Incidentally Discovered Papillary Thyroid Microcarcinoma in Patients Undergoing Thyroid Surgery for Benign Disease

IntroductionIncidence of thyroid carcinoma (TC) has grown significantly over the last few decades worldwide, partly due to the increase detection of small thyroid microcarcinoma (TMc). TMc are tumors with a maximal diameter ≤ 1 cm, identified during histopathology examination following a thyroidectomy performed for reasons not pertaining to malignancy. The aim of this study is to investigate the prevalence of papillary thyroid microcarcinoma (PTMc) according to the nature of benign pathology that submit patients to thyroid surgery and its trend evolution.MethodsRetrospective cohort analysis of 1815 patients who underwent total thyroidectomy for non-malignant disease from 2005 to 2020. ResultsThe mean age of subjects was 53.5 years, with a higher proportion of women (1481, 82.1%). A total of 167 PTMc (9.3%) were incidentally discovered. Multivariate logistic regression analysis shows no differences in prevalence according to sex or age in patients with PTMc compared to those with final benign histology. Multinodular goiter increases the risk of PTMc with an odds ratio of 2.2 (p=0.001) compared to Hashimoto's thyroiditis and Graves´ disease (GD). There is a statistically significant increase in the incidence of PTMc in the group operated between 2017-2020 vs. 2005-2008 (p=0.005)ConclusionOverall prevalence of PTMc in patients who underwent thyroid surgery for benign disease was 9.3%. Thyroid nodular hyperplasia was the most frequent benign pathology associated to this occult cancer as compared to Hashimoto or GD. Gender and age were not correlated with prevalence of TMc. Over the years, surgical findings of PTMc have grown, particularly in the 2017-2020 period.

Diagnostic Efficacy of Ultrasound, Cytology, and BRAFV600E Mutation Analysis and Their Combined Use in Thyroid Nodule Screening for Papillary Thyroid Microcarcinoma

BackgroundUltrasound, cytology, and BRAFV600E mutation analysis were applied as valuable tools in the differential diagnosis of thyroid nodules. The aim of the present study was to evaluate the diagnostic efficiency of the three methods and their combined use in screening for papillary thyroid microcarcinoma (PTMC).MethodsA total of 1,081 patients with 1,157 thyroid nodules (0.5–1 cm in maximum diameter) classified as thyroid imaging reporting and data system (TIRADS) 4–5 were recruited. All patients underwent ultrasound, fine-needle aspiration (FNA) examination, and an additional BRAFV600E mutation test. TIRADS and Bethesda System for Reporting Thyroid Cytopathology (BSRTC) were adopted to judge the ultrasound and cytological results. The receiver operating characteristic (ROC) curve was established to assess the diagnostic values of different methods.ResultsOf the 1,157 nodules, 587 were benign and 570 were PTMCs. BRAFV600E mutation test had highest sensitivity (85.4%), specificity (97.1%), accuracy (91.4%), and area under the ROC curve (Az) value (0.913) among the three methods. The combination of BSRTC and BRAFV600E mutation analysis yielded a considerably high sensitivity (96.0%), accuracy (94.3%), and negative predictive value (95.9%) than either BSRTC or BRAFV600E mutation alone (P < 0.0001 for all comparisons). Of all the methods, the combined use of the three methods produced the best diagnostic performance (Az = 0.967), which was significantly higher than that (Az = 0.943) for the combination of BSRTC and BRAFV600E mutation (P < 0.0001). The diagnostic accuracy of the molecular method in the 121 nodules with indeterminate cytology was 90.1% (109/121), which was significantly higher than that of TIRADS classification, 74.4% (90/121) (P = 0.002).ConclusionThe combined use of ultrasound, cytology, and BRAFV600E mutation analysis is the most efficient and objective method for diagnosing PTMC. Both BRAFV600E mutation and TIRADS classification are potentially useful adjuncts to differentiate thyroid nodules, especially indeterminate samples classified as BSRTC III.

Patient Age Is Significantly Related to Distant Metastasis of Papillary Thyroid Microcarcinoma

ObjectiveDistant metastasis in papillary thyroid microcarcinoma (PTMC) is rare but fatal, and its relationship with patient age remains unclear. The objective of this study was to examine the association between age at diagnosis and metachronous distant metastasis in PTMC.MethodsConsecutive patients who underwent thyroidectomy for PTC measuring 10 mm or less at a tertiary hospital from January 2000 to December 2016 were enrolled. Patients who had evidence of distant metastasis at diagnosis or underwent postoperative radioiodine (RAI) ablation were excluded. A Cox proportional hazards model with restricted cubic splines (RCS) was applied to examine the association between age at diagnosis and distant metastasis.ResultsA total of 4,749 patients were evaluated. The median age was 44 years (range, 8–78 years), and 3,700 (78%) were female. After a median follow-up of 65 months, 21 distant metastases (20 lung, 1 liver) were recognized. A univariate Cox proportional model using a 5-knot RCS revealed a significant overall (p = 0.01) and a potential nonlinear association (p = 0.08) between distant metastasis and age at diagnosis. In multivariate analysis, age at diagnosis, extrathyroidal extension (ETE), and lymph node metastasis (pN+) were independent risk factors for distant metastasis. Compared with the middle-aged group (30–45 years old), younger and older patients had a higher risk of distant metastasis [HR, 95% CI, p-value, age ≤ 30, 4.54 (0.91–22.60), 0.06, age > 45, 6.36 (1.83–22.13), <0.01].ConclusionAge at diagnosis is associated with metachronous distant metastasis of PTMC, and patients with younger or older age have a higher risk of distant metastasis than middle-aged patients.