Reflectance Confocal Microscopy Criteria Research Articles

Reflectance confocal microscopy of facial neoplasms: Follicular involvement as a clue to diagnosis.

Facial skin is characterized by high density of follicles. Facial neoplasms may present overlapping clinical and dermoscopic findings. Our goal was to evaluate and compare, via reflectance confocal microscopy (RCM), follicular involvement in facial neoplasms. We retrospectively searched our image database, between January 2008 and December 2020, for all facial lesions with (1) a standardized set of clinical, dermoscopic, and RCM images, and (2) a biopsy-proven diagnosis of lentigo maligna/lentigo maligna melanoma (LM/LMM, n= 39), basal cell carcinoma (BCC, n= 51), squamous cell carcinoma in situ (SCCIS, n= 5), actinic keratosis (AK, n= 11), and lichen-planus-like keratosis (LPLK, n= 18). Two readers jointly evaluated the RCM images for a set of predefined features of follicular involvement. Diffuse obliteration of follicles was frequent in BCC (88%), while follicular infiltration by refractile dendritic cells and/or by bright round nucleated cells was common in melanoma (90% and 44%, respectively). Extension of atypical keratinocytes down follicles was more prominent among SCCIS than AK (80% vs. 45%, p= 0.01). In most LPLK (89%), there was follicular sparing. Evaluation of RCM criteria centering on the follicles can be useful in the differential diagnosis between common facial neoplasms.

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

Amelanotic/hypomelanotic lentigo maligna and lentigo maligna melanoma (AHLM/LMM) may be very difficult to diagnose at an early stage. To quantify the predictive value of dermoscopic and reflectance confocal microscopy (RCM) features for AHLM/LMM. 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. 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. 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.

In Vivo Reflectance Confocal Microscopy as a Response Monitoring Tool for Actinic Keratoses Undergoing Cryotherapy and Photodynamic Therapy.

Simple SummaryThe assessment of actinic keratoses (AKs) in prevention and therapeutic trials, as well as clinical practice, could significantly benefit from the incorporation of non-invasive imaging technology. Such technology has the potential to enhance the objective evaluation of clinical and subclinical AKs with the added advantage of sequential monitoring. In vivo reflectance confocal microscopy (RCM) allows for the non-invasive imaging of AKs at a cellular level. We aimed to establish an in in vivo RCM protocol for AK response monitoring, ultimately leading to more reliable characterization of longitudinal responses and therapy optimization.Reflectance confocal microscopy (RCM) presents a non-invasive method to image actinic keratosis (AK) at a cellular level. However, RCM criteria for AK response monitoring vary across studies and a universal, standardized approach is lacking. We aimed to identify reliable AK response criteria and to compare the clinical and RCM evaluation of responses across AK severity grades. Twenty patients were included and randomized to receive either cryotherapy (n = 10) or PDT (n = 10). Clinical assessment and RCM evaluation of 12 criteria were performed in AK lesions and photodamaged skin at baseline, 3 and 6 months. We identified the RCM criteria that reliably characterize AK at baseline and display significant reduction following treatment. Those with the highest baseline odds ratio (OR), good interobserver agreement, and most significant change over time were atypical honeycomb pattern (OR: 12.7, CI: 5.7–28.1), hyperkeratosis (OR: 13.6, CI: 5.3–34.9), stratum corneum disruption (OR: 7.8, CI: 3.5–17.3), and disarranged epidermal pattern (OR: 6.5, CI: 2.9–14.8). Clinical evaluation demonstrated a significant treatment response without relapse. However, in grade 2 AK, 10/12 RCM parameters increased from 3 to 6 months, which suggested early subclinical recurrence detection by RCM. Incorporating standardized RCM protocols for the assessment of AK may enable a more meaningful comparison across clinical trials, while allowing for the early detection of relapses and evaluation of biological responses to therapy over time.

Pigmented lesion on the face: which is the chance of being melanoma using reflectance confocal microscopy features?

