Flat scalp melanoma dermoscopic and reflectance confocal microscopy features correspond to histopathologic type and lesion location.

BACKGROUND: Dermoscopy and Reflectance Confocal Microscopy (RCM) features of scalp melanoma according to lesion location and histopathology have not been fully investigated. OBJECTIVES: To reveal dermoscopic and RCM features of scalp melanoma according to lesion location and histopathology. METHODS: We retrospectively retrieved images of suspicious, atypical excised, flat melanocytic lesions of the scalp, assessed on dermoscopy and RCM at five centres, from June 2007 to April 2020. Lesions were classified according to histopathological diagnoses of nevi, lentigo maligna melanoma (LM/LMM) or superficial spreading melanoma (SSM). Clinical, dermoscopic and RCM images were evaluated; LM/LMM and SSM subtypes were compared through multivariate analysis. RESULTS: Two hundred forty-seven lesions were included. In situ melanomas were mostly LM (81.3%), while invasive melanomas were mostly SSM (75.8%). Male sex, baldness and chronic sun-damaged skin were associated with all types of melanomas and in particular with LM/LMM. LMs were mostly located in the vertex area and SSM in the frontal (OR: 8.8; P < 0.05, CI 95%) and temporal (OR: 16.7; P < 0.005, CI 95%) areas. The dermoscopy presence of pseudo-network, pigmented rhomboidal structures, obliterated hair follicles and annular-granular pattern were associated with LM diagnoses, whereas bluish-white veil was more typical of SSM. Observations on RCM of atypical roundish and dendritic cells in the epidermis were associated with SSM (42.4%) and dendritic cells with LM (62.5%) diagnoses. Folliculotropism on RCM was confirmed as a typical sign of LM. CONCLUSIONS: Flat scalp melanomas reveal specific dermoscopic and RCM features according to histopathologic type and scalp location.

Nodular skin lesions: correlation of reflectance confocal microscopy and optical coherence tomography features.

BACKGROUND: Nodular lesions have common clinical appearance but different prognoses. Differential diagnosis between melanoma (MM), basal cell carcinoma (BCC) and dermal naevus (DN) poses a challenge in clinical practice. Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) are promising non-invasive imaging techniques, potentially able to decrease redundant biopsies. RCM allows in vivo visualization of skin down to the papillary dermis at almost histological resolution, while OCT, particularly dynamic OCT (D-OCT), provides images deeper within the dermis and reveals the vascular pattern. OBJECTIVES: To identify correlating features observed with RCM and OCT associated with the different nodular lesion diagnoses. METHODS: We retrospectively assessed 68 nodular lesions (30 MM, 20 BCC and 18 DN) with RCM and subsequently OCT. At the end of the study, evaluations were matched with histopathological diagnosis and statistical analysis was performed. RESULTS: In MM, 57% (17/30) evidenced both cerebriform nests at RCM and icicle-shaped structures at OCT, with higher average Breslow index. In 80% of BCCs with basaloid islands at RCM, OCT showed ovoid structures. More than half of DN (56%) showed hyporeflective nests at OCT and either dense nests or dense and sparse nests at RCM. CONCLUSIONS: The combined use of RCM and OCT offers a better understanding of the morphological architecture of nodular lesions, correlating RCM parameters with OCT and vice versa, assisting in turn with early differential diagnosis of malignant and benign nodular lesions. The correlation between icicle-shaped structures and cerebriform nests in MM and their association with Breslow index requires future research.

A comparative dermoscopic and reflectance confocal microscopy study of naevi and melanoma with negative pigment network.

