Solitary Papillary Thyroid Microcarcinoma Research Articles

Inter-observer variation in two-dimensional and three-dimensional ultrasound measurement of papillary thyroid microcarcinoma

BackgroundsThe reliable ultrasound (US) measurements of papillary thyroid microcarcinoma (PTMC) are very important during active surveillance. This prospective study was design to investigate the inter-observer reliability and agreement of two- dimensional ultrasound(2DUS) and three-dimensional ultrasound(3DUS) in the measurement of maximum diameter and volume for PTMC.MethodsThis prospective study included 51 consecutive patients with solitary PTMC confirmed by biopsy. Two independent observers performed measurements of each tumor using a standardized measurement protocol. The maximum diameter was the largest one of the three diameters measured on the largest transverse and longitudinal 2DUS images. 2DUS volume was calculated using ellipsoid formula method. The virtual organ computer aided analysis(VOCAL) was used to determine 3DUS volume. The inter-observer reliability was assessed using intraclass correlation coefficient(ICC) with 95% confidence intervals(CIs). Bland-Altman analysis was used to evaluate agreement, and expressed as a bias with 95% limits of agreement(LOA).ResultsThe maximum diameter was 0.78 ± 0.14 cm. Volume measured by 3DUS was significantly smaller than that by 2DUS(0.163 ± 0.074 cm3 vs. 0.175 ± 0.078 cm3, P = 0.005). The ICCs of inter-observer reliability of maximum diameter, 2DUS volume and 3DUS volume was 0.922(0.864–0.955), 0.928(0.874–0.959), and 0.974(0.955–0.985), respectively. The ICCs of 2DUS and 3DUS volume was 0.955(0.909–0.976). The inter-observer agreement of maximum diameter, 2DUS volume and 3DUS volume was 1.096(0.7322 to 1.459), 1.008(0.5802–1.435), and 1.011(0.7576–1.265), respectively. The inter-observer agreement of 2DUS and 3DUS volume was 1.096(0.7322 to 1.459).ConclusionMaximum diameter had the lowest degree of observer variation among all the measurements. Volume measured by 3DUS had lower variability and higher repeatability than that by 2DUS, which might be helpful to provide more reliable estimates of tumor size for PTMC.

Long-Term Efficacy of Ultrasound-Guided Laser Ablation for Papillary Thyroid Microcarcinoma: Results of a 10-Year Retrospective Study.

Background: The aim of this study was to evaluate the 10-year efficacy and safety of laser ablation (LA) for the treatment of solitary papillary thyroid microcarcinoma (PTMC). Methods: LA was performed on patients with low-risk PTMC (diagnosed using fine-needle aspiration cytology) who refused or were ineligible for surgery between 2008 and 2011. Ultrasonography was performed to evaluate the ablated volumes and potential recurrences on the day after the procedure, as well as at 1 week, 1, 3, and 6 months, and every 6 months thereafter for 10 years. Computed tomography (CT) with contrast enhancement and positron emission tomography/CT was performed to evaluate local recurrences and distant metastases. Results: A total of 90 PTMCs in 90 patients were treated in a single session of LA, and the procedure was well tolerated by the patients. The mean follow-up duration was 112 months. By 3-10 months after the LA, all the ablation areas had disappeared or presented as scars. The disappearance rate was 100% after 12 months. Thyroid hormone and autoantibody levels did not change significantly after the treatment. Three patients experienced transient voice changes, but each recovered within 1 month. Additional PTMC foci were subsequently detected in previously untreated areas in five patients (5.5%) 17-56 months after the treatment. A metastatic lymph node was detected in one patient (1.1%) within two months of the treatment; however, it was determined to be an undetected cancer metastasis, rather than a recurrence. All the patients with recurrence underwent surgery, and there were no instances of recurrence after >5 years. Conclusions: LA is effective and safe for the treatment of low-risk PTMCs. A thorough examination of multifocality and lymph node metastasis status is required before considering LA treatment.

Clinical Analysis of Risk Factors for Cervical Lymph Node Metastasis in Papillary Thyroid Microcarcinoma: A Retrospective Study of 3686 Patients.