Facial melanoma presents itself as a brownish macula, being difficult to differentiate it from benign pigmented lesions of the face on clinical examination. Reflectance confocal microscopy (RCM) assists in diagnosing facial lesions in which dermoscopy has limitations, allowing to increase the diagnostic accuracy. The study aimed to analyze the RCM features of pigmented isolated lesions of the face for diagnosing melanoma. Also, we sought to establish the chance of a pigmented lesion on the face being a melanoma using RCM criteria. In this retrospective and prospective study, 105 clinical pigmented lesions on the face underwent RCM, and cytoarchitectural features in the epidermis, the dermo-epidermal junction (DEJ), and dermis were described. For statistical analysis, the exact chi-square test was applied to the RCM criteria. The odds ratio was estimated using univariate logistic regression. Finally, we used the multiple logistic regression method for creating a nomogram to predict the chance of a lesion being a melanoma. After univariate and multivariate logistic regression, atypical round nucleated cells within the epidermis, pagetoid spread, and follicular dendritic cells presented as statistically significant features. Then, a complex nomogram was created to give the chance of a pigmented lesion on the face being a melanoma. The presence of these three features resulted in a 98% probability for melanoma. This study allowed to estimate the diagnosis of melanoma on the face, using RCM, practicable and feasible in the daily routine, through the presence of some RCM nomogram criteria.

A Comparative Study of Pigmented and Non-pigmented Basal Cell Carcinoma in Reflectance Confocal Microscopy.

Basal cell carcinoma (BCC) is a common skin cancer, especially in the elderly population. The probability of BCC development increases past the age of 55. Dermoscopy and reflectance confocal microscopy (RCM) are two modern tools useful in the diagnosis of BCC. This is a retrospective study conducted on a group of 21 patients with a confirmed diagnosis of BCC. All patients were examined by dermoscopy and RCM. Dermoscopic images were taken using a videodermoscope. RCM was performed in three layers: epidermal, dermoepidermal junction (DEJ), and superficial dermal layer. In each layer, a few RCM criteria of basal cell carcinoma diagnosis were taken into consideration. Dermoscopy of pigmented BCCs revealed blue globules of pigment (p<0.05), gray and blue ovoid nests, which were absent in the entire non-pigmented carcinomas group. In RCM, the epidermis showed no differences between pigmented and non-pigmented carcinomas, however, significant differences were observed at the DEJ. In pigmented BCCs, cordlike structures and plump atypical cells were observed (p<0.05), while in non-pigmented carcinomas, dark silhouettes were present (p<0.05). To our knowledge, that is the first study comparing features between pigmented and non-pigmented BCC by RCM. Pigmented and non-pigmented BCCs presented different features in both dermoscopy and RCM. Furthermore, RCM revealed more discriminating features at the DEJ than dermoscopy, thus can be more efficient in the differential diagnosis of difficult BCC.

Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel.

Actinic keratosis is a common skin disease that may progress to invasive squamous cell carcinoma if left untreated. Ingenol mebutate has demonstrated efficacy in field treatment of actinic keratosis. However, molecular mechanisms on ingenol mebutate response are not yet fully understood. In this study, we evaluated the gene expression profiles of actinic keratosis lesions before and after treatment with ingenol mebutate using microarray technology. Actinic keratoses on face/scalp of 15 immunocompetent patients were identified and evaluated after treatment with topical ingenol mebutate gel 0.015%, applied once daily for 3 consecutive days. Diagnostic and clearance of lesions was determined by clinical, dermoscopic, and reflectance confocal microscopy criteria. Lesional and non-lesional skin biopsies were subjected to gene expression analysis profiled by Affymetrix microarray. Differentially expressed genes were identified, and enrichment analyses were performed using STRING database. At 8 weeks post-treatment, 60% of patients responded to ingenol mebutate therapy, achieving complete clearance in 40% of cases. A total of 128 differentially expressed genes were identified following treatment, and downregulated genes (114 of 128) revealed changes in pathways important to epidermal development, keratinocyte differentiation and cornification. In responder patients, 388 downregulated genes (of 450 differentially expressed genes) were also involved in development/differentiation of the epidermis, and immune system-related pathways, such as cytokine and interleukin signaling. Cluster analysis revealed two relevant clusters showing upregulated profile patterns in pre-treatment actinic keratoses of responders, as compared to non-responders. Again, differentially expressed genes were mainly associated with cornification, keratinization and keratinocyte differentiation. Overall, the present study provides insight into the gene expression profile of actinic keratoses after treatment with ingenol mebutate, as well as identification of genetic signatures that could predict treatment response.

