Clinical and molecular features of progressive papillary thyroid microcarcinoma

In recent decades, the prevalence of thyroid cancer has risen substantially, with papillary thyroid microcarcinoma (PTMC) constituting over 50% of cases. Although most PTMCs exhibit indolent growth and a favorable prognosis, some present an increased risk of recurrence and an unfavorable prognosis due to high-risk characteristics such as lymph node metastasis, extrathyroidal extension, and distant metastasis. The early identification of clinically progressing PTMC remains elusive. In this review, the authors summarize findings from PTMC progression-related literature, highlighting that factors such as larger tumor size, cervical lymph node metastasis, extrathyroidal extension, younger age, higher preoperative serum thyroid-stimulating hormone levels, family history, and obesity positively correlate with PTMC progression. The role of multifocality in promoting PTMC progression; however, remains contentious. Furthermore, recent studies have shed light on the impact of mutations, such as BRAF and TERT mutations, on PTMC progression. Researchers have identified several mRNAs, noncoding RNAs, and proteins associated with various features of PTMC progression. Some studies propose that peripheral and tumor tissue-infiltrating immune cells could serve as biomarkers for the clinical progression of PTMC. Collectively, these clinical and molecular features offer a rationale for the early detection and the development of precision theranostic strategies of clinically progressive PTMC.