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Featured researches published by Ralph P. Braun.


Archives of Dermatology | 2008

Dermoscopic Evaluation of Amelanotic and Hypomelanotic Melanoma

Scott W. Menzies; Juergen Kreusch; Karen Byth; Maria A. Pizzichetta; Ashfaq A. Marghoob; Ralph P. Braun; Josep Malvehy; Susana Puig; Giuseppe Argenziano; Iris Zalaudek; Harold S. Rabinovitz; Margaret Oliviero; Horacio Cabo; Verena Ahlgrimm-Siess; Michelle Avramidis; Pascale Guitera; H. Peter Soyer; Giovanni Ghigliotti; Masaru Tanaka; Ana Perusquia; Gianluca Pagnanelli; Riccardo Bono; Luc Thomas; Giovanni Pellacani; David Langford; Domenico Piccolo; Karin Terstappen; Ignazio Stanganelli; Alex Llambrich; Robert H. Johr

OBJECTIVE To determine the predictive dermoscopic features of amelanotic and hypomelanotic melanoma. DESIGN A total of 105 melanomas (median Breslow thickness, 0.76 mm), 170 benign melanocytic lesions, and 222 nonmelanocytic lesions lacking significant pigment (amelanotic, partially pigmented, and light colored) were imaged using glass-plate dermoscopy devices and scored for 99 dermoscopic features. Diagnostic models were derived from and tested on independent randomly selected lesions. SETTING Predominantly hospital-based clinics from 5 continents. MAIN OUTCOME MEASURES Sensitivity, specificity, and odds ratios for individual features and models for the diagnosis of melanoma and malignancy. RESULTS The most significant negative predictors of melanoma were having multiple (>3) milialike cysts (odds ratio, 0.09; 95% confidence interval, 0.01-0.64), comma vessels with a regular distribution (0.10; 0.01-0.70), comma vessels as the predominant vessel type (0.16; 0.05-0.52), symmetrical pigmentation pattern (0.18; 0.09-0.39), irregular blue-gray globules (0.20; 0.05-0.87), and multiple blue-gray globules (0.28; 0.10-0.81). The most significant positive predictors were having a blue-white veil (odds ratio,13; 95% confidence interval, 3.9-40.0), scarlike depigmentation (4.4; 2.4-8.0), multiple blue-gray dots (3.5; 1.9-6.4), irregularly shaped depigmentation (3.3; 2.0-5.3), irregular brown dots/globules (3.2; 1.8-5.6), 5 to 6 colors (3.2; 1.6-6.3), and predominant central vessels (3.1; 1.6-6.0). A simple model distinguishing melanomas from all nonmelanomas had a sensitivity of 70% and a specificity of 56% in the test set. A model distinguishing all malignant lesions from benign lesions had a sensitivity of 96% and a specificity of 37%. Conclusion Although the diagnostic accuracy of dermoscopy for melanoma lacking significant pigment is inferior to that of more pigmented lesions, features distinguishing the former from benign lesions can be visualized on dermoscopic evaluation.


Archives of Dermatology | 2009

Reflectance Confocal Microscopy Criteria for Squamous Cell Carcinomas and Actinic Keratoses

Ayelet Rishpon; Nancy Kim; Alon Scope; Leeor Porges; Margaret Oliviero; Ralph P. Braun; Ashfaq A. Marghoob; Christi Alessi Fox; Harold S. Rabinovitz

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.


Archives of Dermatology | 2011

Dermoscopy of pigmented lesions of the mucosa and the mucocutaneous junction: results of a multicenter study by the International Dermoscopy Society (IDS).

