Reflectance Confocal Microscopy Features Research Articles

A Prospective Double-Blinded Comparison of Reflectance Confocal Microscopy with Conventional Histopathology for In Vivo Assessment in Oral Cancer.

We investigated reflectance confocal microscopy (RCM) as a possible non-invasive approach for the diagnosis of cancer and real-time assessment of surgical margins. In a phase I study on 20 patients, we established the RCM imaging morphological features that distinguish OSCC from normal tissue with a newly developed intra-oral RCM probe. Our subsequent phase II prospective double-blinded study in 60 patients tested the diagnostic accuracy of RCM against histopathology. Five RCM videos from the tumor and five from normal surrounding mucosa were collected on each patient, followed by a 3-mm punch biopsy of the imaged area. An experienced RCM reader, who was blinded to biopsy location and histological diagnosis, examined the videos from both regions and classified each as "tumor" or "not-tumor" based on RCM features established in phase I. Hematoxylin and eosin slides from the biopsies were read by a pathologist who was blinded to RCM results. Using histology as the gold standard, we calculated the sensitivity and specificity of RCM. We report a high agreement between the blinded readers (95% for normal tissue and 81.7% for tumors), high specificity (98.3%) and negative predictive values (96.6%) for normal tissue identification, and high sensitivity (90%) and positive predictive values (88.2%) for tumor detection. RCM imaging is a promising technology for non-invasive in vivo diagnosis of OSCC and for real-time intraoperative evaluation of mucosal surgical margins. Its inherent constraint, however, stems from the diminished capability to evaluate structures located at more substantial depths within the tissue.

Vitiligo Treated with Combined Piperine-Based Topical Treatment and Narrowband Ultraviolet B Therapy: Follow-Up with Reflectance Confocal Microscopy.

Reflectance confocal microscopy (RCM) has a defined in vivo morphology of vitiligo and re-pigmentation. Combination therapies seem more effective than monotherapies. We aim to describe the clinical and RCM features of re-pigmentation with combined narrowband ultraviolet B (NB-UVB) and piperine-based topical treatment in localized vitiligo. Eight patients enrolled at a single center received combined treatment: topical treatment was applied twice daily + NB-UVB twice weekly for 2 × 2-month periods. Clinical changes were analyzed by the Vitiligo Noticeability Scale (VNS) and percentage of re-pigmentation. The evaluator agreement was assessed. Predefined RCM features had the presence/absence of (i) blood vessels, (ii) dendritic cells, and the quantity of (i) an irregular honeycombed pattern and (ii) non-pigmented papillae. Clinical and RCM monitoring was performed at the baseline, 2, 3, 5, and 7 months. Macules were "slightly less noticeable" with 25-50% re-pigmentation. Irregular honeycomb patterns and non-pigmented papillae were significantly less frequently observed, and in less extended areas (T1 vs. T2, p = 0.039; T0 vs. T1, p = 0.005 and T2 vs. T4, p = 0.033). Dendritic cells and blood vessels improved, with significant changes in blood vessels (T1 vs. T2, p = 0.005 and T3 vs. T4, p = 0.008). RCM confirms the morphological changes induced by combined treatment for localized vitiligo.

Dermoscopy and reflectance confocal microscopy finding of different anatomic sites of Langerhans cell histiocytosis.

Recognizing Langerhans cell histiocytosis (LCH) might be a challenge due to its rarity. Reflectance confocal microscopy (RCM) and dermoscopy were emergent promising non-invasive technique as auxiliary tools in diagnosis of different skin conditions. However, the RCM and dermoscopic features of LCH had been less investigated. To reveal the common RCM and dermoscopic features of LCH. Forty cases of LCH were retrospectively analyzed according to age, locations, clinical, RCM, and dermoscopic features from September 2016 to December 2022. To reveal the differences and common in clinical, RCM, and dermoscopic features that occur in different anatomic location. In the study, sites of predilection include the trunk 31/40 (77.5%), extremity 21/40 (52.5%), face 14/40 (35%), scalp 11/40 (27.5%), vulvar 4/40 (10%), and nail 2/40 (5%). All LCHs had the common RCM features. There were significant differences in clinical and dermoscopic features for age and lesion anatomic site. The common dermoscopic features for scalp, face, trunk, and extremity were the erythematous scaly rash, purplish-red globules or patches, scar-like streaks with ectatic vessels. While the features for nail LCH were purpuric striae, onycholysis and purulent scaly rash, and the erosive erythematous plaque and purulent scaly rash for vulvar LCH. The common RCM features of all LCH showed a focal highly reflective dense image in the surface keratin layer, epidermis architectural disarray, obscuration of dermo-epidermal junction, numerous polygonal, large, medium reflective, short dendrites cells in the epidermis, and dermis. All LCH involving the vulvar and nail did not manifest skin lesions. RCM and dermoscopy showed promising value for diagnosis and differentiation of LCH.

