patients with NALMM. These results indicate that NALMM is more frequent than previously reported, suggesting that the associated nevus could interact or even act as a precursor for LM/LMM. Future studies with larger samples allied to techniques like confocal microscopy and molecular analysis are essential to determine this biological link between nevus and LM/LMM.

Double Immunohistochemical Labelling of PRAME and Melan A in Slow Mohs Biopsy Margin Assessment of Lentigo Maligna and Lentigo Maligna Melanoma.

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.

Risk factors of lentigo maligna as compared to other melanoma subtypes.

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. 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. 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. 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. 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.

Clinical and histopathological features of lentigo maligna and lentigo maligna melanoma: a retrospective analysis in Korea.

Lentigo maligna (LM) and lentigo maligna melanoma (LMM) are rare in Asian countries. The histopathological diagnosis of LM is often challenging, and misdiagnosis is common. Although histopathologic features of LM/LMM are known, statistical analysis of them were scarcely reported. In this study, we aimed to investigate the histopathological characteristics of LM/LMM in Korean patients and identify key histopathological clues distinguishing LM from benign lentigo. We performed a retrospective study of the clinical and histopathological features of patients diagnosed with LM/LMM at our center between 2011 and 2022. We assessed the histopathological features in each case based on 16 pathological criteria according to previous literature. Pathologically confirmed cases of benign lentigo were analyzed for comparison. Twenty-one patients (10 with LM and 11 with LMM) were analyzed. Several statistically significant difference existed between the features of LM and benign lentigo (N = 10), including asymmetry of overall structure (p < 0.001), cytologic atypia (p < 0.001), predominant single-cell proliferation (p < 0.001), melanocytic nests (p = 0.033), melanocytes forming rows (p = 0.003), pagetoid spread of melanocytes (p < 0.001), and hair follicle invasion by atypical melanocytes (p < 0.001). Degree of solar elastosis was more severe in group "Age ≥ 60" (p = 0.015), and group "Diameter ≥ 20 mm" (p = 0.043). Presence of elongated rete ridges were less common in the older than 60 age group (p = 0.015) and group "Diameter ≥ 20 mm." Invasion was associated with mitosis (p = 0.001, OR 49.285), multinucleated cells (p = 0.035, OR 17.769), and degree of lymphocyte infiltration (p = 0.004). This study investigated the clinical and histopathologic characteristics of LM and LMM in Koreans. Although histopathological diagnosis is challenging, especially in the early stages of LM, our data showed essential histopathological changes in architectural, cytological, and dermal patterns. Considering the potential aggressiveness of LM/LMM, it is essential to recognize its histopathological features and provide timely management.