Esther Chung

Cross‐sectional analysis of the dermoscopic patterns and structures of melanocytic naevi on the back and legs of adolescents

Junctional (flat) naevi predominate on the extremities, whereas dermal (raised) naevi are found primarily on the head, neck and trunk. Few studies have investigated the anatomical site prevalence of melanocytic naevi categorized using dermoscopy.

Screening for Acral Lentiginous Melanoma in Dark-Skinned Individuals

Amid a growing appreciation of the harms associated with cancer screening, there has been recent emphasis on education and opportunistic screening for acral lentiginous melanoma (ALM) in dark-skinned individuals.1 Furthermore, articles have highlighted disparities in melanoma education and detection in dark-skinned individuals.2,3 While early detection has the greatest potential for reducing melanoma mortality in the short term, it is important to carefully consider incidence, survival, and mortality in populations targeted for screening. In dark-skinned patients, could increased pressure to detect ALM lead to significant harms in return for minimal benefit? It is well established that for dark-skinned individuals, ALM makes up the highest proportion of all melanoma subtypes.4 However, in a large epidemiologic study of ALM, Bradford et al4 found that the incidence of ALM was similar in non-Hispanic whites and blacks (1.8 per 1 000 000 person-years). What accounts for the differences in overall melanoma incidence and melanomaspecific survival between these groups is the low incidence of UV radiation–induced melanomas in darkskinned individuals, not any difference in ALM susceptibility or prognosis. Survival from ALM is very similar across racial groups. While 5-year ALM survival rates are slightly higher in non-Hispanic whites than in blacks (82.6% vs 77.2%), 10-year survival rates in non-Hispanic whites are slightly lower than in blacks (69.4% vs 71.5%). When ALM was controlled for tumor thickness or stage, no statistically significant differences were found among all racial groupsinboth5-and10-yearsurvivalrates,suggestingthat ALM is being detected at similar stages of evolution in both groups. The recent emphasis on increased efforts for early detection of ALM is highly analogous to attempts to increase pediatric melanoma awareness. Here, too, there is a strong desire to prevent any deaths from melanoma, but the absolute numbers of deaths are low and the potential harms of overdiagnosis are significant. A search within the United States Surveillance, Epidemiology, and End Results registries revealed melanoma mortality counts of less than 10 for all age groups younger than 15 years, for each year from 1973 to 2011. For individuals aged 15 to 19 years, mortality counts were 11 or less for each year from 1991 to 2011. Despite low mortality and the absence of formal screening recommendations, an epidemic of biopsies in children has occurred, likely fueled by increased public education and awareness of melanoma (eg, ABCDE [asymmetry, border irregularity, color variegation, diameter >6 mm, and evolving] criteria) and the dynamic nature of nevi in childhood and adolescence. In fact, more than 2 million nevi are estimated to have been biopsied between 2009 and 2013 in the United States in individuals 19 years and younger in order to detect 1940 melanomas, resulting in a number needed to biopsy of 1035.5 The effect of these biopsies on mortality, if any, is unknown. The ratio of benign to malignant biopsy results for melanoma is determined by diagnostic accuracy and the underlying disease prevalence of a population targeted for screening. Sensitivity and specificity of the evaluation of suspicious pigmented lesions with dermoscopy are on the order of 0.87 and 0.91, respectively. While diagnostic accuracy likely varies with experience and expertise, disease prevalence has an even bigger effect on predictive value and benign to malignant ratios. A comparison of specialized screening centers with general dermatology practices found a difference in benign to malignant ratios of 1:8.7 vs 1:29.4, respectively, which was cited to be partially a result of screening individuals with different underlying incidences of melanoma.6 A disease prevalence of 1 melanoma in every 29.4 concerning pigmented lesions would lead to a positive predictive value of 24.7% and a negative predictive value of 99.5%.6 An identical diagnostic accuracy applied to screening the palms, soles, and nails of dark-skinned individuals, assuming twice as many concerning background benign acral pigmented nevi,7 would equate to a positive predictive value of 14.1%, a negative predictive value of 99.8%, and an estimated number needed to biopsy of 59. The opportunity costs, financial costs, and morbidity associated with these invasive procedures need to be carefully considered, especially in the absence of a demonstrated effect on mortality in this setting. Unknown is the effect of longitudinal melanonychia, which is informally accepted to be significantly more common in darkly pigmented individuals, on the above estimates. In addition, although studies have shown that dermoscopy aids in the diagnosis of ALM, few studies have specifically examined the dermoscopic features of the full spectrum of benign and malignant acral pigmented lesions in dark-skinned individuals. In light of the increased prevalence of lesions in this population, the specificity of dermoscopy to distinguish ALM from benign acral pigmented lesions in dark-skinned individuals is an especially important issue. In the case of acral pigmented lesions, perhaps more concerning than the potential number of biopsies is the morbidity and harms associated with identification and surgical removal of numerous dysplasias and borderline lesions identified as a result of increased detection pressure. Acral nevi are well described in dermatopathology literature as being often misdiagnosed (most frequently false-positive but also false-negative diagnoses) owing to unique site-related atypia and common VIEWPOINT

Streaks in pigmented squamous cell carcinoma in situ

DERMOSCOPIC APPEARANCE Dermoscopy revealed focal streaks at the periphery and within the borders of the lesion (Fig 2). The streaklike projections did not converge toward the geometric center of the lesion as seen inmelanocytic lesions, nor did they connect to a common base to form a leaflike structure as is seen in pigmented basal cell carcinoma (BCC). Scattered brown dots, some aligned linearly, were also present.

Clinical and Dermoscopic Features of Cutaneous Melanoacanthoma

Clinical and Dermoscopic Features of Cutaneous Melanoacanthoma Cutaneous melanoacanthoma (CM) is traditionally considered to be a heavily pigmented variant of seborrheic keratosis (SK).1 The characteristic histologic feature of CM is the presence of large, highly dendritic, melanin-rich melanocytes spread throughout an acanthotic epidermis.2 Owing to their pigmentation, CMs may mimic the clinical appearance of melanoma.1 Although the dermoscopic features of SK are well defined, little is known about the dermoscopic features of CM.3,4 Our objective was to evaluate the clinical and dermoscopic features of CM.

Factors in Early Adolescence Associated With a Mole-Prone Phenotype in Late Adolescence

Importance Nevi are important phenotypic risk factors for melanoma in adults. Few studies have examined the constitutional and behavioral factors associated with a mole-prone phenotype in adolescents. Objective To identify host, behavioral, and dermoscopic factors in early adolescence (age, 14 years) that are associated with a mole-prone phenotype in late adolescence (age, 17 years). Design, Setting, and Participants A prospective observational cohort study from the Study of Nevi in Children was conducted from January 1, 2009, to December 31, 2014, with a 2- to 3-year follow-up. A total of 569 students from the school system in Framingham, Massachusetts, were enrolled in the 8th or 9th grade (baseline; mean [SD] age, 14.4 [0.7] years). The overall retention rate was 73.3%, and 417 students were reassessed in the 11th grade. Main Outcome and Measures Mole-prone phenotype in the 11th grade, defined as total nevus count of the back and 1 randomly selected leg in the top decile of the cohort or having any nevi greater than 5 mm in diameter. Results Of the 417 students assessed at follow-up in the 11th grade (166 females and 251 males; mean [SD] age, 17.0 [0.4] years), 111 participants (26.6%) demonstrated a mole-prone phenotype: 69 students (62.2%) with 1 nevus greater than 5 mm in diameter, 23 students (20.7%) with total nevus count in the top decile, and 19 students (17.1%) with both characteristics. On multivariate analysis, baseline total nevus count (adjusted odds ratio, 9.08; 95% CI, 4.0-23.7; P < .001) and increased variability of nevus dermoscopic pattern (adjusted odds ratio, 4.24; 95% CI, 1.36-13.25; P = .01) were associated with a mole-prone phenotype. Conclusions and Relevance This study found clinically recognizable factors associated with a mole-prone phenotype that may facilitate the identification of individuals at risk for melanoma. These findings could have implications for primary prevention strategies and help target at-risk adolescents for higher-intensity counseling about sun protection and skin self-examination.

Lymphangitic papules caused by Nocardia takedensis

The Nocardia genus, belonging to the order Actinomycetales, is a group of gram-positive saprophytic bacteria that are found ubiquitously in the environment. In 2005, Nocardia takedensis was isolated from moat sediment and sludge around the Takeda shrine in Japan and reported as a novel species.1, 2 This species shows highest sequence similarity to Nocardia beijingensis (98.1%-98.3%), Nocardia brasiliensis (97.9%-98.0%), and Nocardia tenerifensis (97.9%-97.9%) based on 16S rRNA sequencing.1 We describe a case of cutaneous nocardiosis caused by N takedensis, which, to our knowledge, is the first report of an infection caused by this species in the United States.

Towards three‐dimensional temporal monitoring of naevi: a comparison of methodologies for assessing longitudinal changes in skin surface area around naevi