Dermoscopic and reflectance confocal microscopy features of Netherton syndrome.

Dermoscopic and reflectance confocal microscopy features of Netherton syndrome.

Reflectance Confocal Microscopy and Dermoscopy of Facial Pigmented and Non-Pigmented Actinic Keratosis Features before and after Photodynamic Therapy Treatment

Actinic keratosis (AK), due to its widespread prevalence, as well as the possibility of progression to an invasive form of squamous cell carcinoma, requires treatment regardless of the clinical stage. New imaging techniques, such as in vivo reflectance confocal microscopy (RCM), significantly increase the accuracy of diagnosis and allow noninvasive evaluation of the therapeutic efficacy of the ongoing treatment. Our objective was to evaluate the prevalence of specific (video)dermoscopy and RCM features of pigmented and classical subtypes of AK before and after photodynamic therapy (PDT) treatment. We included patients with facial grade II AKs (25 pigmented, 275 non-pigmented) were included in the study. Skin lesions were evaluated by (video)dermoscopy and RCM at the baseline and three months after PDT. In classic AK, the most frequent dermoscopic findings were fine wavy vessels (96%), scale (92%), microerosions (48%), and “strawberry” pattern (36%), while pigmented AK was characterized mostly by “rhomboidal pattern” (80%), scale (60%), white globules (48%), “jelly sign”, and superficial pigmentation (40%). RCM’s most characteristic classic AK findings were abnormal honeycomb pattern in the spinous layer, epidermal inflammatory infiltrate, and solar elastosis that were present in 96% of lesions. Pigmented AKs presented mostly with dark central areas of parakeratosis (72%), mottled pigmentation (72%), dermal inflammatory infiltrate (64%), solar elastosis (60%), and abnormal honeycomb pattern in the spinous layer (56%). Dermoscopically, PDT resulted in complete disappearance of the “rhomboidal pattern” in both classical and pigmented AKs, “starburst pattern” and “jelly sign” in classical AKs, and inner gray halo, “rosette sign” and central crust in pigmented AKs. Three months after one PDT session, RCM evaluation showed mostly solar elastosis in both classical and pigmented AK subtypes, epidermal inflammatory infiltrate in classical AKs, and dermal inflammatory infiltrate in pigmented AKs. New noninvasive imaging techniques such as RCM and (video)dermoscopy can help practitioners better visualize the efficacy of the ongoing PDT treatment in either classical or pigmented AK subtypes.

Melanoma clinicopathological groups characterized and compared with dermoscopy and reflectance confocal microscopy

Dermoscopic and reflectance confocal microscopy (RCM) correlations between morphologic groups of melanoma have not yet been described. Describe and compare dermoscopic and RCM features of cutaneous melanomas with histopathological confirmation. Single center, retrospective analysis of consecutive melanomas evaluated with RCM (2015-2019). Lesions were clinically classified as typical, nevus-like, amelanotic/nonmelanoma skin cancer (NMSC)-like, seborrheic keratosis (SK)-like and lentigo/lentigo maligna (LM)-like. Presence or absence of common facial and nonfacial melanoma dermoscopic and RCM patterns were recorded. Clusters were compared with typical lesions by multivariate logistic regression. Among 583 melanoma lesions, significant differences between clusters were evident (compared to typical lesions). Observation of dermoscopic features (>50% of lesions) in amelanotic/NMSC-like lesions consistently displayed 3 patterns (atypical network, atypical vascular pattern+regression structures), and nevus-like and SK-like lesions and lentigo/LM-like lesions consistently displayed 2 patterns (atypical network+regression structures, and nonevident follicles+heavy pigmentation intensity). Differences were less evident with RCM, as almost all lesions were consistent with melanoma diagnosis. Small SK-like lesions sample, single RCM analyses (no reproduction of outcome). RCM has the potential to augment our ability to consistently and accurately diagnose melanoma independently of clinical and dermoscopic features.

