Molecular Diagnostics and Clinicopathologic Spectrum of Kinase Fusion-Positive Spindle Cell Neoplasms of the Oral and Maxillofacial Region: A Systematic Review and Pooled Patient-Level Analysis.
Carlos M Ardila, Eliana Pineda-Vélez, Alejandro I Díaz-Laclaustra
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In 30 seconds
This systematic review and pooled patient-level analysis characterized kinase fusion-positive spindle cell neoplasms of the oral and maxillofacial region using published reports. Fifteen reports yielded 15 unique patients after deduplication; median age was 8 years (range, neonatal period-65 years), and 9 patients (60.0%) were pediatric. NTRK1 or NTRK3 alterations occurred in 10/15 patients (66.7%), while RAF1, MET, and BRAF alterations were also identified. Molecular testing’s diagnostic or therapeutic contribution could be reconstructed in 7/15 patients. Matched kinase inhibition was documented in two patients, including a rapid and durable response to larotrectinib in one patient.
Key findings
- NTRK1 or NTRK3 alterations were found in 10/15 patients (66.7%); RAF1 alterations occurred in 3/15 (20.0%).
- A partner-defined fusion was identified in 11/15 tumors; molecular evidence was classified as Tier A in 11, Tier B in three, and Tier C in one.
- A specific diagnostic or therapeutic contribution of molecular testing was reconstructed in 7/15 patients, commonly through diagnostic refinement or establishment.
- Molecularly matched kinase inhibition was documented in two patients; one LMNA::NTRK1-positive maxillary tumor responded rapidly and durably to larotrectinib.
Why it matters
These tumors span a heterogeneous clinicopathologic spectrum, so morphology and immunophenotype alone may not establish their classification. The review indicates that molecular testing can clarify diagnoses and identify kinase drivers with potential therapeutic relevance in selected cases. It also shows that the published evidence remains too limited to estimate prevalence or compare treatment effects.
What to keep in mind
The evidence base comprised only 15 unique patients from published reports and was molecularly selected; the authors state that it cannot support population prevalence estimates or comparative conclusions about treatment effects.