Perifollicular linear projections: A dermatoscopic criterion for the diagnosis of lentigo maligna on the face.

BACKGROUND: Lentigo maligna (LM) can mimic benign, flat, pigmented lesions and can be challenging to diagnose. OBJECTIVE: To describe a new dermatoscopic feature termed "perifollicular linear projections (PLP)" as a diagnostic criterion for LM on the face. METHODS: Retrospective study on reflectance confocal microscopy and dermatoscopy images of flat facial pigmented lesions originating from 2 databases. PLP were defined as short, linear, pigmented projections emanating from hair follicles. Dermatoscopy readers were blinded to the final histopathologic diagnosis. RESULTS: From 83 consecutive LMs, 21/83 (25.3%) displayed "bulging of hair follicles" on reflectance confocal microscopy and 18 of these 21 (85.7%), displayed PLP on dermatoscopy. From a database of 2873 consecutively imaged and biopsied lesions, 252 flat-pigmented facial lesions were included. PLP was seen in 47/76 melanomas (61.8%), compared with 7/176 lesions (3.9%) with other diagnosis (P < .001). The sensitivity was 61.8% (95% CI, 49.9%-72.7%), specificity 96.0% (95% CI, 92.9%-98.4%). PLP was independently associated with LM diagnosis on multivariate analysis (OR 26.1 [95% CI, 9.6%-71.0]). LIMITATIONS: Retrospective study. CONCLUSION: PLP is a newly described dermatoscopic criterion that may add specificity and sensitivity to the early diagnosis of LM located on the face. We postulate that PLP constitutes an intermediary step in the LM progression model.

Clinical Utility of an AI-powered, Handheld Elastic Scattering Spectroscopy Device on the Diagnosis and Management of Skin Cancer by Primary Care Physicians.

BACKGROUND: Patients with lesions suspicious for skin cancer often present to primary care physicians (PCPs), who may have limited training in skin cancer diagnosis. OBJECTIVE: To measure the impact of an adjunctive handheld device for PCPs that employs elastic scattering spectroscopy (ESS) on the diagnosis and management of skin cancer. METHODS: Fifty-seven PCPs evaluated 50 clinical images of skin lesions (25 malignant and 25 benign), first without and then with knowledge of the handheld ESS device output, and in each case indicated if a lesion was likely to be benign or malignant. RESULTS: The diagnostic sensitivity of the PCPs with and without the use of the ESS device was 88% (95% CI, 84%-92%) and 67% (95% CI, 62%-72%), respectively (P < .0001). In contrast, no significant difference was observed in the diagnostic specificity. The management sensitivity of the physicians with and without the use of the ESS device was 94% (95% CI, 91%-96%) and 81% (95% CI, 77%-85%), respectively (P = .0009). Similarly, no significant difference was observed in the management specificity. CONCLUSION: The use of the ESS device may have the potential to help improve skin cancer diagnosis and confidence in management decision-making in a primary care setting.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Evaluation of RCM criteria centering on the follicles can be useful in the differential diagnosis between common facial neoplasms.

The skin through reflectance confocal microscopy -Historical background, technical principles, and its correlation with histopathology

Abstract Since its first introduction into medical practice, reflectance confocal microscopy (RCM) has been a valuable non-invasive diagnostic tool for the assessment of benign and malignant neoplasms of the skin. It has also been used as an adjunct for diagnosing equivocal cutaneous neoplasms that lack characteristic clinical or dermoscopic features. The use of RCM has led to a decreased number of biopsies of benign lesions. Multiple published studies show a strong correlation between RCM and histopathology thereby creating a bridge between clinical aspects, dermoscopy, and histopathology. Dermatopathologists may potentially play an important role in the interpretation of confocal images, by their ability to correlate histopathologic findings. RCM has also been shown to be an important adjunct to delineating tumoral margins during surgery, as well as for monitoring the non-surgical treatment of skin cancers. Advanced technology with smaller probes, such as the VivaScope 3000, has allowed access to lesions in previously inaccessible anatomic locations. This review explains the technical principles of RCM and describes the most common RCM features of normal skin with their corresponding histological correlation.