PurposeTo investigate the risk factors for cervical lymph node metastasis (LNM) in papillary thyroid microcarcinoma (PTMC).Patients and MethodsIn total, 3686 patients with PTMC who underwent initial surgery in Shanghai Jiao Tong University affiliated Sixth People’s Hospital from January 2010 to December 2019 were retrospectively analyzed. Univariate and multivariate analyses were conducted to identify risk factors associated with cervical LNM.ResultsMale gender [odds ratio (OR) =1.420, P <0.001], age <55 years (OR =2.128, P <0.001), tumor size >6.5 mm (OR =2.112, P <0.001), lymphovascular invasion (LVI) (OR =2.110, P =0.016), multifocality (OR =1.358, P =0.022), extrathyroidal extension (ETE) (OR =1.598, P <0.001), and lateral LNM (LLNM) (OR =6.383, P <0.001) served as independent risk factors for central LNM (CLNM). Moreover, male gender (OR =1.668, P =0.001), tumor size >6.5 mm (OR =2.223, P <0.001), chronic lymphocytic thyroiditis (OR =1.402, P =0.021), LVI (OR =4.582, P <0.001), ETE (OR =1.393, P=0.023), and CLNM (OR =6.212, P <0.001) served as independent risk factors for LLNM. Furthermore, solitary PTMC with lesions in the upper third of the thyroid gland were more associated with LLNM than lesions in the other regions.ConclusionThis study suggests that meticulous evaluation of risk factors associated with LNM is required in order to guide the surgical treatment of PTMC patients in clinical practice.

The occurrence of and predictive factors for multifocality and bilaterality in patients with papillary thyroid microcarcinoma.

Thyroidectomy or hemithyroidectomy may be performed as treatment for papillary thyroid microcarcinoma (PTMC). However, in cases of bilateral PTMCs, only thyroidectomies should be recommended. Sometimes bilateral PTMC may be undetected in presurgical evaluations, so reoperation might be necessary after a partial thyroid resection. The aim of this study was to assess the occurrence of and predictive factors for the multifocality and bilaterality of PTMCs.We performed a retrospective review of 4716 consecutive patients with thyroid tumors. Of these patients, 434 (9.2%) had thyroid malignancies. All patients underwent thyroidectomies with central and/or lateral lymph node dissection between January 2008 and December 2017. PTMC was identified in 177 (3.75%) individuals.Solitary PTMC was observed in 114 (64.4%) patients, multifocal PTMC was seen in 48 (27.1%) patients, and bilateral PTMC was detected in 15 (8.5%) patients. The occurrence of solitary PTMC increased from 11.1% in 2008 to 61.9% in 2017. The occurrence of multifocal tumors significantly decreased from 77.8% in 2008 to 6.3% to 18.4% in 2013 to 2016 (P < .05). The occurrence of bilateral tumors, with respect to all PTMC cases, did not change during the 10-year period. We observed significantly higher rates of hypoechogenicity, more microcalcifications, more irregular margins, larger tumor sizes, and higher vascularity in the patients with multifocal and bilateral tumors than in the patients with solitary tumors (P < .0001 for all).The occurrence of bilateral PTMC is not very common. In patients with PTMC, thyroidectomy should be considered when microcalcifications, an irregular tumor shape, unclear margins, hypoechogenicity, high vascularity, and a large tumor size are observed. These clinicopathological features are prognostic factors for multifocal and bilateral PTMC.