Reflectance confocal microscopy as a complementary diagnostic tool for greyish-brown dermatoses in children.

Mastocytosis, lichen planus pigmentosus (LPP), fixed drug eruption (FDE) and café-au-lait macules (CALM) have a similar appearance, often lead to misdiagnosis and missed diagnoses. At the outpatient clinic at Tianjin Children's Hospital in 21 patients with mastocytosis, 18 with LPP, 11 with FDE and 12 with CALM we evaluated the characteristics and distinguishing features of their dermatoses using reflectance confocal microscopy (RCM). In mastocytosis, the dermal papillary rings generally had a significantly increased bright refractive index and the superficial dermis was filled with moderate refractive flocculent material. In LPP, the dermal papillary rings were absent and numerous different-sized cellular structures were densely distributed in the superficial dermis. In FDE, the dermal papillary rings were intact with a significantly increased bright refractive index. In CALM, normal dermal papillary rings were detected with a uniformly slightly increased refractive index and no obvious abnormality in the superficial dermis. RCM allows for real-time visualization of the major key diagnostic and distinguishing features of four greyish-brown dermatoses in children.

Concordance of in vivo reflectance confocal microscopy and horizontal-sectioning histology in skin tumours.

In vivo reflectance confocal microscopy (RCM) enables the study of architectural and cytological aspects in horizontal sections, which closely correlate with histologic features. However, traditional histopathological vertical sections cannot totally reproduce the image of the in vivo RCM horizontal section. To evaluate the concordance between in vivo RCM and histopathologic transverse sections for melanocytic lesions, basal cell carcinoma and seborrheic keratoses. Prospectively collected benign melanocytic and non-melanocytic tumours diagnosed by dermoscopy were evaluated for common RCM features and compared to histopathology in horizontal sections with haematoxylin and eosin staining. A total of 44 skin tumours including 19 melanocytic lesions (nine compound, five junctional and five intradermal nevi), 12 basal cell carcinomas and 13 seborrheic keratoses were collected in the Department of Dermatology of Hospital Clinic of Barcelona. The RCM features that had statistically significant agreement with the histopathological horizontal sections were the preserved and visible honeycomb pattern, well defined DEJ, small bright particles, dermal nests, tumour islands and dark silhouettes, clefting, collagen bundles, thickened collagen bundles and cytologic atypia. Histopathology evaluation of horizontal sections of skin tumours can be correlated with main RCM findings. The results of this study have improved the understanding and interpretation of RCM features in relation to skin tumours, thus reinforcing the utility of RCM as a diagnostic tool.

Dermoscopic and reflectance confocal microscopic features of children scabies.

To summarize the image features of dermatoscopy and reflectance confocal microscopy (RCM) in children with scabies, and to explore the clinical significance in the diagnosis of children scabies. A retrospective analysis was conducted on 102 children scabies diagnosed clinically in the dermatology outpatient department of Tianjin Children's Hospital from April 2018 to June 2022. All children were examined by dermatoscopy and RCM, and images were collected. 102 patients, 92 patients (90.2%) showed characteristic dermoscopic manifestations: white tunnels and small brown or dark brown triangular structures at their ends. 91 patients (89.2%) showed characteristic reflectance confocal microscopic manifestations: tunnels, scabies mites, feces, and eggs in the epidermal layer. All patients showed different degrees of non-specific manifestations of dermoscopy and RCM. Children scabies have typical dermatoscopic and reflectance confocal microscopic characteristics, and dermatoscopy and RCM are effective non-invasive diagnostic methods with high clinical application value in the diagnosis and differential diagnosis of children scabies.

