BRAF Status in Papillary Microcarcinomas of the Thyroid Gland: a Brief Review

: Papillary thyroid microcarcinoma (PTMC) is defined by the World Health Organization as papillary cancer measuring 10 mm or less in diameter. Generally, PTMC shows an indolent clinical behavior with a good prognosis, although a minority of PTMC is characterized by an aggressive course. However, efforts to identify this aggressive subset of PTMC after surgery remain inconclusive. : Several oncogenic pathways have been identified in thyroid cancer and have been applied translationally to improve prognosis and clinical management. In particular, the BRAFV600E mutation was found more frequently in large, aggressive, recurrent and advanced tumors. : We aimed at reviewing studies on BRAFV600E mutation as a prognostic factor in PTMC.

Genomic and Transcriptomic Characterization of Papillary Microcarcinomas With Lateral Neck Lymph Node Metastases

Context Most papillary microcarcinomas (PMCs) are indolent and subclinical. However, as many as 10% can present with clinically significant nodal metastases. Objective and Design Characterization of the genomic and transcriptomic landscape of PMCs presenting with or without clinically important lymph node metastases. Subjects and Samples Formalin-fixed paraffin-embedded PMC samples from 40 patients with lateral neck nodal metastases (pN1b) and 71 patients with PMC with documented absence of nodal disease (pN0). Outcome Measures To interrogate DNA alterations in 410 genes commonly mutated in cancer and test for differential gene expression using a custom NanoString panel of 248 genes selected primarily based on their association with tumor size and nodal disease in the papillary thyroid cancer TCGA project. Results The genomic landscapes of PMC with or without pN1b were similar. Mutations in TERT promoter (3%) and TP53 (1%) were exclusive to N1b cases. Transcriptomic analysis revealed differential expression of 43 genes in PMCs with pN1b compared with pN0. A random forest machine learning–based molecular classifier developed to predict regional lymph node metastasis demonstrated a negative predictive value of 0.98 and a positive predictive value of 0.72 at a prevalence of 10% pN1b disease. Conclusions The genomic landscape of tumors with pN1b and pN0 disease was similar, whereas 43 genes selected primarily by mining the TCGA RNAseq data were differentially expressed. This bioinformatics-driven approach to the development of a custom transcriptomic assay provides a basis for a molecular classifier for pN1b risk stratification in PMC.

Diagnostic Accuracy of Preoperative Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Detecting Occult Papillary Thyroid Microcarcinomas in Benign Multinodular Goitres

Objective. To investigate the diagnostic accuracy of neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios in detecting occult papillary thyroid microcarcinomas in benign, multinodular goitres. Methods. 397 total thyroidectomy patients were identified from the institutional thyroid surgery database between 2007 and 2016 (94 males, 303 females, mean age 53 ± 14.5 years). NLR and PLR were calculated as the absolute neutrophil and absolute platelet counts divided by the absolute lymphocyte count, respectively, based on the preoperative complete blood cell count. Results. NLR was significantly higher in carcinomas and microcarcinomas compared to benign pathology (p=0.026), whereas a direct association could not be established for PLR. Both NLR and PLR scored low in all parameters of diagnostic accuracy, with overall accuracy ranging between 45 and 50%. Conclusions. As surrogate indices of the systemic inflammatory response, NLR and PLR are inexpensive and universally available from routine blood tests. Although we found higher NLR values in cases of malignancy, NLR and PLR cannot effectively predict the presence of occult papillary microcarcinomas in otherwise benign, multinodular goitres.

The Importance of the 2015 American Thyroid Association Guidelines for Adults with Thyroid Nodules and Differentiated Thyroid Cancer in Minimising Overdiagnosis and Overtreatment of Thyroid Carcinoma

The 2015 guidelines from the American Thyroid Association for adults with thyroid nodules and differentiated thyroid may be particularly important in minimising potential harm from overdiagnosis and overtreatment of thyroid tumours by providing more restrictive indications for biopsy of thyroid nodules, by considering active surveillance programs, as an alternative to surgery, for papillary microcarcinomas, and by recommending more conservative surgical approaches and a more judicious use of radioiodine.