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.

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.

Concordance of reflectance confocal microscopy and gene expression profiling for melanocytic lesions with uncertain malignant potential: A case series.

For a small yet significant proportion of melanocytic lesions, histopathologic analysis may be unable to definitively evaluate malignant potential. These cases may signify a specific need for newer ancillary diagnostic technologies, including in vivo reflectance confocal microscopy (RCM) and gene expression profiling (GEP), both of which are highly sensitive in the diagnosis of melanoma. We report four cases of clinically suspicious melanocytic lesions that lacked definitive malignant features on histopathology and that were aided by use of RCM and GEP. Three of the four cases showed concordance between RCM and GEP in the diagnosis of melanoma. In one case, RCM was suggestive of melanoma; on the other hand, GEP and histopathology supported a final diagnosis of compound Spitz nevus. These cases support the role of RCM as a novel, non-invasive diagnostic tool to aid in the diagnosis of clinically suspicious melanocytic lesions with uncertain malignant potential, although RCM may have relatively lower accuracy for some atypical spitzoid lesions.

Keratinocyte Carcinomas in Immunocompromised Patients Are Reduced After Administration of the Nonavalent Human Papillomavirus Vaccine.

Immunosuppression, as seen in solid organ transplant recipients, is highly associated with the development of keratinocyte carcinomas (KCs). Reducing the level of immunosuppression lowers the incidence of KCs but at the cost of increased potential morbidity and mortality. Recent studies have revealed a greater prevalence of HPV DNA, especially that of β-HPV, in KCs of immunocompromised patients compared to KCs of immunocompetent individuals. A prior report demonstrated that the HPV vaccine was associated with reducing KC incidence in immunocompetent patients. The nonavalent HPV vaccine was administered to two immunosuppressed individuals with histories of multiple prior KCs. Both patients are male, with Patient 1 being a liver transplant recipient who was on tacrolimus for an extended period and Patient 2 having Crohn’s disease and currently being treated with mercaptopurine. The treatment was well tolerated without adverse events and was associated with dramatic reductions in average incidence of KCs/year in both patients. Patient 1 demonstrated an 88% reduction in new KCs/year (87% squamous cell carcinomas (SCCs); 100% basal cell carcinomas (BCCs) post-injection of the intramuscular vaccine and Patient 2 demonstrated a 63% reduction in incidence of KCs/year (30% SCCs; 100% BCCs). Evidence links the β-HPV genera to the development of SCCs and actinic keratoses. The nonavalent HPV vaccine, containing antigens of the α-HPV genera, may also induce humoral immunity to β-HPV due to shared expression of L1 and L2 capsid proteins. The HPV vaccine may be an effective tool in the prevention of KCs in immunosuppressed patients. J Drugs Dermatol. 2022;21(5):526-528. doi:10.36849/JDD.6536.

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: 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 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.

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.

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.

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.

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 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.

In vivo reflectance confocal microscopy image interpretation for the dermatopathologist.

Reflectance confocal microscopy (RCM) is a technology utilized for bedside diagnosis of cutaneous pathology by non-invasive, in vivo, cellular-level imaging. With the recent establishment of reimbursement codes by the US Centers for Medicaid and Medicare Services, RCM is now likely to be employed by clinical dermatologists and impact decision making on skin cancer management. Dermatopathologists, therefore, would benefit from learning how to interpret RCM images and how RCM findings correlate with histopathological criteria of diagnosis. This review briefly explains the principles behind RCM image acquisition, describes the key RCM features of normal skin, and delineates the RCM characteristics of frequently observed benign and malignant neoplasms.

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.

Accuracy of dermatoscopy for the diagnosis of nonpigmented cancers of the skin.

