[COMPREHENSIVE GUIDELINES AND INDICATIONS FOR DIGITAL MONITORING OF PATIENTS AT HIGH-RISK FOR MELANOMA: A POSITION PAPER BY THE ISRAELI ASSOCIATION FOR DERMATOLOGY].

INTRODUCTION: Early detection may lead to reduced morbidity and mortality from melanoma. This study aims to establish guidelines for selecting patients suitable for digital monitoring of skin lesions. METHODS: A literature review was conducted, followed by consensus among experts appointed by the Israeli Dermatology Association. RESULTS: Two effective methods for early melanoma diagnosis were identified: Total-body photography (TBP) and digital dermoscopy. TBP involves capturing clinical images of the entire skin area for long-term monitoring (6-12 months). Digital dermoscopy focuses on close-up images of distinct lesions for short-term monitoring (3-4 months). Various risk factors for melanoma were identified, including genetic and familial factors, as well as demographic and phenotypic characteristics. Based on these risk factors and feasibility of clinical follow-up, a comprehensive list of indications for TBP was developed, categorized into three groups based on the expected level of benefit. Digital dermoscopy surveillance is recommended for patients with flat or slightly raised skin lesions showing dermoscopic features that do not definitively indicate melanoma. DISCUSSION: TBP significantly improves early melanoma detection, enhancing sensitivity and specificity while reducing unnecessary biopsies. However, due to its high cost and limited coverage by the Israeli public health care system, prioritizing patients who would benefit most from TBP is crucial. The compiled list of indications aligns with international recommendations and provides further details within the article.

Expert Agreement on the Presence and Spatial Localization of Melanocytic Features in Dermoscopy.

Dermoscopy aids in melanoma detection; however, agreement on dermoscopic features, including those of high clinical relevance, remains poor. In this study, we attempted to evaluate agreement among experts on exemplar images not only for the presence of melanocytic-specific features but also for spatial localization. This was a cross-sectional, multicenter, observational study. Dermoscopy images exhibiting at least 1 of 31 melanocytic-specific features were submitted by 25 world experts as exemplars. Using a web-based platform that allows for image markup of specific contrast-defined regions (superpixels), 20 expert readers annotated 248 dermoscopic images in collections of 62 images. Each collection was reviewed by five independent readers. A total of 4,507 feature observations were performed. Good-to-excellent agreement was found for 14 of 31 features (45.2%), with eight achieving excellent agreement (Gwet's AC >0.75) and seven of them being melanoma-specific features. These features were peppering/granularity (0.91), shiny white streaks (0.89), typical pigment network (0.83), blotch irregular (0.82), negative network (0.81), irregular globules (0.78), dotted vessels (0.77), and blue-whitish veil (0.76). By utilizing an exemplar dataset, a good-to-excellent agreement was found for 14 features that have previously been shown useful in discriminating nevi from melanoma. All images are public (www.isic-archive.com) and can be used for education, scientific communication, and machine learning experiments.

Paradoxical effect of epinephrine on lesion redness and vascularity.

INTRODUCTION: Epinephrine is commonly used in combination with local anesthetic (lidocaine/epinephrine) due to its beneficial vasoconstrictive properties. Typically, pallor is appreciated after injection as a sign of effect; however, we observed that some cutaneous malignancies paradoxically revealed increased redness and vascularity after injection of lidocaine/epinephrine. In this study, we investigate this phenomenon among a series of biopsied lesions to identify characteristics of lesions associated with increased redness and/or vascularity. OBJECTIVES: To determine characteristics of lesions which become redder or more vascular after injection with lidocaine/epinephrine prior to biopsy. METHODS: This cross-sectional study consisted of a convenience sample of lesions scheduled for biopsy. Lesions were photographed prior to and 7 min after injection of lidocaine/epinephrine as a part of standard care. Two readers blinded to study objectives and histopathological diagnosis assessed lesions for changes in redness and vascular features. RESULTS: Fifty-four lesions from 47 patients-61.7% male, mean age 64.8 years, age-range 24-91 were included. Thirty-six lesions were biopsy confirmed malignant, with 5 in situ and 31 invasive malignancies; the remaining 18 lesions were benign. In comparison with non-malignant lesions, malignant lesions were associated with an increase in clinically appreciable vascular features after injection of lidocaine/epinephrine, X2 (1) = 21.600, p < 0.001. Further stratification into benign, in situ, and invasive lesions strengthened the association, X2 (1) = 23.272, p < 0.001. CONCLUSIONS: Combination lidocaine/epinephrine has been shown to paradoxically increase the visibility of vessels seen in cutaneous malignancies. This is consistent with prior literature suggesting aberrant adrenergic signaling in neoangiogenic vessels.