Reflectance confocal microscopy for noninvasive examination of nonmelanocytic tumors and virus-associated skin lesions in organ transplant recipients.

Drug-induced immunosuppression is necessary to prevent rejection of the foreign organ in transplanted patients, but neoplastic and virus-associated skin diseases are frequent complications. Reflectance confocal microscopy (RCM) recently emerged as a promising tool for the early diagnosis of skin lesions. A total of 61 skin lesions, among them 20 basal cell carcinomas, six Bowen's diseases, 23 actinic keratoses, and 12 verrucae, were analyzed. All lesions were clinically evaluated followed by RCM evaluation by two independent dermatologists and histological examination. For the diagnosis of basal cell carcinoma, a sensitivity of 100% by both investigators (INV I+II) and a specificity of 100% by INV I and 80% by INV II were achieved. The sensitivity average rate for RCM features reached by both investigators ranged between 60% and 100%, and the specificity between 55% and 90%. For the diagnosis of actinic keratosis, a concordant sensitivity of 94.4% and a specificity of 80% (INV I) and 60% (INV II) were detected. The sensitivity average rate of specific RCM criteria ranged between 72.3% and 97.2%, whereas specificity ranged between 20% and 90%. Regarding verrucae, RCM confirmed the histological diagnosis with a sensitivity of 85.7% (INV I) and 100% (INV II), while specificity was 100% and 80%, respectively. Reflectance confocal microscopy resulted to be a reliable tool for the noninvasive diagnosis of neoplastic and virus-associated skin changes in organ transplant recipients. Nevertheless, given the frequency and diagnostic complexity of the hyperkeratotic lesions occurring post-transplantation, larger cohorts of patients are required to confirm and consolidate these findings.

A Retrospective Study of the Diagnostic Accuracy of In Vivo Reflectance Confocal Microscopy for Basal Cell Carcinoma Diagnosis and Subtyping.

Current national and European guidelines recommend distinct management approaches for basal cell carcinoma (BCC) based on tumor location, size, and histopathological subtype. In vivo reflectance confocal microscopy (RCM) is a non-invasive skin imaging technique which may change the diagnostic pathway for BCC patients. This study aimed to determine the sensitivity and specificity of RCM for BCC diagnosis, assess the predictive values of several confocal criteria in correctly classifying BCC subtypes, and evaluate the intraobserver reliability of RCM diagnosis for BCC. We conducted a retrospective study in two tertiary care centers in Bucharest, Romania. We included adults with clinically and dermoscopic suspect BCCs who underwent RCM and histopathological examination of excision specimens. For RCM examinations, we used the VivaScope 1500 and histopathology of the surgical excision specimen was the reference standard. Of the 123 cases included in the analysis, BCC was confirmed in 104 and excluded in 19 cases. RCM showed both high sensitivity (97.1%, 95% CI (91.80, 99.40)) and specificity (78.95%, 95% CI (54.43, 93.95)) for detecting BCC. Several RCM criteria were highly predictive for BCC subtypes: cords connected to the epidermis for superficial BCC, big tumor islands, peritumoral collagen bundles and increased vascularization for nodular BCC, and hyporefractile silhouettes for aggressive BCC. Excellent intraobserver agreement (κ = 0.909, p < 0.001) was observed. This data suggests that RCM could be used for preoperative diagnosis and BCC subtype classification in patients with suspected BCCs seen in tertiary care centers.

Nipple and areola lesions: Dermoscopy and reflectance confocal microscopy features

To the Editor: Only case reports have analyzed the dermoscopic and reflectance confocal microscopy (RCM) features of the lesions of nipple and areola complex (NAC).1-3 We retrospectively evaluated the clinical, dermoscopic, and RCM features of 131 consecutive NAC lesions diagnosed at 13 University Centers (Tables I and II). The final diagnosis was based on histopathology or on clinical follow-up for ≥1 year to confirm benignity. Three experts in noninvasive skin imaging (EC, MA, and SG) independently evaluated dermoscopic and RCM criteria blinded from the diagnosis.

