Multiple Mutations Detected Preoperatively May Predict Aggressive Behavior of Papillary Thyroid Cancer and Guide Management--A Case Report.
BACKGROUND
Multiple gene mutations in thyroid nodules are rare. The presence of several oncogenic mutations could be associated with aggressive biological behavior of tumors.


METHODS
A 60-year-old female presented to her physician after she felt a lump in her neck. On ultrasound, she was found to have a 1.4 cm × 0.8 cm × 1.3 cm nodule in the isthmus and a 0.5 cm × 0.6 cm × 0.6 cm nodule with irregular margins and hypoechogenicity in the right thyroid lobe, warranting fine-needle aspiration (FNA). Cytological examination of the smaller nodule yielded a diagnosis of atypia of undetermined significance (AUS/FLUS, Bethesda Category III). The aspirate was submitted for molecular testing using the next-generation sequencing ThyroSeq(®) v2 panel. The test revealed four distinct mutations: BRAF (p.V600E), TERT (C228T), PIK3CA (p.H1047R), and AKT1 (p.E17K). Presence of multiple oncogenic mutations in the FNA specimen was highly indicative of cancer, and suggestive of a cancer with propensity toward more aggressive biological behavior. Four weeks after the FNA results were available, the patient underwent total thyroidectomy. This was followed by radioactive iodine ablation after the final pathology revealed a 0.5 cm papillary thyroid carcinoma (PTC) with extrathyroidal extension and positive resection margins (pT3 stage).


CONCLUSIONS
Herein, the first case of four mutations preoperatively detected in a subcentimeter thyroid nodule that was confirmed to be a PTC with aggressive biological behavior is reported.


CONCLUSIONS
The judicious indication of FNA and use of molecular screening can potentially help in predicting aggressive behavior of small-sized thyroid cancers and in identifying patients who may benefit from early and more extensive therapy.
1 Division of Endocrinology and Diabetes, University of Minnesota , Minneapolis, Minnesota.
Rupendra T
RT
Shrestha
2 Division of Molecular and Genomic Pathology, Department of Pathology, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
Arivarasan
A
Karunamurthy
3 Division of Pathology, University of Minnesota , Minneapolis, Minnesota.
Khalid
K
Amin
2 Division of Molecular and Genomic Pathology, Department of Pathology, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
Yuri E
YE
Nikiforov
1 Division of Endocrinology and Diabetes, University of Minnesota , Minneapolis, Minnesota.
M Luiza
ML
Caramori
D002277:Carcinoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002291:Carcinoma, Papillary; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008875:Middle Aged; D009154:Mutation; D037981:Neck Dissection; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D057234:Preoperative Period; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016606:Thyroid Nodule / Q000235:genetics / Q000473:pathology / Q000628:therapy; D013965:Thyroidectomy; D047368:Tumor Burden
D007457:Iodine Radioisotopes; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C494918:AKT1 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt; C509186:TERT protein, human; D019098:Telomerase