The skin through reflectance confocal microscopy - Historical background, technical principles, and its correlation with histopathology.

Since its first introduction into medical practice, reflectance confocal microscopy (RCM) has been a valuable non-invasive diagnostic tool for the assessment of benign and malignant neoplasms of the skin. It has also been used as an adjunct for diagnosing equivocal cutaneous neoplasms that lack characteristic clinical or dermoscopic features. The use of RCM has led to a decreased number of biopsies of benign lesions. Multiple published studies show a strong correlation between RCM and histopathology thereby creating a bridge between clinical aspects, dermoscopy, and histopathology. Dermatopathologists may potentially play an important role in the interpretation of confocal images, by their ability to correlate histopathologic findings. RCM has also been shown to be an important adjunct to delineating tumoral margins during surgery, as well as for monitoring the non-surgical treatment of skin cancers. Advanced technology with smaller probes, such as the VivaScope 3000, has allowed access to lesions in previously inaccessible anatomic locations. This review explains the technical principles of RCM and describes the most common RCM features of normal skin with their corresponding histological correlation.

Reflectance confocal microscopy: Melanocytic and nonmelanocytic.

Reflectance confocal microscopy (RCM) is a noninvasive imaging tool that has the potential to revolutionize dermatology. Extensive research in this area in conjunction with the recent assignment of reimbursement codes has made the clinical use of this technology a practical reality. Though there is awareness and use of this technology at large academic centers, a knowledge gap still remains in interpreting RCM images among the dermatology community. We review the key RCM features of melanocytic and nonmelanocytic lesions to provide guidance in distinguishing benign entities from malignant dermatologic neoplasms.

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

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.

Reflectance confocal microscopy: Diagnostic criteria of common benign and malignant neoplasms, dermoscopic and histopathologic correlates of key confocal criteria, and diagnostic algorithms.

Reflectance confocal microscopy (RCM) is a high-resolution, noninvasive tool that is currently approved by the US Food and Drug Administration for obtaining and interpreting images of the skin and cutaneous neoplasms with the goal of decreasing unnecessary biopsy procedures in patients with benign lesions. The second article in this continuing medical education series focuses on identifying key criteria for the diagnosis of common skin cancers-melanoma, basal cell carcinoma, and squamous cell carcinoma. We contrast these findings with RCM features of common benign lesions-melanocytic nevi, solar lentigo, seborrheic keratosis, lichen planus-like keratosis, and sebaceous hyperplasia. We also correlate the dermoscopic and histopathologic findings with the RCM features.

Reflectance confocal microscopy: Principles, basic terminology, clinical indications, limitations, and practical considerations.

Reflectance confocal microscopy (RCM) is a noninvasive imaging tool used for in vivo visualization of the skin. It has been extensively studied for use in the evaluation of equivocal cutaneous neoplasms to decrease the number of biopsy procedures in patients with benign lesions. Furthermore, its applications are broadening to include presurgical cancer margin mapping, tumor recurrence surveillance, monitoring of ablative and noninvasive therapies, and stratification of inflammatory disorders. With the approval of category I Current Procedural Terminology reimbursement codes for RCM image acquisition and interpretation, use of this technology has been increasingly adopted by dermatologists. The first article in this 2-part continuing medical education series highlights basic terminology, principles, clinical applications, limitations, and practical considerations in the clinical use of RCM technology.

Reflectance confocal microscopy terminology glossary for melanocytic skin lesions: A systematic review.