Lesions Mimicking Melanoma at Dermoscopy Confirmed Basal Cell Carcinoma: Evaluation with Reflectance Confocal Microscopy

Background: Atypical basal cell carcinoma (BCC), characterized by equivocal dermoscopic features typical of malignant melanoma (MM), can be difficult to diagnose. Reflectance confocal microscopy (RCM) enables in vivo imaging at nearly histological resolution. Objectives: To evaluate with RCM atypical melanocytic lesions identified in dermoscopy, according to common RCM criteria for the differential diagnosis of BCC, and to identify representative RCM parameters for superficial (sBCCs) and nonsuperficial (nsBCCs) basal cell carcinomas (BCCs). Methods: A retrospective analysis of consecutive patients evaluated with RCM, selecting excised lesions classified at dermoscopy with ≥1 score from the re visited 7-point checklist, mimicking melanoma, registered between 2010 and 2016. Cluster analysis identified BCC subclassifications. Results: Of 178 atypical lesions, 34 lesions were diagnosed as BCCs with RCM. Lesions were confirmed BCCs with histopathology. Dermoscopic features included atypical network (55.9%) and regression structures (35.5%) associated with sBCCs, and an atypical vascular pattern (58.8%) and irregular blotches (58.8%) with nsBCCs. Hierarchical cluster analysis identified 2 clusters: cluster 1 (100% sBCCs) was characterized by the presence of cords connected to the epidermis (90%, p < 0.001), tumor islands located in the epidermis (100%, p < 0.001), smaller vascular diameter (100%, p < 0.001) and solar elastosis (90%, p = 0.017), and cluster 2 (nsBCCs 85%) was defined by the dermic location of tumor islands (87.5%, p < 0.001) with branch-like structures (70.8%, p = 0.007) and surrounding collagen (83.3%, p = 0.012), peripheral palisading (83.3%, p = 0.012) and coiled vascular morphology (79.2%, p < 0.001) with a larger vascular diameter (50%, p < 0.001). Conclusions: RCM is able to diagnose BCCs mimicking melanoma at dermoscopy and seems able to identify sBCCs and nsBCCs.

In vivo dermoscopic and confocal microscopy multistep algorithm to detect in situ melanomas.

Although several dermoscopic features of in situ melanoma have been identified, data on confocal features of in situ melanoma are still lacking. To identify reflectance confocal microscopy (RCM) features of in situ melanoma and to develop a diagnostic score combining dermoscopy and RCM. In total, 120 in situ melanoma and 213 nevi (test set) were retrospectively analysed to assess the presence of dermoscopic and RCM criteria. Facial and acral lesions were excluded. Spearman's correlation, univariate and multivariate regression models were used to identify features significantly correlated with in situ melanoma diagnosis. Multivariate results on the test set allowed the development of a multistep algorithm, that was tested on a validation set of 100 lesions. The dermoscopic findings of an atypical network and regression were independent predicting factors for in situ melanoma diagnosis [odds ratio (OR) 3·44, 95% CI (confidence interval) 1·70-6·97 and OR 4·17, 95% CI 1·93-9·00, respectively]. Significant confocal predictors for malignancy were epidermal pagetoid spread (OR 2·83, 95% CI 1·32-6·04) and junctional cytological atypia (OR 3·39, 95% CI 1·38-8·30 if focal, OR 8·44, 95% CI 3·21-22·16 if widespread). A multistep diagnostic algorithm able to predict in situ melanoma with a sensitivity of 92·5% and a specificity of 61% was developed. The validation set confirmed the high diagnostic value (sensitivity 92%, specificity 58%). An easy and reproducible multistep algorithm for in situ melanoma detection is suggested, that can be routinely used in tertiary centres.

Reflectance Confocal Microscopy Criteria of Pigmented Squamous Cell Carcinoma In Situ.