Morphological features of benign pigmented ear lesions: a cross-sectional study.

BACKGROUND: The morphology of benign pigmented lesions on the ears has been scarcely studied. METHODS: We prospectively screened all patients presenting to a pigmented lesion clinic at a tertiary academic hospital, between November 2015 and August 2016, for the presence of benign pigmented ear lesions. Clinical and dermoscopic images were obtained for all lesions. Additionally, we performed a retrospective analysis of reflectance confocal microscopy (RCM) of benign pigmented ear lesions and a retrospective analysis of clinical and dermoscopic findings of biopsy-confirmed ear melanomas. RESULTS: In total, 165 patients (median age 48, 53% female) contributed 708 benign pigmented ear lesions to the study. Participants with multiple body nevi and those with an atypical nevus phenotype (multiple body nevi and ≥ one atypical nevus) had a higher mean number of ear lesions than those without multiple body nevi (4.5 and 5.4 vs. 3.9, P < 0.05). The most common diagnoses were nevus (35%) and solar lentigo (34%), followed by pigmented lentiginous macules (PLM) (27%). Dermoscopically scattered pigmented small globules/dots were observed in 30% of nevi and 17% of PLMs. RCM analysis of 24 ear lesions showed a comparable frequency of RCM-clods between nevi and PLMs. Analysis of 29 ear melanomas revealed larger lesions with more complex dermoscopic patterns. CONCLUSION: Multiple body nevi, and particularly an atypical nevus phenotype, were associated with having more pigmented ear lesions. Based on RCM analysis, PLMs of the ear likely represent small nevi. Ear melanomas tend to be larger and dermoscopically complex compared to ear nevi.

Cutaneous Malignancies After Kidney and Simultaneous Pancreas-Kidney Transplantations.

BACKGROUND: Organ transplant recipients are at increased risk of nonmelanotic skin cancers (NMSC). Scarce data exist regarding secondary malignancies developing post-simultaneous pancreas-kidney (SPK) transplantations. Our aim was to assess long-term risk of skin cancers among kidney alone (KA) and SPK transplantation recipients. METHODS: In this study, 521 patients who underwent KA or SPK transplantation at our medical center were observed up by dedicated nephrologists and dermatologists. SPK transplantation recipients were matched with a control group of KA transplantation recipients based on demographic and clinical data. A multivariate analysis was performed to find independent cancer risk factors. RESULTS: Patients who developed skin cancer were generally older, had a fair skin type, and had a higher incidence of NMSC before transplantation. Older age and fair skin type were independent risk factors on multivariate analysis. SPK transplantation in itself was not an independent risk factor. Cancer recurrence was associated with older age and male sex. Darker skin type and lowered immunosuppressive burden were protective. CONCLUSION: In contrast to previous studies, the use of antithymocytic agents or SPK transplantation were not independently associated with increased skin cancer risk in this multivariate analysis. These findings emphasize the complex interplay between posttransplantation NMSC and various clinical and epidemiologic risk parameters.

Optical imaging guided- 'precision' biopsy of skin tumors: a novel approach for targeted sampling and histopathologic correlation.

Dermoscopy and reflectance confocal microscopy (RCM) are two noninvasive, optical imaging tools used to facilitate clinical diagnosis. A biopsy technique that produces exact correlation with optical imaging features is not previously reported. To evaluate the applications of a novel feature-focused 'precision biopsy' technique that correlates clinical-dermoscopy-RCM findings with histopathology. This was a prospective case-series performed during August 2017 and June 2019 at a tertiary care cancer. We included consecutive patients requiring a precise dermoscopy-RCM-histopathologic correlation. We performed prebiopsy dermoscopy and both wide probe and handheld RCM of suspicious lesions. Features of interest were isolated with the aid of paper rings and a 2 mm punch biopsy was performed in the dermoscopy- or RCM-highlighted area. Tissue was processed either en face or with vertical sections. One-to-one correlation with histopathology was obtained. Twenty-three patients with 24 lesions were included in the study. The mean age was 64.6 years (range 22-91 years); there were 16 (69.6%) males, 14 (58.3%) lesions biopsied were on head and neck region. We achieved tissue-conservation diagnosis in 100% (24/24), 13 (54.2%) were clinically equivocal lesions, six (25%) were selected for 'feature correlation' of structures on dermoscopy or RCM, and five (20.8%) for 'correlation of new/unknown' RCM features seen on follow-up. The precision biopsy technique described herein is a novel method that facilitates direct histopathological correlation of dermoscopy and RCM features. With the aids of optical imaging devices, accurate diagnosis may be achieved by minimally invasive tissue extraction.

