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.

Is sentinel lymph node biopsy needed for lentigo maligna melanoma?

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.

The limited value of sentinel lymph node biopsy in lentigo maligna melanoma: A nomogram based on the results of 29 years of the nationwide dutch pathology registry (PALGA).

BACKGROUND: Lentigo maligna melanoma (LMM) predominantly presents in the head and neck of the elderly. The value of sentinel lymph node biopsy (SLNB) for LMM patients remains to be determined, as the reported average yield of positive lymph nodes is less than 10%. In this nationwide cohort study, we wanted to identify LMM patients with an increased risk of SLNB-positivity. METHODS: LMM with an SLNB indication according to the 8th AJCC melanoma guidelines were retrospectively identified from the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA). A penalized (LASSO) logistic regression analysis was performed to determine the optimal combination of clinicopathological factors to predict a positive SLNB. RESULTS: Between 1991 and 2020, 1989 LMM patients met our inclusion criteria. SLNB was performed in 16.7% (n = 333) and was positive in 7.5% (25/333). The false-negative rate was 21.9%. Clinically detectable regional lymph node (LN) metastases were found in 1.3% (n = 25). Clinicopathological characteristics best predictive for SLNB-positivity (Odds ratio; 95% CI) were age (0.95; 0.91-0.99), ulceration 1.59 (0.44-4.83), T4-stage (1.81; 0.43-6.2), male sex (1.97; 0.79-5.27), (lymph)angioinvasion (5.07; 0.94-23.31), and microsatellites (7.23; 1.56-32.7) (C-statistic 0.75). During follow-up, regional LN recurrences were detected in 4.2% (83/1989) of patients, of which the majority (74/83) had no evidence of regional LN metastases at baseline. CONCLUSION: Our findings confirm the limited SLNB-positivity in LMM patients. Based on the identified high-risk clinicopathological features, a nomogram was developed to predict the risk of a positive SLNB.

Dermoscopy of atypical pigmented lesions of the face: Variation according to facial areas.

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.

Periocular invasive melanoma manifestation in a patient using bimatoprost: case report and literature review.

Prostaglandin F2a 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.

A cohort analysis of surgically treated primary head and neck lentigo maligna (melanoma): Prognostic value of melanoma subtype and new insights in the clinical value of guideline adherence.

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.

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

Introduction: 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. Methods: 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. Results: 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). Conclusion: 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.

Pigmented Macules on the Head and Neck: A Systematic Review of Dermoscopy Features.

Introduction: Differentiating early melanoma from other flat pigmented lesions on the head and neck is challenging both clinically and dermoscopically, partly due to the wide differential diagnosis and the lack of specific diagnostic algorithms. Objectives: To review publications covering the dermoscopic features of pigmented macules on the head and neck. Methods: Embase and PubMed (Medline) database from January 2015 to January 2021 were searched using a four-step search. Keywords used were dermoscopy/dermatoscopy or epiluminescence microscopy, lentigo maligna, lentigo maligna melanoma, lichen-planus-like-keratosis, solar lentigo, seborrheic keratosis, pigmented actinic keratosis (PAK), pigmented Bowen disease (pBD), pigmented intraepidermal carcinoma (pIEC) and head and neck. Results: The commonest reported dermoscopic features of facial melanoma were irregular dots, atypical dots/globules, asymmetric pigmented follicular openings, rhomboid gray/black structures, increased vascular network, brown globules/dots and a pattern of circles. Pseudopods, radial streaming, blue white veil, irregular blotches, scar-like depigmentation and atypical pigment network were recorded in low frequencies. For PAK, pBD and pIEC perifollicular erythema, white/yellow surface scale, linear wavy vessels around hair follicles, hair follicular openings surrounded by a white halo, evident follicles or follicular or keratotic plugs, rosette sign and sharply demarcated borders were the salient features. Conclusions: Further studies are needed to determine the dermoscopic criteria for pigmented melanocytic and non-melanocytic lesions on the head and neck. Furthermore, there is a gap in the knowledge of site-specific dermoscopic features on specific sites, namely ears, nose, cheeks, scalp and neck which will also benefit from further studies.

Combined Mohs Micrographic Surgery in a Collision Tumor.

We present the case of a 73-year-old male patient with a collision tumor in the right ear, consisting of a basal cell carcinoma and melanoma in situ. He was managed with Mohs micrographic surgery combining paraffin-embedded sections and frozen sections. Multiple surgical stages were required to obtain tumor-free margins. The surgical defect was reconstructed by plastic surgery, achieving the preservation of the ear. The technique of combining two processing sections is useful in the treatment of the collision of basal cell carcinoma with malignant melanoma.

Clinical features associated with the invasive component in lentigo maligna of the head and neck: A retrospective study of 175 cases.

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

Clinical findings are not helpful in detecting lentigo maligna melanoma in patients with biopsy-proven lentigo maligna.

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.

Introduction to Head and Neck Melanoma: A Dermatologist's Perspective.

