Abstract
Most 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 BRAFV600E 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 BRAFV600E 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.
Highlights
The vast majority of human thyroid cancers are differentiated and pathological examination reveals that most of these are papillary thyroid cancers (PTC)
Papillary thyroid microcarcinoma (PTMC) are small thyroid tumors (≤1 cm in diameter) that belong to the lowrisk well-differentiated PTC, which are probably of little clinical significance, and do not affect patient survival (Arem et al, 1999; Lloyd et al, 2004; Pazaitou-Panayiotou et al, 2007; Shaha et al, 2007)
While additional robust prospective studies are required, there is a body of evidence suggesting that BRAFV600E-positive PTMCs show aggressive behavior, whereas BRAFV600E-negative PTMCs have a good prognosis
Summary
The vast majority of human thyroid cancers are differentiated and pathological examination reveals that most of these are papillary thyroid cancers (PTC). Papillary thyroid microcarcinoma (PTMC) are small thyroid tumors (≤1 cm in diameter) that belong to the lowrisk well-differentiated PTC, which are probably of little clinical significance, and do not affect patient survival (Arem et al, 1999; Lloyd et al, 2004; Pazaitou-Panayiotou et al, 2007; Shaha et al, 2007). It is important to distinguish between PTMC in a clinically recognized malignant thyroid micro nodule and an incidental (asymptomatic) PTMC found after thyroidectomy performed for other indications (e.g., benign thyroid diseases) or during thyroid ultrasound. Papillary thyroid microcarcinomas may be categorized as: (i) PTMC found at autopsy or incidentally at histology, (ii) PTMC found incidentally during thyroid or neck ultrasound and diagnosed before surgery by cytology on thyroid fine needle aspiration (FNA) material, and (iii) clinical PTMC (i.e., tumors whose presenting symptoms were loco-regional or distant metastases). Several recent studies have suggested that US-detected PTMC (Figure 1) is a different disease entity from PTMC detected www.frontiersin.org
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