BACKGROUND: Negative pigment network (NPN) is a dermoscopic structure observed more frequently among melanomas than naevi. Precise tissue correlates of NPN are still elusive. OBJECTIVE: To describe the reflectance confocal microscopy (RCM) findings underlying NPN in melanocytic neoplasms. METHODS: We retrospectively identified all melanocytic neoplasms displaying dermoscopic NPN that were imaged with RCM and subsequently biopsied between 2011 and 2015. Images from study lesions (n = 50) were evaluated for dermoscopic and RCM Criteria. Histopathological correlational study was performed in a subset of cases (n = 15). RESULTS: The study data set consisted of 21 melanomas (42%) and 29 naevi (58%). Melanomas showed more frequently irregularly shaped globules than naevi (62% vs. 28%, P = 0.03); NPN also tended to be more asymmetrically located among melanomas (86%) than naevi (62%), albeit not significant (P = 0.06). Under RCM, we observed three patterns of dermal papillae (DP): (i) 'Dark DP' - whereby DP were devoid of nests and often surrounded by a junctional proliferation as thick-Rings - this pattern was less common among melanomas (n = 10, 48%) than naevi (n = 23, 79%, P = 0.02); (ii) 'Bulging DP' - whereby junctional nests of melanocytes protrude into the DP, often in association with junctional proliferation as Meshwork - with comparable frequency among melanomas (n = 12, 57%) and naevi (n = 23, 79%, P = 0.09) and (iii) 'Expanded DP' - whereby junctional and/or dermal nests filled and expanded the DP, often in association with dermal-epidermal junction (DEJ) Clod pattern - seen more commonly among melanomas (n = 15, 71%) than naevi (n = 6, 21%, P < 0.001). Dermoscopy-RCM correlation and comparison to histopathological findings show that the hypo-pigmented lines of NPN correlate with broadened epidermal retes, which often show overlying surface dells and wedge-shaped hypergranulosis, while the pigmented globules of NPN correlate with a predominantly-junctiona of melanocytes along and between the elongated retes. CONCLUSIONS: Dermoscopic NPN correlates with three DEJ RCM patterns with differing frequency between naevi and melanomas.

Seborrheic keratoses mimicking melanoma unveiled by in vivo reflectance confocal microscopy.

BACKGROUND: Seborrheic keratoses (SebK) with atypical dermoscopy presentation are increasingly reported. These lesions do not exhibit typical dermoscopy features of SebK and sometimes mimic melanoma, thus complicating the differential diagnosis. Reflectance confocal microscopy (RCM) is a non-invasive tool, which allows an in vivo imaging of the skin. The study objectives were to evaluate the agreement between RCM classification and histological diagnoses, and the reliability of well-known RCM criteria for SebK in the identification of SebK with atypical dermoscopy presentation. MATERIALS AND METHODS: We retrospectively analysed at RCM excised lesions presenting in dermoscopy ≥1 score at revisited 7-point checklist. The study population consisted of cases showing no melanocytic RCM findings. Lesions were investigated for distinct non-melanocytic RCM features, blinded from histopathology diagnoses. Histopathology matching was then performed before statistical analysis. RESULTS: The study consisted of 117 cases, classified at RCM as SebK (71 cases), dermatofibroma (18 cases), basal cell carcinoma (13 cases), squamous cell carcinoma (2 cases), and "non-specific" (13 cases). Overall K strength of agreement at histopathology matching proved 0.76. Of the 71 cases classified at RCM with SebK, agreement was achieved in 97%. CONCLUSION: Reflectance confocal microscopy classification proved high agreement with histopathology for SebK with atypical dermoscopy presentations, allowing an early differential diagnosis. RCM features in this group of lesions were similar to those described for typical cases of SebK, and may assist clinician therapy decision making, whilst avoiding unnecessary excisions.

Reflectance confocal microscopy and optical coherence tomography for the diagnosis of bullous pemphigoid and pemphigus and surrounding subclinical lesions.

BACKGROUND: Diagnosis of bullous pemphigoid (BP) and pemphigus is based on clinical features, histology, immunofluorescence and laboratory data. OBJECTIVES: To evaluate features of BP and pemphigus at reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in order to provide a rapid non-invasive bed-side diagnosis. Secondary objective was to evaluate the detectability of clinically non-visible lesions. METHODS: This was an observational, retrospective, multicentre study in which patients with suspicious lesions for BP or pemphigus underwent clinical assessment, RCM, OCT, blood tests and skin biopsy for histological and direct immunofluorescence examinations from January 2014 to December 2015. A total of 72 lesions in 24 selected patients were evaluated. Additionally, apparently unaffected skin at two different distances [near (1-2 cm) and far (2-3 cm)] from each lesion was examined to test subclinical lesion detectability. RESULTS: RCM was able to detect subepidermal and intra-epidermal blisters, respectively, in 75% and 50% of the patients affected by BP and pemphigus. At OCT, the exact blister level was identified in all patients. Acantholytic cells were observed only at RCM in pemphigus (62.5%). Fibrin deposition inside the blisters was only found in BP, evidenced both at RCM and OCT. Among patients with BP, subclinical blisters were detected in nine (9.4%) clinically healthy skin, while among patients with pemphigus were observed in 10 (20.8%) apparently unaffected skin. CONCLUSION: RCM and/or OCT provide useful information for a rapid diagnosis of BP and pemphigus and for the identification of biopsy site. Combined use of RCM and OCT is optimal because associates the higher resolution of RCM with the greater penetration depth of OCT. OCT could be an optimal tool for treatment monitoring, especially in the cases of subclinical lesions. However, histopathologic and immunologic examinations remain the gold standard for establishing the final diagnosis.

