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Updated: Aug 15, 2026
An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
Published on: April 17, 2013
Histological features of BRAF V600E-mutant anaplastic thyroid carcinoma
Tiffany Y Chen1, Jochen H Lorch2, Kristine S Wong1
1Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Aims:
Treatment with a BRAF inhibitor, alone or in combination with a MEK inhibitor, may be considered for BRAF-mutant anaplastic thyroid carcinoma (ATC). The purpose of this study was to characterise the histology of BRAF V600E-mutant ATC.
Methods And Results:
We identified 28 ATC that were consecutively resected between 2003 and 2019. All tumour slides for each case were evaluated for the presence of a precursor tumour and for ATC morphology (sarcomatoid, pleomorphic giant cell, epithelioid or squamous). BRAF V600E mutation status was determined by BRAF V600E IHC or molecular analysis (OncoPanel NGS). Eighteen (64%) ATC had an associated well-differentiated precursor, including 10 (36%) with associated papillary thyroid carcinoma (PTC) and eight (29%) with associated follicular thyroid carcinoma (FTC) or Hürthle cell carcinoma (HCC). Most ATC (19 cases, 68%) demonstrated a mixed anaplastic morphology. Squamous morphology was present in four cases. Ten (36%) ATC had a BRAF V600E mutation. All ATC that had a PTC precursor had a BRAF V600E mutation (and all ATC with a BRAF V600E mutation had a PTC precursor), whereas no ATC with an FTC or HCC precursor had a BRAF V600E mutation. All four cases of ATC with a squamous morphology had a PTC precursor and a BRAF V600E mutation.
Conclusion:
In our cohort, the presence of a PTC precursor predicted the presence of the BRAF V600E mutation, whereas ATC with an FTC or HCC precursor lacked a BRAF V600E mutation. A squamous morphology was associated with the presence of a PTC precursor and a BRAF V600E mutation.
Insights
BRAF V600E-mutant anaplastic thyroid carcinoma (ATC) with a papillary thyroid carcinoma (PTC) precursor frequently harbors the BRAF V600E mutation. Conversely, ATC with follicular thyroid carcinoma (FTC) or Hürthle cell carcinoma (HCC) precursors lack this mutation.
Area of Science:
- Oncology
- Pathology
- Genetics
Background:
- Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy.
- BRAF inhibitors are considered for BRAF-mutant ATC.
- Histological characterization of BRAF V600E-mutant ATC is important for treatment selection.
Purpose of the Study:
- To characterize the histology of BRAF V600E-mutant anaplastic thyroid carcinoma.
- To investigate the association between precursor histology and BRAF V600E mutation status in ATC.
Main Methods:
- Retrospective analysis of 28 ATC cases resected between 2003 and 2019.
- Evaluation of tumor slides for precursor tumor presence and ATC morphology (sarcomatoid, pleomorphic giant cell, epithelioid, squamous).
- BRAF V600E mutation status determined by immunohistochemistry (IHC) or next-generation sequencing (NGS).
Main Results:
- 18 (64%) ATC had a well-differentiated precursor (10 PTC, 8 FTC/HCC).
- 10 (36%) ATC harbored the BRAF V600E mutation.
- All ATC with a PTC precursor had a BRAF V600E mutation; no ATC with FTC/HCC precursor had the mutation.
- Squamous morphology was associated with PTC precursor and BRAF V600E mutation.
Conclusions:
- Papillary thyroid carcinoma (PTC) precursor predicts BRAF V600E mutation in ATC.
- Follicular thyroid carcinoma (FTC) or Hürthle cell carcinoma (HCC) precursors are associated with the absence of BRAF V600E mutation.
- Squamous morphology in ATC is linked to PTC precursor and BRAF V600E mutation.