Ultrasound-guided laser ablation versus surgery for solitary papillary thyroid microcarcinoma: a retrospective study

Objectives: To compare the clinical outcomes of ultrasound-guided laser ablation (LA) and surgery for treatment of solitary papillary thyroid microcarcinoma (PTMC).Methods: A total of 81 consecutive patients with solitary PTMC were included in this retrospective study. Among them, 36 received LA and 45 underwent surgery. Surgery was performed by hemithyroidectomy with unilateral central neck dissection. The follow-up consisted of a physical examination, neck ultrasonography, chest X-ray or CT scan and thyroid function tests. The procedure time, hospital stay, complication and recurrence rates were compared between the two groups after treatment.Results: The follow-up period for the LA and surgical group were 49.2 ± 4.5 months (range, 30–54 months) and 48.5 ± 6.2 months (range, 24–54 months), respectively. The mean hospital stay and procedure time in the LA group were shorter than those in the surgical group. After LA, the largest diameter and average volume decreased from 4.7 ± 1.4 mm to 0.2 ± 0.8 mm, and from 43.2 ± 38.8 mm3 to 0.7 ± 4.1 mm3 (p < .05 for both), respectively. The complication rates and recurrence rates did not differ between the LA group (2.8% [1 of 36] and 5.6% [2 of 36]) and the surgical group (6.7% [3 of 45] and 6.7% [3 of 45]) (p > .05 for both). No distant metastasis occurred in the either group during the follow-up period.Conclusions: Compared with hemithyroidectomy with unilateral central neck dissection, ultrasound-guided LA was also a safe and effective therapy for treating solitary PTMC, and it may be considered as a treatment alternative for patients who are ineligible or refusal to undergo surgery.

Predictive factors of lateral lymph node metastasis in solitary papillary thyroid microcarcinoma without gross extrathyroidal extension

Solitary papillary thyroid microcarcinoma (PTMC) without gross extrathyroidal extension (ETE) were the main candidates for active surveillance (AS). Predictive factors of lateral lymph node metastasis (LLNM) in solitary PTMC without gross ETE were essential but still unknown. Altogether, 171 patients of solitary PTMC without gross ETE were enrolled in ourstudy and divided into two groups. Group A: 123 patients without lateral lymph nodedissection (LLND) were considered to be LLNM negative because there was nolateralrecurrence by at least 8-year follow up for all patients. Group B: 48 patients with LLND were considered to be LLNM positive which confirmed by postoperative pathology. Multivariate logistic regression showed male gender, upper location of tumor and diameter of tumor ≥7mm to be predictive factors (odds ratio=4.237 [confidence interval (CI) 1.365-13.149, p=0.012; odds ratio=2.933 [CI 1.117-7.700, p=0.029; odds ratio=4.557 [CI 1383-15.016, p=0.013) for LLNM in solitary PTMC patients without gross ETE. Multiple level metastasis happened in 29 (60.42%) cases while single level metastasis in 19 (39.58%). Within the lateral cervical lymph node chain, level Ⅲ nodes were consistently the most frequently involved (38/48, 79%), following by level Ⅳ (27/48, 56%), level Ⅱ (25/48, 52%) and level V (5/48, 10%). Most interesting, there are 12 (12/48, 25%) skip metastatic (positive in lateral neck and negative in central neck) patients among LLNM positive group. Male gender, upper location of tumor and diameter of tumor ≥0.7cm to be predictive factors of LLNM in solitary PTMC without gross ETE.

The sonographic characteristics of papillary thyroid microcarcinoma and its risk evaluation of cervical lymphatic metastasis

Objective To investigate the sonographic characteristics of papillary thyroid microcarcinoma(PTMC) and the preoperative prediction value for cervical lymphatic metastasis of PTMC. Methods Three hundred and fifty-eight PTMC patients who were confirmed by pathology and accepted partly or totally thyroidectomy and neck dissection were collected to analyze the sonographic characteristics, all patients were classified according to multifocal carcinoma nodules and solitary carcinoma nodules; cervical lymphatic metastasis or not; the maximum diameter of carcinoma nodules. Univariate analysis and Logistic regression analysis were used. Results Compared with solitary PTMC, multifocal PTMC was prone to emerge blood flow signals, heterogeneity, cervical lymphatic metastasis(all P 1 cm, irregular edge, irregular shape, microcalcification, capsular invasion(all P<0.05). With Logistic regression analysis, the independent risk factors of cervical lymphatic metastasis in PTMC were multifocality and capsular invasion. Combining multifocality and capsular invasion, which area under the ROC(AUC) was 0.807. Conclusions Combining multifocality and capsular invasion significantly improves the risk of cervical lymphatic metastasis in PTMC by ultrasonography. Key words: Ultrasonography; Thyroid neoplasms; Lymphatic metastasis

Association between BRAFV600E mutation and the clinicopathological features of solitary papillary thyroid microcarcinoma.

