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Published on: June 7, 2019
MED15::ATF1-Rearranged Tumor: A Novel Cutaneous Tumor With Melanocytic Differentiation
Jennifer S Ko1, Julie Lemahieu2, Steven D Billings1
1Department of Pathology, Cleveland Clinic, Cleveland, Ohio.
Abstract:
We recently described novel dermal tumors with melanocytic differentiation and morphologic and biological similarities to cutaneous clear cell sarcoma, including CRTC1::TRIM11 cutaneous tumor, and clear cell tumors with melanocytic differentiation and either ACTIN::MITF or MITF::CREM. Here, we describe a series of 3 patients presenting with tumors reminiscent of CRTC1::TRIM11 cutaneous tumor, found to demonstrate a novel MED15::ATF1 fusion. All 3 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 3 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-Melan-A (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 a 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 emphasize the potential for aggressive biologic behavior, which should be considered in patient management planning.
Insights
A novel pediatric dermal tumor with melanocytic differentiation, characterized by a MED15::ATF1 fusion, exhibits aggressive behavior and potential for metastasis. Early diagnosis and comprehensive management are crucial for patient outcomes.
Area of Science:
- Dermatopathology
- Pediatric Oncology
- Molecular Pathology
Background:
- Previously identified novel dermal tumors with melanocytic differentiation include CRTC1::TRIM11, ACTIN::MITF, and MITF::CREM fusions.
- These tumors share similarities with cutaneous clear cell sarcoma, indicating a spectrum of melanocytic neoplasms.
Observation:
- A series of three pediatric patients (ages 5-16) presented with dermal tumors resembling CRTC1::TRIM11 cutaneous tumors.
- Histopathological examination revealed highly cellular tumors with epithelioid cells, high mitotic rates, and melanocytic marker expression (SOX10, MITF).
- Tumors exhibited varied expression of S100, Melan-A, HMB45, and Pan-Melanoma markers.
Findings:
- Whole-exome RNA sequencing identified a novel MED15::ATF1 gene fusion in all three cases.
- Two cases showed complete excision without recurrence, while one case developed regional lymph node metastasis.
- The metastatic case was successfully treated with multimodal therapy including surgery, radiation, and immunotherapy (nivolumab).
Implications:
- The MED15::ATF1 fusion defines a new subtype of pediatric dermal tumor with melanocytic differentiation.
- This tumor type demonstrates a potential for aggressive biologic behavior, necessitating careful clinical management.
- Recognition of this entity is crucial for accurate diagnosis and appropriate treatment planning in pediatric patients.
