Nucera, CarmeloPontecorvi, Alfredo2013-03-112012Nucera, Carmelo, and Alfredo Pontecorvi. 2012. Clinical outcome, role of BRAF\(^{V600E}\), and molecular pathways in papillary thyroid microcarcinoma: Is it an indolent cancer or an early stage of papillary thyroid cancer? Frontiers in Endocrinology 3:33.1664-2392http://nrs.harvard.edu/urn-3:HUL.InstRepos:10385012Most human thyroid cancers are differentiated papillary carcinomas (PTC). Papillary thyroid microcarcinomas (PTMC) are tumors that measure 1 cm or less. This class of small tumors has proven to be a very common clinical entity in endocrine diseases. PTMC may be present in 30–40% of human autopsies and is often identified incidentally in a thyroid removed for benign clinical nodules. Although PTMC usually has an excellent long-term prognosis, it can metastasize to neck lymph nodes; however deaths related to this type of thyroid tumor are very rare. Few data exist on molecular pathways that play a role in PTMC development; however, two molecules have been shown to be associated with aggressive PTMC. S100A4 (calcium-binding protein), which plays a role in angiogenesis, extracellular matrix remodeling, and tumor microenvironment, is over-expressed in metastatic PTMC. In addition, the BRAF\(^{V600E}\) mutation, the most common genetic alteration in PTC, is present in many PTMC with extra thyroidal extension and lymph node metastasis. Importantly, recently developed selective [e.g., PLX4720, PLX4032 (Vemurafenib, also called RG7204)] or non-selective (e.g., Sorafenib) inhibitors of BRAF\(^{V600E}\) may be an effective treatment for patients with BRAFV600E-expressing PTMCs with aggressive clinical–pathologic features. Here, we summarize the clinical outcome, cancer genetics, and molecular mechanisms of PTMC.en-USpapillary thyroid microcarcinomaBRAF\(^{V600E}\) mutationextracellular matrixangiogenesistumor microenvironmentclinical outcomegeneticsneck lymph node metastasisJournal Article2013-03-1110.3389/fendo.2012.00033