Dynamic optical coherence tomography evaluation in locally advanced basal cell carcinoma during sonidegib treatment.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer in the Caucasian population. It has a multifactorial pathogenesis, in which constitutive activation of the Sonic Hedgehog signalling (SHH) pathway (via mutations in PTCH1 or SMO genes) represents by far the most common genetic aberration. The introduction of vismodegib and sonidegib, two SHH pathway inhibitors, changed the therapeutic approach of locally advanced and metastatic BCCs. EADO's (European Association of Dermato-Oncology) new staging system refers to these as 'difficult-to-treat' BCCs. OBJECTIVE: The aim was to evaluate sonidegib's effectiveness in patients affected by difficult-to-treat BCCs by using non-invasive diagnostic techniques. METHODS: We retrospectively evaluated 14 patients (4 females, 10 males; mean age 77 ± 11 years) affected by difficult-to-treat BCCs treated with oral sonidegib 200 mg/day that were followed with total body videodermoscopy (V-Track, Vidix 4.0) and dynamic optical coherence tomography (D-OCT, VivoSight Dx) since May 2022. Considering the risk of rhabdomyolysis routine blood tests, especially for creatine kinase concentrations, were performed. All treated patients were inserted in the BasoCare database, which aims to offer support to patients taking sonidegib. Complete and partial responses were evaluated by the overall reduction of the number of lesions and their individual sizes. Safety was evaluated by assessing the occurrence and severity of adverse reactions. RESULTS: Eighty per cent achieved complete clearance and 75% reduction of diameter. D-OCT scans performed at every follow-up showed concordance with clinical appearance and demonstrated reduction of hyporeflective structures, that is, islets of tumour cells and overall improvement of morphology. CONCLUSION: Sonidegib can be considered an effective treatment option in cases where surgery or radiotherapy would be unfeasible or has previously failed, although pigmented lesions did not show complete clearance, suggesting that there are factors other than the SHH pathway involved in tumour growth. Videodermoscopy and D-OCT were useful in the quick and seamless follow-up of lesions and added valuable information in assessing efficacy.

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.

The impact of anatomical location and sun exposure on the dermoscopic recognition of atypical nevi and early melanomas: usefulness of an integrated clinical-dermoscopic method (iDScore).

BACKGROUND: The anatomical location of atypical melanocytic skin lesion (aMSL) was never combined into an algorithm for discriminating early melanomas (EM) from atypical nevi (AN). AIMS: To investigate the impact of body location on the intuitive diagnosis performed in teledermoscopy by dermatologists of different skill levels. A further aim was to evaluate how the integration of the body location could improve an algorithm-aided diagnosis. METHODS: We retrospectively collected 980 standardized dermoscopic images of aMSL cases (663 AN, 317 EM): data on the anatomical location were collected according to 15 body sites classified into 4 macro-areas of chronically/frequently/seldom/rarely exposure. Through a teledermatology web platform, 111 variously skilled dermoscopists performed either the intuitive diagnosis and 3 algorithm-assisted diagnostic tests (i.e. iDScore, 7-point checklist, ABCD rule) on each case, for a total of 3330 examinations. RESULTS: In the rarely photoexposed area (side, bottom, abdomen), AN were the most tricky (i.e. highest quote of false positives), due to a frequent recognition of dermoscopic features usually considered as suggestive for melanoma in these lesions; the EM at these sites received the highest quote of false negatives, being generally interpreted as 'featureless' according to these traditional parameters, that were more frequently displayed on the chronically photoexposed area. In rarely and seldom photoexposed area, intuitive diagnosis fails to achieve adequate accuracy for all aMSLs, as the ABCD rule and the 7-point checklist; by applying the iDScore algorithm the diagnostic performance was increased by 15% in young and 17% in experts. CONCLUSIONS: The body location of an aMSL can affect the quality of intuitive dermoscopic diagnosis, especially in sun-protected areas. Accuracy can be improved by using the iDScore algorithm that assigns a different partial score of each body site.

A validated photonumeric cellulite severity scale for the area above the knees: the knee cellulite severity score.

BACKGROUND: Treatment for cellulite above the knees is increasingly requested. However, a classification of cellulite of this area has not yet been developed. OBJECTIVE: To validate the proposed knee cellulite severity score (KCSS) for the assessment of cellulite and skin laxity above the knee. MATERIALS AND METHODS: Based on standardized photographs of cellulite and skin laxity above the knees of 57 females (114 knees), three key morphological aspects of cellulite were identified. A photonumeric KCSS was developed and validated by three independent assessors. RESULTS: The three key cellulite morphological features (number of depressions, depth of depressions and presence of laxity) are each graded from 0 to 3, producing a classification of no lesions (0), mild (1-3), moderate (4-6) and severe (7-9). Evaluators at different time points repeated similar classifications (intraclass correlation coefficient >0.9), which were also similar among the assessors (inter-observer reliability >0.9). All three key morphological aspects were deemed necessary, and positively contributed, to the overall scale (item-total correlation analysis values >0.89, P < 0.05). CONCLUSIONS: The KCSS is a consistent, comprehensive, reliable, and reproducible tool for standardized and objective assessment of the severity of cellulite and skin laxity above the knees.