BACKGROUND: There is lack of uniformity in the reflectance confocal microscopy (RCM) terminology for melanocytic lesions. OBJECTIVE: To review published RCM terms for melanocytic lesions and identify redundant, synonymous terms. METHODS: A systematic review of original research articles adhering to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was conducted until August 15, 2018. Two investigators gathered all published RCM terms used to describe melanoma and melanocytic nevi. Synonymous terms were grouped based on similarity in definition and in histopathologic correlation. RESULTS: Out of 156 full-text screened articles, 59 studies met the inclusion criteria. We identified 209 terms; 191 (91.4%) corresponding to high-magnification/cellular-level terms and 18 (8.6%) corresponding to low-magnification/architectural patterns terms. The overall average use frequency of RCM terms was 3.1 times (range, 1-31). By grouping of individual RCM terms based on likely synonymous definitions and by eliminating terms lacking clear definition, the total number of RCM terms could be potentially reduced from 209 to 40 terms (80.8% reduction). LIMITATIONS: Non-English and non-peer-reviewed articles were excluded. CONCLUSIONS: This systematic review of published RCM terms identified significant terminology redundancy. It provides the basis for subsequent terminology consensus on melanocytic neoplasms.

The role of reflectance confocal microscopy in differentiating melanoma in situ from dysplastic nevi with severe atypia: A cross-sectional study.

BACKGROUND: Melanoma in situ and dysplastic nevi with severe atypia present overlapping histopathologic features. Reflectance confocal microscopy findings can be integrated with the dermatopathology report to improve differentiation between melanoma and dysplastic nevi with severe atypia. OBJECTIVE: To compare prevalence of reflectance confocal microscopy findings between melanoma in situ and dysplastic nevi with severe atypia. METHODS: This retrospective observational study compared reflectance confocal microscopy findings in dermatopathologically diagnosed dysplastic nevi with severe atypia and melanoma in situ, collected between 2007 and 2017 at a private pigmented-lesion clinic. Concordant pathologic diagnosis was defined as unanimous agreement between 3 dermatopathologists who independently reviewed all cases; all other cases were classified as discordant. RESULTS: The study included 112 lesions, 62 concordant melanomas in situ, 28 concordant dysplastic nevi with severe atypia, and 22 discordant lesions. In comparing reflectance confocal microscopy findings in concordant cases, melanoma in situ showed more frequently than dysplastic nevi with severe atypia the presence of epidermal atypical melanocytes as round cells (19/62 vs 0/28; P < .001) and dendritic cells (50/62 vs 6/28; P < .001), as well as a diffuse distribution of epidermal atypical melanocytes (50/54 vs 3/6; P = .002). In contrast, dysplastic nevi with severe atypia showed the presence of dense melanocytic nests more frequently than melanoma in situ did (15/28 vs 14/62; P = .003). LIMITATIONS: The study was based on a limited number of lesions originating from a single clinic. CONCLUSIONS: Reflectance confocal microscopy findings may help differentiate a subset of dysplastic nevi with severe atypia from melanoma in situ.

Association of Multiple Aggregated Yellow-White Globules With Nonpigmented Basal Cell Carcinoma.

Importance: Basal cell carcinoma (BCC) is the most common skin cancer. Dermoscopic imaging has improved diagnostic accuracy; however, diagnosis of nonpigmented BCC remains limited to arborizing vessels, ulceration, and shiny white structures. Objective: To assess multiple aggregated yellow-white (MAY) globules as a diagnostic feature for BCC. Design, Setting, and Participants: In this retrospective, single-center, case-control study, nonpigmented skin tumors, determined clinically, were identified from a database of lesions consecutively biopsied during a 7-year period (January 1, 2009, to December 31, 2015). A subset of tumors was prospectively diagnosed, and reflectance confocal microscopy, optical coherence tomography, and histopathologic correlation were performed. Data analysis was conducted from July 1 to September 31, 2019. Exposures: Investigators evaluated for the presence or absence of known dermoscopic criteria. MAY globules were defined as aggregated, white-yellow structures visualized in polarized and nonpolarized light. Main Outcomes and Measures: The primary outcome was the diagnostic accuracy of MAY globules for the diagnosis of BCC. Secondary objectives included the association with BCC location and subtype. Interrater agreement was estimated. Results: A total of 656 nonpigmented lesions from 643 patients (mean [SD] age, 63.1 [14.9] years; 381 [58.1%] male) were included. In all, 194 lesions (29.6%) were located on the head and neck. A total of 291 (44.4%) were BCCs. MAY globules were seen in 61 of 291 BCC cases (21.0%) and in 3 of 365 other diagnoses (0.8%) (P < .001). The odds ratio for diagnosis of BCC was 32.0 (96% CI, 9.9-103.2). The presence of MAY globules was associated with a diagnosis of histologic high-risk BCC (odds ratio, 6.5; 95% CI, 3.1-14.3). The structure was never seen in cases of superficial BCCs. Conclusions and Relevance: The findings suggest that MAY globules may have utility as a new BCC dermoscopic criterion with a high specificity. MAY globules were negatively associated with superficial BCC and positively associated with deeper-seated, histologic, higher-grade tumor subtypes.

