Comparison of Immunohistochemistry for PRAME With Cytogenetic Test Results in the Evaluation of Challenging Melanocytic Tumors

Abstract

PRAME (PReferentially expressed Antigen in MElanoma) is a melanoma-associated antigen. Although diffuse immunoreactivity for PRAME is found in most primary cutaneous melanomas, melanocytic nevi express PRAME usually only in a subpopulation of tumor cells or not at all. Hence, testing for PRAME expression has the potential to provide useful information for the assessment for diagnostically ambiguous melanocytic neoplasms. Many of the latter tumors are currently studied by cytogenetic methods for ancillary evidence in support of or against a diagnosis of melanoma. In this study we analyzed 110 diagnostically problematic melanocytic tumors comparing results for PRAME immunohistochemistry (IHC) with those from fluorescence in situ hybridization and/or single nucleotide polymorphism-array, and each with the final diagnostic interpretation. In 90% of cases there was concordance between PRAME IHC and cytogenetic tests results, and in 92.7% concordance between PRAME IHC and the final diagnosis. The high concordance between PRAME IHC and cytogenetic test results as well as the final diagnosis supports the use of PRAME IHC as an ancillary test in the evaluation of ambiguous primary cutaneous melanocytic neoplasms, especially given its practical advantage of lower cost and faster turnaround over cytogenetic or gene expression studies. However, our results indicate that PRAME IHC and cytogenetic tests for melanocytic tumors are not entirely interchangeable and on occasion each type of test may yield false-negative or false-positive results.

PRAME expression in melanocytic proliferations with intermediate histopathologic or spitzoid features

“…A summary of PRAME results by type of lesion is provided in We note that the threshold for defining diffuse staining in our cohort (60%) differs from the cutoff of 75% established by Lezcano et al 14,15,19 Six of our 24 non-spitzoid melanomas (25%), none of which were desmoplastic, would be considered non-diffuse with the higher In summary, this study expands on the diagnostic utility of PRAME by demonstrating its lack of diffuse expression in atypical but benign melanocytic proliferations, facilitating their distinction from melanoma. This study also reinforces that PRAME expression in spitzoid neoplasms should be interpreted in the context of histopathologic features, and correlation with cytogenetic and/or molecular studies may be required for diagnostic classification.…”

“…18 Lezcano et al more recently showed a strong concordance between PRAME expression and cytogenetic studies in ambiguous melanocytic neoplasms. 19 In that study, PRAME was reported as scores designating diffuse or non-diffuse staining for an aggregated group of neoplasms. Further study of the pattern of PRAME expression in diagnostically challenging melanocytic lesions is merited.…”

Metastatic PRAME-Expressing Juvenile Spitzoid Melanoma on the Buttock

“…Since the diagnosis of primary Spitzoid melanoma by conventional methods (for example, conventional ABCDE [asymmetry, border irregularity, color variation, diameter >6 mm, and evolution] criteria, dermoscopy, histopathological diagnosis by HE staining) is challenging [ 2 , 5 ], recently, several diagnostic tools were developed [ 5 , 6 , 7 , 8 , 9 , 10 ]. Indeed, Bahrami et al [ 5 ] reviewed the molecular biology of pediatric melanoma, including Spitzoid melanoma, suggesting that the specific kinase gene fusion (including NTRK1, NTRK3, ALK, ROS1, RET, MET, and BRAF) might be useful for the diagnosis of Spitzoid melanoma [ 5 , 6 , 7 ].…”

“…Although these molecular biological methods are useful for the diagnosis of Spitzoid neoplasm, institutes that can employ these expensive methods are limited. Notably, Lezcano et al [ 2 ] evaluated the IHC of PRAME for challenging melanocytic tumors, including Spitzoid melanoma, by cytogenetic test, and the result suggested the high sensitivity (75.0%) and specificity (98.8%) of PRAME IHC for the diagnosis of Spitzoid melanoma. This report suggested the use of PRAME IHC as a supportive test in the evaluation of pediatric melanoma including Spitzoid melanoma [ 2 ].…”

“…Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated antigen that was first identified through analysis of the specificity of tumor-reactive T-cell clones derived from a patient with metastatic cutaneous melanoma [ 1 ]. Since the number of institutes that can perform these methods might be limited, PRAME is useful to distinguish melanoma from other melanocytic disorders (e.g., Spitz nevus) that are difficult to diagnose by conventional methods alone [ 2 ]. In this report, we describe a case of PRAME-expressing Spitzoid melanoma on the buttock that metastasized to the inguinal lymph nodes.…”