DEAR EDITOR, Although change in a skin lesion is a sensitive clue to the diagnosis of melanoma, all skin lesions grow at some point during their lifespan. Few studies have assessed how skin lesions change in size relative to the body. Rhodes et al. estimated the relative growth of congenital naevi in infants by comparing changes in naevus surface area (referred to hereafter simply as ‘area’) with regional body area changes calculated using height and weight data and adjusted for age. They found disproportionate growth in the first 6 months followed by proportionate growth thereafter. As body sites change at different rates and are influenced by age, sex and environmental factors, it is unclear whether this approach is uniformly valid or whether other methodologies might be more applicable. Until recently, measuring change in skin area was not readily feasible (i.e. paper cast or palm techniques), but the advent of three-dimensional (3D) stereophotogrammetrybased imaging in dermatology clinics now offers an opportunity for precise study of perilesional area changes. Here we compared 3D-imaging-observed area changes with those calculated from two-dimensional (2D) imaging or inferred from height and weight data. This is part of the Study of Nevi in Children (SONIC), which to our knowledge is the first to follow naevi longitudinally using 3D imaging. SONIC was approved by the Harvard University Institutional Review Board and adhered to the guidelines of the Declaration of Helsinki. Participant accrual and data collection have been reported previously. Relevantly to this study, participants had 180° anterior and posterior 3D body images and 2D overview images of the back and legs captured at baseline (age ~14 years) and 3 years later using standardized poses, along with height and weight measurements. Three-dimensional images were obtained using a customized Vectra Body System (Canfield Scientific, Inc., Fairfield, NJ, U.S.A.), which had a stereocapture array of twelve 21-megapixel digital single-lens reflex cameras configured to meet the study capture field, and photographic texture-resolution requirements. The calibrated dimensional imaging system collected each image in under 4 ms to produce a 3D model. Vectra systems have been validated for accuracy and are in clinical use. Digital 2D images were obtained using a Phase One P25 Camera Back, Hasselblad 503w Camera System, 2kWatt Studio Flash System (Canfield Scientific, Inc.). The area around naevi (or ‘perilesional area’) was measured on 3D and 2D images using four neighbouring landmark naevi (‘anchors’) that surrounded the naevus. These ‘anchors’ had to be clearly visible at both time points (Fig. 1). When four neighbouring landmark naevi could not be identified, the index naevus was used as the fourth landmark. In a pilot experiment using 3D images of a single participant taken 15 min apart, we explored the precision and repeatability of the 3D Vectra body system and use of perilesional area measurements for 10 back naevi. We found a mean coefficient of variability of 1 04%, supporting the reproducibility of this approach. To explore further the area change measurements, we calculated the 3D and 2D regional area, defined as the area of the upper back, lower back or lower leg (Fig. 2), and the total body surface area (TBSA) (TBSA = xHM; where x, y and z are constants equalling 0 02667, 0 38217 and 0 53937, respectively; H is height and M is mass). A convenience sample of 93 naevi from 65 participants (33 male) was chosen from the upper back (n = 29), lower back (n = 21), upper leg (n = 22) and lower leg (n = 21). Feasibility of naevus perilesional area measurements was required for inclusion, and we overselected naevi on the lower back and legs to include similar proportions by anatomical site (Appendix S1 and Tables S1–3; see Supporting Information). The mean 3D perilesional area increased after 3 years by 16 1% (95% confidence interval 13 0–19 3). There was nearly perfect interand intraobserver reliability (intraclass correlation coefficient of 0 99 for both measures). To assess the accuracy of the 3D imaging system and measurement tool, coloured adhesive dots that were originally placed adjacent to naevi during photography sessions for tracking purposes were randomly selected from 10 participants, and their diameters were measured at both time points. The mean diameter was 12 83 0 13 mm, comparable with the manufacturer’s reported specification of 12 70 mm. Nonvisible landmark naevi located on curved surfaces precluded 2D perilesional area measurements in 29 cases (31%). For the 64 naevi with both 2D and 3D perilesional area measurements, 3D perilesional area measurements were consistently greater than 2D (baseline 69 0 vs. 59 4 cm; follow-up 87 5 vs. 72 6 cm; P < 0 001), but there was no difference in the mean change between 3D and 2D perilesional area (17 0% vs. 17 6%, P = 0 8).

Reference values for skin microanatomy: A systematic review and meta-analysis of ex vivo studies

Background Few studies have characterized reference values of normal human skin microanatomy parameters. Objective To quantify histologic measurements of epidermal thickness, melanocyte density, hair follicle density, and eccrine gland density as a function of age and anatomic site. Method We searched the PubMed, Embase, Web of Science, and Cochrane databases for articles published through May 25, 2017. Two reviewers independently screened 2016 articles; 327 relevant articles and 151 additional articles found via forward or reference citations underwent full‐text review by 1 of 4 reviewers for relevance, data extraction, and critical appraisal. Weighted averages, meta‐analysis, and meta‐regression were used in statistical analysis. Results A total of 56 articles were included; when all anatomic locations were used, the overall estimates for epidermal thickness, melanocyte density, hair follicle density, and eccrine gland density were 99.75 &mgr;m (95% confidence interval [CI], 83.25‐116.25), 955.05 cells/mm2 (95% CI. 880.89‐1029.21), 1.40 hairs/mm2 (95% CI. 0.91‐1.89), and 1.28 glands/mm2 (95% CI. 0.91‐1.64), respectively. Limitations There was significant data heterogeneity across studies, possibly because of differences in histological techniques and absence of standardized microanatomy definitions. Conclusions We established summary estimates for normal human skin microanatomy parameters.

Cutaneous adverse drug reaction associated with oral temozolomide presenting as dermal and subcutaneous plaques and nodules.

Temozolomide (TMZ) is an alkylating drug most often used in the treatment of primary brain malignancies. Herein, we report an unusual cutaneous adverse drug reaction (ADR) associated with TMZ and characterized by temporally distinct dermal and subcutaneous hypersensitivity reactions.