Predictive Factors of Recurrence for Multifocal Papillary Thyroid Microcarcinoma With Brafv600e Mutation: A Single Center Study of 1,207 Chinese Patients

Abstract

Background: The American Thyroid Association (ATA) guidelines risk stratify Braf v600e mutated multifocal papillary thyroid microcarcinoma (BMPTMC) into different recurrence risk groups by the extent of extrathyroidal extension (ETE). These findings and modifications for BMPTMC need to be verified in additional studies. Methods: A retrospective cohort study was conducted in BMPTMC patients who underwent total thyroidectomy (TT) and central lymph node dissection (CLND) from 2008 to 2013. Overall, 1,207 patients were included, and predictive factors were identified by univariate and multivariate analysis over a mean 7.5-year follow up. Results: BMPTMC with ETE to capsule shows the same recurrence rate (3.8%) with intrathyroidal BMPTMC. Moreover, BMPTMC with ETE only to strap muscle, which belongs to high-risk group according to ATA guideline, shows relatively lower recurrence rate (13.3%) compared with some intermediate risk categories such as cN1 and >5 pN1. Multivariate analysis using a Cox proportional hazards regression model shows that total tumor diameter (TTD) is associated with significantly higher recurrence for BMPTMC with or without other risk factors (Hazard Ratio (HRO) = 9.86 [95%CI 5.35–18.20], p = 0.00; HRO = 2.32 [95%CI 1.12–4.85], p = 0.02; respectively), while Hashimoto thyroiditis (HT) is found to be protective against the recurrence (HRO = 0.51 [95%CI 0.33–0.79], p = 0.00; HRO = 0.47 [95%CI 0.25–0.89], p = 0.02; respectively). Conclusions: Taken together, capsular ETE and gross ETE to the strap muscles did not have the expected significant influence on recurrence for Chinese BMPTMC patients who underwent TT and CLND. Rather than the extent of ETE, TTD and the lack of HT were identified as predictors for recurrence among BMPTMC with or without other risk factors (vascular invasion, cN1, pN1>5, pN1>3 cm).

Impact of Gross Strap Muscle Invasion on Outcome of Differentiated Thyroid Cancer: Systematic Review and Meta-Analysis

“…Increasing evidence suggests that DTC patients with only gSMI have the same DFS as those with microscopic ETE (11). In our previous study, we also found that only four of 30 (13.3%) Braf-mutated thyroid papillary microcarcinoma patients with gSMI were diagnosed with recurrence (12). Accordingly, Shaha (13) suggested that a detailed distinction of gross ETE should be performed.…”

Hemithyroidectomy for Thyroid Cancer: A Review

“…Preoperative molecular testing results influencing the extent of surgery are very controversial. The mutation BRAFV600E is common in up to 60% of papillary thyroid carcinomas [10][11][12]. Some studies suggest that the presence of a BRAFV600E mutation predicts more aggressive behavior [12].…”

“…In contrast, TERT promotor mutations, alone or in combination with BRAFV600E mutations predict a high risk of recurrence or more aggressive disease course; thus, total thyroidectomy is recommended if these mutations are present [10,[12][13][14]. However, most of the studies addressing the impact of these genetic mutations relied on retrospective analysis of previously treated patients [10][11][12][13][14], and more prospective studies will be needed to elucidate a clear role of these genetic markers in the risk stratification and subsequent management of patients with differentiated thyroid cancer.…”

Clinical and ultrasonic risk factors for high‐volume central lymph node metastasis in cN0 papillary thyroid microcarcinoma: A retrospective study and meta‐analysis

“…Husniye et al demonstrated that the presence of HT has no effect on ultrasonography features, fine‐needle aspiration biopsy outcomes, or histological findings of PTC lesions but is negatively associated with aggressive histopathological behaviour in PTMC 66 . Additionally, Xue et al 67 suggest that HT is protective against recurrence. However, Yin et al 68 show that HT is independently and positively linked to LNM in female PTMC patients aged <55 years.…”