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Emerging Concepts in the Diagnosis and Work-up of Thyroid Cancer. Short Presentation in Emerging Concepts (SPEC). Thyroid Nodules. Found in 4-7% of U.S. adults Approximately 5% are malignant. Fine needle aspiration (FNA) mainstay of diagnosis Bethesda system: Six diagnostic categories - PowerPoint PPT Presentation
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Emerging Concepts in the Diagnosis and Work-up of
Thyroid Cancer
Short Presentation in Emerging Concepts (SPEC)
Thyroid Nodules
• Found in 4-7% of U.S. adults– Approximately 5% are malignant.
• Fine needle aspiration (FNA) mainstay of diagnosis
• Bethesda system:– Six diagnostic categories– Correlate with risk of malignancy and
recommended clinical management
Bethesda Diagnostic Categories(2009)
Papillary thyroid carcinoma (PTC)
• Approximately 85% of thyroid cancers• Often (50-60%) harbor mutations in BRAF gene
– Point mutation at codon 600 results in substitution of glutamate for valine (V600E)
– Most common mutation in PTC
• Mutation found more often in conventional and tall-cell variants
PTC Variant % Positive for BRAF V600E
Conventional PTC 60%
Tall-cell PTC 77%
Follicular variant PTC 12%
BRAF
V600E mutation leads to constitutive activation of the mitogen activated protein kinase (MAPK) signaling pathway
Atypia of Undetermined Significance
• 10-15% of fine needle aspirations (FNAs)
• 5-15% risk of malignancy
• Often referred for diagnostic thyroidectomy– Low but defined risk of complications
BRAF in diagnosis of PTC
• BRAF V600E is VERY SPECIFIC (99.8%) for PTC.– BRAF mutation is very strong evidence of PTC
• BRAF V600E is NOT SENSITIVE for PTC (49.5%)– Failure to detect a BRAF mutation does NOT rule out
PTC.
• Niche for BRAF testing in cases with indeterminate cytology?
• BRAF testing can increase the ability of FNA biopsy to reach a diagnosis.
Studies evaluating BRAF in thyroid FNAs
BRAF and PTC prognosis
• Numerous studies have found that PTC with mutated BRAF have more aggressive features– Extrathyroidal extension, regional metastasis, etc.– Even applies to small lesions (less than 1.0 cm)
• However, excellent prognosis in general for PTC– Over 95% 10-year survival rate– Targeted therapy against BRAF unlikely to markedly
improve survival
BRAF testing
• Predominantly occurs via PCR– Assay should have the ability to detect the
mutation in the background of normal cells seen in the cytology
• Can be performed on:– Residual cytology sample in preservative
solution after cytological examination– Formalin fixed paraffin embedded tissue
blocks and slides
Conclusions
• BRAF testing can aid in diagnosing papillary thyroid carcinoma from cytology samples– Particularly useful with indeterminate cytology
• Identifies PTC with more aggressive features.– May help identify patients needing surgery.
• No current role in therapy selection– Full prognostic significance still unknown
Selected Resources
Melck AL, Yip L, Carty SE. The utility of BRAF testing in the management of papillary thyroid cancer. Oncologist. 2010;15:1285-1293.
Nikiforova MN, Kimura ET, Gandhi M, et al. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab 2003;88:5399-5404
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