Melanie Warycha

Meta-analysis of sentinel lymph node positivity in thin melanoma (≤1 mm)

Despite the lack of an established survival benefit of sentinel lymph node (SLN) biopsy, this technique has been increasingly applied in the staging of thin (≤1 mm) melanoma patients, without clear evidence to support this recommendation. The authors performed a meta‐analysis to estimate the risk, potential predictors, and outcome of SLN positivity in this group of patients.

Role of radiologic imaging at the time of initial diagnosis of stage T1b‐T3b melanoma

In patients with T1b‐T3b cutaneous melanoma the utility of radiologic imaging at the time of diagnosis is unclear. Whether initial imaging led to a change in stage or treatment plan was investigated.

Changes in the presentation of nodular and superficial spreading melanomas over 35 years.

Nodular melanoma (NM) may be biologically aggressive compared with the more common superficial spreading melanoma (SSM), with recent data suggesting underlying genetic differences between these 2 subtypes. To better define the clinical behavior of NMs, the authors compared their clinical and histopathologic features to those of SSMs at their institution, a tertiary referral center, over 3 decades.

Phosphorylated 4E-BP1 is associated with poor survival in melanoma.

Purpose: Both phosphatidylinositol 3-kinase/AKT and RAS/mitogen-activated protein kinase signal transduction pathways mediate 4E-BP1 phosphorylation, releasing 4E-BP1 from the mRNA cap and permitting translation initiation. Given the prevalence of PTEN and BRAF mutations in melanoma, we first examined translation initiation, as measured by phosphorylated 4E-BP1 (p-4E-BP1), in metastatic melanoma tissues and cell lines. We then tested the association between amounts of total and p-4E-BP1 and patient survival. Experimental Design: Seven human metastatic melanoma cells lines and 72 metastatic melanoma patients with accessible metastatic tumor tissues and extended follow-up information were studied. Expression of 4E-BP1 transcript, total 4E-BP1 protein, and p-4E-BP1 was examined. The relationship between 4E-BP1 transcript and protein expression was assessed in a subset of patient tumors (n = 41). The association between total and p-4E-BP1 levels and survival was examined in the larger cohort of patients (n = 72). Results: 4E-BP1 was hyperphosphorylated in 4 of 7 melanoma cell lines harboring both BRAF and PTEN mutations compared with untransformed melanocytes or RAS/RAF/PTEN wild-type melanoma cells. 4E-BP1 transcript correlated with 4E-BP1 total protein levels as measured by the semiquantitative reverse-phase protein array (P = 0.012). High levels of p-4E-BP1 were associated with worse overall and post-recurrence survival (P = 0.02 and 0.0003, respectively). Conclusion: Our data show that translation initiation is a common event in human metastatic melanoma and correlates with worse prognosis. Therefore, effective inhibition of the pathways responsible for 4E-BP1 phosphorylation should be considered to improve the treatment outcome of metastatic melanoma patients.

The Diagnostic Performance of Expert Dermoscopists vs a Computer-Vision System on Small-Diameter Melanomas

OBJECTIVE To evaluate the performance of dermoscopists in diagnosing small pigmented skin lesions (diameter </= 6 mm) compared with an automatic multispectral computer-vision system. DESIGN Blinded comparison study. SETTING Dermatologic hospital-based clinics and private practice offices. Patients From a computerized skin imaging database of 990 small (</= 6-mm) pigmented skin lesions, all 49 melanomas from 49 patients were included in this study. Fifty randomly selected nonmelanomas from 46 patients served as a control. MAIN OUTCOME MEASURES Ten dermoscopists independently examined dermoscopic images of 99 pigmented skin lesions and decided whether they identified the lesions as melanoma and whether they would recommend biopsy to rule out melanoma. Diagnostic and biopsy sensitivity and specificity were computed and then compared with the results of the computer-vision system. RESULTS Dermoscopists were able to correctly identify small melanomas with an average diagnostic sensitivity of 39% and a specificity of 82% and recommended small melanomas for biopsy with a sensitivity of 71% and specificity of 49%, with only fair interobserver agreement (kappa = 0.31 for diagnosis and 0.34 for biopsy). In comparison, in recommending biopsy to rule out melanoma, the computer-vision system achieved 98% sensitivity and 44% specificity. CONCLUSIONS Differentiation of small melanomas from small benign pigmented lesions challenges even expert physicians. Computer-vision systems can facilitate early detection of small melanomas and may limit the number of biopsies to rule out melanoma performed on benign lesions.