Andreas Blum; Olga Simionescu; Giuseppe Argenziano; Ralph P. Braun; Horacio Cabo; Astrid Eichhorn; Herbert Kirchesch; Josep Malvehy; Ashfaq A. Marghoob; Susana Puig; Fezal Ozdemir; Wilhelm Stolz; Isabelle Tromme; Ulrike Weigert; Ingrid H. Wolf; Iris Zalaudek; Harald Kittler

OBJECTIVE To better characterize the dermoscopic patterns of mucosal lesions in relation to the histopathologic characteristics. DESIGN Retrospective and observational study. SETTING Fourteen referral pigmented lesion clinics in 10 countries. PATIENTS A total of 140 pigmented mucosal lesions (126 benign lesions, 11 melanomas, 2 Bowen disease lesions, and 1 metastasis) from 92 females (66%) and 48 males (34%) were collected from October 2007 through November 2008. MAIN OUTCOME MEASURES Scoring the dermoscopic patterns (dots, globules, or clods, circles, lines, or structureless) and colors (brown, black, blue, gray, red, purple, and white) and correlation with the histopathologic characteristics. RESULTS Based on univariate analysis and 2 diagnostic models, the presence of structureless zones inside the lesions with blue, gray, or white color (the first model) had a 100% sensitivity for melanoma and 92.9% sensitivity for any malignant lesion, and 82.2% and 83.3% specificity for benign lesions in the group with melanoma lesions and the group with malignant lesions, respectively. Based on the colors (blue, gray, or white) only (the second model), the sensitivity for the group with melanoma was 100% and for the group with any malignant lesion was 92.9%, and the specificity was 64.3% and 65.1%, respectively. Patients with malignant lesions were significantly older than patients with benign lesions (mean [SD] ages, 60.1 [22.8] years vs 43.2 [17.3] years, respectively). CONCLUSION The combination of blue, gray, or white color with structureless zones are the strongest indicators when differentiating between benign and malignant mucosal lesions in dermoscopy.


Archives of Dermatology | 2009

Reflectance confocal microscopy and features of melanocytic lesions: An internet-based study of the reproducibility of terminology

Giovanni Pellacani; Marco Vinceti; Sara Bassoli; Ralph P. Braun; Salvador González; Pascale Guitera; Caterina Longo; Ashfaq A. Marghoob; Scott W. Menzies; Susana Puig; Alon Scope; Stefania Seidenari; Josep Malvehy

OBJECTIVE To test the interobserver and intraobserver reproducibility of the standard terminology for description and diagnosis of melanocytic lesions in in vivo confocal microscopy. DESIGN A dedicated Web platform was developed to train the participants and to allow independent distant evaluations of confocal images via the Internet. SETTING Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy. PARTICIPANTS The study population was composed of 15 melanomas, 30 nevi, and 5 Spitz/Reed nevi. Six expert centers were invited to participate at the study. Intervention Evaluation of 36 features in 345 confocal microscopic images from melanocytic lesions. MAIN OUTCOME MEASURE Interobserved and intraobserved agreement, by calculating the Cohen kappa statistics measure for each descriptor. RESULTS High overall levels of reproducibility were shown for most of the evaluated features. In both the training and test sets there was a parallel trend of decreasing kappa values as deeper anatomic skin levels were evaluated. All of the features, except 1, used for melanoma diagnosis, including roundish pagetoid cells, nonedged papillae, atypical cells in basal layer, cerebriform clusters, and nucleated cells infiltrating dermal papillae, showed high overall levels of reproducibility. However, less-than-ideal reproducibility was obtained for some descriptors, such as grainy appearance of the epidermis, junctional thickening, mild atypia in basal layer, plump bright cells, small bright cells, and reticulated fibers in the dermis. Conclusion The standard consensus confocal terminology useful for the evaluation of melanocytic lesions was reproducibly recognized by independent observers.