BACKGROUND: Nonpigmented skin cancer is common, and diagnosis with the unaided eye is error prone. OBJECTIVE: To investigate whether dermatoscopy improves the diagnostic accuracy for nonpigmented (amelanotic) cutaneous neoplasms. METHODS: We collected a sample of 2072 benign and malignant neoplastic lesions and inflammatory conditions and presented close-up images taken with and without dermatoscopy to 95 examiners with different levels of experience. RESULTS: The area under the curve was significantly higher with than without dermatoscopy (0.68 vs 0.64, P < .001). Among 51 possible diagnoses, the correct diagnosis was selected in 33.1% of cases with and 26.4% of cases without dermatoscopy (P < .001). For experts, the frequencies of correct specific diagnoses of a malignant lesion improved from 40.2% without to 51.3% with dermatoscopy. For all malignant neoplasms combined, the frequencies of appropriate management strategies increased from 78.1% without to 82.5% with dermatoscopy. LIMITATIONS: The study deviated from a real-life clinical setting and was potentially affected by verification and selection bias. CONCLUSIONS: Dermatoscopy improves the diagnosis and management of nonpigmented skin cancer and should be used as an adjunct to examination with the unaided eye.

Standardization of terminology in dermoscopy/dermatoscopy: Results of the third consensus conference of the International Society of Dermoscopy.

BACKGROUND: Evolving dermoscopic terminology motivated us to initiate a new consensus. OBJECTIVE: We sought to establish a dictionary of standardized terms. METHODS: We reviewed the medical literature, conducted a survey, and convened a discussion among experts. RESULTS: Two competitive terminologies exist, a more metaphoric terminology that includes numerous terms and a descriptive terminology based on 5 basic terms. In a survey among members of the International Society of Dermoscopy (IDS) 23.5% (n = 201) participants preferentially use descriptive terminology, 20.1% (n = 172) use metaphoric terminology, and 484 (56.5%) use both. More participants who had been initially trained by metaphoric terminology prefer using descriptive terminology than vice versa (9.7% vs 2.6%, P < .001). Most new terms that were published since the last consensus conference in 2003 were unknown to the majority of the participants. There was uniform consensus that both terminologies are suitable, that metaphoric terms need definitions, that synonyms should be avoided, and that the creation of new metaphoric terms should be discouraged. The expert panel proposed a dictionary of standardized terms taking account of metaphoric and descriptive terms. LIMITATIONS: A consensus seeks a workable compromise but does not guarantee its implementation. CONCLUSION: The new consensus provides a revised framework of standardized terms to enhance the consistent use of dermoscopic terminology.

Clinical and dermoscopic characteristics of melanomas on nonfacial chronically sun-damaged skin.

BACKGROUND: Melanomas on chronically sun-damaged skin (CSDS) can be difficult to identify and often manifest morphologic features that overlap with benign lesions. OBJECTIVE: We describe and analyze the clinical and dermoscopic characteristics of melanomas on nonfacial CSDS. METHODS: Melanoma cases on nonfacial CSDS were retrospectively identified from the biopsy specimen logs of 6 melanoma clinics. Clinical and dermoscopic images were combined into 1 database. Demographics, clinical, dermoscopic, and histopathologic information were analyzed. Descriptive frequencies were calculated. RESULTS: One hundred eighty-six cases met the inclusion criteria: 142 melanomas in situ (76%) and 39 invasive (21%; mean thickness, 0.49 mm). Lentigo maligna was the most common histopathologic subtype (n = 76; 40.9%). The most frequent dermoscopic structures were granularity (n = 126; 67.7%) and angulated lines (n = 82; 44%). Vascular structures were more frequent in invasive melanomas (56% vs 12% of in situ melanomas). Most manifested 1 of 3 dermoscopic patterns: patchy peripheral pigmented islands, angulated lines, and tan structureless with granularity pattern. LIMITATIONS: This was a retrospective study, and evaluators were not blinded to the diagnosis. In addition, interobserver concordance and sensitivity and specificity for dermoscopic structures were not evaluated. CONCLUSION: Outlier lesions manifesting dermoscopic structures, such as granularity, angulated lines, or vessels and any of the 3 described dermoscopic patterns should raise suspicion for melanoma.

Through the looking glass: Basics and principles of reflectance confocal microscopy.

Reflectance confocal microscopy (RCM) offers high-resolution, noninvasive skin imaging and can help avoid obtaining unnecessary biopsy specimens. It can also increase efficiency in the surgical setting by helping to delineate tumor margins. Diagnostic criteria and several RCM algorithms have been published for the differentiation of benign and malignant neoplasms. We provide an overview of the basic principles of RCM, characteristic RCM features of normal skin and cutaneous neoplasms, and the limitations and future directions of RCM.