Reflectance confocal microscopy features of vulvar lichen sclerosus in Chinese juvenile girls.

Vulvar lichen sclerosus (VLS) is a chronic inflammatory dermatosis of unknown pathogenesis, characterized by porcelain-white atrophic plaques around the vulvar and anal areas in girls. With this communication, we performed the study on 16 female girls with clinically and histologically confirmed VLS, described the main identifying characteristics of the lesions in reflectance confocal microscopy (RCM) and elucidated the corresponding relationship between RCM findings and histology. We recommend RCM, a noninvasive technique, as a complementary diagnostic tool for VLS.

Lentigo maligna and lentigo maligna melanoma in-vivo differentiation with dermoscopy and reflectance confocal microscopy: a retrospective, multi-center study.

Dermoscopic predictors of lentigo maligna (LM) and lentigo maligna melanoma (LMM) have been recently reported, but these have not been reported in reflectance confocal microscopy (RCM). (i) To validate dermoscopic predictors for LM/LMM, (ii) to identify RCM patterns in LM and LMM and (iii) correlations between dermoscopic and RCM features in LM and LMM. A retrospective, multicenter study of consecutive lesions with histologically proven LM or LMM subtypes of the head and face, with complete sets of dermoscopic and RCM images. A total of 180 lesions were included (n=40 LMM). Previously reported differential dermoscopic features for LM subtypes were confirmed. Other features significantly associated with LMM diagnosis included irregular hyperpigmented areas, shiny white streaks, atypical vessels, and light brown color at dermoscopy and medusa head-like structures, dermal nests and nucleated cells within the papillae at RCM (p<0.05). Correlations among LM lesions between dermoscopic and RCM features included brown to-gray dots and atypical cells (epidermis), grey color and inflammation and obliterated follicles and medusa head-like structures. Among LMM lesions, significant correlations included obliterated follicles with folliculotropism, both irregular hyperpigmented areas and irregular blotches with widespread atypical cell distribution (epidermis), dermal nests and nucleated cells within the papillae (dermis). Irregular blotches were also associated with medusa head-like structures (dermal epidermal junction [DEJ]). Dermoscopic and RCM features can assist in the in-vivo identification of LM histopathological subtypes and many are correlated. RCM 3-dimensional analysis of skin layers allows the identification of invasive components in the DEJ and dermis.

Detection of sebaceous gland hyperplasia with dermoscopy and reflectance confocal microscopy.

Sebaceous gland hyperplasia (SGH) is a benign cutaneous proliferation of the sebaceous glands that are mostly present on the face or the neck of older adults. They typically appear as single or multiple soft umbilicated papules; however, in challenging cases, it can be difficult to distinguish them from trichoepitheliomas, base cell carcinomas, or other tumors. Although pathological results have diagnostic value, the significance of non-invasive examinations in diagnosis and differential diagnosis is also worth exploring. This study aimed to describe the dermoscopic and reflectance confocal microscopy (RCM) features of SGH. A total of 31 patients diagnosed with SGH, according to clinical and histopathological standards, were examined using dermoscopy and RCM between March 2018 and January 2022. Dermoscopically, lesions revealed a yellowish-red background and a faint-yellow background in 25 (80.65%) and six cases (19.35%), respectively. White-yellowish lobulated structures in the center of the lesion were present in 31 patients (100%) and umbilications in 19 patients (61.29%). Crown vessels at the periphery of the lesions were observed in 11 patients (35.48%), whereas irregular linear vessels were observed on the surface of the lesions in 18 patients (58.06%). Under RCM, all lesions presented a honeycomb pattern in the epidermis and the typical morulae-shaped sebaceous lobules in the dermis. A dilated follicular infundibulum was observed in 15 patients (48.39%) and dilated vessels in 26 patients (83.87%). Dermoscopy and RCM enabled us to describe the imaging features of SGH. Combining these two useful tools provides a non-invasive basis for accurate clinical diagnosis.

In vivo reflectance confocal microscopy findings in a case of atypical fibroxanthoma.