Dynamic optical coherence tomography of skin blood vessels - proposed terminology and practical guidelines.

BACKGROUND: Dynamic optical coherence tomography (D-OCT) has recently been introduced in dermatology. In contrast to 'Standard' OCT imaging, which exclusively relies on the morphological analysis of the tissue, D-OCT allows the in vivo visualization of blood flow. Preliminary D-OCT data showed differences in the vascularization of nevus to melanoma transition, suggesting that this technology may help to differentiate between benign and malignant lesions. OBJECTIVE: Several factors may influence the quality of D-OCT imaging. Therefore, standard operating procedures as well as a common terminology are required for better validation and comparison of the images. METHODS: Here, we present practical guidelines for optimal image acquisition and a proposed terminology on vascular patterns observed by D-OCT. RESULTS: Dynamic OCT allows the morphologic distinction of different vascular shapes (e.g. dots, blobs, curves, lines), their distribution and organization within skin lesions. CONCLUSION: D-OCT adds functional information on skin microvasculature and the vascular networks within lesions.

Reinterpreting dermoscopic pigment network with reflectance confocal microscopy for identification of melanoma-specific features.

BACKGROUND: Pigment network is an important dermoscopic feature for melanocytic lesions, but alterations in grid line thickness are also observed in melanomas. OBJECTIVE: To investigate features of thick, thin and mixed pigment networks at dermoscopy and their respective features at reflectance confocal microscopy (RCM) for differential diagnosis, correlated with histology. METHODS: All melanocytic lesions with histological diagnosis, evaluated between January 2010 and May 2014, were enrolled and classified according to dermoscopy evaluation of the pigment networks: thin, thick and mixed. RESULTS: Thin network in melanoma was characterized by a honeycombed pattern (P < 0.001), dendritic cells (P < 0.001), atypical ringed pattern (P = 0.035) and structureless area (P = 0.012), whereas round cells (P < 0.001), dendritic cells (P < 0.001) and atypical meshwork pattern (<0.001) characterized thick network in melanoma. Mixed network type in melanoma shared honeycombed (P = 0.049) and typical ringed patterns (P = 0.045) in the thin area and round cells (P < 0.001) and atypical meshwork pattern (P < 0.001) in the thick area. Thin network in nevi was characterized by cobblestone (P < 0.001) and typical ringed patterns (P = 0.035), whereas thick network in nevi showed a typical meshwork pattern (P < 0.001). Mixed nevi shared the same features and patterns, but more frequently with inflammatory infiltrate (P = 0.047). CONCLUSION: Differential diagnosis between melanocytic lesions (nevi or melanoma) in thin, thick and mixed pigment networks observed at dermoscopy can be assisted by RCM to improve diagnostic accuracy.

The smart approach: feasibility of lentigo maligna superficial margin assessment with hand-held reflectance confocal microscopy technology.

BACKGROUND: Lentigo maligna may be challenging to clear surgically. OBJECTIVE: To evaluate feasibility of using superficial skin cuts as RCM imaging anchors for attaining negative surgical margins in lentigo maligna. METHODS: Included patients presented with lentigo maligna near cosmetically sensitive facial structures. We evaluated, with hand-held-RCM, microscopic clearance of melanoma beyond its dermoscopically detected edges. Evaluated margins were annotated using shallow skin cuts. If a margin was positive at 'first-step' RCM evaluation, we sequentially advanced the margin radially outward at that segment by 2-mm intervals until an RCM-negative margin was identified. Prior to final surgical excision, we placed sutures at the outmost skin cuts to allow comparison of RCM and histopathological margin assessments. Primary outcome measure was histopathological verification that RCM-negative margins were clear of melanoma. RESULTS: The study included 126 first-step margin evaluations in 23 patients, median age 70 years (range: 43-91). Seventeen patients (74%) had primary in-situ melanoma and six (26%) invasive melanoma, mean thickness 0.3 mm (range 0.2-0.4 mm). Six cases (26%) showed complete negative RCM margins on 'first-step', 11 (48%) were negative at 'second-step', and four (17%) at 'third-step'. In two additional cases (9%), margins clearance could not be determined via RCM due to widespread dendritic cells proliferation. The RCM-negative margins in all 21 cases proved clear of melanoma on histopathology. Of the 15 cases that returned at 1-year follow-up, none showed any residual melanoma on dermoscopic and RCM examinations. Interobserver reproducibility showed fair agreement between bedside RCM reader and blinded remote-site reader, with Spearman's rho of 0.48 and Cohen's kappa of 0.43; using bedside reader as reference, the remote reader's sensitivity was 92% and specificity 57% in positive margin detection. CONCLUSIONS: Margin mapping of lentigo maligna with hand-held-RCM, using superficial skin cuts, appears feasible. This approach needs validation by larger studies.

