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Case Reports

Abstract

Background: Spitz melanocytic tumors harboring MAP3K8 kinase fusion/truncation range from benign to malignant.  They typically demonstrate nodular growth and enlarged, pleomorphic epithelioid cells that are less spindled compared to most Spitz tumors. Case:  A 34-year-old woman presented with a pigmented arm lesion. Histology revealed a wedge-shaped compound melanocytic proliferation with adnexal accentuation and without epidermal hyperplasia.  Junctional melanocytes were arranged in small nests with bridging across the rete, and single cells with lateral pagetoid spread.  Dermal melanocytes were arranged in loose broad fascicles, small densely packed nests and single cells. Melanocytes showed moderate amounts of uniformly dustily pigmented cytoplasm and monomorphic mildly enlarged ovoid nuclei with open chromatin and prominent small nucleoli.  Occasional relatively small multinucleated cells were observed. HMB-45 expression was diffusely retained and p16 expression was lost.  Next-generation sequencing demonstrated a truncating MAP3K8 rearrangement, chromosome 3p loss, proximal 3p gain, and distal 12q loss.  Tumor mutation burden was 8.9 mutations/Mb.  A diagnosis of high-grade atypical Spitz tumor was made, and conservative re-excision was recommended. No recurrences have occurred. Discussion: The current case expands the morphologic spectrum of MAP3K8 Spitz tumors to include relatively smaller, monomorphic fusiform cells with fascicular growth, diffuse/even dusty pigment, and a wedge-shaped silhouette. Diffuse HMB45 staining and loss of p16 expression are common in MAP3K8-driven Spitz tumors. Conclusion: Recognition of MAP3K8 Spitz tumors with unusual morphology is important to aid in appropriate classification.  Although morphologic and immunophenotypic features are frequently worrisome, lethality has not been observed in the absence of aberrant TERT expression.