Clinical and dermoscopic features of atypical fibroxanthoma (AFX) are mostly non-diagnostic, so other in vivo diagnostic tools may give additional clues for accurate clinical diagnosis, such as in vivo reflectance confocal microscopy (RCM). However, there has been scarce data on RCM features of AFX in the literature, in only clear cell type. Herein we present a case of epithelioid cell predominant type AFX with RCM findings.

Preliminary evaluation of penile papule dermatoses with reflectance confocal microscopy in children.

Owing to their similar appearance, lichen striatus (LS), lichen nitidus (LN), juvenile xanthogranuloma (JXG), and molluscum contagiosum (MC) on the penis often lead to misdiagnosis and missed diagnosis, especially in children. In vivo evaluation of penile dermatoses with reflectance confocal microscopy (RCM) is helpful in the diagnosis of these ambiguous lesions in children. We recruited 12 patients with LS, nine with LN, seven with JXG, and nine with MC and evaluated the characteristics and distinguishing features of the four kinds of papule dermatoses on the penis using RCM. The four dermatoses all had unique RCM features. LS generally showed focally destroyed dermal papillary rings, with numerous mononuclear cell clusters aggregated inside the papillary rings, and highly refractive clumps were observed. For LN, the dermal papillary rings were completely destroyed and arranged in a solitary, enlarged, cavity-like structure, in which round cells, particulate matter structures, and plump cellular structures were aggregated; the adjacent skin was completely normal. In JXG, the dermal papillary rings were significantly dilated, and the superficial dermis was filled with different-sized large bright ring cells; smaller, refractive, roundish structures; and particulate matter. For MC, the normal structures completely disappeared; the lesions were arranged in a crater-shaped structure; and a mass-like substance formed by the aggregation of multiple, uniform, roundish structures was observed within the crater. RCM allows for real-time visualization of major key diagnostic and distinguishing features of four papule dermatoses, LS, LN, JXG, and MC, on the penis in children.

High-speed reflectance confocal microscopy of human skin at 1251-1342 nm.

Reflectance confocal microscopy (RCM) is an imaging method that can noninvasively visualize microscopic features of the human skin. The utility of RCM can be further improved by increasing imaging speed. In this paper, we report high-speed RCM imaging of human skin with a frame rate that is over 10 times faster and an area imaging rate that is 6-9 times faster than those of commercially available RCM devices. The higher imaging speed was achieved using a high-speed RCM technique, termed spectrally encoded confocal microscopy (SECM). SECM uses a diffraction grating and a high-speed, wavelength-swept source to conduct confocal imaging at a very high rate. We developed a handheld SECM probe using a scanned-grating approach. The SECM probe was used in conjunction with a wavelength-swept source with a spectral band of 1251-1342 nm. The SECM probe achieved high lateral resolution of 1.3-1.6 µm and an axial resolution of 3.5 µm. SECM images of the human skin (image size = 439 × 439 µm2 ) obtained at 100 frames/s clearly show previously reported RCM features of the human skin in vivo with adequate image quality. The fast imaging speed allowed for the rapid acquisiton of volumetric SECM image data (200 frames covering a depth range of 200 µm) within 2 s. The use of 1251-1342 nm provided sufficient signal level and contrast required to visualize key cellular morphologic features. These preliminary results demonstrate that high-speed SECM imaging of the human skin at 1251-1342 nm is feasible.

The differential diagnosis of lichenoid keratosis and seborrheic keratosis with reflectance confocal microscopy: a preliminary study.

