The Role of 5-Hydroxymethylcytosine as a Potential Epigenetic Biomarker in a Large Series of Thyroid Neoplasms.

Cytosine modifications at the 5-carbon position play a critical role in gene expression regulation and have been implicated in cancer development. 5-Hydroxymethylcytosine (5hmC), arising from 5-methylcytosine (5-mC) oxidation, has shown promise as a potential malignancy marker due to its depletion in various human cancers. However, its significance in thyroid tumors remains underexplored, primarily due to limited data. In our study, we evaluated 5hmC expression levels by immunohistochemistry in a cohort of 318 thyroid tumors. Our analysis revealed significant correlations between 5hmC staining extension scores and nodule size, vascular invasion, and oncocytic morphology. Nuclear 5hmC staining intensity demonstrated associations with focality, capsule status, extrathyroidal extension, vascular invasion, and oncocytic morphology. Follicular/oncocytic adenomas exhibited higher 5hmC expression than uncertain malignant potential (UMP) or noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), as well as malignant neoplasms, including papillary thyroid carcinomas (PTCs), oncocytic carcinomas (OCAs), follicular thyroid carcinomas (FTCs), and invasive encapsulated follicular variants of PTC (IEFV-PTC). TERT promoter mutation cases showed notably lower values for the 5hmC expression, while RAS (H, N, or K) mutations, particularly HRAS mutations, were associated with higher 5hmC expression. Additionally, we identified, for the first time, a significant link between 5hmC expression and oncocytic morphology. However, despite the merits of these discoveries, we acknowledge that 5hmC currently cannot segregate minimally invasive from widely invasive tumors, although 5hmC levels were lower in wi-FPTCs. Further research is needed to explore the potential clinical implications of 5hmC in thyroid tumors.

Subcentimetric Papillary Thyroid Carcinoma: Does the Diagnosis Kind Impact Prognosis?

INTRODUCTION: Subcentimetric papillary thyroid carcinoma (SPTC) (papillary thyroid carcinoma with less than 10 mm in size) usually presents an excellent prognosis, with few aggressive reported cases. Given the globally increased incidence of SPTC, physicians are struggling with the need to identify prognostic factors to stratify SPTC. The aim was to compare clinicopathological variables and prognosis between clinically and incidentally diagnosed SPTC. Materials and methodsː This is a retrospective observational study on patients with SPTC who underwent thyroidectomy between 2002 and 2015. Two groups were considered: G1 (n=60 (61.9%)), clinical diagnosis (Bethesda III-VI cytology in the thyroid tumor/in cervical lymphadenopathies) and G2 (n=37 (38.1%)), incidental diagnosis (thyroidectomy for benign thyroid pathology). The histological material was reviewed, and molecular analysis of the BRAF, RAS, and TERT promoter (TERTp) genes was performed. Resultsː Ninety-seven individuals were included, 60 (61.9%) of which were from G1, with a predominance of female sex (n=83 (85.6%)). Individuals of G1 were younger (53.0±14.2 versus 59.3±13.9 years; p=0.035), were more frequently treated with 131-iodine (39.2% versus 13.4%; p=0.007), had the largest diameter (8 (p25-p75: 7-9) versus 5 (p25-p75: 4-6.5) mm; p<0.001), and higher frequency of minimal extracapsular invasion (45% versus 24.3%; p=0.041). Increased tumor size was the only independent predictor of a clinical diagnosis (p<0.001). Conclusionsː Clinically and incidentally diagnosed SPTC showed excellent medium- to long-term prognosis. A larger SPTC was more likely a driver of clinical detection than a marker of tumor aggressiveness, but caution should be taken as contradictory data persists.