Journal of The American Academy of Dermatology | 2012

The significance of crystalline/chrysalis structures in the diagnosis of melanocytic and nonmelanocytic lesions

Yevgeniy Balagula; Ralph P. Braun; Harold S. Rabinovitz; Stephen W. Dusza; Alon Scope; Ines Mordente; Katherine Siamas; Ashfaq A. Marghoob

BACKGROUND Crystalline/chrysalis structures (CS) are white shiny streaks that can only be seen with polarized dermatoscopy. OBJECTIVES We sought to estimate the prevalence and assess the clinical significance of CS in melanocytic and nonmelanocytic lesions. METHODS This was a prospective observational study in which dermatoscopic assessment of lesions was recorded in consecutive patients examined during a 6-month period. In addition, a data set of biopsy-proven melanomas was retrospectively analyzed. RESULTS In all, 11,225 lesions in 881 patients were prospectively examined. Retrospectively, 229 melanomas imaged with polarized dermatoscopy were analyzed. In the prospective data set, a median of 12.7 lesions (range, 1-54) were evaluated per patient. None of clinically diagnosed Clark nevi (n = 9750, 86.8%) demonstrated CS. Overall, CS were observed in 206 (1.8%) lesions, most commonly dermatofibromas and scars among nonbiopsied lesions. A total of 265 (2.4%) lesions were biopsied, including 20 melanomas and 36 nevi. Among biopsied malignant lesions, CS were most commonly observed in basal cell carcinoma (47.6%) and invasive melanomas (84.6%). Melanomas were more likely to have CS than biopsied nevi (odds ratio = 9.7, 95% confidence interval 2.7-34.1). In the retrospective data set, CS were more commonly observed among invasive melanomas (41%) compared with in situ melanomas (17%) (odds ratio = 3.4, 95% confidence interval 1.9-6.3, P < .001). The prevalence of CS correlated with increased melanoma thickness (P = .001). LIMITATIONS Biopsied lesions represent a small percentage of the total number of lesions evaluated. CONCLUSION Among biopsied malignant lesions, CS are most commonly observed in basal cell carcinoma and invasive melanomas and rarely seen in nevi. In melanoma, CS may reflect increased tumor thickness and progression.


Dermatologic Surgery | 2008

Differences in Dermoscopic Images from Nonpolarized Dermoscope and Polarized Dermoscope Influence the Diagnostic Accuracy and Confidence Level: A Pilot Study

Steven Q. Wang; Stephen W. Dusza; Alon Scope; Ralph P. Braun; Alfred W. Kopf; Ashfaq A. Marghoob

BACKGROUND Studies have demonstrated differences in colors and dermoscopic structures observed with polarized dermoscopes (PDs) and nonpolarized dermoscopes (NPDs). OBJECTIVE The objective was to evaluate whether diagnosis and diagnostic confidence changes when viewing dermoscopic images from NPDs and PDs. METHODS A total of 100 dermatologists participated in the study. Twenty-five pigmented lesions were shown in the study, consisting of 7 seborrheic keratoses (SK), 3 basal cell carcinomas, 2 atypical nevi, 5 malignant melanomas (MM), 3 dermatofibromas, 3 blue nevi, and 2 hemangiomas. Two images of each lesion (one NPD and one PD) were included. The McNemar test and paired t-test were used for the statistical analysis. RESULTS Ninety-one participants completed the study. Significant differences in the diagnoses were observed for the SK, atypical nevus, and MM images. Seventy-five percent and 59% of the final participants correctly diagnosed SK when presented with the NPD and PD images, respectively. For MM, 23 and 34% made the correct diagnoses with the NPD and PD images, respectively. CONCLUSIONS Viewing lesions with NPD versus PD can affect the diagnosis and diagnostic confidence of physicians that are novices with dermoscopy. Further studies including physicians at different expertise levels and a larger sample of lesions are needed to further explore the differences.