Lichenoid keratosis (LK, or lichen planus-like keratosis, LPLK) and seborrheic keratosis (SK) present as similar benign keratotic lesions on cosmetically sensitive area, but require different therapies. Both lesions can be easily differentiated based on histological evaluation of biopsy materials. However, the biopsies may cause scarring and result in hyper-pigmentation, which reduces the compliance of the patients to be treated. In this study, we investigated the role of reflectance confocal microscopy (RCM) in the non-invasive differential diagnosis of LK and SK. Cases with facial brown patches or plaques suspicious of SK were enrolled in the study. After written informed consent was obtained, the lesions were photographed, imaged by RCM, and then biopsied. The RCM findings were analyzed and correlated with histology results. Evaluation of the RCM pictures and confirmation with histological results were conducted by two independent dermatologists. In total, 10 cases were enrolled in the study. The main characteristics of LK lesions observed by RCM were the disarray of the dermal-epidermal junction (DEJ), and marked inflammatory infiltrates in the superficial dermis; while prominent cerebriform pattern, or elongated cords with bulbous projections without significant inflammation reaction, were the features of SK. Among the 10 cases, clinically suspicious of facial SK, 4 were determined as LK, 6 as SK by RCM imaging, and all the RCM findings were confirmed by histological results. The RCM features of LK and SK have significant difference, highlighting the important role of RCM in the differential diagnosis of LK and SK, avoiding biopsies and allowing safe treatments.

Management of lentiginous melanoma with imiquimod assessed by reflectance confocal microscopy.

