Objective: Here we present 2 cases of papillary thyroid microcarcinomas (PMCs) that had metastasized at presentation. The 2015 American Thyroid Association and the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) criteria do not recommend biopsy of the majority of subcentimeter thyroid nodules, as PMCs are mostly indolent with excellent prognosis. However, the paradigm of active surveillance presents a conundrum on how to identify the rare patient with distant metastatic disease while avoiding unnecessary intervention in the majority. Methods: After initial discovery of incidental lesions on chest computed tomography, core or wedge biopsies of the lung lesion were performed. Thyroid nodules on ultrasound were classified by TI-RADS. Tumor DNA was sequenced, annotated, filtered on 119 known cancer genes, and filtered for variants with an exome allele frequency of <0.001. Results: A 70-year-old woman and a 29-year-old woman presented with incidental pulmonary lesions on computed tomography scan. Lung biopsy revealed lung metastases from papillary thyroid carcinoma. The thyroid nodules in both patients were TI-RADS 3 and American Thyroid Association low-suspicion. Molecular testing showed a c.1721C>G mutation (p.Thr574Ser) in the TSHR gene in patient 1 and a codon 61 mutation in the NRAS gene in patient 2. Both patients were iodine-avid, with complete structural remission in one patient and ongoing treatment with evidence of structural response in the other. Conclusion: The 2 presentations demonstrate unexpected and concerning behavior of PMCs. Both thyroid tumors were subcentimeter in diameter, meaning they would have escaped detection using traditional risk-stratification algorithms in active surveillance. Further knowledge of tumor genetics and microenvironment may assist in predicting tumor behavior in PMCs.
A Novel Adenomatous Polyposis Coli Gene Mutation of Cribriform-Morular Variant Papillary Thyroid Carcinoma: A Case Report