JAMA Dermatology | 2015

Skin Cancer Diagnosis With Reflectance Confocal Microscopy: Reproducibility of Feature Recognition and Accuracy of Diagnosis

Francesca Farnetani; Alon Scope; Ralph P. Braun; Salvador González; Pascale Guitera; Josep Malvehy; Marco Manfredini; Ashfaq A. Marghoob; Elvira Moscarella; Margaret Oliviero; Susana Puig; Harold S. Rabinovitz; Ignazio Stanganelli; Caterina Longo; Carlotta Malagoli; Marco Vinceti; Giovanni Pellacani

IMPORTANCE Reflectance confocal microscopy (RCM) studies have been performed to identify criteria for diagnosis of skin neoplasms. However, RCM-based diagnosis is operator dependent. Hence, reproducibility of RCM criteria needs to be tested. OBJECTIVE To test interobserver reproducibility of recognition of previously published RCM descriptors and accuracy of RCM-based skin cancer diagnosis. DESIGN, SETTING, AND PARTICIPANTS Observational retrospective web-based study of a set of RCM images collected at a tertiary academic medical center. Nine dermatologists (6 of whom had ≥3 years of RCM experience) from 6 countries evaluated an RCM study set from 100 biopsy-proven lesions, including 55 melanocytic nevi, 20 melanomas, 15 basal cell carcinomas, 7 solar lentigines or seborrheic keratoses, and 3 actinic keratoses. Between June 15, 2010, and October 21, 2010, participanting dermatologists, blinded to histopathological diagnosis, evaluated 3 RCM mosaic images per lesion for the presence of predefined RCM descriptors. MAIN OUTCOMES AND MEASURES The main outcome was identification of RCM descriptors with fair to good interrater agreement (κ statistic, ≥0.3) and independent correlation with malignant vs benign diagnosis on discriminant analysis. Additional measures included sensitivity and specificity for diagnosis of malignant vs benign for each evaluator, for majority diagnosis (rendered by ≥5 of 9 evaluators), and for experienced vs recent RCM users. RESULTS Eight RCM descriptors showed fair to good reproducibility and were independently associated with a specific diagnosis. Of these, the presence of pagetoid cells, atypical cells at the dermal-epidermal junction, and irregular epidermal architecture were associated with melanoma. Aspecific junctional pattern, basaloid cords, and ulceration were associated with basal cell carcinomas. Ringed junctional pattern and dermal nests were associated with nevi. The mean sensitivity for the group of evaluators was 88.9% (range, 82.9%-100%), and the mean specificity was 79.3% (range, 69.2%-90.8%). Majority diagnosis showed sensitivity of 100% and specificity of 80.0%. Sensitivity was higher for experienced vs recent RCM users (91.0% vs. 84.8%), but specificity was similar (80.0% vs. 77.9%). CONCLUSIONS AND RELEVANCE The study highlights key RCM diagnostic criteria for melanoma and basal cell carcinoma that are reproducibly recognized among RCM users. Diagnostic accuracy increases with experience. The higher accuracy of majority diagnosis suggests that there is intrinsically more diagnostic information in RCM images than is currently used by individual evaluators.


Australasian Journal of Dermatology | 2009

Congenital melanocytic naevi.

Ivanka Kovalyshyn; Ralph P. Braun; Ashfaq A. Marghoob

Congenital melanocytic naevi, consisting of clusters of naevo‐melanocytes, develop in utero. Although many congenital naevi are visible at birth, some may not become evident until later in life. The timing of naevo‐melanocyte proliferation, senescence and melanogenesis may all contribute towards determining when a naevus will become clinically manifest on the skin. Besides the fact that congenital melanocytic naevi may be aesthetically displeasing, resulting in a multitude of psychosocial issues, they also increase the risk for developing cutaneous melanoma, leptomeningeal melanoma, neurocutaneous melanocytosis, malformations of the brain and, rarely, other tumours such as rhabdomyosarcoma and liposarcoma. Whereas the risk of developing malignancy in association with congenital naevi is dependent, to some extent, on the size of the naevus, the risk of developing neurocutaneous melanocytosis correlates best with the number of satellite naevi. Management of patients with congenital melanocytic naevi requires individualization, taking into account the naevus size and location, and the risk of developing cutaneous melanoma or neurocutaneous melanocytosis. When contemplating treatment options, it is important to set realistic expectations and to address the possible aesthetic and functional outcomes, while at the same time addressing the risk for developing cutaneous and/or extracutaneous melanoma.


