Different Threshold of Malignancy for RAS-like Thyroid Tumors Causes Significant Differences in Thyroid Nodule...

Area of Science:

• Endocrinology
• Oncology
• Pathology

Background:

• Histopathological diagnosis of papillary thyroid carcinomas (PTCs) faces observer variation, particularly regarding RAS-like nuclear changes.
• Diagnostic thresholds for PTC nuclear features differ between Asian and Western pathologists, influenced by factors like malpractice concerns.
• This variation leads to inconsistent classification of tumors with subtle RAS-like changes, impacting diagnostic accuracy and patient cohorts.

Purpose of the Study:

• To investigate the impact of observer variation in diagnosing papillary thyroid carcinoma (PTC) on BRAFV600E mutation incidence.
• To analyze the prognostic implications of differing diagnostic thresholds for PTC in Asian and Western patient cohorts.
• To re-evaluate pre-2017 thyroid carcinoma prognostic analyses based on Western cohorts with potential misclassification of indolent tumors.

Main Methods:

• Comparative analysis of histopathological diagnostic criteria for RAS-like nuclear changes in PTC.
• Review of published data on BRAFV600E mutation frequencies in PTC from Asian and Western patient cohorts.
• Evaluation of the influence of diagnostic thresholds on tumor classification and subsequent prognostic assessments.

Main Results:

• Higher incidence of BRAFV600E mutations (50-90%) in PTC from Asian countries compared to Western cohorts (35-50%) due to differing diagnostic thresholds.
• Western cohorts may include indolent RAS-like tumors in the PTC category, inflating BRAFV600E mutation rates and suggesting aggressive behavior.
• The BRAFV600E test lacks prognostic value in Asian PTC patients as indolent tumors are typically excluded from the PTC diagnosis.

Conclusions:

• Observer variation in diagnosing PTC significantly influences BRAFV600E mutation detection and interpretation.
• The BRAFV600E test's prognostic utility is cohort-dependent, with Western data potentially skewed by misclassified indolent tumors.
• Re-evaluation of thyroid carcinoma prognoses and clinical guidelines established before 2017 is necessary due to potential misclassification in Western cohorts.