MED15::ATF1-rearranged tumor: a novel cutaneous tumor with melanocytic differentiation.

We recently described novel dermal tumors with melanocytic differentiation and morphologic and biologic similarity to cutaneous clear cell sarcoma, including CRTC1::TRIM11 cutaneous tumor (CTCT), and clear cell tumors with melanocytic differentiation and either ACTIN::MITF (CCTMAM) or MITF::CREM (CCTMMC). Here we describe a series of three patients presenting with tumors reminiscent of CTCT, found to demonstrate a novel MED15::ATF1 fusion. All three patients were children (5-16 years old). Primary excision of Case 1 showed a circumscribed wedge-shaped silhouette with peripheral intercalation into collagen fibers and scattered lymphoid aggregates. All three tumors abutted the epidermis; one showed a junctional component. Tumors were highly cellular and comprised of monomorphic, oval to round epithelioid cells arranged in vague nests and short fascicles in variably fibrotic stroma. Mitotic rate was high (hotspot 6 - 12/mm2), without atypical mitoses. Necrosis was focally present in Case 3. All cases showed strong, diffuse nuclear staining for SOX10 and MITF (2/2), but showed variable expression for S100 protein (1/3) and other melanocytic markers- MelanA (focal in 2/3), HMB45 (focal in 1/3), and Pan-Melanoma (patchy in 1/1). Whole exome RNA sequencing demonstrated a MED15::ATF1 fusion without any other notable alterations. Cases 1 and 2 were completely excised without recurrence (12 months). Case 3 developed grossly apparent regional lymph node spread shortly after primary biopsy. The patient was treated with wide excision, radiation, cervical lymph node dissection (4/46 with >75% lymph node replacement), and neoadjuvant and adjuvant nivolumab (alive without disease at cycle 11). This series is presented to aid in future diagnosis of this novel dermal tumor with melanocytic differentiation, and to emphasize the potential for aggressive biologic behavior, which should be considered in patient management planning.