In vivo monitoring of topical therapy for acne with reflectance confocal microscopy.

BACKGROUND: Acne vulgaris is a common disease of the pilosebaceous unit. The aim of the study was to evaluate compartment-specific treatment action through the microscopic non-invasive imaging of skin changes. METHODS: Mild-moderate acne patients, that were prescribed a topical anti-acne product, were followed by clinical and reflectance confocal microscopy (RCM) imaging every 14 days to 6 weeks. Mean and standard deviation of the scores were analyzed for each time point. RESULTS: After 2 weeks, the RCM count of papules/pustules and the RCM scores of exocytosis and dermal inflammation, decreased substantially. After 4 weeks, the RCM number of comedos was reduced. After 6 weeks, the number of regular follicles increased, while the infundibula with thickened bright border decreased significantly. CONCLUSION: The progressive reduction in the clinical scores was correlated with the improvement of the RCM parameters. RCM study of acne skin showed a different timing for inflammatory and hyperkeratotic components to achieve a significant reduction during topical therapy with the association of retinoid and antibacterial molecules. The microscopic changes observed showed the regularization of the skin and the improvement of acne related features. RCM may represent a useful tool for the objective assessment of treatment efficacy and individual response evaluation.

Acne: morphologic and vascular study of lesions and surrounding skin by means of optical coherence tomography.

BACKGROUND: Acne vulgaris is a disease of the pilosebaceous unit, characterized by hyper-keratinization process, comedos formation and inflammatory reactions. OBJECTIVE: The definition of the morphology and the vascularization of acne lesions by means of dynamic optical coherence tomography (D-OCT), to non-invasively define the alterations occurring during the acne development and patient therapeutic management. METHODS: A set of standardized clinical pictures and D-OCT images were acquired from 114 acne lesions of 31 volunteers, presenting mild to moderate acne and evaluated by experts. Fifteen patients treated with oral antibiotics were followed during time at 0, 20, 40, and 60 days. RESULTS: Optical coherence tomography enabled to identify vascular and morphological aspects characterizing different types of acne lesions. Oral antibiotic treatment improved the morphologic features and decreased the digitally reconstructed vascular signal during time. CONCLUSION: The characterization of acne lesions and the identification of vascular pattern in acne lesions through D-OCT, corresponding to blood vessel dilation and inflammatory associated hyper-vascularization, may have important clinical consequences in the assessment of acne severity, therapeutic decisions and treatment efficacy monitoring.

Validation of Dynamic optical coherence tomography for non-invasive, in vivo microcirculation imaging of the skin.

OBJECTIVES: Dynamic optical coherence tomography (D-OCT) is an angiographic variation of OCT that non-invasively provides images of the in vivo microvasculature of the skin by combining conventional OCT images with flow data. The objective of this study was to investigate and report on the D-OCT technique for imaging of the vascular networks in skin as well as to validate the method by comparing the results against already accepted blood flow measuring tools. METHODS: 35 healthy subjects were recruited for the multicentre study, consisting of three experiments set up to examine the vascular blood perfusion during different induced physiologic changes in the blood flow. In order to validate the D-OCT images against existing techniques for blood flow measuring we performed consecutive D-OCT, chromametry and laser speckle contrast imager (LSCI) measurements on identical skin sites in all of the experiments. Blinded observer evaluations were performed in order to evaluate the vascular morphology in the D-OCT images. RESULTS: The results showed a statistically significant positive correlation between the D-OCT measurements and the LCSI flux measurements (rs=0.494; 95% CI [0.357, 0.615]; p<0.001), and also the redness a* measurements were positively correlated with the D-OCT measurements (r=0.48; 95% CI [0.406, 0.55]). D-OCT was able to reliably image and identify morphologic changes in the vascular network consistent with the induced physiological changes of blood flow. CONCLUSION: This study has initiated validation of the use of D-OCT for imaging of skin blood flow. Our results showed that D-OCT was able to reliably image and identify changes in the skin vasculature consistent with the induced physiological blood flow changes. These basic findings support the use of D-OCT imaging for in vivo microcirculation imaging of the skin.

