BRAFV600E mutation in papillary thyroid microcarcinoma: a genotype–phenotype correlation

Abstract

BRAF V600E mutation has emerged as a marker of aggressive behavior in papillary thyroid carcinoma but its significance in microcarcinoma is not entirely clear. One-hundred and twenty-nine papillary thyroid microcarcinomas were tested for BRAF V600E mutation by single-strand conformation polymorphism, and their clinicopathologic features (age, sex, tumor size, multifocality, nodal metastases, histologic subtype, tumor cell morphology, architecture, tumor-associated stromal reaction, tumor interface to non-neoplastic thyroid (well circumscribed vs infiltrative), extrathyroidal extension, lymphovascular invasion, intratumoral multinucleated giant cells, and adjacent non-neoplastic thyroid pathology) were examined. Compared with tumors without the mutation (39/129, 30%), the mutated microcarcinomas (90/129, 70%) showed significantly higher prevalence of infiltrative tumor borders (78/90 vs 23/39, P ¼ 0.001), tumor-associated stromal desmoplasia/fibrosis and/or sclerosis (80/90 vs 25/39, P ¼ 0.002), classic nuclear features of papillary thyroid carcinoma (90/90 vs 35/39, P ¼ 0.008) and cystic change (43/90 vs 11/39, P ¼ 0.05). BRAF V600E mutation was more frequent in classic (75%), tall cell (91%), and other variants (470%) than in follicular variant (21%) of papillary thyroid microcarcinoma. Tumors without the mutation were significantly more likely to be solid, well circumscribed, and lacked desmoplasia/fibrosis or sclerosis. However, on multivariate analysis, only the follicular variant of papillary microcarcinoma was significantly associated with the absence of mutation (odds ratio (95% confidence interval): 0.09 (0.01-0.54)). Lymph node metastases (n ¼ 24) were more frequent in microcarcinomas with mutation than without (21/24 vs 3/24, P ¼ 0.02). All patients with lateral cervical node metastasis (n ¼ 9), and all but one tumor with extrathyroidal extension (n ¼ 17/18) showed BRAF V600E mutation. No significant differences were noted in age, sex, tumor size, multifocality, lymphovascular invasion, psammoma bodies, stromal calcification, intratumoral multinucleated osteoclastic-type giant cells, and lymphocytic infiltration between the two groups of tumors. BRAF V600E mutation is an early event in thyroid carcinogenesis, and is associated with distinctive morphology and aggressive features even in papillary thyroid microcarcinomas.

Is BRAFV600E mutation a marker for central nodal metastasis in small papillary thyroid carcinoma?

“…It was interesting to find that the BRAFCve group had significantly less coexisting HT on histology (34.6 vs 52.5%, P!0.001). This finding appeared to concur with previous studies which found reduced peritumoral lymphocytic infiltration in BRAFCve PTCs (Sargent et al 2006, Virk et al 2013. Although the precise reason for this remains unclear, a recent study demonstrated that tumors with coexisting HT behaved less aggressively and had a better prognosis than those without coexisting HT (Dvorkin et al 2013).…”

E-cadherin expression and cell proliferation in the primary tumor and metastatic lymph nodes of papillary thyroid microcarcinoma

“…A previous study by Knauf et al (40) suggested that PTC with B-raf mutation has the potential to acquire aggressive characteristics through EMT by the stimulation of TGF-β. B-raf mutations are frequently found in PTMCs and are associated with distinctive morphology and aggressive behaviour (12,41).…”

Aggressive Variants of Papillary Thyroid Microcarcinoma Are Associated with Extrathyroidal Spread and Lymph-Node Metastases: A Population-Level Analysis

“…BRAF V600E has been shown in mPTC to be associated with tumor size, extrathyroidal extension, multifocality, nodal metastases, and advanced stage (43)(44)(45)(46). Furthermore, the mutation is highly prevalent in TCV, with reports ranging from 66% to 100% (43,(46)(47)(48)(49)(50). While the molecular pathogenesis of DSV is less well studied, RET/PTC rearrangements appear to predominate (51).…”