Reflectance confocal microscopy diagnostic accuracy for malignant melanoma in different clinical settings: systematic review and meta-analysis.

BACKGROUND: The diagnostic accuracy of reflectance confocal microscopy (RCM) of cutaneous malignant melanoma (MM) seems promising. However, clinical scenarios in which RCM is most useful are still to be established. OBJECTIVES: To assess the diagnostic accuracy of RCM for MM diagnosis according to study design, lesion type and diagnostic modality. Secondary outcomes include a comparison with dermoscopy. METHODS: A systematic literature search was conducted on PubMed, Embase, Scopus and Cochrane Public Library Databases for English articles published prior to January 2019. Statistical analyses were conducted with Meta-Disc v. 1.4, STATA 14.0 software and the QUADAS-2 tool. RESULTS: A total of 32 studies (7352 lesions) were included in the meta-analysis. Pooled sensitivity and specificity resulted 92% (95% CI: 0.91-0.93) and 70% (95% CI: 0.69-0.71), respectively. According to study design, diagnostic sensitivity was high for all study types, confirming a lower specificity for prospective interventional studies. Diagnostic accuracy remained high for all lesion types, with the highest specificity obtained for consecutive lesions of 77% (95% CI: 0.75-0.78) vs. 65% (95% CI: 0.63-0.66) for lesions highly suspicious for MM. RCM diagnostic accuracy was superior to dermoscopy, most notably in terms of specificity of 56% (95% CI: 0.52-0.60) vs. 38% (95% CI: 0.34-0.42), respectively. Studies were generally assessed across all domains as low or unclear risk of bias with a mainly low concern regarding applicability of evidence. Publication bias was asymmetrical (11.2 ± 4.0; 95% CI 2.97-19.43; P < 0.01). CONCLUSIONS: Independent of study design, RCM has a high diagnostic power for MM detection, and unnecessary excisions are reduced compared to dermoscopy. This reduction is most evident in non-decisional RCM scenarios and for lesions analysed at RCM consecutively compared to those selected highly suspicious for MM. However, the scarcity, heterogeneity and bias associated with the data in literature should be considered when interpreting present conclusions.

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.

The association between pesticide use and cutaneous melanoma: a systematic review and meta-analysis.

BACKGROUND: The incidence of cutaneous melanoma (CM), the deadliest form of skin cancer, has gradually increased in the last decades among populations of European origin. Epidemiological studies suggested that farmers and agricultural workers are at an increased risk of CM because they were exposed to pesticides. However, little is known about the relationship between pesticides and CM. OBJECTIVES: To investigate the association between exposure to pesticides and CM by systematically reviewing the literature. Secondary aim was to determine the categories of pesticides mainly involved in CM development. METHODS: A systematic review of the literature was performed up to September 2018 using MEDLINE, Embase and Web of Science. Studies assessing CM risk in licensed pesticide applicators were considered. Strict criteria were established to select independent studies and risk estimates; random effect models, taking into account heterogeneity, were applied. A pooled risk estimate for CM was calculated for the use of each type of pesticide and type of exposure. Between-study and estimate heterogeneity was assessed and publication bias investigated. RESULTS: A total of nine studies (two case-controls and seven cohorts) comprising 184 389 unique subjects were included. The summary relative risks for the categories 'herbicides - ever exposure', 'insecticides - ever exposure', 'any pesticide - ever exposure' and 'any pesticide - high exposure' resulted 1.85 [95% confidence interval (CI): 1.01, 3.36], 1.57 (95% CI: 0.58, 4.25), 1.31 (95% CI: 0.85, 2.04) and 2.17 (95% CI: 0.45, 10.36), respectively. Herbicides and insecticides had no between-study heterogeneity (I2  = 0%), while a significant heterogeneity (I2  > 50%) was detected for the high exposure to any pesticide. No indication for publication bias was found. CONCLUSIONS: Individuals exposed to herbicides are at an increased risk of CM. Future properly designed observational studies are required to confirm this finding.

Validation of an integrated dermoscopic scoring method in an European teledermoscopy web platform: the iDScore project for early detection of melanoma.