Non-invasive diagnosis of pink basal cell carcinoma: how much can we rely on dermoscopy and reflectance confocal microscopy?

BACKGROUND: Non-pigmented 'pink' cutaneous lesions in differential diagnosis with basal cell carcinoma may present a challenge for clinicians. Our objective was to determine the potential improvement of diagnostic accuracy using combined dermoscopy-reflectance confocal microscopy (RCM) image evaluation. METHODS: Two hundred and sixty clinically equivocal 'pink' cutaneous lesions were evaluated retrospectively. Reader accuracy was tested with dermoscopy images only vs. RCM and combined dermoscopy-RCM images. RESULTS: Out of 260 equivocal 'pink' cutaneous lesions, there were 114 basal cell carcinomas within a total of 140 malignancies that included 12 melanomas, 13 squamous cell carcinomas, and 1 other malignancy type. Dermoscopy only evaluation resulted in an overall sensitivity of 85.1% and specificity of 92.4%, resulting in a positive predictive value (PPV) of 89.8%, with 1 of 12 melanomas misdiagnosed. RCM evaluation resulted in an overall sensitivity of 85.1% and specificity of 93.8%, resulting in a PPV of 91.5%, with no melanomas misdiagnosed. Combined dermoscopy-RCM evaluation resulted in an overall sensitivity of 77.2% and specificity of 96.6%, resulting in a PPV of 94.6%. CONCLUSION: The combination of dermoscopy-RCM evaluation significantly improves the accuracy and safety threshold in equivocal 'pink' cutaneous lesions in the differential diagnosis of basal cell carcinoma.

In vivo, micro-morphological vascular changes induced by topical brimonidine studied by Dynamic optical coherence tomography.

BACKGROUND: Brimonidine is a selective α2 adrenergic receptor agonist with potent vasoconstrictive activity topically used for treatment of facial flushing and erythema caused by rosacea. Direct evidence for the in vivo morphology changes in skin vessels induced by topical application of brimonidine is limited. Dynamic optical coherence tomography is a novel technology that combines conventional OCT with information on flow and thereby provides supplementary information about the microvasculature. Dynamic OCT is non-invasive and creates high-resolution in vivo images of skin to a depth of maximum 2 mm. OBJECTIVE: The objective of this study was to examine and describe micro-morphological skin vessel changes in normal skin exposed to brimonidine gel using Dynamic OCT. MATERIALS AND METHODS: A total of 35 healthy subjects from three European clinical dermatology centres were included in the study. A normal skin area on the cheek was marked and clinically photographed. Brimonidine gel 0.33% was applied on the area and chromaticity measurements; laser speckle measurements and Dynamic OCT images were acquired at baseline and 60 min after application. The images were subsequently described in detail and quantitatively analysed. RESULTS: All the measurement tools (chromaticity, laser speckle, Dynamic OCT showed highly significant (P < 0.001) quantitative differences in blood flow before and after the application of brimonidine. In 58% of the subjects the Dynamic OCT images showed notable changes in the morphology of the blood vessel network after application of brimonidine including a marked reduction in the abundance and the diameter of the blood vessels. CONCLUSION: The vascular constriction induced by topical brimonidine gel 0.33% was visualized in vivo by Dynamic OCT and confirmed by quantitative measurements and analyses. This study shows that Dynamic OCT can detect characteristic morphological changes in the vessels and may potentially aid the monitoring of treatment effects on skin vessels following topical or laser treatment.

Diagnostic accuracy of reflectance confocal microscopy for lesions typified by dermoscopic island.

INTRODUCTION: Dermoscopic island (DI) is a dermoscopic clue for the diagnosis of thin melanoma (MM). However, its positive predictive value is about 50% and several naevi with DI are unnecessarily excised. Reflectance confocal microscopy (RCM) is a second level non-invasive imaging tool that increases diagnostic accuracy for MM. OBJECTIVE: To evaluate diagnostic RCM features of pigmented lesions typified by the presence of DI and calculate RCM diagnostic accuracy for MM diagnosis. METHODS: All lesions with DI were retrieved from a database of 1964 cases. RCM diagnoses were given without being aware of the histopathological diagnoses. The number of MMs among lesions presenting with DI and the sensitivity and specificity of RCM for MM were assessed. The frequencies of dermoscopic and RCM features were calculated to evaluate significant differences in naevi and MMs showing DI (Chi-square test). Independently significant RCM criteria for MM were identified by discriminant analysis. RESULTS: Sixty-three (3.2%) out of 1964 lesions presented DI. Among them, 30.2% were in situ MMs and 12.7% invasive MMs. Sensitivity and specificity of RCM for the diagnosis of MM in case of DI was 88.9%. Pagetoid cells (Wilks' lambda .804, P < 0.001) and atypical cells at dermo-epidermal junction (Wilks' lambda .762, P < 0.001) were identified to differentiate MM from naevi. CONCLUSION: Our study confirmed that DI could be a sign of early MMs and underlined that RCM could be a good tool to discriminate MMs and naevi in the presence of DI because it can identify the presence of cytological atypia.

Reflectance confocal microscopy correlates of dermoscopic patterns of facial lesions help to discriminate lentigo maligna from pigmented nonmelanocytic macules.

BACKGROUND: The clinical recognition of lentigo maligna (LM) and LM melanoma can be very challenging due to the overlapping features it shares with other pigmented macules of the skin. Noninvasive diagnostic techniques can assist in the differential diagnosis. OBJECTIVES: To identify reflectance confocal microscopy (RCM) indicators for LM through the identification of in vivo microscopic substrates of the main dermoscopic features seen in flat pigmented lesions of the face. METHODS: Retrospective analysis of 60 pigmented lesions (LM, invasive melanoma, solar lentigo/flat seborrhoeic keratosis, lichen planus-like keratosis, pigmented actinic keratosis) was carried out. The main dermoscopic patterns and RCM features were described. A new method for correlating RCM with dermoscopic patterns was developed. RESULTS: Pseudonetwork (37 of 60 lesions) and annular granular structures (37 of 60 lesions) were the most frequent dermoscopic patterns, followed by pigmented blotches (27 of 60 lesions). Upon RCM examination, pseudonetwork and blotches differed in melanomas and other nonmelanocytic lesions. These differences included the intraepidermal proliferation of atypical cells (predominantly dendritic-shaped with adnexal tropism) and the presence of a meshwork pattern at the junction. Also, annular granular structures exhibited dendritic cells almost exclusively in melanoma, with no difference between melanomas and nonmelanocytic lesions for the junctional and upper dermal pattern (characterized by dermal inflammation). Fingerprinting was mostly present in nonmelanocytic lesions or corresponded to an overlap with solar lentigo in melanomas. CONCLUSIONS: RCM is useful for identifying the histological substrate of dermoscopic features in pigmented lesions of the face. It can provide a better definition of the lesion areas, enabling an improved diagnostic approach.

Melanoma and naevi with a globular pattern: confocal microscopy as an aid for diagnostic differentiation.

BACKGROUND: Dermoscopically, one of the most common findings in melanocytic lesions is a globular pattern. A regular globular pattern is a common finding in naevi. Melanoma can also show a globular pattern, with globules typically irregular in size, colour and distribution. OBJECTIVES: To investigate the likelihood of diagnosing melanoma according to distinct dermoscopic and confocal aspects. METHODS: Dermoscopic and confocal aspects of 83 excised melanocytic lesions dermoscopically showing globules were analysed. RESULTS: Our study population included 39 acquired melanocytic naevi, 16 Spitz naevi and 28 melanomas. Univariate analysis showed that regular distribution of globules on dermoscopy is associated with a ninefold lower risk for melanoma, whereas an irregular distribution is associated with an almost 10-fold increased risk for melanoma. Concerning confocal features, dense nests are associated with a fivefold lower risk for melanoma, whereas loosely arranged nests are associated with an almost sixfold risk for melanoma; moreover, the presence of round cells is associated with a 17-fold lower risk for melanoma, whereas pleomorphic cells are associated with an almost 16-fold risk for melanoma. CONCLUSIONS: So that melanoma is not missed, clinicians should carefully analyse globular lesions in adults, focusing, in particular, on the distribution of globules and on the presence of confocal cytological atypia.