Gene Expression Analysis Differentiates Melanomas from Spitz Nevi.

INTRODUCTION: Pediatric Spitz nevi can pose significant diagnostic challenges to both clinicians and dermatopathologists when the current image-recognition based gold standard is employed. PRAME (preferentially expressed antigen in melanoma) and/or LINC (long intergeneic non-coding RNA 518) gene expression in adult patients in samples obtained non-invasively via adhesive patches differentiates primary melanomas from atypical nevi and other pigmented lesions with a NPV of over 99%, a sensitivity of 91%, and a specificity of 69%, to help clinicians rule out melanoma and the need for surgical biopsies of atypial pigmented lesions with suspicion for melanoma. Surgically obtained melanomas from adult patients show the same gene expression pattern. METHODS: In this study, we investigate gene expression patterns of pigmented lesions from FFPE tissue block samples (n=23, 9 male, 14 female patients, median age 12) with a focus on differentiating Spitz nevi from melanomas in children and young adults. RESULTS: PRAME levels were significantly (P less than 0.001) increased based on normalized Ct cycle counts (lower cycle counts indicate higher expression levels) in melanomas (mean Ct 33.83 + 0.54, 95% CI 32.85-34.80) when compared to Spitz nevi (mean Ct 37.21 + 0.98, 95% CI 35.41-39.01) or common nevi (mean Ct 36.94 + 0.80, 95% CI 35.47-38.40), respectively. LINC and 4 control genes showed similar expression levels in all 3 pigmented lesion groups investigated. Clinically and histopathologically complex pediatric Spitz nevi demonstrated gene expression signatures almost identical to gene expression signatures of common pediatric nevi but different from melanomas in children and young adults. DISCUSSION: PRAME but not LINC gene expression can be a valuable molecular aid to differentiate melanomas from Spitz nevi, groups of pigmented lesions that can be particularly difficult to assess in children and young adults. J Drugs Dermatol. 2018;17(5):574-576.

Utility of a Noninvasive 2-Gene Molecular Assay for Cutaneous Melanoma and Effect on the Decision to Biopsy.

Importance: Expression of long intergenic non-protein coding RNA 518 (LINC00518) and preferentially expressed antigen in melanoma (PRAME) genes, obtained via noninvasive adhesive patch biopsy, is a sensitive and specific method for detection of cutaneous melanoma. However, the utility of this test in biopsy decisions made by dermatologists has not been evaluated. Objective: To determine the utility of the pigmented lesion assay (PLA) for LINC00518/PRAME expression in decisions to biopsy a series of pigmented skin lesions. Design, Setting, and Participants: In this secure web-based, multiple-reader-multiple-case study, 45 board-certified dermatologists each evaluated 60 clinical and dermoscopic images of clinically atypical pigmented lesions, first without and then with PLA gene expression information and were asked whether the lesions should be biopsied. Data were collected from March 24, 2014, through November 13, 2015. Interventions: Participants were given a report for each lesion, which included the results of an assay for expression of LINC00518/PRAME and a PLA score with data on the predictive values of the information provided. Main Outcomes and Measures: Biopsy sensitivity and specificity with vs without PLA data. Results: Forty-five dermatologists (29 male and 16 female) performed the evaluation. After incorporating the PLA into their decision as to whether to biopsy a pigmented lesion suggestive of melanoma, dermatologists improved their mean biopsy sensitivity from 95.0% to 98.6% (P = .01); specificity increased from 32.1% to 56.9% (P < .001) with PLA data. Conclusions and Relevance: The noninvasive PLA enables dermatologists to significantly improve biopsy specificity while maintaining or improving sensitivity. This result may increase the number of early melanomas biopsied and reduce the number of benign lesions biopsied, thereby improving patient outcomes and reducing health care costs.

Lip augmentation dermal filler reactions, histopathologic features.

Instances of perioral and labial foreign body reactions to a variety of injectable dermal fillers were selected from the oral and maxillofacial pathology and dermatopathology archives at Pacific Pathology Laboratory of San Diego with the objective being to engender a compilation of histopathologic characteristics that allow the pathologist to identify the inciting materials. All cases of foreign body reactions located in the lips and perioral regions were reviewed by four pathologists, retaining those cases with a history of injection lip augmentation as well as those with histologic features previously documented to represent dermal filler substances. In selected cases, Alcian blue pH 2.5 with and without hyaluronidase pretreatment was performed. Immunohistochemical markers for macrophages (CD 68), adipocytes (S-100) and keratinocytes (AE1/AE2) were undertaken. All instances presented as single or multiple submucosal plaques, nodules or swellings. Natural polymers including collagen, hyaluronate, hydroxyapatite, poly-L-lactate and synthetic polymers including carboxymethyl cellulose, dimethylpolysiloxane, and polyethyl methacrylate induce histologically unique features that allow for their identification. Host histopathologic responses included nodule without foreign body reaction, nodule with chronic inflammation, granuloma with epithelioid histiocytic and multinucleated giant cell reaction. Dermal filler foreign body host reactions in conjunction with the morphology of the foreign materials themselves are unique and can be differentiated from one another microscopically.