The B-Raf proto-oncogene serine/threonine kinase (BRAF)V600E mutation is an important oncogene in the development of papillary thyroid carcinoma (PTC) and has been identified as a risk factor for poor prognosis in patients with PTC. However, whether the BRAFV600E mutation is a prognostic marker in patients with solitary papillary thyroid microcarcinoma (sPTMC) has not yet been established. The present study aimed to identify the association between BRAFV600E mutation and the clinicopathological features of patients with sPTMC. A total of 108 patients with sPTMC who underwent surgery at the Cancer Institute and Hospital of the Chinese Academy of Medical Sciences between December 2010 and December 2012 were analyzed retrospectively. Exon 15 of the BRAF gene was amplified using the polymerase chain reaction and direct sequencing was performed to detect the BRAFV600E mutation. Statistical analysis was subsequently performed using SPSS software (version 16.0). The association between BRAFV600E mutation and clinicopathological features of sPTMC was tested with the χ2 test or Fisher's exact test, as appropriate. There were 27 males and 81 females in the cohort, who were aged between 22 and 66 years old, with an average age of 42 years. The BRAFV600E mutation was found in 59 out of 108 (54.6%) patients with sPTMC. The presence of the BRAFV600E mutation was demonstrated to be significantly associated with extrathyroidal extension (P=0.019), advanced Tumor-Node-Metastasis stage (P=0.007) and the presence of autoimmune thyroiditis (P=0.010). The BRAFV600E mutation was not significantly associated with gender, anatomic location or subtype of sPTMC (P>0.05). In addition, the BRAFV600E mutation indicated poor prognosis in patients with sPTMC. These results suggest that the BRAFV600E mutation is a risk factor for poor prognosis in patients with sPTMC. This knowledge will aid in the risk stratification and post-operative management of patients with sPTMC.

Therapeutic Outcomes of Patients with Multifocal Papillary Thyroid Microcarcinomas and Larger Tumors.

A retrospective review of 626 patients with multifocal papillary thyroid carcinoma (PTC) including 147 patients (23.5%) with multifocal papillary thyroid microcarcinoma (PTMC) from a total of 2,536 patients with PTC who visited the Chang Gung Medical Center in Linkou, Taiwan, was performed. A comparison of the clinical features between 626 multifocal and 1,910 solitary PTC cases showed that patients in the multifocal PTC group were older and had a smaller mean tumor size, a more advanced tumor-node-metastasis (TNM) stage, and a higher percentage of nonremission status compared to patients in the solitary PTC group. Of the 626 patients with multifocal PTC, the group with larger tumors showed a more advanced TNM stage, a higher percentage of lymph node metastasis and soft tissue invasion, and a higher nonremission rate compared to the multifocal PTMC group. Of the 626 patients with multifocal PTC, 25 patients (4%) died during a mean follow-up period of 7.1 ± 5.3 years. Kaplan-Meier survival curves showed a significantly lower survival rate associated with multifocal PTMC compared to that with solitary PTMC.

Solitary Papillary Thyroid Microcarcinoma (0.3 cm in Diameter) Presenting Multiple Distant Metastases at the Time of Diagnosis

Papillary thyroid microcarcinoma (PTMC) is defined as being 1 cm or less in diameter. Although the prognosis of PTMC is known to be more favorable than that of papillary thyroid carcinoma greater than 1 cm in diameter, pathologic factors suggesting aggressiveness, such as multifocality and lymph node invasion, have been reported to be highly prevalent in PTMC. However, the rate of distant metastasis in patients with PTMC is very low. Many investigators have reported that initial distant metastasis was detected only in patients with PTMC greater than 0.4 cm in diameter, however these cases have involved only one organ, usually the lung. We report here on an extremely unusual case of solitary PTMC (0.3 cm in diameter) presenting multiple distant metastases at the time of diagnosis.