Melanoma is often initially evaluated by the dermatologist. A methodical evaluation requires complete history and detailed clinical physical examination and appropriate decisions regarding biopsies. Accurate diagnosis and staging require clinicopathologic correlation and an excellent relationship with the dermatopathologist. Subsequent definitive treatment may be managed entirely by the dermatologist or might require a multidisciplinary team of specialists.

The impact of haematoxylin-eosin staining and immunohistochemistry of lentigo maligna and lentigo maligna melanoma margins on local recurrence

Background: Local recurrence of lentigo maligna melanoma (LMM) and lentigo maligna (LM) continue to be challenging following surgical treatment and aftercare. Objectives: To investigate haematoxylin-eosin staining and immunohistochemistry of the tumour margins of LM and LMM and evaluate the impact of these data on local recurrence. Materials & Methods: In total, 489 tumours were included in this retrospective single-centre study, among them 199 (40.7%) LMs and 290 (59.3%) LMMs. All tumours were excised using micrographiccontrolled surgery. Additional immunohistochemistry staining of the tumour margins was performed in 35 specimens (7.2%). Results: Based on haematoxylin-eosin staining alone, 82/454 tumours (18.1%) were shown to develop local recurrence compared to 3/35 tumours (8.6%) when additional immunohistochemistry was performed. Conclusion: Following micrographic-controlled surgery, the additional use of immunohistochemistry of tumour margins of LM/LMM reduced the risk of local recurrence, although this was not statistically significant.

Indoor Tanning and the Risk of Overall and Early-Onset Melanoma and Non-Melanoma Skin Cancer: Systematic Review and Meta-Analysis.

The aim of this study was to examine the association between indoor tanning use and the risk of overall and early-onset (age < 50) melanoma and non-melanoma skin cancer (NMSC). To evaluate the association between indoor tanning and skin cancer, a systematic review of the literature published until July 2021 was performed using PubMed, EMBASE, and MEDLINE. Summary relative risk (RR) from 18 studies with 10,406 NMSC cases and 36 studies with 14,583 melanoma cases showed significant association between skin cancer and indoor tanning (melanoma, RR= 1.27, 95% CI 1.16-1.39; NMSC, RR = 1.40, 95% CI 1.18-1.65; squamous cell carcinoma (SCC), RR = 1.58, 95% CI 1.38-1.81; basal cell carcinoma (BCC), RR = 1.24, 95% CI 1.00-1.55). The risk was more pronounced in early-onset skin cancer (melanoma, RR = 1.75, 95% CI 1.14-2.69; NMSC, RR = 1.99, 95% CI 1.48-2.68; SCC, RR = 1.81, 95% CI 1.38-2.37; BCC, RR = 1.75, 95% CI 1.15-2.77). Moreover, first exposure at an early age (age ≤ 20 years) and higher exposure (annual frequency ≥ 10 times) to indoor tanning showed increasing risk for melanoma (RR = 1.47, 95% CI 1.16-1.85; RR = 1.52, 1.22-1.89) and NMSC (RR = 2.02, 95% CI 1.44-2.83; RR = 1.56, 95% CI 1.31-1.86). These findings provide evidence supporting primary prevention policies regulating modifiable behaviors to reduce the additional risk of skin cancer among younger adults.

Lentigo Maligna.

Lentigo maligna (LM) is a melanocytic neoplasm found on chronically sun-exposed areas of the body, particularly the head and neck. It commonly occurs in the elderly and has been referred to as a "senile freckle." It has also been termed "Hutchinson melanotic freckle," as it was first described by John Hutchinson in 1892. LM is defined as melanoma in situ and thus confined to the epidermis. LM lesions that invade the dermis are termed lentigo maligna melanoma, 1 of the 4 subtypes of malignant melanoma.

Folliculotropism in head and neck lentigo maligna and lentigo maligna melanoma.

BACKGROUND: Lentigo maligna (LM) and lentigo maligna-melanoma (LMM) are histotypes of melanoma arising in skin with cumulative solar radiation damage. The extension of atypical melanocytes to the hair follicle (folliculotropism) is a histopathological feature of LM/LMM. Its role has not been totally clarified, but it may be correlated to treatment response in LM or to progression in LMM. OBJECTIVE: This retrospective, multicentric study aims to identify dermatoscopic features associated with folliculotropism in LMs/LMMs. PATIENTS AND METHODS: We analyzed cases of head and neck LMs/LMMs diagnosed between 2005-2014 at Melanoma Units, University of Bologna/Modena/Florence/Siena (Italy), Nice (France): 25 LMs and 73 LMMs were included. RESULTS: Grey circles (44 %) indicated an isthmic/bulb level of involvement, which were completely absent in the infundibular LM lesions (P = 0.041). In the group of LMMs, light/dark brown pseudonetwork and light brown structureless areas were an indicator of diffuse distribution of malignant melanocytes in the follicular units (P < 0.001 and P = 0.001, respectively), while grey circles indicated focal or diffuse distribution (P < 0.001). CONCLUSIONS: A better understanding of the extension of malignant melanocytes is helpful, aiding clinicians in their decision to perform a radical excision or obtaining a biopsy in the most invasive area of the lesion, which includes potential folliculotropism.

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

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