The “dysplastic” nevus

Dysplastic nevi have become an increasing focus clinically, with evidence that they are associated with a higher risk of developing melanoma. However, there still is contention regarding the significance of dysplastic nevi. This contribution provides an overview of the history, epidemiology, genetics, clinical and histologic features, and procedures for clinical management of dysplastic nevi. Since dysplastic nevi were described originally in 1978, a great deal of research has examined the epidemiology of these lesions and the genetic factors related to the development of dysplastic nevi. However, there is disagreement regarding the clinical management of dysplastic nevi and the histologic definition of dysplastic nevi. Current recommendations include preventative measures, such as sun protection and careful surveillance and biopsies of suspicious lesions as needed. The advent of new technologies, such as computer-vision systems, have the potential to significantly change treatment of dysplastic nevi in the future.

Comparative effectiveness of nonpurpuragenic 595-nm pulsed dye laser and microsecond 1064-nm neodymium:yttrium-aluminum-garnet laser for treatment of diffuse facial erythema: A double-blind randomized controlled trial

BACKGROUND Facial erythema is a common symptom that responds to vascular laser treatment, but there are few comparative studies. OBJECTIVE We sought to compare the effectiveness of microsecond 1064-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser with nonpurpuragenic 595-nm pulsed dye laser (PDL) for diffuse facial erythema. METHODS This was a split-face, double-blind randomized controlled trial. Bilateral cheeks received 4 treatments each at one month intervals with PDL or Nd:YAG. Spectrophotometer measurements, digital photographs, pain scores, and patient preferences were recorded. RESULTS Sixteen patients enrolled and 2 dropped out. Fourteen patients, all skin types I to III, 57% women, mean age 42 years, completed the study and were analyzed. Spectrophotometer readings changed after both PDL (8.9%) and Nd:YAG (2.5%), but varied by treatment type, with PDL reducing facial redness 6.4% more from baseline than Nd:YAG (P = .0199; 95% confidence interval -11.6 to -1.2). Pain varied (P = .0028), with Nd:YAG associated with less pain, at 3.07, than PDL at 3.87. Subjects rated redness as improved by 52% as a result of PDL, and 34% as a result of Nd:YAG (P = .031; 95% confidence interval -34.6 to -1.94). No serious adverse events were observed. LIMITATIONS Lasers settings are not standardized across devices. CONCLUSION Facial erythema is safely and effectively treated with PDL and Nd:YAG. Nonpupuragenic PDL may be more effective for lighter-skinned patients, but microsecond Nd:YAG may be less painful.

Analysis of the benign to malignant ratio of lesions biopsied by a general dermatologist before and after the adoption of dermoscopy.

A lthough the benefits of using dermoscopy as a diagnostic aid are well described, dermoscopy currently remains underutilized in the United States. According to a recent survey of US academic dermatologists, reasons cited for lack of utilization included lack of training, logistical constraints, and the belief that the procedure was not helpful. Also, some clinicians may be apprehensive about introducing dermoscopy into their practices because many of the studies that highlight the benefits of dermoscopy have been conducted by pigmented lesion specialists (PLSs). The purpose of our pilot study was to assess changes in the management of pigmented lesions by a general dermatologist after the introduction of dermoscopy. As our end point, we calculated the benign to malignant ratio (BMR) for biopsied pigmented lesions having a clinical differentialdiagnosisofdysplasticnevusand/ormelanoma.Togauge theperformanceof thegeneraldermatologist,wecompared his results to thoseofanexperienceddermoscopyuserwho primarily sees patients with pigmented skin lesions.