Lentiginous melanoma (LM) has poorly defined margins and may be subject to inaccurate assessment by traditional methods, including clinical evaluation and dermoscopy.1 Imiquimod, a topical immunomodulatory agent, has been used as an alternative to surgical treatment for LM, but concern for incomplete tumour clearance limits its widespread adoption. Reflectance confocal microscopy (RCM) is a high-resolution, non-invasive imaging technique and a reliable diagnostic tool to identify LM, with a sensitivity of 85% and specificity of 76%.2 Given LM often presents on cosmetically sensitive regions such as the face, non-invasive therapy and monitoring techniques, such as imiquimod and RCM, respectively, may be preferred. We systematically reviewed the literature on LM treated with imiquimod and assessed by RCM. We identified 10 relevant publications and graded the evidence using the Joanna Briggs Institute (JBI) critical appraisal tool (Table 1, Supplementary Figure S1). Across all studies, there was a total of 168 participants, of which 114 were female and 54 were male. Participants' ages ranged from 33 to 90. Facial LM was the most common type of LM evaluated in all publications reviewed. In 7/10 publications, a treatment regimen of imiquimod 5% daily, five times per week was utilised. The average length of imiquimod treatment in the evaluated studies was approximately 10 weeks. Studies reproducibly demonstrated imiquimod as a potential treatment alternative to traditional surgical excision. Furthermore, RCM margin evaluation had high concordance with gold standard histopathology (Table 1). For the studies that specified evaluation time points, RCM assessment was performed four or more weeks after treatment with imiquimod. One prospective study (n = 20) reported LM histopathologic clearance with imiquimod in 75% of patients. RCM identified 93% of the responders with no false negatives (compared to histopathology) at 12 weeks and 12 months after treatment. Responders continued to have histopathological clearance for a mean of 34 months3 Several retrospective studies demonstrated imiquimod to be an adequate treatment for LM with concurrent RCM monitoring. In one study (n = 18) evaluating 5-year recurrence rates of LM after imiquimod treatment, all 18 patients had histopathologically clear margins 3 months post-treatment. Long-term tumour clearance (mean follow-up 7.4 years) measured by RCM revealed no evidence of recurrence in any patient.9 In another retrospective study (n = 34), 33/34 patients demonstrated initial therapeutic response with imiquimod as measured by RCM and histopathology. Seven patients had LM recurrence within a mean of 3.07 years. RCM measurements significantly correlated with histopathology results (r = 0.7335, p = 0.0001).5 Another retrospective study detected recurrence in 1/7 patients treated with imiquimod at 1-year follow-up (tumour had previously recurred five times). This patient was treated with a subsequent course of imiquimod, and no recurrence was detected via RCM evaluation at 40 months following this second treatment.1 A subsequent retrospective study (n = 28) demonstrated complete clearance in 25/28 participants treated with imiquimod. In comparison to histopathological evaluation for tumour recurrence, RCM had a specificity of 94% and a sensitivity of 100%.7 In a case series of three participants treated with imiquimod for LM, two achieved complete clearance and had no recurrence after an 18-month follow-up period, evaluated by RCM and histopathology concordantly. One patient achieved partial clearance at initial evaluation by RCM, but was lost to follow-up.6 An additional case series included two patients with LM treated with imiquimod. One patient achieved complete clearance after 3 months of therapy and remained disease-free 2 years after treatment. The other patient failed 7 months of treatment and required surgical excision. RCM was concordant with histopathological evaluation in both cases.10 A randomized controlled trial evaluated imiquimod as a neoadjunvant treatment prior to surgery. Researchers compared the pre-surgical treatment of LM with imiquimod versus placebo. Prior to surgery, pre-determined RCM features, such as non-edged dermal papillae, were significantly decreased in the imiquimod arm (n = 21) versus placebo (n = 19) after 1 month of treatment (p < 0.001). RCM was concordant with histology in 19 of 21 patients (90%) with no false negatives.11 Current data demonstrate that imiquimod can be effectively utilised in the treatment of LM. This review is limited by varying follow-up times for long-term tumour recurrence monitoring. Prior data have shown that the median time to LM recurrence after treatment is 3.8 years12 Two of the included publications had a follow-up period greater than 3.8 years. In these studies, a tumour recurrence was detected in 10/34 patients. Given that, imiquimod alone may not be sufficient for complete LM clearance and may be more suitable as an adjunctive therapy. Larger prospective studies are warranted to explore the limitations of and an appropriate clinical scenario for imiquimod as monotherapy for LM treatment. RCM demonstrated margin evaluation concordance or significant positive correlation with histopathology in 9/10 publications. Of particular clinical importance, in the 8 studies that reported concordance rates, there were no false negatives when RCM was used to evaluate for residual LM following imiquimod treatment. This supports its potential use as a non-invasive and reliable method to monitor imiquimod treatment of LM. This letter received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors declare that there is no conflict of interest. Joseph Han: Conceptualization (Lead); Data curation (Lead); Formal analysis (Lead); Investigation (Lead); Methodology (Lead); Project administration (Lead); Validation (Lead); Visualization (Lead); Writing – original draft (Lead); Writing – review & editing; Lead. Hansen Tai: Conceptualization (Lead); Data curation (Lead); Formal analysis (Lead); Investigation (Lead); Methodology (Lead); Project administration (Lead); Validation (Lead); Visualization (Lead); Writing – original draft (Lead); Writing – review & editing (Lead). Dina Poplausky: Data curation (Equal); Formal analysis (Equal); Investigation (Equal); Methodology (Equal); Project administration (Equal); Validation (Equal); Visualization (Equal); Writing – original draft (Equal); Writing – review & editing (Equal). Jade Young: Data curation (Equal); Formal analysis (Equal); Investigation (Equal); Methodology (Equal); Project administration (Equal); Validation (Equal); Visualization (Equal); Writing – original draft (Equal); Writing – review & editing; Equal. Rishab Revankar: Data curation (Equal); Investigation (Equal). Peter Baek: Data curation (Equal); Investigation (Equal); Samantha Walsh: Data curation (Lead); Methodology (Lead); Nicholas Gulati: Conceptualization (Lead); Methodology (Lead); Project administration (Lead); Supervision (Lead); Writing – review & editing (Lead). This article received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Not applicable. The data that supports the findings of this study are available in the supplementary material of this article. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Dermoscopy and reflection confocal microscope features of pigmented prurigo.

