High-Grade Follicular Cell-Derived Non-Anaplastic Thyroid Carcinoma: Correlating Extent of Invasion and Mutation Profile with Oncologic Outcome
Authors' conclusion
HGFCTC comprises different subgroups with different clinical behaviors determined by the extent of vascular invasion and degree of infiltration. Excellent recurrence and survival outcomes occur in encapsulated noninvasive and minimally invasive tumors compared to infiltrative tumors. Infiltrative tumors are largely "BRAF-like," whereas encapsulated angioinvasive tumors are "RAS-like." Encapsulated noninvasive tumors have a particularly unique molecular profile consisting of DICER1 mutations and a lack of BRAFV600E mutations.
Study context
- Population
- Patients who had surgery for HGFCTC (incl. encapsulated noninvasive neoplasms of follicular cells with high-grade features), 1986–2020; 50% infiltrative, 33% encapsulated angioinvasive, 18% encapsulated noninvasive/minimally invasiveNGS in 117
- Participants
- 252 patients
- Exposure
- HGFCTC subgroups by extent of invasion
- Outcome
- Disease-specific survival
- Follow-up
- 5 years
Methodological detailssingle-center
- Single-center
Main finding
As reported in the abstract
P = 0.0002
Observational data: associations, not effects.
Further findings
Presentation in infiltrative tumors
- T3/T4 disease with infiltrative tumors
- 71%
- Regional metastases with infiltrative tumors
- 55%
- Distant metastases with infiltrative tumors
- 25%
- Infiltrative significantly more likely to present with these
- P ≤ 0.003
- Regional or distant metastases at presentation, encapsulated noninvasive or minimally invasive
- 0
Common mutations (NGS, 117 patients)
- TERT
- 42%
- BRAFV600E
- 29%
- NRAS
- 27%
- EIF1AX
- 11%
- TP53
- 9%
Pathways altered
- RTK/RAS/RAF/MAPK
- 69%
- PI3K/AKT/MTOR
- 14%
- Histone methyltransferases
- 9%
- SWI/SNF chromatin remodeling complex
- 8%
Mutation drivers by subgroup
- Infiltrative subgroup mainly BRAFV600E-driven; encapsulated angioinvasive and minimally invasive subgroups NRAS-driven
- Encapsulated noninvasive tumors: different profile, DICER1 main driver
Original publication
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