Pigmented squamous cell carcinoma in situ (pSCCis) is difficult to diagnose based on clinical and dermoscopic examination. Reflectance confocal microscopy (RCM) allows noninvasive differentiation between malignant and benign pigmented skin lesions. We determined the frequency of key RCM features of pSCCis and correlated the RCM criteria with the corresponding dermoscopic and histopathologic criteria. The study included 28 lesions with biopsy-proven diagnosis of pSCCis derived from 28 patients. Clinical, dermoscopic, and RCM images of these lesions were retrospectively analyzed by 3 independent observers. Assessment for the presence of RCM criteria revealed scale or parakeratosis (20/28; 71%); irregular honeycomb pattern in the spinous-granular layer (28/28; 100%); spindle-shaped cells with dendritic branches infiltrating the epidermis (12/28; 43%); edged papillae (24/28; 86%), and dilated looped blood vessels within the papillae (18/28; 64%). Fifty-three percent of the cases displayed at least 4 RCM criteria and 96% of cases displayed at least 3 RCM criteria. We propose that the diagnosis of pSCCis could be established based on 1 major criterion-irregular honeycomb pattern-and 2 of the following minor criteria-scale or parakeratosis, spindle-shaped cells with dendritic branches infiltrating the epidermis, edged papillae, and dilated looped blood vessels within the papillae.

Analysis of debrided and non-debrided invasive squamous cell carcinoma skin lesions by in vivo reflectance confocal microscopy before and after therapy.

Hyperkeratosis hinders the application of reflectance confocal microscopy (RCM) to image squamous cell carcinoma (SCC). Not all lesions with SCC show hyperkeratosis, and these lesions can be directly imaged. However, lesions with hyperkeratosis can be treated by debriding the hyperkeratotic surface for further imaging. RCM was used to investigate patients with suspected SCC. Lesions without obvious keratosis underwent direct RCM examinations. Lesions with obvious keratosis were treated by debriding the hyperkeratotic surface. The following main RCM criteria were used to diagnose invasive SCC: atypical keratinocytes arranged in nests, islands, and disarrangement patterns; an atypical honeycomb pattern; the absence of a cobblestone pattern; and non-edged dermal papillae. Other characteristics of invasive SCC observed by confocal microscopy included keratin pearl structures, hyperkeratosis, and inflammatory cell infiltration. During the follow-up period after treatment, both the cobblestone pattern and edged dermal papillae were as important as the typical honeycomb pattern in suggesting a normal skin structure. Our findings indicate RCM is a valuable tool to noninvasively examine the histology of invasive SCC before and after therapy.

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

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. To evaluate diagnostic RCM features of pigmented lesions typified by the presence of DI and calculate RCM diagnostic accuracy for MM diagnosis. 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. 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. 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.

Skin Cancer Diagnosis With Reflectance Confocal Microscopy: Reproducibility of Feature Recognition and Accuracy of Diagnosis.

Reflectance confocal microscopy (RCM) studies have been performed to identify criteria for diagnosis of skin neoplasms. However, RCM-based diagnosis is operator dependent. Hence, reproducibility of RCM criteria needs to be tested. To test interobserver reproducibility of recognition of previously published RCM descriptors and accuracy of RCM-based skin cancer diagnosis. Observational retrospective web-based study of a set of RCM images collected at a tertiary academic medical center. Nine dermatologists (6 of whom had ≥3 years of RCM experience) from 6 countries evaluated an RCM study set from 100 biopsy-proven lesions, including 55 melanocytic nevi, 20 melanomas, 15 basal cell carcinomas, 7 solar lentigines or seborrheic keratoses, and 3 actinic keratoses. Between June 15, 2010, and October 21, 2010, participanting dermatologists, blinded to histopathological diagnosis, evaluated 3 RCM mosaic images per lesion for the presence of predefined RCM descriptors. The main outcome was identification of RCM descriptors with fair to good interrater agreement (κ statistic, ≥0.3) and independent correlation with malignant vs benign diagnosis on discriminant analysis. Additional measures included sensitivity and specificity for diagnosis of malignant vs benign for each evaluator, for majority diagnosis (rendered by ≥5 of 9 evaluators), and for experienced vs recent RCM users. Eight RCM descriptors showed fair to good reproducibility and were independently associated with a specific diagnosis. Of these, the presence of pagetoid cells, atypical cells at the dermal-epidermal junction, and irregular epidermal architecture were associated with melanoma. Aspecific junctional pattern, basaloid cords, and ulceration were associated with basal cell carcinomas. Ringed junctional pattern and dermal nests were associated with nevi. The mean sensitivity for the group of evaluators was 88.9% (range, 82.9%-100%), and the mean specificity was 79.3% (range, 69.2%-90.8%). Majority diagnosis showed sensitivity of 100% and specificity of 80.0%. Sensitivity was higher for experienced vs recent RCM users (91.0% vs. 84.8%), but specificity was similar (80.0% vs. 77.9%). The study highlights key RCM diagnostic criteria for melanoma and basal cell carcinoma that are reproducibly recognized among RCM users. Diagnostic accuracy increases with experience. The higher accuracy of majority diagnosis suggests that there is intrinsically more diagnostic information in RCM images than is currently used by individual evaluators.