Reflectance confocal microscopy may enhance the accuracy of histopathologic diagnosis: A case series.

Although histopathology is the time-honored gold standard diagnostic measure in dermatology, several factors may detract from an accurate microscopic diagnosis. Limiting factors include: human error, suboptimal biopsy-site selection or biopsy technique, and inherent restrictions of vertical tissue sectioning that lead to incomplete microscopic evaluation of the lesion. Reflectance confocal microscopy (RCM) is a non-invasive imaging tool that allows for the cellular-level examination of the lesion, at a horizontal plane, which may complement the subsequent vertical histopathological tissue examination. Herein, we report a case series whereby prebiopsy RCM examination enhanced the accuracy of histopathological diagnosis or allowed for a critical appraisal of initial histopathological misdiagnosis.

Melanoma on chronically sun-damaged skin: Lentigo maligna and desmoplastic melanoma.

There are multiple, genetically distinct pathways that give rise to melanoma. Melanomas on sun-damaged skin (MSDS), including lentigo maligna and desmoplastic melanoma, have distinct genetic profiles and are uniquely linked to chronic ultraviolet exposure. In this article, we discuss the etiologies of lentigo maligna and desmoplastic melanoma, emerging diagnostic adjuncts that might be helpful for accurately identifying these lesions, and the clinical relevance of their frequent co-occurrence. We present unique and overlapping features of these entities and discuss challenges in MSDS management, including margin assessment, excision, and the potential role of nonsurgical therapy. Last, we address the role of immunotherapy in invasive disease. Understanding MSDS as distinct from melanoma arising on intermittently sun-exposed or sun-protected skin will ultimately help optimize patient outcomes.

Deep Learning and Handcrafted Method Fusion: Higher Diagnostic Accuracy for Melanoma Dermoscopy Images.

This paper presents an approach that combines conventional image processing with deep learning by fusing the features from the individual techniques. We hypothesize that the two techniques, with different error profiles, are synergistic. The conventional image processing arm uses three handcrafted biologically inspired image processing modules and one clinical information module. The image processing modules detect lesion features comparable to clinical dermoscopy information-atypical pigment network, color distribution, and blood vessels. The clinical module includes information submitted to the pathologist-patient age, gender, lesion location, size, and patient history. The deep learning arm utilizes knowledge transfer via a ResNet-50 network that is repurposed to predict the probability of melanoma classification. The classification scores of each individual module from both processing arms are then ensembled utilizing logistic regression to predict an overall melanoma probability. Using cross-validated results of melanoma classification measured by area under the receiver operator characteristic curve (AUC), classification accuracy of 0.94 was obtained for the fusion technique. In comparison, the ResNet-50 deep learning based classifier alone yields an AUC of 0.87 and conventional image processing based classifier yields an AUC of 0.90. Further study of fusion of conventional image processing techniques and deep learning is warranted.

Reflectance Confocal Microscopy Can Help the Dermatopathologist in the Diagnosis of Challenging Skin Lesions.

Despite the successful assignment of Current Procedural Terminology codes, there are barriers to incorporating in vivo reflectance confocal microscopy (RCM) into daily practice. Importantly, the dermatopathologist can play a key role in interpreting RCM images and can use these images to correlate with histopathology. Herein, we describe, using a case series, how RCM can be incorporated into the dermatopothalogist's practice. We also summarize the criteria for RCM diagnosis of common neoplasms.

Reflectance confocal microscopy terminology glossary for nonmelanocytic skin lesions: A systematic review.