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.

Melanoma risk stratification of individuals with a high-risk naevus phenotype - A pilot study.

BACKGROUND/OBJECTIVES: High a naevus counts and atypical naevi are risk factors for cutaneous melanoma. However, many individuals with a high-risk naevus phenotype do not develop melanoma. In this study, we describe the clinical and dermoscopic attributes of naevi associated with melanoma in a high-risk naevus phenotype population. METHODS: This single-centre, hospital-based case-control study included 54 prospectively enrolled adult patients ≥18 years old with a high-risk naevus phenotype (18 cases with a history of melanoma and 36 age- and gender-matched controls without a history of melanoma). We analysed clinical and dermoscopic images of the 20 largest naevi for each participant. RESULTS: Cases had a higher mean age than controls (48.2 vs. 39.1 years, P = 0.007) but there was no difference in the male-to-female ratio between groups. Nearly, all participants (97%) were Fitzpatrick skin type II or III. Naevi in cases were more likely to be truncal, (72.6% vs. 53.6%, P = 0.01), particularly anterior truncal, (29.2% vs. 14.4%, P < 0.001) and larger than 8 mm (17.4% vs. 7.8%%, P = 0.01) compared to controls. CASH score of naevi did not differ between groups. Naevi in cases were more likely to have a multicomponent dermoscopic pattern than in controls (18.4% vs. 12.6%, P = 0.02). CONCLUSION: Larger naevi, truncal naevi, and naevi, with a multicomponent dermoscopic pattern may be risk factors for melanoma among individuals with a high-risk naevus phenotype. Further studies are needed to validate these findings.

Assessment of the Safety Risk of Dermatoscope Magnets in Patients With Cardiovascular Implanted Electronic Devices.

Importance: Cardiovascular implanted electronic devices (CIEDs) are susceptible to electromagnetic interference. Dermatologists regularly use devices containing magnets, including dermatoscopes and their attachments, which could pose a hazard to patients with CIEDs. Objective: To investigate the safety risk of magnets in dermatoscopes to patients with CIEDs. Design, Setting, and Participants: This cross-sectional observational study was conducted between January 1, 2018, and March 31, 2018, in a controlled laboratory setting. Two experiments were performed. In the first experiment (performed in the Dermatology Service at Memorial Sloan Kettering Cancer Center, New York), dermatoscopes that contain magnets were obtained from 3 manufacturers. Using a magnometer, the magnetic field strength of the dermatoscopes was measured over the magnet; at the faceplate; and at a distance of 0.5 cm, 1 cm and 15 cm away from the faceplate. In the second experiment (performed in the University Heart Center Zurich, Zurich, Switzerland), ex vivo measurements were conducted to determine how the dermatoscopes affected old-generation and new generation CIEDs (pacemakers and implantable defibrillators). Main Outcomes and Measures: Magnetic field strength as measured directly over the dermatoscope magnet; at the faceplate; and at distances of 0.5 cm, 1 cm, and 15 cm from the faceplate. Pacemaker and defibrillator operation when exposed to dermatoscopes. Results: After conducting 24 measurements, the magnetic field (measured in gauss [G]) strength varied between 24.26 G and 163.04 G over the dermatoscope magnet, between 2.22 G and 9.98 G at the dermatoscope faceplate, between 0.82 G and 2.4 G at a distance of 0.5 cm, and between 0.5 G and 1.04 G at a distance of 1 cm; it was 0 for all devices at a 15 cm distance. The field strength at the faceplate was found to be generally below the CIED industry standard safety threshold. None of the dermatoscopes in the ex vivo experiment exerted any demonstrable disruptions or changes to the CIEDs. Conclusions and Relevance: In real life, dermatoscope magnets likely present no measurable safety risk to patients with CIEDs. Using the polarized noncontact mode permits dermoscopy to be performed at least 0.5 cm from the skin surface, where the magnetic field strength was well below the 5-G safety threshold.

Accuracy and confidence in the clinical diagnosis of basal cell cancer using dermoscopy and reflex confocal microscopy.