Integration of reflectance confocal microscopy in sequential dermoscopy follow-up improves melanoma detection accuracy.

Successful treatment of melanoma depends on early diagnosis, but its varied clinical presentation means that no single noninvasive method or criterion can provide reliable detection in all cases. To determine whether combining sequential dermoscopy imaging with reflectance confocal microscopy (RCM) can improve melanoma detection and reduce the burden of unnecessary excisions. We conducted a retrospective study with median follow-up of 25months. We included equivocal pigmented lesions that lacked clear dermoscopy criteria for melanoma at baseline but were excised subsequently because of changes during digital monitoring. RCM imaging was performed before excision. Main melanoma dermoscopy features, seven-point checklist score at baseline, and changes in structure and/or colour, and development of new melanoma-specific criteria at follow-up (scored as major, moderate or minor) were considered. Main melanoma RCM criteria were evaluated and diagnosis was made. Histopathological diagnosis was the reference standard for defining parameter frequency and diagnostic accuracy. Seventy lesions were included. Major changes were more frequently correlated with melanoma diagnosis, although one-third (four of 12) of melanomas showed moderate or minor changes. Cytological atypia and architectural disarrangement on RCM were correlated with melanoma diagnosis. A correct melanoma diagnosis was achieved with RCM in almost all cases (11 of 12, 92%). Referring for excision only those lesions with RCM-positive features and/or presenting major changes at digital dermoscopy follow-up, theoretically 27 of 58 naevi could be saved from surgery. Integration of RCM in the clinical and instrumental strategy for managing difficult pigmented lesions provided additional diagnostic information useful in the decision-making process.

Towards an in vivo morphologic classification of melanocytic nevi

Nevi are common benign neoplasms and the main diagnostic entity in the differential diagnosis of melanoma. Reflectance confocal microscopy (RCM), a novel technique for skin imaging at cellular-level magnification, has been shown to be useful for differentiating nevi from melanoma. However, systematic studies of the specific RCM features of nevi are still lacking. To describe the characteristic RCM features of common melanocytic nevi and to correlate them with histopathology. A total of 180 biopsy-proven nevi were imaged with RCM prior to excision. RCM images were evaluated for the overall nevus pattern and presence of specific RCM criteria. Upon histopathology, nevi were analysed for thickness using adapted Breslow depth and Clark's level grading. Observed RCM patterns varied according to anatomic depth of nevi. Junctional nevi were mainly characterized on RCM by a Ringed pattern, indicating a predominantly single cell proliferation of melanocytes; in contrast, the junctional component of compound nevi appeared on RCM as a Meshwork pattern, indicating a predominantly nested-proliferation. In compound nevi, the size of dermal nests was related to the thickness of nevi. Moreover, nevi extending deeper into the dermis were more likely to display a junctional component that extended laterally beyond the dermal component and appeared on RCM as either Ringed or Meshwork pattern. Intradermal nevi showed on RCM, in almost all cases, large clods. The possibility for in vivo histopathological classification of nevi may help in attaining a better understanding of the origin of nevi and of nevus-related melanoma risk.

