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Background  Molecular testing of thyroid nodules is a diagnostic tool used to better understand the nature of thyroid nodules. The aim of this study is to better comprehend the relationship between specific mutations and aggressive behavior of the tumour as demonstrated on postoperative pathological analysis.    Methods  A retrospective chart review of 103 cases was performed. Included were patients who had undergone molecular testing using a panel that tests for 9 mutations (ThyGenX®) and were found to have malignant tumours. The following gene alterations were found pre-operatively in the nodules:  BRAF V600E  ( n  = 32),  BRAF K601E  ( n  = 4),  NRAS  ( n  = 11),  HRAS  ( n  = 4),  KRAS  ( n  = 3),  RET/PTC1  rearrangement ( n  = 1),  TERT  promoter ( n  = 2),  PAX8-PPARγ  rearrangement ( n  = 1), and 45 cases where no mutation was detected. Aggressive behavior was defined by extra-thyroidal extension (ETE), lymph node metastasis (LN+), and the following variants of papillary thyroid carcinoma: tall cell, solid, diffuse sclerosing, columnar cell and hobnail. Chi-squared testing was performed to compare groups.    Results  The group with  BRAF V600E, RET/PTC1  rearrangement, and  TERT  promoter mutations was associated with ETE 37.1%, and LN+ 45.7% of the time compared to 4.3 and 13.0% in the group with other mutations, and 4.4 and 4.4% in the group with no mutations ( p -value 0.02,  p -value < 0.001, p-value 0.006). In addition, the  BRAF V600E, RET/PTC1  rearrangement ,  and  TERT  mutations group demonstrated tall cell variants (17.1%), columnar cell variants (5.7%), and hobnail variants (3%). The other mutations group demonstrated columnar cell variants (4.3%), and the no mutations group demonstrated solid variants (2.2%).    Conclusions  In this study,  BRAF V600E, RET/PTC1  rearrangement ,  and  TERT  mutations were associated with aggressive behaving thyroid malignancies as defined above. Molecular testing may be a useful method to anticipate aggressive tumour types and therefore assist in planning the extent and timing of surgery.

Molecular mutations as a possible factor for determining extent of thyroid surgery