JAMA Dermatology | 2013

Dermoscopic evaluation of nodular melanoma

Scott W. Menzies; Fergal J. Moloney; Karen Byth; Michelle Avramidis; Giuseppe Argenziano; Iris Zalaudek; Ralph P. Braun; Josep Malvehy; Susana Puig; Harold S. Rabinovitz; Margaret Oliviero; Horacio Cabo; Riccardo Bono; Maria A. Pizzichetta; Magdalena Claeson; Daniel C Gaffney; H. Peter Soyer; Ignazio Stanganelli; Richard A. Scolyer; Pascale Guitera; John W. Kelly; Olivia McCurdy; Alex Llambrich; Ashfaq A. Marghoob; Pedro Zaballos; Herbert Kirchesch; Domenico Piccolo; Jonathan Bowling; Luc Thomas; Karin Terstappen

IMPORTANCE Nodular melanoma (NM) is a rapidly progressing potentially lethal skin tumor for which early diagnosis is critical. OBJECTIVE To determine the dermoscopy features of NM. DESIGN Eighty-three cases of NM, 134 of invasive non-NM, 115 of nodular benign melanocytic tumors, and 135 of nodular nonmelanocytic tumors were scored for dermoscopy features using modified and previously described methods. Lesions were separated into amelanotic/hypomelanotic or pigmented to assess outcomes. SETTING Predominantly hospital-based clinics from 5 continents. MAIN OUTCOME MEASURES Sensitivity, specificity, and odds ratios for features/models for the diagnosis of melanoma. RESULTS Nodular melanoma occurred more frequently as amelanotic/hypomelanotic (37.3%) than did invasive non-NM (7.5%). Pigmented NM had a more frequent (compared with invasive non-NM; in descending order of odds ratio) symmetrical pigmentation pattern (5.8% vs 0.8%), large-diameter vessels, areas of homogeneous blue pigmentation, symmetrical shape, predominant peripheral vessels, blue-white veil, pink color, black color, and milky red/pink areas. Pigmented NM less frequently displayed an atypical broadened network, pigment network or pseudonetwork, multiple blue-gray dots, scarlike depigmentation, irregularly distributed and sized brown dots and globules, tan color, irregularly shaped depigmentation, and irregularly distributed and sized dots and globules of any color. The most important positive correlating features of pigmented NM vs nodular nonmelanoma were peripheral black dots/globules, multiple brown dots, irregular black dots/globules, blue-white veil, homogeneous blue pigmentation, 5 to 6 colors, and black color. A model to classify a lesion as melanocytic gave a high sensitivity (>98.0%) for both nodular pigmented and nonnodular pigmented melanoma but a lower sensitivity for amelanotic/hypomelanotic NM (84%). A method for diagnosing amelanotic/hypomelanotic malignant lesions (including basal cell carcinoma) gave a 93% sensitivity and 70% specificity for NM. CONCLUSIONS AND RELEVANCE When a progressively growing, symmetrically patterned melanocytic nodule is identified, NM needs to be excluded.


Clinics in Dermatology | 2009

Dermoscopy: what's new?

Ralph P. Braun; Margaret Oliviero; Isabel Kolm; Lars E. French; Ashfaq A. Marghoob; Harold Rabinovitz

Dermoscopy has been described as a useful tool for the early diagnosis of melanoma and the differential diagnosis of pigmented lesions of the skin. This has been proven by three independent meta analyses of the literature. Dermoscopy is a fast evolving field with a high number of new publications every year. Initially, the use of dermoscopy was limited to pigmented lesions, but it is used more and more in other situations. It has become an important tool for the diagnosis of nail pigmentations, hair and scalp disorders, and so forth. In this article we try to provide an update on recent trends and developments in dermoscopy.

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Ashfaq A. Marghoob

Memorial Sloan Kettering Cancer Center

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Iris Zalaudek

Medical University of Graz

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Susana Puig

University of Barcelona

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Giuseppe Argenziano

Seconda Università degli Studi di Napoli

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