Differentiation Between Balanitis and Carcinoma In Situ Using Reflectance Confocal Microscopy

Zoon plasma cell balanitis is a benign inflammatory disease of genital skin. It may be difficult to clinically distinguish between balanitis and carcinoma in situ (CIS); thus, a biopsy may be needed to exclude malignant disease. Reflectance confocal microscopy (RCM) is an in vivo imaging method to get morphologic information about architecture and single cells in the skin. To evaluate the ability of RCM to differentiate between balanitis and CIS compared with the gold standard histopathologic methods. Observer blinded study. A referral center. Fifteen patients with balanitis or CIS. Patients were assessed by clinical, histologic, and RCM findings. All lesions were imaged with the Vivascope 1500. In 5 cases of balanitis, the surrounding, noninvolved skin also was evaluated. Local recurrence, nodal metastasis, disease-specific death, overall death. The clinical diagnoses showed 9 cases of balanitis and 6 cases of CIS. With histopathologic analysis, 12 cases of balanitis and cases of CIS were diagnosed, and RCM evaluation confirmed these diagnoses. The most relevant RCM criteria for CIS were atypical honeycomb pattern, disarranged epidermal pattern, and round nucleated cells. Balanitis showed a nucleated honeycomb pattern and vermicular vessels. Scattered small bright cells and round vessels were present in all lesions. The adjacent normal skin showed a typical honeycomb pattern and round papillary vessels. We were able to differentiate between balanitis and CIS. Reflectance confocal microscopy may help to avoid biopsies at this sensitive site.

Seborrheic keratosis: Reflectance confocal microscopy features and correlation with dermoscopy

Differentiation between seborrheic keratosis (SK) and skin cancers may be difficult. Reflectance confocal microscopy (RCM) enables noninvasive assessment of skin neoplasms at cellular-level resolution. We sought to describe RCM features of SK and to correlate these RCM findings with dermoscopic structures. Clinical, dermoscopic, and RCM images of 45 consecutive SK were obtained at a private and university dermatology clinic. Fourteen SK were biopsied because of equivocal clinical or dermoscopic features. With RCM, all SK displayed a regular honeycomb pattern of the epidermis and densely packed, round to polymorphous, well-circumscribed dermal papillae at the dermoepidermal junction, features suggestive of a benign neoplasm. RCM features indicating the diagnosis of SK were also observed, including epidermal projections (43/45 SK; 96%) and keratin-filled invaginations (36/45 SK; 80%) at the lesion surface; corneal pseudocysts at epidermal layers (19/45 SK; 42%); and melanophages (21/45 SK; 47%) and dilated round and linear blood vessels (21/45 SK; 47%) in the papillary dermis. Of biopsied SK, 93% (13/14) displayed at least 3 characteristic RCM findings in the absence of RCM features suggestive of malignancy. This was a limited study sample and retrospective study design. SK display a distinct set of RCM criteria despite their variable clinical and dermoscopic appearances.

Confocal features of equivocal facial lesions on severely sun-damaged skin: Four case studies with dermatoscopic, confocal, and histopathologic correlation

Facial skin has a distinct histologic architecture and reveals specific dermatoscopic features. Diagnosis of lentigo maligna on the face is often challenging because of the overlap of clinical and morphologic features with other lesions. We aim to show the value of reflectance confocal microscopy (RCM) as a noninvasive diagnostic tool for facial lesions and to increase knowledge of RCM morphologic features among the scientific community. We describe a series of 4 facial lesions on severely sun-damaged skin that was evaluated via RCM immediately after face-to-face examination, followed by shave biopsy for histopathological analysis. Lesions included a lentigo maligna, a pigmented seborrheic keratosis, pigmented basal cell carcinoma, and a pigmented actinic keratosis. In the presented cases, RCM enabled an accurate diagnosis. The study describes morphologic features on selected cases, but does not test accuracy of RCM criteria. RCM is a useful adjuvant for the accurate and precise diagnosis of equivocal facial lesions.