Evaluation of MITF, SOX10, MART-1, and R21 Immunostaining for the Diagnosis of Residual Melanoma In Situ on Chronically Sun-Damaged Skin.

BACKGROUND: Melanocytic immunostains can assist in margin evaluation of melanoma in situ (MIS) excisions; however, their accuracy and reliability relative to hematoxylin & eosin (H&E) is yet to be determined. OBJECTIVE: The objective of this study was to evaluate the sensitivity, specificity, and concordance of 4 melanocyte-specific immunostains for diagnosing MIS occurring on chronically sun-damaged skin. MATERIALS AND METHODS: Serial permanent sections from representative areas of negative margin and residual tumor were stained using H&E, MITF, MART-1, SOX10, and R21 and examined in a blinded fashion. The study set included 100 digital microscopy images from 10 cases of MIS excisions from the face. Two board-certified dermatopathologists, 4 fellowship-trained Mohs surgeons, 2 Mohs fellows, and 2 dermatology residents independently reviewed the 100 images. RESULTS: The average melanocyte density was 11 versus 28 melanocytes per 0.5 mm for chronically sun-damaged skin versus residual MIS on H&E, respectively. Statistically significantly higher melanocyte densities were observed using MITF, MART-1, and SOX10 on negative margins. The sensitivity and interobserver concordance was highest using MITF and SOX10. The intraobserver agreement on 4 duplicate images was 85%. CONCLUSION: In conclusion, the nuclear immunostains (MITF and SOX10) show the most promise for improving the diagnosis of MIS in chronically sun-damaged skin.

Digital imaging biomarkers feed machine learning for melanoma screening.

We developed an automated approach for generating quantitative image analysis metrics (imaging biomarkers) that are then analysed with a set of 13 machine learning algorithms to generate an overall risk score that is called a Q-score. These methods were applied to a set of 120 "difficult" dermoscopy images of dysplastic nevi and melanomas that were subsequently excised/classified. This approach yielded 98% sensitivity and 36% specificity for melanoma detection, approaching sensitivity/specificity of expert lesion evaluation. Importantly, we found strong spectral dependence of many imaging biomarkers in blue or red colour channels, suggesting the need to optimize spectral evaluation of pigmented lesions.

Acquired aquagenic papulotranslucent acrokeratoderma.

Aquagenic papulotranslucent acrokeratoderma isa rare condition with the development of white-totransluscentpapules and plaques after exposureto water. While the first report was described asan autosomal dominant hereditary condition,there have since been acquired cases reported inassociation with cystic fibrosis, with prior exposureto a drug, or as an idiopathic condition. We presenta 24-year-old man with acquired aquagenicpapulotranslucent acrokeratoderma that has beenpresent since infancy, without a family history,without prior drug exposure, and without anypersonal or family history of cystic fibrosis. Thus fartreatment with urea cream, calipotriene ointment,vitamin E cream, and clobetasol ointment hasbeen ineffective. Our patient will be treated withbotulinum toxin.

Gardner-Diamond syndrome.

Gardner-Diamond syndrome, which also is knownas autoerythrocyte sensitization disorder, is a raresyndrome of inflammatory, edematous papulesthat evolve into painful ecchymoses on the trunkand lower legs after a period of stress with no priorhistory of trauma. This syndrome usually occurs inwomen with a history of psychiatric disorders, themost common one being depression. Although theexact mechanism of injury is not well understood,it is hypothesized that these patients haveautoantibodies to phosphatidylserine, which is aphospholipid membrane component in erythrocytes.Treatment for this disorder includes symptomatictherapies and psychotropic medications to treat theunderlying psychiatric disorder.

Cutis verticis gyrata.

Cutis verticis gyrata that involves only the face isa rare presentation of this even rarer cutaneousanomaly. We present a 61-year-old man, whodeveloped primary essential progressive cutis verticisgyrata of the face.

'Do UC the melanoma?' Recognising the importance of different lesions displaying unevenness or having a history of change for early melanoma detection.

BACKGROUND/OBJECTIVES: Many melanomas are of a diameter smaller than 6 mm and may lack classical asymmetry, border irregularity and colour variegation (ABCD). The objectives of this article are to characterise the fidelity of melanomas diagnosed in a high-risk clinic to the ABCD and to review potential methods for early clinical detection of melanoma. METHODS: All cases of primary melanoma diagnosed by one clinician at the Memorial Sloan-Kettering Cancer Center over the past 11 years were evaluated for the presence of the ABCD. The melanomas were analysed for asymmetry of contour, unevenness in distribution of colours and textures, border irregularity, number of colours present and diameter. RESULTS: In all, 236 melanomas were analysed. Of these, asymmetry of contour was present in 65% and 94% demonstrated unevenness in the distribution of colours and textures. The borders were regular in 12% of the melanomas and colour variegation was present in 63%. In total, 28% of the lesions were small, with a diameter less than 6 mm. This study was limited by the subjectivity of clinical lesion analysis. CONCLUSION: We put forward for your consideration a new mnemonic: 'Do UC (different, uneven, changing) the melanoma?' This mnemonic encompasses differential, analytical and comparative cognition strategies for an enhanced early detection of melanoma.

Pediatric orthopedic conditions in Charcot-Marie-Tooth disease: a literature review.

PURPOSE OF REVIEW: To provide the pediatrician with a comprehensive overview of the orthopedic considerations and potential issues in a child with Charcot-Marie-Tooth (CMT) disease. CMT is not one disease but rather a myriad of genetic and biochemical processes that manifest in a final common pathway of physical impairment with cardinal orthopedic elements. RECENT FINDINGS: This review incorporates the most current research on CMT, including its orthopedic elements, and the opinion of specialists in pediatric orthopedics specifically in the areas of foot and ankle, hip dysplasia and spinal deformity. SUMMARY: This article provides a framework for pediatricians to understand the complex and variable natural history of CMT with regard to neurologically produced musculoskeletal changes.