BACKGROUND: Diagnosis of suspected basal cell carcinoma (BCC) is typically confirmed with incisional biopsy before referral to final surgery. OBJECTIVE: To investigate the clinical confidence and accuracy of physicians making a diagnosis of BCC based on dermoscopic and reflectance confocal microscopy (RCM) features. METHODS: This study was designed as a simulation to determine the certainty and willingness to refer to surgery without previous biopsy confirmation of BCC. Study subjects were identified with suspected BCC. Dermoscopic and RCM lesion images were obtained before biopsy. Eight clinicians with various expertise levels blindly interpreted these images and chose among four hypothetical treatment options: definite BCC, refer directly to surgery without biopsy; other malignancy, perform biopsy for diagnosis; uncertain diagnosis, perform biopsy; benign, do not biopsy. Decisions for treatment were based on dermoscopic images alone and, subsequently, on dermoscopic and RCM images combined. RESULTS: The sensitivity for referral to surgery without biopsy was 67.6% with the use of dermoscopy; the positive predictive value (PPV) was 97.0%. Adding RCM increased the sensitivity to 76.5% and the PPV to 98.6%. CONCLUSIONS: Dermoscopy provides a high PPV for BCC. The addition of RCM to dermoscopy increases diagnostic sensitivity, particularly in less experienced dermoscopists. Physician behavior might be different if actual referrals were made for surgery without biopsy.

Reflectance confocal microscopy criteria for squamous cell carcinomas and actinic keratoses.

OBJECTIVE: To identify criteria for the diagnosis of squamous cell carcinoma (SCC) and actinic keratosis (AK) by in vivo reflectance confocal microscopy (RCM). DESIGN: Prospective RCM imaging of lesions suspected clinically and/or dermoscopically to be SCC or AK, followed by RCM assessment of the biopsy-proven SCCs and AKs. SETTING: Private skin cancer clinic, Plantation, Florida. Patients A total of 38 lesions in 24 patients were assessed, including 7 AKs, 25 SCCs in situ, 3 invasive SCCs, and 3 keratoacanthomas. Interventions Prior to undergoing biopsy, all lesions were assessed by RCM. RESULTS: Mosaic RCM images at the stratum corneum level revealed scale in 29 SCCs (95%) and in all 7 AKs. Polygonal nucleated cells at the stratum corneum were seen in 3 SCCs (10%) and 1 AK (14%). All 38 cases displayed an atypical honeycomb and/or a disarranged pattern of the spinous-granular layer of the epidermis; round nucleated cells were seen in the spinous-granular layer in 20 SCCs (65%) and 1 AK (14%). Round blood vessels in the superficial dermis were seen in 28 SCCs (90%) and 5 AKs (72%). CONCLUSIONS: An increasing frequency of abnormal RCM features can be observed across the spectrum of keratinocytic neoplasias. The presence of an atypical honeycomb or a disarranged pattern of the spinous-granular layer, round nucleated cells at the spinous-granular layer, and round blood vessels traversing through the dermal papilla are the key RCM features of SCC.

Telangiectasia macularis eruptiva perstans: unusual presentation and treatment.

A 41-year-old woman presented with a 2-month history of pruritus and a generalized dermatitis that developed initially on the head and spread to the trunk, legs, and buttocks. The pruritus caused extreme discomfort and was not relieved by antihistamines or topical steroid treatment. The patient denied flushing, syncope, and vomiting. Her medical history included asthma treated with salmeterol/fluticasone propionate inhaler, and status post silicone breast augmentation. Physical examination revealed a papular dermatitis on the trunk and extremities composed of lesions up to 0.5 cm in diameter, surrounded by excoriation marks (Figure 1). There was no hepatosplenomegaly or lymphadenopathy. Darier's sign was negative. Results of complete blood count, peripheral blood film examination, and liver function tests were all with normal limits. A biopsy specimen taken from a lesion and stained with hematoxylin-eosin showed telangiectasias, with an increased number of mast cells around blood vessels (Figure 2). Positive Giemsa (Figure 3) and c-kit stain (Figure 4) indicated an increased number of mast cells. Bone marrow aspiration and total body CT performed to rule out systemic involvement showed no pathology. Protein electrophoresis was normal. Serum tryptase and histamine were within normal limits, and 24-hour urine collection for histamine was normal. Narrow-band UV-B treatment was begun 3 times weekly, reduced to twice weekly after 2 months, and then stopped. The first few treatments resulted in significant relief of the pruritus and regression of lesions. After 3 months without treatment, the patient remained free of pruritus and lesions.