Incomplete Excision Rate for Lentigo Maligna and Associated Risk Factors.

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.

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).

Utilizing deep learning model for assessing melanocytic density in resection margins of lentigo maligna.

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.

Extrafacial lentigo maligna: A progression model and enhanced diagnostic techniques using dermatoscopy and reflectance confocal microscopy.

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.

Radiation and Melanoma: Where Are We Now?

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.

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.

Melanocyte Density in the Diagnosis of Melanoma In Situ in Sun-Damaged Skin.

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.

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

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.

Review on the Role of Paraffin-embedded Margin-controlled Mohs Micrographic Surgery to Treat Skin Tumors.

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.

Incidence trends of lentigo maligna and lentigo maligna melanoma in the United States from 2000 to 2019.

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.

The combination of dermoscopy and reflectance confocal microscopy increases the diagnostic confidence of amelanotic/hypomelanotic lentigo maligna.

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.

Dermoscopy of Lentiginous Melanomas and Equivocal Benign Pigmented Macules of the Scalp: A Case-Control Multicentric Study.

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.

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.

Lentigo maligna and lentigo maligna melanoma in patients younger than 50†years: a multicentre international clinical-dermoscopic study.

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.

Melanoma clinicopathological groups characterized and compared with dermoscopy and reflectance confocal microscopy.

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.

Sentinel lymph node biopsy for lentigo maligna melanoma under local anaesthesia.

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.

Perifollicular linear projections: A dermatoscopic criterion for the diagnosis of lentigo maligna on the face.

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.

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.