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.

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.

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.

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.

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.