BACKGROUND: Although live and teledermoscopic examination has been successfully used to achieve non-invasive diagnosis of melanocytic skin lesions (MSLs), early melanoma (EM) and atypical nevi (AN) continue to be a challenge, and none of the various algorithms proposed have been sufficiently accurate. We designed a scoring classifier diagnostic method, the iDScore that combines clinical data of the patient with dermoscopic features of the MSL. OBJECTIVE: To test the accuracy of the iDScore in differentiating EM from AN in a teledermoscopy setting and to compare it with intuitive diagnosis, the ABCD rule and the seven-point checklist. MATERIALS AND METHODS: A dedicated teledermoscopy web platform was designed. This involved the following: (i) collecting a large integrated clinical-historical-dermoscopic data set of difficult MSLs from eight European dermatology centres; (ii) online testing, education and training in using the iDScore. A total of 904 images were combined with age, sex, lesion diameter and body site data and evaluated on the platform by 111 participants with four levels of skill in dermoscopy. Each testing session consisted of 30 blind cases to examine consecutively by the above four methods. 'Management decisions' and personal participant data were also recorded. RESULTS: iDScore-aided diagnosis achieved satisfactory diagnostic accuracy for all lesions, irrespective of centre of affiliation, showing an average AUC of 0.776 in all participant testing sessions. All skill groups improved their accuracy by 10-16% with respect to intuitive diagnosis and the other methods, showing high concordance and avoiding wrong management decisions. CONCLUSION: We demonstrated the validity of the iDScore method for managing suspicious MSLs in a large multicentric data set and a teledermoscopic setting. The platform designed for the iDScore project provides ready support for physicians of any dermoscopy skill level and is useful for education and training.

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 evolution of healthy skin to acne lesions: a longitudinal, in vivo evaluation with reflectance confocal microscopy and optical coherence tomography.

BACKGROUND: Comedogenesis is defined as the process of the development of a new comedo, which is of great importance for the understanding of acne. OBJECTIVE: To evaluate the formation and evolution of acne lesions from clinically unaffected skin of patients with mild-moderate acne to characterize the morphological changes and natural resolution by means of in vivo reflectance confocal microscopy (RCM) and dynamic optical coherence tomography (D-OCT). METHODS: Ten patients with mild-moderate acne, not assuming any topical or systemic therapy, comprised between 12 and 30 years of age, were recruited. A target area of 4 × 4 mm of the face, without acne lesions at baseline, was selected. A set of standardized clinical pictures, RCM and D-OCT images were acquired weekly for 6 weeks and evaluated. RESULTS: Seventy full sets of clinical, RCM and D-OCT images were analysed. The appearance of acne lesion is preceded by an increase of large bright follicles in the area corresponding to infundibular keratinization, followed by increment of inflammation parameter, such as increased of small bright cells upon RCM and vascular network upon D-OCT, which return to normal after the resolution of acute inflammation. CONCLUSION: Acne skin dynamics is complex and seems characterized by the early increase in the number of dysmorphic pilosebaceous units and the hyperkeratinization of the acroinfundibulum of the pilosebaceous duct prior to the occurrence of inflammatory events around the follicle. The processes of hyperkeratinization and inflammatory phenomena may generate a pathologic vicious cycle, which characterizes acne through progressive worsening and a self-sustainment mechanism.

Morphological classification of melanoma metastasis with reflectance confocal microscopy.

BACKGROUND: Cutaneous malignant melanoma metastases differential diagnosis is challenging, as clinical and dermoscopic features can simulate primary melanoma or other benign or malignant skin neoplasms, and in-vivo reflectance confocal microscopy could assist. Our aim was to identify specific reflectance confocal microscopy features for cutaneous malignant melanoma metastases, and epidermal and dermal involvement. METHODS: A retrospective, multicentre observational study of lesions with proven cutaneous malignant melanoma metastases diagnosis between January 2005 and December 2016. Lesions were retrospectively assessed according to morphological features observed at reflectance confocal microscopy. Potential homogeneous subgroups of epidermal or dermal involvement were investigated with cluster analysis. RESULTS: Cutaneous malignant melanoma metastases (51 lesions in 29 patients) exhibited different frequencies of features according to metastasis dermoscopy patterns. Lesions classified at dermoscopy with nevus-like globular and non-globular patterns were more likely to be epidermotropic, showing characteristics of epidermal and dermal involvement at reflectance confocal microscopy. Other dermoscopy pattern classifications were more likely to be dermotropic, showing characteristics od dermal involvement at reflectance confocal microscopy. Distinguishing features at reflectance confocal microscopy included irregular (78%) and altered (63%) epidermis, pagetoid infiltration (51%), disarranged junctional architecture (63%), non-edged papillae (76%), dense and sparse, and cerebriform nests in the upper dermis (74%), and vascularity (51%). Cluster analysis identified three groups, which were retrospectively correlated with histopathological diagnoses of dermotropic and epidermotropic diagnoses (P < 0.001). The third cluster represents lesions with deep dermis morphological changes, which were too deep for evaluation with reflectance confocal microscopy. CONCLUSIONS: Specific reflectance confocal microscopy features of cutaneous malignant melanoma metastases for correct diagnosis, and subtype diagnosis, seem achievable in most cases where morphological alterations are located above the deep dermis.