Novel fusion sarcomas including targetable NTRK and ALK

Area of Science:

• Oncology
• Molecular Pathology
• Genomics

Background:

• Distinctive molecular signatures in emerging cancers necessitate advanced diagnostic algorithms.
• Fusion sarcomas present diagnostic challenges requiring integrated clinicoradiologic, morphologic, and molecular analysis.

Observation:

• Six fusion sarcomas (2020-2021) were analyzed using clinicoradiology, morphology, phenotype, and next-generation sequencing (NGS).
• Tumors included novel KANK1-NTRK2 and ERC1-ALK fusions, alongside CIC-DUX4 and STAT6-NAB2 fusions.
• Patient ages ranged from 2 to 73 years, with tumors located in the chest wall, neck, or extremities.

Findings:

• A novel KANK1-NTRK2 sarcoma exhibited aggressive behavior with metastases.
• An ERC1-ALK fusion sarcoma, a low-grade infiltrative tumor, responded successfully to ALK-inhibitor therapy (Crizotinib).
• CIC-DUX4 tumors showed rapid metastasis, and a solitary fibrous tumor presented with intermediate-risk stratification.

Implications:

• The identification of new fusion partners like KANK1 and TPR in NTRK/ALK sarcomas suggests unusual high-grade morphology and behavior.
• Integrated diagnostic approaches combining clinicoradiologic, morphologic, and molecular data are crucial for accurate sarcoma classification.
• Targeted therapies, such as ALK inhibitors, offer promising treatment avenues for specific fusion-driven sarcomas, potentially avoiding extensive surgery.