Evaluation and treatment of symptomatic pes planus.

PURPOSE OF REVIEW: To provide the pediatrician with a comprehensive synopsis of pediatric pes planus, also known as flatfoot. The term pes planus is a physical finding that generates some confusion in the medical community because it describes a spectrum of conditions that are diagnosed and managed differently. RECENT FINDINGS: Some of the recent data incorporated in this review come from pediatric, orthopaedic, and podiatric literature. These sources describe the clinical features and the latest treatment options for pes planus. SUMMARY: This article will provide some guidance to evaluate and treat the many causes of pediatric pes planus. Nonsurgical and operative management will be discussed.

Feasibility and Efficacy of Patient-Initiated Mobile Teledermoscopy for Short-term Monitoring of Clinically Atypical Nevi.

IMPORTANCE: Patient-driven mobile teledermoscopy may be applicable for monitoring of skin lesions. OBJECTIVE: To assess the feasibility, efficacy, and patient receptivity of teledermoscopy for short-term monitoring of clinically atypical nevi. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study performed at an institutional referral center in New York. Consecutive patients 18 years or older, with 1 or more clinically atypical nevi that required short-term monitoring and were accessible by a mobile imaging device were recruited for the study. All 34 patients consented to the study, and 29 completed follow-up. Dermoscopic images were obtained in the office-based setting by a dermatologist and with an iPhone by the patient at baseline and follow-up (3-4 months). Patients completed surveys that included questions about skincare awareness and attitudes toward teledermoscopy. Standard dermoscopic images were evaluated by the office-based dermatologist, and mobile dermoscopic images were sent via the Internet to a teledermatologist to evaluate image quality and presence of significant clinical lesion change. The decisions of the teledermatologist and office-based dermatologist were compared. MAIN OUTCOMES AND MEASURES: (1) Feasibility of using mobile dermatoscope by patients, (2) diagnostic concordance of teledermoscopy vs conventional office-based visit, and (3) patient receptivity to teledermoscopy for short-term monitoring of nevi. RESULTS: Of the 29 patients who completed the study, 28 (97%) were able to acquire baseline and follow-up images that were subsequently deemed evaluable by the teledermatologist. The diagnostic concordance between conventional office-based visits and teledermoscopy encounters was 0.87 (SE, 0.13) (κ statistic). In addition, patients reported high receptivity to teledermoscopy for short-term monitoring of nevi. CONCLUSIONS AND RELEVANCE: Results from this pilot study suggest that teledermoscopy is feasible and effective as a method for short-term monitoring of clinically atypical nevi. The implementation of teledermoscopy can potentially enhance patient convenience, optimize physician scheduling, and promote efficiency.

Growth-Curve Modeling of Nevi With a Peripheral Globular Pattern.

IMPORTANCE: Although nevi with a peripheral rim of globules (peripheral globular nevi [PGN]) observed with dermoscopy are associated with enlarging melanocytic nevi, their actual growth dynamics remain unknown. Because change is a sensitive but nonspecific marker for melanoma, beginning to understand the growth patterns of nevi may improve the ability of physicians to differentiate normal from abnormal growth and reduce unnecessary biopsies. OBJECTIVE: To study the growth dynamics and morphologic evolution of PGN on dermoscopy. DESIGN, SETTING, AND PARTICIPANTS: A total of 84 participants with 121 PGN from September 1, 1999, through May 1, 2013, were identified retrospectively. Cohorts were recruited from the Memorial Sloan Kettering Cancer Center; Melanoma Unit of the Hospital Clinic, University of Barcelona; and Study of Nevi in Children. All 3 cohorts underwent longitudinal monitoring with serial dermoscopic imaging of their PGN. Data analysis was performed from May 1, 2014, through April 1, 2015. MAIN OUTCOMES AND MEASURES: Establishment of the natural growth curve of PGN. The secondary aim was to establish the median time to growth cessation in those PGN for which the size eventually stabilized and/or had begun to decrease during the study period. RESULTS: The median duration of follow-up was 25.1 (range, 2.0-114.4) months. Most of the nevi (116 [95.9%]) enlarged at some point during sequential monitoring. The rate of increase in the surface area of PGN varied among cohorts and ranged from -0.47 to 2.26 mm2/mo (mean rate, 0.25 [95% CI, 0.14-0.36] mm2/mo). The median time to growth cessation in the 26 PGN that stabilized or decreased in size (21.5%) was 58.6 months. All lesions changed in a symmetric manner and 91 (75.2%) displayed a decrease in the density of peripheral globules over time. CONCLUSIONS AND RELEVANCE: Nevi displaying a peripheral globular pattern enlarged symmetrically with apparent growth cessation occurring during a span of 4 to 5 years. Our results reiterate the important concept that not all growth is associated with malignancy.

Melanoma patient self-detection: a review of efficacy of the skin self-examination and patient-directed educational efforts.

Early detection of cutaneous melanoma results in reduced morbidity and mortality. Although screening by physicians has been shown effective, the role of skin self-examination (SSE) in melanoma secondary prevention is less well studied. Various methods and educational strategies have been implemented to empower patients to perform efficacious SSEs. Patient demographics play an important role in their likelihood to examine their own skin and ability to detect melanoma. Visual aids such as total body photography and dermoscopy, which have improved physician exams, are becoming elements accessible to patients for augmentation of self-exam. This review examines the literature of SSE in melanoma detection.

Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair.

Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1(-/-) mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1(-/-) mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1(-/-) callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair.