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Updated: Mar 6, 2026
09:49
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
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Spitz Nevi With Novel BRAF Fusions: A Report of Two Cases With Striking Morphologic Features
Zachary Corey1, Danica Wiredja, Nicholas Willard
1Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO.
The American Journal of Dermatopathology
|March 4, 2026
Summary
Two Spitz nevi cases reveal novel BRAF fusions (AHNAK::BRAF and PDE4DIP::BRAF), expanding the molecular understanding of these melanocytic lesions. Neurotropism emerged as a key morphologic indicator for these BRAF fusion-driven Spitz nevi.
Area of Science:
- Dermatopathology
- Molecular Pathology
- Oncology
Background:
- Spitz neoplasms are a diverse group of melanocytic lesions with shared clinical and histologic traits.
- BRAF fusions are identified in a small subset (5%-6%) of Spitz neoplasms, with limited characterized fusion partners.
Purpose of the Study:
- To report two cases of Spitz nevi harboring novel BRAF fusions.
- To correlate specific morphologic findings with these newly identified molecular alterations.
Main Methods:
- Histopathologic examination including immunohistochemistry for PRAME and p16.
- Next-generation sequencing to identify BRAF fusion partners.
- Morphologic analysis focusing on patterns like neurotropism and angiotropism.
Main Results:
- Case 1: A novel AHNAK::BRAF fusion was identified in a Spitz nevus with intraepidermal/dermal proliferation, lack of maturation, neurotropism, and angiotropism.
- Case 2: A novel PDE4DIP::BRAF fusion was found in a Spitz nevus with epithelioid/spindle cell proliferation, Spitzoid features, neurotropism, and stromal entrapment.
- Both fusions retained the BRAF kinase domain but lacked N-terminal regulatory regions.
Conclusions:
- These findings broaden the known molecular landscape of Spitz neoplasms.
- Neurotropism may serve as a significant morphologic predictor for BRAF fusion-positive Spitz nevi.
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