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.

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.

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.

Is reflectance confocal microscopy useful in the differential diagnosis of extra facial lentigo maligna? A retrospective multicentric case-control study.

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.

Surgical margin mapping for lentigo maligna and lentigo maligna melanoma: traditional technique (visual inspection with dermoscopy) versus combined paper tape and reflectance confocal microscopy technique.

BACKGROUND: The detection of subclinical margin in lentigo maligna/lentigo maligna melanoma (LM/LMM) can be challenging for the dermatologist. Reflectance confocal microscopy (RCM) enables to observe in vivo atypical melanocytes beyond the clinical margins. The aim of this study is to establish which of these methods (clinical examination and dermoscopy versus "Paper tape - RCM") is more precise to define the lesion margin and to reduce the number of re-intervention and overtreatments in cosmetically sensitive areas. METHODS: Fifty-seven cases of LM/LMM were analyzed during 2016-2022. Pre-surgical mapping procedures in 32 lesions were effectuated with dermatoscopy. Furthermore, pre-surgical mapping procedures in 25 lesions were effectuated with RCM and paper tape. RESULTS: RCM method's accuracy to detect subclinical margins was 92.0%. In 24 of 25 cases, the lesions were excised completely during the first intervention. In 20 of 32 cases analyzed with dermoscopy, a second surgical intervention was effectuated. CONCLUSION: The RCM paper method allows us to delineate subclinical margin more accurately and reduce overtreatment, especially in sensitive areas, such as the face and neck.

Lentigo maligna melanoma mapping using reflectance confocal microscopy correlates with staged excision: A prospective study.

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.

Amelanotic/hypomelanotic lentigo maligna: Dermoscopic and confocal features predicting diagnosis.

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.

Dermoscopic changes in 22 extrafacial in situ and invasive lentiginous melanomas

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.

Complex management of lentigo maligna in the setting of chrysiasis, argyriasis, and tattoo using in vivo reflectance confocal microscopy.

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.

Effect of reflectance confocal microscopy compared to dermoscopy in the diagnostic accuracy of lentigo maligna: A meta-analysis.

INTRODUCTION: Many concerns were raised about the sensitivity and specificity outcome of reflectance confocal microscopy compared to dermoscopy for the diagnosis of lentigo maligna. However, the reported relationships between their sensitivity and specificity were variable. Our meta-analysis was performed to clarify this relationship. METHODS: A systematic literature search up to July 2020 was performed and six included studies had 479 subjects at the baseline with 294 undergoing lentigo maligna diagnoses. They were reporting relationships between sensitivity and specificity outcome of reflectance confocal microscopy compared to dermoscopy for the diagnosis of lentigo maligna. Mean difference (MD) with 95% confidence intervals (CIs) was calculated to evaluate the prognostic role of the sensitivity and specificity of reflectance confocal microscopy compared to dermoscopy for the diagnosis of lentigo maligna using the continuous method with a random or fixed-effect model. RESULTS: Reflectance confocal microscopy was significantly related to higher specificity (MD, 19.10; 95% CI, 0.93-37.28, P = .04) compared to dermoscopy in lentigo maligna diagnosis. However, reflectance confocal microscopy was only relatively but not significantly related to higher sensitivity (MD, 14.56; 95% CI, 0.29-28.83, P = .05) compared to dermoscopy in lentigo maligna diagnosis. CONCLUSIONS: Based on this meta-analysis, the reflectance confocal microscopy compared to dermoscopy in lentigo maligna diagnosis had a significantly higher specificity and relatively higher sensitivity. This relationship forces us to recommend reflectance confocal microscopy in lentigo maligna diagnosis for better outcomes and to avoid any possible false-negative results. Further studies are required.

Reflectance confocal microscopy and its role in the follow-up of a topical treatment for lentigo maligna.

BACKGROUND: In recent years, there has been an ongoing interest in topical treatment for lentigo maligna (LM) as imiquimod 5% cream owing to the localization of this tumor and the advanced age of patients; however, the efficacy of imiquimod 5% cream is controversial, and the rate of local relapses is about 25-53%. Reflectance confocal microscopy (RCM) is a noninvasive diagnostic tool useful not only for diagnostic purpose but also for monitoring the response to the local treatment of LM. Our aim was to demonstrate the role of RCM in the follow-up of a topical treatment with imiquimod 5% cream in clinical practice. METHODS: We report three patients with histopathologically confirmed LM who were not candidates for surgery and were successfully treated with imiquimod 5% cream. In such patients, dermatoscopic images and reflectance confocal microscopy were useful to evaluate treatment response and to verify long-term clinical benefits during the follow-up visits. RESULTS: No relapses were observed in our patients 18 months after the end of treatment; although, continuous follow-up visits are needed in these patients. CONCLUSIONS: In the case series presented herein, we highlight the importance of RCM as a noninvasive tool to monitor the efficacy of imiquimod to treat LM during and after treatment. Detailed confocal images of two of our patients allowed us to establish the persistence of atypical cells and to continue treatment, although clinical and dermatoscopic examinations showed "apparent complete remission" after the first cycle of therapy.