BACKGROUND: There is lack of uniformity in reflectance confocal microscopy (RCM) terminology for nonmelanocytic lesions (NMLs). OBJECTIVE: To review published RCM terms for NMLs and identify likely synonymous terms. METHODS: We conducted a systematic review of original research articles published up to August 19, 2017, adhering to Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines. Two investigators gathered all published RCM terms used to describe basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and seborrheic keratosis/solar lentigo/lichen planus-like keratosis (SK/SL/LPLK). Synonymous terms were grouped on the basis of similarity in definition and histopathologic correlates. RESULTS: The inclusion criteria was met by 31 studies. Average frequency of use per term was 1.6 (range 1-8). By grouping synonymous terms, the number of terms could be reduced from 58 to 18 for BCC, 58 to 36 for SCC, 23 to 12 for SK/SL/LPLK, and from 139 to 66 terms (52.5% reduction) in total. The frequency of term usage stratified by anatomic layer (suprabasal epidermis vs epidermal basal layer, dermoepidermal junction, and superficial dermis) was 27 (25.7%) versus 78 (74.2%) for BCC; 60 (64.5%) versus 33 (34.5%) for SCC, and 15 (45.4%) versus 18 (54.5%) for SK/SL/LPLK, respectively. LIMITATIONS: Articles that were not peer reviewed were excluded. CONCLUSION: Systematic review of published RCM terms provides the basis for future NMLs terminology consensus.

Lichen planus-like keratosis: clinical applicability of in vivo reflectance confocal microscopy for an indeterminate cutaneous lesion.

Lichen planus-like keratosis (LPLK) is an involuting cutaneous lesion often presenting between the fifth and seventh decades of life. These lesions typically appear abruptly as a solitary macule, papule, or plaque that continuously evolves as it undergoes regression. Clinical and dermoscopic features of LPLK can mimic both benign and malignant lesions, often prompting biopsy for accurate diagnosis. We describe a case of LPLK developing in a patient with a history of multiple skin cancers, including melanoma. Dermoscopy revealed peripheral granules and a central area with pinkish-brown pigmentation and a disorganized pattern with shiny white structures and rosettes. Handheld reflectance confocal microscopy (RCM) showed a typical honeycomb pattern with millia-like cysts and comedo-like openings, and lacked pagetoid and dendritic cells. Based on the benign features seen with RCM, the lesion was followed until complete regression was observed. In conclusion, we describe a case of LPLK with clinically and dermoscopically indeterminate features that was successfully monitored with RCM. We intend to highlight the utility of RCM as a diagnostic aid in equivocal lesions in order to prevent unnecessary excisional procedures.

Reflectance confocal microscopy features of melanomas on the body and non-glabrous chronically sun-damaged skin.

BACKGROUND: Melanoma remains a challenge to diagnose, especially when appearing on the background of chronically sun-damaged skin (CSDS). Our goal was to identify and quantify the reflectance confocal microscopy (RCM) features of melanoma on non-facial CSDS. METHODS: Included lesions were biopsy-proven melanomas, from anatomic sites other than the face, neck, scalp and acral skin, with histopathologic finding of solar elastosis in the underlying dermis. All included lesions underwent clinical, dermoscopic and RCM imaging, obtained in a standardized fashion, prior to biopsy. All images were retrospectively analyzed by four observers. RESULTS: We identified 33 melanomas from 33 patients with 63.6% male patients and overall mean age of 72.8 years. The salient RCM features included an atypical honeycomb or disarranged epidermal pattern (81.8%), pagetoid infiltration of the epidermis by both round and/or dendritic melanocytes (100%), focal proliferation of predominantly dendritic melanocytes as sheets (78.8%), foci with non-edged papillae (84.8%), junctional thickening (60.6%), areas of irregular ring or meshwork pattern (78.8%), and underlying thickened collagen bundles (51.5%). CONCLUSION: Non-facial CSDS melanomas share features similar to other melanoma types including pagetoid cells and non-edged papillae. The focal proliferation of dendritic pagetoid cells in sheets is similar to that seen in facial CSDS melanomas.