Pigmented prurigo (PP) is a chronic and recurrent inflammatory skin disease. PP is not common clinically, but it is easily misdiagnosed because of its diversified clinical manifestations in different stages. We retrospectively analyzed the clinical, histopathological, dermoscopy, and reflectance confocal microscopy (RCM) features of 20 patients diagnosed as PP. The female predominance ratio was revealed with male to female of 1:4. Seven female patients were on a diet (without staple food) and one patient had a history of diabetes. Eight cases were suffered in spring, six cases in winter, three cases in summer, and three cases in autumn. Multiple sites were involved in 13 cases. Four patients had urticarial papules and plaques. Nineteen patients had erythematous papules with reticular distribution, of which 14 cases accompanied reticulate hyperpigmentation, four cases with papulovesicle, and two cases accompanied with pustules. One patient only showed reticulate hyperpigmentation. In the early lesions, dermatoscopy showed pink oval lesions, punctate or linear vessels, and pale yellow rings around the skin lesions. RCM is characterized by spongiosis, spongy vesicle, neutrophils scattered in the epidermis, which was consistent with epidermis spongiosis, neutrophils infiltrating into the upper epidermis and necrotic keratinocytes in histopathology. In the fully developed lesions, dermatoscopy showed pink lesions with brown pigment granules in the center and linear vessels in the edge. RCM showed that demarcation of epidermis and dermis is not clear, and inflammatory cells can be seen in the upper dermis and histopathologically lesions assumed a patchy lichenoid pattern, and the inflammatory cells infiltrating the dermis were dominated by lymphocytes. In the late lesions, dermatoscopy showed grainy grayish-brown or yellowish-brown pigmentation surrounding the hair follicle merging with each other. RCM showed that pigment granules were increased on the ring of basal cells, inflammatory cells were sparsely infiltrated in the dermal papilla and superficial layer, and epidermis slightly hyperplastic, with melanophages and a few lymphocytes infiltrating the superficial dermis in histopathology. PP is easily misdiagnosed and not always occurs in those on a restrictive diet. A combination of dermatoscopy and RCM is helpful for its diagnosis of PP.

Skin ageing: Clinical aspects and in vivo microscopic patterns observed with reflectance confocal microscopy and optical coherence tomography.

Few studies have combined high-resolution, non-invasive imaging, such as standardized clinical images, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), for age-related skin change characterization according to age groups. This study aimed to correlate clinical manifestations of ageing with skin cytoarchitectural background observed with high-resolution, non-invasive imaging according to age-related skin pattern distribution. A set of 140 non-pathological facial skin images were retrospectively retrieved from a research database. Subjects, aged between 20 and 89, were divided into 7 age groups. Clinical features were explored with VISIA, including hyperpigmentation, skin texture, wrinkles, pores and red areas, quantified and expressed as automated absolute scores. Previously described RCM and OCT epidermal and dermal features associated with ageing were investigated. All features were assessed for distribution and correlation among age groups. Significant direct correlations between age and clinical features were proven for cutaneous hyperpigmentation, skin texture, wrinkles and red areas. As age advances, RCM epidermal irregular honeycomb and mottled pigmentation are more frequently observed and collagen is more frequently coarse, huddled and curled, while the epidermis in OCT is thickened and the dermal density is decreased with more disrupted collagen fibres. RCM and OCT feature changes correlate directly and indirectly as well as correlating directly and indirectly with standardized clinical images. Clinical manifestations of ageing correlate with skin cytoarchitectural background observed with RCM and OCT. In conclusion, complimentary information between standardized clinical images and high-resolution, non-invasive imaging will assist in the development of future studies dedicated to skin ageing assessment and treatment effectiveness.

In vivo evaluation of vulvar lichen sclerosus with reflectance confocal microscopy and therapeutic monitoring in children.

Vulvar lichen sclerosus (VLS) in girls presents with itching, dysuria, and constipation and may result in the loss of vulvar architecture. In patients with an ambiguous clinical presentation, reflectance confocal microscopy (RCM) could be a helpful noninvasive diagnostic tool. The aim of this study was to describe the RCM characteristics of VLS and explore the clinical application value of RCM in therapeutic monitoring. Sixteen patients with VLS were included in the study. All patients were periodically evaluated clinically with RCM, and different treatment regimens were given based on the patient's clinical appearances and RCM features. Some major key diagnostic features of VLS can be observed by RCM, including round to oval cyst-like structures with medium-to-low-refractive keratinoid substances (75%), thinning of the epidermal thickness (100%), destruction of the ring-like structures around dermal papillae (100%), disorderly distributed coarse medium-refractive fibrous material (100%),polygonal, plump, high-refractive cellular structures and linear low-refractive canalicular structures (100%). All of these characteristics had a high correspondence with histopathological features. The clinical manifestations improved after individualized treatment regimens based on the clinical appearances and RCM features. RCM allows the visualization of major key diagnostic features of VLS and represents a valid option for objective therapeutic monitoring.