Shedding of distinct cryptic collagen epitope (HU177) in sera of melanoma patients.

Purpose: Extracellular matrix remodeling during tumor growth plays an important role in angiogenesis. Our preclinical data suggest that a newly identified cryptic epitope (HU177) within collagen type IV regulates endothelial and melanoma cell adhesion in vitro and angiogenesis in vivo. In this study, we investigated the clinical relevance of HUI77 shedding in melanoma patient sera. Experimental Design: Serum samples from 291 melanoma patients prospectively enrolled at the New York University Medical Center and 106 control subjects were analyzed for HU177 epitope concentration by a newly developed sandwich ELISA assay. HU177 serum levels were then correlated with clinical and pathologic parameters. Results: Mean HU177 epitope concentration was 5.8 ng/mL (range, 0-139.8 ng/mL). A significant correlation was observed between HU177 concentration and nodular melanoma histologic subtype [nodular, 10.3 ± 1.6 ng/mL (mean ± SE); superficial spreading melanoma, 4.5 ± 1.1 ng/mL; all others, 6.1 ± 2.1 ng/mL; P = 0.01 by ANOVA test]. Increased HU177 shedding also correlated with tumor thickness (≤1.00 mm, 3.8 ± 1.1 ng/mL; 1.01-3.99 mm, 8.7 ± 1.3 ng/mL; ≥4.00 mm, 10.3 ± 2.4 ng/mL; P = 0.003 by ANOVA). After multivariate analysis controlling for thickness, the correlation between higher HU177 concentration and nodular subtype remained significant (P = 0.03). The mean HU177 epitope concentration in control subjects was 2.4 ng/mL. Conclusions: We report that primary melanoma can induce detectable changes in systemic levels of cryptic epitope shedding. Our data also support that nodular melanoma might be biologically distinct compared with superficial spreading type melanoma. As targeted interventions against cryptic collagen epitopes are currently undergoing phase I clinical trial testing, these findings indicate that patients with nodular melanoma may be more susceptible to such targeted therapies.

Flammability of topical preparations and surgical dressings in cutaneous and laser surgery: A controlled simulation study

BACKGROUND Surgical fires are a rare, but serious complication of dermatologic procedures involving electrosurgical and laser devices. Given the lack of data regarding basic fire safety principles, many dermatologists remain unaware of this potential risk. OBJECTIVE We evaluated the flammability of topical preparations and surgical drapes commonly encountered in the immediate operative field during cutaneous and laser surgery. METHODS Surgical dressings, drapes, and pork belly skin were examined for fire risk upon exposure to isopropyl alcohol, chlorhexidine gluconate, and aluminum chloride under dry, saturated, and damp conditions. Both electrosurgery and a carbon-dioxide laser were used as ignition sources. RESULTS At least some char was observed in 86 of 126 simulated conditions (68%). Flames occurred in 2 test conditions: dry underpad drapes and cotton balls exposed to the carbon-dioxide laser. In general, drapes and dressings dampened or saturated with isopropyl alcohol failed to ignite with electrofulguration or electrodessication, although sparks and moderate char developed on pork belly skin and the underpad drape. Materials dampened or saturated with chlorhexidine gluconate, which contains isopropyl alcohol, generated less smoke and char compared with materials exposed to aluminum chloride, which does not contain alcohol. LIMITATIONS Future studies may assess the flammability of materials in the setting of oxygen supplementation. CONCLUSION In common cutaneous surgical environments, electrosurgery or ablative laser may lead to char and rarely to fire. Char may be seen in up to two thirds of simulated conditions, and in a minute proportion of conditions, fire is observed.