Track: Clinical Studies

Abstract:

Histone H3 lysine 27 trimethylation (H3K27me3) is an epigenetic modification associated with transcriptional repression and is expressed diffusely within the nuclei of normal tissues. Loss of H3K27me3 expression has been reported in malignant peripheral nerve sheath tumors, certain melanomas, and other neoplasms. While its diagnostic utility has been explored in adult conventional melanomas, its role in pediatric melanocytic lesions, particularly Spitz neoplasms, remains poorly characterized. True Spitz melanocytic tumors, which are predominantly seen in the pediatric population, range from benign lesions to malignant melanomas. Their histomorphology and molecular landscape differ significantly from conventional melanocytic neoplasms, and accurate classification often relies on advanced and costly molecular techniques such as genomic sequencing. Recent advancements in sequencing technology have improved classification, diagnosis, and prognostication, but distinguishing between atypical Spitz tumors and Spitz melanomas continues to present a significant diagnostic challenge for dermatopathologists. Given the potential diagnostic value of H3K27me3 in adult melanomas, we evaluated its expression in pediatric Spitz melanocytic lesions. In this retrospective study, archived formalin-fixed, paraffin-embedded specimens of benign, borderline, and malignant Spitz tumors were retrieved. All cases were confirmed as true Spitz melanocytic neoplasms based on immunohistochemistry and/or molecular findings. Adequate specimens were immunostained for H3K27me3 and categorized as showing complete loss, partial loss, or complete retention of nuclear expression. Preliminary results demonstrated distinct H3K27me3 staining patterns in Spitz melanocytic tumors compared with adult conventional melanomas. The expression patterns, along with their correlation to additional immunohistochemical markers and morphological features, are examined and discussed in this study.

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Paige Parrack